N-terminal fragment shedding contributes to signaling of the full-length adhesion receptor ADGRL3.

Most adhesion GPCRs undergo autoproteolytic cleavage during receptor biosynthesis, resulting in non-covalently bound N- and C-terminal fragments (NTF and CTF) that remain associated during receptor trafficking to the plasma membrane. While substantial evidence supports increased G protein signaling when just the CTF is expressed, there is an ongoing debate about whether NTF removal is required to initiate signaling in the context of the wild-type receptor. Here, we use adhesion GPCR latrophilin-3 (ADGRL3) as a model receptor to investigate tethered agonist-mediated activation.

Glaucoma Screening and Referral Risk Factors in a High-Risk Population: Follow-up Study of the Manhattan Vision Screening Study (NYC-SIGHT).

Prcis: Community-based eye health screenings that incorporated fundus photography and optometric exams in a high-risk NYC population effectively identified a higher than average number of participants that required an in-office glaucoma evaluation.

Purpose: To report glaucoma screening rates and risk factors associated with referral for in-office glaucoma evaluation in the Manhattan Vision Screening and Follow-up Study (NYC-SIGHT).

Methods: In this 5-year, cluster-randomized clinical trial, eligible individuals aged 40 and older were recruited from affordable housing developments and senior centers.

Isolation and structure of broad SIV-neutralizing antibodies reveal a proximal helical MPER epitope recognized by a rhesus multi-donor class.

The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques.

Radon Exposure and Gestational Diabetes.

Importance: Understanding environmental risk factors for gestational diabetes (GD) is crucial for developing preventive strategies and improving pregnancy outcomes.

Objective: To examine the association of county-level radon exposure with GD risk in pregnant individuals.

Design, Setting, And Participants: This multicenter, population-based cohort study used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) cohort, which recruited nulliparous pregnant participants from 8 US clinical centers between October 2010 and September 2013.

Windows in the ICU and Postoperative Delirium: A Retrospective Cohort Study.

Objectives: The ICU built environment-including the presence of windows-has long been thought to play a role in delirium. This study investigated the association between the presence or absence of windows in patient rooms and ICU delirium.

Design: Retrospective single institution cohort study.

Risk of Incident Cancer in Veterans with Diabetes Who Use Metformin Versus Sulfonylureas.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans. This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfonylureas for diabetes between 2001 to 2012.

Impact of population screening for Lynch syndrome insights from the All of Us data.

Lynch Syndrome (LS) is a common genetic cancer condition that allows for personalized cancer prevention and early cancer detection in identified gene carriers. We used data from the All of Us (AOU) Research Initiative to assess the prevalence of LS in the general U.S.

Evaluation and adaptation of a two-way text messaging intervention in the WIC breastfeeding peer counseling program: A qualitative analysis.

Breastfeeding (BF) is vital for maternal and infant health, yet post-hospital discharge support remains a challenge. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides BF peer counseling prenatally and up to 1-year postpartum among low-income women in the United States. The Lactation Advice Through Texting Can Help (LATCH) intervention is an evidence-based two-way text messaging intervention that provides BF education and support in the WIC peer counseling program.

Improving Patient Experience by Understanding Barriers and Incentives to Telehealth Adoption Among Physicians at a Large Academic Medical Center.

Patients benefit from and appreciate the option to use telehealth with their providers. Such patient expectations have therefore led to new questions about the factors that affect providers' willingness to adopt telehealth as part of their clinical practice. We interviewed 19 physicians across four specialties with differential rates of telehealth use (Psychiatry, Anesthesiology, Physical Medicine & Rehabilitation [PM&R], and Ophthalmology) to discern the barriers and incentives to telehealth adoption among physicians.

FAP-Targeted SPECT/CT and PET/CT Imaging for Breast Cancer Patients.

Breast cancer presents a significant global health challenge, necessitating continued innovation in diagnostic and therapeutic approaches. Recent advances have led to the identification of cancer-associated fibroblasts, which are highly prevalent in breast cancers and express fibroblast activation proteins (FAPs), as critical targets. FAP-specific radiotracers, when used with PET/CT and SPECT/CT, have significant potential for improving early breast cancer detection, staging, treatment response monitoring, and therapeutic intervention.

Medical large language models are vulnerable to data-poisoning attacks.

The adoption of large language models (LLMs) in healthcare demands a careful analysis of their potential to spread false medical knowledge. Because LLMs ingest massive volumes of data from the open Internet during training, they are potentially exposed to unverified medical knowledge that may include deliberately planted misinformation. Here, we perform a threat assessment that simulates a data-poisoning attack against The Pile, a popular dataset used for LLM development.

Supporting the Individualized Use of Digital Tools in Community Mental Health: The Technology Specialist Pilot Study.

This pilot study evaluated the feasibility of the technology specialist intervention, which assists clients in achieving mental health recovery and well-being goals via existing digital tools in a real-world community mental health setting. Thirteen adult clients with serious mental illness and their providers completed baseline, 3-, and 6-month assessments, including goal setting, self-efficacy, activation, and acceptability measures, along with weekly ecological momentary assessments. Clients selected goals and corresponding tools, used the tools steadily, and showed improvement in activation and self-efficacy.

