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Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities.

The African turquoise killifish is an exciting new vertebrate model for aging studies. A significant challenge for any model organism is the control over its diet in space and time. To address this challenge, we created an automated and networked fish feeding system. Our automated feeder is designed to be open-source, easily transferable, and built from widely available components. Compared to manual feeding, our automated system is highly precise and flexible. As a proof of concept for the feeding flexibility of these automated feeders, we define a favorable regimen for growth and fertility for the African killifish and a dietary restriction regimen where both feeding time and quantity are reduced. We show that this dietary restriction regimen extends lifespan in males (but not in females) and impacts the transcriptomes of killifish livers in a sex-specific manner. Moreover, combining our automated feeding system with a video camera, we establish a quantitative associative learning assay to provide an integrative measure of cognitive performance for the killifish. The ability to precisely control food delivery in the killifish opens new areas to assess lifespan and cognitive behavior dynamics and to screen for dietary interventions and drugs in a scalable manner previously impossible with traditional vertebrate model organisms.

The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity.

Abstract Background Despite it being a global pandemic, there is little research examining the clinical features of severe COVID-19 in sub-Saharan Africa. This study aims to identify predictors of mortality in COVID-19 patients at Kinshasa Medical Center (KMC). Methods In this retrospective, observational, cohort study carried out at the Kinshasa Medical Center (KMC) between March 10, 2020 and July 10, 2020, we included all adult inpatients (≥ 18 years old) with a positive COVID-19 PCR result. The end point of the study was survival. The study population was dichotomized into survivors and non-survivors group. Kaplan–Meier plot was used for survival analyses. The Log-Rank test was employed to compare the survival curves. Predictors of mortality were identified by Cox regression models. The significance level of p value was set at 0.05. Results 432 patients with confirmed COVID-19 were identified and only 106 (24.5%) patients with moderate, severe or critical illness (mean age 55.6 ± 13.2 years old, 80.2% were male) were included in this study, of whom 34 (32%) died during their hospitalisation. The main complications of the patients included ARDS in 59/66 (89.4%) patients, coagulopathy in 35/93 (37.6%) patients, acute cardiac injury in 24/98 (24.5%) patients, AKI in 15/74 (20.3%) patients and secondary infection in 12/81 (14.8%) patients. The independent predictors of mortality were found to be age [aHR 1.38; 95% CI 1.10–1.82], AKI stage 3 [aHR 2.51; 95% CI 1.33–6.80], proteinuria [aHR 2.60; 95% CI 1.40–6.42], respiratory rate [aHR 1.42; 95% CI 1.09–1.92] and procalcitonin [aHR 1.08; 95% CI 1.03–1.14]. The median survival time of the entire group was 12 days. The cumulative survival rate of COVID-19 patients was 86.9%, 65.0% and 19.9% respectively at 5, 10 and 20 days. Levels of creatinine (p = 0.012), were clearly elevated in non-survivors compared with survivors throughout the clinical course and increased deterioration. Conclusion Mortality rate of COVID-19 patients is high, particularly in intubated patients and is associated with age, respiratory rate, proteinuria, procalcitonin and acute kidney injury.

Introduction: Evaluation of the eruption of mandibular third molars in orthopantomograms (OPGs) is a method of forensic age assessment. The objective of our study was to provide valid reference data for this trait within a population of black South Africans. The study was guided by the criteria for reference studies in age assessment., Materials and Methods: A study population from Pretoria, South Africa comprising 670 OPGs obtained from 338 black females and 332 black males aged between 15.00 and 25.97 years was analysed. All OPGs were performed for medical indication during the period from 2011 to 2022 and were retrospectively evaluated. From the 670 OPGs, a total of 1021 mandibular third molars were evaluated. The assessment of mandibular third molars was conducted using the staging scale presented by Olze et al. in 2012. Two experienced dentists evaluated the OPGs independently of each other. If the two examiners diverged in their assessments, a consensus stage was assigned., Results: As expected, the mean, median and minimal age increased with higher stages for both teeth and both sexes. The minimum age recorded for stage D, indicating complete tooth eruption, was 15.79 years in females and 16.62 years in males., Conclusion: As it is the case for previous reference studies in other countries, placing exclusive reliance on the evaluation of mandibular third molar eruption is inadequate for ascertaining the age of majority among Black South Africans. Future studies need to examine if our results are transferable to other countries in Sub-Saharan Africa., (© 2024. The Author(s).)

