bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salivary profiles of 11-oxygenated androgens follow a diurnal rhythm in patients with congenital adrenal hyperplasia
Authors: Nowotny Hanna , Auer Matthias K. , Lottspeich Christian , Schmidt Heinrich , Dubinski Ilja , Bidlingmaier Martin , Adaway Jo , Hawley James , Keevil Brian , Reisch Nicole 
Published: February 2021

AbstractContextSeveral studies have highlighted the importance of the 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as potential biomarkers for monitoring patients with 21-hydroxylase deficiency (21OHD).ObjectiveTo analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD.Design, Setting, and ParticipantsCross-sectional single center study including 34 patients with classic 21OHD (men=14; women=20) and 32 BMI- and age-matched controls (men=15; women=17).Outcome MeasuresSalivary concentrations of the following steroids were analyzed by LC-MS/MS: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT).ResultsSimilar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11-OHA4:male patients Δmean= 79 %; male controls Δmean= 81%; female patients Δmean= 33 %; female controls Δmean= 91 %;11KT:male patients Δmean= 64 %; male controls Δmean= 60 %; female patients Δmean= 49 %; female controls Δmean= 81 %). Significant correlations between the area under the curve (AUC) for 17OHP and 11KT (r(p)male= 0.741**; r(p)female= 0.842****), and 11OHA4 (r(p)male= 0.385n.s.; r(p)female= 0.527*) were observed in patients but not in controls.ConclusionsAdrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.
Bronchoscopy in COVID19 ARDS patients on mechanical ventilation – a prospective study
Authors: Mehta Ravindra , Bansal Sameer , Kumar Ashwin , Thorbole Anmol , Chakravarthi L , Kalpakam Hariprasad 
Published: February 2021

AbstractBackgroundBronchoscopy has been done sparingly in COVID19 patients due to the risk of aerosol generation, with few reports describing its clinical utility. We describe a study on bronchoscopy in mechanically ventilated (MV) COVID-19 patients outlining the procedural, clinical, utilitarian and safety aspects.MethodsBedside bronchoscopy was performed in suspected or confirmed COVID-19 cases on MV; only positive cases were included in the study. Demographic, clinical, bronchoscopic and laboratory findings were noted and analysed.Results98 procedures were performed on 61 patients, mean age of 62.1 years, 51 (83.6%) males. 42 patients (69%) had at least 1 co-morbidity. Major indications for bronchoscopy were new radiographic infiltrates with clinical deterioration, increased endotracheal tube (ETT) secretions and haemorrhagic secretions/hemoptysis. Common findings were copious secretions in 87 (88.8%), purulent in 61%, mucoid in 18%, haemorrhagic in 7% and frothy in 14% cases. Morphologically, hyperaemic airways were seen in 85 (86.7%) cases, ranging from mild (61%) to moderate-severe (39%). On the management front, antibiotics were changed in 31 (31.6%) cases based on bronchoscopic findings. Other significant changes included reduction or stopping of steroids and anticoagulation, fluid, and diuretic adjustment and ETT repositioning. The incidence of bacterial superinfection was also high (54% culture positivity for various bacteria), a significant number (94%) with multi-drug resistant organisms. Fungi were seen in 7 cases (7.1%). Pneumocystis jiroveci was not seen and cytology did not show any viral inclusions. Therapeutic mucus plug removal was done in 30 cases (30.6%), and hemoptysis control in 4% cases. The procedures were safe with no complications, and none of the HCW developed any COVID19 infection.ConclusionBronchoscopy in critically ill MV COVID-19 patients contributes on both diagnostic and therapeutic fronts and can significantly influence management decisions. With adequate precautions and standard protocols, it is safe for both HCW and patients.
Human mobility and COVID-19 transmission: a systematic review and future directions
Authors: Zhang Mengxi , Wang Siqin , Hu Tao , Fu Xiaokang , Wang Xiaoyue , Hu Yaxin , Halloran Briana , Cui Yunhe , Liu Haokun , Liu Zhimin , Bao Shuming 
Published: February 2021

AbstractWithout a widely distributed vaccine, controlling human mobility has been identified and promoted as the primary strategy to mitigate the transmission of COVID-19. Many studies have reported the relationship between human mobility and COVID-19 transmission by utilizing the spatial-temporal information of mobility data from various sources. To better understand the role of human mobility in the pandemic, we conducted a systematic review of articles that measure the relationship between human mobility and COVID-19 in terms of their data sources, statistical models, and key findings. Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we selected 47 articles from Web of Science Core Collection up to September 2020. Restricting human mobility reduced the transmission of COVID-19 spatially, although the effectiveness and stringency of policy implementation vary temporally and spatially across different stages of the pandemic. We call for prompt and sustainable measures to control the pandemic. We also recommend researchers 1) to enhance multi-disciplinary collaboration; 2) to adjust the implementation and stringency of mobility-control policies in corresponding to the rapid change of the pandemic; 3) to improve statistical models used in analyzing, simulating, and predicting the transmission of the disease; and 4) to enrich the source of mobility data to ensure data accuracy and suability.
SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection
Authors: Cohen Carolyn A , Li Athena PY , Hachim Asmaa , Hui David SC , Kwan Mike YW , Tsang Owen TY , Chiu Susan S , Chan Wai Hung , Yau Yat Sun , Kavian Niloufar , Ma Fionn NL , Lau Eric HY , Cheng Samuel MS , Poon Leo LM , Peiris JS Malik , Valkenburg Sophie A 
Published: February 2021

AbstractSARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults remains unclear. We quantified the SARS-CoV-2 specific T cell responses in adults and children (<13 years of age) with RT-PCR confirmed asymptomatic and symptomatic infection for long-term memory, phenotype and polyfunctional cytokines. Acute and memory CD4+T cell responses to structural SARS-CoV-2 proteins significantly increased with age, whilst CD8+T cell responses increased with time post infection. Infected children had significantly lower CD4+and CD8+T cell responses to SARS-CoV-2 structural and ORF1ab proteins compared to infected adults. SARS-CoV-2-specific CD8+T cell responses were comparable in magnitude to uninfected negative adult controls. In infected adults CD4+T cell specificity was skewed towards structural peptides, whilst children had increased contribution of ORF1ab responses. This may reflect differing T cell compartmentalisation for antigen processing during antigen exposure or lower recruitment of memory populations. T cell polyfunctional cytokine production was comparable between children and adults, but children had a lower proportion of SARS-CoV-2 CD4+T cell effector memory. Compared to adults, children had significantly lower levels of antibodies to β-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses was increased in children during acute infection indicating rapid co-ordination of the T and B cell responses. However total monocyte responses were reduced in children which may be reflective of differing levels of inflammation between children and adults. Therefore, reduced prior β-coronavirus immunity and reduced activation and recruitment ofde novoresponses in children may drive milder COVID-19 pathogenesis.
A Dynamic Bayesian Model for Identifying High-Mortality Risk in Hospitalized COVID-19 Patients
Authors: Momeni-Boroujeni Amir , Mendoza Rachelle , Stopard Isaac J. , Lambert Ben , Zuretti Alejandro 
Published: February 2021

AbstractIntroductionAs COVID-19 hospitalization rates remain high, there is an urgent need to identify prognostic factors to improve treatment. Our analysis, to our knowledge, is one of the first to quantify the risk associated with dynamic clinical measurements taken throughout the course of hospitalization.MethodsWe collected data for 553 PCR-positive COVID-19 patients admitted to hospital whose eventual outcomes were known. The data collected for the patients included demographics, comorbidities and laboratory values taken at admission and throughout the course of hospitalization. We trained multivariate Markov prognostic models to identify high-risk patients at admission along with a dynamic measure of risk incorporating time-dependent changes in patients’ laboratory values.ResultsFrom the set of factors available upon admission, the Markov model determined that age >80 years, history of coronary artery disease and chronic obstructive pulmonary disease increased mortality risk. The lab values upon admission most associated with mortality included neutrophil percentage, RBC, RDW, protein levels, platelets count, albumin levels and MCHC. Incorporating dynamic changes in lab values throughout hospitalization lead to dramatic gains in the predictive accuracy of the model and indicated a catalogue of variables for determining high-risk patients including eosinophil percentage, WBC, platelets, pCO2, RDW, LUC count, alkaline phosphatase and albumin.ConclusionOur prognostic model highlights the nuance of determining risk for COVID-19 patients and indicates that, rather than a single variable, a range of factors (at different points in hospitalization) are needed for effective risk stratification.
Parental lifespan and polygenic risk score of longevity are associated with white matter hyperintensities
Authors: Dong Chao , Thalamuthu Anbupalam , Jiang Jiyang , Mather Karen A. , Brodaty Henry , Sachdev Perminder S. , Wen Wei 
Published: February 2021

AbstractHuman longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain ageing. In this study, we investigated the associations of parental lifespan (parental age at death) and polygenic risk score for longevity (longevity-PRS) with structural magnetic resource imaging (MRI) brain metrics considered to reflect the brain ageing process. We used a discovery sample (N = 19136) from the UK Biobank and a replication sample (N =809) from the Sydney Memory and Ageing Study and the Older Australian Twins Study. We found lower cerebral white matter hyperintensity (WMH) volumes to be significantly associated with longer parental lifespan in the discovery and replication samples and higher longevity-PRS in the discovery sample and a similar trend in the replication sample. The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus. Additionally, the effects of longevity-PRS on the association were more prominent in males, especially in the older-male group. Our findings suggest that human longevity-related genes may have an influence on WMH burden, suggesting WMH volume may be a biomarker for longevity and an ageing endophenotype.
Status of hypertension control in urban slums of Central India : A Community health worker based two-year follow up
Authors: Abhijit Pakhare , Anuja Lahiri , Neelesh Shrivastava , K N Subba , Kurra Veera Durga Vaishnavi , Ankur Joshi , Shubham Atal , Sagar Khadanga , Rajnish Joshi 
Published: February 2021

