bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards reduction in bias in epidemic curves due to outcome misclassification through Bayesian analysis of time-series of laboratory test results: Case study of COVID-19 in Alberta, Canada and Philadelphia, USA
Authors: Burstyn Igor , Goldstein Neal D. , Gustafson Paul 
Published: April 2020

AbstractThe aim of our work was to better understand misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves. We examined publically available time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, about the sensitivity and specificity of the PCR-based diagnostic test. Data originated from Alberta, Canada (available on 3/28/2020) and city of Philadelphia, USA (available on 3/31/2020). Our analysis revealed that the data were compatible with near-perfect specificity but it was challenging to gain information about sensitivity (prior and posterior largely overlapped). We applied these insights to uncertainty/bias analysis of epidemic curves into jurisdictions under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the observed and adjusted epidemic curves likely fall within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. In the extreme scenario, hundreds of undiagnosed cases, even among tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves, a task for which the Bayesian method we presented is well-suited.
Testing the association between blood type and COVID-19 infection, intubation, and death
Authors: Zietz Michael , Zucker Jason , Tatonetti Nicholas P. 
Published: April 2020

AbstractThe rapid global spread of the novel coronavirus SARS-CoV-2 has strained healthcare and testing resources, making the identification and prioritization of individuals most at-risk a critical challenge. Recent evidence suggests blood type may affect risk of severe COVID-19. We used observational healthcare data on 14,112 individuals tested for SARS-CoV-2 with known blood type in the New York Presbyterian (NYP) hospital system to assess the association between ABO and Rh blood types and infection, intubation, and death. We found slightly increased infection prevalence among non-O types. Risk of intubation was decreased among A and increased among AB and B types, compared with type O, while risk of death was increased for type AB and decreased for types A and B. We estimated Rh-negative blood type to have a protective effect for all three outcomes. Our results add to the growing body of evidence suggesting blood type may play a role in COVID-19.
Fast SARS-CoV-2 detection by RT-qPCR in preheated nasopharyngeal swab samples
Authors: Alcoba-Florez Julia , González-Montelongo Rafaela , Íñigo-Campos Antonio , García-Martínez de Artola Diego , Gil-Campesino Helena ,   The Microbiology Technical Support Team, Ciuffreda Laura , Valenzuela-Fernández Agustín , Flores Carlos 
Published: April 2020

AbstractThe current reference for COVID-19 diagnosis is based on the detection of SARS-CoV-2 on RNA extracts using one-step retrotranscription and quantitative PCR (RT-qPCR). Based on the urgent need for high-throughput COVID-19 screening, we tested the performance of three alternative, simple and affordable protocols to rapidly detect SARS-CoV-2, overcoming the long and tedious RNA extraction step. Although with an average increase of 6.1 (± 1.6) cycles compared to standard tests with RNA extracts, we show that RT-qPCR yielded consistent results in nasopharyngeal swab samples that were subject to a direct 70°C incubation for 10 min. Our findings provide viable options to overcome any supply chain issue and help to increase the throughput of diagnostic tests by using any qPCR device, thereby complementing standard COVID-19 testing.
Brief Analysis of the ARIMA model on the COVID-19 in Italy
Authors: Ding Guorong , Li Xinru , Jiao Fan , Shen Yang 
Published: April 2020

AbstractCoronavirus disease 2019 (COVID-19) has been considered as a global threat infectious disease, and various mathematical models are being used to conduct multiple studies to analyze and predict the evolution of this epidemic. We statistically analyze the epidemic data from February 24 to March 30, 2020 in Italy, and proposes a simple time series analysis model based on the Auto Regressive Integrated Moving Average (ARIMA). The cumulative number of newly diagnosed and newly diagnosed patients in Italy is preprocessed and can be used to predict the spread of the Italian COVID-19 epidemic. The conclusion is that an inflection point is expected to occur in Italy in early April, and some reliable points are put forward for the inflection point of the epidemic: strengthen regional isolation and protection, do a good job of personal hygiene, and quickly treat the team leaders existing medical forces. It is hoped that the “City Closure” decree issued by the Italian government will go in the right direction, because this is the only way to curb the epidemic.
Temporal rise in the proportion of both younger adults and older adolescents among COVID-19 cases in Germany: evidence of lesser adherence to social distancing practices?
Authors: Goldstein Edward , Lipsitch Marc 
Published: April 2020

