bluuebunny/crossref_metadata_2025_split huggingface dataset:
The misleading illusion of COVID-19 confirmed case data: alternative estimates and a monitoring tool
Authors: Macías-Ordóñez Rogelio , Villaseñor-Amador Damián 
Published: May 2020

AbstractConfirmed Case Data have been widely cited during the current COVID-19 pandemic as an estimate of the spread of the SARS-CoV-2 virus. However, their central role in media, official reports and decision-making may be undeserved and misleading. Previously published Infection Fatality Rates were weighted by age structure in the 50 countries with more reported deaths to obtain country-specific rates. For each country, the number of infections up to the Infection Date (23 days ago = Incubation Period + Onset to Death period) and the present percentage of immune population were estimated using Infection Fatality Rate, the number of reported deaths (which is less prone to undersampling), and projecting back to Infection Date. We then estimated a Detection Index for each country as the percentage of estimated infections that confirmed cases represent. Assuming that detection remains constant after Infection Date, we estimated the number of deaths and the estimated percentage of the population of each country expected to be immune up to 23 days into the future. Estimated Infection Fatality Rates are higher in Europe. In most countries, confirmed cases currently represent less than 30% of estimated infections on Infection Date, and this value decreases with time. Countries with flat curves throughout the pandemic show the lowest immunity percentages and these values seem unlikely to change in the near future, suggesting that they remain vulnerable to new outbreaks. Estimates for some countries with low Infection Fatality Rates suggest a still steep increase in the number of casualties in the next three weeks. Countries that did not control initial outbreaks seem to have reached higher immunity percentages, although mostly still under 5%. We provide the code to monitor the trajectories of these estimates in 178 countries throughout the COVID-19 pandemic.
SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors
Authors: Shomuradova Alina S. , Vagida Murad S. , Sheetikov Savely A. , Zornikova Ksenia V. , Kiryukhin Dmitry , Titov Aleksei , Peshkova Iuliia O. , Khmelevskaya Alexandra , Dianov Dmitry V. , Malasheva Maria , Shmelev Anton , Serdyuk Yana , Bagaev Dmitry V. , Pivnyuk Anastasia , Shcherbinin Dmitrii S. , Maleeva Alexandra V. , Shakirova Naina T. , Pilunov Artem , Malko Dmitry B. , Khamaganova Ekaterina G. , Biderman Bella , Ivanov Alexander , Shugay Mikhail , Efimov Grigory A. 
Published: May 2020

SummaryUnderstanding the hallmarks of the adaptive immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed the antibody and T-cell reactivity in COVID-19 convalescent patients and healthy donors sampled both prior to and during the pandemic. The numbers of SARS-CoV-2-specific T cells were increased in healthy donors examined during COVID-19. Combined with the absence of symptoms and humoral response across that group, this finding suggests that some individuals might be protected by T-cell cross-reactivity. In convalescent patients we observed public and diverse T-cell response to SARS-CoV-2 epitopes, revealing T-cell receptor motifs with germline-encoded features. Bulk CD4+ and CD8+ T-cell responses to Spike glycoprotein were mediated by groups of homologous T-cell receptors, some of them shared across multiple donors. Overall, our results demonstrate that T-cell response to SARS-CoV-2, including the identified set of specific T-cell receptors, can serve as a useful biomarker for surveying viral exposure and immunity.
Spread dynamics of SARS-CoV-2 epidemic in China: a phylogenetic analysis
Authors: GuoHu Hong , Qing Guan , Qing Mao 
Published: May 2020

AbstractBackgroundSince December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic and infected millions of people. As the first country proclaimed the SARS-CoV-2 outbreak, China implemented travel ban measure, and curbed the epidemic quickly. We performed a phylogenetic analysis to reveal the spread dynamics detail of SARS-CoV-2 in China and the impact of travel ban on SARS-CoV-2.MethodFocusing on SARS-CoV-2 sequences collected from China in public database released as of March 31, 2020, we performed a Bayesian inference phylogenetic analyses to estimate the effective population size (Ne) curve of SARS-CoV-2 epidemic. Furthermore, we displayed the geographic spread mode of SARS-CoV-2 among different China regions by using Bayesian stochastic search variable selection (BSSVS) method.ResultsThe most recent common ancestor (tMRCA) of SARS-CoV-2 in China was traced back to December 9, 2019. According the Ne estimation and geographic spread reconstruction, January 25, 2020 was considered as the crucial time point during the SARS-CoV-2 epidemic in China,which was 2 days after the travel ban implemented. On the point, the tendency of viral population size changed from ascending to decreasing, and the cross-regional spread paths were blocked.ConclusionsTravel ban is an effective measure to intervene in the spread of SARS-CoV-2, It is necessary to continue efforts in research for prevention and control measures.
Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying ‘high-risk’ comorbidities in a paediatric population
Authors: Issitt RW , Booth J , Bryant WA , Spiridou A , Taylor AM , du Pré P , Ramnarayan P , Hartley J , Cortina-Borja M , Moshal K , Dunn H , Hemingway H , Sebire NJ 
Published: May 2020

