bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 infection induces the production of autoantibodies in severe COVID-19 patients in an age-dependent manner
Authors: Fonseca Dennyson Leandro M , Filgueiras Igor Salerno , Marques Alexandre HC , Vojdani Elroy , Halpert Gilad , Ostrinski Yuri , Baiocchi Gabriela Crispim , Plaça Desirée Rodrigues , Freire Paula P. , Pour Shahab Zaki , Moll Guido , Catar Rusan , Lavi Yael Bublil , Silverberg Jonathan I. , Zimmerman Jason , de Miranda Gustavo Cabral , Carvalho Robson F , Khan Taj Ali , Heidecke Harald , Dalmolin Rodrigo JS , Luchessi Andre Ducati , Ochs Hans D. , Schimke Lena F. , Amital Howard , Riemekasten Gabriela , Zyskind Israel , Rosenberg Avi Z , Vojdani Aristo , Shoenfeld Yehuda , Cabral-Marques Otavio 
Published: December 2022

ABSTRACTAge is a significant risk factor for the coronavirus disease 2019 (COVID-19) outcomes due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, diabetes, chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health & disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 outcomes (with 71 mild, 61 moderate, and 27 severe patients) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multivariate regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid β peptide, β catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe elderly COVID-19 patients. Follow-up analysis using binomial regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies indicated a significantly increased likelihood of developing a severe COVID-19 phenotype, presenting a synergistic effect on worsening COVID-19 outcomes. These findings provide new key insights to explain why elderly patients less favorable outcomes have than young individuals, suggesting new associations of distinct autoantibody levels with disease severity.
Protocol for a Real-Time Electronic Health Record Implementation of a Natural Language Processing and Deep Learning Clinical Decision Support Tool: A Use-Case for an Opioid Misuse Screener in Hospitalized Adults
Authors: Afshar Majid , Adelaine Sabrina , Resnik Felice , Mundt Marlon P. , Long John , Leaf Margaret , Ampian Theodore , Wills Graham J , Schnapp Benjamin , Chao Michael , Brown Randy , Joyce Cara , Sharma Brihat , Dligach Dmitriy , Burnside Elizabeth S. , Mahoney Jane , Churpek Matthew M , Patterson Brian W. , Liao Frank 
Published: December 2022

ABSTRACTThe clinical narrative in the electronic health record (EHR) carries valuable information for predictive analytics, but its free-text form is difficult to mine and analyze for clinical decision support (CDS). Large-scale clinical natural language processing (NLP) pipelines have focused on data warehouse applications for retrospective research efforts. There remains a paucity of evidence for implementing open-source NLP engines to provide interoperable and standardized CDS at the bedside. This clinical protocol describes a reproducible workflow for a cloud service to ingest, process, and store clinical notes as Health Level 7 messages from a major EHR vendor in an elastic cloud computing environment. We apply the NLP CDS infrastructure to a use-case for hospital-wide opioid misuse screening using an open-source deep learning model that leverages clinical notes mapped to standardized medical vocabularies. The resultant NLP and deep learning pipeline can process clinical notes and provide decision support to the bedside within minutes of a provider entering a note into the EHR for all hospitalized patients. The protocol includes a human-centered design and an implementation framework with a cost-effectiveness and patient outcomes analysis plan.
Enhancing the sensitivity of rapid antigen detection test (RADT) of different SARS-CoV-2 variants and lineages using fluorescence-labeled antibodies and a fluorescent meter
Authors: Nasrallah Gheyath K. , Ali Fatma , Younes Salma , Al-Khatib Heba A. , Al-Thani Asmaa A. , Yassine Hadi M. 
Published: December 2022

