Novel tertiary diarylethylamines as functionally selective agonists of the kappa opioid receptor.

Novel kappa opioid receptor (KOR) agonists that preferentially activate G-protein signaling versus β-arrestin-2 recruitment are described. Starting from a literature-reported phenol-containing diphenethylamine KOR agonist, structure-activity relationship (SAR) studies revealed replacement of the phenol with various non-hydroxylated bicyclic heteroaromatics led to tertiary diarylethylamines which retained KOR agonist activity and improved metabolic stability in human liver microsomes. Further optimizations produced compound 39, a potent activator of G-protein signaling (GTPγS EC = 14 nM, 83 % E) that did not elicit a β-arrestin-2 recruitment functional response (E < 10 %).

Global impact of 10- and 13-valent pneumococcal conjugate vaccines on pneumococcal meningitis in all ages: the PSERENADE project.

Background: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally.

Methods: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally.

Neurodevelopmental Follow-Up in Children with Intrauterine and Perinatal Exposure to Chikungunya Virus.

Objective: To investigate the effects of intrauterine and perinatal exposure to chikungunya virus (CHIKV) on neurodevelopment in infants and toddlers.

Study Design: We conducted a cohort study comparing children with intrauterine or perinatal exposure to maternal CHIKV infection with unexposed controls in Rio de Janeiro, Brazil. Neurodevelopment was assessed with General Movement Assessments (GMA) in the first six months of life, and the Bayley-III Scales of Infant and Toddler Development and Modified Checklist for Autism in Toddlers (M-CHAT) for older children.

Regulation of NLRP3/TRIM family signaling in gut inflammation and colorectal cancer.

CRC (Colorectal cancer) ranks among the most prevalent tumors in humans and remains a leading cause of cancer-related mortality worldwide. Numerous studies have highlighted the connection between inflammasome over-activation and the initiation and progression of CRC. The activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome is dependent on the nuclear NF-kβ (Nuclear Factor kappa-light-chain-enhancer of activated B cells) pathway, leading to the maturation and release of inflammatory cytokines such as IL-1ß (Interleukin 1 beta) and IL-18 (Interleukin 18).

Validity of diagnosis codes to identify a dermatomyositis cohort from electronic health records.

Introduction: Dermatomyositis (DM) is an uncommon idiopathic inflammatory myopathy resulting in characteristic patterns of cutaneous lesions and myositis. Observational evidence related to the disease is limited by small case cohorts. We aimed to evaluate the validity of specialist-specific diagnostic coding for DM in an outpatient clinical database.

Communication-efficient federated learning of temporal effects on opioid use disorder with data from distributed research networks.

Objective: To develop a distributed algorithm to fit multi-center Cox regression models with time-varying coefficients to facilitate privacy-preserving data integration across multiple health systems.

Materials And Methods: The Cox model with time-varying coefficients relaxes the proportional hazards assumption of the usual Cox model and is particularly useful to model time-to-event outcomes. We proposed a One-shot Distributed Algorithm to fit multi-center Cox regression models with Time varying coefficients (ODACT).

Family functioning in adolescents and young adults with differences of sex development.

Objective: Family functioning influences various psychosocial outcomes for individuals with pediatric chronic health conditions (e.g., Leeman, J.

Cytoplasmic expression of trans-active response DNA-binding protein-43 in aged mice display hippocampal sclerosis-like degeneration and neuronal loss with reduced lifespan.

Trans-active response DNA-binding protein-43 (TDP-43) is the major pathological protein in motor neuron disease and TDP-43 pathology has been described in the brains of up to 50% of patients with Alzheimer disease (AD). Hippocampal sclerosis of aging (HS-A), an age-related neuropathology characterized by severe neuronal loss and gliosis in CA1 and/or subiculum, is found in ∼80% of cases that are positive for phosphorylated TDP-43. HS-A is seen as a co-pathology in cases with AD, limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), and frontotemporal degeneration.

The association of medical cannabis use with quality of life in Illinois' opioid alternative pilot program.

Background: In Illinois, the Opioid Alternative Pilot Program (OAPP) was launched to expand access to medical cannabis to use as a direct substitute for opioids. Although therapeutic benefits have been reported in reducing opioid use, there is an absence of literature that examines how medical cannabis use impacts an individual's quality of life (QoL). This study examines the association of medical cannabis use with QoL among the first enrollees in OAPP.

Emotional intelligence as a predictor of functional outcomes in psychotic disorders.

Psychotic disorders are associated with significant impairment in psychosocial functioning, yet mechanisms associated with this impairment remain poorly understood. Emotional intelligence, a component of social cognition, is associated with psychosocial functioning in this population. However, prior work has used relatively small samples, reported inconsistent relations between functioning domains and emotional intelligence, and inconsistently considered negative symptoms.

Estimating the generation time for influenza transmission using household data in the United States.

The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially since the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023.

Exploring Bangladeshi English as a foreign language learners' mindfulness and engagement in the online learning context.

This empirical study investigates the relationship between mindfulness and online engagement among Bangladeshi English as a Foreign Language (EFL) learners during the Covid-19 pandemic. A mixed-methods approach was employed, combining quantitative data from the Langer Mindfulness Scale (LMS) and the Online Student Engagement Scale (OSES) with qualitative data from open-ended responses. A total of 215 university students participated in the study, providing insights into their mindfulness levels and engagement in online learning.

Global research trends of BRUE (brief resolved unexplained event) or formerly ALTE (apparent life-threatening event): A comprehensive visualization and bibliometric analysis from 1988 to 2024.

Objective: This study aimed to conduct a comprehensive bibliometric analysis of the literature on Brief Resolved Unexplained Event (BRUE) and its predecessor, Apparent Life-Threatening Event (ALTE), from 1988 to 2024, in order to identify research trends, collaborative networks, and areas of focus in this field.

