bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge, attitude and practices on intermittent preventive treatment in pregnant women with malaria: a mixed method facility-based study in Western Kenya
Authors: Mukala Joseph , Mogere Dominic , Kirira Peter , Kanoi Bernard N. , Akinyi Violet , Kobia Francis , Waweru Harrison , Gitaka Jesse
Published: October 2023

Intermittent preventive treatment remains a core strategy for malaria prevention in pregnancy. Sulfadoxine-pyrimethamine is recommended for all pregnant women in malaria prone zones. It is scheduled monthly at each antenatal care visit up to 36 weeks. Here, we sought to assess the knowledge, attitude and practices on intermittent preventive treatment in pregnant women with malaria in Webuye hospital. Prior to the enrollment, ethical approval and permissions were sought from relevant institutions, as well as consents obtained from 140 participants aged between 18-49 years with gestation about 16 weeks. Malaria test was conducted via either microscopy or rapid test and participants were split into malaria positive and negative cohorts. Closed and open-ended questionnaire were administered to the participants and two focus group discussions were organized to collect their views. The results were expressed in percentage and Chi-square of association at a p-value equal or less than 0.05 (95%). Qualitative data were analyzed by the means of MAXQDA software. Our analysis revealed that there was a significant difference between the proportion of negative and positive groups among mothers’ knowledgeable on the side effects (p-value = 0.001), different doses (p-value = 0.012). Those who were informed about intermittent preventive treatment before administration (p-value = 0.003). The proportion of mothers knowledgeable about side effects and different doses were higher among the malaria positive group as compare to the negative with 52.9% versus 25.7% and 20.0% versus 5.7% respectively. Moreover, 76.3% of respondents reported that intermittent preventive treatment prevents malaria, 30.9% had the opinion that it causes abortion. Expectant women who were aware of the benefits of this strategy had this to say; “This medicine helps to reduce the effects of malaria and prevents mother to contract malaria”.However, those unaware had this to say;“I have never been told about something like that but it prevents diseases”. Those whoknew about the schedule and side effects said“It is given three doses during each antenatal visit”.Therefore, good knowledge, attitude and practices of intermittent preventive treatment are key for control and prevention of malaria in endemic prone areas.
Effects of the maternal and fetal proteome on birth weight: a Mendelian randomization analysis
Authors: McBride Nancy , Fernández-Sanlés Alba , Al Arab Marwa , Bond Tom A. , Zheng Jie , Magnus Maria C. , Corfield Elizabeth C. , Clayton Gemma L , Hwang Liang-Dar , Beaumont Robin N. , Evans David M. , Freathy Rachel M. , Gaunt Tom R. , Lawlor Deborah A , Borges Maria Carolina
Published: October 2023

Background

Fetal growth is an important indicator of survival, regulated by maternal and fetal genetic and environmental factors. However, little is known about the underlying molecular mechanisms. Proteins play a major role in a wide range of biological processes and could provide key insights into maternal and fetal molecular mechanisms regulating fetal growth.

Method

We used intergenerational two-sample Mendelian randomization to explore the effects of 1,139 maternal and fetal genetically-instrumented plasma proteins on birth weight. We used genome-wide association summary data from the Early Growth Genetics (EGG) consortium (n=406,063 with maternal and/or fetal genotype), with independent replication in the Norwegian Mother, Father and Child Cohort Study (MoBa; n=74,932 mothers and n=62,108 offspring). Maternal and fetal data were adjusted for the correlation between fetal and maternal genotype, to distinguish their independent genetic effects.

Results

We found that higher genetically-predicted maternal levels of NEC1 increased birth weight (mean-difference: 12g (95% CI [6g, 18g]) per 1 standard deviation protein level) as did PRS57 (20g [10g, 31g]) and ULK3 (140g [81g, 199g]). Higher maternal levels of Galectin_4 decreased birth weight (-206g [-299g, -113g]). In contrast, in the offspring, higher genetically-predicted offspring levels of NEC1 decreased birth weight (-10g [-16g, -5g]), alongside sLeptin_R (-8g [-12g, -4g]), and UBS3B (-78g [-116g, -41g]). Higher fetal levels of Galectin_4 increased birth weight (174g [89g, 258g]). We replicated these results in MoBa, and found supportive evidence for shared causal variants from genetic colocalization analyses and protein-protein network associations.

