bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a Trans-Ancestry Polygenic Risk Score for Type 2 Diabetes in Diverse Populations
Authors: Ge Tian , Patki Amit , Srinivasasainagendra Vinodh , Lin Yen-Feng , Irvin Marguerite Ryan , Tiwari Hemant K. , Armstrong Nicole , Davis Brittney H. , Perez Emma , Gainer Vivian , Benoit Barbara , O’Connor Mark J. , Narayan Renuka , Etheridge Bethany , Stamou Maria , Leong Aaron , Udler Miriam S. , Choi Karmel W. , Miles Ayme D. , Kiryluk Krzysztof , Khan Atlas , Chen Chia-Yen , Feng Yen-Chen Anne , Huang Hailiang , Cimino James J. , Murphy Shawn , Weiss Scott T. , Lange Christoph , Ng Maggie C. Y. , Smoller Jordan W. , Lebo Matthew S. , Meigs James B. , Limdi Nita A. , Karlson Elizabeth W. 
Published: September 2021

ABSTRACTType 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic risk scores (PRS) have shown promise to complement established clinical risk factors and intervention paradigms, and improve early diagnosis and prevention of T2D. However, to date, T2D PRS have been most widely developed and validated in individuals of European descent. Comprehensive assessment of T2D PRS in non-European populations is critical for an equitable deployment of PRS to clinical practice that benefits global populations. Here we integrate T2D GWAS in European, African American and East Asian populations to construct a trans-ancestry T2D PRS using a newly developed Bayesian polygenic modeling method, and evaluate the PRS in the multi-ethnic eMERGE study, four African American cohorts, and the Taiwan Biobank. The trans-ancestry PRS was significantly associated with T2D status across the ancestral groups examined, and the top 2% of the PRS distribution can identify individuals with an approximately 2.5-4.5 fold of increase in T2D risk, suggesting the potential of using the trans-ancestry PRS as a meaningful index of risk among diverse patients in clinical settings. Our efforts represent the first step towards the implementation of the T2D PRS into routine healthcare.
Olfactory Bulb and Amygdala Gene Expression Changes in Subjects Dying with COVID-19
Authors: Piras Ignazio S. , Huentelman Matthew J. , Walker Jessica E. , Arce Richard , Glass Michael J. , Vargas Daisy , Sue Lucia I. , Intorcia Anthony J. , Nelson Courtney M. , Suszczewicz Katsuko E. , Borja Claryssa L. , Desforges Marc , Deture Michael , Dickson Dennis W. , Beach Thomas G. , Serrano Geidy E. 
Published: September 2021

ABSTRACTIn this study we conducted RNA sequencing on two brain regions (olfactory bulb and amygdala) from subjects who died from COVID-19 or who died of other causes. We found several-fold more transcriptional changes in the olfactory bulb than in the amygdala, consistent with our own work and that of others indicating that the olfactory bulb may be the initial and most common brain region infected. To some extent our results converge with pseudotime analysis towards common processes shared between the brain regions, possibly induced by the systemic immune reaction following SARS-CoV-2 infection. Changes in amygdala emphasized upregulation of interferon-related neuroinflammation genes, as well as downregulation of synaptic and other neuronal genes, and may represent the substrate of reported acute and subacute COVID-19 neurological effects. Additionally, and only in olfactory bulb, we observed an increase in angiogenesis and platelet activation genes, possibly associated with microvascular damages induced by neuroinflammation. Through coexpression analysis we identified two key genes (CAMK2Bfor the synaptic neuronal network andCOL1A2for the angiogenesis/platelet network) that might be interesting potential targets to reverse the effects induced by SARS-CoV-2 infection. Finally, in olfactory bulb we detected an upregulation of olfactory and taste genes, possibly as a compensatory response to functional deafferentation caused by viral entry into primary olfactory sensory neurons. In conclusion, we were able to identify transcriptional profiles and key genes involved in neuroinflammation, neuronal reaction and olfaction induced by direct CNS infection and/or the systemic immune response to SARS-CoV-2 infection.
Spread of Gamma (P.1) sub-lineages carrying Spike mutations close to the furin cleavage site and deletions in the N-terminal domain drives ongoing transmission of SARS-CoV-2 in Amazonas, Brazil
Authors: Naveca Felipe Gomes , Nascimento Valdinete , Souza Victor , de Lima Corado André , Nascimento Fernanda , Silva George , Mejía Matilde , Brandão Maria Júlia , Costa Ágatha , Duarte Débora , Pessoa Karina , Jesus Michele , Gonçalves Luciana , Fernandes Cristiano , Mattos Tirza , Abdalla Ligia , Santos João Hugo , Martins Alex , Chui Fabiola Mendonça , Val Fernando Fonseca , Melo Gisely Cardoso de , Simão Mariana Xavier , Sampaio Vanderson de Souza , Mourão Maria Paula , Lacerda Marcus Vinícius , Batista Érika Lopes Rocha , Magalhães Alessandro Leonardo Álvares , Dábilla Nathânia , Pereira Lucas Carlos Gomes , Vinhal Fernando , Miyajima Fabio , Dias Fernando Braga Stehling , dos Santos Eduardo Ruback , Coêlho Danilo , Ferraz Matheus , Lins Roberto , Wallau Gabriel Luz , Delatorre Edson , Gräf Tiago , Siqueira Marilda Mendonça , Resende Paola Cristina , Bello Gonzalo 
Published: September 2021

