Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction-associated steatohepatitis.

Hepatocyte apoptosis is a key feature of metabolic dysfunction-associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene ) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid-defined (HF-CDAA) diet.

Toward Health Equity: A Workshop Report on the State of the Science of Obesity Interventions for Adults.

Objective: From October 18-20, 2022, the National Institutes of Health held a workshop to examine the state of the science concerning obesity interventions in adults to promote health equity. The workshop had three objectives: (1) Convene experts from key institutions and the community to identify gaps in knowledge and opportunities to address obesity, (2) generate recommendations for obesity prevention and treatment to achieve health equity, and (3) identify challenges and needs to address obesity prevalence and disparities, and develop a diverse workforce.

Methods: A three-day virtual convening.

The life cycle of infection prevention and antimicrobial stewardship projects and interventions: the dynamic interplay of implementation and de-implementation science (Part I of II).

In Antimicrobial Stewardship and Infection Prevention and Control, programmatic goals often strive to achieve clinical benefit by practice change in the direction of doing less. Practically, this may include reducing the number of tests ordered, encouraging shorter and more narrow courses of antimicrobials, or discontinuing practices that are no longer contextually appropriate. Because promoting practice change in the direction of doing less is a critical aspect of day-to-day operations in Antimicrobial Stewardship and Infection Prevention and Control, the goals of this Research Committee White Paper are to provide a roadmap and framework for leveraging principles of implementation and de-implementation science in day-to-day practice.

Leveraging de-implementation science to promote infection prevention and stewardship: a roadmap and practical examples (Part II of II).

De-implementation of established practices is a common challenge in infection prevention and antimicrobial stewardship and a necessary part of the life cycle of healthcare quality improvement programs. Promoting de-implementation of ineffective antimicrobial use and increasingly of low-value diagnostic testing are cornerstones of stewardship practice. Principles of de-implementation science and the interplay of implementation and de-implementation are discussed in part I of this Society for Healthcare Epidemiology of America White Paper Series.

Clinical comparison of four commercial MRI phantoms on a 0.35T MR-linac using a standard clinical TRUFI sequence at a single institution.

Purpose: Real‑time magnetic resonance-guided radiation therapy (MRgRT) integrates MRI with a linear accelerator (Linac) for gating and adaptive radiotherapy, which requires robust image‑quality assurance over a large field of view (FOV). Specialized phantoms capable of accommodating this extensive FOV are therefore essential. This study compares the performance of four commercial MRI phantoms on a 0.

Natural history and development of a novel composite endpoint in patients with alcohol-associated Hepatitis: Data from a prospective multicenter study.

Background: The clinical course and outcomes of alcohol-associated hepatitis (AH) remain poorly understood. Major adverse liver outcomes (MALO) do not capture the added risk of return to drinking (RTD). We examined the natural history of AH and developed a composite endpoint using a contemporary observational cohort of AH.

The Effects of Anakinra on Cardiorespiratory Fitness in Heart Failure Stratified by Age in Phase II Clinical Trials.

Cardiorespiratory fitness (CRF) in heart failure (HF) declines with age. Interleukin-1 (IL-1) is a pro-inflammatory cytokine involved in aging and HF. We aimed to determine the changes in CRF before and after treatment with anakinra, recombinant IL-1 receptor antagonist, in patients with HF stratified according to age below and above 60 years in phase II clinical trials.

Vortioxetine for Major Depressive Disorder in Children: 12-Week Randomized, Placebo-Controlled Study.

Objective: To evaluate efficacy, safety, and tolerability of vortioxetine in children ages 7 to 11 years with major depressive disorder.

Method: Patients meeting criteria for incomplete improvement in depressive symptoms (Children's Depression Rating Scale-Revised [CDRS-R] total score ≥40 plus <40% reduction and Parent Global Assessment Global Improvement score >2) after 4 weeks of single-blind lead-in treatment with a brief psychosocial intervention plus placebo were randomized 1:1:1:1 to 8-week double-blind treatment with brief psychosocial intervention and placebo, vortioxetine 10 mg/day, vortioxetine 20 mg/day, or fluoxetine 20 mg/day. Following preplanned interim analysis, enrollment to fluoxetine was stopped, and patients were randomized 1:1:1 to placebo, vortioxetine 10 mg, or vortioxetine 20 mg.

