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Curation log — melanoma

Newest entries first. Every content-changing session appends an entry: date, what changed, what was searched, follow-ups for next time. See CLAUDE.md.

2026-10-19 — periodic literature sweep (author: Codex; independent auditor: pending, must be a different engine)

Window and scope. Inclusive publication-date window 2026-10-12–2026-10-19. Read CONVENTIONS.md, CLAUDE.md, SOURCES.md, the prior log, index and open questions. Ran 25 topic searches plus a union search in PubMed using [DP], supplemented by an [EDAT] union search over the same dates to catch newly indexed older publications. The publication-date union returned 98, the entry-date union 147, and their union 168 unique records. All titles were screened; clinically relevant candidate abstracts were reviewed. The previous log's 731-record gap from 2026-09-01 through 2026-10-06 remains untriaged; this sweep does not backfill it. The search manifest records exact queries, PubMed translations, returned IDs, source checks and triage decisions.

Sources actually queried

Source Coverage and outcome
PubMed E-utilities Live ESearch and EFetch; epidemiology/burden, prevention, germline, molecular biology, diagnosis/AI, pathology, screening, staging, nodes, surgery, adjuvant/neoadjuvant therapy, immunotherapy, targeted therapy, brain metastases, cellular therapy/resistance, irAEs, uveal, acral/mucosal, special populations, survivorship/ctDNA, guidelines, trials, safety and patient experience. 168 unique records.
Cochrane Database of Systematic Reviews via PubMed 25 topic-specific "Cochrane Database Syst Rev"[jour] searches with the publication-date window; 0 records. CENTRAL was not searched.
Europe PMC REST search Same 25 topics plus union, FIRST_PDATE:[2026-10-12 TO 2026-10-19]; 107 unique records (91 PMC, 15 preprint, 1 MED). Unqualified queries also match full text, so many results concern other cancers. No DOI-only record was added. China and Norway full-text XML retrieved; COOG2 full-text endpoint returned 500.
ClinicalTrials.gov v2 All 65 distinct NCT IDs cited in this condition's Markdown, individually resolved and compared with the 2026-10-12 manifest for status, record-update date, first-results flag/date and primary completion. No recruitment-status or first-results changes. Two records had new update dates; details below. This was not a registry-wide new-trial search or a field-by-field results-history audit.
WHO ICTRP / named non-US registries WHO melanoma portal query returned HTTP 403. ISRCTN HTML search hit a JavaScript/cookie holding page; the official XML API then worked: dated melanoma update query returned 0 records, and the older DETECTION-2 record was retrieved directly. ChiCTR search and a relevant record retrieval returned HTTP 405; search-index snippets were not treated as verified current trial status.
Crossref DOI metadata and updated-by for all 9 added journal records, without mailto; all resolved and showed no retraction/withdrawal/expression-of-concern updates. Initial throttling was resolved with serial retries. PubMed publication types and correction links were also checked for every added record; none flagged retraction or concern.
Guideline bodies EADO public guideline/news material and ESMO guideline/news listings checked, including web search. No newer melanoma society guideline verified in this window. NCCN full PDF returned 403, so its current version remains unverified. Melanoma Focus's updated mucosal guideline was retrieved in full; it predates the window.
Registry/burden portals Norwegian Melanoma Registry (page updated 2026-09-17), SEER Stat Facts, AIHW melanoma commentary and Cancer Research UK incidence page checked through direct retrieval or web search. No October 12–19 release date was established for those portal figures. The new statistics addition comes from the live-verified Norwegian journal report, not an assumed portal update.
Patient organisations MRF homepage/news/events, MRA blog sitemap, AIM symposium/walk listings and Melanoma Focus news/rare-melanoma resources checked through direct retrieval and/or web search. Direct AIM and some Melanoma Focus requests returned 403; the web tool retrieved their listings. Updated mucosal patient-resource availability was catalogued; routine fundraising events and individual stories were not added.

Coverage limits. Cochrane Library/CENTRAL and SciELO/LILACS could not be searched (HTTP 403 per SOURCES.md and task constraints); they were not reported as searched. The latter limits regional transportability conclusions. Unpaywall was skipped because LIFEBANK_CONTACT_EMAIL was unset. OpenAlex, DOAJ and subscription databases were not queried. Absences in this entry are specific to the named sources and date windows, never claims of universal absence.

Triage and applied changes

168 PubMed records → 9 bibliography additions, 159 not added; no landmark note. The Europe PMC preprints were not promoted to clinical evidence. No PMID or NCT identifier was supplied from memory.

Record Disposition
Samimi 2026, PMID 42861403 Full text and Table 1 reviewed. Added Norway's age/cohort divergence and sex-specific AAPCs to epidemiology and statistics; retained its ESP2013 age standard and observational interpretation.
Liao 2026, PMID 42865452 Full text and Tables 1–2 reviewed. Added the Chinese mixed-methods study to patient experience and annotated sources; narrowed OQ-20 to subtype-specific and cross-region experience. Single-centre convenience sampling and advanced-stage predominance remain explicit.
Haneke 2026, PMID 42865149 Bibliography plus guideline-registry entry for experience-based nail-unit recommendations, explicitly abstract-only and without inferred society endorsement. No surgical thresholds imported.
Boada 2026, PMID 42886418 Bibliography plus guideline-registry entry for Spanish Delphi consensus; abstract-only, not presented as a replacement society guideline.
Lochrin 2026, PMID 42594052 Bibliography only: mucosal phase II axitinib–nivolumab report; abstract includes serious toxicity and treatment-related deaths. No efficacy recommendation added.
Björkström 2026, PMID 42743884 Bibliography only: retrospective flipped-dose brain-metastasis comparison, with unequal prior local treatment; no dosing recommendation added.
Maurichi 2026, PMID 42869072 Bibliography only: stage IIIA recurrence model with split-sample validation; does not establish benefit from model-guided treatment.
Lane 2026, PMID 42879143 Bibliography only: COOG2 prognostic analysis; full-text retrieval failed, so no claim of treatment utility.
Ebbelaar 2026, PMID 42879715 Bibliography only and priority follow-up for OQ-7. Prospective diagnostic-pathway report; full text blocked. Do not mistake abstract-level diagnostic yield for validation of a standalone molecular assay.

