DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.

Hepatoblastoma (HBL) and fibrolamellar hepatocellular carcinoma (FLC) are the most common liver malignancies in children and young adults. FLC oncogenesis is associated with the generation of the fusion kinase, DNAJB1-PKAc (J-PKAc). J-PKAc has been found in 90% of FLC patients' tumors but not in other liver cancers.

Cpeb1 remodels cell type-specific translational program to promote fear extinction.

Protein translation is crucial for fear extinction, a process vital for adaptive behavior and mental health, yet the underlying cell-specific mechanisms remain elusive. Using a Tet-On 3G genetic approach, we achieved precise temporal control over protein translation in the infralimbic medial prefrontal cortex () during fear extinction. In addition, our results reveal that the disruption of cytoplasmic polyadenylation element binding protein 1 (Cpeb1) leads to notable alterations in cell type-specific translational programs, thereby affecting fear extinction.

The Influence of Project ECHO and Integrated Behavioral Health in Primary Care on Emergency Department Visits Among Youth Diagnosed with Depression.

Rates of depression among youth and emergency department (ED) visits for un- or under-treated symptoms are on the rise. Early identification and treatment of depression is imperative at the patient, program, system, and population levels. This paper examines the individual and cumulative impact of Project ECHO and the inclusion of IBH services in pediatric primary care practices on mental health-related ED rates among youth diagnosed with depression for those practices.

Studying Rare Movement Disorders: From Whole-Exome Sequencing to New Diagnostic and Therapeutic Approaches in a Modern Genetic Clinic.

Rare movement disorders often have a genetic etiology. New technological advances have increased the odds of achieving genetic diagnoses: next-generation sequencing (NGS) (whole-exome sequencing-WES; whole-genome sequencing-WGS) and long-read sequencing (LRS). In 2017, we launched a WES program for patients with rare movement disorders of suspected genetic etiology.

In toto biological framework: Modeling interconnectedness during human development.

Recent advancements in pluripotent stem cell and synthetic tissue technology have brought significant breakthroughs in studying early embryonic development, particularly within the first trimester of development in humans. However, during fetal stage development, investigating further biological events represents a major challenge, partly due to the evolving complexity and continued interaction across multiple organ systems. To bridge this gap, we propose an "in toto" biological framework that leverages a triad of technologies: synthetic tissues, intravital microscopy, and computer vision to capture in vivo cellular morphodynamics, conceptualized as single-cell choreography.

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.

Virtual and In-Person Multiple Mini-interviews: A Comparison of Two Modalities in Regard to Bias.

Purpose: To examine the characteristics between virtual multiple mini-interview (vMMI) and in-person interviews (ipMMI) in regard to difference in performance between applicant-reported gender identity and racial groups.

Methods: Retrospective multiple mini-interview (MMI) data from two vMMI interview cycles (2021 and 2022) consisting of 627 applicants and four ipMMI cycles (2017-2020) consisting of 2248 applicants. Comparisons were made between applicant subgroups including reported gender (male and female) and minority status (URiM and non-URiM).

An updated overview on long-acting therapeutics for the prevention and treatment of human immunodeficiency virus (HIV) from a perspective of pharmaceutics.

Conventional drug formulations release active pharmaceutical ingredients (APIs) immediately after administration, while long-acting (LA) drug products are designed for prolonged therapeutic effects, thereby reducing administration frequency and improving patient compliance. The development of LA therapeutics for chronic disease treatment has significantly helped patients adhere to their regimens, reducing the need for daily doses and easing the burden on healthcare systems. Advances in treatment have transformed Human Immunodeficiency Virus (HIV) into a manageable chronic disease, and efforts are underway to eliminate HIV in the future.

Pediatric Neuroimaging of Multiple Sclerosis and Neuroinflammatory Diseases.

Using a pediatric-focused lens, this review article briefly summarizes the presentation of several demyelinating and neuroinflammatory diseases using conventional magnetic resonance imaging (MRI) sequences, such as T1-weighted with and without an exogenous gadolinium-based contrast agent, T2-weighted, and fluid-attenuated inversion recovery (FLAIR). These conventional sequences exploit the intrinsic properties of tissue to provide a distinct signal contrast that is useful for evaluating disease features and monitoring treatment responses in patients by characterizing lesion involvement in the central nervous system and tracking temporal features with blood-brain barrier disruption. Illustrative examples are presented for pediatric-onset multiple sclerosis and neuroinflammatory diseases.

Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.

Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune checkpoint blockade (ICB) remains a critical clinical challenge, characterized by variable response rates and non-durable benefits. However, growing research into the complex intrinsic and extrinsic characteristics of tumors has advanced our understanding of the mechanisms behind ICI resistance, potentially improving treatment outcomes.

STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a cystic lung disease that primarily affects women. LAM is caused by the invasion of metastatic smooth muscle-like cells into the lung parenchyma, leading to abnormal cell proliferation, lung remodeling and progressive respiratory failure. LAM cells have TSC gene mutations, which occur sporadically or in people with Tuberous Sclerosis Complex.

Intestinal E. coli-produced yersiniabactin promotes profibrotic macrophages in Crohn's disease.

