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PF490 PRESENCE OF BRAFV600E MUTATION IN CHILDHOOD LCH CORRELATES WITH MULTISYSTEM DISEASE AND A POOR SURVIVAL

2019· article· en· W4390458072 on OpenAlexaff
Prateek Bhatia, Minu Singh, Radhika Srinivasan, Nandita Kakkar, Anne Tréhan, Dipika Bansal

Bibliographic record

VenueHemaSphere · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsPediatric Oncology Group
Fundersnot available
KeywordsMedicineSanger sequencingMutationInternal medicineRetrospective cohort studyDiseasePediatricsGastroenterologyGeneticsBiologyGene

Abstract

fetched live from OpenAlex

Background: Reports in LCH have observed BRAFV600E mutation in 35–40% cases of LCH and have demonstrated its relation with poor outcome. Aims: The aim of the study was to detect the presence of BRAFV600E mutation in children with LCH and to correlate with survival. Methods: Retrospective, Single centre, Case‐control study. Biopsy or FNAC diagnosed and immunochemistry confirmed (CD1a and S‐100 +ve) cases of LCH over 5‐years were retrieved. RQ‐PCR as well as Sanger sequencing for BRAFV600E mutation was performed. Ten cases of non‐LCH histiocytic proliferations were run as controls. Results: Thirty‐five LCH cases enrolled. 4 cases were excluded due to poor quality of DNA and 2 due to lack of follow up. The mean age was 2.5 years (0.4–11 yrs). Unisystem involvement was noted in 13/28 (46.5%) cases and multisystem in 15/28 (53.5%), including 13 with risk organ involvement. Of the 28 samples run on RQ‐PCR, BRAFV600E mutation was identified in 6/28 (21%) cases. The copy number threshold (Ct) values of positive cases ranged from 25.8–34.1 with a mean of 30.2. Sanger sequencing in all 28 samples confirmed positivity in 5/6 cases. One case did not yield reportable reads. There were no false negatives noted. Ten events (36%) were recorded, including 4 (14%) disease relapse, 3 (11%) deaths and 3 (11%) with progressive disease. All patients positive for mutation had multisystem involvement (100%) (p 0.0348), an EFS at 3‐years of 17% vs. 72% in negative group (p 0.0110) and an OS of 32.5% vs. 82% (p 0.0330). The lower BRAFV600E positivity than west could be likely due to archival samples and degraded DNA. Summary/Conclusion: The frequency for BRAFV600E positivity was low (21%), however, all positive cases had multisystem involvement and a poor 3‐year survival, confirming BRAFV600E to be a poor prognostic marker. image

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)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.004
GPT teacher head0.211
Teacher spread0.207 · 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 designObservational
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".

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Citations0
Published2019
Admission routes1
Has abstractyes

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