bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Clinical Performance of the Abbott Panbio with Nasopharyngeal, Throat and Saliva Swabs Among Symptomatic Individuals with COVID-19
Authors: Stokes William , Berenger Byron M. , Portnoy Danielle , Scott Brittney , Szelewicki Jonas , Singh Takshveer , Venner Allison A. , Turnbull LeeAnn , Pabbaraju Kanti , Shokoples Sandy , Wong Anita A. , Gill Kara , Guttridge Tracy , Proctor Dustin , Hu Jia , Tipples Graham 
Published: January 2021

ABSTRACTBACKGROUNDPoint of Care Testing (POCT) SARS-CoV-2 antigen tests, such as the Abbott Panbio, have great potential to help combat the COVID-19 pandemic. The Panbio is Health Canada approved for the detection of SARS-CoV-2 in symptomatic individuals within the first 7 days of COVID-19 symptom onset(s).METHODSSymptomatic adults recently diagnosed with COVID-19 in the community were recruited into the study. Paired nasopharyngeal (NP), throat, and saliva swabs were collected, with one paired swab tested immediately with the Panbio, and the other transported in universal transport media and tested using reverse-transcriptase polymerase chain reaction (RT-PCR). Positive percent agreement (PPA) was calculated. Subsequently, individuals within 7 days of symptom onset who presented to community assessment centres for SARS-CoV-2 testing had Panbio testing completed and paired with RT-PCR results from parallel NP or throat swabs.RESULTS145 individuals were included in the study. Collection of throat and saliva was stopped early due to poor performance (throat PPA 57.7%, n=61, and saliva PPA 2.6%, n=41). NP swab PPA was 87.7% [n=145, 95% confidence interval 81.0% - 92.7%]. There were 1,641 symptomatic individuals tested by Panbio in community assessment centres, with 268/1641 (16.3%) positive for SARS-CoV-2. There were 37 false negatives, corresponding to a PPA of 86.2% [81.5% - 90.1%].CONCLUSIONSThe Panbio test reliably detects most cases of SARS-CoV-2 from adults in the POCT community setting presenting within 7 days of symptom onset using nasopharyngeal swabs. Throat and saliva swabs are not reliable specimens for the Panbio.
Diagnostic performance and clinical implications of rapid SARS-CoV-2 antigen testing in Mexico using real-world nationwide COVID-19 registry data
Authors: Bello-Chavolla Omar Yaxmehen , Antonio-Villa Neftali Eduardo , Fernández-Chirino Luisa , Guerra Enrique C. , Fermín-Martínez Carlos A. , Márquez-Salinas Alejandro , Vargas-Vázquez Arsenio , Bahena-López Jessica Paola 
Published: January 2021

ABSTRACTBACKGROUNDSARS-CoV-2 testing capacity is important to monitor epidemic dynamics and as a mitigation strategy. Given difficulties of large-scale quantitative reverse transcription polymerase chain reaction (qRT-PCR) implementation, rapid antigen tests (Rapid Ag-T) have been proposed as alternatives in settings like Mexico. Here, we evaluated diagnostic performance of Rapid Ag-T for SARS-CoV-2 infection and its associated clinical implications compared to qRT-PCR testing in Mexico.METHODSWe analyzed data from the COVID-19 registry of the Mexican General Directorate of Epidemiology up to April 30th, 2021 (n=6,632,938) and cases with both qRT-PCR and Rapid Ag-T (n=216,388). We evaluated diagnostic performance using accuracy measures and assessed time-dependent changes in the Area Under the Receiver Operating Characteristic curve (AUROC). We also explored test discordances as predictors of hospitalization, intubation, severe COVID-19 and mortality.RESULTSRapid Ag-T is primarily used in Mexico City. Rapid Ag-T have low sensitivity 37.6% (95%CI 36.6-38.7), high specificity 95.5% (95%CI 95.1-95.8) and acceptable positive 86.1% (95%CI 85.0-86.6) and negative predictive values 67.2% (95%CI 66.2-69.2). Rapid Ag-T has optimal diagnostic performance up to days 3 after symptom onset, and its performance is modified by testing location, comorbidity, and age. qRT-PCR (-) / Rapid Ag-T (+) cases had higher risk of adverse COVID-19 outcomes (HR 1.54 95% CI 1.41-1.68) and were older, qRT-PCR (+)/ Rapid Ag-T(-) cases had slightly higher risk or adverse outcomes and ≥7 days from symptom onset (HR 1.53 95% CI 1.48-1.59). Cases detected with rapid Ag-T were younger, without comorbidities, and milder COVID-19 course.CONCLUSIONSRapid Ag-T could be used as an alternative to qRT-PCR for large scale SARS-CoV-2 testing in Mexico. Interpretation of Rapid Ag-T results should be done with caution to minimize the risk associated with false negative results.
Production and assessment of monoclonal antibodies against the SpyCas9 protein ofStreptococcus pyogenes
Authors: Park Mi-Jin , Park Jongjin , Park Slki , Choe Sunghwa 
Published: January 2021

