bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Telerehabilitation in Physical Therapist Practice: An Umbrella and Mapping Review With Meta–Meta-Analysis
Authors: Suso-Martí Luis , La Touche Roy , Herranz-Gómez Aida , Angulo-Díaz-Parreño Santiago , Paris-Alemany Alba , Cuenca-Martínez Ferran
Published: February 2021

Objective

Telerehabilitation is an option that should be adapted as soon as possible to face the crisis caused by coronavirus disease 2019. An umbrella and mapping review with meta–meta-analysis (MMA) of the available scientific evidence was performed to determine whether telerehabilitation could be an effective alternative to conventional rehabilitation in physical therapist practice.

Methods

A systematic review of reviews and a synthesis of the findings of all systematic evidence published to date with a visual map and a meta–meta-analysis (MMA) were performed. A systematic search was realized in Cochrane Database of Systematic Reviews, MEDLINE (PubMed), and Google Scholar. Two independent reviewers performed a data analysis and assessed the quality of the included reviews, assessing the risk of bias using ROBIS.

Results

Twenty-nine articles that met the inclusion criteria were selected and divided according to the type of patient targeted for rehabilitation (patients with cardiorespiratory, musculoskeletal, and neurological conditions). The MMA regarding physical function between telerehabilitation and usual care rehabilitation did not reveal a statistically significant difference for patients with cardiorespiratory and musculoskeletal conditions. For patients with neurological conditions, the MMA revealed a statistically significant but negligible effect size in 6 reviews in favor of telerehabilitation (standardized mean difference = 0.18; 95% CI = 0.03–0.34).

Conclusion

The results of the present review showed that telerehabilitation offers positive clinical results, even comparable to conventional face-to-face rehabilitation approaches.

Impact

The advantages of lower cost and less interference by the rehabilitation processes in patients’ daily life could justify implementing telerehabilitation in clinical settings in the coronavirus disease 2019 era.
The need for mass testing and the proper post-COVID-19 test behavior in the Philippines
Authors: Mendoza Abelardo Jose M , dela Cruz Moriah Dianne M , Gozum Ivan Efreaim A , Galang Joseph Renus F
Published: February 2021

In a recent article, the researcher asked if people’s behavior after receiving negative COVID-19 tests contribute to the spread of the virus. It was discussed that even though testing mitigated the coronavirus spread, false confidence among those who have negative results contributed to the spread of the virus. This article, then, proposes that there is a need for mass testing for new virus variants and a foundation for proper behavior after testing.
Goths, Huns, and The Dream of the Rood
Authors: Neidorf Leonard
Published: February 2021

This article argues that two poems concerned with legends of Goths and Huns, the Old Norse Hlǫðskviða and the Old High German Hildebrandslied, provide an illuminating literary context for The Dream of the Rood. The critical utility of these poems inheres in their ability to delineate more precisely the intertextual relationship that obtains between The Dream of the Rood and the vernacular tradition of heroic poetry. When the poem is read in this context, Christ appears not to be vaguely heroic, but to be modelled on a specific type of hero: the intransigent youth who compels his unwilling adversary to fight him and ultimately take his life. The figures of Hlǫð and Hadubrand are shown to constitute the most relevant extant realizations of this type, while related examples from Waltharius and the Finnsburg fragment are adduced in order to confirm that the type was both traditional and widespread.
An Application of the Resource-Based Dynamic Process Model in the Context of Retirement Planning
Authors: Noone Jack , Earl Joanne , Stephens Christine , Rafalski Julia , Allen Joanne , Alpass Fiona , Topa Gabriela
Published: February 2021

Retirement planning is a widely promoted activity to enhance wellbeing for aging populations. However, there is limited follow-up data to understand the antecedents of multi-dimensional retirement planning activities, the resources such activities produce or the explanatory mechanisms. This research draws on recent theorizing, which suggests that retirement planning may play a mediating role in explaining how pre-retirement antecedents are transformed into retirement resources. Antecedents, planning and retirement resources were examined using 3 waves of follow-up data collected in 2006, 2008, and 2014. Four hundred thirty-five people originally employed in 2008 and retired by 2014 participated in the study. Health, income, and a positive retirement attitude (T1) were the strongest predictors of retirement planning (T2), but job satisfaction and occupation also played smaller predictive roles. Financial planning (T2) predicted health, psychosocial, and financial resources in retirement (T3). However, health, lifestyle, and psychosocial planning played a minimal role in explaining retirement resources, and only financial planning demonstrated noteworthy evidence of mediation. Findings can help to inform policy decisions by identifying those at greatest risk of not planning, and to isolate the factors most likely to explain the longer-term effects of planning. Understanding which resources are predicted by different domains of planning will also help inform the targeting of interventions.
Comparing health care system and physician practice influences on social risk screening
Authors: Frehn Jennifer L. , Brewster Amanda L. , Shortell Stephen M. , Rodriguez Hector P.
Published: February 2021

Background

Health care systems can support dissemination of innovations, such as social risk screening in physician practices, but to date, no studies have examined the association of health system characteristics and practice-level adoption of social risk screening.

Purpose

The aim of the study was to examine the association of multilevel organizational capabilities and adoption of social risk screening among system-owned physician practices.

