Notch dimerization provides robustness against environmental insults and is required for vascular integrity.

The Notch intracellular domain (NICD) regulates gene expression during development and homeostasis in a transcription factor complex that binds DNA either as monomer, or cooperatively as dimers. Mice expressing Notch dimerization-deficient (NDD) alleles of Notch1 and Notch2 have defects in multiple tissues that are sensitized to environmental insults. Here, we report that cardiac phenotypes and DSS (Dextran Sodium Sulfate) sensitivity in NDD mice can be ameliorated by housing mice under hypo-allergenic conditions (food/bedding).

Tau Pathology Drives Disease-Associated Astrocyte Reactivity in Salt-Induced Neurodegeneration.

Dietary high salt intake is increasingly recognized as a risk factor for cognitive decline and dementia, including Alzheimer's disease (AD). Recent studies have identified a population of disease-associated astrocytes (DAA)-like astrocytes closely linked to amyloid deposition and tau pathology in an AD mouse model. However, the presence and role of these astrocytes in high-salt diet (HSD) models remain unexplored.

Circulating and Magnetic Resonance Imaging Biomarkers of Intestinal Fibrosis in Small Bowel Crohn's Disease.

Background: We previously identified circulating and MRI biomarkers associated with the surgical management of Crohn's disease (CD). Here we tested associations between these biomarkers and ileal resection inflammation and collagen content.

Methods: Fifty CD patients undergoing ileal resection were prospectively enrolled at 4 centers.

Lessons Learned in Virtual Launch of an Antenatal Opioid Exposure Study During the COVID-19 Pandemic.

Background: The COVID-19 pandemic prompted researchers to develop new ways to design and launch studies and recruit and retain participants. Pregnant women and infants are considered vulnerable populations in research, and families affected by substance use are particularly difficult to recruit and retain. Recruitment for studies involving medical technologies such as MRI can also be difficult due to misconceptions and fear of the technologies.

A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and as a Combination Vaccine Candidate.

Background: Noroviruses, which cause epidemic acute gastroenteritis, and parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CSP) of sporozoite are the glycan receptor-binding domains of the two pathogens for host cell attachment, making them excellent targets for vaccine development. Modified norovirus P domains self-assemble into a 24-meric octahedral P nanoparticle (P NP).

Risk factors affecting polygenic score performance across diverse cohorts.

Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed the effects of covariate stratification and interaction on body mass index (BMI) PGS (PGS) across four cohorts of European (N = 491,111) and African (N = 21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R differences among strata.

Is temperament associated with academic school readiness in children born very preterm?

Research Findings: Temperament, which can be assessed as early as three months, is associated with school readiness and later academic achievement in children born full term. Although children born preterm demonstrate a dysregulated temperament and are at significant risk for lower school readiness, we found no studies investigating whether early temperament is associated with school readiness in this at-risk population. Investigating whether temperament is a precursor of academic risk in preterm children can facilitate early identification and possible intervention efforts.

October 2024 ACIP Meeting Update: Influenza, COVID-19, RSV and Other Vaccines.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The ACIP met October 23-24, 2024, to discuss influenza vaccines, chikungunya vaccines, coronavirus disease (COVID-19) vaccines, RSV immunizations, meningococcal vaccines, human papillomavirus (HPV) vaccines, pneumococcal vaccines, and adult and child/adolescent immunization schedule revisions. This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population.

Alkaline urine is associated with increased risk of calcium phosphate nephrolithiasis in medically complex children receiving enteral nutrition.

Introduction: Calcium phosphate stones are commonly found in medically complex children (MCC) receiving enteral feeds. The objective of this study is to investigate the etiology for calcium phosphate stones in this patient population.

Study Design: This is a retrospective cohort study of gastrostomy fed, MCC who presented to a high-volume Pediatric Stone Center from 2015 to 2019.

Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.

Prescriptions (Rx) for Prevention: Clinical Tools for Integrating Environmental Health into Pediatric Clinical Care.

The integration of environmental health (EH) into routine clinical care for children is in its early stages. The vision of pediatric EH is that all clinicians caring for children are aware of and able to help connect families to needed resources to reduce harmful environmental exposures and increase health-enhancing ones. Environmental exposures include air pollution, substandard housing, lead, mercury, pesticides, consumer products chemicals, drinking water contaminants, industrial facility emissions and, increasingly, climate change-related extreme weather and heat events.

Comparison of the Ease-of-use and Preference Between Two Aromatherapy Delivery Methods in the Perioperative Setting.

Purpose: Nurses at the study hospitals had implemented aromatherapy as an evidence-based intervention to alleviate nausea, pain, and anxiety in patients in the perioperative setting. Initially, they were approved to administer aromatherapy using large, multidose bottles with gauze as the method of delivery; however, nurses recognized that there were many disadvantages to using this method. This led to a nurse-driven initiative to create a new delivery method for aromatherapy with the aid of the Center for Innovation at the organization.

Genomic sequencing in diverse and underserved pediatric populations: parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

Purpose: Limited evidence evaluates parents' perceptions of their child's clinical genomic sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research (CSER) consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.

Methods: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure.

The 2022 ADEA Climate Study in U.S. and Canadian Dental Schools and Allied Dental Programs: Methodological Considerations.