AbstractRT-qPCR is considered the gold standard for diagnosis of COVID-19; however, it is laborious, time-consuming, and expensive. RADTs have evolved recently as relatively inexpensive methods to address these shortcomings, but their performance for detecting different SARS-COV-2 variants remains limited. RADT test performance could be enhanced using different antibody labeling and signal detection techniques. Here, we aimed to evaluate the performance of two Wondfo antigen RADTs for detecting different SARS-CoV-2 variants: (i) the conventional colorimetric RADT (Ab-conjugated with gold beads); and (ii) the new Finecare™ RADT (Ab-coated fluorescent beads). Finecare™ is a meter used for the detection of a fluorescent signal. 187 frozen nasopharyngeal swabs collected in Universal transport (UTM) that are RT-qPCR positive for different SARS-CoV-2 variants were selected, including 60 Alpha, 59 multiple Delta, and 108 multiple Omicron variants. 60 flu and 60 RSV-positive samples were included as negative controls (total sample number=349). The conventional RADT showed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 62.4% (95%CI: 54-70), 100% (95%CI: 97-100), 100% (95%CI: 100-100), and 58% (95%CI: 49-67) respectively. These measurements were enhanced using the Finecare™ RADT: sensitivity, specificity, PPV, and NPV were 92.6% (95%CI: 89.08-92.3), 96% (95%CI: 96-99.61), 98% (95%CI: 89-92.3), and 85% (95%CI: 96-99.6) respectively. The sensitivity of both RADTs could be greatly underestimated because nasopharyngeal swab samples collected UTM and stored at −80 °C were used. Despite that, our results indicate that the Finecare™ RADT is appropriate for clinical laboratory and community-based surveillance due to its high sensitivity and specificity.
Optimizing COVID-19 testing strategies on college campuses: evaluation of the health and economic costs
Authors: Johnson Kaitlyn E. , Pasco Remy , Woody Spencer , Lachmann Michael , Johnson-Leon Maureen , Bhavnani Darlene , Klima Jessica , Paltiel A. David , Fox Spencer J. , Meyers Lauren Ancel 
Published: December 2022

AbstractColleges and universities in the US struggled to provide safe in-person education throughout the COVID-19 pandemic. Testing coupled with isolation is a nimble intervention strategy that can be tailored to mitigate health and economic costs, as the virus and our arsenal of medical countermeasures continue to evolve. We developed a decision-support tool to aid in the design of university-based testing strategies using a mathematical model of SARS-CoV-2 transmission. Applying this framework to a large public university reopening in the fall of 2021 with a 60% student vaccination rate, we find that the optimal strategy, in terms of health and economic costs, is twice weekly antigen testing of all students. This strategy provides a 95% guarantee that, throughout the fall semester, case counts would not exceed the CDC’s original high transmission threshold of 100 cases per 100k persons over 7 days. As the virus and our medical armament continue to evolve, testing will remain a flexible tool for managing risks and keeping campuses open. We have implemented this model as anonline toolto facilitate the design of testing strategies that adjust for COVID-19 conditions, university-specific parameters, and institutional goals.Author SummaryAs a part of the COVID-19 response team at a large public university in the US, we performed an analysis that considered together, the potential health and economic costs of different testing policies for the student body. University administrators had to weigh the up-front effort needed to implement wide scale testing against the potential costs of responding to high levels of disease on campus in the Fall of 2021, after vaccines were widely available but vaccination rates among college students were uncertain. The results presented here are applied to this specific instance, but theonline toolprovided can be tailored to university specific parameters, the epidemiological conditions, and the goals of the university. As we confront newly emerging variants of COVID-19 or novel pathogens, consideration of both the health and economic costs of proactive testing may serve as a politically tractable and cost-effective disease mitigation strategy.
Prevalence of and risk factors for Tuberculosis among health care workers in Yogyakarta, Indonesia
Authors: Main Stephanie , Triasih Rina , Greig Jane , Hidayat Arif , Brilliandi Immanuel Billy , Khodijah Syarifah , Chan Geoff , Wilks Nova , Elizabeth Parry Amy , Nababan Betty , du Cros Philipp , Dwihardiani Bintari 
Published: December 2022