Methodology

Secondary analyses of the 2018 National Survey of Healthcare Organizations and Systems were conducted. Multilevel linear regression models examined physician practice and system characteristics associated with practice adoption of screening for five social risks (food insecurity, housing instability, utility needs, interpersonal violence, and transportation needs), accounting for clustering of practices within systems using random effects.

Results

System-owned practices screened for an average of 1.7 of the five social risks assessed. The intraclass correlation indicated 16% of practice variation in social risk screening was attributable to differences between their health systems owners, with 84% attributable to differences between individual practices. Practices owned by systems with multiple hospitals screened for an additional 0.44 social risks (p = .046) relative to practices of systems without hospitals. Practice characteristics associated with social risk screening included health information technology capacity (β = 0.20, p = .005), innovation culture (β = 0.26, p < .001), and patient engagement strategies (β = 0.57, p < .001).

Conclusions

Health care system capabilities account for less variation in physician practice adoption of social risk screening compared to practice-level capabilities.

Practice Implications

Efforts to expand social risk screening among system-owned physician practices should focus on supporting practice capabilities, including enhancing health information technology, promoting an innovative organizational culture, and advancing patient engagement strategies.
Representation of Minority Groups in Key Pelvic Floor Disorder Trials
Authors: Mckay Elishia R. , Davila Jonathan L. , Lee Justin A. , Rolston Renee , Agalliu Ilir , Abraham Nitya E.
Published: February 2021

Background

Multicenter randomized clinical trials on pelvic floor disorders (PFDs) support evidence-based care. However, many of these studies include homogenous study populations lacking diversity. Heterogeneous sampling allows for greater generalizability while increasing knowledge regarding specific subgroups. The racial/ethnic makeup of key pelvic floor disorder (PFD) trials has not been examined.

Objective

This study aimed to investigate racial/ethnic representation in major PFD clinical trials in comparison to racial/ethnic distribution of PFD in the National Health and Nutritional Examination Survey (NHANES).

Methods

Demographic data were extracted from completed PFD Network (PFDN) and Urinary Incontinence Treatment Network studies, which have resulted in nearly 200 publications. Prevalence of PFD by race/ethnicity was obtained from the NHANES. A representative index (Observed “n” by PFD study/Expected “n” based on the NHANES-reported prevalence) was calculated as a measure of representation. Meta-analyses were performed for each outcome and overall with respect to race/ethnicity.

Results

Eighteen PFDN/Urinary Incontinence Treatment Network studies were analyzed. White women comprised 70%–89% of PFD literature; Black women, 6%–16%; Hispanic women, 9%–15%; Asians, 0.5%–6%; and American Indians, 0%–2%. Representation of White women was higher in 13 of 18 PFDN studies compared with the NHANES prevalence data. Representation of Black women was either decreased or not reported in 10 of 18 index studies compared with the NHANES prevalence data. Hispanic women were absent or underrepresented in 7 of 18 PFDN studies compared with the prevalence data.

Conclusions

Our examination of PFDN and other landmark trials demonstrates inconsistent reporting of minority subgroups, limiting applicability with respect to minority populations. Our study suggests that PFD research would benefit from targeted sampling of minority groups.
Pelvic Organ Prolapse Surgery in the Elderly and Frail: Safety of a Reconstructive Versus Obliterative Approach
Authors: Chapman Graham C. , Slopnick Emily A. , Roberts Kasey , Sheyn David , El-Nashar Sherif A. , Mangel Jeffrey M. , Hijaz Adonis K.
Published: February 2021

Objectives

The aim of this study was to compare the risk of complications associated with obliterative surgery versus reconstructive surgery in elderly and frail patients undergoing surgery for pelvic organ prolapse.

Methods

We performed a retrospective cohort study utilizing the American College of Surgeons National Surgical Quality Improvement Program Database from 2010 to 2017. We compared characteristics and perioperative complications in patients aged 80 years or older who underwent obliterative surgery versus reconstructive surgery. Multivariate logistic regression and propensity score matching were used to control for confounding. A subanalysis was performed that included patients who were considered frail as defined by the National Surgical Quality Improvement Program Modified Frailty Index 5.

Results

Of 1,654 total patients, reconstructive surgery was performed in 56.9% of patients, and obliterative surgery was performed in 43.1%. The respective composite complication rates were 9.2% and 9.8% (P = 0.69), whereas severe complications were experienced by 1.9% in the reconstructive group versus 0.8% in the obliterative group (P = 0.07). On multivariate logistic regression, reconstructive surgery was not significantly associated with the composite complication rate (adjusted odds ratio, 1.0; 95% confidence interval, 0.7–1.4; P = 0.80). After propensity score matching, composite complications did not differ between groups, but the rate of severe complications was significantly higher in patients who underwent reconstructive surgery compared with obliterative surgery (2.1% vs 0.8%; odds ratio, 2.53; 95% confidence interval, 1.01–6.36; P = 0.05). In frail patients only, complication rates did not differ between groups.

