Exploring the druggability of the UEV domain of human TSG101 in search for broad-spectrum antivirals.

The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disruption of TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of host-oriented broad-spectrum antivirals with low susceptibility to resistance. TSG101 is a challenging target characterized by an extended and flat binding interface, low affinity for PTAP ligands, and complex binding energetics.

Childhood idiopathic nephrotic syndrome: recent advancements shaping future guidelines.

Childhood idiopathic nephrotic syndrome is an important pediatric kidney disease associated with significant morbidities and even mortality. Several guidelines have been developed to standardize the terminology and patient care among the pediatric nephrology community. Since the publication of these guidelines, there have been major breakthroughs in the disease management and the understanding of underlying pathogenesis through multi-omics investigations, including the identification of anti-nephrin autoantibodies, genetic susceptibility loci, and the pathogenic role of B cell subsets.

COMPOSIT study: evaluating osimertinib combination with targeted therapies in EGFR-mutated non-small cell lung cancer.

Introduction: The emergence of diverse resistance mechanisms after osimertinib therapy, including on-target epidermal growth factor receptor (EGFR) mutations and off-target alterations, warrants investigation of novel therapeutics to overcome these challenges and improve patient outcomes.

Methods: COMPOSIT was a French, retrospective, multicenter, cohort study of the effectiveness and tolerability of osimertinib in combination with other targeted therapies in patients with advanced EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC) who harbored other oncogenic drivers as primary or acquired resistance mechanisms. Real-world progression-free survival (rwPFS), overall survival (OS), and objective response rate (ORR) were the primary endpoints.

Impacts of acid mine drainage remediation in the largest gold mine of Latin America on natural water bodies in the Dominican Republic.

Impacts of the acid mine drainage (AMD) remediation are investigated on the largest gold mine in Latin America, located in the Dominican Republic. Geochemical analysis of suspended matter in water performed in 2022 on water bodies located downstream to the mine, namely, the Margajita River and Lake Hatillo, are compared with analyses made in 2007, before the AMD remediation. The results for the Margajita River show a strong decrease in heavy metal and metalloid concentrations in the dissolved phase for Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd, Sb, and Pb (between 89.

Kidney Function Decline After COVID-19 Infection.

Importance: COVID-19 infection has been associated with acute kidney injury. However, its possible association with long-term kidney function is not well understood.

Objective: To investigate whether kidney function decline accelerated after COVID-19 compared with after other respiratory tract infections.

Extracellular Optogenetics to Interrogate Unmodified Primary Cell Functions.

Optogenetics often requires genetic modification of the target cells to enable the expression of specific optogenetic tools, making it difficult to study primary cells in their native state. We have recently generated a fully extracellular optogenetic system for reversible light control of T cell receptor (TCR) activation on murine naïve T cells, a cell model that is very difficult to manipulate genetically. This molecular system is very versatile and can be easily modified to study different cell systems in different species.

Efficacy of a 2-MNG-Containing Depigmenting Serum in the Treatment of Post-Inflammatory Hyperpigmentation.

Background: Post-inflammatory hyperpigmentation (PIHP) predominantly affects patients with melanin-rich skin, significantly impacting them psychosocially due to more frequent and severe pigmentary changes. In this study, the efficacy of a novel depigmenting agent 2-mercaptonicotinoyl glycine (Melasyl) in a dermocosmetic (DC) serum formulation is assessed as a stand-alone treatment of PIHP without sunscreen.

Materials And Methods: Thirty-two Mauritian subjects aged 18-50 years of phototype IV-VI presenting mild acne (GEA2) and moderate to severe PIHP (PAHPI > 10) participated in this study.

Influence of pericardium on ventricular mechanical interdependence in an isolated biventricular working pig heart model.

The pericardium plays an important role in mechanical interactions between the right (RV) and left (LV) ventricles, referred to as ventricular interdependence. However, the exact mechanisms of its supportive role remain unknown. The present study aimed to evaluate specifically ventricular interdependence in a model of isolated biventricular working heart of large mammal, which is in absence of neurohormonal influence or series interactions, and to evaluate the impacts of intact pericardium on this phenomenon.

