bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 vaccine acceptance and its socio-demographic and emotional determinants: a multi-country cross-sectional study
Authors: de Figueiredo A. , Simas C. , Larson H. J. 
Published: June 2021

BackgroundMultiple COVID-19 vaccines have now been licensed for human use, with other candidate vaccines in different stages of development. Effective and safe vaccines against COVID-19 are essential to achieve global control of the pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), but multiple factors, including vaccine supply and vaccine confidence, will be key for high rates of global uptake. Confidence in COVID-19 vaccines, socio-demographic status, and recent emotional status are likely to be key drivers of COVID-19 vaccine acceptance. In this study, we explore these determinants of COVID-19 vaccination intent across17 countries worldwide.MethodsIn this large-scale multi-country study, we explore intent to accept a COVID-19 vaccine and the socio-demographic and emotional determinants of uptake for 17 countries and over 19,000 individuals surveyed in June and July 2020 via nationally representative samples. We used Bayesian ordinal logistic regressions to probe the relationship between intent to accept a COVID-19 vaccine and individuals’ socio-demographic status, their confidence in COVID-19 vaccines, and their recent emotional status. Gibbs sampling was used for Bayesian model inference, with 95% Bayesian highest posterior density intervals used to capture uncertainty.FindingsIntent to accept a COVID-19 vaccine is highest in India, where 77.8% (95% HPD, 75.5 to 80.0%) of respondents strongly agreeing that they would take a new COVID-19 vaccine if it were available. The Democratic Republic of Congo (15.5%, 12.2 to 18.6%) and France (26.4%, 23.7 to 29.2%) have the lowest share of respondents who strongly agree that they would accept a COVID-19. Confidence in the safety, importance, and effectiveness of COVID-19 vaccines are the most widely informative determinants of vaccination intent. Socio-demographic and emotional determinants played a lesser role, with being male and having higher education was associated with increased uptake intent in five countries and being fearful of catching COVID-19 also a strong determinant of uptake intent.InterpretationBarriers to COVID-19 vaccine acceptance will be highly country and context dependent. These findings highlight the importance of regular monitoring of COVID-19 vaccine confidence to identify groups less likely to vaccinate and to monitor the impact of vaccination policies on uptake behaviour.
IL10RB as a key regulator of COVID-19 host susceptibility and severity
Authors: Voloudakis Georgios , Hoffman Gabriel , Venkatesh Sanan , Lee Kyung Min , Dobrindt Kristina , Vicari James M. , Zhang Wen , Beckmann Noam D. , Jiang Shan , Hoagland Daisy , Bian Jiantao , Gao Lina , Corvelo André , Cho Kelly , Lee Jennifer S. , Iyengar Sudha K. , Luoh Shiuh-Wen , Akbarian Schahram , Striker Robert , Assimes Themistocles L. , Schadt Eric E. , Merad Miriam , tenOever Benjamin R. , Charney Alexander W. ,   Mount Sinai COVID-19 Biobank,   VA Million Veteran Program COVID-19 Science Initiative, Brennand Kristen J. , Lynch Julie A. , Fullard John F. , Roussos Panos 
Published: June 2021

AbstractBackgroundRecent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes and readily available compounds that reduce COVID-19 host susceptibility is a critical next step.MethodsWe integrate COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX) and perturbargen signatures to identify candidate genes and compounds that reverse the predicted gene expression dysregulation associated with COVID-19 susceptibility. The top candidate gene is validated by testing both its GReX and observed blood transcriptome association with COVID-19 severity, as well as byin vitroperturbation to quantify effects on viral load and molecular pathway dysregulation. We validate thein silicodrug repositioning analysis by examining whether the top candidate compounds decrease COVID-19 incidence based on epidemiological evidence.ResultsWe identifyIL10RBas the top key regulator of COVID-19 host susceptibility. Predicted GReX up-regulation ofIL10RBand higherIL10RBexpression in COVID-19 patient blood is associated with worse COVID-19 outcomes.In vitroIL10RB overexpression is associated with increased viral load and activation of immune-related molecular pathways. Azathioprine and retinol are prioritized as candidate compounds to reduce the likelihood of testing positive for COVID-19.ConclusionsWe establish an integrative data-driven approach for gene target prioritization. We identify and validateIL10RBas a suitable molecular target for modulation of COVID-19 host susceptibility. Finally, we provide evidence for a few readily available medications that would warrant further investigation as drug repositioning candidates.
A comparison of four commercially available RNA extraction kits for wastewater surveillance of SARS-CoV-2 in a college population
Authors: O’Brien Megan , Rundell Zachary C. , Nemec Michelle D. , Langan Laura M. , Back Jeffrey A. , Lugo Joaquin N. 
Published: June 2021

