bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for outcomes of COVID-19 patients: an observational study of 795 572 patients in Russia
Authors: Demkina A.E. , Morozov S.P. , Vladzymyrskyy A.V. , Kljashtorny V.G. , Guseva O.I. , Pugachev P.S. , Artemova O.R. , Reshetnikov R.V. , Gombolevskiy V.A. , Ryabinina M.N. 
Published: November 2020

AbstractBackgroundSeveral factors that could affect survival and clinical outcomes of COVID-19 patients require larger studies and closer attention.ObjectiveTo investigate the impact of factors including whether COVID-19 was clinically or laboratory-diagnosed, influenza vaccination, former or current tuberculosis, HIV, and other comorbidities on the hospitalized patients’ outcomes.DesignObservational nationwide cohort study.PatientsAll subjects, regardless of age, admitted to 4,251 Russian hospitals indexed in the Federal Register of COVID-19 patients between March 26, 2020, and June 3, 2020. All included patients for which complete clinical data were available were divided into two cohorts, with laboratory- and clinically verified COVID-19.MeasurementsWe analyzed patients’ age and sex, COVID-19 ICD-10 code, the length of the hospital stay, and whether they required ICU treatment or invasive mechanical ventilation. The other variables for analysis were: verified diagnosis of pulmonary disease, cardiovascular disease, diseases of the endocrine system, cancer/malignancy, HIV, tuberculosis, and the data on influenza vaccination in the previous six months.ResultsThis study enrolled 705,572 COVID-19 patients aged from 0 to 121 years, 50.4% females. 164,195 patients were excluded due to no confirmed COVID-19 (n=143,357) or insufficient and invalid clinical data (n=20,831). 541,377 participants were included in the study, 413,950 (76.5%) of them had laboratory-verified COVID-19, and 127,427 patients (23.5%) with the clinical verification. Influenza vaccination reduced the risk of transfer to the ICU (OR 0.76), mechanical ventilation requirement (OR 0.74), and the risk of death (HR 0.77). TB increased the mortality risk (HR 1.74) but reduced the likelihood of transfer to the ICU (OR 0.27). HIV comorbidity significantly increased the risks of transfer to the ICU (OR 2.46) and death (HR 1.60). Patients with the clinically verified COVID-19 had a shorter duration of hospital stay (HR 1.45) but a higher risk of mortality (HR 1.08) and the likelihood of being ventilated (OR 1.36). According to the previously published data, age, male sex, endocrine disorders, and cardiovascular diseases increased the length of hospital stay, the risk of death, and transfer to the ICU.LimitationsThe study did not include a control group of subjects with no COVID-19. Because of that, some of the identified factors could not be specific for COVID-19.ConclusionsInfluenza vaccination could reduce the severity of the hospitalized patients’ clinical outcomes, including mortality, regardless of age, social, and economic group. The other factors considered in the study did not reduce the assessed risks, but we observed several non-trivial associations that may optimize the management of COVID-19 patients.
Emergence of Novel SARS-CoV-2 Variants in the Netherlands
Authors: Urhan Aysun , Abeel Thomas 
Published: November 2020

AbstractIn this study, we analyzed SARS-CoV-2 genomes in the Netherlands, in the context of global viral population since the beginning of the pandemic. We have identified the most variant sites on the whole genome as well as the stable, conserved ones on the S and N proteins. We found four mutations, S:D614G, NSP12b:P314L, NSP3:F106F, to be the most frequent ones that dominate the SARS-CoV-2 population outside of China. We detected novel variants of SARS-CoV-2 almost unique to the Netherlands that form localized clusters, indicating community spread. We emphasize that while SARS-CoV-2 is evolving, and the number of mutations from the reference sequence is increasing, we observe only little diversity in the new variants as we enter the later stages of the pandemic. Our analyses suggest we have diverged away from the current SARS-CoV-2 reference enough that the reference should be re-evaluated to represent the current viral population more accurately. We assert our work provides valuable information on the genetic diversity of SARS-CoV-2 and its local dynamics in the Netherlands, especially for DNA-based diagnostic, therapeutic or vaccine development against COVID-19. We suggest sequence-based analyses should opt for a consensus representation to adequately cover the genomic variation observed.
Human genomics of the humoral immune response against polyomaviruses
Authors: Hodel F. , Chong A.Y. , Scepanovic P. , Xu Z.M. , Naret O. , Thorball C.W. , Rüeger S. , Marques-Vidal P. , Vollenweider P. , Begemann M. , Ehrenreich H. , Brenner N. , Bender N. , Waterboer T. , Mentzer A. J. , Hill A.V.S. , Hammer C. , Fellay J. 
Published: November 2020

