A human metabolic map of pharmacological perturbations reveals drug modes of action.

Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.

Drug-induced differential culturability in diverse strains of Mycobacterium tuberculosis.

Under stress, bacteria display selective growth propensities on solid and liquid media. For Mycobacterium tuberculosis (Mtb), differentially culturable bacteria have been found in tuberculosis (TB) patient sputa. We hypothesized that antibiotic treatment can induce selective culturability in Mtb.

Different keratoconus definitions can lead to substantial prevalence disparities in population-based studies.

This report explores the prevalence of keratoconus in a population-based cohort of adults aged 40 or older according to ten different definitions. All Rotterdam Study participants with reliable Pentacam scans and no prior corneal refractive surgery were cross-sectionally analysed (n = 2660). First, we applied a novel evidence-based definition.

Comparative analysis of salivary cytokine profiles in newly diagnosed pediatric patients with cancer and healthy children.

Salivary cytokines have the potential to serve as biomarkers for evaluating cancer progression and treatment response in specific cancer types. This study explored salivary cytokine profiles in pediatric cancer patients and healthy controls, examining changes during chemotherapy. We conducted a prospective study involving newly diagnosed cancer patients and healthy controls under 19 years old.

The Impact of Changing Physicians on Compliance with Management of Myopia Progression.

Background: The global incidence of high myopia is increasing, with projections indicating a rise from 3 to 10% of the global population by 2050. Effective treatment options exist to reduce myopia progression, but their success is contingent on patient adherence. This study assesses the impact of changes in treating physicians on adherence to therapy to control myopia progression.

Abiraterone acetate fixed-dosed combinations with ibuprofen-based therapeutic eutectic and deep eutectic solvents.

In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent.

Acute effect of aerobic exercise on inhibitory control and task-related heart rate variability in preadolescent children.

Objectives: To investigate whether a single session of aerobic exercise improves inhibitory control in preadolescent children and whether this effect is mediated by changes in parasympathetic activity.

Design: In this experimental study, an intervention and control group were pair-matched by age, sex and moderate-to-vigorous physical activity.

Method: 114 participants either completed a 20-min moderately-intense exercise bout on a cycling ergometer or watched a 20-min video.

Towards contrast-agnostic soft segmentation of the spinal cord.

Spinal cord segmentation is clinically relevant and is notably used to compute spinal cord cross-sectional area (CSA) for the diagnosis and monitoring of cord compression or neurodegenerative diseases such as multiple sclerosis. While several semi and automatic methods exist, one key limitation remains: the segmentation depends on the MRI contrast, resulting in different CSA across contrasts. This is partly due to the varying appearance of the boundary between the spinal cord and the cerebrospinal fluid that depends on the sequence and acquisition parameters.

Net Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: The net clinical effect of early vs later direct oral anticoagulant (DOAC) initiation after atrial fibrillation-associated ischemic stroke is unclear.

Objective: To investigate whether early DOAC treatment is associated with a net clinical benefit (NCB).

Design, Setting, And Participants: This was a post hoc analysis of the Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation (ELAN) open-label randomized clinical trial conducted across 103 sites in 15 countries in Europe, the Middle East, and Asia between November 6, 2017, and September 12, 2022, with a 90-day follow-up.

Simulation of adaptive immune receptors and repertoires with complex immune information to guide the development and benchmarking of AIRR machine learning.

Machine learning (ML) has shown great potential in the adaptive immune receptor repertoire (AIRR) field. However, there is a lack of large-scale ground-truth experimental AIRR data suitable for AIRR-ML-based disease diagnostics and therapeutics discovery. Simulated ground-truth AIRR data are required to complement the development and benchmarking of robust and interpretable AIRR-ML methods where experimental data is currently inaccessible or insufficient.

Management of Patients with Myocardial Injury After Noncardiac Surgery: A Retrospective Chart Review.

Background: Myocardial injury after noncardiac surgery (MINS) is associated with an increased incidence of cardiac morbidity and mortality. Little is known about how these patients are managed.

Methods: We performed a single-centre retrospective chart review of patients referred to a postoperative clinic with the diagnosis of MINS.

Couple-Based Intervention to Improve HIV Care Engagement for Women and their Partners in KwaZulu-Natal, South Africa: Outcomes of a Pilot Randomized Controlled Trial.

We evaluated a couple-based intervention targeting human immunodeficiency virus (HIV) care needs of women, with the option to support HIV-related needs of male partners. Adult women with HIV adherence difficulties in a monogamous relationship with a male partner for ≥6 months were recruited in KwaZulu-Natal, South Africa. Twenty couples were randomized (1:1) to either START Together, a five-session manualized behavioral intervention, or treatment as usual, adherence counseling referral.

A systematic review and meta-analyses of the temporal stability and convergent validity of risk preference measures.

Understanding whether risk preference represents a stable, coherent trait is central to efforts aimed at explaining, predicting and preventing risk-related behaviours. We help characterize the nature of the construct by adopting a systematic review and individual participant data meta-analytic approach to summarize the temporal stability of 358 risk preference measures (33 panels, 57 samples, 579,114 respondents). Our findings reveal noteworthy heterogeneity across and within measure categories (propensity, frequency and behaviour), domains (for example, investment, occupational and alcohol consumption) and sample characteristics (for example, age).

