bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic Profiling in Biracial Cohorts Implicates DC-SIGN as a Mediator of Genetic Risk in COVID-19
Authors: Katz Daniel H. , Tahir Usman A. , Ngo Debby , Benson Mark , Bick Alexander G. , Pampana Akhil , Gao Yan , Keyes Michelle J. , Correa Adolfo , Sinha Sumita , Shen Dongxiao , Yang Qiong , Robbins Jeremy M. , Chen Zsu-Zsu , Cruz Daniel E. , Peterson Bennet , Natarajan Pradeep , Vasan Ramachandran S. , Smith J. Gustav , Wang Thomas J. , Wilson James G. , Gerszten Robert E. 
Published: June 2020

Brief SummaryCOVID-19 is one of the most consequential pandemics in the last century, yet the biological mechanisms that confer disease risk are incompletely understood. Further, heterogeneity in disease outcomes is influenced by race, though the relative contributions of structural/social and genetic factors remain unclear.1,2Very recent unpublished work has identified two genetic risk loci that confer greater risk for respiratory failure in COVID-19: theABOlocus and the 3p21.31 locus.3To understand how these loci might confer risk and whether this differs by race, we utilized proteomic profiling and genetic information from three cohorts including black and white participants to identify proteins influenced by these loci. We observed that variants in theABOlocus are associated with levels of CD209/DC-SIGN, a known binding protein for SARS-CoV and other viruses,4as well as multiple inflammatory and thrombotic proteins, while the 3p21.31 locus is associated with levels of CXCL16, a known inflammatory chemokine.5Thus, integration of genetic information and proteomic profiling in biracial cohorts highlights putative mechanisms for genetic risk in COVID-19 disease.
Estimation of effects of contact tracing and mask adoption on COVID-19 transmission in San Francisco: a modeling study
Authors: Worden Lee , Wannier Rae , Blumberg Seth , Ge Alex Y. , Rutherford George W. , Porco Travis C. 
Published: June 2020

AbstractThe current COVID-19 pandemic has spurred concern about what interventions may be effective at reducing transmission. The city and county of San Francisco imposed a shelter-in-place order in March 2020, followed by use of a contact tracing program and a policy requiring use of cloth face masks. We used statistical estimation and simulation to estimate the effectiveness of these interventions in San Francisco. We estimated that self-isolation and other practices beginning at the time of San Francisco’s shelter-in-place order reduced the effective reproduction number of COVID-19 by 35.4% (95% CI, −20.1%–81.4%). We estimated the effect of contact tracing on the effective reproduction number to be a reduction of approximately 44% times the fraction of cases that are detected, which may be modest if the detection rate is low. We estimated the impact of cloth mask adoption on reproduction number to be approximately 8.6%, and note that the benefit of mask adoption may be substantially greater for essential workers and other vulnerable populations, residents return to circulating outside the home more often. We estimated the effect of those interventions on incidence by simulating counterfactual scenarios in which contact tracing was not adopted, cloth masks were not adopted, and neither contact tracing nor cloth masks was adopted, and found increases in case counts that were modest, but relatively larger than the effects on reproduction numbers. These estimates and model results suggest that testing coverage and timing of testing and contact tracing may be important, and that modest effects on reproduction numbers can nonetheless cause substantial effects on case counts over time.
Poorly known aspects of flattening the curve of COVID-19
Authors: Debecker Alain , Modis Theodore 
Published: June 2020

AbstractThis work concerns the too-often mentioned flattening of the curve of COVID-19. The diffusion of the virus is analyzed with logistic-curve fits on the 25 countries most affected at the time of the writing and in which the diffusion curve was more than 95% completed. A negative correlation observed between the final number of infections and the slope of the logistic curve corroborates a result obtained long time ago via an extensive simulation study. There is both theoretical arguments and experimental evidence for the existence of such correlations. The flattening of the curve results in a retardation of the curve’s midpoint, which entails an increase in the final number of infections. It is possible that more lives are lost at the end by this process. Our analysis also permits evaluation of the various governments’ interventions in terms of rapidity of response, efficiency of the actions taken (the amount of flattening achieved), and the number of days by which the curve was delayed. Not surprisingly, early decisive response proves to be the optimum strategy among the countries studied.
COVID-19 and associations with frailty and multimorbidity: a prospective analysis of UK Biobank participants
Authors: Woolford S J , D’Angelo S , Curtis E M , Parsons C M , Ward K A , Dennison E M , Patel H P , Cooper C , Harvey N C 
Published: June 2020

