Novel and potent MICA/B antibody is therapeutically effective in mutant lung cancer models.

Background: Concurrent (STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could pose an alternative therapeutic strategy through activation of natural killer (NK) cells.

Methods: Expression of NK cell activating ligands in NSCLC cell line and patient data were analyzed. Cell surface expression of MICA/B in NSCLC cell lines was determined through flow cytometry while ligand shedding in both patient blood and cell lines was determined through ELISA.

Phase 1/2 trial of XPO1 inhibitor selinexor plus docetaxel in previously treated, advanced KRAS mutant non-small cell lung cancer.

Purpose: Patients with KRAS mutant non-small cell lung cancer (NSCLC) have limited therapeutic options. Based on activity of nuclear export inhibition in preclinical models, we evaluated this strategy in previously treated advanced KRAS mutant NSCLC.

Patients And Methods: The primary outcome of this multi-center phase 1/2 dose escalation trial of selinexor plus docetaxel was safety and tolerability.

Association among diabetes, cardiovascular disease and mortality in patients hospitalised for COVID-19: an analysis of the American Heart Association COVID-19 CVD Registry.

Objective: To examine inpatient COVID-19-related outcomes among patients with and without diabetes alone or with a history of established heart failure (HF) or established atherosclerotic cardiovascular disease (ASCVD).

Design: Observational study; longitudinal analysis of registry data.

Setting: Hospitals in the USA reporting to the American Heart Association (AHA) COVID-19 Registry from January 2020 to May 2021.

Neurological Monitoring and Management for Adult Extracorporeal Membrane Oxygenation Patients: Extracorporeal Life Support Organization Consensus Guidelines.

Background: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support.

Methods: These guidelines are based on clinical practice consensus recommendations and scientific statements.

Numb provides a fail-safe mechanism for intestinal stem cell self-renewal in adult midgut.

Stem cell self-renewal often relies on asymmetric fate determination governed by niche signals and/or cell-intrinsic factors but how these regulatory mechanisms cooperate to promote asymmetric fate decision remains poorly understood. In adult midgut, asymmetric Notch (N) signaling inhibits intestinal stem cell (ISC) self-renewal by promoting ISC differentiation into enteroblast (EB). We have previously showed that epithelium-derived BMP promotes ISC self-renewal by antagonizing N pathway activity (Tian and Jiang, 2014).

ETV2 transcriptionally activates Rig1 gene expression and promotes reprogramming of the endothelial lineage.

ETV2 is an essential transcription factor as Etv2 null murine embryos lack all vasculature, blood and are lethal early during embryogenesis. Previous studies have established that ETV2 functions as a pioneer factor and directly reprograms fibroblasts to endothelial cells. However, the underlying molecular mechanisms regulating this reprogramming process remain incompletely defined.

Creeping Fat-Derived Free Fatty Acids Induce Hyperplasia of Intestinal Muscularis Propria Muscle Cells: A Novel Link Between Fat and Intestinal Stricture Formation in Crohn's Disease.

Background & Aims: In Crohn's disease, wrapping of mesenteric fat around the bowel wall, so-called "creeping fat," is highly associated with strictures. The strongest contributor to luminal narrowing in strictures is a thickening of the human intestinal muscularis propria (MP). We investigated creeping fat-derived factors and their effect on mechanisms of human intestinal MP smooth muscle cell (HIMC) hyperplasia.

Outcomes of patients with acute liver failure not listed for liver transplantation: A cohort analysis.

Background: Acute liver failure (ALF) is a rare condition leading to morbidity and mortality. Liver transplantation (LT) is often required, but patients are not always listed for LT. There is a lack of data regarding outcomes in these patients.

Results of a National Delphi consensus on the outpatient management of pediatric psychogenic nonepileptic seizures in the United States.

Background And Objectives: The purpose of this study was to develop national consensus based on expert opinion on the optimal outpatient care model of pediatric psychogenic nonepileptic seizures (PNES).

Methods: A core working group (CWG) within the PNES special interest group of the Pediatric Epilepsy Research Consortium was established. The CWG developed a rigorous scoring rubric to select experts in pediatric PNES within the United States of America and a three-round Delphi study was conducted to assess consensus on key components of the management of pediatric PNES in the outpatient setting.

Education Research: Educating Child Neurology Residents About Psychogenic Nonepileptic Seizures: A Needs Assessment.

Background And Objectives: Psychogenic nonepileptic seizures (PNES) are difficult to differentiate from epileptic seizures (ES) even for neurologists who see these conditions frequently. This difficulty is due to overlapping semiologic findings between the 2 diagnoses. Previous studies have shown that trainees, including neurology trainees, are not accurate in differentiating PNES from ES.

