LG-73CHARACTERIZATION OF GANGLIOGLIOMA AS A NEURODEVELOPMENTAL DISORDER
Bibliographic record
Abstract
INTRODUCTION: Gangliogliomas (GG) are low-grade, well differentiated neuroepithelial tumours of the central nervous system (CNS) comprised of neoplastic glial and neuronal cells. From microarray data, gangliogliomas overexpress the homeobox gene DLX2 required for differentiation and migration of inhibitory interneurons in the embryonic forebrain. We are interested in the role DLX2 plays in specifying neural progenitor fate. We hypothesize that in CNS progenitors, DLX2 regulates neural versus glial cell fate decisions. METHODS: DLX2 expression was examined in a cohort of ganglioglioma FFPE sections using immunohistochemistry and dual immunofluorescence labelling. Co-localization of DLX2 with glial fibrillary acidic protein (GFAP; glial marker) and synaptophysin (neural marker) was carried out. BRAF V600E mutation status was also assessed. RESULTS: In our discovery cohort of 30 patient samples (Instituto Giannina Gaslini), 10 samples expressed DLX2. In our validation cohort of 42 patients (University of Alberta), 6 of 12 tumours examined so far have the V600E mutation. One heavily pretreated patient with progressive cervicomedullary disease has had a very good partial response to BRAF inhibitor therapy. 16 of 26 samples studied to date expressed nuclear DLX2. All 16 DLX2(+) tumours co-expressed GFAP and synaptophysin. CONCLUSIONS: Our results support that GG arise from bipotential CNS progenitors arrested at the neuronal-glial cell fate “decision” point. As an alternative to offering adjunct therapy using chemotherapy and/or radiation for recurrent/progressive disease, biological or differentiation-based treatments could be considered +/- BRAF inhibitors for those GG with or without the V600E mutation, respectively. Correlation of BRAF mutational status and DLX2 expression is in progress.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".