Massachusetts General Hospital

Metabolomic profiling reveals distinct and shared biology in COPD and IPF

Chronic Obstructive Pulmonary disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic pulmonary disorders with distinct pathologies but shared risk factors. Metabolomics may provide insights into mechanisms. To identify metabolites associated with COPD and IPF, and to...

MitoGPS: A Mitochondrial DNA G‐Quadruplex‐Targeting Strategy for Tumor‐Preferential Type I Photodynamic Therapy

ABSTRACT Photodynamic therapy (PDT) is a clinically promising, minimally invasive cancer treatment offering precise spatiotemporal control. However, achieving preferential tumor accumulation remains a critical challenge, which limits therapeutic efficacy and induces off‐target to...

“I Just Need Guidance Through This Maze I’m Going Through”: Addressing Unmet Basic and Mental Health Needs to Facilitate Engagement in HIV Prevention Services in the Context of Stimulant Use

There is a global syndemic of HIV, mental health challenges, substance use, and structural barriers. Critical to local HIV prevention efforts is understanding this syndemic in the context of rising stimulant use to inform intervention development. Adhering to the EPIS model, we c...

Hypoxia-activated scleraxis a mediates epicardial progenitor differentiation into a unique cardiac perivascular cell type

Abstract The epicardium is a crucial source of progenitor cells and paracrine signals that support heart development and regeneration. However, the molecular mechanisms that guide epicardial cell fate decisions remain incompletely understood. Here, we identify the transcription f...

An ex vivo gut mucosal explant assay to compare HIV tissue susceptibility shows increased HIV susceptibility with methamphetamine exposure

Background: mucosal explant models for HIV assess viral replication but do not fully capture the ability of tissue to support productive infection and transfer to target cells, an important indicator of tissue susceptibility. Additional tools to investigate relative mucosal susce...

“As soon as it’s trying to be persuasive, my skepticism kicks in”: A qualitative study to co-design vaccine communication strategies with vaccine hesitant adults in Canada

Vaccine hesitancy continues to impede vaccine uptake in Canada. Few interventions directly engage hesitant adults in co-designing communication materials. This study aimed to co-develop and evaluate digital vaccine communication messages with hesitant adults in Canada to improve...

Early improvement in depressive symptoms after pallidothalamic tract deep brain stimulation for drug-induced dystonia

Stimulation for lithium-induced dystoniaLong-term exposure to psychotropic agents, including lithium and dopamine D2/D3 partial agonists such as brexpiprazole, has been associated with delayed and sometimes persistent

Variation in In-Hospital Emergency Transfer Rates Across Pediatric Hospitals

BACKGROUND: Clinical deterioration with late escalation, termed emergency transfer (ET), is a key safety metric. However, national benchmarking is limited by variable definitions. We sought to estimate pooled ET rates and assess variation across pediatric hospitals. METHODS: We p...

Rare variant effect estimation and polygenic risk prediction

Abstract Due to their low frequency, estimating the effect of rare variants is challenging. Here, we propose RareEffect, a method that first estimates gene- or region-based heritability and then each variant effect size using an empirical Bayes approach. Our method uses a varianc...

Development of a Tool to Assess Competency in Bronchoscopic Lung Volume Reduction Via Endobronchial Valve Placement

RATIONALE: Bronchoscopic lung volume reduction (BLVR) is an established treatment option for severe emphysema, improving lung function and quality of life. Despite its growing use, there are no standardized, validated tools to assess operator competency in performing BLVR, limiti...

Proliferative control of the saccular-stage developing mouse lung requires the histone methylation activity of KMT2D

KMT2D, the histone methyltransferase and core component of the COMPASS/MLL4 complex, has been implicated in developmental diseases such as Kabuki Syndrome, interstitial lung disease, and congenital diaphragmatic hernia, with clear links to pediatric pulmonary disorders. Despite t...

Scanning X-ray microdiffraction studies of protein accumulation and tissue loss in thin sections of human brain tissue in Alzheimer’s disease

Neurodegeneration in Alzheimer's disease is characterized by accumulation of pathological protein deposits including Aβ plaques, tau tangles and diffuse neuropil threads accompanied by wide-spread tissue loss. While dense protein deposits are readily observed by conventional meth...

The role of biomarkers across the care continuum in acute heart failure

Acute heart failure (AHF) remains a global health challenge, characterized by high morbidity, mortality, and frequent rehospitalizations. The heterogeneity of clinical presentations in AHF and its complex underlying pathophysiology complicates diagnosis, risk stratification, and...

Multimodal profiling of pro-inflammatory protease activity identifies caspase-1 as a target for lung cancer interception

Abstract The systemic inhibition of IL-1b, a key mediator of pulmonary inflammation, has been shown to reduce the incidence of lung cancer in patients in years following treatment, but knowledge gaps surrounding its activation and role in the tumor microenvironment are hindering...

Directed Evolution of an Escherichia coli Secretor Strain Using the Curli Pathway

Abstract A key goal of many bacterial engineering projects is to produce protein, due to their potent chemical and material functions. However, recombinant proteins are usually produced intracellularly, and secreting arbitrary proteins directly into an extracellular environment i...

Platelet Reactivity and Sex Differences: Clinical Implications for Women

Platelets are central to hemostasis and thrombosis. Excessive platelet activation contributes to arterial thrombotic events, including myocardial infarction, ischemic stroke, and complications of peripheral artery disease, whereas excessive platelet inhibition increases bleeding...

Psychoactive Medication Prescribing After Critical Illness in American Adults Not Justified by a Documented Supporting Diagnosis

Objectives: To describe psychoactive medication (PM) prescribing in the 30 days after an ICU admission requiring mechanical ventilation not supported by a documented diagnosis in American adults not prescribed a PM before ICU admission. This nondiagnostically supported PM prescri...

Rural-Urban Disparities in Contemporary Systemic Therapy for Advanced Prostate Cancer

This cross-sectional study examines the associations of rural-urban residence and race with receipt of systemic therapy for advanced prostate cancer.

Durability of wrist denervation for osteoarthritis: a multicentre outcome study

INTRODUCTION: Traditional surgical treatments for wrist osteoarthritis, such as arthrodesis or arthroplasty, are invasive and irreversibly compromise joint motion. Wrist denervation offers a less invasive alternative aimed at pain relief while preserving mobility. However, its du...

Deletion of the Salmonella pathogenicity island 2 gene, spiC , in attenuated Salmonella Typhimurium VNP20009 optimizes its potential for bacterial schwannoma therapy

ABSTRACT Recent advances in systems biology and immunotherapy have spurred the use of bacteria as therapeutic vehicles for cancer treatment. Currently, Bacillus Calmette–Guérin remains the only FDA-approved bacterial strain for high-risk, non–muscle-invasive bladder cancer. Altho...