Objective: Dental disease is frequently used as a proxy for diet and overall health of individuals of past populations. The aim of this study is to investigate dental disease in a sample of enslaved African individuals recovered from an urban dump (15th-17th centuries) in Lagos, Portugal., Design: In all, 81 African individuals (>12 years old) were analysed (19 males, 49 females, and 13 of unknown sex), in a total of 2283 alveoli, 2061 teeth, and 2213 interdental septa. Analysed oral pathologies include dental caries, periodontal disease, and ante-mortem tooth loss. Dental wear was also recorded., Results: Dental caries affected 52.0 % of the teeth, although only 31.9 % were cavitated lesions. In all, 96.3 % of the individuals presented at least one cariogenic lesion. Gingivitis and periodontitis were recorded in 56.7 % and 19.0 % of the septa, respectively. Only one male individual had all septal areas healthy. Ante-mortem tooth loss was recorded in 38.3 % of the individuals, in a total of 96 teeth lost (4.2 %). Regarding occlusal wear, 70.8 % of the surfaces were recorded with grades 1-3., Conclusions: The frequencies of the oral pathological conditions observed may not only reflect a cariogenic diet (rich in starches and with a high frequency of meals) but also the conditions during the maritime voyage of the first victims of the North Atlantic slave trade (xerostomia due to lack of water, sea sickness and vomiting, vitamin C deficiency, poor hygiene), and also the impact intentional dental modifications had on the dentitions., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diagnosing diabetes by shortening the OGTT to 1-h and substituting 1-h post-load glucose (PG) ≥ 209 mg/dL for 2-h PG≥200 mg/dL has been proposed. One-hour PG≥209 mg/dL is from a meta-analysis without any African-descent populations. Our data suggest 1-h PG≥183 mg/dL maybe more optimal for Africans. As with waist circumference guidelines, population-specific thresholds may be appropriate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: The COVID-19 pandemic negatively impacted mental health in the general population in Britain. Ethnic minority people suffered disproportionately, in terms of health and economic outcomes, which may contribute to poorer mental health. We compare the prevalence of depression and anxiety across 18 ethnic groups in Britain during the COVID-19 pandemic., Methods: Secondary analysis of cross-sectional data (February-November 2021) from 12,161 participants aged 18-60 years old (N with data on outcomes = 11,540 for depression & 11,825 for anxiety), obtained from the Evidence for Equality National Survey (EVENS). Data were weighted to account for selection bias and coverage bias. Weighted regression models examined ethnic differences in depression (Centre for Epidemiologic Studies Depression Scale) and anxiety (Generalised Anxiety Disorder-7). Effect modification analyses explored whether ethnic differences in outcomes were consistent within age and sex sub-groups., Results: Compared to White British people, greater odds of anxiety caseness (and greater anxiety symptoms) were observed for Arab (OR = 2.57; 95 % CI = 1.35-4.91), Mixed White and Black Caribbean (1.57; 1.07-2.30), any other Black (2.22, 1.28-3.87) and any other Mixed (1.58; 1.08-2.31) ethnic groups. Lower odds of depression caseness (and lower depressive symptoms) were identified for Chinese (0.63; 0.46-0.85), Black African (0.60; 0.46-0.79), and any other Asian (0.55; 0.42-0.72) ethnic groups., Limitations: Cross-sectional data limits the opportunity to identify changes in ethnic inequalities in mental health over time., Conclusions: We have identified certain ethnic groups who may require more targeted mental health support to ensure equitable recovery post-pandemic. Despite finding lower levels of depression for some ethnic groups, approximately one third of people within each ethnic group met criteria for depression., Competing Interests: Declaration of competing interest SVK was co-chair of the Scottish Government's Expert Reference Group on Ethnicity and COVID-19 and a member of the UK Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aims: Coronary heart disease morbidity and mortality are higher in people of South Asian origin than in those of African origin. We investigated whether as young adults without diabetes, people in Mauritius of South Asian descent (Indians) would show a more adverse cardiovascular risk profile that those of predominantly African descent (Creoles), and whether this could be explained by ethnic differences in visceral adiposity or other fat distribution patterns., Methods: The study was conducted in 189 young non-physically active adults, with the following measurements conducted after an overnight fast: anthropometry (weight, height, waist circumference), whole-body and regional body composition by dual-energy x-ray absorptiometry, blood pressure, and blood assays for glycemic (glucose and HbA1c) and lipid profile (triglycerides and cholesterols)., Results: The results indicate higher serum triglycerides and lower HDL cholesterol in men than in women, and in Indians than in Creoles (p < 0.001). No significant differences due to sex or ethnicity are observed in body mass index and waist circumference, but indices of visceral adiposity (visceral/android, visceral/subcutaneous) and visceral-to-peripheral adiposity ratio (visceral/gynoid, visceral/limb) were significantly higher in men than in women, and in Indians than in Creoles. The significant effects of sex and ethnicity on blood lipid profile were either completely abolished or reduced to a greater extent after adjusting for the ratio of visceral-to-peripheral adiposity than for visceral adiposity per se., Conclusions: In young adults in Mauritius, Indians show a more adverse pattern of body fat distribution and blood lipid risk profile than Creoles. Differences in their fat distribution patterns, however, only partially explain their differential atherogenic lipid risk profile, amid a greater impact of visceral-to-peripheral adiposity ratio than that of visceral adiposity per se on sex and ethnic differences in cardiovascular risks; the former possibly reflecting the ratio of hazardous (visceral) adiposity and protective (peripheral) superficial subcutaneous adiposity., (© 2024. The Author(s).)

