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.

SUMO-mediated regulation of H3K4me3 reader SET-26 controls germline development in C. elegans.

Sumoylation is a posttranslational modification essential for multiple cellular functions in eukaryotes. ULP-2 is a conserved SUMO protease required for embryonic development in Caenorhabditis elegans. Here, we revealed that ULP-2 controls germline development by regulating the PHD-SET domain protein, SET-26.

Alterations in Response Switching in Parkinson's Disease: New Insights Into Cueing.

Switching, a critical executive function, can manifest as task switching (TS) or response switching (RS). Although TS impairments in Parkinson's disease (PD) are well-studied, RS, especially in contexts requiring adaptive behavior to external or internal cues, is less explored. This study evaluated the impact of PD on RS under exogenous and endogenous cueing.

US Tobacco 21 Policies and Potential Mortality Reductions by State.

Importance: Research shows that Tobacco 21 (T21) policies with a minimum legal access age for tobacco products of 21 years reduce smoking, yet their impact varies across US states due to differences in smoking behaviors, mortality rates, and policy coverage.

Objective: To quantify potential reductions in smoking-attributable mortality associated with Tobacco 21 policies for each of the 50 states and Washington, DC.

Design, Setting, And Participants: The Cancer Intervention Surveillance and Modeling Network (CISNET) Tobacco Control Policy Model of smoking was used with detailed state-specific data on smoking initiation, smoking cessation and mortality rates as they vary by age, gender, and birth cohort for 50 US states and the District of Columbia.

An update of a systematic review and meta-analyses exploring flavours in intervention studies of e-cigarettes for smoking cessation.

Aims: To determine patterns of e-cigarette flavour use (sweet, tobacco, menthol/mint) in interventional studies of e-cigarettes for stopping smoking, and to estimate associations between flavours and smoking/vaping outcomes.

Methods: Update of secondary data analyses, including meta-analyses subgrouped by flavour provision and narrative syntheses, incorporating data from January 2004 to February 2024. Eligible studies were identified from a Cochrane review.

Galactocerebroside Lipid Nanotubes, a Model Membrane System for Studying Membrane-Associated Proteins on a Molecular Scale.

Galactocerebroside lipid nanotubes are membrane-mimicking systems for studying the function and structure of proteins involved in membrane shape remodeling, such as in intracellular trafficking, cell division, and migration or involved in the formation of membrane contact sites. They exhibit a constant and small diameter of 30 nm and a length of up to 2 μm. They can be functionalized with lipid ligands, providing a large binding surface for protein without membrane shape remodeling.

Exploring Gender Differences in Receipt of the 5As for Smoking Cessation for Recently-Diagnosed Cancer Patients (ECOG-ACRIN EAQ171CD).

Introduction: Smoking cessation is important for men and women diagnosed with cancer. Oncology clinicians should encourage all patients to quit and offer resources to help them do so, following the 5As framework (Ask, Advise, Assess, Assist, and Arrange follow-up).

Method: This study tests gender differences in self-reported receipt of the 5As by an oncology provider among 306 recently-diagnosed male and female cancer patients.

Clinical-Demographic Profile, Prognostic Factors and Outcomes in Classic Follicular Lymphoma Stratified by Staging and Tumor Burden: Real-World Evidence from a Large Latin American Cohort.

Clinical staging (CS) and tumor burden (TB) play a significant role in FL prognosis and direct its up-front therapy. The aim of this study is to report prognostic factors and clinical outcomes in newly-diagnosed FL patients stratified according to CS and TB in early-stage (ES) disease, advanced-stage with low tumor burden (AS-LTB) and advanced-stage with high tumor burden (AS-HTB). Two hundred fourteen patients with FL grades 1-3A had baseline clinical characteristics and outcomes assessed.

Epigenome-wide Association Analysis of Mitochondrial Heteroplasmy Provides Insight into Molecular Mechanisms of Disease.

The relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA (nDNA) methylation (CpGs) remains to be studied. We conducted an epigenome-wide association analysis of heteroplasmy burden scores across 10,986 participants (mean age 77, 63% women, and 54% non-White races/ethnicities) from seven population-based observational cohorts. We identified 412 CpGs (FDR p < 0.

Integrating Whole Genome and Transcriptome Sequencing to Characterize the Genetic Architecture of Isoform Variation and its Implications for Health and Disease.

We created a comprehensive whole blood splice variation quantitative trait locus (sQTL) resource by analyzing isoform expression ratio (isoform-to-gene) in Framingham Heart Study (FHS) participants (discovery: n=2,622; validation: n=1,094) with whole genome (WGS) and transcriptome sequencing (RNA-seq) data. External replication was conducted using WGS and RNA-seq from the Jackson Heart Study (JHS, n=1,020). We identified over 3.