Conclusions

We find strong evidence for causal effects, sometimes in opposing directions, of maternal and fetal genetically-instrumented proteins on birth weight. These provide new insights into maternal and fetal molecular mechanisms regulating fetal growth, involving glucose metabolism, energy balance, and vascular function that could be used to identify new intervention targets to reduce the risk of fetal growth disorders, and their associated adverse maternal and fetal outcomes.
A Genome-Wide Association Study (GWAS) meta-analysis of post-traumatic osteoarthritis of the knee (GO-PTOA): Protocol for Analysis Plan
Authors: McDonald Merry-Lynn , Richman Joshua , Boer Cindy , Kalsoum Raneem , Dochtermann Daniel , Barker Tyler , Briem Kristin , Hatzikotoulas Konstantinos , Hollis Benjamin , Jostins-Dean Luke , Magi Reedik , Reimann Ene ,   EstBB Research Team, Southam Lorraine , Styrkarsdottir Unnur , Tiwari Hemant , Van Meurs Joyce , Zeggini Eleftheria , Singh Jasvinder , Watt Fiona E.
Published: October 2023

Post Traumatic Osteoarthritis (PTOA) of the knee is osteoarthritis (OA) occurring specifically after a significant acute injury to the joint. Approximately 50% of people with significant knee joint injuries, such as anterior cruciate ligament (ACL) rupture, develop symptomatic radiographic OA within 10 years. Although impacts of the disease are well-described, there is little known about the genetic risk of developing OA after a knee injury relative to idiopathic OA. There is an unmet clinical need to understand the aetiology of PTOA, which will help us to understand, predict and prevent PTOA.

In this Analysis Plan, we describe our methodological approach to performing a Genome Wide Association Study (GWAS) meta-analysis, developed by the Genetics of Osteoarthritis consortium (GO)-PTOA working group. We aim to determine if genetic variants associate with PTOA following a knee joint injury and understand whether these variants are similar to or different from those associated with idiopathic knee OA (iOA).

Summary statistics from six international cohorts and biobanks will be included in the meta-analysis. We have harmonized an approach to identify cases of acute knee injury, knee PTOA cases as well as controls. Our three main objectives are to identify genetic variation associated with:

knee PTOA independent of knee iOA

knee PTOA compared with knee injured controls without OA

knee PTOA compared with controls over 40 years of age without injury or OA Although not part of our primary analysis, we also plan to identify genetic variation associated with the onset of knee PTOA in a time-to-event analysis in the future.

Where resources allow, sensitivity analyses for all aims will be carried out, adjusting for body mass index (BMI). For case-control analyses, either a logistic regression or linear mixed model (LMM) will be used. For later time-to-event analysis, a matched case-control Cox Proportion Hazards (PH) regression model will be applied. Cohorts will share their summary statistics with the central analysis site conducting the single meta-analysis for each GWAS, which is likely to be carried out in either METAL or GWAMA.

Findings from this work will potentially improve our understanding of PTOA pathogenesis and aetiology. Better understanding of genetic determinants could contribute to more accurate prognostic modelling and precision medicine in the future.
Is Recovery Just the Beginning? Persistent Symptoms and Health and Performance Deterioration in Post-COVID-19, non-hospitalised University Students - A Cross-Sectional Study
Authors: Latifi Ashkan , Flegr Jaroslav
Published: October 2023

Many individuals experience persistent symptoms such as deteriorated physical and mental health, increased fatigue, and reduced cognitive performance months after recovering from COVID-19. Current data are limited on the long-term trajectory of these symptoms and their prevalence in milder cases. Our study aimed to assess the persistent effects of COVID-19 on physical and mental health, fatigue, and cognitive performance in a cohort of 214 students, averaging 21.8 years of age. Of these, 148 had contracted COVID-19 but were not hospitalized, with the time since infection ranging from 1 to 39 months. We utilized a comprehensive panel of cognitive tests to measure intelligence, memory, and psychomotor skills, and a detailed anamnestic questionnaire to evaluate physical and mental health. While contracting COVID-19 did not significantly impact overall health and performance, it was associated with increased reports of fatigue. However, the reported severity of the disease had a pronounced negative influence on physical health, mental well-being, fatigue, and reaction time. Trends of improvement in physical and mental health, as well as error rate, were observed within the first two years post-infection. However, fatigue and reaction time showed a trend of deterioration. Beyond the two-year mark, physical health and error rate continued to improve, while mental health began to deteriorate. Fatigue and reaction time continued to decline. Overall, our findings suggest that some effects of contracting COVID-19 can persist or even deteriorate over time, even in younger individuals who had mild cases that did not require hospitalization.
Ancestry-specific regulatory and disease architectures are likely due to cell-type-specific gene-by-environment interactions
Authors: Wang Juehan , Gazal Steven
Published: October 2023