Conclusions

In patients aged 80 years or older, the overall rate of complications did not differ between those who underwent reconstructive surgery versus obliterative surgery. However, propensity score matching identified an increased risk of the most severe complications in patients who underwent reconstructive surgery.
Evaluating social and spatial inequalities of large scale rapid lateral flow SARS-CoV-2 antigen testing in COVID-19 management: An observational study of Liverpool, UK (November 2020 to January 2021)
Authors: Green Mark A. , García-Fiñana Marta , Barr Ben , Burnside Girvan , Cheyne Christopher P. , Hughes David , Ashton Matthew , Sheard Sally , Geddes Andrew , Rankin John , Buchan Iain E.
Published: February 2021

Objective

To explore social and spatial inequalities in uptake and case-detection of rapid lateral flow SARS-CoV-2 antigen tests (LFTs) offered to people without symptoms of COVID-19.

Design

Observational study.

Setting

Liverpool, UK.

Participants

496 784 residents.

Intervention

Free LFTs to all people living and working in Liverpool (6th November 2020 to 31st January 2021).

Main outcome measures

Residents who received a LFT, residents who had multiple LFTs, and positive test results.

Results

214 525 residents (43%) received a LFT identifying 5557 individuals as positive cases of COVID-19 (1.3%) between 6th November 2020 and 31st January 2021. 89 047 residents had more than one test (18%). Uptake was highest in November when there was military assistance. High uptake was observed again in the week preceding Christmas and was sustained into a national lockdown. Overall uptake and repeat testing were lower among males (e.g. 40% uptake over the whole period), Black Asian and other Minority Ethnic groups (e.g. 27% uptake for ‘Mixed’ ethnicity) and in the most deprived areas (e.g. 32% uptake in most deprived areas). These population groups were also more likely to have received positive tests for COVID-19. Spatial regression models demonstrated that uptake and repeat testing were lower in areas of higher deprivation, areas located further from test sites and areas containing populations less confident in the using Internet technologies. Positive tests were spatially clustered in deprived areas.

Conclusions

Large-scale voluntary asymptomatic community testing saw social, ethnic, and spatial inequalities in an ‘inverse care’ pattern, but with an added digital exclusion factor. COVID-19 testing and support to isolate need to be more accessible to the vulnerable communities most impacted by the pandemic, including non-digital means of access.

What is already known on this topic

Testing asymptomatic individuals with rapid lateral flow SARS-CoV-2 antigen devices detects the most infectious individuals who otherwise would have been unaware they were likely to infect others.

Liverpool (UK) conducted the world’s first whole population, open-access, voluntary asymptomatic testing programme for COVID-19 management.

The impacts of such testing on inequalities are unknown.

What this study adds

Testing uptake was lower, and test positivity was higher, among deprived populations, Black Asian and other Minority Ethnic groups and areas classified as having low Internet use.

Population-wide asymptomatic testing programmes need to account for social, spatial, and digital access issues in their design, communication and delivery to minimise inequalities in outcomes.
Digital cognitive behavioural therapy for insomnia and primary care costs in England: an interrupted time series analysis
Authors: Sampson Chris , Bell Eleanor , Cole Amanda , Miller Christopher B. , Rose James
Published: February 2021

Background

Sleepio is an automated digital programme that delivers cognitive behavioural therapy for insomnia. Sleepio has been proven effective in improving sleep difficulties. However, evidence for the possible impact of Sleepio use on health care costs in the United Kingdom has not previously been developed. In this study, we assessed the effect of a population-wide rollout of Sleepio in terms of primary care costs in the National Health Service (NHS) in England.

Methods

The study was conducted in the Thames Valley region of England, where access to Sleepio was made freely available to all residents between October 2018 and January 2020. We use primary care data for people with relevant characteristics from nine general practices in Buckinghamshire. The study relies on a quasi-experimental design, using an interrupted time series to compare the trend in primary care costs before and after the rollout of Sleepio. Primary care costs include general practice contacts and prescriptions. Segmented regression analysis was used to estimate primary and secondary outcomes.

Results

For the 10,704 patients included in our sample, the total saving over the 65-week follow-up period was £71,027. This corresponds to £6.64 per person in our sample or around £70.44 per Sleepio user. Secondary analyses suggest that savings may be driven primarily by reductions in prescriptions.

Conclusion

Sleepio rollout reduced primary care costs. National adoption of Sleepio may reduce primary care costs by £20 million in the first year. The expected impact on primary care costs in any particular setting will depend on the uptake of Sleepio.
Vagus nerve cross-sectional area in patients with Parkinson’s Disease – an ultrasound case-control study
Authors: Horsager Jacob , Walter Uwe , Fedorova Tatyana D , Andersen Katrine B. , Skjærbæk Casper , Knudsen Karoline , Okkels Niels , Weitzel-Mudersbach Paul von , Dyrskog Stig Eric , Bergholt Bo , Borghammer Per
Published: February 2021

Background

Vagal parasympathetic neurons are prone to degeneration in Parkinson’s disease (PD). High-resolution ultrasound can precisely estimate the cross-sectional area (CSA) of peripheral nerves. Here, we tested the hypothesis that vagus CSA is reduced in PD.

Methods

We included 56 healthy controls (HCs) and 63 patients with PD. Using a high-end ultrasound system equipped with a high-frequency transducer, five images were obtained of each nerve. The hypoechoic neuronal tissue was delineated offline with dedicated software and the CSA extracted.

