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Record W3202968128 · doi:10.1126/scitranslmed.abc0497

Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas

2021· article· en· W3202968128 on OpenAlexaff
Pooja Panwalkar, Benita Tamrazi, Derek Dang, Chan Chung, Stefan R. Sweha, Siva Kumar Natarajan, Matthew Pun, Jill Bayliss, Martin P. Ogrodzinski, Drew Pratt, Brendan Mullan, Debra Hawes, Fusheng Yang, Chao Lü, Benjamin R. Sabari, Abhinav Achreja, Jin Heon, Olamide Animasahun, Marcin Cieślik, Christopher Dunham, Stephen Yip, Juliette Hukin, Joanna J. Phillips, Miriam Bornhorst, Andrea M. Griesinger, Andrew M. Donson, Nicholas K. Foreman, Hugh Garton, Jason Heth, Karin M. Muraszko, Javad Nazarian, Carl Koschmann, Li Jiang, Mariella G. Filbin, Deepak Nagrath, Marcel Kool, Andrey Korshunov, Stefan M. Pfister, Richard J. Gilbertson, C. David Allis, Arul M. Chinnaiyan, Sophia Y. Lunt, Stefan Blüml, Alexander R. Judkins, Sriram Venneti

Bibliographic record

VenueScience Translational Medicine · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsChildren's & Women's Health Centre of British ColumbiaBC Children's HospitalUniversity of British Columbia
FundersNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesNational Cancer InstituteEMD SeronoNational Institutes of HealthUniversity of California, San FranciscoRobert Connor Dawes FoundationCancer Research UKIncyteCERNRudi Schulte Research InstituteChildren's Hospital Los AngelesIan's Friends FoundationAmgenA. Alfred Taubman Medical Research InstituteAstraZenecaPfizerHyundai Hope On WheelsDamon Runyon Cancer Research Foundation
KeywordsEpigeneticsMetabolic pathwayEpendymomaBiologyCancer researchEpigenesisPosterior fossaMedicineBioinformaticsNeuroscienceComputational biologyGeneticsDNA methylationPathologyGeneAnatomyGene expression

Abstract

fetched live from OpenAlex

, a key component of the metabolic regulator AMP-activated protein kinase (AMPK), also showed H3K27ac enrichment in PFAs and EZHIP-WT NSCs. The AMPK activator metformin lowered EZHIP protein concentrations, increased H3K27me3, suppressed TCA cycle metabolism, and showed therapeutic efficacy in vitro and in vivo in patient-derived PFA xenografts in mice. Our data indicate that PFAs and EZHIP-WT–expressing NSCs are characterized by enhanced glycolysis and TCA cycle metabolism. Repurposing the antidiabetic drug metformin lowered pathogenic EZHIP, increased H3K27me3, and suppressed tumor growth, suggesting that targeting integrated metabolic/epigenetic pathways is a potential therapeutic strategy for treating childhood ependymomas.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.456
Threshold uncertainty score0.420

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.014
GPT teacher head0.265
Teacher spread0.250 · 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 teacher head, 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

Citations59
Published2021
Admission routes1
Has abstractyes

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