Harvard University

Conservation of Long G4-rich (LG4) genomic enhancer regulations

Long G4-rich regions (LG4s) are defined as DNA sequences containing a high density of guanine triplets capable of forming non-B DNA structures called G-quadruplexes (G4s). These regions frequently overlap with enhancers, which are regulatory DNA elements that modulate gene expres...

Evaluation of the Relative Citation Ratio Versus the H-Index as Measures of Citation-Based Scholarly Influence in Academic Neurosurgery

BACKGROUND AND OBJECTIVES: Evaluating citation-based scholarly influence among academic faculty is foundational to academic medicine, as retention, promotion, and tenure to govern career advancement at every level. The h-index has been the standard metric across fields, including...

Hyperpolarized [2– 13 C]Pyruvate Identifies a Mitochondria‐Active Hepatocellular Carcinoma Phenotype With Vulnerability to Mitochondrial Inhibition

ABSTRACT Hepatocellular carcinoma (HCC) exhibits metabolic heterogeneity that is not fully characterized by glycolysis‐focused spectroscopic profiling. This study investigated whether in vitro hyperpolarized (HP) [2‐ 13 C]pyruvate NMR spectroscopy can identify a mitochondria‐acti...

A dependency map enhanced with next-generation 3D cancer models

Despite advances in precision oncology, effective personalized treatments are still lacking for most patients with cancer1. The Cancer Dependency Map (DepMap) accelerates this field by systematically identifying cancer vulnerabilities in diverse preclinical models. Data from over...

Carrying Firearms and Suicide Risk Among Adolescents

Importance Firearms are the most lethal method of suicide across all ages, with case fatality rates exceeding 90%, warranting urgent public health concern. Understanding how carrying of firearms by adolescents and suicide risk vary by race and ethnicity and by stringency of state...

Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study

Abstract Objective To estimate the magnitude of reduction in major adverse cardiovascular events (MACE) that would be observed in clinical practice from adding tirzepatide to standard of care treatment. Design Population based cohort study, using a design, data, and analytical ap...

Spatiotemporal-switchable 2D NIR-II single-atom nanozyme for single-cell–level surgical navigation and glioblastoma phototherapy

Single-cell–level resolution tumor therapy represents an advanced strategy against glioblastoma but lacks suitable theranostic agents. Here, we developed a spatiotemporal-switchable, two-dimensional (2D), bismuthene-based second near-infrared window (NIR-II) nanozyme. In this pla...

Fecal microbiome transplant in food allergy in humans and mice identifies a role for bile acid metabolites in oral tolerance

The gut microbiome has been implicated in the pathogenesis of food allergy (FA), prompting microbiome-focused interventions. We evaluated, in a phase 1 open-label trial (NCT02960074), the safety and efficacy of oral encapsulated fecal microbiome transplantation (FMT) in 15 adults...

RTF2 and CLASPIN localize CHK1 to the replication fork to control S-phase progression

The essential kinase ataxia telangiectasia and Rad3-related (ATR) monitors the replicative (S) phase of the cell cycle to ensure faithful propagation of genetic material. While much is known about the mechanisms governing ATR activity at replication forks, how its effector checkp...

Novel Autoantibodies in Rheumatoid Arthritis: Translational Prospects from Seronegative Breakthrough to Precision Diagnosis and Treatment

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic, erosive synovitis. While significant progress and breakthroughs have been made in disease diagnosis through basic research and clinical practice, approximately 30%–40% of seronegative RA patients still e...

A compendium of next-generation patient-derived models for diverse cancers

Abstract The development of new therapeutics and the validation of pathogenetic cancer mechanisms require representative laboratory models 1,2 . However, existing collections represent only a fraction of the diversity observed in human cancer 2–4 . Recent technologies have enable...

Designing clinical AI for patient-centered support beyond the visit: the PACT framework for health systems

Clinical AI has advanced rapidly for bounded in-visit tasks such as prediction, documentation, and message generation, yet many costly failures in care occur outside the encounter when follow-up, handoffs, and communication break down. We argue that the next challenge for clinica...

A non-neuronal fMRI signal: both a confound and an opportunity for insight

Abstract Functional magnetic resonance imaging (fMRI) is widely used to investigate brain function. However, interpretation of the blood oxygen level-dependent (BOLD) signal is complicated by the fact that it reflects both neuronal activity and vascular physiology. This problem i...

MedKGent: a large language model agent framework for constructing temporally evolving medical knowledge graph

The rapid expansion of medical literature challenges the scalable structuring of domain knowledge. Knowledge Graphs (KGs) offer a solution, yet current construction methods lack generalizability and ignore the temporal dynamics of evolving knowledge. To address this, we introduce...

Activation of the angiotensin II type I receptor by a nonpeptide agonist

The angiotensin II type I receptor (AT1R) is a G protein–coupled receptor that regulates the cardiovascular system and as a result is one of the most successful pharmacological targets for the treatment of hypertension. Within the angiotensin receptor pharmacological landscape, a...

Cost-Effectiveness of Endovascular vs Open Surgery for Chronic Limb-Threatening Ischemia

Importance: Choosing between endovascular and open (bypass) surgical revascularization for chronic limb-threatening ischemia has major implications for clinical practice. Objective: To evaluate the cost-effectiveness of endovascular vs bypass surgical revascularization. Design, S...

Epigenetic changes reveal that vitamin B12 intake is associated with lower insulin resistance in older adults

Abstract Background Dietary choices influence both risk and development of type 2 diabetes (T2D), but the precise mechanisms remain incompletely described. Dietary intake and lifestyle behaviors can alter epigenetic states with subsequent modulations on gene expression which then...

Survey Authentication Challenges During a Geriatrics Knowledge Assessment Pilot

ABSTRACT Background In this methodological Brief Report, we describe a multi‐institutional survey authentication challenge encountered during pilot deployment of the Age‐Friendly Knowledge Assessment Tool (AF‐KAT), a geriatrics knowledge assessment for graduating medical students...

Access to Anticancer Drug Trials for Adolescents With Cancer in the United States

BACKGROUND: Adolescents with cancer are generally underrepresented in clinical trials. The extent to which cancer drug clinical trials have become more age inclusive over time is not clear. METHODS: We utilized ClinicalTrials.gov to identify cancer drug trials from 2005 to 2025 i...

A Gap Analysis of Deep Brain Stimulation for Childhood‐Onset Movement Disorders

BACKGROUND: Deep brain stimulation (DBS) is an established and increasingly utilized therapy for childhood-onset movement disorders. However, pediatric DBS poses unique challenges that are not adequately addressed by adult-derived paradigms. OBJECTIVE: To identify key gaps in the...