The Value of ROH Metrics for Predicting Morbidity: Insights From a Large Cohort Analysis of Chromosomal Microarray.

This retrospective cohort study aimed to define the optimal Regions of Homozygosity (ROH) size cut-offs for prediction of morbidity, based on 13 483 Chromosomal Microarray Analyses (CMA). Receiver operating characteristic (ROC) curves were generated, and area under the curve (AUC) was used to assess the predictive capability of total ROH percentage (TRPS), ROH number and ROH segment size in distinguishing between healthy (n=6,196) and affected (n=6,839) cohorts. The metrics were examined for telomeric and interstitial segments, distinct TRPS categories, and across different ancestral origins.

Galectin-3 secreted by triple-negative breast cancer cells regulates T cell function.

Triple-negative breast cancer (TNBC) is an aggressive subtype that accounts for 10-15 % of breast cancer. Current treatment of high-risk early-stage TNBC includes neoadjuvant chemo-immune therapy. However, the substantial variation in immune response prompts an urgent need for new immune-targeting agents.

Assessment of insulin-degrading enzyme inhibitor for the treatment of corneal erosion in a rat model.

Background: Diabetes poses a risk to diabetic keratopathy in up to two-thirds of patients. Insulin-degrading enzyme (IDE) is a protease that can break down insulin and several growth factors and may impair wound healing. Increased IDE levels have been found in fluid from diabetic skin ulcers.

A Variable Clinical Presentation of Hemoglobin City of Hope.

Hemoglobin City of Hope (Hb-COH), NC_000011.9(NM_000518.5):c.

Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies.

Background: The role of circulating endothelial progenitor cells (cEPCs) in vascular repair and their association to cardiovascular protection is well established.

Objectives: We examined the effect of proprotein convertase subtilisin kexin type 9 monoclonal antibodies (PCSK9 mAb) on cEPCs in adults with hypercholesterolemia and cardiovascular disease, aiming to establish a pleotropic class effect.

Methods: Non-interventional prospective study in patients with cardiovascular disease treated with either evolocumab or alirocumab.

Cobalt Toxicity Induces Retinopathy and Optic Neuropathy in Mice.

Purpose: To explore the effect of cobalt toxicity on vision.

Methods: A total of 103 wild-type (WT) mice were injected with cobalt chloride by two routes in different concentrations: single intravenous (IV) high or low doses (total, n = 43); or daily repeated intraperitoneal (IP) high (three days) or low (28 days, 56 days) dose, and low-dose cobalt with added minocycline (56 days) (total, n = 60); 10 WT mice served as a control group. An additional group of 17 immunodeficient NOD scid gamma (NSG) mice were injected IV or IP with cobalt, and 10 NSG mice served as control.

2q13 Distal Microdeletion: Considering Evidence for an Emerging Syndrome Versus Susceptibility Locus: Twenty-Five New Cases and Review of the Literature.

This study investigates distal 2q13 microdeletion, presenting the largest cohort to date, including prenatal cases, alongside a comprehensive literature review. A retrospective analysis was conducted on distal 2q13 microdeletions from clinical charts and laboratory reports. The cohort was divided into "clinically indicated" and "not-clinically indicated" groups based on the reason for chromosomal microarray testing.

GPATCH11 variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment.

Here we conduct a study involving 12 individuals with retinal dystrophy, neurological impairment, and skeletal abnormalities, with special focus on GPATCH11, a lesser-known G-patch domain-containing protein, regulator of RNA metabolism. To elucidate its role, we study fibroblasts from unaffected individuals and patients carrying the recurring c.328+1 G > T mutation, which specifically removes the main part of the G-patch domain while preserving the other domains.

MicroRNAs as Biomarkers for Uveitis in Juvenile Idiopathic Arthritis.

Purpose: Uveitis associated with juvenile idiopathic arthritis (JIA-U) is a clinically silent vision-impairing disease. Early detection and aggressive treatment are crucial for optimal visual outcome. Alterations in levels of microRNAs (miRNAs) are characteristic of autoimmune diseases.

Factors Associated With Biologic Therapy After Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis.

Background: Patients with ulcerative colitis (UC) undergoing proctocolectomy and ileal pouch-anal anastomosis (IPAA) may eventually require biologic therapy. Factors associated with biologic therapy after IPAA have not been previously studied.

Methods: All patients with UC after total proctocolectomy and IPAA who were followed at Rabin Medical Center comprehensive pouch clinic and who consented to prospective observational follow-up were included.

Structure-Function Correlation in Cobalt-Induced Brain Toxicity.

Cobalt toxicity is difficult to detect and therefore often underdiagnosed. The aim of this study was to explore the pathophysiology of cobalt-induced oxidative stress in the brain and its impact on structure and function. Thirty-five wild-type C57B16 mice received intraperitoneal cobalt chloride injections: a single high dose with evaluations at 24, 48, and 72 h ( = 5, each) or daily low doses for 28 ( = 5) or 56 days ( = 15).

Higher risk and earlier onset glaucoma in Cushing's syndrome.

Purpose: Glaucoma incidence in patients with endogenous Cushing's syndrome (CS) has never been established. We aim to assess the risk for glaucoma among CS patients compared to controls and determine the age of disease onset.

Methods: A nationwide retrospective matched-cohort study of patients with endogenous CS diagnosed between 2000 and 2023.

Novel TSPO Ligand 2-Cl-MGV-1 Can Counteract Lipopolysaccharide Induced Inflammatory Response in Murine RAW264.7 Macrophage Cell Line and Lung Models.

We assessed the anti-inflammatory activity of the TSPO ligand 2-Cl-MGV-1. Lipopolysaccharide (LPS) was used to induce inflammatory response in a murine RAW264.7 macrophage model (LPS: 100 ng/mL) and a mouse model (C57BL/6) of lung inflammation (LPS: 5 mg/kg).

Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy.

T cell inhibitory mechanisms prevent autoimmune reactions, while cancer immunotherapy aims to remove these inhibitory signals. Chronic ultraviolet (UV) exposure attenuates autoimmunity through promotion of poorly understood immune-suppressive mechanisms. Here we show that mice with subcutaneous melanoma are not responsive to anti-PD1 immunotherapy following chronic UV irradiation, given prior to tumor injection, due to the suppression of T cell killing ability in skin-draining lymph nodes.

A Discrepancy in the Reports on Life Events Between Parents and Their Depressed Children Is Associated with Lower Responsiveness to SSRI Treatment.

Exposure to a range of stressful life events (SLE) is implicated in youth psychopathology. Previous studies point to a discrepancy between parents'/children's reports regarding stressful life events. No study systematically assessed the correlation between such discrepancies and psychopathology in depressed youth.

Fetal whole genome sequencing as a clinical diagnostic tool: Advantages, limitations and pitfalls.

Genome-wide sequencing, which includes exome sequencing and genome sequencing, has revolutionized the diagnostics of genetic disorders in both postnatal and prenatal settings. Compared to exome sequencing, genome sequencing enables the detection of many additional types of genomic variants, although this depends on the bioinformatics pipelines used. Variant classification might vary among laboratories.