bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian estimation of cell-type-specific gene expression per bulk sample with prior derived from single-cell data
Authors: Wang Jiebiao , Roeder Kathryn , Devlin Bernie 
Published: August 2020

AbstractWhen assessed over a large number of samples, bulk RNA sequencing provides reliable data for gene expression at the tissue level. Single-cell RNA sequencing (scRNA-seq) deepens those analyses by evaluating gene expression at the cellular level. Both data types lend insights into disease etiology. With current technologies, however, scRNA-seq data are known to be noisy. Moreover, constrained by costs, scRNA-seq data are typically generated from a relatively small number of subjects, which limits their utility for some analyses, such as identification of gene expression quantitative trait loci (eQTLs). To address these issues while maintaining the unique advantages of each data type, we develop a Bayesian method (bMIND) to integrate bulk and scRNA-seq data. With a prior derived from scRNA-seq data, we propose to estimate sample-level cell-type-specific (CTS) expression from bulk expression data. The CTS expression enables large-scale sample-level downstream analyses, such as detecting CTS differentially expressed genes (DEGs) and eQTLs. Through simulations, we demonstrate that bMIND improves the accuracy of sample-level CTS expression estimates and power to discover CTS-DEGs when compared to existing methods. To further our understanding of two complex phenotypes, autism spectrum disorder and Alzheimer’s disease, we apply bMIND to gene expression data of relevant brain tissue to identify CTS-DEGs. Our results complement findings for CTS-DEGs obtained from snRNA-seq studies, replicating certain DEGs in specific cell types while nominating other novel genes in those cell types. Finally, we calculate CTS-eQTLs for eleven brain regions by analyzing GTEx V8 data, creating a new resource for biological insights.
Heterogenous susceptibility to R-pyocins in populations ofPseudomonas aeruginosasourced from cystic fibrosis lungs
Authors: Mei Madeline , Thomas Jacob , Diggle Stephen P. 
Published: August 2020

AbstractBacteriocins are proteinaceous antimicrobials produced by bacteria which are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced byPseudomonas aeruginosa. Due to their anti-pseudomonal activity, R-pyocins have potential as therapeutics in infection.P. aeruginosais a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF).P. aeruginosafrom CF lung infections develop increasing resistance to antibiotics, making new treatment approaches essential.P. aeruginosapopulations become phenotypically and genotypically diverse during infection, however, little is known of the efficacy of R-pyocins against heterogeneous populations. R-pyocins vary by subtype (R1-R5), distinguished by binding to different residues on the lipopolysaccharide (LPS). Each type varies in killing spectrum, and each strain produces only one R-type. To evaluate the prevalence of different R-types, we screenedP. aeruginosastrains from the International Pseudomonas Consortium Database (IPCD) and from our biobank of CF strains. We found that (i) R1-types were the most prevalent R-type among strains from respiratory sources; (ii) there is a large number of strains lacking R-pyocin genes, and (iii) isolates collected from the same patient have the same R-type. We then assessed the impact of intra-strain diversity on R-pyocin susceptibility and found a heterogenous response to R-pyocins within populations, likely due to differences in the LPS core. Our work reveals that heterogeneous populations of microbes exhibit variable susceptibility to R-pyocins and highlights that there is likely heterogeneity in response to other types of LPS-binding antimicrobials, including phage.ImportanceR-pyocins have potential as alternative therapeutics againstPseudomonas aeruginosain chronic infection, however little is known about the efficacy of R-pyocins in heterogeneous bacterial populations.P. aeruginosais known to become resistant to multiple antibiotics, as well as evolve phenotypic and genotypic diversity over time; thus it is particularly difficult to eradicate in chronic cystic fibrosis (CF) lung infections. In this study, we found thatP. aeruginosapopulations from CF lungs maintain the same R-pyocin genotype but exhibit heterogeneity in susceptibility to R-pyocins from other strains. Our findings suggest there is likely heterogeneity in response to other types of LPS-binding antimicrobials, such as phage, highlighting the necessity of further studying the potential of LPS-binding antimicrobial particles as alternative therapies in chronic infections.
Persistent bacterial coinfection of a COVID-19 patient caused by a genetically adaptedPseudomonas aeruginosachronic colonizer
Authors: Qu Jiuxin , Cai Zhao , Liu Yumei , Duan XiangKe , Han Shuhong , Zhu Yuao , Jiang Zhaofang , Zhang Yingdan , Zhuo Chao , Liu Yang , Liu Yingxia , Liu Lei , Yang Liang 
Published: August 2020