Establishing Minimal Clinically Important Differences for the Cognitive and Linguistic Scale (CALS) in Pediatric Neurorehabilitation.

The Cognitive and Linguistic Scale (CALS) was developed to serially monitor cognitive recovery of children and young people after severe acquired brain injury (ABI), during inpatient rehabilitation. The CALS can be used to derive Cognitive Ability Estimates (CAE) which are Rasch-propertied (unidimensional, interval-scale) and therefore may be ideally applied for use in research including within the context of clinical trials. Here, we used established statistical distribution-based and expert consensus-based methods to estimate the Minimal Clinically Important Difference (MCID) for CAE derived from the CALS.

Deconstructing the Monolith: An Educational Module for Understanding Disparities Within Asian American, Native Hawaiian, and Pacific Islander Populations.

Introduction: Asian American, Native Hawaiian, and Pacific Islander (AANHPI) people represent one of the largest and most rapidly growing groups in the United States and are often aggregated as a homogeneous, rather than diverse, population in medical research and education. Currently, few educational interventions focus on the disaggregation of AANHPI patient populations and the improvement of knowledge about health disparities that affect AANHPI patients.

Methods: We developed, implemented, and facilitated a workshop for medical students to address AANHPI health disparities, adaptable for in-person and online formats.

Novel rhesus macaque immunoglobulin germline genes identified by three sequencing approaches.

Introduction: Rhesus macaques have long been a focus of research for understanding immune responses to human pathogens due to their close phylogenetic relationship with humans. As rhesus macaque antibody germlines show high degrees of polymorphism, the spectrum of database-covered genes expressed in individual macaques remains to be determined.

Methods: Here, four rhesus macaques infected with SHIV became a study of interest because they developed broadly neutralizing antibodies against HIV-1.

Prevalence of Depression in Older Adults and the Potential Protective Role of Volunteering: Findings From the LongROAD Study.

Background: As the US population continues to age, depression and other mental health issues have become a significant challenge for healthy aging. Few studies, however, have examined the prevalence of depression in community-dwelling older adults in the United States.

Methods: Baseline data from the Longitudinal Research on Aging Drivers study were analyzed to examine the prevalence and correlates of depression in a multisite sample of community-dwelling adults aged 65-79 years who were enrolled and assessed between July 2015 and March 2017.

The breast cancer genetic testing experience: probing the potential utility of an online decision aid in risk perception and decision making.

Background: Despite the association of pathogenic variants (PVs) in cancer predisposition genes with significantly increased risk of breast cancer (BC), uptake of genetic testing (GT) remains low, especially among ethnic minorities. Our prior study identified that a patient decision aid, RealRisks, improved patient-reported outcomes (including worry and perceived risk) relative to standard educational materials. This study examined patients' GT experience and its influence on subsequent actions.

The potential impact of optimal blood pressure treatment intensity to reduce disparities in dementia between Black and White individuals.

Background: Black adults have higher dementia risk than White adults. Whether tighter population-level blood pressure (BP) control reduces this disparity is unknown.

Objective: Estimate the impact of optimal BP treatment intensity on racial disparities in dementia.

Low-Dose Oral Ginger Improves Daily Symptom Scores in Asthma.

A significant number of individuals with asthma have poorly controlled daily symptoms and utilize dietary supplements such as ginger in a quest for improved symptom control; however, its effectiveness at improving the control of symptoms is unproven. We questioned whether low-dose oral ginger would improve subjective and objective measurements of asthma control in mild-to-moderate asthmatics. We performed a randomized, placebo-controlled, double-blinded study of a low dose (1 g twice daily) of a dietary supplement of ginger in 32 mild-to-moderate uncontrolled asthmatics over a 2-month trial period while maintaining daily conventional asthma therapies.

A Thermo-responsive collapse system for controlling heterogeneous cell localization, ratio and interaction for three-dimensional solid tumor modeling.

Cancer immunotherapy using engineered cytotoxic effector cells has demonstrated significant potential. The limited spatial complexity of existing models, however, poses a challenge to mechanistic studies attempting to approve existing approaches of effector cell-mediated cytotoxicity within a three-dimensional, solid tumor-like environment. To gain additional experimental control, we developed an approach for constructing three-dimensional (3D) culture models using smart polymers that form temperature responsive hydrogels.

Auditory and Visual Thalamocortical Connectivity Alterations in Unmedicated People with Schizophrenia: An Individualized Sensory Thalamic Localization and Resting-State Functional Connectivity Study.

Background: Converging evidence from clinical neuroimaging and animal models has strongly implicated dysfunction of thalamocortical circuits in the pathophysiology of schizophrenia. Preclinical models of genetic risk for schizophrenia have shown reduced synaptic transmission from auditory thalamus to primary auditory cortex, which may represent a correlate of auditory disturbances such as hallucinations. Human neuroimaging studies, however, have found a generalized increase in resting state functional connectivity (RSFC) between whole thalamus and sensorimotor cortex in people with schizophrenia (PSZ).

A multiplex method for rapidly identifying viral protease inhibitors.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation.