Human TSC2 mutant cells exhibit aberrations in early neurodevelopment accompanied by changes in the DNA Methylome.

Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. While benign tumors in the heart, lungs, kidney, and brain are all hallmarks of the disease, the most severe symptoms of TSC are often neurological, including seizures, autism, psychiatric disorders, and intellectual disabilities. TSC is caused by loss of function mutations in the TSC1 or TSC2 genes and consequent dysregulation of signaling via mechanistic Target of Rapamycin Complex 1 (mTORC1).

Plasma Circulating Metabolites Associated With Steatotic Liver Disease and Liver Enzymes: A Multiplatform Population-Based Study.

Background And Aims: Steatotic liver disease (SLD) is the most common chronic liver disease strongly associated with metabolic dysfunction, but its pathogenesis remains incompletely understood. Exploring plasma circulating metabolites may help in elucidating underlying mechanisms and identifying new biomarkers for SLD.

Methods: We examined cross-sectionally the association between plasma metabolites and SLD as well as liver enzymes using data from 4 population-based cohort studies (Rotterdam study, Avon Longitudinal Study of Parents and Children, The Insulin Resistance Atherosclerosis Family Study, and Study of Latinos).

Dendriform pulmonary ossification in military combat veterans: A case series.

Dendriform pulmonary ossification (DPO) is a rare condition characterized by mature bone formation in the lung. DPO has been linked to various conditions, but little is known about the link between DPO and hazardous airborne exposures. We queried research databases of military personnel evaluated for deployment-related respiratory diseases at two occupational pulmonary medicine clinics (Colorado, USA) for diagnoses of DPO, and summarized demographics, Gulf War military deployment history, medical history, and pulmonary function testing.

EyeLiner: A Deep Learning Pipeline for Longitudinal Image Registration Using Fundus Landmarks.

Objective: Detecting and measuring changes in longitudinal fundus imaging is key to monitoring disease progression in chronic ophthalmic diseases, such as glaucoma and macular degeneration. Clinicians assess changes in disease status by either independently reviewing or manually juxtaposing longitudinally acquired color fundus photos (CFPs). Distinguishing variations in image acquisition due to camera orientation, zoom, and exposure from true disease-related changes can be challenging.

Creating a family health history interview protocol for use with undergraduate health professional students: A scoping review.

Background: Family health history can be used as a health promotion tool to assess health risk, improve data collection and disease prevention, initiate interventions, and motivate behavioral change, but its utility as a public health tool has not been fully explored. Collecting information for a family health history can be a challenging task. However, it is an important skill for undergraduate students to learn, particularly those in pre-health majors.

Context-specific eQTLs provide deeper insight into causal genes underlying shared genetic architecture of critically ill COVID-19 and idiopathic pulmonary fibrosis.

Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

Sex Differences in Circadian Timing and Biological Night in Adolescents.

Circadian rhythms, intrinsic 24-h cycles that drive rhythmic changes in behavior and physiology, are important for normal physiology and health. Previous work in adults has identified sex differences in circadian rhythms of melatonin, temperature, and the intrinsic period of the human circadian timing system. However, less is known about sex differences in circadian rhythms at other developmental stages.

Overcoming the technical challenge of venous resection with pancreatectomy: Which factors determine survival?

Background: Pancreatectomy with venous resection (PVR) is nowadays considered standard. However, there is still concern about increased postoperative morbidity and impaired long-term outcome depending on the type of venous resection and reconstruction. The aim was to investigate the predictors of morbidity and long-term survival in patients undergoing PVR in a high-volume center.

Sexual identity, sexual behavior, and drug use behaviors among people who use drugs in the rural U.S.

Introduction: People who use drugs (PWUD) are at risk of HIV infection, but the frequency and distribution of transmission-associated behaviors within rural communities is not well understood. Further, while interventions designed to more explicitly affirm individuals' sexual orientation and behaviors may be more effective, descriptions of behavior variability by orientation are lacking. We sought to describe how disease transmission behaviors and overdose risk vary by sexual orientation and activity among rural PWUD.

Comparison of Chart Review and Administrative Data in Developing Predictive Models for Readmissions in Chronic Obstructive Pulmonary Disease.

This study aimed to evaluate the performance of machine learning models for predicting readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) based on administrative data and chart review data. The study analyzed 4,327 patient encounters from the University of Chicago Medicine to assess the risk of readmission within 90 days after an acute exacerbation of COPD. Two random forest prediction models were compared.

Neurobehavioral Symptoms Partially Mediate the Effects of Depression and PTSD on Participation for Veterans With Mild Traumatic Brain Injury: A Cross-Sectional Study.

Objective: To examine whether neurobehavioral symptoms mediate the relationship between comorbid mental health conditions (major depressive disorder [MDD] and/or posttraumatic stress disorder [PTSD]) and participation restriction among Veterans with mild traumatic brain injury (mTBI).

Setting: Veterans Health Administration (VHA).

Participants: National sample of Veterans with mTBI who received VHA outpatient care between 2012 and 2020.

Sex Differences in Early/Unplanned Separation Among US Service Members With a History of Mild Traumatic Brain Injury.

Objective: To investigate the incidence of early/unplanned (E/U) separations following mild traumatic brain injury (mTBI) and assess whether sex impacts the hazard of separation.

