Bilingual Perspectives of Functional Dyspepsia Management in People from Underserved Areas.

Introduction: Disorders of gut-brain interaction (DGBIs), like functional dyspepsia (FD), are prevalent and challenging conditions. In other gastrointestinal (GI) disorders, individuals from underserved areas (UAs) have difficulty accessing care. Little is known about UA FD patient perspectives of their care, especially in those with limited English proficiency (LEP).

Evaluation of Intestinal Permeability Using Serum Biomarkers in Learning Early About Peanut Allergy Trial.

Background: Intestinal barrier dysfunction may lead to a break in tolerance and development of food allergy (FA). There is contradictory evidence on whether intestinal permeability (IP) is altered in IgE-mediated FA. Thus, we sought to determine whether IP differed between children with eczema who did (FA group) or did not (atopic controls, ACs) develop FA and whether peanut sensitization, allergy, and early introduction impacted IP using serum biomarkers zonulin, soluble CD14, and Intestinal Fatty Acid Binding Protein among randomly selected participants enrolled in the Learning Early About Peanut allergy trial.

Prevalence and characteristics of group standardized letters of evaluation in emergency medicine: A cross-sectional observational study.

Background: The standardized letter of evaluation (SLOE) for emergency medicine (EM) is a well-established tool for residency selection. While previous work characterizes the utility and outcomes related to SLOE use, less is known about SLOE authorship patterns and trends.

Objective: The objective was to measure the prevalence of group SLOEs in EM over time, characterize the role groups represented in group SLOEs, and compare the rating practices of groups of authors versus single authors.

Sex-specific Associations of Gene Expression with Alzheimer's Disease Neuropathology and Ante-mortem Cognitive Performance.

The biological mechanisms underlying women's increased Alzheimer's disease (AD) prevalence remain undefined. Previous case/control studies have identified sex-biased molecular pathways, but sex-specific relationships between gene expression and AD endophenotypes, particularly sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated sex-specific associations between gene expression and post-mortem β-amyloid and tau as well as antemortem longitudinal cognition.

Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors.

Introduction: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown.

Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry).

Results: We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis.

From Text to Translation: Using Language Models to Prioritize Variants for Clinical Review.

Despite rapid advances in genomic sequencing, most rare genetic variants remain insufficiently characterized for clinical use, limiting the potential of personalized medicine. When classifying whether a variant is pathogenic, clinical labs adhere to diagnostic guidelines that comprehensively evaluate many forms of evidence including case data, computational predictions, and functional screening. While a substantial amount of clinical evidence has been developed for these variants, the majority cannot be definitively classified as 'pathogenic' or 'benign', and thus persist as 'Variants of Uncertain Significance' (VUS).

Transcriptome-wide outlier approach identifies individuals with minor spliceopathies.

RNA-sequencing has improved the diagnostic yield of individuals with rare diseases. Current analyses predominantly focus on identifying outliers in single genes that can be attributed to cis-acting variants within the gene locus. This approach overlooks causal variants with trans-acting effects on splicing transcriptome-wide, such as variants impacting spliceosome function.

A semi-empirical Bayes approach for calibrating weak instrumental bias in sex-specific Mendelian randomization studies.

Strong sex differences exist in sleep phenotypes and also cardiovascular diseases (CVDs). However, sex-specific causal effects of sleep phenotypes on CVD-related outcomes have not been thoroughly examined. Mendelian randomization (MR) analysis is a useful approach for estimating the causal effect of a risk factor on an outcome of interest when interventional studies are not available.

Academic Pursuits in Teleradiology: At the Crossroads of Technology, Radiology, and Implementation.

Teleradiology is an essential part of modern radiology practice. It enhances efficiencies in image interpretation by improving availability and accessibility of radiologists. Being at the crossroads of technology, diagnostic radiology, and complex workflows, teleradiology provides abundant opportunities for academic engagement and innovative workflows, and allows for research and publication encompassing these multiple facets.

Uncertainty estimation in diagnosis generation from large language models: next-word probability is not pre-test probability.

Objective: To evaluate large language models (LLMs) for pre-test diagnostic probability estimation and compare their uncertainty estimation performance with a traditional machine learning classifier.

Materials And Methods: We assessed 2 instruction-tuned LLMs, Mistral-7B-Instruct and Llama3-70B-chat-hf, on predicting binary outcomes for Sepsis, Arrhythmia, and Congestive Heart Failure (CHF) using electronic health record (EHR) data from 660 patients. Three uncertainty estimation methods-Verbalized Confidence, Token Logits, and LLM Embedding+XGB-were compared against an eXtreme Gradient Boosting (XGB) classifier trained on raw EHR data.

A standards-based application for improving platelet transfusion workflow.

