bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Drought Tolerance of Seven Potato Varieties on Volcanic Ash Soils in a Medium-Term Trial
Authors: Martínez Ingrid , Muñoz Manuel , Acuña Ivette , Uribe Marco
Published: June 2021

One of the main factors limiting the productivity of potatoes (Solanum tuberosum L.) is water stress. Two irrigation systems: full irrigation (I) and rainfed conditions (R), were compared over the growing seasons from 2012–13 to 2019–20. The evaluated varieties were Desiree, Karú-INIA, Patagonia-INIA, Puyehue-INIA, Yagana-INIA, Yaike, and Porvenir. This study determined (i) the yield and tuber size distribution, (ii) their relationship between productivity and environmental conditions, and (iii) the most drought-tolerant varieties based on drought tolerance indices. Nine indices including yield index (YI), tolerance index (TOL), mean productivity (MP), geometric mean productivity (GMP), harmonic mean (Harm), stress tolerance index (STI), harmonic mean productivity (HMP), yield reduction (Yr), and stress susceptible index (SSI) were calculated by using tuber yield under I and R conditions. Tuber yield under R conditions decreased by 27 and 34%. However, the highest yield under R conditions occurred in years with more precipitation between 60 and 120 days after planting (DAP; ±60 mm). Under R conditions, the varieties Porvenir, Patagonia-INIA, Yaike, and Puyehue-INIA showed more tolerance to water stress. Water stress negatively affected tuber size distribution, reducing the production of tubers with size >65 mm by 50–60%. The best indices to study drought tolerance were TOL, MP, GMP, Harm, STI, and HMP. This study suggests that in southern Chile, an area with big yield potential, typically cultivated as rainfed, with cool temperate climate conditions and favorable soil properties for potatoes, as Andisols, available rainfall is still a constraint for yield. Therefore, using more water stress-tolerant varieties and providing supplementary irrigation between 60 and 120 DAP are critical to optimize yield and avoid the failure of the crop in years with remarkably low precipitations, which will be more pronounced in the future according to weather trends. These results exemplify how much we can lose in productivity in rainfed conditions even in one of the most favorable areas for growing potatoes in the world and how risky this situation can be for the performance of the potato farms in the future.
Stigmatizing Attitudes Toward Depression Among Male and Female, Medical and Non-medical Major College Students
Authors: He Haoyu , Wu Qiuxia , Hao Yuzhu , Chen Shubao , Liu Tieqiao , Liao Yanhui
Published: June 2021

Background: Stigma is often reported to be a barrier to the treatment and rehabilitation of depression. However, little is known about stigma toward people with depression among college students in China.

Methods: Using a questionnaire with a case vignette describing depression, a total of 1,056 students from nine colleges/universities in Hunan Province of China were included in this study. The questionnaire addressed the attitudes toward depression and the desire for keeping a distance from depressed individuals. The current study explored the stigma attitudes of college students toward people with depression and the desire for social distancing, as well as the gender (male and female) and major (medical and non-medical) differences.

Results: Over half of the respondents agreed that people described in the vignette were “dangerous” (60.7%) and “could snap out of the problem” (58.7%). Compared with female students, males were more likely to agree that “If I had this problem, I would not tell anyone” (7.0 vs. 13.2%, p = 0.001); compared with non-medical students, medical students were more likely to agree that “The problem is a sign of personal weakness” (38.0 vs. 50.0%, p < 0.001). A lot of respondents would be unwilling to “marry into the family of people with depression” (71.1%) or “work closely with them” (45.1%). Compared with male students, females were more unwilling to “work closely with them” (40.3 vs. 47.5%, p = 0.026).

Conclusion: This study found that a high proportion of Chinese college students showed stigma toward and desire for social distancing from people with depression, male students and medical major students showed higher stigma in some subscale items toward people with depression. The present results suggest that more anti-stigma interventions should be applied for Chinese college students to help prevent or reduce stigma attitudes toward people with depression.
A Research Agenda to Better Understand the Human Dimensions of Energy Transitions
Authors: Steg Linda , Perlaviciute Goda , Sovacool Benjamin K. , Bonaiuto Marino , Diekmann Andreas , Filippini Massimo , Hindriks Frank , Bergstad Cecilia Jacobbson , Matthies Ellen , Matti Simon , Mulder Machiel , Nilsson Andreas , Pahl Sabina , Roggenkamp Martha , Schuitema Geertje , Stern Paul C. , Tavoni Massimo , Thøgersen John , Woerdman Edwin
Published: June 2021

