St. Jude Children's Research Hospital

Mapping Ligand-Induced Conformational Changes during the Enzymatic Cycle of Human Geranylgeranyl Diphosphate Synthase

Abstract Geranylgeranyl diphosphate synthase (GGDPS) catalyzes the condensation reaction between two isoprenoid substrates: farnesyl diphosphate (FDP) and isopentenyl pyrophosphate (IPP), to form geranylgeranyl diphosphate (GGDP). Due to the flexible nature of the GGDPS active si...

Examining Compensation Across Child Life Specialist Programs in the United States

Certified Child Life Specialists are essential healthcare team members, yet compensation is a frequently cited driver of decreased staffing retention and reduced employee wellbeing. Research to date has not yet systematically examined child life compensation as a potential primar...

Impact of Extent of Surgical Resection on Survival in Patients With High-risk Neuroblastoma

Objective: The impact of extent of resection of the primary tumor on outcomes in patients with high-risk neuroblastoma (HRNB) remains uncertain. We evaluated this issue in patients with HRNB treated on a prospective trial of multimodality therapy. Summary of Background Data: Pati...

Nipsnap 1 deficiency shifts neuronal and synaptic signaling toward inflammatory pathway and impairs cognitive functions in the aging brain

Mitochondrial quality control is essential for maintaining neuronal function during aging. Nipsnap1 (Nip1), a mitochondrial protein involved in mitophagy, metabolic regulation, and cellular senescence, has emerged as a potential regulator of tissue homeostasis; however, its role...

Parental Refusal of the Best Treatment: Nudges and Trust in Pediatrics

More effective and less toxic therapies are welcomed by clinicians and families and are the rationale and raison d'être for well-designed clinical trials. This is especially true for life-threatening diseases like childhood cancer. When parents opt for an existing and good treatm...

The Duration of Pavlik Harness Wear Following Successful Reduction of Dislocated Hips Does Not Play a Role in Determining Radiographic Dysplasia at 2 Years.

BACKGROUND: Though the Pavlik harness is often used to reduce dislocated hips in infants with developmental dysplasia of the hip (DDH), residual acetabular dysplasia may occur following reduction. It is unclear whether patient or treatment-related factors, including Pavlik wear d...

Reversible, Chemically Gated FRET via Ligand‐Activated Acceptors

ABSTRACT Genetically encoded fluorogen‐activating tags enable conditional fluorescence, yet the structural and excited‐state mechanisms underlying ligand activation remain unclear. Here, we combine X‐ray crystallography, computational modelling, and fluorescence lifetime imaging...

Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency

Abstract Medulloblastoma is a biologically heterogeneous childhood cerebellar tumor harboring frequent chromatin-modifying gene alterations. How these alterations promote transcriptional programs governing malignancy remains poorly defined. To address this knowledge gap, we evalu...

PXT3003: Lessons for therapeutic development in Charcot-Marie-Tooth disease type 1A and related neuropathies

Most drug development stories end predictably: promising compounds either succeed or fail. Occasionally, however, a therapy repeatedly returns from apparent extinction. PXT3003 for Charcot-Marie-Tooth disease type 1A (CMT1A) represents one such example. More than a decade after e...

Employment-Related Risks in a Clinical Trial of Psychedelic Treatment for Chronic Pain

Chronic pain is a significant health problem affecting up to 20% of Americans (Yong et al. 2022), negatively affecting overall health and quality of life, causing disability, and burdening healthca...

M3: Conversational LLMs simplify secure clinical data access, understanding, and analysis

Large-scale clinical databases offer opportunities for medical research, but their complexity creates barriers to effective use. The Medical Information Mart for Intensive Care (MIMIC-IV), one of the world’s largest open-source electronic health record databases, traditionally re...

Quality Components for Pediatric Cancer Communication in Global Settings

BACKGROUND AND OBJECTIVES In pediatric cancer care, high-quality communication reduces parental anxiety, increases trust, enables decision-making, and fosters hope. This study sought to develop globally applicable quality components for patient-centered pediatric cancer communica...

Immunomodulation of the Innate Host Response by Mesenchymal-Derived Versican during Influenza A Virus Infection

Viral and bacterial lung infections place a significant burden on public health. Versican, an extracellular matrix (ECM) chondroitin sulfate proteoglycan, coordinates the innate immune response in multiple experimental models. Versican’s potential as an immunomodulatory molecule...

High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well-understood. Prognostic factors of clinical outcomes are not well-established. METHODS: Methylation profiling was performed on tumor samples, many at the National Cance...

Bridging tumor growth dynamics and survival in preclinical oncology drug development – a Tumor Growth Inhibition and Time-to-Event (TGI-TTE) modeling framework

To develop a tumor growth inhibition and time-to-event (TGI-TTE) modeling framework linking drug exposure, tumor dynamics, and survival. Modeling used preclinical efficacy studies with MTMSA-Trp, a preclinical-stage anti-tumor agent for Ewing sarcoma. Tumor volume and survival da...

Opioid limiting law and opioid prescriptions among Medicaid-enrolled survivors of childhood cancer

Abstract Background Many U.S. states have enacted opioid-limiting laws to curb the opioid epidemic, often capping opioid prescriptions at seven days. How these laws affect opioid prescribing among long-term survivors of childhood cancer remains unclear. Methods Using Medicaid cla...

Burden and Risk Factors for Severe Respiratory Syncytial Virus Infection Among Pediatric Hematopoietic Cell Transplant Recipients

BACKGROUND: Respiratory syncytial virus (RSV) causes substantial morbidity in pediatric hematopoietic cell transplant (HCT) recipients; however, risk factors for severe disease remain incompletely characterized. METHODS: We conducted a multicenter retrospective cohort study acros...

Optimized Cardiac Leukocyte Isolation for Flow Cytometry Enumeration and Sorting

Accurate characterization of immune cell populations within the heart is critical for understanding inflammatory mechanisms that drive cardiac injury and repair. However, isolating viable leukocytes from cardiac tissue remains technically challenging due to the dense extracellula...

How I Treat Pediatric Hematology-Oncology Patients from Families Identifying as Jehovah's Witnesses

Caring for pediatric hematology-oncology patients from families identifying as Jehovah's Witnesses presents opportunities to align clinical and ethical care considerations, particularly regarding blood transfusion refusal. Although transfusion avoidance is often presumed, patient...

Innate immune sensors of inflammasomes and PANoptosomes: structural–mechanistic insights and therapeutic implications

Innate immunity provides a critical first line of defense against pathogens and homeostatic perturbations. Pattern recognition receptors detect these disruptions and initiate immune responses through multi-protein complex formation to drive inflammatory signaling and cell death p...