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Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis.

Citation integrity

Major revisionpanel verdict · 2026-09-03

Citation Integrity Audit Report

Manuscript: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis

Scope of Audit

The following categories are in play and have been checked:

  1. Reference Resolvability — all in-text citations must map to a resolvable reference (DOI/PMID/full citation)
  2. Claim–Citation Support — factual and quantitative claims attributed to references must be plausibly contained in those references
  3. Quotation/Number Fidelity — where specific values or statements are attributed to sources, they should match the source

Findings by Category

Reference Resolvability

Status: PASS with minor caveats

All 51 numbered references in the reference list include sufficient identifiers (DOI, PMID, or full journal citation). The manuscript uses standard numbered citation format and all in-text citations map to entries in the reference list.

Unverifiable references (checked via tools):

The following references could not be fully verified as existing or accessible via standard databases, but are not load-bearing to central claims:

  • Ref. 27 (Website, doi: 10.1161/ATVBAHA.114.3052) — listed as "Website" with only a DOI; no title or authors given. This is a formatting anomaly but the DOI is resolvable in principle.

No dead or unresolvable references identified. All references with standard citations (author, year, journal, PMID/DOI) are resolvable.

Claim–Citation Support

Status: MOSTLY PASS; one unverifiable claim and several unconfirmed attributions

Load-bearing claims checked:

  1. Claim: "TRKB-null mice exhibit defects in pericyte migration and VSMC function" (Discussion, attributed to Ref. 36)

    • Finding: Ref. 36 (Donovan et al., 2000, Development) is titled "Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization."
    • Status: UNVERIFIABLE — The reference title and abstract focus on BDNF as an endothelial survival factor, not on TRKB-null mice or pericyte/VSMC defects. The claim may be supported in the paper's text, but cannot be confirmed from the citation alone. Raise as question to authors.

  2. Claim: "NT3-null mice display vascular abnormalities and impaired cardiac morphogenesis" (Discussion, attributed to Refs. 37–38)

    • Ref. 37: Tessarollo et al., 1994, PNAS — title: "Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons"
    • Ref. 38: Donovan et al., 1996, Nat Genet — title: "Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development"
    • Status: PARTIALLY VERIFIABLE — Ref. 38 title directly supports the cardiac development claim. Ref. 37 title does not mention vascular abnormalities (focuses on sensory neurons). The vascular abnormalities claim is unverifiable from Ref. 37 alone. Raise as question.

  3. Claim: "NOTCH3 amplifies NOTCH signaling through a positive feedback loop via transcriptional induction of the NOTCH ligand JAGGED1" (Discussion, attributed to Ref. 39)

    • Ref. 39: Liu et al., 2009, Circ Res — title: "NOTCH3 expression is induced in mural cells through an autoregulatory loop that requires endothelial-expressed JAGGED1"
    • Status: VERIFIABLE — Title directly supports the claim of an autoregulatory loop involving NOTCH3 and JAGGED1. ✓

  4. Claim: "Synovial capillaries have been implicated as a driver of synovial tissue fibrosis which leads to poor treatment outcome in RA" (Introduction, attributed to Ref. 1)

    • Ref. 1: Bhamidipati et al., 2025, bioRxiv — title: "Spatial patterning of fibroblast TGFβ signaling underlies treatment resistance in rheumatoid arthritis"
    • Status: UNVERIFIABLE — The reference is a preprint (bioRxiv, 2025) with a title focused on TGFβ signaling and treatment resistance, not explicitly on synovial capillaries as drivers of fibrosis. The claim may be in the paper but cannot be confirmed from the title. Raise as question.

  5. Claim: "Endothelial cells provide crucial signals in orchestrating synovial fibroblast differentiation in RA" (Results section, attributed to Refs. 2 and 13)

    • Ref. 2: Tamiato et al., 2024, Circ Res — title: "Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis"
    • Status: NOT SUPPORTED — This reference is about cardiac pericytes and age-related dysfunction, not RA or endothelial–fibroblast crosstalk. HARD FLAG: Misattributed citation.
    • Ref. 13: Veale & Fearon, 2018, Lancet — title: "The pathogenesis of psoriatic arthritis"
    • Status: UNVERIFIABLE — The reference is about psoriatic arthritis, not RA. While there may be overlap in vascular biology, the claim about endothelial–fibroblast crosstalk in RA is not clearly supported by a psoriasis paper. Raise as question.

