bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-existing antibodies targeting a linear epitope on SARS-CoV-2 S2 cross-reacted with commensal gut bacteria and shaped vaccine induced immunity
Authors: Jia Liqiu , Weng Shufeng , Wu Jing , Tian Xiangxiang , Zhang Yifan , Wang Xuyang , Wang Jing , Yan Dongmei , Wang Wanhai , Fang Fang , Zhu Zhaoqin , Qiu Chao , Zhang Wenhong , Xu Ying , Wan Yanmin 
Published: July 2021

AbstractThe origins of pre-existing SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the pre-existing S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by pre-existing antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we proved that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 specific monoclonal antibodies were isolated from naïve SPF mice and proved to cross-react with commensal gut bacteria collected from both human and mouse. Mice with high levels of pre-existing S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of pre-existing S2 and P144 reactive antibodies correlated positively with RBD specific binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Finally, we provided data demonstrating that immunization of a SARS-CoV-2 S DNA vaccine could alter the gut microbiota compositions of mice.
Adding a reaction-restoration type transmission rate dynamic law to the basic SEIR COVID-19 model
Authors: Córdova-Lepe F. , Vogt-Geisse K. 
Published: July 2021

AbstractThe classical SEIR model, being an autonomous system of differential equations, has important limitations when representing a pandemic situation. Particularly, the geometric unimodal shape of the epidemic curve is not what is generally observed. This work introduces theβSEIR model, which adds to the classical SEIR model a differential law to model the variation in the transmission rate. It considers two opposite thrives generally found in a population: first, reaction to disease presence that may be linked to mitigation strategies, which tends to decrease transmission, and second, the urge to return to normal conditions that pulls to restore the initial value of the transmission rate. Our results open a wide spectrum of dynamic variabilities in the curve of new infected, which are justified by reaction and restoration thrives that affect disease transmission over time. Some of these dynamics have been observed in the existing COVID-19 disease data. In particular and to further exemplify the potential the model proposed in this article, we show its capability of capturing the evolution of the number of new confirmed cases of Chile and Italy for several months after epidemic onset, while incorporating a reaction to disease presence with decreasing adherence to mitigation strategies, as well as a seasonal effect on the restoration of the initial transmissibility conditions.
Persistence of neutralizing antibodies a year after SARS-CoV-2 infection
Authors: Haveri Anu , Ekström Nina , Solastie Anna , Virta Camilla , Österlund Pamela , Isosaari Elina , Nohynek Hanna , Palmu Arto A. , Melin Merit 
Published: July 2021

AbstractUnderstanding for how long antibodies persist following Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection provides important insight into estimating the duration of immunity induced by infection.We assessed the persistence of serum antibodies following wild-type SARS-CoV-2 infection six and twelve months after diagnosis in 367 individuals of whom 13% had severe disease requiring hospitalization. We determined the SARS-CoV-2 spike (S-IgG) and nucleoprotein IgG concentrations and the proportion of subjects with neutralizing antibodies (NAb). We also measured the NAb titers among a smaller subset of participants (n=78) against a wild-type virus (B.1) and three variants of concern (VOCs): Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2).We found that NAb against the wild-type virus and S-IgG persisted in 89% and 97% of subjects for at least twelve months after infection, respectively. IgG and NAb levels were higher after severe infection. NAb titers were significantly lower against variants compared to the wild-type virus.
Rapid and Quantitative Detection of Human Antibodies Against the 2019 Novel Coronavirus SARS CoV2 and its Variants as a Result of Vaccination and Infection
Authors: Taubner Benjamin , Peredo-Wende Ruben , Ramani Ananthakrishnan , Singh Gurpreet , Strle Klemen , Cady Nathaniel C. 
Published: July 2021

ABSTRACTMeasuring the antibody response to 2019 SARS CoV2 is critical for diagnostic purposes, monitoring the prevalence of infection, and for gauging the efficacy of the worldwide vaccination effort COVID-19. In this study, a microchip-based grating coupled fluorescent plasmonic (GC-FP) assay was used to measure antibody levels that resulted from COVID-19 infection and vaccination. In addition, we measured the relative antibody binding towards antigens from variants CoV2 virus variants, strains B.1.1.7 (UK) and B.1.351 (S. African). Antibody levels against multiple antigens within the SARS CoV2 spike protein were significantly elevated for both vaccinated and infected individuals, while those against the nucleocapsid (N) protein were only elevated for infected individuals. GC-FP was effective for monitoring the IgG-based serological response to vaccination throughout the vaccination sequence, and could also resolve acute (within hours) increases in antibody levels. A significant decrease in antibody binding to antigens from the B.1.351 variant, but not B.1.1.7, was observed for all vaccinated subjects when measured by GC-FP as compared to the 2019 SARS CoV2 antigens. These results were corroborated by competitive ELISA assay. Collectively, the findings suggest that GC-FP is a viable, rapid, and accurate method for measuring both overall antibody levels to CoV2 and relative antibody binding to viral variants during infection or vaccination.
The I-KID Study Protocol: Evaluation of Efficacy, Outcomes and Safety of a New Infant Haemodialysis and Ultrafiltration Machine in Clinical Use: a Randomised Clinical Investigation using a Cluster Stepped-wedge Design
Authors: Lambert Heather J , Sharma Shriya , Matthews John NS 
Published: July 2021

