bluuebunny/crossref_metadata_2025_split huggingface dataset:
Animal Model Prescreening: Pre-exposure to SARS-CoV-2 impacts responses in the NHP model
Authors: Ricks Keersten M. , Herbert Andrew S. , Koehler Jeffrey W. , Kuehnert Paul A. , Clements Tamara L. , Shoemaker Charles J. , Kuehne Ana I. , O’Brien Cecilia M. , Coyne Susan R. , Delp Korey L. , Akers Kristen S. , Dye John M. , Hooper Jay W. , Smith Jeffrey M. , Kugelman Jeffrey R. , Beitzel Brett F. , Gibson Kathleen M. , Johnston Sara C. , Minogue Timothy D. 
Published: July 2020

AbstractCOVID-19 presents herculean challenges to research and scientific communities for producing diagnostic and treatment solutions. Any return to normalcy requires rapid development of countermeasures, with animal models serving as a critical tool in testing vaccines and therapeutics. Animal disease status and potential COVID-19 exposure prior to study execution may severely bias efficacy testing. We developed a toolbox of immunological and molecular tests to monitor countermeasure impact on disease outcome and evaluate pre-challenge COVID-19 status. Assay application showed critical necessity for animal pre-screening. Specifically, real-time PCR results documented pre-exposure of an African Green Monkey prior to SARS-CoV-2 challenge with sequence confirmation as a community-acquired exposure. Longitudinal monitoring of nasopharyngeal swabs and serum showed pre-exposure impacted both viral disease course and resulting immunological response. This study demonstrates utility in a comprehensive pre-screening strategy for animal models, which captured the first documented case of community-acquired, non-human primate infection.One Sentence SummaryPre-exposure to SARS-CoV-2 affects biomarker responses in animal models, highlighting a need for robust pre-screening protocols prior to medical countermeasure studies.
Conserved heterodimeric GTPase Rbg1/Tma46 promotes efficient translation in eukaryotic cells
Authors: Zeng Fuxing , Li Xin , Pires-Alves Melissa , Chen Xin , Hawk Christopher W. , Jin Hong 
Published: July 2020

ABSTRACTConserved developmentally-regulated GTP-binding (Drg) proteins and their binding partner Dfrp proteins are known to be important for embryonic development, cellular growth control, differentiation and proliferation. Here, we report that the yeast Drg1/Dfrp1 ortholog, Rbg1/Tma46, facilitates translational initiation, elongation and termination via suppressing prolonged ribosome pausing. Consistent with the genome-wide observations, Rbg1 reverses the growth defect resulting from translation stalling and stabilizes mRNAs against no-go decay. Furthermore, we provide a cryoEM structure of the 80S ribosome bound with Rbg1/Tma46 that reveals the molecular interactions responsible for Rbg1/Tma46 function. The Rbg1 subunit binds to the GTPase association center of the ribosome and the A-tRNA, and the N-terminal zinc finger domain of Tma46 subunit binds to the 40S, establishing an interaction critical for the complex ribosomal association. Our results answer the fundamental question on how a paused ribosome resumes translation and show that Drg1/Dfrp1 proteins play a critical role in ensuring orderly translation.
Conserved Genomic Terminals of SARS-CoV-2 as Co-evolving Functional Elements and Potential Therapeutic Targets
Authors: Chan Agnes. P. , Choi Yongwook , Schork Nicholas J. 
Published: July 2020

ABSTRACTTo identify features in the genome of the SARS-CoV-2 pathogen responsible for the COVID-19 pandemic that may contribute to its viral replication, host pathogenicity, and vulnerabilities, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from other well-characterized human and animal coronavirus genomes. Our analyses suggest the presence of unique sequence signatures in the 3’-untranslated region (UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2, SARS-CoV, as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host microRNA-mediated interaction between the 3’-UTR and human microRNA hsa-miR-1307-3p based on predicted, yet extensive, complementary base-pairings and similar interactions involving the Influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3’-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection, and the exploitation of conserved features in the 3’-UTR as therapeutic targets warrant further investigation.
Differential spatial computations in ventral and lateral face-selective regions are scaffolded by structural connections
Authors: Finzi Dawn , Gomez Jesse , Nordt Marisa , Rezai Alex A. , Poltoratski Sonia , Grill-Spector Kalanit 
Published: July 2020