AbstractThe biotechnological applications of the programmable DNA-cleaving enzymes known as clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) continue to expand from agricultural trait development to therapeutic gene therapies. The Cas9 CRISPR system isolated fromStreptococcus pyogenes(SpyCas9) is classified as class II, which is popular due to high efficiency and robustness. Antibodies that specifically detect SpyCas9 could expand the applicability of this enzyme. Here, we report on the development of monoclonal antibodies against SpyCas9. Four hybridoma cells were selected for their expression of anti-SpyCas9. Hybridoma supernatant contained reactive and highly specific antibodies to SpyCas9. Anti-SpyCas9 antibody was purified and was non-selective against six other bacterial Cas9 proteins. SpyCas9 protein could be detected in HEK293T cells in decreasing amounts over a 48 hour period, indicating the antibody could be used to detect residual levels of SpyCas9 remaining following cell treatment with a CRISPR/SpyCas9 system. The anti-SpyCas9 antibody may help researchers facilitate Cas9 for further study for the use of techniques such as enzyme-linked immunosorbent assays (ELISAs), western blot, immunoprecipitation, and immunohistochemical staining.
A metagenomic-based study of two sites from the Barbadian reef system
Authors: Simpson S , Bettauer V , Ramachandran A , Kramer S , Mahon S , Medina M , Valles Y , Dumeaux V , Valles H , Walsh D , Hallett MT 
Published: January 2021

AbstractWe study the microbiome of sea water collected from two locations of the Barbadian coral reefs. The two sites differ in several environmental and ecological variables including their endogenous benthic community in addition to their proximity to urban development and runoffs from inland watersheds. The composition of the microbial community was estimated using whole genome DNA shotgun sequencing. Although both sites exhibit a similar degree of richness, the less urbanized site (Maycocks reef at Hangman’s Bay) is strongly concentrated with phototrophs. In comparison, the more urbanized location (Bellairs Research Institute) is enriched for copiotrophs, macroalgal symbionts and marine-related disease-bearing organisms from taxa scattered across the tree of life. Overall, our samples and associated measurements of chemical and environmental qualities of the water are in line with previous marine microbiome profiles of warm ocean surface waters. This suggests our approach captures salient information regarding the state of each coral reef site and sets the stage for larger longitudinal studies of coral reef dynamics in Barbados.
Graph Signal Processing on protein residue networks helps in studying its biophysical properties
Authors: Srivastava Divyanshu , Bagler Ganesh , Kumar Vibhor 
Published: January 2021

AbstractUnderstanding the physical and chemical properties of proteins is vital, and many efforts have been made to study the emergent properties of the macro-molecules as a combination of long chains of amino acids. Here, we present a graph signal processing based approach to model the biophysical property of proteins. For each protein inter-residue proximity-based network is used as basis graph and the respective amino acid properties are used as node-signals. Signals on nodes are decomposed on network’s Laplacian eigenbasis using graph Fourier transformations. We found that the intensity in low-frequency components of graph signals of residue features could be used to model few biophysical properties of proteins. Specifically, using our approach, we could model protein folding-rate, globularity and fraction of alpha-helices and beta-sheets. Our approach also allows amalgamation of different types of chemical and graph theoretic properties of residue to be used together in a multi-variable regression model to predict biophysical properties.
Spike protein disulfide disruption as a potential treatment for SARS-CoV-2
Authors: Grishin Andrey M. , Dolgova Nataliya V. , Harms Shelby , Pickering Ingrid J. , George Graham N. , Falzarano Darryl , Cygler Miroslaw 
Published: January 2021

