In-silico heart model phantom to validate cardiac strain imaging.

The quantification of cardiac strains as structural indices of cardiac function has a growing prevalence in clinical diagnosis. However, the highly heterogeneous four-dimensional (4D) cardiac motion challenges accurate "regional" strain quantification and leads to sizable differences in the estimated strains depending on the imaging modality and post-processing algorithm, limiting the translational potential of strains as incremental biomarkers of cardiac dysfunction. There remains a crucial need for a feasible benchmark that successfully replicates complex 4D cardiac kinematics to determine the reliability of strain calculation algorithms.

Estimating prevalence of rare genetic disease diagnoses using electronic health records in a children's hospital.

Rare genetic diseases (RGDs) affect a significant number of individuals, particularly in pediatric populations. This study investigates the efficacy of identifying RGD diagnoses through electronic health records (EHRs) and natural language processing (NLP) tools, and analyzes the prevalence of identified RGDs for potential underdiagnosis at Cincinnati Children's Hospital Medical Center (CCHMC). EHR data from 659,139 pediatric patients at CCHMC were utilized.

Developmental control of rod number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells.

Photoreception is essential for the development of the visual system, shaping vision's first synapse to cortical development. Here, we find that the lighting environment controls developmental rod apoptosis via Opn4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). Using genetics, sensory environment manipulations, and computational approaches, we establish a pathway where light-dependent glutamate released from ipRGCs is detected via a transiently expressed glutamate receptor (Grik3) on rod precursors within the inner retina.

Alloreactive memory CD4 T cells promote transplant rejection by engaging DCs to induce innate inflammation and CD8 T cell priming.

Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such as IL-6, IL-1β, and IL-12, are also associated with rejection of organ transplants. However, the pathways of innate immune activation in allogeneic transplantation are unclear.

Protocol for establishing inducible CRISPRd system for blocking transcription factor-binding sites in human pluripotent stem cells.

Transcription factor (TF) gene knockout or knockdown experiments provide comprehensive downstream effects on gene regulation. However, distinguishing primary direct effects from secondary effects remains challenging. To assess the direct effect of TF binding events, we present a protocol for establishing a doxycycline (Dox)-inducible CRISPRd system in human pluripotent stem cells (hPSCs).

Differential contributions of performance-based and parental reports of executive functioning on memory in pediatric focal and generalized epilepsies.

Children with epilepsy often experience deficits in both executive functioning (EF) and memory. However, how these two domains interact and relate to specific epilepsy types remains unclear. This study compared two groups of children: those with localization-related epilepsy (LRE) and those with genetic generalized epilepsy (GGE).

Regulation of MYC by CARD14 in human epithelium is a determinant of epidermal homeostasis and disease.

Caspase recruitment domain family member 14 (CARD14) and its variants are associated with both atopic dermatitis (AD) and psoriasis, but their mechanistic impact on skin barrier homeostasis is largely unknown. CARD14 is known to signal via NF-κB; however, CARD14-NF-κB signaling does not fully explain the heterogeneity of CARD14-driven disease. Here, we describe a direct interaction between CARD14 and MYC and show that CARD14 signals through MYC in keratinocytes to coordinate skin barrier homeostasis.

Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease.

Gaucher disease (GD) is caused by biallelic GBA1/Gba1 mutations that encode defective glucocerebrosidase (GCase). Progranulin (PGRN, encoded by GRN/Grn) is a modifier of GCase, but the interplay between PGRN and GCase, specifically GBA1/Gba1 mutations, contributing to GD severity is unclear. Mouse models were developed with various dosages of Gba1 D409V mutation against the PGRN deficiency (Grn-/-) [Grn-/-;Gba1D409V/WT (PG9Vwt), Grn-/-;Gba1D409V/D409V (PG9V), Grn-/-;Gba1D409V/Null (PG9VN)].

NF1-dependent disruption of the blood-nerve-barrier is improved by blockade of P2RY14.

The blood-nerve-barrier (BNB) that regulates peripheral nerve homeostasis is formed by endoneurial capillaries and perineurial cells surrounding the Schwann cell (SC)-rich endoneurium. Barrier dysfunction is common in human tumorigenesis, including in some nerve tumors. We identify barrier disruption in human deficient neurofibromas, which were characterized by reduced perineurial cell glucose transporter 1 (GLUT1) expression and increased endoneurial fibrin(ogen) deposition.

SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus.

Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes ("eGenes", whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated.