Diagnostic Approach and Management of Iliac Artery Endofibrosis in Athletes: A Scoping Review.

Iliac artery endofibrosis (IAE) is a rare vascular condition with an estimated global prevalence of 0.01%. It primarily affects endurance athletes, especially cyclists, and often presents with exercise-induced leg discomfort or reduced performance.

Evaluating Long-Term Effectiveness of Cystic Fibrosis Modulator Therapies After Rapid Adoption: A Dual-Approach Study.

Rationale: Modulator therapies like ivacaftor have revolutionized clinical management of cystic fibrosis (CF), showing marked short-term benefits in trials but heterogeneous findings in long-term observational studies. Since newer modulators have become the standard of care for the majority living with CF in the U.S.

24R,25(OH)D regulates tumorigenesis in estrogen sensitive laryngeal cancer cells via membrane-associated receptor complexes in ER+ and ER- cells.

This study examined the effects of 24R,25-dihydroxyvitamin D (24R,25(OH)D) in estrogen-responsive laryngeal cancer tumorigenesis in vivo, the mechanisms involved, and whether the ability of the tumor cells to produce 24R,25(OH)D locally is estrogen-dependent. Estrogen receptor alpha-66 positive (ER+) UM-SCC-12 cells and ER- UM-SCC-11A cells responded differently to 24R,25(OH)D in vivo; 24R,25(OH)D enhanced tumorigenesis in ER+ tumors but inhibited tumorigenesis in ER- tumors. Treatment with 17β-estradiol (E) for 24 h reduced levels of CYP24A1 protein but increased 24R,25(OH)D production in ER+ cells; treatment with E for 9 min reduced CYP24A1 at 24 h and reduced 24R,25(OH)D production in ER- cells.

Influence of Preoperative Cervical Spine Curvature in Postoperative Radiographic Outcomes Following Anterior Cervical Discectomy and Fusion: A Single-Center Retrospective Study.

Background Anterior cervical discectomy and fusion (ACDF) is a common surgical procedure that patients undergo for cervical disc herniations and degenerative disc disease, aimed at relieving radicular symptoms and restoring cervical alignment. The impact of preoperative kyphotic cervical imbalance versus preoperative lordosis on postoperative radiographic outcomes in ACDF patients is unclear. The purpose of this study is to examine how preoperative cervical sagittal balance can influence quantified postoperative cervical sagittal balance.

Maintenance of Periodontally Compromised Teeth Using Periodontal Splints.

Periodontal splints offer a noninvasive and inexpensive treatment modality to stabilize mobile teeth. This study evaluated periodontal splints to examine their longevity and long-term stability. A retrospective chart review was performed for patients who received splints on mandibular or maxillary anterior teeth.

How Isomer and Conformer Structures Impact Dissociation Dynamics of Alkane Radical Cations.

Ionization of alkanes to form radical cations activates their otherwise unreactive C-H bonds, facilitating important chemical processes such as hydrocarbon cracking. This work investigates the radical cation dissociation dynamics of hexane (CH) structural isomers by using femtosecond time-resolved mass spectrometry and quantum chemical calculations. All five isomers exhibit competition between the yields of fragment ions arising from direct C-C bond cleavage or dissociative rearrangement with hydrogen migration on dynamical time scales of ∼50-300 fs, suggesting that hydrogen migration in the metastable cations operates on such short time scales.

Significant Pathology in Young Infants Presenting With Hypothermia: A Multicenter Study.

Objective: Hypothermia in young infants is often attributed to immature thermoregulation but may be the harbinger of significant pathology. We aimed to determine the prevalence and type of significant pathology in young infants aged 90 days or younger presenting with hypothermia (≤36.0 °C) and explore associations between this outcome and presenting characteristics and evaluation.