AbstractThe coronaviral pandemic is exerting a tremendously detrimental impact on global health, quality of life and the world economy, emphasizing the need for effective medications for current and future coronaviral outbreaks as a complementary approach to vaccines. The Spike protein, responsible for cell receptor binding and viral internalization, possesses multiple disulfide bonds raising the possibility that disulfide-reducing agents might disrupt Spike function, prevent viral entry and serve as effective drugs against SARS-CoV-2. Here we show the first experimental evidence that reagents capable of reducing disulfide bonds can inhibit viral infection in cell-based assays. Molecular dynamics simulations of the Spike receptor-binding domain (RBD) predict increased domain flexibility when the four disulfide bonds of the domain are reduced. This flexibility is particularly prominent for the surface loop, comprised of residues 456-490, which interacts with the Spike cell receptor ACE2. Consistent with this finding, the addition of exogenous disulfide bond reducing agents affects the RBD secondary structure, lowers its melting temperature from 52 to 36-39°C and decreases its binding affinity to ACE2 by two orders of magnitude at 37°C. Finally, the reducing agents dithiothreitol (DTT) and tris(2-carboxyethyl)phosphine (TCEP) inhibit viral replication at high µM – low mM levels with a negligible effect on cell viability at these concentrations. The antiviral effect of monothiol-based reductants N-Acetyl-L-cysteine (NAC) and reduced glutathione (GSH) was not observed due to decreases in cell viability. Our research demonstrates the clear potential for medications that disrupt Spike disulfides as broad-spectrum anticoronaviral agents and as a first-line defense against current and future outbreaks.
Synonymous Mutation Generator: a web tool for designing RNAi-resistant sequences
Authors: Ong Joseph Y. 
Published: January 2021

AbstractRNA interference (RNAi) is a useful technique for knocking down a protein of interest, allowing for the study of the function of a gene product. However, RNAi techniques are prone to off-target effects, such as non-specific knockdown of genes besides the protein of interest. An important control and companion to RNAi knockdown experiments is the rescue experiment, wherein gene function is restored by expression of an RNAi-resistant construct of the protein of interest. Generating an RNAi-resistant construct of the protein of interest involves generating silent mutations within the coding sequence of the protein so that the resulting amino acid product is the same, but the protein mRNA is no longer a target for the RNAi. Here, Synonymous Mutation Generator, a Python-based web tool that takes an input DNA coding sequence and outputs a synonymous DNA coding sequence that is RNAi-resistant, is described. This web tool should be a useful resource for researchers cloning RNAi-resistant constructs. Synonymous Mutation Generator is easy to use and can be found atjong2.pythonanywhere.com, and the source code is available on GitHub.
SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection
Authors: Havervall Sebastian , Falk August Jernbom , Klingström Jonas , Ng Henry , Greilert-Norin Nina , Gabrielsson Lena , Salomonsson Ann-Christin , Isaksson Eva , Rudberg Ann-Sofie , Hellström Cecilia , Andersson Eni , Olofsson Jennie , Skoglund Lovisa , Yousef Jamil , Pin Elisa , Christ Wanda , Olausson Mikaela , Hedhammar My , Tegel Hanna , Mangsbo Sara , Phillipson Mia , Månberg Anna , Hober Sophia , Nilsson Peter , Thålin Charlotte 
Published: January 2021

AbstractCurrent SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1965 healthcare workers, of which 381 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in most participants, 96%, at least four months post infection, despite having had no or mild symptoms. Virus neutralization capacity was confirmed by microneutralization assay in 91% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 80% of previously anti-nucleocapsid IgG positive healthcare workers. Both anti-spike and anti-nucleocapsid IgG levels were significantly higher in previously hospitalized COVID-19 patients four months post infection than in healthcare workers four months post infection (p=2*10−23 and 2*10−13 respectively). Although the magnitude of humoral response was associated with disease severity, our findings support a durable and functional humoral response after SARS-CoV-2 infection even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.
What is the value of community oximetry monitoring in people with SARS-CoV-2? – A prospective, open-label clinical study
Authors: Wilcock Jane , Grafton-Clarke Ciaran , Coulson Tessa 
Published: January 2021

