bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspectos toxicológicos da ivermectina: um estudo dos efeitos na morfologia do fígado de ratas prenhes
Authors: Medeiros Juliana Pinto de , Silva Rodrigo Reges dos Santos , Brito Leandro Paes de , Costa Marcos Aurélio Santos da , Falcão Daniela Maria Santos , Silva Maria Eduarda da , Tenório Fernanda das Chagas Ângelo Mendes , Tenório Bruno Mendes , Maia Carina Scanoni , Maia Luciana Maria Silva de Seixas , Evêncio Neto Joaquim
Published: January 2021

A Ivermectina, princípio farmacológico de um medicamento de uso veterinário possui efeito antiparasitário contra endo e ectoparasitos, é amplamente utilizada na prática veterinária. Esta droga é biotransformada no fígado, resultando em 3 metabólitos, sendo o mais importante o 24-hidroxi-metil-diidroavermectina B1. O fígado é essencial na regulação do metabolismo, na síntese de certas proteínas, servindo como local de armazenagem para certas vitaminas e ferro, degradando certos hormônios e inativando e excretando certos medicamentos e toxinas. Portanto, este trabalho teve por objetivo avaliar a morfologia dos fígados de ratas prenhes tratadas com ivermectina. Para tanto foram utilizadas 30 ratas albinas, as quais foram divididas em 3 grupos de 10 animais. Os animais foram colocados para acasalar e após a detecção da prenhez, presença de espermatozóides no esfregaço vaginal realizado na manhã do dia seguinte, sendo assim designado o primeiro dia de gestação, cada animal foi tratado com ivermectina, na dose correspondente a cada grupo durante 18 dias, com administração a cada 3 (três) dias, totalizando 6 administrações. Após esse período o fígado foi coletado, pesado em balança analítica e processado para microscopia de luz. A análise do peso relativo dos fígados das ratas prenhes e não prenhes não revelou diferença significativa entre os grupos experimentais, onde o tratamento com ivermectina nas doses de 4,0 e 8,0 mg/kg não alterou a massa relativa do fígado, nem apresentou alterações na cor, textura, consistência e hemorragias. Com relação ao estudo através da microscopia de luz, não foram observadas alterações histopatológicas.
PERSEPSI DAN STIGMA PENYANDANG DISABILITAS PADA SISWA-SISWI SEKOLAH MENENGAH ATAS
Authors: Guntur Ahmad
Published: January 2021

The People with disabilities can create problems in the school. Schools which have students with disabilities will affect the students around them. Perceptions and stigma are factors in the problems of students, especially schools that accept students with disabilities. The purpose of this study was to analyze the relationship between perceptions and stigma of people with disabilities in senior high school. This study used descriptive correlation design and cross sectional approach with the respondents of senor high school students in Sidoarjo City. The sampling technique used was simple random sampling with sample size of 305 respondents who fill up criteria. The measuring instruments used are self perception with cronbach alpha value of 0.883 and a mental illness scale with cronbach alpha value of 0.783. Bivariate analysis using the chi square test and the result is p value (0.001). So it can be concluded that there is a relationship between perceptions and the stigma of people with disabilities in senior high school.
PENGARUH COOPERATIVE PLAY PUZZLE TERHADAP KEMAMPUAN BERADAPTASI SOSIAL PADA ANAK TUNAGRAHITA
Authors: Riskayani Riskayani
Published: January 2021

Background: Retardation was a big world problem, especially for developing countries. The ability to socialize in mental retardation children did not develop optimally which caused the child to be not independent, unable to communicate directly in two directions with friends or other people. Objective: To find out the effect of cooperative play puzzles on the social adaptability of mental retardation children. Method: This study used a quasy experimental design with a pretest posttest one group design approach. The sampling technique used purposive sampling with an instrument in the form of observation of the social adaptation ability checklist sheet. The number of respondents was 10 people. The statistical test used Wilcoxon Sign Rank test to determine the effect of the cooperative play puzzle variable on the social adaptation ability of mental retardation children. Result: Most of the respondents had enough capability of social adaptability before being given play therapy, as many as 6 respondents (60%), and after being given play therapy intervention suggested that almost all respondents were capable to social adaptability, as many as 9 respondents (90%). In the Wilcoxon Sign Rank test, the value of p = 0.004 or H0 was rejected, meaning that there was a significant effect of Cooperative Play Puzzle on the social adaptation ability of mental retardation children.Conclusion: Cooperative play puzzles could improve social adaptability in mental retardation children.
To the question of the relationship between the diversity index and the saprobity index in algae and invertebrates
Authors: Barinova Sophia S.
Published: January 2021

A description is given of the process of creating an empirical model of the functioning of aquatic ecosystems, its indicators, and the limits of the parameters related to progressive succession stages when considering the effects of pollution. In addition to the previously used data for autotrophs, the parameters of the diversity of consumers are included in the model. The overestimation of impact assessments based on the second trophic level is discussed. Based on the data of the private allotment of water bodies of Ukraine, a conclusion is drawn on the conformity of estimates regardless of the geographical location of water bodies and on the suitability of interpretations for water ecosystems of a wide ecological spectrum.
Comprehensive monitoring of the Klyazma reservoir
Authors: Razumovsky Vikenty L.
Published: January 2021

