Characterization and effective expansion of CD4CD8 TCRαβ T cells from individuals living with type 1 diabetes.

CD4CD8 TCRαβ (double-negative [DN]) T cells represent a rare T cell population that promotes immunological tolerance through various cytotoxic mechanisms. In mice, autologous transfer of DN T cells has shown protective effects against autoimmune diabetes and graft-versus-host disease. Here, we characterized human DN T cells from people living with type 1 diabetes (PWT1D) and healthy controls.

Impact of SARS-CoV-2 vaccination and of seasonal variations on the innate immune inflammatory response.

Introduction: The innate immune response is an important first checkpoint in the evolution of an infection. Although adaptive immunity is generally considered the immune component that retains antigenic memory, innate immune responses can also be affected by previous stimulations. This study evaluated the impact of vaccination on innate cell activation by TLR7/8 agonist R848, as well as seasonal variations.

A methodological approach to assess the ropy character of stirred acid dairy gels based on the measure of adhesiveness.

This work aims to evaluate the potential and limits of adhesiveness measurement using a texturometer to assess the ropiness of acid dairy gels for starter selection. Commercial yogurts of various formulations and textures were used to assess the ability of adhesiveness to detect ropiness and to compare performance of different probes. Chemically acidified gels using different concentrations of glucono-delta-lactone (GDL) were tested to determine the effect of pH on adhesiveness.

Performance modulations phase-locked to action depend on internal state.

Previous studies have shown that perceptual performance can be modulated at specific frequencies phase-locked to self-paced motor actions, but findings have been inconsistent. To investigate this effect at the population level, we tested 50 participants who performed a self-paced button press followed by a threshold-level detection task, using both fixed- and random-effects analyses. Contrary to expectations, the aggregated data showed no significant action-related modulation.

Leveraging Model Master Files for Long-Acting Injectables.

The U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a public workshop on May 2-3, 2024, titled "Considerations and Potential Regulatory Applications for a Model Master File (Lachaine et al Can J Psychiatry.

Hilbert transform analysis of the mouse scotopic electroretinogram reveals two distinct bursts of oscillatory potentials with progressively dimmer flashes.

Purpose: Study the scotopic oscillatory potentials (OPs) in mice over a wide range of flash luminance levels using the Hilbert transform (HT) to extract new features of the high frequency components of the electroretinogram (ERG).

Methods: Scotopic ERGs [Intensity: - 6.3 to 0.

Intramyocellular lipid use is altered with exercise in males with childhood-onset obesity despite no differences in substrate oxidation.

Objective: Compared to adulthood-onset obesity (AO), those with childhood-onset obesity (CO) are at greater risk of metabolic disease. However, the differences between these two obesity phenotypes are not clear. The aim of this study is to investigate how the age of obesity onset (CO vs.

Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial.

Background: CheckMate 8HW prespecified dual primary endpoints, assessed in patients with centrally confirmed microsatellite instability-high or mismatch repair-deficient status: progression-free survival with nivolumab plus ipilimumab compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab compared with nivolumab alone, regardless of previous systemic treatment for metastatic disease. In our previous report, nivolumab plus ipilimumab showed superior progression-free survival versus chemotherapy in first-line microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer in the CheckMate 8HW trial. Here, we report results from the prespecified interim analysis for the other primary endpoint of progression-free survival for nivolumab plus ipilimumab versus nivolumab across all treatment lines.

Topography of putative bi-directional interaction between hippocampal sharp-wave ripples and neocortical slow oscillations.

Systems consolidation relies on coordination between hippocampal sharp-wave ripples (SWRs) and neocortical UP/DOWN states during sleep. However, whether this coupling exists across the neocortex and the mechanisms enabling it remains unknown. By combining electrophysiology in mouse hippocampus (HPC) and retrosplenial cortex (RSC) with wide-field imaging of the dorsal neocortex, we found spatially and temporally precise bi-directional hippocampo-neocortical interaction.

Toward cognitive models of misophonia.

Misophonia is a disorder in which specific common sounds such as another person breathing or chewing, or the ticking of a clock, cause an atypical negative emotional response. Affected individuals may experience anger, irritability, annoyance, disgust, and anxiety, as well as physiological autonomic responses, and may find everyday environments and contexts to be unbearable in which their 'misophonic stimuli' (often called 'trigger sounds') are present. Misophonia is gradually being recognized as a genuine problem that causes significant distress and has negative consequences for individuals and their families.

Advancing stroke rehabilitation: the role of wearable technology according to research experts.

Background: Advancements in wearable technology have created new opportunities to monitor stroke survivors' behaviors in daily activities. Research insights are needed to guide its adoption in clinical practice, address current gaps, and shape the future of stroke rehabilitation. This project aims to: (1) Understand stroke rehabilitation researchers' perspectives on the opportunities, challenges, and clinical relevance of wearable technology for stroke rehabilitation, and (2) Identify necessary next steps to integrate wearable technology in research and clinical practice.

Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial.

Background And Aims: An expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity-the waist-to-height ratio (WHtR)-focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.

Methods: The PARAGON-HF trial randomized 4796 patients with heart failure and ejection fraction ≥45% to valsartan or sacubitril/valsartan.

Impact of expressive intentions on upper-body kinematics in two expert pianists.