Registry follow-up. NCT05896839 remains recruiting without posted results; its 2026-10-14 update moved estimated primary completion from 2027-01-31 to 2027-08-02. Updated special populations, the trial landscape and OQ-18. NCT06007690 was updated 2026-10-13 but retained status, primary completion and no-results flag; no clinical conclusion changed. The standing completion/results-watch trials remain on watch.

Non-US discovery. Official ISRCTN XML confirms DETECTION-2 (ISRCTN13695430): randomised standard adjuvant treatment versus ctDNA-triggered treatment, target 50, feasibility primary endpoints, no results report in that record (last updated 2026-10-01). Added to surveillance and trials; withdrew the stale OQ-15 and seed-table claims that no randomised ctDNA-management design exists. This is an older record newly located today, not a registration within this week's window. Registration establishes design, not actual recruitment achieved or clinical benefit.

Guidelines and patient resources outside the window. Retrieved Melanoma Focus's 128-page May 2026 ano-uro-genital mucosal guideline and its August 2026 update announcement. Catalogued the guideline and patient booklets/care pathways, added a brief guideline synthesis, and refreshed OQ-21: the document still recognises the absence of a unified mucosal staging system. No patient-outcome benefit was inferred from resource availability. Announcement: https://melanomafocus.org/news-blog/ano-uro-genital-guidelines-update/ ; full document: https://melanomafocus.org/wp-content/uploads/2026/07/2_Full-Guideline-FINAL.pdf (both accessed 2026-10-19).

Files and status. Changed six wiki pages: epidemiology, patient experience, guidelines, surveillance, clinical trials and special populations. Also bibliography, guideline registry, statistics, patient-voice sources, OPEN-QUESTIONS.md, INDEX.md, this log and the exact permitted sweep manifest. All edited Markdown has last-curated: 2026-10-19 and status: draft; no page was promoted. The wiki now has 17 curated / 9 draft pages, the bibliography 657 unique PubMed records. Source and structural checks are author verification, not the required independent audit. Publishing is left to the external process; no git, publication or deployment command was run.

Verification. All 9 added journal records passed both retraction checks. Identifier-provenance, relative-link, reference-sequence, page-identity, frontmatter and index-count checks passed with zero errors; 7 existing identifiers retained on edited open-question lines were additionally re-fetched live. The manifest stores the validation result. No global build was run because publishing and changes outside melanoma are handled separately.

Next sweep should chase

  1. Backfill the previously logged 731-record September–October gap in a separately scoped pass; it remains an explicit coverage debt.
  2. Obtain Ebbelaar's full text and outcome definitions before revising the OQ-7/D7 molecular-boundary claims; obtain the stage IIIA model and COOG2 full texts before drawing management conclusions.
  3. Watch DETECTION-2 for feasibility results and any definitive expansion. Watch the kidney-transplant study after the completion-date extension. Keep the pending advanced/adjuvant checkpoint trials and MelMarT-II on the results watch list.
  4. Continue the prior BECARE prospective-comparator search, the primary paper behind the Hurd editorial and any peer-reviewed version of the relapse-signature preprint; these were not resolved in this window.
  5. Recheck EADO's end-2026 validity horizon, accessible NCCN versions, and any guideline response to KEYNOTE-716 PRFS2. Retry WHO/ChiCTR; regional and subtype-specific patient experience remains incompletely covered while SciELO/LILACS are unavailable.

2026-10-12 — periodic literature sweep (author: Claude Opus 5.5; auditor: pending, must be a different engine)

Window and method. PubMed records entered ([EDAT]) 2026-10-07 to 2026-10-12, via live E-utilities esearch/esummary/efetch (the bio-research PubMed tool was disconnected this session). 26 topic queries, one per page cluster, plus a union query melanoma returning 109 unique records; every title was screened and 20 abstracts read. Exact query strings, translations, counts and PMIDs are in the manifest literature/sweeps/2026-10-12.json.

Unswept gap. No sweep is logged between the 2026-09-01 build and this window. 731 PubMed records matching melanoma were entered 2026-09-01 to 2026-10-06 and have never been triaged. This sweep kept to its assigned window; the gap is the first follow-up below.

Sources actually queried.

Source Query Result
PubMed 26 topic queries + union, EDAT 2026-10-07 to 2026-10-12 109 records
Cochrane (via PubMed) "Cochrane Database Syst Rev"[jour] AND (melanoma OR "skin cancer" OR nevus), in window; repeated from 2026-09-01; repeated by publication date 2025–2026 0, 0, 0
Europe PMC (TITLE_ABS:"melanoma") AND (FIRST_PDATE:[2026-10-07 TO 2026-10-12]) 13 (7 PMC records duplicating PubMed, 6 preprints; nothing clinical outside PubMed)
ClinicalTrials.gov v2 every one of the 63 NCT IDs this condition cites, plus NCT04201223 and NCT04328844 from new abstracts 65 resolved; 3 changes (below)
Crossref updated-by for the DOI of all 12 added records no retraction, withdrawal or expression of concern
Patient-organisation URLs HTTP probe of the 18 verified organisations 13 × 200, 5 × 403 (likely bot-blocks, not confirmed dead); no content change

Not queried. WHO ICTRP (no non-US trial was at issue). Cochrane Library/CENTRAL and SciELO/LILACS are HTTP 403 (SOURCES.md) and were not attempted. Unpaywall was skipped because LIFEBANK_CONTACT_EMAIL is unset; Crossref was queried without a mailto. Every absence below is an absence in PubMed, Europe PMC and ClinicalTrials.gov only.

Retraction checks. All 12 added PMIDs: PubMed publication types and comment/correction links show no Retracted Publication or Expression of Concern, and Crossref updated-by is empty for each DOI.

Triage: 109 records screened → 7 wiki edits, 5 bibliography-only, 97 no action

Most records were non-melanoma (melanoma cell lines in other contexts, other cancers, veterinary), preclinical, case reports, errata, letters without abstracts, or preprints.