The Social Sciences and Humanities (SSH) have a key role to play in understanding which factors and policies would motivate, encourage and enable different actors to adopt a wide range of sustainable energy behaviours and support the required system changes and policies. The SSH can provide critical insights into how consumers could be empowered to consistently engage in sustainable energy behaviour, support and adopt new technologies, and support policies and changes in energy systems. Furthermore, they can increase our understanding of how organisations such as private and public institutions, and groups and associations of people can play a key role in the sustainable energy transition. We identify key questions to be addressed that have been identified by the Platform for Energy Research in the Socio-economic Nexus (PERSON, see person.eu), including SSH scholars who have been studying energy issues for many years. We identify three main research themes. The first research theme involves understanding which factors encourage different actors to engage in sustainable energy behaviour. The second research theme focuses on understanding which interventions can be effective in encouraging sustainable energy behaviour of different actors, and which factors enhance their effects. The third research theme concerns understanding which factors affect public and policy support for energy policy and changes in energy systems, and how important public concerns can best be addressed as to reduce or prevent resistance.
Developmental Topographical Disorientation With Concurrent Face Recognition Deficit: A Case Report
Authors: Rusconi Maria Luisa , Fusi Giulia , Stampatori Chiara , Suardi Angelo , Pinardi Chiara , Ambrosi Claudia , Costa Tommaso , Mattioli Flavia
Published: June 2021

Developmental topographical disorientation (DTD) has been defined as a developmental deficit in human navigational skills in the absence of congenital or acquired brain damage. We report the case of Lost In Space Again (LISA), a 22-year-old woman with a normal development and no clinical history of neurological or psychiatric diseases, evaluated twice, with an interval of 5 years. The magnetic resonance imaging (MRI) examination did not reveal any morphological alteration, while diffusion tensor imaging (DTI) showed a structural connectivity deficit (a decreased fractional anisotropy—FA) in the parieto–prefrontal and parieto–premotor pathway. The behavioral assessment showed different deficits in spatial and navigational tasks, which seemed to be connected to a poor ability to form a cognitive map of the environment. Moreover, LISA displayed a poor performance in high-level face encoding and retrieval. The aim of this case report is to share new insight about DTD in order to deepen the knowledge of this specific neurodevelopmental disorder. In conclusion, this novel DTD case (1) supports the hypothesis of the existence of different DTD subtypes; (2) sustains the evidence that DTD can co-occur (or not) with deficit in face recognition; and (3) highlights the need for an in-depth examination from both a neurocognitive and behavioral point of view of a possible common developmental defect between the formation of cognitive maps and the recognition of faces that might be in mental imagery skills. Future directions will be also discussed.
Glutathione S-Transferase Polymorphisms and Clinical Characteristics in Autism Spectrum Disorders
Authors: Mandic-Maravic Vanja , Mitkovic-Voncina Marija , Pljesa-Ercegovac Marija , Savic-Radojevic Ana , Djordjevic Miroslav , Ercegovac Marko , Pekmezovic Tatjana , Simic Tatjana , Pejovic-Milovancevic Milica
Published: June 2021

Background: Autism spectrum disorders (ASD) are a heterogeneous group of developmental disorders, with different levels of symptoms, functioning, and comorbidities. Recent findings suggested that oxidative stress and genetic variability in glutathione S-transferases (GSTs) might increase the risk of ASD development. We aimed to determine whether GST polymorphisms influence the severity of symptoms as well as the cognitive and adaptive abilities in children with ASD.

Methods: The sample included 113 ASD cases. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The clinical characteristics were determined with Autism Diagnostic Interview-Revised (ADI-R) in all of the participants. In non-verbal participants, we explored the adaptive functioning using the Vineland Adaptive Behavior Scale II, while in verbal participants, we used the Wechsler Abbreviated Scale of Intelligence (WASI).

Results: It was shown that the GSTA1*CC genotype was a predictor of a lower non-verbal communication impairment as well as of a lower chance of having seizures during life. GSTM1-active genotype predicted a higher adaptive functioning. The predictive effect of GSTA1, GSTM1, and GSTT1 genotype was moderated by exposure during pregnancy (maternal smoking and medication). The GSTP1*IleIle genotype was significantly associated to a better cognitive functioning in children with ASD.

Conclusion: Besides the complex gene-environment interaction for the specific risk of developing ASD, there is also a possible complexity of interactions between genetic and environmental factors influencing the level of symptoms and impairment in people with ASD. Detoxification and antioxidant enzymes, such as GSTA1, might contribute to the core of this complexity.
Developmental Considerations in Obsessive Compulsive Disorder: Comparing Pediatric and Adult-Onset Cases
Authors: Geller Daniel A. , Homayoun Saffron , Johnson Gabrielle
Published: June 2021

There appear to be two peaks of incidence of Obsessive Compulsive Disorder (OCD), one with a pre-adolescent onset and another in early adulthood. As new cases are added, the cumulative prevalence of OCD increases, but the great majority of cases have an onset in youth. The notion that early onset OCD represents a unique developmental subtype of the disorder has been considered by many researchers based on several specific age-related factors. Ascertainment and early intervention in affected youth is critical to abbreviate the functional impairments associated with untreated illness. In this paper we review the clinical, familial and translational biomarker correlates seen in early onset OCD that support the notion of a developmental subtype and discuss implications for research and treatment aimed at this cohort. The importance of cognitive, academic and social development tasks of childhood and adolescence, illness-specific and familial factors, and immune-mediated inflammatory factors are discussed, with their implications for management.
Knowledge, Attitude, and Practice of Healthcare Providers Toward Novel Coronavirus 19 During the First Months of the Pandemic: A Systematic Review
Authors: Tegegne Gobezie T. , Kefale Belayneh , Engidaw Melaku Tadege , Degu Amsalu , Tesfa Desalegn , Ewunetei Amien , Yazie Taklo Simeneh , Molla Mulugeta
Published: June 2021

Introduction: Coronavirus disease (COVID-19) is a highly contagious viral infection that has spread to every corner of the world. Lack of knowledge among healthcare providers (HCPs) about diseases such as COVID-19 may delay the diagnosis, disease spread, and produce poor infection control practices. Hence, this systematic review aimed to summarize the knowledge, attitudes, and practices (KAP) of HCPs toward COVID-19 during the first months of the pandemic.