Multi-ancestry genome-wide association studies (GWAS) have highlighted the existence of variants with ancestry-specific effect sizes. Understanding where and why these ancestry-specific effects occur is fundamental to understanding the genetic basis of human diseases and complex traits. Here, we characterized genes differentially expressed across ancestries (ancDE genes) at the cell-type level by leveraging single-cell RNA-seq data in peripheral blood mononuclear cells for 21 individuals with East Asian (EAS) ancestry and 23 individuals with European (EUR) ancestry (172K cells); then, we tested if variants surrounding those genes were enriched in disease variants with ancestry-specific effect sizes by leveraging ancestry-matched GWAS of 31 diseases and complex traits (averageN= 90K and 267K in EAS and EUR, respectively). We observed that ancDE genes tend to be cell-type-specific, to be enriched in genes interacting with the environment, and in variants with ancestry-specific disease effect sizes, suggesting the impact of shared cell-type-specific gene-by-environment (GxE) interactions between regulatory and disease architectures. Finally, we illustrated how GxE interactions might have led to ancestry-specificMCL1expression in B cells, and ancestry-specific allele effect sizes in lymphocyte count GWAS for variants surroundingMCL1. Our results imply that large single-cell and GWAS datasets in diverse populations are required to improve our understanding on the effect of genetic variants on human diseases.
Determinants of mosaic chromosomal alteration fitness
Authors: Pershad Yash , Mack Taralynn , Poisner Hannah , Jakubek Yasminka A , Stilp Adrienne M , Mitchell Braxton D , Lewis Joshua P , Boerwinkle Eric , Loos Ruth J , Chami Nathalie , Wang Zhe , Barnes Kathleen , Pankratz Nathan , Fornage Myriam , Redline Susan , Psaty Bruce M , Bis Joshua C , Shojaie Ali , Silverman Edwin K , Cho Michael H , Yun Jeong , DeMeo Dawn , Levy Daniel , Johnson Andrew , Mathias Rasika , Taub Margaret , Arnett Donna , North Kari , Raffield Laura M , Carson April , Doyle Margaret F , Rich Stephen S. , Rotter Jerome I. , Guo Xiuqing , Cox Nancy , Roden Dan M , Franceschini Nora , Desai Pinkal , Reiner Alex , Auer Paul L , Scheet Paul , Jaiswal Siddhartha , Weinstock Joshua S , Bick Alexander G
Published: October 2023

Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well-understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our estimates of mCA fitness were correlated (R2= 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using a theoretical probability distribution. Individuals with lymphoid-associated mCAs had a significantly higher white blood cell count and faster clonal expansion rate. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identifiedTCL1A,NRIP1, andTERTlocus variants as modulators of mCA clonal expansion rate.
Understanding the variant landscape, and genetic epidemiology of Multiple Endocrine Neoplasia in India
Authors: Vatsyayan Aastha , Bhardwaj Juhi , Agrawal Srashti Jyoti , Saikia Bhaskar Jyoti , Arvinden VR , Senthivel Vigneshwar , Trehan Suruchi , Pandhare Kavita , Imran Mohamed , Bhoyar Rahul C , Divakar Mohit Kumar , Mishra Anushree , Jolly Bani , Sivasubbu Sridhar , Scaria Vinod
Published: October 2023

Aim

Multiple Endocrine Neoplasia (MEN) is a familial cancer syndrome that encompasses several different types of endocrine tumors. The disease has three main types, namely MEN1, MEN2 and MEN4 that may or may not overlap phenotypically, but are caused by genetic mutations in three different genes, namelyRET, MEN1andCDKN1Brespectively. Genetic testing for effective diagnosis, improved prognosis, and treatment is recommended as part of of clinical practice guidelines, which makes establishment of accurate pathogenicity classification of variants across the three genes essential. However, few resources offer such classification, especially in a population specific manner.

Materials and Methods

Using the gold-standard ACMG/AMP guidelines for variant classification, we have systematically classified variants reported across theRET, MEN1andCDKN1Bgenes reported in the IndiGen dataset, and established the genetic epidemiology of MEN in the Indian population. We have additionally classified variants from ClinVar and Mastermind, and made all variant classifications freely accessible in the form of a database called MAPVar. Finally, we have designed a primer panel for accurate, cost-effective diagnosis of the three MEN types.

Results

We have established the genetic prevalence of MEN in the Indian population to be the following: 1 in nearly 341 individuals is a likely carrier of MEN linked pathogenicRETmutations in the Indian population.

We have compiled ACMG-classified variants from three large datasets to create an exhaustive compendium of MEN-linked variants called MEN-Associated Pathogenic Variants (MAPVar). The database is available at:https://clingen.igib.res.in/MAPVar/We have also designed an NGS primer panel across two pools covering all 33 exonic regions of the three genes through 38 amplicons.

Conclusion

Our work establishes that MEN is prevalent disorder in India, with MEN2 variants being the most reported of the three types. This indicates the need of more genomic studies of MEN variants to establish a more comprehensive variant landscape specific to Indian populations.