AbstractLocalized wastewater surveillance has allowed for public health officials to gain a broader understanding of SARS-CoV-2 viral prevalence in the community allowing public health officials time to prepare for impending outbreaks. Given variable levels of virus in the population through public health interventions, proper concentration and extraction of viral RNA is a key step in ensuring accurate detections. With many commercial RNA extraction kits and methodologies available, the performance of 4 different kits were evaluated for SARS-CoV-2 RNA detection in wastewater, specifically focusing on their applicability to lower population densities such as those at university campus dorms. Raw wastewater samples were collected at 4 sites on a college campus over a 24 hour period as a composite sample. Included in these sites was an isolation site that housed students that tested positive for Covid-19 via nasopharyngeal swabs. These samples were analyzed using the following kits: Qiagen All Prep PowerViral DNA/RNA kit, New England BioLabs Monarch RNA MiniPrep Kit, and Zymo Quick RNA-Viral Kit, and the Zymo Quick-RNA Fecal/Soil Microbe MicroPrep Kit. All four sites were processed according to the manufacturer’s guidelines. Extractions were then quantified with RT-qPCR one-step reactions using an N2 primer and a linearized plasmid standard. While the Zymo Quick-RNA Fecal/Soil Microbe MicroPrep Kit (also known as the Zymo Environ Water RNA Kit) only recovered approximately 73% (+/- 38%) SARS-CoV-2 RNA compared to the Zymo Quick-RNA Viral kit, it was the most time efficient kit to yield comparable results. This extraction kit had a cumulative processing time of approximately five hours compared, while the other three kits had processing times between approximately 9 and 9.5 hours. Based on the current research, the most effective kits for smaller population densities are pellet based and include a homogenization, inhibitor removal, and RNA preservation step.Highlights-Samples from smaller population densities make concentrating RNA vital for detection-Pelleting may provide for more timely concentration and extraction of SARS-CoV-2 RNA-RNA shields and PCR inhibitor removal may increase detection of RNA during RT-qPCRAbstract Figure
The COVID-19 pandemic storm in India subsides, but the calm is still far away
Authors: Nesteruk Igor 
Published: June 2021

ABSTRACTIn May 2021, the number of new COVID-19 patients in India began to decline, as predicted by the generalized SIR-model (susceptible-infected-removed). The calculations of the final size of this pandemic wave and its duration probably were too pessimistic. New SIR simulations with the use of fresher datasets are necessary in order to update the predictions and to calculate the difference between the registered (laboratory-confirmed) and real number of cases.
Ten months of temporal variation in the clinical journey of hospitalised patients with COVID-19: an observational cohort
Authors:   ISARIC Clinical Characterisation Group, Hall Matthew 
Published: June 2021