ABSTRACTBackgroundHealthcare workers (HCWs) are at risk of contracting TB, particularly when in high tuberculosis (TB) burden settings. Routine surveillance data and evidence are limited on the burden of TB amongst HCWs in Indonesia.ObjectiveTo measure the prevalence of TB infection (TBI) and disease among HCWs in four healthcare facilities in Yogyakarta and explore risk factors for TBI.MethodsA cross-sectional TB screening study targeted all HCWs from four pre-selected facilities (1 hospital, 3 primary care) in Yogyakarta, Indonesia. Voluntary screening included symptom assessment, Chest X-ray (CXR), Xpert MTB/RIF (if indicated) and tuberculin skin test (TST). Analyses were descriptive and included multivariable logistic regression.ResultsOf 792 HCWs, 681 consented (86%) to the screening; 59% (n=401) were female, 62% were medical staff (n=421), 77% worked in the one participating hospital (n=524), and the median time working in the health sector was 13 years (IQR: 6-25 years). Nearly half had provided services for people with TB (46%, n=316) and 9% reported ever having TB (n=60).Among participants with presumptive TB (15%, n=99/662), none were diagnosed microbiologically or clinically with active TB disease. TBI was detected in 25% (95% CI: 22-30; n=112/441) of eligible HCWs with a TST result. A significant association was found between TB infection and being male (adjusted Odds Ratio (aOR) 2.02 (95%CI: 1.29-3.17)), currently working in the participating hospital compared to primary care (aOR 3.15 (95%CI: 1.75-5.66)), and older age (1.05 OR increase per year of life between 19-73 years (95%CI: 1.02-1.06)).ConclusionThis study supports prioritisation of HCWs as a high-risk group for TB infection and disease, and the need for comprehensive prevention and control programs in Indonesia. Further, it identifies characteristics of HCWs in Yogyakarta at higher risk of TBI, who could be prioritised in screening programs if universal coverage of prevention and control measures cannot be achieved.
Circular RNA circPLOD2 regulates pericyte function by targeting the transcription factor KLF4
Authors: Glaser Simone Franziska , Brezski Andre , Baumgarten Nina , Klangwart Marius , Heumüller Andreas W. , Maji Ranjan Kumar , Leisegang Matthias S. , Guenther Stefan , Zehendner Christoph M. , John David , Schulz Marcel H. , Zarnack Kathi , Dimmeler Stefanie 
Published: December 2022

AbstractCircular RNAs (circRNAs) are generated by back-splicing and control cellular signaling and phenotypes. Pericytes stabilize the capillary structure and play an important role in the formation and maintenance of new blood vessels. Here, we characterized hypoxia-regulated circRNAs in human pericytes and showed that circPLOD2 is induced by hypoxia and regulates pericyte function. Silencing of circPLOD2 increased pericyte proliferation, endothelial-pericyte interaction and tube formation. Transcriptional profiling of circPLOD2-depleted cells and epigenomic analyses revealed widespread changes in gene expression and identified the circPLOD2-dependent regulation of the transcription factor KLF4 as a key effector of these changes. Importantly, overexpression ofKLF4was sufficient to reverse the effects on pericyte proliferation and endothelial-pericyte interactions observed after circPLOD2 depletion. Together, these data revealed a novel function of circPLOD2 in the control of pericyte proliferation and capillary formation and showed that circPLOD2-mediated regulation of KLF4 significantly contributes to the transcriptional response to hypoxia.HighlightscircPLOD2 is upregulated in hypoxia in human vascular pericytesSelective depletion of circPLOD2, but not linearPLOD2mRNA, changes pericyte migration and endothelial-pericyte interactioncircPLOD2 depletion triggers widespread changes in gene expression that are mirrored in the transcriptional hypoxia responseEpigenomic analyses pinpoint the transcription factor KLF4 as a central player in circPLOD2-mediated expression changesKLF4overexpression is sufficient to rescue the changes in pericyte function caused by circPLOD2 depletion
Nanoscaled discovery of a shunt rifamycin fromSalinispora arenicolausing a three-colour GFP-taggedStaphylococcus aureusmacrophage infection assay
Authors: Pham Nhan T. , Alves Joana , Sargison Fiona A. , Cullum Reiko , Wildenhain Jan , Fenical William , Butler Mark S. , Mead David A. , Duggan Brendan M. , Fitzgerald J. Ross , La Clair James J. , Auer Manfred 
Published: December 2022

