Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

Ciliary Body Medulloepithelioma: Clinical and Pathologic Challenges with a Focus on Molecular Genetics.

Objective: Ciliary body medulloepithelioma (CBME), a pediatric intraocular tumor with potential for locally aggressive behavior and metastasis, may present with a diverse spectrum of clinical and histopathologic features leading to diagnostic and management challenges. Examination of unusual CBME cases highlights challenges and modern diagnostic techniques which facilitate accurate diagnosis and guide management.

Methods: A retrospective clinicopathologic analysis of 6 patients with unusual clinical or pathologic features of CBME was performed.

Emergence of a novel reassortant highly pathogenic avian influenza clade 2.3.4.4b A(H5N2) Virus, 2024.

Reassortant highly pathogenic avian influenza A(H5N2) clade 2.3.4.

Investigation of Genomic and Transcriptomic Risk Factors of Clopidogrel Response in African Americans.

Clopidogrel, an anti-platelet drug, is used to prevent thrombosis after percutaneous coronary intervention. Clopidogrel resistance results in recurring ischemic events, with African Americans (AA) suffering disproportionately. The aim of this study was to discover novel biomarkers of clopidogrel resistance in African Americans using genome and transcriptome data.

Clinical, immunophenotypic, and genomic findings of acute myeloid leukemia with RAM immunophenotype: Comparison with other CD56-positive acute leukemias.

Background: Acute myeloid leukemia (AML) with RAM immunophenotype is a newly recognized high-risk AML immunophenotypic subcategory characterized by blasts with bright expression of CD56 and weak to absent expression of CD45, HLA-DR, and CD38, as first described by the Children's Oncology Group (COG). The relationship between AML-RAM and other CD56-positive acute leukemias is unclear. The goal of this study is to characterize the clinicopathological characteristics of AML with RAM phenotype and compare them with other CD56 co-expressing acute leukemias.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Energy Resolved Mass Spectrometry Data from Surfaced Induced Dissociation Improves Prediction of Protein Complex Structure.

Native Mass Spectrometry (nMS) is a versatile technique for elucidating protein structure. Surface-Induced Dissociation (SID) is an activation method in tandem MS predominantly employed for determining protein complex stoichiometry alongside information about interface strengths. SID-nMS data can be collected over a range of acceleration energies, yielding Energy Resolved Mass Spectrometry (ERMS) data.

Pain and Frailty in Childhood Cancer Survivors: A Narrative Review.

A significant proportion of childhood cancer survivors experience persistent health problems related to cancer or cancer treatment exposures, including accelerated or early onset of aging. Survivors are more likely than non-cancer peers to present a frail phenotype suggestive of reduced physiologic reserve and have symptoms that interfere with function in daily life, including pain. Studies in the general population, mostly among older adults, suggest that pain is a significant contributor to development and progression of frail health.

Nutritional support in children treated for advanced adrenocortical carcinoma.

Purpose: Adrenocortical carcinoma (ACC) is a rare, aggressive pediatric malignancy. Advanced ACC requires multimodal treatment, including surgery and systemic chemotherapy including cisplatin, etoposide, doxorubicin, and mitotane. This is associated with significant gastrointestinal toxicity, resulting in many patients being unable to complete scheduled therapy.

Elucidating the dual roles of apoptosis and necroptosis in diabetic wound healing: implications for therapeutic intervention.

Wound healing is a complex and multistep biological process that involves the cooperation of various cell types. Programmed cell death, including apoptosis and necrotizing apoptosis, plays a crucial role in this process. Apoptosis, a controlled and orderly programmed cell death regulated by genes, helps eliminate unnecessary or abnormal cells and maintain internal environmental stability.

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.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Pediatric relapsed/refractory ALK+ anaplastic large cell lymphoma treatment and outcomes in the targeted drug era.

Treatment options for patients with relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK) inhibitors. However, there is no standard treatment and limited published data evaluating their use. The goal of this retrospective study is to describe current real-world treatment and outcomes of pediatric, adolescent, and young adult patients with R/R ALK-positive ALCL.

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 .

