bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene-level analysis of rare variants in 363,977 whole exome sequences identifies an association of GIGYF1 loss of function with type 2 diabetes
Authors: Deaton Aimee M. , Parker Margaret M. , Ward Lucas D. , Flynn-Carroll Alexander O. , BonDurant Lucas , Hinkle Gregory , Akbari Parsa , Lotta Luca A. ,   Regeneron Genetics Center,   DiscovEHR Collaboration, Baras Aris , Nioi Paul 
Published: January 2021

AbstractSequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and to find novel contributors to human disease. We used gene-based collapsing tests to identify genes associated with glucose, HbA1c and type 2 diabetes (T2D) diagnosis in 363,977 exome-sequenced participants in the UK Biobank. We identified associations for variants in GCK, HNF1A and PDX1, which are known to be involved in Mendelian forms of diabetes. Notably, we uncovered novel associations for GIGYF1, a gene not previously implicated by human genetics, in diabetes. GIGYF1 predicted loss of function (pLOF) variants associated with increased levels of glucose (0.77 mmol/L increase, p = 4.42 × 10-12) and HbA1c (4.33 mmol/mol, p = 1.28 × 10-14) as well as T2D diagnosis (OR = 4.15, p= 6.14 ×10-11). Multiple rare variants contributed to these associations, including singleton variants. GIGYF1 pLOF also associated with decreased cholesterol levels as well as an increased risk of hypothyroidism. The association of GIGYF1 pLOF with T2D diagnosis replicated in an independent cohort from the Geisinger Health System. In addition, a common variant association for glucose and T2D was identified at the GIGYF1 locus. Our results highlight the role of GIGYF1 in regulating insulin signaling and protecting from diabetes.Author SummaryGenetic studies focused on high impact variants in protein-coding regions of the genome can provide valuable insight into the biology of human disease. As these variants tend to be rare, studying them requires large cohort sizes and methods to aggregate variants that are likely to have a similar biological impact. We studied how rare genetic variants contribute to type 2 diabetes (T2D) using sequencing data from 363,977 participants in the UK Biobank, employing methods to aggregate variants at the level of individual genes. As well as identifying genes known to be involved in inherited forms of diabetes, we uncovered a novel association for GIGYF1. GIGYF1 loss of function associated with increased risk of T2D and increased levels of the diabetes biomarkers glucose and HbA1c. This association was also seen in an independent dataset. GIGYF1 encodes a protein that binds a negative regulator of the insulin receptor that has not been well-characterized in the literature. By highlighting the importance of GIGYF1 in modulating insulin signaling these results may lead to new therapeutic approaches for diabetes as well as a new appreciation for GIGYF1 loss of function as a genetic risk factor for T2D.
Mental health and wellbeing amongst people with informal caring responsibilities across different time points during the COVID-19 pandemic: A population-based propensity score matching analysis
Authors: Mak Hei Wan , Bu Feifei , Fancourt Daisy 
Published: January 2021

AbstractAimsDue to a prolonged period of national and regional lockdown measures during the coronavirus (COVID-19) pandemic, there has been an increase reliance on informal care and a consequent increase in care intensity for informal carers. In light of this, the current study compared the experiences of carers and non-carers on various mental health and wellbeing measures across 5 key time points during the pandemic.MethodsData analysed were from the UCL COVID -19 Social Study. Our study focused on 5 time points in England: (i) the first national lockdown (March-April 2020; N=12,053); (ii) the beginning of lockdown rules easing (May 2020; N=24,374); (iii) further easing (July 2020; N=21,395); (iv) new COVID-19 restrictions (September 2020; N=4,792); and (v) the three-tier system restrictions (October 2020; N=4,526). We considered 5 mental health and wellbeing measures-depression, anxiety, loneliness, life satisfaction and sense of worthwhile. Propensity score matching were applied for the analyses.ResultsWe found that informal carers experienced higher levels of depressive symptoms and anxiety than non-carers across all time points. During the first national lockdown, carers also experienced a higher sense of life being worthwhile. No association was found between informal caring responsibilities and levels of loneliness and life satisfaction.ConclusionGiven that carers are an essential national health care support, especially during a pandemic, it is crucial to integrate carers’ needs into healthcare planning and delivery. These results highlight there is a pressing need to provide adequate and targeted mental health support for carers during and following this pandemic.
A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants
Authors: Jones Christine Elizabeth , Calvert Anna , Southern Jo , Matheson Mary , Andrews Nick , Khalil Asma , Cuthbertson Hannah , Hallis Bassam , England Anna , Heath Paul T , Miller Elizabeth 
Published: January 2021

