Cycling Molecular Assemblies for Selective Cancer Cell Golgi Disruption.

The Golgi apparatus is a critical organelle responsible for intracellular trafficking and signaling, orchestrating essential processes such as protein and lipid sorting . Dysregulation of its function has been implicated in various pathologies, including obesity, diabetes, and cancer, highlighting its importance as a potential therapeutic target. Despite this, the development of tools to selectively target the Golgi in specific cell types remain a significant unmet challenge in imaging and drug discovery.

Injectable Estradiol Use in Transgender and Gender-Diverse Individuals in the U.S.: A Multicenter Retrospective Study.

Context: Guidelines for use of injectable estradiol esters (valerate [EV] and cypionate [EC]) among transgender and gender diverse (TGD) individuals designated male at birth vary considerably, with many providers noting supraphysiologic serum estradiol concentrations based on current dosing recommendations.

Objectives: 1. Determine dose of injectable estradiol (subcutaneous [SC] and intramuscular [IM]) needed to reach guideline-recommended estradiol concentrations for TGD adults using EC/EV.

Inhibition of DKK-1 by WAY262611 Inhibits Osteosarcoma Metastasis.

Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood. Patients who present with metastatic disease at diagnosis or relapse have a very poor prognosis, and this has not changed over the past four decades. The Wnt signaling pathway plays a role in regulating osteogenesis and is implicated in OS pathogenesis.

Inhibition of DKK-1 by WAY262611 Inhibits Osteosarcoma Metastasis.

Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood. Patients who present with metastatic disease at diagnosis or relapse have a very poor prognosis, and this has not changed over the past four decades. The Wnt signaling pathway plays a role in regulating osteogenesis and is implicated in OS pathogenesis.

VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma.

Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies.

Atypical hemolytic uremic syndrome during induction chemotherapy in neuroblastoma, a rare phenomenon or common congenital predisposition?

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy sometimes associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury arise due to aberrant complement protein activation in the circulation. A 13-month-old boy with metastatic neuroblastoma (NB) developed aHUS during his first cycle of induction chemotherapy with germline testing revealing a complement factor H (CFH) gene mutation, currently classified as a variant of uncertain significance (VUS).

Polyamine Depletion by D, L-alpha-difluoromethylornithine Inhibits Ewing Sarcoma Metastasis by Inducing Ferroptosis.

Polyamine metabolism and signaling play important roles in multiple cancers but have not previously been studied in Ewing sarcoma. Here, we show that blocking polyamine synthesis with D, L-alpha-difluoromethylornithine (DFMO) causes a G1 cell cycle arrest, dose-dependent decreases in sarcosphere formation from Ewing sarcoma cell lines growing in non-adherent conditions and a decrease in clonogenic growth in soft agar. Further, we utilized our orthotopic implantation/amputation model of Ewing sarcoma metastasis to demonstrate that DFMO slowed primary tumor growth in addition to limiting metastasis.

Tabelecleucel for EBV+ PTLD after allogeneic HCT or SOT in a multicenter expanded access protocol.

Patients with Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disease (EBV+ PTLD) in whom initial treatment fails have few options and historically low median overall survival (OS) of 0.7 months after allogeneic hematopoietic cell transplant (HCT) and 4.1 months after solid organ transplant (SOT).

RNA helicase DDX3 regulates RAD51 localization and DNA damage repair in Ewing sarcoma.

We previously demonstrated that RNA helicase DDX3X (DDX3) can be a therapeutic target in Ewing sarcoma (EWS), but its role in EWS biology remains unclear. The present work demonstrates that DDX3 plays a unique role in DNA damage repair (DDR). We show that DDX3 interacts with several proteins involved in homologous recombination, including RAD51, RECQL1, RPA32, and XRCC2.

Experience informed procedural skills training.

Background: Paediatric critical care (PCC) physicians must perform several emergent procedures independently and competently-requiring transition from novice to competent over a 3-year fellowship. However, skill acquisition is not uniform. Individualised training, adapted to the unique experiences and requirements of each trainee, may enhance competency.

Delayed Solid Tumor Presentations in Adolescent and Young Adults Patients in the Bronx.

Adolescent and young adults (AYAs) require support from their parents and caregivers. While there are formal programs available for patients with complex medical problems, <20% of pediatric practices are performing transition readiness processes in patients aged 12-17 years to effective transition. Although cancer is the most common cause of disease-related death in AYAs in high-income countries, AYA oncology patients have not attained the same clinical improvements as pediatric patients, and their outcomes remain poorer.

