bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cardiovascular Side Effects of Electroconvulsive Therapy and Their Management
Authors: Hermida Adriana P. , Mohsin Mamoona , Marques Pinheiro Ana P. , McCord Elizabeth , Lisko John C. , Head Lyndsay W.
Published: October 2021

Electroconvulsive therapy (ECT) remains stigmatized in the broader medical community because of misunderstandings about treatment procedures, mortality rates, and cardiovascular complications. Electroconvulsive therapy causes periprocedural hemodynamic variability because of the surges in parasympathetic and sympathetic nervous systems after the administration of the electrical charge. Patients experience an increase in cardiac workload, which is potentially dangerous for patients with preexisting heart disease. Several findings suggest that cardiac complications occur most frequently in patients with underlying cardiovascular disease. We describe the cardiovascular complications that may result from ECT treatment and offer insight on how to mitigate these concerns if they occur. PubMed was queried using terms “electroconvulsive therapy” and “cardiovascular adverse effects.” A table is provided with the common cardiovascular side effects of ECT and the most recent evidence-based treatment strategies to manage them. Generally, ECT is a safe procedure in which complications are minor and manageable. Most major complications caused by ECT are related to the cardiovascular system; however, with an appropriate pre-ECT evaluation and a comprehensive multidisciplinary team approach, the cardiovascular complications can be well managed and minimized. Providing proper cardiac clearance can prevent cardiac complications and provide timely care to treatment-resistant populations who are at risk for excessive morbidity and suicide.
Adding climate change to the mix: responses of aquatic ectotherms to the combined effects of eutrophication and warming
Authors: Rodgers Essie M.
Published: October 2021

The threat of excessive nutrient enrichment, or eutrophication, is intensifying across the globe as climate change progresses, presenting a major management challenge. Alterations in precipitation patterns and increases in temperature are increasing nutrient loadings in aquatic habitats and creating conditions that promote the proliferation of cyanobacterial blooms. The exacerbating effects of climate warming on eutrophication are well established, but we lack an in-depth understanding of how aquatic ectotherms respond to eutrophication and warming in tandem. Here, I provide a brief overview and critique of studies exploring the cumulative impacts of eutrophication and warming on aquatic ectotherms, and provide forward direction using mechanistically focused, multi-threat experiments to disentangle complex interactions. Evidence to date suggests that rapid warming will exacerbate the negative effects of eutrophication on aquatic ectotherms, but gradual warming will induce physiological remodelling that provides protection against nutrients and hypoxia. Moving forward, research will benefit from a greater focus on unveiling
cause and effect
mechanisms behind interactions and designing treatments that better mimic threat dynamics in nature. This approach will enable robust predictions of species responses to ongoing eutrophication and climate warming and enable the integration of climate warming into eutrophication management policies.
Parakeet: a digital twin software pipeline to assess the impact of experimental parameters on tomographic reconstructions for cryo-electron tomography
Authors: Parkhurst James M. , Dumoux Maud , Basham Mark , Clare Daniel , Siebert C. Alistair , Varslot Trond , Kirkland Angus , Naismith James H. , Evans Gwyndaf
Published: October 2021

In cryo-electron tomography (cryo-ET) of biological samples, the quality of tomographic reconstructions can vary depending on the transmission electron microscope (TEM) instrument and data acquisition parameters. In this paper, we present Parakeet, a ‘digital twin’ software pipeline for the assessment of the impact of various TEM experiment parameters on the quality of three-dimensional tomographic reconstructions. The Parakeet digital twin is a digital model that can be used to optimize the performance and utilization of a physical instrument to enable
in silico
optimization of sample geometries, data acquisition schemes and instrument parameters. The digital twin performs virtual sample generation, TEM image simulation, and tilt series reconstruction and analysis within a convenient software framework. As well as being able to produce physically realistic simulated cryo-ET datasets to aid the development of tomographic reconstruction and subtomogram averaging programs, Parakeet aims to enable convenient assessment of the effects of different microscope parameters and data acquisition parameters on reconstruction quality. To illustrate the use of the software, we present the example of a quantitative analysis of missing wedge artefacts on simulated planar and cylindrical biological samples and discuss how data collection parameters can be modified for cylindrical samples where a full 180° tilt range might be measured.
Alicyclobacillus mali sp. nov., Alicyclobacillus suci sp. nov. and Alicyclobacillus fructus sp. nov., thermoacidophilic sporeforming bacteria isolated from fruit beverages
Authors: Roth Katerina , Rana Yadwinder Singh , Daeschel Devin , Kovac Jasna , Worobo Randy , Snyder Abigail B.
Published: October 2021

Six thermo-acidophilic, spore-forming strains were isolated from a variety of juice products and were characterized genetically and phenotypically. According to 16S rRNA and rpoB gene phylogenetic analyses and average nucleotide identity comparisons against the species demarcation cutoff at <95 %, these six strains were determined to represent three novel species of