Safety and Efficacy of Adipose-Derived Mesenchymal Stem Cell Therapy for Ischemic Heart Disease: A Systematic Review.

Background: Cell therapy using adipose-derived mesenchymal stem cells (ADSCs) shows great potential as a treatment for cardiovascular diseases.

Objective: We conducted a systematic review to describe the safety and efficacy of ADSCs in ischemic heart disease.

Methods: We searched PubMed/MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS (from inception to March 2024) for clinical studies involving ADSCs in patients with ischemic heart disease.

Implementation and impact of a surgical dashboard on pediatric tonsillectomy outcomes: A quality improvement study.

Introduction: In pediatric tonsillectomy management, the consistent tracking of surgical outcomes and adherence to guidelines are vital. This study explores how a surgical dashboard can serve as a tool in research analysis, translating AAO-HNSF guidelines into measurable performance improvements.

Methods: Using a prospective registry from three pediatric hospitals, a Tableau dashboard was constructed to graphically visualize key demographic and postoperative outcomes (including intensive care unit [ICU] utilization, 30-day emergency department (ED) visits, and postoperative bleed rates) in children undergoing tonsillectomy from 2020 to 2024.

Urinary Free Glycosaminoglycans Identify Adults at High Risk of Developing Early-stage High-grade Bladder Cancer.

Background And Objective: Screening for bladder cancer (BCa) could reduce mortality via early detection of early-stage high-grade (Ta/T1 N0 M0 grade 2-3) disease. Noninvasive biomarkers could aid in screening, but current markers lack the specificity required. The urinary free glycosaminoglycan profile (GAGome) is a promising biomarker for early detection of BCa metabolism.

Role of the X Chromosome in Alzheimer Disease Genetics.

Importance: The X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD.

Objectives: To perform the first large-scale X chromosome-wide association study (XWAS) of AD.

Design, Setting, And Participants: This was a meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer's Disease Genetics Consortium, the Alzheimer's Disease Sequencing Project, the UK Biobank, the Finnish health registry, and the US Million Veterans Program.

Impact of virtual simulation vs. Video refresher training on NRP simulation performance: a randomized controlled trial.

Objective: To assess the impact of NRP virtual simulations (eSim™), video or no refresher training, on simulation performance, six months after a provider course; and to evaluate eSim™ acceptability.

Study Design: In this multi-site randomized controlled trial, NRP providers from four U.S.

Upregulation of Xbp1 in NPY/AgRP neurons reverses diet-induced obesity and ameliorates leptin and insulin resistance.

The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes are not fully understood. In this study, we show that induction of the unfolded protein response transcription factor, spliced X-box binding protein 1 (Xbp1s), in Agouti-Related Peptide (AgRP) neurons alone, is sufficient to not only protect against but also significantly reverse diet-induced obesity (DIO) as well as improve leptin and insulin sensitivity, despite activation of endoplasmic reticulum stress. We also demonstrate that constitutive expression of Xbp1s in AgRP neurons contributes to improved insulin sensitivity and glucose tolerance.

Hypoxia-driven heterogeneous expression of α5 integrin in glioblastoma stem cells is linked to HIF-2α.

Despite numerous molecular targeted therapies tested in glioblastoma (GBM), no significant progress in patient survival has been achieved in the last 20 years in the overall population of GBM patients except with TTfield setup associated with the standard of care chemoradiotherapy. Therapy resistance is associated with target expression heterogeneity and plasticity between tumors and in tumor niches. We focused on α5 integrin implicated in aggressive GBM in preclinical and clinical samples.

Loss of transient receptor potential channel 5 causes obesity and postpartum depression.

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain.

Clinical and economic implications of false-positive heparin-induced thrombocytopenia immunoassays: utility of the 4T score.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition induced by platelet-activating IgG antibodies that recognize PF4/heparin complexes. Diagnosis of HIT relies on enzyme immunologic assays (EIAs) and functional assays [serotonin release assay (SRA)]. Our institution uses a latex immunoturbidimetric assay (LIA), which has shown a positive-predictive value (PPV) of 55.

ClickSAM: Fine-tuning Segment Anything Model using click prompts for ultrasound image segmentation.

The newly released Segment Anything Model (SAM) is a popular tool used in image processing due to its superior segmentation accuracy, variety of input prompts, training capabilities, and efficient model design. However, its current model is trained on a diverse dataset not tailored to medical images, particularly ultrasound images. Ultrasound images tend to have a lot of noise, making it difficult to segment out important structures.