Methods: A systematic review was conducted according the PRISMA guidelines, and the protocol was registered on PROSPERO (CRD42020191742). A relevant article search was performed on EMBASE, PubMed, CINAHL, Scopus, and the Google Scholar database. The methodological quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. The median percentage of HCPs with good KAP was computed.

Results: Twenty studies involving 12,072 HCPs were included in the review process. Median percentages of 75.8% (IQR: 69.3–87.7%), 74.6% (IQR: 54.4–74.6), and 79.8% (IQR: 67.0–79.8%) of HCPs had good knowledge, and positive attitude and practice, respectively. Although the reported risk factors were inconsistent among studies, age, gender, level of education, experience, infection prevention training, and sources of information were associated with knowledge of HCPs. In addition, being elderly, having a high level of education, absence of chronic illness, and good knowledge and practice were significantly associated with the attitude of HCPs. Further, types of profession, experience, age, level of education, use of personnel protective equipment, and gender were significantly associated with the practice of HCPs.

Conclusions: Approximately, three-fourths of HCPs had good knowledge, attitudes, and practices toward COVID-19 during the first months of the pandemic, although the percentage of HCPs was inconsistent in different study settings. In addition, associated factors of KAP were inconsistent among studies; hence, stake holders should target locally identified risk factors to design relevant education packages and infection prevention training to halt the rapid transmission of COVID-19.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191742, identifier: CRD42020191742.
Promoting University Students' Mental Health: A Systematic Literature Review Introducing the 4M-Model of Individual-Level Interventions
Authors: Nair Bhavana , Otaki Farah
Published: June 2021

Objective:The purpose of this study is to systematically review recently published individual student-level interventions aimed at alleviating the burden of mental health challenges faced by the students and/ or at equipping them with coping mechanism that will foster their resilience.

Methods:This study relied on a systematic literature review. PubMed dataset was used; the search was confined to the following period: July 2016-December 2020.

Results:A total of 1,399 records were identified by the electronic search, out of which 40 studies were included in this study. The authors inductively identified four overlapping categories of interventions across all included articles, and coded them as follows: Mindfulness, Movement, Meaning, and Moderator. Accordingly, each study was linked to at least one of four overlapping categories based on the nature of the intervention(s) under investigation, leading to differing assortments of categories.

Conclusions:The 4M-Model generated by this study encourages focusing on devising holistic, university-based interventions that embrace the individuality of students to improve their mental health through elements of mindfulness, movement, meaning, and moderator. Through this focused approach, university counselors are enabled to design interventions that address students' physical, psychological, emotional, and social needs.
Microbiological Aspects of Root Canal Infections and Disinfection Strategies: An Update Review on the Current Knowledge and Challenges
Authors: Wong Jasmine , Manoil Daniel , Näsman Peggy , Belibasakis Georgios N. , Neelakantan Prasanna
Published: June 2021

The oral cavity is the habitat of several hundreds of microbial taxa that have evolved to coexist in multispecies communities in this unique ecosystem. By contrast, the internal tissue of the tooth, i.e., the dental pulp, is a physiologically sterile connective tissue in which any microbial invasion is a pathological sign. It results in inflammation of the pulp tissue and eventually to pulp death and spread of inflammation/infection to the periradicular tissues. Over the past few decades, substantial emphasis has been placed on understanding the pathobiology of root canal infections, including the microbial composition, biofilm biology and host responses to infections. To develop clinically effective treatment regimens as well as preventive therapies, such extensive understanding is necessary. Rather surprisingly, despite the definitive realization that root canal infections are biofilm mediated, clinical strategies have been focused more on preparing canals to radiographically impeccable levels, while much is left desired on the debridement of these complex root canal systems. Hence, solely focusing on “canal shaping” largely misses the point of endodontic treatment as the current understanding of the microbial aetiopathogenesis of apical periodontitis calls for the emphasis to be placed on “canal cleaning” and chemo-mechanical disinfection. In this review, we dissect in great detail, the current knowledge on the root canal microbiome, both in terms of its composition and functional characteristics. We also describe the challenges in root canal disinfection and the novel strategies that attempt to address this challenge. Finally, we provide some critical pointers for areas of future research, which will serve as an important area for consideration in Frontiers in Oral Health.
The City of São Paulo's Environmental Quota: A Policy to Embrace Urban Environmental Services and Green Infrastructure Inequalities in the Global South
Authors: Caetano Paulo Mantey Domingues , Pereira Hélia Maria Santa Bárbara , Figueiredo Lara Cavalcanti Ribeiro , Sepe Patrícia Marra , Giatti Leandro Luiz
Published: June 2021