AbstractThis study characterized a genetically adaptedPseudomonas aeruginosasmall colony variant isolated from a COVID-19 patient who suffered persistent bacterial coinfection and eventually recovered from critical illness. Specification and modification of the isolates discovered at genomic and transcriptomic levels with aligned phenotypic observations indicated that these isolates formed excessive biofilm with elevated quorum sensing systems.
Interpretation of exercise-induced changes in human skeletal muscle mRNA expression depends on the timing of the post-exercise biopsies
Authors: Kuang Jujiao , McGinley Cian , Lee Matthew J-C , Saner Nicholas J , Garnham Andrew , Bishop David J 
Published: August 2020

ABSTRACTAimExercise elicits a range of adaptive responses in skeletal muscle that include changes in mRNA expression. To better understand the health benefits of exercise training, it is essential to investigate the underlying molecular mechanisms of skeletal muscle adaptations to exercise. However, most studies have assessed the molecular events at a few convenient time points within a short time frame post exercise, and the variations of gene expression kinetics have not been addressed systematically.MethodMuscle biopsies were collected from nine participants at baseline and six time points (0, 3, 9, 24, 48, and 72 h) following a session of high-intensity interval exercise. We assessed the mRNA content of 23 gene isoforms from the muscle samples.ResultThe temporal patterns of target gene expression were highly variable and the mRNA contents detected were largely dependent on the muscle sample timing. The maximal levels of mRNA content of all tested target genes were observed between 3 to 48 h post exercise.ConclusionOur findings highlight a critical gap in knowledge regarding the molecular response to exercise, where the use of a few time points within a short period after exercise has led to an incomplete understanding of the molecular responses to exercise. The timing of muscle sampling for individual studies needs to be carefully chosen based on existing literature and preliminary analysis of the molecular targets of interest. We propose that a comprehensive time-course analysis on the exercise-induced transcriptional response in humans will significantly benefit the field of exercise molecular biology.
Rapid evolution promotes fluctuation-dependent species coexistence
Authors: Yamamichi Masato , Letten Andrew D. 
Published: August 2020

AbstractRecent studies have demonstrated that rapid contemporary evolution can play a significant role in regulating population dynamics on ecological timescales. Here we identify a previously unrecognized mode by which rapid evolution can promote species coexistence via temporal fluctuations and a trade-off between competitive ability and the speed of adaptive evolution. We show that this interaction between rapid evolution and temporal fluctuations not only increases the range of coexistence conditions under a gleaner-opportunist trade-off (i.e., low minimum resource requirement [R*] vs. high maximum growth rate), but also yields stable coexistence in the absence of a classical gleaner-opportunist trade-off. Given the propensity for both oscillatory dynamics and divergent rates of adaptation (including rapid evolution and phenotypic plasticity) in the real world, we argue that this expansion of fluctuation-dependent coexistence theory provides an important overlooked solution to the so-called ‘paradox of the plankton’.
The Epidemiology Characteristics of Positive COVID-19 patients in a Caribbean Territory
Authors: Gopaul Chavin D. , Ventour Dale , Trotman Michelle , Thomas Davlin 
Published: August 2020

AbstractBackgroundThe purpose of the study is to determine the epidemiology of COVID-19 in a Caribbean Territory by the characterisation of patients in terms of, the numbers, socio demographics and associated co-morbidities. This comparison was done between local cases and imported cases. There have been no prior studies on COVID-19 in the Caribbean and as such this paper attempts to discuss the patterns associated with COVID-19 patients in the Caribbean.MethodsThis study determined the epidemiology of COVID-19 in a Caribbean territory using retrospective data. Analysis was performed using Excel and SPSS 22.0.ResultsThe majority of patients were female (61.9%) vs male (38.0%). The majority of the population were between 45 -64 yrs (43.4%) followed by above 65 at 28.8%. Cough was the most common presenting complaint at 44.9%, with fever being second 37.1%. The majority of female participants had a travel history at 61.9%, while males were 38.0 %. The occurrence of cough was high among both local cases (46.4%) and imported cases (47.6%).ConclusionsThese patterns can inform clinicians and other health care workers on the unique findings associated with COVID-19 positive patients especially those in the Caribbean region
Kinetics of viral clearance and antibody production across age groups in SARS-CoV-2 infected children
Authors: Bahar Burak , Jacquot Cyril , Mo Yunchuan D. , DeBiasi Roberta L. , Campos Joseph , Delaney Meghan 
Published: August 2020

