Larsucosterol for the Treatment of Alcohol-Associated Hepatitis.

Background: Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy.

Methods: In this phase 2b trial, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized. All patients received supportive care as determined by investigators.

Diversity in Medical School, Orthopaedic Surgery Residency, and ACGME-Accredited Foot and Ankle Orthopaedic Surgery Fellowship Training by Gender, Race, and Ethnicity.

Introduction: Increasing diversity in the US health care workforce is a topic of increasing scrutiny and interest. This study analyzes the pipeline of demographic diversity for Accreditation Council for Graduate Medical Education (ACGME)-accredited foot and ankle orthopaedic surgery fellowship training.

Methods: This was a cross-sectional study of medical students, orthopaedic surgery residents, and orthopaedic foot and ankle fellows at US-accredited training programs from 2013 to 2022.

Comparative transcriptomic rhythms in the mouse and human prefrontal cortex.

Introduction: Alterations in multiple subregions of the human prefrontal cortex (PFC) have been heavily implicated in psychiatric diseases. Moreover, emerging evidence suggests that circadian rhythms in gene expression are present across the brain, including in the PFC, and that these rhythms are altered in disease. However, investigation into the potential circadian mechanisms underlying these diseases in animal models must contend with the fact that the human PFC is highly evolved and specialized relative to that of rodents.

Aldosterone and Potassium in Heart Failure: Overcoming This Major Impediment in Clinical Practice.

Aldosterone is a key regulator of fluid and electrolyte balance in the body. It is often dysregulated in heart failure (HF) and is a key driver of cardiac remodelling and worse clinical outcomes. Potassium regulation is essential for normal cardiac, gastrointestinal and neuromuscular function.

BCG-Induced DNA Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing the Risk for Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Background: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.

Methods: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline).

Biochemical mechanisms and molecular interactions of vitamins in cancer therapy.

Recently, the potential role of vitamins in cancer therapy has attracted considerable research attention. However, the reported findings are inconsistent, with limited information on the biochemical and molecular interactions of different vitamins in various cancer cells. Importantly, the presence of vitamin receptors in tumor cells suggests that vitamins play a significant role in the molecular and biochemical interactions in cancers.

Ferroptosis in kidney disease: a bibliometric analysis from 2012 to 2024.

Background And Aims: Ferroptosis, a novel concept of programmed cell death proposed in 2012, in kidney disease, has garnered significant attention based on evidence of abnormal iron deposition and lipid peroxidation damage in the kidney. Our study aim to examine the trends and future research directions in the field of ferroptosis in kidney disease, so as to further explore the target or treatment strategy for clinical treatment of kidney disease.

Material And Methods: A thorough survey using the Web of Science Core Collection, focusing on literature published between 2012 and 2024 examining the interaction between kidney disease and ferroptosis was conducted.

Continuous risk monitoring and management of heart failure: Rationale and design of the ALLEVIATE-HF trial.

Aims: Early identification and management of worsening heart failure (HF) is necessary to prevent disease progression and hospitalizations. The ALLEVIATE-HF (Algorithm Using LINQ Sensors for Evaluation and Treatment of Heart Failure) trial is a prospective, randomized, controlled, double-blind, multicentre trial that aims to assess the safety and efficacy of using the Reveal LINQ™ insertable cardiac monitor (ICM) in patients with HF to continuously monitor and evaluate HF risk status and guide timely interventions.

Methods: The ICM algorithm uses parameters derived from electrocardiogram (atrial fibrillation [AF], ventricular rate during AF, heart rate variability, and night heart rate), three-axis accelerometer (patient activity duration), and subcutaneous bioimpedance (fluid volume, respiration rate).

Exploring the clinical profiles and management of juvenile dermatomyositis in Africa: a survey of African rheumatology care providers.

Background: There are limited studies of juvenile dermatomyositis (JDM) in low and middle-income countries (LMIC). Many demonstrate delays to care, high prevalence of severe manifestations, and high mortality. Given the disease-associated damage with JDM, understanding JDM in Africa further is critical.

A novel label-free method to determine equilibrium dissociation constants of antibodies binding to cell surface proteins.

Solution-based affinity assays are used for the selection and characterization of proteins that could be developed into therapeutic molecules. However, these assays have limitations for cell-surface proteins as in most cases their purification requires detergent solubilization and are unlikely to assume conformations in solution that resemble their native states in cell membranes. This report describes a novel electrochemiluminescence-based method, called MSD-CAT, for the affinity analysis of antibodies binding to cell-surface receptors.

Informed Consent and Shared Decision-Making in Modern Medicine. Case-based Approach, Current Gaps and Practical Proposal.

Advances in personalized medicine and Systems Biology have introduced probabilistic models and error discovery to cardiovascular care, aiding disease prevention and procedural planning. However, clinical application faces cultural, technical, and methodological hurdles. Patient autonomy remains essential, with shared decision-making (SDM) gaining importance in managing complex cardiovascular treatment options.

Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase.

The mitochondrial flavoenzymes proline dehydrogenase (PRODH) and hydroxyproline dehydrogenase (PRODH2) catalyze the first steps of proline and hydroxyproline catabolism, respectively. The enzymes are targets for chemical probe development because of their roles in cancer cell metabolism (PRODH) and primary hyperoxaluria (PRODH2). Mechanism-based inactivators of PRODH target the FAD by covalently modifying the N5 atom, with N-propargylglycine (NPPG) being the current best-in-class of this type of probe.

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.

Examining Mammalian facial behavior using Facial Action Coding Systems (FACS) and combinatorics.

There has been an increased interest in standardized approaches to coding facial movement in mammals. Such approaches include Facial Action Coding Systems (FACS), where individuals are trained to identify discrete facial muscle movements that combine to create a facial configuration. Some studies have utilized FACS to analyze facial signaling, recording the quantity of morphologically distinct facial signals a species can generate.

Genetic Services in Appalachia Conference Series.

This study examined the data generated as part of a seven-session webinar series that focused on genetics care provision in the medically underserved, rural Appalachian region and examined how these services have adapted to challenging practice environments. Barriers and facilitators to care in our region were considered. Data included a baseline survey of registrants, transcripts of sessions, and feedback about sessions.

Transaxillary endovascular aortic aneurysm repair using a reverse mounted Gore Excluder endograft for a patient with abdominal aortic aneurysm and severe iliofemoral occlusive disease.

Adverse iliofemoral anatomy represents a unique challenge for endovascular aortic aneurysm repair (EVAR). This report describes a transaxillary EVAR in a patient with severe iliofemoral occlusive disease and an infrarenal aortic aneurysm. A reversely mounted Gore Excluder graft was advanced and deployed in the infrarenal aorta using the left axillary artery.

Generative artificial intelligence in graduate medical education.

Generative artificial intelligence (GenAI) is rapidly transforming various sectors, including healthcare and education. This paper explores the potential opportunities and risks of GenAI in graduate medical education (GME). We review the existing literature and provide commentary on how GenAI could impact GME, including five key areas of opportunity: electronic health record (EHR) workload reduction, clinical simulation, individualized education, research and analytics support, and clinical decision support.

Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy.

Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by lower lip pits and orofacial clefts (OFCs). With a prevalence of approximately 1 in 35,000 live births, it is the most common form of syndromic clefting and may account for ~2% of all OFCs. The majority of VWS is attributed to genetic variants in IRF6 (~70%) or GRHL3 (~5%), leaving up to 25% of individuals with VWS without a molecular diagnosis.

Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia.

Background: Writer's cramp (WC) dystonia is an involuntary movement disorder with distributed abnormalities in the brain's motor network. Prior studies established the potential for repetitive transcranial magnetic stimulation (rTMS) to either premotor cortex (PMC) or primary somatosensory cortex (PSC) to modify symptoms. However, clinical effects have been modest with limited understanding of the neural mechanisms hindering therapeutic advancement of this promising approach.

A novel TERT variant associated with a telomere biology disorder and challenges in variant classification.

Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single length analysis ().

Re-evaluation of mastodon material from Oregon and Washington, USA, Alberta, Canada, and Hidalgo and Jalisco, Mexico.

The presence of at least two contemporaneous Pleistocene mastodon taxa in North America ( and ) invites re-examination of specimens at the geographic margins of each species in order to determine range boundaries, overlaps, and fluctuations. Third molars from Oregon in the United States, as well as from Hidalgo and Jalisco in Mexico, were found to be morphologically consistent with . Washington in the United States includes a number of specimens that could not be confidently assigned to either taxon.

Systematic Review of Granulomatous Invasive Fungal Sinusitis Management.

Objectives: Granulomatous invasive fungal sinusitis (GIFS) affects immunocompetent individuals. There is ongoing debate over whether surgery, antifungal medication, or a combined approach is the best treatment. This article summarizes reports about GIFS and its management.

A 5-year single-center review of seropositivity in kidney transplant candidates in Central Texas.

Introduction: is a soil-transmitted helminth that can lead to life-threatening hyperinfection in transplant recipients. Targeted screening based on social history alone may preclude a large proportion of seropositive patients. Our institution implemented universal screening for kidney transplant candidates.

Body mass index and sleep disorders after moderate-to-severe traumatic brain injury - a national TBI model systems study.

Objective: To examine the relationship between body mass index (BMI), newly developed sleep disorders and functional outcome after moderate-to-severe traumatic brain injury (msTBI).

Methods: Retrospective data from the TBI Model Systems National Database was analyzed, focusing on the independent association between BMI, sleep disorder diagnosis, and functional outcome as measured by the Extended Glasgow Outcome Scale (GOSE) at 1-year post-injury. Linear and logistic regression were used.