bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for diabetes and impaired glucose metabolism in Qatar: models’ development and validation
Authors: Sadek Khaled , Abdelhafez Ibrahim , Al-Hashimi Israa , Al-Shafi Wadha , Tarmizi Fatihah , Al-Marri Hissa , Alzohari Nada , Balideh Mohammad , Carr Alison 
Published: April 2021

AbstractAimTo establish two scoring models for identifying individuals at risk of developing Impaired Glucose Metabolism (IGM) and Type two Diabetes Mellitus (T2DM) in Qatari.Materials and MethodsA sample of 2000 individuals, from Qatar BioBank, was evaluated to determine features predictive of T2DM and IGM. Another sample of 1000 participants was obtained for external validation of the models. Several scoring models screening for T2DM were evaluated and compared to the model proposed by this study.ResultsAge, gender, waist-to-hip-ratio, history of hypertension and hyperlipidemia, and levels of educational were statistically associated with the risk of T2DM and constituted the Qatari diabetes risk score (QDRISK). Along with, the 6 aforementioned variables, the IGM model showed that BMI was statistically significant. The QDRISK performed well with an area under the curve (AUC) 0.870 and 0.815 in the development and external validation cohort, respectively. The QDRISK showed overall better accuracy and calibration compared to other evaluated scores. The IGM model showed good accuracy and calibration, AUCs 0.796 vs. 0.774 in the development and external validation cohorts, respectively.ConclusionsThis study developed a Qatari-specific risk scores to identify high risk individuals and can guide the development of a nationwide primary prevention program.
Sex and gender differences in COVID testing, hospital admission, presentation, and drivers of severe outcomes in the DC/Maryland region
Authors: Scully Eileen P. , Schumock Grant , Fu Martina , Massaccesi Guido , Muschelli John , Betz Joshua , Klein Eili Y. , West Natalie E. , Robinson Matthew , Garibaldi Brian T. , Bandeen-Roche Karen , Zeger Scott , Klein Sabra L. , Gupta Amita ,   for the JH-CROWN registry team
Published: April 2021

Structured AbstractBackgroundRates of severe illness and mortality from SARS-CoV-2 are greater for males, but the mechanisms for this difference are unclear. Understanding the differences in outcomes between males and females across the age spectrum will guide both public health and biomedical interventions.MethodsRetrospective cohort analysis of SARS-CoV-2 testing and admission data in a health system. Patient-level data were assessed with descriptive statistics and logistic regression modeling was used to identify features associated with increased male risk of severe outcomes.ResultsIn 213,175 SARS-CoV-2 tests, despite similar positivity rates (8.2%F vs 8.9%M), males were more frequently hospitalized (28%F vs 33%M). Of 2,626 hospitalized individuals, females had less severe presenting respiratory parameters and males had more fever. Comorbidity burden was similar, but with differences in specific conditions. Medications relevant for SARS-CoV-2 were used at similar frequency except tocilizumab (M>F). Males had higher inflammatory lab values. In a logistic regression model, male sex was associated with a higher risk of severe outcomes at 24 hours (odds ratio (OR) 3.01, 95%CI 1.75, 5.18) and at peak status (OR 2.58, 95%CI 1.78,3.74) among 18-49 year-olds. Block-wise addition of potential explanatory variables demonstrated that only the inflammatory labs substantially modified the OR associated with male sex across all ages.ConclusionHigher levels of clinical inflammatory labs are the only features that are associated with the heightened risk of severe outcomes and death for males in COVID-19.Trial registrationNAFundingHopkins inHealth; COVID-19 Administrative Supplement (HHS Region 3 Treatment Center), Office of the ASPR; NIH/NCI U54CA260492 (SK), NIH/NIA U54AG062333 (SK).
Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2
Authors: Deepak Parakkal , Kim Wooseob , Paley Michael A. , Yang Monica , Carvidi Alexander B. , El-Qunni Alia A. , Haile Alem , Huang Katherine , Kinnett Baylee , Liebeskind Mariel J. , Liu Zhuoming , McMorrow Lily E. , Paez Diana , Perantie Dana C. , Schriefer Rebecca E. , Sides Shannon E. , Thapa Mahima , Gergely Maté , Abushamma Suha , Klebert Michael , Mitchell Lynne , Nix Darren , Graf Jonathan , Taylor Kimberly E. , Chahin Salim , Ciorba Matthew A. , Katz Patricia , Matloubian Mehrdad , O’Halloran Jane A. , Presti Rachel M. , Wu Gregory F. , Whelan Sean P.J. , Buchser William J. , Gensler Lianne S. , Nakamura Mary C. , Ellebedy Ali H. , Kim Alfred H.J. 
Published: April 2021