AbstractBackgroundPertussis vaccines containing three or five pertussis antigens are recommended in pregnancy in many countries, but no studies have compared the effect on infants’ antigen-specific immunoglobulin G (IgG) concentrations. The aim of this study was to compare anti-pertussis IgG responses following primary immunization in infants of mothers vaccinated with TdaP5-IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP3-IPV in pregnancy (three pertussis antigens).MethodsThis multi-centre phase IV randomized clinical trial was conducted in a tertiary referral centre and primary care sites in England from 2014-2016. Women were randomized to receive TdaP5-IPV (n=77) or TdaP3-IPV (n=77) at 28-32 gestational weeks. A non-randomized control group of 44 women who had not received a pertussis-containing vaccine in pregnancy and their 47 infants were enrolled postpartum.ResultsFollowing infant primary immunization, there was no difference in the geometric mean concentrations (GMCs) of anti-pertussis toxin, filamentous haemagglutinin or pertactin IgG between infants born to women vaccinated with TdaP5-IPV (n=67) or TdaP3-IPV (n=63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP5-IPV and TdaP3-IPV vaccinated mothers compared to infants born to unvaccinated mothers (n=45) (geometric mean ratio: 0.71 [0.56-0.90] and 0.78 [0.61-0.98], respectively); by 13 months of age, this difference was no longer observed.ConclusionBlunting of anti-pertussis toxin IgG response following primary immunization occurs in infants born to women vaccinated with TdaP5-IPV and TdaP3-IPV, with no difference between maternal vaccines. The blunting effect had resolved by 13 months of age. These results may be helpful for countries considering which pertussis-containing vaccine to recommend for use in pregnancy.Clinical Trials identifierClinicalTrials.gov: NCT02145624
An interactive COVID-19 virus Mutation Tracker (CovMT) with a particular focus on critical mutations in the Receptor Binding Domain (RBD) region of the Spike protein
Authors: Alam Intikhab , Radovanovic Aleksandar , Incitti Roberto , Kamau Allan , Alarawi Muhammad , Azhar Esam I. , Gojobori Takashi 
Published: January 2021

AbstractAlmost one year has passed since the appearance of SARS-CoV-2, causing the COVID-19 pandemic. The number of confirmed SARS-Cov-2 cases worldwide has now reached ∼92 million, with 2 million reported deaths (https://covid19.who.int). Nearly 400,000 SARS-Cov-2 genomes were sequenced from COVID-19 samples and added to public resources such as GISAID (https://gisaid.org). With the vaccines becoming available or entering trials (https://covid19.trackvaccines.org), it is vital to keep track of mutations in the genome of SARS-CoV-2, especially in the Spike protein’s Receptor Binding Domain (RBD) region, which could have a potential impact on disease severity and treatment strategies.1–3 In the wake of a recent increase in cases with a potentially more infective RBD mutation (N501Y) in the United Kingdom, countries worldwide are concerned about the spread of this or similar variants. Impressive sampling and timely increase in sequencing efforts related to COVID-19 in the United Kingdom (UK) helped detect and monitor the spread of the new N501Y variant. Similar sequencing efforts are needed in other countries for timely tracking of this or different variants. To track geographic sequencing efforts and mutations, with a particular focus on RBD region of the Spike protein, we present our daily updated COVID-19 virus Mutation Tracker system, see https://www.cbrc.kaust.edu.sa/covmt.
High-altitude is associated with better short-term survival in critically ill COVID-19 patients admitted to the ICU
Authors: Jaramillo Pablo R. Morocho , Simbaña-Rivera Katherine , Silva Javier V. Velastegui , Gómez-Barreno Lenin , Campoverde Ana B. Ventimilla , Cevallos Juan F. Novillo , Guanoquiza Washington E. Almache , Cedeño Guevara Silvio L. , Castro Luis G. Imba , Puerta Nelson A. Moran , Valladares Alex W. Guayta , Lister Alex , Ortiz-Prado Esteban 
Published: January 2021