Hypothesis/purpose: The prevalence of trochlear dysplasia is common in different populations., Background: The prevalence of trochlear dysplasia in the general population, categorised by sex, race, age, and body mass index, has been sparse. This study aimed to define the prevalence of trochlear dysplasia based on the latter categories., Study Design: Cohort retrospective study., Methods: 1162 skeletal mature healthy femora were obtained from a CT-scan-based modelling system (SOMA). Thin slice CT scans were acquired exclusively for medical indications such as polytrauma (20%), CT angiography (70%) and other reasons (i.e. Total Joint Replacement) (10%). Trochlear dysplasia was measured using Pfirmann's method. Patient demographics such as age, race and sex were recorded., Results: The overall prevalence of trochlear dysplasia is 4.5% and is far more common in Asian female patients compared to Caucasian, African and Middle Eastern knees., Conclusion: Overall, the prevalence of dysplasia in the general population was determined to be 4.5%, with female patients being more likely to suffer from the condition. Patients of Asian and Caucasian race were more likely to have trochlear dysplasia, while Middle Eastern male patients displayed more dysplastic values than their female counterparts., (© 2024. The Author(s).)

Purpose: This study was conducted to investigate the root canal anatomy of maxillary first molars in Black South Africans., Methods: Micro-computed tomography was used to investigate 101 maxillary first molars (53 teeth from the right, 48 from the left; 50 male and 51 female teeth). The number of root canals in each tooth was determined, and the relationship between side, sex and age was analyzed using chi-squared test. To determine intra- and inter-observer reliability, Cohen's kappa coefficients were calculated., Results: Intra- and inter-rater agreements of 96.92% and 98.08% were achieved, respectively. Most teeth contained either three or four canals, but a second, third and fourth mesio-buccal canal was found in 60.39%, 5.94% and 0.99% of teeth, respectively. The disto-buccal and palatal roots contained predominantly single canals, but additional canals were noted in 2.97% and 1.98% of teeth. Four canals were common in females and teeth on the right side often contained a second mesio-buccal canal. However, the prevalence of a third mesio-buccal canal was higher in males than in females., Conclusion: The teeth studied showed diversity and variations between sexes and arch sides. These findings will aid clinicians in endodontic treatment and will be applicable for educational purposes.

Little is known about the economic impact of disability grants for people living with schizophrenia in low- and middle- income countries. In this brief report, we show that receipt of disability benefits is significantly associated (β = 0.105, p < 0.0001) with increased household and personal wealth in large sample of people living with schizophrenia in South Africa (n = 1154). This study provides further support for the use of disability grants as a mechanism to protect people living with schizophrenia and their families against the economic costs associated with schizophrenia., (© 2023. The Author(s).)

