Population size, income and poor sanitation interact to explain widespread streamwater contamination by antidepressants in the Metropolitan Region of São Paulo.

The expansion of urban settlements over native environments may expose biodiversity to a host of emerging contaminants, with unintended ecological effects. This study evaluated patterns of contamination of streamwater by antidepressants in the Upper Tietê River Basin, a watershed of high social, economic and environmental relevance for comprising both the largest urban settlement in South America (the Metropolitan Region of São Paulo) and remnants of a globally important biodiversity hotspot (the Atlantic Rainforest). We sampled 53 third-order streams draining catchments regularly distributed across a gradient in urban cover.

AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

Suture Anchor Fixation of the Pediatric Posteromedial and Posterolateral Menisco-Tibial Ligament Complex Matches or Exceeds Native Tissue Strength: A Cadaveric Study.

Objectives: To compare the biomechanical strength and stiffness of the native posteromedial and posterolateral meniscotibial ligament complex (MTLC) to suture anchor repair of the MTLC.

Methods: Biomechanical testing was performed on 24 fresh-frozen pediatric human knees. Four conditions were tested: native posteromedial MTLC (n=14), native posterolateral MTLC (n=14), posteromedial MTLC repair (n=5), and posterolateral MTLC repair (n=5).

Towards measurements of absolute membrane potential in Bacillus subtilis using fluorescence lifetime.

Membrane potential (MP) changes can provide a simple readout of bacterial functional and metabolic state or stress levels. While several optical methods exist for measuring fast changes in MP in excitable cells, there is a dearth of such methods for absolute and precise measurements of steady-state membrane potentials (MPs) in bacterial cells. Conventional electrode-based methods for the measurement of MP are not suitable for calibrating optical methods in small bacterial cells.

Association between activity quotient and cause-specific mortality - A prospective cohort study of 0.5 million participants in Asia.

Background: Regular physical activity (PA) is important for reducing the risk of chronic diseases and improving overall health. Activity Quotient (AQ) is a novel metric that translates heart rate during PA into a weekly score, providing an objective measure of an individual's PA. We prospectively examined the association of AQ with cancer and cardiovascular (CVD) mortality outcomes, the two major causes of death, in a Taiwanese population.

Bridging the Gap: Advancing Latine Representation in Child and Adolescent Psychiatry Amidst US Demographic Shifts.

The United States is witnessing a demographic transformation, with the Latine population rapidly growing. As the nation's demographics evolve, the underrepresentation of Latine child and adolescent psychiatry (CAP) professionals compared to their proportion in the broader population underscores a pressing gap that requires prompt and focused efforts. This discrepancy is particularly concerning given the documented mental health inequities affecting Latine youth.

A spatiotemporal and machine-learning platform facilitates the manufacturing of hPSC-derived esophageal mucosa.

Human pluripotent stem cell-derived tissue engineering offers great promise for designer cell-based personalized therapeutics, but harnessing such potential requires a deeper understanding of tissue-level interactions. We previously developed a cell replacement manufacturing method for ectoderm-derived skin epithelium. However, it remains challenging to manufacture the endoderm-derived esophageal epithelium despite possessing a similar stratified epithelial structure.

RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.

Pre-mRNA 3' processing is an integral step in mRNA biogenesis. However, where this process occurs in the nucleus remains unknown. Here, we demonstrate that nuclear speckles (NSs), membraneless organelles enriched with splicing factors, are major sites for pre-mRNA 3' processing in human cells.

Cemiplimab in recurrent cervical cancer: Final analysis of overall survival in the phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial.

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9).

Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks.

The chain mediating role of social support and coping strategy: Type D personality and psychological distress among Chinese COPD patients.

This study examines how coping strategies and social support mediate the relationship between type D personality and psychological distress in COPD patients. A sample of 351 patients completed surveys on demographics, psychological distress (Kessler Psychological Distress Scale), social support (Social Support Self-Rating Scale), coping strategies (Chinese version of Medical Coping Modes Questionnaire), and type D personality (Type D Personality Scale). Using structural equation modeling (SEM) via AMOS 23.

Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

Transport mechanisms of the anthropogenic contaminant sulfamethoxazole in volcanic ash soils at equilibrium pH evaluated using the HYDRUS-1D model.

The volcanic soils in Chile, where a significant portion of agricultural activities take place, are impacted by the presence of veterinary drugs, including sulfamethoxazole (SMX). The study examines how different soil types influence the movement and retention of sulfamethoxazole (SMX) across four regions of Chile, focusing on conditions at a neutral pH of 7.0.

Association between diffusion tensor imaging measurements and cognitive performances in people with multiple sclerosis: A systematic review and meta-analysis.

Background: Alterations in structural connectivity of brain networks have been linked to complex cognitive functions in people with multiple sclerosis (PwMS). However, a definitive consensus on the optimal diffusion tensor imaging (DTI) markers as indicators of cognitive performance remains incomplete and inconclusive. This systematic review and meta-analysis aimed to explore the evidence on the correlation between DTI metrics and cognitive functions in PwMS.

An examination of ambulatory care code specificity utilization in ICD-10-CM compared to ICD-9-CM: implications for ICD-11 implementation.