Prevalence of Ishihara Test Failures in a Large Cohort of Military Conscripts.

Purpose: Color vision deficiency (CVD) is a common vision disorder. It is predominantly caused by inherited photopigment abnormalities in the retina. The absolute number of cases with CVD is expected to increase worldwide with the growing population.

How should the advancement of large language models affect the practice of science?

Large language models (LLMs) are being increasingly incorporated into scientific workflows. However, we have yet to fully grasp the implications of this integration. How should the advancement of large language models affect the practice of science? For this opinion piece, we have invited four diverse groups of scientists to reflect on this query, sharing their perspectives and engaging in debate.

Noise-Tolerant Force Calculations in Density Functional Theory: A Surface Integral Approach for Wavelet-Based Methods.

We introduce a method for computing quantum mechanical forces through surface integrals over the stress tensor within the framework of the density functional theory. This approach avoids the inaccuracies of traditional force calculations using the Hellmann-Feynman theorem when applied to multiresolution wavelet representations of orbitals. By integrating the quantum mechanical stress tensor over surfaces that enclose individual nuclei, we achieve highly accurate forces that exhibit superior consistency with the potential energy surface.

Cartilage thickness can be accurately measured intraoperatively in total knee arthroplasty: A step further in calipered kinematic alignment.

Introduction: Kinematic alignment (KA) in total knee arthroplasty (TKA) is by definition a pure femoral resurfacing procedure aiming to restore the individual prearthritic anatomy. However, when a 2 mm compensation is systematically used on the worn side, the variability in cartilage thickness in the unworn compartment might alter the accuracy of the technique. This study aimed to validate two intraoperative femoral cartilage thickness measurement techniques by comparing them to the photographic method, which measures cartilage thickness through pixel analysis of bone-cut images.

Dose Evaluation and Optimization of Amoxicillin in Children Treated for Lyme Disease.

Amoxicillin is commonly used to treat erythema migrans in the first stage of Lyme disease in children, with a recommended dose of 50 mg/kg/day, administered three times a day (q8h). This model-based simulation study aimed to determine whether splitting the same daily dose into two administrations (q12h) would provide comparable drug exposure. A pharmacokinetic model suitable for a pediatric population (age: 1 month to 18 years, weight: 4-80 kg) was selected through a literature review.

AdvantAGE: Implementation and Evaluation of an Interprofessional Transitional Care Model for Frail Older Adults-Protocol of an Effectiveness-Implementation Hybrid Study.

Aim: To implement and evaluate an Advanced Practice Nurse-led transitional care model (AdvantAGE) to reduce rehospitalisation rates in frail older adults discharged from a Swiss geriatric hospital.

Design: The study adopts an effectiveness-implementation hybrid design (Type 1) to simultaneously evaluate the effectiveness of the care model and explore the implementation process.

Methods: The primary outcome, the 90-day rehospitalisation rate, will be evaluated using a matched-cohort design with a prospective intervention group and a retrospective control group.

Psychological stressors of imprisonment and coping of older incarcerated persons: a qualitative interview study.

Background: Imprisonment has a major impact on a person's psychological well-being. The proportion of older imprisoned persons is dramatically increasing worldwide, and they are likely to have greater physical and mental health needs compared to younger persons in prisons. However, there is currently a lack of research on the psychological stressors and the coping strategies of older imprisoned persons.

Effects of light on biological functions and human sleep.

The nonvisual effects of light in humans are mainly conveyed by a subset of retinal ganglion cells that contain the pigment melanopsin which renders them intrinsically photosensitive (= intrinsically photosensitive retinal ganglion cells, ipRGCs). They have direct connections to the main circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus and modulate a variety of physiological processes, pineal melatonin secretion, autonomic functions, cognitive processes such as attention, and behavior, including sleep and wakefulness. This is because efferent projections from the SCN reach other hypothalamic nuclei, the pineal gland, thalamus, basal forebrain, and the brainstem.

The influence of genotype on the natural history of types 1 - 3 spinal muscular atrophy.

The severity of spinal muscular atrophy (SMA) is inversely correlated with the number of survival of motor neuron 2 (SMN2) copies an individual has. This observational, retrospective analysis of natural history data included untreated individuals with a genetic diagnosis of types 1-3 SMA and stratified disease-related characteristics by SMN2 copy number. The outcomes investigated were time to: death, permanent ventilation, respiratory support, feeding support, scoliosis surgery, and achievement and loss of motor milestones.

Risk stratification for violent behavior in critically ill patients: Current assessment tools.

Background: Workplace violence (WPV) presents challenges in intensive care units (ICUs) calling for reliable prediction of violence. This narrative review aimed to identify and evaluate risk assessment tools from acute care settings which are or might be used to predict violent behavior in adult ICU patients focusing on their performance and clinical utility.

Methods: A screening of PubMed, Scopus and Google Scholar was conducted to identify risk scores used in the acute care setting such as emergency departments, hospitals and ICUs.