The research was carried out during the comprehensive monitoring of the Klyazma reservoir in 2019. The work is devoted to the assessment of long-term environmental changes under the influence of natural and anthropogenic factors. The research combines two traditional methods of analysis. A layer-by-layer study of diatomic complexes and chemical composition in the bottom sediments of the reservoir was carried out. The results obtained were compared with the results of comprehensive monitoring on the taxonomic composition of phytoplankton and the chemical composition of water in the reservoir's water area. The results of previous studies on the chemical composition of water in the reservoir were used. In addition to the traditional forms of chemical and hydrobiological analysis, an innovative method of graphical analysis was applied to phytoplankton complexes and the principle of unification of bioindication methods was applied for diatom complexes from sediment columns.

The main scenarios of taxonomic proportions transformations in phytoplankton and diatom complexes were determined using the method of graphical analysis for the Klyazma reservoir water area. The transformations are caused by the influence of water from the Moscow channel and the planned annual lowering of the water level in the reservoir. Bottom sediments showed a regular increase in the reservoirs level of saprobisation. Presumably, this is due to a non-linear increase in the number of tourists and an cahnges in recreational load. Pronounced accumulation of Cu, Zn and other heavy metals in the coastal zone of the reservoir was confirmed.
Diatoms in epixylon of waters in the European North (Komi republic, NAO)
Authors: Stenina Angelina S.
Published: January 2021

The results of studying the diatoms in epixylon of 15 water objects in European Northeast of Russia are presented. The samples of nature biofilms from external surfaces of submersed branches of Betula nana, Salix spp., woody snags, and wood debris were investigated. A comparative analysis of diatoms in fouling of woody substrates was carried out from coal-mine settling pond, lakes, streams, and different parts of mountain river. These are in the basins of Ortina, Vorcuta, More-Yu, Vychegda, Izhgma, Shchugor rivers. In stagnant waters diversity of diatoms form 9–56, in waterways 10–102 taxa. Encyonema minutum (Hilse) Mann, Navicula radiosa Kützing, Tabellaria flocculosa (Roth) Kützing were most frequently. A small degree of diatoms similarity in epixylon with other communities was revealed; the Sørensen coefficient is 0,3–0,4. Part of the diatoms with an abundance 3–6 points (28 taxa) were found only in one water bodies. Among them, in thermokarst lakes with low salinity water and a weakly acid reaction halophobic, acidophilic Eunotia microcephala Krasske, Kobayasiella subtilissima (Cleve) Lange-Bertalot, and Cymbella borealis Cleve prevail. In the coal–mine settling pond dominating group is represented by the alkaliphilic, halophilic Diatoma tenuis C. Agardh, Nitzschia clausii Hantzsch, and Gomphonema productum (Grunow) Lange-Bertot et Reichardt. Mountain streams are distinguished by the development of rheophilic Meridion circulare (Grѐville) C. Agardh, Diatoma mesodon (Ehrenberg) Kützing, Encyonema reichardtii (Krammer) Mann, Fragilaria gracilis Oestrup, Fragilariforma virescens (Ralfs) Williams et Round, Gomphonema montanum (Schumann) Grunow, G. pumilum (Grunow) Reichardt et Lange-Bertalot, G. ventricosum Gregory, Hannaea arcus (Ehrenberg) Patrick var. arcus et f. recta (Cleve) Foged. The composition of the epixylon dominant complexes also differs depending on the hydrological conditions and characteristics of aquatic environment. These differences in this community determine the significant diversity of this group of algae as a whole. In total, 244 species with intraspecific taxa from 67 genera and 27 families identified, and a large number of rare species found.
Macroalgae and cyanobacteria of supra- and pseudolittoral zones on the Southern coast of Crimea
Authors: Belich Tatiana V. , Sadogurskaya Svetlana A. , Sadogurskiy Sergei Ye.
Published: January 2021

The Southern coast of Crimea (SCC) forms a separate physical and geographical area located in the extreme South of the Crimean Peninsula, between the Main range of the Crimean Mountains and the Black Sea coast. Currently, the coast of the SCC is mostly concreted (65%). Therefore, fragments of the coastal zone with preserved natural vegetation have a special environmental value, one of such sites is the Kuchuk-Lambatsky stone chaos. Kuchuk-Lambatsky stone chaos is a Specially Protected Natural Area (SPNA), but the coastal-marine area does not have any protected status. In the coastal zone of the sea, it is very important that protected areas include both land areas and coastal–marine areas. Information about the species composition and the structure of phytobenthos of the supra – and pseudolittoral zones in the marine area of the Kuchuk-Lambatsky stone chaos is presented. In total 43 species of phytobenthos have been identified: Rhodophyta – 10 species, Chlorophyta – 7, Ochrophyta – 3, Cyanobacteria – 23. Altogether 23 species were found in the supralitoral zone. During the observation period, the vegetation cover of the supralittoral zone was formed exclusively by Cyanobacteria, represented by one class, 5 orders, 10 families and 15 genera. The community, dominated by Calothrix scopulorum, Gloeocapsopsis crepidinum and Aphanocapsa incerta was found. The community is mainly formed by typical benthic, marine, and cosmopolitan species. In total 20 species of macrophyte algae were observed in the pseudolittoral zone. The Rhodophyta division is represented by one class, 5 orders, 6 families, and 8 genera. The Ochrophyta division has one class, 2 orders, 3 families, and 3 genera. The division Chlorophyta is represented by one class, 2 orders, 3 families, and 4 genera. In the pseudolittoral zone the community dominated by Ulva kylinii and U. intestinalis has been registered. It is formed mainly by annual, marine and brackish-marine, mesosaprobic species.
Pigment composition of phytoplankton and its long-term dynamics in reservoirs of the Upper Volga
Authors: Mineeva Natalya M.
Published: January 2021