SummaryThe Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated as Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly Δ144 or Δ141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we found no overrepresentation of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sub-lineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting new variants with higher infectivity are expected to increase.
Characterizing cerebral metabolite profiles in anorexia and bulimia nervosa and their associations with habitual behavior
Authors: Westwater Margaret L. , Murley Alexander G. , Diederen Kelly M.J. , Carpenter T. Adrian , Ziauddeen Hisham , Fletcher Paul C. 
Published: September 2021

AbstractBackgroundAnorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered brain structure and function, as well as increased habitual behavior. This neurobehavioral profile may implicate neurochemical changes in the pathogenesis of these illnesses. Altered glutamate, myo-inositol and N-acetyl aspartate (NAA) concentrations are reported in restrictive AN, yet whether these extend to binge-eating disorders, or relate to habitual traits in affected individuals, remains unknown.MethodsUsing single-voxel proton magnetic resonance spectroscopy, we measured glutamate, myo-inositol and NAA in 85 women [n=22 AN (binge-eating/purging subtype; AN-BP), n=33 BN, n=30 controls]. Spectra were acquired from the right inferior lateral prefrontal cortex and the right occipital cortex. To index habitual behavior, participants performed an instrumental learning task and completed the Creature of Habit Scale. Exploratory analyses examined associations between metabolites and habitual behavior.ResultsWomen with AN-BP, but not BN, had reduced myo-inositol and NAA concentrations relative to controls in both voxels. Patient groups had intact performance on the instrumental learning task; however, both groups reported increased routine behaviors compared to controls. Women with BN also reported greater automatic behaviors, and automaticity was related to reduced prefrontal glutamate and NAA in the AN-BP group.DiscussionFindings extend previous reports of reduced myo-inositol and NAA levels in AN to AN-BP, which may reflect disrupted axonal-glial signaling. Although we found inconsistent support for increased habitual behavior in AN-BP and BN, we identified preliminary associations between prefrontal metabolites and automaticity in AN-BP. These results provide further evidence of unique neurobiological profiles across binge-eating disorders.
mRNA COVID-19 Vaccination and Development of CMR-confirmed Myopericarditis
Authors: Kafil Tahir , Lamacie Mariana M , Chenier Sophie , Taggart Heather , Ghosh Nina , Dick Alexander , Small Gary , Liu Peter , Beanlands Rob S , Mielniczuk Lisa , Birnie David , Crean Andrew M 
Published: September 2021

During the process of open peer review on MedRxiv we quickly received a number of messages from reviewers concerned that there was a problem with our reported incidence of myocarditis post mRNA vaccination. Our reported incidence appeared vastly inflated by an incorrectly small denominator (ie number of doses administered over the time period of the study). We reviewed the data available at Open Ottawa and found that there had indeed been a major underestimation, with the actual number of administered doses being more than 800,000 (much higher than quoted in the paper).In order to avoid misleading either colleagues or the general public and press, we the authors unanimously wish to withdraw this paper on the grounds of incorrect incidence data. We thank the many peer reviewers who went out of their way to contact us and point out our error. We apologize to anyone who may have been upset or disturbed by our report.In summary, the authors have withdrawn this manuscript because of a major error pertaining to the quoted incidence data. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Monocytic Subsets and Their Signature Genes Differentially Impact Cortex and Cognition in First-Episode Schizophrenia
Authors: Chen Song , Chithanathan Keerthana , Fan Fengmei , Xiu Meihong , Fan Hongzhen , Cui Yimin , Zhang Ping , Yu Ting , Yang Fude , Tian Baopeng , Hong L. Elliot , Tan Yunlong , Tian Li 
Published: September 2021