Additionally, genetic testing is an effective tool used against MEN. Our panel offers a means of swift testing, and the MAPVar resource offers an exhaustive compendium of ACMG-classified MEN variants, that can act as a ready reference to aid in interpretation of genetic testing results, as well as better understanding genetic variants in clinical as well as research settings.
Persistence of geographic barriers to maternal care services following a health system strengthening initiative in rural Madagascar
Authors: Ihantamalala Felana A. , Randriamihaja Mauricianot , Miller Ann C. , Rakotonanahary Rado J.L. , Raza-Fanomezanjanahary Mbolatiana , Kotchofa Jacques Aubin , Randriamanambintsoa Marius , Ramarson Haja , Razafinjato Benedicte , Rasoanandrasana Vololoniaina , Bonds Matthew , Finnegan Karen E. , Garchitorena Andres
Published: October 2023

Background

Geographic access to healthcare continues to pose a significant challenge for pregnant women in rural areas of sub-Saharan Africa, resulting in consistently high rates of maternal mortality. Geographic barriers can persist even in settings where financial barriers have been reduced and health system strengthening (HSS) efforts are in place. The aim of this study is to combine analyses of a population-representative cohort and geolocated maternal consultation data at the village level to gain a precise understanding of spatiotemporal changes in the utilization of maternal care services in a rural district of Madagascar benefiting from HSS support.

Methods

We collected monthly information on antenatal care visits, deliveries and postnatal visits from the registries of 18 primary care health centers in Ifanadiana District, from 2016 to 2018. Similar data were collected from a district-representative cohort via surveys on over 1500 households done in 2016 and 2018. We estimated precise travel time from each village to the nearest health center to understand spatio-temporal variations in maternal care access, and to assess the impact of geographic barriers via statistical analyses.

Results

Women who lived within a one-hour walk from a health facility in the HSS catchment area had rates of per capita utilization of most maternal health services were roughly twice that those who lived 1-2 hours away and three times higher than those who lived over 2 hours away. The exception was the first antenatal care visit (ANC1), for which travel time had more modest effect. Improvements to primary care services due to HSS in this setting were only observed among women living within two hours from health centers. Statistical models revealed that women’s travel time from a health facility was the strongest determinant of maternal care service utilization.

Conclusion

This study shows how a combination of geo-located health system information and population-representative data can help assess the impact of geographical barriers to maternal care in rural areas of sub-Saharan Africa. It highlights that women who live more than 2 hours from a health facility had virtually no access to maternal health services despite efforts in place to reduce financial barriers to care and strengthen the health system.
Understanding the genetic epidemiology of hereditary breast cancer in India using whole genome data from 1029 healthy individuals
Authors: Vatsyayan Aastha , Mathur Prerika , Bhoyar Rahul C , Imran Mohamed , Senthivel Vigneshwar , Divakar Mohit Kumar , Mishra Anushree , Jolly Bani , Sivasubbu Sridhar , Scaria Vinod
Published: October 2023

Aim

Breast cancer is the most highly reported cancer in India as well as globally (Globocan 2020). Genetic testing could help tackle the increasing cancer burden by enabling carriers of pathogenic variants obtain an early diagnosis through increased surveillance, and help guide treatment, and in some cases enable prevention. However, accurate interpretation of variant pathogenicity must be established in a population-specific manner to ensure effective use of genetic testing. Further, sinceBRCA1andBRCA2are importance breast cancer genes, even rare variants must be studied for their potential effect on the disease.

Materials and Methods

We query the IndiGen data obtained from whole genome sequencing of 1029 Indian individuals, and perform variant classification of all reported BRCA variants according to the gold-standard ACMG/AMP guidelines to establish disease epidemiology. We further implement machine learning approaches to classify all reported non-benign variants, and create a ready-reference of variants classified in a manner close to ACMG guidelines at scale.

Results

We determined the genetic prevalence to be the following: 1 in nearly 341 individuals forBRCA1, and 1 in nearly 170 individuals forBRCA2are likely to be carriers of pathogenic mutations. Overall, 1 in nearly 114 individuals are likely to be carriers of pathogenic BRCA mutations. Further, using the brca-NOVUS tool, we classified 1,54,045 genetic variants across 18 population sets and 4 large variant repositories as either pathogenic or benign.

Conclusion

The high population prevalence indicates a greater need of studying genetic variants linked with breast cancer in an Indian population specific manner. To the best of our knowledge, this is the first and most comprehensive population-scale genetic epidemiological study of BRCA-linked breast cancer variants reported from India.
The spread of a validated molecular marker of artemisinin partial resistancepfkelch13R622I and association withpfhrp2/3deletions in Eritrea
Authors: Mihreteab Selam , Anderson Karen , Molina - de la Fuente Irene , Sutherland Colin J. , Smith David , Cunningham Jane , Beshir Khalid B , Cheng Qin
Published: October 2023