Abstract Background Globally, cardiovascular disease (CVD) accounts for 45% of all chronic non-communicable disease deaths and 31% of all deaths. CVD has remained the primary cause of death in the world for the past fifteen years. Compared to other continents, CVD and its risk factors are highly prevalent in Africa, but the continent also displays a low-level of knowledge and awareness of CVD, and poor perception of its risk factors. Little research has been done on the connection between the daily lived experiences of African people and the high prevalence and poor perception of CVD and its risk factors on the African continent. The aim of this study is to provide an in-depth understanding of the daily, lived experiences of African people and the connections between these experiences and the prevention, control, and management of CVD and its risk factors. Methods A systematic search was performed in PubMed, CINAHL, EMBASE, Psych INFO, and Web of Science databases to identify published English qualitative studies of CVD and its risk factors. Qualitative metasynthesis included structured techniques of data immersion and quality appraisal, thematic synthesis, and reciprocal translation. Results Seven studies met the inclusion criteria. Four major themes were identified from the metasynthesis: 1) understanding and beliefs about CVD; 2) perceived causes/risk factors for CVD; 3) understanding and belief about obesity; 4) perceived treatment options for CVD. The metasynthesis identified a consistent disconnect among African people between seeing CVD as a deadly and chronic disease and their perceptions of the minimal signs and symptoms of the disease in the early stages. This was further compounded by the gap between traditional healers and health care professionals. Conclusions Perceptions of CVD, its risk factors, and treatments were influenced by religious and cultural factors. Given the minimal signs and symptoms experienced in the early stages of the disease, there was a consistent disconnect among African people between seeing CVD as a deadly and chronic illness. Further investigations of the religious and cultural influences and educational programs related to these areas of disconnect are needed to improve the knowledge, attitudes, and beliefs of African people.

Background: Despite it being a global pandemic, there is little research examining the clinical features of severe COVID-19 in sub-Saharan Africa. This study aims to identify predictors of mortality in COVID-19 patients at Kinshasa Medical Center (KMC).Methods: In this retrospective, observational, cohort study carried out at the Kinshasa Medical Center (KMC) between March 10, 2020 and July 10, 2020, we included all adult inpatients (≥ 18 years old) with a positive COVID-19 PCR result. The end point of the study was survival. The study population was dichotomized into survivors and non-survivors group. Kaplan-Meier plot was used for survival analyses. The Log-Rank test was employed to compare the survival curves. Predictors of mortality were identified by Cox regression models. The significance level of p value was set at 0.05.Results: 432 patients with confirmed COVID-19 were identified and only 106 (24.5%) patients with moderate, severe or critical illness (mean age 55.6 ± 13.2 years old, 80.2% were male) were included in this study, of whom 34 (32%) died during their hospitalisation. The main complications of the patients included ARDS in 59/66 (89.4%) patients, coagulopathy in 35/93 (37.6%) patients, acute cardiac injury in 24/98 (24.5%) patients, AKI in 15/74 (20.3%) patients and secondary infection in 12/81 (14.8%) patients. The independent predictors of mortality were found to be age [aHR 1.38; 95% CI 1.10-1.82], AKI stage 3 [aHR 2.51; 95% CI 1.33-6.80], proteinuria [aHR 2.60; 95% CI 1.40-6.42], respiratory rate [aHR 1.42; 95% CI 1.09-1.92] and procalcitonin [aHR 1.08; 95% CI 1.03-1.14]. The median survival time of the entire group was 12 days. The cumulative survival rate of COVID-19 patients was 86.9%, 65.0% and 19.9% respectively at 5, 10 and 20 days. Levels of creatinine (p = 0.012), were clearly elevated in non-survivors compared with survivors throughout the clinical course and increased deterioration.Conclusion: Mortality rate of COVID-19 patients is high, particularly in intubated patients and is associated with age, respiratory rate, proteinuria, procalcitonin and acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation., Methods: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS., Results: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10 -39 ; OR = 4.73, p = 2 × 10 -10 ; OR = 2.3, p = 7.49 × 10 -9 , respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10 -7 ), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10 -16 ). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10 -6 )., Conclusions: In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2., (© 2024. The Author(s).)