AbstractBackgroundThe novel human coronavirus, SARS-CoV-2, has affected at least 218 countries worldwide. Some geographical and environmental factors are positively associated with a better or worse prognosis concerning COVID-19 disease and with lower or higher SARS-CoV-2 transmission. High altitude exposure has been associated with lower SARS-CoV-2 attack rates; nevertheless, the role of chronic high-altitude exposure on the clinical outcome of critically ill COVID-19 patients has not been studied.ObjectiveTo compare the clinical course and outcomes of critically ill patients with COVID-19 hospitalized in two intensive care units (ICU) located at low and high altitude.Exposure and OutcomeTo explore the effect of two different elevations (10 m vs 2,850 m above sea level) on COVID-19 clinical outcome and survival.MethodsA prospective cohort, two-center study in confirmed COVID-19 adult patients admitted to a low altitude (Sea level) and high altitude (2,850 m) ICU units in Ecuador was conducted. Two hundred and thirty confirmed COVID-19 patients were enrolled from March 15thto July 15th, 2020. Sociodemographic, clinical, laboratory and imaging parameters including supportive therapies, pharmacological treatments and medical complications were reported and compared between the low and high-altitude groups.ResultsThe median age of all the patients was 60 years, 64.8% were men and 35.2% were women. A total of 105 (45.7%) patients had at least one underlying comorbidity, the most frequent being chronic diseases, such as hypertension (33.5%), diabetes (16.5%), and chronic kidney failure (5.7%). The APACHE II scale at 72 hours was especially higher in the low-altitude group with a median of 18 points (IQR: 9.5-24.0), compared to 9 points (IQR: 5.0-22.0) obtained in the group of high altitude. There is evidence of a difference in survival in favor of the high-altitude group (p = 0.006), the median survival being 39 days, compared to 21 days in the low altitude group.ConclusionThere has been a substantial improvement in survival amongst people admitted to the high-altitude critical care unit. High altitude living was associated with improved survival, especially among patients with no comorbidities. COVID-19 patients admitted to the high-altitude ICU unit have improved severity-of-disease classification system scores at 72 hours and reported better respiratory and ventilatory profiles than the low altitude group.
Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients
Authors: Bliddal Sofie , Banasik Karina , Pedersen Ole Birger , Nissen Ioanna , Cantwell Lisa , Schwinn Michael , Tulstrup Morten , Westergaard David , Ullum Henrik , Brunak Søren , Tommerup Niels , Feenstra Bjarke , Geller Frank , Ostrowski Sisse Rye , Grønbæk Kirsten , Nielsen Claus Henrik , Nielsen Susanne Dam , Feldt-Rasmussen Ulla 
Published: January 2021

