Haynessteensen9615

lerate progress. Despite little progress in some areas, maternal and child undernutrition remains a major global health concern, particularly as improvements since 2000 might be offset by the COVID-19 pandemic.Phenotype prediction is a key goal for medical genetics. Unfortunately, most genome-wide association studies are done in European populations, which reduces the accuracy of predictions via polygenic scores in non-European populations. Here, we use population genetic models to show that human demographic history and negative selection on complex traits can result in population-specific genetic architectures. For traits where alleles with the largest effect on the trait are under the strongest negative selection, approximately half of the heritability can be accounted for by variants in Europe that are absent from Africa, leading to poor performance in phenotype prediction across these populations. Further, under such a model, individuals in the tails of the genetic risk distribution may not be identified via polygenic scores generated in another population. We empirically test these predictions by building a model to stratify heritability between European-specific and shared variants and applied it to 37 traits and diseases in the UK Biobank. Across these phenotypes, ∼30% of the heritability comes from European-specific variants. We conclude that genetic association studies need to include more diverse populations to enable the utility of phenotype prediction in all populations.Sodium glucose co-transporter (SGLT) 2 inhibitors reduce the risk of kidney failure in patients with and without type 2 diabetes (T2D). BAY 2402234 Although the precise underlying mechanisms for these nephroprotective effects are incompletely understood, various hypotheses have been proposed including reductions in intraglomerular pressure through restoration of tubuloglomerular feedback, blood pressure reduction and favorable effects on vascular function, reduction in tubular workload and hypoxia, and metabolic effects resulting in increased autophagy. Here, we review these mechanisms, which may also explain the beneficial effects of SGLT2 inhibitors on kidney function in patients without T2D.Understanding the mechanisms underlying how T cells become dysfunctional in a tumor microenvironment (TME) will greatly benefit cancer immunotherapy. We found that increased CD36 expression in tumor-infiltrating CD8+ T cells, which was induced by TME cholesterol, was associated with tumor progression and poor survival in human and murine cancers. Genetic ablation of Cd36 in effector CD8+ T cells exhibited increased cytotoxic cytokine production and enhanced tumor eradication. CD36 mediated uptake of fatty acids by tumor-infiltrating CD8+ T cells in TME, induced lipid peroxidation and ferroptosis, and led to reduced cytotoxic cytokine production and impaired antitumor ability. Blocking CD36 or inhibiting ferroptosis in CD8+ T cells effectively restored their antitumor activity and, more importantly, possessed greater antitumor efficacy in combination with anti-PD-1 antibodies. This study reveals a new mechanism of CD36 regulating the function of CD8+ effector T cells and therapeutic potential of targeting CD36 or inhibiting ferroptosis to restore T cell function.It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T cells. These T cells express increased Voltage-Dependent Anion Channel 1 (VDAC1), accompanied by gene programs and functional characteristics linked to mitochondrial dysfunction and apoptosis. The percentage of these cells increases in elderly patients and correlates with lymphopenia. Importantly, T cell apoptosis is inhibited in vitro by targeting the oligomerization of VDAC1 or blocking caspase activity. We also observe an expansion of myeloid-derived suppressor cells with unique metabolic phenotypes specific to COVID-19, and their presence distinguishes severe from mild disease. Overall, the identification of these metabolic phenotypes provides insight into the dysfunctional immune response in acutely ill COVID-19 patients and provides a means to predict and track disease severity and/or design metabolic therapeutic regimens.

Access to COVID-19 testing remained a salient issue during the early months of the pandemic, therefore this study aimed to identify 1) regional and 2) socioeconomic predictors of perceived ability to access Coronavirus testing.

An online survey using social media-based advertising was conducted among U.S. adults in April 2020. Participants were asked whether they thought they could acquire a COVID-19 test, along with basic demographic, socioeconomic and geographic information.

A total of 6,378 participants provided data on perceived access to COVID-19 testing. In adjusted analyses, we found higher income and possession of health insurance to be associated with perceived ability to access Coronavirus testing. Geographically, perceived access was highest (68%) in East South Central division and lowest (39%) in West North Central. Disparities in health insurance coverage did not directly correspond to disparities in perceived access to COVID-19 testing.

Sex, geographic location, income, and insurance status were associated with perceived access to COVID-19 testing; interventions aimed at improving either access or awareness of measures taken to improve access are warranted. These findings from the pandemic's early months shed light on the importance of disaggregating perceived and true access to screening during such crises.

Sex, geographic location, income, and insurance status were associated with perceived access to COVID-19 testing; interventions aimed at improving either access or awareness of measures taken to improve access are warranted. These findings from the pandemic's early months shed light on the importance of disaggregating perceived and true access to screening during such crises.