AbstractFace-processing occurs across ventral and lateral visual streams, which are involved in static and dynamic face perception, respectively. However, the nature of spatial computations across streams is unknown. Using functional MRI and novel population receptive field (pRF) mapping, we measured pRFs in face-selective regions. Results reveal that spatial computations by pRFs in ventral face-selective regions are concentrated around the center of gaze (fovea), but spatial computations in lateral face-selective regions extend peripherally. Diffusion MRI reveals that these differences are mirrored by a preponderance of white matter connections between ventral face-selective regions and foveal early visual cortex (EVC), while connections with lateral regions are distributed more uniformly across EVC eccentricities. These findings suggest a rethinking of spatial computations in face-selective regions, showing that they vary across ventral and lateral streams, and further propose that spatial computations in high-level regions are scaffolded by the fine-grain pattern of white matter connections from EVC.
Bi-directional Impacts of Heterotypic Interactions in Engineered 3D Human Cardiac Microtissues Revealed by Single-Cell RNA-Sequencing and Functional Analysis
Authors: Hookway Tracy A. , Matthys Oriane B. , Joy David A. , Sepulveda Jessica E. , Thomas Reuben , McDevitt Todd C. 
Published: July 2020

AbstractTechnological advancements have enabled the design of increasingly complex engineered tissue constructs, which better mimic native tissue cellularity. Therefore, dissecting the bi-directional interactions between distinct cell types in 3D is necessary to understand how heterotypic interactions at the single-cell level impact tissue-level properties. We systematically interrogated the interactions between cardiomyocytes (CMs) and cardiac non-myocytes in 3D self-assembled tissue constructs in an effort to determine the phenotypic and functional contributions of cardiac fibroblasts (CFs) and endothelial cells (ECs) to cardiac tissue properties. One week after tissue formation, cardiac microtissues containing CFs exhibited improved calcium handling function compared to microtissues comprised of CMs alone or CMs mixed with ECs, and CMs cultured with CFs exhibited distinct transcriptional profiles, with increased expression of cytoskeletal and ECM-associated genes. However, one month after tissue formation, functional and phenotypic differences between heterotypic tissues were mitigated, indicating diminishing impacts of non-myocytes on CM phenotype and function over time. The combination of single-cell RNA-sequencing and calcium imaging enabled the determination of reciprocal transcriptomic changes accompanying tissue-level functional properties in engineered heterotypic cardiac microtissues.
Multi-omic profiling of primary mouse neutrophils reveals a pattern of sex and age-related functional regulation
Authors: Lu Ryan , Taylor Shalina , Contrepois Kévin , Ellenberger Mathew , Sampathkumar Nirmal K. , Benayoun Bérénice A. 
Published: July 2020

SummaryNeutrophils are the most abundant white blood cells in humans and constitute one of the first lines of defense in the innate immune response. Neutrophils are extremely short-lived cells, which survive less than a day after reaching terminal differentiation. Thus, little is known about how organismal aging, rather than the daily cellular aging process, may impact neutrophil biology. In addition, accumulating evidence suggests that both immunity and organismal aging are sex-dimorphic. Here, we describe a multi-omic resource of mouse primary bone marrow neutrophils from young and old female and male mice, at the transcriptomic, metabolomic and lipidomic levels. Importantly, we identify widespread age-related and sex-dimorphic regulation of ‘omics’ in neutrophils, specifically regulation of chromatin. Using machine-learning, we identify candidate molecular drivers of age-related and sex-dimorphic transcriptional regulation of neutrophils. We leverage our resource to predict increased levels/release of neutrophil elastase in male mice. To date, this dataset represents the largest multi-omics resource for the study of neutrophils across biological sex and ages. This resource identifies molecular states linked to neutrophil characteristics linked to organismal age or sex, which could be targeted to improve immune responses across individuals.
Community factors associated with local RSV epidemic patterns: a spatiotemporal modeling study
Authors: Zheng Zhe , Pitzer Virginia E. , Warren Joshua L. , Weinberger Daniel M. 
Published: July 2020