Breaking down the tumor immune infiltration within pediatric sarcomas.

Immunotherapies are a promising therapeutic option, yet for a variety of reasons, these treatments have achieved limited success against sarcomas. The immunosuppressive tumor microenvironment (TME) of sarcomas as well as lack of predictive biomarkers, decreased T-cell clonal frequency, and high expression of immunosuppressive infiltrating cells has thus far prevented major success using immunotherapies. By breaking down the TME into its individual components and understanding how the various cell types interact with each other as well as in the context of the complex immune microenvironment, can lead to effective therapeutic immunotherapy treatments, potentially improving outcomes for those with metastatic disease.

How Augmenting Reality Changes the Reality of Simulation: Ethnographic Analysis.

Background: Simulation-based medical education (SBME) provides key medical training for providers to safely and ethically practice high-risk events. Augmented reality (AR)-enhanced simulation projects digital images of realistic examination findings into a participant's field of view, which allows nuanced physical examination findings such as respiratory distress and skin perfusion to be prominently displayed. It is unknown how AR compares to traditional mannequin (TM)-based simulation with regard to influencing participant attention and behavior.

RNA Helicase DDX3 Regulates RAD51 Localization and DNA Damage Repair in Ewing Sarcoma.

We previously demonstrated that RNA helicase DDX3X (DDX3) can be a therapeutic target in Ewing sarcoma (EWS), but its role in EWS biology remains unclear. The present work demonstrates that DDX3 plays a unique role in DNA damage repair (DDR). We show that DDX3 interacts with several proteins involved in homologous recombination, including RAD51, RECQL1, RPA32, and XRCC2.

Respiratory Failure Due to Idiopathic Pneumonia Syndrome in a Pediatric Patient After Recipient-derived Allogeneic Chimeric Antigen Receptor T-Cell Therapy.

Idiopathic pneumonia syndrome (IPS) is a life-threatening complication of hematopoietic cell transplantation, but it is not clearly described following chimeric antigen receptor (CAR) T-cell therapy. We describe a child who developed IPS after receiving tisagenlecleucel for post-hematopoietic cell transplantation relapsed acute lymphoblastic leukemia and had a remarkable improvement after treatment with corticosteroids and etanercept. We discuss the implications of cytokine signaling in IPS and immunologic considerations of allogeneic CAR T cells.

Impact of race/ethnicity and language preferences on pediatric ALL survival outcomes.

Background: Ethnic and racial disparities have recently been observed both in treatment-related toxicities and rates of long-lasting cure in acute lymphoblastic leukemia (ALL) and acute lymphoblastic lymphoma (ALLy), the most common pediatric malignancy. Despite significant improvements in overall survival in the recent past, a large number of children die from aggressive disease.

Methods: We performed a retrospective cohort analysis of 274 pediatric ALL/ALLy patients within Montefiore Health System from 2004 to 2021 to determine differences in all-cause mortality within the Pediatric Hematologic Malignancies Cohort using Cox Proportional Hazard regression modeling, adjusted for age at diagnosis, race/ethnicity, administration of intensive chemotherapy, preferred language, maximum glucose, and hypertension.

Live Cell Imaging Reveals HBV Capsid Translocation from the Nucleus To the Cytoplasm Enabled by Cell Division.

Hepatitis B virus (HBV) capsid assembly is traditionally thought to occur predominantly in the cytoplasm, where the virus gains access to the virion egress pathway. To better define sites of HBV capsid assembly, we carried out single cell imaging of HBV Core protein (Cp) subcellular trafficking over time under conditions supporting genome packaging and reverse transcription in Huh7 hepatocellular carcinoma cells. Time-course analyses including live cell imaging of fluorescently tagged Cp derivatives showed Cp to accumulate in the nucleus at early time points (~24 h), followed by a marked re-distribution to the cytoplasm at 48 to 72 h.

First-Time Use of the Seraph 100 Microbind Affinity Blood Filter in an Adolescent Patient with Severe COVID-19 Disease: A Case Report.

The Seraph 100 Microbind Affinity Blood Filter (Seraph 100) is a hemoperfusion device designed to adsorb bacteria, viruses, and toxins when added to extracorporeal circuits. The FDA granted emergency use authorization in adults, but this device had never been utilized in children. A 17-year-old patient with asthma presented with respiratory distress due to COVID-19.