AbstractBackgroundThere is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an ongoing infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high density unit (HDU), while novel treatment modalities may reduce the time course of illness. On the other hand, limited resources at times of high demand may lead to rationing of resources, with less beneficial consequences. Despite little evidence on how the values of such variables change over the course of a crisis (such as the current COVID-19 pandemic), they may nevertheless be used as proxies for disease severity, outcome measures for clinical trials, and to inform planning and logistics. We hypothesise that variation of this kind has been present over the first year of the pandemic.Methods and FindingsWe investigate such time trends in an extremely large international cohort of 142,540 patients with symptom onset of, or hospital admission for, COVID-19 during 2020. The variables investigated are time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, case fatality ratio (CFR) and total length of hospital stay. Time from hospital symptom onset to hospital admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December. ICU/HDU admission was more frequent from June to August, while there were only modest time trends in time from hospital admission to ICU/HDU. The CFR was lowest from June to August, a trend mostly driven by patients with no ICU/HDU admission. Raw numbers for overall hospital stay showed little overall variation over the time period, but further examination reveals a clear decline in time to discharge for ICU/HDU survivors. The main limitations are that these are predominantly severe COVID-19 cases, and that there are temporal, spatial and demographic biases present in an observational study of this kind.ConclusionsOur results establish that variables of these kinds have limitations when used as outcome measures in a rapidly-evolving situation.
BrainXcan identifies brain features associated with behavioral and psychiatric traits using large scale genetic and imaging data
Authors: Liang Yanyu , Melia Owen , Caroll Timothy J. , Brettin Thomas , Brown Andrew , Im Hae Kyung 
Published: June 2021

AbstractAdvances in brain MRI have enabled many discoveries in neuroscience. Comparison of brain MRI features between cases and controls have highlighted potential causes of psychiatric and behavioral disorders (complex traits). However, due to the cost of collecting MRI data and the difficulty in recruiting particular patient groups, most studies have small sample sizes, limiting their reliability. Furthermore, reverse causality complicates interpretation because many observed brain differences are the result rather than the cause of the disease. Here we propose a method (BrainXcan) that leverages the power of large-scale genome-wide association studies (GWAS) and reference brain MRI data to discover new mechanisms of disease etiology and validate existing ones. BrainXcan tests the association with genetic predictors of brain MRI-derived features and complex traits to pinpoint relevant region-specific and cross-brain features. As this approach requires only genetic data, BrainXcan allows us to test a host of hypotheses on mental illness, across many disorders and MRI modalities, using existing public data resources. For example, our method shows that reduced axonal density across the brain is associated with the risk of schizophrenia, consistent with the disconnectivity hypothesis. We also find structural features in the hippocampus, amygdala, and anterior cingulate cortex, among others associated with schizophrenia risk highlighting the potential of our approach, which uses orthogonal lines of evidence to inform the biology of complex traits.
SHORTENING TIME FOR ALCOHOL ACCESS DRIVES UP FRONT-LOADING BEHAVIOR, BRINGING CONSUMPTION IN MALE RATS TO THE LEVEL OF FEMALES
Authors: Flores-Bonilla A. , De Oliveira B. , Silva-Gotay A. , Lucier K. , Richardson H.N. 
Published: June 2021

AbstractAlcohol can have more detrimental effects on mental health in women, even when intake is comparable or higher in men. This may relate to a differential pattern of drinking, e.g., how rapidly alcohol is consumed. We used operant procedures to gain insight into sex differences in the drinking dynamics of rats. Adult male and female Wistar rats underwent operant training to promote voluntary drinking of 10% (w/v) alcohol (8 rats/sex). We tested how drinking patterns changed after manipulating the effort required for alcohol (fixed ratio, FR), as well as the length of time in which animals had access to alcohol (self-administration session length). Rats were tested twice within the 12 hours of the dark cycle, at 2 hours (early sessions) and 10 hours into the dark cycle (late sessions). As expected, adult females consumed significantly more alcohol than males in the 30-minute sessions with the FR1 paradigm. Alcohol consumption within females was higher in the late sessions compared to early sessions, whereas this difference was not found within males. “Front-loading” of alcohol (heavier drinking in the first five minutes of the session) was the primary factor underlying higher consumption in females, and this sex difference was accentuated in the late sessions. Increasing the effort required from FR1 to FR3 reduced alcohol drinking in both sexes. Front-loading behavior remained in females in both early and late sessions, whereas males exhibited minimal front-loading behavior only in the early sessions. Compressing drinking access to 15-minutes drove up front-loading behavior, producing total alcohol intake levels that were comparable in both sexes. This strategy could be useful for exploring sex differences in the effect of voluntary alcohol drinking on the brain. Our findings also highlight the importance of the time of testing for detecting sex differences in drinking behavior.HighlightsVoluntary alcohol drinking is higher in adult female rats compared to adult male rats. This sex difference is most pronounced in the later phase of the dark cycle, and when the operant effort is minimal (when 1 lever press gives 1 reward: fixed ratio 1, FR1).Higher alcohol intake in females is primarily due to “front-loading,” or the rapid consumption of alcohol within the first 5 minutes of access.Increasing the effort required to obtain alcohol from FR1 to FR3 dampens “front-loading” drinking behavior, resulting in similar levels of total intake in males and females.Compressing the time of access to 15 minutes drives up “front-loading” to such a degree that animals end up consuming more alcohol in total than they do in 30-minute sessions. In males, this increase in drinking is large enough that it eliminates the sex difference in total alcohol intake.Visual Abstract
CeLINC, a fluorescence-based protein-protein interaction assay in C. elegans
Authors: Kroll Jason R , Remmelzwaal Sanne , Boxem Mike 
Published: June 2021