ABSTRACTBackgroundRespiratory syncytial virus (RSV) causes a large burden of morbidity in infants, young children, and the elderly. The timing of RSV seasonal epidemics exhibits strong spatial patterns within the United States. Spatial variability in the timing of RSV epidemics provides an opportunity to probe the factors driving transmission of the virus.MethodsWe evaluated competing hypotheses about the associations between RSV epidemic timing at the ZIP-code level and household size, population density, school district boundaries, commuting patterns, and geographic proximity. We used hierarchical Bayesian models with monthly ZIP-code level hospitalization data from New York, New Jersey, and Connecticut between July 1997 and June 2014 to investigate these hypotheses.ResultsEarly epidemic timing across ZIP codes was associated with large household sizes and high population density, and nearby ZIP codes shared similar epidemic timing. Variations in epidemic timing attributed to commuting patterns or school district boundaries are negligible.ConclusionOur results suggest RSV epidemics take off faster in areas with more household crowding and higher population density, and that epidemic spread follows a spatial diffusion process based on geographic proximity. With several vaccines against RSV under development, it is important to understand the drivers of RSV transmission and disease in order to maximize population protection of a vaccine program. Our findings can inform more effective control measures against RSV, such as vaccine programs and household infection control, and guide future studies on the transmission dynamics of RSV.
Association between consumption of fermented vegetables and COVID-19 mortality at a country level in Europe
Authors: Fonseca Susana C , Rivas Ioar , Romaguera Dora , Quijal Marcos , Czarlewski Wienczyslawa , Vidal Alain , Fonseca Joao A , Ballester Joan , Anto Josep M , Basagana Xavier , Cunha Luis M , Bousquet Jean 
Published: July 2020

AbstractBackgroundMany foods have an antioxidant activity and nutrition may mitigate COVID-19. Some of the countries with a low COVID-19 mortality are those with a relatively high consumption of traditional fermented foods. To test the potential role of fermented foods in COVID-19 mortality in Europe, we performed an ecological study.MethodsThe European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database was used to study the country consumption of fermented vegetables, pickled/marinated vegetables, fermented milk, yoghurt and fermented sour milk. We obtained the COVID-19 mortality per number of inhabitants from the Johns Hopkins Coronavirus Resource Center. EuroStat data were used for data on potential confounders at the country level including Gross Domestic Product (GDP) (2019), population density (2018), percentage of people older than 64 years (2019), unemployment rate (2019) and percentage obesity (2014, to avoid missing values). Mortality counts were analyzed with quasi-Poisson regression models - with log of population as an offset - to model the death rate while accounting for over-dispersion.ResultsOf all the variables considered, including confounders, only fermented vegetables reached statistical significance with the COVID-19 death rate per country. For each g/day increase in the average national consumption of fermented vegetables, the mortality risk for COVID-19 decreased by 35.4% (95% CI: 11.4%, 35.5%). Adjustment did not change the point estimate and results were still significant.DiscussionThe negative ecological association between COVID-19 mortality and consumption of fermented vegetables supports the a priory hypothesis previously reported. The hypothesis needs to be tested in individual studies performed in countries where the consumption of fermented vegetables is common.
The relative power of individual distancing efforts and public policies to curb the COVID-19 epidemics*
Authors: Aubert Cécile , Augeraud-Véron Emmanuelle 
Published: July 2020