AbstractIntroductionThe I-KID study aims to determine the clinical efficacy, outcomes and safety of a novel non-CE-marked infant haemodialysis machine, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared to currently available therapy in the UK. NIDUS is specifically designed for renal replacement therapy in small babies between 0.8 and 8 kilograms.Methods and analysisThe clinical investigation is taking place in six UK centres. This is a randomised clinical investigation using a cluster stepped-wedge design. The study aims to recruit 95 babies requiring renal replacement therapy in paediatric intensive care units over 20 months.RegistrationIRAS ID number: 170481MHRA Reference: CI/2017/0066ISRCT Number: 13787486CPMS ID number: 36558NHS REC reference: 16/NE/0008Eudamed number: CIV-GB-18-02-023105Link to full protocol v6.0: https://fundingawards.nihr.ac.uk/award/14/23/26What is known about this subjectBabies in paediatric intensive care unit (PICU) may develop acute renal failure and require therapeutic support.Renal replacement options for babies are limited because of their small size and limitations of technology.Current haemodialysis and filtration systems in use in UK are not recommended or licensed for children under 8kg.What this study hopes to addRenal replacement methods for infants under 8kg in PICU will be compared.The efficacy, outcomes and safety of a new infant haemodialysis device will be assessed.Usability of the new device in normal clinical settings outside of the development centre will be examined.
THE COMPARISON OF THREE REAL-TIME PCR KITS FOR SARS-COV-2 DIAGNOSIS REVEALS DISCREPANCIES ON THE IDENTIFICATION OF POSITIVE COVID-19 CASES AND DISPERSION ON THE VALUES OBTAINED FOR THE DETECTION OF SARS-COV-2 VARIANTS
Authors: Santibáñez Álvaro , Luraschi Roberto , Barrera-Avalos Carlos , Vallejos-Vidal Eva , Alarcón Javiera , Cayunao Javiera , Mella Andrea , Figueroa Maximiliano , Hernández Felipe , Plaza Bárbara , Inostroza-Molina Ailen , Valdés Daniel , Imarai Mónica , Acuña-Castillo Claudio , Reyes-López Felipe E. , Sandino Ana María 
Published: July 2021

ABSTRACTThe COVID-19 pandemic has generated a huge challenge and threat to public health throughout the world population. Reverse transcription associated with real-time Polymerase Chain Reaction (RT-qPCR) has been the gold-standard molecular tool for diagnosis and detection of the SARS-CoV-2. Currently, it is used as the main strategy for testing, traceability, and control of positive cases For this reason, the on-top high demand for reagents has produced stock-out on several occasions and the only alternative to keep population diagnosis has been the use of different RT-qPCR kits. Therefore, we evaluate the performance of three of the commercial RT-qPCR kits currently in use for SARS-CoV-2 diagnosis in Chile, consisting in: TaqMan 2019-nCoV Assay Kit v1 (Thermo). Real-Time Fluorescent RT-PCR Kit for Detecting SARS-CoV-2 (BGI), and LightCycler® Multiplex RNA Virus Master (Roche). Results of quantification cycle (Cq) and relative fluorescence units (RFU) obtained from their RT-qPCR reactions revealed important discrepancies on the total RNA required for the identification of SARS-CoV-2 genes and diagnosis. Marked differences between kits in samples with 30>Cq value< 34 was observed. Samples with positive diagnoses for Covid-19 using the Thermo Fisher kit had different results when the same samples were evaluated with Roche and BGI kits. The displacement on the Cq value for SARS-CoV-2 identification between the three different RT-qPCR kits was also evident when the presence of single nucleotide variants was evaluated in the context of genomic surveillance. Taken together, this study emphasizes the special care adjusting RT-qPCR reaction conditions of the different kits must be taken by all the laboratories before carrying out the detection of SARS-CoV-2 genes from total RNA nasopharyngeal swab (NPS) samples.
The Reliability and Validity of the Hebrew Patient Health Questionnaire (PHQ-9) in the General Population
Authors: Yona Tomer , Weisman Asaf , Gottlieb Uri , Lin Eshed , Masharawi Youssef 
Published: July 2021

