Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling.

Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs).

Moving toward Equity through Embedded ELSI Ethnography.

This paper describes the unique values of, challenges within, and opportunities presented by embedded ELSI ethnography. Drawing from our six-year embedded ELSI study of the WISDOM (Women Informed to Screen Depending on Measures of Risk) trial, we present three examples of the variable ways we engaged with the WISDOM trial's scientific team. WISDOM is a preference-sensitive, pragmatic, randomized controlled trial of risk-based breast cancer screening informed by genomics.

Receiving a Pathogenic Variant in a Population Breast Cancer Screening Trial: A Mixed Method Study.

Introduction: Risk-based breast cancer screening aims to address persistent high morbidity and mortality. This study examined the experience of participants in the Women Informed to Screen Depending on Measures of Risk (WISDOM) trial who received a pathogenic variant in one of nine high or moderate penetrance breast cancer genes.

Methods: Participants completed a brief survey (n = 181) immediately following the results disclosure and 1 year later.

Integrating Indigenous midwives into a comprehensive primary care setting.

Canada has been unique in the modern era for limiting midwives from providing sexual health and perinatal care to families. Prohibitions on midwifery practice were finally lifted in Prince Edward Island in 2024, yet midwives' scope of practice continues to be restricted in most jurisdictions. The Canadian Midwifery Regulators Council recently recommended midwives should be able to practice their full scope.

Identifying protective factors for gender diverse adolescents' mental health.

Few studies have disentangled differences in victimization exposures and mental health symptoms among gender diverse subgroups, nor considered the role of potential protective factors in ameliorating the impact of victimization on gender diverse youths' mental health. Here we report findings from a secondary data analysis, in which we address this gap by analyzing cross-sectional survey data (N = 11,264 in the final analytic sample) from a population-based survey of youth in participating school districts in a large Midwestern U.S.

Impact of the COVID-19 Pandemic on Emergency Department Encounters in a Major Metropolitan Area.

Background: The end of 2019 marked the emergence of the COVID-19 pandemic. Public avoidance of health care facilities, including the emergency department (ED), has been noted during prior pandemics.

Objective: This study described pandemic-related changes in adult and pediatric ED presentations, acuity, and hospitalization rates during the pandemic in a major metropolitan area.

Navigating Stigma in Romantic Relationships Where One or Both Partners Sell Sexual Services.

Romantic relationships are an important part of our social identities and well-being. In this paper, we report on qualitative findings with thirty Canadian couples, interviewed together, where it was known that one or both partners sell sexual services for a living. We asked a series of open-ended questions related to the background of the couple's relationship, their day-to-day interactions and work-related stressors.

Genetic ancestry and diagnostic yield of exome sequencing in a diverse population.

It has been suggested that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental/subcontinental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. Cases (N = 845) with suspected genetic disorders underwent ES for diagnosis.

Participant perceptions of changes in psychosocial domains following participation in an adaptive deep brain stimulation trial.

Background: There has been substantial controversy in the neuroethics literature regarding the extent to which deep brain stimulation (DBS) impacts dimensions of personality, mood, and behavior.

Objective/hypothesis: Despite extensive debate in the theoretical literature, there remains a paucity of empirical data available to support or refute claims related to the psychosocial changes following DBS.

Methods: A mixed-methods approach was used to examine the perspectives of patients who underwent DBS regarding changes to their personality, authenticity, autonomy, risk-taking, and overall quality of life.

The role of polygenic risk scores in breast cancer risk perception and decision-making.

Polygenic risk scores (PRS) have the potential to improve the accuracy of clinical risk assessments, yet questions about their clinical validity and readiness for clinical implementation persist. Understanding how individuals integrate and act on the information provided by PRS is critical for their effective integration into routine clinical care, yet few studies have examined how individuals respond to the receipt of polygenic risk information. We conducted an embedded Ethical, Legal, and Social Implications (ELSI) study to examine if and how unaffected participants in a US population breast cancer screening trial understood and utilized PRS, as part of a multifactorial risk score combining traditional risk factors with a genetic risk assessment, to make screening and risk-reduction decisions.

Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry.

Purpose: It has been hypothesized that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort.

Methods: Cases (N=845) with suspected genetic disorders underwent ES for diagnosis.

