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Managing drug–drug interactions with mavacamten : A focus on combined use of antiarrhythmic drugs and anticoagulants

Mavacamten is a selective, allosteric, and reversible cardiac myosin inhibitor, representing the first disease-specific treatment for obstructive hypertrophic cardiomyopathy (HCM) that targets the core pathophysiological mechanism of this condition. Clinical evidence supports its efficacy in improving symptoms, cardiac function, and remodeling, thereby supplementing established treatment regimens.

Are competent citizens critical democrats? Political resources and evaluations of democratic institutions

This article examines how cognitive resources such as internal efficacy and political knowledge relate to citizens’ ability to evaluate democratic institutions. Using original survey data from the United States (N = 1093), we find, first, that internal efficacy is associated with more positive assessments of democratic institutions in general. Conversely, political knowledge is associated with mor

The role of trust in the international climate negotiations

In this paper, we examine the role of trust in the international climate negotiations. We (1) identify forms of trust inferred from institutional designs, (2) analyse effects of institutional design on social and political trust and (3) describe the relationship between social and political trust in international climate change negotiations. We do this by combining document analysis, literature re

Functional characterization of tRNA-derived small RNAs in stem cells

Transfer RNA (tRNA)-derived RNAs (tDRs) are abundant small RNAs with emerging roles in development and tumorigenesis. Increasing evidence indicates that tDRs regulate stem cell homeostasis and differentiation, often altered in disease, highlighting the importance of fully characterizing their role in stem cell biology. Multiple studies point to protein synthesis as a crucial target of tDR-mediated

Age at onset as an index of genetic heterogeneity in major psychiatric and substance use disorders

Background Robust clinical indices of etiologic heterogeneity for psychiatric disorders are rare. We investigate whether age at onset (AAO) reflects genetic heterogeneity, utilizing Genetic Risk Ratios (GRR) derived from Family Genetic Risk Scores (FGRS). Methods We examined, in individuals born in Sweden 1940-2003, whether AAO for five primary disorders - drug use disorder (DUD), alcohol use diso

Guidelines for the correct use of the nomenclature of biochemical indices of bone status : a position statement of the Joint IOF Working Group and IFCC Committee on Bone Metabolism

The presented guidelines are an update of the position paper, endorsed by the International Osteoporosis Foundation (IOF), on nomenclature of bone markers published over 2 decades ago. Novel insight into bone biology and pathophysiology of bone disorders has highlighted the increasing relevance of new and known mediators implicated in various aspects of bone metabolism. This updated guideline prop

Enhanced diffusion through multivalency

The diffusion of macromolecules, nanoparticles, viruses, and bacteria is essential for targeting hosts or cellular destinations. While these entities can bind to receptors and ligands on host surfaces, the impact of multiple binding sites—referred to as multivalency—on diffusion along strands or surfaces is poorly understood. Through numerical simulations, we have discovered a significant accelera

A two-phase epigenome-wide four-way gene–smoking interaction study of overall survival for early-stage non-small cell lung cancer

High-order interactions associated with non-small cell lung cancer (NSCLC) survival may elucidate underlying molecular mechanisms and identify potential therapeutic targets. Our previous work has identified a three-way interaction among pack-year of smoking (the number of packs of cigarettes smoked per day multiplied by the number of years the person has smoked) and two DNA methylation probes (cg0

Transcellular transport of 18F-deoxyglucose via facilitative glucose channels in experimental peritoneal dialysis

Background: Local and systemic side effects of glucose remain major limitations of peritoneal dialysis (PD). Glucose transport during PD is thought to occur via inter-endothelial pathways, but recent results show that phloretin, a general blocker of facilitative glucose channels (glucose transporters [GLUTs]), markedly reduced glucose diffusion capacity indicating that some glucose may be transfer

Impact of Varying Velocities and Solvation Boxes on Alchemical Free-Energy Simulations

Alchemical free-energy perturbation (FEP) is an accurate and thermodynamically stringent way to estimate relative energies for the binding of small ligands to biological macromolecules. It has repeatedly been pointed out that a single simulation normally stays near the starting point in phase space and therefore underestimates the uncertainty of the results. Therefore, it is better to run an ensem