Alicyclobacillus

. The isolates were designated FSL-W10-0018T, FSL-W10-0037, FSL-W10-0048, VF-FSL-W10-0049T, FSL-W10-0057 and FSL-W10-0059T. All six isolates were Gram-positive, motile, rod shaped, contained menaquinone 7 as the major respiratory quinone and had ω-cyclohexane C17 : 0 as a major fatty acid. They were all able to grow aerobically in a range of acidic and moderate thermal conditions. Only isolates FSL-W10-0048 and VF-FSL-W10-0049T were able to produce guaiacol. The following names are proposed for the three new species: Alicyclobacillus mali sp. nov. (type strain FSL-W10-0018T
=DSM 112016T=NCIMB 15266T); Alicyclobacillus suci sp. nov (VF-FSL-W10-0049T=DSM 112017T=NCIMB 15265T); and Alicyclobacillus fructus sp. nov. (FSL-W10-0059T=DSM 112018T=NCIMB 15264T).
Yangia mangrovi sp. nov., a novel member of the Roseobacter clade isolated from mangrove soil and emended description of Yangia pacifica Dai et al. 2006
Authors: Verma Ashish , Sundharam Shiva S. , Pal Yash , Bisht Bhawana , Yadav Pooja , Krishnamurthi Srinivasan
Published: October 2021

During a study of the bacterial diversity of mangrove habitats, a novel Gram-stain-negative, rod-shaped bacterium designated as SAOS 153DT was isolated. Sequence alignment and molecular phylogenetic analyses based on 16S rRNA and core gene sequence of strain SAOS 153DT with closely related taxa revealed a sequence identity of 99.4 % and clustering with

Yangia pacifica

DX5-10T. The fatty acids summed feature 8 (C18:1
ω7c/C18:1
ω6c) and the lipids phosphatidylglycerol, phosphatidylethanolamine and an unknown phospholipid were the major components of the cell wall. The only ubiquinone type present was Q-10. The genomic DNA G+C content of the strain calculated from whole genome sequencing was 66.9 mol%. These chemotaxonomic and genomic characteristics supported the molecular phylogenetic analysis and placed the strain well within the radiation of the genus

Yangia

. The overall genome related indices using digital DNA–DNA hybridization (35.4 %) and ortho-average nucleotide identity (88.1 %) values were much lower than the recommended thresholds for species delineation, which further consolidated the novel species status of strain SAOS 153DT within the genus

Yangia

as Yangia mangrovi sp. nov. The type strain is SAOS 153DT (=JCM 31345T=KCTC 52280T=MTCC 12749T).
Interferon responses to norovirus infections: current and future perspectives
Authors: Jahun Aminu S. , Goodfellow Ian G.
Published: October 2021

Human noroviruses (HuNoVs) are increasingly becoming the main cause of transmissible gastroenteritis worldwide, with hundreds of thousands of deaths recorded annually. Yet, decades after their discovery, there is still no effective treatment or vaccine. Efforts aimed at developing vaccines or treatment will benefit from a greater understanding of norovirus-host interactions, including the host response to infection. In this review, we provide a concise overview of the evidence establishing the significance of type I and type III interferon (IFN) responses in the restriction of noroviruses. We also critically examine our current understanding of the molecular mechanisms of IFN induction in norovirus-infected cells, and outline the diverse strategies deployed by noroviruses to supress and/or avoid host IFN responses. It is our hope that this review will facilitate further discussion and increase interest in this area.
The Genetic Determinants of Aortic Distension
Authors: Pirruccello James P. , Choi Seung Hoan , Chaffin Mark D. , Nekoui Mahan , Chou Elizabeth L. , Jurgens Sean J. , Friedman Samuel F. , Juric Dejan , Stone James R. , Batra Puneet , Ng Kenney , Philippakis Anthony A. , Lindsay Mark E. , Ellinor Patrick T.
Published: October 2021

As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous blood delivery to peripheral arteries. Distension during systole and recoil during diastole conserves ventricular energy and is enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and prematurely in vascular disease. To discover genetic determinants of aortic distensibility we trained a deep learning model to quantify aortic size throughout the cardiac cycle and calculate aortic distensibility and aortic strain in 42,342 participants in the UK Biobank with available cardiac magnetic resonance imaging. In up to 40,028 participants with genetic data, common variant analysis identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were specific to strain or distensibility and were not identified in a thoracic aortic diameter GWAS within the same samples. Loci associated with both aortic diameter and aortic strain or distensibility demonstrated a consistent, inverse directionality. Transcriptome-wide analyses, rare-variant burden tests, and analyses of gene expression in single nucleus RNA sequencing of human aorta were performed to prioritize genes at individual loci. Loci highlighted multiple genes involved in elastogenesis, matrix degradation, and extracellular polysaccharide generation. Characterization of the genetic determinants of aortic function may provide novel targets for medical intervention in aortic disease.
A randomized, controlled, feasibility study of RD-X19 in patients with mild-to-moderate COVID-19 in the outpatient setting
Authors: Stasko Nathan , Cockrell Adam S. , Kocher Jacob F. , Henson Ibrahim , Emerson David , Wang Ye , Smith Jonathan R. , Henderson Nathan H. , Wood Hillary , Bradrick Shelton S. , Jones Terry , Santander Jorge , McNeil John G.
Published: October 2021