AbstractLockdown curbs the COVID-19 epidemics but at huge costs. Public debates question its impact compared with reliance on individual responsibility. We aim at understanding how rationally chosen self-protective behavior impacts the spread of the epidemics. We want to, first, assess the value of lockdown compared to a counterfactual that incorporates self-protection efforts under unknown disease prevalence; and second, assess how individual behavior modify the epidemic dynamics when mandatory policies are relaxed. We couple an SLIAR model, that includes asymptomatic transmission, with utility maximization: Individuals trade off economic and wellbeing costs from physical distancing with a lower infection risk. Effort depends on risk aversion, perceptions, and the value of contacts. In a Nash equilibrium, individual uncoordinated efforts yield average contact intensity, which drives epidemic transmission. Equilibrium effort differs markedly from constant, stochastic or proportional contacts reduction. It adjusts to reported cases in a way that creates a slightly decreasing plateau in epidemic prevalence. Calibration on French data shows that the number of deaths with no lockdown but equilibrium efforts is only 1/6 to 1/10 of the number predicted with business-as-usual. However, lockdown saves at least 50% more lives than individual efforts alone. Prolonged weaker restrictions prevent an exponential rebound. Public policies post-lockdown have a limited impact as they partly crowd out individual efforts. Compulsory mask wearing helps resume activity but has no impact on the epidemic. Communication that increases risk salience is more effective.
SYSTEMATIC REVIEW PROTOCOL: The reporting standards of Randomised Clinical Trials in leading medical journals between 2019-2020
Authors: McErlean Mairead , Samways Jack , Godolphin Peter , Chen Yang 
Published: July 2020

This is a systematic review protocol which outlines the basis and methodology for our intended review which at the time of writing is in the study screening phase. Our aim is to answer the fundamental questions:To systematically identify RCTs published in the four leading medical journals between January 1st 2019 to May 31st 2020.To assess the quality of reporting of such RCTs using the CONSORT 2010 statement.To identify any association with medical specialty or size or type of RCT and the rate of adherence to the CONSORT 2010 statement.
HPV cervical infections and serological status in vaccinated and unvaccinated women
Authors: Murall Carmen Lia , Reyné Bastien , Selinger Christian , Bernat Claire , Boué Vanina , Grasset Sophie , Groc Soraya , Rahmoun Massilva , Bender Noemi , Bonneau Marine , Foulongne Vincent , Graf Christelle , Picot Eric , Picot Marie-Christine , Tribout Vincent , Waterboer Tim , Bravo Ignacio G , Reynes Jacques , Segondy Michel , Boulle Nathalie , Alizon Samuel 
Published: July 2020

AbstractUnderstanding genital infections by Human papillomaviruses (HPVs) remains a major public health issue, especially in countries where vaccine uptake is low. We investigate HPV prevalence and antibody status in 150 women (ages 18 to 25) in Montpellier, France. At inclusion and one month later, cervical swabs, blood samples and questionnaires (for demographics and behavioural variables) were collected. Oncogenic, non-vaccine genotypes HPV51, HPV66, HPV53, and HPV52 were the most frequently detected viral genotypes overall. Vaccination status, which was well-balanced in the cohort, showed the strongest (protective) effect against HPV infections, with an associated odds ratio for alphapapillomavirus detection of 0.45 (95% confidence interval: [0.22;0.58]). We also identified significant effects of age, number of partners, body mass index, and contraception status on HPV detection and on coinfections. Type-specific IgG serological status was also largely explained by the vaccination status. IgM seropositivity was best explained by HPV detection at inclusion only. Finally, we identify a strong significant effect of vaccination on genotype prevalence, with a striking under-representation of HPV51 in vaccinated women. Variations in HPV prevalence correlate with key demographic and behavioural variables. The cross-protective effect of the vaccine against HPV51 merits further investigation.
Mental health, substance use and viral load suppression in adolescents receiving ART at a large paediatric HIV clinic in South Africa
Authors: Haas Andreas D. , Technau Karl-Günter , Pahad Shenaaz , Braithwaite Kate , Madzivhandila Mampho , Sorour Gillian , Sawry Shobna , Maxwell Nicola , Groote Per von , Tlali Mpho , Davies Mary-Ann , Egger Matthias ,   for the IeDEA Southern Africa Collaboration
Published: July 2020