AbstractHuman polyomaviruses are widespread in human populations and are able to cause severe disease in immunocompromised individuals. There remains an incomplete understanding of the potential impact of human genetic variation on inter-individual responses to polyomaviruses.To identify human genetic determinants of the humoral immune response against polyomaviruses, we performed genome-wide association studies and meta-analyses of qualitative and quantitative immunoglobulin G (IgG) responses against the major capsid protein VP1 of Human polyomavirus 6 (HPyV6), BK virus (BKPyV), JC virus (JCPyV), Merkel Cell Polyomavirus (MCPyV) and WU polyomavirus (WUPyV), in a total of 15,660 individuals of European ancestry from CoLaus, UK Biobank and GRAS, three independent studies.We observed significant associations for all tested viruses: JCPyV, HPyV6 and MCPyV associated with HLA class II variation; BKPyV and JCPyV with variants in the FUT2 gene, responsible for secretor status; MCPyV with variants in the STING1 gene, involved in interferon induction; and WUPyV with a functional variant in the MUC1 gene, previously associated with risk for gastric cancer.These results provide insights into the genetic control of a family of very prevalent human viruses, highlighting genes and pathways that play a modulating role in human humoral immunity.
Gender-affirming care, mental health, and economic stability in the time of COVID-19: a global cross-sectional study of transgender and non-binary people
Authors: Jarrett Brooke A. , Peitzmeier Sarah M. , Restar Arjee , Adamson Tyler , Howell Sean , Baral Stefan , Beckham S. Wilson 
Published: November 2020

ABSTRACTBackgroundTransgender and non-binary people are disproportionately burdened by barriers to quality healthcare, mental health challenges, and economic hardship. This study examined the impact of the novel coronavirus disease (COVID-19) pandemic and subsequent control measures on gender-affirming care, mental health, and economic stability among transgender and non-binary people globally.MethodsWe collected global cross-sectional data from 964 transgender and non-binary adult users of the Hornet and Her apps from April to August 2020 to characterize changes in gender-affirming care, mental health, and economic stability as a result of the COVID-19 pandemic. We conducted Poisson regression models to assess if access to gender-affirming care and ability to live according to one’s gender were related to depressive symptoms, anxiety, and changes in suicidal ideation.ResultsIndividuals resided in 76 countries, including Turkey (27.4%,n=264/964) and Thailand (20.6%,n=205). A majority were non-binary (66.8%,n=644) or transfeminine (29.4%,n=283). Due to the COVID-19 pandemic, 55.0% (n=320/582) reported reduced access to gender- affirming resources, and 38.0% (n=327/860) reported reduced time lived according to their gender. About half screened positive for depression (50.4%,442/877) and anxiety (45.8%,n=392/856). One in six (17.0%,n=112/659) expected losses of health insurance, and 77.0% (n=724/940) expected income reductions. The prevalence of depressive symptoms, anxiety, and increased suicidal ideation were 1.63 (95% CI: 1.36-1.97), 1.61 (95% CI: 1.31-1.97), and 1.74 (95% CI: 1.07-2.82) times higher for individuals whose access to gender- affirming resources was reduced versus not.DiscussionThe COVID-19 pandemic has reduced access to gender-affirming resources and the ability of transgender and non-binary people to live according to their gender worldwide. These reductions may drive the increased depressive symptoms, anxiety, and suicidal ideation reported in this sample. To improve transgender and non-binary health globally, increased access to gender-affirming resources should be achieved through policies (e.g., digital prescriptions), flexible interventions (e.g., telehealth), and support for existing transgender health initiatives.
Applying Machine Learning to Evaluate for Fibrosis in Chronic Hepatitis C
Authors: Akella Aravind , Akella Sudheer 
Published: November 2020

