Columbia University Irving Medical Center

Omic risk scores are associated with COPD-related traits across three cohorts

Background: Chronic obstructive pulmonary disease (COPD) exhibits marked heterogeneity in lung function decline, mortality, exacerbations, and other disease-related outcomes. Omic risk scores (ORS) estimate the cumulative contribution of omics, such as the transcriptome, proteome...

Structural identification of the RY12 domain of RyR1 as an ADP sensor and the target of the malignant hyperthermia therapeutic dantrolene

Malignant hyperthermia (MH) is a life-threatening pharmacogenetic condition triggered by volatile anesthetics, which activate pathogenic RyR1 mutants. The small molecule therapeutic dantrolene has long been used to treat MH. However, the binding site and mechanism of dantrolene r...

Sex Differences in a Contemporary, Real-World Cohort of Patients with Transthyretin Amyloid Cardiomyopathy Treated with Tafamidis

INTRODUCTION: Tafamidis improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) versus placebo. ATTR-CM has historically been considered a predominantly male disease, and women are underrepresented in prior studies. Sex-specific data in contemporary pati...

Intervention Design for Individual Behavior Change in Stroke Prevention Trials

Stroke prevention requires that patients follow recommended health behaviors. However, few stroke behavioral interventions have been shown to produce clinically significant behavior change in clinical trials, likely thwarted in the design process by limited application of behavio...

Estimating the carcinogenesis timelines in early-onset versus late-onset cancers and changes across birth cohorts

Abstract Understanding the timing of key mutational events in cancer development is critical for informing cancer prevention and detection strategies, particularly for early-onset cases that have increased in recent years. Yet intermediate mutational events are challenging to obs...

Unsupervised discovery of functional sequence patterns from protein language model with MotifAE

Protein language models (pLMs) learn sequence patterns at evolutionary scale, but these patterns remain inaccessible within these “black box” models. To discover them, we developed MotifAE, an unsupervised framework based on the sparse autoencoder (SAE) architecture that projects...

A Finite Element Model of Pregnancy Derived From Maternal Sonography: Effect of Uterine And Cervical Structural Properties on Cervical Mechanical Loading

Identification and treatment of pregnancies at risk for preterm birth is a central challenge in obstetric research. Many of the known causes of preterm birth originate from mechanical failure in reproductive tissues. To better understand the biomechanical environment of the gravi...

Cell Saver Use is Not Associated With Increased Morbidity But Reflects Transfusion Burden in Pediatric Spinal Deformity Surgery: A Retrospective Cohort Study

STUDY DESIGN: Retrospective cohort study. INTRODUCTION: Cell saver (CS) is widely used in spinal fusion to reduce exposure to allogeneic transfusion, which carries risks such as infection and prolonged hospitalization. Pediatric spinal fusion is frequently associated with signifi...

Gene Silencer Therapy in Transthyretin Amyloid Cardiomyopathy

Importance: Gene-silencing therapies reduce hepatic transthyretin (TTR) production and have been evaluated in phase 3 trials in TTR amyloid cardiomyopathy (ATTR-CM). However, differences in trial design and background therapies have limited assessment of the overall treatment eff...

Effect of Aficamten on Cardiac Structure and Function in Patients with Symptomatic Nonobstructive Hypertrophic Cardiomyopathy

BACKGROUND: Aficamten significantly improved both functional capacity and patient-reported health status in patients with symptomatic nonobstructive hypertrophic cardiomyopathy in the phase 3 randomized, placebo-controlled ACACIA-HCM trial (Assessment Comparing Aficamten to Place...

Milvexian with Antiplatelet Therapy after Acute Coronary Syndrome Event

BackgroundPatients are at increased risk for recurrent ischemic events after an acute coronary syndrome event. Milvexian, an oral factor XIa inhibitor, may reduce the risk of major adverse clinical events with minimal bleeding risk. MethodsIn this phase 3, randomized, placebo-con...

Aficamten for Symptomatic Nonobstructive Hypertrophic Cardiomyopathy

BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) is a common condition that is associated with substantial morbidity and no proven medical therapy. Whether treatment with aficamten, a cardiac myosin inhibitor, can benefit patients with this condition is unknown. METHO...

Economic hardship and mental health following a national trauma and amid ongoing conflict: a longitudinal cohort study

Abstract Purpose Exposure to war and terrorism increases the risk of mental health problems and often leads to economic hardship, which can further heighten psychological distress. This longitudinal study examined the extent of economic hardship experienced during the Israel–Hama...

Global Efficacy of Aficamten in Nonobstructive Hypertrophic Cardiomyopathy: Results From ACACIA-HCM

BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (nHCM) is associated with significant morbidity with no approved treatment. Aficamten is a cardiac myosin inhibitor targeting excess contractility and diastolic impairment, the predominant mechanism responsible for adverse ou...

Learning precise segmentation of neurofibrillary tangles from rapid manual point annotations

Accumulation of abnormal tau protein into neurofibrillary tangles (NFTs) is a pathologic hallmark of Alzheimer disease (AD). Accurate detection of NFTs in tissue samples can reveal relationships with clinical, demographic, and genetic features through deep phenotyping. However, e...

Understanding the Research Needs and Educational Methods of Surgeons to Help Guide Future Spine Deformity Research: A Survey of AO Spine Members

Study Design Cross-sectional survey. Objective Outcomes research has significantly shaped patient management in spine deformity care, while the dissemination of research remains a challenge. To guide future research directions, this study surveyed AO Spine members to identify the...

International migration of Africa-born health workers: a scoping review of drivers and policies, 2010–2024

Africa faces a critical shortage of human resources for health (HRH), crucial for improving population health. We described drivers of and policies to manage the migration of Africa-born HRH from source (African) countries in Africa to destination (non-African) countries. We cond...

All-optical multimodal mapping of single-cell-type-specific metabolic activities via REDCAT

Abstract Metabolism is fundamental to cell function, yet its activities vary across tissue environments. Resolving these processes in situ at single-cell resolution is crucial for understanding physiology in health and disease. However, existing methods lack biochemical specifici...

Intracranial delivery of neuron-preferential lipid nanoparticles for gene-editing activity in mouse brain

Lipid nanoparticles (LNPs) are promising non-viral vectors for central nervous system (CNS) gene therapy, but effective delivery is limited by the blood-brain barrier and cell-type specificity. Here, we combined intracranial delivery with high-throughput, cluster-based screening...

Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis

Immune checkpoint inhibitor (ICI) myocarditis is a rare but frequently fatal immune-related adverse event of cancer immunotherapy. Understanding the mechanisms of this toxicity is critical to balancing treatment with maintenance of antitumor immunity. Using integrated spatial and...