Introduction: Expression is a key aspect of music performance. Studies on pianists' gestures and expression have mainly documented the impact of their expressive intentions on proximal segments and head linear kinematics. It remains unclear how pianists' expressive intentions influence joint angular kinematics as well as exposure to risk factors of injury, such as poor overall posture and distal jerky movements, two kinematic factors linked to injury.

Principles of visual cortex excitatory microcircuit organization.

Synapse-specific connectivity and dynamics determine microcircuit function but are challenging to explore with classic paired recordings due to their low throughput. We therefore implemented optomapping, a ∼100-fold faster two-photon optogenetic method. In mouse primary visual cortex (V1), we optomapped 30,454 candidate inputs to reveal 1,790 excitatory inputs to pyramidal, basket, and Martinotti cells.

IGF-1 Assessment During Weekly Somatrogon Treatment in Pediatric Patients With GH Deficiency.

Context: In patients with GH deficiency (GHD) receiving GH treatment, IGF-1 concentrations are used by physicians to monitor treatment safety and efficacy and guide dosing decisions. Somatrogon is a long-acting GH approved as a once-weekly treatment for pediatric GHD. Somatrogon administration results in characteristic changes in the IGF-1 profile, with values measured at 96 hours postdose representing mean IGF-1 concentrations that best reflect overall somatrogon exposure.

Decentralized clinical trials are better for the participants and for the planet: the case study of a double-blind randomized controlled trial in Singapore (PROMOTE study).

Introduction: Novel technologies have enabled the decentralization of many aspects of clinical trials, but little research has been done on the impact of these changes on the participant experience, trial operations, or the environment.

Methods: A fully decentralized clinical trial conducted in Singapore is used as a case study to evaluate the operational outcomes, environmental impact (via life cycle assessment), and participants experience (qualitative interviews) of the decentralized model compared to a traditional study with in-person visits.

Results: The decentralized study achieved high participant retention rates (97%) and high completion rates for clinical data, even for biological samples.

Individual characteristics influencing the general population's level of knowledge of end-of-life practices: a cross-sectional study.

Background: Informed end-of-life decision-making requires a high level of death literacy. We still know little about the general population's level of knowledge and its determinants.

Aim: To assess knowledge of the general population regarding the legal status and definitions of various end-of-life practices, and to compare the level of knowledge according to individual characteristics known to influence death literacy.

The asymmetry engine: how plants harness asymmetries to shape their bodies.

Plant development depends on growth asymmetry to establish body plans and adapt to environmental stimuli. We explore how plants initiate, propagate, and regulate organ-wide growth asymmetries. External cues, such as light and gravity, and internal signals, including stochastic cellular growth variability, drive these asymmetries.

A review of clinical applications of pharmacokinetic simulations for a 2-month long-acting injectable formulation of aripiprazole.

Aripiprazole 2-month ready-to-use (Ari 2MRTU) is a long-acting injectable antipsychotic that was approved for use in Europe in March 2024, for the maintenance treatment of schizophrenia in adult patients stabilized with aripiprazole; it is administered via gluteal intramuscular injection once every two months. This review examines population pharmacokinetic model-based simulations relevant to the use of Ari 2MRTU in Europe, accompanied by expert commentary that contextualizes the simulations and highlights the potential implications of the availability of Ari 2MRTU for patients, caregivers, and clinicians. Various simulations conducted across 8 weeks (representing the first dosing interval), or 32 weeks (representing maintenance dosing) demonstrated an aripiprazole exposure profile for Ari 2MRTU that was similar to aripiprazole once-monthly (AOM), but with an extended dosing interval.

Impact of cariprazine on body weight and blood pressure among adults with bipolar I disorder, schizophrenia, or major depressive disorder in a real-world setting.

Background: Atypical antipsychotics are a common treatment for serious mental illness, but many are associated with adverse effects, including weight gain and cardiovascular issues, and real-world experience may differ from clinical trial data. Cariprazine has previously demonstrated a favorable safety and tolerability profile in clinical trials. Here, we evaluated the effects of cariprazine on body weight and blood pressure for bipolar I disorder (BP-I), schizophrenia, or as adjunctive treatment for major depressive disorder (MDD) using real-world data.

Diagnostic performance of artificial intelligence in detection of renal cell carcinoma: a systematic review and meta-analysis.

Objectives: The detection of renal cell carcinoma (RCC) tumors in the earlier stages is of great importance for more effective treatment. Encouraged by the key role of imaging in the management of RCC, we conducted a systematic review and meta-analysis of the studies that made use of artificial intelligence (AI) for the detection of RCC to quantitatively determine the performance of AI for distinguishing related renal lesions.

Materials And Methods: PubMed, Scopus, CENTRAL, and Embase electronic databases were systematically searched in November 2024 to identify studies that applied AI for the detection or classification of RCC.

Daily and Prospective Associations Between Responses to Sexual Rejection and Sexual Well-Being and Relationship Satisfaction in Couples Coping with Sexual Interest/Arousal Disorder.

Prior cross-sectional research established that four distinct responses to sexual rejection are associated with sexual and relationship well-being among couples affected by Sexual Interest/Arousal Disorder (SIAD). Examining these associations daily and prospectively will provide insight into within-person variations, temporality, and directionality. Women and gender-diverse individuals diagnosed with SIAD and their partners (N = 232 couples) completed a baseline survey, 56-day diary, and 6-month follow-up survey, assessing responses to sexual rejection, sexual satisfaction, dyadic sexual desire, sexual distress, and relationship satisfaction.