  6. Claim: "Vascular endothelial cells play an important role in driving pathogenic fibroblast expansion and axonal sprouting in RA" (Introduction, attributed to Refs. 14 and 15)

    • Ref. 14: Wei et al., 2020, Nature — title: "Notch signalling drives synovial fibroblast identity and arthritis pathology"
    • Status: VERIFIABLE — This is a known RA paper on NOTCH signaling in fibroblasts. ✓
    • Ref. 15: Bai et al., 2024, Sci Transl Med — title: "Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis"
    • Status: VERIFIABLE — Title directly supports the claim about fibroblasts and axonal sprouting in RA. ✓

  7. Claim: "NOTCH3 plays a crucial role in vascular fibroblast differentiation" (Introduction, attributed to Ref. 16)

    • Ref. 16: Domenga et al., 2004, Genes Dev — title: "Notch3 is required for arterial identity and maturation of vascular smooth muscle cells"
    • Status: VERIFIABLE — Title directly supports NOTCH3's role in vascular cell differentiation. ✓

  8. Claim: "Pericytes and VSMCs are distinct yet closely related mural cell types that associate with specific endothelial subtypes" (Discussion, attributed to Refs. 34–35)

    • Ref. 34: Armulik et al., 2011, Dev Cell — title: "Pericytes: developmental, physiological, and pathological perspectives, problems, and promises"
    • Ref. 35: Gaengel et al., 2009, Arterioscler Thromb Vasc Biol — title: "Endothelial-mural cell signaling in vascular development and angiogenesis"
    • Status: VERIFIABLE — Both titles support the claim about mural cell types and their associations. ✓
Non-load-bearing claims:
  • References to general RA immunopathology (Refs. 32, 40) and FDA approval status of TRK inhibitors (Refs. 28–31, 42–43) are standard background citations and appear appropriate.

Quotation and Number Fidelity

Status: PASS

No direct quotations from prior work are presented in the manuscript. Quantitative claims (e.g., fold-changes in gene expression, p-values) are from the authors' own experiments and not attributed to prior work, so this category does not apply.

Self-Citation and Citation Inflation

Status: SOFT FLAG — Moderate self-citation

The manuscript cites Ref. 1 (Bhamidipati et al., 2025, bioRxiv) extensively, which appears to be a closely related preprint from the same group. This is not inappropriate (the prior work is directly relevant), but readers should note that the foundational spatial transcriptomics cohort and some analytical methods are from that preprint. This is disclosed in the text ("we expanded our spatial transcriptomic analysis from a cohort of treatment-naive patients") but the degree of overlap is not quantified.

Retracted or Predatory Sources

Status: PASS

No retracted papers or predatory venues identified among the 51 references. All cited journals are established, peer-reviewed publications.

Summary of Issues

IssueSeverityStatusResolution
Ref. 36 (TRKB-null mice claim)HARDUnverifiableAuthors should confirm that Donovan et al. 2000 supports the pericyte/VSMC defect claim, or provide additional citation
Ref. 37 (NT3-null vascular abnormalities)HARDUnverifiableAuthors should clarify whether Tessarollo et al. 1994 supports the vascular claim or if a different reference is intended
Ref. 2 (endothelial–fibroblast crosstalk in RA)HARDMisattributedTamiato et al. 2024 is about cardiac pericytes, not RA. This citation appears incorrect; authors should verify and correct
Ref. 13 (endothelial–fibroblast crosstalk in RA)HARDUnverifiableVeale & Fearon 2018 is about psoriatic arthritis, not RA. Authors should clarify relevance or substitute with an RA-specific reference
Ref. 1 (synovial capillaries and fibrosis)SOFTUnverifiableBhamidipati et al. 2025 is a preprint; authors should confirm the claim is in that paper or provide additional citation
Ref. 27 (formatting anomaly)SOFTPresent but poorly formatted"Website" entry with only DOI; recommend adding title and authors for clarity

Recommendations for Authors

  1. Verify Refs. 2 and 13 — Both appear to be misattributed or off-topic for the claim about endothelial–fibroblast crosstalk in RA. Substitute with appropriate RA literature or remove the citations.

  2. Clarify Refs. 36 and 37 — Confirm that these papers support the specific claims about TRKB-null and NT3-null mice, or provide additional citations that do.

  3. Expand Ref. 1 citation — If the foundational cohort and methods come from Bhamidipati et al. 2025, consider a more explicit statement of what is novel in the present manuscript versus what is reanalysis of that cohort.

  4. Format Ref. 27 — Add title and authors to the "Website" entry for completeness.

Audit completed: 51 references checked; 4 HARD issues (misattribution or unverifiable support for load-bearing claims); 2 SOFT issues (formatting, preprint status).

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