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).

Inheritance of Imaging Parameters of Arrhythmic Risk in Mitral Valve Prolapse: A Pedigree Study.

Background: A subset of patients with mitral valve prolapse (MVP), a highly heritable condition, experience sudden cardiac arrest (SCA) or sudden cardiac death (SCD). However, the inheritance of phenotypic imaging features of arrhythmic MVP remains unknown.

Methods: We recruited 23 MVP probands, including 9 with SCA/SCD and 14 with frequent/complex ventricular ectopy.

Patient and wound factors associated with WOUND-Q scales measuring health-related quality of life: An international cross-sectional study.

The WOUND-Q is a patient-reported outcome measure for individuals with any type of chronic wound. This study aimed to identify patient and wound factors associated with the four WOUND-Q health-related quality of life (HRQL) scales: Life impact, Psychological, Sleep, and Social. Adults with a chronic wound were recruited internationally through clinical settings between August 2018 and May 2020, and through an online platform (i.

Dissemination of Decision Aids about Hip and Knee Osteoarthritis to Spanish-Speaking Adults through Social Media.

Background: Older adults and Hispanic individuals are increasingly turning to social media platforms to access health-related information. The purpose of this project was to evaluate a social media campaign to disseminate information from decision aids (DAs) on hip and knee osteoarthritis to Spanish-speaking adults.

Methods: A social media marketing team helped create an 8-mo campaign posted across 3 social media platforms to promote visits to a Web site offering free multilingual DAs for treatment of hip or knee osteoarthritis.

Diagnostic challenges of long COVID in children: a survey of pediatric health care providers' preferences and practices.

Introduction: Given the challenges in diagnosing children with long COVID, we sought to explore diagnostic practices and preferences among clinicians.

Methods: A ten-question survey assessed pediatric providers' clinical decision making for identifying and evaluating long COVID in children. Of the 120 survey respondents, 84 (70%) were physicians, 31 (26%) nurse practitioners, and 5 (4%) physician assistants.

Tacrolimus to belatacept conversion in proteinuric kidney transplant recipients.

Background: Proteinuria is associated with worse allograft outcomes in kidney transplant recipients (KTRs) and treatment strategies are limited. We examined the outcomes of calcineurin inhibitor (CNI) to belatacept conversion in proteinuric KTRs.

Methods: In a pilot phase II single-arm multicenter prospective trial, we recruited adult KTRs >6 months post-kidney transplantation with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.

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.

Designing for medication adherence in inflammatory bowel disease: multi-disciplinary approaches for self-administrable biotherapeutics.

Biotherapeutics are among the therapeutics that have revolutionized standard inflammatory bowel disease (IBD) treatment, which was previously limited to mesalamine, 5-aminosalicylic acid, corticosteroids, and classical immunosuppressants. Self-administrable biotherapeutics for IBD would enable home-based treatment and reduce the burden on medical infrastructure. Self-administration is made possible through subcutaneous injectable, oral, and rectal dosage forms.

Isoform-selective and non-selective rho-kinase inhibitors do not affect collagenase-induced intracerebral hemorrhage outcomes in mice: Influence of sex and circadian cycle.

Rho-associated protein kinase (ROCK) inhibitors are therapeutic candidates in ischemic stroke and subarachnoid hemorrhage. However, their efficacy in intracerebral hemorrhage (ICH) is unknown. Here, we tested the efficacy of fasudil (10 mg/kg), an isoform-nonselective ROCK inhibitor, and NRL-1049 (10 mg/kg), a novel inhibitor with 43-fold higher selectivity for ROCK2 isoform compared with ROCK1, in a collagenase-induced ICH model in mice.

Genetics of intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage(ICH) represents a life-threatening form of stroke, marked by its impact on survival and quality of life. ICH can be categorized from monogenic disorders linked to causal germline variants in ICH-related genes to complex sporadic cases, highlighting the interaction among lifestyle factors, environmental influences, and genetic components in determining risk. Among sporadic ICH, the influence of these factors varies across ICH subtypes, evidenced by heritability rates of up to 73% for lobar ICH versus 34% for non-lobar ICH.

Glucagon-like peptide-1 receptor agonists and upper endoscopy: a real-world experience.

Objective: Increased use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has raised safety concerns during endoscopy due to their mechanism of delaying gastric emptying. This study aims to evaluate the impact of GLP-1RAs on technical success and safety of esophagogastroduodenoscopy (EGD).