ABSTRACTBackgroundIndividuals with chronic inflammatory diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the effectiveness of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management.MethodsWe conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination.ResultsCompared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization.ConclusionsCID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.
Evaluation of the performance of SARS-CoV-2 antibody assays for the longitudinal population-based study of COVID-19 spread in St. Petersburg, Russia
Authors: Barchuk Anton , Shirokov Daniil , Sergeeva Mariia , Tursun-zade Rustam , Dudkina Olga , Tychkova Varvara , Barabanova Lubov , Skougarevskiy Dmitriy , Danilenko Daria 
Published: April 2021

BackgroundAn evident geographical variation in the SARS-CoV-2 spread requires seroprevalence studies based on local tests with robust validation against already available antibody tests and neutralization assays. This report summarizes the evaluation of antibody tests used in the representative population-based serological study of SARS-CoV-2 in Saint Petersburg, Russia.MethodsWe used three different antibody tests throughout the study: chemiluminescent microparticle immunoassay (CMIA) Abbott Architect SARS-CoV-2 IgG, Enzyme-linked immunosorbent assay (ELISA) CoronaPass total antibodies test, and ELISA SARS-CoV-2-IgG-EIA-BEST. Clinical sensitivity was estimated with the SARS-CoV-2 PCR test as the gold standard and specificity in pre-pandemic sera samples using the cut-off recommended by manufacturers. Paired and unpaired serum sets were used. Measures of concordance were also calculated in the seroprevalence study sample against the microneutralization test (MNA).FindingsSensitivity was equal to 91.1% (95% CI: 78.8–97.5) and 90% (95% CI: 76.4–96.4) for ELISA Coronapass and ELISA Vector-Best respectively. It was equal to 63.1% (95% CI (50.2–74.7) for CMIA Abbott. Specificity was equal to 100% for all the tests. Comparison of ROCs for three tests has shown lower AUC for CMIA Abbott, but not for ELISA Coronapass and CMIA Abbott. The cutoff SC/O ratio of 0.28 for CMIA-Abbott resulted in a sensitivity of 80% at the same full level of specificity. In less than one-third of the population-based study participants with positive antibody test results, we detected neutralizing antibodies in titers 1:80 and above. There was a moderate correlation between antibody assays results and MNA.InterpretationOur validation study encourages the use of local antibody tests for population-based SARS-CoV-2 surveillance and sets the reference for the seroprevalence correction. Available tests are sensitive enough to detect antibodies in most individuals with previous positive PCR tests with a follow-up of more than 5 months. The Abbott Architect SARS-CoV-2 IgG’s sensitivity can be significantly improved by incorporating a new cut-off. Relying on manufacturers’ test characteristics for correction of reported prevalence estimates may introduce bias to the study results.FundingPolymetal International plc
Antibody response to SARS-CoV-2 mRNA vaccines in pregnant women and their neonates
Authors: Prabhu Malavika , Murphy Elisabeth A. , Sukhu Ashley C. , Yee Jim , Singh Sunidhi , Eng Dorothy , Zhao Zhen , Riley Laura E. , Yang Yawei J. 
Published: April 2021

SummaryPregnant women were excluded from initial clinical trials for COVID-19 vaccines1–2, thus the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies are just beginning to be studied4–5.
High-Potency Polypeptide-based Inhibition of Enveloped-virus Glycoproteins
Authors: Ma Jianpeng , Acevedo Adam Campos , Wang Qinghua 
Published: April 2021

