bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequencing SARS-CoV-2 Genomes from Saliva
Authors: Alpert Tara , Vogels Chantal B.F. , Breban Mallery I. , Petrone Mary E. ,   Yale IMPACT Research Team, Wyllie Anne L. , Grubaugh Nathan D. , Fauver Joseph R. 
Published: June 2021

SummaryGenomic sequencing is crucial to understanding the epidemiology and evolution of SARS-CoV-2. Often, genomic studies rely on remnant diagnostic material, typically nasopharyngeal swabs, as input into whole genome SARS-CoV-2 next-generation sequencing pipelines. Saliva has proven to be a safe and stable specimen for the detection of SARS-CoV-2 RNA via traditional diagnostic assays, however saliva is not commonly used for SARS-CoV-2 sequencing. Using the ARTIC Network amplicon-generation approach with sequencing on the Oxford Nanopore MinION, we demonstrate that sequencing SARS-CoV-2 from saliva produces genomes comparable to those from nasopharyngeal swabs, and that RNA extraction is necessary to generate complete genomes from saliva. In this study, we show that saliva is a useful specimen type for genomic studies of SARS-CoV-2.
Japanese Project for Telepsychiatry Evaluation during COVID-19: Treatment Comparison Trial (J-PROTECT): Rationale, design, and methodology
Authors: Kishimoto Taishiro , Kinoshita Shotaro , Bun Shogyoku , Sato Yasunori , Kitazawa Momoko , Kikuchi Toshiaki , Sado Mitsuhiro , Takamiya Akihiro , Mimura Masaru , Nakamae Takashi , Abe Yoshinari , Kanazawa Tetsufumi , Kawabata Yasuo , Tomita Hiroaki , Abe Koichi , Hishimoto Akitoyo , Asami Takeshi , Suda Akira , Watanabe Yoshinori , Amagai Toru , Sakuma Kei , Kida Hisashi , Funayama Michitaka , Kimura Hiroshi , Sato Aiko , Fujiwara Shuichiro , Nagao Kiichiro , Sugiyama Naoya , Takamiya Maki , Kodama Hideyuki , Azekawa Takaharu 
Published: June 2021

ABSTRACTIntroductionThe COVID-19 pandemic has had a profound impact on the mental health of people around the world. Anxiety related to infection, stress and stigma caused by the forced changes in daily life have reportedly increased the incidence and symptoms of depression, anxiety disorder and obsessive-compulsive disorder. Under such circumstances, telepsychiatry is gaining importance and attracting a great deal of attention. However, few large pragmatic clinical trials on the use of telepsychiatry targeting multiple psychiatric disorders have been conducted to date.MethodsThe targeted study cohort will consist of adults (>18 years) who meet the DSM-5 diagnostic criteria for either (1) depressive disorders, (2) anxiety disorders, or (3) obsessive-compulsive and related disorders. Patients will be assigned in a 1:1 ratio to either a “telepsychiatry group” (at least 50% of visits to be conducted using telemedicine, with at least one face-to-face treatment [FTF] every six months) or an “FTF group” (all visits to be conducted FTF, with no telemedicine). Both groups will receive the usual treatment covered by public medical insurance. The study will utilize a master protocol design in that there will be primary and secondary outcomes for the entire group regardless of diagnosis, as well as the outcomes for each individual disorder group.DiscussionThis study will be a non-inferiority trial to test that the treatment effect of telepsychiatry is not inferior to that of FTF alone. This study will provide useful insights into the effect of the COVID-19 pandemic on the practice of psychiatry.Trial RegistrationjRCT1030210037, Japan Registry of Clinical Trials (jRCT)
Age-dependent inequalities in HIV/STI burden and care receipt among men and transgender persons who have sex with men in Nairobi
Authors: Smith Adrian D , Fearon Elizabeth , Kabuti Rhoda , Irungu Erastus , Kungu Mary , Babu Hellen , Nyabuto Chrispo , Muthoga Peter , Weatherburn Peter , Bourne Adam , Kimani Joshua 
Published: June 2021