Receptor kinase LecRK-I.9 regulates cell wall remodelling during lateral root formation in Arabidopsis.

Assembling and remodelling the cell wall is essential for plant development. Cell wall dynamics is controlled by cell wall proteins, polysaccharide biosynthesis, and a variety of sensor and receptor systems. LecRK-I.

Evaluating the quality and readability of ChatGPT-generated patient-facing medical information in rhinology.

Purpose: The artificial intelligence (AI) chatbot ChatGPT has become a major tool for generating responses in healthcare. This study assessed ChatGPT's ability to generate French preoperative patient-facing medical information (PFI) in rhinology at a comparable level to material provided by an academic source, the French Society of Otorhinolaryngology (Société Française d'Otorhinolaryngologie et Chirurgie Cervico-Faciale, SFORL).

Methods: ChatGPT and SFORL French preoperative PFI in rhinology were compared by analyzing responses to 16 questions regarding common rhinology procedures: ethmoidectomy, sphenoidotomy, septoplasty, and endonasal dacryocystorhinostomy.

Evaluation of antibiotic treatment initiation and duration practices in primary care. Cross-sectional study in two French multi-professional health centers.

Antibiotic resistance poses a significant human and economic burden. In France, which ranks among the highest consumers of antibiotics in Europe, 93% of prescriptions are issued in primary care, primarily for respiratory tract infections. It is crucial to limit both the indications and the duration of antibiotic prescriptions, with recently updated recommendations in France aimed at achieving this goal.

Molecular Xenomonitoring (MX) allows real-time surveillance of West Nile and Usutu virus in mosquito populations.

West Nile Virus (WNV) and Usutu virus (USUV) circulate through complex cryptic transmission cycles involving mosquitoes as vectors, birds as amplifying hosts and several mammal species as dead-end hosts. Both viruses can be transmitted to humans through mosquito bites, which can lead to neuroinvasive and potentially fatal disease. Notably, WNV can also be transmitted through blood donations and organ transplants.

An interkinetic envelope surrounds chromosomes between meiosis I and II in C. elegans oocytes.

At the end of cell division, the nuclear envelope reassembles around the decondensing chromosomes. Female meiosis culminates in two consecutive cell divisions of the oocyte, meiosis I and II, which are separated by a brief transition phase known as interkinesis. Due to the absence of chromosome decondensation and the suppression of genome replication during interkinesis, it has been widely assumed that the nuclear envelope does not reassemble between meiosis I and II.

Treatments and Treatment Predictors in Patients With Substance Use Disorders and Comorbid Attention-Deficit/Hyperactivity Disorder: First Results From the International Naturalistic Cohort Study of ADHD and SUD (INCAS).

Treatment of attention-deficit/ hyperactivity disorder (ADHD) in patients with a substance use disorder (SUD) and comorbid ADHD (SUD +ADHD) may have positive effects on the outcome of both conditions, but controversy exists regarding the preferred ADHD treatment in these patients. Little is known about the treatments that are provided for these patients in routine addiction care practice and the factors that are associated with treatment provision. To describe the treatments provided in everyday clinical practice and to explore factors associated with ADHD treatment provision in patients with SUD +ADHD.

Estimating the proportion of beneficial mutations that are not adaptive in mammals.

Mutations can be beneficial by bringing innovation to their bearer, allowing them to adapt to environmental change. These mutations are typically unpredictable since they respond to an unforeseen change in the environment. However, mutations can also be beneficial because they are simply restoring a state of higher fitness that was lost due to genetic drift in a stable environment.

Endothelial Response to Blood-Brain Barrier Disruption in the Human Brain.