Targeting EPHB2/ABL1 restores antitumor immunity in preclinical models of ependymoma.

Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.

CD44-Mediated Metabolic Rewiring is A Targetable Dependency of IDH-Mutant Leukemia.

Recurrent IDH mutations catalyze NADPH-dependent production of oncometabolite R-2HG for tumorigenesis. IDH inhibition provides clinical response in a subset of acute myeloid leukemia (AML) cases; however, most patients develop resistance, highlighting the need for more effective IDH-targeting therapies. By comparing transcriptomic alterations in isogenic leukemia cells harboring CRISPR base-edited IDH mutations, we identify the activation of adhesion molecules including CD44, a transmembrane glycoprotein, as a shared feature of IDH-mutant leukemia, consistent with elevated CD44 expression in IDH-mutant AML patients.

A computational tool to infer enzyme activity using post-translational modification profiling data.

Enzymes play a pivotal role in orchestrating complex cellular responses to external stimuli and environmental changes through signal transduction pathways. Despite their crucial roles, measuring enzyme activities is typically indirect and performed on a smaller scale, unlike protein abundance measured by high-throughput proteomics. Moreover, it is challenging to derive the activity of enzymes from proteome-wide post-translational modification (PTM) profiling data.

CT, MRI, and FDG PET/CT in the Assessment of Lymph Node Involvement in Pediatric Hodgkin Lymphoma: An Expert Consensus Definition by an International Collaboration on Staging Evaluation and Response Criteria Harmonization for Children, Adolescent, and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL).

Staging of pediatric Hodgkin lymphoma is currently based on the Ann Arbor classification, incorporating the Cotswold modifications and the Lugano classification. The Cotswold modifications provide guidelines for the use of CT and MRI. The Lugano classification emphasizes the importance of CT and PET/CT in evaluating both Hodgkin lymphoma and non-Hodgkin lymphoma but focuses on adult patients.

BRAT1 - a new therapeutic target for glioblastoma.

Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.

Implementation of a Faith Community Nursing Transition of Care Program in the USA: A Propensity Score Matching Analysis.

Faith community nursing (FCN) is a specialty nursing practice that integrates spiritual and religious practices into patient care. This study aimed to quantitatively assess the impact of the standardized FCN transition of care (TOC) program on the rate of hospital readmission and length of stay (LOS) through propensity score matching and difference-in-differences methods. Compared with those in the non-FCN group (n = 409), patients in the FCN group (n = 66) had a reduced likelihood of hospital readmission at 30, 90, and 180 days after discharge (by 8.

A comparative evaluation of CRISPR-Cas9 allele editing systems in : challenging research in a challenging bug.

is an emergent fungal pathogen of significant interest for molecular research because of its unique nosocomial persistence, high stress tolerance and common multidrug resistance. To investigate the molecular mechanisms of these or other phenotypes, a handful of CRISPR-Cas9 based allele editing tools have been optimized for . Nonetheless, allele editing in this species remains a significant challenge and different systems have different advantages and disadvantages.

Impacts of Ethical Dilemmas and Moral Distress in Pediatric Hematology Oncology Nurses.

Purpose: To assess the level of moral distress (MD) and perceptions of ethical climate among pediatric hematology/oncology (PHO) nurses and to identify bioethics topics where increased education was desired.

Methods: In this cross-sectional study, we administered the 26-item Swedish Moral Distress Scale-Revised (sMDS-R), specifically revised and validated for pediatric oncology, in conjunction with the Clinical Ethics Needs Assessment Survey (CENAS). Electronic surveys were sent to inpatient and outpatient PHO nurses.

Interplay of canonical and LIMK mediated non-canonical BMP signaling is essential for regulating differential thickness and invagination during chick forebrain roof plate morphogenesis.

Telencephalic hemisphere formation is a complex and precisely timed process, which begins in the chick forebrain with an invagination in the middle of the roof plate. However, the factor(s) that determine the position/site of invagination in the roof plate remain to be elucidated. In this study, we have demonstrated that as development proceeds, a region of lower thickness appears in the middle of the roof plate, which marks the position where the invagination begins.