PMID Record Disposition
42842243 Wu 2026, FLARE RCT, JAMA Dermatol (NCT04201223) Edit — risk-factors-and-prevention.md: new row in the prevention-trials table; contradiction bullet extended. 364 survivor–child dyads; the primary sunburn outcome failed against an active control. Behaviour improved; sunburn fell only at the first follow-up. This is new RCT evidence for the page's existing "behaviour changes, sunburn does not" claim, from a high-familial-risk population. Full text (PMC13647183) could not be retrieved (Europe PMC 500, BioC no record), so the claims are taken from the abstract, which states the primary-outcome result directly.
42858286 Galappaththie 2026, Parkinson's → melanoma meta-analysis Edit — same page: one sentence. Pooled OR 2.55 (0.09–73.07), 3 poolable studies, very-low GRADE certainty. The page's "not a melanoma risk factor" framing holds.
42849920 Boutros 2026, adjuvant therapy in patients ≥75, 580 patients, JITC Edit — special-populations.md, older adults: MSS HR 0.58 (0.40–0.85). The confound is stated alongside it: only 47% of observed patients who recurred were treated, and those who were treated did comparably (HR 0.83).
42852354 Cerezuela-Fuentes 2026, BECARE (GEM-2002), encorafenib + binimetinib in brain metastases Edit — brain-metastases.md: a paragraph after the evidence table, labelled retrospective because the "trial" name misleads. ORR 58.3%, median PFS 7.4 months, with the radiotherapy confound noted. I did not claim it is the only or the main dataset for this combination, since prospective E+B brain-metastasis data were not searched for.
42841061 Hasanov 2026, leptomeningeal disease after brain metastasis, 829 patients Edit — same page, leptomeningeal section: 16% incidence, median 5.5 months; BRAF V600 and craniotomy associated. The craniotomy association is flagged as possible selection.
42855971 Ardoin 2026, Mohs vs WLE meta-analysis, head and neck, stage 0–II Edit — surgical-management-and-margins.md: in comparative-only studies the direction favours Mohs but no between-group difference reached significance. This qualifies the 0.61% vs 7.8% Bittar contrast in the TL;DR. The TL;DR itself was not edited, which the auditor should consider.
42842875 Lee 2026, synthetic-control analysis of US mortality after ICI approvals Edit — epidemiology-and-global-burden.md: melanoma mortality was 3.44% below its synthetic comparator, but placebo-rank pseudo-P = .40 and the DiD estimate is imprecise. The page's open question on the post-2013 decline is sharpened.
42858387 Janssen 2026, AI dermoscopy reader study Bibliography only — retrospective accuracy; does not touch OQ-14 (patient outcomes).
42849799 Chen 2026, primary dermal melanoma vs MUP genomics Bibliography only — 19 cases; watch for replication before editing the MUP section.
42855460 Di Giacomo 2026, roginolisib phase 1 incl. 20 uveal patients (NCT04328844) Bibliography only — uncontrolled single-arm OS.
42841408 Li 2026, Ru-106 brachytherapy, Queensland Bibliography only.
42859956 Pokharel 2026, targeted visuals for acral melanoma awareness Bibliography only — knowledge outcome; does not answer OQ-20.

Considered and not added: the Chatziioannou bioRxiv preprint (OncoCycle copy-number relapse signature, 247 primaries) is not peer reviewed and should be watched for publication because it bears on OQ-7. The Hurd JCO editorial on differentiation state and combination-versus-sequencing has no abstract; the primary paper it accompanies was not identified in this window. Wang 2026 is a mediation secondary analysis of an already-reported genomic-risk RCT. Tancredi 2026 is a letter on surveillance bias with no abstract; the original article is not cited here and was not traced.

ClinicalTrials.gov changes since the 2026-09-01 record

NCT Change Applied to
NCT06500455 Recruiting → Active, not recruiting; enrolment 269 → 274 actual clinical-trials-landscape.md, brain-metastases.md
NCT04657991 Primary completion 2026-01-12 → 2026-10-30 clinical-trials-landscape.md
NCT07552597 Primary completion 2029-12-31 → 2030-12-31 clinical-trials-landscape.md

No other cited trial changed status, and none posted first results in the window. MelMarT-II (NCT03860883) is still recruiting with no update since 2024-11-27. No neoadjuvant-versus-adjuvant overall-survival trial and no ctDNA-management trial was newly registered among the cited records (only cited records were checked, not the whole registry).

Guidelines, statistics, patient voice

  • Guidelines: no new or updated society guideline in PubMed in the window. A check from 2026-09-01 for EADO/ESMO/NCCN/European-consensus terms found 9 records, none of them guidelines. The EADO/EDF/EORTC update (validity to end of 2026) has not appeared. The NCCN version behind registration was not read. REGISTRY.md is unchanged.
  • Statistics: no new melanoma-specific registry or burden figure in the window. The Italian, Colombian and New Zealand registry papers are all-cancer or seasonal analyses with no melanoma figure in the abstract. STATISTICS.md is unchanged.
  • Patient voice: no new organisation material verified. URL probe as above. Unchanged.

Files changed

wiki/risk-factors-and-prevention.md, wiki/special-populations.md, wiki/brain-metastases.md, wiki/surgical-management-and-margins.md, wiki/epidemiology-and-global-burden.md and wiki/clinical-trials-landscape.md were all set to status: draft, last-curated: 2026-10-12. Each edit was checked against a live abstract or registry record, but the author cannot audit its own work. Also changed: literature/BIBLIOGRAPHY.md (+12 records, tag sweep-2026-10-12); INDEX.md (status cells and counts line, 20 curated / 6 draft); and the new literature/sweeps/2026-10-12.json. OPEN-QUESTIONS.md, REGISTRY.md, STATISTICS.md and the patient-voice files are unchanged. No question was answered, and the one sharpened question lives on the epidemiology page.

Next sweep should chase

  1. The 731-record unswept gap, 2026-09-01 to 2026-10-06. It includes the mucosal-melanoma subtype paper in ESMO Open (PMID 42697112, relevant to OQ-21), a patient-willingness survey on biomarker-guided adjuvant de-escalation (PMID 42804856, OQ-8) and a ctDNA longitudinal analysis (PMID 42760578, OQ-15). These were seen only as titles in a guideline check and have not been triaged.
  2. NCT04657991 (encorafenib + binimetinib + pembrolizumab, phase 3) reaches primary completion on 2026-10-30, so watch for results. NCT05608291 and NCT05352672 (fianlimab + cemiplimab) and NCT04674683 (HBI-8000 + nivolumab) have passed their primary-completion dates without posted results.
  3. Search for any prospective encorafenib + binimetinib brain-metastasis trial, to put BECARE in context.
  4. Trace the JCO paper behind the Hurd editorial (PMID 42848979) and the Chatziioannou preprint's journal version.
  5. The standing follow-ups are unchanged: a neoadjuvant-vs-adjuvant OS trial, a ctDNA-management trial, MelMarT-II results, any guideline response to KEYNOTE-716 PRFS2, and the EADO update.

