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.

Introduction to the DETeCD-ADRD special issue.

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

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.

A descriptive examination of rurality in the Environmental influences on Child Health Outcomes Cohort: Implications, illustrations, and future directions.

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

Stomach and duodenal ulcer as a cause of death in patients with cancer: a cohort study.

Introduction: Non-cancer deaths are now becoming a significant threat to the health of cancer patients. Death from stomach and duodenal ulcer is linked to cancer due to the side effects of treatment and its pathogenesis. However, guidelines for identifying cancer patients at the highest risk of death from stomach and duodenal ulcer remain unclear.

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.

Psychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions.

Structural inequality linked to brain volume and network dynamics in aging and dementia across the Americas.

Structural inequality, the uneven distribution of resources and opportunities, influences health outcomes. However, the biological embedding of structural inequality in aging and dementia, especially among underrepresented populations, is unclear. We examined the association between structural inequality (country-level and state-level Gini indices) and brain volume and connectivity in 2,135 healthy controls, and individuals with Alzheimer's disease and frontotemporal lobe degeneration from Latin America and the United States.

Current Approaches to Optimize Donor Heart for Transplantation.

Heart transplantation remains a critical therapy for patients with end-stage heart failure, offering incremental survival and improved quality of life. One of the key components behind the success of heart transplantation is the condition and preservation of the donor heart. In this review, we provide a comprehensive overview of ischemic reperfusion injury, risk factors associated with primary graft dysfunction, current use of various preservation solutions for organ procurement and recent advancements in donor heart procurement technologies.

Cholangiocarcinoma Targeted Therapies: Mechanisms of Action and Resistance.

Cholangiocarcinoma is an aggressive bile duct malignancy with heterogeneous genomic features. Although most patients receive standard-of-care chemotherapy/immunotherapy, genomic changes that can be targeted with established or emerging therapeutics are common. Accordingly, precision medicine strategies are transforming the next-line treatment for patient subsets.

Do female and male chests feel the same? A comprehensive quantitative sensory analysis.

Introduction: There is growing interest in understanding chest sensory function due to the significant morbidity associated with impaired sensation following nerve injury. While the baseline quantitative sensory and pain thresholds in female and male patients have been studied in various other anatomic areas, there is little knowledge on quantitative sensation at the chest as well as the presence of possible gender differences. Therefore, this study aimed to conduct a comprehensive quantitative sensory analysis to determine if female and male chests feel the same.

Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex.

Objective: To assess the interrelationship between cortical lesions and cortical thinning and volume loss in people with multiple sclerosis within cortical networks, and how this relates to future cognition.

Methods: In this longitudinal study, 230 people with multiple sclerosis and 60 healthy controls underwent 3 Tesla MRI at baseline and neuropsychological assessment at baseline and 5-year follow-up. Cortical regions (N = 212) were divided into seven functional networks.

More Than Body Parts: A New Ethos of Anatomy Education.

A new ethos of anatomy education goes beyond the learning of body parts in the traditional curriculum. In the traditional curriculum, the focus of only providing information on the structure of the human body left certain learning opportunities overlooked, marginalized, or dismissed as irrelevant; thus, opportunities to foster and shape professional attributes in health care learners were lost. Furthermore, changes in curricula structures and reductions in anatomy teaching hours have necessitated a transformation in how anatomy education is perceived and delivered.

Adults With Head and Neck Burns Experience Worse Long-Term Outcomes and Require More Reconstructive Surgeries: A Burn Model System Study.

Background: Adults living with head and neck burn injuries experience psychosocial consequences due to scarring as well as functional disabilities. However, the impact of head and neck burns on long-term self-reported psychosocial outcomes, return to work, and need for reconstructive surgery has not been well described. This study investigates the unique longitudinal problems in psychosocial and functional recovery faced by adults with head and neck burn injuries.

Bereaved Parents' Perceptions of the Doll Reenactment After Sudden Unexpected Infant Deaths.

Background And Objectives: A death scene investigation is required to determine sudden infant death syndrome, and a doll reenactment optimizes the information obtained. The aim of this study was to explore how acutely bereaved parents experience doll reenactments that are conducted after the sudden and unexpected deaths of their infants.

Methods: A mixed-methods design, including surveys and semi-structured interviews, was used in a cross-sectional, national study to explore the experiences of doll reenactment among 45 bereaved parents.

Ischemic Stroke in Women: Understanding Sex-Specific Risk Factors, Treatment Considerations, and Outcomes.

Ischemic stroke is a major cause of mortality and disability and has become a significant public health concern among women. Overall, women have more ischemic stroke events than men, in part due to their longer life span, and also suffer from more severe stroke-related disabilities compared to men. Women are also more likely than men to present with atypical non-focal neurological symptoms, potentially leading to delayed diagnosis and treatment.

Impact of Baseline Hypoalbuminemia on Long-Term Survival Following Acute Myocardial Infarction According to Body Mass Index.

Serum albumin and body mass index (BMI, kg/m) have been associated with outcomes following acute myocardial infarction (AMI). Aiming to assess whether the mortality risk inflicted by hypoalbuminemia (<3.5 g/dL) in this context is influenced by BMI, we conducted a retrospective analysis of AMI survivors hospitalized during 2004-2017.

Modulating exosomal communication between macrophages and melanoma cancer cells via cyclodextrin-based nanosponges loaded with doxorubicin.

The cellular components of the tumor microenvironment (TME) comprise cancer cells and nonmalignant cells including stromal and immune cells. Exosomes are extracellular vesicles secreted by various types of cells that play a crucial role in intercellular communications within TME. The main goal of this study was to elucidate how exosomes of macrophage cells treated with doxorubicin (DOX) and DOX-loaded cyclodextrin-based nanosponges (DOX-CDNSs), affect melanoma cancer cell proliferation.

Aldolase B Deficient Mice Are Characterized by Hepatic Nucleotide Sugar Abnormalities.

Hereditary fructose intolerance (HFI) is characterized by liver damage and a secondary defect in N-linked glycosylation due to impairment of mannose phosphate isomerase (MPI). Mannose treatment has been shown to be an effective treatment in a primary defect in MPI (i.e.

A Morphologic Analysis of Thumb Ulnar Collateral Ligament Avulsion Fracture Fragments and Risk Factors for Surgical Treatment.

Background: There is debate regarding nonoperative versus surgical treatment of thumb ulnar collateral ligament (UCL) tears with avulsion fractures. The aim of this study was to evaluate the fragment size in relation to the UCL footprint size in patients with an avulsion fracture injury and to find risk factors associated with surgical treatment.

Methods: In a cohort of avulsion fracture injury patients, the largest side of the fragment was divided by the average reported UCL footprint size (ff-ratio), and a logistic regression was performed to find variables associated with surgery.