AbstractInteractions among proteins are fundamental for life and determining whether two particular proteins physically interact can be essential for fully understanding a protein’s function. We present C. elegans light-induced co-clustering (CeLINC), an optical binary protein-protein interaction assay to determine whether two proteins interact in vivo. Based on CRY2/CIB1 light-dependent oligomerization, CeLINC can rapidly and unambiguously identify protein-protein interactions between pairs of fluorescently tagged proteins. A fluorescently tagged bait protein is captured using a nanobody directed against the fluorescent protein (GFP or mCherry) and brought into artificial clusters within the cell. Co-localization of a fluorescently tagged prey protein in the cluster indicates a protein interaction. We tested the system with an array of positive and negative reference protein pairs. Assay performance was extremely robust with no false positives detected in the negative reference pairs. We then used the system to test for interactions among apical and basolateral polarity regulators. We confirmed interactions seen between PAR-6, PKC-3, and PAR-3, but observed no physical interactions among the basolateral Scribble module proteins LET-413, DLG-1, and LGL-1. We have generated a plasmid toolkit that allows use of custom promoters or CRY2 variants to promote flexibility of the system. The CeLINC assay is a powerful and rapid technique that can be widely applied in C. elegans due to the universal plasmids that can be used with existing fluorescently tagged strains without need for additional cloning or genetic modification of the genome.SummaryWe have developed a protein-protein interaction assay for C. elegans to investigate whether pairs of proteins interact in vivo. C. elegans light-induced co-clustering (CeLINC) is based on trapping a fluorescently-tagged bait protein into artificial clusters, and observing whether candidate interacting prey proteins co-cluster with the bait protein. CeLINC can be widely applied as a single set of universal plasmids can be used with existing strains expressing fluorescently-tagged proteins.
SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator
Authors: Hysenaj Lisiena , Little Samantha , Kulhanek Kayla , Gbenedio Oghenekevwe M. , Rodriguez Lauren , Shen Alan , Lone Jean-Christophe , Lupin-Jimenez Leonard C. , Bonser Luke R. , Serwas Nina K. , Bahl Kriti , Mick Eran , Li Jack Z. , Ding Vivianne W. , Matsumoto Shotaro , Maishan Mazharul , Simoneau Camille , Fragiadakis Gabriela , Jablons David M. , Langelier Charles R. , Matthay Michael , Ott Melanie , Krummel Matthew , Combes Alexis J. , Sil Anita , Erle David J. , Kratz Johannes R. , Roose Jeroen P. 
Published: June 2021

AbstractSARS coronavirus-2 (SARS-CoV-2) is causing a global pandemic with large variation in COVID-19 disease spectrum. SARS-CoV-2 infection requires host receptor ACE2 on lung epithelium, but epithelial underpinnings of variation are largely unknown. We capitalized on comprehensive organoid assays to report remarkable variation in SARS-CoV-2 infection rates of lung organoids from different subjects. Tropism is highest for TUBA- and MUC5AC-positive organoid cells, but levels of TUBA-, MUC5A-, or ACE2-positive cells do not predict infection rate. We identify surface molecule Tetraspanin 8 (TSPAN8) as novel mediator of SARS-CoV-2 infection, which is not downregulated by this specific virus. TSPAN8 levels, prior to infection, strongly correlate with infection rate and TSPAN8-blocking antibodies diminish SARS-CoV-2 infection. We propose TSPAN8 as novel functional biomarker and potential therapeutic target for COVID-19.
Hierarchical Harmonization of Atom-Resolved Metabolic Reactions Across Metabolic Databases
Authors: Jin Huan , Moseley Hunter N. 
Published: June 2021