Objective: Thrombocytopenia is a common complication of hematopoietic stem-cell transplantation (HSCT), though many patients will become immune refractory to platelet transfusions over time. We built and evaluated an electronic health record (EHR)-integrated, standards-based application that enables blood-bank clinicians to match platelet inventory with patients using data previously not available at the point-of-care, like human leukocyte antigen (HLA) data for donors and recipients.

Materials And Methods: The web-based application launches as an EHR-embedded application or as a standalone application.

SGLT2i and Primary Prevention of Cancer Therapy-Related Cardiac Dysfunction in Patients With Diabetes.

Background: Specific cancer treatments can lead to cancer therapy-related cardiac dysfunction (CTRCD). Sodium glucose cotransporter-2 inhibitors (SGLT2is) can potentially prevent these cardiotoxic effects.

Objectives: This study sought to determine whether SGLT2i use is associated with a lower incidence of CTRCD in patients with type 2 diabetes mellitus (T2DM) and cancer, exposed to potentially cardiotoxic antineoplastic agents, and without a prior documented history of cardiomyopathy or heart failure.

Associations of fire smoke and other pollutants with incident rheumatoid arthritis and rheumatoid arthritis-associated interstitial lung disease.

Objective: Determine whether pollutants such as fire smoke-related particulate matter smaller than 2.5 microns (PM) are associated with incident rheumatoid arthritis (RA) and RA-associated interstitial lung disease (RA-ILD).

Methods: This case-control study used Veterans Affairs data 10/1/2009-12/31/2018.

Environmental Risk Factors for Systemic Lupus Erythematosus through the Lens of Social Determinants of Health.

Systemic lupus erythematosus (SLE) is a serious multisystem autoimmune disease, marked by alarming sociodemographic inequities. In the U.S.

Patient-Centric Approach for the Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease in Older People.

Purpose Of Review: The purpose of this review is to outline considerations for treating older adults with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) as it relates to infection, comorbidities, cancer, and quality of life.

Recent Findings: The recent 2023 American College of Rheumatology/American College of Chest Physicians guideline conditionally recommended specific disease-modifying antirheumatic drugs (DMARDs), antifibrotics, and short-term glucocorticoids to treat RA-ILD. Since RA-ILD often affects older adults, we contextualize these pharmacologic options related to infection, gastrointestinal (GI) effects, cancer, cardiovascular disease, and quality of life.

Frailty index predicts adverse short- and long-term outcomes in older adults with rib fractures.

Background: Older adults with rib fractures pose an increasing clinical and financial burden on healthcare. Identifying and addressing the increased risk of adverse outcomes has been a key objective in geriatric co-management of surgical patients. The Comprehensive Geriatric Assessment-based Frailty Index (FI-CGA) is a useful predictor of complications and mortality in older adults, but its value in rib fracture management remains unclear.

Update on Mast Cell Biology.

Mast cells (MCs) are heterogeneous tissue-resident effector cells thought to play central roles in allergic inflammatory disease, yet the degree of heterogeneity and nature of these roles has remained elusive. In recent years, advances in tissue culture systems, pre-clinical mouse models, and the continued spread of single-cell RNA sequencing has greatly advanced our understanding of MC phenotypes in health and disease. These approaches have identified novel interactions of MC subsets with immune cells, neurons, and tissue structural cells, changing our understanding of how MCs both drive and help resolve tissue inflammation, reshape tissue microenvironments, and influence host behavior.

Prevalence and impact of parental co-morbid anxiety and depression during the first 2 years postpartum in China.

Background: Parental postpartum co-morbid anxiety and depression negatively impact personal well-being, family dynamics, and child developmental outcomes. This study investigates the prevalence of co-morbid anxiety and depression in both mothers and fathers during the first 2 years postpartum in China, and to explore its associations with parental family support, maternal health-related quality of life (HRQoL), and child development.

Methods: This cross-sectional study was conducted in China, involving families with children aged 0-2 years who participated in community child health care.

Baseline predictors of cross-sectional and longitudinal performance on the symbol digit modalities test in individuals with multiple sclerosis.

Background: Cognitive impairment occurs frequently in persons with multiple sclerosis (PwMS) at some point in the course of the disease. However, not all PwMS develop cognitive difficulties suggesting a role for important moderating factors. We examined baseline predictors of cross-sectional and longitudinal change in cognitive performance in PwMS.

Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials.

Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.

Unsupervised deep learning of electrocardiograms enables scalable human disease profiling.

The 12-lead electrocardiogram (ECG) is inexpensive and widely available. Whether conditions across the human disease landscape can be detected using the ECG is unclear. We developed a deep learning denoising autoencoder and systematically evaluated associations between ECG encodings and ~1,600 Phecode-based diseases in three datasets separate from model development, and meta-analyzed the results.

Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.