RNA in plasma extracellular vesicles of adolescent rhesus macaques reveal immune, bioenergetic and microbial imprints of early life adversity - an exploratory analysis.

Background: Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of psychosomatic disorders in adolescence and adulthood. Most investigations into biological processes that have been perturbed by ELA have profiled DNA methylation in whole blood and coalesced around perturbations of immunobiology being centrally insulted by ELA.

Methods: To identify novel molecular signatures that are enduringly perturbed by childhood maltreatment, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (CONT, n = 7, 4M 3F) or maltreatment in infancy (MALT, n = 6, 3M 3F).

Leaving Academia: Dual-Career Relationships and Partners' Attrition from Academic Careers.

Background: More than one third of academics are coupled with another academic, with more women being in such dual-career relationships. Little is known about how these couples' experiences affect their attrition from or persistence in academia.

Methods: We analyzed survey data of academics at 100 U.

Tagraxofusp, a CD123-targeted therapy, for chronic myelomonocytic leukemia: final results of a phase 1/2 study.

Chronic myelomonocytic leukemia (CMML) is an aggressive hematologic neoplasm characterized by an expansion of CD123 monocytes and plasmacytoid dendritic cells (pDCs). pDC bone marrow clusters in CMML have been associated with higher rates of acute myeloid leukemia transformation. We evaluated tagraxofusp, a CD123-targeted therapy, in a phase 1/2 trial for patients with CMML.

Clinical psychedelic research in adolescents: a scoping review and overview of ethical considerations.

The potential use of psychedelic-assisted therapy for adolescents with mental illness has sparked both interest and concern. Modern psychedelic research has focused on adults, and adolescents younger than 18 years are typically excluded due to ethical and legal challenges. To explore whether adolescents have been included in 21st century psychedelic research, we conducted a scoping review of the medical literature from January, 2000, to April, 2025.

Audiological outcomes of the Cochlear Osia 2 bone conduction system implanted under expanded indications in a pediatric population.

Objective: Evaluate the audiological outcomes of the Cochlear Osia 2 Bone Conduction System implanted in children ages 5-11 years old.

Design: A pivotal, prospective, open-label, multicentre clinical trial to expand access to the Osia 2 system to children ages 5-11 years old.

Study Sample: Children aged 5-11 years old who presented with either (1) a conductive or mixed hearing loss where the pure tone average bone conduction threshold (measured at 500, 1000, 2000, and 3000 Hz) was ≤ 55 dB HL or (2) single-sided deafness where the ear to be implanted had a profound sensorineural hearing loss and the pure tone average air conduction threshold (measured at 500, 1000, 2000, and 3000 Hz) in the contralateral ear was ≤ 20 dB HL.

Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind, placebo-controlled, randomised, phase 3 trial.

Background: Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalisation for heart failure in patients with heart failure and reduced ejection fraction (HFrEF) following a recent worsening event. The aim of the VICTOR trial was to assess the effect of vericiguat in patients with HFrEF without recent heart failure worsening.

Methods: In this double-blind, placebo-controlled, phase 3 trial, conducted at 482 sites across 36 countries, patients aged 18 years or older with HFrEF (left ventricular ejection fraction of ≤40%) without heart failure hospitalisation within 6 months or outpatient intravenous diuretic use within 3 months before randomisation were randomly assigned (1:1) using an intervention randomisation system with interactive response technology to oral vericiguat (target 10 mg dose) or matching placebo.

A new generation of N-heterocyclic carbene (NHC) gold-selenolato complexes as potent anticancer agents: distinct synthetic routes and evaluation in 2D and 3D cancer models.

Two distinct synthetic pathways are disclosed that lead to new gold-selenolato complexes, stabilized by N-heterocyclic carbenes (NHCs). The weak base route can provide facile access to phenylselenolate complexes of gold, using both NHC and phopshine ligands. In addition, the pathway based on the carbometallation of elemental selenium enables the construction of a more diverse library of products, based on substituted aryl-selenide fragments whose selenol congeners are not commercially available.

Benchmarking Missing Data Imputation Methods for Time Series Using Real-World Test Cases.

