Mortality risk among individuals who smoke opioids compared with those who inject: A propensity score-matched cohort analysis of United States national treatment data.

Background And Aims: Opioid smoking is becoming more common in the United States. The aim of this analysis was to estimate relative mortality risk among those who primarily smoke opioids compared with those who inject.

Design: Retrospective propensity score-matched cohort analysis.

Prescribing rate, healthcare utilization, and expenditure of older adults using potentially inappropriate medications in China: A nationwide cross-sectional study.

Background: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China.

Methods: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017.

Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39.

Microglia and the border-associated macrophages contribute to the modulation of cerebral blood flow, but the mechanisms have remained uncertain. Here, we show that microglia regulate the cerebral blood flow baseline and the responses to whisker stimulation or intra-cisternal magna injection of adenosine triphosphate, but not intra-cisternal magna injection of adenosine in mice model. Notably, microglia repopulation corrects these cerebral blood flow anomalies.

Genomic sequencing: the case for equity of care in the era of personalized medicine.

Over the past two decades, genomic sequencing (exome and genome) has proven to be critical in providing a faster and more accurate diagnosis as well as tailored treatment plans for a variety of populations. Despite its potential, disparities in access to genomic sequencing persist, predominantly among underrepresented and socioeconomically disadvantaged groups and populations. This inequity stems from factors such as: 1) high costs of sequencing, 2) significant gaps in insurance coverage, 3) limited availability of genetic services in many healthcare institutions and geographic areas, and 4) lack of diversity in genetic research and databases.

Persistent exclusion of non-English speakers in Pediatric research: a national analysis using ClinicalTrials.gov.

Over one-fifth of US households speak a language other than English. While some studies have documented language-based disparities in pediatric clinical research, they are limited in scope and not representative of all US pediatric trials. Because language-based exclusion, if extensive, would limit the generalizability of the results of the research, we performed a systematic analysis of language-based eligibility criteria across all 4982 US pediatric interventional clinical trials registered on ClinicalTrials.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

CD45-PET is a robust, non-invasive tool for imaging inflammation.

Imaging inflammation holds immense potential for advancing the diagnosis, treatment and prognosis of many conditions. The lack of a specific and sensitive positron emission tomography (PET) probe to detect inflammation is a critical challenge. To bridge this gap, we present CD45-PET imaging, which detects inflammation with exceptional sensitivity and clarity in several preclinical models.

Multiscale footprints reveal the organization of cis-regulatory elements.

Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

RELMβ sets the threshold for microbiome-dependent oral tolerance.

Tolerance to dietary antigens is critical for avoiding deleterious type 2 immune responses resulting in food allergy (FA) and anaphylaxis. However, the mechanisms resulting in both the maintenance and failure of tolerance to food antigens are poorly understood. Here we demonstrate that the goblet-cell-derived resistin-like molecule β (RELMβ) is a critical regulator of oral tolerance.

Association of environmental, demographic and clinical parameters with physical activity in children with asthma.

Personal characteristics, unfavorable weather conditions and air pollution have been linked with reduced physical activity in children. However, among children with asthma the effects of these parameters remain unclear. This study objectively quantified the physical activity of children with asthma and evaluated its association with environmental, personal, and clinical parameters.

Medical School Curriculum Evaluation to Improve Health Equity Education.

Following the birth of Black Lives Matter, USA medical students advocated for greater commitment to health equity from their schools. In response to such concerns, in 2015, the Yale School of Medicine formed a committee for diversity, inclusion, and social justice and a committee on lesbian, gay, bisexual, transgender, queer, questioning, and intersex affairs. Based on their efforts, our Educational Policy and Curriculum Committee commissioned a student-faculty-led task force to survey the curriculum and make recommendations toward the creation of a health equity curriculum.

Joint Physical-Psychosocial Frailty and Risks of All-Cause and Cause-Specific Premature Mortality.

Background: The importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individual physical and psychosocial factors.

Design: A total of 381,295 participants with no history of cancer or cardiovascular disease (CVD) were recruited from the UK Biobank cohort.

Validating the RISE Communication Play Protocol as a Diagnostic Tool for Autism in Early Childhood: A Pilot Study.

There are few validated remote tools that can be used to assess for autism and to capture subtle changes in children's social communication over time. Recently, user-centered design principles were applied to develop a parent-mediated remote assessment, the Reciprocal Imitation and Social Engagement Child Play Protocol (RISE CPP) to enable researchers to capture micro-level behaviors in children, while promoting useability for researchers and families, reducing caregiver burden, and maintaining reliability. This paper describes a pilot study to validate the RISE CPP as a tool to support clinician diagnosis of autism.

In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.

Huntington's disease, one of more than 50 inherited repeat expansion disorders, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT. Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies.

FABP4 as a therapeutic host target controlling SARS-CoV-2 infection.

Host metabolic fitness is a critical determinant of infectious disease outcomes. Obesity, aging, and other related metabolic disorders are recognized as high-risk disease modifiers for respiratory infections, including coronavirus infections, though the underlying mechanisms remain unknown. Our study highlights fatty acid-binding protein 4 (FABP4), a key regulator of metabolic dysfunction and inflammation, as a modulator of SARS-CoV-2 pathogenesis, correlating strongly with disease severity in COVID-19 patients.

Fabrication of nonplanar tapered fibers to integrate optical and electrical signals for neural interfaces in vivo.

Implantable multifunctional probes have transformed neuroscience research, offering access to multifaceted brain activity that was previously unattainable. Typically, simultaneous access to both optical and electrical signals requires separate probes, while their integration into a single device can result in the emergence of photogenerated electrical artifacts, affecting the quality of high-frequency neural recordings. Among the nontrivial strategies aimed at the realization of an implantable multifunctional interface, the integration of optical and electrical capabilities on a single, minimally invasive, tapered optical fiber probe has been recently demonstrated using fibertrodes.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Evaluating pulmonary stenosis and regurgitation impact on cardiac strain and strain rate in a porcine model via magnetic resonance feature tracking.

Background: Pulmonary stenosis (PS) is common in congenital heart disease and an integral finding in Tetralogy of Fallot (TOF). Pulmonary regurgitation (PR) is more commonly found following surgery in repaired TOF. We aimed to evaluate the haemodynamic effects of PS and PR on cardiac physiology in a porcine model using cardiac magnetic resonance-based feature tracking (CMR-FT) deformation imaging.

Enhancing social functioning using multi-user, immersive virtual reality.

Rates of loneliness and other forms of social disconnection have been increasing worldwide. Prior studies have suggested that brief behavioral interventions can teach skills that may improve social functioning and connection but, currently, access to such interventions is limited. One previously untested approach for addressing this gap is to teach these skills using immersive, multi-user virtual reality (VR).

Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq.

Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that includes the template-pseudoknot (t/PK) and the three-way junction (CR4/5). These hTR domains bind the telomerase reverse transcriptase (hTERT) protein and are essential for telomerase activity. Here, we probe hTR structure in living cells using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and ensemble deconvolution analysis.

Diversity in the medical research ecosystem: a descriptive scientometric analysis of over 49 000 studies and 150 000 authors published in high-impact medical journals between 2007 and 2022.

Objectives: Health research that significantly impacts global clinical practice and policy is often published in high-impact factor (IF) medical journals. These outlets play a pivotal role in the worldwide dissemination of novel medical knowledge. However, researchers identifying as women and those affiliated with institutions in low- and middle-income countries (LMICs) have been largely under-represented in high-IF journals across multiple fields of medicine.