Objective: The ICD-10-CM classification system contains more specificity than its predecessor ICD-9-CM. A stated reason for transitioning to ICD-10-CM was to increase the availability of detailed data. This study aims to determine whether the increased specificity contained in ICD-10-CM is utilized in the ambulatory care setting and inform an evidence-based approach to evaluate ICD-11 content for implementation planning in the United States.

Long-Term Safety and Efficacy of Bimekizumab in Axial Spondyloarthritis: 2-Year Results from Two Phase 3 Studies.

Objectives: Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)‑17F in addition to IL-17A, previously demonstrated efficacy and was well tolerated to 1 year in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA). Here, we report bimekizumab safety and efficacy to 2 years.

Methods: Patients completing week 52 in the phase 3 studies BE MOBILE 1 (nr-axSpA; NCT03928704) and 2 (r‑axSpA; NCT03928743) were eligible for an ongoing open‑label extension (OLE; NCT04436640).

SP-DTI: Subpocket-Informed Transformer for Drug-Target Interaction Prediction.

Motivation: Drug-target interaction (DTI) prediction is crucial for drug discovery, significantly reducing costs and time in experimental searches across vast drug compound spaces. While deep learning has advanced DTI prediction accuracy, challenges remain: (i) existing methods often lack generalizability, with performance dropping significantly on unseen proteins and cross-domain settings; (ii) current molecular relational learning often overlooks subpocket-level interactions, which are vital for a detailed understanding of binding sites.

Results: We introduce SP-DTI, a subpocket-informed transformer model designed to address these challenges through: (i) detailed subpocket analysis using the Cavity Identification and Analysis Routine (CAVIAR) for interaction modeling at both global and local levels, and (ii) integration of pre-trained language models into graph neural networks to encode drugs and proteins, enhancing generalizability to unlabeled data.

Early Reinitiation of Obesity Pharmacotherapy Post Laparoscopic Sleeve Gastrectomy in Youth: A Retrospective Cohort Study.

Background: Bariatric surgery is the most effective intervention for severe pediatric obesity, but a subset of youth experience suboptimal weight loss and/or recurrent weight gain. Early re-initiation of obesity pharmacotherapy postoperatively may improve outcomes, though this has not been evaluated in pediatric populations.

Methods: A retrospective cohort study at a tertiary care children's hospital evaluated the safety and efficacy of reintroducing obesity pharmacotherapy within six weeks after laparoscopic sleeve gastrectomy (LSG).

"The Brain is…": A Survey of the Brain's Many Definitions.

A reader of the peer-reviewed neuroscience literature will often encounter expressions like the following: 'the brain is a dynamic system', 'the brain is a complex network', or 'the brain is a highly metabolic organ'. These expressions attempt to define the essential functions and properties of the mammalian or human brain in a simple phrase or sentence, sometimes using metaphors or analogies. We sought to survey the most common phrases of the form 'the brain is…' in the biomedical literature to provide insights into current conceptualizations of the brain.

Assessing the Risk of Sexually Transmitted Infections among Men who have Sex with Men in San Francisco during COVID-19: A Socio-ecological Analysis.

Background: Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections, a disparity that has only worsened in recent years. During the COVID-19 pandemic, an overall increasing trend remained.

Methods: We utilized data from the MSM cycle of the National HIV Behavioral Surveillance (NHBS) study in San Francisco, California, conducted from June 2021 through December 2021, to identify socio-ecological disruptions during the COVID-19 pandemic that were associated with sexually transmitted infections.

Comparison of tibiofibular syndesmosis stability following treatment of proximal, middle, and distal third fibula fractures.

Purpose: While treatment modalities for Maisonneuve fractures involving the proximal third of the fibula are established, no studies to date have reported outcomes associated with syndesmotic-only fixation of middle third fibular shaft fractures. The purpose of this study was to evaluate outcomes associated with syndesmotic-only fixation in the treatment of Maisonneuve fractures involving the middle third of the fibula.

Methods: A retrospective review was conducted on 257 cases of syndesmotic ankle instability with associated fibular fractures at a level 1 trauma center between 2013 and 2023.

Revealing Toxicological Mechanisms of Small Molecules Using Chemical Biology.

Defining the underlying toxicological mechanisms of various small molecules is of utmost importance in understanding the pathogenesis of chemical exposure-related human diseases and developing safe and effective therapeutics. Herein, we discuss the toxicological mechanisms of different small molecules utilizing the different tools of chemical biology.

Safety of accessing brachial veins for large-bore upper extremity venous thrombectomy using ClotTriever Thrombectomy System.

Purpose: To evaluate access site adverse events following ClotTriever-mediated large-bore mechanical thrombectomy via small upper extremity deep veins (< 6-mm).

Materials And Methods: Twenty patients, including 24 upper extremity venous access sites, underwent ClotTriever-mediated large-bore thrombectomy of the upper extremity and thoracic central veins for symptomatic deep vein obstruction unresponsive to anticoagulation. Patients without follow-up venous duplex examinations (n = 3) were excluded.

Assessing Mitigation Translocation as a Tool to Reduce Human-great Horned owl Conflicts.

The great horned owl (Bubo virginianus) is a generalist predator that inhabits wide-ranging territories that are relatively stable throughout the year. These owls are also involved in a variety of human-owl conflicts, including killing of domestic poultry, predating colonially nesting seabirds and shorebirds, and pose a hazard to safe aircraft operations. Managing these conflict situations presents unique challenges as great horned owls are nocturnally active and occupy a wide range of habitats.