Brief, Family-Centered, Videoconference-Based Behavioral Insomnia Program in Elementary School-Aged Pediatric Cancer Survivors: A Proof-of-Concept Study.

Pediatric cancer survivors are at heightened risk for insomnia. Though behavioral interventions are the recommended approach, there are not enough trained clinicians. No known published trials have been conducted among school-aged survivors, despite them having unique age-related sleep issues.

High dose inactivated influenza vaccine inconsistently improves heterologous antibody responses in an elderly human cohort.

Background: Older adults often mount a weak immune response to standard inactivated influenza vaccines. To induce a stronger response and better protection, a high-dose (HD) version of the inactivated Fluzone vaccine is recommended for individuals >65 years of age. While better immunogenicity and protection against the vaccine strain has been shown, it is not known if the HD vaccine also induces a robust antibody response to heterologous strains.

Parental Acceptance of Human Papillomavirus Vaccination Among Females Treated for Childhood Cancer and/or With Hematopoietic Stem Cell Transplantation: A Cross-Sectional Study.

Background: Survivors of childhood cancer (CCS) and hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of human papillomavirus (HPV)-associated malignancies. Although HPV vaccination is recommended for these groups, parental acceptance remains uncertain.

Procedure: We recruited caregivers of female CCS/HSCT aged ≥9 years from the Shanghai Children's Medical Center (SCMC) vaccination clinic.

Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.

Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice.

The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit.

Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit.

Exiting a germinal zone (GZ) initiates a cascade of events that promote neuronal maturation and circuit assembly. Developing neurons and their progenitors must interpret various niche signals-such as morphogens, guidance molecules, extracellular matrix components, and adhesive cues-to navigate this region. How differentiating neurons in mouse brains integrate and adapt to multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown.

Targeting Senescent Stemlike Subpopulations in Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia.

Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is driven by genetic alterations that induce constitutive kinase signaling and is associated with chemoresistance and high relapse risk in children and adults. Preclinical studies in the most common CRLF2-rearranged/JAK pathway-activated Ph-like ALL subtype have shown variable responses to JAK inhibitor-based therapies, suggesting incomplete oncogene addiction and highlighting a need to elucidate alternative biologic dependencies and therapeutic vulnerabilities, while the ABL-class Ph-like ALL subtype appears preferentially sensitive to SRC/ABL- or PDGFRB-targeting inhibitors. Which patients may be responsive versus resistant to tyrosine kinase inhibitor (TKI)-based precision medicine approaches remains a critical knowledge gap.

Modeling GATA2 deficiency in mice: the R396Q mutation disrupts normal hematopoiesis.

GATA2 deficiency is an autosomal dominant germline disorder of immune dysfunction and bone marrow failure with a high propensity for leukemic transformation. While sequencing studies have identified several secondary mutations thought to contribute to malignancy, the mechanisms of disease progression have been difficult to identify due to a lack of disease-specific experimental models. Here, we describe a murine model of one of the most common GATA2 mutations associated with leukemic progression in GATA2 deficiency, Gata2.

A Trivalent Live Vaccine Elicits Cross-Species Protection Against Acute Otitis Media in a Murine Model.

: Acute otitis media (AOM) is a common pediatric infection worldwide and is the primary basis for pediatric primary care visits and antibiotic prescriptions in children. Current licensed vaccines have been incompletely ineffective at reducing the global burden of AOM, underscoring a major unmet medical need. The complex etiology of AOM presents additional challenges for vaccine development, as it can stem from multiple bacterial species including , , and .

Population Pharmacokinetic and Pharmacodynamic Study of Palbociclib in Children and Young Adults with Recurrent, Progressive, or Refractory Brain Tumors.

Palbociclib, an oral CDK 4/6 inhibitor, was evaluated in a Pediatric Brain Tumor Consortium (PBTC) phase 1 (NCT02255461; PBTC-042) study to treat children and young adults with recurrent, progressive, or refractory brain tumors. The objectives of this study were to characterize the palbociclib population pharmacokinetics in children enrolled on PBTC-042, to conduct a population pharmacodynamic analysis in this patient population, and to perform a simulation study to assess the role of palbociclib exposure on neutropenia and thrombocytopenia. The palbociclib population pharmacokinetics and pharmacodynamics were characterized in this patient population (n = 34 patients; 4.

