bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimated SARS-CoV-2 Seroprevalence in Children and Adolescents in Mississippi, May Through September 2020
Authors: Hobbs Charlotte V. , Drobeniuc Jan , Kittle Theresa , Williams John , Byers Paul , Panayampalli Subbian S. , Stephenson Meagan , Kim Sara S. , Patel Manish M. , Flannery Brendan ,   CDC COVID-19 Response Team,   CDC COVID-19 Task Force Microbial Pathogenesis and Immune Response Laboratory.
Published: February 2021

AbstractCase-based tracking of COVID-19 in children and adolescents may underestimate infection, and compared with adults there is little pediatric SARS-CoV-2 seroprevalence data. To assess evidence of previous SARS-CoV-2 infections among children and adolescents in Mississippi, serologic testing for antibodies to SARS-CoV-2 was conducted on a convenience sample of residual serum specimens collected for routine laboratory testing by an academic medical center laboratory during May 17 through September 19, 2020. Seroprevalence by calendar month was standardized to the state population by race/ethnicity; cumulative numbers of infections were estimated by extrapolating seroprevalence to all those aged <18 years in Mississippi. Serum specimens from 1,603 individuals were tested; 175 (10.9%) were positive for SARS-CoV-2 antibodies. Among 1,579 (98.5%) individuals for whom race/ethnicity was known, the number testing positive was 16 (23.2%) of 69 Hispanic individuals, 117 (13.0%) of 901 non-Hispanic Black individuals and 30 (5.3%) of 565 non-Hispanic White individuals. Population-weighted seroprevalence estimates among those aged <18 years increased from 2.6% in May to 16.9% in September 2020. Cumulative numbers of infections extrapolated from seroprevalence data, however, were estimated at 117,805 (95% confidence interval [CI] = 68,771–168,708), suggesting that cases in children and adolescents are much higher than what was reported to the Mississippi State Department of Health (9,044 cases during this period). Further data to appreciate the burden of pediatric disease to inform public health policy is urgently needed.
Uncorrected cardiac malformation is the major risk factor for death in patients with dextrocardia
Authors: Lu Xiaofeng , Dang Wenzhu , Li Shenglin , Wang Xu , Gao Bingren , Liu Debin 
Published: February 2021

AbstractBackground/ObjectivesDextrocardia is rare in the general population. We aimed to analyze the clinical characteristics and risk factors for survival rate of dextrocardia patients during 2013 to 2018 in our hospital, through a specialized Hospital Information System.MethodsA retrospective study of patients with dextrocardia was performed through Hospital Information System. International Classification of Diseases 10 was searched to identify eligible cases from January 2013 to December 2018 in our hospital. Medical records were reviewed to acquire the basic information of dextrocardia patients.ResultsAmong 9304 patients diagnosed with congenital heart disease in past six years, 48 (0.51%) had dextrocardia. Among 48 dextrocardia patients, 28 (58.33%) had situs inversus viscerum, 20 (41.67%) had cardiac malformation, nine (18.75%) had other malformations and 16 (33.33%) had no malformation. Compared with patients with uncorrected cardiac malformation, patients without cardiac malformation were older (43.5000 vs 0.4583 years, P<0.001). The dextrocardia patients’ age of onset correlated significantly with cardiac malformation. Multivariable logistic model showed the significant risk factor for survival rate was uncorrected cardiac malformation (odds ratio, 22.2391; P <0.001). However, situs inversus (odds ratio, 1.9750; P= 0.4399) or pneumonia (odds ratio, 4.2610; P= 0.0849) itself was not a significant risk factor for survival rate. Kaplan–Meier plot shown that dextrocardia patients with uncorrected cardiac malformation had lower survival rate than those without cardiac malformation (P<0.0001), and there is no significant difference between healthy cohort and patients with pure dextrocardia with or without situs inversus (P=0.25).ConclusionsDextrocardia remains a rare finding in population, even in the group of patients with known congenital heart disease. Dextrocardia was associated with various malformations besides cardiac malformation. Uncorrected cardiac malformation, which should be paid high attention in the developing countries, is the main risk factor for death in patients with dextrocardia, and pure dextrocardia with or without situs inversus has no effect on survival rate of dextrocardia patients.
Neighborhood Disadvantage and Active, Disabled and Total Life Expectancy Among Community-living Older Persons
Authors: Gill Thomas M. , Zang Emma X. , Murphy Terrence E. , Leo-Summers Linda , Gahbauer Evelyne A. , Festa Natalia , Falvey Jason R. , Han Ling 
Published: February 2021