AbstractBackgroundThere is uncertainty about the role of different age groups in propagating the SARS-CoV-2 epidemics in different countries, particularly under current social distancing practices.MethodsWe used the Robert Koch Institute data on weekly COVID-19 cases in different age groups in Germany. To minimize the effect of changes in healthcare seeking behavior (e.g. for older adults) and testing practices, we included the following eight 5-year age groups in the analyses: 10-14y through 45-49y. For each age group g, we considered the proportion PL(g) of individuals in age group g among all detected cases aged 10-49y during weeks 13-14, 2020 (later period), as well as corresponding proportion PE(g) for weeks 10-11, 2020 (early period), and defined the relative risk RR(g) for the age group g to be the ratio RR (g) = PL(g)/PE(g). For each pair of age groups g1, g2, a higher value of RR(g1) compared to RR(g2), or, alternatively, a value above 1 for the odds ratio OR (g1, g2) = RR(g1)/RR(g2) for a COVID-19 case to be in group g1 vs. g2 for the later vs. early periods is interpreted as the relative increase in the population incidence of SARS-Cov-2 in the age group g1 compared to g2 for the later vs. early period.ResultsThe relative risk RR(g) was highest for individuals aged 20-24y (RR=1.4(95% CI (1.27,1.55))), followed by individuals aged 15-19y (RR=1.14(0.99,1.32)), aged 30-34y (RR= 1.07(0.99,1.16)), aged 25-29y (RR= 1.06(0.98,1.15)), aged 35-39y (RR=0.95(0.87,1.03)), aged 40-44y (RR=0.9(0.83,0.98)), aged 45-49y (RR=0.83(0.77,0.89)) and aged 10-14y (RR=0.78(0.64,0.95)). For the age group 20-24y, the odds ratio relative to any other age group for a case to be during the later vs. early period was significantly above 1. For the age group 15-19y, the odds ratio relative to any other age group either above 35y or 10-14y for a case to be during the later vs. early period was significantly above 1.ConclusionsThe observed relative increase with time in the prevalence of individuals aged 15-34y (particularly those aged 20-24y) among detected COVID-19 cases in Germany is unlikely to be explained by increases in the likelihood of seeking medical care or the likelihood of being tested for individuals in those age groups compared to individuals aged 35-49y or 10-14y, and should be indicative of the actual increase in the prevalence of individuals aged 15-34y among SARS-CoV-2 infections in the German population. That increase likely reflects elevated mixing among individuals aged 15-34y (particularly those aged 20-24y) compared to other age groups, possibly due to lesser adherence to social distancing practices.
Distal-less genesDlx1/Dlx2repress oligodendrocyte genesis through transcriptional inhibition ofOlig2expression in the developing vertebrate forebrain
Authors: Jiang Qiang , Zagozewski Jamie , Godbout Roseline , Eisenstat David D. 
Published: April 2020

ABSTRACTIn this study, we demonstrate that mouse DLX2 binds to theOlig2gene locus in mouse embryonic forebrainin vivo. We further confirm the specificity and the transcriptional repressive effect of the bindingin vitro. Furthermore, loss ofDlx1/2function leads to increasedOlig2expression in the ventral embryonic mouse forebrainin vivo. As well, we demonstrate that chicken DLX1 binds to one chicken Olig2 gene domainin vitro, and overexpression ofDlx1is sufficient to repressOlig2expression in the developing chicken forebrainin ovo. Chicken DLX1 with a mutation eliminating its DNA binding ability is unable to bind to theOlig2probein vitro, and abrogates its repressive function onOlig2expressionin ovo. Our results establish thatDlx1/2is both necessary and sufficient to repress oligodendrocyte specification mediated via direct transcriptional inhibition ofOlig2expression in the developing vertebrate forebrain.
DIVA: natural navigation inside 3D images using virtual reality
Authors: Beheiry Mohamed El , Godard Charlotte , Caporal Clément , Marcon Valentin , Ostertag Cécilia , Sliti Oumaima , Doutreligne Sébastien , Fournier Stéphane , Hajj Bassam , Dahan Maxime , Masson Jean-Baptiste 
Published: April 2020

AbstractAs three-dimensional microscopy becomes commonplace in biological re-search, there is an increasing need for researchers to be able to view experimental image stacks in a natural three-dimensional viewing context. Through stereoscopy and motion tracking, commercial virtual reality headsets provide a solution to this important visualization challenge by allowing researchers to view volumetric objects in an entirely intuitive fashion. With this motivation, we present DIVA, a user-friendly software tool that automatically creates detailed three-dimensional reconstructions of raw experimental image stacks that are integrated in virtual reality. In DIVA’s immersive virtual environment, users can view, manipulate and perform volumetric measurements on their microscopy images as they would to real physical objects. In contrast to similar solutions, our software provides high-quality volume rendering with native TIFF file compatibility. We benchmark the software with diverse image types including those generated by confocal, light-sheet and electron microscopy. DIVA is available athttps://diva.pasteur.frand will be regularly updated.
High glucose attenuates Ca2+influx in cytotoxic T lymphocytes upon target recognition
Authors: Zou Huajiao , Schwär Gertrud , Zhao Renping , Alansary Dalia , Yin Deling , Schwarz Eva C. , Niemeyer Barbara , Qu Bin 
Published: April 2020