AbstractAntimicrobial resistance has emerged as an urgent global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent.Staphylococcus aureusis a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival ofS. aureusin macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by GFP-taggedStaphylococcus aureusas a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a novel, active rifamycin analogue. Our findings indicate a promising new approach to the identification of anti-microbial compounds with macrophage intracellular activity. The novel antibiotic identified here may represent a useful addition to our armoury in tackling the silent pandemic of antimicrobial resistance.
Endometrial adhesion G protein-coupled receptors are dynamically expressed across the menstrual cycle and expression is altered by ovarian stimulation
Authors: Kalakota Nischelle , Lemenze Alexander , George Lea , Zhao Qingshi , Wu Tracy , Morelli Sara S. , Douglas Nataki C. , Babwah Andy V. 
Published: December 2022

ABSTRACTOvarian stimulation (OS), utilized for the development of multiple ovarian follicles for IVF, induces supraphysiologic levels of E2 and an early rise in P4 that disrupt endometrial differentiation and decreases implantation rates or result in placental insufficiency and pregnancy complications. To improve pregnancy rates and reduce the risk of pregnancy complications associated with IVF, it is crucial to advance our molecular understanding of the molecular regulation of endometrial differentiation. Previous studies from our laboratory suggest G protein-coupled receptors (GPCRs) are important regulators of endometrial differentiation. To investigate this further, using a retrospective dataset, we identified all GPCRs expressed across the proliferative and secretory phase of the menstrual cycle and found that many members of the adhesion G protein-coupled receptor (ADGR) family are dynamically expressed. For each ADGR subfamily exhibiting differentially-expressed genes across the cycle, their expression was investigated by RT-PCR in the non-pregnant mouse uterus and decidua on E7.5 of pregnancy. For those genes expressed in the E7.5 decidua, their expression was further quantified by qPCR across early mouse pregnancy. The RT-PCR screen revealed expression of 13 ADGRs (4 of the 9 subfamilies) in E7.5 decidua and among these genes, many were differentially expressed between E0.5 and E5.5 or 6.5 and between E5.5 and E6.5. The dynamic expression of the ADGRs across the menstrual cycle and in early mouse pregnancy, suggests theseADGRsare E2- and/or P4-regulated genes. We therefore hypothesized that for theseADGRgenes, mRNA expression would be disrupted in an OS cycle. This hypothesis was tested on endometrial biopsies collected in the secretory phase from prospective cohorts of women in natural and OS cycles. Consistent with the retrospective dataset, our data revealed that members of theADGRgene family are expressed in the secretory phase of the natural menstrual cycle and for the first time, we show that their expression is altered by ovarian stimulation.
Risk of Type 1 Diabetes in Children is Not Increased after SARS-CoV-2 Infection: A Nationwide Prospective Study in Denmark
Authors: Noorzae Rohina , Junker Thor Grønborg , Hviid Anders , Wohlfahrt Jan , Olsen Sjurdur F. 
Published: December 2022

Structured AbstractObjectiveIt has been hypothesized that SARS-CoV-2 infection in children can increase risk of developing type 1 diabetes.Research Design and MethodsWe undertook a prospective analysis based on all children in Denmark where we investigated the association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes, using information from several different national Danish registers. Denmark had one of the highest test-rates per capita in the world during the pandemic.ResultsWe did not observe a higher risk of a first time diagnosis of type 1 diabetes in children 30 days or more after a positive SARS-CoV-2 test, compared to children with a history of only negative SARS-CoV-2 tests (Hazard ratio 0.85, 95% CI 0.70, 1.04).ConclusionsOur data do not support that SARS-CoV-2 infection is associated with type 1 diabetes, or that type 1 diabetes should be a special focus after a SARS-CoV-2 infection in children.Article HighlightsWhy did we undertake this study?Studies have shown an association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes, supporting the possibility of a viral etiology in type 1 diabetes and adding to concerns regarding adverse health consequences of COVID-19.What is the specific question(s) we wanted to answer?Is the risk of new onset type 1 diabetes increased among children in the period after SARS-CoV-2 infection?What did we find?We estimated the relative risk of being diagnosed with type 1 diabetes after a positive compared to a negative SARS-CoV-2 test, to 0.85 (95% CI 0.70, 1.04).What are the implications of our findings?Our data do not support an association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes among children.Twitter SummaryA study based on all children in Denmark does not show any association between #SarsCoV2 infection and subsequent risk of #Type1Diabetes among persons < 18 years. #Type1Diabetes should not be a special focus after a #SarsCoV2 infection in children.
Validation of a decision-analytic model for the cost-effectiveness analysis of a risk-stratified National Breast Screening Programme in the United Kingdom
Authors: Wright Stuart J , Gray Ewan , Rogers Gabriel , Donten Anna , Payne Katherine 
Published: December 2022

