bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful Community Discharge Among Older Adults With Traumatic Brain Injury in Skilled Nursing Facilities
Authors: Evans Emily , Gutman Roee , Resnik Linda , Zonfrillo Mark R. , Lueckel Stephanie N. , Kumar Raj G. , DeVone Frank , Dams-O'Connor Kristen , Thomas Kali S.
Published: February 2021

Objective:

To identify patient, injury, and functional status characteristics associated with successful discharge to the community following a skilled nursing facility (SNF) stay among older adults hospitalized following traumatic brain injury (TBI).

Setting:

Skilled nursing facilities.

Participants:

Medicare fee-for-service beneficiaries admitted to an SNF after hospitalization for TBI.

Design:

Retrospective cohort study using Medicare administrative data merged with the National Trauma Data Bank using a multilayered Bayesian record linkage approach.

Main Outcome Measure:

Successful community discharge: discharged alive within 100 days of SNF admission and remaining in the community for 30 days or more without dying or admission to a healthcare facility.

Results:

Medicaid enrollment, incontinence, decreased independence with activities of daily living, and cognitive impairment were associated with lower odds of successful discharge, whereas race “other” was associated with higher odds of successful discharge. Injury factors including worse injury severity (Glasgow Coma Scale and Abbreviated Injury Scale scores) and fall-related injury mechanism were not associated with successful discharge.

Conclusion:

Among older adults with TBI who discharge to an SNF, sociodemographic and functional status characteristics are associated with successful discharge and may be useful to clinicians for discharge planning. Acute injury severity indices may have limited utility in predicting discharge disposition once a patient is admitted to an SNF for post–acute care.
Extracorporeal Cardiopulmonary Resuscitation in Adults. Interim Guideline Consensus Statement From the Extracorporeal Life Support Organization
Authors: Richardson Alexander (Sacha) C. , Tonna Joseph E. , Nanjayya Vinodh , Nixon Paul , Abrams Darryl C. , Raman Lakshmi , Bernard Stephen , Finney Simon J. , Grunau Brian , Youngquist Scott T. , McKellar Stephen H. , Shinar Zachary , Bartos Jason A. , Becker Lance B. , Yannopoulos Demetris , BˇELOHLÁVEK Jan , Lamhaut Lionel , Pellegrino Vincent
Published: February 2021

Disclaimer:

Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being deployed for selected patients in cardiac arrest who do not attain a native circulation with conventional CPR (ECPR). This ELSO guideline is intended to be a practical guide to implementing ECPR and the early management following establishment of ECMO support. Where a paucity of high-quality evidence exists, a consensus has been reached amongst the authors to provide guidance to the clinician. This guideline will be updated as further evidence in this field becomes available.
Incorporating the Laplacian Filter with a Three-Stream Multi-Channel Convolutional Neural Network for Improved Abnormality Detection in Knee MRIs
Authors: Kumar Rahul , Bhansali Rohan
Published: February 2021

Abstract

Despite ACL and meniscus tears being among the most common movement induced injuries, they are often the most difficult to diagnose due to the variable severity with which these tears occur. Typically, magnetic resonance imaging (MRI) scans are used for diagnosing ligament tears, but performing and analyzing these scans is time consuming and expensive due to the necessitation of a radiologist or professional orthopedic specialist. Consequently, we developed a custom three-stream convolutional neural network (CNN) architecture that contains multiple channels to automate the diagnosis of ACL and meniscus tears from MRI scans. Our algorithm utilizes the sagittal, coronal, and axial slices to maximize feature extraction. Furthermore, we apply the Laplace Operator on the MRI scan images to evaluate and compare its propensity in different medical imaging modalities. The algorithm attained an accuracy of 92.80%, significantly higher than that of orthopedic diagnosis accuracy. Our results point towards the feasibility of shallow, multi-channel CNNs and the ability of the Laplace Operator to improve performance metrics for MRI scan diagnosis.
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

Context

Several 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).

Objective

To analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD.

Design, Setting, and Participants

Cross-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 Measures

Salivary 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).

Results

Similar 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.

Conclusions

Adrenal 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

Background

Bronchoscopy 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.

Methods

Bedside 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.

Results

98 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.