Cerebral endothelial cell (EC) injury and blood-brain barrier (BBB) permeability contribute to neuronal injury in acute neurological disease states. Preclinical experiments have used animal models to study this phenomenon, yet the response of human cerebral ECs to BBB disruption remains unclear. In our Phase 1 clinical trial (NCT04528680), we used low-intensity pulsed ultrasound with microbubbles (LIPU/MB) to induce transient BBB disruption of peri-tumoral brain in patients with recurrent glioblastoma.

Evaluation of a personalized auditory-cognitive training on the improvement of speech understanding in noise in cochlear implanted patients.

Objective: The cochlear implant is a commonly used implantable device for the auditory rehabilitation of severe bilateral sensorineural hearing loss. The effectiveness of the implant, depends on many factors, including intensive auditory training, which is crucial. Intelligibility in a noisy environment is a current issue and poses a major difficulty for implanted patients.

Intracisternal AAV9-MAG- Vector Reverses Motor Deficits in Adult Adrenomyeloneuropathy Mice.

Worldwide, thousands of male patients who carry ATP Binding Cassette Subfamily D Member 1 () mutations develop adrenomyeloneuropathy (AMN) in mid-adulthood, a debilitating axonopathy of the spinal cord. Today AAV gene therapy brings the most hope for this orphan disease. We previously reported that an AAV9-MAG- vector injected intravenously in the neonatal period prevented the disease in 2-year-old mice, the AMN mouse model.

Is Tumor Growth Influenced by the Bone Remodeling Process?

In this study, we develop a comprehensive model to investigate the intricate relationship between the bone remodeling process, tumor growth, and bone diseases such as multiple myeloma. By analyzing different scenarios within the Basic Multicellular Unit, we uncover the dynamic interplay between remodeling and tumor progression. The model developed developed in the paper are based on the well accepted Komarova's and Ayati's models for the bone remodeling process, then these models were modified to include the effects of the tumor growth.

Predicting corneal decompensation in Fuchs endothelial corneal dystrophy with Scheimpflug tomography and clinical parameters.

Purpose: This study aims to evaluate the efficacy of various tomographic indices, both established and novel, in predicting endothelial decompensation leading to either spontaneous corneal transplantation or transplantation following cataract surgery in patients with Fuchs endothelial corneal dystrophy (FECD).

Methods: In this cross-sectional, retrospective study, we reviewed the files of 93 eyes from 54 FECD patients undergoing regular follow-up. We recorded clinical metrics such as morning visual disturbance (MVD) and corrected distance visual acuity.

Optimization and analytical validation of the Allplex HPV28 genotyping assay for use in first-void urine samples.

Despite first-void urine (FVU) being increasingly recognized as a credible specimen for human papillomavirus (HPV) detection, there is a lack of well-validated testing methods providing full quantitative genotyping required for vaccine impact monitoring from FVU samples. The Allplex HPV28 assay, capable of individually detecting 28 HPV genotypes, presents a promising method. We aimed to evaluate its genotype-specific performance on FVU samples, following optimization of FVU preanalytics.

A Copper-Binding Peptide with Therapeutic Potential against Alzheimer's Disease: From the Blood-Brain Barrier to Metal Competition.

Alzheimer's disease (AD) is the most common form of dementia worldwide. AD brains are characterized by the accumulation of amyloid-β peptides (Aβ) that bind Cu and have been associated with several neurotoxic mechanisms. Although the use of copper chelators to prevent the formation of Cu-Aβ complexes has been proposed as a therapeutic strategy, recent studies show that copper is an important neuromodulator that is essential for a neuroprotective mechanism mediated by Cu binding to the cellular prion protein (PrP).

Disentangling collective coupling in vibrational polaritons with double quantum coherence spectroscopy.

Vibrational polaritons are formed by strong coupling of molecular vibrations and photon modes in an optical cavity. Experiments have demonstrated that vibrational strong coupling can change molecular properties and even affect chemical reactivity. However, the interactions in a molecular ensemble are complex, and the exact mechanisms that lead to modifications are not fully understood yet.