AbstractBackgroundThere is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social ‘shielding’ (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Children’s Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities.MethodsRoutine clinical data were extracted retrospectively from the Institution’s Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance.FindingsBetween 1st March and 15th May 2020, 166 children (<18 years of age) presented to a specialist children’s hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9 - 14] years vs median 1 [0.1 - 5.7.5] years respectively, p<0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p=0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p<0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p=0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population.InterpretationCOVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing ‘COVID-19 vulnerable’ medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented.
Heat Shock Protein 27 Immune Complex Upregulates LDLR Expression Thereby Reducing Plasma Cholesterol and Atherogenesis
Authors: Chen Yong-Xiang , Shi Chunhuai , Deng Jingti , Diao Catherine , Maarouf Nadia , Rosin Matthew , Shrivastava Vipul , Hu Angie A. , Bharadwa Sonya , Adijiang Ayinuer , Ulke-Lemee Annegret , Gwilym Brenig , Hellmich Alexandria , Malozzi Christopher , Batulan Zarah , Dean Jonathan L. E. , Ramirez F. Daniel , Liu Jingwen , Gerthoffer William T. , O’Brien Edward R. 
Published: May 2020

AbstractElevated Heat Shock Protein 27 levels predict relative freedom from cardiovascular events. In ApoE-/-mice HSP27 over-expression or twice daily subcutaneous injections reduce blood and plaque cholesterol levels, inflammation and atherogenesis. While natural antibodies to HSP27 are present in human blood their role is unknown. Here, we show that blood levels of both HSP27 and anti-HSP27 IgG antibodies are elevated in healthy controls compared to patients with cardiovascular disease. ApoE-/-mice vaccinated with recombinant HSP25 (murine ortholog) develop elevated anti-HSP25 IgG antibodies and reduced levels of cholesterol, inflammation and atherosclerosis. The effects on cholesterol metabolism were divergent: increased hepatic LDLR expression and reduced plasma PCSK9 levels.In vitro, a polyclonal anti-HSP27 IgG antibody combined with rHSP27 to upregulate hepatocyte LDLR expression via an NF-kB-dependent pathway that is independent of SREBP2 expression and intracellular cholesterol levels. HSP27 immunotherapy represents a novel means of lowering not only cholesterol but also PCSK9.
Validation of an LC-MS/MS Assay for the Simultaneous Determination of Bictegravir, Doravirine, and Raltegravir in Human Plasma
Authors: Schauer Amanda P. , Sykes Craig , Cottrell Mackenzie L , Kashuba Angela DM 
Published: May 2020

AbstractBictegravir (BIC), an integrase inhibitor, and doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor, were recently approved by the US FDA for HIV treatment and are recommended first line treatment options. Because certain clinical scenarios warrant using them in combination, we developed a fully validated LC-MS/MS method for simultaneous measurement of BIC and DOR, along with a legacy integrase inhibitor, raltegravir (RAL), in human plasma over a clinically relevant 1000-fold range for each analyte. These analytes were extracted from the plasma by protein precipitation with their stable, isotopically labeled internal standards (BIC-d5,13C6-DOR, and RAL-d6). Following extraction, samples were analyzed by reverse phase chromatography on a Waters Atlantis T3 C18 (50×2.1mm, 3um particle size) column with subsequent detection by electrospray ionization in positive ion mode on an AB Sciex API-5000 triple quadrupole mass spectrometer. The assay was linear (R2>0.994) over the selected calibration ranges (20.0-20,000ng/mL (BIC), 3.00-3,000ng/mL (DOR), and 10.0-10,000 (RAL)). The assay was accurate (inter-assay %Bias ≤±8.5) and precise (inter-assay %CV ≤11.4). This method was validated according to FDA guidance for industry and can be used to assess the pharmacokinetics of two newly approved antiretrovirals, or to support therapeutic drug monitoring for modern antiretroviral therapy.
Tracking cortical representations of facial attractiveness using time-resolved representational similarity analysis
Authors: Kaiser Daniel , Nyga Karen 
Published: May 2020

