ASAP1 and ARF1 regulate myogenic differentiation in rhabdomyosarcoma by modulating TAZ activity.

Despite aggressive, multimodal therapies, the prognosis of patients with refractory or recurrent rhabdomyosarcoma (RMS) has not improved in four decades. Because RMS resembles skeletal muscle precursor cells, differentiation-inducing therapy has been proposed for patients with advanced disease. In RAS-mutant PAX fusion-negative RMS (FN-FMS) preclinical models, MEK1/2 inhibition (MEKi) induces differentiation, slows tumor growth, and extends survival.

Corneal Collagen Cross-linking for Keratoconus in Pediatric and Developmentally Delayed Patients.

Purpose: Corneal cross-linking (CXL) is the standard of care in patients with keratoconus but presents unique challenges in children and developmentally delayed patients. We present our clinical decision-making algorithm, CXL surgical technique, and outcomes in these groups.

Methods: A retrospective chart review was undertaken at a tertiary referral center of all patients who underwent CXL for keratoconus at University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between October 1, 2017, and April 1, 2021.

Effects of gene replacement therapy with resamirigene bilparvovec (AT132) on skeletal muscle pathology in X-linked myotubular myopathy: results from a substudy of the ASPIRO open-label clinical trial.

Background: X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital muscle disease caused by mutations in the MTM1 gene that result in profound muscle weakness, significant respiratory insufficiency, and high infant mortality. There is no approved disease-modifying therapy for XLMTM. Resamirigene bilparvovec (AT132; rAAV8-Des-hMTM1) is an investigational adeno-associated virus (AAV8)-mediated gene replacement therapy designed to deliver MTM1 to skeletal muscle cells and achieve long-term correction of XLMTM-related muscle pathology.

Pediatric oral fluorescein angiography: a retrospective review from a single institution.

Purpose: To describe our experience with locally developed evidence-based guidelines for oral fluorescein angiography (FA) for retinal imaging in children.

Methods: The medical records of consecutive pediatric patients (≤18 years of age) at University of Pittsburgh Medical Center Children's Hospital Eye Center who underwent oral FA between November 1, 2018, and April 1, 2022, were reviewed retrospectively. Adherence to or deviation from the guidelines was noted at the time of testing.

Thygeson's superficial punctate keratitis in children.

Objective: To describe the first paediatric case series of Thygesons' superficial punctate keratitis (TSPK) with management outcomes.

Methods: A retrospective chart review was done for all children either diagnosed at initial presentation or referred with TSPK from 01/2012 to 08/2021 at a tertiary children's hospital. Records were assessed for signs, symptoms, diagnosis, steroid and cyclosporine 0.

A Knock-In Mouse Model of Thymoma With the GTF2I L424H Mutation.

Introduction: The pathogenesis of thymic epithelial tumors remains largely unknown. We previously identified GTF2I L424H as the most frequently recurrent mutation in thymic epithelial tumors. Nevertheless, the precise role of this mutation in tumorigenesis of thymic epithelial cells is unclear.

Spatial meta-transcriptomics reveal associations of intratumor bacteria burden with lung cancer cells showing a distinct oncogenic signature.

Background: The lung intratumor microbiome influences lung cancer tumorigenesis and treatment responses, but detailed data on the extent, location, and effects of microbes within lung tumors are missing, information needed for improved prognosis and treatment.

Methods: To address this gap, we developed a novel spatial meta-transcriptomic method simultaneously detecting the expression level of 1,811 host genes and 3 microbe targets (bacteria, fungi, and cytomegalovirus). After rigorous validation, we analyzed the spatial meta-transcriptomic profiles of tumor cells, T cells, macrophages, other immune cells, and stroma in surgically resected tumor samples from 12 patients with early-stage lung cancer.

Receptivity of Hospitalized Older Adults and Family Caregivers to Prognostic Information about Aging, Injury, and Frailty: A Qualitative Study.

Background: Frailty is the leading prognosticator for poor outcomes and palliative care among older adults. Delivery of negative prognostic information entails potentially difficult conversations about decline and death.

Objective: The study aims were to: 1) examine hospitalized older adults' and family caregivers' receptivity to general (vs.

Computational stabilization of T cell receptors allows pairing with antibodies to form bispecifics.

Recombinant T cell receptors (TCRs) can be used to redirect naïve T cells to eliminate virally infected or cancerous cells; however, they are plagued by low stability and uneven expression. Here, we use molecular modeling to identify mutations in the TCR constant domains (Cα/Cβ) that increase the unfolding temperature of Cα/Cβ by 20 °C, improve the expression of four separate α/β TCRs by 3- to 10-fold, and improve the assembly and stability of TCRs with poor intrinsic stability. The stabilizing mutations rescue the expression of TCRs destabilized through variable domain mutation.

A Pilot Quality Improvement Project to Reduce Preoperative Fasting Duration in Pediatric Inpatients.

Unlabelled: Despite guidelines allowing clear liquids up to 2 hours before anesthesia, preoperative fasting for pediatric inpatients is often unnecessarily prolonged. This delay can lead to prolonged recovery time and increased postoperative pain. Efforts to reduce fasting duration in pediatric surgical patients is an evolving standard in pediatric anesthesiology.

Management of Menopause and the Role For Hormone Therapy.

