Rapid Adaptation to Prevent Drug Use (RAPD): protocol of a pilot randomized trial to enhance the impact of an evidence-based intervention for youth.

Background: Drug use trends change rapidly among youth, leaving intervention experts struggling to respond promptly. Delays in responses can lead to preventable morbidity and mortality. The COVID-19 pandemic underscored the need for implementation science to facilitate rapid, equitable responses using existing treatment and prevention efforts.

MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays.

Multiplexed assays of variant effect (MAVEs) are a critical tool for researchers and clinicians to understand genetic variants. Here we describe the 2024 update to MaveDB ( https://www.mavedb.

Documentation of lead exposure-associated comorbidity among 4538 workers in China.

Background: Systematic documentation of morbidity with exposure assessment in a large group of lead (Pb)-exposed workers in China.

Methods: Using the cluster sampling method, Pb-exposed workers were recruited from a factory in the Henan Province, China. The morbidity information and blood lead concentration (BLC) from each worker were collected.

Cardiovascular and thromboembolic outcomes with immune checkpoint inhibitors in gastroesophageal cancer: a propensity score-matched cohort study.

Background: Immune checkpoint inhibitors (ICIs) have been associated with an increased risk of cardiovascular and thromboembolic events. However, the incidence of cardiovascular and thromboembolic events associated with ICIs in gastroesophageal cancers is unknown.

Methods: We performed a propensity score-matched cohort study using the TriNetX Analytics Network database, which comprises de-identified data from over 130 participating healthcare institutions.

Exploring and validating associations between six systemic inflammatory indices and ischemic stroke in a middle-aged and old Chinese population.

Background: Inflammation and maladaptive immune mechanisms have been substantiated as integral components in the critical pathological processes of the injury cascade in ischemic stroke (IS). This study aimed to explore the associations between six systemic inflammatory indices and IS in a Chinese population.

Methods: This was a case-control study based on the retrospective review of electronic medical records from two hospitals in Shandong Province, China.

Epidemiology of Coronavirus Disease 2019-Associated Fungal Infections in the Intensive Care Unit: A Single-Center Retrospective Study.

Introduction: Invasive fungal disease (IFD) is a morbid superinfection that can arise in critically ill patients with COVID-19 infection. Studies evaluating the full spectrum of COVID-19-associated fungal infections remain limited.

Methods: Single-center retrospective study assessing IFD in patients with COVID-19, hospitalized for ≥ 72 h in the intensive care unit (ICU) between 02/25/20 and 02/28/22 (n = 1410).

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Diversity and consequences of structural variation in the human genome.

The biomedical community is increasingly invested in capturing all genetic variants across human genomes, interpreting their functional consequences and translating these findings to the clinic. A crucial component of this endeavour is the discovery and characterization of structural variants (SVs), which are ubiquitous in the human population, heterogeneous in their mutational processes, key substrates for evolution and adaptation, and profound drivers of human disease. The recent emergence of new technologies and the remarkable scale of sequence-based population studies have begun to crystalize our understanding of SVs as a mutational class and their widespread influence across phenotypes.

Development of a 3D cephalometric index to grade severity of dentofacial deformity in patients with juvenile idiopathic arthritis.

This investigation aimed to develop a radiographic 3D cephalometric index to grade severity of dentofacial deformity in patients with juvenile idiopathic arthritis (JIA), and to perform a validation against expert evaluations. Data were collected from a population-based Nordic JIA cohort of 240 patients that received a cone-beam computed tomography (CBCT) scan approximately 17 years after onset of JIA. The cohort was randomized into two groups: A baseline group for establishing the index (n = 210) and a test group (n = 30).

Time to HIV viral rebound and frequency of post-treatment control after analytical interruption of antiretroviral therapy: an individual data-based meta-analysis of 24 prospective studies.

The only current strategy to test efficacy of novel interventions for sustained HIV control without antiretroviral therapy (ART) among people with HIV (PWH) is through an analytical treatment interruption (ATI). Inclusion of 'placebo' controls in ATIs poses ethical, logistical, and economic challenges. To understand viral dynamics and rates of post-treatment control (PTC) after ATI among PWH receiving either placebo or no intervention, we undertook an individual-participant data meta-analysis.

Concussion and depressive symptoms in high school students: impact of physical activity and substance use.

Objective: To investigate the association between concussion history and depressive symptoms after adjusting for physical activity, substance use, and illicit drug use.

Methods: We analysed data from the Adolescent Behaviour and Experiences Survey, a nationally representative survey of adolescents in the USA. Our independent variables were history of concussion in the 12 months preceding survey completion; self-reported weekly physical activity (days per week with >60 min of physical activity, 0-7 scale); substance use over the past 30 days (yes vs no) and illicit drug use throughout lifetime (yes vs no).

Engineered allogeneic stem cells orchestrate T lymphocyte driven immunotherapy in immunosuppressive leptomeningeal brain metastasis.

Background: Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy in lung to leptomeningeal brain metastasis (LLBM) remains poor.

Methods: A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed to idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic clinical LLBM.

Structural and functional analysis of the Nipah virus polymerase complex.

Nipah virus (NiV) is a bat-borne, zoonotic RNA virus that is highly pathogenic in humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a promising drug target. We determined the cryoelectron microscopy (cryo-EM) structure of the NiV polymerase complex, comprising the large protein (L) and phosphoprotein (P), and performed structural, biophysical, and in-depth functional analyses of the NiV polymerase.

Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer's disease.

In Alzheimer's disease (AD) research, the 5xFAD mouse model is commonly used as a heterozygote crossed with other genetic models to study AD pathology. We investigated whether the parental origin of the 5xFAD transgene affects plaque deposition. Using quantitative light-sheet microscopy, we found that paternal inheritance of the transgene led to a 2-fold higher plaque burden compared with maternal inheritance, a finding consistent across multiple 5xFAD colonies.

Cardiovascular Complications During Delivery Hospitalization in Patients With Psoriasis.

Background: Psoriasis in pregnancy is associated with adverse maternal outcomes. However, there are limited data on this subject.

Objectives: The purpose of our study was to investigate the association between psoriasis and related cardiovascular complications during delivery.

Optimizing energy threshold selection for low-concentration contrast agent quantification in small animal photon-counting CT.

Gold nanoparticles (GNPs) are widely used for biological research and applications. The in-vivo concentration of GNPs is usually low due to biological safety concerns, thus posing a challenge for imaging. This work investigates on optimal energy threshold selection in photon-counting detector(PCD)-based CT (PCCT) for the quantification of low-concentration GNPs.

Middle meningeal artery embolization for chronic subdural hematoma in the nonagenarian population.

Background: The estimated incidence of chronic subdural hematomas (cSDH) in the general population is projected to nearly double over the next decade, likely making it the most commonly treated cranial neurosurgical condition in adults by 2030. We investigated the outcomes of middle meningeal artery embolization (MMAe) as either a primary or adjunctive treatment for cSDH in nonagenarian patients.

Methods: We retrospectively reviewed all patients 90 years of age or older treated with middle meningeal artery embolization for cSDH from 2018 to 2024 at two academic institutions.

Biotin mitigates the development of manganese-induced, Parkinson's disease-related neurotoxicity in and human neurons.

Chronic exposure to manganese (Mn) induces manganism and has been widely implicated as a contributing environmental factor to Parkinson's disease (PD), featuring notable overlaps between the two in motor symptoms and clinical hallmarks. Here, we developed an adult model of Mn toxicity that recapitulated key parkinsonian features, spanning behavioral deficits, neuronal loss, and dysfunctions in lysosomes and mitochondria. Metabolomics analysis of the brain and body tissues of these flies at an early stage of toxicity identified systemic changes in the metabolism of biotin (also known as vitamin B) in Mn-treated groups.

Use of Claims to Assess Outcomes and Treatment Effects in the Evolut Low Risk Trial.

Background: Food and Drug Administration-mandated postmarket studies for transcatheter aortic valve replacement in low-risk populations plan to use passively collected registry data linked to claims for long-term follow-up out to 10 years. Therefore, it is critically important to understand the validity of these claims-based end points. We sought to evaluate the ability of administrative claims with () codes to identify trial-adjudicated end points and reproduce treatment comparisons of aortic valve replacement in the Evolut Low Risk Trial.

Pseudorabies virus infection triggers pUL46-mediated phosphorylation of connexin-43 and closure of gap junctions to promote intercellular virus spread.

Gap junctions (GJs) play a pivotal role in intercellular communication between eukaryotic cells, including transfer of biomolecules that contribute to the innate and adaptive immune response. However, if and how viruses affect gap junction intercellular communication (GJIC) remains largely unexplored. Here, we describe how the alphaherpesvirus pseudorabies virus (PRV) triggers ERK1/2-mediated phosphorylation of the main gap junction component connexin 43 (Cx43) and closure of GJIC, which depends on the viral protein pUL46.

Frontline Clinic Administrator Perspectives on Extreme Weather Events, Clinic Operations, and Climate Resilience.

Climate-sensitive extreme weather events are increasingly impacting frontline clinic operations. We conducted a national, cross-sectional survey of 284 self-identified administrators and other staff at frontline clinics determining their attitudes toward climate change and the impacts, resilience, and preparedness of clinics for extreme weather events. Most respondents (80.

Mindfulness Training vs Recovery Support for Opioid Use, Craving, and Anxiety During Buprenorphine Treatment: A Randomized Clinical Trial.

Importance: During buprenorphine treatment for opioid use disorder (OUD), risk factors for opioid relapse or treatment dropout include comorbid substance use disorder, anxiety, or residual opioid craving. There is a need for a well-powered trial to evaluate virtually delivered groups, including both mindfulness and evidence-based approaches, to address these comorbidities during buprenorphine treatment.

Objective: To compare the effects of the Mindful Recovery Opioid Use Disorder Care Continuum (M-ROCC) vs active control among adults receiving buprenorphine for OUD.

Genomic Drivers of Coronary Artery Disease and Risk of Future Outcomes After Coronary Angiography.

Importance: Disease characteristics of genetically mediated coronary artery disease (CAD) on coronary angiography and the association of genomic risk with outcomes after coronary angiography are not well understood.

Objective: To assess the angiographic characteristics and risk of post-coronary angiography outcomes of patients with genomic drivers of CAD: familial hypercholesterolemia (FH), high polygenic risk score (PRS), and clonal hematopoiesis of indeterminate potential (CHIP).

Design, Setting, And Participants: A retrospective cohort study of 3518 Mass General Brigham Biobank participants with genomic information who underwent coronary angiography was conducted between July 18, 2000, and August 1, 2023.