AbstractBackgroundIn people with COVID-19, hypoxia at the time of admission is known to be related to mortality. Monitoring of oxygen saturations (SpO2) is therefore an increasingly common part of community-based care, with the aim of improving the identification of adults who are deteriorating. We set out to investigate whether rigid SpO2 triggers, or absolute change in SpO2, is more indicative of deterioration in COVID-19.MethodsA prospective, uncontrolled, open-label study in a large UK general practice was conducted between May and November 2020. Participants recorded twice daily oximetry and symptom diary for 14 days after test-confirmed COVID-19. Primary outcomes were the proportion of people whose SpO2 dropped to ≤ 94% and ≤ 92%, the average maximum reduction in SpO2, and admission to hospital. We also investigated the relationship between MRC Dyspnoea scale, modified Roth score, and SpO2 through correlation analyses.Results52 participants were recruited, following which 41 participants completed the study. The average age was 45.9 years with 63.4% identifying as female. The mean maximum reduction in SpO2 was 2.8%. The average time to maximum reduction in SpO2 was 6.4 days. Nine participants (22.0%) had a reduction in SpO2 to ≤94%. Three of these had a reduction in SpO2 to ≤92%, for which all three were admitted to hospital. Modified Roth score and SpO2 were weakly positively correlated (.31). MRC dyspnoea scale score and SpO2 were moderately negatively correlated (-.53).ConclusionsA reduction in SpO2 to ≤92% was found to be highly predictive for admission to hospital. Modified Roth score or MRC dyspnoea scale scores should not be used as proxy measures for oximetry. This study contributes to the ongoing narrative around community-based oximetry and provides insight and recommendations for those currently engaging in or planning to roll out similar schemes.Strengths and limitations of this studyThis study is pragmatically designed to answer an important clinical question in primary care.This study focused on previously published values of SpO2 for triggering escalation of care and therefore provides answers based on current clinical practice.11 of the 52 patients who were recruited into the study did not return their oximeter or oximetry diary at the end of the study period.We did not validate the accuracy or reliability of the oximetry / symptom diaries, as these were self-completed by the participants themselves.Other than admission to hospital and mortality within the study period, no other clinical outcomes have been recorded.Funding statementThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.Competing interestsJane Wilcock has no competing interests to declare.Ciaran Grafton-Clarke has no competing interests to declare.Tessa Coulson has no competing interests to declare.
Dynamic persistence of intracellular bacterial communities of uropathogenicEscherichia coliin a human bladder-chip model of urinary tract infections
Authors: Sharma Kunal , Dhar Neeraj , Thacker Vivek V. , Simonet Thomas M. , Signorino-Gelo François , Knott Graham , McKinney John D. 
Published: January 2021

AbstractUropathogenicEscherichia coli(UPEC) proliferate within superficial bladder umbrella cells to form intracellular bacterial communities (IBCs) during early stages of urinary tract infections. However, the dynamic responses of IBCs to host stresses and antibiotic therapy are difficult to assessin situ. We develop a human bladder-chip model wherein umbrella cells and bladder microvascular endothelial cells are co-cultured under flow in urine and nutritive media respectively, and bladder filling and voiding mimicked mechanically by application and release of linear strain. Using time-lapse microscopy, we show that rapid recruitment of neutrophils from the vascular channel to sites of infection leads to swarm and neutrophil extracellular trap formation but does not prevent IBC formation. Subsequently, we tracked bacterial growth dynamics in individual IBCs through two cycles of antibiotic administration interspersed with recovery periods which revealed that the elimination of bacteria within IBCs by the antibiotic was delayed, and in some instances, did not occur at all. During the recovery period, rapid proliferation in a significant fraction of IBCs reseeded new foci of infection through bacterial shedding and host cell exfoliation. These insights reinforce a dynamic role for IBCs as harbours of bacterial persistence, with significant consequences for non-compliance with antibiotic regimens.
Mapping the mechanical microenvironment in the ovary
Authors: Hopkins Thomas I. R. , Bemmer Victoria L. , Franks Stephen , Dunlop Carina , Hardy Kate , Dunlop Iain E. 
Published: January 2021

