Causally Mapping the Cerebellum in Children and Young Adults: from Motor to Cognition.

While the cerebellum's role in orchestrating motor execution and routines is well established, its functional role in supporting cognition is less clear. Previous studies claim that motricity and cognition are mapped in different areas of the cerebellar cortex, with an anterior/posterior dichotomy. However, most of the studies supporting this claim either use correlational methods (neuroimaging) or are lesion studies that did not consider central covariates (such as age, gender, treatment presence, and deep nuclei impairment) known to influence motor and cognitive recoveries in patients.

Establishing a living biobank of pediatric high-grade glioma and ependymoma suitable for cancer pharmacology.

Background: Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help defining new therapeutic options for pediatric brain tumors.

Nanopore Sequencing as a Cutting-Edge Technology for Medulloblastoma Classification.

Background: Medulloblastoma (MB) is one of the most prevalent embryonal malignant brain tumors. Current classification organizes these tumors into four molecular subgroups (WNT, SHH, Group 3, and Group 4 MB). Recently, a comprehensive classification has been established, identifying numerous subtypes, some of which exhibit a poor prognosis.

Clinical characteristics and outcome of central nervous system tumors harboring NTRK gene fusions.

Purpose: TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients.

Experimental Design: We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors.

Conjugation Mediates Large-Scale Chromosomal Transfer in Streptomyces Driving Diversification of Antibiotic Biosynthetic Gene Clusters.

Streptomyces are ubiquitous soil-dwelling bacteria with large, linear genomes that are of special importance as a source of metabolites used in human and veterinary medicine, agronomy, and industry. Conjugative elements (actinomycetes integrative and conjugative elements, AICEs) are the main drivers of Streptomyces Horizontal Gene Transfer. AICE transfer has long been known to be accompanied by mobilization of chromosomal DNA.

A Review of GO-AJA's Impact on Adolescents and Young Adults with Cancer in France: A Decade of Progress and Challenges.

The "Groupe Onco-hématologie Adolescents Jeunes Adultes" (GO-AJA) born in 2012 is a French collaborative group. It focuses on heterogeneity and unmet needs for AYA with cancer. This article highlights GO-AJA's achievements and future prospects, emphasizing its role in structuring a professional national network, improving AYAs' comprehensive care and strengthening the roles of coordinating nurses.

Why do mobile genetic elements transfer DNA of their hosts?

The prokaryote world is replete with mobile genetic elements (MGEs) - self-replicating entities that can move within and between their hosts. Many MGEs not only transfer their own DNA to new hosts but also transfer host DNA located elsewhere on the chromosome in the process. This could potentially lead to indirect benefits to the host when the resulting increase in chromosomal variation results in more efficient natural selection.

Synteruptor: mining genomic islands for non-classical specialized metabolite gene clusters.

Microbial specialized metabolite biosynthetic gene clusters (SMBGCs) are a formidable source of natural products of pharmaceutical interest. With the multiplication of genomic data available, very efficient bioinformatic tools for automatic SMBGC detection have been developed. Nevertheless, most of these tools identify SMBGCs based on sequence similarity with enzymes typically involved in specialised metabolism and thus may miss SMBGCs coding for undercharacterised enzymes.

Retrospective experience of children with relapsed brain tumors treated with oral combination of axitinib and metronomic etoposide.

Metronomic chemotherapy-based combinations have received interest for relapsed/refractory malignancies. Preclinical and clinical studies showed activity of metronomic etoposide and axitinib. We report our retrospective experience in six children treated with axitinib and metronomic etoposide for refractory/relapsed brain tumors as an "off-label" combination.

Bone Morphogenic Proteins in Pediatric Diffuse Midline Gliomas: How to Make New Out of Old?

The BMP pathway is one of the major signaling pathways in embryonic development, ontogeny and homeostasis, identified many years ago by pioneers in developmental biology. Evidence of the deregulation of its activity has also emerged in many cancers, with complex and sometimes opposing effects. Recently, its role has been suspected in Diffuse Midline Gliomas (DMG), among which Diffuse Intrinsic Pontine Gliomas (DIPG) are one of the most complex challenges in pediatric oncology.

Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

Purpose: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization.

Correction of non-random mutational biases along a linear bacterial chromosome by the mismatch repair endonuclease NucS.

The linear chromosome of Streptomyces exhibits a highly compartmentalized structure with a conserved central region flanked by variable arms. As double strand break (DSB) repair mechanisms play a crucial role in shaping the genome plasticity of Streptomyces, we investigated the role of EndoMS/NucS, a recently characterized endonuclease involved in a non-canonical mismatch repair (MMR) mechanism in archaea and actinobacteria, that singularly corrects mismatches by creating a DSB. We showed that Streptomyces mutants lacking NucS display a marked colonial phenotype and a drastic increase in spontaneous mutation rate.

