Antiviral Use Among Children Hospitalized With Laboratory-Confirmed Influenza Illness: A Prospective, Multicenter Surveillance Study.

Background: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children.

Methods: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network.

Maternal Low-Protein Diet Leads to Mitochondrial Dysfunction and Impaired Energy Metabolism in the Skeletal Muscle of Male Rats.

A prenatal low-protein (LP) diet disrupts glucose homeostasis in adult offspring. Skeletal muscles are one of the main sites of glucose clearance, and mitochondria residing in the muscle fibers are central to glucose homeostasis. Our previous studies indicated that impaired mitochondrial health is central to dysregulated glucose metabolism in the gastrocnemius muscle of the LP-programmed female rats.

Co-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia.

CRLF2 rearrangements occur in >50% of Ph-like and Down syndrome (DS)-associated B-acute lymphoblastic leukemia (ALL) and induce constitutive kinase signaling targetable by the JAK1/2 inhibitor ruxolitinib under current clinical investigation. While chimeric antigen receptor T cell (CART) immunotherapies have achieved remarkable remission rates in children with relapsed/refractory B-ALL, ~50% of CD19CART-treated patients relapse again, many with CD19 antigen loss. We previously reported preclinical activity of thymic stromal lymphopoietin receptor-targeted cellular immunotherapy (TSLPRCART) against CRLF2-overexpressing ALL as an alternative approach.

Optimal Maternal Ventilation During Laparotomy with General Anesthesia in Pregnancy in the Ovine Model.

Background: General anesthesia during pregnancy is not uncommon, for example, for trauma surgery, cerclage, or cesarean delivery. Current recommendations are to maintain maternal partial pressure of carbon dioxide in arterial blood (paCO2) at 30 mm Hg, which is based solely on the average maternal paCO2 in awake pregnant women. However, there is no evidence that this target, compared to other targets, would enable optimal conditions for the fetus during general anesthesia.

Identification of an early subset of cerebellar nuclei neurons in mice.

Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium.

Implementing and Assessing Climate Change Education in a Pediatrics Residency Curriculum.

For physicians to effectively combat the growing health crisis that is climate change, they should begin learning during medical training about its health implications. However, there is little data on residents' knowledge of the climate crisis, and even less data regarding the effectiveness and acceptability of climate change education in graduate medical training programs. To incorporate a new educational session on the health implications of climate change into a residency curriculum and evaluate the acceptability of the session and its effects on residents' knowledge, attitudes, and perceptions of the topic.

Improving Automated Deep Phenotyping Through Large Language Models Using Retrieval Augmented Generation.

Background: Diagnosing rare genetic disorders relies on precise phenotypic and genotypic analysis, with the Human Phenotype Ontology (HPO) providing a standardized language for capturing clinical phenotypes. Traditional HPO tools, such as Doc2HPO and ClinPhen, employ concept recognition to automate phenotype extraction but struggle with incomplete phenotype assignment, often requiring intensive manual review. While large language models (LLMs) hold promise for more context-driven phenotype extraction, they are prone to errors and "hallucinations," making them less reliable without further refinement.

New Approaches to Respiratory Syncytial Virus Prevention and Treatment.

There have been several recent advances in the prevention of lower respiratory tract disease (LRTD) due to respiratory syncytial virus (RSV) infection in older adults and young children. Three different vaccines are now approved for use in older adults; one of these vaccines is also approved for use in pregnant individuals for the prevention of LRTD due to RSV in their infants. In addition, a new monoclonal antibody is available to prevent RSV LRTD in infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.

Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood.

Background & Aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons.

Characteristics of autoantibody-positive individuals without high-risk HLA-DR4-DQ8 or HLA-DR3-DQ2 haplotypes.

Aims/hypothesis: Many studies of type 1 diabetes pathogenesis focus on individuals with high-risk HLA haplotypes. We tested the hypothesis that, among islet autoantibody-positive individuals, lacking HLA-DRB1*04-DQA1*03-DQB1*0302 (HLA-DR4-DQ8) and/or HLA-DRB1*0301-DQA1*0501-DQB1*0201 (HLA-DR3-DQ2) is associated with phenotypic differences, compared with those who have these high-risk HLA haplotypes.

Methods: We classified autoantibody-positive relatives of individuals with type 1 diabetes into four groups based on having both HLA-DR4-DQ8 and HLA-DR3-DQ2 (DR3/DR4; n=1263), HLA-DR4-DQ8 but not HLA-DR3-DQ2 (DR4/non-DR3; n=2340), HLA-DR3-DQ2 but not HLA-DR4-DQ8 (DR3/non-DR4; n=1607) and neither HLA-DR3-DQ2 nor HLA-DR4-DQ8 (DRX/DRX; n=1294).

Combined bioinformatic and splicing analysis of likely benign intronic and synonymous variants reveals evidence for pathogenicity.