Results

In the initial PD vs. HC comparison, no statistically significant differences were observed in mean left vagus CSA (HC: 1.97mm2, PD: 1.89mm2, P=0.36) or in mean right vagus CSA (HC: 2.37mm2, PD: 2.23mm2, P=0.17). The right vagus CSA was significantly larger than the left vagus CSA in both groups (P<0.0001). Females were overrepresented in the HC group and presented with generally smaller vagus CSAs. Consequently, sex-adjusted CSA was significantly smaller for the right vagus nerve of the PD group (P=0.041), but not for the left.

Conclusion

A small but significant reduction in sex-adjusted right vagus CSA was observed in patients with PD. The left vagus CSA was not significantly reduced in patients with PD. Ultrasound may not be a suitable method to detecting vagal axonal loss in individual patients.
covid19.Explorer: A web application and R package to explore United States COVID-19 data
Authors: Revell Liam J.
Published: February 2021

Appearing at the end of 2019, a novel virus (later identified as SARS-CoV-2) was characterized in the city of Wuhan in Hubei Province, China. As of the time of writing, the disease caused by this virus (known as COVID-19) has already resulted in over 3 million deaths worldwide. SARS-CoV-2 infections and deaths, however, have been highly unevenly distributed among age groups, sexes, countries, and jurisdictions over the course of the pandemic. Herein, I present a tool (the covid19.Explorer R package and web application) that has been designed to explore and analyze publicly available United States COVID-19 infection and death data from the 2020/21 U.S. SARS-CoV-2 pandemic. The analyses and visualizations that this R package and web application facilitate can help users better comprehend the geographic progress of the pandemic, the effectiveness of non-pharmaceutical interventions (such as lockdowns and other measures, which have varied widely among U.S. states), and the relative risks posed by COVID-19 to different age groups within the U.S. population. The end result is an interactive tool that will help its users develop an improved understanding of the temporal and geographic dynamics of the SARS-CoV-2 pandemic, accessible to lay people and scientists alike.
IMMUNO-COV™ v2.0: Development and Validation of a High-Throughput Clinical Assay for Measuring SARS-CoV-2-Neutralizing Antibody Titers
Authors: Vandergaast Rianna , Carey Timothy , Reiter Samantha , Lathrum Chase , Lech Patrycja , Gnanadurai Clement , Haselton Michelle , Buehler Jason , Narjari Riya , Schnebeck Luke , Roesler Anne , Sevola Kara , Suksanpaisan Lukkana , Bexon Alice , Naik Shruthi , Brunton Bethany , Weaver Scott C. , Rafael Grace , Tran Sheryl , Baum Alina , Kyratsous Christos A. , Peng Kah Whye , Russell Stephen J.
Published: February 2021

Neutralizing antibodies are key determinants of protection from future infection, yet well-validated high-throughput assays for measuring titers of SARS-CoV-2-neutralizing antibodies are not generally available. Here we describe the development and validation of IMMUNO-COV™ v2.0 a scalable surrogate virus assay, which titrates antibodies that block infection of Vero-ACE2 cells by a luciferase-encoding vesicular stomatitis virus displaying SARS-CoV-2 spike glycoproteins (VSV-SARS2-Fluc). Antibody titers, calculated using a standard curve consisting of stepped concentrations of SARS-CoV-2 spike monoclonal antibody, correlated closely (p < 0.0001) with titers obtained from a gold-standard PRNT50% assay performed using a clinical isolate of SARS-CoV-2. IMMUNO-COV™ v2.0 was comprehensively validated using data acquired from 242 assay runs performed over seven days by five analysts, utilizing two separate virus lots, and 176 blood samples. Assay performance was acceptable for clinical use in human serum and plasma based on parameters including linearity, dynamic range, limit of blank and limit of detection, dilutional linearity and parallelism, precision, clinical agreement, matrix equivalence, clinical specificity and sensitivity, and robustness. Sufficient VSV-SARS2-Fluc virus reagent has been banked to test 5 million clinical samples. Notably, a significant drop in IMMUNO-COV™ v2.0 neutralizing antibody titers was observed over a six-month period in people recovered from SARS-CoV-2 infection. Together, our results demonstrate the feasibility and utility of IMMUNO-COV™ v2.0 for measuring SARS-CoV-2-neutralizing antibodies in vaccinated individuals and those recovering from natural infections. Such monitoring can be used to better understand what levels of neutralizing antibodies are required for protection from SARS-CoV-2, and what booster dosing schedules are needed to sustain vaccine-induced immunity.
Circulatory Cytokines and Chemokines Profile in Human Coronaviruses: A systematic review and meta-analysis
Authors: Zawawi Ayat , Naser Abdallah Y , Alwafi Hassan , Minsahwi Faisal
Published: February 2021

Background

SARS, MERS, and COVID-19 share similar characteristics as the genetic homology of SARS-CoV-2 compared to SARS-CoV and MERS-CoV is 80% and 50% respectively and cause similar clinical features. Uncontrolled release of proinflammatory mediators (cytokine storm) by activated immune cells in SARS, MERS, and COVID-19 leads to severe phenotype development.

Aim

This systematic review and meta-analysis aimed to evaluate the inflammatory cytokines profile associated with severe human coronavirus diseases, including three stains: MERS-CoV, SARS-CoV SARS-CoV-2, in severe patients.