AbstractSpecific manipulation of proteins post-translationally remains difficult. Here we report results of a general approach that uses a partial sequence of a protein to efficiently modulate the expression level of the native protein. When applied to coronavirus, human immunodeficiency virus, Ebolavirus, respiratory syncytial virus and influenza virus, polypeptides containing highly conserved regions of the viral glycoproteins potently diminished expression of the respective native proteins. In the cases of coronavirus and influenza virus where multiple strains were tested, the polypeptides were equally effective against glycoproteins of other coronavirus and influenza strains with sequence identity as low as 27%, underscoring their high insensitivity to mutations. Thus, this method provides a platform for developing high-efficacy broad-spectrum anti-viral inhibitors, as well as a new way to alter expression of essentially any systems post-translationally.
“It’s possibly made us feel a little more alienated”: How people from ethnic minority communities conceptualise COVID-19 and its influence on engagement with testing
Authors: Vandrevala Tushna , Alidu Lailah , Hendy Jane , Shafi Shuja , Ala Aftab 
Published: April 2021

ABSTRACTObjectivesThe cultural beliefs, practices and experiences of ethnic minority groups, alongside structural inequalities and the political economy play a critical, but overlooked role in health promotion. The current study aims to address this deficit; understanding how these groups conceptualise COVID-19, and how this influences engagement in testing, with the future aim of developing targeted communications to address the challenges of testing uptake.MethodBlack (African and Caribbean) and South Asian (Indian, Pakistani and Bangladeshi) community members were purposefully recruited across the UK. Fifty-seven semi-structured interviews were conducted and analysed using principles of Grounded Theory.ResultsThe findings illustrate that Black and South Asian’s conceptualise COVID-19 as a disease that makes them visible to others outside their community; in having more severe risk and suffering worst consequences; resulting in fear, stigmatisation and alienation. Views about COVID-19 were embedded in cultural beliefs, relating to culturally specific ideas around disease, such as ill-health being God’s will. Challenges brought about by the pandemic were conceptualised as one of many struggles, with the saliency of the virus contextualised against life experiences. These themes and others influenced engagement with COVID-19 testing. Testing waslessabout accessing timely and effective treatment for themselves, and more about acting to protect the family and community. Testing symbolised a loss of income, anxiety and isolation, accentuated by issues of mistrust of the system, and not being valued, or being treated unfairly.ConclusionIn tackling these challenges, we conclude that health communications should focus on counterbalancing the mistrust, alienation and stigmatisation that act as barriers to testing, with trust built using local credible sources.
Colony stimulating factor 1 signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands
Authors: Hason Martina , Mikulasova Tereza , Machonova Olga , Pombinho Antonio , van Ham Tjakko J , Irion Uwe , Nüsslein-Volhard Christiane , Bartunek Petr , Svoboda Ondrej 
Published: April 2021