These studies aimed to further understand the antiviral effects of safe, visible light and demonstrate a therapeutic effect of an investigational treatment device for outpatients with mild to moderate COVID-19. RD-X19 is a handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses that are well-tolerated in an in vitro human epithelial tissue model, the monochromatic visible light delivered by RD-X19 results in light-initiated expression of IL-1α and IL-1β cytokines with corresponding inhibition of SARS-CoV-2 replication. A randomized, double-blind, sham-controlled early feasibility study using the investigational device enrolled 31 subjects with a positive SARS-CoV-2 antigen test and possessing at least two moderate COVID-19 signs and symptoms. Subjects were randomized 2:1 (RD-X19 to sham), treated twice daily for four days, and evaluated over one week. Prespecified outcome measures included assessments of SARS-CoV-2 viral load and clinical assessments of COVID-19. There were no local application site reactions and no device-related adverse events. The time-weighted average change in log viral load throughout the study demonstrated a favorable reduction for RD-X19 compared to sham and at the end of study the mean change in log10 viral load was -3.29 for RD-X19 and -1.81 for sham at Day 8, demonstrating a treatment benefit of -1.48 [95% confidence internal (CI), -2.88 to -0.071]. Among the clinical outcome measures, differences between RD-X19 and sham were also observed, with a 57-hour reduction of median time to sustained resolution of COVID-19 signs and symptoms.
Mathematical modeling of COVID-19 in British Columbia: an age-structured model with time-dependent contact rates
Authors: Iyaniwura Sarafa A. , Falcão Rebeca C. , Ringa Notice , Adu Prince A. , Spencer Michelle , Taylor Marsha , Colijn Caroline , Coombs Daniel , Janjua Naveed Z. , Irvine Michael A , Otterstatter Michael
Published: October 2021

Following the emergence of COVID-19 at the end of 2019, several mathematical models have been developed to study the transmission dynamics of this disease. Many of these models assume homogeneous mixing in the underlying population. However, contact rates and mixing patterns can vary dramatically among individuals depending on their age and activity level. Variation in contact rates among age groups and over time can significantly impact how well a model captures observed trends. To properly model the age-dependent dynamics of COVID-19 and understand the impacts of interventions, it is essential to consider heterogeneity arising from contact rates and mixing patterns. We developed an age-structured model that incorporates time-varying contact rates and population mixing computed from the ongoing BC Mix COVID-19 survey to study transmission dynamics of COVID-19 in British Columbia (BC), Canada. Using a Bayesian inference framework, we fit four versions of our model to weekly reported cases of COVID-19 in BC, with each version allowing different assumptions of contact rates. We show that in addition to incorporating age-specific contact rates and mixing patterns, time-dependent (weekly) contact rates are needed to adequately capture the observed transmission dynamics of COVID-19. Our approach provides a framework for explicitly including empirical contact rates in a transmission model, which removes the need to otherwise model the impact of many non-pharmaceutical interventions. Further, this approach allows projection of future cases based on clear assumptions of age-specific contact rates, as opposed to less tractable assumptions regarding transmission rates.
Evidence for Influenza and RSV interaction from 10 years of enhanced surveillance in Nha Trang, Vietnam, a modelling study
Authors: Waterlow Naomi R , Toizumi Michiko , van Leeuwen Edwin , Nguyen Hien-Anh Thi , Myint-Yoshida Lay , Eggo Rosalind M , Flasche Stefan
Published: October 2021

Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for heterologous ecological changes following vaccination. We aimed to estimate the population level impact of their interaction.

We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit it’s parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam.

The data supported either a 41% (95%CrI: 36 - 54) reduction in heterologous acquisition during infection and for 10.0 days (95%CrI 7.1 -12.8) thereafter, or no cross protection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0 - 11.4); or 16.6 fold (95%CrI 14.5 - 18.4) in the respective scenarios. Absence of either pathogen was not to the detriment of the other.

We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.
ABO blood group type does not influence the level of SARS-CoV-2 antibody response in convalescent plasma donors
Authors: Žiberna Klemen , Jazbec Katerina , Jež Mojca , Mali Polonca , Potokar Urška Rahne , Rožman Primož
Published: October 2021

The association of ABO blood group types with the COVID-19 disease has been confirmed by several studies, with the blood group A-type patients being more susceptible and prone to more severe clinical course of disease. Similarly, some authors explored the association of ABO-types and the levels of anti-SARS-CoV-2 antibodies in convalescents. The recent reports mostly support a theory that non-O blood group convalescents present with higher levels of anti-SARS-CoV-2 antibodies. Since these findings were based on small convalescent cohorts, we quantified the anti-SARS-CoV-2 antibodiy levels in four larger cohorts of total 3185 convalescent plasma donors with three commercial serological tests and one standard neutralizing antibody test. The majority of donors had undergone a mild form of disease and the median time of sampling was 66 days after the onset of COVID-19 symptoms. None of the antibody quantitation methods showed an association of the ABO blood group types with the level of anti-SARS-CoV-2 antibodies. The same result is evident in the group of vaccinated individuals (n=370) as well as in the groups stratified into three post-COVID-19 periods (0-60, 60-120, and 120-180 days). In conclusion we can state that the ABO blood group type does not influence the level of SARS-CoV-2 antibody response in COVID-19 convalescent plasma donors.
The Relationship Between Food Security and Dietary Patterns Status with COVID-19 in Northeastern Iran: Protocol for a Case-Control Study
Authors: Badri-Fariman Sepideh , Pourghassem-Gargari Bahram , Badri-Fariman Mahtab , Pourfridoni Mohammad , Daneshi-Maskooni Milad
Published: October 2021

