A blood-based DNA damage signature in patients with Parkinson's disease is associated with disease progression.

Aging is the main risk factor for Parkinson's disease (PD), yet our understanding of how age-related mechanisms contribute to PD pathophysiology remains limited. We conducted a longitudinal analysis of blood samples from the Parkinson's Progression Markers Initiative cohort to investigate DNA damage in PD. Patients with PD exhibited disrupted DNA repair pathways and biased suppression of longer transcripts, indicating age-related, transcription-stalling DNA damage.

Relapsed rhabdomyosarcoma: treatment recommendations from the European pediatric soft tissue sarcoma study group (EpSSG).

At least one-third of patients with localized rhabdomyosarcoma (RMS) and 60-70% of patients with metastatic RMS experience progressive disease or relapse. Following relapse, outcomes generally remain poor with limited treatment options and a high risk of subsequent recurrence. Optimal treatment requires a multidisciplinary approach incorporating chemotherapy with local control.

Innovative Training to Improve Childhood Cancer Knowledge Among Primary Health Care Providers: Evaluating a Blended Learning Program in Kenya.

Purpose: Early detection and timely referral are vital to improving childhood cancer outcomes in low- and middle-income countries. However, training primary health care providers (HCPs) remains challenging because of limited time and resources. This study assesses the knowledge of primary health care workers after a blended learning program on childhood cancer and examines impact on referrals.

Harmonized Immune Recovery Monitoring after HCT: Evidence & Practical Guidance from the Westhafen Intercontinental Group.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative option for patients with high-risk malignancies and non-malignant disorders. Long-term survival depends on robust immune reconstitution (IR), which governs overall immune homeostasis and risks of infection, graft-versus-host disease, and relapse. However, despite its centrality to post-transplant outcomes, IR is not consistently monitored across transplant centers, limiting ability to generate meaningful, comparable, and translatable data.

γδ T cells are the prime antitumoral T cells in pediatric neuroblastoma.

High-risk pediatric neuroblastoma patients have a dismal survival rate despite intensive treatment regimens. New treatment options are thus required. Even though HLA expression in neuroblastoma is low and immune cell infiltrates are limited, the presence of tumor-infiltrating lymphocytes (TILs) is indicative of better patient survival.

Imaging changes with or without neurological symptoms after proton therapy in pediatric posterior fossa tumors; initial experience of the Dutch national cohort.

Background And Purpose: The incidence of proton therapy (PT)-related imaging changes in the central nervous system, and associated symptoms, varies widely in literature. The aim of this study was to assess imaging changes after implementation of intensity-modulated pencil beam scanning in a national cohort of pediatric posterior fossa (PF) tumors.

Materials And Methods: All pediatric PF tumor patients treated in the XXX with PT between 06-2018 and 12-2022 were analyzed.

White paper on the current state of imaging biomarkers in paediatric oncology.

In paediatric oncology, imaging biomarkers play an increasing role in diagnostic imaging and research. They can be used for prediction, detection, staging, and grading of diseases, as well as for assessment of response to treatment. Imaging biomarkers are complementary to tissue-based biomarkers, enabling a more personalised approach in oncology care.

Expansion of the Candidozyma haemuli Species Complex - The Novel Species Candidozyma molenica, Isolated from Clinical and Environmental Sources.

Due to the recent unprecedented global rise of Candidozyma auris in hospital environments the members of the Candidozyma haemuli species complex have raised significant interest of clinicians and researchers. Until the finding of C. auris, the species complex did not receive much attention as the known pathogenic species were only rarely encountered in hospitals and clinical diagnostic laboratories.

cIMPACT-NOW update 11: Proposal on adaptation of diagnostic criteria for IDH- and H3-wildtype diffuse high-grade gliomas and for posterior fossa ependymal tumors.

The Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy (cIMPACT-NOW) updates provide guidelines for the diagnosis of central nervous system (CNS) tumors and suggestions for future World Health Organization (WHO) classification. Following publication of the fifth edition WHO Classification of CNS Tumors (WHO CNS5) in 2021, the cIMPACT-NOW working group "Clarification" reviewed WHO CNS5 and prioritized two topics for further elucidation: (a) distinction of Glioblastoma, IDH-wildtype from Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype and (b) clarification of subgroups of posterior fossa (PF) ependymal tumors. Recommendations regarding the IDH- and H3-wildtype diffuse high-grade gliomas include: (1) use caution assigning CNS WHO grade 4 (diagnosis of Glioblastoma, IDH-wildtype) to a "TERT promoter only", histologically low-grade, IDH-wildtype tumor; (2) EGFR gene amplification and +7/-10 chromosome copy number alterations should not be used as solitary defining features for diagnosing high-grade gliomas as Glioblastoma, IDH-wildtype in patients <40 years of age; (3) Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype should be considered in the differential diagnosis in adults, especially those <40 years of age; (4) PDGFRA alteration, EGFR alteration, or MYCN amplification count as key molecular features of Diffuse pediatric-type high-grade glioma, H3-wildtype, and IDH-wildtype only in patients <25 years.