AbstractBackgroundNeighborhood disadvantage is a novel social determinant of health that could adversely affect the functional well-being and longevity of older persons. We evaluated whether estimates of active, disabled and total life expectancy differ on the basis of neighborhood disadvantage after accounting for individual-level socioeconomic characteristics and other prognostic factors.MethodsWe used data on 754 community-living older persons from South Central Connecticut, who completed monthly assessments of disability from 1998 to 2020. Scores on the area deprivation index were dichotomized at the 80thstate percentile to distinguish neighborhoods that were disadvantaged (81-100) from those that were not (1-80).ResultsWithin 5-year age increments from 70 to 90, active and total life expectancy were consistently lower in participants from neighborhoods that were disadvantaged versus not disadvantaged, and these differences persisted and remained statistically significant after adjustment for individual-level race/ethnicity, education, income, and other prognostic factors. At age 70, adjusted estimates (95% CI) for active and total life expectancy (in years) were 12.3 (11.5-13.1) and 15.0 (13.8-16.1) in the disadvantaged group and 14.2 (13.5-14.7) and 16.7 (15.9-17.5) in the non-disadvantaged group. At each age, participants from disadvantaged neighborhoods spent a greater percentage of their projected remaining life disabled, relative to those from non-disadvantaged neighborhoods, with adjusted values (SE) ranging from 17.7 (0.8) vs. 15.3 (0.5) at age 70 to 55.0 (1.7) vs. 48.1 (1.3) at age 90.ConclusionsLiving in a disadvantaged neighborhood is associated with lower active and total life expectancy and a greater percentage of projected remaining life disabled.
Modelling the impact of contact tracing of symptomatic individuals on the COVID-19 epidemic
Authors: Amaku Marcos , Covas Dimas Tadeu , Coutinho Francisco Antonio Bezerra , Azevedo Raymundo Soares , Massad Eduardo 
Published: February 2021

AbstractOBJECTIVESWith declining numbers of COVID-19 cases in the State of São Paulo, Brazil, social distancing measures were gradually being lifted. The risk of an increase in the number of cases, however, cannot be overlooked. Even with the adoption of non-pharmaceutical interventions, such as restrictions on mass gatherings, wearing masks, and complete or partial closure of schools, other public health measures may help to control the epidemic. We aimed to evaluate the impact of the contact tracing of symptomatic individuals on the COVID-19 epidemic regardless of the use of diagnostic testing.METHODSWe developed a mathematical model that includes isolation of symptomatic individuals and tracing of contacts to assess the effects of the contact tracing of symptomatic individuals on the COVID-19 epidemic in the State of São Paulo.RESULTSFor a selection efficacy (proportion of isolated contacts who are infected) of 80%, cases and deaths may be reduced by 80% after 60 days when 5000 symptomatic individuals are isolated per day, each of them together with 10 contacts. On the other hand, for a selection efficacy of 20%, the number of cases and deaths may be reduced by approximately 40% and 50%, respectively, compared with the scenario in which no contact tracing strategy is performed.CONCLUSIONContact tracing of symptomatic individuals may be a potential alternative strategy when the number of diagnostic tests available is not sufficient for a massive testing strategy.
Ibrutinib as a Potential Therapeutic for Cocaine Use Disorder
Authors: Huggett Spencer B. , Hatfield Jeffrey S. , Walters Joshua D. , McGeary John E. , Welsh Justine W. , Mackay Trudy F. C. , Anholt Robert R. H. , Palmer Rohan H.C. 
Published: February 2021