Background

Food insecurity is defined as the limited or uncertain availability of enough food for a consistently active and healthy life. COVID-19 is a highly transmissible viral infection with high mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, or the uncommon severe pneumonia. This study assesses the relationship between food security and dietary patterns status with COVID-19 in the North Khorasan province, Iran.

Methods

This case-control study will be conducted in the men and women aged 20-60 years improved from COVID-19 infection. The cases (n=124) and controls (n=124) were selected according to the eligibility criteria, including recently improved COVID-19 according to the positive COVID-19 PCR test. People referred to public and private laboratories or employees of public and private factories, offices, and departments of hospitals and universities (for the cases) and negative PCR tests without any clinical signs of COVID-19 infection (for the controls). The North Khorasan province was the target place. The groups are matched for age, sex, and body mass index (BMI). The assessments will include anthropometric measurements and general demographic, USDA 18-item food security (18item-FSSM), and 147-item food frequency (FFQ) questionnaires. Finally, the determination of the relationship between food security and dietary patterns status and associated socioeconomic factors with COVID-19 is done. P-value will be <0.05.

Discussion

This study would be the first assessment of the relationship between food security and dietary patterns status with COVID-19 disease. It may help planners and policymakers to manage food insecurity and unhealthy dietary patterns and later increasing the immune system and decreasing the incidence of COVID-19. Further studies are suggested.
COVID-19 Observations from Hospitalized Ward Patients in the Northern Emirates: A Practice Only Preached
Authors: Qureshi Shahab , Kampani Drishti D. , Hassan Al-Qutbi Tara Ali , Mohamed Aalya , Alfaresi Mubarak
Published: October 2021

Background

The COVID-19 pandemic has established itself as the defining global health crisis of this time. The study describes the clinical profile of hospitalized, non-ICU patients with COVID-19 in the United Arab Emirates (UAE) during its second wave, through January-March 2021. It also highlights the use of antibiotic stewardship principles in patients admitted with COVID-19.

Methodology

An observational, retrospective study was conducted with 110 participants from Sheikh Khalifa General Hospital – Umm Al Quwain in the UAE. Pregnant women, patients who were admitted to/transferred to/discharged from the intensive care unit, patients who were receiving antibiotics prior to admission were excluded from the study.

Results

Population was 58.2% male with a mean age of 51.2 (± 14.6) years; 69.1% had at least one comorbidity and 61.8% were classified as severe COVID-19 disease. Mean WBC count was 6.03 ± 2.70 × 109 cells/L with a mean CRP of 83.3 ± 14.6 mg/L. 4.2% of the tested (20.9%) blood cultures performed were positive. Immunomodulators (67.26%), prophylactic anticoagulants (90%), anti-viral drugs (83.61%) were primary modalities of therapy. Empiric antibiotic use was limited to 9.1% of population.

Conclusion

Our study highlighted that the population admitted to the hospital in the second wave of the COVID-19 pandemic in the UAE were mostly male, older with higher prevalence of comorbidities. Given the limited knowledge of the new disease, we took bold but calculated clinical measures to maintain antibiotic stewardship practice and brought antibiotic prescribing to extraordinary low level not seen during the COVID-19 pandemic.
Early COVID-related Acute Kidney Injury Recovery May Course with Hydroelectrolytic Disorders in Patients With High Risk of Insensible Fluid Loss
Authors: Braga Barbosa Géssica Sabrine , de Jesus Torres de Melo Ana Gabriela , Gomes Ribeiro Rayra , del Pilar Via Reque Cortes Daniela , Sandoval Cabrera Carla Paulina , Santos Andrade Filho Rubens , Tamborra Pantaroto Guilherme , de Castro Paul Schultze Bruno , Paula Gilberto Alvarenga , Rodrigues Camila Eleuterio
Published: October 2021

Background

Acute Kidney Injury (AKI) may occur in more than 30% of COVID hospitalized patients, and renal recovery is poorly described.

Aim

We aimed to evaluate the renal short-term recovery profile of COVID-related AKI (COV+) compared to COVID-unrelated AKI (COV-).

Design

case-control retrospective single-center study

Methods

All patients admitted to the Hospital das Clínicas, University of São Paulo, who recovered AKI from April to June of 2020 (COV+, n=98) and from August to October of 2019 (COV-, n=50) were analyzed. Recovery was defined by spontaneous serum creatinine drop or withdrawal of dialysis. Serum electrolytes were analyzed during the first five days of recovery.