Introducing Holographic Surgical Navigation in Pediatric Wilms' Tumor Patients: A Feasibility Study During Total Nephrectomy.

Wilms' tumor is a common pediatric renal malignancy. In selected cases, nephron-sparing surgery (NSS) may be employed as part of the surgical approach. To prevent positive margins, optimal understanding of the tumor-kidney edge is essential.

Correction: Kalisvaart et al. Relative Wash-In Rate in Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a New Prognostic Biomarker for Event-Free Survival in 82 Patients with Osteosarcoma: A Multicenter Study. 2024, , 1954.

In the original publication [...

Evaluating the Implementation Success of an Intensity-Adapted Guideline for Pediatric Acute Myeloid Leukemia in Malawi: An Observational-Implementation Study Protocol.

Acute myeloid leukemia (AML) is most often incurable in low-resource settings. To address this challenge, the International Society of Paediatric Oncology (SIOP) developed an intensity-adapted AML practice guideline in 2019. Here, we present the protocol of an observational-implementation study evaluating the SIOP guideline in Malawi.

Multilineage involvement in ABL-class fusion-positive pediatric B-cell acute lymphoblastic leukemia: CML-like biology.

Not available.

Feasibility, Barriers, and Facilitators of Long-Term Physical Activity Tracking During Treatment: Interview Study Among Childhood Cancer Patients.

Background: Children with cancer are at risk of reduced physical activity. Gaining insight into physical activity using smartwatches could improve understanding of individual potential during treatment, support early recognition of aberrant physical activity, and enable tailored support.

Objective: This study aimed to explore the feasibility, barriers, facilitators, and considerations of long-term physical activity tracking using a smartwatch during childhood cancer treatment.

The immune landscape of pediatric (extra)cranial solid tumors: A systematic review and integration of immunohistochemistry and single-cell RNA sequencing data.

Background: Immunotherapies achieved remarkable success in adult cancers, yet their efficacy in pediatric brain and extracranial solid tumors remains limited. Insights into the unique immune landscape of pediatric tumors are crucial to improve immunotherapies for pediatric patients.

Methods: We performed a systematic search for studies reporting immunohistochemistry (IHC), single-cell- or single-nucleus RNA-sequencing (sc/snSeq) data on the immune landscape of pediatric tumors.

ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.

Background And Aims: Deficiency of the phospholipid transporter ATP8B1 causes infantile-onset progressive familial intrahepatic cholestasis type I (PFIC1). Pre-transplant PFIC1 patients often present with mild dyslipidaemia. This raises the possibility that PFIC1 patients, besides cholestasis, may also experience defects in glucose and lipid metabolism.

Small round cell sarcoma tumoroid biobank reveals CIC::DUX4 sarcoma vulnerability to MCL-1 inhibition.

Small round cell sarcomas (SRCS) are highly aggressive tumors in soft tissues and bone of mostly children and young adults. Despite being different in many aspects, including genetics, possible cell-of-origin, and pathology, patients with any of these entities all receive the same therapeutic regimen. Although several pre-clinical models of Ewing sarcoma have been established, such as cell lines and patient-derived tumor xenografts, few models exist for other SRCS.

Single-cell multi-omics characterize colorectal tumors, adjacent healthy tissue and matched (tumor) organoids identifying CRC-unique features.

Colorectal cancer (CRC) arises in the colorectal tissue driven by genetic disorder or the accumulation of somatic mutations, leading to abnormal epithelial cell growth. In this study, we employed single-nucleus multi-omics analysis, including single-nucleus RNA-seq and single-nucleus ATAC-seq, on over 100,000 high-quality nuclei to investigate the molecular landscape of both primary tissue and patient-derived organoids (PDOs). Our analysis showed that normal PDOs (N-PDOs) derived from tissue adjacent to tumors replicate the cellular composition and differentiation trajectory of colorectal crypts.

Nephrotoxicity and kidney outcomes in pediatric oncology patients.

Background: Acute kidney injury (AKI) is a serious complication during pediatric cancer treatment. Nephrotoxic medication may increase the risk of developing AKI, which may necessitate modifications to standard treatment and may also increase the risk of chronic kidney disease (CKD). This study investigates the incidence of AKI, the impact of nephrotoxic medications and the association between AKI and the development of CKD.

Impact of 3D cell culture hydrogels derived from basement membrane extracts or nanofibrillar cellulose on CAR-T cell activation.

Hydrogel-based 3D culture systems are increasingly used for preclinical evaluation of cell-based immunotherapies, including chimeric antigen receptor T (CAR-T) cells. However, hydrogel properties can influence T cell behavior, potentially affecting interpretation of immunotherapy studies. We assessed CD4 T and CAR-T cell responses in two chemically undefined matrices-Matrigel and basement membrane extract (BME)- and in a synthetic nanofibrillar cellulose (NFC) hydrogel.