bluuebunny/crossref_metadata_2025_split huggingface dataset:
covid19.Explorer: A web application and R package to explore United States COVID-19 data
Authors: Revell Liam J. 
Published: February 2021

ABSTRACTAppearing at the end of 2019, a novel virus (later identified as SARS-CoV-2) was characterized in the city of Wuhan in Hubei Province, China. As of the time of writing, the disease caused by this virus (known as COVID-19) has already resulted in over 3 million deaths worldwide. SARS-CoV-2 infections and deaths, however, have been highly unevenly distributed among age groups, sexes, countries, and jurisdictions over the course of the pandemic. Herein, I present a tool (the covid19.Explorer R package and web application) that has been designed to explore and analyze publicly available United States COVID-19 infection and death data from the 2020/21 U.S. SARS-CoV-2 pandemic. The analyses and visualizations that this R package and web application facilitate can help users better comprehend the geographic progress of the pandemic, the effectiveness of non-pharmaceutical interventions (such as lockdowns and other measures, which have varied widely among U.S. states), and the relative risks posed by COVID-19 to different age groups within the U.S. population. The end result is an interactive tool that will help its users develop an improved understanding of the temporal and geographic dynamics of the SARS-CoV-2 pandemic, accessible to lay people and scientists alike.
IMMUNO-COV™ v2.0: Development and Validation of a High-Throughput Clinical Assay for Measuring SARS-CoV-2-Neutralizing Antibody Titers
Authors: Vandergaast Rianna , Carey Timothy , Reiter Samantha , Lathrum Chase , Lech Patrycja , Gnanadurai Clement , Haselton Michelle , Buehler Jason , Narjari Riya , Schnebeck Luke , Roesler Anne , Sevola Kara , Suksanpaisan Lukkana , Bexon Alice , Naik Shruthi , Brunton Bethany , Weaver Scott C. , Rafael Grace , Tran Sheryl , Baum Alina , Kyratsous Christos A. , Peng Kah Whye , Russell Stephen J. 
Published: February 2021

ABSTRACTNeutralizing antibodies are key determinants of protection from future infection, yet well-validated high-throughput assays for measuring titers of SARS-CoV-2-neutralizing antibodies are not generally available. Here we describe the development and validation of IMMUNO-COV™ v2.0 a scalable surrogate virus assay, which titrates antibodies that block infection of Vero-ACE2 cells by a luciferase-encoding vesicular stomatitis virus displaying SARS-CoV-2 spike glycoproteins (VSV-SARS2-Fluc). Antibody titers, calculated using a standard curve consisting of stepped concentrations of SARS-CoV-2 spike monoclonal antibody, correlated closely (p < 0.0001) with titers obtained from a gold-standard PRNT50% assay performed using a clinical isolate of SARS-CoV-2. IMMUNO-COV™ v2.0 was comprehensively validated using data acquired from 242 assay runs performed over seven days by five analysts, utilizing two separate virus lots, and 176 blood samples. Assay performance was acceptable for clinical use in human serum and plasma based on parameters including linearity, dynamic range, limit of blank and limit of detection, dilutional linearity and parallelism, precision, clinical agreement, matrix equivalence, clinical specificity and sensitivity, and robustness. Sufficient VSV-SARS2-Fluc virus reagent has been banked to test 5 million clinical samples. Notably, a significant drop in IMMUNO-COV™ v2.0 neutralizing antibody titers was observed over a six-month period in people recovered from SARS-CoV-2 infection. Together, our results demonstrate the feasibility and utility of IMMUNO-COV™ v2.0 for measuring SARS-CoV-2-neutralizing antibodies in vaccinated individuals and those recovering from natural infections. Such monitoring can be used to better understand what levels of neutralizing antibodies are required for protection from SARS-CoV-2, and what booster dosing schedules are needed to sustain vaccine-induced immunity.
Circulatory Cytokines and Chemokines Profile in Human Coronaviruses: A systematic review and meta-analysis
Authors: Zawawi Ayat , Naser Abdallah Y , Alwafi Hassan , Minsahwi Faisal 
Published: February 2021