METRO-PD1: Phase 1 study of nivolumab in combination with metronomic chemotherapy in children and adolescents with relapsing/refractory solid tumors.

Background: This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors.

Objectives: To evaluate the feasibility and safety of the three regimens METHODS: Patients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C).

Antiseizure effect of MEK inhibitor in a child with neurofibromatosis type 1-Developmental and epileptic encephalopathy and optic pathway glioma.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder due to a mutation in NF1 gene, resulting in phenotypically heterogeneous systemic manifestations. Patients with NF1 are prone to develop neoplasms of the central nervous system (CNS) and are particularly at risk for optic pathway gliomas (OPG). Epilepsy is another recognized neurologic complication in patients with NF1, with a prevalence estimated between 4% and 14%.

Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen: A Nonrandomized Controlled Trial.

Importance: Medulloblastoma recurrence in patients who have previously received irradiation has a dismal prognosis and lacks a standard salvage regimen.

Objective: To evaluate the response rate of pediatric patients with medulloblastoma recurrence using an antiangiogenic metronomic combinatorial approach (Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial [MEMMAT]).

Design, Setting, And Participants: This phase 2, investigator-initiated, multicenter nonrandomized controlled trial assessed 40 patients with relapsed or refractory medulloblastoma without a ventriculoperitoneal shunt who were younger than 20 years at original diagnosis.

Dynamics of the Streptomyces chromosome: chance and necessity.

Streptomyces are prolific producers of specialized metabolites with applications in medicine and agriculture. Remarkably, these bacteria possess a large linear chromosome that is genetically compartmentalized: core genes are grouped in the central part, while the ends are populated by poorly conserved genes including antibiotic biosynthetic gene clusters. The genome is highly unstable and exhibits distinct evolutionary rates along the chromosome.

Respective Roles of Surgery, Chemotherapy, and Radiation Therapy for Recurrent Pediatric and Adolescent Ependymoma: A National Multicentric Study.

Purpose: Half of the children and adolescents treated for intracranial ependymoma experience recurrences that are not managed in a standardized manner. This study aimed to retrospectively evaluate recurrence treatments.

Methods And Materials: We assessed overall survival (OS) and progression-free survival (PFS) after a first relapse in a population of patients from the Pediatric Ependymoma Photons Protons and Imaging study (PEPPI study) who were treated with surgery and radiation therapy in French Society of Childhood Cancer reference centers between 2000 and 2013.

The TLR3 L412F polymorphism prevents TLR3-mediated tumor cell death induction in pediatric sarcomas.

Toll-like receptor 3 (TLR3) is a pattern recognition receptor mainly known for its role in innate immune response to infection. Indeed, binding of double-stranded RNA (dsRNA) to TLR3 triggers a pro-inflammatory cascade leading to cytokine release and immune cell activation. Its anti-tumoral potential has emerged progressively, associated with a direct impact on tumor cell death induction and with an indirect action on immune system reactivation.

Genome Analysis of a Variant of M145 with High Lipid Content and Poor Ability to Synthetize Antibiotics.

M145 is a model strain extensively studied to elucidate the regulation of antibiotic biosynthesis in species. This strain abundantly produces the blue polyketide antibiotic, actinorhodin (ACT), and has a low lipid content. In a process designed to delete the gene encoding the isocitrate lyase () of the glyoxylate cycle, an unexpected variant of was obtained besides deletion mutants.

Posterior fossa ependymoma in children: A long-term single-center experience.

Introduction: Ependymomas in the posterior fossa have poor prognosis. This study reports a single-center pediatric series, focusing on the value of surgical resection.

Material And Methods: A single-center retrospective study included all patients operated on by the senior author (CM) for posterior fossa ependymoma from 2002 to 2018.

Afatinib in paediatric patients with recurrent/refractory ErbB-dysregulated tumours: Results of a phase I/expansion trial.

Aim: This phase I/expansion study assessed the safety, pharmacokinetics and preliminary antitumor activity of afatinib in paediatric patients with cancer.

Methods: The dose-finding part enroled patients (2-<18 years) with recurrent/refractory tumours. Patients received 18 or 23 mg/m/d afatinib orally (tablet or solution) in 28-d cycles.

Phase I Study of a Combination of Fluvastatin and Celecoxib in Children with Relapsing/Refractory Low-Grade or High-Grade Glioma (FLUVABREX).

Preclinical data support the activity of celecoxib and fluvastatin in high-grade (HGG) and low-grade gliomas (LGG). A phase I trial (NCT02115074) was designed to evaluate the safety of this combination in children with refractory/relapsed HGG and LGG using four dose levels of fluvastatin with a fixed daily dose of celecoxib. A Continual Reassessment Method was used for fluvastatin dose escalation.