AbstractMacrophage colony-stimulating factor receptor (M-CSFR/CSF1R) signaling is crucial for the differentiation, proliferation, and survival of myeloid cells. Therapeutic targeting of the CSF1R pathway is a promising strategy in many human diseases, including neurological disorders or cancer. Zebrafish are commonly used for human disease modeling and preclinical therapeutic screening. Therefore, it is necessary to understand the proper function of cytokine signaling in zebrafish to reliably model human-related diseases. Here, we investigate the roles of zebrafish Csf1rs and their ligands - Csf1a, Csf1b and Il34, in embryonic and adult myelopoiesis. The proliferative effect of exogenous Csf1a on embryonic macrophages is connected to both receptors as it is diminished in bothcsf1raΔ5bpandcsf1rbΔ4bpmutants. There is no evident effect of Csf1b in zebrafish embryonic myelopoiesis. Further, we uncover an unknown role of Csf1rb in zebrafish granulopoiesis. Deregulation of Csf1rb signaling leads to failure in myeloid differentiation resulting in neutropenia throughout the whole lifespan. Surprisingly, Il34 signaling through Csf1rb seems to be of high importance as bothcsf1rbΔ4bpandil34Δ5bpdeficient zebrafish larvae lack granulocytes. Our single-cell RNA sequencing analysis of adult whole kidney marrow (WKM) hematopoietic cells suggests thatcsf1rbis expressed mainly by blood and myeloid progenitors and that the expression ofcsf1raandcsf1rbis non-overlapping. We point out differentially expressed genes important in hematopoietic cell differentiation and immune response in selected WKM populations. Our findings could improve the understanding of myeloid cell function and lead to the further study of CSF1R pathway deregulation in disease, mostly in cancerogenesis.Key points:csf1raandcsf1rbare indispensable for macrophage differentiation and together withcsf1aregulate embryonic macrophage fates in zebrafishcsf1rbis important for granulocyte differentiation and migration and together withil34it regulates embryonic granulocytic fates in zebrafish
ADNKA overcomes SARS-CoV2-mediated NK cell inhibition through non-spike antibodies
Authors: Fielding CA , Sabberwal P , Williamson JC , Greenwood EJD , Crozier TWM , Zelek W , Seow J , Graham C , Huettner I , Edgeworth JD , Price D , Morgan BP , Ladell K , Eberl M , Humphreys IR , Merrick B , Doores K , Wilson SJ , Lehner PJ , Wang ECY , Stanton RJ 
Published: April 2021

AbstractThe outcome of infection is dependent on the ability of viruses to manipulate the infected cell to evade immunity, and the ability of the immune response to overcome this evasion. Understanding this process is key to understanding pathogenesis, genetic risk factors, and both natural and vaccine-induced immunity. SARS-CoV-2 antagonises the innate interferon response, but whether it manipulates innate cellular immunity is unclear. An unbiased proteomic analysis determined how cell surface protein expression is altered on SARS-CoV-2-infected lung epithelial cells, showing downregulation of activating NK ligands B7-H6, MICA, ULBP2, and Nectin1, with minimal effects on MHC-I. This correlated with a reduction in NK cell activation, identifying a novel mechanism by which SARS-CoV2 antagonises innate immunity. Later in the disease process, strong antibody-dependent NK cell activation (ADNKA) developed. These responses were sustained for at least 6 months in most patients, and led to high levels of pro-inflammatory cytokine production. Depletion of spike-specific antibodies confirmed their dominant role in neutralisation, but these antibodies played only a minor role in ADNKA compared to antibodies to other proteins, including ORF3a, Membrane, and Nucleocapsid. In contrast, ADNKA induced following vaccination was focussed solely on spike, was weaker than ADNKA following natural infection, and was not boosted by the second dose. These insights have important implications for understanding disease progression, vaccine efficacy, and vaccine design.
The Evolutionary History of Wild, Domesticated, and FeralBrassica oleracea(Brassicaceae)
Authors: Mabry Makenzie E. , Turner-Hissong Sarah D. , Gallagher Evan Y. , McAlvay Alex C. , An Hong , Edger Patrick P. , Moore Jonathan D. , Pink David A. C. , Teakle Graham R. , Stevens Chris J. , Barker Guy , Labate Joanne , Fuller Dorian Q. , Allaby Robin G. , Beissinger Timothy , Decker Jared E. , Gore Michael A. , Pires J. Chris 
Published: April 2021

