Metals in Motion: Understanding Labile Metal Pools in Bacteria.

Metal ions are essential for all life. In microbial cells, potassium (K) is the most abundant cation and plays a key role in maintaining osmotic balance. Magnesium (Mg) is the dominant divalent cation and is required for nucleic acid structure and as an enzyme cofactor.

Athlete Selective Androgen Receptor Modulators Abuse: A Systematic Review.

Background: Selective androgen receptor modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. Because of their performance-enhancing implications, SARMs are increasingly abused by athletes. To date, SARMs have no Food and Drug Administration approved use, and recent case reports associate the use of SARMs with deleterious effects such as drug-induced liver injury, myocarditis, and tendon rupture.

Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).

Evaluation of Safety and Efficacy of a Single Lorecivivint Injection in Patients with Knee Osteoarthritis: A Multicenter, Observational Extension Trial.

Introduction: Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials.

Methods: This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36 months as data inferences became limited.

Medical & Socioeconomic Risk Factors Associated with Lack of Neurodevelopmental Evaluation Following Neonatal Cardiac Surgery.

Neonates with congenital heart disease (CHD) who undergo cardiopulmonary bypass (CPB) are at high-risk for unfavorable neurodevelopmental (ND) outcomes and are recommended for ND evaluation (NDE); however, poor rates have been reported. We aimed to identify risk factors associated with lack of NDE. This single-center retrospective observational study included neonates < 30 days old who underwent CPB and survived to discharge between 2012 and 2018.

Historical redlining and clustering of present-day breast cancer factors.

Purpose: Historical redlining, a 1930s-era form of residential segregation and proxy of structural racism, has been associated with breast cancer risk, stage, and survival, but research is lacking on how known present-day breast cancer risk factors are related to historical redlining. We aimed to describe the clustering of present-day neighborhood-level breast cancer risk factors with historical redlining and evaluate geographic patterning across the US.

Methods: This ecologic study included US neighborhoods (census tracts) with Home Owners' Loan Corporation (HOLC) grades, defined as having a score in the Historic Redlining Score dataset; 2019 Population Level Analysis and Community EStimates (PLACES) data; and 2014-2016 Environmental Justice Index (EJI) data.

Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.

Unsupervised self-organising map classification of Raman spectra from prostate cell lines uncovers substratified prostate cancer disease states.

Prostate cancer is a disease which poses an interesting clinical question: Should it be treated? Only a small subset of prostate cancers are aggressive and require removal and treatment to prevent metastatic spread. However, conventional diagnostics remain challenged to risk-stratify such patients; hence, new methods of approach to biomolecularly sub-classify the disease are needed. Here we use an unsupervised self-organising map approach to analyse live-cell Raman spectroscopy data obtained from prostate cell-lines; our aim is to exemplify this method to sub-stratify, at the single-cell-level, the cancer disease state using high-dimensional datasets with minimal preprocessing.

Thyroid disorders in patients with human immunodeficiency virus infection: a meta-analysis.

Background: Thyroid disorders have significant clinical sequelae, including impaired growth in children, metabolic abnormalities, and impaired cognitive function. However, available studies on burden of thyroid diseases in people with human immunodeficiency virus (HIV), particularly its prevalence and its interaction with HIV related factors (like CD4 count), are controversial. This review aimed to provide a comprehensive summary and analysis on the extent of thyroid dysfunctions in this population.

Machine learning models predicting risk of revision or secondary knee injury after anterior cruciate ligament reconstruction demonstrate variable discriminatory and accuracy performance: a systematic review.

Background: To summarize the statistical performance of machine learning in predicting revision, secondary knee injury, or reoperations following anterior cruciate ligament reconstruction (ACLR), and to provide a general overview of the statistical performance of these models.

Methods: Three online databases (PubMed, MEDLINE, EMBASE) were searched from database inception to February 6, 2024, to identify literature on the use of machine learning to predict revision, secondary knee injury (e.g.

Factors influencing communication issues during hospital discharge for older adults in 11 high-income countries: a secondary analysis of the 2021 International Health Policy Survey.

Objectives: To determine the prevalence of hospital discharge communication problems with older adults, compare them across countries and determine factors associated with those problems.

Design: Secondary analysis of cross-sectional survey data.

Setting: 2021 Commonwealth Fund International Health Policy (IHP) Survey of Older Adults conducted across 11 high-income countries, including Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the UK and the USA.

Influencing basic behavioral mechanisms of action while targeting daily walking in sedentary adults at risk for cardiovascular disease: randomised factorial design protocol.

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, though it may be prevented by increasing physical activity (PA). When behaviour change techniques (BCTs) are bundled together, they increase PA, though which individual BCTs increase PA (and the behavioural mechanism of action (MoA) responsible for said increase) have not been studied. The aim of this study is to conduct a randomised factorial experiment to determine which of four BCTs significantly engage the proposed MoA-self-efficacy for PA-in adults at risk for CVD.

Endoscopic management of carefully selected asymptomatic body stuffers.

The guidelines from the European and American Societies for Gastrointestinal Endoscopy discourage endoscopic retrieval of drug bags in body stuffers. However, recent evidence challenges this stance, demonstrating successful bag retrieval without fatal outcomes. We present two distinct cases illustrating varying outcomes of intervention.

The public health risks of counterfeit pills.

Synthetic illicit drugs, such as nitazenes and fentanyls, are becoming commonplace in countries around the world, including in Europe, Australia, and Latin America, which raises concern for overdose crises like those seen in North America. An important dimension of the risk represented by synthetic drugs is the fact that they are increasingly packaged in counterfeit pill form. These pills-often indistinguishable from authentic pharmaceuticals-have substantially widened the scope of populations susceptible to synthetic drug overdose in North America (eg, among adolescents experimenting with pills or tourists from the USA seeking psychoactive medications from pharmacies in Mexico).

How is Telehealth Used to Increase Access to Specialty Palliative Care? A Systematic Review.

Context: Specialty palliative care remains inaccessible for many with serious illness, especially in rural areas. Telehealth may be one solution.

Objectives: To describe how telehealth increases access to specialty palliative care, describe facilitators and barriers to its use, and summarize evidence of patient benefits.

Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

Low-dose aspirin use in low-risk nulliparous pregnancies: a systematic review and meta-analysis of randomized controlled trials.

Objective: To assess the efficacy of low-dose aspirin in the prevention of adverse outcomes in low-risk, nulliparous singleton pregnancies.

Data Sources: PubMed, Ovid MEDLINE, Scopus, Cochrane Library, clinicaltrials.gov, and ScienceDirect were searched from their inception to August 5, 2023.

Convolutional Neural Networks for the segmentation of hippocampal structures in postmortem MRI scans.

Background: The hippocampus plays a crucial role in memory and is one of the first structures affected by Alzheimer's disease. Postmortem MRI offers a way to quantify the alterations by measuring the atrophy of the inner structures of the hippocampus. Unfortunately, the manual segmentation of hippocampal subregions required to carry out these measures is very time-consuming.