AbstractThe killing efficiency of cytotoxic T lymphocytes (CTLs) is tightly regulated by intracellular Ca2+concentration. Glucose is the key energy source for CTLs, lack of which significantly impairs CTL activation, proliferation and effector functions. The impact of high glucose on Ca2+influx in CTLs remains largely elusive. In this work, we stimulated primary human CD8+T cells in medium containing either 25 mM (high glucose, HG) or 5.6 mM glucose (normal glucose, NG). We found that store-operated calcium entry (SOCE) induced by thapsigargin (Tg) is elevated in HG-cultured CTLs compared to their counterparts in NG. Unexpectedly, the Ca2+influx elicited by recognition of target cells is reduced in HG-cultured CTLs. Under HG condition,STIM1andSTIM2, the calcium sensors in the endoplasmic reticulum (ER), were down-regulated;ORAI1, the main structural component of calcium-release activated channels, remained unchanged, whereasORAI2andORAI3were up-regulated. The fraction of necrosis of HG-cultured CTLs was enhanced after killing without affecting glucose uptake. Thus, our findings reveal that HG has a distinctive impact on Tg-evoked SOCE and target recognition-induced Ca2+influx in CTLs and causes more CTL death after killing, suggesting a novel regulatory role of high glucose on modulating CTL functions.
Protein Kinase D promotes activity-dependent AMPA receptor endocytosis in hippocampal neurons
Authors: Oueslati Morales Carlos O. , Ignácz Attila , Bencsik Norbert , Rátkai Anikó Erika , Lieb Wolfgang S. , Eisler Stephan A. , Szűcs Attila , Schlett Katalin , Hausser Angelika 
Published: April 2020

AbstractAMPA type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the brain. The continuous trafficking of AMPARs into and out of synapses is a core feature of synaptic plasticity, which is considered as the cellular basis of learning and memory. The molecular mechanisms underlying the postsynaptic AMPAR trafficking, however, are still not fully understood. In this work, we demonstrate that the Protein Kinase D (PKD) family promotes basal and activity-induced AMPAR endocytosis in primary hippocampal neurons. Pharmacological inhibition of PKD increased synaptic levels of GluA1-containing AMPARs, slowed down their endocytic trafficking and increased neuronal network activity. By contrast, ectopic expression of constitutive active PKD decreased the synaptic level of AMPARs, while increasing their co-localization with early endosomes. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity.
3D genome evolution and reorganization in theDrosophila melanogasterspecies group
Authors: Torosin Nicole S. , Anand Aparna , Golla Tirupathi Rao , Cao Weihuan , Ellison Christopher E. 
Published: April 2020

AbstractTopologically associating domains, or TADs, are functional units that organize chromosomes into 3D structures of interacting chromatin. TADs play an important role in regulating gene expression by constraining enhancer-promoter contacts; there is evidence that deletion of TAD boundaries leads to aberrant expression of neighboring genes. While the mechanisms of TAD formation have been well-studied, current knowledge on the extent of TAD conservation across species is inconclusive. Due to the integral role TADs play in gene regulation, their structure and organization is expected to be conserved during evolution. However, more recent research suggests that TAD structures diverge relatively rapidly. We use Hi-C chromosome conformation capture to measure evolutionary conservation of whole TADs and TAD boundary elements betweenD. melanogasterandD. triauraria, two early-branching species from themelanogasterspecies group which diverged ~15 million years ago. We find that 75% of TAD boundaries are orthologous while only 25% of TAD domains are conserved and these are enriched for Polycomb-repressed chromatin. Our results show that TADs have been reorganized since the common ancestor ofD. melanogasterandD. triauraria, yet the sequence elements that specify TAD boundaries remain highly conserved. We propose that evolutionary divergence in 3D genome organization results from shuffling of conserved boundary elements across chromosomes, breaking old TADs and creating new TAD architectures. This result supports the existence of distinct TAD subtypes: some may be evolutionarily flexible while others remain highly conserved due to their importance in restricting gene-regulatory element interactions.
Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis
Authors: Kumar Nilesh , Mishra Bharat , Mehmood Adeel , Athar Mohammad , Mukhtar M. Shahid 
Published: April 2020

AbstractCOVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrated multiomics data pertaining to lung epithelial cells-specific coexpression network and human interactome to generateCalu-3-specific human-SARS-CoV-2Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity.
The preservative sorbic acid targets respiration, explaining the resistance of fermentative spoilage-yeast species
Authors: Stratford M. , Vallières C. , Geoghegan I.A. , Archer D.B. , Avery S.V. 
Published: April 2020

