Oncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.

Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

A detailed spatiotemporal atlas of the white matter tracts for the fetal brain.

This study presents the construction of a comprehensive spatiotemporal atlas of white matter tracts in the fetal brain for every gestational week between 23 and 36 wk using diffusion MRI (dMRI). Our research leverages data collected from fetal MRI scans, capturing the dynamic changes in the brain's architecture and microstructure during this critical period. The atlas includes 60 distinct white matter tracts, including commissural, projection, and association fibers.

Barriers to Research for Academic Otologists/Neurotologists in the United States.

Objective: The physician-scientist workforce is shrinking in the United States. Academic otologists/neurotologists face a diverse set of barriers to successful careers. We aimed to characterize the factors affecting contemporary otology/neurotology surgeon-scientists.

Angiotensin-Receptor Blockers Prevent Vestibular Schwannoma-Associated Hearing Loss.

Background Introduction: Vestibular schwannoma (VS) tumors typically present with sensorineural hearing loss (SNHL). Losartan has recently demonstrated prevention of tumor-associated SNHL in a mouse model of VS through suppression of inflammatory and pro-fibrotic factors, and the current study investigates this association in humans.

Methods: This is a retrospective study of patients with unilateral VS and hypertension followed with sequential audiometry at a tertiary referral hospital from January 1994 to June 2023.

Voices of Nanomedicine: Blueprint Guidelines for Collaboration in Addressing Global Unmet Medical Needs.

The "" under this Perspective underline the importance of interdisciplinary collaboration and partnerships across several disciplines, such as medical science and technology, medicine, bioengineering, and computational approaches, in bridging the gap between research, manufacturing, and clinical applications. Effective communication is key to bridging team gaps, enhancing trust, and resolving conflicts, thereby fostering teamwork and individual growth toward shared goals. Drawing from the success of the COVID-19 vaccine development, we advocate the application of similar collaborative models in other complex health areas such as nanomedicine and biomedical engineering.

Use of Financial Hardship as a Metric for Assessing Financial Toxicity in Surgical Trauma Patients.

Background: Financial toxicity is the detrimental impact of health care costs that must be mitigated to achieve universal health coverage. Catastrophic health expenditure (CHE) is widely used to measure financial toxicity but does not capture patient perspectives of unaffordable health care costs. Financial hardship (FH), a patient-reported outcome measure, is currently underutilized but may be an important adjunct metric.

Glaucoma Screening and Referral Risk Factors in a High-Risk Population: Follow-up Study of the Manhattan Vision Screening Study (NYC-SIGHT).

Prcis: Community-based eye health screenings that incorporated fundus photography and optometric exams in a high-risk NYC population effectively identified a higher than average number of participants that required an in-office glaucoma evaluation.

Purpose: To report glaucoma screening rates and risk factors associated with referral for in-office glaucoma evaluation in the Manhattan Vision Screening and Follow-up Study (NYC-SIGHT).

Methods: In this 5-year, cluster-randomized clinical trial, eligible individuals aged 40 and older were recruited from affordable housing developments and senior centers.

Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture.

Measuring virus in biofluids is complicated by confounding biomolecules coisolated with viral nucleic acids. To address this, we developed an affinity-based microfluidic device for specific capture of intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our approach used an engineered angiotensin-converting enzyme 2 to capture intact virus from plasma and other complex biofluids.

Tunneled Pleural Catheters: An Effective Nonsurgical Alternative for Nonexpandable Lung in Chronic Pleural Infection.

Background: Open window thoracostomy (OTW) is the standard of care for debilitated patients with chronic pleural infection and nonexpandable lungs (NEL) who are not candidates for major surgical intervention. Tunneled pleural catheters (TPC) offer tremendous treatment potential in this setting based on their efficacy in malignant pleural effusion and NEL. We aim to assess the efficacy, safety, and health care utilization of TPC in this setting.

Enhanced Costimulation Blockade With αCD154, αCD2, and αCD28 to Promote Heart Allograft Tolerance in Nonhuman Primates.

Background: Long-term renal allograft acceptance has been achieved in macaques using a transient mixed hematopoetic chimerism protocol, but similar regimens have proven unsuccessful in heart allograft recipients unless a kidney transplant was performed simultaneously. Here, we test whether a modified protocol based on targeting CD154, CD2, and CD28 is sufficient to prolong heart allograft acceptance or promote the expansion of regulatory T cells.

Methods: Eight macaques underwent heterotopic allo-heart transplantation from major histocompatibility complex-mismatched donors.

Genome-wide association study of varenicline-aided smoking cessation.

Introduction: Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with the highest therapeutic efficacy of any pharmacological smoking cessation aid and a 12-month cessation rate of 26%. Genetic variation may be associated with varenicline response, but to date no genome-wide association studies of varenicline response have been published.

Methods: In this study, we investigated the genetic contribution to varenicline effectiveness using two electronic health record-derived phenotypes.