Conclusion

Bronchoscopy 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

Without 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

SARS-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

Introduction

As 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.

Methods

We 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.

Results

From 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.

Conclusion

Our 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

Human 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

Background

Hypertension 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.

Methods

We 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.

Results

Of 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.

Conclusions

We 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

We 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.

Highlights

tDCS-DOSE had a linear effect on finger sequence performance for both hands

rCBF 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

To 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

Background

Maternal 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 presentation

A 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.

Conclusion

Here, 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

We 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

Background

South 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.

Methods

A 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.

Results

Of 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.

Conclusions

The 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%.
Arabic validation and cross-cultural adaptation of the 5C scale for assessment of COVID-19 vaccines psychological antecedents
Authors: ElHafeez Samar Abd , Shaaban Ramy , Elbarazi Iffat , ElMakhzangy Rony , Aly Maged Ossama , Alnagar Amr , Yacoub Mohamed , Saeh Haider M. El , Eltaweel Nashwa , Alqutub Sulafa T , Ghazy Ramy Mohamed
Published: February 2021

Background

In the Arab countries, there has not been yet a specific validated questionnaire that can assess the psychological antecedents of COVID-19 vaccine among the general population. This study, therefore, aimed to translate, culturally adapt, and validate the 5C scale into the Arabic language.

Methods

The 5C scale was translated into Arabic by two independent bilingual co-authors, and then subsequently translated back into English. After reconciling translation disparities, the final Arabic questionnaire was disseminated into four randomly selected Arabic countries (Egypt, Libya, United Arab Emirates (UAE), and Saudi Arabia). Data from 350 Arabic speaking adults (aged ≥18 years) were included in the final analysis. Convergent, discriminant, exploratory and confirmatory factor analyses were carried out. Internal consistency was assessed by Cronbach alpha.

Results

Age of participants ranged between 18 to 73 years; 57.14% were females, 37.43% from Egypt, 36.86%, from UAE, and 30% were healthcare workers. The 5 sub-scales of the questionnaire met the criterion of internal consistency (Cronbach alpha ≥0.7). Convergent validity was identified by the significant inter-item and item-total correlation (P<0.001). Discriminant validity was reported as inter-factor correlation matrix (<0.7). Exploratory factor analysis indicated that the 15 items of the questionnaire could be summarized into five factors. Confirmatory factor analysis confirmed that the hypothesized five-factor model of the 15-item questionnaire was satisfied with adequate psychometric properties and fit with observed data (RMSEA=0.060,GFI=0.924, CFI=0.957, TLI=0.937, SRMR=0.076 & NFI=906).

Conclusion

the Arabic version of the 5C scale is a valid and reliable tool to assess the psychological antecedents of COVID-19 vaccine among Arab population.
Estimating vaccine confidence levels among future healthcare workers and their trainers: A quantitative study protocol
Authors: Oduwole Elizabeth O. , Mahomed Hassan , Ayele Birhanu T. , Wiysonge Charles S.
Published: February 2021

Introduction

The outbreak of novel coronavirus disease 2019 (COVID-19) caught the world off guard in the first quarter of the year 2020. To stem the tide of this pandemic, the development, testing, and pre-licensure approval for emergency use of some COVID 19 vaccine candidates were accelerated. This led to raised public concern about their safety and efficacy, compounding the challenges of vaccine hesitancy which was already declared one of the top ten threats to global health in the year 2019. The onus of managing and administering these vaccines to a skeptical populace when they do become available rests mostly on the shoulders of healthcare workers (HCWs). Therefore, the vaccine confidence levels of HCWs becomes critical to the success of vaccination endeavors, especially COVID 19 vaccination. This proposed study aims to estimate the level of vaccine confidence and the intention to receive a COVID 19 vaccine among future HCWs and their trainers at a specific university in Cape Town, South Africa, and to identify any vaccination concerns early for targeted intervention.

Methods and analysis

An online survey will be distributed to current staff and students of an academic institution for HCWs. The survey questionnaire will consist of a demographic questions section consisting of six items and a vaccine confidence section comprising six items in Likert scale format.

A multinomial logistic regression model will be employed to identify factors associated with vaccine confidence and intention. The strength of association will be assessed using odds ratio and its 95% confidence interval. Statistical significance will be defined at a p-value <0.05.