AbstractIntroductionThere are few data on the prevalence of mental health problems among adolescents living with HIV in low- and middle-income countries and the evidence on associations between mental health problems and viral load suppression is inconsistent. We assessed the prevalence of mental health problems among adolescents receiving antiretroviral therapy (ART) at a large paediatric HIV clinic in South Africa and examined associations between mental health problems and viral load suppression.MethodsWe implemented routine mental health screening at Rahima Moosa Mother and Child Hospital in Johannesburg. Adolescents aged 10-19 years were offered screening for depression (Patient Health Questionnaire-9 [PHQ-9]), suicide (Adolescent Innovations Project [AIP]-handbook), anxiety (General Anxiety Disorder-7 [GAD-7]), trauma (Primary Care PTSD Screen for DSM-5 [PC-PTSD-5]), and substance use (CAGE Adapted to Include Drugs [CAGE-AID]) at each routine HIV care visits. We assessed screening outcomes between February 1, 2018, and January 1, 2020 and calculated odds ratios for associations between positive screening outcomes and unsuppressed viral load (>400 HIV-RNA copies/ml).ResultsOut of 1,203 adolescents who attended the clinic, 1,088 (90.4%) were screened at a median age of 13 years (IQR 10-15). In total, 97 (8.9%) screened positive: 48 (4.4%) for depression (PHQ-9 ≥ 10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD-7 ≥ 10), 38 (3.2%) for trauma (PC-PTSD-5 ≥ 3), and 18 (1.7%) for substance use (CAGE-AID ≥ 2). Positive screening for depression (aOR 2.39, 95% CI 1.02-5.62), trauma (aOR 3.18, 95% CI 1.11-9.07), substance use (aOR 7.13, 95% CI 1.60-31.86), or any mental health condition (aOR 2.17, 95% CI 1.17-4.02) were strongly associated with unsuppressed viral load.ConclusionsHIV-positive adolescents who are affected by mental health or substance use problems are a highly vulnerable population, who merit specific clinical attention. Strategies for screening and management of mental health and substance use problems in adolescents on ART in low- and middle-income countries need to be developed and evaluated.
Are men dying more than women by COVID-19?
Authors: de Melo Thaise Pinto , Silva Delvan Alves , Barbosa Alexandre Naime 
Published: July 2020

AbstractWe aimed to clarify if the infection and death rate by COVID-19 differ among gender in the top 50 countries with the highest death rates. Also, we investigated if secondary variables such as HDI, number of hospital beds, average age, temperature, percentage of elderly, smoker and obesity are contributing to the variability observed among countries. Meta-analyses and meta-regressions approaches were applied to official public data reported by the Word Health Organization and governments until May, 2020. A random effect model was used for the meta-analysis and heterogeneity was calculated by I2 statistic. There was not significative difference between men and women to be infected by COVID-19 (P = 0.42), though a significative difference was observed for death rate (P < 0.0001). High heterogeneity was observed among countries. For both infection and death rates this variability was mainly explained by the HDI (42.3% and 54.2%), average age (40.9% and 40.3%) and temperature (30.1% and 39.3%). Man are dying more than women around the word by COVID-19. Countries with highest HDI present less difference between sexes. These results reinforce that public politics promoting social isolation, health care and general well-being of the population are key factors in combating COVID-19.
Human chromosomal-scale length variation and severity of COVID-19 infection using the UK Biobank dataset
Authors: Toh Chris , Brody James P. 
Published: July 2020

AbstractIntroductionThe course of COVID-19 varies from asymptomatic to severe (acute respiratory distress, cytokine storms, and death) in patients. The basis for this range in symptoms is unknown. One possibility is that genetic variation is responsible for the highly variable response to infection. We evaluated how well a genetic risk score based on chromosome-scale length variation and machine learning classification algorithms could predict severity of response to SARS-CoV-2 infection.MethodsWe compared 981 patients from the UK Biobank dataset who had a severe reaction to SARS-COV-2 infection before 27 April 2020 to a similar number of age matched patients drawn for the general UK Biobank population. For each patient, we built a profile of 88 numbers characterizing the chromosome-scale length variability of their germ line DNA. Each number represented one quarter of the 22 autosomes. We used the machine learning algorithm XGBoost to build a classifier that could predict whether a person would have a severe reaction to Covid-19 based only on their 88-number classification.ResultsWe found that the XGBoost classifier could differentiate between the two classes at a significant level p = 2 · 10 as measured against a randomized control and p = 3 · 10 measured against the expected value of a random guessing algorithm (AUC=0.5). However, we found that the AUC of the classifier was only 0.51, too low for a clinically useful test.Conclusion