AbstractBackgroundHypertension is a leading cause of cardiovascular diseases and its control is poor. There is heterogeneity in levels of blood-pressure control among various population sub-groups. The present study was conducted within the framework of National Program for prevention and control of cancer, diabetes, cardiovascular diseases and stroke (NPCDCS) in India. It aims to estimate proportion of optimal blood pressure control and identify potential risk factors pertaining to uncontrolled hypertension consequent to initial screening.MethodsWe assembled a cohort of individuals with hypertension confirmed in a baseline screening in sixteen urban slum clusters of Bhopal (2017-2018). Sixteen Accredited Social Health Activists (ASHAs) were trained from within these slums. Individuals with hypertension were linked to primary care providers and followed-up for next two years. Obtaining optimal blood-pressure control (defined as SBP< 140 and DBP<90 mm of Hg) was a key outcome.ResultsOf a total of 6174 individuals, 1571 (25.4%) had hypertension, of which 813 were previously known and 758 were newly detected during baseline survey. Two year follow up was completed for 1177 (74.9%). Blood-pressure was optimally controlled in 301 (26%) at baseline, and in 442 (38%) individuals at two years (absolute increase of 12%; 95% CI 10.2-13.9). Older age, physical-inactivity, higher BMI and newly diagnosed hypertension were significantly associated with uncontrolled blood-pressure.ConclusionsWe found about six of every ten individuals with hypertension were on-treatment, and about four were optimally controlled. These findings provide a benchmark for NPCDCS, in terms of achievable goals within short periods of follow-up.
Effects of tDCS Dose and Electrode Montage on regional cerebral blood flow and motor behavior
Authors: Shinde Anant , Lerud Karl , Munsch Fanny , Alsop David C , Schlaug Gottfried 
Published: February 2021

AbstractWe used three dose levels (Sham, 2mA, and 4mA) and two different electrode montages (unihemispheric or bihemispheric) to examine DOSE and MONTAGE effects on regional cerebral blood flow (rCBF) as a surrogate marker of neural activity, and on a finger sequence task, as a surrogate behavioral measure drawing on brain regions targeted by transcranial direct current stimulation (tDCS). We placed the anodal electrode over the right motor region (C4) while the cathodal or return electrode was placed either over a left supraorbital region (unihemispheric montage) or over the left motor region (C3 in the bihemispheric montage). Performance changes in the finger sequence task for both hands (left hand: p = 0.0026, and right hand: p = 0.0002) showed a linear tDCS dose response but no montage effect. rCBF in the right hemispheric perirolandic area increased with dose under the anodal electrode (p = 0.027). In contrast, in the perirolandic ROI in the left hemisphere, rCBF showed a trend to increase with dose (p = 0.053) and a significant effect of montage (p = 0.00004). The bihemispheric montage showed additional rCBF increases in frontomesial regions in the 4mA condition but not in the 2mA condition. Furthermore, we found correlations between rCBF changes in the right perirolandic region and improvements in the finger sequence task performance (FSP) for the left and right hand. Our data support not only a strong direct tDCS dose effect for rCBF and FSP as surrogate measures of targeted brain regions but also indirect effects on rCBF in functionally connected regions (e.g., frontomesial regions), particularly in the higher dose condition and on FSP of the ipsilateral hand (to the anodal electrode). At a higher dose and irrespective of polarity, a wider network of sensorimotor regions is positively affected by tDCS.HighlightstDCS-DOSE had a linear effect on finger sequence performance for both handsrCBF changes in both perirolandic ROIs demonstrated tDCS-DOSE effects, and left perirolandic ROI demonstrated tDCS-MONTAGE effects.Simulated current intensity in the left and right perirolandic ROI strongly correlated with the contralateral hand’s finger sequence performance.tDCS-Tolerability scores did not correlate with change in rCBF or finger sequence performance of the left hand.Graphical Abstract
Myelin biogenesis is associated with pathological ultrastructure that is resolved by microglia during development
Authors: Djannatian Minou , Weikert Ulrich , Safaiyan Shima , Wrede Christoph , Deichsel Cassandra , Kislinger Georg , Ruhwedel Torben , Campbell Douglas S. , van Ham Tjakko , Schmid Bettina , Hegermann Jan , Möbius Wiebke , Schifferer Martina , Simons Mikael 
Published: February 2021