AbstractMachine learning (ML) is proving to be an appealing analytical tool as modern medicine progresses towards preventative care. Clinical risk prediction models built using ML offer the potential for more effective diagnostic modalities without the need for invasive procedures. With such models, healthcare practitioners may be empowered towards a more preventative approach in management, thus improving clinical outcomes. The management of patients with chronic Hepatitis C is incomplete without considering the presence and extent of liver fibrosis, which is traditionally assessed with biopsy of liver tissue. Although non-invasive testing alternatives to liver biopsy are gaining popularity, they are considered limited due to inadequate accuracy and were designed to be complementary to liver biopsy. In this study, our aim is to build clinical risk models to predict the extent of fibrosis in patients with chronic Hepatitis C using ML algorithms. We developed nine ML algorithms based on an Egyptian cohort dataset, relying only on patient demographics and commonly-obtained serum laboratory values. One of our models was able to evaluate for fibrosis with an accuracy of 0.81, sensitivity of 0.95, and specificity of 0.73. Furthermore, most of our models outperformed many current diagnostic alternatives to liver biopsy for the evaluation of fibrosis in this patient population.
Inflexible Updating of the Self-Other Divide During a Social Context in Autism; Psychophysical, Electrophysiological, and Neural Network Modeling Evidence
Authors: Noel Jean-Paul , Paredes Renato , Terrebonne Emily , Feldman Jacob I. , Woynaroski Tiffany , Cascio Carissa J. , Seriès Peggy , Wallace Mark T. 
Published: November 2020

AbstractAutism spectrum disorder (ASD) is a heterogenous disorder predominantly characterized by social and communicative differences, but increasingly recognized to also alter (multi)sensory function. To face the heterogeneity and ubiquity of ASD, researchers have proposed models of statistical inference operating at the level of ‘computations’. Here, we attempt to bridge both across domains – from social to sensory – and levels of description – from behavioral computations to neural ensemble activity to a biologically-plausible artificial neural network – in furthering our understanding of autism. We do so by mapping visuo-tactile peri-personal space (PPS), and examining its electroencephalography (EEG) correlates, in individuals with ASD and neurotypical individuals during both a social and non-social context given that (i) the sensory coding of PPS is well understood, (ii) this space is thought to distinguish between self and other, and (iii) PPS is known to remap during social interactions. In contrast to their neurotypical counterparts, psychophysical and EEG evidence suggested that PPS does not remap in ASD during a social context. To account for this observation, we then employed a neural network model of PPS and demonstrate that PPS remapping may be driven by changes in neural gain operating at the level of multisensory neurons. Critically, under the anomalous excitation-inhibition (E/I) regime of ASD, this gain modulation does not result in PPS resizing. Overall, our findings are in line with recent statistical inference accounts suggesting diminished flexibility in ASD, and further these accounts by demonstrating within an example relevant for social cognition that such inflexibility may be due to E/I imbalances.
Constructing Graphs from Genetic Encodings
Authors: Barabási Dániel L. , Czégel Dániel 
Published: November 2020

AbstractOur understanding of real-world connected systems has benefited from studying their evolution, from random wirings and rewirings to growth-dependent topologies. Long overlooked in this search has been the role of the innate: networks that connect based on identity-dependent compatibility rules. Inspired by the genetic principles that guide brain connectivity, we derive a network encoding process that can utilize wiring rules to reproducibly generate specific topologies. To illustrate the representational power of this approach, we propose stochastic and deterministic processes for generating a wide range of network topologies. Specifically, we detail network heuristics that generate structured graphs, such as feed-forward and hierarchical networks. In addition, we characterize a Random Genetic (RG) family of networks, which, like Erdős-Rényi graphs, display critical phase transitions, however their modular underpinnings lead to markedly different behaviors under targeted attacks. The proposed framework provides a relevant null-model for social and biological systems, where diverse metrics of identity underpin a node’s preferred connectivity.
Plasma proteomics reveals tissue-specific cell death and mediators of cell-cell interactions in severe COVID-19 patients
Authors: Filbin Michael R. , Mehta Arnav , Schneider Alexis M. , Kays Kyle R. , Guess Jamey R. , Gentili Matteo , Fenyves Bánk G. , Charland Nicole C. , Gonye Anna L.K. , Gushterova Irena , Khanna Hargun K. , LaSalle Thomas J. , Lavin-Parsons Kendall M. , Lilly Brendan M. , Lodenstein Carl L. , Manakongtreecheep Kasidet , Margolin Justin D. , McKaig Brenna N. , Rojas-Lopez Maricarmen , Russo Brian C. , Sharma Nihaarika , Tantivit Jessica , Thomas Molly F. , Gerszten Robert E. , Heimberg Graham S. , Hoover Paul J. , Lieb David J. , Lin Brian , Ngo Debby , Pelka Karin , Reyes Miguel , Smillie Christopher S. , Waghray Avinash , Wood Thomas E. , Zajac Amanda S. , Jennings Lori L. , Grundberg Ida , Bhattacharyya Roby P. , Parry Blair Alden , Villani Alexandra-Chloé , Sade-Feldman Moshe , Hacohen Nir , Goldberg Marcia B. 
Published: November 2020

SummaryCOVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 COVID-19 patients and 78 symptomatic controls over serial timepoints using two complementary approaches, we uncover COVID-19 host immune and non-immune proteins not previously linked to this disease. Integration of plasma proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage, plasmablast, and T cell effector proteins. By comparing patients who died to severely ill patients who survived, we identify dynamic immunomodulatory and tissue-associated proteins associated with survival, providing insights into which host responses are beneficial and which are detrimental to survival. We identify intracellular death signatures from specific tissues and cell types, and by associating these with angiotensin converting enzyme 2 (ACE2) expression, we map tissue damage associated with severe disease and propose which damage results from direct viral infection rather than from indirect effects of illness. We find that disease severity in lung tissue is driven by myeloid cell phenotypes and cell-cell interactions with lung epithelial cells and T cells. Based on these results, we propose a model of immune and epithelial cell interactions that drive cell-type specific and tissue-specific damage in severe COVID-19.
Comparative gene pathway analysis during adolescent binge-EtOH exposure, withdrawal, and following abstinence
Authors: Nato Alejandro Q. , Ata Ul Mustafa Hafiz , Sexton Hannah G. , Moore Scott D. , Denvir James , Primerano Donald A. , Risher Mary-Louise 
Published: November 2020

ABSTRACTIntroductionBinge drinking is common among adolescents and young adults and is associated with an increased risk of developing alcohol use disorder (AUD) and long-term cognitive deficits. We analyzed RNA-seq data from male Sprague Dawley rats to identify candidate genes that may play a role in the acute and chronic changes in cognitive function during binge-like adolescent alcohol/EtOH exposure and after a period of abstinence.MethodsAt postnatal day (PND) 30, male rats received chronic intermittent EtOH across 16 days. RNA was extracted from hippocampal tissue and sequenced at two acute timepoints, PND 35 and PND 46, and after 24 days forced abstinence (PND 70). We processed RNA-seq data, compiled gene counts, and performed normalization and differential expression analysis (DESeq2). Gene set enrichment analysis was performed through the R package fgsea. Gene sets of the Molecular Signatures Database (MSigDB) collections were used to identify gene pathways that were dysregulated following EtOH exposure. We also evaluated overlapping gene pathways that were affected across all timepoints.ResultsMultiple gene pathway analyses revealed that EtOH has robust effects on neuroinflammation, cellular remodeling, sleep, and bioenergetics. Changes were heavily dependent on whether gene expression was assessed during acute EtOH exposure or after abstinence. Genes involved in sleep regulation were selectively impacted during the acute timepoints, whereas dysregulation of genes involved in bioenergetics were only impacted after abstinence. The most striking changes occurred in genes that regulate neuroinflammatory processes and cellular remodeling.ConclusionThese data reveal acute and chronic effects of EtOH on multiple gene pathways that persist across analytic approaches and identify genes that have increased sensitivity to EtOH. These findings contribute to our understanding of the temporal effects of adolescent EtOH exposure and how gene pathway dysregulation contributes to the protracted emergence of neuronal remodeling in the hippocampus during a critical period of brain maturation.
Seeking an optimal dosing regimen for OZ439-DSM265 combination therapy for treating uncomplicated falciparum malaria
Authors: Dini Saber , Zaloumis Sophie G , Price David J , Gobeau Nathalie , Kümmel Anne , Cherkaoui Mohammed , Moehrle Joerg J , McCarthy James S , Simpson Julie A 
Published: November 2020