Ethics and dissemination

Ethics approval has been obtained for the study from Stellenbosch University (HREC Reference # S19/01/014 (PhD)). The results will be shared with relevant health authorities, presented at conferences, and published in a peer-reviewed journal.

ARTICLE SUMMARY

Strengths and limitations of this study

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The proposed study will generate baseline knowledge of the vaccine confidence among future healthcare workers and their trainers in its specific context.

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It will contribute to addressing the knowledge gap about the intention to receive a COVID 19 vaccine among health care workers in Africa.

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It will enable the early identification of vaccine concerns of healthcare workers while they are still in training and assist in informing tailored measures to address them.

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A limitation of the study is the possibility of a low response rate which is an inherent challenge of online surveys.
The intersectional role of paternal gender-equitable attitudes and maternal empowerment on child undernutrition in India
Authors: Sharma Anupam Joya , Subramanyam Malavika Ambale
Published: February 2021

Objectives

Undernutrition is a major global health concern, especially for the low- and middle-income countries. Despite several programmatic efforts by the government, prevalence of undernutrition among Indian children under five years was about 38% in 2015. While studies have extensively investigated the influence of sociodemographic and maternal related factors on child undernutrition, the paternal factors and their interactions with other causal factors are understudied. To fill this gap, we conducted an intersectional analysis to assess the relationship between maternal, paternal, and wealth related factors with stunting and severe stunting among underfives in India.

Methods

We used a sample of 22,867 mother-father-child triads from the fourth round of India’s National Family Health Survey (2015-16). We fitted survey adjusted logistic regression models and further adjusted our models for several sociodemographic variables. Results: Our statistical models revealed that even among children from poorer households, those with either an empowered mother or a father with gender-equitable attitudes versus those with none such parents, had a lower odds of stunting (AOR: 0.92, CI: 0.84, 1.02) and severe stunting (AOR: 0.87, CI:0.77, 0.98), independent of all covariates.

Conclusion

We argue that while women’s autonomy could reduce the risk of child undernutrition, focusing on men’s attitudes towards gender equity also holds promise for reducing undernutrition. Our findings not only underscore how patriarchy is embodied in undernourished children, but also suggest programmatic interventions to address this deep-rooted scourge in India.
Network analysis identifies DAPK3 as a potential biomarker for lymphovascular invasion and prognosis of colon adenocarcinoma
Authors: Chen Huey-Miin , MacDonald Justin A.
Published: February 2021

Adenocarcinoma of the colon is the fourth most common malignancy worldwide with significant rates of mortality. Hence, the identification of novel molecular biomarkers with prognostic significance is of particular importance for improvements in treatment and patient outcome. Clinical traits and RNA-Seq data of 551 patient samples and 18,205 genes in the UCSC Toil Recompute Compendium of TCGA TARGET and GTEx datasets (restricted to |Primary_site| = colon) were obtained from the Xena platform. Weighted gene co-expression network analysis was completed, and 24 unique modules were assembled to specifically examine the association between gene networks and cancer cell invasion. One module, containing 151 genes, was significantly correlated with lymphatic invasion, a histopathological feature of higher-risk colon cancer. Search tool for the retrieval of interacting genes/proteins (STRING) and gene ontology (GO) analyses identified the module to be enriched in genes related to cytoskeletal organization and apoptotic signaling, suggesting involvement in tumor cell survival and migration along with epithelial-mesenchymal transformation. Of genes that were differentially expressed and significant for overall survival, DAPK3 (death-associated protein kinase 3) was revealed as the pseudo-hub of the module. Although DAPK3 expression was reduced in colon cancer patients, survival analysis revealed that high expression of DAPK3 was significantly correlated with greater lymphovascular invasion and poor overall survival.
Slow phase-locked endogenous modulations support selective attention to sound
Authors: Kachlicka Magdalena , Laffere Aeron , Dick Fred , Tierney Adam
Published: February 2021

