Phosphoribosyl pyrophosphate synthetase 1 () associated retinal degeneration: an international study.

Introduction: Phosphoribosyl pyrophosphate synthetase 1 () is an X-linked gene critical for nucleotide metabolism. Pathogenic variants cause three overlapping phenotypes: Arts syndrome (severe neurological disease), Charcot-Marie-Tooth type 5 [CMTX5] (peripheral neuropathy), and non-syndromic sensorineural hearing loss (SNHL). Each may be associated with retinal dystrophy.

Expanding the Functions of KHSRP Protein: Insights into DNA G-Quadruplex Binding.

KHSRP (KH-type splicing regulatory protein) is a multifunctional nucleic acid-binding protein that regulates various cellular processes, with critical roles in controlling gene expression. G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in essential cellular activities, including gene expression, and are recognized as potential therapeutic targets in cancer. The biological functions of G4s are mediated by proteins making their formation highly dynamic within cells.

A Maternal Loss-of-Function Variant in KHDC3L Gene Causes a Range of Adverse Pregnancy Outcomes: A Case Report.

Background: The KHDC3L gene encodes a component of the subcortical maternal complex (SCMC). Biallelic mutations in this gene cause 5%-10% of biparental hydatidiform moles (BiHM), and a few maternal deletions in KHDC3L have been identified in women with recurrent pregnancy loss (RPL).

Method: In this study, we had a patient with a history of 10 pregnancy or neonatal losses, including spontaneous abortions, neonatal deaths, and molar pregnancy.

Sexual Health, Pleasure, Justice, and Well-Being in People With Rheumatic and Musculoskeletal Diseases: A Scoping Review Protocol.

Introduction: Sexual health, pleasure, justice (equity in sexual rights and experiences), and well-being are crucial determinants of health and life quality, yet often overlooked in the rheumatic and musculoskeletal diseases (RMD) field. However, this topic has received more attention recently, and there is a need to map the current literature to inform the direction of future studies. Hence, this protocol outlines a scoping review to systematically map existing evidence on sexual health in people with RMD, exploring key themes and identifying evidence gaps across multiple dimensions, including sexual well-being, justice and pleasure.

Advances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies.

FLT3 mutations are among the most common genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Significant advancements have been made in developing FLT3 inhibitors (FLT3Is), such as quizartinib, which have improved treatment outcomes in both newly diagnosed and relapsed/refractory AML. Resistance to FLT3Is remains a major clinical challenge, driven by diverse mechanisms including FLT3 point mutations, cellular escape pathways, and the influence of the bone marrow microenvironment.

Dissecting Methionine Oxidation by Hydrogen Peroxide in Proteins: Thermodynamics, Kinetics, and Susceptibility Descriptors.

The oxidation of Met residues in proteins is a complex process, where protein-specific structural and dynamical features play a relevant role in determining the reaction kinetics. Aiming to a full-side perspective, we report here a comprehensive characterization of Met oxidation kinetics by hydrogen peroxide in a leptin protein case study. To do that, we estimated the reaction-free energy profile of the Met oxidation via a QM/MM approach, while the kinetics of the formation of the reactive species were calculated using classical molecular dynamics (MD) simulations.

A Ge.F.I. Collaborative Study: Evaluating Reproducibility and Accuracy of a DNA-Methylation-Based Age-Predictive Assay for Routine Implementation in Forensic Casework.

The increasing interest in DNA methylation (DNAm) analysis within the forensic scientific community prompted a collaborative project by Ge.F.I.

Aligning corporate social responsibility with artificial intelligence in healthcare in the context of the post-COVID-19 recovery: a viewpoint.

Purpose: This study explores how corporate social responsibility (CSR) and artificial intelligence (AI) can be combined in the healthcare industry during the post-COVID-19 recovery phase. The aim is to showcase how this fusion can help tackle healthcare inequalities, enhance accessibility and support long-term sustainability.

Design/methodology/approach: Adopting a viewpoint approach, the study leverages existing literature and case studies to analyze the intersection of CSR and AI.

Unprecedented carbonic anhydrase inhibition mechanism: Targeting histidine 64 side chain through a halogen bond.

2,2'-Thio-bis(4,6-dichlorophenol), namely bithionol, is a small molecule endowed with a multifaceted bioactivity. Its peculiar polychlorinated phenolic structure makes it a suitable candidate to explore its potentialities in establishing interaction patterns with enzymes of MedChem interest, such as the human carbonic anhydrase (hCA) metalloenzymes. Herein, bithionol was tested on a panel of specific hCAs through the stopped-flow technique, showing a promising micromolar inhibitory activity for the hCA II isoform.

Greater improvement in insulin sensitivity per unit weight loss associated with tirzepatide versus semaglutide: An exploratory analysis.

Aims: To explore the relationship between weight loss and insulin sensitivity in response to tirzepatide or semaglutide.

Materials And Methods: We conducted a post hoc exploratory analysis of a 28-week, double-blind, randomized trial in people with type 2 diabetes treated with metformin, randomized to tirzepatide 15 mg, semaglutide 1 mg or placebo. We evaluated the relationship between change in body weight and change in insulin sensitivity determined from hyperinsulinemic euglycemic clamp (M value), or from mixed-meal tolerance testing (Matsuda index).

Evaluation of glomerular filtration rate estimation through plasma clearance of iohexol in seagulls (Larus michahellis).