Dissolution of Once-Nightly Sodium Oxybate in Soft Foods and Alternative Liquid Reconstitution Vehicles.

Purpose: Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness (EDS) and can occur with or without cataplexy. Once-nightly sodium oxybate (ON-SXB) is approved for the treatment of cataplexy or EDS in patients 7 years of age or older with narcolepsy. ON-SXB contains both immediate-release and pH-dependent, controlled-release granules designed to be reconstituted in water and administered orally once at bedtime.

Rationale and Design of the Comparative Effectiveness of ICD Versus Non-ICD Therapy in Contemporary Heart Failure Patients at a Low Risk for Arrhythmic Death (CONTEMP-ICD) trial.

Background: Current recommendations for a prophylactic (primary prevention) implantable cardioverter defibrillator (ICD) in patients with both ischemic and non-ischemic heart failure with reduced ejection fraction (HFrEF) originate from clinical trials conducted in selected patients over 20 years ago that showed an overall statistically significant survival benefit associated with a primary prevention ICD in the range of 23%-34%. The recent introduction of angiotensin receptor-neprilysin inhibitors [ARNI] and sodium glucose co-transporter 2 inhibitors [SGLT2i]) was shown to further reduce the risk of sudden cardiac death (SCD) in patients with HFrEF. Thus, there is an unmet need appropriately designed comparative effectiveness clinical trials aimed to reassess the survival benefit of a primary prevention ICD in contemporary patients with HFrEF.

Training Volume and Training Frequency Changes Associated with Boston Marathon Race Performance.

Background: Physical training influences competitive marathon performance, including training volume and training frequency changes (TFCs) pre-race. Training intensity distribution (i.e.

Short-Term Complications of Preoperative Weight Loss Strategies in Total Knee Arthroplasty: Bariatric Surgery versus Glucagon-Like Peptide-1 Receptor Agonists.

Introduction: Obesity is an increasingly prevalent comorbidity that confers greater risks of postoperative complications following total joint arthroplasty, underscoring the need for viable preoperative weight loss. The objective of this study was to compare the risk of 90-day adverse events in patients undergoing total knee arthroplasty (TKA) following bariatric surgery versus treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA).

Methods: A retrospective review of a national research network from May 1, 2005, to February 12, 2025, identified patients undergoing TKA with bariatric surgery or GLP-1 RA prescriptions in the 18 months preceding their joint arthroplasty.

Transposable elements are dysregulated in brains of individuals with major depressive disorder.

Transposable elements (TEs) are repetitive DNA sequences capable of being transcribed and re-integrated, or transposed, into distinct loci throughout the genome. While thought to be largely transcriptionally silenced in brain, TE transcription is increasingly recognized as dynamic and involved in human health and disease states, including in disorders of the brain. In this study, we annotated TE transcripts in publicly available RNA sequencing (RNAseq) of postmortem human brain tissue to investigate the expression profile of TE transcripts in individuals with major depressive disorder (MDD) compared to healthy controls.

Association Between Disability and Life Satisfaction, Participation, and Psychological Health: A Traumatic Brain Injury Model Systems Study.

Background And Objectives: Moderate-to-severe traumatic brain injury (TBI) can result in disability across physical, social, and cognitive domains. The Glasgow Outcome Scale-Extended (GOSE), which evaluates global function, is the most frequently used TBI outcome measure. However, the GOSE may not capture all domains of recovery.

Impact of Subthalamic Nucleus Deep Brain Stimulation on Gastrointestinal Symptoms and Gastric Emptying in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis evaluates the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in improving gastric motility in patients with Parkinson's disease (PD).

Materials And Methods: A systematic search was conducted in Scopus, Web of Science, PubMed, and Cochrane CENTRAL until December 15, 2024. Observational studies and clinical trials evaluating DBS effects on gastric motility and gastric emptying in patients with PD were included.