Background: Human immunodeficiency virus (HIV) and antiretroviral treatment (ART) are both associated with hypercoagulability. Altered clot properties could be a potential mechanism thereof. We aimed to investigate the association of HIV and ART, with fibrinogen and plasma clot properties in a group of Black South Africans., Methods: At baseline, 151 newly diagnosed people living with HIV (PLWH) and 176 controls were recruited. Some PLWH subsequently commenced with ARTs (n = 70) while others remained ART-naïve (n = 81). Fibrinogen and clot properties (turbidity assay) were investigated from baseline to 5-year follow-up. A sub-group of 21 women (n = 10 ART-treated; n = 11 ART-naïve) with HIV was systematically selected and matched with 12 controls, and additional clot properties (rheometry, permeability and fibre diameter) were investigated., Results: Fibrinogen was lower in the HIV groups compared to the controls, while % γ' fibrinogen was higher. PLWH had shorter lag times and lower maximum absorbance than the controls (p<0.05). Their CLTs on the other hand were longer. Most variables increased over time in all groups, but differences in the degree of change over time was observed for lag time (p = 0.024) and permeability (p = 0.03). Participants who commenced with ART had a tendency of delayed clot formation (p = 0.08) and increased clot permeability (p = 0.005)., Conclusion: PLWH had lower total fibrinogen concentration and formed less dense clots. They also formed clots that were more difficult to lyse, which likely not resulted from altered clot properties. ART use (NNRTI's) had a moderately protective effect, delaying clot formation, and increasing clot permeability., Competing Interests: None of the authors have any competing interests to declare., (Copyright: © 2024 Bakali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study documents the incidences of complete and partial metopism and their possible relationship to frontal sinus volume (FSV) in a sample of modern adult black South Africans with a view to evaluating the hypothesis that metopism affects frontal sinus hypoplasia. FSV was measured from CT scans and the incidence of metopism was recorded from direct observations of dried cadaveric crania. The sex of each individual was known. Four linear cranial dimensions were used to compute a geometric mean by which to scale FSV. The incidence of partial metopism (38%) is comparable to that reported for other population samples, although there is considerable variation among these global sample frequencies. It is significantly more common in male than female South Africans. FSV in individuals with complete metopism is smaller than average but not inordinately so. On the other hand, FSV is significantly larger in individuals with partial metopism than in those that do not present with this sutural remnant. The data on FSV in individuals with and without partial metopism contradict the hypothesis that there is a relationship between partial metopism and frontal sinus hypoplasia. As such, the metopic remnant evinced by the Late Pleistocene cranium from Hofmeyr, South Africa is unlikely to be related to its very small FSV., (© 2023 American Association for Anatomy.)

Competing Interests: Disclosures R.J.B. reported receiving research grants/grants pending awarded to his institution from Merck & Co, Inc, and serving on the scientific advisory board for Merck & Co, Inc, ViiV Healthcare, Gilead Sciences, Inc, Shionogi, and Janssen Pharmaceuticals. P.T. has received compensation for consultation services from Merck, Gilead, and ViiV Healthcare. Additionally, the University of Pennsylvania has been granted financial support in the form of research grants for conducting HIV-related studies from the National Institutes of Health, Merck, Gilead, ViiV Healthcare, Sangamo, Takeda and Janssen Pharmaceuticals. The other author reports no conflicts.

Genotype imputation is now fundamental for genome-wide association studies but lacks fairness due to the underrepresentation of references from non-European ancestries. The state-of-the-art imputation reference panel released by the Trans-Omics for Precision Medicine (TOPMed) initiative improved the imputation of admixed African-ancestry and Hispanic/Latino samples, but imputation for populations primarily residing outside of North America may still fall short in performance due to persisting underrepresentation. To illustrate this point, we imputed the genotypes of over 43,000 individuals across 123 populations around the world and identified numerous populations where imputation accuracy paled in comparison to that of European-ancestry populations. For instance, the mean imputation r-squared (Rsq) for variants with minor allele frequencies between 1% and 5% in Saudi Arabians (n = 1,061), Vietnamese (n = 1,264), Thai (n = 2,435), and Papua New Guineans (n = 776) were 0.79, 0.78, 0.76, and 0.62, respectively, compared to 0.90-0.93 for comparable European populations matched in sample size and SNP array content. Outside of Africa and Latin America, Rsq appeared to decrease as genetic distances to European-ancestry reference increased, as predicted. Using sequencing data as ground truth, we also showed that Rsq may over-estimate imputation accuracy for non-European populations more than European populations, suggesting further disparity in accuracy between populations. Using 1,496 sequenced individuals from Taiwan Biobank as a second reference panel to TOPMed, we also assessed a strategy to improve imputation for non-European populations with meta-imputation, but this design did not improve accuracy across frequency spectra. Taken together, our analyses suggest that we must ultimately strive to increase diversity and size to promote equity within genetics research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