Missing data is pervasive in healthcare. Many imputation methods exist to fill in missing values, yet most were evaluated using randomly deleted values rather than the actual mechanisms they were designed to address. We aimed to determine real-world accuracy for missing data imputation with three missing data mechanisms (missing completely at random, MCAR; missing at random, MAR; and not missing at random, NMAR) for state of the art and commonly used imputation methods.

Automated chromatin profiling with spa-ChIP seq uncovers the impacts of condition variations.

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a well-established method for studying the genomic localization of DNA-associated proteins. Yet, while useful, most ChIP-seq protocols include multiple manual steps that can introduce inconsistency and make it burdensome to analyze large sample sets, limiting the inclusion of appropriate replicates and other controls. Although some of these challenges were addressed by incorporation of liquid handling platforms, most of those previous efforts have automated only a subset of the ChIP-seq steps.

Weakly Supervised Deep Learning for Monitoring Sleep Apnea Severity Using Coarse-grained Labels.

Sleep apnea, a prevalent sleep-related breathing disorder, often remains undiagnosed and untreated in a large patient population due to the need of extensive manual annotations on various physiological signals for clinical diagnosis. Despite the surge of interest in applying machine learning to automate apnea detection, the effectiveness of existing techniques highly relies on strongly supervised learning that requires massive finely labeled training data for sufficiently short time intervals - a requirement often unmet due to the prohibitively high cost of manual labeling in clinical practice. In this article, we incorporate clinical knowledge to establish a weakly supervised deep learning framework for automatically estimating the latent fine-grained apnea severity when only coarse-grained labels indicating apnea presence are available in the training data.

Is It Scientifically Possible To 'Cure" Reward Deficiency Syndrome (RDS) Via Transplice Molecular Genetic Technology?

In 1995, Kenneth Blum coined the term "Reward Deficiency Syndrome'(RDS) to provide the mental health field with an umbrella term expressing a dissatisfaction of everyday experiences due to a dysregulation of dopaminergic dysregulation especially the DRD2 Taq A1 polymorphism presenting with up to a 40% reduction of D2 receptors in brain tissue with two copies. While the concept of RDS as the actual real umbrella of all mental illness unlike the current DSM-V (the brain is not carved out as portrayed by this important psychiatric manual) awaits further intensive research. In fact, Steven Hyman (former director of NIMH) suggests otherwise and has urged for research related to etiological causes instead to help explain the failings of mental health.

Hospital-at-home for acute complicated diverticulitis: a single-arm feasibility study.

Introduction: Non-operative management (NOM) of acute complicated diverticulitis (ACD) has become the preferred approach. A Hospital-at-Home (HaH) program at our institution launched to provide NOM for ACD. This study evaluated the HaH program feasibility for well-selected patients.

Assessing PFAS and Their Precursor Transformation in a Landfill Leachate-Impacted Wastewater Treatment Plant.

Despite growing concern over polyfluoroalkyl and perfluoroalkyl substances (PFAS), comprehensive evaluations of their behavior in wastewater treatment plants (WWTPs) influenced by landfill leachate remain limited. This study introduces a novel, integrated framework to investigate the fate, transformation, and persistence of PFAS across various treatment stages within a full-scale WWTP uniquely impacted by a mixture of domestic wastewater and industrial landfill leachate. By combining advanced targeted analysis using USEPA Draft Method 1633 with extractable organic fluorine (EOF) quantification and total oxidizable precursor (TOP) assays, this approach offers a comprehensive, multidimensional characterization of PFAS behavior.

Investigation of blood-brain barrier penetration and pharmacokinetics of a new formulation of cyanide antidote dimethyl trisulfide.

Objective: During cyanide poisoning, the rescue of vital organs like the brain is urgent. However, due to the presence of the blood-brain barrier (BBB), the currently available cyanide antidotes cannot reach the brain. Dimethyl trisulfide (DMTS) is a potent cyanide antidote and has excellent BBB permeability.

Crystal structures of agonist-bound human cannabinoid receptor CB.

Cannabinoid receptor 1 (CB) is the primary target of the partial agonist Δ-tetrahydrocannabinol (Δ-THC), the psychoactive constituent of marijuana. Here we report two agonist-bound crystal structures of human CB in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841). The two CB-agonist complexes reveal important conformational changes in the overall structure relative to the antagonist-bound state, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G protein-binding region.

