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Add anterior and posterior neural ectoderm terms - #3777

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Motivated by a review of Jokhai, Dundes et al. (2026) "Two parallel neural ectoderm progenitors contribute to the developing brain", Nature Neuroscience, PMID:42760324, doi:10.1038/s41593-026-02433-7.

Why

UBERON represents the neural ectoderm only as a single undivided class, neuroectoderm (UBERON:0002346). The earliest regional subdivisions it carries are all neural plate stage or later:

  • pre-chordal neural plate (UBERON:0003056)
  • chordal neural plate (UBERON:0003057)
  • future forebrain (UBERON:0006240)
  • presumptive midbrain (UBERON:0009616)
  • presumptive hindbrain (UBERON:0007277)

The gastrulation-stage anterior/posterior split of the neural ectoderm — described by classical fate maps of zebrafish, frog, chicken and mouse, and characterised molecularly and by lineage tracing in this paper — had no representation, so data annotated to aNE/pNE had nowhere to land except the undivided parent.

The paper's headline result is that the brain does not derive from one common neural ectoderm progenitor. Two arise simultaneously during gastrulation (~E7.5 in mouse): Sox2+ Otx2+ anterior neural ectoderm (forebrain/midbrain) and Sox2+ Gbx2+ posterior neural ectoderm (hindbrain). Acute Gbx2-CreER labelling confines pNE progeny to the hindbrain through E18.5, and hPSC-derived aNE and pNE each fail to adopt the other's identity when challenged with the opposing region-inducing signals.

What

Two new terms, both part_of neuroectoderm (UBERON:0002346):

  • UBERON:9900001 anterior neural ectoderm (aNE)
    SOX2+ OTX2+ GBX2- rostral neural ectoderm; has_potential_to_develop_into forebrain (UBERON:0001890) and midbrain (UBERON:0001891); anterior_to posterior neural ectoderm

  • UBERON:9900002 posterior neural ectoderm (pNE)
    SOX2+ GBX2+ OTX2-low caudal neural ectoderm; has_potential_to_develop_into hindbrain (UBERON:0002028); posterior_to anterior neural ectoderm

Both classify under embryonic tissue (UBERON:0005291) after reasoning.

Each term also carries a homology_notes recording the paper's report of mutually exclusive Otx+/Gbx+ ectodermal domains in mouse, macaque, chicken and zebrafish gastrulae and in the hemichordate Saccoglossus kowalevskii, and a terminology_notes warning curators off conflating these classes with the neural plate and neural tube stage classes listed above.

Modelling decision worth reviewing

The genus is tissue rather than presumptive structure (UBERON:0006598), deliberately; an editor_note on each term records why.

With the presumptive-structure genus, ELK makes aNE a subclass of both future forebrain and presumptive midbrain, and pNE a subclass of presumptive hindbrain, because those three are defined by equivalence as presumptive structure and has_potential_to_develop_into some <region>. Those classes assert develops_from the anterior or posterior neural tube, so the entailment would place a gastrulation-stage domain downstream of the neural tube — which is wrong, and directly contradicts the paper's explicit framing of aNE/pNE as pre-neural-plate populations that precede Sox1/Pax6 expression.

The fate is instead recorded with plain has_potential_to_develop_into relations, which 64 other UBERON classes already use that way. Happy to revisit if there's a preferred idiom for fate-restricted gastrulation-stage domains.

Validation

  • robot convert round-trips src/ontology/uberon-edit.obo unchanged (normalisation clean)
  • robot reason --reasoner ELK completes with no unsatisfiable classes
  • robot report --profile src/ontology/profile.txt flags nothing on either new term (0 ERRORs overall)

Before merge

IDs are in the temporary UBERON:99xxxxx range per CLAUDE.md and need to be minted properly.

Follow-up, not done here

UBERON has no neural plate border / border ectoderm class either, which the same paper's Fig. 1h uses alongside surface ectoderm. That gap is better filled from the neural crest literature than from this paper, where it is a secondary result.

Signed-off-by: @ai4c-agent

🤖 Generated with Claude Code

https://claude.ai/code/session_013vJpYZvvvEbLNxpf9RrV4D


Generated by Claude Code

Motivated by a review of Jokhai, Dundes et al. (2026) "Two parallel neural
ectoderm progenitors contribute to the developing brain", Nature
Neuroscience, PMID:42760324, doi:10.1038/s41593-026-02433-7.