ABSTRACTObjectiveTo assess the psychometric properties of the Hebrew version of the Patient Health Questionnaire (PHQ-9) in the general population.MethodsUsing an online survey, we assessed test-retest reliability with a two-week time interval. A total of 118 participants enrolled in the study, of whom 103 completed the survey twice. Each participant filled out the PHQ-9 and the 12-Item Short Form Survey (SF-12). Our statistical analysis includes Cronbach’s alpha, Intraclass Correlation Coefficient (ICC2,1), Spearman’s rank correlation coefficient, Standard Error of Measurement (SEM), and Minimal Detectable Change (MDC).ResultsInternal consistency of the Hebrew version of the PHQ-9 ranged from α=0.79-0.83. The test-retest reliability of the questionnaire is good (ICC2,1= 0.81), and it is moderately and negatively correlated to the mental component of the SF-12 (Spearman ρ= -0.57, p< .05). The SEM of the PHQ-9 is 1.83 points, and the MDC was found to be 5 points.ConclusionThe Hebrew version of the PHQ-9 is valid and reliable for screening self-reported depressive symptoms online in the general Hebrew-speaking population.
PRISMA2020: an R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis
Authors: Haddaway Neal R. , Page Matthew J. , Pritchard Chris C. , McGuinness Luke A. 
Published: July 2021

AbstractBackgroundReporting standards, such as PRISMA aim to ensure that the methods and results of systematic reviews are described in sufficient detail to allow full transparency. Flow diagrams in evidence syntheses allow the reader to rapidly understand the core procedures used in a review and examine the attrition of irrelevant records throughout the review process. Recent research suggests that use of flow diagrams in systematic reviews is poor and of low quality and called for standardised templates to facilitate better reporting in flow diagrams. The increasing options for interactivity provided by the Internet gives us an opportunity to support easy-to-use evidence synthesis tools, and here we report on the development of tools for the production of PRISMA 2020-compliant systematic review flow diagrams.Methods and FindingsWe developed a free-to-use, Open Source R package and web-based Shiny app to allow users to design PRISMA flow diagrams for their own systematic reviews. Our tools allow users to produce standardised visualisations that transparently document the methods and results of a systematic review process in a variety of formats. In addition, we provide the opportunity to produce interactive, web-based flow diagrams (exported as HTML files), that allow readers to click on boxes of the diagram and navigate to further details on methods, results or data files. We provide an interactive example here;https://driscoll.ntu.ac.uk/prisma/.ConclusionsWe have developed a user-friendly suite of tools for producing PRISMA 2020-compliant flow diagrams for users with coding experience and, importantly, for users without prior experience in coding by making use of Shiny. These free-to-use tools will make it easier to produce clear and PRISMA 2020-compliant systematic review flow diagrams. Significantly, users can also produce interactive flow diagrams for the first time, allowing readers of their reviews to smoothly and swiftly explore and navigate to further details of the methods and results of a review. We believe these tools will increase use of PRISMA flow diagrams, improve the compliance and quality of flow diagrams, and facilitate strong science communication of the methods and results of systematic reviews by making use of interactivity. We encourage the systematic review community to make use of these tools, and provide feedback to streamline and improve their usability and efficiency.
Variation in COVID-19 excess mortality by age, sex, and province within Italy
Authors: Henry Nathaniel , Elagali Ahmed , Nguyen Michele , Chipeta Michael , Moore Catrin 
Published: July 2021

1AbstractAlthough previous evidence suggests that the infection fatality rate from COVID-19 varies by age and sex, and that transmission intensity varies geographically within countries, no study has yet explored the age-sex-space distribution of excess mortality associated with the COVID pandemic. By applying the principles of small-area estimation to existing models formulations for excess mortality, this study develops a method for assessing excess mortality across small populations and assesses the pattern of COVID excess mortality by province, year, week, age group, and sex in Italy from March through May 2020. We estimate that 53,200 excess deaths occurred across Italy during this time period, compared to just 35,500 deaths where COVID-19 was registered as the underlying cause of death. Out of the total excess mortality burden, 97% of excess deaths occurred among adults over age 60, and 68% of excess deaths were concentrated among adults over age 80. The burden of excess mortality was unevenly distributed across the country, with just three of Italy’s 107 provinces accounting for 32% of all excess mortality. This method for estimating excess mortality can be adapted to other countries where COVID-19 diagnostic capacity is still insufficient, and could be incorporated into public health rapid response systems.
Cloud-based DIA data analysis module for signal refinement improves accuracy and throughput of large datasets
Authors: Christianson Karen E. , Jaffe Jacob. D. , Carr Steven A. , Jacome Alvaro Sebastian Vaca 
Published: July 2021

