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.

Causal Inference With Observational Data and Unobserved Confounding Variables.

Experiments have long been the gold standard for causal inference in Ecology. As Ecology tackles progressively larger problems, however, we are moving beyond the scales at which randomised controlled experiments are feasible. To answer causal questions at scale, we need to also use observational data -something Ecologists tend to view with great scepticism.

Identifying and targeting key driver genes for collagen production within the 11q13/14 breast cancer amplicon.

Breast cancers of the IntClust-2 type, characterized by amplification of a small portion of chromosome 11, have a median survival of only five years. Several cancer-relevant genes occupy this portion of chromosome 11, and it is thought that overexpression of a combination of driver genes in this region is responsible for the poor outcome of women in this group. In this study we used a gene editing method to knock out, one by one, each of 198 genes that are located within the amplified region of chromosome 11 and determined how much each of these genes contributed to the survival of breast cancer cells.

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.

Factors Associated With Semaglutide Initiation Among Adults With Obesity.

Importance: Semaglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist medication, was approved for weight management in individuals with obesity in June 2021. There is limited evidence on factors associated with uptake among individuals in this subgroup without diabetes.

Objective: To explore factors associated with semaglutide initiation among a population of commercially insured individuals with obesity but no diagnosed diabetes.

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.

Pyrimidinergic P2Y1-Like Nucleotide Receptors Are Functional in Rat Conjunctival Goblet Cells.

Purpose: To investigate the presence of uridine-5'-triphosphate (UTP)-activated P2Y1-like nucleotide receptors (P2Y2R, P2Y4R, and P2Y6R) in conjunctival goblet cells (CGCs) and determine if they increase intracellular Ca2+ concentration ([Ca2+]i) and induce mucin secretion.

Methods: Adult, male rat conjunctiva was used for culture of CGCs. To investigate the expression of P2YRs, mRNA was extracted from CGCs and used for reverse transcription PCR (RT-PCR) with commercially obtained primers specific to P2Y2R, P2Y4R, and P2Y6R.

Comparative Effectiveness of Individual Sodium-Glucose Cotransporter 2 Inhibitors.

Importance: Evidence on cardiovascular benefits and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors is mainly from placebo-controlled trials. Therefore, the comparative effectiveness and safety of individual SGLT-2 inhibitors remain unknown.

Objective: To compare the use of canagliflozin or dapagliflozin with empagliflozin for a composite outcome (myocardial infarction [MI] or stroke), heart failure hospitalization, MI, stroke, all-cause death, and safety outcomes, including diabetic ketoacidosis (DKA), lower-limb amputation, bone fracture, severe urinary tract infection (UTI), and genital infection and whether effects differed by dosage or cardiovascular disease (CVD) history.

A Descriptive Analysis of the Seasonal Patterns of Bone Stress Injury Incidence in Division I Collegiate Distance Runners.

Background: A bone stress injury (BSI) is a common overuse injury in collegiate athletes, particularly cross-country and track and field runners. Limited work describes the seasonality of BSIs or the differences in rates and anatomic locations of BSIs in collegiate runners.

Purpose: To describe seasonally related trends in anatomic locations of BSIs in National Collegiate Athletic Association (NCAA) Division I male and female middle- and long-distance runners.

Generative Artificial Intelligence in Anatomic Pathology.

Context.—: Generative artificial intelligence (AI) has emerged as a transformative force in various fields, including anatomic pathology, where it offers the potential to significantly enhance diagnostic accuracy, workflow efficiency, and research capabilities.

Objective.

MAPK pathway activating alteration and immunotherapy efficacy in squamous cell lung carcinoma: results from the randomized, prospective SQUINT trial.

Background: The role of activating alterations in the MAPK pathway in predicting immunotherapy efficacy in lung squamous cell carcinoma (LSCC) patients is largely unknown. The aims of the randomized, phase II SQUINT trial were to assess the efficacy of nivolumab plus ipilimumab (NI) versus platinum-based chemotherapy plus nivolumab (N-CT) and to identify clinically available biomarkers of response to immunotherapy in patients with advanced or metastatic LSCC.

Methods: SQUINT was an open-label, randomized, parallel, non-comparative, phase II trial of NI versus N-CT in chemo-naïve, metastatic or recurrent LSCC adult patients.

Return to Sport and Graft Failure Rates After Primary Anterior Cruciate Ligament Reconstruction With a Bone-Patellar Tendon-Bone Versus Hamstring Tendon Autograft: A Systematic Review and Meta-analysis.

Background: Anterior cruciate ligament (ACL) tears are frequent injuries in athletes that often require surgical reconstruction so that patients may return to their previous levels of performance. While existing data on patient-reported outcomes are similar between bone-patellar tendon-bone (BTB) and hamstring tendon (HT) autografts, the literature regarding return to sport (RTS), return to previous levels of sport activity, and graft failure rate remains limited.

Purpose: To compare rates of RTS, return to previous activity levels, and graft retears among athletes undergoing primary ACL reconstruction using a BTB versus HT autograft.

Impact of lesion preparation-induced calcified plaque defects in vascular intervention for atherosclerotic disease: in silico assessment.

