Randomized Controlled Trial of the Effects of High-Dose Ondansetron on Clinical Symptoms and Brain Connectivity in Obsessive-Compulsive and Tic Disorders.

Objective: Sensory phenomena (SP) are aversive sensations driving repetitive behaviors in obsessive-compulsive disorder (OCD) and Tourette's disorder that are not well addressed by standard treatments. SP are related to the functioning of an interoceptive-sensorimotor circuit that may be modulated by the 5-HT receptor antagonist ondansetron. The present study employed an experimental medicine approach to test the effects of 4 weeks of high-dose ondansetron compared to placebo on SP severity and brain connectivity in a cohort of individuals with OCD and/or Tourette's disorder.

Room Temperature Ethene to Propene (ETP) Tandem Catalysis using Single Crystalline Solid-State Molecular Pre-Catalysts.

A tandem catalytic ensemble of solid-state molecular organometallic (SMOM) crystalline pre-catalysts are deployed under batch or flow conditions for the ethene to propene process (ETP). These catalysts operate at ambient temperature and low pressure, via sequential ethene dimerization, butenes isomerization and cross-metathesis. Under flow conditions the on-stream ethene conversion (55%), initial propene selectivity (92%), stability (71% selectivity after 7 hrs) and low temperature/pressures are competitive with the best-in-class heterogenous systems, marking a new, in crystallo, approach to ETP.

Use of Resonant Acoustic Fields as Atmospheric-Pressure Ion Gates.

Ion optics are crucial for spectrometric methods such as mass spectrometry (MS) and ion mobility spectrometry (IMS). Among the wide selection of ion optics, temporal ion gates are of particular importance for time-of-flight MS (TOF-MS) and drift-tube IMS. Commonly implemented as electrostatic ion gates, these optics offer a rapid, efficient means to block ion beams and form discrete ion packets for subsequent analysis.

Context-specific eQTLs provide deeper insight into causal genes underlying shared genetic architecture of critically ill COVID-19 and idiopathic pulmonary fibrosis.

Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

Development of Electronic Objective Structured Clinical Examinations (e-OSCEs) for Prosthodontic Clinical Assessment.

Introduction: Objective Structured Clinical Examinations (OSCEs) serve as a reliable assessment tool for clinical and competency evaluation. Traditional OSCEs, involving live patients, present logistical challenges and evoke student anxiety. In an effort to create a comprehensive clinical series of examinations, electronic OSCEs (e-OSCEs) were developed for assessing clinical competencies in prosthodontics at a large dental school.

IQ Survey Results on Current Industry Practices-Part 1: Immunogenicity Risk Assessment.

An immunogenicity risk assessment (IRA) is a relatively new expectation of health authorities that is increasingly incorporated into the drug development process across the pharmaceutical/biotech industry. The guiding principle for an IRA includes a comprehensive evaluation of product- and patient-related factors that may influence the immunogenic potential of a biotherapeutic drug and a potential action plan. The Immunogenicity Working Group from the IQ Consortium (Clinical Pharmacology Leadership Group) has conducted a survey to understand the current practices for conducting IRAs and relevant aspects of bioanalysis.

Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.

Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).

Descriptive Epidemiology of Complete ACL Tears in the Skeletally Immature Population: A Prospective Multicenter PLUTO Study.

Background: Anterior cruciate ligament (ACL) injuries are common in pediatric and adolescent patients. Understanding this population's injury characteristics and treatment strategies is vital for managing this high-risk group.

Purpose: To report the descriptive epidemiology and treatment strategies of a large cohort of skeletally immature patients with complete ACL tears.

Using capacity assessments and tailored technical assistance to advance trauma informed care integration at the organizational level.

Background: The prevalence of trauma among individuals with HIV has prompted efforts to integrate trauma-informed care (TIC) into HIV care and treatment to improve health outcomes. A TIC Implementation Model, developed by a US capacity-building organization focuses on organizational changes, aligning cultural and physical environments, emphasizing values like safety and trustworthiness, engaging leadership, and training staff in skills-based TIC services. Despite growing research, gaps remain in understanding the relationship between organizational capacity, provider knowledge, and the dosage of technical assistance (TA) required to sustain TIC integration.

The impact of dietary patterns on gut microbiota for the primary and secondary prevention of cardiovascular disease: a systematic review.

Background: Previous studies found that it is promising to achieve the protective effects of dietary patterns on cardiovascular health through the modulation of gut microbiota. However, conflicting findings have been reported on how dietary patterns impact gut microbiota in individuals either established or at risk of cardiovascular disease (CVD). Our systematic review aimed to explore the effect of dietary patterns on gut microbiota composition and on risk factors for CVD in these populations.

Myricetin exposure reduces PC differentiation in vitro in primary human B cells.

Background: The process of B cell activation and plasma cell (PC) formation involves morphological, transcriptional, and metabolic changes in the B cell. Blocking or reducing PC differentiation is one approach to treat autoimmune diseases that are characterized by the presence of pathogenic autoantibodies. Recent studies have suggested the potential of myricetin, a natural flavonoid with anti-inflammatory and antioxidant properties, to block or reduce PC differentiation.