AbstractBackgroundSARS, MERS, and COVID-19 share similar characteristics as the genetic homology of SARS-CoV-2 compared to SARS-CoV and MERS-CoV is 80% and 50% respectively and cause similar clinical features. Uncontrolled release of proinflammatory mediators (cytokine storm) by activated immune cells in SARS, MERS, and COVID-19 leads to severe phenotype development.AimThis systematic review and meta-analysis aimed to evaluate the inflammatory cytokines profile associated with severe human coronavirus diseases, including three stains: MERS-CoV, SARS-CoV SARS-CoV-2, in severe patients.MethodPubMed, Embase, and Cochrane Library databases were searched up to July 2020. Randomized and Observational studies reporting the inflammatory cytokines associated with severe and non-severe human coronavirus diseases, including MERS-CoV, SARS-CoV SARS-CoV-2 were included. Two reviewers independently screened articles, extracted data, and assessed the quality of included studies. Meta-analysis was performed using a random-effects model with a 95% confidence interval (CI) to estimate the pooled mean of inflammatory biomarkers.ResultsA high level of circulating IL-6 could be associated with the severity of the three strains of coronaviruses infection. TNF, IL-10, and IL-8 is associated with the severity of COVID-19. Increased circulating levels of CXCL10/IP10 and CCL2/MCP-1 might also be related to the severity of MERS.ConclusionThis study suggests that the immune response and immunopathology in the three severe human coronavirus strains are similar to some extent. These findings highlight that nearly all studies reporting severe cases of SARS, MERS, and COVID-19 have been associated with elevated levels of IL-6, which could be used as a potential therapeutic target to improve patients’ outcomes in severe cases.
“Incidence and Outcomes of Pulmonary embolism among hospitalized COVID-19 patients”
Authors: Badr Omaima Ibrahim , Alwafi Hassan , Elrefaey Wael Aly , Naser Abdallah Y , Shabrawishi Mohammed 
Published: February 2021

AbstractBackgroundPatients with COVID-19 may be at high risk for thrombotic complications due to excess inflammatory response and stasis of blood flow. This study aims to assess the incidence of pulmonary embolism among hospitalized patients with COVID-19, risk factors and the impact on survival.MethodA retrospective case-control study was conducted at Al-Noor Specialist Hospital in, Saudi Arabia between March 15, 2020, and June 15, 2020. Patients with confirmed COVID-19 diagnosis by a real-time polymerase chain reaction (PCR) and confirmed diagnosis of pulmonary embolism by Computed Tomography pulmonary angiogram (CTPA) formed the case group. Patients with confirmed COVID-19 diagnosis by a real-time polymerase chain reaction (PCR) and without confirmed diagnose of pulmonary embolism formed the control group. Logistic regression analysis was used to identify predictors of pulmonary embolism and its survival.ResultsA total of 159 patients participated were included in the study, of which 51 were the cases (patients with pulmonary embolism) and 108 patients formed the control group (patients without pulmonary embolism). The incidence of PE among hospitalized was around 32%. Smoking history, low level of oxygen saturation and higher D-dimer values were important risk factors that were associated with a higher risk of developing PE (p< 0.05). Higher respiratory rate was associated with higher odds of death, and decrease the possibility of survival among hospitalised patients with PE.ConclusionPulmonary embolism is common among hospitalized patients with COVID-19. Preventive measures should be considered for hospitalized patients with smoking history, low level of oxygen saturation, high D-dimer values, and high respiratory rate.
Protective lipid-lowering genetic variants in healthy older individuals without coronary heart disease
Authors: Lacaze Paul , Riaz Moeen , Sebra Robert , Hooper Amanda J , Pang Jing , Tiller Jane , Polekhina Galina , Tonkin Andrew M , Reid Christopher M , Zoungas Sophia , Murray Anne M , Nicholls Stephen J , Watts Gerald F , Schadt Eric , McNeil John J 
Published: February 2021