ABSTRACTCocaine use presents a worldwide public health problem with high socioeconomic cost. Current treatments for cocaine use disorder (CUD) are suboptimal and rely primarily on behavioral interventions. To explore pharmaceutical treatments for CUD, we analyzed genome-wide gene expression data from publically availble human brain tissues (midbrain, hippocampus and prefrontal cortex neurons) from 71 individuals (mean age = 39.9, 100% male, 36 with CUD and 35 matched controls). We leveraged the L1000 database to investigate molecular associations between neuronal mRNA profiles from 825 repurposable compounds (e.g., FDA approved) with human CUD gene expression in the brain. We identified 16 compounds that were negatively associated with CUD gene expression patterns across all brain regions (padj < 0.05), all of which outperformed current targets undergoing clinical trials for CUD (all padj > 0.05). We tested the effectiveness of these compounds using independent transcriptome-wide in vitro (neuronal cocaine exposure; n=18) and in vivo (mouse cocaine self-administration; prefrontal cortex, hippocampus and midbrain; n = 12-15) datasets. Among these medications, Ibrutinib demonstrated negative associations with both neuronal cocaine exposure and mouse cocaine self-administration. To obtain experimental confirmation of therapeutic effects of Ibrutinib on CUD, we used the Drosophila melanogaster model, which enables highthroughput quantification of behavioral responses in defined genetic backgrounds and controlled environmental conditions. Ibrutinib altered cocaine-induced changes in startle response and reduced the occurrence of cocaine-induced seizures (n = 61-142 per group; sex: 51%female). Our results identify Ibrutinib, an FDA approved medication, as a potential therapeutic for cocaine neurotoxicity.
Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease
Authors: Xiao Zhenxu , Wu Xue , Wu Wanqing , Yi Jingwei , Liang Xiaoniu , Ding Saineng , Zheng Li , Luo Jianfeng , Gu Hongchen , Zhao Qianhua , Xu Hong , Ding Ding 
Published: February 2021

AbstractBackgroundPlasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the association with cognitive domains along the spectrum of cognitive performance deterioration have seldom been reported.MethodsWe recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis of AD, amnestic mild cognitive impairment, and normal cognition (NC). Each participant was administered the neuropsychological tests assessing the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the Single molecule array platform.ResultsAlong with plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, and NfL, p-tau181 significantly increased across the groups with the incremental CDR scores from NC (CDR = 0) to severe AD (CDR = 3). Compared with other biomarkers, p-tau181 had a stronger correlation with Global cognition (r= −0.494,P< 0.001), Memory (r= −0.417,P< 0.001), Attention (r= −0.388,P< 0.001), Visuospatial function (r= −0.328,P< 0.001), and Language (r= −0.123,P= 0.014). Among AD participants with CDR ≥ 1, higher p-tau181 was correlated with worse Global cognition (r= −0.295,P< 0.001), Memory (r= −0.172,P= 0.045), and Attention (r= −0.184,P= 0.031).ConclusionsPlasma p-tau181 had a stronger correlation with cognitive domains than other biomarkers, especially in late-stage AD. It could reflect the AD pathology in vivo and may be a promising blood-based biomarker in clinical settings.
Self-assembling SARS-CoV-2 nanoparticle vaccines targeting the S protein induces protective immunity in mice
Authors: Liu Xingjian , Song Haozhi , Jiang Jianmin , Gao Xintao , Yi Yongzhu , Shang Yuting , Li Jialei , Li Dan , Zeng Zhen , Li Yinü , Zhang Zhifang 
Published: February 2021

AbstractThe spike (S), a homotrimer glycoprotein, is the most important antigen target in the research and development of SARS-CoV-2 vaccine. There is no doubt that fully simulating the advanced structure of this homotrimer in the subunit vaccine development strategy is the most likely way to improve the immune protective effect of the vaccine. In this study, the preparation strategies of S protein receptor-binding domain (RBD) trimer, S1 region trimer, and ectodomain (ECD) trimer nanoparticles were designed based on ferritin nanoparticle self-assembly technology. The Bombyx mori baculovirus expression system was used to prepare these three nanoparticle vaccines with high expression levels in the silkworm. The immune results of mice show that the nanoparticle vaccine prepared by this strategy can not only induce an immune response by subcutaneous administration but also effective by oral administration. Given the stability of these ferritin-based nanoparticles vaccine, easy-to-use and low-cost oral immunization strategy can make up for the vaccination blind areas caused by the shortage of ultralow-temperature equipment and medical resources in underdeveloped areas. And the oral vaccine is also a very potential candidate to cut off the spread of SARS-CoV-2 in domestic and farmed animals, especially in stray and wild animals.
Targeting CTP Synthetase 1 to Restore Interferon Induction and Impede Nucleotide Synthesis in SARS-CoV-2 Infection
Authors: Rao Youliang , Wang Ting-Yu , Qin Chao , Espinosa Bianca , Liu Qizhi , Ekanayake Arunika , Zhao Jun , Savas Ali Can , Zhang Shu , Zarinfar Mehrnaz , Liu Yongzhen , Zhu Wenjie , Graham Nicholas , Jiang Taijiao , Zhang Chao , Feng Pinghui 
Published: February 2021