ABSTRACTTo enable rapid propagation of action potentials, axons are ensheathed by myelin, a multilayered insulating membrane formed by oligodendrocytes. Most of the myelin is generated early in development, in a process thought to be error-free, resulting in the generation of long-lasting stable membrane structures. Here, we explored structural and dynamic changes in CNS myelin during development by combining ultrastructural analysis of mouse optic nerves by serial block face scanning electron microscopy and confocal time-lapse imaging in the zebrafish spinal cord. We found that myelin undergoes extensive ultrastructural changes during early postnatal development. Myelin degeneration profiles were engulfed and phagocytosed by microglia in a phosphatidylserine-dependent manner. In contrast, retractions of entire myelin sheaths occurred independently of microglia and involved uptake of myelin by the oligodendrocyte itself. Our findings show that the generation of myelin early in development is an inaccurate process associated with aberrant ultrastructural features that requires substantial refinement.
Newborn Antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination
Authors: Gilbert Paul , Rudnick Chad 
Published: February 2021

AbstractBackgroundMaternal vaccination for Influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies. Similar newborn protection would be expected after maternal vaccination against SARS-CoV-2 (the virus responsible for COVID-19). There is a significant and urgent need for research regarding safety and efficacy of vaccination against SARS-CoV-2 during pregnancy. Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination.Case presentationA vigorous, healthy, full-term female was born to a COVID-19 naïve mother who had received a single dose of mRNA vaccine for SARS-CoV-2 three weeks prior to delivery. Cord blood antibodies (IgG) were detected to the S-protein of SARS-CoV-2 at time of delivery.ConclusionHere, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination.
Using a household structured branching process to analyse contact tracing in the SARS-CoV-2 pandemic
Authors: Fyles Martyn , Fearon Elizabeth , Overton Christopher ,   University of Manchester COVID-19 Working Group, Wingfield Tom , Medley Graham F , Hall Ian , Pellis Lorenzo , House Thomas 
Published: February 2021

AbstractWe explore strategies of contact tracing, case isolation and quarantine of exposed contacts to control the SARS-CoV-2 epidemic using a branching process model with household structure. This structure reflects higher transmission risks among household members than among non-household members, and is also the level at which physical distancing policies have been applied. We explore implementation choices that make use of household structure, and investigate strategies including two-step tracing, backwards tracing, smartphone tracing and tracing upon symptom report rather than test results. The primary model outcome is the effect on the growth rate of the epidemic under contact tracing in combination with different levels of physical distancing, and we investigate epidemic extinction times to indicate the time period over which interventions must be sustained. We consider effects of non-uptake of isolation/quarantine, non-adherence, and declining recall of contacts over time. We find that compared to self-isolation of cases but no contact tracing, a household-based contact tracing strategy allows for some relaxation of physical distancing measures; however, it is unable to completely control the epidemic in the absence of other measures. Even assuming no imported cases and sustainment of moderate distancing, testing and tracing efforts, the time to bring the epidemic to extinction could be in the order of months to years.
Field performance evaluation of the PanBio rapid SARS-CoV-2 antigen assay in an epidemic driven by 501Y.v2 (lineage B.1.351) in the Eastern Cape, South Africa
Authors: Akingba Oluwakemi Laguda , Sprong Kaitlin , Hardie Diana Ruth 
Published: February 2021

AbstractBackgroundSouth Africa was the African country most severely affected by the SARS-CoV-2 pandemic during 2020, experiencing 2 waves of infection. During the first wave, diagnostics were largely based on reverse transcription-linked PCR (RT-PCR). The Abbott PanBio antigen test was deployed during the 2nd wave which was driven by emergence of the 501Y.v2 variant. At the time of evaluation in mid-November 2020, 501Y.v2 was the dominant circulating virus in Nelson Mandela Bay, in the Eastern Cape Province.MethodsA prospective diagnostic evaluation study was undertaken, during a period of high community transmission, to evaluate the field performance of the PanBio antigen RTD. Testing was conducted at mobile community testing centres on 677 ambulant patients seeking SARS-CoV-2 testing. RT-PCR was performed on the original naso-pharyngeal antigen swabs to evaluate test performance.ResultsOf 146 RT-PCR positive individuals, 101 were RTD positive in the clinic. The antigen RTD had an overall sensitivity of 69.2% (95%CI 61.4, 75.8) and specificity of 99.0% (95%CI 98.8, 99.3) in this clinical context. Sensitivity was strongly dependent on the amount of virus in clinical samples, as reflected by the PCR cycle threshold (CT) value, with 100% detection in samples where the CT was <20, 96% with CT between 20-25, 89% with CT between 26-30 and 64% when CT was 31-35.ConclusionsThe assay reliably detected 501Y.v2 infections in ambulatory ill patients. Assay sensitivity was >90% in patients with high viral loads who are expected to be most infectious. Negative and positive predictive values were also >90%.