How maximal whole-body and segmental angular momenta relate to fastball speeds in high school baseball pitchers.

Generation of whole-body and segmental rotations are important objectives of baseball pitching and may be quantified using angular momentum about the body's center of mass (L). However, the characteristics of L during baseball pitching are not well understood, and it is not known whether generating more whole-body or segmental L would be beneficial for the performance outcome of fastball speeds. We characterized whole-body and segmental L and hypothesized that ball speed would positively associate with maximum whole-body, pelvis, trunk, pitching upper arm, forearm, and hand L.

Deep dictionary learning with reconstruction for texture recognition.

Texture recognition underpins critical applications in industrial quality control, robotic manipulation, and biomedical imaging. Traditional deep dictionary learning methods for texture recognition often emphasize deep feature extraction. However, they tend to lose crucial features as model depth increases, which can reduce their overall effectiveness.

Early life adversity increases risk for chronic post-traumatic pain, data from humans and rodents.

Traumatic stress exposures (TSEs) are common in life. Although most individuals recover after a TSE, a substantial subset develop adverse post-traumatic neuropsychiatric sequelae such as chronic post-traumatic musculoskeletal pain (CPMP). Vulnerability factors for CPMP are poorly understood, which hinders identification of high-risk individuals for targeted interventions.

Integrative Genomic and Immune Profiling to Identify and Characterize High-Risk Subgroups in Acute Myeloid Leukemia: Development of a 20-Gene Predictive Signature and Its Clinical Implications.

Acute myeloid leukemia (AML) is a heterogeneous malignancy with diverse genetic mutations and oncogenic pathways influencing treatment response. Despite therapeutic advances, relapse and resistance remain persistent issues. This study integrates genomic and transcriptomic profiling to identify biomarkers of high-risk AML, informing personalized medicine strategies.

Emotion identification and emotion sensitivity following interpersonal and non-interpersonal traumatic experiences: Results from the AURORA study.

Social cognition is an important mechanism linking trauma to psychopathology; however, current models fail to explain individual differences in social cognition after trauma exposure. We investigated whether the interpersonal nature of trauma exposure helps to explain variability in social cognitive outcomes. Our sample was derived from the AURORA study, a national initiative involving intensive follow-up of trauma survivors for one year.

Dynamic and Static Resting-State Functional Connectivity of Canonical Networks in Military and Civilian Populations with Posttraumatic Stress Disorder and/or Mild Traumatic Brain Injury.

Background: Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are associated with alterations in the functional connectome, specifically in canonical resting state networks including the default mode (DMN), central executive (CEN), and salience networks (SN). Comorbid PTSD+mTBI is linked to worse functional outcomes, but little is known about effects on the functional connectome.

Methods: We investigated brain phenotypes from resting-state fMRI associated with PTSD (n=326), mTBI (n=448), and comorbid PTSD+mTBI (n=289) in military veterans and civilians (n=1526) from ENIGMA-TBI and -PTSD.

Assessment of Small Vessel Density Changes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalophy (CADASIL) by High-Resolution Black-Blood MRI.

Background: Direct assessments of cerebral small vessels in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) remain a challenge.

Purpose: To investigate changes of cerebral small vessels in CADASIL using iso-0.5 mm black-blood MRI.

Return-to-Sport Recommendations in Athletes Requiring Cervical Spine Surgery: A Modified Delphi Consensus Survey of Expert Opinion.

Study Design: Modified Delphi consensus survey.

Objective: To survey expert opinion on postoperative return-to-sport (RTS) decisions in athletes requiring cervical spine surgery.

Summary Of Background Data: Postoperative sport participation recommendations for athletes requiring cervical spine surgery are lacking, and management of these athletes remains challenging.

A Linear-Regression-Based Method for Determining Surface Tension from Variation in Interfacial Curvature.

We develop a new linear-regression-based method for determining surface tension, γ, from interfacial curvature. Across a static fluid-fluid interface, γ is balanced by the difference in hydrostatic pressure, Δ. The balance is described by the Young-Laplace relation: Δ = γ (1 + 2), where 1 + 2 is the sum of the principal interfacial curvatures.