SUMMARYThe newly emerged SARS-CoV-2 caused a global pandemic with astonishing mortality and morbidity. The mechanisms underpinning its highly infectious nature remain poorly understood. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 (CTPS1) to promote CTP synthesis and suppress interferon (IFN) induction. Screening a SARS-CoV-2 expression library identified ORF7b and ORF8 that suppressed IFN induction via inducing the deamidation of interferon regulatory factor 3 (IRF3). Deamidated IRF3 fails to bind the promoters of classic IRF3-responsible genes, thus muting IFN induction. Conversely, a shRNA-mediated screen focused on cellular glutamine amidotransferases corroborated that CTPS1 deamidates IRF3 to inhibit IFN induction. Functionally, ORF7b and ORF8 activate CTPS1 to promotede novoCTP synthesis while shutting down IFN induction.De novosynthesis of small-molecule inhibitors of CTPS1 enabled CTP depletion and IFN induction in SARS-CoV-2 infection, thus impeding SARS-CoV-2 replication. Our work uncovers a strategy that a viral pathogen couples immune evasion to metabolic activation to fuel viral replication. Inhibition of the cellular CTPS1 offers an attractive means for developing antiviral therapy that would be resistant to SARS-CoV-2 mutation.
ORFhunteR: an accurate approach for the automatic identification and annotation of open reading frames in human mRNA molecules
Authors: Grinev Vasily V. , Yatskou Mikalai M. , Skakun Victor V. , Chepeleva Maryna K. , Nazarov Petr V. 
Published: February 2021

AbstractMotivationModern methods of whole transcriptome sequencing accurately recover nucleotide sequences of RNA molecules present in cells and allow for determining their quantitative abundances. The coding potential of such molecules can be estimated using open reading frames (ORF) finding algorithms, implemented in a number of software packages. However, these algorithms show somewhat limited accuracy, are intended for single-molecule analysis and do not allow selecting proper ORFs in the case of long mRNAs containing multiple ORF candidates.ResultsWe developed a computational approach, corresponding machine learning model and a package, dedicated to automatic identification of the ORFs in large sets of human mRNA molecules. It is based on vectorization of nucleotide sequences into features, followed by classification using a random forest. The predictive model was validated on sets of human mRNA molecules from the NCBI RefSeq and Ensembl databases and demonstrated almost 95% accuracy in detecting true ORFs. The developed methods and pre-trained classification model were implemented in a powerful ORFhunteR computational tool that performs an automatic identification of true ORFs among large set of human mRNA molecules.Availability and implementationThe developed open-source R package ORFhunteR is available for the community at GitHub repository (https://github.com/rfctbio-bsu/ORFhunteR), from Bioconductor (https://bioconductor.org/packages/devel/bioc/html/ORFhunteR.html) and as a web application (http://orfhunter.bsu.by).
Bacterium-Enabled Transient Gene Activation by Artificial Transcription Factor for Resolving Gene Regulation in Maize
Authors: Zhao Mingxia , Peng Zhao , Qin Yang , Zhang Ling , Tian Bin , Chen Yueying , Liu Yan , Lin Guifang , Zheng Huakun , He Cheng , Lv Kaiwen , Trick Harold N. , Liu Yunjun , Cho Myeong-Je , Park Sunghun , Wei Hairong , Zheng Jun , White Frank F. , Liu Sanzhen 
Published: February 2021

ABSTRACTCellular functions are diversified through intricate transcription regulations, and an understanding gene regulation networks is essential to elucidating many developmental processes and environmental responses. Here, we employed the Transcriptional-Activator Like effectors (TALes), which represent a family of transcription factors that are synthesized by members of the γ-proteobacterium genusXanthomonasand secreted to host cells for activation of targeted host genes. Through delivery by the maize pathogen,Xanthomonas vasicolapv.vasculorum, designer TALes (dTALes), which are synthetic TALes, were used to induce the expression of the maize geneglossy3(gl3), a MYB transcription factor gene involved in the cuticular wax biosynthesis. RNA-Seq analysis of leaf samples identified 146gl3downstream genes. Eight of the nine known genes known to be involved in the cuticular wax biosynthesis were up-regulated by at least one dTALe. A top-down Gaussian graphical model predicted that 68gl3downstream genes were directly regulated by GL3. A chemically induced mutant of the gene Zm00001d017418 from thegl3downstream gene, encoding aldehyde dehydrogenase, exhibited a typical glossy leaf phenotype and reduced epicuticular waxes. The bacterial protein delivery of artificial transcription factors, dTALes, proved to be a straightforward and powerful approach for the revelation of gene regulation in plants.
Loss of ClpP Function inClostridioides difficile630 Significantly Impacts Sporulation Systems
Authors: Bishop Catherine E. , Shadid Tyler , Lavey Nathan P. , Kempher Megan L. , Ahsan Nagib , Ballard Jimmy D. , Duerfeldt Adam S. 
Published: February 2021