Methods: We analyzed articles indexed in Scopus and Web of Science using various bibliometric indicators. The visualization of bibliometric networks was performed using VOSviewer and bibliometrix.

Biofiltration for odor mitigation in water resource recovery facilities.

Odor emissions, primarily from anthropogenic activities like waste treatment and industrial processes, pose significant challenges in urban areas, particularly near water resource recovery facilities. While these emissions are generally not toxic, they can adversely affect community wellbeing and investment, prompting stricter regulations in some regions. For example, New York State's hydrogen sulfide guidelines are more stringent than federal standards.

Managed honey bees, Apis mellifera (Hymenoptera: Apidae), face greater risk from parasites and pathogens than mosquito control insecticide applications.

As the primary pollinator for many crops, honey bees (Apis mellifera) are critically important to food production and the agricultural economy. Adult mosquito control is often suspected by the public and commercial beekeepers to harm honey bees, creating conflicts between industries. To investigate this matter, a two-year field study was conducted on vegetated wetlands in Salt Lake City, Utah, U.

A comparative life cycle analysis of Sol-Char and anaerobic digestion sanitation systems.

In this study, we compared the Sol-Char sanitation system with an Anaerobic Digestion (AD) system using Life Cycle Assessment (LCA) to evaluate their environmental impacts. Since both systems offer opportunities for human waste treatment and resource recovery, understanding their performance is crucial. This comparison aims to determine their environmental impacts while considering diverse factors, such as energy production and nutrient recovery.

Body Image and sex among postpartum women.

Body image and sexuality both pertain to the body. Positive experiences in one domain are generally associated with positive experiences in the other. Yet, less is known about body image among postpartum women specifically.

Effects of exercise and transient estradiol exposure in middle-aged female rats.

The benefits of estrogen treatment on cognition in middle-aged and older women are dependent on many factors, including the timing of treatment. Moreover, the potential interactive effects with other lifestyle factors, such as exercise, are poorly understood. In this study, we tested for lasting benefits of independent and combined treatment with estrogen and voluntary exercise initiated in midlife, using a rat model of menopause.

Trends and Disparities in Prostate Cancer Mortality in the United States (1999-2020).

Background: Prostate cancer is a leading cause of cancer-related mortality among men in the United States. Over the past two decades, the observed decline in prostate cancer mortality can be attributed to advancements in screening, early detection, and treatment. However, persistent disparities related to race, geography, and age highlight the need for targeted interventions to improve outcomes.

Association of Epstein-Barr Virus and its clinical relevance in Human Papillomavirus-negative oral squamous cell carcinoma: A cohort study from South India.

Objective: The study assessed the prevalence and clinical implications of Epstein Barr Virus (EBV)-positive but Human Papillomavirus (HPV)-negative oral squamous cell carcinoma (OSCC) in a tertiary care hospital setting. The overall goal was to elucidate the potential impact of EBV on OSCC disease progression and prognosis.

Design: A total of 134 surgically resected and histopathologically confirmed OSCC tumor biopsies were collected from a tertiary care hospital.

Responsible Design, Integration, and Use of Generative AI in Mental Health.

Generative artificial intelligence (GenAI) shows potential for personalized care, psychoeducation, and even crisis prediction in mental health, yet responsible use requires ethical consideration and deliberation and perhaps even governance. This is the first published theme issue focused on responsible GenAI in mental health. It brings together evidence and insights on GenAI's capabilities, such as emotion recognition, therapy-session summarization, and risk assessment, while highlighting the sensitive nature of mental health data and the need for rigorous validation.

Use of multi-modal non-contrast MRI to predict functional outcomes after stroke: A study using DP-pCASL, DTI, NODDI, and MAP MRI.

Purpose: This study aims to assess whether water exchange rate (k), a surrogate for blood-brain barrier (BBB) permeability, is associated with functional outcomes in patients with acute ischemic stroke (AIS).

Methods: We studied 22 AIS patients enrolled from 1/2022 to 4/2024 who underwent multi-modal non-contrast imaging on a 3.0-Tesla scanner, including DP-pCASL, DTI, NODDI and MAP imaging.

How partisan news outlets frame vested interests in climate change.

This paper reports a theoretically-driven quantitative content analysis of news media discourse on climate change, its effects, and solutions to understand how US news discourse differs from widely supported scientific conclusions on global climate. Despite the dire warnings and calls to action, US public opinion on the causes and solutions to climate change remain divided. In the global context, the US's split views are anomalous and may be an artifact of the US media's coverage of the climate crisis.

Development and evaluation of the modified and standardized rainfall anomaly indices for extreme variability analysis.

This study introduces two refined rainfall anomaly indices-the Modified Rainfall Anomaly Index (MRAI) and the Standardized Rainfall Anomaly Index (SRAI)-to address limitations in the traditional Rainfall Anomaly Index (RAI). The existing RAI struggles to effectively capture extreme wet and dry rainfall conditions and relies on a simplistic formulation. To evaluate these indices on a continental scale, data from the Integrated Multi-Satellite Retrievals for GPM (IMERG) was used for the Conterminous United States (CONUS), enabling scalability to ungaged locations and beyond.

Trends, characteristics, and outcomes of pregnancy in women with attention-deficit hyperactivity disorder: A nationwide analysis.

Objective: To assess clinical and obstetric characteristics associated with pregnant patients with a diagnosis of attention-deficit hyperactivity disorder (ADHD).

Methods: This serial cross-sectional study queried the Agency of Healthcare Research and Quality's Healthcare Cost and Utilization Project National Inpatient Sample. The study population was 16,759,786 hospital deliveries from 2016 to 2020.