Setting: Military Health System (MHS).

Participants: Active duty service members (N = 75,730) with an initial mTBI diagnosis in military records between January 2011 and January 2018.

Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials.

Brain Function Outcomes of Recent and Lifetime Cannabis Use.

Importance: Cannabis use has increased globally, but its effects on brain function are not fully known, highlighting the need to better determine recent and long-term brain activation outcomes of cannabis use.

Objective: To examine the association of lifetime history of heavy cannabis use and recent cannabis use with brain activation across a range of brain functions in a large sample of young adults in the US.

Design, Setting, And Participants: This cross-sectional study used data (2017 release) from the Human Connectome Project (collected between August 2012 and 2015).

Racial Disparities in Time to Huntington Disease Diagnosis in North America: An ENROLL-HD Analysis.

Background And Objectives: There are well-documented racial and ethnic disparities in access to neurologic care and disease-specific outcomes. Although contemporary clinical and neurogenetic understanding of Huntington disease (HD) is thanks to a decades-long study of a Venezuelan cohort, there are a limited number of studies that have evaluated racial and ethnic disparities in HD. The goal of this study was to evaluate disparities in time from symptom onset to time of diagnosis of HD.

Improving safety in the performance of robotic urinary diversions: a narrative review.

Urinary diversions are performed for a wide variety of indications, including bladder removal for cancer treatment, post-cancer treatment complications, trauma, or bladder pain. The robotic approach has been increasingly used in performing urinary diversions since the introduction of the surgical robot. A PubMed keyword search was performed on September 14, 2023 with the terms: robotic and urinary diversion.

Comparative analysis of ambient, in-home, and personal exposures reveals associations between breathing zone pollutant levels and asthma exacerbations in high-risk children.

Background: Air pollution is associated with poor asthma outcomes in children. However, most studies focus on ambient or indoor monitor pollution levels. Few studies evaluate breathing zone exposures, which may be more consequential for asthma outcomes.

Intervention Stage Completion and Behavioral Health Outcomes: An Integrated Behavioral Health and Primary Care Randomized Pragmatic Trial.

Purpose: We performed a pragmatic, cluster randomized controlled trial of a comprehensive practice-level, multistage practice transformation intervention aiming to increase behavioral health integration in primary care practices and improve patient outcomes. We examined associations between completion of intervention stages and patient outcomes across a heterogeneous national sample of primary care practices.

Methods: Forty-two primary care practices across the United States with colocated behavioral health and 2,945 patients with multiple chronic medical and behavioral health conditions completed surveys at baseline, midpoint, and 2-year follow-up.

Retinoid signaling in pancreas development, islet function, and disease.

All-trans retinoic acid (ATRA) signaling is essential in numerous different biological contexts. This review highlights the diverse roles of ATRA during development, function, and diseases of the pancreas. ATRA is essential to specify pancreatic progenitors from gut tube endoderm, endocrine and exocrine differentiation, and adult islet function.

Methods to Adjust for Confounding in Test-Negative Design COVID-19 Effectiveness Studies: Simulation Study.

Background: Real-world COVID-19 vaccine effectiveness (VE) studies are investigating exposures of increasing complexity accounting for time since vaccination. These studies require methods that adjust for the confounding that arises when morbidities and demographics are associated with vaccination and the risk of outcome events. Methods based on propensity scores (PS) are well-suited to this when the exposure is dichotomous, but present challenges when the exposure is multinomial.

Provider perception of the acceptability, appropriateness, and feasibility of a transdiagnostic intervention in a youth partial hospitalization setting: A mixed methods implementation process evaluation.

Partial hospitalization programs (PHPs) are increasingly relied upon to provide intensive mental health treatment for youth with acute and severely impairing mental health symptoms, yet very few interventions have been adapted to fit this unique delivery context. Transdiagnostic treatments hold promise for addressing the complex clinical presentations and workflow needs of PHP programs, but more work is needed to understand factors that influence successful implementation. We conducted a formative implementation process evaluation to identify barriers and facilitators of acceptability, appropriateness, and feasibility of implementing an evidence-based transdiagnostic intervention in a PHP setting and further targets for intervention and implementation adaptation.

The primary mechanism for highly potent inhibition of HIV-1 maturation by lenacapavir.

Lenacapavir (LEN) is a highly potent, long-acting antiretroviral medication for treating people infected with muti-drug-resistant HIV-1 phenotypes. The inhibitor targets multifaceted functions of the viral capsid protein (CA) during HIV-1 replication. Previous studies have mainly focused on elucidating LEN's mode of action during viral ingress.

"No Matter the Age or Medical Complexity, People Benefit From That Intensity of Exercise": A Mixed-Methods Study Describing Rehabilitation Provider Perceptions of High-Intensity Resistance Training Among Veterans Receiving Post-Acute Care.

Background: In skilled nursing facilities (SNFs), i-STRONGER is a novel, high-intensity resistance training approach that incorporates progressive resistance training to promote greater improvements in patient function compared to usual care. To inform large-scale expansion of i-STRONGER as standard-of-care in SNFs, this mixed-methods study assessed rehabilitation providers' perceptions of i-STRONGER and purported needs for its adoption.

Methods: Forty-three rehabilitation providers participated in an 18-week, interactive i-STRONGER training program.