A draft human pangenome reference.

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels.

Lower-risk substance use guidelines accessible by youth.

Background: Lower-risk substance use guidelines (LRSUGs) are an evidence-based harm reduction strategy used to provide information to people who use drugs so they can reduce harms associated with substance use.

Objectives: This study aimed to identify LRSUGs accessible to youth and to characterize the recommendations within these guidelines. The overall goal is to identify gaps in current LRSUGs and to inform researchers and policymakers of the kinds of health information youth can access.

Bayesian chemical reaction neural network for autonomous kinetic uncertainty quantification.

Chemical reaction neural network (CRNN), a recently developed tool for autonomous discovery of reaction models, has been successfully demonstrated on a variety of chemical engineering and biochemical systems. It leverages the extraordinary data-fitting capacity of modern deep neural networks (DNNs) while preserving high interpretability and robustness by embedding widely applicable physical laws such as the law of mass action and the Arrhenius law. In this paper, we further developed Bayesian CRNN to not only reconstruct but also quantify the uncertainty of chemical kinetic models from data.

Action of the Photochrome Glyght on GABAergic Synaptic Transmission in Mouse Brain Slices.

Glyght is a new photochromic compound described as an effective modulator of glycine receptors at heterologous expression, in brain slices and in zebrafish larvae. Glyght also caused weak inhibition of GABA-mediated currents in a cell line expressing α1/β2/γ2 GABA receptors. However, the effects of Glyght on GABAergic transmission in the brain have not been analysed, which does not allow a sufficiently comprehensive assessment of the effects of the compound on the nervous system.

Portrayals of wild primates in documentary films: reason for concern?

Documentaries are the primary means by which many people observe the behavior of wild primates. By influencing layperson perceptions of wild primates, documentaries could impact viewer conservation-related beliefs and behaviors and, therefore, the well-being of wild primates. To investigate such portrayals, we examined documentaries depicting the four species that were most represented in documentaries: rhesus macaque, chimpanzee, ring-tailed lemur, and mountain gorilla.

"If relatives inherited the gene, they should inherit the data." Bringing the family into the room where bioethics happens.

Biological kin share up to half of their genetic material, including predisposition to disease. Thus, variants of clinical significance identified in each individual's genome can implicate an exponential number of relatives at potential risk. This has renewed the dilemma over family access to research participant's genetic results, since prevailing U.

Post-trial access in implanted neural device research: Device maintenance, abandonment, and cost.

Background: Clinical trial participants who benefit from experimental neural devices for the treatment of debilitating and otherwise treatment-resistant conditions are generally not ensured continued access to effective therapy or maintenance of devices at the conclusion of trials.

Objective/hypothesis: Post-trial obligations have been extensively examined in the context of drug trials, but there has been little empirical examination of stakeholder perspectives regarding these obligations in the rapidly growing field of neural device research.

Methods: This study examined the perspectives of 44 stakeholders (i.

A qualitative study of unaffected ATM and CHEK2 carriers: How participants make meaning of 'moderate risk' genetic results in a population breast cancer screening trial.

Relatively little is known about experiences of individuals with a pathogenic variant in a moderately penetrant breast cancer gene, particularly those without a personal history of cancer. The WISDOM trial is testing a model of risk-based breast cancer screening that integrates genomic (nine genes and polygenic risk) and other risk factors. In the context of an embedded Ethical, Legal, and Social Implications (ELSI) study of WISDOM, we conducted qualitative interviews at two timepoints post-result disclosure with 22 ATM and CHEK2 carriers.

Researchers' Ethical Concerns About Using Adaptive Deep Brain Stimulation for Enhancement.

The capacity of next-generation closed-loop or adaptive deep brain stimulation devices (aDBS) to read (measure neural activity) and write (stimulate brain regions or circuits) shows great potential to effectively manage movement, seizure, and psychiatric disorders, and also raises the possibility of using aDBS to electively (non-therapeutically) modulate mood, cognition, and prosociality. What separates aDBS from most neurotechnologies (e.g.

Emotional Attention: From Eye Tracking to Computational Modeling.

Attending selectively to emotion-eliciting stimuli is intrinsic to human vision. In this research, we investigate how emotion-elicitation features of images relate to human selective attention. We create the EMOtional attention dataset (EMOd).