In 2013 the urban authority for São Paulo city, Brazil, was interested in incorporating environmental aspects into the urban licensing process of diverse urban developments. To overcome concepts related simply to soil sealing, the initiative gave rise to a wide range of principles associated with environmental services and the consideration that green areas in this megacity are unequally distributed. Given the costs involved in analyzing each case and the legal uncertainty among entrepreneurs, it has become a tradition in Brazil for authorities in charge of urban licensing to follow general regulations rather than case-by-case studies, except in high-impact developments. In response, the São Paulo municipal government developed during the period from 2013 to 2016 a governing instrument to deal with these issues, known as the Environmental Quota (EQ). For that, the following guiding principles were established: (a) it should have a solid theoretical basis, with incentives for consistent public participation; (b) it should be flexible in such a way that it can provide a general framework within which a project designer can make decisions, rather than a set of rigidly determined solutions; and (c) it should consider inequalities in the availability of urban green infrastructure throughout the city. This paper will first detail the political-institutional context in which the EQ and its guidelines were established and implemented, then provide a general overview of the tool and the theoretical frameworks within which it was developed, and, finally, discuss the complex social decision-making process of its legal constraints. Moreover, it analyzes the implementation and application of the EQ to examine its effectiveness and how it relates to the city's gentrification. Furthermore, it is considered the replicability potential of the EQ to expand both the supply and distribution of green infrastructure and environmental services throughout the urban environment and, thus, contribute toward mitigating the intricate problems of urban environments in the Global South.
Applying P-Technique Factor Analysis to Explore Person-Specific Models of Readiness-to-Exercise
Authors: Strohacker Kelley , Keegan Richard , Beaumont Cory T. , Zakrajsek Rebecca A.
Published: June 2021

Recent research in exercise prescription and periodization has emphasized the importance of subjective experience, both in medium- and long-term monitoring, but also in the acute experience. Emerging evidence also highlights an important role of subjective readiness (pre-exercise mental and physical states) in determining how exercise is experienced, and in acutely modifying the prescribed exercise intensity. The concept of “readiness-to-exercise” shows promise in enabling and informing this acute decision-making to optimize the experiences and outcomes of exercise. While subjective experiences can be effectively assessed using psychometric scales and instruments, these are often developed and deployed using cross-sectional samples, with resulting structures that reflect a normative pattern (nomothetic). These patterns may fail to reflect individual differences in sensitivity, experience and saliency (idiographic). We conducted this research with the primary aim of comparing the nomothetical and idiographic approaches to modeling the relatively novel concept of readiness-to-exercise. Study 1 (nomothetic) therefore analyzed data collected from 572 participants who completed a one-time survey using R-technique factor analysis. Results indicated a four-factor structure that explained 60% of the variance: “health and fitness;” “fatigue;” “vitality” and “physical discomfort.” Study 2 (idiographic) included a sample of 29 participants who completed the scale multiple times, between 42 and 56 times: permitting intra-individual analysis using separate P-technique factor analyses. Our analyses suggested that many individuals displayed personal signature, or “profiles” of readiness-to-exercise that differed in structure from the nomothetic form: only two participants' personal signatures contained four structures as modeled in Study 1, whereas the majority demonstrated either two or three factors. These findings raise important questions about how experiential data should be collected and modeled, for use in research (conceptual development and measurement) and applied practice (prescribing, monitoring)—as well as in more applied research (implementation, effectiveness).
Design of a High-Throughput Real-Time PCR System for Detection of Bovine Respiratory and Enteric Pathogens
Authors: Goecke Nicole B. , Nielsen Bodil H. , Petersen Mette B. , Larsen Lars E.
Published: June 2021

Bovine respiratory and enteric diseases have a profound negative impact on animal, health, welfare, and productivity. A vast number of viruses and bacteria are associated with the diseases. Pathogen detection using real-time PCR (rtPCR) assays performed on traditional rtPCR platforms are costly and time consuming and by that limit the use of diagnostics in bovine medicine. To diminish these limitations, we have developed a high-throughput rtPCR system (BioMark HD; Fluidigm) for simultaneous detection of the 11 most important respiratory and enteric viral and bacterial pathogens. The sensitivity and specificity of the rtPCR assays on the high-throughput platform was comparable with that of the traditional rtPCR platform. Pools consisting of positive and negative individual field samples were tested in the high-throughput rtPCR system in order to investigate the effect of an individual sample in a pool. The pool tests showed that irrespective of the size of the pool, a high-range positive individual sample had a high influence on the cycle quantification value of the pool compared with the influence of a low-range positive individual sample. To validate the test on field samples, 2,393 nasal swab and 2,379 fecal samples were tested on the high-throughput rtPCR system as pools in order to determine the occurrence of the 11 pathogens in 100 Danish herds (83 dairy and 17 veal herds). In the dairy calves, Pasteurella multocida (38.4%), rotavirus A (27.4%), Mycoplasma spp. (26.2%), and Trueperella pyogenes (25.5%) were the most prevalent pathogens, while P. multocida (71.4%), Mycoplasma spp. (58.9%), Mannheimia haemolytica (53.6%), and Mycoplasma bovis (42.9%) were the most often detected pathogens in the veal calves. The established high-throughput system provides new possibilities for analysis of bovine samples, since the system enables testing of multiple samples for the presence of different pathogens in the same analysis test even with reduced costs and turnover time.
Optimization of the Weighted Multi-Facility Location Problem Using MS Excel
Authors: Němec Petr , Stodola Petr , Pecina Miroslav , Neubauer Jiří , Blaha Martin
Published: June 2021

