bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of remdesivir in COVID-19 patients with a simulated two-arm controlled study
Authors: Hsu Chen-Yang , Lai Chao-Chih , Yen Amy Ming-Fang , Chen Sam Li-Sheng , Chen Hsiu-Hsi 
Published: May 2020

AbstractWhile the recent study on the compassionate use of remdesivir for COVID-19 patients has shown a 68% clinical improvement7 it is a one-arm study that renders the evaluation of the efficacy in reducing death and the length of stay of hospitalization intractable due to a lacking of the control group. We came up with a two-arm controlled study design to simulate the treated and the untreated (control group) group by applying two respective transition models to the empirical data on dynamics of the disease severity (Figure 2 of the original article7) that are classified into low- (no and low oxygen supplement), medium- (non-invasive ventilator and high oxygen supplement), and high-(ECMO and invasive ventilator) from enrolment until discharge, death or the end of follow-up. By using a simulated two-arm controlled study, the remdesivir treatment group as opposed to the control group led to a statistically significantly 29% (95% CI: 22-35%) reduction of death from COVID-19. The treated group also revealed a 33% (95% CI 28-38%) significantly higher odds of discharge than the control group. The median time to discharge for the treated group (5.5 days, 16.5 days, and 29.5 days for low-, medium-, and high-risk state, respectively) was around half of those of the control arm. Our results with a simulated two-arm controlled study have not only corroborated the efficacy of remdesivir but also made great contribution to designing a further large-scale randomized controlled trial. They have significant implications for reducing transmission probability and infectious time of COVID-19 patients when contacting with susceptible health care workers during hospitalization.Key PointsQuestionWhat is the efficacy of remdesivir in reducing advanced disease state or death from COVID-19 and the length of stay of hospitalization?FindingsRemdesivir treatment results in a 33% significantly higher odds of discharge, a 29% significantly lower risk of death, and a 39% significantly lower risk for the combined endpoint of severe status and death. The median time to discharge for the remdesivir treated group was around half of the median time-to-discharge compared with the control arm.MeaningRemdesivir is effective in treating COVID-19 patients in terms of enhancing recovery and accelerating discharge.
Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients
Authors: Tuaillon E , Bolloré K , Pisoni A , Debiesse S , Renault C , Marie S , Groc S , Niels C , Pansu N , Dupuy AM , Morquin D , Foulongne V , Bourdin A , Le Moing V , Van de Perre P 
Published: May 2020

AbstractSARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests.In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA.Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell® POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon).The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.
The disproportionate rise in COVID-19 cases among Hispanic/Latinx in disadvantaged communities of Orange County, California: A socioeconomic case-series
Authors: Chow Daniel S. , Soun Jennifer E. , Glavis-Bloom Justin , Weinberg Brent , Chang Peter D. , Mutasa Simukayi , Monuki Edwin , Park Jung In , Xie Xiaohui , Bota Daniela , Wu Jie , Thompson Leslie , Amin Alpesh N. , Khan Saahir , Boden-Albala Bernadette 
Published: May 2020

AbstractBackgroundRecent epidemiological evidence has demonstrated a higher rate of COVID-19 hospitalizations and deaths among minorities. This pattern of race-ethnic disparities emerging throughout the United States raises the question of what social factors may influence spread of a highly transmissible novel coronavirus. The purpose of this study is to describe race-ethnic and socioeconomic disparities associated with COVID-19 in patients in our community in Orange County, California and understand the role of individual-level factors, neighborhood-level factors, and access to care on outcomes.MethodsThis is a case-series of COVID-19 patients from the University of California, Irvine (UCI) across six-weeks between 3/12/2020 and 4/22/2020. Note, California’s shelter-in-place order began on 3/19/2020. Individual-level factors included race-ethnicity status were recorded. Neighborhood-level factors from census tracts included median household income, mean household size, proportion without a college degree, proportion working from home, and proportion without health insurance were also recorded.ResultsA total of 210-patients tested were COVID-19 positive, of which 73.3% (154/210) resided in Orange County. Hispanic/Latinx patients residing in census tracts below the median income demonstrated exponential growth (rate = 55.9%, R2 = 0.9742) during the study period. In addition, there was a significant difference for both race-ethnic (p < 0.001) and income bracket (p = 0.001) distributions prior to and after California’s shelter-in-place. In addition, the percentage of individuals residing in neighborhoods with denser households (p = 0.046), lower levels of college graduation (p < 0.001), health insurance coverage (p = 0.01), and ability to work from home (p < 0.001) significantly increased over the same timeframe.Conclusions and RelevanceOur study examines the race-ethnic disparities in Orange County, CA, and highlights vulnerable populations that are at increased risk for contracting COVID-19. Our descriptive case series illustrates that we also need to consider socioeconomic factors, which ultimately set the stage for biological and social disparities.
The Social and Economic Factors Underlying the Incidence of COVID-19 Cases and Deaths in US Counties
Authors: Mukherji Nivedita 
Published: May 2020

