Evaluating the impact of modeling choices on the performance of integrated genetic and clinical models.

Purpose: The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results. We performed multiple modeling experiments integrating clinical and demographic data from electronic health records (EHR) with genetic data to understand which decisions may affect performance.

Racial and Ethnic Differences in Long-Term Outcomes among Individuals with Opioid Use Disorder at Opioid Treatment Programs.

Objectives: Racial and ethnic differences in long-term outcomes associated with medications for opioid use disorder (MOUD) are poorly understood.

Methods: The present analyses were based on 751 participants with opioid use disorder (OUD) who were initially recruited from opioid treatment programs located in California, Connecticut, Oregon, Pennsylvania, and Washington and participated in a randomized controlled trial and at least one follow-up interview. 9.

Association between stress hyperglycemia ratio and mortality in patients with heart failure complicated by sepsis.

Individuals afflicted with heart failure complicated by sepsis often experience a surge in blood glucose levels, a phenomenon known as stress hyperglycemia. However, the correlation between this condition and overall mortality remains unclear. 869 individuals with heart failure complicated by sepsis were identified from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and categorized into five cohorts based on their stress hyperglycemia ratio (SHR).

Development and validation of a mortality predictive model for ICU patients with primary pulmonary hypertension.

There is a lack of an effective prognostic model for predicting outcomes in patients with primary pulmonary hypertension (PPH). A retrospective analysis was conducted on PPH patients from MIMIC and eICU databases. A predictive model was developed to assess mortality risk.

Concordance and test-retest consistency of sleep biomarker-based neurodegenerative disorder profiling.

Biomarkers that aid in early detection of neurodegeneration are needed to enable early symptomatic treatment and enable identification of people who may benefit from neuroprotective interventions. Increasing evidence suggests that sleep biomarkers may be useful, given the bi-directional relationship between sleep and neurodegeneration and the prominence of sleep disturbances and altered sleep architectural characteristics in several neurodegenerative disorders. This study aimed to demonstrate that sleep can accurately characterize specific neurodegenerative disorders (NDD).

Cellular senescence offers distinct immunological vulnerabilities in cancer.

Chronic damage following oncogene induction or cancer therapy can produce cellular senescence. Senescent cells not only exit the cell cycle but communicate damage signals to their environment that can trigger immune responses. Recent work has revealed that senescent tumor cells are highly immunogenic, leading to new ways to activate antitumor immunosurveillance and potentiate T cell-directed immunotherapies.

Comparative survival of sleeve gastrectomy versus Roux-en-Y gastric bypass in adults with obesity: a systematic review and meta-analysis.

Background: The difference in survival between sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) remains controversial.

Objective: To investigate the comparative survival difference between SG and RYGB in adults with morbid obesity.

Setting: A meta-analysis.

Brain phosphoproteomic analysis identifies diabetes-related substrates in Alzheimer's disease pathology in older adults.

Introduction: Type 2 diabetes increases the risk of Alzheimer's disease (AD) dementia. Insulin signaling dysfunction exacerbates tau protein phosphorylation, a hallmark of AD pathology. However, the comprehensive impact of diabetes on patterns of AD-related phosphoprotein in the human brain remains underexplored.

The role of neuropsychological assessment in the evaluation of patients with cognitive-behavioral change due to suspected Alzheimer's disease and other causes of cognitive impairment and dementia.

The Alzheimer's Association convened a Diagnostic Evaluation, Testing, Counseling and Disclosure Clinical Practice Guideline workgroup to help combat the major global health challenges surrounding the timely detection, accurate diagnosis, and appropriate disclosure of mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD) or other diseases that cause these types of cognitive-behavioral disorders. The newly published clinical practice guidelines are proposed as a structured approach to evaluation. The purpose of the present article is to provide a clinical perspective on the use of neuropsychology within the new framework and practice guidelines outlined under the Diagnostic Evaluation, Testing, Counseling and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD) recommendations for primary care and specialty care.