Method

PubMed, Embase, and Cochrane Library databases were searched up to July 2020. Randomized and Observational studies reporting the inflammatory cytokines associated with severe and non-severe human coronavirus diseases, including MERS-CoV, SARS-CoV SARS-CoV-2 were included. Two reviewers independently screened articles, extracted data, and assessed the quality of included studies. Meta-analysis was performed using a random-effects model with a 95% confidence interval (CI) to estimate the pooled mean of inflammatory biomarkers.

Results

A high level of circulating IL-6 could be associated with the severity of the three strains of coronaviruses infection. TNF, IL-10, and IL-8 is associated with the severity of COVID-19. Increased circulating levels of CXCL10/IP10 and CCL2/MCP-1 might also be related to the severity of MERS.

Conclusion

This study suggests that the immune response and immunopathology in the three severe human coronavirus strains are similar to some extent. These findings highlight that nearly all studies reporting severe cases of SARS, MERS, and COVID-19 have been associated with elevated levels of IL-6, which could be used as a potential therapeutic target to improve patients’ outcomes in severe cases.
“Incidence and Outcomes of Pulmonary embolism among hospitalized COVID-19 patients”
Authors: Badr Omaima Ibrahim , Alwafi Hassan , Elrefaey Wael Aly , Naser Abdallah Y , Shabrawishi Mohammed
Published: February 2021

Background

Patients with COVID-19 may be at high risk for thrombotic complications due to excess inflammatory response and stasis of blood flow. This study aims to assess the incidence of pulmonary embolism among hospitalized patients with COVID-19, risk factors and the impact on survival.

Method

A retrospective case-control study was conducted at Al-Noor Specialist Hospital in, Saudi Arabia between March 15, 2020, and June 15, 2020. Patients with confirmed COVID-19 diagnosis by a real-time polymerase chain reaction (PCR) and confirmed diagnosis of pulmonary embolism by Computed Tomography pulmonary angiogram (CTPA) formed the case group. Patients with confirmed COVID-19 diagnosis by a real-time polymerase chain reaction (PCR) and without confirmed diagnose of pulmonary embolism formed the control group. Logistic regression analysis was used to identify predictors of pulmonary embolism and its survival.

Results

A total of 159 patients participated were included in the study, of which 51 were the cases (patients with pulmonary embolism) and 108 patients formed the control group (patients without pulmonary embolism). The incidence of PE among hospitalized was around 32%. Smoking history, low level of oxygen saturation and higher D-dimer values were important risk factors that were associated with a higher risk of developing PE (p< 0.05). Higher respiratory rate was associated with higher odds of death, and decrease the possibility of survival among hospitalised patients with PE.

Conclusion

Pulmonary embolism is common among hospitalized patients with COVID-19. Preventive measures should be considered for hospitalized patients with smoking history, low level of oxygen saturation, high D-dimer values, and high respiratory rate.
Protective lipid-lowering genetic variants in healthy older individuals without coronary heart disease
Authors: Lacaze Paul , Riaz Moeen , Sebra Robert , Hooper Amanda J , Pang Jing , Tiller Jane , Polekhina Galina , Tonkin Andrew M , Reid Christopher M , Zoungas Sophia , Murray Anne M , Nicholls Stephen J , Watts Gerald F , Schadt Eric , McNeil John J
Published: February 2021

Background

Disruptive genetic variants in thePCSK9andAPOBgenes result in lower serum low-density lipoprotein cholesterol (LDL-C) levels and confer protection against coronary heart disease (CHD). Few studies have measured the prevalence and selective advantage of such variants among healthy older individuals without prior CHD events.

Methods and Results

We performed targeted sequencing of thePCSK9andAPOBgenes in 13,131 healthy older individuals without CHD aged 70 years or older enrolled into the ASPirin in Reducing Events in the Elderly (ASPREE) trial. We detected predicted loss-of-function (pLoF) variants in thePCSK9andAPOBgenes, and associated variant carrier status with blood lipid levels. We detected 22 different rarePCSK9/APOBcandidate variants with lipid-lowering effect, carried by 104 participants (carrier rate 1 in 126). Rare variant carrier status was associated with 19.4 mg/dl (14.6%) lower LDL-C, compared with non-carriers (P=<0.001, adjusted for statin use). Statin prescriptions were less prevalent in rare variant carriers (16%) than non-carriers (35%). ThePCSK9R46L variant (rs11591147-T) was associated with 15.5mg/dl (11.8%) lower LDL-C in heterozygotes, and 25.2 mg/dl (19.2%) lower LDL-C in homozygotes, respectively (both P=<0.001).

Conclusions

Lipid-lowering genetic variants are carried by healthy older individuals and contribute to CHD-free survival.
The epidemiological characteristics of the primary health care based COVID-19 swabbed persons in Qatar, March- October 2020
Authors: Al-Kuwari Mohamed Ghaith , Abdulmalik Mariam Ali , Bakri Ahmad Haj , Kandy Mujeeb Chettiyam , Abdulla Maha Youssef , Gibb John
Published: February 2021

Background

In March 2020, Qatar started reporting increased numbers of COVID-19 positive cases. National preventive measures were put in place and testing plan has been developed to respond to the pandemic with the primary health care as the main provider. The study aims to describe the epidemiological characteristics of COVID-19 at the primary health care level in Qatar and to examine the factors associated with the positivity rate.