AbstractBackgroundGay, bisexual and other men who have sex with men (GBMSM) and transgender persons (TP) bear high burdens of HIV and other sexually transmitted infections (STIs) in sub-Saharan Africa, yet evidence of HIV care coverage for these groups is sparse from the region despite prevailing stigma and discrimination towards these groups.Methods618 GBMSM/TP were recruited in Nairobi between May to December 2017 using respondent-driven sampling. Participants reported recent sexual behaviour, HIV testing and care receipt, and symptoms of STIs. Participants tested for HIV using Kenyan testing algorithms and GeneXpert methods, syphilis, viral hepatitis and ano-genital gonorrhoea and chlamydia. We assessed associations with HIV status and detectable HIV viral load using multivariable robust Poisson regression models.Findings26.4% (286/618) were HIV positive of whom 76.5% were status aware, 65.3% were on ART, and 47.4% were virally suppressed (<50 copies/ml). Participants 18-22 years old were less likely to be status aware, be receiving ART or to have achieved viral suppression. Mean log viral load was 3.14 log higher in 18-22 year olds compared to older participants. Bacterial STIs were frequently detected at both urethral and rectal sites and a majority of infections at both sites were asymptomatic by self-report (rectal 82.2%, urethral 90.8%).InterpretationEngagement in the HIV diagnosis and care cascade among GBMSM/TP in Kenya is markedly better than in most sub-Saharan African countries. However it falls short of achievements among the general population in the country and cascades achieved in GBMSM in high income settings. Young men and transgender persons who have sex with men are least well served by the current configuration of adult key population services, and programmes should identify and address the sexual, social and developmental needs of adolescent and young key populations
The effect of D-cycloserine on brain processing of breathlessness over pulmonary rehabilitation - an experimental medicine study
Authors: Finnegan Sarah L. , Harrison Olivia K. , Booth Sara , Dennis Andrea , Ezra Martyn , Harmer Catherine J. , Herigstad Mari , Guillaume Bryan , Nichols Thomas E. , Rahman Najib M. , Reinecke Andrea , Renaud Olivier , Pattinson Kyle T.S. 
Published: June 2021

AbstractBackgroundPulmonary rehabilitation is the best treatment for chronic breathlessness in COPD but there remains an unmet need to improve efficacy. Pulmonary rehabilitation has strong parallels with exposure-based cognitive behavioural therapies (CBT), both clinically and in terms of brain activity patterns. The partial NMDA-receptor agonist, D-cycloserine has shown promising results in enhancing efficacy of CBT, thus we hypothesised that it would similarly augment the effects of pulmonary rehabilitation in the brain. Positive findings would support further development in phase 3 clinical trials.Methods72 participants with mild-to-moderate COPD were recruited to a double-blind pre-registered (ID: NCT01985750) experimental medicine study running parallel to a pulmonary rehabilitation course. Participants were randomised to 250mg D-cycloserine or placebo, administered immediately prior to the first four sessions of pulmonary rehabilitation. Primary outcome measures were differences between D-cycloserine and placebo in brain activity in the anterior insula, posterior insula, anterior cingulate cortices, amygdala and hippocampus following completion of pulmonary rehabilitation. Secondary outcomes included the same measures at an intermediate time point and voxel-wise difference across wider brain regions.ResultsNo difference between D-cycloserine and placebo groups was observed across the primary or secondary outcome measures. Questionnaire and measures of respiratory function showed no group difference.ConclusionsThis is the first study testing brain-active drugs in pulmonary rehabilitation. Rigorous trial methodology and validated surrogate end-points maximised statistical power. Although increasing evidence supports therapeutic modulation of NMDA pathways to treat symptoms, we conclude that a phase 3 clinical trial of D-cycloserine would not be worthwhile.Key MessagesWhat is the key question?Does the partial NMDA-receptor agonist, D-cycloserine, augment the effects of pulmonary rehabilitation on breathlessness related brain activity?What is the bottom line?Rigorous trial methodology and validated surrogate end-points revealed no effect of D-cycloserine on breathlessness related brain activity across pulmonary rehabilitation.Why read on?This study highlights both the value of functional magnetic resonance imaging in “de-risking” expensive clinical trials and provides detailed investigation of brain-targeted points for pharmacological treatments of breathlessness.
Using deep learning to predict age from liver and pancreas magnetic resonance images allows the identification of genetic and non-genetic factors associated with abdominal aging
Authors: Le Goallec Alan , Diai Samuel , Collin Sasha , Prost Jean-Baptiste , Vincent Théo , Patel Chirag J. 
Published: June 2021

