frontiers / frontier
Current answer
No synthesized decision answer has been authored yet. The current reading is assembled from the frontier’s strongest accepted findings, shown below.
Frontier operating path
A frontier is the bounded record object. The record holds accepted state, the engine routes reviewed work back into it, the body renders derived maps, and proof fixes the release boundary.
record
Finding bundles, source records, evidence atoms, typed links, review events, and trails are the canonical frontier record.
open state →
engine
Sources, gaps, attempts, checks, benchmark runs, and reviewable changes return through Workbench and Review before state changes.
inspect review →
body
Graphs, briefs, atlases, and constellations materialize accepted records into navigable bodies. They guide work; they do not become the record.
open graph →
proof
Proof packets, citation packages, source manifests, and release pins make the current state portable and replayable.
open proof →
next action
Open reviewable changes are waiting for checks and reviewer authority before they can change accepted state.
inspect review →
Signals show what can change this record next: review queues, campaign work, benchmark gaps, proof boundaries, contested findings, and event history.
review signal
review waitingOpen reviewable changes need checks and reviewer authority before the record changes.
inspect review →
gap signal
no evaluationsNo evaluation records are attached to this frontier. A benchmark, validation, replication, or peer-review record would make the review boundary stronger.
inspect benchmarks →
health signal
event historyThe frontier has a replayable event trail. Inspect it to see which agents, reviewers, or capabilities changed the record and why.
inspect trails →
A frontier is the record. Work enters as gaps, attempts, reviewable changes, checks, and reviews before accepted events update proof, atlases, and constellations.
gapframing
A missing experiment, unresolved contradiction, extraction defect, or stale proof cell worth reviewing.
reviewable changework
A reviewable frontier-state change with affected findings, evidence, rationale, checks, and expected proof impact.
attemptwork
An agent, capability, procedure, system, or human run with input material, declared output material, environment, disclosures, failure state, and cited artifacts.
checkgate
A schema, provenance, contradiction, benchmark, proof, or evaluation result over a reviewable change or release.
reviewgate
A human or authorized reviewer decision over a reviewable change, check, candidate gap, or contested finding.
eventaccepted
A signed, reviewable state transition that changes the Vela-backed frontier record.
releaseaccepted
A citation-ready bundle of source state, proof artifacts, mirrors, and known caveats.
Finding types
115 findingsReview state
115 findingsTop findings
all stateH3K27M mutations (lysine-to-methionine substitutions at position 27 of histone H3.3 or H3.1) are present in 80-90% of diffuse midline gliomas and diffuse intrinsic pontine gliomas, occurring as early somatic events during pons development
0.95vf_b0ee9364cb5635e1FDA grants accelerated approval to dordaviprone (August 6, 2025) for pediatric (age ≥1 year) and adult patients with progressive H3K27M-mutant DMG post-prior therapy, based on 20% objective response rate and durable disease control; first-ever systemic therapy approval for this indication.
0.95vf_82179ae647552ad2Diffuse hemispheric glioma with H3 G34 mutation (H3G34R/V) represents a molecularly distinct entity from H3 K27M diffuse midline glioma, characterized by supratentorial hemispheric location, preferential occurrence in adolescents/young adults, and fundamentally different epigenetic landscape centered on H3K36 methylation dysregulation rather than H3K27me3 reduction.
0.95vf_0b5f0d0ee73eb867H3K27M mutations drive global H3K27 hypomethylation and euchromatin remodeling, creating a pediatric-specific epigenetic landscape absent in typical adult GBMs.
0.95vf_945677df9a84a8b7Patients with H3K27M-mutant DMG demonstrate median overall survival of 10.1-14.4 months from diagnosis, with 5-year survival <2%, compared to 54-60 Gy focal radiotherapy as the only standard-of-care intervention showing modest survival benefit
0.93vf_730821613735146bBIOMEDE trial (N=233, diffuse intrinsic pontine glioma): None of three targeted-therapy arms (erlotinib, dasatinib, everolimus) + radiation exceeded radiotherapy alone on primary OS endpoint, revealing fundamental inadequacy of single-pathway inhibition in pediatric HGG.
0.93vf_26edfbefc6b5cbb8Pediatric high-grade gliomas are biologically distinct from adult counterparts; histone H3 mutations (H3K27M, H3G34R/V) are present in approximately 80 percent of midline pediatric HGGs and are nearly absent in adult GBM, defining separate WHO 2021 entities.
0.92vf_8d289f0d2f89f8baH3K27M acts as a dominant-negative inhibitor of PRC2, impeding genome-wide H3K27me3 and H3K27me2 spread while paradoxically retaining methylation at CpG island regions, creating a globally silenced epigenome with selective promoter derepression
0.92vf_e38529682f65a609ONC201 (dordaviprone) demonstrates a 20% objective response rate and 40% disease control rate in pooled analyses of recurrent H3K27M-mutant diffuse midline glioma across five clinical trials (n=50), with median response duration of 11.2 months.
0.92vf_bfa0b46128b73855ACVR1 R206H mutations occur in ~25% of DIPG cases and constitutively activate BMP signaling through the ALK2 kinase domain, independent of ligand binding.
0.92vf_e664284b89862208Infant-type hemispheric gliomas harbor RTK fusions (ALK 47%, NTRK 22.5%, ROS1 20.4%) in 86.5% of cases, versus rare fusions in adult GBM.
0.92vf_67cef1807019cd59Adult Stupp protocol (concurrent TMZ + radiotherapy) produced no survival benefit in pediatric GBM/HGG (ACNS0126 trial), unlike its 14.6-month OS benefit in adults.
0.92vf_78a0cedf2d1cceb5Showing 12 of 115. Clone the full state with vela registry pull vfr_10815170943966df.