Method

Retrospective data analysis for all the cases screened for COVID-19 at the primary health care level in Qatar between the 11th of March and 31st of October 2020. The study analyzed the demographic characteristics of the tested persons and non-communicable disease burden, positivity rate by month, nationality, and age-group, factors associated with the positivity rate.

Results

Between the 11th of March and the 31st of October 2020, 285,352 persons were tested for SARS-CoV-2, with a median age (IQR) of 32 (22-43) years. 59.9% were from the Middle East and North Africa region and 29.6% originally from Asia. Overall, among them, 11.2% had diabetes mellitus and 11.4% had hypertension. The epidemiological curve showed a steep increase in positivity rate from March till June 2020 at the highest rate of 21.4% in June 2020. The highest positivity rate was observed among Asian males at 20.3%. The positivity rates were almost the same among the tested persons for SARS-CoV-2 in the main three age-groups (0-18, 19-39, 40-59) at 13%, 14.5%, and 14.0%, respectively. In a multi regression model, being a male was associated with a higher risk (OR 1.16; 95% CI 1.13 to 1.18). Persons originally from Asia were at higher risk than those originally from the Middle East and North Africa (OR 1.5; 95% CI 147 to 1.54). COVID-19 infection was higher among those presenting with clinical symptoms than those asymptomatic (OR. 4.16; 95% CI 4.05 to 4.28).

Conclusion

The epidemic predominantly affected younger ages and males namely coming from Asia. At the primary health care level, COVID-19 infection rate was higher among those who presented with clinical symptoms. The scale-up of the testing at the primary health care level helped in detecting more cases and was reflected in a steady increase in the positivity rate to be flattened afterward.
Implementation of Mercury Biomonitoring in German Adults using Dried Blood Spot Sampling in Combination with Direct Mercury Analysis
Authors: Schweizer Ann-Kathrin , Kabesch Michael , Quartucci Caroline , Bose-O’Reilly Stephan , Rakete Stefan
Published: February 2021

Venous blood is a preferred matrix for the determination of total mercury (Hg) in human biomonitoring but has some drawbacks such as the requirement for an uninterrupted cold chain for transport and storage and the need of medical personnel for sample collection. Therefore, we tested and implemented a simpler and less expensive method for measuring Hg in human blood using dried blood spots (DBS). For method development, we investigated the influence of different storage conditions (temperature, storage vessel, time) on DBS samples. For method validation, we compared DBS and venous blood and investigated whether DBS sampling is suitable for measuring Hg in the general population in countries with low Hg exposure such as Germany. Based on our results, we found that pre-cleaned glass tubes were most suitable for storage of DBS samples, as this allowed the samples to remain stable for at least four weeks even at high temperatures (40°C). When comparing venous blood and DBS, a very good correlation (r=0.95, p<0.01) and high precision of DBS (mean relative standard deviation 8.2% vs. 7.2% in venous blood samples) were observed. Comparing the recoveries of both matrices in different concentration ranges, the scattering of the recoveries decreases with increasing Hg concentration. The same applies to the mean recoveries. Overall, we found comparable results for DBS and whole blood using direct Hg analysis. Furthermore, we demonstrated that DBS are suitable for Hg biomonitoring in the general population in Germany and improved the storage conditions for the DBS.
Country differences in transmissibility, age distribution and case-fatality of SARS-CoV-2: a global ecological analysis
Authors: Favas Caroline , Jarrett Prudence , Ratnayake Ruwan , Watson Oliver J , Checchi Francesco
Published: February 2021

Introduction

SARS-CoV-2 has spread rapidly across the world yet the first pandemic waves in many low-income countries appeared milder than initially forecasted through mathematical models. Hypotheses for this observed difference include under-ascertainment of cases and deaths, country population age structure, and immune modulation secondary to exposure to endemic parasitic infections. We conducted a country-level ecological study to describe patterns in key SARS-CoV-2 outcomes by country and region and to explore possible associations of the potential explanatory factors with these outcomes.

Methods

We collected publicly available data at country level and compared them using standardisation techniques. We then explored the association between exposures and outcomes using alternative approaches: random forest (RF) regression and linear (LM) regression. We adjusted for potential confounders and plausible effect modifications.

Results

Altogether, data on the mean time-varying reproduction number (mean Rt) were available for 153 countries, but standardised averages for the age of cases and deaths and for the case-fatality ratio (CFR) could only be computed for 61, 39 and 31 countries respectively. While mean Rt was highest in the WHO Europe and Americas regions, median age of death was lower in the Africa region even after standardisation, with broadly similar CFR. Population age was strongly associated with mean Rt and the age-standardised median age of observed cases and deaths in both RF and LM models. The models highlighted other plausible roles of population density, testing intensity and co-morbidity prevalence, but yielded uncertain results as regards exposure to common parasitic infections.