Hormone therapy remains the most effective treatment for menopausal symptoms but decisions are complex, requiring an assessment of benefits and risks and determination of best treatment type, dose, and duration. Benefits exceed risks for most women with bothersome menopausal symptoms or high risk for fracture if initiated under age 60 years or within 10 years since menopause. Long-term mortality and safety data from the Women's Health Initiative is reassuring, with no increase in deaths from cardiovascular disease or cancer compared with placebo after 18 years of follow-up and a trend towards less mortality in those who initiate hormone therapy ages 50 to 59 years.

Beyond estrogen: advances in tissue selective estrogen complexes and selective estrogen receptor modulators.

Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have variable estrogen agonist and antagonist activities in different target tissues. Tamoxifen is an anti-estrogen in the breast used for treatment and prevention of breast cancer, with estrogen agonist activity in the uterus. Raloxifene prevents and treats osteoporosis and prevents breast cancer, and can be safely combined with vaginal but not systemic estrogen.

Multi-disciplinary evaluation of a 5-month-old with hypertrophic cardiomyopathy related to a functional adrenocortical tumor.

Background Hypertrophic cardiomyopathy (HCM) in childhood is a rare diagnosis, and associations with adrenocortical tumors (ACTs) have been rarely reported in the pediatric literature. Case presentation We present a case of a 5-month-old who presented with HCM and during the evaluation for hypertension was found to have elevated glucocorticoids, mineralocorticoids, androgens and urine metanephrines. During preoperative evaluation, he developed shock followed by cardiogenic collapse requiring extracorporeal membrane oxygenation (ECMO); however, he did not survive.

Integrated Genomic Comparison of Mouse Models Reveals Their Clinical Resemblance to Human Liver Cancer.

Hepatocellular carcinoma (HCC) is a heterogeneous disease. Mouse models are commonly used as preclinical models to study hepatocarcinogenesis, but how well these models recapitulate molecular subtypes of human HCC is unclear. Here, integration of genomic signatures from molecularly and clinically defined human HCC ( = 11) and mouse models of HCC ( = 9) identified the mouse models that best resembled subtypes of human HCC and determined the clinical relevance of each model.

Hemodynamics and Perfusion in Premature Infants During Transfusion.

Background: Premature infants may require packed red blood cell transfusions, but current guidelines lack empirical evidence and vary among institutions and prescribers.

Objective: To compare the physiological changes in cardiovascular hemodynamics and oxygen delivery between premature infants with anemia who receive packed red blood cell transfusions and premature infants without anemia.

Methods: The study was a prospective observational cohort investigation of 75 premature infants.

Structure-function relationships for the selective inhibition of human 3β-hydroxysteroid dehydrogenase type 1 by a novel androgen analog.

3β-Hydroxysteroid dehydrogenase type 1 (3β-HSD1) is selectively expressed in human placenta, mammary glands and breast tumors in women. Human 3β-HSD2 is selectively expressed in adrenal glands and ovaries. Based on AutoDock 3 and 4 results, we have exploited key differences in the amino acid sequences of 3β-HSD1 (Ser194, Arg195) and 3β-HSD2 (Gly194, Pro195) by designing a selective inhibitor of 3β-HSD1.

Schiff base complexes of copper and zinc as potential anti-colitic compounds.

The design, synthesis and activity of polymodal compounds for the treatment of inflammatory bowel disease are reported. The compounds, being based on a metal-Schiff base motif, are designed to degrade during intestinal transit to release the bioactive components in the gut. The compounds have been developed sequential with the biomodal compounds combining copper or zinc with a salicylaldehyde adduct.

Perioperative opioid administration in children with and without developmental delay undergoing outpatient dental surgery.

Study Objective: Prior research has indicated that children with developmental delay (DD) experience qualitative and quantitative differences in health care (Boulet et al., 2009). In the perioperative setting, there is concern that children with DD may be more likely to experience postoperative complications including agitation and nausea/vomiting than typically developing patients (TDP).

Gsk3 is a metabolic checkpoint regulator in B cells.

B cells predominate in a quiescent state until an antigen is encountered, which results in rapid growth, proliferation and differentiation of the B cells. These distinct cell states are probably accompanied by differing metabolic needs, yet little is known about the metabolic control of B cell fate. Here we show that glycogen synthase kinase 3 (Gsk3) is a metabolic sensor that promotes the survival of naive recirculating B cells by restricting cell mass accumulation.

Comparing domain interactions within antibody Fabs with kappa and lambda light chains.

IgG antibodies are multi-domain proteins with complex inter-domain interactions. Human IgG heavy chains (HCs) associate with light chains (LCs) of the κ or λ isotype to form mature antibodies capable of binding antigen. The HC/LC interaction involves 4 domains: VH and CH1 from the HC and VL and CL from the LC.

Loss of c-Met signaling sensitizes hepatocytes to lipotoxicity and induces cholestatic liver damage by aggravating oxidative stress.

Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels.

Possible role of anti-SSA/Ro antibodies in the pathogenesis of pulmonary hypertension.

Introduction: There are many different causes of pulmonary hypertension and the pathogenesis of the disease is still being elucidated. Although they are not the most common, autoimmunity and inflammation have been identified as possible causes. No one autoantibody has been identified as the definite cause of pulmonary hypertension.