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.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.

Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.

The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.

A Prospective, Randomized, Noninferiority Study to Evaluate the Safety and Effectiveness of Steerable Ureteroscopic Renal Evacuation Compared with Standard Ureteroscopy: 30-Day Results of the ASPIRE Study.

We report the first multicenter, prospective, randomized noninferiority controlled trial of steerable ureteroscopic renal evacuation (SURE) for nephrolithiasis treatment. Candidates for laser lithotripsy ≥18 years with ≥1 renal stone ≥7 mm and 7-20 mm stone burden were randomized 1:1 SURE ureteroscopy (URS). SURE was performed using the CVAC Aspiration System, a novel steerable irrigation-aspiration catheter.

A foundation model for generalized brain MRI analysis.

Artificial intelligence (AI) applied to brain magnetic resonance imaging (MRI) has the potential to improve disease diagnosis and management but requires algorithms with generalizable knowledge that can perform well in a variety of clinical scenarios. The field has been constrained, thus far, by limited training data and task-specific models that do not generalize well across patient populations and medical tasks. Foundation models, by leveraging self-supervised learning, pretraining, and targeted adaptation, present a promising paradigm to overcome these limitations.

Considerations for building and using integrated single-cell atlases.

The rapid adoption of single-cell technologies has created an opportunity to build single-cell 'atlases' integrating diverse datasets across many laboratories. Such atlases can serve as a reference for analyzing and interpreting current and future data. However, it has become apparent that atlasing approaches differ, and the impact of these differences are often unclear.

Omnigene-Gut ensures fecal microbiome stability in the pediatric population.

Increasing evidence exists that the gut microbiome influences toxicity as well as outcomes in a variety of cancers. To investigate the role of the gut microbiome in pediatric neuro-oncology, microbiome analysis has been included in multiple prospective pediatric neuro-oncology clinical trials (NCT05009992, NCT04732065, NCT04775485). In these trials, the OMNIgene-GUT preservation tubes are used for the collection of the feces.

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.

Search for Soft Unclustered Energy Patterns in Proton-Proton Collisions at 13 TeV.

The first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics.

Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial.

Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.

Retrospective Comparison of Targeted Anticancer Drugs Predicted by the CNS-TAP Tool Versus Those Selected by a Molecularly Driven Tumor Board in Children With DIPG.

The recent trial Pediatric Neuro-Oncology Consortium 003 (PNOC003) utilized a molecular tumor board to recommend personalized treatment regimens based on tumor sequencing results in children with DIPG. We separately developed the Central Nervous System Targeted Agent Prediction (CNS-TAP) tool, which numerically scores targeted anticancer agents using preclinical, clinical, and patient-specific data. We hypothesized that highly scored agents from CNS-TAP would overlap with the PNOC003 tumor board's recommendations.

Search for the Z Boson Decay to ττμμ in Proton-Proton Collisions at sqrt[s]=13 TeV.

The first search for the Z boson decay to ττμμ at the CERN LHC is presented, based on data collected by the CMS experiment at the LHC in proton-proton collisions at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 138  fb^{-1}. The data are compatible with the predicted background. For the first time, an upper limit at the 95% confidence level of 6.

A (sub)field guide to quality control in hippocampal subfield segmentation on high-resolution T-weighted MRI.

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements.

Targeted Deletion of Fibroblast Growth Factor 23 Rescues Metabolic Dysregulation of Diet-induced Obesity in Female Mice.

Fibroblast growth factor 23 (FGF23) is a bone-secreted protein widely recognized as a critical regulator of skeletal and mineral metabolism. However, little is known about the nonskeletal production of FGF23 and its role in tissues other than bone. Growing evidence indicates that circulating FGF23 levels rise with a high-fat diet (HFD) and they are positively correlated with body mass index (BMI) in humans.

Observation of the decay.

Using proton-proton collision data corresponding to an integrated luminosity of collected by the CMS experiment at , the decay is observed for the first time, with a statistical significance exceeding 5 standard deviations. The relative branching fraction, with respect to the decay, is measured to be , where the first uncertainty is statistical, the second is systematic, and the third is related to the uncertainties in and .

Observation of Enhanced Long-Range Elliptic Anisotropies Inside High-Multiplicity Jets in pp Collisions at sqrt[s]=13 TeV.

A search for collective effects inside jets produced in proton-proton collisions is performed via correlation measurements of charged particles using the CMS detector at the CERN LHC. The analysis uses data collected at a center-of-mass energy of sqrt[s]=13  TeV, corresponding to an integrated luminosity of 138  fb^{-1}. Jets are reconstructed with the anti-k_{T} algorithm with a distance parameter of 0.

Image processing tools for petabyte-scale light sheet microscopy data.

Light sheet microscopy is a powerful technique for high-speed three-dimensional imaging of subcellular dynamics and large biological specimens. However, it often generates datasets ranging from hundreds of gigabytes to petabytes in size for a single experiment. Conventional computational tools process such images far slower than the time to acquire them and often fail outright due to memory limitations.

Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.

Objective: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.

Methods: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.

Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency.

Tissue-resident memory T (T) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common T cell fate remains poorly understood. Here, we show that whereas skin T cells strictly require transforming growth factor β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β to drive T cells in the small intestine.

Sustained Performance of Cardiac Arrest Prevention in Pediatric Cardiac Intensive Care Units.

Importance: The Pediatric Cardiac Critical Care Consortium (PC4) cardiac arrest prevention (CAP) quality improvement (QI) project facilitated a decreased in-hospital cardiac arrest (IHCA) incidence rate across multiple hospitals. The sustainability of this outcome has not been determined.

Objective: To examine the IHCA incidence rate at participating hospitals after the QI project ended and discern which factors best aligned with sustained improvement.