Results

Among 333 COV+ patients, 98 recovered from AKI (29.4%), while 50 of 177 COV-patients recovered (28.2%). The COV- group presented higher prevalence of chronic morbidities, while the COV+ group had a worse acute clinical course requiring vasoactive drugs (VAD), mechanical ventilation (MV) and dialysis. COVID-19 diagnosis was associated with need of mecxhanical ventilation, dialysis, presence of fever, and higher use of any diuretic drug during first days of recovery. The presence of fever and mechanical ventilation were the predictors associated with intravascular volume depletion surrogates (daily progressive rising in sodium levels and elevation in serum urea: creatinine ratio). Neither COVID-19 nor diuretics use seem to be independent risk factors for this.

Conclusions

Intravascular volume depletion surrogates are more common in short-term AKI-recovery of patients presenting fever and mechanical ventilation, commons features in SARS-CoV2 infection.
Establishing CREATE: Lessons learned in setting up a training environment for early-career researchers in respiratory medicine
Authors: Christian Katherine , Hey-Cunningham Alison , Corte Tamera , Goh Nicole , Jaffar Jade , Reynolds Paul , Teoh Alan , Troy Lauren
Published: October 2021

Background

The purpose of the National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis (CRE-PF) is to improve and extend the lives of patients living with pulmonary fibrosis through the development of a comprehensive and integrated program of basic and clinical research and education across Australia. A key objective of the CRE-PF was establishment of a unique national training scheme, CREATE, for early-career researchers (ECRs) in respiratory research. CREATE ECRs are broadly drawn from two main fields of researchers: clinicians and scientists, where clinicians tend to be involved in part-time translational research and scientists are involved in broad scientific research including laboratory or genetic research, health economics or population research.

Methods

We describe the CREATE Program which, with limited budget and the assistance of key organisations, has provided funding opportunities (scholarships, fellowships, prizes, travel and collaboration grants), professional development (mentoring program, symposia, presentation opportunities and on-line training) and fostered a connected, supportive research community for respiratory ECRs.

Results

The CREATE program has successfully fostered the development of the supported researchers, contributing substantially to the future of pulmonary fibrosis research in Australia. During the life of the program the CRE-PF has offered 10 PhD scholarships and five postdoctoral fellowships, awarded 13 travel grants and three grants to promote collaboration between ECRs from different institutes. A mentoring program has been established and CREATE Symposia have been held in association with key meetings. During COVID-19 restrictions, a series of virtual research meetings has offered 12 CREATE ECRs from seven universities the opportunity to present their research to a national audience.

CREATE research-related achievements are impressive, including over 80 first-author publications by ECRs, and many conference presentations. Contributions to the research community, measured by committee membership, is also strong.

Conclusions

In spite of a very limited budget, wide geographic distribution of participants and the multi-disciplinary nature of the cohort, we have succeeded in providing a unique, supportive academic development environment for CREATE ECRs. Lessons learned in the process of developing this program include the importance of leveraging funding, being flexible, building networks and seeking and responding to ECR input.
From raw data to a score: Comparing quantitative methods that construct multi-level composite implementation strength scores of family planning programs in Malawi
Authors: Pattnaik Anooj , Mohan Diwakar , Zeger Scott , Kanyuka Mercy , Kachale Fannie , Marx Melissa A.
Published: October 2021

Background

Data that capture implementation strength can be combined in multiple ways across content and health system levels to create a summary measure that can help us to explore and compare program implementation across facility catchment areas. Summary indices can make it easier for national policymakers to understand and address variation in strength of program implementation across jurisdictions. In this paper we describe development of an index that we used to describe the district-level strength of implementation of Malawi’s national family planning program.

Methods

To develop the index, we used data collected during a 2017 national, health facility- and community health worker Implementation Strength Assessment survey in Malawi to test different methods to combine indicators within and then across domains (4 methods – simple additive, weighted additive, principal components analysis, exploratory factor analysis) and combine scores across health facility and community health worker levels (2 methods – simple average and mixed effects model) to create a catchment area-level summary score for each health facility in Malawi. We explored how well each model captures variation and predicts couple-years protection and how feasible it is to conduct each type of analysis and the resulting interpretability.

Results

We found little difference in how the four methods combined indicator data at the individual and combined levels of the health system. However, there were major differences when combining scores across health system levels to obtain a score at the health facility catchment area level. The scores resulting from the mixed effects model were able to better discriminate differences between catchment area scores compared to the simple average method. The scores using the mixed effects combination method also demonstrated more of a dose-response relationship with couple-years protection.