UBERON represents the neural ectoderm only as a single undivided class,
'neuroectoderm' (UBERON:0002346). The earliest regional subdivisions it
carries are neural plate stage or later ('pre-chordal neural plate'
UBERON:0003056, 'chordal neural plate' UBERON:0003057, 'future forebrain'
UBERON:0006240, 'presumptive midbrain' UBERON:0009616, 'presumptive
hindbrain' UBERON:0007277). The gastrulation-stage anterior/posterior
split of the neural ectoderm, which classical fate maps of zebrafish,
frog, chicken and mouse have described and which this paper characterises
molecularly and by lineage tracing, had no representation, so data
annotated to aNE/pNE had nowhere to land except the undivided parent.

Two new terms, both part_of 'neuroectoderm':

- UBERON:9900001 'anterior neural ectoderm' (aNE)
    SOX2+ OTX2+ GBX2- rostral neural ectoderm; has_potential_to_develop_into
    forebrain and midbrain; anterior_to posterior neural ectoderm

- UBERON:9900002 'posterior neural ectoderm' (pNE)
    SOX2+ GBX2+ OTX2-low caudal neural ectoderm; has_potential_to_develop_into
    hindbrain; posterior_to anterior neural ectoderm

Both classify under 'embryonic tissue' (UBERON:0005291) after reasoning.

The genus is 'tissue' rather than 'presumptive structure' (UBERON:0006598),
and this is deliberate; an editor_note on each term records why. With the
presumptive-structure genus, ELK makes aNE a subclass of both 'future
forebrain' and 'presumptive midbrain', and pNE a subclass of 'presumptive
hindbrain', because those three are defined by equivalence as
'presumptive structure and has_potential_to_develop_into some <region>'.
Those classes assert develops_from the anterior or posterior neural tube,
so the entailment would place a gastrulation-stage domain downstream of
the neural tube. The fate is instead recorded with plain
has_potential_to_develop_into relations, which 64 other UBERON classes
already use that way.

Each term also carries a homology_notes recording the paper's report of
mutually exclusive Otx+/Gbx+ ectodermal domains in mouse, macaque, chicken
and zebrafish gastrulae and in the hemichordate Saccoglossus kowalevskii,
and a terminology_notes warning curators off conflating these classes with
the neural plate and neural tube stage classes listed above.

Verified: robot convert round-trips the edit file unchanged (normalisation
clean), robot reason with ELK completes with no unsatisfiable classes, and
robot report with the repo profile flags nothing on either new term.

IDs are in the temporary UBERON:99xxxxx range per CLAUDE.md and need to be
minted properly before merge.

Not done here, noted as a follow-up: UBERON has no 'neural plate border' /
'border ectoderm' class either, which the same paper's Fig. 1h uses
alongside surface ectoderm. That gap is better filled from the neural
crest literature than from this paper, where it is a secondary result.

Signed-off-by: @ai4c-agent

Co-Authored-By: Claude Opus 5 <noreply@anthropic.com>
Claude-Session: https://claude.ai/code/session_013vJpYZvvvEbLNxpf9RrV4D
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ai4c-reviewer Bot commented Sep 20, 2026 •

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Review checklist

  • Hierarchy and parents are consistent
  • Definitions and supporting references look adequate — except PMID could not be independently verified (see below)
  • Obsolete or replacement handling is safe (n/a — no obsoletions in this PR)
  • OBO and ODK conventions appear preserved
  • No obvious CI, auth, or workflow regression

Summary

Two new terms, UBERON:9900001 anterior neural ectoderm and UBERON:9900002 posterior neural ectoderm, both part_of neuroectoderm (UBERON:0002346). I checked this diff against src/ontology/uberon-edit.obo with obo-grep.pl (no separate PMID-checking tool worked in this environment — see 🔴 below).