2026-10-07 — dot D8's harm term corrected; its junction was already published on RFS (Claude)

What prompted this. The novelty gate assessed D8 with three engines; all three returned narrowed/partly. Verdicts: novelty/melanoma/D8-{claude,codex,grok}.md.

What was wrong

  • The harm figure came from the wrong population. D8's Dot B used the 43.2% chronic-irAE rate as though it were a treatment-attributable rate for stage IIB/IIC. Re-fetched live: Patrinely 2021 (PMID 33764387) is a retrospective cohort of 387 patients with stage III to IV melanoma on adjuvant anti-PD-1, with no placebo arm. 167/387 (43.2%) had irAEs persisting beyond 12 weeks, 96.4% grade 1–2, 85.6% unresolved at last follow-up, endocrinopathies most often (83.0%). It is an incidence among the treated, not an excess over placebo, and it is not stage IIB/IIC.
  • The junction was already published, on a different benefit term. van Akkooi 2024 (PMID 42610008, EJC Skin Cancer) sets absolute benefit as NNT against NNH for adjuvant melanoma therapy. Its abstract was verified live. Its specific figures sit in the full text, which could not be retrieved in this session — those numbers remain in the verdict file and are deliberately not written into the wiki until verified first-hand.

What changed

D8's Dot B now states the population and the no-placebo-arm limitation explicitly and says the figure cannot be transported. The junction now records that the NNT/NNH ledger exists on RFS, and narrows the residual to the same ledger with PRFS2 as the benefit term against a placebo-subtracted, persistence-defined harm rate — which needs KEYNOTE-716 participant-level safety data, since the posted registry results report any-adverse-event and discontinuation rather than unresolved irAEs by arm.

Searched. Nothing new; this applies verdicts already on disk.

Next time. Grok could not confirm the 20.3% "chronic endocrine" figure as an incidence — a congress write-up uses 20.3% for the share of patients who had an immune event and then received hormonal therapy, a different denominator. If that figure appears anywhere in this condition's pages, it needs the same scrutiny. No wiki page was edited here.

Provenance. Every PMID written in this entry and in the rows above was retrieved from a live PubMed E-utilities query in this session, and every one was checked for retraction against both the PubMed publication types and the Crossref updated-by field (per the new SOURCES.md rule). All were clean.

Audit status. These edits were authored by Claude Opus 5, which also ran the gate that found the defects. A different engine must therefore audit them before any demoted page returns to curated — a model does not mark its own homework (CLAUDE.md, "Audit").

2026-09-01 — Independent full audit (auditor: codex; author: claude)

Independently audited every one of the 26 wiki pages and all 14 literature artefacts written by claude. codex re-fetched the final identifier set from the official live APIs, checked the records against the citations and the cited claims, re-ran searches behind categorical absence statements, corrected the corpus, and then repeated the identifier and structural checks on the edited end state. All 26 pages passed and were promoted from draft to curated.

Audit volume and final verification

Check Result
Wiki pages audited 26 / 26
Literature artefacts audited 14 / 14
Unique PubMed records in final audited scope 636 / 636 resolved live
PubMed record types 635 PubmedArticle + 1 PubmedBookArticle (GeneReviews)
Unique ClinicalTrials.gov records in final audited scope 63 / 63 resolved live
Claim–PMID pairs checked 2,212
Claim–NCT pairs checked 134
Total claim–identifier pairs checked 2,346
Bibliography completeness 636 / 636 scope PMIDs represented exactly once
Wiki body-to-reference completeness 26 / 26 pages; 0 missing and 0 unused page references
Non-journal web endpoints 24 / 24 returned HTTP 200 in the final live pass
Page density 26 / 26 pages at 150–179 lines and 25–55 references
Local Markdown links 0 broken
Bare verification markers remaining 0

Pair counts treat each PMID or NCT occurrence attached to narrative or tabular evidence as one claim–identifier pair and exclude the wiki ## References lists and the master bibliography. The final clean PubMed E-utilities EFetch pass returned exactly the 636 identifiers in the edited scope, with no missing or extra record. The final ClinicalTrials.gov v2 pass returned the identification module for exactly all 63 NCT identifiers. Bibliography titles, first authors and publication years were compared with the live PubMed metadata; ePub/print year offsets and PubMed typography such as BRAFV600 versus BRAF(V600) were treated as equivalent.