AbstractBackgroundFrailty and multimorbidity have been suggested as risk factors for severe COVID-19 disease.AimsWe investigated whether frailty and multimorbidity were associated with risk of hospitalisation with COVID-19 in the UK Biobank.Methods502,640 participants aged 40-69 years at baseline (54-79 years at COVID-19 testing) were recruited across UK 2006-10. A modified assessment of frailty using Fried’s classification was generated from baseline data. COVID-19 test results (England) were available 16/03/2020-01/06/2020, mostly taken in hospital settings. Logistic regression was used to discern associations between frailty, multimorbidity and COVID-19 diagnoses, adjusting for sex, age, BMI, ethnicity, education, smoking and number of comorbidity groupings, comparing COVID-19 positive, COVID-19 negative and non-tested groups.Results4,510 participants were tested for COVID-19 (positive=1,326, negative=3,184). 497,996 participants were not tested. Compared to the non-tested group, after adjustment, COVID-19 positive participants were more likely to be frail (OR=1.3 [95% CI=1.1, 1.7]), report slow walking speed (OR=1.3 [1.1, 1.6]), report two or more falls in the past year (OR=1.3 [1.0, 1.5]) and be multimorbid (≥4 comorbidity groupings vs 0-1: OR=1.9 [1.5, 2.3]). However, similar strength of associations were apparent when comparing COVID-19 negative and non-tested groups. Furthermore, frailty and multimorbidity were not associated with COVID-19 diagnoses, when comparing COIVD-19 positive and COVID-19 negative participants.Discussion and conclusionsFrailty and multimorbidity do not appear to aid risk stratification, in terms of a positive versus negative results of COVID-19 testing. Investigation of the prognostic value of these markers for adverse clinical sequelae following COVID-19 disease is urgently needed.
Evaluation of the number of undiagnosed infected in an outbreak using source of infection measurements
Authors: Melka Akiva B , Louzoun Yoram 
Published: June 2020

ABSTRACTIn times of outbreaks, an essential requirement for better monitoring is the evaluation of the number of undiagnosed infected individuals. An accurate estimate of this fraction is crucial for the assessment of the situation and the establishment of protective measures. In most current studies using epidemics models, the total number of infected is either approximated by the number of diagnosed individuals or is dependent on the model parameters and assumptions, which are often debated. We here study the relationship between the fraction of diagnosed infected out of all infected, and the fraction of infected with known contaminator out of all diagnosed infected. We show that those two are approximately the same in exponential models and across most models currently used in the study of epidemics, independently of the model parameters. As an application, we compute an estimate of the effective number of infected by the COVID-19 virus in Israel.
A Novel Approach to Monitoring the COVID-19 Pandemic using Emergency Department Discharge Diagnoses
Authors: Duber Herbert C. , Hall M. Kennedy , Jablonowski Karl , Stern Susan A. , Mokdad Ali H , Flaxman Abraham D 
Published: June 2020

AbstractIntroductionTracking the COVID-19 pandemic using existing metrics such as confirmed cases and deaths are insufficient for understanding the trajectory of the pandemic and identifying the next wave of cases. In this study, we demonstrate the utility of monitoring the daily number of patients with COVID-like illness (CLI) who present to the Emergency Department (ED) as a tool that can guide local response efforts.MethodsUsing data from two hospitals in King County, WA, we examined the daily volume of CLI visits, and compare them to confirmed COVID cases and COVID deaths in the County. A linear regression model with varying lags is used to predict the number of daily COVID deaths from the number of CLI visits.ResultsCLI visits appear to rise and peak well in advance of both confirmed COVID cases and deaths in King County. Our regression analysis to predict daily deaths with a lagged count of CLI visits in the ED showed that the R2 value was maximized at 14 days.ConclusionsED CLI visits are a leading indicator of the pandemic. Adopting and scaling up a CLI monitoring approach at the local level will provide needed actionable evidence to policy makers and health officials struggling to confront this health challenge.
Early childhood linear growth faltering in low- and middle-income countries
Authors: Benjamin-Chung Jade , Mertens Andrew , Colford John M , Hubbard Alan E , van der Laan Mark J , Coyle Jeremy , Sofrygin Oleg , Cai Wilson , Nguyen Anna , Pokpongkiat Nolan N , Djajadi Stephanie , Seth Anmol , Jilek Wendy , Jung Esther , Chung Esther O , Rosete Sonali , Hejazi Nima , Malenica Ivana , Li Haodong , Hafen Ryan , Subramoney Vishak , Häggström Jonas , Norman Thea , Brown Kenneth H. , Christian Parul , Arnold Benjamin F. ,   members of the ki Child Growth Consortium
Published: June 2020