This article presents the possibilities in solving the Weighted Multi-Facility Location Problem and its related optimization tasks using a widely available office software—MS Excel with the Solver add-in. To verify the proposed technique, a set of benchmark instances with various point topologies (regular, combination of regular and random, and random) was designed. The optimization results are compared with results achieved by a metaheuristic algorithm based on simulated annealing principles. The influence of the hardware configuration on the performance achieved by MS Excel Solver is also examined and discussed from both the execution time and accuracy perspectives. The experiments showed that this widely available office software is practical for solving even relatively complex optimization tasks (Weighted Multi-Facility Location Problem with 100 points and 20 centers, which consists of 40 continuous optimization variables in two-dimensional space) with sufficient quality for many real-world applications. The method used is described in detail and step-by-step using an example.
The Sequential Behavior Pattern Analysis of Broiler Chickens Exposed to Heat Stress
Authors: Branco Tatiane , Moura Daniella Jorge de , de Alencar Nääs Irenilza , da Silva Lima Nilsa Duarte , Klein Daniela Regina , Oliveira Stanley Robson de Medeiros
Published: June 2021

Broiler productivity is dependent on a range of variables; among them, the rearing environment is a significant factor for proper well-being and productivity. Behavior indicates the bird’s initial response to an adverse environment and is capable of providing an indicator of well-being in real-time. The present study aims to identify and characterize the sequential pattern of broilers’ behavior when exposed to thermoneutral conditions (TNZ) and thermal stress (HS) by constant heat. The research was carried out in a climatic chamber with 18 broilers under thermoneutral conditions and heat stress for three consecutive days (at three different ages). The behavior database was first analyzed using one-way ANOVA, Tukey test by age, and Boxplot graphs, and then the sequence of the behaviors was evaluated using the generalized sequential pattern (GSP) algorithm. We were able to predict behavioral patterns at the different temperatures assessed from the behavioral sequences. Birds in HS were prostrate, identified by the shorter behavioral sequence, such as the {Lying down, Eating} pattern, unlike TNZ ({Lying down, Walking, Drinking, Walking, Lying down}), which indicates a tendency to increase behaviors (feeding and locomotor activities) that guarantee the better welfare of the birds. The sequence of behaviors ‘Lying down’ followed by ‘Lying laterally’ occurred only in HS, which represents a stressful thermal environment for the bird. Using the pattern mining sequences approach, we were able to identify temporal relationships between thermal stress and broiler behavior, confirming the need for further studies on the use of temporal behavior sequences in environmental controllers.
Singing Transcription from Polyphonic Music Using Melody Contour Filtering
Authors: He Zhuang , Feng Yin
Published: June 2021

Automatic singing transcription and analysis from polyphonic music records are essential in a number of indexing techniques for computational auditory scenes. To obtain a note-level sequence in this work, we divide the singing transcription task into two subtasks: melody extraction and note transcription. We construct a salience function in terms of harmonic and rhythmic similarity and a measurement of spectral balance. Central to our proposed method is the measurement of melody contours, which are calculated using edge searching based on their continuity properties. We calculate the mean contour salience by separating melody analysis from the adjacent breakpoint connective strength matrix, and we select the final melody contour to determine MIDI notes. This unique method, combining audio signals with image edge analysis, provides a more interpretable analysis platform for continuous singing signals. Experimental analysis using Music Information Retrieval Evaluation Exchange (MIREX) datasets shows that our technique achieves promising results both for audio melody extraction and polyphonic singing transcription.
The Relationship between Training Load Measures and Next-Day Well-Being in Rugby Union Players
Authors: Taylor Richard , Myers Tony D. , Sanders Dajo , Ellis Matthew , Akubat Ibrahim
Published: June 2021

The aim of this study is to identify the relationship between different internal and external load measures and next day subjective wellbeing. With institutional ethics approval, ten academy rugby union players (Five forwards, and five backs) with a local National League One club agreed to participate in the study (aged; 18.4 ± 1.0 years, height; 181.3 ± 5.9 cm, body mass 85.9 ± 13.0 kg, VO2max 56.2 ± 6.8 mL·kg−1·min−1). Before the 6-week in-season data collection period, participants completed an incremental treadmill test to determine lactate thresholds at 2 mmol·L−1 (LT) and 4 mmol·L−1 and the heart rate blood lactate (HR-BLa) profile for individualized training impulse (iTRIMP) calculations. Internal training load was quantified using Banister’s TRIMP, Edward’s TRIMP, Lucia’s TRIMP, individualised TRIMP and session-RPE. External training load was reported using total distance, PlayerLoadTM, high-speed distances (HSD) > 18 km∙h−1 and >15 km∙h−1, and individualized high-speed distance (iHSD) based on each player’s velocity at OBLA. On arrival and prior to all training sessions players completed a well-being questionnaire (WB). Bayesian linear mixed model analysis identified that a range of internal and external load measures explained between 30% and 37% of next-day total wellbeing and between 65% and 67% of next-day perceived stress. All other internal and external load measures demonstrated very weak to moderate relationships (R2 = 0.08 to 0.39) with all other wellbeing components. Internal sRPE, iTRIMP and bTRIMP loads alongside external HSD loads provide coaches with the most practical measures to influence players’ perceived wellbeing.
Sugar Fructose Triggers Gut Dysbiosis and Metabolic Inflammation with Cardiac Arrhythmogenesis
Authors: Cheng Wan-Li , Li Shao-Jung , Lee Ting-I , Lee Ting-Wei , Chung Cheng-Chih , Kao Yu-Hsun , Chen Yi-Jen
Published: June 2021