AbstractWith age, abdominal organs and tissue undergo important changes. For example, liver volume declines, fatty replacement increases in the pancreas, and patients become more vulnerable to age-related diseases such as non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, fibrosis, cirrhosis, type two diabetes, cancer, gallstones and inflammatory pancreatic disease. Detecting early abdominal aging and identifying factors associated with this phenotype could help delay the onset of such diseases. In the following, we built the first abdominal age predictor by training convolutional neural networks to predict age from 45,552 liver magnetic resonance images [MRIs] and 36,784 pancreas MRIs (R-Squared=73.3±0.6; root mean squared error=3.70±0.03). Attention maps show that the prediction is driven not only by liver and pancreas anatomical features, but also by surrounding organs and tissue. We defined accelerated abdominal aging as the difference between abdominal age and chronological age, a phenotype which we found to be partially heritable (h_g2=26.3±1.9%). Accelerated abdominal aging is associated with seven single nucleotide polymorphisms in six genes (e.g PNPT1, involved in RNA metabolic processes). Similarly, it is associated with biomarkers (e.g body impedance), clinical phenotypes (e.g chest pain), diseases (e.g hypertension), environmental (e.g smoking) and socioeconomic (e.g education) variables, suggesting potential therapeutic and lifestyle interventions to slow abdominal aging. Our predictor could be used to assess the efficacy or emerging rejuvenating therapies on the abdomen.
Assessment of COVID-19 vaccine hesitancy among Zimbabweans: A rapid national survey
Authors: Mundagowa Paddington T. , Tozivepi Samantha N. , Chiyaka Edward T. , Mukora-Mutseyekwa Fadzai , Makurumidze Richard 
Published: June 2021

AbstractBackgroundTo minimise the devastating effects of the coronavirus disease 2019 (COVID-19) pandemic, scientists hastily developed a vaccine. However, the scale-up of the vaccine is likely to be hindered by the widespread social media misinformation. We, therefore, conducted a study to assess the COVID-19 vaccine hesitancy among Zimbabweans.MethodsWe conducted a descriptive online cross-sectional survey using a self-administered questionnaire among adults. The questionnaire assessed willingness to be vaccinated; socio-demographic characteristics, individual attitudes and perceptions, effectiveness, and safety of the vaccine. Multivariable logistic regression analysis was utilized to examine the independent factors associated with vaccine uptake.ResultsWe analysed data for 1168 participants, age range of 19-89 years with the majority being females (57.5%). Half (49.9%) of the participants reported that they would accept the COVID-19 vaccine. The majority were uncertain about the effectiveness of the vaccine (76.0%) and its safety (55.0%). About half lacked trust in the government’s ability to ensure the availability of an effective vaccine and 61.0% mentioned that they would seek advice from a healthcare worker to vaccinate. Age 55 years and above [vs 18-25 years - Adjusted Odds Ratio (AOR): 2.04, 95% Confidence Interval (CI): 1.07-3.87], chronic disease [vs no chronic disease - AOR: 1.72, 95%CI: 1.32-2.25], males [vs females - AOR: 1.84, 95%CI: 1.44-2.36] and being a healthcare worker [vs not being a health worker – AOR: 1.73, 95%CI: 1.34-2.24] were associated with increased likelihood to vaccinate. History of COVID-19 infection [vs no history - AOR: 0.45, 95%CI: 0.25-0.81) and rural residence [vs urban - AOR: 0.64, 95%CI: 0.40-1.01] were associated with reduced likelihood to vaccinate.ConclusionWe found half of the participants willing to vaccinate against COVID-19. The majority lacked trust in the government and were uncertain about vaccine effectiveness and safety. The policymakers should consider targeting geographical and demographic groups which were unlikely to vaccinate with vaccine information, education, and communication to improve uptake.
Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta-glucan food supplement in a randomized, parallel-group pilot clinical study
Authors: Raghavan Kadalraja , Dedeepiya Vidyasagar Devaprasad , Ikewaki Nobunao , Sonoda Tohru , Iwasaki Masaru , Preethy Senthilkumar , Abraham Samuel JK 
Published: June 2021