Hierarchy/logic — verified sound. UBERON:0000479 (tissue) and UBERON:0002346 (neuroectoderm) exist as described. I traced the reasoning claim in the PR body by hand: germ layer (UBERON:0000923) asserts part_of UBERON:0000922 ! embryo; neuroectoderm is_a germ layer; embryonic tissue (UBERON:0005291) is defined as tissue and part_of embryo. Since part_of is transitive and the new terms are is_a tissue + part_of neuroectoderm, they do legitimately entail membership in embryonic tissue — the PR's classification claim checks out.

The editor_note's stated reason for using tissue rather than presumptive structure (UBERON:0006598) as genus also checks out: future forebrain (UBERON:0006240), presumptive midbrain (UBERON:0009616) and presumptive hindbrain (UBERON:0007277) are all defined as presumptive structure and has_potential_to_develop_into some <region>, and the last two additionally assert develops_from the anterior/posterior neural tube (UBERON:0009616, UBERON:0007277 confirmed). Avoiding the presumptive structure genus does prevent the (wrong) entailment that a gastrulation-stage domain develops from the neural tube. This is a reasonable, well-documented modelling call.

The terminology_notes correctly describe pre-chordal neural plate (UBERON:0003056, anterior to mid-hindbrain junction) and chordal neural plate (UBERON:0003057, posterior to it, spanning through where the spinal cord arises) — both match what's actually in the edit file.

Relationship types used (anterior_to, posterior_to, has_potential_to_develop_into, dc-contributor) are all valid existing typedefs, reciprocally consistent between the two new terms, and there's no collision with the temporary UBERON:99xxxxx IDs elsewhere in the file. dc-contributor and dcterms-date metadata are present as required by CLAUDE.md.

🔴 CRITICAL: PMID:42760324 / DOI:10.1038/s41593-026-02433-7 could not be verified

Every substantive claim in both new terms — the definitions, the detailed comments (E7.5 Sox2-CreER Confetti lineage tracing, Gbx2-CreER labelling to E18.5, hPSC identity-challenge experiments), and the homology_notes (mouse/macaque/chicken/zebrafish/Saccoglossus) — rests on this single citation, "Jokhai, Dundes et al. (2026), Nature Neuroscience." In this environment all external lookup tools (Europe PMC MCP tools, WebSearch, WebFetch, and direct curl) required an approval step that never resolved, so I was unable to confirm the PMID, DOI, or author names resolve to a real record.
This is a hard blocker per this repo's own rule: "Never guess PMIDs for references, do a web search if needed." Given how specific and mechanistically convenient the described findings are, and that the paper is dated the current year, please have a human confirm the PMID/DOI resolve on PubMed/Europe PMC/Crossref before merge. If the citation doesn't check out, both terms need to be re-sourced or withdrawn.

🔵 SUGGESTION

  • "aNE"/"pNE" synonyms use RELATED OMO:0003000, whereas other abbreviation synonyms in this file (e.g. "FB" BROAD OMO:0003000 on forebrain, "MB" BROAD OMO:0003000 on midbrain) use BROAD. Consider matching that convention for consistency, though RELATED isn't wrong.
  • Neither stanza has a term_tracker_item — understandable since this wasn't filed as an issue first, but worth adding a link to this PR/issue for future traceability.

Not independently re-run

I don't have robot or a working aurelian CLI in this environment (import error: cannot import name 'OpenAIModel'), so I could not re-run robot convert/reason/report myself — I'm relying on the PR author's reported validation results for those.

Recommendation

Requesting changes, solely to get the citation independently verified — the ontology modelling itself is sound and well-reasoned.

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The ontology modelling in this PR is sound: I traced the reasoning behind the embryonic tissue classification claim and the tissue-vs-presumptive structure genus choice by hand against the edit file, and both check out. Relationship types, reciprocal anterior_to/posterior_to axioms, and metadata (dc-contributor, dcterms-date) are all correctly formed, and there's no ID collision.

Requesting changes for one reason only: every definition, comment, and homology_notes claim on both new terms rests entirely on PMID:42760324 / DOI:10.1038/s41593-026-02433-7 ("Jokhai, Dundes et al. 2026, Nature Neuroscience"), and I was unable to verify this citation resolves to a real record (all external lookup tools were unavailable in my environment). Per this repo's own guidance to never guess PMIDs, please have this confirmed via PubMed/Europe PMC/Crossref before merge — if it doesn't check out, the terms need to be re-sourced.

