Response to azathioprine treatment in autoimmune hepatitis is dependent on glutathione transferase genotypes.

Background: Azathioprine (AZA) is part of the standard treatment for autoimmune hepatitis (AIH). The first step in the complex bioconversion of AZA to active metabolites is mediated by glutathione transferases (GSTs).

Aims: Elucidate the association between GSTM1 and GSTT1 copy number variation (CNV), genetic variation in GSTA2, GSTP1, and inosine-triphosphate-pyrophosphatase, and the response to AZA in AIH.

HP1 Promotes the Centromeric Localization of ATRX and Protects Cohesion by Interfering Wapl Activity in Mitosis.

Background: α thalassemia/mental retardation syndrome X-linked (ATRX) serves as a part of the sucrose nonfermenting 2 (SNF2) chromatin-remodeling complex. In interphase, ATRX localizes to pericentromeric heterochromatin, contributing to DNA double-strand break repair, DNA replication, and telomere maintenance. During mitosis, most ATRX proteins are removed from chromosomal arms, leaving a pool near the centromere region in mammalian cells, which is critical for accurate chromosome congression and sister chromatid cohesion protection.

Design and early progress of the Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial.

Background: The usual antithrombotic treatment for symptomatic intracranial atherosclerotic stenosis (ICAS) consists of dual treatment with clopidogrel and aspirin for 90 days followed by aspirin alone but the risk of recurrent stroke remains high up to 12 months. The Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial was designed to determine whether other combinations of dual antithrombotic therapy are superior to clopidogrel and aspirin.

Methods: CAPTIVA is an ongoing, prospective, double-blinded, three-arm clinical trial at over 100 sites in the United States and Canada that will randomize 1683 high-risk subjects with a symptomatic infarct attributed to 70-99% stenosis of a major intracranial artery to 12 months of treatment with (1) ticagrelor (180 mg loading dose, then 90 mg twice daily), (2) low-dose rivaroxaban (2.

Evaluation of Silver Recovery from High-Sulphur Mining Waste Using Thiourea-Oxalate System.

Mine tailings are a byproduct of mineral extraction and often pose an environmental challenge due to the contamination of soil and water bodies with dissolved metals. However, this type of waste offers the opportunity for the recovery of valuable metals such as silver (Ag). In the present investigation, an integral analysis of a sample of tailings was carried out, addressing granulometry, elemental composition, neutralization potential (NP), and acid potential (AP), as well as mineralogy, for the dissolution of silver from this type of waste.

The HOX Gene Family's Role as Prognostic and Diagnostic Biomarkers in Hematological and Solid Tumors.

The HOX gene family encodes for regulatory transcription factors that play a crucial role in embryogenesis and differentiation of adult cells. This highly conserved family of genes consists of thirty-nine genes in humans that are located in four clusters, A-D, on different chromosomes. While early studies on the HOX gene family have been focused on embryonic development and its related disorders, research has shifted to examine aberrant expression of HOX genes and the subsequent implication in cancer prediction and progression.

Causal Estimands for Analyses of Averted and Avertible Outcomes due to Infectious Disease Interventions.

During the coronavirus disease (COVID-19) pandemic, researchers attempted to estimate the number of averted and avertible outcomes due to vaccination campaigns to quantify public health impact. However, the estimands used in these analyses have not been previously formalized. It is also unclear how these analyses relate to the broader framework of direct, indirect, total, and overall causal effects under interference.

CD14CD16 classical monocyte subset secreting IL-1ß and IL-10 is associated with 'Tuberculosis Resisters' phenotype.

Mycobacterium tuberculosis (M.tb) infection can lead to various outcomes, including active tuberculosis or latent tuberculosis infection (LTBI). Household contacts of TB cases have a high risk of acquiring LTBI.

Contextual Factors that Influence Antibiotic Prescribing: A Discrete Choice Experiment of GP Registrars.