SummaryGlobally 149 million children under five are estimated to be stunted (length more than 2 standard deviations below international growth standards). Stunting, a form of linear growth faltering, increases risk of illness, impaired cognitive development, and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering— a key consideration for defining critical windows to deliver preventive interventions. We performed the largest pooled analysis of longitudinal studies in low- and middle-income countries to date (n=32 cohorts, 52,640 children, ages 0-24 months), allowing us to identify the typical age of linear growth faltering onset and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to age 3 months. From 0 to 15 months, less than 5% of children per month reversed their stunting status, and among those who did, stunting relapse was common. Early timing and low reversal rates emphasize the importance of preventive intervention delivery within the prenatal and early postnatal phases coupled with continued delivery of postnatal interventions through the first 1000 days of life.
Plasma from recovered COVID19 subjects inhibits spike protein binding to ACE2 in a microsphere-based inhibition assay
Authors: Gniffke Edward P. , Harrington Whitney E. , Dambrauskas Nicholas , Jiang Yonghou , Trakhimets Olesya , Vigdorovich Vladimir , Frenkel Lisa , Sather D. Noah , Smith Stephen E.P. 
Published: June 2020

AbstractHigh throughput serological tests that can establish the presence and functional activity of anti-SARS-COV2 antibodies are urgently needed. Here we present microsphere-based Flow Cytometry assays that quantify both anti-spike IgGs in plasma, and the ability of plasma to inhibit the binding of spike protein to angiotensin converting enzyme 2 (ACE2). First, we detected anti-spike-trimer IgGs in 22/24 and anti-spike-receptor-binding-domain (RBD) IgGs in 21/24 COVID+ subjects at a median of 36 (range 14-73) days following documented SARS-CoV-2 RNA (+) secretions. Next, we find that plasma from all 22/24 subjects with anti-trimer IgGs inhibited ACE2-trimer binding to a greater degree than controls, and that the degree of inhibition correlated with anti-trimer IgG levels. Depletion of trimer-reactive Igs from plasma reduced ACE2-trimer inhibitory capacity to a greater degree than depletion of RBD-reactive Igs, suggesting that inhibitory antibodies act by binding both within and outside of the RBD. Amongst the 24 subjects, presence of fever was associated with higher levels of anti-trimer IgG and inhibition of binding to human ACE2. This inhibition assay may be broadly useful to quantify the functional antibody response of recovered COVID19 patients or vaccine recipients in a cell-free assay system.
Phylogenomics ofMycobacterium africanumreveals a new lineage and a complex evolutionary history
Authors: Coscolla Mireia , Brites Daniela , Menardo Fabrizio , Loiseau Chloe , Borrell Sonia , Otchere Isaac Darko , Asante-Poku Adwoa , Asare Prince , Sánchez-Busó Leonor , Gehre Florian , N’Dira Sanoussi C. , Antonio Martin , Dissou Affolabi , Ruiz-Rodriguez Paula , Fyfe Janet , Böttger Erik C. , Becket Patrick , Niemann Stefan , Alabi Abraham S. , Grobusch Martin P. , Kobbe Robin , Parkhill Julian , Beisel Christian , Fenner Lukas , Meehan Conor J. , Harris Simon R , De Jong Bouke C. , Yeboah-Manu Dorothy , Gagneux Sebastien 
Published: June 2020

AbstractHuman tuberculosis is caused by members of theMycobacterium tuberculosisComplex (MTBC). The MTBC comprises several human-adapted lineages known asM. tuberculosissensu stricto as well as two lineages (L5 and L6) traditionally referred to asM. africanum. Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known on their genomic diversity, phylogeography and evolution. Here, we analyzed the genomes of 365 L5 and 326 L6 strains, plus five related genomes that had not been classified into any of the known MTBC lineages, isolated from patients from 21 African countries.Our population genomic and phylogeographical analyses show that the unclassified genomes belonged to a new group that we propose to name MTBC Lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences between L5 and L6 strains with respect to their phylogeographical substructure, genetic diversity and association with drug resistance. In conclusion, our study sheds new light onto the genomic diversity and evolutionary history ofM. africanum,and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of tuberculosis in Africa and globally.
Rhesus macaques as a tractable physiological model of human ageing
Authors: Chiou Kenneth L. , Montague Michael J. , Goldman Elisabeth A. , Watowich Marina M. , Sams Sierra N. , Song Jeff , Horvath Julie E. , Sterner Kirstin N. , Ruiz-Lambides Angelina V. , Martínez Melween I. , Higham James P. , Brent Lauren J. N. , Platt Michael L. , Snyder-Mackler Noah 
Published: June 2020

AbstractResearch in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from shorter-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research due to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population.
Urokinase receptor associates with TLR4 interactome to promote LPS response
Authors: Kiyan Yulia , Tkachuk Sergei , Gorrasi Anna , Ragno Pia , Dumler Inna , Haller Hermann , Shushakova Nelli 
Published: June 2020