ABSTRACTBackgroundDisruptive genetic variants in thePCSK9andAPOBgenes result in lower serum low-density lipoprotein cholesterol (LDL-C) levels and confer protection against coronary heart disease (CHD). Few studies have measured the prevalence and selective advantage of such variants among healthy older individuals without prior CHD events.Methods and ResultsWe performed targeted sequencing of thePCSK9andAPOBgenes in 13,131 healthy older individuals without CHD aged 70 years or older enrolled into the ASPirin in Reducing Events in the Elderly (ASPREE) trial. We detected predicted loss-of-function (pLoF) variants in thePCSK9andAPOBgenes, and associated variant carrier status with blood lipid levels. We detected 22 different rarePCSK9/APOBcandidate variants with lipid-lowering effect, carried by 104 participants (carrier rate 1 in 126). Rare variant carrier status was associated with 19.4 mg/dl (14.6%) lower LDL-C, compared with non-carriers (P=<0.001, adjusted for statin use). Statin prescriptions were less prevalent in rare variant carriers (16%) than non-carriers (35%). ThePCSK9R46L variant (rs11591147-T) was associated with 15.5mg/dl (11.8%) lower LDL-C in heterozygotes, and 25.2 mg/dl (19.2%) lower LDL-C in homozygotes, respectively (both P=<0.001).ConclusionsLipid-lowering genetic variants are carried by healthy older individuals and contribute to CHD-free survival.
The epidemiological characteristics of the primary health care based COVID-19 swabbed persons in Qatar, March- October 2020
Authors: Al-Kuwari Mohamed Ghaith , Abdulmalik Mariam Ali , Bakri Ahmad Haj , Kandy Mujeeb Chettiyam , Abdulla Maha Youssef , Gibb John 
Published: February 2021

AbstractBackgroundIn March 2020, Qatar started reporting increased numbers of COVID-19 positive cases. National preventive measures were put in place and testing plan has been developed to respond to the pandemic with the primary health care as the main provider. The study aims to describe the epidemiological characteristics of COVID-19 at the primary health care level in Qatar and to examine the factors associated with the positivity rate.MethodRetrospective data analysis for all the cases screened for COVID-19 at the primary health care level in Qatar between the 11th of March and 31st of October 2020. The study analyzed the demographic characteristics of the tested persons and non-communicable disease burden, positivity rate by month, nationality, and age-group, factors associated with the positivity rate.ResultsBetween the 11th of March and the 31st of October 2020, 285,352 persons were tested for SARS-CoV-2, with a median age (IQR) of 32 (22-43) years. 59.9% were from the Middle East and North Africa region and 29.6% originally from Asia. Overall, among them, 11.2% had diabetes mellitus and 11.4% had hypertension. The epidemiological curve showed a steep increase in positivity rate from March till June 2020 at the highest rate of 21.4% in June 2020. The highest positivity rate was observed among Asian males at 20.3%. The positivity rates were almost the same among the tested persons for SARS-CoV-2 in the main three age-groups (0-18, 19-39, 40-59) at 13%, 14.5%, and 14.0%, respectively. In a multi regression model, being a male was associated with a higher risk (OR 1.16; 95% CI 1.13 to 1.18). Persons originally from Asia were at higher risk than those originally from the Middle East and North Africa (OR 1.5; 95% CI 147 to 1.54). COVID-19 infection was higher among those presenting with clinical symptoms than those asymptomatic (OR. 4.16; 95% CI 4.05 to 4.28).ConclusionThe epidemic predominantly affected younger ages and males namely coming from Asia. At the primary health care level, COVID-19 infection rate was higher among those who presented with clinical symptoms. The scale-up of the testing at the primary health care level helped in detecting more cases and was reflected in a steady increase in the positivity rate to be flattened afterward.
Implementation of Mercury Biomonitoring in German Adults using Dried Blood Spot Sampling in Combination with Direct Mercury Analysis
Authors: Schweizer Ann-Kathrin , Kabesch Michael , Quartucci Caroline , Bose-O’Reilly Stephan , Rakete Stefan 
Published: February 2021