AbstractAccumulating evidence supports involvement of innate immunity in the pathophysiology of schizophrenia. Monocytes are a highly heterogeneous population, subcategorized into classical (CD14++CD16−), intermediate (CD14++CD16+) and nonclassical subsets (CD14+CD16++). How monocytic subsets may shape brain structures and functions remains unclear. The primary goal of this cross-sectional study was to investigate the inter-relationships among monocytic subsets and their specific transcriptomic profiles, cerebral cortical thickness, and cognitive functions in first-episode schizophrenia (FES) patients. We performed whole-blood RNA sequencing (RNAseq) in 128 FES patients and 111 healthy controls (HCs) along with MATRICS Consensus Cognitive Battery (MCCB) measurement, as well as neuroimaging and flow cytometry among partial participants. RNAseq revealed significantly changed expressions of 54 monocytic signature genes in FES patients compared to HCs, especially for intermediate and nonclassical monocytic subsets, with the most outstanding alterations being downregulated S100 Calcium Binding Protein A (S100A) and upregulated Interferon Induced Transmembrane Protein (IFITM) family members, respectively. The percentage of nonclassical monocytes was decreased in FES patients. Cortical thicknesses and MCCB performance were expectantly reduced in FES patients too. Interestingly, negative inter-relationships of monocytic signature genes with both cortical thicknesses and cognition were found in HCs, which were weakened or even reversed in FES patients. Furthermore, the lateral occipital cortex fully mediated the negative effect of a classical monocytic gene Ribonuclease A Family Member 2 (RNASE2) on visual learning in patient group. This study suggests that monocytic dysfunctions play an essential role in cognitive deficit of schizophrenia, and their subtypes should be considered in future research.One Sentence SummaryDysfunctions of monocytic subsets play an essential role in cortex and cognitive deficit of schizophrenia
Should the family have a role in deceased organ donation decision-making? A systematic review of public knowledge and attitudes towards organ procurement policies in Europe
Authors: Molina-Pérez Alberto , Delgado Janet , Frunza Michaela , Morgan Myfanwy , Randhawa Gurch , Reiger-Van de Wijdeven Jeantine , Schicktanz Silke , Schiks Eline , Wöhlke Sabine , Rodríguez-Arias David 
Published: September 2021

AbstractGoalTo assess public knowledge and attitudes towards the role of the family in deceased organ donation in Europe.MethodsA systematic search was conducted in CINHAL, MEDLINE, PAIS Index, Scopus, PsycINFO, and Web of Science. These databases were last searched on December 15th, 2017. Eligibility criteria were empirical studies conducted in Europe from 2008 to 2017 and addressing either knowledge or attitudes by the public towards the consent system, including the involvement of the family in the decision-making process, for post-mortem organ retrieval. Each record was screened by two or more independent reviewers in three phases. Data collection from each report was performed by two or more independent reviewers.ResultsOf the 1,482 results, 467 reports were assessed in full-text form, and 33 were included in this synthesis. Studies show that a majority of the public support the family’s involvement in organ retrieval decision-making and, in particular, their role as surrogate decision-maker when the deceased has expressed no preference.ConclusionsA common conceptual framework and validated well-designed questionnaires are needed to address the role of the family in future studies. The findings should be considered in the development of Government policy and guidance regarding the role of families in deceased organ donation.
The role of social support in achieving weight loss in adults in the Caribbean aiming to achieve remission of type 2 diabetes: A cross-case analysis
Authors: Bartholomew Latoya , Unwin Nigel , Guell Cornelia , Bynoe Karen , Murphy Madhuvanti M. 
Published: September 2021

AbstractBackgroundRemission of type 2 diabetes through weight loss is possible in a high proportion of persons with a recent diagnosis, but a major challenge is achieving sufficient weight loss.ObjectivesIn the first study of this type in the Caribbean, we investigated factors associated with successful weight loss in adults in a diabetes remission intervention. We hypothesized that differences in social support may have influenced differences in weight loss achieved by participants in the Barbados Diabetes Reversal Study (BDRS).MethodsA comparative case study was conducted. Quantitative data for the primary outcome measure of weight reduction (the participants’ baseline and 8-month weights) were assessed to identify the 6 participants with the highest and 6 participants with the lowest weight loss. The 8-week (low-calorie diet phase) and 8-month (weight maintenance phase) interview transcripts for each participant were then analysed via qualitative thematic analysis to explore factors related to social support.ResultsInformal and formal support were identified for both categories of participants. Cases were similar with respect to their sources of support however dissimilarities were found in (1) the depth of support received; (2) access to supportive environments and (3) diversity of social supportive networks. Participants in the top weight loss group reported consistency in the levels of support received over the low-calorie diet and weight maintenance phases of the study while the converse was true for those of the bottom weight loss group.ConclusionStudy findings suggest that individuals aiming at type 2 diabetes remission benefit from strong social support networks. These networks provide tangible assistance and facilitate the sharing and discussion of strategies for weight reduction. Future studies should facilitate in-depth understanding of how formal and informal supportive networks can aid sustained dietary diabetes remission and long-term weight maintenance.
The immunogenetics of viral antigen response is associated with sub-type specific glioma risk and survival
Authors: Guerra Geno , Kachuri Linda , Wendt George , Hansen Helen M. , Mack Steven J. , Molinaro Annette M. , Rice Terri , Bracci Paige , Wiencke John K. , Kasahara Nori , Eckel-Passow Jeanette E , Jenkins Robert B. , Wrensch Margaret , Francis Stephen S. 
Published: September 2021

