Improving the Health and Environmental Health Literacy of Professionals: Evaluating the Effect of a Virtual Intervention on Phthalate Environmental Health Literacy.

The American College of Obstetricians and Gynecologists provided updated guidance in 2021, recommending that reproductive health professionals should include discussion of environmental exposures with their patients. However, environmental health is seldom included in medical training, with endocrine-disrupting chemicals, such as phthalates-linked to adverse pregnancy outcomes-being among the least discussed. We developed a one-hour virtual educational intervention to train reproductive health professionals on the routes of phthalate exposure, potential associated health impacts, and suggestions on how to discuss exposure reduction with patients.

Pneumonia in Patients with Chronic Lymphocytic Leukemia Treated with Venetoclax-Based Regimens: A Real-World Analysis of the Polish Adult Leukemia Group (PALG).

Background/objectives: Patients with chronic lymphocytic leukemia (CLL) are susceptible to infections that can affect their clinical outcomes.

Aims: The aims of this study were to assess the following: (1) the incidence of pneumonia in CLL patients treated with venetoclax-based regimens in a real-world setting, (2) the risk factors for event-free survival (EFS), and (3) overall survival (OS).

Methods: This multicenter study included 322 patients from eight centers.

Neurodevelopmental outcomes in children exposed in utero to dolutegravir- or efavirenz-based ART.

Objective: To examine the impact of in utero exposure to dolutegravir (DTG)- or efavirenz (EFV)-based antiretroviral treatment (ART) on child neurodevelopmental (ND) outcomes.

Design: Prospective cohort design, enrolling 3 cohorts of 2-year-olds: children HIV-negative born to mothers with HIV (CHEU) receiving either DTG-based or EFV-based 3-drug ART during pregnancy, and children born to mothers without HIV (CHUU).

Methods: Primary child ND outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and compared between cohorts using generalized estimating equation models adjusted for confounders.

Refinement of a Published Gene-Physical Activity Interaction Impacting HDL-Cholesterol: Role of Sex and Lipoprotein Subfractions.

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).

High prevalence of reverse transcriptase inhibitors associated resistance mutations among people living with HIV on dolutegravir-based antiretroviral therapy in Francistown, Botswana.

Objectives: We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.

Methods: The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana's national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200-999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL).

Deep learning-based prediction of chemical accumulation in a pathogenic mycobacterium.

Drugs must accumulate at their target site to be effective, and inadequate uptake of drugs is a substantial barrier to the design of potent therapies. This is particularly true in the development of antibiotics, as bacteria possess numerous barriers to prevent chemical uptake. Designing compounds that circumvent bacterial barriers and accumulate to high levels in cells could dramatically improve the success rate of antibiotic candidates.

FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses.

Exposure to saturated fatty acids (SFAs), such as palmitic acid, can lead to cellular metabolic dysfunction known as lipotoxicity. Although canonical adaptive metabolic processes like lipid storage or desaturation are known cellular responses to saturated fat exposure, the link between SFA metabolism and organellar biology remains an area of active inquiry. We performed a genome-wide CRISPR knockout screen in human epithelial cells to identify modulators of SFA toxicity.

Inflammatory Monocytes Increase Prior to Detectable HIV-1 Rebound Viremia.

The persistence of HIV-1 proviruses in latently infected cells allows viremia to resume upon treatment cessation. To characterize the resulting immune response, we compare plasma proteomics and single-cell transcriptomics of peripheral blood mononuclear cells (PBMCs) before, during, and after detectable plasma viremia. We observe unique transcriptional signatures prior to viral rebound including a significant increase in CD16 monocytes with increased anti-viral gene expression.

Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors.

Background: Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.

Methods: Including 1,236 CRC tumors from three observational studies, we conducted T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay.

The blood metabolome of cognitive function and brain health in middle-aged adults - influences of genes, gut microbiome, and exposome.

Increasing evidence suggests the involvement of metabolic alterations in neurological disorders, including Alzheimer's disease (AD), and highlights the significance of the peripheral metabolome, influenced by genetic factors and modifiable environmental exposures, for brain health. In this study, we examined 1,387 metabolites in plasma samples from 1,082 dementia-free middle-aged participants of the population-based Rotterdam Study. We assessed the relation of metabolites with general cognition (G-factor) and magnetic resonance imaging (MRI) markers using linear regression and estimated the variance of these metabolites explained by genes, gut microbiome, lifestyle factors, common clinical comorbidities, and medication using gradient boosting decision tree analysis.

