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Record W3010272507 · doi:10.1016/j.ccell.2020.02.002

Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas

2020· article· en· W3010272507 on OpenAlexafffund
Jérôme Fortin, Ruxiao Tian, Ida Zarrabi, Graham Hill, Eleanor Williams, Gonzalo Sánchez‐Duffhues, Midory Thorikay, Parameswaran Ramachandran, Robert Siddaway, Jong Fu Wong, Annette Wu, Lorraine N. Apuzzo, Jillian Haight, Annick You-Ten, Bryan E. Snow, Andrew Wakeham, David J. Goldhamer, Daniel Schramek, Alex N. Bullock, Peter ten Dijke, Cynthia Hawkins, Tak W. Mak

Bibliographic record

VenueCancer Cell · 2020
Typearticle
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalUniversity of TorontoUniversity Health NetworkSickKids FoundationHospital for Sick ChildrenPrincess Margaret Cancer Centre
FundersEshelman Institute for Innovation, University of North Carolina at Chapel HillJanssen PharmaceuticalsNational Institute of Arthritis and Musculoskeletal and Skin DiseasesFonds de Recherche du Québec - SantéBayerNederlandse Federatie van Universitair Medische CentraFundação de Amparo à Pesquisa do Estado de São PauloBrain Tumour CharityAbbVieNovartis PharmaCanada Foundation for InnovationCure Starts Now FoundationOntario Ministry of Economic Development and InnovationWellcome TrustMerck KGaAZonMwKoninklijke Nederlandse Akademie van WetenschappenBoehringer IngelheimTakeda Pharmaceuticals U.S.A.PfizerCanadian Institutes of Health ResearchInnovative Medicines InitiativeCancer Genomics CentreHeart FoundationCancer Research SocietyGenome CanadaAlex's Lemonade Stand Foundation for Childhood Cancer
KeywordsCarcinogenesisGliomaMutantBiologyCancer researchMedicineNeuroscienceGeneticsCancerGene

Abstract

fetched live from OpenAlex

upregulates transcription factors which control differentiation and DIPG cell fitness. Furthermore, we characterize E6201 as a dual inhibitor of ACVR1 and MEK1/2, and demonstrate its efficacy toward tumor cells in vivo. Collectively, our results describe an oncogenic mechanism of action for ACVR1 mutations, and suggest therapeutic strategies for DIPGs.

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)0.000
metaresearch head score (Gemma)0.000
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: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.016
GPT teacher head0.257
Teacher spread0.241 · 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

Citations97
Published2020
Admission routes2
Has abstractyes

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