Harvard University

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...

Pseudomonas aeruginosa-derived volatile organic compounds modulate AhR signaling to dysregulate airway mucus homeostasis

Pseudomonas aeruginosa frequently infects chronically diseased lungs and exacerbates airway mucus hypersecretion and failure in clearance. P. aeruginosa is metabolically versatile and secretes multiple volatile organic compounds (VOCs), which have been scrutinized as potential bi...

Challenges and approaches to genetic variants of uncertain significance in clinical practice and research

Despite advances in sequencing technologies and variant interpretation frameworks, many variants identified in genetic testing, particularly missense variants, remain classified as variants of uncertain significance (VUS), posing ongoing challenges in diagnosis and clinical manag...

A clinical analysis of the presentation of depression in Pakistan

Background Major depressive disorder is a leading cause of disability worldwide, yet its clinical presentation varies substantially across cultural contexts. In many low- and middle-income settings, including Pakistan, depression is frequently expressed through somatic rather tha...

Safety and Tolerability of Chronic Carvedilol in Pediatric Dilated Cardiomyopathy: A Report from the Pediatric Cardiomyopathy Registry

Long-term studies on safety of beta-blockers in pediatric heart failure (HF) are scant. We describe the safety profile, dose ranges, and tolerability of carvedilol in pediatric dilated cardiomyopathy (DCM). The Pediatric Cardiomyopathy Registry (PCMR) was used to identify patient...

The Role of Assignment in Defining and Identifying Causal Effects in Randomized Trials

In randomized trials, the per-protocol effect is defined as the effect of being assigned a treatment strategy and receiving treatment according to the assigned strategy; therefore, it encompasses the effect of the treatment strategy and any effect of assignment that does not oper...

Comprehensive Analysis of US Health Care Spending on Injuries

BACKGROUND: Traumatic injury affects every age group, payer, and care setting in the United States, yet how injury-related spending distributes across these dimensions has not been comprehensively quantified. OBJECTIVE: To estimate US health care spending on injuries in 2022 by m...

Money, Meals, and Marketing in Medicine: A 13‐Year Follow‐Up Survey of Physicians

Pharmaceutical company marketing to physicians is known to impact prescribing patterns. In 2011, we surveyed medical students and residents about physician/industry relationships. In 2024, we resurveyed the same participants to study changes in their behaviors over time and their...

Longitudinal evaluation of sleep disturbances in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

Abstract Purpose The current study examines longitudinal changes in sleep disturbances and the risks they pose for new-onset health conditions in survivors of childhood cancer. Methods Five-year survivors ( N = 1081; median [range] age 50.0 [45.2–55.0] years) and siblings ( N = 2...

Common Food Emulsifiers Impair Epithelial Barrier Integrity and Trigger Pro‐Inflammatory Responses and IgE Production

The global rise in allergic and autoimmune diseases since the 1960s has been associated with environmental disruptions of epithelial barriers, particularly in the gastrointestinal tract. Among the implicated factors are food emulsifiers, which have become increasingly prevalent i...

Right hippocampal volume and attenuated psychotic symptoms distinguish subgroups of youth with common patterns of temporoparietal effective connectivity

Abstract Associations between patterns of brain connectivity and brain structural features have transdiagnostic relevance to psychopathology. There is considerable evidence for disruptions to the hippocampus and temporoparietal brain systems in psychotic disorders. The present st...

Associations between metabolic dysfunction–associated steatotic liver disease and physical and mental health–related quality of life in older adults

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a common, often overlooked liver condition. Its impact on quality-of-life in older adults is not well understood. We examined the association between MASLD and physical and mental quality of life in a well-charac...

Allele-specific chromatin architecture shapes imprinted domains and coordinates a distal enhancer and antisense transcription at the mouse Mest-Copg2 domain

Genomic imprinting results in parent-of-origin-dependent gene expression, but how three-dimensional genome organization contributes to imprinted gene regulation remains unclear. Using Capture Hi-C in mouse cortex and primary cortical neurons, we identified parental allele-specifi...

Osteochondral Autograft Options for Reconstruction of Intra-articular Distal Humerus and Proximal Ulna Injuries in Physiologically Young Patients

Purpose Surgical options are limited for distal humerus and proximal ulna injuries with articular bone loss in physiologically young patients. Osteochondral grafts are a potential treatment option between open reduction internal fixation and arthroplasty that does not impart life...

Characteristics of Patients Undergoing Revision Thumb CMC Arthroplasty

Purpose The purpose of this study was to describe the demographic and operative characteristics of patients undergoing revision thumb carpometacarpal (CMC) arthroplasty and to characterize technique transitions from primary to revision surgery. Methods A retrospective review of r...

Analysis of serum NMR metabolomics in fibrotic diseases of the myocardium

INTRODUCTION: Heart failure accounts for more than 43% of annual deaths worldwide, and isdriven by widespread pathological remodeling, in which myocardial fibrosis plays an important role. Currently, accurate clinical diagnosis of myocardialfibrosis (MF) remains difficult, with e...

Dismantling structural inequities in global prevention of childhood and adolescent non-communicable diseases

Non-communicable diseases (NCDs) account for a growing proportion of morbidity and disability among children and adolescents worldwide. Contemporary NCD preventive strategies are predominantly adult-centric, resulting in delayed prevention and widening inequities, particularly in...

Children With Complex Chronic Conditions in the Child Protective Services

OBJECTIVES: Little is known about the prevalence and outcomes for children with complex chronic conditions (CCCs) in the Child Protective Services (CPS) system. We aimed to determine the prevalence and associations of CCC designation across CPS outcomes and years among a group of...

Bacillus subtilis YpeB holds SleB inactive, preventing cortex peptidoglycan degradation during spore dormancy

ABSTRACT Bacterial endospores are encased in a thick layer of specialized peptidoglycan called the cortex that is essential for core dehydration and heat resistance. Spore germination and outgrowth require cortex degradation by enzymes that are deposited in the spore during sporu...

Enabling Functional Independence: A Scoping Review of Upper Extremity Assistive Devices for Adults With Progressive Neuromuscular Diseases

BACKGROUND: Assistive technology offers an important means of compensating for lost upper extremity function in adults with progressive neuromuscular diseases (NMD), enabling participation in daily activities, supporting independence, and promoting quality of life. However, the r...