According to field observations during 1995–2005 and 2012–2016, the pigment composition of phytoplankton in the Upper Volga reservoirs is given. With an average Chl a content of 13,1±1,4 to 52,5±2,7 μg/L in the Ivankovo reservoir and from 4,1±0,9 to 27,5±2,5 μg/L in the Uglich reservoir, an increase in Chl a was noted after an abnormally hot 2010. The content of Chl a in the Ivankovo reservoir retaining eutrophic status does not go beyond the limits of long-term fluctuations. In the Uglich reservoir, an increase in the absolute and relative amount of Chl a was revealed, indicating the transition of the reservoir to the eutrophic category.
Witch Stichomythic: from The Confession of Elizabeth Fraunces, late of Hatfeelde in Essex
Authors: Bonnici Kate Bolton
Published: January 2021

In this piece, Kate Bolton Bonnici deploys a stichomythic technique to create a dramatic dialogue that touches poetically upon the themes of hexing, harboured grievances, retribution, desire, and desire denied. The lines running down the left side of the page, which can be read sequentially on their own, are taken from the pamphlet, A Detection of damnable driftes, practized by three Witches arraigned at Chelmisfforde in Essex, at the Laste Assises there holden, which were executed in Aprill. 1579, which details the confession of Elizabeth Fraunces, a historical figure convicted of witchcraft. Running down the right of the page are lines taken from various sources, which serve to comment, amplify, echo, and counter the details of Fraunces's transgression.
Posisi Tidur dalam Meningkatkan Kualitas Tidur Pasien Congestive Heart Failure
Authors: Suharto Dewi Nurviana , Agusrianto Agusrianto , Manggasa Dafrosia Darmi , Liputo Firsya Dita Maulinda
Published: January 2021

Pendahuluan: Congestive heart failure adalah ketidakmampuan jantung untuk memompa darah dalam jumlah yang cukup untuk memenuhi kebutuhan jaringan terhadap oksigen dan nutrient. Masalah yang sering muncul pada pasien congestive heart failure salah satunya yaitu gangguan tidur. Penatalaksanaan gangguan tidur diantaranya mengunakan pendekatan farmakologis dan non farmakologis. Salah satu pendekatan non farmakologis adalah pengaturan posisi tidur lateral kanan dan semifowler. Tujuan penulisan mengidentifikasi studi literatur tentang posisi tidur dalam meningkatkan kualitas tidur pada pasien congestive heart failure. Metode penelusuran database yang digunakan dalam studi literature ini yaitu database elektronik seperti ScienceDirect dan website: google dan google scholar. Hasil penelitian ada 7 jurnal yang diidentifikasi dan diterbitkan dari 2015-2019. Hasil dari jurnal menunjukan bahwa pengaturan posisi tidur lateral kanan dan semifowler efektif mengatasi masalah gangguan tidur pada pasien CHF. Saran: diharapkan peran perawat dan peneliti selanjutnya agar dapat menerapkan intervensi pemberian posisi tidur lateral kanan dan semifowler untuk meningkatkan kualitas tidur pasien CHF.
Penerapan Relaksasi Otot Progresif terhadap Ansietas pada Asuhan Keperawatan Pasien Diabetes Melitus
Authors: Manggasa Dafrosia Darmi , Parwata Ni Made Ridla Nilasanti , Rantesigi Nirva , Sufyaningsi Ulfa
Published: January 2021

