Mapping cells through time and space with moscot.

Single-cell genomic technologies enable the multimodal profiling of millions of cells across temporal and spatial dimensions. However, experimental limitations hinder the comprehensive measurement of cells under native temporal dynamics and in their native spatial tissue niche. Optimal transport has emerged as a powerful tool to address these constraints and has facilitated the recovery of the original cellular context.

Internalized HIV Stigma, Sleep Problems, and Depressive Symptoms in People with HIV in Botswana.

This study investigates the impact of internalized HIV stigma on sleep problems and depression in people living with HIV (PLWH) in Botswana. It also explores whether sleep problems mediate the relationship between internalized HIV stigma and depressive symptoms, given that sleep disturbance is a symptom of depression and often predates a depressive episode. Secondary analysis was conducted using baseline data from a pilot randomized controlled trial on 58 virally unsuppressed PLWH in Gaborone, Botswana.

Multiplexed siRNA Immunoassay Unveils Spatial and Quantitative Dimensions of siRNA Function, Abundance, and Localization In Vitro and In Vivo.

Small interfering RNAs (siRNAs) have been successfully used as therapeutics to silence disease-causing genes when conjugated to ligands or formulated in lipid nanoparticles to target relevant cell types for efficacy while sparing other cells for safety. To support the development of new methods for delivery of siRNA therapeutics, we developed and characterized a panel of antibodies generated against chemically modified nucleotides used in therapeutic siRNA molecules, identifying a monoclonal antibody that detects a broad range of siRNA representing distinct sequences and modification patterns. By integrating this anti-siRNA antibody with additional reagents, we created a multiplex siRNA immunoassay that simultaneously quantifies siRNA uptake, trafficking, and silencing activity.

Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS.

Sevenless, the Drosophila homologue of ROS1 (University of Rochester Sarcoma) (herein, dROS1) is a receptor tyrosine kinase (RTK) essential for the differentiation of Drosophila R7 photoreceptor cells. Activation of dROS1 is mediated by binding to the extracellular region (ECR) of the GPCR (G protein coupled receptor) BOSS (Bride Of Sevenless) on adjacent cells. Activation of dROS1 by BOSS leads to subsequent downstream signaling pathways including SOS (Son of Sevenless).

A new phylogenetic framework for the genus Kalanchoe (Crassulaceae) and implications for infrageneric classification.

Background And Aims: Kalanchoe is a diverse genus in the Crassulaceae, with centres of diversity in Madagascar and sub-Saharan Africa. The genus is known for its popularity in horticulture, its use as a model system for research on CAM photosynthesis and vegetative reproduction, its high invasive potential, and its use in traditional medicine. The genus-rank circumscription and infrageneric classification of Kalanchoe have been the subject of debate for centuries, especially regarding the status and rank of what is now treated as K.

Building a Digital Health Research Platform to Enable Recruitment, Enrollment, Data Collection, and Follow-Up for a Highly Diverse Longitudinal US Cohort of 1 Million People in the All of Us Research Program: Design and Implementation Study.

Background: Longitudinal cohort studies have traditionally relied on clinic-based recruitment models, which limit cohort diversity and the generalizability of research outcomes. Digital research platforms can be used to increase participant access, improve study engagement, streamline data collection, and increase data quality; however, the efficacy and sustainability of digitally enabled studies rely heavily on the design, implementation, and management of the digital platform being used.

Objective: We sought to design and build a secure, privacy-preserving, validated, participant-centric digital health research platform (DHRP) to recruit and enroll participants, collect multimodal data, and engage participants from diverse backgrounds in the National Institutes of Health's (NIH) All of Us Research Program (AOU).

Protective behavioral strategies and alcohol consequences following a group-based motivational intervention for young adults experiencing homelessness.

Objective: Young adults experiencing homelessness are at high risk for alcohol-related consequences, but protective behavioral strategies (PBS) have not been investigated as a harm reduction approach in this population. This study examines longitudinal associations between PBS and alcohol-related consequences following a group-based alcohol intervention.