While cholesterol is essential, a high level of cholesterol is associated with the risk of cardiovascular diseases. Genome-wide association studies (GWASs) have proven successful in identifying genetic variants that are linked to cholesterol levels, predominantly in white European populations. However, the extent to which genetic effects on cholesterol vary across different ancestries remains largely unexplored. Here, we estimate cross-ancestry genetic correlation to address questions on how genetic effects are shared across ancestries. We find significant genetic heterogeneity between ancestries for cholesterol traits. Furthermore, we demonstrate that single nucleotide polymorphisms (SNPs) with concordant effects across ancestries for cholesterol are more frequently found in regulatory regions compared to other genomic regions. Indeed, the positive genetic covariance between ancestries is mostly driven by the effects of the concordant SNPs, whereas the genetic heterogeneity is attributed to the discordant SNPs. We also show that the predictive ability of the concordant SNPs is significantly higher than the discordant SNPs in the cross-ancestry polygenic prediction. The list of concordant SNPs for cholesterol is available in GWAS Catalog. These findings have relevance for the understanding of shared genetic architecture across ancestries, contributing to the development of clinical strategies for polygenic prediction of cholesterol in cross-ancestral settings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rapid aging in American society will be disproportionately concentrated among the foreign-born. Immigrants in the United States (U.S.) are a heterogeneous population, yet little is known regarding their differences in disability later in life by region of origin. We use data from the National Health Interview Survey on respondents ages 60+ ( n  = 313,072) and employ gender-specific logistic models to predict reports of any activity of daily living (ADL) disability. After accounting for socioeconomic factors, compared to their U.S.-born non-Hispanic (NH) White counterparts, the odds of reporting ADL disability were higher among U.S.-born respondents that are Hispanic, NH Black, and NH Multiracial as well as respondents with Mexican, Puerto Rican, Cuban, Russian/former Soviet, Middle Eastern, East Asian, and South Asian origins. Also, Dominican, African, and Southeast Asian women-and European men-reported high odds of ADL disability. Our results highlight heterogeneity in the disability profiles of foreign-born older adults in the U.S.., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This paper explores the explanatory models of mental challenges among Black Africans in England. It argues that understanding these models is critical for providing culturally appropriate care to this population. The study employed qualitative methodology, and interpretative phenomenological analysis (IPA). Twelve mental health service users who are living in England and self-identified as first or second-generation Black Africans were purposively selected. The data were gathered using face-to-face semistructured interviews. Data were manually analysed in accordance with IPA concepts of searching for common, unique and idiosyncratic themes across transcripts. The findings revealed three themes Black Africans associated to their explanatory model of mental health challenges: complexities of migration, African-centred worldview and negative life experiences. To help alleviate the Eurocentric nature of mental health practice in England, it is hoped that this explanatory model will become an integral part of mental health practice in England and around the world., (© 2023 The Authors. Nursing Inquiry published by John Wiley & Sons Ltd.)

Background: Globally, cardiovascular disease (CVD) accounts for 45% of all chronic non-communicable disease deaths and 31% of all deaths. CVD has remained the primary cause of death in the world for the past fifteen years. Compared to other continents, CVD and its risk factors are highly prevalent in Africa, but the continent also displays a low-level of knowledge and awareness of CVD, and poor perception of its risk factors. Little research has been done on the connection between the daily lived experiences of African people and the high prevalence and poor perception of CVD and its risk factors on the African continent. The aim of this study is to provide an in-depth understanding of the daily, lived experiences of African people and the connections between these experiences and the prevention, control, and management of CVD and its risk factors.Methods: A systematic search was performed in PubMed, CINAHL, EMBASE, Psych INFO, and Web of Science databases to identify published English qualitative studies of CVD and its risk factors. Qualitative metasynthesis included structured techniques of data immersion and quality appraisal, thematic synthesis, and reciprocal translation.Results: Seven studies met the inclusion criteria. Four major themes were identified from the metasynthesis: 1) understanding and beliefs about CVD; 2) perceived causes/risk factors for CVD; 3) understanding and belief about obesity; 4) perceived treatment options for CVD. The metasynthesis identified a consistent disconnect among African people between seeing CVD as a deadly and chronic disease and their perceptions of the minimal signs and symptoms of the disease in the early stages. This was further compounded by the gap between traditional healers and health care professionals.Conclusions: Perceptions of CVD, its risk factors, and treatments were influenced by religious and cultural factors. Given the minimal signs and symptoms experienced in the early stages of the disease, there was a consistent disconnect among African people between seeing CVD as a deadly and chronic illness. Further investigations of the religious and cultural influences and educational programs related to these areas of disconnect are needed to improve the knowledge, attitudes, and beliefs of African people. [ABSTRACT FROM AUTHOR]