Eritrea is the first African country to switch away from exclusive use of HRP2-based RDTs for the detection ofP. falciparumdue to high prevalence ofpfhrp2/3-deletedP. falciparumparasites causing false-negative RDT results. While heavy reliance on malaria RDTs played a significant role in the rapid expansion ofpfhrp2/3-deleted parasites in Eritrea, we hypothesize that the use of antimalarial (artesunate-amodiaquine) may have also contributed to their spread. We conducted a retrospective investigation of mutations in the propeller domain of theP. falciparum kelch13gene in samples collected in 2016 (n=50) from the Northern Red Sea Zone before the RDT switch away from HRP2-RDTs and in samples collected in 2018-2020 (n=587) from the Gash Barka, Anseba and Debub Zones after the RDT switch. No mutations were identified in the 2016 samples. However, in 2018-2019 samples, we detected five different single non-synonymous mutations. The most prevalent mutation waspfk13R622I, which was detected in samples collected from all health centres, with an overall prevalence of 11.9% (ranging from 5.9% to 28%). Parasites carrying the R622I mutation have diverse microsatellite marker haplotypes, indicating that they had evolved multiple times from different genetic backgrounds. The prevalencepfk13R622I was significantly higher in singlepfhrp3-deleted parasites (18.0%) compared to parasites withoutpfhrp2/3deletions (6.2%) and dualpfhrp2/3-deleted parasites (9.0%), suggesting association between thepfk13R622I mutation and thepfhrp2/3deletions in Eritrea. Continuous monitoring the trends inpfhrp2/3andpfk13mutants is needed to inform effective malaria management strategies in Eritrea.
Different perspectives on Quality in clinical education of physical therapy students – protocol of a scoping review
Authors: Walter Matthias M , Rogan Slavko , Schurz Alexander P , Zinzen Evert
Published: October 2023

Background

Clinical education (CE) plays a crucial role in physical therapy education, yet there is a notable absence of established quality characteristics for its implementation.

Objectives

This scoping review aims to elucidate how various stakeholders define and describe the quality of CE in higher education for physical therapy students. Additionally, it seeks to identify commonalities and distinctions in the application of the term “quality” in the context of CE.

Methods

Peer-reviewed studies encompassing physical therapy students, clinical instructors, lecturers in physical therapy education, physical therapy educational sites, and supervising physical therapists in internships across all clinical fields will be included in the review. A comprehensive search strategy will be employed, utilizing multiple electronic databases, including MEDLINE, EMBASE, the Cochrane Library, ERIC, Education Research Complete, Education Database, and CINAHL. Eligibility screening will be independently conducted by two reviewers. Data extraction will be presented in a tabular or graphical format, aligning with the review’s objectives.

Discussion

Insights gleaned from this study hold the potential to inform targeted interventions and improvements in CE, ultimately enhancing the learning outcomes and satisfaction of physical therapy students. This endeavor seeks to bridge the existing gap in defining and achieving quality in clinical education within the realm of physical therapy higher education.
Investigating the impact of physical activity on mitochondrial function in Parkinson’s disease (PARKEX): Study protocol for a randomised controlled clinical trial
Authors: Magaña Juan Carlos , Deus Cláudia M. , Baldellou Laura , Avellanet M , Gea-Rodríguez E , Calzada Silvia Enriquez , Laguna Ariadna , Martínez-Vicente Marta , Hernández-Vara Jorge , Giné-Garriga Maria , Pereira Susana P. , Montané Joel
Published: October 2023

Parkinson’s disease (PD) is characterized by the progressive dopaminergic neuron degeneration, resulting in striatal dopamine deficiency. Mitochondrial dysfunction and oxidative stress are associated with PD pathogenesis. Physical activity (PA) has been shown to ameliorate neurological impairments and to impede age-related neuronal loss. In addition, skin fibroblasts have been identified as surrogate indicators of pathogenic processes correlating with clinical measures. The PARKEX study aims to compare the effects of two different PA programs, analyzing the impact on mitochondrial function in patients’ skin fibroblasts as biomarkers for disease status and metabolic improvement. Early-stage PD patients (n=24, H&Y stage I to III) will be randomized into three age– and sex-matched groups. Group 1 (n=8) will undergo basic physical training (BPT) emphasizing strength and resistance. Group 2 (n=8) will undergo BPT combined with functional exercises (BPTFE), targeting the sensorimotor pathways that are most affected in PD (proprioception-balance-coordination) together with cognitive and motor training (Dual task training). Group 3 (n=8) will serve as control (sedentary group; Sed). Participants will perform three sessions per week for 12 weeks. Assessment of motor function, quality of life, sleep quality, cognitive aspects and humor will be conducted pre– and post-intervention. Patient skin fibroblasts will be collected before and after the intervention and characterized in terms of metabolic remodeling and mitochondrial bioenergetics. Ethical approval has been given to commence this study. This trial is registered at clinicaltrials.gov (NCT05963425)
Assessment of Sociodemographic Factors Associated with Time to Self-reported COVID-19 Infection Among a Large Multi-Center Prospective Cohort Population in the Southeastern United States
Authors: Beron Andrew J. , Yukich Joshua O. , Berry Andrea A. , Correa Adolfo , Keating Joseph , Bott Matthew , Wierzba Thomas F , Weintraub William S. , Friedman-Klabanoff DeAnna J. , Mongraw-Chaffin Morgana , Gibbs Michael A. , Taylor Yhenneko J. , Kissinger Patricia J. , Hayes Devin , Schieffelin John S. , Burke Brian K. , Oberhelman Richard A.
Published: October 2023

Objective

We aimed to investigate sociodemographic factors associated with self-reported COVID-19 infection.