Monitoring Use of Language Interpreting Services for Patients with Limited English Proficiency: Methods to Match Patient Medical Records with Interpreter Billing Logs.

Background: Over 60 million patients in the USA have limited English proficiency (LEP) and experience barriers in care. Still, there exists no standardized method of monitoring the utilization of language interpreting services (LIS).

Objective: To introduce a methodological approach to systematically monitor utilization of LIS for LEP patients.

Cardiovascular disease, bone fracture, and all-cause mortality risks among postmenopausal women by arthritis and veteran status: A multistate Markov transition analysis.

Arthritis, a chronic inflammatory condition linked to cardiovascular disease (CVD) and bone fracture, is more frequent among military veterans and postmenopausal women. This study examined correlates of arthritis and relationships of arthritis with risks of developing CVD, bone fractures, and mortality among postmenopausal veteran and non-veteran women. We analyzed longitudinal data on 135,790 (3,436 veteran and 132,354 non-veteran) postmenopausal women from the Women's Health Initiative who were followed-up for an average of 16 years between enrollment (1993-1998) and February 17, 2024.

Raynaud Syndrome Associated with Medication for Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Background: Raynaud syndrome (RS) is a peripheral vasculopathy characterised be impaired acral perfusion typically manifesting as skin discolouration with pallor, cyanosis and/or erythema, and increased sensitivity to cold. RS may be primary or secondary to systemic disease, lifestyle and environmental factors or medication. RS has been reported with medication to treat ADHD, but we found no recent comprehensive overview of the literature.

End-to-End Deep Learning Prediction of Neoadjuvant Chemotherapy Response in Osteosarcoma Patients Using Routine MRI.

This study aims to develop an end-to-end deep learning (DL) model to predict neoadjuvant chemotherapy (NACT) response in osteosarcoma (OS) patients using routine magnetic resonance imaging (MRI). We retrospectively analyzed data from 112 patients with histologically confirmed OS who underwent NACT prior to surgery. Multi-sequence MRI data (including T2-weighted and contrast-enhanced T1-weighted images) and physician annotations were utilized to construct an end-to-end DL model.

Microenvironmental determinants of endothelial cell heterogeneity.

During development, endothelial cells (ECs) undergo an extraordinary specialization by which generic capillary microcirculatory networks spanning from arteries to veins transform into patterned organotypic zonated blood vessels. These capillary ECs become specialized to support the cellular and metabolic demands of each specific organ, including supplying tissue-specific angiocrine factors that orchestrate organ development, maintenance of organ-specific functions and regeneration of injured adult organs. Here, we illustrate the mechanisms by which microenvironmental signals emanating from non-vascular niche cells induce generic ECs to acquire specific inter-organ and intra-organ functional attributes.

Robotic Versus Open Placement of Hepatic Artery Infusion Pumps.

Background: A growing number of centers offer hepatic artery infusion pump (HAIP) chemotherapy for advanced liver malignancies. While small series have demonstrated feasibility of robotic HAIP placement, comparison of outcomes with open placement is lacking. We compared outcomes after robotic versus open HAIP placement.

Coeliac disease: complications and comorbidities.

Coeliac disease is an autoimmune disease characterized by small intestinal villus atrophy and inflammation upon exposure to gluten. It has a global prevalence of approximately 1%. Although the gluten-free diet can be an effective treatment, this diet is burdensome with practical difficulties and frequent inadvertent gluten exposure.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Mutant p53 regulates a distinct gene set by a mode of genome occupancy that is shared with wild type.

To directly examine the interplay between mutant p53 or Mdm2 and wild type p53 in gene occupancy and expression, an integrated RNA-seq and ChIP-seq analysis was performed in vivo using isogenically matched mouse strains. Response to radiation was used as an endpoint to place findings in a biologically relevant context. Unexpectedly, mutant p53 and Mdm2 only inhibit a subset of wild type p53-mediated gene expression.

Urology on a changing planet: links between climate change and urological disease.

Urological diseases and their varied forms of management warrant special attention in the setting of climate change. Regarding urological cancers, climate change will probably increase the incidence and severity of cancer diagnoses through exposures to certain environmental risk factors, while simultaneously disrupting cancer care delivery and downstream outcomes. Regarding benign urological diseases, a burgeoning body of work exists on climate-related heat waves, dehydration, urolithiasis, renal injury and infectious and vector-borne diseases.

Leveraging synthetic data to improve regional sea level predictions.

The rapid increase in sea levels driven by climate change presents serious risks to coastal communities around the globe. Traditional prediction models frequently concentrate on developed regions with extensive tide gauge networks, leaving a significant gap in data and forecasts for developing countries where the tide gauges are sparse. This study presents a novel deep learning approach that combines TimesGAN with ConvLSTM to enhance regional sea level predictions using the more widely available satellite altimetry data.