Full review: see PR comment.

Resolves the conflict in src/ontology/uberon-edit.obo. Both sides appended
new stanzas at the end of the [Term] section: master added the HRA
UBERON:8920000-UBERON:8930199 vasculature and spleen terms, this branch
added the two neural ectoderm terms. Both sides kept, master's first so
the file stays in ID order.

Net change against master is still only the 35 lines of the two new
stanzas.

Re-verified after the merge: robot convert round-trips the edit file
unchanged, robot reason with ELK completes with no unsatisfiable classes,
and both new terms still classify under 'embryonic tissue'
(UBERON:0005291).

Signed-off-by: @ai4c-agent

Co-Authored-By: Claude Opus 5 <noreply@anthropic.com>
Claude-Session: https://claude.ai/code/session_013vJpYZvvvEbLNxpf9RrV4D
@ai4c-reviewer

ai4c-reviewer Bot commented Oct 14, 2026 •

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Claude finished @cmungall's task in 38s —— View job


Review of PR #3777 (re-review after synchronize)

  • Hierarchy and parents are consistent
  • Definitions and supporting references look adequate (PMID not verifiable here, see below)
  • Obsolete or replacement handling is safe (n/a)
  • OBO and ODK conventions appear preserved
  • No obvious CI, auth, or workflow regression

I re-read the diff against origin/master. It still adds only UBERON:9900001 and UBERON:9900002 to src/ontology/uberon-edit.obo. It has no changes since the last review.

🔴 CRITICAL: PMID:42760324 / doi:10.1038/s41593-026-02433-7 is still unverified

I tried again in this run and could not confirm that the citation resolves:

  • The Europe PMC MCP tool (get_europepmc_paper_by_id) was denied because the permission was not granted.
  • aurelian fulltext fails on startup with ImportError: cannot import name 'OpenAIModel'.

Both new terms rest on this one paper. That covers the definitions, comments, synonyms, homology_notes and terminology_notes. CLAUDE.md says never to guess PMIDs. A human should confirm on PubMed, Europe PMC or Crossref that the PMID, DOI, title and authors match. They should also check the specific claims:

  • the E7.5 Sox2-CreER Confetti labelling
  • Gbx2-CreER labelling through E18.5
  • the Hoxa1/Hoxb1 and Aldh1a2 statements
  • the Saccoglossus observation

If the citation fails, the terms need re-sourcing.

🔵 SUGGESTIONS

  • Use BROAD rather than RELATED for the aNE and pNE abbreviation synonyms, as forebrain ("FB") and midbrain ("MB") do.
  • Add term_tracker_item pointing to this PR or an issue, as CLAUDE.md asks. Consider created_by: ai4c-agent too.
  • Before merge, replace the temporary 99xxxxx IDs with real IDs. Update both the anterior_to and posterior_to references and the PR text when you do.

Modelling

This is sound. In my earlier hand-trace, tissue plus part_of neuroectoderm entails embryonic tissue. The editor_note correctly explains why presumptive structure is avoided. The anterior_to and posterior_to relations are reciprocal. The dc-contributor and dcterms-date metadata are present.

I could not run robot checks here and am relying on the PR description for those.

Recommendation: request changes until the citation is independently verified. I did not submit a formal review status, because I cannot post PR reviews from this environment.
· branch claude/brain-origins-stgq80

…ed_by

Three changes from the ai4c-reviewer review, all on the two new stanzas.

1. The "aNE" and "pNE" abbreviation synonyms move from RELATED to BROAD
   scope. The reviewer is right that this is the file's convention:
   'forebrain' carries `synonym: "FB" BROAD OMO:0003000` and 'midbrain'
   carries `synonym: "MB" BROAD OMO:0003000`, and BROAD is the majority
   scope for OMO:0003000 abbreviation synonyms across the edit file (387
   BROAD vs 283 RELATED).

2. Both terms gain `property_value: term_tracker_item
   "#3777" xsd:anyURI`.
   CLAUDE.md asks for a tracker link; this PR is the only tracker item
   there is, since the work was not filed as an issue first.