AbstractFollicle development in the human ovary must be tightly regulated to ensure cyclical release of oocytes (ovulation), and disruption of this process is a common cause of infertility. Recent ex vivo studies suggest that follicle growth may be mechanically regulated, however the actual mechanical properties of the follicle microenvironment have remained unknown. Here we map and quantify the mechanical microenvironment in mouse ovaries using colloidal probe atomic force microscope (AFM) indentation, finding an overall mean Young’s Modulus 3.3 ± 2.5 kPa. Spatially, stiffness is low at the ovarian edge and centre, which are dominated by extra-follicular ECM, and highest in an intermediate zone dominated by large follicles. This suggests that large follicles should be considered as mechanically dominant structures in the ovary, in contrast to previous expectations. Our results provide a new, physiologically accurate framework for investigating how mechanics impacts follicle development and will underpin future tissue engineering of the ovary.
Elucidating biosynthetic pathway of piperine using comparative transcriptome analysis of leaves, root and spike inPiper longumL
Authors: Dantu Prem Kumar , Prasad Mrinalini , Ranjan Rajiv 
Published: January 2021

AbstractPiper longum(Pipli; Piperaceae) is an important spice valued for its pungent alkaloids, especially piperine. Albeit, its importance, the mechanism of piperine biosynthesis is still poorly understood. The Next Generation Sequencing (NGS) forP. longumleaves, root and spikes was performed using Illumina platform, which generated 16901456, 54993496 and 22900035, respectively of high quality reads. Inde novoassemblyP. longum173381 numbers of transcripts were analyzed. Analysis of transcriptome data from leaf, root and spike showed gene families that were involved in the biosynthetic pathway of piperine and other secondary metabolites. To validate differential expression of the identified genes, 27 genes were randomly selected to confirm the expression level by quantitative real time PCR (qRT-PCR) based on the up regulation and down regulation of differentially expressed genes obtained through comparative transcriptome analysis of leaves and spike ofP. longum. With the help of UniProt database the function of all characterized genes was generated.
Is maternal thyroid hormone deposition subject to a trade-off between self and egg because of iodine? An experimental study in rock pigeon
Authors: Sarraude Tom , Hsu Bin-Yan , Ruuskanen Suvi , Groothuis Ton 
Published: January 2021

AbstractMaternal hormones constitute a key signalling pathway for mothers to shape offspring phenotype and fitness. Thyroid hormones (THs; triiodothyronine, T3and thyroxine, T4) are metabolic hormones known to play crucial roles in embryonic development and survival in all vertebrates. During early developmental stages, embryos exclusively rely on the exposure to maternal THs, and maternal hypothyroidism can cause severe embryonic maldevelopment. The TH molecule includes iodine, an element that cannot be synthesised by the organism. Therefore, TH production may become costly when environmental iodine availability is low. This may yield a trade-off for breeding females between allocating the hormones to self or to their eggs, potentially to the extent that it even influences the number of laid eggs. In this study, we investigated whether low dietary iodine may limit TH production and transfer to the eggs in a captive population of Rock pigeons(Columba livia).We provided breeding females with an iodine-restricted (I- diet) or iodine-supplemented diet (I+ diet) and measured the resulting circulating and yolk iodine and TH concentrations and the number of eggs laid. Our iodine-restricted diet successfully decreased both circulating and yolk iodine concentrations compared to the supplemented diet, but not circulating or yolk THs. This indicates that mothers may not be able to independently regulate hormone exposure for self and their embryos. However, egg production was clearly reduced in the I- group, with fewer females laying eggs. This result shows that restricted availability of iodine does induce a cost in terms of egg production. Whether females reduced egg production to preserve THs for themselves or to prevent embryos from exposure to low iodine and/or THs is as yet unclear.