AbstractThis paper uncovers the socioeconomic and health/lifestyle factors that can explain the differential impact of the coronavirus pandemic on different parts of the United States. Using a dynamic panel representation of an epidemiological model of disease spread, the paper develops a Vulnerability Index for US counties from daily reported number of cases over a 20-day period of rapid disease growth. County-level economic, demographic, and health factors are used to explain the differences in the values of this index and thereby the transmission and concentration of the disease across the country. These factors are also used to examine the number of reported deaths. The paper finds that counties with high median income have a high incidence of cases but reported lower deaths. Income inequality as measured by the Gini coefficient, is found to be associated with more deaths and more cases. The remarkable similarity in the distribution of cases across the country and the distribution of distance-weighted international passengers served by the top international airports is evidence of the spread of the virus by way of international travel. The distributions of age, race, and health risk factors such as obesity and diabetes are found to be particularly significant factors in explaining the differences in mortality across counties. Counties with better access to health care as measured by the number of primary care physicians per capita have lower deaths, and so do places with more health awareness as measured by flu vaccination prevalence. Environmental health conditions such as the amount of air pollution is found to be associated with counties with higher deaths from the virus. It is hoped that research such as these will help policymakers to develop risk factors for each region of the country to better contain the spread of infectious diseases in the future.
Assessing biosynthetic gene cluster diversity in a multipartite nutritional symbiosis between herbivorous turtle ants and conserved gut symbionts
Authors: Chanson Anaïs , Moreau Corrie S. , Duplais Christophe 
Published: May 2020

AbstractIn insect-microbe nutritional symbioses the symbiont supplements the low nutrient diet of the host by producing amino acids and vitamins, and degrading lignin or polysaccharides. In multipartite mutualisms composed of multiple symbionts from different taxonomical orders, it has been suggested that in addition to the genes involved in the nutritional symbiosis the symbionts maintain genes responsible for the production of metabolites putatively playing a role in the maintenance and interaction of the bacterial communities living in close proximity. To test this hypothesis we investigated the diversity of biosynthetic gene clusters (BGCs) in the genomes and metagenomes of obligate gut symbionts associated with the herbivorous turtle ants (genus:Cephalotes). We studied 17Cephalotesspecies collected across several geographical areas to reveal that (i) mining bacterial metagenomes and genomes provides complementary results demonstrating the robustness of this approach with metagenomic data, (ii) symbiotic gut bacteria have a high diversity of BGCs which is correlated with host geography but not host phylogeny, (iii) the majority of the BGCs comes from the bacteria involved in the nutritional symbiosis supporting conserved metabolic functions for colonization, communication and competition in the gut environment, (iv) phylogenetic analysis of arylpolyene, polyketide (PK), and siderophore shows high similarity between BGCs of a single symbiont across different ant host species, while non-ribosomal peptide (NRP) shows high similarity between BGCs from different bacterial orders within a single host species suggesting multiple mechanisms for genome evolution of these obligate mutualistic gut bacteria.
Deletion of porcineBOLLcauses defective acrosomes and subfertility in Yorkshire boars
Authors: Nosková Adéla , Wurmser Christine , Crysnanto Danang , Sironen Anu , Uimari Pekka , Fries Ruedi , Andersson Magnus , Pausch Hubert 
Published: May 2020

SummaryA recessively inherited sperm defect of Finnish Yorkshire boars was detected more than a decade ago. Affected boars produce ejaculates that contain many spermatozoa with defective acrosomes resulting in low fertility and small litters. The acrosome defect was mapped to porcine chromosome 15 but the causal mutation has not been identified. We re-analyzed microarray-derived genotypes of affected boars and performed a haplotype-based association study. Our results confirmed that the acrosome defect maps to a 12.24 Mb segment of porcine chromosome 15 (P=3.38 × 10−14). In order to detect the mutation causing defective acrosomes, we sequenced the genomes of two affected and three unaffected boars to an average coverage of 11-fold. Read-depth analysis revealed a 55 kb deletion that segregates with the acrosome defect. The deletion encompasses theBOLLgene encoding the boule homolog, RNA binding protein which is an evolutionarily highly conserved member of theDAZ(deleted in azoospermia) gene family. Lack ofBOLLexpression causes spermatogenic arrest and sperm maturation failure in many species. Our study reveals that absence ofBOLLis associated with a sperm defect also in pigs. The acrosomes of boars that carry the deletion in the homozygous state are defective suggesting that lack of porcine BOLL compromises acrosome formation. Our findings warrant further research to investigate the precise function ofBOLLduring spermatogenesis and sperm maturation in pigs.
Conserved long-range base pairings are associated with pre-mRNA processing of human genes
Authors: Kalmykova Svetlana , Kalinina Marina , Denisov Stepan , Mironov Alexey , Skvortsov Dmitry , Guigó Roderic , Pervouchine Dmitri 
Published: May 2020