Introduction: Antimicrobial resistance is a global emergency related to overprescribing of antibiotics. Few studies have explored how prescribing behaviours may change as the consequence of changing resistance. Understanding how contextual factors influence antibiotic prescribing will facilitate improved communication strategies to promote appropriate antibiotic prescribing.

Paracetamol prior to catheter balloon insertion for labor induction - A randomized controlled trial: paracetamol prior to catheter-balloon insertion for labor induction.

Background: Assessing maternal pain and satisfaction following administration of paracetamol vs. placebo prior to catheter balloon placement.

Methods: Primiparous women at term admitted for medically-indicated labor induction were randomized to receive intravenous paracetamol 1 gram in 100cc normal saline (N=71) or placebo of 100cc normal saline (N=70) prior to catheter balloon insertion.

Outcomes of chronic limb-threatening ischemia revascularization in patients with chronic kidney disease in the BEST-CLI trial.

Background: Chronic limb-threatening ischemia (CLTI) in patients with chronic kidney disease (CKD) has a high risk of poor outcomes. We aimed to compare the outcomes of lower extremity revascularization in patients with CLTI stratified by CKD severity in patients enrolled in the prospective, randomized Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial.

Methods: The BEST-CLI trial dataset was queried to categorize patients into three groups according to CKD stage.

Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality.

Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I-III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy.

Phage therapy could be key to conquering persistent bacterial lung infections in children.

Persistent bacterial lung infections in children lead to significant morbidity and mortality due to antibiotic resistance. In this paper, we describe how phage therapy has shown remarkable efficacy in preclinical and clinical studies, demonstrating significant therapeutic benefits through various administration routes. Ongoing trials are evaluating its safety and effectiveness against different pathogens.

Evidence-Based Application of Natriuretic Peptides in the Evaluation of Chronic Heart Failure With Preserved Ejection Fraction in the Ambulatory Outpatient Setting.

Background: Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient setting is unknown because previous studies lacked objective reference standards.

Methods: Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation.

Burnt Plastic (Pyroplastic) from the M/V Ship Fire and Plastic Spill Contain Compounds That Activate Endocrine and Metabolism-Related Human and Fish Transcription Factors.

In May 2021, the M/V ship fire disaster led to the largest maritime spill of resin pellets (nurdles) and burnt plastic (pyroplastic). Field samples collected from beaches in Sri Lanka nearest to the ship comprised nurdles and pieces of pyroplastic. Three years later, the toxicity of the spilled material remains unresolved.

Using NMR Spectroscopy to Evaluate Metal-Ligand Bond Covalency for the f Elements.

ConspectusUnderstanding f element-ligand covalency is at the center of efforts to design new separations schemes for spent nuclear fuel, and is therefore of signficant fundamental and practical importance. Considerable effort has been invested into quantifying covalency in f element-ligand bonding. Over the past decade, numerous studies have employed a variety of techniques to study covalency, including XANES, EPR, and optical spectroscopies, as well as X-ray crystallography.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Psychometric Validation of the Hemophilia Functional Ability Scoring Tool (Hemo-FAST).

Background:  The Hemophilia Functional Ability Scoring Tool (Hemo-FAST), consisting of a patient-reported outcome (PRO) part and a clinician-reported outcome (ClinRO) part, was developed as a rapid and effective tool to assess functional mobility in clinical practice. This study (NCT04731701) aimed to validate the psychometric properties of Hemo-FAST for assessment of joint health in people with haemophilia (PwH).

Methods:  PwH A or B aged ≥18 years completed questionnaires including the PRO part of Hemo-FAST and the short-form 36 health survey (SF-36) during one study visit.

Peripheral blood age-sensitive immune markers in multiple sclerosis: relation to sex, cytomegalovirus status, and treatment.

Background: Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood.

Methods: We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays.

Deep Learning-Enabled Assessment of Right Ventricular Function Improves Prognostication After Transcatheter Edge-to-Edge Repair for Mitral Regurgitation.