Purpose: Clinical variant analysis pipelines likely have poor sensitivity to the effects on splicing from variants beyond 10 to 20 bases of exon-intron boundaries. Here, we demonstrate the value of SpliceAI to inform curation of rare variants previously classified as benign/likely benign (B/LB) under current guidelines.

Methods: Exome sequencing data from 576 pediatric cancer patients enrolled in the Texas KidsCanSeq study were filtered for intronic or synonymous variants absent from population databases, predicted to alter splicing via SpliceAI (>0.

Further delineation of the SCAF4-associated neurodevelopmental disorder.

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder.

Long-Term Urinary and Sexual Outcomes in Pediatric Genitourinary Rhabdomyosarcoma Survivors: A Qualitative Study.

Purpose: Genitourinary rhabdomyosarcoma (GU-RMS) often requires multimodal therapy treatment including radiation, chemotherapy, and radical surgery for disease control. The long-term effects of the disease and associated treatments are unclear. We sought to investigate the long-term genitourinary quality of life for adult survivors of pediatric GU-RMS.

Cardiovascular disease in adults with osteogenesis imperfecta: Clinical characteristics, care recommendations and research priorities identified using a modified Delphi technique.

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI.

Cognitive Behavioral Therapy Factors Related to Outcomes in Depression Among Youth with HIV.

Purpose: This is a secondary analysis of a multi-site, cluster (site) randomized trial of the efficacy of a combined Health and Wellness Cognitive Behavior Therapy (H&W CBT) and medication management approach for depression in youth with HIV (YWH) compared to standard care. In this study, we explored the association between H&W CBT factors and depression outcomes after 24 weeks of treatment to discover treatment elements associated with symptom reduction.

Methods: Participants (12-24 years of age) were YWH in the United States (US) diagnosed with moderate to severe depression [Quick Inventory of Depressive Symptomatology (QIDS), Clinician-Rated score ≥ 11].

Advances in tuberculosis biomarkers: unravelling risk factors, active disease and treatment success.

Tuberculosis (TB) is a major global health threat and demands improved diagnostic and treatment monitoring methods. Conventional diagnostics, such as sputum smear microscopy and culture, are limited by slow results and low sensitivity, particularly in certain patient groups. Recent advances in biomarker research offer promising solutions in three key areas: risk of disease, diagnosis of active disease and monitoring of treatment response.

Artificial intelligence in tuberculosis: a new ally in disease control.

The challenges to effective tuberculosis (TB) disease control are considerable, and the current global targets for reductions in disease burden seem unattainable. The combination of complex pathophysiology and technical limitations results in difficulties in achieving consistent, reliable diagnoses, and long treatment regimens imply serious physiological and socioeconomic consequences for patients. Artificial intelligence (AI) applications in healthcare have significantly improved patient care regarding diagnostics, treatment and basic research.

Physicochemical and Microbiological Stability of Ursodiol Oral Compounded Suspensions.

Objective: In the United States, ursodiol is commercially available as solid dosage forms, which represents a problem for children who cannot swallow capsules or tablets. There is a lack of an age-appropriate formulation for ursodiol, and the extemporaneous preparation of an oral suspension with an extended beyond-use-date (BUD) may represent a good therapeutic alternative for the pediatric population. However, all pharmacists need validated stability studies to prepare oral liquids with high quality and safety.

Evaluation of Stress Ulcer Prophylaxis in Pediatric General Medicine Patients After Transfer From the Intensive Care Unit and at Discharge.

Objectives: The primary aim of this study was to determine continuation rates of stress ulcer prophylaxis (SUP) upon transfer from a pediatric intensive care unit (PICU) to a general medicine unit and upon hospital discharge. The secondary aim was to identify patient characteristics or concomitant medications that were associated with continuation of SUP at transfer from the PICU.

Methods: This retrospective chart review included patients who were initiated on acid suppression for SUP in the PICU between June 2021 and May 2022 and subsequently transferred to a general medicine unit prior to discharge.

Epinephrine Versus Dopamine in Children, What Is the Current Evidence and What Do We Need? A Systematic Review and Meta-analysis.

Introduction: Pediatric patients often receive vasoactive agents following cardiothoracic surgery or when in shock. The use of vasoactive agents varies between different settings and has largely changed because of anecdotal observations or small observational studies. Although vasoactive agents are frequently used, there are limited studies in pediatric populations comparing them to one another.

Does machine learning improve prediction accuracy of the Endoscopic Third Ventriculostomy Success Score? A contemporary Hydrocephalus Clinical Research Network cohort study.

Purpose: This Hydrocephalus Clinical Research Network (HCRN) study had two aims: (1) to compare the predictive performance of the original ETV Success Score (ETVSS) using logistic regression modeling with other newer machine learning models and (2) to assess whether inclusion of imaging variables improves prediction performance using machine learning models.

Methods: We identified children undergoing first-time ETV for hydrocephalus that were enrolled prospectively at HCRN sites between 200 and 2020. The primary outcome was ETV success 6 months after index surgery.