The Proteomics of T-Cell and Early T-Cell Precursor (ETP) Acute Lymphocytic Leukemia: Prognostic Patterns in Adult and Pediatric-ETP ALL.

Background: The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.

Learning predictive signatures of HLA type from T-cell repertoires.

T cells recognize a wide range of pathogens using surface receptors that interact directly with peptides presented on major histocompatibility complexes (MHC) encoded by the HLA loci in humans. Understanding the association between T cell receptors (TCR) and HLA alleles is an important step towards predicting TCR-antigen specificity from sequences. Here we analyze the TCR alpha and beta repertoires of large cohorts of HLA-typed donors to systematically infer such associations, by looking for overrepresentation of TCRs in individuals with a common allele.

Practical approach to quantitative liver and pancreas MRI in children.

Quantitative abdominal magnetic resonance imaging (MRI) offers non-invasive, objective assessment of diseases in the liver, pancreas, and other organs and is increasingly being used in the pediatric population. Certain quantitative MRI techniques, such as liver proton density fat fraction (PDFF), R2* mapping, and MR elastography, are already in wide clinical use. Other techniques, such as liver T1 mapping and pancreas quantitative imaging methods, are emerging and show promise for enhancing diagnostic sensitivity and treatment monitoring.

The St. Jude Global Academy: A Multifaceted Education Program to Expand Pediatric Oncology Workforce Capacity.

There is currently a global shortage of healthcare professionals equipped to handle the rising burden of childhood cancer. St. Jude Global is an initiative to improve survival rates of children with cancer worldwide while improving access to quality care.

Development of Receptor Desolvation Scoring and Covalent Sampling in DOCK 6: Methods Evaluated on a RAS Test Set.

Molecular docking methods are widely used in drug discovery efforts. RAS proteins are important cancer drug targets, and are useful systems for evaluating docking methods, including accounting for solvation effects and covalent small molecule binding. Water often plays a key role in small molecule binding to RAS proteins, and many inhibitors─including FDA-approved drugs─covalently bind to oncogenic RAS proteins.

Frailty and neurocognitive impairments in Chinese survivors of childhood cancer.

Purpose: This study aimed to evaluate the prevalence and predictors of frailty and the association between frailty and neurocognitive impairments among Chinese survivors of childhood cancer.

Methods: A total of 185 survivors of childhood cancer were recruited from a long-term follow-up clinic in Hong Kong (response rate: 94.4%; 48.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Characterizing Sensitivity to Vincristine, Irinotecan, and Telomerase-targeted Therapy in Diffuse Anaplastic Wilms Tumor Patient-derived Xenografts.

Background: Patients with diffuse anaplastic Wilms tumor (DAWT) experience relatively poor oncologic outcomes. Previous work has described mechanisms of telomerase upregulation in DAWT, posing a potential therapeutic target.

Methods: We assessed in vitro sensitivity to vincristine, irinotecan, and telomerase-targeting drug 6-thio-2'-deoxyguanosine (6 dG) in DAWT cell lines WiT49 and PDM115 and in spheroids derived from cell lines and four DAWT patient-derived xenografts (PDX).

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

Latent epigenetic programs in Müller glia contribute to stress and disease response in the retina.

Previous studies have demonstrated the dynamic changes in chromatin structure during retinal development correlate with changes in gene expression. However, those studies lack cellular resolution. Here, we integrate single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) with bulk data to identify cell-type-specific changes in chromatin structure during human and murine development.

Trends in childhood cancer: Incidence and survival analysis over 45 years of SEER data.

Background: The SEER Registry contains U.S. cancer statistics.

Social Risks and Nonadherence to Recommended Cancer Screening Among US Adults.

Importance: Research indicates that social drivers of health are associated with cancer screening adherence, although the exact magnitude of these associations remains unclear.

Objective: To investigate the associations between individual-level social risks and nonadherence to guideline-recommended cancer screenings.

Design, Setting, And Participants: This cross-sectional study used 2022 Behavioral Risk Factor Surveillance System data from 39 US states and Washington, DC.