SETDB1 suppresses NK cell-mediated immunosurveillance in acute myeloid leukemia with granulo-monocytic differentiation.

Monocytic acute myeloid leukemia (AML) responds poorly to current treatments, including venetoclax-based therapy. We conducted in vivo and in vitro CRISPR-Cas9 library screenings using a mouse monocytic AML model and identified SETDB1 and its binding partners (ATF7IP and TRIM33) as crucial tumor promoters in vivo. The growth-inhibitory effect of Setdb1 depletion in vivo is dependent mainly on natural killer (NK) cell-mediated cytotoxicity.

Pseudomonas aeruginosa Infection and Inflammation in Cystic Fibrosis: A Pilot Study With Lung Explants and a Novel Histopathology Scoring System.

Purpose: Pseudomonas aeruginosa is the predominant bacterial pathogen colonizing the cystic fibrosis (CF) lung. Mixed populations of nonmucoid and mucoid variants of P. aeruginosa have been isolated from the CF airway.

Protocol for establishing inducible CRISPR interference system for multiple-gene silencing in human pluripotent stem cells.

Inducible loss-of-function strategies are crucial for understanding gene function. However, creating inducible, multiple-gene knockout models is challenging and time-consuming. Here, we present a protocol for establishing a doxycycline-inducible CRISPR interference (CRISPRi) system to concurrently silence multiple genes in human induced pluripotent stem cells (hPSCs).

Maintenance of acetabular correction following PAO: a multicenter study comparing stainless-steel and titanium screws.

Stainless-steel screws are commonly used for fragment fixation during periacetabular osteotomy (PAO) at our institutions. Titanium is reserved for patients with documented nickel allergies. Titanium screws possess a significantly lower Young's modulus than stainless steel and, therefore, potentially less resistance to physiologic loading.

Advanced Diagnostic and Therapeutic Bronchoscopy in Pediatrics.

Advanced diagnostic and therapeutic flexible bronchoscopy in children is a rapidly evolving field. Recent advances in technology and awareness of indications, risks, and benefits by pediatric providers have greatly increased the use of advanced techniques in children. This review highlights advanced diagnostic procedures including assessment of endobronchial lesions, mediastinal/hilar masses, and peripheral lung nodules as well as therapeutic techniques for restoring airway lumen patency, managing persistent air leaks, and treating tracheoesophageal fistulas in children as well as the potential to spare these patients more invasive procedures.

Small Animal Models to Study Herpes Simplex Virus Infections.

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two of the most prevalent human viruses worldwide. They are known to cause a variety of diseases including genital herpes, meningitis, encephalitis, cold sores and herpes stromal keratitis. The seropositive rate for HSV-1 is around 90%, whereas for HSV-2 it remains around 20-25% for the general adult population.

Exploring Diagnostic Priorities: The Role of Colonic Manometry in Evaluating Pediatric Patients with Intractable Idiopathic Constipation Prior to Sacral Nerve Stimulation.

Background: Despite the limited understanding of its precise mechanism of action, sacral nerve stimulation (SNS) has proven to be helpful for pediatric patients with constipation, particularly those with fecal incontinence. It is unclear whether the outcome of SNS is impacted by normal or abnormal colonic motility. Our study aimed to determine whether colonic manometry results had an impact on the outcome of SNS as a treatment in pediatric patients with refractory idiopathic constipation.

Safety, Tolerability, and EEG-Based Target Engagement of STP1 (PDE3,4 Inhibitor and NKCC1 Antagonist) in a Randomized Clinical Trial in a Subgroup of Patients with ASD.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003).

The effect of including dynamic imaging derived airway wall motion in CFD simulations of respiratory airflow in patients with OSA.

Obstructive sleep apnea (OSA) is an airway disease caused by periodic collapse of the airway during sleep. Imaging-based subject-specific computational fluid dynamics (CFD) simulations allow non-invasive assessment of clinically relevant metrics such as total pressure loss (TPL) in patients with OSA. However, most of such studies use static airway geometries, which neglect physiological airway motion.

Rapid abdominopelvic MR imaging in the emergency department: establishing a program and addressing the challenges.

Utilization of magnetic resonance imaging (MRI) in the pediatric emergency room or urgent care setting for abdominopelvic indications has been increasing. The creation and implementation of rapid urgent MRI programs can have various challenges. The purpose of this article is to describe a framework for the creation of a rapid urgent abdominopelvic MRI program in the pediatric emergency room setting.