Percutaneous coronary interventions in highly calcified atherosclerotic lesions are challenging due to the high mechanical stiffness that significantly restricts stent expansion. Intravascular lithotripsy (IVL) is a novel vessel preparation technique with the potential to improve interventional outcomes by inducing microscopic and macroscopic cracks to enhance stent expansion. However, the exact mechanism of action for IVL is poorly understood, and it remains unclear whether the improvement in-stent expansion is caused by either the macro-cracks allowing the vessel to open or the micro-cracks altering the bulk material properties.

Everyday ethnic discrimination and early substance use based on hair samples in high-risk racial/ethnic minority early adolescents.

Objectives: Although racially and ethnically minoritized youth are more likely to experience adverse effects of substance use, and substance use before age 14 is strongly associated with an elevated risk of later substance use disorders, there is limited research identifying risk factors for early substance use. The study examined the role of experiencing ethnic discrimination from teachers, other adults outside of school, and other students in predicting early substance use (measured with hair toxicology reports).

Methods: The study used data from the Adolescent Brain Cognitive Development Study.

Parsing the existential isolation-outcome association into its within- and between-patient components in naturalistic psychotherapy.

Complementing the oft-studied construct of isolation, research has increasingly focused on existential isolation (EI), or the subjective feeling of separateness in one's experience. In the clinical realm, several studies have demonstrated that higher EI is associated with more severe mental health problems at a single cross-section of time. Moreover, one study showed that higher pretreatment EI predicted worse psychotherapy outcomes.

Shear-Stress Initiates Signal Two of NLRP3 Inflammasome Activation in LPS-Primed Macrophages through Piezo1.

The innate immune system is tightly regulated by a complex network of chemical signals triggered by pathogens, cellular damage, and environmental stimuli. While it is well-established that changes in the extracellular environment can significantly influence the immune response to pathogens and damage-associated molecules, there remains a limited understanding of how changes in environmental stimuli specifically impact the activation of the NLRP3 inflammasome, a key component of innate immunity. Here, we demonstrated how shear stress can act as Signal 2 in the NLRP3 inflammasome activation pathway by treating LPS-primed immortalized bone marrow-derived macrophages (iBMDMs) with several physiologically relevant magnitudes of shear stress to induce inflammasome activation.

Improved Annotation of Asthma Gene Variants with Cell Type Deconvolution of Nasal and Lung Expression-Quantitative Trait Loci.

Asthma is a genetically complex inflammatory airway disease associated with over 200 Single nucleotide polymorphisms (SNPs). However, the functional effects of many asthma-associated SNPs in lung and airway epithelial samples are unknown. Here, we aimed to conduct expression quantitative trait loci (eQTL) analysis using a meta-analysis of nasal and lung samples.

Bacterium-Phage Symbiosis Facilitates the Enrichment of Bacterial Pathogens and Antibiotic-Resistant Bacteria in the Plastisphere.

The plastisphere, defined as the ecological niche for microbial colonization of plastic debris, has been recognized as a hotspot of pathogenic and antibiotic-resistant bacteria. However, the interactions between bacteria and phages facilitated by the plastisphere, as well as their impact on microbial risks to public health, remain unclear. Here, we analyzed public metagenomic data from 180 plastisphere and environmental samples, stemming from four different habitats and two plastic types (biodegradable and nonbiodegradable plastics) and obtained 611 nonredundant metagenome-assembled genomes (MAGs) and 4061 nonredundant phage contigs.

Longer disease progression milestone-free time in people with amyotrophic lateral sclerosis treated versus not treated with intravenous edaravone: results from an administrative claims analysis.

To estimate time-to-progression milestones in people with amyotrophic lateral sclerosis (PALS) treated versus not treated with intravenous (IV) edaravone (Radicava IV, Mitsubishi Tanabe Pharma America [MTPA], hereafter "IV edaravone") in a real-world setting. IV edaravone is US FDA approved for the treatment of ALS and was shown in clinical trials to slow the rate of physical functional decline. This retrospective observational analysis included PALS continuously enrolled in Optum's Clinformatics Data Mart between 8 August 2017 and 31 December 2021.

Neighborhood Socioeconomic Status and Breastfeeding Initiation and Duration Among Primiparous Black Women.

Social determinants of health account for racial inequities in breastfeeding rates in the United States. There is a gap in the role of neighborhood socioeconomic status (NSES) as it relates to breastfeeding disparities. Using longitudinal data from the Black Women's Health Study, we assessed associations of NSES with breastfeeding initiation and duration in a cohort of primiparous U.

SLO co-opts host cell glycosphingolipids to access cholesterol-rich lipid rafts for enhanced pore formation and cytotoxicity.

Unlabelled: Streptolysin O (SLO) is a virulence determinant of group A (), the agent of streptococcal sore throat and severe invasive infections. SLO is a member of a family of bacterial pore-forming toxins known as cholesterol-dependent cytolysins, which require cell membrane cholesterol for pore formation. While cholesterol is essential for cytolytic activity, accumulating data suggest that cell surface glycans may also participate in the binding of SLO and other cholesterol-dependent cytolysins to host cells.