ABSTRACTA small number (10-20) of yeast species cause major spoilage in foods. Spoilage yeasts of soft drinks are resistant to preservatives like sorbic acid and they are highly fermentative, generating large amounts of carbon dioxide gas. Conversely, many yeast species derive energy from respiration only and most of these are sorbic acid-sensitive, so prevented from causing spoilage. This led us to hypothesize that sorbic acid may specifically inhibit respiration. Tests with respiro-fermentative yeasts showed that sorbic acid was more inhibitory to bothSaccharomyces cerevisiaeandZygosaccharomyces bailiiduring respiration (of glycerol) compared with fermentation (of glucose). The respiration-only speciesRhodotorula glutiniswas equally sensitive when growing on either carbon source, suggesting that ability to ferment glucose specifically enables sorbic acid-resistant growth. Sorbic acid inhibited the respiration process more strongly than fermentation. We present a dataset supporting a correlation between the level of fermentation and sorbic acid resistance across 191 yeast species. Other weak acids, C2 – C8, inhibited respiration in accordance with their partition coefficients, suggesting that effects on mitochondrial respiration were related to membrane localization rather than cytosolic acidification. Supporting this, we present evidence that sorbic acid causes production of reactive oxygen species, the formation of petite (mitochondria-defective) cells, and Fe-S cluster defects. This work rationalises why yeasts that can grow in sorbic acid-preserved foods tend to be fermentative in nature. This may inform more-targeted approaches for tackling these spoilage organisms, particularly as the industry migrates to lower-sugar drinks, which could favour respiration over fermentation in many spoilage yeasts.IMPORTANCESpoilage by yeasts and moulds is a major contributor to food and drink waste, which undermines food security. Weak acid preservatives like sorbic acid help to stop spoilage but some yeasts, commonly associated with spoilage, are resistant to sorbic acid. Different yeasts generate energy for growth by the processes of respiration and/or fermentation. Here we show that sorbic acid targets the process of respiration, so fermenting yeasts are more resistant. Fermentative yeasts are also those usually found in spoilage incidents. This insight helps to explain the spoilage of sorbic acid-preserved foods by yeasts and can inform new strategies for effective control. This is timely as sugar content of products like soft drinks is being lowered, which may favour respiration over fermentation in key spoilage yeasts.
Photosynthetic sea slugs inflict protective changes to the light reactions of the chloroplasts they steal from algae
Authors: Havurinne Vesa , Tyystjärvi Esa 
Published: April 2020

AbstractSacoglossan sea slugs are able to maintain functional chloroplasts inside their own cells, and mechanisms that allow preservation of the chloroplasts are unknown. We found that the slugElysia timidainflicts changes to the photosynthetic light reactions of the chloroplasts it steals from the algaAcetabularia acetabulum. Working with a large continuous laboratory culture of both the slugs (>500 individuals) and their prey algae, we show that the plastoquinone pool of slug chloroplasts remains oxidized, which can suppress reactive oxygen species formation. Slug chloroplasts also rapidly build up a strong proton motive force upon a dark-to-light transition, which helps them to rapidly switch on photoprotective non-photochemical quenching of excitation energy. Finally, our results suggest that chloroplasts insideE. timidarely on flavodiiron proteins as electron sinks during rapid changes in light intensity. These photoprotective mechanisms are expected to contribute to the long-term functionality of the chloroplasts inside the slugs.
Selection and gene flow define polygenic barriers between incipient butterfly species
Authors: Van Belleghem Steven M. , Cole Jared M. , Montejo-Kovacevich Gabriela , Bacquet Caroline N. , McMillan W. Owen , Papa Riccardo , Counterman Brian A. 
Published: April 2020

AbstractCharacterizing the genetic architecture of species boundaries remains a difficult task. Hybridizing species provide a powerful system to identify the factors that shape genomic variation and, ultimately, identify the regions of the genome that maintain species boundaries. Unfortunately, complex histories of isolation, admixture and selection can generate heterogenous genomic landscapes of divergence which make inferences about the regions that are responsible for species boundaries problematic. However, as the signal of admixture and selection on genomic loci varies with recombination rate, their relationship can be used to infer their relative importance during speciation. Here, we explore patterns of genomic divergence, admixture and recombination rate among hybridizing lineages across theHeliconius eratoradiation. We focus on the incipient species,H. eratoandH. himera, and distinguish the processes that drive genomic divergence across three contact zones where they frequently hybridize. Using demographic modeling and simulations, we infer that periods of isolation and selection have been major causes of genome-wide correlation patterns between recombination rate and divergence between these incipient species. Upon secondary contact, we found surprisingly highly asymmetrical introgression between the species pair, with a paucity ofH. eratoalleles introgressing into theH. himeragenomes. We suggest that this signal may result from a current polygenic species boundary between the hybridizing lineages. These results contribute to a growing appreciation for the importance of polygenic architectures of species boundaries and pervasive genome-wide selection during the early stages of speciation with gene flow.