Fructose is a main dietary sugar involved in the excess sugar intake-mediated progression of cardiovascular diseases and cardiac arrhythmias. Chronic intake of fructose has been the focus on the possible contributor to the metabolic diseases and cardiac inflammation. Recently, the small intestine was identified to be a major organ in fructose metabolism. The overconsumption of fructose induces dysbiosis of the gut microbiota, which, in turn, increases intestinal permeability and activates host inflammation. Endotoxins and metabolites of the gut microbiota, such as lipopolysaccharide, trimethylamine N-oxide, and short-chain fatty acids, also influence the host inflammation and cardiac biofunctions. Thus, high-fructose diets cause heart–gut axis disorders that promote cardiac arrhythmia. Understanding how gut microbiota dysbiosis-mediated inflammation influences the pathogenesis of cardiac arrhythmia may provide mechanisms for cardiac arrhythmogenesis. This narrative review updates our current understanding of the roles of excessive intake of fructose on the heart-gut axis and proposes potential strategies for inflammation-associated cardiac vascular diseases.
Normative Data for Ten Neuropsychological Tests for the Guatemalan Pediatric Population Updated to Account for Vulnerability
Authors: Ibáñez-Alfonso Joaquín A. , Company-Córdoba Rosalba , García de la Cadena Claudia , Simpson Ian C. , Rivera Diego , Sianes Antonio
Published: June 2021

The Guatemalan pediatric population is affected by a high incidence of poverty and violence. The previous literature showed that these experiences may ultimately impact cognitive performance. The aim of this article is to update the standardized scores for ten neuropsychological tests commonly used in Guatemala considering vulnerability. A total of 347 healthy children and adolescents from 6 to 17 years of age (M = 10.83, SD = 3) were assessed, controlling for intelligence, mental health and neuropsychological history. The standard scores were created using multiple linear regression and standard deviations from residual values. The predictors included were the following: age, age squared (age2), mean parental education (MPE), mean parental education squared (MPE2), gender, and vulnerability, as well as their interaction. The vulnerability status was significant in the scores for language, attention and executive functions. To the best of our knowledge, this is the first study that includes the condition of vulnerability in the calculation of neuropsychological standard scores. The utility of this update is to help in the early detection of special needs in this disadvantaged population, promoting more accurate interventions in order to alleviate the negative effects that living in vulnerable conditions has on children and adolescents.
Genomics of Gulf War Illness in U.S. Veterans Who Served during the 1990–1991 Persian Gulf War: Methods and Rationale for Veterans Affairs Cooperative Study #2006
Authors: Radhakrishnan Krishnan , Hauser Elizabeth R. , Polimanti Renato , Helmer Drew A. , Provenzale Dawn , McNeil Rebecca B. , Maffucci Alysia , Quaden Rachel , Zhao Hongyu , Whitbourne Stacey B. , Harrington Kelly M. , Vahey Jacqueline , Gelernter Joel , Levey Daniel F. , Huang Grant D. , Gaziano John Michael , Concato John , Aslan Mihaela
Published: June 2021

Background: Approximately 697,000 members of the U.S. Armed Forces were deployed to the Persian Gulf in support of the 1990–1991 Persian Gulf War (GW). Subsequently, many deployed and some non-deployed veterans developed a chronic multi-symptom illness, now named Gulf War Illness (GWI). This manuscript outlines the methods and rationale for studying the genomics of GWI within the Million Veteran Program (MVP), a VA-based national research program that has linked medical records, surveys, and genomic data, enabling genome-wide association studies (GWASs). Methods: MVP participants who served in the military during the GW era were contacted by mail and invited to participate in the GWI study. A structured health questionnaire, based on a previously tested instrument, was also included in the mailing. Data on deployment locations and exposures, symptoms associated with GWI, clinical diagnoses, personal habits, and health care utilization were collected. Self-reported data will be augmented with chart reviews and structured international classification of disease codes, to classify participants by GWI case status. We will develop a phenotyping algorithm, based on two commonly used case definitions, to determine GWI status, and then conduct a nested case-control GWAS. Genetic variants associated with GWI will be investigated, and gene–gene and gene–environment interactions studied. The genetic overlap of GWI with, and causative mechanisms linking this illness to, other health conditions and the effects of genomic regulatory mechanisms on GWI risk will also be explored. Conclusions: The proposed initial GWAS described in this report will investigate the genomic underpinnings of GWI with a large sample size and state-of-the-art genomic analyses and phenotyping. The data generated will provide a rich and expansive foundation on which to build additional analyses.
Oxidative Stress Biomarkers in Urine of Metal Carpentry Workers Can Be Diagnostic for Occupational Exposure to Low Level of Welding Fumes from Associated Metals
Authors: Buonaurio Flavia , Astolfi Maria Luisa , Pigini Daniela , Tranfo Giovanna , Canepari Silvia , Pietroiusti Antonio , D’Alessandro Iacopo , Sisto Renata
Published: June 2021