AbstractBackgroundReports of persistent symptoms after hospitalization with COVID-19 have raised concern of a “long COVID” syndrome. This study aimed at characterizing acute and persistent symptoms in non- hospitalized patients with polymerase chain reaction (PCR) confirmed COVID-19.MethodsCohort study of 445 non-hospitalized participants identified via the Danish Civil Registration System with a SARS-CoV-2-positive PCR-test and available biobank samples for genetic analyses. Participants received a digital questionnaire on demographics and COVID-19-related symptoms. Persistent symptoms: symptoms >four weeks (in sensitivity analyses >12 weeks).Results445 participants were included, of whom 34% were asymptomatic. Most common acute symptoms were fatigue, headache, and sneezing, while fatigue and reduced smell and taste were reported as most severe. Persistent symptoms, most commonly fatigue and memory and concentration difficulties, were reported by 36% of 198 symptomatic participants with follow-up >four weeks. Risk factors for persistent symptoms included female sex (women 44% vs. men 24%, odds ratio 2.7, 95%CI:1.4-5.1, p=0.003) and BMI (odds ratio 1.1, 95%CI:1.0-1.2, p=0.001).ConclusionAmong non-hospitalized PCR-confirmed COVID-19 patients one third were asymptomatic while one third of symptomatic participants had persistent symptoms illustrating the heterogeneity of disease presentation. These findings should be considered in future health care planning and policy making related to COVID-19.
An Online Risk Calculator for Rapid Prediction of In-hospital Mortality from COVID-19 Infection
Authors: Evans Daniel S. , Kim Kyoung Min , Jiang Xiaqing , Jacobson Jessica , Browner Warren , Cummings Steven R. 
Published: January 2021

AbstractPrediction of mortality from COVID-19 infection might help triage patients to hospitalization and intensive care. To estimate the risk of inpatient mortality, we analyzed the data of 13,190 adult patients in the New York City Health + Hospitals system admitted for COVID-19 infection from March 1 to June 30, 2020. They had a mean age 58 years, 40% were Latinx, 29% Black, 9% White and 22% of other races/ethnicities and 2,875 died. We used Machine learning (Gradient Boosted Decision Trees; XGBoost) to select predictors of inpatient mortality from demographics, vital signs and lab tests results from initial encounters. XGBoost identified O2 saturation, systolic and diastolic blood pressure, pulse rate, respiratory rate, age, and BUN with an Area Under the Receiver Operating Characteristics Curve = 94%. We applied CART to find cut-points in these variables, logistic regression to calculate odds-ratios for those categories, and assigned points to the categories to develop a score. A score = 0 indicates a 0.8% (95% confidence interval, 0.5 – 1.0%) risk of dying and ≥ 12 points indicates a 98% (97-99%) risk, and other scores have intermediate risks. We translated the models into an online calculator for the probability of mortality with 95% confidence intervals (as pictured):Abstract Figuredanielevanslab.shinyapps.io/COVID_mortality/
Local adaptations of Mediterranean sheep and goats through an integrative approach
Authors: Serranito Bruno , Cavalazzi Marco , Vidal Pablo , Taurisson-Mouret Dominique , Ciani Elena , Bal Marie , Rouvellac Eric , Servin Bertrand , Moreno-Romieux Carole , Tosser-Klopp Gwenola , Hall Stephen J. G. , Lenstra Johannes A. , Pompanon François , Benjelloun Badr , Da Silva Anne 
Published: January 2021

ABSTRACTIn a context of climate change, identifying the genes underlying adaptations to extreme environments is essential. Small ruminants are adapted to a wide variety of habitats and thus, are promising study models. Here, we considered 17 goat and 25 sheep local Mediterranean breeds, in Italy, France and Spain. We proposed, and empirically tested a new methodology to highlight selection signatures in relation to the environments. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original geographical cradle, including transhumant pastoral areas. For both species, the cradles were arranged along latitudinal gradient of aridity and altitude. Then we used the programs PCAdapt and LFMM. Considering cradles, instead of current GPS coordinates, markedly improved the sensitivity of the LFMM analyses. All the results combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles. Some of these genes, have been found implicated in lipid metabolism (SUCLG2, BMP2), hypoxia/heat stress (UBE2R2/UBAP2), lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). For the intergenic region between PCDH9 and KLH1, as well as NBEA, identified in both species, the adaptive role could be strong. We found for RXFP2, associated with sheep horn development, and MSRB3 and SLC26A4, both associated with hearing of sheep, a strong association with the environment gradient. We conclude that our new methodology, which considers breeds in their historical, environmental and anthropological context, provides novel and essential information on local breeds and their unique adaptations.
Separable pupillary signatures of perception and action during perceptual multistability
Authors: Brascamp Jan W. , de Hollander Gilles , Wertheimer Michael D. , DePew Ashley N. , Knapen Tomas 
Published: January 2021