Environmental Mixtures Analysis (E-MIX) Workflow and Methods Repository.

Human exposure to complex, changing, and variably correlated mixtures of environmental chemicals has presented analytical challenges to epidemiologists and human health researchers. There have been a wide variety of recent advances in statistical methods for analyzing mixtures data, with most of these methods having open-source software for implementation. However, there is no one-size-fits-all method for analyzing mixtures data given the considerable heterogeneity in scientific focus and study design.

The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup.

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup.

Prevalence of chlamydia, gonorrhoea, and trichomoniasis among male and female general populations in sub-Saharan Africa from 2000-2024: A systematic review and meta-regression analysis.

Background: Sub-Saharan Africa (SSA) has the highest sexually transmitted infection (STI) prevalence globally, but information about trends and geographic variation is limited by sparse aetiologic studies, particularly among men. This systematic review assessed chlamydia, gonorrhoea, and trichomoniasis prevalence by sex, sub-region, and year, and estimated male-to-female prevalence ratios for SSA.

Methods: We searched Embase, MEDLINE, Global Health, PubMed, and African Index Medicus for studies measuring STI prevalence among general populations from January 1, 2000, to September 17, 2024.

Factors and Outcomes Associated With Using Scratch-Cooked, Organic, and Locally Grown Foods in School Meals in California.

Background: Incorporating scratch-cooked, organic, and locally grown foods into school meal programs can enhance meal quality and support local food systems.

Methods: 430 California school food authorities were surveyed to (1) evaluate their use of scratch-cooked, organic, and locally grown foods in their programs; (2) identify demographic and operational characteristics related to this use; and (3) analyze the relationship between serving more of these foods and perceived barriers to student meal participation. Poisson and logistic regression models, adjusted for SFAs' demographic characteristics, were used.

Implementation research logic model in the design and execution of eHealth innovations for maternal and newborn healthcare in Ethiopia.

Background: The use of eHealth innovations is becoming increasingly important in improving health outcomes, especially for maternal and newborn health. However, planning and executing these innovations can be challenging due to their complex nature. To provide guidance and clarity on implementation approaches, researchers need to use implementation research (IR) tools.

The additive effect of the stress hyperglycemia ratio on type 2 diabetes: a population-based cohort study.

Background: The stress hyperglycemia ratio (SHR) has recently gained attention as a marker for acute hyperglycemia, which has been linked to adverse clinical outcomes. However, its independent role in the development of type 2 diabetes (T2D) remains understudied. This cohort study aimed to assess the association between SHR and the incidence of T2D.

High organofluorine concentrations in municipal wastewater affect downstream drinking water supplies for millions of Americans.

Wastewater receives per- and polyfluoroalkyl substances (PFAS) from diverse consumer and industrial sources, and discharges are known to be a concern for drinking water quality. The PFAS family includes thousands of potential chemical structures containing organofluorine moieties. Exposures to a few well-studied PFAS, mainly perfluoroalkyl acids (PFAA), have been associated with increased risk of many adverse health outcomes, prompting federal drinking water regulations for six compounds in 2024.

Human mobility and malaria risk in peri-urban and rural communities in the Peruvian Amazon.

Background: While the global burden of malaria cases has decreased over the last two decades, the disease remains a major international threat, even on the rise in many regions. More than 85% of Peruvian malaria cases are in the Amazonian region of Loreto. Internal mobility primarily related to occupation is thought to be primarily responsible for maintaining endemicity and introducing and reintroducing malaria parasites into areas of anophelism, a challenge for malaria eradication.

Evaluating hypothetical prevention strategies for internalizing symptoms in the general population and at-risk children.

Objective: Specific modifiable factors (e.g., screen time [ST], sleep duration, physical activity, or social connections) are targets for reducing depression risk in adults.

Invited Commentary: Why use methods that require proportional hazards?

We recently questioned the utility of testing for proportional hazards in survival analysis. Here we expand on why the proportional hazards assumption is both implausible and unnecessary in most medical studies, particularly in randomized trials. We conclude that using survival analysis methods that do not rely on proportional hazards is typically the preferred course of action.