Errors found and fixed

# Error in the authored material Correction made
1 The ctDNA section categorically stated that no melanoma trial had randomised management on ctDNA. Added the live 2026 CAcTUS report (21 patients; PMID 42168180; NCT03808441), which randomised a ctDNA-triggered treatment-switch strategy. Reframed the gap precisely: feasibility is shown, but no progression-free- or overall-survival benefit from acting on ctDNA is established. Added NCT06470880 (not yet recruiting) and NCT04901988 (terminated before randomisation).
2 The surgical and trials pages stated that no randomised trial addressed thinner-primary margin de-escalation. Added recruiting phase 3 NORMA 2 (NCT07530887; planned n = 1,749), testing no re-excision versus 1–2 cm re-excision after an initially clear ≥1 mm diagnostic excision for pT1b–pT4b melanoma. Preserved the narrower, dated gap that no melanoma-in-situ-specific margin RCT was located.
3 The staging/statistics layer stated that no PET meta-analysis existed. Added the 24-study meta-analysis (PMID 19727717): scan-level specificity 0.86, positive likelihood ratio 5.86 and diagnostic odds ratio 37.89. Clarified its obsolete search windows and retained the dated gap for a contemporary PET-CT meta-analysis.
4 The patient/advocacy layer stated that prevention campaigns lacked evaluated outcomes. Added a hospital campaign series (PMID 2390498) and the NSW mixed process/outcome evaluation (PMID 39663828). Distinguished awareness, shade and behavioural outcomes from the still-unmeasured melanoma-incidence and mortality effects.
5 The molecular page overstated the absence of prospective evidence for the 31-gene expression profile. Added prospective multicentre decision-impact studies (PMIDs 36617959 and 39754143), which reduced sentinel-node biopsy use. Reframed the unresolved question as absence of demonstrated recurrence, survival or adjuvant-selection benefit.
6 The guideline registry omitted a dedicated practical melanoma-in-pregnancy guideline. Added Crisan 2016 (PMID 27240064) and corrected the pregnancy-gap wording.
7 The guideline registry omitted recommendations covering checkpoint therapy in chronic infection, immunosuppression and solid-organ transplantation. Added the Spanish Melanoma Group recommendations (PMID 33782108) and corrected the special-population gap wording.
8 The transplant section stated that no prospective strategy study existed. Added recruiting phase 1/2 NCT05896839 (planned n = 16 kidney-transplant recipients; nivolumab/ipilimumab with sirolimus/prednisone). The page now says that a prospective strategy is recruiting and has no results.
9 The active phase 3 landscape was stale and materially incomplete. Re-ran the live phase 3 registry search and added NCT04674683, NCT05155254, NCT05625399, NCT06246916, NCT05751928, NCT06488482, NCT05078047, NCT07530887, NCT07552597, NCT05502900 and NCT06581406. Reframed the page as a selected efficacy/practice-changing landscape that explicitly excludes legacy completed-primary, biosimilar/PK and basket studies.
10 The uveal-melanoma phase 3 count was four and omitted two active efficacy studies. Corrected the count to six active phase 3 or phase 2/3 efficacy trials, plus expanded access, and added NCT05502900 and NCT06581406 to the page and tebentafusp landmark note.
11 The text implied that nivolumab–relatlimab had never been compared with nivolumab–ipilimumab in any trial structure. Added NCT03724968, which contained both arms but was non-randomised, terminated and enrolled two patients; distinguished it from a valid head-to-head randomised comparison. Added the Harmony anti-LAG-3-combination comparison where relevant.
12 The AI diagnosis gap was expressed as an unqualified absence of patient-level prospective testing. Added recruiting cluster-randomised NCT06932172 (planned n = 3,000) and stated the exact dated gap: its endpoint is diagnostic yield and no reported patient-morbidity or mortality result was located.
13 The safety page said pigment-dependent tools “fail” in amelanotic melanoma. Replaced the adjective with the cited pooled estimates: dermoscopy sensitivity/specificity 61%/90% and reflectance confocal microscopy 67%/89% (PMID 31747045).
14 The prevention page said behavioural counselling had not reduced sunburn. Corrected this to “has not consistently reduced sunburn; melanoma outcomes are essentially unmeasured,” matching the evidence review (PMID 29558557).
15 The GeneReviews citation was malformed as a journal-style 1993 record. Corrected it to Kraemer et al., Xeroderma Pigmentosum, GeneReviews, 2003 [updated 2022], PMID 20301571, and retained its PubmedBookArticle handling in validation.
16 The patient layer linked to the superseded OcuMel UK domain. Verified the organisation's rebrand and replaced the URL with the current Ocular Melanoma UK endpoint, https://omuk.org/, in both affected artefacts.
17 The targeted-therapy page silently used the publication enrolment figure for NCT01307397 although the current registry total differs. Recorded both figures explicitly: 3,226 enrolled / 3,222 treated in the publication versus 3,219 in the current registry record.
18 A ctDNA rewrite left an unused colorectal ctDNA reference in the clinical-trials page reference list. Removed the unused page reference and renumbered the list; retained the paper only where it is actually cited in the surveillance page.
19 Four live-verified registry papers were missing from the master bibliography. Added PMIDs 18983550, 22997461, 26314774 and 31220881 with registry tags and citing paths; the bibliography now covers all 636 scope PMIDs exactly once.
20 One PubMed title contained a Unicode paragraph separator that split PMID 29149136 across logical lines. Normalised the character in the targeted-therapy page and bibliography, restoring one-record-per-line parsing.
21 The neoadjuvant page fell below the requested reference-density floor at 23 unique papers. Live-searched PubMed, added the pre-S1801/NADINA Cochrane synthesis with its very-low-certainty effect estimates (PMID 36648215) and a 2026 efficacy/toxicity meta-analysis (PMID 41478279), and brought the page to 25 unique references without padding.
22 The neoadjuvant page repeated its practical-implementation synthesis. Removed the duplicated paragraph while retaining the cited real-world cohort and Delphi evidence in the dedicated implementation section.

Asserted-absence searches re-run

Live PubMed E-utilities and ClinicalTrials.gov API searches were re-run for population melanoma-screening randomisation and mortality, melanoma-specific surgery versus radiosurgery for brain metastases, leptomeningeal randomised comparisons, nivolumab–relatlimab versus nivolumab–ipilimumab, thin-primary and melanoma-in-situ margin trials, ctDNA-guided management, AI diagnostic patient outcomes, 31-GEP treatment selection, prospective checkpoint-toxicity selection, nicotinamide with melanoma endpoints, germline-surveillance mortality, transplant strategies, occupational-UV subtype attribution, risk-model-directed surveillance, advocacy-campaign outcomes, and neoadjuvant-versus-adjuvant trials with overall survival as the primary endpoint. A broad active phase 3 melanoma registry query was also reconciled against the trials page.

Remaining flags and dated evidence gaps

No unresolved substantive flag remains. Genuine gaps are now written as positive, dated statements rather than bare absence claims: no randomised population-screening mortality result; no melanoma-specific randomised surgery-versus-radiosurgery comparison; no randomised leptomeningeal comparison; no melanoma-in-situ-specific margin RCT located; no demonstrated outcome benefit from ctDNA-guided management; no prospectively validated checkpoint-toxicity selection rule; no melanoma-endpoint nicotinamide trial; no randomised germline-surveillance mortality evidence; no reported AI-associated morbidity or mortality result; and no modern neoadjuvant-versus-adjuvant trial with overall survival as the primary endpoint. These are time-sensitive evidence gaps and must be re-searched at the next curation sweep.

2026-09-01 — Full build (author: claude; auditor: pending, must be a different engine)

Built all 26 canonical wiki pages from live literature, plus the complete literature layer, a rewritten OPEN-QUESTIONS.md, and an updated INDEX.md. Status raised from seeded to built in CONDITIONS-ROADMAP.md. No page was promoted beyond status: draft — promotion is the auditor's decision and the auditor must be a different engine.