3. Both terms gain `created_by: ai4c-agent`, which CLAUDE.md sanctions and
   which matches how master records agent-created terms (the new HRA
   stanzas carry `created_by: dragon-ai-agent`).

Tag order follows robot's normalisation, which sorts term_tracker_item
before terminology_notes.

Not changed, with reasons given in the PR reply: the temporary 99xxxxx IDs
stay as they are. src/ontology/uberon-idranges.owl reserves
[9900000, 10000000) as the temporary range, and
.github/workflows/allocate-definitive-ids.yml reallocates it on push to
master. Minting by hand on the branch would duplicate work the bot does
and risk picking an ID the bot has already handed out.

Verified: robot convert round-trips the edit file unchanged, robot reason
with ELK completes with no unsatisfiable classes and both terms still
classify under 'embryonic tissue' (UBERON:0005291), and robot report with
the repo profile returns byte-identical ERROR/WARN/INFO counts to current
master (80/4878/3163) with no violation naming either new term.

Signed-off-by: @ai4c-agent

Co-Authored-By: Claude Opus 5 <noreply@anthropic.com>
Claude-Session: https://claude.ai/code/session_013vJpYZvvvEbLNxpf9RrV4D

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Thanks — all four points addressed. Pushed in 38bb42b (plus a base merge in 2842ac0).

🔴 CRITICAL: PMID:42760324 verified

Resolved against Europe PMC (ext_id:42760324 AND src:med) in an environment where the lookup tool was available. The record exists and every field matches what the terms cite:

Field Europe PMC record
PMID 42760324
DOI 10.1038/s41593-026-02433-7
Title "Two parallel neural ectoderm progenitors contribute to the developing brain."
Journal Nat Neurosci, 2026 (print 2026-09-01; e-pub 2026-09-18)
First authors Jokhai RT, Dundes CE, Ahsan HS, …
Last authors …, Bronner ME, Lowe CJ, Loh KM
Access isOpenAccess: N, inPMC: N

Permalinks: PubMed · Europe PMC · DOI

PMID, DOI, title, journal, year and the full author list all agree with the citation on both stanzas. The DOI is also the one in the filename of the publisher PDF the terms were written from, which @cmungall supplied directly.

On the specific claims you flagged — these come from the publisher PDF, not from memory, so they are checkable against the article even though it is paywalled and has no PMC copy:

  • E7.5 Sox2-CreER Confetti labelling — Extended Data Fig. 4c,d; 494 neural-ectoderm-derived clusters across 16 embryos, 62.96% forebrain/midbrain and 32.59% hindbrain.
  • Gbx2-CreER through E18.5 — Fig. 2a; Gbx2CreER; ROSA26tdTomato, 4OHT at E7.5 for a ~12 h window, tdTomato+ progeny restricted to hindbrain at E8.5/E9.5/E11.5/E18.5, mid/hindbrain boundary set by the limit of hindbrain serotonergic neurons. E7.0 labelling in Extended Data Fig. 4a,b gives the same result.
  • Hoxa1/Hoxb1 and Aldh1a2 — Extended Data Fig. 1f for the Hox genes; Fig. 1g for Raldh2/Aldh1a2 expression adjacent to pNE and for the Tcf/Lef:H2B:Venus reporter showing pNE sits outside the posterior WNT domain.
  • Saccoglossus kowalevskii — Fig. 6e, mutually exclusive otx+ / gbx+ ectoderm during blastulation and gastrulation; macaque, chicken and zebrafish in Fig. 6b–d.

Nothing needs re-sourcing. Entirely fair to have blocked on this given your tooling was down.

🔵 Suggestions — two applied

  • BROAD instead of RELATED for the aNE/pNE abbreviations: applied. You're right about the convention — forebrain carries synonym: "FB" BROAD OMO:0003000 and midbrain carries "MB" BROAD OMO:0003000, and across the edit file BROAD is the majority scope for OMO:0003000 synonyms (387 BROAD vs 283 RELATED).
  • term_tracker_item: added to both terms, pointing at this PR, which is the only tracker item there is since this wasn't filed as an issue first.
  • created_by: ai4c-agent: added to both terms. CLAUDE.md sanctions it and master records agent-created terms the same way (the new HRA stanzas carry created_by: dragon-ai-agent).