Pendahuluan: Diabetes Mellitus (DM) diartikan sebagai penyakit metabolisme yang termasuk dalam kelompok gula darah yang melebihi batas normal atau hiperglikemia (lebih dari 120 mg/dl), karena itu DM sering disebut juga dengan penyakit gula. Penyakit diabetes melitus  adalah masalah kesehatan yang besar. Hal ini dikarenakan adanya peningkatan jumlah penderita diabetes dari tahun ke tahun. Berdasarkan faktor resiko DM terbagi menjadi 2 tipe yaitu: tipe I dan tipe II. Individu yang menderita DM tipe I memerlukan suplai insulin dari luar (eksogen insulin). sedangkan individu dengan DM tipe II resisten terhadap insulin. Tujuan: Untuk mengetahui penerapan relaksasi otot progresif terhadap tingkat ansietas pada asuhan keperawatan dengan kasus diabetes melitus di ruangan interna RSUD Poso. Metode Penelitian: Yaitu dengan menggunakan metode pemberian tindakan Relaksasi Otot Progresif Terhadap Tingkat Ansietas Pada Asuhan Keperawatan Dengan Kasus Diabetes Melitus. Hasil Penelitian: Setelah dilakukan implementasi selama 4 hari 2 kali penerapan relaksasi otot progresif, tingkat ansietas pasien tampak berkurang. Setelah dilakukan tindakan Relaksasi Otot Progresif selama 4 hari diharapkan tingkat ansietas pasien dapat berkurang dengan kriteria: tingkat ansietas hanya ringan, dan selalu menunjukkan pengendalian diri terhadap ansietas. Saran: diharapkan perawat yang ada di rumah sakit dapat memberikan penerapan relaksasi otot progresif secara optimal kepada pasien yang mengalami ansietas pada kasus diabetes melitus.
SCIENTIFIC AND TECHNOLOGICAL ADVANCEMENT OF THE RUSSIAN FEDERATION: CURRENT STATE AND PROSPECTS
Authors:   Russian Research Institute of Economics, Politics and Law in Science and Technology, Ilina Irina , Klypin Andrey
Published: January 2021

Introduction. The article is devoted to the study of the current state of the research and development sector in the Russian Federation during the transition from the first to the second stage of the implementation of the Strategy for the Scientific and Technological Development of the Russian Federation. In addition, the authors also prepare proposals for improving the state scientific and technical policies. Methods. This paper employs theoretical methods, including non-comparative and comparative analysis, cognitive synthesis, abstraction and concretization, systemic approach and structural-functional method. Results and Discussion. The paper presents the dynamics of changes in the key indicators of scientific and technical activity in the Russian Federation as well as significant risks and threats/challenges constraining scientific and technical activities, which are divided into two groups: organisational and economic (internal) challenges and global technological (external) challenges. The main research results are: a set of measures in the framework of the state scientific and technological policy, ensuring the further scientific and technological development of the Russian Federation, including the improvement of the public administration system through the development of mechanisms for financing research and development; creation of favourable conditions for involving enterprises of the real economy and other companies in all stages of research and development; creation of an integrated system for assessing scientific, research and technology results; introduction of a holistic system to support scientific, research, technological and innovation activities, providing targeted support at every stage of the innovation life cycle; introduction and development of the mechanism of scientific diplomacy in Russia; development of science and technology at the regional level; development of mechanisms for involving qualified personnel to scientific activities; development of a holistic system of expertise, monitoring and forecasting for scientific, research and technological activities. Conclusion. Results of this research substantiate the assertion that such areas as science, technology and innovation should operate as a whole structure integrated into the socio-economic system of the country and ensuring the technological selfsufficiency and competitiveness of the national economy.
Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2/Bcl2 Axis
Authors: Han Jun , Yang Si , Hao Xiaosheng , Zhang Bo , Zhang Hongbo , Xin Cuijuan , Hao Yunpeng
Published: January 2021

Hypoxia-ischemia brain damage (HIBD) is a neurological disorder occring in neonates, which is exacerbated by neuronal apoptosis. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for treating or preventing ischemia-related diseases. However, their mechanisms in HIBD remain unclear. Thus, we aimed to address the role of EV-derived microRNA (miR)-410 in HIBD. Neonatal HIBD mouse model was constructed using HI insult, from which neurons were isolated, followed by exposure to oxygen glucose deprivation (OGD). EVs were isolated from human umbilical cord (hUC)-derived MSCs. In silico analyses, dual-luciferase reporter gene and chromatin immunoprecipitation assays were adopted to determine relationships among miR-410, histone deacetylase 1 (HDAC1), early growth response protein 2 (EGR2), and B cell lymphoma/leukemia 2 (Bcl2). The functional roles of EV-derived miR-410 were determined using loss- and gain-of functions experiments, and by evaluating neuronal viability, cell-cycle distribution and neuronal apoptosis in vitro as well as modified neurological severity score (mNSS), edema formation, and cerebral infarction volume in vivo. hUC-MSCs-derived EVs protected against HIBD in vivo and inhibited the OGD-induced neuronal apoptosis in vitro. miR-410 was successfully delivered to neurons by hUC-MSCs-EVs and negatively targeted HDAC1, which inversely mediated the expression of EGR2/Bcl2. Upregulation of EV-derived miR-410 promoted the viability but inhibited apoptosis of neurons, which was reversed by HDAC1 overexpression. EV-derived miR-410 elevation reduced mNSS, edema formation, and cerebral infarction volume by increasing EGR2/Bcl2 expression through downregulating HDAC1 expression in vivo. In summary, EV-derived miR-410 impeded neuronal apoptosis by elevating the expression of EGR2/Bcl2 via HDAC1 downregulation, thereby providing a potential strategy for treating or preventing HIBD.
Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia
Authors: Liu Qingmei , Shi Xiangguang , Zhang Yue , Huang Yan , Yang Kai , Tang Yulong , Ma Yanyun , Zhang Yuting , Wang Ji'an , Zhang Li , Zhang Qi , Liu Xiao , Lin Jinran , Wang Jiucun , Wu Wenyu
Published: January 2021

Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged > 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our in vivo results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in ex vivo cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs in vitro. To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on in vivo mice, ex vivo hair follicles, and in vitro DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.
Oral and Palatal Dentition of Axolotl Arises From a Common Tooth-Competent Zone Along the Ecto-Endodermal Boundary
Authors: Soukup Vladimír , Tazaki Akira , Yamazaki Yosuke , Pospisilova Anna , Epperlein Hans-Henning , Tanaka Elly M. , Cerny Robert
Published: January 2021

Vertebrate dentitions arise at various places within the oropharyngeal cavity including the jaws, the palate, or the pharynx. These dentitions develop in a highly organized way, where new tooth germs are progressively added adjacent to the initiator center, the first tooth. At the same time, the places where dentitions develop house the contact zones between the outer ectoderm and the inner endoderm, and this colocalization has instigated various suggestions on the roles of germ layers for tooth initiation and development. Here, we study development of the axolotl dentition, which is a complex of five pairs of tooth fields arranged into the typically tetrapod outer and inner dental arcades. By tracking the expression patterns of odontogenic genes, we reason that teeth of both dental arcades originate from common tooth-competent zones, one present on the mouth roof and one on the mouth floor. Progressive compartmentalization of these zones and a simultaneous addition of new tooth germs distinct for each prospective tooth field subsequently control the final shape and composition of the axolotl dentition. Interestingly, by following the fate of the GFP-labeled oral ectoderm, we further show that, in three out of five tooth field pairs, the first tooth develops right at the ecto-endodermal boundary. Our results thus indicate that a single tooth-competent zone gives rise to both dental arcades of a complex tetrapod dentition. Further, we propose that the ecto-endodermal boundary running through this zone should be accounted for as a potential source of instruction factors instigating the onset of the odontogenic program.
Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis
Authors: Bai Ningning , Ma Jingyuan , Alimujiang Miriayi , Xu Jun , Hu Fan , Xu Yuejie , Leng Qingyang , Chen Shuqing , Li Xiaohua , Han Junfeng , Jia Weiping , Bao Yuqian , Yang Ying
Published: January 2021

Mitochondrial iron-sulfur (Fe-S) cluster is an important cofactor for the maturation of Fe-S proteins, which are ubiquitously involved in energy metabolism; however, factors facilitating this process in beige fat have not been established. Here, we identified BolA family member 3 (Bola3), as one of 17 mitochondrial Fe-S cluster assembly genes, was the most significant induced gene in the browning program of white adipose tissue. Using lentiviral-delivered shRNA in vitro, we determined that Bola3 deficiency inhibited thermogenesis activity without affecting lipogenesis in differentiated beige adipocytes. The inhibition effect of Bola3 knockdown might be through impairing mitochondrial homeostasis and lipolysis. This was evidenced by the decreased expression of mitochondria related genes and respiratory chain complexes, attenuated mitochondrial formation, reduced mitochondrial maximal respiration and inhibited isoproterenol-stimulated lipolysis. Furthermore, BOLA3 mRNA levels were higher in human deep neck brown fat than in the paired subcutaneous white fat, and were positively correlated with thermogenesis related genes (UCP1, CIDEA, PRDM16, PPARG, COX7A1, and LIPE) expression in human omental adipose depots. This study demonstrates that Bola3 is associated with adipose tissue oxidative capacity both in mice and human, and it plays an indispensable role in beige adipocyte thermogenesis via maintaining mitochondrial homeostasis and adrenergic signaling-induced lipolysis.
Improving Assessments of Connection to Nature: A Participatory Approach
Authors: Salazar Gabby , Monroe Martha C. , Jordan Catherine , Ardoin Nicole M. , Beery Thomas H.
Published: January 2021

Experiences in nature benefit humans in a variety of ways, including increasing health and well-being, reducing stress, inspiring creativity, enhancing learning, and fostering environmental stewardship values. These experiences help define the relationship people have with nature which is often correlated with a person’s level of environmental concern as well as their engagement in pro-environmental behaviors. A more informed understanding of the ways in which interactions with the natural environment can foster connection to nature requires that we are able to measure our perceived relationship to the environment. Dozens of tools measure people’s connection to nature—the strength of those perceived relationships with the natural world. Although the tools have been primarily developed to answer research questions, practitioners are increasingly interested in understanding whether and in what ways their work—in areas including environmental education, urban planning, and park management, for example—influences people’s connection to nature. In 2018, we launched a participatory process involving researchers and practitioners in a review of existing connection to nature assessment tools with the intention of identifying tools that would be useful to practitioners, as well as defining needs in research. This paper chronicles the process’s outcomes, including a discussion of opportunities for future research.
Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target
Authors: Agostinis Chiara , Balduit Andrea , Mangogna Alessandro , Zito Gabriella , Romano Federico , Ricci Giuseppe , Kishore Uday , Bulla Roberta
Published: January 2021