Use of and Steering to Pharmacies Owned by Insurers and Pharmacy Benefit Managers in Medicare.

Importance: The prevalence of pharmacies owned by integrated insurers and pharmacy benefit managers (PBMs), or insurer-PBMs, is of growing regulatory concern. However, little is known about the role of these pharmacies in Medicare, in which pharmacy network protections may influence market dynamics.

Objective: To evaluate the prevalence of insurer-PBM-owned pharmacies and the extent to which insurer-PBMs steer patients to pharmacies they own in Medicare.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Heart failure outcomes captured by adverse event reporting in participants with type 2 diabetes and atherosclerotic cardiovascular disease: Observations from the VERTIS CV trial.

Aims: In VERTIS CV, ertugliflozin was associated with a 30% risk reduction for adjudication-confirmed, first and total hospitalizations for heart failure (HHF) in participants with type 2 diabetes and atherosclerotic cardiovascular disease. We evaluated the impact of ertugliflozin on the broader spectrum of all reported heart failure (HF) events independent of adjudication confirmation.

Methods And Results: Data from participants who received ertugliflozin (5 or 15 mg) were pooled and compared versus placebo.

Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy.

Background: In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different F-labeled PSMA ligands to today's standard radiopharmaceutical Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.

"It's more than a ride" veteran perceptions of peer specialist qualities and activities that were most valuable for post-incarceration reentry: a qualitative analysis.

Background: Reentry veterans experience many barriers to achieving physical and psychological well-being. While peer specialists can provide important support to veterans as they readjust to life post-incarceration, their specific activities and qualities most valued by veterans are not well known. The Post-Incarceration Engagement (PIE) intervention, coordinated with VA's Health Care for Reentry Veterans (HCRV) program, links reentry veterans with a peer specialist who provides connection to services and social-emotional support during the reentry process.

Sacubitril/valsartan versus valsartan initiation in patients naïve to renin-angiotensin system inhibitors: Insights from PARAGLIDE-HF.

Aims: Whether prior treatment with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) modifies efficacy and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure (HF) and ejection fraction (EF) >40% is unclear, thus Sac/Val according to ACEi/ARB status at baseline was assessed.

Methods And Results: This was a pre-specified analysis of Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF (PARAGLIDE-HF), a double-blind, randomized controlled trial of Sac/Val versus valsartan, categorizing patients according to baseline ACEi/ARB status. The primary endpoint was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8.

Histological staining of tick bite skin biopsies for spirochetes and Powassan virus RNA.

is a vector of several human pathogens in the United States, including the cause of Lyme disease, and Powassan virus (POWV), an emerging cause of severe encephalitis. Skin biopsies from tick bite sites are frequently collected and tested for the presence of spirochetes ( spp.), which remain elusive.

Windows in the ICU and Postoperative Delirium: A Retrospective Cohort Study.

Objectives: The ICU built environment-including the presence of windows-has long been thought to play a role in delirium. This study investigated the association between the presence or absence of windows in patient rooms and ICU delirium.

Design: Retrospective single institution cohort study.

State-Level Helmet Use Laws, Helmet Use, and Head Injuries in EMS Patients Involved in Motorcycle Collisions.

Objectives: Motorcycle helmets save lives and reduce serious injury after motorcycle collisions (MCC). In 2022, 18 states had laws requiring helmet use by motorcyclists aged ≥21 years. Our objective was to compare helmet use and head trauma in emergency medical services (EMS) patients involved in MCC in states with and without helmet use laws.

Carotid artery atherosclerosis: mechanisms of instability and clinical implications.

Cardiovascular disease remains a prominent cause of disability and premature death worldwide. Within this spectrum, carotid artery atherosclerosis is a complex and multifaceted condition, and a prominent precursor of acute ischaemic stroke and other cardiovascular events. The intricate interplay among inflammation, oxidative stress, endothelial dysfunction, lipid metabolism, and immune responses participates in the development of lesions, leading to luminal stenosis and potential plaque instability.

Impact of Baseline Thrombocytopenia on Early Outcomes in Patients With Acute Venous Thromboembolism.

Managing acute venous thromboembolism (VTE) in patients with thrombocytopenia is challenging. We used data from the RIETE registry to investigate the impact of baseline thrombocytopenia on early VTE-related outcomes, depending on the initial presentation as pulmonary embolism (PE) or isolated lower-limb deep vein thrombosis (DVT). From March 2003 to November 2022, 90 418 patients with VTE were included.

Epistaxis Versus Nonepistaxis Bleeding in Anticoagulated Patients With Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial.

Background: Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized.

Methods And Results: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) randomized 21 105 patients with atrial fibrillation and CHADS2 risk score ≥2 to higher-dose edoxaban regimen (60 mg daily, dose-reduced to 30 mg), lower-dose edoxaban regimen (30 mg, dose reduced to 15 mg, daily), or warfarin. Bleeds were adjudicated using International Society on Thrombosis and Haemostasis criteria.