Background: Right ventricular (RV) function has a well-established prognostic role in patients with severe mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) and is typically assessed using echocardiography-measured tricuspid annular plane systolic excursion. Recently, a deep learning model has been proposed that accurately predicts RV ejection fraction (RVEF) from 2-dimensional echocardiographic videos, with similar diagnostic accuracy as 3-dimensional imaging. This study aimed to evaluate the prognostic value of the deep learning-predicted RVEF values in patients with severe MR undergoing TEER.

Differentiation of Atherosclerotic Carotid Plaque Components With Dual-Energy Computed Tomography.

Objectives: Carotid plaque vulnerability is a strong predictor of recurrent ipsilateral stroke, but differentiation of plaque components using conventional computed tomography (CT) is suboptimal. The aim of our study was to evaluate the ability of dual-energy CT (DECT) to characterize atherosclerotic carotid plaque components based on the effective atomic number and effective electron density using magnetic resonance imaging (MRI) and, where possible, histology as the reference standard.

Materials And Methods: Patients with recent cerebral ischemia and a ≥2-mm carotid plaque underwent computed tomography angiography and MRI.

Incorporating Lymph Node Size at CT as an N1 Descriptor in Clinical N Staging for Lung Cancer.

Background The ninth edition of the TNM classification for lung cancer revised the N2 categorization, improving patient stratification, but prognostic heterogeneity remains for the N1 category. Purpose To define the optimal size cutoff for a bulky lymph node (LN) on CT scans and to evaluate the prognostic value of bulky LN in the clinical N staging of lung cancer. Materials and Methods This retrospective study analyzed patients who underwent lobectomy or pneumonectomy for lung cancer between January 2013 and December 2021, divided into development (2016-2021) and validation (2013-2015) cohorts.

Evaluation of ocular surface temperature in post-COVID-19 patients with different degrees of fever via infrared thermal imaging.

This study aimed to evaluate ocular surface temperature (OST) in post-COVID-19 patients with different degrees of fever via infrared thermal imaging. There were 16 participants (32 eyes) in the control group, 22 participants (44 eyes) in the moderate and low post-COVID-19 fever group (M & L fever group), and 18 participants (36 eyes) in the high post-COVID-19 fever group (H fever group). All participants underwent an ophthalmic slit lamp examination and ocular thermography.

Accelerated enzyme engineering by machine-learning guided cell-free expression.

Enzyme engineering is limited by the challenge of rapidly generating and using large datasets of sequence-function relationships for predictive design. To address this challenge, we develop a machine learning (ML)-guided platform that integrates cell-free DNA assembly, cell-free gene expression, and functional assays to rapidly map fitness landscapes across protein sequence space and optimize enzymes for multiple, distinct chemical reactions. We apply this platform to engineer amide synthetases by evaluating substrate preference for 1217 enzyme variants in 10,953 unique reactions.

Location-specific net water uptake and malignant cerebral edema in acute anterior circulation occlusion ischemic stroke.

Background And Purpose: Early identification of malignant cerebral edema (MCE) in patients with acute ischemic stroke is crucial for timely interventions. We aimed to identify regions critically associated with MCE using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) to evaluate the association between location-specific-net water uptake (NWU) and MCE.

Materials And Methods: This multicentre, retrospective cohort study included patients with acute ischemic stroke following large anterior circulation occlusion.

Green synthesis of Ag-Fe bimetallic nanoparticles using fungal filtrates: unlocking multifunctional medical and environmental applications.

The current investigation focuses on synthesizing Ag-Fe bimetallic nanoparticles (AgFe-BMNPs) using cell-free filtrates of the as a novel fungal reducing agent. The optical, morphological, and surface properties of these fungus-fabricated AgFe-BMNPs and their monometallic counterparts (AgNPs and FeNPs) were analyzed using sophisticated nanotechnology instruments. The UV-visible spectrum showed peaks at 231 nm and 415 nm for BMNPs and 450 nm and 386 nm for AgNPs and FeNPs, respectively.