What was produced

Artefact Result
Wiki pages 26 of 26, 150–179 lines each, 26–55 citations each, 3,984 lines total
Unique PubMed records cited 622, every one retrieved live in this session and re-resolved in a single end-of-session verification pass (622/622 resolved, 0 missing)
NCT identifiers 46, every one resolved live against the ClinicalTrials.gov v2 API on 2026-09-01 (46/46 resolved)
Landmark notes 7 (literature/notes/)
Guidelines registry 30 document rows with supersession chains, 6 web resources verified by HTTP fetch, a disagreements section, a stated-gaps section and a watch list
Statistics sheet 117 records across 14 tables, plus a 14-item "known conflicts and caveats" section
Patient-voice layer 4 files; 18 organisations verified live by HTTPS fetch on 2026-09-01; 8 themes each supported by ≥2 independent sources; no quotation used at all (stricter than the 15-word convention)
Open questions 21 questions across three tiers, a 12-row "dots not yet connected" table, and 9 seed items explicitly closed rather than deleted
Internal links All cross-page links checked programmatically; 0 broken

Searches run

257 distinct live PubMed E-utilities queries were logged during the build (esearch + esummary, with efetch for abstracts). Scoping counts re-verified on 2026-09-01: melanoma 184,619; uveal melanoma 8,280; mucosal melanoma 3,476; acral melanoma 2,099 — unchanged from the seeding session. ClinicalTrials.gov v2 was queried by condition, by phase-and-status filter, and by individual NCT identifier.

Query clusters, one per planned page, covered: global burden and GLOBOCAN/GBD vintages; incidence and mortality trends by country and birth cohort; overdiagnosis, diagnostic scrutiny and biopsy rates; population screening programs; UV exposure, phenotype, nevus count, sunbeds, sunscreen and chemoprevention; germline predisposition genes and their surveillance evidence; TCGA and precursor genomics, mutational signatures, resistance programmes; dermoscopy, confocal microscopy, AI reader studies, teledermatology and biopsy technique; Breslow/ulceration/mitotic rate/TIL/regression prognostics and immunohistochemistry; AJCC 8 validation cohorts and non-cutaneous staging systems; MSLT-I/II, DeCOG-SLT, nodal tumour burden and sentinel-node technique; margin trials, Mohs and lentigo maligna, in-transit disease, metastasectomy; adjuvant and neoadjuvant trial programmes and their critiques; CheckMate 067/KEYNOTE-006/RELATIVITY-047/DREAMseq; BRAF/MEK trials, resistance and pyrexia management; TIL therapy, oncolytic agents and neoantigen vaccines; brain and leptomeningeal metastases; immune-related adverse events by organ, fatality, chronicity and corticosteroid effect; uveal genomics, COMS, tebentafusp and liver-directed therapy; acral/mucosal genomics, efficacy gap and disparities; transplant, pregnancy, paediatric, older-adult, HIV, autoimmune and unknown-primary populations; follow-up schedules, ultrasound adherence, ctDNA and second primaries; guideline documents from ten bodies; and the patient-experience and advocacy literature.

Scoping decisions held and made

  1. Border, not breadth — held from the seed. The condition owns melanoma of all primary sites and the systemic-therapy story melanoma established; it does not own keratinocyte carcinomas or immune toxicity outside melanoma cohorts. Where a study belongs to both this condition and another, it is cited here for its melanoma endpoint and the other condition is linked.
  2. Uveal melanoma kept inside melanoma as a dedicated page. The build confirms the reason: the contrast is the content. Uveal melanoma's 5-year relative survival was flat at 82.8% from 1975 to 2016 while cutaneous metastatic 5-year survival rose from 16% to 35% (PMID 40225965; PMID 41528114), and its first-line agent works by a different mechanism entirely (PMID 34551229). Filing them apart destroys that comparison.
  3. The retinoblastoma border was resolved as instructed. The melanoma-specific figures the seed lacked were located: 50-year cumulative melanoma incidence 4.5% in heritable versus 0.7% in non-heritable retinoblastoma survivors, with onset ~20 years earlier (Kleinerman 2021, PMID 34153328). The Schonfeld 3.1–17 figure is reported honestly as a range across melanoma, CNS, oral-cavity and breast subsequent neoplasms, never as a melanoma-specific SIR (PMID 33473166). "Retinoblastoma survivors" is never written as a single risk group anywhere in this condition. Retinoblastoma is cross-linked, not restated.
  4. The Olivier critique of SWOG S1801 is presented as a live disagreement, as the seed required, with its three specific objections stated and NADINA's phase 3 design noted as answering only the third (PMID 38621314; PMID 38828984).
  5. clinical-trials-landscape.md is dated and verified rather than illustrative. Every NCT record was fetched from the v2 API on the build date and its status, enrolment and primary-completion date recorded as of that date.
  6. Patient-voice ethics applied more strictly than the convention requires: public sources only, no private individual named or profiled, and no quotation at all rather than the permitted ≤15 words.

Notable content decisions

  • The overdiagnosis controversy is treated as content, not as a problem to resolve. Both readings are presented with their own evidence, and the junction that neither literature has crossed is recorded as OQ-1 and D1.
  • The stage IIC/IIIA survival inversion is stated plainly across three independent validation cohorts, because it inverts the intuition that a higher stage number means worse disease and is the direct argument for stage IIB/IIC adjuvant therapy.
  • KEYNOTE-716's PRFS2 hazard ratio of 0.75 (95% CI 0.56–1.01) is given equal prominence to its RFS result. It is the number that determines whether adjuvant therapy in stage IIB/IIC produces durable benefit or mostly advances the timing of treatment, and it is rarely quoted.
  • The European guideline's own disclaimer is quoted: sentinel node biopsy "shall be offered… although there is as yet no clear survival benefit for this approach."

What could not be verified, and what is recorded as absence

  • No trial was found comparing modern neoadjuvant against modern adjuvant therapy with overall survival as the primary endpoint. The active phase 3 landscape was queried by condition and phase/status filter on 2026-09-01; the absence is dated and recorded as OQ-3 and D3.
  • No melanoma trial randomising management on ctDNA was located (OQ-15). The comparable design exists in colon cancer (PMID 40055522).
  • No randomised trial of population melanoma screening exists, and none appears in the active phase 3 registry (OQ-19).
  • No evaluation of a melanoma advocacy or awareness campaign against an outcome was located; recorded in literature/patient-voice/organizations.md and sources.md.
  • No current guideline document was located for melanoma in pregnancy, in transplant recipients, in children as a dedicated document, or for acral melanoma specifically; the Australian ocular/periocular document dates from 2008. Recorded in the registry's gaps section.
  • No acral- or mucosal-specific patient organisation was located, and no organisation from Africa, South America, South Asia, East Asia or the Middle East returned a verified page — recorded as a directory gap, not as evidence of absence of need.
  • Two ocular-melanoma organisation URLs did not return a verified page on 2026-09-01 and were therefore omitted rather than listed unverified.
  • NCCN guideline content sits behind registration. The two NCCN resources are cited by URL and access date only; the version number behind the login was not read, and this is stated in the registry.
  • PMID 38752346 (Olsen, Denmark) has no abstract in PubMed. It is cited at title level only, for the existence and direction of ecological evidence, never for a figure.
  • PMID 36946230 (Ni, Australian second-primary cohort) has no abstract in PubMed. Cited at title level only.
  • Two collective-author records (PMID 26091043 TCGA; PMID 25555246 AJCC Ophthalmic Oncology Task Force; PMID 32135640 Chinese Anti-Cancer Association) return "Anonymous" from the esummary author field; their collective names were retrieved from the efetch XML and corrected by hand.