ABSTRACTUnderstanding the evolutionary history of crops, including identifying wild relatives, helps to provide insight for designing new approaches in crop breeding efforts. CultivatedBrassica oleraceahas intrigued researchers for centuries due to its wide diversity in forms, which include cabbage, broccoli, cauliflower, kale, kohlrabi, and Brussels sprouts. Yet, the evolutionary history of this species remains understudied. With such different vegetables produced from a single species,B. oleraceais a model organism for understanding the power of artificial selection. Persistent challenges in the study ofB. oleraceainclude conflicting hypotheses regarding domestication and the identity of the closest living wild relative. Using a diversity panel of 224 accessions, which represents 14 differentB. oleraceacrop types and nine potential wild progenitor species, we integrate phylogenetic and population genetic techniques with ecological niche modeling, archaeological, and literary evidence to examine relationships among cultivars and wild relatives to clarify the origin of this horticulturally important species. Our analyses point to the Aegean endemicB. creticaas the closest living relative of cultivatedB. oleracea, supporting an origin of cultivation in the Eastern Mediterranean region. Additionally, we identify several feral lineages, suggesting that cultivated plants of this species are able to revert to a wild-like state with relative ease. By expanding our understanding of the evolutionary history inB. oleracea, these results contribute to a growing body of knowledge on crop domestication that will facilitate continued breeding efforts including adaptation to changing environmental conditions.
Pre-diabetes increases tuberculosis disease severity, while high body fat without impaired glucose tolerance is protective
Authors: Sinha Roma , Ngo Minh Dao , Bartlett Stacey , Bielefeldt-Ohmann Helle , Keshvari Sahar , Hasnain Sumaira Z. , Donovan Meg L. , Kling Jessica C. , Blumenthal Antje , Chen Chen , Short Kirsty R. , Ronacher Katharina 
Published: April 2021

AbstractType 2 diabetes (T2D) is a well-known risk factor for tuberculosis (TB), but little is known about pre-diabetes and the relative contribution of impaired glucose tolerancevs. obesity towards susceptibility to TB. Here, we developed a preclinical model of pre-diabetes and TB. Mice fed a high fat diet (HFD) for 12 weeks presented with impaired glucose tolerance and hyperinsulinemia compared to mice fed normal chow diet (NCD). Infection withM. tuberculosis(Mtb) H37Rvafter the onset of dysglycemia was associated with significantly increased lung pathology, lower concentrations of TNF-a, IFN-g, IFN-β and IL-10 and a trend towards higher bacterial burden at 3 weeks post infection. To determine whether the increased susceptibility of pre-diabetic mice to TB is reversible and is associated with dysglycemia or increased body fat mass, we performed a diet reversal experiment. Pre-diabetic mice were fed a NCD for 10 additional weeks (HFD/NCD) at which point glucose tolerance was restored, but body fat mass remained higher compared to control mice that consumed NCD throughout the entire experiment (NCD/NCD). Upon Mtb infection HFD/NCD mice had significantly lower bacterial burden compared to NCD/NCD mice and this was accompanied by restored IFN-γ responses. Our findings demonstrate that pre-diabetes increases susceptibility to TB, but a high body mass index without dysglycemia is protective. This murine model offers the opportunity to further study the underlying immunological, metabolic and endocrine mechanisms of this association.
Controlling multiple COVID-19 epidemic waves: an insight from a multi-scale model linking the behavior change dynamics to the disease transmission dynamics
Authors: Tang Biao , Zhou Weike , Wang Xia , Wu Hulin , Xiao Yanni , Tang Sanyi 
Published: April 2021

AbstractCOVID-19 epidemics exhibited multiple waves regionally and globally since 2020. It is important to understand the insight and underlying mechanisms of the multiple waves of COVID-19 epidemics in order to design more efficient non-pharmaceutical interventions (NPIs) and vaccination strategies to prevent future waves. We propose a multi-scale model by linking the behavior change dynamics to the disease transmission dynamics to investigate the effect of behavior dynamics on COVID-19 epidemics using the game theory. The proposed multi-scale model was calibrated and key parameters related to disease transmission dynamics and behavioral dynamics with/without vaccination were estimated based on COVID-19 epidemic data and vaccination data. Our modeling results demonstrate that the feedback loop between behavior changes and COVID-19 transmission dynamics plays an essential role in inducing multiple epidemic waves. We find that the long period of high-prevalence or persistent deterioration of COVID-19 epidemics could drive almost all population to change their behaviors and maintain the altered behaviors, however, the effect of behavior changes faded out gradually along the progress of epidemics. This suggests that it is essential not only to have persistent, but also effective behavior changes in order to avoid subsequent epidemic waves. In addition, our model also suggests the importance to maintain the effective altered behaviors during the initial stage of vaccination, and to counteract relaxation of NPIs, it requires quick and massive vaccination to avoid future epidemic waves.