Introduction to the DETeCD-ADRD special issue.

This special issue contains multiple articles related to the DETeCD-ADRD guideline.

Fluid overload trajectories and mortality in hemodialysis patients.

Background: Fluid overload remains critical in managing patients with end-stage kidney disease. However, there is limited empirical understanding of fluid overload's impact on mortality. This study analyzes fluid overload trajectories and their association with mortality in hemodialysis patients.

Effect of a minimum floor price law for tobacco products on tobacco sales in Oakland, California, USA: a synthetic difference-in-differences analysis.

Background: In May 2020, Oakland became the most populous city in California to implement a minimum floor price law (MFPL), requiring tobacco retailers to sell cigarettes and cigars at $8 or more per pack/package. Policy enforcement began in August 2020.

Methods: We estimated changes in cigarette and cigar prices and unit sales for Oakland versus a matched comparator during the first 20 months following MFPL implementation using a synthetic difference-in-differences approach.

TIMP-2 Promotes Wound Healing by Suppressing Matrix Metalloproteinases and Inflammatory Cytokines in Corneal Epithelial Cells.

Tissue inhibitors of metalloproteinases (TIMPs) modulate extracellular matrix (ECM) remodeling for maintaining homeostasis and promoting cell migration and proliferation. Pathological conditions can alter TIMP homeostasis and aggravate disease progression. The roles of TIMPs have been studied in tissue-related disorders; however, their contributions to tissue repair during corneal injury are undefined.

Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists.

Background And Aims: We sought to ascertain how prior exposure to TNF antagonists impacts treatment response with various classes of advanced therapies in patients with ulcerative colitis (UC), through a systematic review and meta-analysis.

Methods: Through a systematic review of multiple databases through June 30, 2024, we identified 17 RCTs in 8871 adults with moderate-severe UC who were treated with different advanced therapies vs. placebo, and reported efficacy in induction of clinical remission, stratified by prior exposure to TNF antagonists.

Discovery of a Pseudomonas aeruginosa-specific small molecule targeting outer membrane protein OprH-LPS interaction by a multiplexed screen.

The surge of antimicrobial resistance threatens efficacy of current antibiotics, particularly against Pseudomonas aeruginosa, a highly resistant gram-negative pathogen. The asymmetric outer membrane (OM) of P. aeruginosa combined with its array of efflux pumps provide a barrier to xenobiotic accumulation, thus making antibiotic discovery challenging.

Aging-induced changes in lymphatic muscle cell transcriptomes are associated with reduced pumping of peripheral collecting lymphatic vessels in mice.

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the gene transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing.

The T cell receptor sequence influences the likelihood of T cell memory formation.

The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual's immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells.

Machine Learning Boosted Entropy-Engineered Synthesis of CuCo Nanometric Solid Solution Alloys for Near-100% Nitrate-to-Ammonia Selectivity.

Nanometric solid solution alloys are utilized in a broad range of fields, including catalysis, energy storage, medical application, and sensor technology. Unfortunately, the synthesis of these alloys becomes increasingly challenging as the disparity between the metal elements grows, due to differences in atomic sizes, melting points, and chemical affinities. This study utilized a data-driven approach incorporating sample balancing enhancement techniques and multilayer perceptron (MLP) algorithms to improve the model's ability to handle imbalanced data, significantly boosting the efficiency of experimental parameter optimization.

Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations.

Objectives: Biallelic HPDL variants have been identified as the cause of a progressive childhood-onset movement disorder, with a broad clinical spectrum from severe neurodevelopmental disorder to juvenile-onset pure hereditary spastic paraplegia type 83. This study aims at delineating the geno- and phenotypic spectra of patients with HPDL-related disease, quantitatively modelling the natural history, and uncovering genotype-phenotype associations.

Methods: A cross-sectional analysis of 90 published and one novel case was performed, employing a Human Phenotype Ontology-based approach.