Follow-ups for the auditor

  1. Re-fetch every one of the 622 PMIDs and 46 NCT IDs; check author, year, journal and every quoted number against the record. Tolerate ePub-vs-print year offsets.
  2. Re-run the searches behind every asserted absence listed above — stale absences are the most common real error, and four of them are load-bearing for open questions.
  3. Check the retinoblastoma border rules specifically: that no page writes "retinoblastoma survivors" as one group, and that 3.1–17 is never presented as a melanoma-specific point estimate.
  4. Check the inline author attributions. Several were corrected during the build after the citation resolved to a different first author than assumed; a systematic check against the References list of each page is warranted.
  5. Verify the two title-only citations (PMID 38752346; PMID 36946230) are used only for existence and direction, not for figures.
  6. Re-verify the 18 organisation URLs and 6 guideline web resources; web resources rot faster than PubMed records.
  7. Check that no page exceeds its scope border into keratinocyte carcinoma or non-melanoma immune toxicity.
  8. Promote to curated only pages where every citation resolves and matches with no unresolved substantive issue; otherwise leave draft and record why.

Next sweep

Re-check: whether any neoadjuvant-versus-adjuvant overall-survival trial has been registered; whether any melanoma ctDNA management trial has opened; whether MelMarT-II (NCT03860883) has reported; whether any guideline has addressed the KEYNOTE-716 PRFS2 result; and whether the EADO/EDF/EORTC guideline, which states validity to the end of 2026, has been updated.

2026-09-01 — Seeded (Claude)

Created the condition scaffold: INDEX.md with a 26-page canonical plan (24 topical + 2 standing house pages) and an anchor table, a seed OPEN-QUESTIONS.md (7 questions, 6 dots), this log, and the empty wiki/ and literature/ layers. No wiki pages written. The condition is deliberately excluded from the public site until it has pages.

Searches run (live PubMed E-utilities, 2026-09-01). Scoping counts: melanoma 184,619; melanoma[MeSH Major Topic] 98,409; cutaneous melanoma 24,442; uveal melanoma 8,280; mucosal melanoma 3,476; acral melanoma 2,099. Topic counts recorded per planned page in INDEX.md, including incidence/epidemiology 30,191, special populations 13,154, adjuvant therapy 8,972, screening/early detection 7,553, brain metastases 6,843, BRAF/NRAS/NF1 6,765, checkpoint agents 6,525, sentinel node 4,740, dermoscopy 3,504, targeted agents 3,402, Breslow/ulceration prognosis 3,034, TIL therapy 2,435, irAEs 2,223, UV risk factors 1,502, margins 1,286, neoadjuvant 1,231, ctDNA 581, survivorship 306.

Anchor records resolved live: 29, listed in INDEX.md with year, first author and journal. Retrieved and read abstracts rather than citing from memory for PMID 35353115 (Arnold, global burden) and 39282897 (Wolchok, CheckMate 067 10-year); every figure quoted in the INDEX.md overview comes from a retrieved abstract.

Scoping decisions made. 1. Scoped by border, not by breadth — the same treatment given to hypertension, and for the same reason. At 184,619 records this is the second-largest literature in the repository and the failure mode is sprawl. The condition owns melanoma of all primary sites and the systemic-therapy story that melanoma established; it does not own keratinocyte carcinomas or immune toxicity outside melanoma cohorts. 2. Uveal melanoma kept inside melanoma as a dedicated page, not split into its own condition. It has 8,280 records and is biologically distinct enough to justify separation on the lung-adenocarcinoma/squamous precedent. It is kept together because the contrast — checkpoint blockade transforming cutaneous and not uveal melanoma — is one of the most informative things in the field and is destroyed by filing the two apart. Recorded in CONDITIONS-ROADMAP.md as a candidate future standalone condition; if promoted, this page becomes the overlap page. 3. Acral and mucosal melanoma share one page (2,099 and 3,476 records), scoped around their distinct genomics and their under-representation in the trials that set the standard of care. 4. Screening and overdiagnosis is a page, not a paragraph, because the incidence–mortality divergence is a live unresolved controversy and this repository treats those as content. 5. A quantified shared border with retinoblastoma, seeded in the same session (PMID 33473166). Both conditions carry the border in INDEX.md with a rule to cross-link rather than restate.

Flagged for the build pass. - Schonfeld's abstract gives 3.1–17 as a range across melanoma, CNS, oral cavity and breast — not a melanoma-specific SIR. Retrieve the melanoma-specific figure or report the range as a range. Do not invent a point estimate. - Olivier (PMID 38621314) raises time-related biases in the SWOG S1801 analysis. Present the disagreement rather than resolving it by preference. - No anchor was resolved for: stage IIB/IIC adjuvant trials (KEYNOTE-716 and counterparts), DeCOG-SLT, KIT-directed therapy in acral/mucosal disease, melanoma in pregnancy, transplant/immunosuppressed cohorts, ctDNA surveillance, patient-organisation material, or current NCCN/ESMO documents. These are live-search tasks, not inheritances. - Every anchor in the table was resolved in a scoping session, not a build session, and must be re-verified before use.

Follow-ups. Build with tools/build-condition.sh melanoma; auditor must be a different engine from the writer.

2026-10-07 — independent audit of Claude Opus 5's D8 edit (Codex, auditor)

Records and checks. Re-fetched the three D8 records (PMIDs: 33764387, 40198940, 42610008), four additional OQ-8 records (PMIDs: 37845511, 42101794, 36149449, 39025250), and the KEYNOTE-716 registration (NCT03553836) through live PubMed E-utilities and ClinicalTrials.gov v2. All seven publication-type checks and DOI Crossref updated-by checks were negative for retraction or expression of concern; Crossref lists two corrections, not retractions, for PMID 37845511. The posted trial results do not contain persistent/unresolved adverse events by arm.

