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Record W2884522547 · doi:10.1080/14737175.2018.1503536

Clinical and pre-clinical utility of genomics in medulloblastoma

2018· review· en· W2884522547 on OpenAlexafffund
Carolina Nör, Vijay Ramaswamy

Bibliographic record

VenueExpert Review of Neurotherapeutics · 2018
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHedgehog Signaling Pathway Studies
Canadian institutionsSickKids FoundationHospital for Sick Children
FundersCanadian Institutes of Health ResearchGarron Family Cancer CentreBrain Tumour Foundation of CanadaAmerican Brain Tumor Association
KeywordsMedulloblastomaSonic hedgehogDiseaseWnt signaling pathwayGenomicsMedicineRisk stratificationOncologyBioinformaticsInternal medicineBiologyCancer researchGeneticsGenomeGene

Abstract

fetched live from OpenAlex

INTRODUCTION: Integrated genomics has significantly advanced our understanding of medulloblastoma heterogeneity. It is now clear that it actually comprises at least four distinct molecular subgroups termed Wnt/Wingless (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4 with stark clinical and biological differences. Areas covered: This paper reviews advances in the classification and risk stratification of medulloblastoma, specifically integrating subgroup with clinical and cytogenetic risk factors, with a summary of the potential to lead to more precise therapies. Moreover, the current state of preclinical modeling is summarized with respect to their utility in generating new treatments and correlation with genomic discoveries. Opportunities and challenges in developing new treatment paradigms are summarized and discussed, specifically new therapies for very high-risk metastatic/MYC-amplified Group 3 and TP53-mutant SHH and reductions in therapy for lower risk groups. Expert commentary: Survival across medulloblastoma has been stagnant for over 30 years, and new treatment paradigms are urgently required. Current therapy significantly over treats a high proportion of patients leaving them with lifelong side effects; while many patients still succumb to their disease. Applying biological advances could improve quality of life for a significant proportion of patients while offering new upfront approaches to the highest risk patients.

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)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.969
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.000
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 head0.126
GPT teacher head0.469
Teacher spread0.342 · 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.

Study designNot applicable
Domainnot available
GenreReview

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

Citations18
Published2018
Admission routes2
Has abstractyes

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