Method: Data come from AWARE, a randomized controlled trial of a group-based motivational intervention to reduce substance use and risky sex compared to usual care.

Observer-rated environmental sensitivity and its characterization at behavioral, genetic, and physiological levels.

This study investigated the psychometric properties of the Highly Sensitive Child-Rating System (HSC-RS), the existence of sensitivity groups, and the characterization of sensitivity at behavioral, genetic, and physiological levels in 541 preschoolers (() = 3.56(0.27); 45%male; 87%Caucasian).

Startle potentiation to unpredictable threat predicts adolescent development of generalized anxiety disorder.

Background: An elevated startle reflex in anticipation of unpredictable threat has been associated with concurrent anxiety disorders. However, only one study to date has examined whether startle potentiation in anticipation of unpredictable threat predicts the development of anxiety disorders.

Method: In a community sample of 309 adolescents, we examined whether the startle reflex in anticipation of predictable or unpredictable threat at age 15 predicted onset of generalized anxiety disorder (GAD) and social anxiety disorder (SAD) at age 18.

Irritability and stress: Prospective, bidirectional relationships in adolescence.

Background: Irritability is a transdiagnostic risk factor for psychopathology and interpersonal problems in youth. However, there is little research on the role of life stress in irritability. The association between stress and irritability may be bidirectional, with irritability leading to stress exposure and stress aggravating irritability.

Matrix-free human lung organoids derived from induced pluripotent stem cells to model lung injury.

Background: Organoids, as near-physiological 3D culture systems, offer new opportunities to study the pathogenesis of various organs in mimicking the cellular complexity and functionality of human organs.

Method: Here we used a quite simple and very practicable method to successfully generate induced pluripotent stem cell (iPSC)-derived human lung organoids (LuOrg) in a matrix-free manner as an alternative to the widely used preclinical mouse models in order to investigate normal lung damage in detail and as close as possible to the patient. We performed detailed morphological and molecular analyses, including bulk and single cell RNA sequencing, of generated lung organoids and evaluated the quality and robustness of our model as a potential in vitro platform for lung diseases, namely radiation-induced lung injury.

Social Media Activities and Affective Well-being in the Daily Life of Emerging Adults.

Previous work suggests that some social media (SM) activities may have detrimental effects on users' affective well-being, whereas other activities can be more adaptive. SM use is typically assessed with global or retrospective measures; it remains unclear how its relation with affect may play out in real-time and in regard to specific SM activities, as opposed to general SM use. The current study investigated the association between specific SM activities (posting, viewing others' posts, liking/commenting, checking replies to one's own posts, direct messaging) and concurrent positive and negative affect in a sample of  = 349 18-year-old emerging adults.

GABA receptor π forms channels that stimulate ERK through a G-protein-dependent pathway.

The rare γ-aminobutyric acid type-A receptor (GABAR) subunit π (GABRP) is highly expressed in certain cancers, where it stimulates growth through extracellular-regulated kinase (ERK) signaling by an uncharacterized pathway. To elucidate GABRP's signaling mechanism, we determined cryoelectron microscopy (cryo-EM) structures of GABRP embedded in native nanodiscs, both in the presence and absence of GABA. Structurally, GABRP homopentamers closely resemble heteropentameric GABAR anion channels, transitioning from a closed "resting" state to an open "active" state upon GABA binding.

Cysteine Rich Intestinal Protein 2 is a copper-responsive regulator of skeletal muscle differentiation and metal homeostasis.

Copper (Cu) is essential for respiration, neurotransmitter synthesis, oxidative stress response, and transcription regulation, with imbalances leading to neurological, cognitive, and muscular disorders. Here we show the role of a novel Cu-binding protein (Cu-BP) in mammalian transcriptional regulation, specifically on skeletal muscle differentiation using murine primary myoblasts. Utilizing synchrotron X-ray fluorescence-mass spectrometry, we identified murine cysteine-rich intestinal protein 2 (mCrip2) as a key Cu-BP abundant in both nuclear and cytosolic fractions.

