Discovery, Optimization, and Preclinical Pharmacology of EP652, a METTL3 Inhibitor with Efficacy in Liquid and Solid Tumor Models.

METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.

HIV and hospitals between knowledge and stigma.

The advent of effective antiretroviral treatments has led to the reclassification of HIV as a chronic disease for those on an effective treatment plan. However, the well-being of individuals with HIV is adversely affected by a number of factors, including stigma and discrimination, which hinder access to healthcare. To address this issue, it is first necessary to understand the current levels of knowledge and stigma surrounding HIV, and consequently, HIV Outcomes Italy has created a survey with the aim of assessing these levels.

Transforming achiral semiconductors into chiral domains with exceptional circular dichroism.

Highly concentrated solutions of asymmetric semiconductor magic-sized clusters (MSCs) of cadmium sulfide, cadmium selenide, and cadmium telluride were directed through a controlled drying meniscus front, resulting in the formation of chiral MSC assemblies. This process aligned their transition dipole moments and produced chiroptic films with exceptionally strong circular dichroism. -factors reached magnitudes as high as 1.

The impact of intermittent preventive treatment in school aged children with dihydroartemisinin piperaquine and artesunate amodiaquine on IgG response against six blood stage Plasmodium falciparum antigens.

Several interventional strategies have been implemented in malaria endemic areas where the burden is high, that include among others, intermittent preventive treatment (IPT), a tactic that blocks transmission and can reduce disease morbidity. However, the implementation IPT strategies raises a genuine concern, intervening the development of naturally acquired immunity to malaria which requires continuous contact with parasite antigens. This study investigated whether dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) IPT in schoolchildren (IPTsc) impairs IgG reactivity to six malaria antigens.

A new computational framework for simulating airway resistance, fraction of exhaled nitric oxide, and diffusing capacity for nitric oxide.

In this paper, we present a new computational framework for the simulation of airway resistance, the fraction of exhaled nitric oxide, and the diffusion capacity for nitric oxide in healthy and unhealthy lungs. Our approach is firstly based on a realistic representation of the geometry of healthy lungs as a function of body mass, which compares well with data from the literature, particularly in terms of lung volume and alveolar surface area. The original way in which this geometry is created, including an individual definition of the airways in the first seven generations of the lungs, makes it possible to consider the heterogeneous nature of the lungs in terms of perfusion and ventilation.

Assessment of the underreporting of rhinitis in patients with asthma: A MASK-air® real-world study.

Rhinitis is a common comorbidity in patients with asthma. However, the frequency of underreported rhinitis in asthma is not known. In this study, we aimed to assess the characteristics of patients with self-reported asthma and no self-reported rhinitis, as well as the extent of the underreporting of rhinitis.

Physiological effects of nasal high flow therapy during exercise in patients with chronic obstructive pulmonary disease: A crossover randomised controlled trial.

Background: Nasal high flow (NHF) has been proposed to sustain high intensity exercise in people with COPD, but we have a poor understanding of its physiological effects in this clinical setting.

Research Question: What is the effect of NHF during exercise on dynamic respiratory muscle function and activation, cardiorespiratory parameters, endurance capacity, dyspnoea and leg fatigue as compared to control intervention.

Study Design And Methods: Randomized single-blind crossover trial including COPD patients.

Origin and In-Office Treatment of Retrograde Cricopharyngeus Dysfunction.

Importance: Retrograde cricopharyngeus dysfunction (R-CPD) is an emerging disorder associated with disabling symptoms. The origin of R-CPD remains unknown.

Objective: To investigate the development of symptoms, diagnosis approach, and therapeutic outcomes of R-CPD in patients treated with in-office botulinum toxin injection (BTI) into the cricopharyngeus.

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial.

Importance: Triple-negative breast cancer is an aggressive subtype with a high incidence in young patients, a high incidence in non-Hispanic Black women, and a high risk of progression to metastatic cancer, a devastating sequela with a 12- to 18-month life expectancy. Until recently, one strategy for treating early-stage triple-negative breast cancer was chemotherapy after surgery. However, it was not known whether the addition of immune therapy to postsurgery chemotherapy would be beneficial.

Cross-cultural validity of the Five-Factor Personality Inventory for ICD-11 across nine countries and validation of a French translation.

This study aimed to assess measurement invariance for the Five-Factor Inventory for (Oltmanns & Widiger, 2020) across nine national samples from four continents ( = 6,342), and to validate a French translation in seven French-speaking national samples. All were convenience samples of adults. Exploratory factor analyses supported a four-factor structure in the French-speaking Western samples (Belgium, Canada, France, and Switzerland) while a three-factor structure was preferred in the French-speaking African samples (Burkina Faso and Togo), and no adequate structure was found in the Indian sample.

Evaluation of severe hypoglycemia management in children and adolescents with type 1 diabetes in a Belgian tertiary pediatric care center: impact of intranasal glucagon and cost analysis.

To evaluate the management and costs of severe hypoglycemia (SH) in children and adolescents with type 1 diabetes (T1D) in our Belgian tertiary pediatric care center. In the EPI-GLUREDIA study, clinical parameters from children and adolescents with T1D were retrospectively analyzed from July 2017 to June 2024. The characteristics of SH and its treatment were collected during the medical consultation following the SH episode.

First branchial cleft anomalies in children: long-term outcome in 16 patients.

Introduction: First branchial cleft anomalies (FBCA) are rare congenital head and neck malformations, often subject to incorrect diagnosis and treatment. We present our experience with FBCA, focusing on clinical presentation, diagnosis, perioperative relation to the facial nerve, surgical approach, complications and patient satisfaction.

Methods: A consecutive cohort of 16 patients undergoing surgical treatment for FBCA between 1999 and 2021 was analyzed.

Cost-effective evaluation of modified ochre soil and its combination with cationic polyacrylamide for municipal wastewater sludge conditioning.

One of the most costly stages of activated sludge wastewater treatment plants is the treatment and dewatering of waste sludge. Chemical conditioning of sludge, as one of the most widespread methods to enhance sludge dewaterability, accounts for a significant portion of operational expenses due to the consumption of expensive polymeric compounds. This research aims to assess the cost-effectiveness of ochre soil, modified with hydrochloric acid, as an affordable mineral for conditioning waste sludge in an activated sludge system.

Ventral Rectopexy: An International Expert Panel Consensus and Review of Contemporary Literature.

Background: Ventral rectopexy has become increasingly utilized in the surgical management of rectal prolapse. There is a need for a contemporary evaluation of the role of the procedure and description of its use in clinical practice.

Objective: To create an international consensus on ventral rectopexy.

Real-world observational data on olfactory dysfunction of the Smell & Taste Clinic of UZ Leuven (Belgium) from 2021-2024.

Background: The COVID-19 pandemic led to a surge in olfactory dysfunction (OD), increasing the need for specialized care. Thi study explores the prevalence, characteristics, and clinical implications of OD in a specialized Smell & Taste Clinic established at the ENT-HNS department of the University Hospitals Leuven (UZ Leuven) in 2021.

Methodology: We included consecutive patients with OD in the observational longitudinal ProspeRo'Scent registry at UZ Leuven between September 2021 and April 2024.

Examining priorities and investments made through the Global Financing Facility for maternal and newborn health: a sub-analysis on quality.

Improving quality of care could avert most of the 4.5 million maternal and neonatal deaths and stillbirths that occur each year. The Global Financing Facility (GFF) aims to catalyse the national scale-up of maternal and newborn health (MNH) interventions through focused investments.

A scoping review and expert consensus on digital determinants of health.

Objective: To map how social, commercial, political and digital determinants of health have changed or emerged during the recent digital transformation of society and to identify priority areas for policy action.

Methods: We systematically searched MEDLINE, Embase and Web of Science on 24 September 2023, to identify eligible reviews published in 2018 and later. To ensure we included the most recent literature, we supplemented our review with non-systematic searches in PubMed® and Google Scholar, along with records identified by subject matter experts.

Measuring adjustment of siblings of children with disabilities: psychometric properties across translations, age groups and informants.

Objectives: The Negative Adjustment Scale (NAS) is used to measure adjustment to having a sibling with a disability. However, several adaptations to the scale have been made, and implementation varies across studies and countries. This study examined the psychometric properties across different versions and provides directions for future use and development of the NAS.

The progress in the field of clinical staging for mental disorders within the last decade: an updated systematic review.

Introduction: Clinical staging aims to refine psychiatric diagnosis by describing mental disorders on a continuum of disorder progression, with the pragmatic goal of improved treatment planning and outcome prediction. The first systematic review on this topic, published a decade ago, included 78 papers, and identified separate staging models for schizophrenia, unipolar depression, bipolar disorder, panic disorder, substance use disorder, anorexia, and bulimia nervosa. The current review updates this review by including new proposals for staging models and by systematically reviewing research based upon full or partial staging models since 2012.

Impact of the Angular Alignment on the Crystal Field and Intrinsic Doping of Bilayer Graphene/BN Heterostructures.

The ability to tune the energy gap in bilayer graphene makes it the perfect playground for the study of the effects of internal electric fields, such as the crystalline field, which are developed when other layered materials are deposited on top of it. Here, we introduce a novel device architecture allowing simultaneous control over the applied displacement field and the crystalline alignment between two materials. Our experimental and numerical results confirm that the crystal field and electrostatic doping due to the interface reflect the 120° symmetry of the bilayer graphene/BN heterostructure and are highly affected by the commensurate state.

Scientific and Regulatory Policy Committee Points to Consider: Proposal and Recommendations to Reduce Euthanasia of Control Nonhuman Primates in Nonclinical Toxicity Studies.

Nonhuman primates (NHPs) have been and remain a highly valuable animal model with an essential role in translational research and pharmaceutical drug development. Based on current regulatory guidelines, the nonclinical safety of novel therapeutics should be evaluated in relevant nonclinical species, which commonly includes NHPs for biotherapeutics. Given the practical and ethical limitations on availability and/or use of NHPs and in line with the widely accepted guiding "3Rs" (replace, reduce, and refine) principles, many approaches have been considered to optimize toxicity study designs to meaningfully reduce the number of NHPs used.