AbstractBackgroundAutism spectrum disorders (ASDs) are a wide range of behavioural disabilities for which there are no definite interventional modalities available. Remedial therapies remain the only option but with varying outcomes. We have evaluated the childhood autism rating scale (CARS) and alpha-synuclein levels in this parallel-group, multiple-arm pilot clinical study after supplementation with a biological response modifier beta-glucan food supplement (Nichi Glucan).MethodsSix subjects with ASD (n = 6) Gr. 1 underwent conventional treatment comprising remedial behavioural therapies and L-carnosine 500 mg per day, and 12 subjects (n = 12) Gr. 2 underwent supplementation with the Nichi Glucan 0.5 g twice daily along with the conventional treatment.ResultsThere was a significant decrease in the CARS score in all of the children of the Nichi Glucan Gr.2 compared to the control (p-value = 0.034517). Plasma levels of alpha-synuclein were significantly higher in Gr. 2 (Nichi Glucan) than in the control group Gr. 1 (p-value = 0.091701).ConclusionImprovement of the behavioural pattern CARS score and a correlating alpha-synuclein level, followed by a safe beta-glucan food supplement, warrants further research on other parameters, such as gut-microbiota evaluation, and relevant neuronal biomarkers which is likely to cast light on novel solutions.
Exploration and analysis of molecularly annotated, 3D models of breast cancer at single-cell resolution using virtual reality
Authors: Bressan Dario , Mulvey Claire M. , Qosaj Fatime , Becker Robert , Grimaldi Flaminia , Coffey Suvi , Vogl Sara Lisa , Kuett Laura , Catena Raul , Dariush Ali , Gonzalez-Fernandez Carlos , Gonzalez-Solares Eduardo A. , Sa’d Mohammad Al , Yoldaş Aybüke Küpcü , Whitmarsh Tristan , Falciatori Ilaria , Watson Spencer S. ,   CRUK IMAXT Grand Challenge Team, Joyce Johanna A. , Walton Nicholas , Bodenmiller Bernd , Harris Owen , Hannon Gregory J. 
Published: June 2021

ABSTRACTA set of increasingly powerful approaches are enabling spatially resolved measurements of growing numbers of molecular features in biological samples. While important insights can be derived from the two-dimensional data that many of these technologies generate, it is clear that extending these approaches into the third and fourth dimensions will magnify their impact. Realizing biological insights from datasets where thousands to millions of cells are annotated with tens to hundreds of parameters in space will require the development of new computational and visualization strategies. Here, we describe Theia, a virtual reality-based platform, which enables exploration and analysis of either volumetric or segmented, molecularly-annotated, three-dimensional datasets, with the option to extend the analysis to time-series data. We also describe our pipeline for generating annotated 3D models of breast cancer and supply several datasets to enable users to explore the utility of Theia for understanding cancer biology in three dimensions.
Anoikis resistance in mammary epithelial cells is mediated by semaphorin 7a Semaphorin-7A and anoikis resistance
Authors: Rutherford Taylor R. , Elder Alan M , Lyons Traci R. 
Published: June 2021

ABSTRACTSemaphorin-7a (SEMA7A), best known as a neuroimmune molecule, plays a diverse role in many cellular processes and pathologies. Here, we show that SEMA7A promotes anoikis resistance in cultured mammary epithelial cells through integrins and activation of pro-survival kinase AKT, which led us to investigate a role for SEMA7A during postpartum mammary gland involution—a normal developmental process where cells die by anoikis. Our results reveal that SEMA7A is expressed on live mammary epithelial cells during involution, that SEMA7A expression is primarily observed in α6-integrin expressing cells, and that luminal progenitor cells, specifically, are decreased in mammary glands of SEMA7A−/− mice during involution. We further identify a SEMA7A-α6/β1-integrin dependent mechanism of mammosphere formation and chemoresistance in mammary epithelial cells and suggest that this mechanism is relevant for recurrence in breast cancer patients.
Predicting protein-membrane interfaces of peripheral membrane proteins using ensemble machine learning
Authors: Chatzigoulas Alexios , Cournia Zoe 
Published: June 2021

AbstractAbnormal protein-membrane attachment is involved in deregulated cellular pathways and in disease. Therefore, the possibility to modulate protein-membrane interactions represents a new promising therapeutic strategy for peripheral membrane proteins that have been considered so far undruggable. A major obstacle in this drug design strategy is that the membrane binding domains of peripheral membrane proteins are usually not known. The development of fast and efficient algorithms predicting the protein-membrane interface would shed light into the accessibility of membrane-protein interfaces by drug-like molecules. Herein, we describe an ensemble machine learning methodology and algorithm for predicting membrane-penetrating amino acids. We utilize available experimental data in the literature for training 21 machine learning classifiers and a voting classifier. Evaluation of the ensemble classifier accuracy produced a macro-averaged F1score = 0.92 and an MCC = 0.84 for predicting correctly membrane-penetrating amino acids on unknown proteins of an independent test set. The python code for predicting protein-membrane interfaces of peripheral membrane proteins is available athttps://github.com/zoecournia/DREAMM.
OpenNeuro: An open resource for sharing of neuroimaging data
Authors: Markiewicz Christopher J. , Gorgolewski Krzysztof J. , Feingold Franklin , Blair Ross , Halchenko Yaroslav O. , Miller Eric , Hardcastle Nell , Wexler Joe , Esteban Oscar , Goncalves Mathias , Jwa Anita , Poldrack Russell A. 
Published: June 2021