Conclusions

The summary measure that was calculated from the mixed effects combination method captured the variation of strength of implementation of Malawi’s national family planning program at the health facility catchment area level. However, the best method for creating an index should be based on pros and cons listed, not least, analyst capacity and ease of interpretability of findings. Ultimately, the resulting summary measure can aid decisionmakers in understanding the combined effect of multiple aspects of programs being implemented in their health system and comparing strengths of programs across geographies.
Multi-ancestry gene-trait connection landscape using electronic health record (EHR) linked biobank data
Authors: Li Binglan , Veturi Yogasudha , Lucas Anastasia , Bradford Yuki , Verma Shefali S. , Verma Anurag , Park Joseph , Wei Wei-Qi , Feng Qiping , Namjou Bahram , Kiryluk Krzysztof , Kullo Iftikhar , Luo Yuan , Pividori Milton , Im Hae Kyung , Greene Casey S. , Ritchie Marylyn D.
Published: October 2021

Understanding genetic factors of complex traits across ancestry groups holds a key to improve the overall health care quality for diverse populations in the United States. In recent years, multiple electronic health record-linked (EHR-linked) biobanks have recruited participants of diverse ancestry backgrounds; these biobanks make it possible to obtain phenome-wide association study (PheWAS) summary statistics on a genome-wide scale for different ancestry groups. Moreover, advancement in bioinformatics methods provide novel means to accelerate the translation of basic discoveries to clinical utility by integrating GWAS summary statistics and expression quantitative trait locus (eQTL) data to identify complex trait-related genes, such as transcriptome-wide association study (TWAS) and colocalization analyses. Here, we combined the advantages of multi-ancestry biobanks and data integrative approaches to investigate the multi-ancestry, gene-disease connection landscape. We first performed a phenome-wide TWAS on Electronic Medical Records and Genomics (eMERGE) III network participants of European ancestry (N = 68,813) and participants of African ancestry (N = 12,658) populations, separately. For each ancestry group, the phenome-wide TWAS tested gene-disease associations between 22,535 genes and 309 curated disease phenotypes in 49 primary human tissues, as well as cross-tissue associations. Next, we identified gene-disease associations that were shared across the two ancestry groups by combining the ancestry-specific results via meta-analyses. We further applied a Bayesian colocalization method, fastENLOC, to prioritize likely functional gene-disease associations with supportive colocalized eQTL and GWAS signals. We replicated the phenome-wide gene-disease analysis in the analogous Penn Medicine BioBank (PMBB) cohorts and sought additional validations in the PhenomeXcan UK Biobank (UKBB) database, PheWAS catalog, and systematic literature review. Phenome-wide TWAS identified many proof-of-concept gene-disease associations, e.g. FTO-obesity association (p = 7.29e-15), and numerous novel disease-associated genes, e.g. association between GATA6-AS1 with pulmonary heart disease (p = 4.60e-10). In short, the multi-ancestry, gene-disease connection landscape provides rich resources for future multi-ancestry complex disease research. We also highlight the importance of expanding the size of non-European ancestry datasets and the potential of exploring ancestry-specific genetic analyses as these will be critical to improve our understanding of the genetic architecture of complex disease.
White matter alterations in focal to bilateral tonic-clonic seizures
Authors: Maher Christina , D’Souza Arkiev , Zeng Rui , Barnett Michael , Kavehei Omid , Nikpour Armin , Wang Chenyu
Published: October 2021

We sought to examine the microstructural white matter differences in patients with focal to bilateral tonic-clonic seizures (FBTCS), compared to those with focal epilepsy without FBTCS, and control participants. Using a superior tract segmentation model, we obtained track-weighted tensor-metrics (TW-TM), implemented through an automated pipeline for image analysis and tract reconstruction. Analysis of covariance was used to compare group differences in the TW-TM for whole-tract and hemispheric tract measurements. We identified several white matter regions that displayed significantly altered white matter in patients with focal epilepsy compared to controls. Further, patients without FBTCS had significantly increased white matter disruption in the inferior fronto-occipital fascicle and the striato-occipital tract. In contrast, patients with FBTCS were more similar to healthy controls in most regions, except for distinct alterations in the inferior cerebellar region compared to the non-FBTCS group and controls. Our study revealed marked alterations in a range of subcortical tracts widely considered critical in the genesis of seizures in focal epilepsy. Our application of TW-TM in a new clinical dataset enabled the identification of specific tracts that may act as a predictive biomarker to distinguish patients who are likely to develop FBTCS.
Resting State fMRI Speech, Language, and Executive Function Network Connectivity in Children with and without Listening Difficulties
Authors: Hoyda Julia C. , Stewart Hannah J. , Vannest Jennifer , Moore David R.
Published: October 2021

Listening Difficulties (LiD) are characterized by a child having reported issues with listening despite exhibiting normal hearing thresholds. LiD can often overlap with other developmental disorders, including speech and language disorders, and involve similar higher-order auditory processing. This study used resting-state functional MRI to examine functional brain networks associated with receptive and expressive speech and language and executive function in children with LiD and typically developing (TD) peers (average age of 10 years).

We examined differences in region-of-interest (ROI)-to-ROI functional connectivity between: (1) the LiD group and the TD group and (2) within the LiD group, those participants who had seen a Speech-Language Pathologist and those who had not. The latter comparison was examined as a way of comparing children with and without speech and language disorders. Connections that differed between groups were analyzed for correlations with behavioral test data.

The results showed functional connectivity differences between the LiD group and TD group in the executive function network and trends in the speech perception network. Differences were also found in the executive network between those LiD participants who had seen an SLP and those who had not.