Background: Current endogenous indicators utilised in avian medicine are not sensitive enough to detect renal disease in its early stages. Alternative markers ought to be examined as a result. The aim is to investigate the accuracy of limited-sampling models for glomerular filtration rate (GFR) in adult seagulls using plasma clearance of iohexol (IOX).

Outcome and safety 90 days after combined airway valve treatment of the right upper and middle lobes in patients with severe pulmonary emphysema.

Background: In COPD patients with severe right-sided emphysema, complete major and incomplete minor fissure, implantation of one-way valves in both the right upper (RUL) and middle lobes (ML) is a possible approach for endoscopic lung volume reduction. The aim of this retrospective analysis was to evaluate the response to therapy and the complication rate at 90 days (90d-FU) after combined RUL-ML valve implantation.

Methods: This retrospective, monocentric study included all patients from the Thoraxklinik Heidelberg who underwent RUL-ML valve treatment between 2012 and 2023 with available follow-up data.

Deep analysis of the major histocompatibility complex genetic associations using covariate analysis and haploblocks unravels new mechanisms for the molecular etiology of Elite Control in AIDS.

Introduction: We have reanalyzed the genomic data from the International Collaboration for the Genomics of HIV (ICGH), focusing on HIV-1 Elite Controllers (EC).

Methods: A genome-wide association study (GWAS) was performed, comparing 543 HIV-1 EC individuals with 3,272 uninfected controls (CTR) of European ancestry. 8 million single nucleotide polymorphisms (SNPs) and HLA class I and class II gene alleles were imputed to compare EC and CTR.

Effectiveness and tolerability of rimegepant in the acute treatment of migraine: a real-world, prospective, multicentric study (GAINER study).

Background: Rimegepant, a novel oral calcitonin gene-related peptide receptor antagonist, has been recently approved for the acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, no data is available regarding real-life effectiveness and tolerability. GAINER, a prospective, multicentric study, aimed to evaluate rimegepant effectiveness and tolerability in the real-world setting.

Lower Circulating Gas6 Levels Are Associated with Bulbar Phenotype and Faster Disease Progression in Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects the motor neurons in the brain and spinal cord. While the exact cause of ALS is not fully understood, a combination of genetic and environmental factors is believed to contribute to its development. Growth arrest-specific 6 (Gas6), a vitamin K-dependent protein, has been recognized to enhance oligodendrocytes and neurons' survival and is associated with different kinds of (neuro)inflammatory conditions.

High-resolution melting analysis for detection of nucleotide mutation markers in the polymerase-acidic (PA) gene of influenza virus that are associated with baloxavir marboxil resistance.

The I38T substitution in the influenza virus polymerase-acidic (PA) subunit is a resistance marker of concern for treatment with the antiviral baloxavir marboxil (BXM). Thus, monitoring PA/I38T mutations is of clinical importance. Here, we developed three rapid and sensitive assays for the detection and monitoring of the PA/I38T mutation.

Two FAM134B isoforms differentially regulate ER dynamics during myogenesis.

Endoplasmic reticulum (ER) plasticity and ER-phagy are intertwined processes essential for maintaining ER dynamics. We investigated the interplay between two isoforms of the ER-phagy receptor FAM134B in regulating ER remodeling in differentiating myoblasts. During myogenesis, the canonical FAM134B1 is degraded, while its isoform FAM134B2 is transcriptionally upregulated.

The combination of hyaluronic acids and collagen boosts human Achilles tendon-derived cell escape from inflammation and matrix remodeling in vitro.

Objective: This study explores whether hyaluronic acid (HA) of different molecular weights and collagen, given their role in tendon extracellular matrix maintenance, have a synergistic effect on human tendon-derived cells, with the aim to improve the treatment of tendinopathy.

Material: Human monocytes (CRL-9855™) and primary Achilles tendon-derived cells.

Treatment: The collagen/HA ratio was based on the formulation of the commercial food supplement TendoGenIAL™.

Respiratory Outcomes and Aspergillus Serology Following Elexacaftor/Tezacaftor/Ivacaftor Therapy in People with Cystic Fibrosis and a History of Aspergillus fumigatus Infection.

Purpose: The study evaluated the effects of elexacaftor/tezacaftor/ivacaftor (ETI) therapy in people with cystic fibrosis (pwCF) and a clinical history of Aspergillus fumigatus (AF) infection.

Methods: This prospective cohort study included pwCF who initiated ETI therapy and had received antifungal treatment in the preceding five years due to allergic bronchopulmonary aspergillosis (ABPA group) or other AF-related clinical manifestations (AF group). A control group of pwCF with no prior respiratory cultures positive for AF was also included.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases: version 1.0.

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neuro-Oncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). Brain metastases are the most common malignant central nervous system (CNS) tumors. PET imaging with radiolabeled amino acids and to lesser extent [F]FDG has gained considerable importance in the assessment of brain metastases, especially for the differential diagnosis between recurrent metastases and treatment-related changes which remains a limitation using conventional MRI.

Implementing recycling in the operating room: a single-center experience.

Background: Climate change poses significant challenges to global health, exacerbated by healthcare systems' carbon footprint and waste generation. Surgical activities contribute to these impacts, necessitating sustainable practices to mitigate environmental harm. This study aims to assess the feasibility and effectiveness of a recycling program in reducing waste, carbon emissions, and disposal costs in the operating rooms (ORs).