ABSTRACTVenous blood is a preferred matrix for the determination of total mercury (Hg) in human biomonitoring but has some drawbacks such as the requirement for an uninterrupted cold chain for transport and storage and the need of medical personnel for sample collection. Therefore, we tested and implemented a simpler and less expensive method for measuring Hg in human blood using dried blood spots (DBS). For method development, we investigated the influence of different storage conditions (temperature, storage vessel, time) on DBS samples. For method validation, we compared DBS and venous blood and investigated whether DBS sampling is suitable for measuring Hg in the general population in countries with low Hg exposure such as Germany. Based on our results, we found that pre-cleaned glass tubes were most suitable for storage of DBS samples, as this allowed the samples to remain stable for at least four weeks even at high temperatures (40°C). When comparing venous blood and DBS, a very good correlation (r=0.95, p<0.01) and high precision of DBS (mean relative standard deviation 8.2% vs. 7.2% in venous blood samples) were observed. Comparing the recoveries of both matrices in different concentration ranges, the scattering of the recoveries decreases with increasing Hg concentration. The same applies to the mean recoveries. Overall, we found comparable results for DBS and whole blood using direct Hg analysis. Furthermore, we demonstrated that DBS are suitable for Hg biomonitoring in the general population in Germany and improved the storage conditions for the DBS.
Country differences in transmissibility, age distribution and case-fatality of SARS-CoV-2: a global ecological analysis
Authors: Favas Caroline , Jarrett Prudence , Ratnayake Ruwan , Watson Oliver J , Checchi Francesco 
Published: February 2021

AbstractIntroductionSARS-CoV-2 has spread rapidly across the world yet the first pandemic waves in many low-income countries appeared milder than initially forecasted through mathematical models. Hypotheses for this observed difference include under-ascertainment of cases and deaths, country population age structure, and immune modulation secondary to exposure to endemic parasitic infections. We conducted a country-level ecological study to describe patterns in key SARS-CoV-2 outcomes by country and region and to explore possible associations of the potential explanatory factors with these outcomes.MethodsWe collected publicly available data at country level and compared them using standardisation techniques. We then explored the association between exposures and outcomes using alternative approaches: random forest (RF) regression and linear (LM) regression. We adjusted for potential confounders and plausible effect modifications.ResultsAltogether, data on the mean time-varying reproduction number (mean Rt) were available for 153 countries, but standardised averages for the age of cases and deaths and for the case-fatality ratio (CFR) could only be computed for 61, 39 and 31 countries respectively. While mean Rt was highest in the WHO Europe and Americas regions, median age of death was lower in the Africa region even after standardisation, with broadly similar CFR. Population age was strongly associated with mean Rt and the age-standardised median age of observed cases and deaths in both RF and LM models. The models highlighted other plausible roles of population density, testing intensity and co-morbidity prevalence, but yielded uncertain results as regards exposure to common parasitic infections.ConclusionsThe average age of a population seems to be an important country-level factor explaining both transmissibility and the median age of observed cases and deaths, even after age-standardisation. Potential associations between endemic infections and COVID-19 are worthy of further exploration but seem unlikely, from this analysis, to be key drivers of the variation in observed COVID-19 epidemic trends. Our study was limited by the availability of outcome data and its causally uncertain ecological design, with the observed distribution of age amongst reported cases and deaths suggesting key differences in surveillance and testing strategy and capacity by country and the representativeness of case reporting of infection. Research at subnational and individual level is needed to explore hypotheses further.
Evaluating the suitability of the case-crossover design under changing baseline outcome risk: A simulation of ambient temperature and preterm birth
Authors: Carrión Daniel , Rush Johnathan , Colicino Elena , Just Allan C. 
Published: February 2021

AbstractCase-crossover (CCO) studies are case-only within-person analyses of associations between acute exposures and outcomes. By design, the CCO is not confounded by time-invariant characteristics. CCO studies assume stable baseline outcome risks. Since the baseline risk of birth increases secularly over gestation, the validity of CCOs of preterm birth (PTB) is not clear. We simulated associations between temperature and PTB in New York State using historical ambient temperature data for LaGuardia Airport and PTB data from the CDC using different control period durations. CCO analyses were conducted with conditional logistic regression. We calculated bias according to the absolute difference between the simulated and estimated effects in the natural log scale, and found that 2-week, 28-day, and 1-month stratified control period selection yielded negligible bias across all simulated effects. Coverage of the 95% confidence intervals was also appropriate across all three control selection strategies. Our findings suggest that the time-stratified CCO should yield appropriate inference in studies of ambient temperature and preterm birth.
A whole-brain imaging-based systems approach to understand origin of addiction in binge-like drinking model
Authors: Stefaniuk Marzena , Pawłowska Monika , Nowicka Klaudia , Barański Marcin , Zielinski Zbigniew , Bijoch Łukasz , Legutko Diana , Majka Piotr , Bednarek Sylwia , Jermakow Natalia , Wójcik Daniel , Kaczmarek Leszek 
Published: February 2021