AbstractWhen we see a face, we rapidly form an impression of its attractiveness. Here, we investigated how rapidly representations of facial attractiveness emerge in the human brain. In an EEG experiment, participants viewed 100 face photographs and rated them for their attractiveness. Using time-resolved representational similarity analysis on the EEG data, we reveal representations of facial attractiveness after 150-200ms of cortical processing. Interestingly, we show that these representations are related to individual participants’ personal attractiveness judgments, suggesting that already early perceptual representations of facial attractiveness convey idiosyncratic attractiveness preferences. Further, we show that these early representations are genuinely related to attractiveness, as they are neither explained by other high-level face attributes, such as face sex or age, nor by features extracted by an artificial deep neural network model of face processing. Together, our results demonstrate early, individually specific, and genuine representations of facial attractiveness, which may underlie fast attractiveness judgments.
Network Preservation Reveals Shared and Unique Biological Processes Associated with Chronic Alcohol Abuse in NAc and PFC
Authors: Vornholt Eric , Mamdani Mohammed , Drake John , McMichael Gowon , Taylor Zachary N. , Bacanu Silviu-Alin , Miles Michael F. , Vladimirov Vladimir I. 
Published: May 2020

ABSTRACTBackgroundExcessive alcohol consumption has become a growing public health concern worldwide due to the potential development of alcohol dependence (AD). Prolonged alcohol abuse leads to dysregulation of the mesocorticolimbic pathway (MCL), effectively disrupting executive functioning and the allostatic conditioning of reward response.MethodsWe utilized weighted gene co-expressed network analysis (WGCNA) and network preservation using a case/control study design (n=35) to identify unique and shared biological processes dysregulated in AD in the prefrontal cortex (PFC) and nucleus accumbens (NAc). We used correlation and regression analyses to identify mRNA/miRNA interactions and local expression quantitative trait loci (cis-eQTL) to identify genetic regulatory mechanisms for networks significantly associated with AD.ResultsNetwork analyses revealed 6 and 3 significant mRNA modules from the NAc and PFC, respectively. Network preservation revealed immune response upregulation in both regions, whereas cellular morphogenesis/localization and cilia-based cell projection processes were upregulated only in the NAc. We observed 4 significantly correlated module eigengenes (ME) between the significant mRNA and miRNA modules in PFC, and 6 significant miRNA/mRNA ME correlations in NAc, with the mir-449a/b cluster emerging as a potential regulator for cellular morphogenesis/localization dysregulation in this brain region. Finally, we identified cis-eQTLs (37 mRNA and 9 miRNA in NAc, and 17 mRNA and 16 miRNA in PFC) which potentially mediate alcohol’s effect in a brain region-specific manner.ConclusionIn agreement with previous reports, we observed a generalized upregulation of immune response processes in subjects with AD, that highlights alcohol’s neurotoxic properties, while simultaneously demonstrating distinct molecular changes in subcortical brain regions as a result of chronic alcohol abuse. Such changes further support previous neuroimaging and physiological studies that emphasize the distinct roles PFC and NAc play in the development of addictive behaviors.
Inclusion of Variants Discovered from Diverse Populations Improves Polygenic Risk Score Transferability
Authors: Cavazos Taylor B. , Witte John S. 
Published: May 2020

ABSTRACTThe majority of polygenic risk scores (PRS) have been developed and optimized in individuals of European ancestry and may have limited generalizability across other ancestral populations. Understanding aspects of PRS that contribute to this issue and determining solutions is complicated by disease-specific genetic architecture and limited knowledge of sharing of causal variants and effect sizes across populations. Motivated by these challenges, we undertook a simulation study to assess the relationship between ancestry and the potential bias in PRS developed in European ancestry populations. Our simulations show that the magnitude of this bias increases with increasing divergence from European ancestry, and this is attributed to population differences in linkage disequilibrium and allele frequencies of European discovered variants, likely as a result of genetic drift. Importantly, we find that including into the PRS variants discovered in African ancestry individuals has the potential to achieve unbiased estimates of genetic risk across global populations and admixed individuals. We confirm our simulation findings in an analysis of HbA1c, asthma, and prostate cancer in the UK Biobank. Given the demonstrated improvement in PRS prediction accuracy, recruiting larger diverse cohorts will be crucial—and potentially even necessary—for enabling accurate and equitable genetic risk prediction across populations.
Effect of methanol fixation on single-cell RNA sequencing data
Authors: Wang Xinlei , Yu Lei , Wu Angela 
Published: May 2020