Urinary concentrations of 16 different exposure biomarkers to metals were determined at the beginning and at the end of a working shift on a group of workers in the metal carpentry industry. Five different oxidative stress biomarkers were also measured, such as the oxidation products of RNA and DNA metabolized and excreted in the urine. The results of workers exposed to metals were compared to those of a control group. The metal concentrations found in these workers were well below the occupational exposure limit values and exceeded the mean concentrations of the same metals in the urine of the control group by a factor of four at maximum. Barium (Ba), mercury (Hg), lead (Pb) and strontium (Sr) were correlated with the RNA oxidative stress biomarker, 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), which was found able to discriminate exposed workers from controls with a high level of specificity and sensitivity. The power of this early diagnostic technique was assessed by means of the ROC curve. Ba, rubidium (Rb), Sr, tellurium (Te), and vanadium (V) were correlated with the level of the protein oxidation biomarker 3-Nitrotyrosine (3-NO2Tyr), and Ba, beryllium (Be), copper (Cu), and Rb with 5-methylcytidine (5-MeCyt), an epigenetic marker of RNA damage. These effect biomarkers can help in identifying those workers that can be defined as “occupationally exposed” even at low exposure levels, and they can provide information about the impact that such doses have on their health.
5′ Region Large Genomic Rearrangements in the BRCA1 Gene in French Families: Identification of a Tandem Triplication and Nine Distinct Deletions with Five Recurrent Breakpoints
Authors: Caputo Sandrine , Telly Dominique , Briaux Adrien , Sesen Julie , Ceppi Maurizio , Bonnet Françoise , Bourdon Violaine , Coulet Florence , Castera Laurent , Delnatte Capucine , Hardouin Agnès , Mazoyer Sylvie , Schultz Inès , Sevenet Nicolas , Uhrhammer Nancy , Bonnet Céline , Tilkin-Mariamé Anne-Françoise , Houdayer Claude , Moncoutier Virginie , Andrieu Catherine ,   French COVAR Group Collaborators, Bièche Ivan , Stern Marc-Henri , Stoppa-Lyonnet Dominique , Lidereau Rosette , Toulas Christine , Rouleau Etienne
Published: June 2021

Background: Large genomic rearrangements (LGR) in BRCA1 consisting of deletions/duplications of one or several exons have been found throughout the gene with a large proportion occurring in the 5′ region from the promoter to exon 2. The aim of this study was to better characterize those LGR in French high-risk breast/ovarian cancer families. Methods: DNA from 20 families with one apparent duplication and nine deletions was analyzed with a dedicated comparative genomic hybridization (CGH) array, high-resolution BRCA1 Genomic Morse Codes analysis and Sanger sequencing. Results: The apparent duplication was in fact a tandem triplication of exons 1 and 2 and part of intron 2 of BRCA1, fully characterized here for the first time. We calculated a causality score with the multifactorial model from data obtained from six families, classifying this variant as benign. Among the nine deletions detected in this region, eight have never been identified. The breakpoints fell in six recurrent regions and could confirm some specific conformation of the chromatin. Conclusions: Taken together, our results firmly establish that the BRCA1 5′ region is a frequent site of different LGRs and highlight the importance of the segmental duplication and Alu sequences, particularly the very high homologous region, in the mechanism of a recombination event. This also confirmed that those events are not systematically deleterious.
Transcript-Level Dysregulation of BCL2 Family Genes in Acute Myeloblastic Leukemia
Authors: Handschuh Luiza , Wojciechowski Pawel , Kazmierczak Maciej , Lewandowski Krzysztof
Published: June 2021

The expression of apoptosis-related BCL2 family genes, fine-tuned in normal cells, is dysregulated in many neoplasms. In acute myeloid leukemia (AML), this problem has not been studied comprehensively. To address this issue, RNA-seq data were used to analyze the expression of 26 BCL2 family members in 27 AML FAB M1 and M2 patients, divided into subgroups differently responding to chemotherapy. A correlation analysis, analysis of variance, and Kaplan-Meier analysis were applied to associate the expression of particular genes with other gene expression, clinical features, and the presence of mutations detected by exome sequencing. The expression of BCL2 family genes was dysregulated in AML, as compared to healthy controls. An upregulation of anti-apoptotic and downregulation of pro-apoptotic genes was observed, though only a decrease in BMF, BNIP1, and HRK was statistically significant. In a group of patients resistant to chemotherapy, overexpression of BCL2L1 was manifested. In agreement with the literature data, our results reveal that BCL2L1 is one of the key players in apoptosis regulation in different types of tumors. An exome sequencing data analysis indicates that BCL2 family genes are not mutated in AML, but their expression is correlated with the mutational status of other genes, including those recurrently mutated in AML and splicing-related. High levels of some BCL2 family members, in particular BIK and BCL2L13, were associated with poor outcome.
Bevacizumab in First-Line Chemotherapy Improves Progression-Free Survival for Advanced Ovarian Clear Cell Carcinoma
Authors: Tate Shinichi , Nishikimi Kyoko , Matsuoka Ayumu , Otsuka Satoyo , Shiko Yuki , Ozawa Yoshihito , Kawasaki Yohei , Shozu Makio
Published: June 2021