AbstractThe efficacy of Artemisinin-based Combination Therapies (ACTs), the first- line treatments of uncomplicated falciparum malaria, has been declining in malaria endemic countries due to the emergence of malaria parasites resistant to these com- pounds. Novel alternative therapies are needed urgently to prevent the likely surge in morbidity and mortality due to failing ACTs. This study investigates the efficacy of the combination of two novel drugs, OZ439 and DSM265, using a biologically informed within-host mathematical model that accounts for the pharmacodynamic interaction between the two drugs. Model parameters were estimated using data from healthy volunteers infected with falciparum malaria collected from four trials: three that administered OZ439 and DSM265 alone, and the fourth a combination of OZ439-DSM265. Posterior predictive simulations of the model were performed to determine efficacious dosing regimens. One such regimen that predicted at least 90% of infected individuals cured 42 days after the administration of the drugs, while within the tolerable dose range, is 800 mg of OZ439 and 450 mg of DSM265. Our model can be used to inform future phase 2 and 3 clinical trials of OZ439-DSM265, fast-tracking the deployment of this combination therapy in the regions where ACTs are failing.
Altered cortical thickness development in 22q11.2 deletion syndrome and association with psychotic symptoms
Authors: Bagautdinova Joëlle , Zöller Daniela , Schaer Marie , Padula Maria Carmela , Mancini Valentina , Schneider Maude , Eliez Stephan 
Published: November 2020

AbstractSchizophrenia has been extensively associated with reduced cortical thickness (CT), and its neurodevelopmental origin is increasingly acknowledged. However, the exact timing and extent of alterations occurring in preclinical phases remain unclear. With a high prevalence of psychosis, 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that represents a unique opportunity to examine brain maturation in high-risk individuals. In this study, we quantified trajectories of CT maturation in 22q11DS and examined the association of CT development with the emergence of psychotic symptoms. Longitudinal structural MRI data with 1-6 time points were collected from 324 participants aged 5-35 years (N=148 22q11DS, N=176 controls), resulting in a total of 636 scans (N=334 22q11DS, N=302 controls). Mixed model regression analyses were used to compare CT trajectories between participants with 22q11DS and controls. Further, CT trajectories were compared between participants with 22q11DS who developed (N=61, 146 scans), or remained exempt of (N=47; 98 scans) positive psychotic symptoms during development. Compared to controls, participants with 22q11DS showed widespread increased CT, focal reductions in the posterior cingulate gyrus and superior temporal gyrus (STG), and accelerated cortical thinning during adolescence, mainly in fronto-temporal regions. Within 22q11DS, individuals who developed psychotic symptoms showed exacerbated cortical thinning in the right STG. Together, these findings suggest that genetic predisposition for psychosis is associated with increased CT starting from childhood and altered maturational trajectories of CT during adolescence, affecting predominantly fronto-temporal regions. In addition, accelerated thinning in the STG may represent an early biomarker associated with the emergence of psychotic symptoms.
A Novel Primer Probe Set for Detection of SARS-CoV-2 by Sensitive Droplet Digital PCR
Authors: Wang Fang , Pervaiz Umar , Tian Hongwei , Mariam Algahdary Omar Ahmed Omar , Hamid Mahasin Abdallah Mohammed , Wang Degui 
Published: November 2020

AbstractBackgroundThe current increase in the spread of (SARS-CoV-2) critically needs a multitarget diagnostic assays to promote analytical sensitivity to facilitate the public health actions.ObjectiveThe aim of this study was to develop a new primer-probe set targeting N gene of SARS-CoV-2 to improve the sensitivity for detection of COVID-19(Corona Virus Disease 2019)in multiplex rRT-PCR (Reversetranscript Realtime PCR) and ddPCR (Droplet Digital PCR).ResultsWe designed primers/probes set N(LZU3) targeting the N gene of 2019-nCov and proved its sensitivity in both rRT-PCR and ddPCR. When the quantity of template was 105 copies/reaction, the mean Ct value of N(LZU3) was 32.563, the detection rate was 91.7%. If the quantity of template was 52.5 copies/reaction, the mean Ct value of N(LZU3) was 33.835, and the detection rate was 83.3%, which were similar with that of N(CDC) and N(USA). The calculated lower limit of detection (LOD) of the new primer-probe set N(LZU3) used in rRT-PCR was 118 copies/reaction. We also did one-step ddPCR for detection the same serial dilution of RNA template. It shows good linearity for primer/probe sets N(LZU3). The calculated lower limit of detection (LOD) of N(LZU3) was 22.4 copies/reaction, which was 1.12 copies/ul.ConclusionThe novel primer-probe set(LZU3) targeting N gene of SARS-CoV-2 could be both used in rRT-PCR and ddPCR with better sensitivity, furthermore, ddPCR method had higer sensitivity than rRT-PCR, hence it could significantly improve SARS-CoV-2 detection efficiency in low virus load and asymptomatic infection.