Conclusions

The average age of a population seems to be an important country-level factor explaining both transmissibility and the median age of observed cases and deaths, even after age-standardisation. Potential associations between endemic infections and COVID-19 are worthy of further exploration but seem unlikely, from this analysis, to be key drivers of the variation in observed COVID-19 epidemic trends. Our study was limited by the availability of outcome data and its causally uncertain ecological design, with the observed distribution of age amongst reported cases and deaths suggesting key differences in surveillance and testing strategy and capacity by country and the representativeness of case reporting of infection. Research at subnational and individual level is needed to explore hypotheses further.
Evaluating the suitability of the case-crossover design under changing baseline outcome risk: A simulation of ambient temperature and preterm birth
Authors: Carrión Daniel , Rush Johnathan , Colicino Elena , Just Allan C.
Published: February 2021

Case-crossover (CCO) studies are case-only within-person analyses of associations between acute exposures and outcomes. By design, the CCO is not confounded by time-invariant characteristics. CCO studies assume stable baseline outcome risks. Since the baseline risk of birth increases secularly over gestation, the validity of CCOs of preterm birth (PTB) is not clear. We simulated associations between temperature and PTB in New York State using historical ambient temperature data for LaGuardia Airport and PTB data from the CDC using different control period durations. CCO analyses were conducted with conditional logistic regression. We calculated bias according to the absolute difference between the simulated and estimated effects in the natural log scale, and found that 2-week, 28-day, and 1-month stratified control period selection yielded negligible bias across all simulated effects. Coverage of the 95% confidence intervals was also appropriate across all three control selection strategies. Our findings suggest that the time-stratified CCO should yield appropriate inference in studies of ambient temperature and preterm birth.
A whole-brain imaging-based systems approach to understand origin of addiction in binge-like drinking model
Authors: Stefaniuk Marzena , Pawłowska Monika , Nowicka Klaudia , Barański Marcin , Zielinski Zbigniew , Bijoch Łukasz , Legutko Diana , Majka Piotr , Bednarek Sylwia , Jermakow Natalia , Wójcik Daniel , Kaczmarek Leszek
Published: February 2021

Many fundamental questions on addiction development are still unanswered. These questions are frequently difficult to address by examining a single brain structure, but can best be addressed at the systems level. Neurons create functional networks that change over time, since brain regions may work together differently in different contexts. We offer a framework for describing the nature behind alcohol binge drinking and the transition to addiction. The present study investigated whole-brain c-Fos expression following reexposure to alcohol in a model of binge-like drinking in mice in IntelliCage. We developed a dedicated image computational workflow to identify c-Fos-positive cells in three-dimensional images obtained after optical tissue clearing and whole-brain imaging in the light-sheet microscope. We analyzed functional networks and brain modularity following reexposure to alcohol. c-Fos levels in brains from animals that were reexposed to alcohol were clearly different from binge drinking animals. Structures involved in reward processing, decision making and characteristic for addictive behaviors stood out particularly. In alcohol reexposed animals differently active structures either gained or lost correlation when compared to the control group.
A genetic program boosts mitochondrial function to power macrophage tissue invasion
Authors: Emtenani Shamsi , Martin Elliott T. , Gyoergy Attila , Bicher Julia , Genger Jakob-Wendelin , Hurd Thomas R. , Köcher Thomas , Bergthaler Andreas , Rangan Prashanth , Siekhaus Daria E.
Published: February 2021

Metabolic adaptation to changing demands underlies homeostasis. During inflammation or metastasis, cells leading migration into challenging environments require an energy boost, however what controls this capacity is unknown. We identify a previously unstudied nuclear protein, Atossa, as changing metabolism inDrosophila melanogasterimmune cells to promote tissue invasion. Atossa’s vertebrate orthologs, FAM214A-B, can fully substitute for Atossa, indicating functional conservation from flies to mammals. Atossa increases mRNA levels of Porthos, an unstudied RNA helicase and two metabolic enzymes, LKR/SDH and GR/HPR. Porthos increases translation of a gene subset, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Respiration measurements and metabolomics indicate that Atossa and Porthos powers up mitochondrial oxidative phosphorylation to produce sufficient energy for leading macrophages to forge a path into tissues. As increasing oxidative phosphorylation enables many crucial physiological responses, this unique genetic program may modulate a wide range of cellular behaviors beyond migration.
Human microglia extensively reconstitute in humanized BLT mice with human interleukin-34 transgene and support HIV-1 brain infection
Authors: Zhang Jianshui , Lohani Saroj Chandra , Cheng Yilun , Wang Tao , Guo Lili , Kim Woong-Ki , Gorantla Santhi , Li Qingsheng
Published: February 2021

Humanized bone marrow-liver-thymic (hu-BLT) mice develop a functional immune system in periphery but have a limited reconstitution of human myeloid cells, especially microglia, in CNS. Further, whether bone marrow derived hematopoietic stem and progenitor cells (HSPCs) can enter the brain and differentiate into microglia in adults remains controversial. To close these gaps, in this study we unambiguously demonstrated that human microglia in CNS were extensively reconstituted in adult NOG mice with human interleukin-34 transgene (hIL34 Tg) from circulating CD34+ HSPCs but no in hu-BLT NOG mice, providing strong evidence that human CD34+ HSPCs can enter adult brain and differentiate into microglia in CNS in the presence of hIL34. Further, the human microglia in the CNS of hu-BLT-hIL34 NOG mice robustly supported HIV-1 infection reenforcing the notion that microglia are the most important target cells of HIV-1 in CNS and demonstrating its great potential as an in vivo model for studying HIV-1 pathogenesis and evaluating curative therapeutics in both periphery and CNS compartments.
Opposing dominance within a color gene block underpins hybrid plumage signal discordance
Authors: de Zwaan Devin R. , Mackenzie Jacqueline , Mikklesen Else , Wood Chris , Wang Silu
Published: February 2021