AbstractObjectivesTo improve understanding of transition from viral infection to viral clearance, and antibody response in pediatric patients with SARS-CoV-2 infection.Study designThis retrospective analysis of children tested for SARS-CoV-2 by RT-PCR and IgG antibody at a quaternary-care, free-standing pediatric hospital between March 13th, 2020 to June 21st, 2020 included 6369 patients who underwent PCR testing and 215 patients who underwent antibody testing. During the initial study period, testing focused primarily on symptomatic children; the later study period included asymptomatic patients who underwent testing as preadmission or preprocedural screening. We report the proportion of positive and negative tests, time to viral clearance, and time to seropositivity.ResultsThe rate of positivity varied over time due to viral circulation in the community and transition from targeted testing of symptomatic patients to more universal screening of hospitalized patients. Median duration of viral shedding (RT-PCR positivity) was 19.5 days and RT-PCR negativity from positivity was 25 days. Of note, patients aged 6 to 15 years demonstrated a longer period of RT-PCR negativity from positivity, compared to patients aged 16 to 22 years (median=32 versus 18 days, p=0.015). Median time to seropositivity from RT-PCR positivity was 18 days while median time to reach adequate levels of neutralizing antibodies (defined as equivalent to 160 titer) was 36 days.ConclusionsThe majority of patients demonstrated a prolonged period of viral shedding after infection with SARS CoV-2. Whether this correlates with persistent infectivity is unknown. Only 17 of 33 patients demonstrated neutralizing antibodies, suggesting that some patients may not mount significant immune responses to infection. It remains unknown if IgG antibody production correlates with immunity and how long measurable antibodies persist and protect against future infection.
Performance assessment of 11 commercial serological tests for SARS-CoV-2 on hospitalized COVID-19 patients
Authors: Serre-Miranda C , Nobrega C , Roque S , Canto-Gomes J , Silva CS , Vieira N , Barreira-Silva P , Alves-Peixoto P , Cotter J , Reis A , Formigo M , Sarmento H , Pires O , Carvalho A , Petrovykh DY , Diéguez L , Sousa JC , Sousa N , Capela C , Palha JA , Cunha PG , Correia-Neves M 
Published: August 2020

ABSTRACTCommercial availability of serological tests to evaluate immunoglobulins (Ig) towards severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has grown exponentially since the onset of COVID-19 (Coronavirus Disease 2019) outbreak. Their thorough validation is of extreme importance before using them as epidemiological tools to infer population seroprevalence, and as complementary diagnostic tools to molecular approaches(e.g. RT-qPCR). Here we assayed commercial serological tests (semiquantitative and qualitative) from 11 suppliers in 126 samples collected from hospitalized COVID-19 patients, and from 36 healthy and HIV-infected individuals (collected at the pre-COVID-19 pandemic). Specificity was above 95% in 9 tests. Samples from COVID-19 patients were stratified by days since symptoms onset (<10, 10-15, 16-21 and >21 days). Tests sensitivity increases with time since symptoms onset, and peaks at 16-21 days for IgM and IgA (maximum: 91.2%); and from 16-21 to >21 days for IgG, depending on the test (maximum: 94.1%). Data from semiquantitative tests show that patients with severe clinical presentation have lower relative levels of IgM, IgA and IgG at <10 days since symptoms onset in comparison to patients with non-severe presentation. At >21 days since symptoms onset the relative levels of IgM and IgG (in one test) are significantly higher in patients with severe clinical presentation, suggesting a delay in the upsurge of Ig against SARS-CoV-2 in those patients.This study highlights the high specificity of most of the evaluated tests, and sensitivity heterogeneity. Considering the virus genetic evolution and population immune response to it, continuous monitoring of commercially available serological tests towards SARS-CoV-2 is necessary.
Strategic anti-SARS-CoV-2 serology testing in a low prevalence pandemic: The COVID-19 Contact (CoCo) Study in health care professionals
Authors: Behrens Georg , Cossmann Anne , Stankov Metodi V. , Schulte Bianca , Streeck Hendrik , Förster Reinhold , Bosnjak Berislav , Willenzon Stefanie , Boeck Anna-Lena , Tran Anh Thu , Thiele Thea , Graalmann Theresa , Kayser Moritz Z. , Scharff Anna Zychlinsky , Dopfer Christian , Horke Alexander , Pink Isabell , Witte Torsten , Wetzke Martin , Ernst Diana , Jablonka Alexandra , Happle Christine 
Published: August 2020