AbstractMetabolic models have been proven to be useful tools in system biology and have been successfully applied to various research fields in a wide range of organisms. A relatively complete metabolic network is a prerequisite for deriving reliable metabolic models. The first step in constructing metabolic network is to harmonize compounds and reactions across different metabolic databases. However, effectively integrating data from various sources still remains a big challenge. Incomplete and inconsistent atomistic details in compound representations across databases is a very important limiting factor. Here, we optimized a subgraph isomorphism detection algorithm to validate generic compound pairs. Moreover, we defined a set of harmonization relationship types between compounds to deal with inconsistent chemical details while successfully capturing atom-level characteristics, enabling a more complete enabling compound harmonization across metabolic databases. In total, 15,704 compound pairs across KEGG (Kyoto Encyclopedia of Genes and Genomes) and MetaCyc databases were detected. Furthermore, utilizing the classification of compound pairs and EC (Enzyme Commission) numbers of reactions, we established hierarchical relationships between metabolic reactions, enabling the harmonization of 3,856 reaction pairs. In addition, we created and used atom-specific identifiers to evaluate the consistency of atom mappings within and between harmonized reactions, detecting some consistency issues between the reaction and compound descriptions in these metabolic databases.
SARS-CoV-2 Infects Syncytiotrophoblast and Activates Inflammatory Responses in the Placenta
Authors: Argueta Lissenya B. , Lacko Lauretta A. , Bram Yaron , Tada Takuya , Carrau Lucia , Zhang Tuo , Uhl Skyler , Lubor Brienne C. , Chandar Vasuretha , Gil Cristianel , Zhang Wei , Dodson Brittany , Bastiaans Jeroen , Prabhu Malavika , Salvatore Christine M. , Yang Yawei J. , Baergen Rebecca N. , tenOever Benjamin R. , Landau Nathaniel R. , Chen Shuibing , Schwartz Robert E. , Stuhlmann Heidi 
Published: June 2021

AbstractSARS-CoV-2 infection during pregnancy leads to an increased risk of adverse pregnancy outcomes. Although the placenta itself can be a target of virus infection, most neonates are virus free and are born healthy or recover quickly. Here, we investigated the impact of SARS-CoV-2 infection on the placenta from a cohort of women who were infected late during pregnancy and had tested nasal swab positive for SARS-CoV-2 by qRT-PCR at delivery. SARS-CoV-2 genomic and subgenomic RNA was detected in 23 out of 54 placentas. Two placentas with high virus content were obtained from mothers who presented with severe COVID-19 and whose pregnancies resulted in adverse outcomes for the fetuses, including intrauterine fetal demise and a preterm delivered baby still in newborn intensive care. Examination of the placental samples with high virus content showed efficient SARS-CoV-2 infection, using RNA in situ hybridization to detect genomic and replicating viral RNA, and immunohistochemistry to detect SARS-CoV-2 nucleocapsid protein. Infection was restricted to syncytiotrophoblast cells that envelope the fetal chorionic villi and are in direct contact with maternal blood. The infected placentas displayed massive infiltration of maternal immune cells including macrophages into intervillous spaces, potentially contributing to inflammation of the tissue. Ex vivo infection of placental cultures with SARS-CoV-2 or with SARS-CoV-2 spike (S) protein pseudotyped lentivirus targeted mostly syncytiotrophoblast and in rare events endothelial cells. Infection was reduced by using blocking antibodies against ACE2 and against Neuropilin 1, suggesting that SARS-CoV-2 may utilize alternative receptors for entry into placental cells.