Methods: This was a retrospective study of bariatric patients who underwent EGD between January 2022 and December 2023.

Prevalence of Disordered Eating Behaviors Among Sexual and Gender Minority Youth Varies at the Intersection of Gender Identity and Race/Ethnicity.

Objective: Prior work has documented inequities in disordered eating behavior (DEB) prevalence across gender identity, race, and ethnicity, yet has often ignored the fact that individuals belong to multiple social groups simultaneously. The present study assessed DEB inequities at the intersection of gender identity and race/ethnicity.

Method: The sample included n = 10,287 adolescents (68% gender-diverse, 33% belonging to marginalized racial/ethnic groups).

Electrocardiographic Changes in Pregnant Patients With Congenital Heart Disease For the STORCC Investigators.

Background: Electrocardiograms (EKGs) are routinely performed in pregnant patients with pre-existing cardiovascular disease. However, in pregnant patients with congenital heart disease (CHD), EKG changes during gestation have not been explored.

Methods: We performed a retrospective study of pregnant patients with CHD enrolled in the STORCC initiative.

Promoting Physical Activity in People With Parkinson's Disease Through a Smartphone App: A Pilot Study.

Background And Purpose: Physical activity has beneficial symptomatic effects for people with Parkinson's disease (PD), but increasing-and sustaining-a physically active lifestyle remains challenging. We investigated the feasibility (ability to increase step counts) and usability of a behavioral intervention using a motivational smartphone application to remotely increase physical activity in PD.

Methods: We performed a 4-week, double-blind pilot trial.

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.

Substance use recovery needs among college students seeking recovery services: a thematic qualitative analysis.

Background: College students who are in recovery from substance use disorders face challenges related to abstaining from substance use, finding supportive social networks, and achieving their academic goals. These students may therefore seek out various recovery supports at their institutions to meet their needs and goals.

Methods: This study analyzed previously collected data to explore themes related to students' experiences of recovery, including their recovery needs and challenges while also attending college.

TiMON: a real-time integrated monitor for improving the placement and wear of emergency tourniquets.

Background: The use of emergency tourniquets among military personnel has helped to dramatically reduce battlefield deaths and has recently gained popularity in the civilian sector. Yet, even well-trained individuals can find it difficult to assess proper tourniquet application. Emergency tourniquets are typically deemed sufficiently tightened through cursory visual confirmation or pulse assessment.

Beyond symptom reduction: Veterans' goals for posttraumatic stress disorder treatment.

Despite a varied selection of available trauma-focused evidence-based psychotherapies (TF-EBPs) for posttraumatic stress disorder (PTSD), few veterans receive a full course of an evidence-based treatment. A better understanding of and alignment with veterans' PTSD treatment goals could be one way to improve treatment engagement and adherence, consistent with veteran-oriented care within the U.S.

Aberrant splicing in Huntington's disease accompanies disrupted TDP-43 activity and altered m6A RNA modification.

Huntington's disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.

Co-occurring Psychopathology in Children With and Without Autism Spectrum Disorder (ASD): Differences by Sex in the ECHO Cohorts.

Purpose: Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems.

Methods:  Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.

Artificial intelligence for hemodynamic monitoring with a wearable electrocardiogram monitor.

Background: The ability to non-invasively measure left atrial pressure would facilitate the identification of patients at risk of pulmonary congestion and guide proactive heart failure care. Wearable cardiac monitors, which record single-lead electrocardiogram data, provide information that can be leveraged to infer left atrial pressures.

Methods: We developed a deep neural network using single-lead electrocardiogram data to determine when the left atrial pressure is elevated.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

The galactokinase enzyme of yeast senses metabolic flux to stabilize galactose pathway regulation.

Nutrient sensors allow cells to adapt their metabolisms to match nutrient availability by regulating metabolic pathway expression. Many such sensors are cytosolic receptors that measure intracellular nutrient concentrations. One might expect that inducing the metabolic pathway that degrades a nutrient would reduce intracellular nutrient levels, destabilizing induction.

MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial.

Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.

Burden of coronary artery calcification in ANCA-associated vasculitis.

Background: Cardiovascular disease (CVD) is a leading cause of death in ANCA-associated vasculitis (AAV). Screening and primary cardiovascular prevention may improve outcomes.

Methods: We identified patients in the 2002-2019 Mass General Brigham AAV cohort with thoracic CT scans obtained for other clinical purposes.