AbstractGPI-anchored uPAR is the receptor for the extracellular serine protease urokinase-type plasminogen activator (uPA). Binding of uPA to uPAR localizes proteolytic cascade activation at the cell surface and can induce intracellular signaling. As uPAR possesses no transmembrane domain, it relies on uPAR cross-talk with various membrane receptors. Though uPAR role in inflammatory processes is well documented, underlying mechanisms are not fully understood. In this study we demonstrate that uPAR is a part of Toll-like receptor 4 (TLR4) interactome. GPI-uPAR and soluble uPAR colocalized with TLR4 on the cell membrane and interacted with scavenger receptor CD36. We show that downregulation of uPAR expression resulted in diminished LPS-induced TLR4 signaling, less activation of NFκB, and decreased secretion of inflammatory mediators in myeloid and non-myeloid cells in vitro. In vivo uPAR−/− mice demonstrated strongly diminished inflammatory response and better organ functions in cecal ligation and puncture mouse polymicrobial sepsis model. Our data show that uPAR can interfere with innate immunity response via TLR4 and this mechanism represents a potentially important target in inflammation and sepsis therapy.
Comparison of manual and automated ventricle segmentation in the maternal immune stimulation rat model of schizophrenia
Authors: Winter Rebecca , Akinola Benson , Barroeta-Hlusicka Elizabeth , Meister Sebastian , Pietzsch Jens , Winter Christine , Bernhardt Nadine 
Published: June 2020

AbstractMaternal immune stimulation (MIS) is strongly implicated in the etiology of neuropsychiatric disorders. Magnetic resonance imaging (MRI) studies provide evidence for brain structural abnormalities in rodents following prenatal exposure to MIS. Reported volumetric changes in adult MIS offspring comprise among others larger ventricular volumes, consistent with alterations found in patients with schizophrenia. Linking rodent models of MIS with non-invasive small animal neuroimaging modalities thus represents a powerful tool for the investigation of structural endophenotypes. Traditionally manual segmentation of regions-of-interest, which is laborious and prone to low intra- and inter-rater reliability, was employed for data analysis. Recently automated analysis platforms in rodent disease models are emerging. However, none of these has been found to reliably detect ventricular volume changes in MIS nor directly compared manual and automated data analysis strategies. The present study was thus conducted to establish an automated, structural analysis method focused on lateral ventricle segmentation. It was applied to ex-vivo rat brain MRI scans. Performance was validated for phenotype induction following MIS and preventive treatment data and compared to manual segmentation. In conclusion, we present an automated analysis platform to investigate ventricular volume alterations in rodent models thereby encouraging their preclinical use in the search for new urgently needed treatments.
Translesion Synthesis by MmLV-, AMV-, and HIV-Reverse Transcriptases Using RNA Templates Containing Inosine, Guanosine, and Their 8-oxo-7,8-Dihydropurine Derivatives
Authors: Glennon Madeline , Skinner Austin , Krutsinger Mara , Resendiz Marino J. E. 
Published: June 2020

ABSTRACTInosine is ubiquitous and essential in many biological processes, including RNA-editing. In addition, oxidative stress on RNA has been a topic of increasing interest due, in part, to its potential role in the development/progression of disease. In this work we probed the ability of three reverse transcriptases to catalyze the synthesis of cDNA in the presence of RNA templates containing inosine (I), 8-oxo-7,8-dihydroinosine (8oxo-I), guanosine (G), or 8-oxo-7,8-dihydroguanosine (8-oxoG), and explored the impact that these purine derivatives have as a function of position. To this end, we used 29-mers of RNA (as template) containing the modifications at position-18 and reverse transcribed DNA using 17-mers, 18-mers, or 19-mers (as primers). Generally reactivity of the viral RTs, MMLV / AMV / HIV, towards cDNA synthesis was similar for templates containing G or I, as well as for those with 8-oxoG or 8-oxoI. Notable differences are 1) that templates containing I enabled the incorporation of dT when using 17-mers (for exploring incorporation of dNTPs opposite the site of interest); 2) that the use of 18-mers of DNA (to explore cDNA synthesis past the lesion) led to DNA elongation inhibition in the case when a G:dA wobble pair was present, while the presence of I, 8-oxoI, or 8-oxoG led to full synthesis of the corresponding cDNA, with the latter two displaying a more efficient process; 3) that HIV-RT is more sensitive to modified base pairs in the vicinity of cDNA synthesis; and 4) that the presence of a modification two positions away from transcription initiation has an adverse impact on the overall process. Steady-state kinetics were established to determine substrate specificities towards canonical dNTPs (N = G, C, T, A). Overall we found evidence that RNA templates containing inosine are likely to incorporate dC > dT > > dA, where reactivity in the presence of dA was found to be pH dependent (process abolished at pH 7.3); and that the absence of the C2-exocyclic amine, as displayed with templates containing 8-oxoI, leads to increased selectivity towards incorporation of dA over dC. The data will be useful in assessing the impact that the presence of inosine and/or oxidatively generated lesions have on viral processes and adds to previous reports where I codes exclusively like G.