Background: To protect healthcare workers (HCWs) from the consequences of disease due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the risk factors that drive exposure and infection within hospitals. Insufficient consideration of key socioeconomic variables is a limitation of existing studies that can lead to bias and residual confounding of proposed risk factors for infection., Methods: The Co-STARs study prospectively enrolled 3679 HCWs between April 2020 and September 2020. We used multivariate logistic regression to comprehensively characterize the demographic, occupational, socioeconomic, and environmental risk factors for SARS-CoV-2 seropositivity., Results: After adjusting for key confounders, relative household overcrowding (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.1-1.9]; P = .006), Black, Black British, Caribbean, or African ethnicity (OR, 1.7 [95% CI, 1.2-2.3]; P = .003), increasing age (ages 50-60 years: OR, 1.8 [95% CI, 1.3-2.4]; P < .001), lack of access to sick pay (OR, 1.8 [95% CI, 1.3-2.4]; P < .001)., Conclusions: Socioeconomic and demographic factors outside the hospital were the main drivers of infection and exposure to SARS-CoV-2 during the first wave of the pandemic in an urban pediatric referral hospital. Overcrowding and out-of-hospital SARS-CoV-2 contact are less amenable to intervention. However, lack of access to sick pay among externally contracted staff is more easily rectifiable. Our findings suggest that providing easier access to sick pay would lead to a decrease in SARS-CoV-2 transmission and potentially that of other infectious diseases in hospital settings., Clinical Trials Registration: NCT04380896., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Complex challenges amongst ageing cohorts of adolescents and adults living with perinatally acquired HIV (PaHIV) may impact on hospitalisation. We report hospitalisation rates and explored predictive factors for hospitalisation in adolescents and adults (10-35 years) living with PaHIV in England., Method: Retrospective observational cohort study over a three-year period 2016-2019. Data collected included cause and duration of hospitalisation, HIV viral load and CD4 lymphocyte count. The primary outcome was overnight hospitalisation. Patients exited at study end/ transfer of care (TOC)/ loss to follow up (LTFU) or death. Maternity/hospital admissions at other centres were excluded. Admission rates per 100 person-years (95% CI) were calculated by age group. Negative binomial regression with generalized estimating equations was performed., Results: 255 patients contributed 689 person-years of follow up. 56% were female and 83% were of a Black, Black British, Caribbean or African ethnicity. At baseline, the median age was 19 years (IQR 16-22). 36 individuals experienced a total of 62 admissions which resulted in 558 overnight stays (median stay was 5 nights). One person died (lymphoma), six had TOC and one was LTFU by the end of the three-year study period. Crude incidence of admission for the whole cohort was 9.0 per 100 PY (6.9-11.6). The respective crude incidence rates were 1.5 PY (0.0-8.2) in those aged 10-14 years and 3.5 PY (1.5-7.0) in the 15-19-year-olds. In those aged 20-24 years it was 14.5 PY (10.1-20.2) and in those >25 years the crude incidence rate was 11.7 PY (6.9-18.5). Factors significantly associated with admission were a CD4 lymphocyte count <200 cells/uL, adjusted IRR 4.0 (1.8-8.8) and a history of a CDC-C diagnosis, adjusted IRR 2.9 (1.6-5.3). 89% admissions were HIV-related: 45% new/current CDC-C diagnoses, 76% due to infection., Conclusions: Hospitalisation rates were four-fold higher in adults (>20 years of age) compared to adolescents (10-19-year-olds). The continuing challenges experienced by PaHIV youth require enhanced multidisciplinary support throughout adulthood., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Johnson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Despite extensive research, HIV-1 remains a global epidemic with variations in pathogenesis across regions and subtypes. The Viral Infectivity Factor (Vif) protein, which neutralizes the host protein APOBEC3G, has been implicated in differences in clinical outcomes among people living with HIV (PLHIV). Most studies on Vif sequence diversity have focused on subtype B, leaving gaps in understanding Vif variations in HIV-1C regions like South Africa. This study aimed to identify and compare Vif sequence diversity in a cohort of 51 South African PLHIV and other HIV-1C prevalent regions., Methods: Sanger sequencing was used for Vif analysis in the cohort, and additional sequences were obtained from the Los Alamos database. Molecular modeling and docking techniques were employed to study the influence of subtype-specific variants on Vif-APOBEC3G binding affinity., Results: The findings showed distinct genetic variations between Vif sequences from India and Uganda, while South African sequences had wider distribution and closer relatedness to both. Specific amino acid substitutions in Vif were associated with geographic groups. Molecular modeling and docking analyses consistently identified specific residues (ARGR19, LYS26, TYR30, TYR44, and TRP79) as primary contributors to intermolecular contacts between Vif and APOBEC3G, essential for their interaction. The Indian Vif variant exhibited the highest predicted binding affinity to APOBEC3G among the studied groups., Conclusions: These results provide insights into Vif sequence diversity in HIV-1C prevalent regions and shed light on differential pathogenesis observed in different geographical areas. The identified Vif amino acid residues warrant further investigation for their diagnostic, prognostic, and therapeutic potential., (© 2023. The Author(s).)