AbstractSingle-cell RNA sequencing (scRNA-seq) has led to remarkable progress in our understanding of tissue heterogeneity in health and disease. Recently, the need for scRNA-seq sample fixation has emerged in many scenarios, such as when samples need long-term transportation, or when experiments need to be temporally synchronized. Methanol fixation is a simple and gentle method that has been routinely applied in scRNA-seq. Yet, concerns remain that fixation may result in biases which may change the RNA-seq outcome. We adapted an existing methanol fixation protocol and performed scRNA-seq on both live and methanol fixed cells. Analyses of the results show methanol fixation can faithfully preserve biological related signals, while the discrepancy caused by fixation is subtle and relevant to library construction methods. By grouping transcripts based on their lengths and GC content, we find that transcripts with different features are affected by fixation to different degrees in full-length sequencing data, while the effect is alleviated in Drop-seq result. Our deep analysis reveals the effects of methanol fixation on sample RNA integrity and elucidates the potential consequences of using fixation in various scRNA-seq experiment designs.
Global Infodemiology of COVID-19: Focus on Google Web Searches and Instagram Hashtags
Authors: Rovetta Alessandro , Bhagavathula Akshaya Srikanth 
Published: May 2020

AbstractBackgroundThough ‘infodemiological’ methods have been used in COVID-19 research, an examination of the extent of infodemic monikers (misinformation) use on the Internet remains limited.ObjectiveTo investigate Internet search behavior related to COVID-19 and examine the circulation of infodemic monikers through two platforms—Google and Instagram—during the current global pandemic.MethodsUsing Google Trends and Instagram hashtags (#), we explored Internet search activities and behaviors related to the COVID-19 pandemic from February 20, 2020, to May 06, 2020. We investigated the names used to identify the virus, health and risk perception, life during the lockdown, and information related to the adoption of COVID-19 infodemic monikers. We computed the average peak volume (APC) with a 95% confidence interval (CI) during the study period for the monikers.ResultsThe top five COVID-19-related terms in the Google searches were “coronavirus”, “corona”, “COVID”, “virus”, “corona virus”, and “COVID-19”. Countries with a higher number of COVID-19 cases had a higher number of COVID-19 queries on Google. The monikers “coronavirus ozone”, “coronavirus laboratory”, “coronavirus 5G”, “coronavirus conspiracy” and “coronavirus bill gates” were widely circulated on the Internet. Searches about ‘tips and cures’ for COVID-19 spiked in relation to the U.S. president speculating about a ‘miracle cure’ and suggesting the injection of disinfectant to treat the virus. Around two-thirds (66.1%) of Instagram users used the hashtags “COVID-19”, and “coronavirus” to disperse virus-related information.ConclusionGlobally, there is a growing interest in COVID-19, and numerous infodemic monikers continue to circulate on the Internet. Based on our findings, we hope to encourage mass media regulators and health organizers to be vigilant and diminish the use and circulation of these infodemic monikers on the Internet, to decrease the spread of misinformation.
Assessment of Workers’ Personal Vulnerability to COVID-19 Using “COVID-AGE”
Authors: Coggon David , Croft Peter , Cullinan Paul , Williams Anthony 
Published: May 2020

AbstractDecisions on fitness for employment that entails a risk of contracting Covid-19 require an assessment of the worker’s personal vulnerability should infection occur. Using recently published UK data, we have developed a risk model that provides estimates of personal vulnerability to Covid-19 according to sex, age, ethnicity, and various comorbidities. Vulnerability from each risk factor is quantified in terms of its equivalence to added years of age. Addition of the impact from each risk factor to an individual’s true age generates their “Covid-age”, a summary measure representing the age of a healthy UK white male with equivalent vulnerability. We discuss important limitations of the model, including current scientific uncertainties and limitations on generalisability beyond the UK setting and its use beyond informing assessments of individual vulnerability in the workplace. As new evidence becomes available, some of these limitations can be addressed. The model does not remove the need for clinical judgement or for other important considerations when managing occupational risks from Covid-19.
Rising evidence of COVID-19 transmission potential to and between animals: do we need to be concerned?
Authors: Akhmetzhanov Andrei R. , Linton Natalie M. , Nishiura Hiroshi 
Published: May 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—the virus that causes coronavirus disease (COVID-19)—has been detected in domestic dogs and cats, raising concerns of transmission from, to, or between these animals. There is currently no indication that feline- or canine-to-human transmission can occur, though there is rising evidence of the reverse. To explore the extent of animal-related transmission, we aggregated 17 case reports on confirmed SARS-CoV-2 infections in animals as of 15 May 2020. All but two animals fully recovered and had only mild respiratory or digestive symptoms. Using data from probable cat-to-cat transmission in Wuhan, China, we estimated the basic reproduction number R0 under this scenario at 1.09 (95% confidence interval: 1.05, 1.13). This value is much lower than the R0 reported for humans and close to one, indicating that the sustained transmission between cats is unlikely to occur. Our results support the view that the pet owners and other persons with COVID-19 in close contact with animals should be cautious of the way they interact with them.