The divergence of plumage color genes is increasingly recognized as important for speciation in songbirds through its influence on social signaling. However, the behavioral mechanisms underlying the eco-evolutionary feedback that acts across species boundaries is poorly understood. The hybrid zone betweenSetophaga occidentalis(SOCC) andS. townsendi(STOW) in the Cascade Mountain range provides a natural observatory to test the interplay between genetics, plumage signals, and territoriality in maintaining nascent species boundaries. Recently, we found that selection within a gene block underpinning color variation (ASIP-RALY) has maintained a stable and narrow hybrid zone. Here we investigated the roles of cheek darkness and flank streaking as plumage signals during simulated territorial intrusion, two melanin-based traits underpinned by ASIP-RALY that reflect opposing dominance of SOCC and STOW alleles. We found that both plumage traits act as honest signals of body size in the territorial sex (i.e., males). The opposing dominance effects of ASIP-RALY resulted in plumage signal discordance for heterozygotes, which in turn was associated with reduced territorial performance, a fitness proxy quantified by vocal and physical responses to a decoy intruder. Taken together, this study highlights a behavioral mechanism underlying selection acting on a simple genetic architecture that shapes species boundary despite gene flow.
The possible fidelity-speed-proofreading cost trade-offs in DNA replication due to the exonuclease proofreading
Authors: Li Qiu-Shi , Shu Yao-Gen , Fu Wen-Bo , Ou-Yang Zhong-Can , Li Ming
Published: February 2021

DNA replication is a high-fidelity information-copying processes which is realized by DNA polymerase (DNAP). The high fidelity was explained on the basis of the well-known kinetic-proofreading mechanism (KPR), under which the so-called fidelity-speed trade-off was studied theoretically. However, numerous biochemical experiments have shown that the high fidelity of DNA replication is achieved due to the initial discrimination of polymerase domain of DNAP, as well as the proofreading of the exonuclease domain of DNAP. This exonuclease-proofreading mechanism (EPR) is totally different from KPR. So the trade-off issues are worth being re-examined under EPR. In this paper, we use the first-passage method recently proposed by us to discuss the possible trade-offs in DNA replication under EPR. We show that there could be no fidelity-speed trade-off under EPR, i.e., the fidelity and the speed can be simultaneously enhanced by EPR in a large range of kinetic parameters. This provides a new perspective to understand the experimental data of the exonuclease activity of T7 DNAP and T4 DNAP. We also show that there exists the fidelity-proofreading cost trade-off, i.e., the fidelity is enhanced at the cost of increasing the futile hydrolysis of dNTP. A possible way to avoid this trade-off is to regulate the rate of DNAP translocation: slowing down the forward translocation (in the presence of the terminal mismatch) can enhance the fidelity without changing the speed and the proofreading cost. Our theoretical analysis offers deeper insights on the kinetics-function relation of DNAP.

PACS numbers: 82.39.-k, 87.15.Rn, 87.16.A-
Modelling the visual world of a velvet worm
Authors: Ljungholm Mikael , Nilsson Dan-E.
Published: February 2021

In many animal phyla, eyes are small and provide only low-resolution vision for general orientation in the environment. Because these primitive eyes rarely have a defined image plane, traditional visual-optics principles cannot be applied. To assess the functional capacity of such eyes we have developed modelling principles based on ray tracing in 3D reconstructions of eye morphology, were refraction on the way to the photoreceptors and absorption in the photopigment are calculated incrementally for ray bundles from all angles withing the visual field. From the ray tracing, we calculate the complete angular acceptance function of each photoreceptor in the eye, revealing the visual acuity for all parts of the visual field. We then use this information to generate visual filters that can be applied to high resolution images or videos to convert them to accurate representations of the spatial information seen by the animal. The method is here applied to the 0.1 mm eyes of the velvet wormEuperipatoides rowelli(Onychophora). These eyes of these terrestrial invertebrates consist of a curved cornea covering an irregular but optically homogeneous lens directly joining a retina packed with photoreceptive rhabdomeres. 3D reconstruction from histological sections revealed an asymmetric eye, where the retina is deeper in the forward-pointing direction. The calculated visual acuity also reveals performance differences across the visual field, with a maximum acuity of about 0.11 cycles/deg in the forward direction despite laterally pointing eyes. The results agree with previous behavioural measurements of visual acuity, and suggest that velvet worm vision is adequate for orientation and positioning within the habitat.

Author summary

It is difficult to understand the roles that vision may have in animals with visual performance very different to our own. Many invertebrates such as flatworms, polychaetes, onychophorans, gastropod molluscs and numerous arthropods have tiny eyes with unknown visual abilities. At best, behavioural experiments can reveal visual performance limits for specific behaviours but they will not give general information about what is visible to the animal, which is crucial for understanding the roles vision may have. Here we use ray tracing applied to accurate anatomical/optical models of the eyes of a velvet worm to reconstruct the visual acuity in all parts of the visual field. We also use the calculated visual performance to closely simulate what animals would see in their natural habitat. The method can be applied to any (preferably small) eye and offers an alternative strategy that may yield information about the visual capacity that is otherwise hard to obtain.