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Record W4386949028 · doi:10.1093/neuonc/noad125

Optimizing preclinical pediatric low-grade glioma models for meaningful clinical translation

2023· article· en· W4386949028 on OpenAlexafffund
Till Milde, Jason Fangusaro, Michael J. Fisher, Cynthia Hawkins, Fausto J. Rodriguez, Uri Tabori, Olaf Witt, Yuan Zhu, David H. Gutmann

Bibliographic record

VenueNeuro-Oncology · 2023
Typearticle
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsUniversity of TorontoHospital for Sick Children
FundersNational Institute of Neurological Disorders and StrokePediatric Brain Tumor FoundationSchool of Medicine, Emory UniversityArray BioPharmaUniversity of California, Los AngelesUniversitätsklinikum HeidelbergPerelman School of Medicine, University of PennsylvaniaU.S. Department of DefenseIan's Friends FoundationSpringworks TherapeuticsDeutsches KrebsforschungszentrumNational Cancer InstituteAlexion PharmaceuticalsUniversity of TorontoEmory UniversityDeutschen Konsortium für Translationale KrebsforschungChildren's National HospitalUniversity of PennsylvaniaHospital for Sick ChildrenPfizerExelixisChildren's Hospital of PhiladelphiaAstraZenecaBrain Tumour Charity
KeywordsMedicineMAPK/ERK pathwayGliomaMicrogliaCentral nervous systemStromal cellOncologyBrain tumorBioinformaticsCancer researchNeuroscienceInternal medicinePathologySignal transductionPsychologyBiologyInflammation

Abstract

fetched live from OpenAlex

Pediatric low-grade gliomas (pLGGs) are the most common brain tumor in young children. While they are typically associated with good overall survival, children with these central nervous system tumors often experience chronic tumor- and therapy-related morbidities. Moreover, individuals with unresectable tumors frequently have multiple recurrences and persistent neurological symptoms. Deep molecular analyses of pLGGs reveal that they are caused by genetic alterations that converge on a single mitogenic pathway (MEK/ERK), but their growth is heavily influenced by nonneoplastic cells (neurons, T cells, microglia) in their local microenvironment. The interplay between neoplastic cell MEK/ERK pathway activation and stromal cell support necessitates the use of predictive preclinical models to identify the most promising drug candidates for clinical evaluation. As part of a series of white papers focused on pLGGs, we discuss the current status of preclinical pLGG modeling, with the goal of improving clinical translation for children with these common brain tumors.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0040.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.150
GPT teacher head0.415
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations15
Published2023
Admission routes2
Has abstractyes

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