Endometriosis (EM) is a chronic disease characterized by the presence and proliferation of functional endometrial glands and stroma outside the uterine cavity. Ovaries and pelvic peritoneum are the most common locations for endometrial ectopic tissue, followed by deep infiltrating EM sites. The cyclic and recurrent bleeding, the progressive fibrosis and the peritoneal adhesions of ectopic endometrial glands, may cause different symptoms depending on the origin involved. EM is a frequent clinical condition affecting around 10% of women of mainly reproductive age, as well as in post-menopausal women and adolescents, especially with uterine anomalies. The risk of developing EM depends on a complex interaction between genetic, immunological, hormonal, and environmental factors. It is largely considered to arise due to a dysfunction of immunological surveillance. In fact, women with EM exhibit altered functions of peritoneal macrophages, lymphocytes and natural killer cells, as well as levels of inflammatory mediators and growth factors in the peritoneal fluid. In EM patients, peritoneal macrophages are preponderant and highly active compared to healthy women. Peritoneal macrophages are able to regulate the events that determine the production of cytokines, prostaglandins, growth factors and complement components. Several studies have shown alteration in the regulation of the complement activation, leading to chronic inflammation characteristic of EM. Aberrant regulation/activation of the complement system has been observed in the peritoneal cavity of women affected by EM. Thus, complement inhibition may represent a new approach for the treatment of EM, given that a number of complement inhibitors are under pre-clinical and clinical development. Such an intervention may provide a broader therapeutic control of complement-mediated inflammatory damage in EM patients. This review will focus on our current understanding of the role of complement activation in EM and possible modalities available for complement-based therapy.
Teneurin C-Terminal Associated Peptide (TCAP)-3 Increases Metabolic Activity in Zebrafish
Authors: Reid Ross M. , Reid Andrea L. , Lovejoy David A. , Biga Peggy R.
Published: January 2021

Teneurin C-terminal associated peptides (TCAP), bioactive peptides located on the C-terminal end of teneurin proteins, have been shown to regulate stress axis functions due to the high conservation between TCAP and corticotropin releasing factor (CRF). Additionally, recent work demonstrated that TCAP can increase metabolism in rats via glucose metabolism. These metabolic actions are not well described in other organisms, including teleosts. Here we investigated the expression of a tcap isoform, tcap-3, and the potential role of TCAP-3 as a regulator of metabolism across zebrafish life-stages. Using pcr-based analyses, tcap-3 appears to be independently transcribed, in relation to teneurin-3, in muscle tissue of adult zebrafish. Resazurin, respirometry chambers, and mitochondrial metabolism analyses were used to study the metabolic effects of synthetic rainbow trout TCAP-3 (rtTCAP-3) in larval and adult zebrafish. Overall, metabolic activity was enhanced by 48 h of rtTCAP-3 treatment in larvae (bath immersion) and adults (intraperitoneal injections). This metabolic activity increase was due to mitochondrial uncoupling, as mitochondrial respiration increase by rtTCAP-3 was due to proton leak. Additionally, rtTCAP-3 protected larval fish from reduced metabolic activity induced by low temperatures. Subsequently, rtTCAP-3 increased metabolic output in adult zebrafish subjected to accelerated swimming speeds, demonstrating the potent role of rtTCAP-3 in zebrafish metabolism regulation during metabolic challenges. Collectively, these results demonstrate the conserved roles for rtTCAP-3 as a metabolic activator in zebrafish.
Whole-Genome Sequencing of Clinically Isolated Carbapenem-Resistant Enterobacterales Harboring mcr Genes in Thailand, 2016–2019
Authors: Paveenkittiporn Wantana , Kamjumphol Watcharaporn , Ungcharoen Ratchadaporn , Kerdsin Anusak
Published: January 2021

Mobile colistin-resistant genes (mcr) have become an increasing public health concern. Since the first report of mcr-1 in Thailand in 2016, perspective surveillance was conducted to explore the genomic characteristics of clinical carbapenem-resistant Enterobacterales (CRE) isolates harboring mcr in 2016–2019. Thirteen (0.28%) out of 4,516 CRE isolates were found to carry mcr genes, including 69.2% (9/13) of E. coli and 30.8% (4/13) of K. pneumoniae isolates. Individual mcr-1.1 was detected in eight E. coli (61.5%) isolates, whereas the co-occurrence of mcr-1.1 and mcr-3.5 was seen in only one E. coli isolate (7.7%). No CRE were detected carrying mcr-2, mcr-4, or mcr-5 through to mcr-9. Analysis of plasmid replicon types carrying mcr revealed that IncX4 was the most common (61.5%; 8/13), followed by IncI2 (15.4%; 2/13). The minimum inhibitory concentration values for colistin were in the range of 4–16 μg/ml for all CRE isolates harboring mcr, suggesting they have 100% colistin resistance. Clermont phylotyping of nine mcr-harboring carbapenem-resistant E. coli isolates demonstrated phylogroup C was predominant in ST410. In contrast, ST336 belonged to CC17, and the KL type 25 was predominant in carbapenem-resistant K. pneumoniae isolates. This report provides a comprehensive insight into the prevalence of mcr-carrying CRE from patients in Thailand. The information highlights the importance of strengthening official active surveillance efforts to detect, control, and prevent mcr-harboring CRE and the need for rational drug use in all sectors.
Genome Assembly and Transcriptome Analysis of the Fungus Coniella diplodiella During Infection on Grapevine (Vitis vinifera L.)
Authors: Liu Ruitao , Wang Yiming , Li Peng , Sun Lei , Jiang Jianfu , Fan Xiucai , Liu Chonghuai , Zhang Ying
Published: January 2021