Objectives: From January 2020 to the end of August 2020, preliminary research gathered data about the need for and the feasibility of an ADEA-led joint Climate Study of dental schools and allied dental programs in the United States and Canada. Informed by these findings, the first ever ADEA-led joint Climate Study took place in 2022. The objectives of this manuscript were to describe the timeline of this climate study and provide information about its methodology, specifically about (a) who participated in this research, (b) what was assessed, (c) how the study was conducted, and (d) how the results were communicated.

Lymph Node Staging and Treatment in Pediatric Patients With Soft Tissue Sarcomas: A Consensus Opinion from the Children's Oncology Group, European paediatric Soft tissue sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe.

Accurate staging of nodal involvement in pediatric sarcoma patients is important to determine correct systemic and local therapy, with the goal to reduce subsequent recurrences. However, differences in lymph node staging strategies, definitions, and treatment protocols between the Children's Oncology Group (COG), European paediatric Soft tissue sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS) complicate comparisons. In this article, we aim to establish internationally recognized recommendations for lymph node assessment and treatment of children and adolescents diagnosed with rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) according to the Consensus Conference Standard Operating Procedure methodology.

Clinical outcomes of switching to lonapegsomatropin from somatropin for treatment of pediatric growth hormone deficiency.

Objectives: This study aimed to assess differences in insulin-like growth factor 1 (IGF-1) levels following the transition from somatropin to lonapegsomatropin in patients with pediatric growth hormone deficiency (GHD). Secondary objectives included the evaluation of dose titrations based on IGF-1 levels, changes in annualized height velocity (AHV) and body mass index (BMI), and assessing reported adverse effects associated with lonapegsomatropin therapy.

Methods: A single-center, retrospective review was conducted including patients diagnosed with pediatric GHD initially treated with somatropin who transitioned to lonapegsomatropin between January 1, 2022, and December 31, 2023.

Granulomatous Variant of Giant Centrifugal Miliaria Profunda in an 8-Month-Old Boy: Expanding the Dermatologic Phenotype of Cardiofaciocutaneous Syndrome.

Miliarias are a group of eccrine disorders characterized by sweat retention due to the occlusion of eccrine ducts. Miliaria profunda is the rarest form of miliaria and occurs when eccrine ducts are obstructed at the dermal-epidermal junction. A granulomatous variant of centrifugal miliaria profunda classic findings of granulomatous infiltrate on histology and centrifugal expansion of deep nodules or plaques.

The Kinesin Kar3 is Required for Endoplasmic Reticulum-Associated Degradation.

Degradation of aberrant, excess, and regulatory proteins at the endoplasmic reticulum (ER) is a conserved feature of eukaryotic cells, disruption of which contributes to disease. While remarkable progress has been made in recent years, mechanisms and genetic requirements for ER-Associated Degradation (ERAD) remain incompletely understood. We recently conducted a screen for genes required for turnover of a model ER translocon-associated substrate of the Hrd1 ubiquitin ligase in .

Spleen stiffness in a healthy pediatric population undergoing liver magnetic resonance elastography.

Background: Splenic stiffness is a potential imaging marker of portal hypertension. Normative spleen stiffness values are needed to define diagnostic thresholds.

Objective: To report stiffness measurements of the spleen in healthy children undergoing liver magnetic resonance (MR) elastography across MRI vendors and field strengths.

Intercellular mRNA transfer alters the human pluripotent stem cell state.

Intercellular transmission of messenger RNA (mRNA) is being explored in mammalian species using immortal cell lines. Here, we uncover an intercellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells under the condition impermissible for primed hPSC culture.

A Case Study of a Female Infant With Primary Hypertrophic Osteoarthropathy Demonstrates That Early Initiation of Celecoxib Slows but Does Not Prevent Symptom Progression.

Primary Hypertrophic Osteoarthropathy (PHOAR1) is characterized by autosomal recessive loss of function variants in 15-hydroxyprostaglandin dehydrogenase (HPGD) leading to digital clubbing, periostosis, pachydermia, and severe hyperhidrosis. HPGD catalyzes the first step of prostaglandin E2 (PGE2) degradation. Selective COX-2 inhibitors have proved beneficial in adults, though it is unknown if early initiation of COX-2 inhibitors can alter the natural history of PHOAR1.

Prepancreatic postduodenal portal vein discovered in a pediatric patient undergoing total pancreatectomy with islet autotransplantation: a case report and review of literature.

Background: Prepancreatic postduodenal portal vein (PPPV) is a rare anatomic variant where the portal vein (PV) runs anterior to the pancreas and posterior to the duodenum. Only 20 cases of PPPV, all in adults, have been reported in literature. We report the first case of PPPV in a pediatric patient discovered intraoperatively during total pancreatectomy with islet autotransplantation (TPIAT) and the third known case in which the PPPV could be isolated intraoperatively.

Wellbeing and quality of life among parents of individuals with Fontan physiology.

Purpose: To examine global and health-related quality of life (QOL) among parents of individuals with Fontan physiology and determine associations with sociodemographic, parent and child-related health, psychological, and relational factors.

Methods: Parents participating in the Australian and New Zealand Fontan Registry (ANZFR) QOL Study (N = 151, Parent Mean age = 47.9 ± 10.