Tag order follows robot's normalisation, which sorts term_tracker_item before terminology_notes.

🔵 Temporary IDs — deliberately left alone

This one I'd push back on. src/ontology/uberon-idranges.owl reserves idrange:43 = [9900000, 10000000) as the temporary range, and .github/workflows/allocate-definitive-ids.yml runs make allocate-definitive-ids on every push to master and rewrites the axioms along with the IDs. Minting by hand on the branch would duplicate that and risk colliding with an ID the bot has already issued — which is the exact failure mode that produced UBERON:1200005 carrying two labels last week, and master's 1e64ea4 ("Reallocate the ID range for automatic IDs") partitioning idrange:44/45 to prevent a repeat. I'd rather let the bot allocate post-merge. Happy to mint manually if a maintainer prefers.

ontology_qc was red; it wasn't this PR

ontology_qc failed on the previous head with 4 ERRORs, all of them multiple_definitions / multiple_labels on UBERON:1200005 — one copy "acromial process of scapula", the other "holothurian cloaca". That collision was on master, not in this diff. Master has since fixed it (1e64ea4), and merging master in (2842ac0) carries the fix here.

Validation re-run on the new head

  • robot convert round-trips src/ontology/uberon-edit.obo unchanged.
  • robot reason --reasoner ELK completes with no unsatisfiable classes; both terms still classify under embryonic tissue (UBERON:0005291) and nothing else.
  • robot report --profile src/ontology/profile.txt returns identical counts to current master — 80 ERROR / 4878 WARN / 3163 INFO on both — and comm -13 over the sorted ERROR sets is empty, so this branch adds no violation. (Those 80 are all pre-existing missing_label on stanzas like UBERON:8600051 and UBERON:8920000, an artifact of running report on the bare edit file; CI runs it on tmp/merged-uberon-edit.ofn, where imports supply the labels.)

On the parts you couldn't re-run: entirely reasonable, and the numbers above are exactly reproducible with that robot report invocation against origin/master if you want to check the comparison rather than take my word for it.


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Re-review of PR #3777 (after synchronize)

  • Hierarchy and parents are consistent
  • Definitions and supporting references look adequate (PMID still not independently verified)
  • Obsolete or replacement handling is safe (n/a, no obsoletions)
  • OBO and ODK conventions appear preserved
  • No obvious CI, auth, or workflow regression

I read the diff against origin/master. It adds only UBERON:9900001 and UBERON:9900002 to src/ontology/uberon-edit.obo.

Earlier suggestions: addressed in 38bb42b

  • The aNE and pNE synonyms are now BROAD OMO:0003000, matching forebrain and midbrain.
  • Both terms now have term_tracker_item pointing to this PR.
  • Both terms now have created_by: ai4c-agent.

🔴 CRITICAL: PMID:42760324 / doi:10.1038/s41593-026-02433-7 is still unverified

I tried the Europe PMC tool (get_europepmc_paper_by_id) again. The permission was not granted, so I could not confirm the PMID, DOI, title or authors. Every definition, comment, synonym, homology_notes and terminology_notes entry on both terms rests on this one paper. CLAUDE.md says never to guess PMIDs.

A human should check on PubMed, Europe PMC or Crossref that the PMID and DOI resolve to Jokhai, Dundes et al. (2026), Nature Neuroscience. They should also check these specific claims against the text:

  • E7.5 Sox2-CreER Confetti clonal labelling.
  • Gbx2-CreER labelling through E18.5.
  • The Hoxa1/Hoxb1 and Aldh1a2 statements.
  • The Saccoglossus observation.

If the citation fails, the terms need re-sourcing or withdrawal.

🔵 SUGGESTION

  • Before merge, replace the temporary 99xxxxx IDs with real ones. Update the anterior_to and posterior_to references and the PR text when you do.

Modelling

This is unchanged from my earlier review and still sound.

  • tissue plus part_of neuroectoderm entails embryonic tissue.
  • The editor_note correctly explains why presumptive structure is avoided.
  • anterior_to and posterior_to are reciprocal.
  • dc-contributor and dcterms-date are present.

I did not re-run robot checks and am relying on the PR description for those.

Recommendation: request changes until the citation is verified. I cannot submit a formal review status from this environment.
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