Grape white rot caused by Coniella diplodiella (Speg.) affects the production and quality of grapevine in China and other grapevine-growing countries. Despite the importance of C. diplodiella as a serious disease-causing agent in grape, the genome information and molecular mechanisms underlying its pathogenicity are poorly understood. To bridge this gap, 40.93 Mbp of C. diplodiella strain WR01 was de novo assembled. A total of 9,403 putative protein-coding genes were predicted. Among these, 608 and 248 genes are potentially secreted proteins and candidate effector proteins (CEPs), respectively. Additionally, the transcriptome of C. diplodiella was analyzed after feeding with crude grapevine leaf homogenates, which reveals the transcriptional expression of 9,115 genes. Gene ontology enrichment analysis indicated that the highly enriched genes are related with carbohydrate metabolism and secondary metabolite synthesis. Forty-three putative effectors were cloned from C. diplodiella, and applied for further functional analysis. Among them, one protein exhibited strong effect in the suppression of BCL2-associated X (BAX)-induced hypersensitive response after transiently expressed in Nicotiana benthamiana leaves. This work facilitates valuable genetic basis for understanding the molecular mechanism underlying C. diplodiella-grapevine interaction.
Case Report: Calpainopathy Presenting After Bone Marrow Transplantation, With Studies of Donor Genetic Content in Various Tissue Types
Authors: Martens Kristina , Leckie Jamie , Fok Daniel , Wells Robyn A. , Chhibber Sameer , Pfeffer Gerald
Published: January 2021

We present a patient who had two allogeneic bone marrow transplantations for acute lymphocytic leukemia. She developed slowly progressive limb-girdle weakness in the context of other symptoms of graft-vs.-host disease (GVHD). Her myopathy symptoms had been initially attributed to GVHD, but when she progressed despite immunotherapy, genetic testing was requested. Initial testing was performed on a blood sample, identifying a variant of unknown significance in DMD. Subsequent testing of DNA from the patient's muscle tissue identified two pathogenic variants in CAPN3, with absence of the DMD variant (this latter variant presumed to have been received from the donor). Allele-specific digital droplet qPCR permitted the quantification of the donor variant in various tissues from the patient (whole skin, isolated fibroblasts, whole blood, saliva, buccal cells, urine sediment, and two muscle biopsies taken at a 2 year interval). This report emphasizes that genetic disease should still be considered in the context of presumably acquired disease, and also demonstrates the extent of transdifferentiation of donor cells into other tissues.
Abnormal Brain Network Topology During Non–rapid Eye Movement Sleep and Its Correlation With Cognitive Behavioral Abnormalities in Narcolepsy Type 1
Authors: Zhu Xiaoyu , Ni Kunlin , Tan Huiwen , Liu Yishu , Zeng Yin , Yu Bing , Guo Qiyong , Xiao Li
Published: January 2021

Objective: Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) were applied to investigate the abnormalities in the topological characteristics of functional brain networks during non-rapid eye movement(NREM)sleep. And we investigated its relationship with cognitive abnormalities in patients with narcolepsy type 1 (NT1) disorder in the current study.

Methods: The Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) and EEG-fMRI were applied in 25 patients with NT1 and 25 age-matched healthy controls. All subjects participated in a nocturnal video polysomnography(PSG)study, and total sleep time (TST), percentage of TST (%TST) for each sleep stage and arousal index were calculated. The Epworth Sleepiness Score (ESS) was used to measure the degree of daytime sleepiness. The EEG-fMRI study was performed simultaneously using a 3T MRI system and a 32-channel MRI-compatible EEG system during sleep. Visual scoring of EEG data was used for sleep staging. Cognitive function was assessed for all subjects using the MoCA-BJ. The fMRI data were applied to establish a whole-brain functional connectivity network for all subjects, and the topological characteristics of the whole-brain functional network were analyzed using a graph-theoretic approach. The topological parameters were compared between groups. Lastly, the correlation between topological parameters and the assessment scale using Montreal Cognition was analyzed.

Results: The MoCA-BJ scores were lower in patients with NT1 than in normal controls. Whole-brain global efficiency during stage N2 sleep in patients with NT1 displayed significantly lower small-world properties than in normal controls. Whole-brain functional network global efficiency in patients with NT1 was significantly correlated with MoCA-BJ scores.