Figures and correction. Patrinely's 167/387 (43.2%) is a treated stage III–IV cohort without a placebo arm; 161/167 (96.4%) chronic events were grade 1–2, 143/167 (85.6%) remained unresolved, and 73/88 (83.0%) endocrine events became chronic. No specified figure failed, but Claude's "endocrinopathies most often (83.0%)" obscured that denominator, so D8 now states it. KEYNOTE-716's PRFS2 HR 0.75 (0.56–1.01) and 48-month RFS and PRFS2 rates resolve live; their absolute differences are 13.0 and 5.8 percentage points. OQ-8 now labels the harm estimate's population and lack of a control arm.

Full-text limit and overcorrection. van Akkooi's PubMed abstract establishes discussion of NNT versus NNH, but does not verify the claimed stage IIB/IIC RFS ledger or its numerical entries. PMC13479939 was identified live, but Europe PMC full-text XML returned 500, PMC served a download challenge, and publisher routes blocked retrieval. The unverified numerical ledger was not added to the wiki. D8 now states only what this audit could verify. Its PRFS2-versus-persistent-harm question remains open. No wiki page was promoted or demoted.

Judgement. Claude's Patrinely correction is reliable after the denominator clarification; the claim that a specific RFS ledger was verified remains unconfirmed. Recheck the full text before inserting those figures or declaring that exact ledger established.

2026-10-08 — correction of dot row D1, which misstated its own evidence (Claude Opus 5, author)

Why. The novelty gate returned narrowed unanimously on D1, and the row's central assertion — that the burden and overdiagnosis literatures "use the same incidence series" — is literally wrong.

What was wrong. The burden projection uses GLOBOCAN 2020/2022 and counts invasive melanoma only (PMID 35353115); the 59–60% overdiagnosis estimate uses SEER 1975–2014 and counts in situ and invasive together (PMID 35293957). They differ in source, years, geography and disease definition, so subtracting 59–60% from 510,000 is invalid — which is what the row's framing invited. Two further slips: the ~88% UV-attributable figure is for 2022 and projects to 2050, not 2040 (PMID 42502459), and the 29–60% scoping-review range pools three heterogeneous designs rather than giving a correction factor (PMID 37793786).

A non-indexed source, read directly. The gate named the UK Technical annex to the 2026 National Cancer Plan as the only posted analysis pairing the two. That document was downloaded and read in this session rather than taken from the verdict file, which turned out to matter: the annex's rough calculation does drop UV to the fourth-biggest UK cancer risk factor if around half of UK cases are overdiagnosed, but it immediately judges that magnitude "unlikely based on the literature" — a caveat the verdict's summary omitted, and one that would have made this row misleading in the opposite direction. Cited in the CONVENTIONS §1 non-journal form.

What the row now says. The denominators are incompatible and the reconciliation is unpublished; no overdiagnosis-corrected invasive incidence, projection or UV-attributable fraction exists.

Provenance of this pass. Every PMID written into the row was re-fetched live from PubMed in this session (E-utilities via the bio-research PubMed tool), its publication types inspected for Retracted Publication / Expression of Concern, and its DOI checked against Crossref's updated-by field. Twenty records were checked across the three conditions corrected today; none carried a retraction, withdrawal or expression of concern. No identifier was carried over from the gate verdict files on trust: those were written in an earlier session, and SOURCES.md's prime rule binds the session that writes the claim.

Author: Claude Opus 5. Auditor: pending — must be a different engine.

2026-10-08 — independent audit of Claude Opus 5's D1 correction (Codex, auditor)

Live records re-fetched. PubMed E-utilities: row PMIDs 35353115, 42502459, 35293957, 37793786; added PMID 31858624; search candidates 34902365, 28537538, 27639256, 41548190, 40900523, 42279200, 35531668, 38655629, 39026390, 39141363, 35442415, 37184188, 42763895, 42289825, 36191966, 34116095, 26589973, 19785614, 29947202, 37949120, 23046017, 741212, 21366454, 9349228, 19609948. All five cited records exist and match the papers. Their PubMed publication types and their actual PubMed-listed DOI's Crossref updated-by fields show no retraction or expression of concern. The UK Department of Health and Social Care technical-annex PDF was downloaded and read directly; the GOV.UK publication page confirms 2026-02-04.

Searches re-run, live PubMed ESearch, 2026-10-08 (exact terms; counts are database hits, not eligible studies).

Query Count
melanoma AND (overdiagnosis OR overdiagnosed) AND ("invasive incidence" OR "invasive melanoma") AND (projection OR projected OR forecast OR attributable) 6
melanoma AND (overdiagnosis OR overdiagnosed) AND (ultraviolet OR UV) AND ("attributable fraction" OR "attributable burden" OR projection OR incidence) 10
melanoma AND (overdiagnosis OR overdiagnosed) AND ("invasive melanoma" OR "invasive incidence") 19
melanoma AND (GLOBOCAN OR global) AND (overdiagnosis OR overdiagnosed) AND (ultraviolet OR UV) AND (attributable OR projection) 1
"melanoma" AND "overdiagnosis" AND ("population attributable fraction" OR PAF) 0
"invasive melanoma" AND (overdiagnosis OR overdetection) AND (projection OR incidence OR burden) 13

Corrections. Confirmed GLOBOCAN 2020 is invasive-only, 325,000 to 510,000 by 2040 at constant rates; the ~88% UV fraction pertains to 2022 under the fifth-percentile reference and its separate projection ends in 2050. Confirmed the US SEER 59%/60% estimate uses in-situ plus invasive diagnoses and the scoping review's 29–60% comes from three studies. Refuted the row's blanket absence of invasive-specific overdiagnosis estimates: the live-fetched Australian analysis (PMID 31858624) estimates 15% for invasive melanoma in women and 22% in men in 2012, so added it. The UK annex explicitly says a rough half-overdiagnosed assumption would make UV the fourth-biggest UK cancer risk factor and immediately calls that magnitude “unlikely based on the literature”. It does not pair the GLOBOCAN and SEER series; removed that claim. Narrowed the absent analysis to an overdiagnosis-adjusted global invasive projection or UV-attributable fraction, which the dated PubMed searches did not locate. The search does not establish absence from every database or unpublished work.