AbstractThe pupil provides a rich, non-invasive measure of the neural bases of perception and cognition, and has been of particular value in uncovering the role of arousal-linked neuromodulation, which alters cortical processing as well as pupil size. But pupil size is subject to a multitude of influences, which complicates unique interpretation. We measured pupils of observers experiencing perceptual multistability -- an ever-changing subjective percept in the face of unchanging but inconclusive sensory input. In separate conditions the endogenously generated perceptual changes were either task-relevant or not, allowing a separation between perception-related and task-related pupil signals. Perceptual changes were marked by a complex pupil response that could be decomposed into two components: a dilation tied to task execution and plausibly indicative of an arousal-linked noradrenaline surge, and an overlapping constriction tied to the perceptual transient and plausibly a marker of altered visual cortical representation. Constriction, but not dilation, amplitude systematically depended on the time interval between perceptual changes, possibly providing an overt index of neural adaptation. These results show that the pupil provides a simultaneous reading on interacting but dissociable neural processes during perceptual multistability, and suggest that arousal-linked neuromodulation shapes action but not perception in these circumstances.
The unique role of parietal cortex in action observation: Functional organization for communicative and manipulative actions
Authors: Urgen Burcu A. , Orban Guy A. 
Published: January 2021

AbstractAction observation is supported by a network of regions in occipito-temporal, parietal, and premotor cortex in primates. Recent research suggests that the parietal node has regions dedicated to different action classes including manipulation, interpersonal, skin-displacing, locomotion, and climbing. The goals of the current study consist of: 1) extending this work with new classes of actions that are communicative and specific to humans, 2) investigating how parietal cortex differs from the occipito-temporal and premotor cortex in representing action classes. Human subjects underwent fMRI scanning while observing three action classes: indirect communication, direct communication, and manipulation, plus two types of control stimuli, static controls which were static frames from the video clips, and dynamic controls consisting of temporally-scrambled optic flow information. Using univariate analysis, MVPA, and representational similarity analysis, our study presents several novel findings. First, we provide further evidence for the anatomical segregation in parietal cortex of different action classes: We have found a new region that is specific for representing human-specific indirect communicative actions in cytoarchitectonic parietal area PFt. Second, we found that the discriminability between action classes was higher in parietal cortex than the other two levels suggesting the coding of action identity information at this level. Finally, our results advocate the use of the control stimuli not just for univariate analysis of complex action videos but also when using multivariate techniques.
CropMetaPop : a population genetics program to simulate the evolution of crop metapopulations
Authors: Thomas Mathieu , Miramon Anne , Naino Jika Abdel Kader , Rouger Baptiste , Hospital Frédéric , Noûs Camille , Goldringer Isabelle 
Published: January 2021

AbstractStochastic simulation programs are useful to study the evolution of crop populations in changing environments. These programs require to take into account some specific features characterizing farmers’ practices such as seed circulation or seed mixing. However such human-mediated evolutionary processes are different from the classical colonization or migration models used in most existing stochastic simulation programs for quantitative population genetics.To fill this gap, CropMetaPop is an individual based forward-time simulation program for quantitative population genetics developed to represent a diversity of socially established rules underlying seed circulation between farmers. For instance, one farmer can give seeds to neighbours according to his stock and receive from them according to his needs. Crop-Metapop also takes into account other important evolutionary forces encountered in crop diversity management systems, such as different population sizes and selection modalities for different populations.CropMetaPop makes it possible to study the impacts of different crop biodiversity management strategies. For this purpose, it simulates the genetic evolution over time of several crop populations submitted to genetic drift and selection and linked by explicitly modeled seed circulation and mixtures.