AbstractThe Gram-positive bacteriumClostridioides difficileis a primary cause of hospital-acquired diarrhea, threatening both immunocompromised and healthy individuals. An important aspect of elucidating mechanisms that driveC. difficilepersistence and virulence relies on developing a more complete understanding of sporulation.C. difficilesporulation is the single determinant of transmission and complicates treatment and prevention due to the chemical and physical resilience of spores. Hence, the identification of potentially druggable targets that significantly attenuate sporulation is important. In this report, we describe the impact of the loss of caseinolytic protease P (ClpP) isoforms inC. difficilestrain 630 on sporulation phenotypes. Using CRISPR-Cas9 nickase mediated genome editing, stop codons were inserted early in the coding sequence forclpP1andclpP2to generateC. difficilemutants that no longer produced ClpP1 or ClpP2. The data show that these genetic modifications lead to altered sporulation phenotypes, germination efficiencies, and cytotoxicity. Comparative proteome profiling ofC. difficile630 WT andclpPmutants reveals potential proteolytic targets of ClpP that are involved in sporulation. These analyses further reveal the potential for preferred co-chaperone interactions for each ClpP isoform. Taken together, our results demonstrate that ClpP, a promising target in other Gram-positive pathogens, holds promise as an anti-sporulation target inC. difficile.
Mendelian Randomization Analysis Using Multiple Biomarkers of an Underlying Common Exposure
Authors: Jin Jin , Qi Guanghao , Yu Zhi , Chatterjee Nilanjan 
Published: February 2021

SummaryMendelian Randomization (MR) analysis is increasingly popular for testing the causal effect of exposures on disease outcomes using data from genome-wide association studies. In some settings, the underlying exposure, such as systematic inflammation, may not be directly observable, but measurements can be available on multiple biomarkers or other types of traits that are coregulated by the exposure. We propose a method for MR analysis on latent exposures (MRLE), which tests the significance for, and the direction of, the effect of a latent exposure by leveraging information from multiple related traits. The method is developed by constructing a set of estimating functions based on the second-order moments of GWAS summary association statistics for the observable traits, under a structural equation model where genetic variants are assumed to have indirect effects through the latent exposure and potentially direct effects on the traits. Simulation studies show that MRLE has well-controlled type I error rates and enhanced power compared to single-trait MR tests under various types of pleiotropy. Applications of MRLE using genetic association statistics across five inflammatory biomarkers (CRP, IL-6, IL-8, TNF-α, and MCP-1) provide evidence for potential causal effects of inflammation on increasing the risk of coronary artery disease, colorectal cancer, and rheumatoid arthritis, while standard MR analysis for individual biomarkers fails to detect consistent evidence for such effects.
Multi-omic characterization of the thermal stress phenome in the stony coralMontipora capitata
Authors: Pathmanathan Jananan S. , Williams Amanda , Stephens Timothy G. , Su Xiaoyang , Chiles Eric N. , Conetta Dennis , Putnam Hollie M. , Bhattacharya Debashish 
Published: February 2021

AbstractWe used network methods to analyze transcriptomic and polar metabolomic data generated from the stress resistant stony coralMontipora capitata. Corals were exposed to ambient or thermal stress conditions over a five-week period that coincided with a mass spawning event of this species. Gene co-expression networks showed that the early thermal stress response involves downregulation of growth and DNA replication, whereas signaling and the immune response are strongly upregulated. Later stages are dominated by suppression of metabolite transport and biomineralization and enhanced expression of transcriptional regulators. Integration of gene-metabolite data demonstrates that the major outcome of the thermal treatment is activation of animal redox stress pathways with detoxification of reactive oxygen species being dominant. Differential regulation of the highly conserved cytochrome P450 gene family was of particular interest with downregulation of CYP1A1, involved in progesterone metabolism, potentially explaining the attenuated mass spawning observed during the sampling period.