AbstractData-independent acquisition (DIA) is a powerful mass spectrometry method that promises higher coverage, reproducibility, and throughput than traditional quantitative proteomics approaches. However, the complexity of DIA data caused by fragmentation of co-isolating peptides presents significant challenges for confident assignment of identity and quantity, information that is essential for deriving meaningful biological insight from the data. To overcome this problem, we previously developed Avant-garde, a tool for automated signal refinement of DIA and other targeted mass spectrometry data. AvG is designed to work alongside existing tools for peptide detection to address the reliability and quantitative suitability of signals extracted for the identified peptides. While its use is straightforward and offers efficient refinement for small datasets, the execution of AvG for large DIA datasets is time-consuming, especially if run with limited computational resources. To overcome these limitations, we present here an improved, cloud-based implementation of the AvG algorithm deployed on Terra, a user-friendly cloud-based platform for large-scale data analysis and sharing, as an accessible and standardized resource to the wider community.
Gut microbiome dysbiosis during COVID-19 is associated with increased risk for bacteremia and microbial translocation
Authors: Venzon Mericien , Bernard-Raichon Lucie , Klein Jon , Axelrad Jordan E. , Zhang Chenzhen , Hussey Grant A. , Sullivan Alexis P. , Casanovas-Massana Arnau , Noval Maria G. , Valero-Jimenez Ana M. , Gago Juan , Putzel Gregory , Pironti Alejandro , Wilder Evan ,   Yale IMPACT Research Team, Thorpe Lorna E. , Littman Dan R. , Dittmann Meike , Stapleford Kenneth A. , Shopsin Bo , Torres Victor J. , Ko Albert I. , Iwasaki Akiko , Cadwell Ken , Schluter Jonas 
Published: July 2021

AbstractThe microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate in a mouse model that SARS-CoV-2 infection can induce gut microbiome dysbiosis, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Comparison with stool samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.
Functional and Structural Segregation of Overlapping Helices in HIV-1
Authors: Safari Maliheh , Jayaraman Bhargavi , Yang Shumin , Smith Cynthia , Fernandes Jason D. , Frankel Alan D. 
Published: July 2021

SummaryOverlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant selective force on a particular nucleotide can be attributed to just one gene. While this arrangement has been observed in regions in which one gene is structured and the other is disordered, we sought to explore how overlapping genes balance constraints when both protein products are structured over the same sequence. We use a combination of sequence analysis, functional assays and selection experiments to examine an overlapped region in HIV-1 that encodes helical regions in both Env and Rev. We find that functional segregation occurs even in this overlap, with each protein spacing its functional residues in a manner that allows a mutable non-binding face of one helix to encode important functional residues on a charged face in the other helix. Additionally, our experiments reveal novel and critical functional residues in Env and have implications for the therapeutic targeting of HIV-1.
Model-based identification of conditionally-essential genes from transposon-insertion sequencing data
Authors: Sarsani Vishal , Aldikacti Berent , He Shai , Zeinert Rilee , Chien Peter , Flaherty Patrick 
Published: July 2021

AbstractThe understanding of bacterial gene function has been greatly enhanced by recent advancements in the deep sequencing of microbial genomes. Transposon insertion sequencing methods combines next-generation sequencing techniques with transposon mutagenesis for the exploration of the essentiality of genes under different environmental conditions. We propose a model-based method that uses regularized negative binomial regression to estimate the change in transposon insertions attributable to gene-environment changes without transformations or uniform normalization. An empirical Bayes model for estimating the local false discovery rate combines unique and total count information to test for genes that show a statistically significant change in transposon counts. When applied to RB-TnSeq (randomized barcode transposon sequencing) and Tn-seq (transposon sequencing) libraries made in strains of Caulobacter crescentus using both total and unique count data the model was able to identify a set of conditionally essential genes for each target condition that shed light on their functions and roles during various stress conditions.Author summaryTransposon insertion sequencing allows the study of bacterial gene function by combining next-generation sequencing techniques with transposon mutagenesis under different genetic and environmental perturbations. Our proposed regularized negative binomial regression method improves the quality of analysis of this data.