Surveillance to better detect and respond to new pathogens remains a major challenge for global public health. The Pasteur Network recently held a brainstorming workshop located in Cameroon attended by Pasteur epidemiological teams from Niger, Central African Republic (CAR), Cameroon, Senegal, and Madagascar to discuss how the Pasteur Network in Africa could use the lessons of COVID-19 to set-up a pilot sentinel surveillance scheme given its expertise and involvement during the pandemic. The possibility of coupling sentinel syndromic and biological surveillance already implemented for influenza surveillance with the recent sequencing capacity put in place by the AFROSCREEN program prompted us to consider strengthening surveillance tools to target "Pathogen X" detection in Africa. The perspective project provided by the Pasteur Network teams and shared with other partners of the AFROSCREEN program will target strengthening of the diagnosis of severe acute respiratory infections (IRAS) and the surveillance of IRAS, the evaluation of the impact of SARS-CoV-2 on the epidemiology of IRAS, and the addition of the detection of new pathogens, called "Pathogen X," based on sequencing capacity and epidemiological criteria from One Health approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tejiokem, Barry, Ratovoson, Yambiyo, Hamidou Lazoumar, Herrant, Madaha and Richard.)

Objective: Precision medicine is an area with great potential for mental health, but has made limited gains prognostically in predicting effective treatments. For refugees exposed to violence, culture may be a crucial factor in predicting treatment outcomes., Method: For this study, 290 participants from three regions (Afghanistan, the Great Lakes region of Africa, and Iraq and Syria) participated in a randomized controlled trial of an advocacy-based intervention. Emotional distress symptoms were measured prior to intervention, midintervention (3 months), postintervention (6 months), and follow-up (6 months after the end of intervention). Number of traumatic events, resource access, social support, and English proficiency were tested for potential predictive effects on intervention outcome., Results: Multilevel generalized linear models revealed that Afghans' ( B = -0.259, SE = 0.108, p = .013), and Great Lakes Africans' ( B = -0.116, SE = 0.057, p = .042) emotional distress symptoms improved as a function of the intervention, while Iraqis and Syrians showed no intervention effects. For Afghans, English proficiency ( B = -0.453, SE = 0.157, p < .01) and social support ( B = -0.179, SE = 0.086, p = .037) were most strongly correlated to emotional distress, while for Africans, resource access ( B = -0.483, SE = 0.082, p < .001) and social support ( B = -0.100, SE = 0.048, p = .040) were the strongest predictors of emotional distress., Conclusions: Response to advocacy-based interventions and active ingredients may be influenced by culture; findings have implications for refugees and precision medicine. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

In studies on the sense of belonging among racialized minorities in Australia, the experiences of Indigenous people and African refugees have been discussed separately. However, because both groups encounter social exclusion due to their blackness, their shared experiences also need to be considered. In this study, I examine the intersections of experiences of blackness and their impacts on people's senses of belonging by using the findings of previous studies in addition to my ongoing fieldwork data on intergroup relationships between both groups. The present study shows that while some individuals of these groups experienced blackness as a deviation from the norm created in the mainstream media, other members reinterpreted or distanced themselves from blackness. Meanwhile, some members of each group found a commonality in blackness with the other group and established their own sense of belonging, stemming from a shared history of colonization, as well as a shared contemporary experience of subordination and exclusion. Awareness of these commonalities in their experiences caused the groups to feel that they were coexisting, rather than competing with each other as indicated by previous studies. The findings indicate a reconciliation of blackness between these two groups and the potential to form a new, shared self-identification as racial minorities in Australia as an alternative to that on the basis of whiteness and Britishness. [ABSTRACT FROM AUTHOR]