Methods

The study population is a multicenter prospective cohort of adult volunteers recruited from healthcare systems located in the mid-Atlantic and southern United States. Between April 2020 and October 2021 participants completed daily online questionnaires about symptoms, exposures, and risk behaviors related to COVID-19, including self-reports of positive SARS CoV-2 detection tests and COVID-19 vaccination. Analysis of time from study enrollment to self-reported COVID-19 infection used a time-varying mixed effects Cox-proportional hazards framework.

Results

Overall, 1,603 of 27,214 study participants (5.9%) reported a positive COVID-19 test during the study period. The adjusted hazard ratio demonstrated lower risk for women, those with a graduate level degree, and smokers. A higher risk was observed for healthcare workers, those aged 18-34, those in rural areas, those from households where a member attends school or interacts with the public, and those who visited a health provider in the last year.

Conclusions

Increased risk of self-reported COVID-19 was associated with specific demographic characteristics, which may help to inform targeted interventions for future pandemics.
Edematous Type of Malnutrition Takes Longer Recovery Time Compared to Severe Wasting (Marasmus): Findings on 6-59 months old children treated for Severe Acute Malnutrition After the War in Northern Ethiopia, 2023: Prospective Longitudinal Study
Authors: Tesfay Wagnew , Abay Mebrahtu
Published: October 2023

Background

Severe acute malnutrition (SAM) is still having public health significance by attributing almost fifty percent of the estimated ten to eleven million deaths encountered in less than five-years old children, imposing nine-fold likelihood of death compared with well-nourished children of similar age group. It increases terrifyingly and become lethal during conflicts due to lack of food, compromised water supply and hygienic practices along with insufficient healthcare services.

Methods

Hospital-based prospective cohort study was conducted using regularly collected programme data of children admitted to the stabilization center in Suhul general hospital from January 1st, 2023 up to July 31st, 2023. To collect the data, pretested structured questionnaire was generated referring to the national SAM management protocol. Then collected data get coded and entered into Microsoft Excel spreadsheet 2016 version. All forms of analyses were done using statistical package for social sciences (SPSS) version 25.

Results

From the total 168 children aged 6-59 months enrolled in the study, ninety-four per cent of them were recovered and transferred to the outpatient therapeutic programme while the rest six per cent of the participants were censored. Appetite test (AHR = 1.874; 95% CI: 1.180-2.978), level of dehydration (AHR = 0.538; 95% CI: 0.361-0.800 for some/moderate dehydration and AHR = 0.250; 95% CI: 0.128-0.489 for severe dehydration or shock), diagnosis at admission (AHR = 0.452; 95% CI: 0.294-0.694), blood transfusion (AHR = 5.559; 95% CI: 2.419-12.773), type of antibiotics (AHR = 0.365; 95% CI: 0.192-0.692) and nasogastric tube feeding (AHR = 0.531; 95% CI: 0.372-0.758) were declared significant predictors of recovery time.

Conclusion

Bottom line of the study shows the inpatient therapeutic feeding center has met the agreed indicators for nutrition interventions during humanitarian crises. We recommend the hospital leadership, the regional health bureau and other humanitarian agencies to stress on training clinical workforce directly involved in patient management and care.
Factors Influencing the Trajectory of COVID-19 Evolution: A Longitudinal Study of 12 Asian Countries
Authors: He Xiaona , Liu Hui , Zeng Fanyan , Gao Wei
Published: October 2023

Background

The effectiveness of different strategies in addressing the COVID-19 pandemic has been assessed, but there is still not enough evidence in Asian countries. This study aims to examine the factors influencing the trajectory of COVID-19 evolution in Asia, to provide insights for optimizing public health policies.

Methods

In this longitudinal analysis, we combined COVID-19 cases and vaccination percentages from Our Word in Data with the policy stringency index from the Oxford COVID-19 Government Response Tracker for 12 Asian countries between January 1, 2021, and September 30, 2022. An agglomerative hierarchical cluster analysis (HCA) was conducted to identify countries with similar COVID-19 evolution trajectories. We also investigated the potential impact of seasonal variations on the virus’ trajectory. The relationship between the level of policy response, vaccination coverage, and COVID-19 cases was explored using Generalized Additive Models (GAMs).

Findings

There were noticeable differences in the evolution trajectory of COVID-19 among the countries. The 12 Asian countries were grouped into two clusters based on evolutionary similarities. Cluster 1 consisted of West Asian countries (Azerbaijan, Turkey, Bahrain, Israel and Lebanon); while Cluster 2 included Japan, South Korea, Singapore, Malaysia, Thailand, Cambodia and Indonesia. The analysis revealed that the stringency index and vaccination coverage were associated with a statistically significant impact (bothPvalues < 0·0001) on the evolution trajectory of COVID-19 (adjR2=0·54). The dose-response relationships demonstrated that the continuous high levels of stringency index (≥87·6) or vaccination coverage (≥ 42·0%) have led to a decrease in COVID-19 infection rates. In early 2021, theadjR2increased to 0·93 for all countries. Furthermore, theadjR2for Cluster 1 and Cluster 2 were 0·86 and 0·90 respectively. All GAMs models have significantly improved compared to null model (Pvalues <0·0001).

