Safety, pharmacokinetics, and pharmacodynamics of sofnobrutinib, a novel non-covalent BTK inhibitor, in healthy subjects: First-in-human phase I study.

Bruton's tyrosine kinase (BTK) is a potential therapeutic target for allergic and autoimmune diseases. This first-in-human phase I study evaluated safety, pharmacokinetic, and pharmacodynamic profiles of sofnobrutinib (formerly AS-0871), a highly selective, orally available, non-covalent BTK inhibitor, in healthy adult subjects. Single ascending doses (SAD; 5-900 mg) and multiple ascending doses (MAD; 50-300 mg twice daily [b.

Integrated measure for training transfer in nursing practice: Development and validation study.

Background: The persistent knowledge-practice gap in nursing, where competencies gained through continuing professional development fail to integrate into practice, remains a significant challenge. Effective transfer of acquired knowledge and skills to the workplace is essential for bridging this gap. However, there is a lack of comprehensive, validated instruments to assess factors influencing training transfer in nursing practice.

Refining the CHA2DS2VASc risk stratification scheme: shall we drop the sex category criterion?

Aims: The CHA2DS2VASc score is recommended for stroke risk stratification in patients with atrial fibrillation (AF). This score assigns one extra point to female sex based on evidence from the early 2000s, suggesting higher thromboembolic risk in women. This incremental risk of thromboembolism in women has decreased over time between 2007 and 2018, becoming non-significant in recent years.

Drug-Drug Interaction Management with the Novel Anti-Cytomegalovirus Agents Letermovir and Maribavir: Guidance for Clinicians.

Letermovir and maribavir have demonstrated efficacy in the prevention and treatment, respectively, of immunosuppressed patients with cytomegalovirus (CMV) infection and disease. These patients often have polypharmacy making them at risk for drug-drug interactions. Both letermovir and maribavir can be perpetrators and victims of drug-drug interactions.

QCD challenges from pp to AA collisions: 4th edition.

This paper is a write-up of the ideas that were presented, developed and discussed at the fourth International Workshop on QCD Challenges from pp to AA, which took place in February 2023 in Padua, Italy. The goal of the workshop was to focus on some of the open questions in the field of high-energy heavy-ion physics and to stimulate the formulation of concrete suggestions for making progresses on both the experimental and theoretical sides. The paper gives a brief introduction to each topic and then summarizes the primary results.

Chemically Stable Group IV-V Transition Metal Carbide Thin Films in Hydrogen Radical Environments.

Hydrogen is a crucial element in the green energy transition. However, its tendency to react with and diffuse into surrounding materials poses a significant challenge. Therefore, developing coatings to protect system components in hydrogen environments (molecular, radicals (H*), and plasma) is essential.

Evaluating the antifibrotic potential of naringenin, asiatic acid, and icariin using murine and human precision-cut liver slices.

Liver fibrosis is an exaggerated wound healing response defined by the excessive accumulation of extracellular matrix. This study investigated the antifibrotic potential of naringenin (NRG), asiatic acid (AA), and icariin (ICA) using murine and human precision-cut liver slices (PCLS). These natural products have shown promise in animal models, but human data are lacking.

Exploring cognitive overload in adults with visual impairment: The association between concentration and fatigue.

Significance: This research contributes to the concept of cognitive overload and the association between concentration and fatigue in individuals with visual impairment (VI). Gaining more insight into these and other factors explaining cognitive overload is essential for a better understanding, prevention, and treatment of fatigue severity in individuals with VI.

Purpose: Individuals with VI need to use additional cognitive resources to compensate for their loss of vision.

The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap.

In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed.

Kinetics of imidazole propionate from orally delivered histidine in mice and humans.

Imidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated in type 2 diabetes (T2D). However, the source of histidine and the role of the gut microbiota remain unclear. We conducted an intervention study in mice and humans, comparing ImP kinetics in mice on a high-fat diet with varying histidine levels and antibiotics, and assessed ImP levels in healthy and T2D subjects with histidine supplementation.

Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap.

Background And Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS.

tRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory.

Post-transcriptional modification of RNA regulates gene expression at multiple levels. ALKBH8 is a tRNA-modifying enzyme that methylates wobble uridines in a subset of tRNAs to modulate translation. Through methylation of tRNA-selenocysteine, ALKBH8 promotes selenoprotein synthesis and regulates redox homeostasis.