The impact of tobacco smoking and smoking cessation on lung cancer and stroke incidence among people with HIV on antiretroviral therapy in South Africa: a simulation modeling study.

Introduction: With declining HIV-related mortality, over 20% of people with HIV (PWH) in South Africa are now over age 50 years, and tobacco-related non-communicable disease burden is increasing. We quantified the impact of smoking and smoking cessation on lung cancer and stroke incidence among PWH in South Africa.

Methods: Using a microsimulation model, we simulated 18 cohorts of initially virologically suppressed PWH over their lifetime, categorised by sex, initial age (35 years/45 years/55 years) and smoking status (current/former/never).

Bimodal aphasia and dysgraphia: Phonological output buffer aphasia and orthographic output buffer dysgraphia in spoken and sign language.

We report a case of crossmodal bilingual aphasia-aphasia in two modalities, spoken and sign language-and dysgraphia in both writing and fingerspelling. The patient, Sunny, was a 42 year-old woman after a left temporo-parietal stroke, a speaker of Hebrew, Romanian, and English and an adult learner, daily user of Israeli Sign language (ISL). We assessed Sunny's spoken and sign languages using a comprehensive test battery of naming, reading, and repetition tasks, and also analysed her spontaneous-speech and sign.

Associations of plasma extracellular microRNAs with new-onset breast cancer in the Framingham heart study.

Breast cancer is the second leading cause of cancer deaths among women. Multiple microRNAs (miRNAs) have been reported to be associated with breast cancer progression or metastasis. The purpose of the current study was to identify plasma extracellular miRNAs associated with incident breast cancer.

Individual Factors That Affect Laypeople's Understanding of Definitions of Medical Jargon.

Objective: Patients have difficulty understanding medical jargon in electronic health record (EHR) notes. Lay definitions can improve patient comprehension, which is the goal of the NoteAid project. We assess whether the NoteAid definitions are understandable to laypeople and whether understandability differs with respect to layperson characteristics.

"Room of Horrors": A Proof-of-Concept Simulation Model for Error Reduction Training in the Emergency Department.

Objective: This pilot study aimed to assess the effectiveness of a "room of horrors" (RoH) simulation in identifying patient safety threats in a pediatric emergency department (PED) and to evaluate health care workers' (HCWs') perceptions of the experience.

Methods: We developed an RoH simulation featuring 25 potential safety hazards derived from actual PED incidents and "never events." The teams of physicians and nurses who participated in the simulation identified as many hazards as they could within a 10-minute window followed by a debriefing session during which errors were corrected and missed hazards were pointed out.

Targeting CD4+ T cell Exhaustion to Improve Future Immunotherapy Strategies.

As of late, reinvigoration of exhausted T cells as a form of immunotherapy against cancer has been a promising strategy. However, inconsistent results highlight the uncertainties in the current understanding of cellular exhaustion and the need for research and better treatment design. In our previous work, we utilized mathematical modeling and analysis to recapitulate and complement the biological understanding of exhaustion in response to growing tumors.

Latent transition analysis of use frequencies for multiple nicotine and tobacco products among US adults.

Background: Given the many nicotine and tobacco products in use, studies of the interdependence of use patterns and transitions are needed.

Methods: Using Waves 1-4 of the PATH Study, we analyzed latent transitions among adults who ever regularly used nicotine or tobacco products at Wave 1 to identify latent use states (n = 12,358) and estimated one-wave transition probabilities. Multinomial logistic regression identified demographic factors associated with transitions.

DNA Methylation Signatures of Cardiovascular Health Provide Insights into Diseases.

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 (LE8) score to reflect CVH in five cohorts with diverse ancestry backgrounds. Epigenome-wide association studies (EWAS) for LE8 score were conducted, followed by bioinformatic analyses.

Plasma Protein Biomarkers of Spirometry Measures of Impaired Lung Function.

Background: Impaired pulmonary function carries significant risks for lung, cardiovascular, and metabolic disorders.

Research Question: Can circulating protein biomarkers of pulmonary function provide insight into the pathophysiologic features of lung function impairment and links to comorbidities?.

Study Design And Methods: We analyzed plasma levels of 2,922 proteins in 32,493 UK Biobank participants (53% female; mean [SD] age, 57 [8] years) to investigate their associations with spirometry measures of lung function (FEV, FVC, FEV to FVC ratio), and with obstructive (n = 4,713) and restrictive (n = 3,886) spirometry patterns.