AbstractGlioma is a highly fatal cancer with prognostically significant molecular subtypes and few known risk factors. Multiple studies have implicated infections in glioma susceptibility, but evidence remains inconsistent. Genetic variants in the human leukocyte antigen (HLA) region modulate host response to infection and have been linked to glioma risk. In this study we leveraged genetic predictors of antibody response to 10 viral antigens to investigate the relationship with glioma risk and survival.Genetic reactivity scores (GRS) for each antigen were derived from genome-wide significant (p<5×10−8) variants associated with immunoglobulin G antibody response in the UK Biobank cohort. We conducted parallel analyses of glioma risk and survival for each GRS and HLA alleles imputed at two-field resolution using data from 3418 glioma patients subtyped by somatic mutations and 8156 controls.Genetic reactivity scores to Epstein-Barr virus (EBV) ZEBRA and EBNA antigens and Merkel cell polyomavirus (MCV) VP1 antigen were associated with glioma risk and survival (Bonferroni-corrected p<0.01). GRSZEBRA and GRSMCV were associated in opposite directions with risk of IDH wild type gliomas (ORZEBRA=0.91, p=0.0099 / ORMCV=1.11, p=0.0054). GRSEBNA was associated with both increased risk for IDH mutated gliomas (OR=1.09, p=0.040) and improved survival (HR=0.86, p=0.010). HLA-DQA1*03:01 was significantly associated with decreased risk of glioma overall (OR=0.85, p=3.96×10−4) after multiple testing adjustment.This first systematic investigation of the role of genetic determinants of viral antigen reactivity in glioma risk and survival provides insight into complex immunogenomic mechanisms of glioma pathogenesis. These results may inform applications of antiviral based therapies in glioma treatment.
Live wildlife trade in markets – a scoping review to inform risk assessment of emerging infectious diseases
Authors: Brookes V.J. , Wismandanu O. , Sudarnika E. , Roby J.A. , Hayes L. , Ward M.P. , Basri C. , Wibawa H. , Davis J. , Indrawan D. , Manyweathers J. , Nugroho W.S. , Windria S. , Hernandez-Jover M. 
Published: September 2021

AbstractWet markets are important for food security in many regions worldwide but have come under scrutiny due to their potential role in the emergence of infectious diseases. The sale of live wildlife has been highlighted as a particular risk, and the World Health Organisation has called for the banning of live, wild-caught mammalian species in markets unless risk assessment and effective regulations are in place. Following PRISMA guidelines, we conducted a global scoping review of peer-reviewed information about the sale of live, terrestrial wildlife in markets that are likely to sell fresh food, and collated data about the characteristics of such markets, activities involving live wildlife, the species sold, their purpose, and animal, human, and environmental health risks that were identified. Of the 59 peer-reviewed records within scope, only 25% (n = 14) focussed on disease risks; the rest focused on the impact of wildlife sale on conservation. Although there were some global patterns (for example, the types of markets and purpose of sale of wildlife), there was wide diversity and huge epistemic uncertainty in all aspects associated with live, terrestrial wildlife sale in markets such that the feasibility of accurate assessment of the risk of emerging infectious disease associated with live wildlife trade in markets is limited. Given the value of both wet markets and wildlife trade and the need to support food affordability and accessibility, conservation, public health, and the social and economic aspects of livelihoods of often vulnerable people, there are major information gaps that need to be addressed to develop evidence-based policy in this environment. This review identifies these gaps and provides a foundation from which information for risk assessments can be collected.
Association between work attendance when experiencing fever or cold symptoms and company characteristics and socioeconomic status in the COVID-19 pandemic in Japanese workers: a cross-sectional study
Authors: Mizuki Kazuyoshi , Okawara Makoto , Hino Ayako , Ando Hajime , Nagata Tomohisa , Tateishi Seiichiro , Tsuji Mayumi , Matsuda Shinya , Fujino Yoshihisa ,   for the CORoNaWork project
Published: September 2021

AbstractObjectiveThis study investigated the association between attending work while experiencing fever or cold symptoms and workers’ socioeconomic background and company characteristics during the COVID-19 pandemic.MethodsA cross-sectional online survey was performed. Of a total of 33,302 participants, 3,676 workers who experienced fever or cold symptoms after April 2020 were included. The odds ratios (ORs) of attending work while sick associated with workers’ socioeconomic background and company characteristics were evaluated using a multilevel logistic model.ResultsThe OR of attending work while sick associated with a lack of policy prohibiting workers from working when ill was 2.75 (95%CI: 2.28–3.20, P<0.001).ConclusionThis study suggests that clear company policies on work and illness can be effective for preventing employees from attending work while sick.