To make sense of complex soundscapes, listeners must select and attend to task-relevant streams while ignoring uninformative sounds. One possible neural mechanism underlying this process is alignment of endogenous oscillations with the temporal structure of the target sound stream. Such a mechanism has been suggested to mediate attentional modulation of neural phase-locking to the rhythms of attended sounds. However, such modulations are compatible with an alternate framework, where attention acts as a filter that enhances exogenously-driven neural auditory responses. Here we attempted to adjudicate between theoretical accounts by playing two tone steams varying across condition in tone duration and presentation rate; participants attended to one stream or listened passively. Attentional modulation of the evoked waveform was roughly sinusoidal and scaled with rate, while the passive response did not. This suggests that auditory attentional selection is carried out via phase-locking of slow endogenous neural rhythms.
Systematic measurement of combination drug landscapes to predictin vivotreatment outcomes for tuberculosis
Authors: Larkins-Ford Jonah , Greenstein Talia , Van Nhi , Degefu Yonatan N. , Olson Michaela C. , Sokolov Artem , Aldridge Bree B.
Published: February 2021

A lengthy multidrug chemotherapy is required to achieve a durable cure in tuberculosis. Variation inMycobacterium tuberculosisdrug response is created by the differing microenvironments in lesions, which generate different bacterial drug susceptibilities. To better realize the potential of combination therapy to shorten treatment duration, multidrug therapy design should deliberately explore the vast combination space. We face a significant scaling challenge in making systematic drug combination measurements because it is not practical to use animal models for comprehensive drug combination studies, nor are there well-validated high-throughputin vitromodels that predict animal outcomes. We hypothesized that we could both prioritize combination therapies and quantify the predictive power of variousin vitromodels for drug development using a dataset of drug combination dose responses measured in multiplein vitromodels. We systematically measuredM. tuberculosisresponse to all 2- and 3-drug combinations among ten antibiotics in eight conditions that reproduce lesion microenvironments. Applying machine learning to this comprehensive dataset, we developed classifiers predictive of multidrug treatment outcome in a mouse model of disease relapse. We trained classifiers on multiple mouse models and identified ensembles ofin vitromodels that best describein vivotreatment outcomes. Furthermore, we found that combination synergies are less important for predicting outcome than metrics of potency. Here, we map a path forward to rationally prioritize combinations for animal and clinical studies using systematic drug combination measurements with validatedin vitromodels. Our pipeline is generalizable to other difficult-to-treat diseases requiring combination therapies.

One Sentence Summary

Signatures ofin vitropotency and drug interaction measurements predict combination therapy outcomes in mouse models of tuberculosis.
Site-specific O-glycosylation analysis of SARS-CoV-2 spike protein produced in insect and human cells
Authors: Bagdonaite Ieva , Thompson Andrew J. , Wang Xiaoning , Søgaard Max , Fougeroux Cyrielle , Frank Martin , Diedrich Jolene K. , Yates John R. , Salanti Ali , Vakhrushev Sergey Y. , Paulson James C. , Wandall Hans H.
Published: February 2021

Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures. SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported. The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence difficult to predict. Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S – insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD). In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD. Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites. However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy. This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
Development of a highly sensitive bioanalytical assay for the quantification of favipiravir
Authors: Curley Paul , Neary Megan , Arshad Usman , Tatham Lee , Pertinez Henry , Box Helen , Rajoli Rajith KR , Valentijn Anthony , Sharp Joanne , Rannard Steve P , Owen Andrew
Published: February 2021

Favipiravir (FAV; T-705) has been approved for use as an anti-influenza therapeutic and has reports against a wide range of viruses (e.g., Ebola virus, rabies and norovirus). Most recently FAV has been reported to demonstrate activity against SARS-CoV-2. Repurposing opportunities have been intensively studied with only limited success to date. If successful, repurposing will allow interventions to become more rapidly available than development of new chemical entities. Pre-clinical and clinical investigations of FAV require robust, reproducible and sensitive bioanalytical assay. Here, a liquid chromatography tandem mass spectrometry assay is presented which was linear from 0.78-200 ng/mL Accuracy and precision ranged between 89% and 110%, 101% and 106%, respectively. The presented assay here has applications in both pre-clinical and clinical research and may be used to facilitate further investigations into the application of FAV against SARS-CoV-2.
De-novointer-regional coactivations of pre-configured local ensembles support memory
Authors: Miyawaki Hiroyuki , Mizuseki Kenji
Published: February 2021