AbstractBackgroundSerology testing is explored for epidemiological research and to inform individuals after suspected infection. During the COVID-19 pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist.MethodsIn a large German university hospital, we performed weekly questionnaire assessments and anti-SARS-CoV-2 IgG measurements with various commercial tests, a novel surrogate virus neutralization test, and a neutralization assay using live SARS-CoV-2.ResultsFrom baseline to week six, n=1,080 screening measurements for anti-SARS CoV-2 (S1) IgG from n=217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12·4 % in week six, p<0.001). In sera of convalescent PCR-confirmed COVID-19 patients, we measured high anti-SARS-CoV-2 IgG levels, obtained highly concordant results from ELISAs using e.g. the S1 spike protein domain and the nucleocapsid protein (NCP) as targets, and confirmed antiviral neutralization. However, in HCP the cumulative incidence for anti-SARS-CoV-2 (S1) IgG was 1.86% for positive and 0.93% for equivocal positive results over the six week study period. Except for one HCP, none of the eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralization against live SARS CoV-2. The only true seroconversion occurred without symptoms and mounted strong functional humoral immunity. Thus, the confirmed cumulative incidence for neutralizing anti-SARS-CoV-2 IgG was 0.47%.ConclusionWhen assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates.
Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection
Authors: Crawford Katharine H.D. , Dingens Adam S. , Eguia Rachel , Wolf Caitlin R. , Wilcox Naomi , Logue Jennifer K. , Shuey Kiel , Casto Amanda M. , Fiala Brooke , Wrenn Samuel , Pettie Deleah , King Neil P. , Chu Helen Y. , Bloom Jesse D. 
Published: August 2020

AbstractMost individuals infected with SARS-CoV-2 develop neutralizing antibodies that target the viral spike protein. Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ~30 and 152 days post-symptom onset from a prospective cohort of 34 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about four-fold from one to four months post-symptom onset. This decline in neutralizing antibody titers was accompanied by a decline in total antibodies capable of binding the viral spike or its receptor-binding domain. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.
The SARS-COV-2 outbreak around the Amazon rainforest: the relevance of the airborne transmission
Authors: Crema Edilson 
Published: August 2020

AbstractBackgroundThis paper presents a global analysis of the SARS-COV-2 outbreak in Brazil.Amazonian States have a much higher contamination rate than the southern and southeastern States. So far, no explanation has been provided for this striking difference that can shed light on the airborne transmission of the virus.Minimizing airborne transmission, health authorities recommend two meters as a safe distance. However, recent experiments reveal that this can be the main form of contagion. There is a lack of theoretical explanation on how airborne transmission works.MethodsTo investigate the spread of SARS-COV-2 in different macro environments, we analyzed the daily official data on the evolution of COVID-19 in Brazil. We compared our epidemiologic results obtained in States with very different climatic characteristics, and that had adopted, almost simultaneously, similar social isolation measures. To understand the virus spread, it was necessary to calculate theoretically the movement and behavior in the air of saliva droplets.FindingsThe transmission of SARS-COV-2 is much faster in the Amazon rainforest region.Our theoretical calculations explain and support the empirical results observed in recent experiments that demonstrate the relevance of aerial transmission of the coronavirus.InterpretationAn onset of collective immunity may have been achieved with a contamination rate of about 15% of the Amazonian population. If confirmed, this result will have an essential impact on the management of the pandemic across the planet.The airborne transmission played a decisive role in the striking difference in the evolution of the pandemic among Brazilian regions.Air humidity is the most important climatic factor in viral spreading, while usual ambient temperatures do not have strong influence.There is no safe indoor distance for the coronavirus transmission. So, mask and eye protection are essential.
CRISPR-based and RT-qPCR surveillance of SARS-CoV-2 in asymptomatic individuals uncovers a shift in viral prevalence among a university population
Authors: Rauch Jennifer N. , Valois Eric , Ponce-Rojas Jose Carlos , Aralis Zach , Lach Ryan S. , Zappa Francesca , Audouard Morgane , Solley Sabrina C. , Vaidya Chinmay , Costello Michael , Smith Holly , Javanbakht Ali , Malear Betsy , Polito Laura , Comer Stewart , Arn Katherine , Kosik Kenneth S. , Acosta-Alvear Diego , Wilson Maxwell Z. , Fitzgibbons Lynn , Arias Carolina 
Published: August 2020

AbstractThe progress of the COVID-19 pandemic profoundly impacts the health of communities around the world, with unique effects on colleges and universities. Here, we examined the prevalence of SARS-CoV-2 in 1808 asymptomatic individuals on a university campus in California, and compared for the first time the performance of CRISPR- and PCR-based assays for large-scale virus surveillance. Our study revealed that there were no COVID-19 cases in our study population in May/June of 2020. Using the same methods, we demonstrated a substantial shift in prevalence approximately one month later, which coincided with changes in community restrictions and public interactions. This increase in prevalence, in a young and asymptomatic population, indicated the leading wave of a local outbreak, and reflected the rising case counts in the surrounding county. Our results substantiate that large, population-level asymptomatic screening using CRISPR- or PCR-based assays is a feasible and instructive aspect of the public health approach within large campus communities.