AbstractThe ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. While DNA employs it for genome replication, RNA molecules fold into complicated secondary and tertiary structures. Current knowledge on functional RNA structures in human protein-coding genes is focused on locally-occurring base pairs. However, chemical crosslinking and proximity ligation experiments have demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved long-range RNA structures in the human transcriptome, which consists of 916,360 pairs of conserved complementary regions (PCCRs). PCCRs tend to occur within introns proximally to splice sites, suppress intervening exons, circumscribe circular RNAs, and exert an obstructive effect on cryptic and inactive splice sites. The double-stranded structure of PCCRs is supported by a significant decrease of icSHAPE nucleotide accessibility, high abundance of A-to-I RNA editing sites, and frequent occurrence of forked eCLIP peaks nearby. Introns with PCCRs show a distinct splicing pattern in response to RNA Pol II slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. Additionally, transcript starts and ends are strongly enriched in regions between complementary parts of PCCRs, leading to an intriguing hypothesis that RNA folding coupled with splicing could mediate co-transcriptional suppression of premature cleavage and polyadenylation events. PCCR detection procedure is highly sensitive with respect tobona fidevalidated RNA structures at the expense of having a high false positive rate, which cannot be reduced without loss of sensitivity. The catalog of PCCRs is visualized through a UCSC Genome Browser track hub.
Resolving spatial complexities of hybridization in the context of the gray zone of speciation in North American ratsnakes (Pantherophis obsoletuscomplex)
Authors: Burbrink Frank T. , Gehara Marcelo , Myers Edward A. 
Published: May 2020

AbstractInferring the history of divergence between species in a framework that permits the presence of gene flow has been crucial for characterizing the gray zone of speciation, which is the period of time where lineages have diverged but have not yet achieved strict reproductive isolation. However, estimates of both divergence times and rates gene flow often ignore spatial information, for example the formation and shape of hybrid zones. Using population genomic data from the eastern ratsnake complex (Pantherophis obsoletus), we infer phylogeographic groups, gene flow, changes in demography, the timing of divergence, and hybrid zone widths. We examine the spatial context of diversification by linking migration and timing of divergence to the location and widths of hybrid zones. Artificial neural network approaches are applied to understand how landscape features and past climate have influenced population genetic structure among these lineages prior to hybridization. Rates of migration between lineages are associated with the width and shape of hybrid zones. Timing of divergence is not related to migration rate across species pairs and is therefore a poor proxy for inferring position in the gray zone. However, timing of divergence is related to the number of loci weakly introgressing through hybrid zones.
Adapt or perish: Evolutionary rescue in a gradually deteriorating environment
Authors: Marrec Loïc , Bitbol Anne-Florence 
Published: May 2020

AbstractWe investigate the evolutionary rescue of a microbial population in a gradually deteriorating environment, through a combination of analytical calculations and stochastic simulations. We consider a population destined for extinction in the absence of mutants, which can only survive if mutants sufficiently adapted to the new environment arise and fix. We show that mutants that appear later during the environment deterioration have a higher probability to fix. The rescue probability of the population increases with a sigmoidal shape when the product of the carrying capacity and of the mutation probability increases. Furthermore, we find that rescue becomes more likely for smaller population sizes and/or mutation probabilities if the environment degradation is slower, which illustrates the key impact of the rapidity of environment degradation on the fate of a population. We also show that our main conclusions are robust across various types of adaptive mutants, including specialist and generalist ones, as well as mutants modeling antimicrobial resistance evolution. We further express the average time of appearance of the mutants that do rescue the population and the average extinction time of those that do not. Our methods can be applied to other situations with continuously variable fitnesses and population sizes, and our analytical predictions are valid in the weak-to-moderate mutation regime.
Dispersal alters the nature and scope of sexually antagonistic variation
Authors: Flintham Ewan O , Savolainen Vincent , Mullon Charles 
Published: May 2020