Several of these connectivity differences, particularly frontal-striatal connections, correlated with performance on behavioral tests: including tests that measure attention, executive function, and episodic memory, as well as speech, vocabulary, and sentence structure.

The results of this study suggest that differences in functional connectivity in brain networks associated with speech perception and executive function may underlie and contribute to listening difficulties.
Seroconversion rate and socioeconomic and ethnic risk factors for SARS-CoV-2 infection in children in a population-based cohort
Authors: Brinkmann F , Diebner HH , Matenar C , Schlegtendal A , Eitner L , Timmesfeld N , Maier C , Lücke T
Published: October 2021

Introduction

Socioeconomic and ethnic background have been discussed as possible risk factors for SARS-CoV-2 infections in children. Improved knowledge could lead way to tailored prevention strategies and help to improve infection control.

Methods

Observational population-based cohort study in children (6mo. - 18 ys.) scheduled for legally required preventive examination and their parents in a metropolitan region in Germany. Primary endpoint was the SARS-CoV-2 seroconversion rate during study period. Risk factors assessed included age, pre-existing medical conditions, socioeconomic factors, and ethnicity.

Results

2124 children and their parents were included. Seroconversion rates among children in all age groups increased by 3-4-fold from 06/2020 to 02/2021. Only 41% of seropositive children were symptomatic. In 51% of infected children at least one parent was also SARS-CoV-2 positive.

Low level of parental education (OR 3.13 (0.72-13.69)) significantly increased the risk of infection. Of the total cohort, 38.5% had a migration background. Specifically, 9% were of Turkish and 5% of Middle Eastern origin. These children had the highest risk for SARS-CoV-2 infections (OR 6.24 (1.38-28.12) and 6.44 (1.14-36.45) after adjustment for other risk factors.

Discussion

Seroprevalence of SARS-CoV-2 infections in children increased by 3-4-fold within the study period. Frequently, more than one family member was infected. Children from families with lower socioeconomic status were at higher risk. The highest risk for SARS-CoV-2 infection was identified in families with Turkish or Middle Eastern background. Culture sensitive approaches are essential to improve infection control and serve as a blueprint for vaccination strategies in this population.

Trial Registration

BMBF funding registration 01KI20173 (Corkid)
Nurses’ Perceptions regarding the antiretroviral therapy services at selected health facilities in Lesotho
Authors: Nyangu Isabel , Nkosi Zerish Zethu
Published: October 2021

Background

In Lesotho, ART services are provided in primary health care (PHC) facilities which are mostly run by nurses.

Purpose

The study aimed to describe perceptions of nurses regarding the antiretroviral therapy services at PHC facilities across six selected districts in Lesotho.

Methods

A cross sectional survey was conducted in which convenience sampling was used to select 214 nurses working at PHC facilities across six districts. They completed a structured self-report questionnaire that collected information on their perceptions using a Likert scale with six options (strongly agree, agree, neutral, disagree, strongly disagree, and no answer). The response rate was 92% (n=197) and data were analyzed using SPSS (23).

Results

Nurses’ perceptions were positive and the same on whether ARVS and other medications were available; they were qualified and competent to provide ART services; they had adequate resources and equipment to provide ART services; they were satisfied with their jobs and the services they provided; and there was monitoring and evaluating system for the ART services. Nurses’ perceptions significantly differed and were mostly negative on whether they were adequately staffed to provide ART services; their organizational structures allowed for the provision of adequate and efficient services; ART services were accessible; and there was adequate and accurate documentation of the ART services they provided.

Conclusions

As nurses are the main health care providers in Lesotho, their perceptions are important in improving service delivery. It is important to standardize ART services across the districts to ensure equitable accessibility in line with service demand.
Sevoflurane-based enhancement of phase-amplitude coupling and localization of the epileptogenic zone
Authors: Wada Keiko , Sonoda Masaki , Firestone Ethan , Sakakura Kazuki , Kuroda Naoto , Takayama Yutaro , Iijima Keiya , Iwasaki Masaki , Mihara Takahiro , Goto Takahisa , Asano Eishi , Miyazaki. Tomoyuki
Published: October 2021

Objective

Phase-amplitude coupling between high-frequency (≥150 Hz) and delta (3-4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone.

Methods

This is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified ‘removed’ and ‘retained’ brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites.

Results

MI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1 MI.

Conclusions

Intraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2 MAC in this small cohort of patients.

Significance

Prospective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation.

Highlights

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We measured the modulation index on intraoperative electrocorticography recording.

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Sevoflurane enhanced the modulation index differentially across the epileptogenic and non- epileptogenic sites.