Inflammatory bowel disease (IBD)-associated fibrosis causes significant morbidity. Mechanisms are poorly understood but implicate the microbiota, especially adherent-invasive Escherichia coli (AIEC). We previously demonstrated that AIEC producing the metallophore yersiniabactin (Ybt) promotes intestinal fibrosis in an IBD mouse model.

Caregiver worry about COVID-19 as a predictor of social mitigation behaviours and SARS-CoV-2 infection in a 12-city U.S. surveillance study of households with children.

Objective: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.

Methods: Data were drawn from a surveillance study of households with children ( = 1913) recruited from 12 U.

A novel minimally invasive neurosurgical cranial fixation device for improved accuracy of intraventricular catheter placement: an experimental animal study.

Background: External ventricular drain (EVD) insertion is one of the most commonly performed neurosurgical procedures. Herein, we introduce a new concept of a cranial fixation device for insertion of EVDs, that reduces reliance on freehand placement and drilling techniques and provides a simple, minimally invasive approach that provides strong fixation to minimal thickness skulls.

Methods: An experimental device for catheter insertion and fixation was designed and tested in both ex-vivo and in-vivo conditions to assess accurate cannulation of the ventricle and to test the strength of fixation to the skull.

YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies.

Long-term durable remission in patients with B cell malignancies following chimeric antigen receptor (CAR)-T cell immunotherapy remains unsatisfactory, often due to antigen escape. Malignant B cell transformation and oncogenic growth relies on efficient ATP synthesis, although the underlying mechanisms remain unclear. Here, we report that YTHDF2 facilitates energy supply and antigen escape in B cell malignancies, and its overexpression alone is sufficient to cause B cell transformation and tumorigenesis.

A single 1-min brain MRI scan for generating multiple synthetic image contrasts in awake children from quantitative relaxometry maps.

Background: Diagnostically adequate contrast and spatial resolution in brain MRI require prolonged scan times, leading to motion artifacts and image degradation in awake children. Rapid multi-parametric techniques can produce diagnostic images in awake children, which could help to avoid the need for sedation.

Objective: To evaluate the utility of a rapid echo-planar imaging (EPI)-based multi-inversion spin and gradient echo (MI-SAGE) technique for generating multi-parametric quantitative brain maps and synthetic contrast images in awake pediatric participants.

Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis.

Clinical and genetic studies strongly support a significant connection between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD) and identify ASCVD as the primary cause of death in NAFLD patients. Understanding the molecular factors and mechanisms regulating these diseases is critical for developing novel therapies that target them simultaneously. Our preliminary immunoblotting experiments demonstrated elevated expression of nidogen 2 (NID2), a basement membrane glycoprotein, in human atherosclerotic vascular tissues and murine steatotic livers.

Lineage labeling with zebrafish Cre and CreERT2 recombinase CRISPR knock-ins.

Background: The ability to generate endogenous Cre recombinase drivers using CRISPR-Cas9 knock-in technology allows lineage tracing, cell type specific gene studies, and validation of inferred developmental trajectories from phenotypic and gene expression analyses. This report describes endogenous zebrafish Cre and CreERT2 drivers generated with GeneWeld CRISPR-Cas9 precision targeted integration.

Results: and knock-ins crossed with ubiquitous -based Switch reporters led to broad labeling in expected mesodermal and neural crest-derived lineages in cardiac, pectoral fins, pharyngeal arch, liver, intestine, and mesothelial tissues, as well as enteric neurons.

Exploring racial disparities in sex trafficking special docket court programs.

Purpose: The United States criminal legal system has a long-standing and well-documented history of perpetuating racial disparities in health and well-being through inequitable policing, sentencing, and incarceration practices. In the last decade, the criminal legal system has re-considered their response to women arrested for solicitation via sex trafficking specialty courts.

Methods: The current study leverages publicly available data from one large Midwestern county to explore the presence of racial disparities within women's referral to, election to participate in, and success within one specialty court program for women in the sex trade.

State of original pediatric radiology research in major radiology journals other than Pediatric Radiology.

Background: Understanding distribution of published pediatric imaging research in radiology journals is relevant to understanding the state of research in the field.

Objective: To understand the current state of published original pediatric imaging research in major clinical radiology journals other than Pediatric Radiology.

Materials And Methods: We reviewed clinical imaging journals from among the top 20 radiology journals according to the Google Scholar h5-index as of June 2024.

The vertebrate segmentation clock drives segmentation by stabilizing Dusp phosphatases in zebrafish.

Pulsatile activity of the extracellular signal-regulated kinase (ERK) controls several cellular, developmental, and regenerative programs. Sequential segmentation of somites along the vertebrate body axis, a key developmental program, is also controlled by ERK activity oscillation. The oscillatory expression of Her/Hes family transcription factors constitutes the segmentation clock, setting the period of segmentation.

Cross-platform DNA motif discovery and benchmarking to explore binding specificities of poorly studied human transcription factors.

A DNA sequence pattern, or "motif", is an essential representation of DNA-binding specificity of a transcription factor (TF). Any particular motif model has potential flaws due to shortcomings of the underlying experimental data and computational motif discovery algorithm. As a part of the Codebook/GRECO-BIT initiative, here we evaluated at large scale the cross-platform recognition performance of positional weight matrices (PWMs), which remain popular motif models in many practical applications.