AbstractThe sharing of research data is essential to ensure reproducibility and maximize the impact of public investments in scientific research. Here we describe OpenNeuro, a BRAIN Initiative data archive that provides the ability to openly share data from a broad range of brain imaging data types following the FAIR principles for data sharing. We highlight the importance of the Brain Imaging Data Structure (BIDS) standard for enabling effective curation, sharing, and reuse of data. The archive presently shares more than 600 datasets including data from more than 20,000 participants, comprising multiple species and measurement modalities and a broad range of phenotypes. The impact of the shared data is evident in a growing number of published reuses, currently totalling more than 150 publications. We conclude by describing plans for future development and integration with other ongoing open science efforts.
Reactivities of the Front Pocket N-Cap Cysteines in Human Kinases
Authors: Liu Ruibin , Zhan Shaoqi , Che Ye , Shen Jana 
Published: June 2021

AbstractDiscovery of targeted covalent inhibitors directed at nucleophilic cysteines is attracting enormous interest. The front pocket (FP) N-cap cysteine has been the most popular site of covalent modification in kinases. Curiously, a long-standing hypothesis associates the N-cap position with cysteine hyper-reactivity; however, traditional computational methods suggest that the FP N-cap cysteines in all human kinases are predominantly unreactive at physiological pH. Here we applied a newly developed GPU-accelerated continuous constant pH molecular dynamics (CpHMD) tool to test the N-cap hypothesis and elucidate the cysteine reactivities. Simulations showed that the N-cap cysteines in BTK/BMX/TEC/ITK/TXK, JAK3, and MKK7 sample the reactive thiolate form to varying degrees at physiological pH; however, those in BLK and EGFR/ERBB2/ERBB4 which contain an Asp at the N-cap+3 position adopt the unreactive thiol form. The latter argues in favor of the base-assisted thiol-Michael addition mechanisms as suggested by the quantum mechanical calculations and experimental structure-function studies of EGFR inhibitors. Analysis revealed that the reactive N-cap cysteines are stabilized by hydrogen bond as well as electrostatic interactions, and in their absence a N-cap cysteine is unreactive due to desolvation. To test a corollary of the N-cap hypothesis, we also examined the reactivities of the FP N-cap+2 cysteines in JNK1/JNK2/JNK3 and CASK. Additionally, our simulations predicted the reactive cysteine and lysine locations in all 15 kinases. Our findings offer a systematic understanding of cysteine reactivities in kinases and demonstrate the predictive power and physical insights CpHMD can provide to guide the rational design of targeted covalent inhibitors.
31,600-year-old human virus genomes support a Pleistocene origin for common childhood infections
Authors: Nielsen Sofie Holtsmark , van Dorp Lucy , Houldcroft Charlotte J. , Pedersen Anders G. , Allentoft Morten E. , Vinner Lasse , Margaryan Ashot , Pavlova Elena , Chasnyk Vyacheslav , Nikolskiy Pavel , Pitulko Vladimir , Pimenoff Ville N. , Balloux François , Sikora Martin 
Published: June 2021

AbstractThe origins of viral pathogens and the age of their association with humans remains largely elusive. To date, there is no direct evidence about the diversity of viral infections in early modern humans pre-dating the Holocene. We recovered two near-complete genomes (5.2X and 0.7X) of human adenovirus C (HAdV-C), as well as low-coverage genomes from four distinct species of human herpesvirus obtained from two 31,630-year-old milk teeth excavated at Yana, in northeastern Siberia. Phylogenetic analysis of the two HAdV-C genomes suggests an evolutionary origin around 700,000 years ago consistent with a common evolutionary history with hominin hosts. Our findings push back the earliest direct molecular evidence for human viral infections by ∼25,000 years, and demonstrate that viral species causing common childhood viral infections today have been in circulation in humans at least since the Pleistocene.
Attracting CEO directors: the case of Latin America
Authors: Rivas Jose Luis , Villamil-Diaz Jairo , Cannella Albert 
Published: June 2021

PurposeTo understand if certain board traits can contribute to attract CEO directorsDesign/methodology/approachPanel data model with firm fixed effects of individual and firm level attributes from 450 public firms in Argentina, Brazil, Chile, Colombia, Mexico and PeruFindingsHigher levels of masters abroad, board ties, government experience and foreign members are all negatively related to the appointment of CEO directorsOriginality/valueThe use of non-performance outcome variable such as CEO experience in the family led emergent environment of Latin America