Interpretation

By strengthening vaccination ahead of susceptible seasons and enhancing personal self-protection measures, the transmission of COVID-19 among the population can be reduced even during the highly infectious Omicron era.

Funding

Senior Talent Startup Fund of Nanchang University
How does treatment coverage and proportion never treated influence the success ofSchistosoma mansonielimination as a public health problem by 2030?
Authors: Kura Klodeta , Mutono Nyamai , Basáñez Maria-Gloria , Coffeng Luc E. , Thumbi S.M. , Anderson Roy M.
Published: October 2023

Background

The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization (WHO) guidelines recommend a broader target of population to include pre-school (pre-SAC) and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration (MDA) by individuals.

Methods

We employed two individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP forSchistosoma. mansoniby considering various levels of the population never treated (NT). We also considered two age intensity profiles, corresponding to a low and high burden of infection in adults.

Results

The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low and moderate transmission areas, EPHP can be achieved within seven years if NT ≤10% and NT <5%, respectively. In high transmission areas, community wide treatment with NT<1% is required to achieve EPHP.

Conclusions

The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimise NT can shorten programme duration.
Dengue Viremia Kinetics and Effects on Platelet Count and Clinical Outcomes: An Analysis of 2340 Patients from Vietnam
Authors: Vuong Nguyen Lam , Ha Quyen Nguyen Than , Hanh Tien Nguyen Thi , Hue Kien Duong Thi , Le Duyen Huynh Thi , Lam Phung Khanh , Hoai Tam Dong Thi , Ngoc Tran Van , Jaenisch Thomas , Simmons Cameron P. , Yacoub Sophie , Wills Bridget A. , Geskus Ronald B.
Published: October 2023

Background

Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage.

Methods

We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models.

Results

Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5-6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes.

Conclusions

This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials.
Dynamics of SARS-CoV-2 Seroprevalence in a Large US population Over a Period of 12 Months
Authors: Karkanitsa Maria , Li Yan , Valenti Shannon , Spathies Jacquelyn , Kelly Sophie , Hunsberger Sally , Yee Laura , Croker Jennifer A. , Wang Jing , Alfonso Andrea Lucia , Faust Mondreakest , Mehalko Jennifer , Drew Matthew , Denson John-Paul , Putman Zoe , Fathi Parinaz , Ngo Tran B. , Siripong Nalyn , Baus Holly Ann , Petersen Brian , Ford Eric W. , Sundaresan Vanathi , Josyula Aditya , Han Alison , Giurgea Luca T. , Rosas Luz Angela , Bean Rachel , Athota Rani , Czajkowski Lindsay , Klumpp-Thomas Carleen , Cervantes-Medina Adriana , Gouzoulis Monica , Reed Susan , Graubard Barry , Hall Matthew D. , Kalish Heather , Esposito Dominic , Kimberly Robert P. , Reis Steven , Sadtler Kaitlyn , Memoli Matthew J
Published: October 2023

Due to a combination of asymptomatic or undiagnosed infections, the proportion of the United States population infected with SARS-CoV-2 was unclear from the beginning of the pandemic. We previously established a platform to screen for SARS-CoV-2 positivity across a representative proportion of the US population, from which we reported that almost 17 million Americans were estimated to have had undocumented infections in the Spring of 2020. Since then, vaccine rollout and prevalence of different SARS-CoV-2 variants have further altered seropositivity trends within the United States population. To explore the longitudinal impacts of the pandemic and vaccine responses on seropositivity, we re-enrolled participants from our baseline study in a 6- and 12-month follow-up study to develop a longitudinal antibody profile capable of representing seropositivity within the United States during a critical period just prior to and during the initiation of vaccine rollout. Initial measurements showed that, since July 2020, seropositivity elevated within this population from 4.8% at baseline to 36.2% and 89.3% at 6 and 12 months, respectively. We also evaluated nucleocapsid seropositivity and compared to spike seropositivity to identify trends in infection versus vaccination relative to baseline. These data serve as a window into a critical timeframe within the COVID-19 pandemic response and serve as a resource that could be used in subsequent respiratory illness outbreaks.
Deep learning-assisted multiple organ segmentation from whole-body CT images
Authors: Salimi Yazdan , Shiri Isaac , Mansouri Zahra , Zaidi Habib
Published: October 2023

Background

Automated organ segmentation from computed tomography (CT) images facilitates a number of clinical applications, including clinical diagnosis, monitoring of treatment response, quantification, radiation therapy treatment planning, and radiation dosimetry.

Purpose

To develop a novel deep learning framework to generate multi-organ masks from CT images for 23 different body organs.