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The modulation index best discriminated these two groups of sites before sevoflurane reached 2 minimum alveolar concentration.
Linking common and rare disease genetics through gene regulatory networks
Authors: Bakker Olivier B. , Claringbould Annique , Westra Harm-Jan , Wiersma Henry , Boulogne Floranne , Võsa Urmo , Symmons Sophie Mulcahy , Jonkers Iris H. , Franke Lude , Deelen Patrick
Published: October 2021

Genetic variants identified through genome-wide association studies (GWAS) are typically non-coding and exert small regulatory effects on downstream genes, but which downstream genes are ultimately impacted and how they confer risk remains mostly unclear. Conversely, variants that cause rare Mendelian diseases are often coding and have a more direct impact on disease development. We demonstrate that common and rare genetic diseases can be linked by studying the gene regulatory networks impacted by common disease-associated variants. We implemented this in the ‘Downstreamer’ method and applied it to 44 GWAS traits and find that predicted downstream “key genes” are enriched with Mendelian disease genes, e.g. key genes for height are enriched for genes that cause skeletal abnormalities and Ehlers-Danlos syndromes. We find that 82% of these key genes are located outside of GWAS loci, suggesting that they result from complex trans regulation rather than being impacted by disease-associated variants in cis. Finally, we discuss the challenges in reconstructing gene regulatory networks and provide a roadmap to improve identification of these highly connected genes for common traits and diseases.
Associations between sustainable development goals accelerators and well-being, by household heads’ disability status among adolescents in Zambia – a cross-sectional study
Authors: Chipanta David , Estill Janne , Stöckl Heidi , Hertzog Lucas , Toska Elona , Chanda Patrick , Mwanza Jason , Kaila Kelly , Matome Chisangu , Tembo Gelson , Keiser Olivia , Cluver Lucie
Published: October 2021

Objectives

We examined associations between accelerators (interventions impacting two or more SDG targets) and well-being indicators among adolescents in Zambia.

Methods

We randomly sampled 1,800 households receiving social cash transfers (SCT) in four districts, surveyed adults 16 years and older. Using multivariable logistic regressions, stratified by household heads disability status, we examined associations between accelerators (SCT, life-long learning (LLL), mobile phone access (MPA)) and seven well-being indicators among adolescents 16 to 24 years old. We predicted adolescents’ probabilities of reporting indicators using marginal effects models.

Results

We included 1,725 adolescents, 881(51.1%) girls. MPA was associated with no poverty (adjusted Odds Ratio [aOR] 2.08, p<0.001), informal cash transfers (aOR 1.82 p=0.004), seeking mental support (aOR 1.61, p=0.020); SCT with no health access restrictions related to disability (aOR 2.56, p=0.004), lesser odds seeking mental support (aOR 0.53, p=0.029); LLL with informal cash transfers (aOR 3.49, p<0.001), lower school enrolment (aOR 0.70, p=0.004). Adolescents living with disabled household heads reported worse poverty, good health, less suicidal ideation.

Conclusions

Accelerators - SCT, LLL, MPA - were associated with well-being indicators. Adolescents living with disabled household heads benefited less.

Relevance to SDGs

This paper shows that adopting accelerators can help achieve SDGs-aligned well-being indicators for adolescents living in poverty. However, accelerators may not offset disability-related inequalities. Adolescents living with disabled household heads may require more attention to achieve the SDGs.

SDGs targets

1.2. no poverty; 1.3.1 social cash transfers, Informal cash transfers; 3. good Health; 3.4. no suicidal ideation; 3.4. seeking mental support; 4.1. school enrolment; 10. no health access restrictions related to disability.
Clinical performance characteristics of the Swift Normalase Amplicon Panel for sensitive recovery of SARS-CoV-2 genomes
Authors: Shrestha Lasata , Lin Michelle J. , Xie Hong , Mills Margaret G. , Bakhash Shah A. Mohamed , Gaur Vinod P. , Livingston Robert J. , Castor Jared , Bruce Emily A. , Botten Jason W. , Huang Meei-Li , Jerome Keith R. , Greninger Alexander L. , Roychoudhury Pavitra
Published: October 2021

Amplicon-based sequencing methods have been central in characterizing the diversity, transmission and evolution of SARS-CoV-2, but need to be rigorously assessed for clinical utility. Here, we validated the Swift Biosciences’ SARS-CoV-2 Swift Normalase Amplicon Panels using remnant clinical specimens. High quality genomes meeting our established library and sequence quality criteria were recovered from positive specimens with a 95% limit of detection of ≥ 40.08 SARS-CoV-2 copies/PCR reaction. Breadth of genome recovery was evaluated across a range of Ct values (11.3 – 36.7, median 21.6). Out of 428 positive samples, 406 (94.9%) generated genomes with < 10% Ns, with a mean genome coverage of 13,545X ± SD 8,382X. No genomes were recovered from PCR-negative specimens (n = 30), or from specimens positive for non-SARS-CoV-2 respiratory viruses (n = 20). Compared to whole-genome shotgun metagenomic sequencing (n = 14) or Sanger sequencing for the spike gene (n = 11), pairwise identity between consensus sequences was 100% in all cases, with highly concordant allele frequencies (R2= 0.99) between Swift and shotgun libraries. When samples from different clades were mixed at varying ratios, expected variants were detected even in 1:99 mixtures. When deployed as a clinical test, 268 tests were performed in the first 23 weeks with a median turnaround time of 11 days, ordered primarily for outbreak investigations and infection control.