(1) Background: We investigated survival outcomes following first-line chemotherapy before and after approval of bevacizumab (Bev) for ovarian cancer in Japan to evaluate the efficacy of Bev for advanced clear cell carcinoma (CCC). (2) Methods: We investigated 28 consecutive patients diagnosed with CCC (stages III/IV) at our hospital between 2008 and 2018. Bev was administered for treatment of advanced CCC after approval in Japan in November 2013. Progression-free survival (PFS) was compared between 10 patients treated before Bev approval (2008–2013, Bev- group) and 18 patients treated after Bev approval (2014–2018, Bev+ group) for first-line chemotherapy. (3) Results: No intergroup difference was observed in patient characteristics. The rate of completeness of resection was higher in the Bev − group (9/10, 90%) than in the Bev+ group (15/18, 83%) (p = 0.044). Eleven (61%) patients in the Bev + group received ≥ 21 cycles of Bev. The median PFS increased from 12.0 months before Bev approval to 29.8 months after Bev approval (Wilcoxon test, p = 0.026). Multivariate analysis showed that performance status (p = 0.049), Bev administration (p = 0.023) and completeness of resection (p = 0.023) were independent prognostic factors for PFS. (4) Conclusions: Bev incorporated into first-line chemotherapy might improve PFS in patients with advanced CCC. We hope that our findings will be confirmed in adequate clinical trials.
Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway
Authors: Lu Ko-Hsiu , Yang Jia-Sin , Hsieh Yi-Hsien , Chu Hsiao-Ju , Chou Chia-Hsuan , Lu Eric Wun-Hao , Lin Chiao-Wen , Yang Shun-Fa
Published: June 2021

Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, using RNA sequencing technology, we found that LCN2 repressed MET gene expression in U2OS cells. Manipulation of LCN2 levels influenced the migratory potential of osteosarcoma cells as cellular migration was enhanced by transfecting with vectors containing a constitutively active LCN2 cDNA and recombinant human LCN2. Moreover, the phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 and ERK 1/2 was decreased by LCN2 knockdown. Furthermore, the use of ERK inhibitor (U0126) and activator (tBHQ) confirmed that the pharmaceutic inhibition of MEK–ERK augmented the LCN2-mediated MET suppression and migration of U2OS and HOS cells. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the MEK–ERK pathway.
Clinical and Molecular Heterogeneity in Patients with Innate Resistance to Anti-PD-1 +/− Anti-CTLA-4 Immunotherapy in Metastatic Melanoma Reveals Distinct Therapeutic Targets
Authors: Gide Tuba N. , Pires da Silva Inês , Quek Camelia , Ferguson Peter M. , Batten Marcel , Shang Ping , Ahmed Tasnia , Menzies Alexander M. , Carlino Matteo S. , Saw Robyn P. M. , Thompson John F. , Scolyer Richard A. , Long Georgina V. , Wilmott James S.
Published: June 2021

While immune checkpoint inhibitors targeting the CTLA-4 and PD-1 receptors have significantly improved outcomes of many patients with metastatic melanoma, there remains a group of patients who demonstrate no benefit. In this study, we sought to characterise patients who do not respond to anti-PD-1-based therapies based on their clinical, genetic and immune profiles. Forty patients with metastatic melanoma who did not respond to anti-PD-1 +/− anti-CTLA-4 treatment were identified. Targeted RNA sequencing (n = 37) was performed on pretreatment formalin-fixed paraffin-embedded (FFPE) melanoma specimens. Patients clustered into two groups based on the expression profiles of 26 differentially expressed genes: an immune gene rich group (n = 17) expressing genes associated with immune and T cell signalling, and a second group (n = 20) expressing genes associated with metabolism, signal transduction and neuronal signalling. Multiplex immunohistochemistry validated significantly higher densities of tumour-infiltrating lymphocytes (TILs) and macrophages in the immune gene-rich group. This TIL-high subset of patients also demonstrated higher expression of alternative immune-regulatory drug targets compared to the TIL-low group. Patients were also subdivided into rapid progressors and other progressors (cut-off 2 mo progression-free survival), with significantly lower TILs (p = 0.04) and CD68+ macrophages (p = 0.0091) in the rapid progressors. Furthermore, a trend towards a higher tumour burden was observed in rapid progressors (p = 0.06). These data highlight the need for a personalised and multilayer (clinical and molecular) approach for identifying the most appropriate treatments for anti-PD-1 resistant patients and provides insight into how individual treatment strategies can be achieved.