Neuronal ensembles in the amygdala, ventral hippocampus, and prefrontal cortex are involved in fear memory; however, how the inter-regional ensemble interactions support memory remains elusive. Using multi-regional large-scale electrophysiology in the afore-mentioned structures of fear-conditioned rats, we demonstrated that local ensembles activated during fear memory acquisition were inter-regionally coactivated during subsequent sleep, which relied on brief bouts of fast network oscillations. During memory retrieval, coactivations reappeared, accompanying fast oscillations. Ensembles contributing to inter-regional coactivation were configured prior to memory acquisition in the amygdala and prefrontal cortex but developed through experience in the hippocampus. Our observation suggests that elements of a given memory are instantly encoded within various brain regions in a pre-configured manner, whereas hippocampal ensembles and the network for inter-regional integration of the distributed information develop in an experience-dependent manner to form a new memory, which is consistent with hippocampal memory index hypothesis.
Transcriptomic profiling of canine atrial fibrillation models after one week of sustained arrhythmia
Authors: Leblanc Francis J.A. , Hassani Faezeh Vahdati , Liesinger Laura , Qi Xiaoyan , Naud Patrice , Birner-Gruenberger Ruth , Lettre Guillaume , Nattel Stanley
Published: February 2021

Background

Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with increased morbidity, mortality, and health-care costs. AF develops over many years and is often related to substantial atrial structural and electrophysiological remodeling. AF may lack symptoms at onset and atrial biopsy samples are generally obtained in subjects with advanced disease, so it is difficult to study earlier-stage pathophysiology in humans.

Methods

Here, we characterized comprehensively the transcriptomic (miRNAseq and mRNAseq) changes in the left atria of two robust canine AF-models after one week of electrically-maintained AF, without or with ventricular rate-control via atrioventricular node-ablation/ventricular pacing.

Results

Our RNA-sequencing experiments identified thousands of genes that are differentially expressed, including a majority that have never before been implicated in AF. Gene-set enrichment analyses highlighted known (e.g. extracellular matrix structure organization) but also many novel pathways (e.g. muscle structure development, striated muscle cell differentiation) that may play a role in tissue remodeling and/or cellular transdifferentiation. Of interest, we found dysregulation of a cluster of non-coding RNAs, including many microRNAs but also theMEG3long non-coding RNA orthologue, located in the syntenic region of the imprinted humanDLK1-DIO3locus. Interestingly (in the light of other recent observations), our analysis identified gene-targets of differentially expressed microRNAs at theDLK1-DIO3locus implicating glutamate signaling in AF pathophysiology.

Conclusions

Our results capture molecular events that occur at an early stage of disease development using well-characterized animal models, and may therefore inform future studies that aim to further dissect the causes of AF in humans.
Electrocommunication signals indicate motivation to compete during dyadic interactions of an electric fish
Authors: Raab Till , Bayezit Sercan , Erdle Saskia , Benda Jan
Published: February 2021

Animals across species compete for limited resources. While in some species competition behavior is solely based on own abilities, others assess their opponents to facilitate these interactions. Using cues and communication signals, contestants gather information about their opponent, adjust their behavior accordingly, and can thereby avoid high costs of escalating fights. We tracked electrocommunication signals, in particular “rises”, and agonistic behaviors of the gymnotiform electric fishApteronotus leptorhynchusin staged competition experiments. A larger body size relative to the opponent was the sole significant predictor for winners. Sex and the frequency of the continuously emitted electric field were only mildly influencing competition outcome. In males, correlations of body-size and winning were stronger than in females and, especially when losing against females, communication and agonistic interactions were enhanced, hinting towards males being more motivated to compete. Fish that lost competitions emitted the majority of rises in dependence on the competitors’ relative size and sex. The emission of rises was costly since it provoked ritualized biting or chasing behaviors by the other fish. Despite winners being accurately predictable based on rise numbers already after the initial 25 minutes, losers continued to emit rises. The number of rises emitted by losers and the duration of chasing behaviors depended in similar ways on physical attributes of contestants. The detailed evaluation of these correlations hint towardsA. leptorhynchusadjusting their competition behavior according to mutual assessment, where rises could signal a loser’s motivation to continue assessment through ritualized fighting.