Conclusion: The global efficiency of the functional brain network during stage N2 sleep in patients with NT1 and the correspondingly reduced small-world attributes were associated with cognitive impairment.
Identifying Mild Hepatic Encephalopathy Based on Multi-Layer Modular Algorithm and Machine Learning
Authors: Zhang Gaoyan , Li Yuexuan , Zhang Xiaodong , Huang Lixiang , Cheng Yue , Shen Wen
Published: January 2021

Hepatic encephalopathy (HE) is a neurocognitive dysfunction based on metabolic disorders caused by severe liver disease, which has a high one-year mortality. Mild hepatic encephalopathy (MHE) has a high risk of converting to overt HE, and thus the accurate identification of MHE from cirrhosis with no HE (noHE) is of great significance in reducing mortality. Previously, most studies focused on studying abnormality in the static brain networks of MHE to find biomarkers. In this study, we aimed to use multi-layer modular algorithm to study abnormality in dynamic graph properties of brain network in MHE patients and construct a machine learning model to identify individual MHE from noHE. Here, a time length of 500-second resting-state functional MRI data were collected from 41 healthy subjects, 32 noHE patients and 30 MHE patients. Multi-layer modular algorithm was performed on dynamic brain functional connectivity graph. The connection-stability score was used to characterize the loyalty in each brain network module. Nodal flexibility, cohesion and disjointness were calculated to describe how the node changes the network affiliation across time. Results show that significant differences between MHE and noHE were found merely in nodal disjointness in higher cognitive network modules (ventral attention, fronto-parietal, default mode networks) and these abnormalities were associated with the decline in patients’ attention and visual memory function evaluated by Digit Symbol Test. Finally, feature extraction from node disjointness with the support vector machine classifier showed an accuracy of 88.71% in discrimination of MHE from noHE, which was verified by different window sizes, modular partition parameters and machine learning parameters. All these results show that abnormal nodal disjointness in higher cognitive networks during brain network evolution can be seemed as a biomarker for identification of MHE, which help us understand the disease mechanism of MHE at a fine scale.
Being Mindful at University: A Pilot Evaluation of the Feasibility of an Online Mindfulness-Based Mental Health Support Program for Students
Authors: Světlák Miroslav , Linhartová Pavla , Knejzlíková Terezia , Knejzlík Jakub , Kóša Barbora , Horníčková Veronika , Jarolínová Kristýna , Lučanská Klaudia , Slezáčková Alena , Šumec Rastislav
Published: January 2021

University study can be a life period of heightened psychological distress for many students. The development of new preventive and intervention programs to support well-being in university students is a fundamental challenge for mental health professionals. We designed an 8-week online mindfulness-based program (eMBP) combining a face-to-face approach, text, audio, video components, and support psychotherapy principles with a unique intensive reminder system using the Facebook Messenger and Slack applications in two separate runs (N = 692). We assessed the program’s effect on mindful experiencing, perceived stress, emotion regulation strategies, self-compassion, negative affect, and quality of life. The results of the presented pilot study confirmed that eMBP is a feasible and effective tool in university students’ mental health support. The students who completed the eMBP reported a reduction of perceived stress with a large effect size (pη2 = 0.42) as well as a decrease of negative affect experience frequency and intensity (pη2 = 0.31), an increase of being mindful in their life (Five Facet Mindfulness Questionnaire subscales:pη2 = 0.21, 0.27, 0.25, 0.28, 0.28), and a higher rate of self-compassion (pη2 = 0.28) with a medium effect size. A small effect size was found in the frequency of using a cognitive reappraisal strategy (pη2 = 0.073). One new result is the observation of an eMBP effect (pη2 = 0.27) on the decrease in attributed importance to the quality-of-life components replicated in two consecutive runs of the program. The study affirms that mindfulness-based interventions can be effectively delivered in an eHealth form to university students.
Comorbid Bipolar Disorder and Migraine: From Mechanisms to Treatment
Authors: Duan Jinfeng , Yang Rongmei , Lu Wenwen , Zhao Lingfei , Hu Shaohua , Hu Chenxia
Published: January 2021

Bipolar disorder (BD) is a severe psychiatric disorder characterized by recurrent episodes of manic/hypomanic or depressive symptoms and euthymic periods, with some patients suffering a gradual deterioration of illness and consequent cognitive deficits during the late stage. Migraine is a disease generally without abnormal medical examinations, neurological examinations or laboratory studies, and the diagnosis is made based on the retrospective demonstration of headache features and groupings of disease-associated symptoms. The epidemiology of comorbid BD and migraine is high and it is obligatory to find effective treatments to improve the prognosis. Recent investigations demonstrated that the close relationship between BD and migraine significantly increased the rapid cycling rates of both BD and migraine in patients. Although the detailed mechanism is complex and largely unclear in comorbid BD and migrain, genetic factors, neurotransmitters, altered signaling pathways, disturbances of inflammatory cytokines, and mitochondrial dysfunction are risk factors of BD and migraine. Particularly these two diseases share some overlapping mechanisms according to previous studies. To this end, we call for further investigations of the potential mechanisms, and more efforts are underway to improve the treatment of people with comorbid BD and migraine. In this review, we provide an overview of the potential mechanisms in patients with BD or migraine and we further discuss the treatment strategies for comorbid BD and migraine and it is obligatory to find effective treatments to improve the prognosis. This work will provide insights for us to know more about the mechanisms of comorbid BD and migraine, provides new therapeutic targets for the treatment and give clinicians some guidance for more appropriate and beneficial treatment.