Serum neurofilament light and glial fibrillary acidic protein levels are not associated with wearing-off symptoms in natalizumab-treated multiple sclerosis patients.

Background: Biomarkers of neuronal and axonal damage (serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP)) may provide insight into the aetiology of natalizumab wearing-off symptoms (WoSs).

Objectives: We investigated the longitudinal association between and predictive value of sNfL and sGFAP and the occurrence of WoS in MS patients treated with natalizumab.

Methods: We performed longitudinal measurements of sNfL and sGFAP in NEXT-MS trial participants who completed a questionnaire about WoS.

A pilot study into the use of phosphorescent sand in glass transfer studies.

Phosphorescent sand is proposed as a model system to study the behaviour of glass particles and support their activity level interpretation. Pilot experiments into the properties of the phosphorescent particles indicate that they are comparable to glass. Phosphorescent particles are charged effectively using ultraviolet illumination.

Self-reported compliance with infection prevention and control of healthcare workers in Dutch residential care facilities for people with intellectual and developmental disabilities during the COVID-19 pandemic: A cross-sectional study.

Background: Compliance of healthcare workers (HCWs) with infection prevention and control (IPC) is crucial to resident safety. Nevertheless, HCWs' compliance with IPC has not been previously studied in a disability care setting.

Objective: To assess levels of self-reported compliance with IPC among HCWs in residential care facilities (RCFs) for people with intellectual and developmental disabilities (IDDs), and to assess whether IPC compliance varies among different professional groups.

Design of the VOILA-intervention study: A 12-week nutrition and resistance exercise intervention in metabolic or mobility compromised Dutch older adults and the response on immune-metabolic, gut and muscle health parameters.

Background: Exercise and nutrition interventions can slow ageing-induced decline in physiology. However, effects are heterogeneous and usually studied separately per outcome domain. In the VOILA study, we simultaneously study various health outcomes relevant for older adults and the inter-individual heterogeneity in response to a lifestyle intervention.

Autoinducer-2 relieves soil stress-induced dormancy of Bacillus velezensis by modulating sporulation signaling.

The collective behavior of bacteria is regulated by quorum sensing (QS). Autoinducer-2 (AI-2) is a common QS signal that regulates the behavior of both Gram-positive and Gram-negative bacteria. Despite the plethora of processes described to be influenced by AI-2 in diverse Gram-negative bacteria, the AI-2-regulated processes in Bacilli are relatively unexplored.

Vitamin D status, physical activity and long-term mortality risk after myocardial infarction: a prospective analysis in the Alpha Omega Cohort.

Aim: In post-myocardial infarction (MI) patients, we examined independent and combined associations of vitamin D status and physical activity (PA) with long-term mortality, including effect modification by health determinants.

Methods: We conducted a prospective analysis of 4,837 MI patients from the Alpha Omega Cohort. Baseline blood samples (2002-2006) were assessed for plasma 25-hydroxyvitamin D (25[OH]D) levels using LC-MS/MS.

Over-the-counter short-acting β-agonist purchase and asthma-related health outcomes: a post hoc analysis of the SABINA III study.

This post-hoc analysis of the SABINA III study evaluated the association of short-acting β-agonist (SABA) prescriptions and self-reported over-the-counter (OTC) SABA purchase in the previous 12 months with asthma-related outcomes using multivariable regression models in 4556 patients (mean age, 48.9 years). Of the 2810 patients prescribed ≥3 SABA canisters, 776 (27.

Electrochemical and Non-Electrochemical Pathways in the Electrocatalytic Oxidation of Monosaccharides and Related Sugar Alcohols into Valuable Products.

In this contribution, we review the electrochemical upgrading of saccharides (e.g., glucose) and sugar alcohols (e.

Local administration of immunotherapy for patients with skin cancer: A systematic review.

Since the introduction of immune checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors, survival has improved significantly for patients with irresectable and metastatic skin cancer, including cutaneous squamous cell cancer and melanoma. However, systemic administration of these drugs is associated with immune related adverse events (irAEs), which can be severe, irreversible and even fatal. To reduce the risk of irAEs associated with systemic exposure to immunotherapeutic drugs, local administration of low doses could be considered.