AbstractIntralocus sexual conflict, or sexual antagonism, occurs when alleles have opposing fitness effects in the two sexes. Previous theory suggests that sexual antagonism is a driver of genetic variation by generating balancing selection. However, most of these studies assume that populations are well-mixed, neglecting the effects of spatial subdivision. Here we use mathematical modelling to show that limited dispersal changes evolution at sexually antagonistic autosomal and X-linked loci due to inbreeding and sex-specific kin competition. We find that if the sexes disperse at different rates, kin competition within the philopatric sex biases intralocus conflict in favour of the more dispersive sex. Furthermore, kin competition diminishes the strength of balancing selection relative to genetic drift, reducing genetic variation in small subdivided populations. Meanwhile, by decreasing heterozygosity, inbreeding reduces the scope for sexually antagonistic polymorphism due to nonadditive allelic effects, and this occurs to a greater extent on the X-chromosome than autosomes. Overall, our results indicate that spatial structure is a relevant factor in predicting where sexually antagonistic alleles might be observed. We suggest that sex-specific dispersal ecology and demography can contribute to interspecific and intragenomic variation in sexual antagonism.
Promoter activity-based case-control association study onSLC6A4highlighting hypermethylation and altered amygdala volume in male patients with schizophrenia
Authors: Ikegame Tempei , Bundo Miki , Okada Naohiro , Murata Yui , Koike Shinsuke , Sugawara Hiroko , Saito Takeo , Ikeda Masashi , Owada Keiho , Fukunaga Masaki , Yamashita Fumio , Koshiyama Daisuke , Natsubori Tatsunobu , Iwashiro Norichika , Asai Tatsuro , Yoshikawa Akane , Nishimura Fumichika , Kawamura Yoshiya , Ishigooka Jun , Kakiuchi Chihiro , Sasaki Tsukasa , Abe Osamu , Hashimoto Ryota , Iwata Nakao , Yamasue Hidenori , Kato Tadafumi , Kasai Kiyoto , Iwamoto Kazuya 
Published: May 2020

AbstractAssociations between altered DNA methylation of the serotonin transporter (5-HTT)-encoding geneSLC6A4and early life adversity, mood and anxiety disorders, and amygdala reactivity have been reported. However, few studies have examined epigenetic alterations ofSLC6A4in schizophrenia (SZ). We examined CpG sites ofSLC6A4, whose DNA methylation levels have been reported to be altered in bipolar disorder, using three independent cohorts of patients with SZ and age-matched controls. We found significant hypermethylation of a CpG site inSLC6A4in male patients with SZ in all three cohorts. We showed that chronic administration of risperidone did not affect the DNA methylation status at this CpG site using common marmosets, and thatin vitroDNA methylation at this CpG site diminished the promoter activity ofSLC6A4. We then genotyped the 5-HTT-linked polymorphic region (5-HTTLPR) and investigated the relationship among 5-HTTLPR, DNA methylation, and amygdala volume using brain imaging data. We found that patients harboring low-activity 5-HTTLPR alleles showed hypermethylation and they showed a negative correlation between DNA methylation levels and left amygdala volumes. These results suggest that hypermethylation of the CpG site inSLC6A4is involved in the pathophysiology of SZ, especially in male patients harboring low-activity 5-HTTLPR alleles.
The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2
Authors: Di Gioacchino Andrea , Šulc Petr , Komarova Anastassia V. , Greenbaum Benjamin D. , Monasson Rémi , Cocco Simona 
Published: May 2020

AbstractCOVID-19 can lead to acute respiratory syndrome, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We find that the CpG content, which we characterize by a force parameter that accounts for statistical constraints acting on the genome at the nucleotidic and amino-acid levels, is, on average, low compared to other pathogenic betacoronaviruses. However, the CpG force widely fluctuates along the genome, with a particularly low value, comparable to the circulating seasonal HKU1, in the spike coding region and a greater value, comparable to SARS and MERS, in the highly expressed nucleocapside coding region (N ORF), whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3’UTRs of all subgenomic RNA. This dual nature of CpG content could confer to SARS-CoV-2 the ability to avoid triggering pattern recognition receptors upon entry, while eliciting a stronger response during replication. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic, finding a signature of CpG loss in regions with a greater CpG force. Sequence motifs preceding the CpG-loss-associated loci in the N ORF match recently identified binding patterns of the Zinc finger Anti-viral Protein. Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven in the SARS-CoV-2 genome, and particularly in the N ORF, by the viral codon bias, the transition-transversion bias and the pressure to lower CpG content.