Development and validation of a rheumatoid arthritis case definition: a machine learning approach using data from primary care electronic medical records.

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disease that is primarily diagnosed and managed by rheumatologists; however, it is often primary care providers who first encounter RA-related symptoms. This study developed and validated a case definition for RA using national surveillance data in primary care settings.

Methods: This cross-sectional validation study used structured electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN).

Latent Structure and Item Functioning of Self-Referent Encoding Task Word Stimuli in Preadolescent Youth.

The Self-Referent Encoding Task (SRET) can be used to measure self-concept via endorsement of trait words, a robust metric associated with depression severity. Our study is the first to investigate the structural validity and item functioning of SRET endorsement scores using confirmatory factor analysis and item response theory. Community-dwelling preadolescent youth ( = 508;  = 12.

Evolutionary origins of temporal discounting: Modeling how time and uncertainty constrain optimal decision-making strategies across taxa.

The propensity of humans and non-human animals to discount future returns for short-term benefits is well established. This contrasts with the ability of organisms to unfold complex developmental sequences over months or years efficiently. Research has focused on various descriptive and predictive parameters of 'temporal discounting' in behavior, and researchers have proposed models to explain temporal preference in terms of fitness-maximizing outcomes.

A comparative analysis of supply chain factors impacting COVID-19 vaccine security in high-income countries (HICs) and low-income and middle-income countries (LMICs).

Introduction: The COVID-19 pandemic focused attention on the importance of vaccine security to national security. Demand for vaccines far exceeded supply when the first COVID-19 vaccines were released. Growing data suggest a non-perfect correlation among vaccine development, production, purchases, deliveries and vaccination rates.

The role of the primary healthcare research community in addressing the social and structural determinants of health: a call to action from NAPCRG 2023.

The need for effective primary healthcare to address social and structural determinants of health and to mitigate health inequalities has been well established. Here, we report on the international forum of the 2023 NAPCRG (formerly known as North American Primary Care Research Group) Annual Meeting. The aim of the forum was to develop principles for action for the primary healthcare research community on addressing social and structural determinants of health.

A viewpoint on stress generation methodology.

This article provides an overview of Stress Generation Methodology. Stress generation is a phenomenon in which individuals with depression or vulnerability to depression experience greater dependent stressful life events (SLEs), defined as stressors in which individuals at least partially contributed to occurrence. The stress generation process demonstrates how depressed individuals shape their environments, contributing to depression maintenance and exacerbation.

Prospective associations between early adolescent reward functioning and later dimensions of psychopathology.

Individual differences in reward functioning have been associated with numerous disorders in adolescence. Given relations with multiple forms of psychopathology, it is unclear whether these associations are disorder specific or reflective of shared variance across multiple disorders. In a sample of adolescents (N = 418), we examined associations between neural and self-reported indices of early reward functioning (age 12) with different levels of a hierarchical psychopathology model assessed later in adolescence (age 18).

Do COVID-19 Infectious Disease Models Incorporate the Social Determinants of Health? A Systematic Review.

Objectives: To identify COVID-19 infectious disease models that accounted for social determinants of health (SDH).

Methods: We searched MEDLINE, EMBASE, Cochrane Library, medRxiv, and the Web of Science from December 2019 to August 2020. We included mathematical modelling studies focused on humans investigating COVID-19 impact and including at least one SDH.

Oscillating US Department of Defense policies and medical record documentation of gender dysphoria in service members: an observational time-series analysis.

Background: United States military policies regarding service by transgender service members have shifted several times within the past decade. The relationships between policy changes and electronic health record documentation of gender dysphoria, a current and historic policy requisite for gender affirming care receipt, in active duty service members remain unknown.

Methods: Bayesian estimator of abrupt change, seasonality, and trend models identified changepoints in the proportion of service members who had new and then historical medical record documentation consistent with gender dysphoria from January 2015 to August 2022.