Methods

A dataset consisting of 3106 CT images (649,398 axial 2D CT slices, 13,640 images/segment pairs) and ground-truth manual segmentation from various online available databases were collected. After cropping them to body contour, they were resized, normalized and used to train separate models for 23 organs. Data were split to train (80%) and test (20%) covering all the databases. A Res-UNET model was trained to generate segmentation masks from the input normalized CT images. The model output was converted back to the original dimensions and compared with ground-truth segmentation masks in terms of Dice and Jaccard coefficients. The information about organ positions was implemented during post-processing by providing six anchor organ segmentations as input. Our model was compared with the online available “TotalSegmentator” model through testing our model on their test datasets and their model on our test datasets.

Results

The average Dice coefficient before and after post-processing was 84.28% and 83.26% respectively. The average Jaccard index was 76.17 and 70.60 before and after post-processing respectively. Dice coefficients over 90% were achieved for the liver, heart, bones, kidneys, spleen, femur heads, lungs, aorta, eyes, and brain segmentation masks. Post-processing improved the performance in only nine organs. Our model on the TotalSegmentator dataset was better than their models on our dataset in five organs out of 15 common organs and achieved almost similar performance for two organs.

Conclusions

The availability of a fast and reliable multi-organ segmentation tool leverages implementation in clinical setting. In this study, we developed deep learning models to segment multiple body organs and compared the performance of our models with different algorithms. Our model was trained on images presenting with large variability emanating from different databases producing acceptable results even in cases with unusual anatomies and pathologies, such as splenomegaly. We recommend using these algorithms for organs providing good performance. One of the main merits of our proposed models is their lightweight nature with an average inference time of 1.67 seconds per case per organ for a total-body CT image, which facilitates their implementation on standard computers.
Effects of System-Level Factors on Race/Ethnic Differences in In-Hospital Mortality after Acute Ischemic Stroke
Authors: Sun Philip , Markovic Daniela , Ibish Abdullah , Faigle Roland , Gottesman Rebecca , Towfighi Amytis
Published: October 2023

Introduction

Stroke mortality has declined, with differential changes by race; stroke is now the 5th leading cause of death overall, but 2nd leading cause of death in Black individuals. Little is known about recent race/ethnic and sex trends in in-hospital mortality after acute ischemic stroke (AIS) and whether system-level factors contribute to possible differences.

Methods

Using the National Inpatient Sample, adults (≥18 years) with a primary diagnosis of AIS from 2006 to 2017 (n=643,912) were identified. We assessed in-hospital mortality by race/ethnicity (White, Black, Hispanic, Asian/Pacific Islander [API], other), sex, and age. Hospitals were categorized by proportion of non-White patients served: <25% (“predominantly White patients”), 25-50% (“mixed race/ethnicity profile”), and ≥50% (“predominantly non-White patients”). Using survey adjusted logistic regression, the association between race/ethnicity and odds of mortality was assessed, adjusting for key sociodemographic, clinical, and hospital characteristics (e.g., age, comorbidities, stroke severity, do not resuscitate orders, and palliative care).

Results

Overall, mortality decreased from 5.0% in 2006 to 2.9% in 2017 (p<0.001). Comparing 2012-2017 to 2006-2011, there was a 68% reduction in mortality odds overall after adjusting for covariates, most prominent in White individuals (69%) and smallest in Black individuals (57%). Compared to White patients, Black and Hispanic patients had lower odds of mortality (adjusted odds ratio (aOR) 0.82, 95% CI 0.78-0.87 and aOR 0.93, 95% CI 0.87-1.00), primarily driven by those >65 years (age x ethnicity interaction p < 0.0001). Compared to White men, Black, Hispanic, and API men, and Black women had lower aOR of mortality. The differences in mortality between White and non-White patients were most pronounced in hospitals predominantly serving White patients (aOR 0.80, 0.74-0.87) compared to mixed hospitals (aOR 0.85, 0.79-0.91) and predominantly non-White hospitals (aOR 0.88, 0.81-0.95; interaction effect: p=0.005).

Discussion

AIS mortality decreased dramatically in recent years in all race/ethnic subgroups. Overall, non-White AIS patients had lower mortality than their White counterparts, a difference that was most striking in hospitals predominantly serving White patients. Further study is needed to understand these differences and to what extent biological, sociocultural, and system-level factors play a role.

Category

Health Services, Quality Improvement, and Patient-Centered Outcomes
Mini-heterochromatin domains constrain thecis-regulatory impact of SVA transposons in human brain development and disease
Authors: Horváth Vivien , Garza Raquel , Jönsson Marie E. , Johansson Pia A. , Adami Anita , Christoforidou Georgia , Karlsson Ofelia , Vallmanya Laura Castilla , Gerdes Patricia , Pandiloski Ninoslav , Douse Christopher H. , Jakobsson Johan
Published: October 2023

SVA retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene-regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here, we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia-parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at theTAF1locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate thecis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increasedTAF1intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized, and their regulatory impact constrained by an innate epigenetic defense system.