AbstractBackgroundThis study follows structured frameworks to assess the internal and external validity of a decision-analytic model-based cost-effectiveness of approaches to implement a risk-stratified national breast screening programme (risk-NBSP) in the United Kingdom (UK).MethodsA pre-defined set of steps were used to conduct the process of validation of a published decision-analytic model-based cost-effectiveness analysis of a risk-NBSP (UK healthcare perspective; lifetime horizon; costs (£; 2019). Internal validation was assessed in terms of: descriptive validity; technical validity; face validity. External validation was assessed in terms of: operational validation; convergent validity (or corroboration); predictive validity.ResultsThe results outline the findings of each step of internal and external validation. The positive aspects of the model in meeting internal validation requirements are shown. The limitations of MANC-RISK-SCREEN are described.ConclusionFollowing a transparent and structured validation process, MANC-RISK-SCREEN has been shown to have good internal validity and satisfactory external validity. We suggest that MANC-RISK-SCREEN provides a robust decision-analytic model to assess the cost-effectiveness of risk-NBSP from the UK perspective.Key points for decision makersThere are emerging suggested adaptations to national screening programmes, such as the introduction of risk-stratification to the national breast screening programme (risk-NBSP) in the United Kingdom (UK)There is a key role for the use of decision-analytic model-based analysis of healthcare interventions, such as a risk-NBSP, that are difficult to evaluate in trials due to the large number of participants required and very long follow up period required.This study follows structured frameworks to assess the internal and external validity of a decision-analytic model-based cost-effectiveness of a potential risk-NBSP. The decision-analytic model is shown to perform to a satisfactory level, with possible limitations described clearly, to inform resource allocation decisions from the perspective of the UK healthcare system.
Factors affecting e-payment acceptance by customers: an empirical study in the Kingdom of Bahrain
Authors: Albastaki Thabet , Hamdan Allam , Albastaki Yousif , Bakir Ali 
Published: December 2022

PurposeConsumers frequently use electronic payments (e-payment) as their first step into formal financial services. The advancement of information and communication technology, on the other hand, has resulted in several achievements for human civilization, altering people’s lives, behaviors and societal measures. This study’s main aim is to investigate issues and identify the factors that are likely to influence customers’ acceptance of implementing e-payment in the Kingdom of Bahrain.Design/methodology/approachA quantitative research approach was adopted to test the influence of e-payment data security, trust, ease of use, usefulness and accessibility on customers’ acceptance of the service. A questionnaire survey was electronically administered to a purposive sample, and 531 responses were returned, achieving the required sample size for the study. Descriptive statistics analysis was used to ascertain data validity and consistency, and regression analysis was used to test the model’s hypotheses.FindingsThe findings of this study demonstrated a high influence of the mentioned factors on the e-payment acceptance of the customers in the Kingdom of Bahrain. The main recommendations are to increase the adoption of e-payment; focus highly on the security factor in e-payment adoption; create a trustworthy e-payment service; strive to make the e-payment services more user-friendly; increase the longevity of the e-payment services by focusing on usefulness; and make e-payment services more accessible.Originality/valueThis study’s potential contribution is to identify the factors that influence e-payment acceptance by customers in Bahrain and draw attention to issues to be considered in adopting new e-payment services.