AbstractMany fundamental questions on addiction development are still unanswered. These questions are frequently difficult to address by examining a single brain structure, but can best be addressed at the systems level. Neurons create functional networks that change over time, since brain regions may work together differently in different contexts. We offer a framework for describing the nature behind alcohol binge drinking and the transition to addiction. The present study investigated whole-brain c-Fos expression following reexposure to alcohol in a model of binge-like drinking in mice in IntelliCage. We developed a dedicated image computational workflow to identify c-Fos-positive cells in three-dimensional images obtained after optical tissue clearing and whole-brain imaging in the light-sheet microscope. We analyzed functional networks and brain modularity following reexposure to alcohol. c-Fos levels in brains from animals that were reexposed to alcohol were clearly different from binge drinking animals. Structures involved in reward processing, decision making and characteristic for addictive behaviors stood out particularly. In alcohol reexposed animals differently active structures either gained or lost correlation when compared to the control group.
A genetic program boosts mitochondrial function to power macrophage tissue invasion
Authors: Emtenani Shamsi , Martin Elliott T. , Gyoergy Attila , Bicher Julia , Genger Jakob-Wendelin , Hurd Thomas R. , Köcher Thomas , Bergthaler Andreas , Rangan Prashanth , Siekhaus Daria E. 
Published: February 2021

SUMMARYMetabolic adaptation to changing demands underlies homeostasis. During inflammation or metastasis, cells leading migration into challenging environments require an energy boost, however what controls this capacity is unknown. We identify a previously unstudied nuclear protein, Atossa, as changing metabolism inDrosophila melanogasterimmune cells to promote tissue invasion. Atossa’s vertebrate orthologs, FAM214A-B, can fully substitute for Atossa, indicating functional conservation from flies to mammals. Atossa increases mRNA levels of Porthos, an unstudied RNA helicase and two metabolic enzymes, LKR/SDH and GR/HPR. Porthos increases translation of a gene subset, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Respiration measurements and metabolomics indicate that Atossa and Porthos powers up mitochondrial oxidative phosphorylation to produce sufficient energy for leading macrophages to forge a path into tissues. As increasing oxidative phosphorylation enables many crucial physiological responses, this unique genetic program may modulate a wide range of cellular behaviors beyond migration.
Human microglia extensively reconstitute in humanized BLT mice with human interleukin-34 transgene and support HIV-1 brain infection
Authors: Zhang Jianshui , Lohani Saroj Chandra , Cheng Yilun , Wang Tao , Guo Lili , Kim Woong-Ki , Gorantla Santhi , Li Qingsheng 
Published: February 2021

AbstractHumanized bone marrow-liver-thymic (hu-BLT) mice develop a functional immune system in periphery but have a limited reconstitution of human myeloid cells, especially microglia, in CNS. Further, whether bone marrow derived hematopoietic stem and progenitor cells (HSPCs) can enter the brain and differentiate into microglia in adults remains controversial. To close these gaps, in this study we unambiguously demonstrated that human microglia in CNS were extensively reconstituted in adult NOG mice with human interleukin-34 transgene (hIL34 Tg) from circulating CD34+ HSPCs but no in hu-BLT NOG mice, providing strong evidence that human CD34+ HSPCs can enter adult brain and differentiate into microglia in CNS in the presence of hIL34. Further, the human microglia in the CNS of hu-BLT-hIL34 NOG mice robustly supported HIV-1 infection reenforcing the notion that microglia are the most important target cells of HIV-1 in CNS and demonstrating its great potential as an in vivo model for studying HIV-1 pathogenesis and evaluating curative therapeutics in both periphery and CNS compartments.