{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40051702", "kind": "science-record", "revision": 4, "content_hash": "sha256:068e442412b0982e2b4ea4c457a7cf40dec8497553aba044b5acb2b3412ecaeb", "created_at": "2026-11-01T20:30:15Z", "updated_at": "2026-11-01T22:56:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "EDN1 and NTF3 in keloid pathogenesis: computational and experimental evidence as novel diagnostic biomarkers for fibrosis and inflammation.", "doi": "10.3389/fgene.2025.1516451", "pmid": "40051702", "authors": ["Hui Gong", "Jing Liu", "Nanji Chen", "Hengguang Zhao", "Bailin He", "Hongpei Zhang", "Wenping Wang", "Yi Tian"], "journal": "Frontiers in genetics", "year": 2025, "abstract": "Objective: To investigate the roles of oxidative stress-related differentially expressed genes (OSRDEGs) in keloid formation and explore their potential value in diagnosis and treatment.\nMethods: Gene expression data from the GEO database, including GSE145725 and GSE44270 as training sets and GSE7890 as a validation set, were utilized. OSRDEGs were identified, followed by Weighted Gene Co-expression Network Analysis (WGCNA), GO/KEGG enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Key genes were further screened through protein-protein interaction (PPI) network analysis and receiver operating characteristic (ROC) curve analysis. miRNA targets, transcription factors (TF), and potential drug targets of these genes were predicted. Immune cell infiltration analysis was performed to assess the association between OSRDEGs and immune cells, which was validated using GSE7890. Finally, the expression of key genes was experimentally validated using quantitative PCR (qPCR), immunohistochemistry (IHC), and hematoxylin-eosin (HE) staining.\nResults: A total of 13 OSRDEGs were identified. WGCNA and functional enrichment analyses revealed that these genes were primarily involved in fibrosis and inflammatory processes in keloids, such as the MAPK signaling pathway, lymphocyte and monocyte proliferation, and inflammatory pathways involving IL-18 and IL-23. PPI network analysis, ROC analysis, and immune infiltration results identified Endothelin-1 (EDN1) and Neurotrophin-3(NTF3) as key genes with high sensitivity and specificity. These genes were positively and negatively correlated with activated mast cells, respectively, suggesting their dual regulatory roles in fibrosis and inflammation. External dataset validation, qPCR, correlation analysis, HE staining, and IHC results demonstrated that EDN1 and NTF3 were highly expressed in keloid tissues and were associated with excessive collagen deposition and immune cell infiltration.\nConclusion: EDN1 and NTF3, as OSRDEGs, play critical roles in the pathogenesis and progression of keloids. They may contribute to fibrosis and inflammation through the regulation of oxidative stress, the MAPK signaling pathway, and mast cell activation. These findings highlight EDN1 and NTF3 as potential diagnostic biomarkers and therapeutic targets, providing novel insights into the pathogenesis and treatment strategies for keloids.", "claims": [{"id": "claim-method", "statement": "Gene expression differences between groups were evaluated using t-tests for two-group comparisons, while one-way ANOVA was applied for comparisons across multiple groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40051702", "locator": "sections[15] \"2.8 Statistical analysis\" paragraph 2", "quote": "Gene expression differences between groups were evaluated using t-tests for two-group comparisons, while one-way ANOVA was applied for comparisons across multiple groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented in the study are deposited in the GEO repository under accession numbers GSE145725, GSE44270, and GSE7890.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40051702", "locator": "sections[40] \"Data availability statement\" paragraph 2", "quote": "The data presented in the study are deposited in the GEO repository under accession numbers GSE145725, GSE44270, and GSE7890."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 13 OSRDEGs were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40051702", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 13 OSRDEGs were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 13 OSRDEGs were identified.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40051702"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE145725"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE145725"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40051702", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2025.1516451", "sha256": 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:40051702", "data:geo:GSE145725"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE145725"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:47:45Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 18104, "completion_tokens": 1228, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40051702", "type": "paper", "label": "pmid:40051702"}, {"id": "source:pmid:40051702", "type": "manuscript", "label": "PMID 40051702 full text"}, {"id": "data:geo:GSE145725", "type": "dataset", "label": "GEO GSE145725"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40051702", "type": "paper", "label": "pmid:40051702"}, {"id": "source:pmid:40051702", "type": "manuscript", "label": "PMID 40051702 full text"}, {"id": "data:geo:GSE145725", "type": "dataset", "label": "GEO GSE145725"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40051702", "type": "extraction", "used": ["source:pmid:40051702"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE145725", "type": "accession_resolution", "used": ["data:geo:GSE145725"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40051702", "parent_hash": "sha256:e287f728e4b39e163e0109247aa1c39b8743d290619a0b68028cb7077d8ce7c5", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE145725 licence not read", "asset:data:geo:GSE145725 not downloaded", "asset:data:geo:GSE44270 licence not read", "asset:data:geo:GSE44270 not downloaded", "asset:data:geo:GSE7890 licence not read", "asset:data:geo:GSE7890 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rimentally validated using quantitative PCR (qPCR), immunohistochemistry (IHC), and hematoxyli", "d inflammation. External dataset validation, qPCR, correlation analysis, HE staining, and IHC", "colors representing changes in logFC. 3.7.1 qPCR analysis of NTF3 and EDN1 in normal skin and", "nd EDN1 in normal skin and keloid tissue The qPCR analysis of NTF3 and EDN1 mRNA expression le"], "order_basis": "paper_text_order:1079", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["lly validated using quantitative PCR (qPCR), immunohistochemistry (IHC), and hematoxylin-eosin (HE) staining.", "antitative PCR (qPCR), immunohistochemistry (IHC), and hematoxylin-eosin (HE) staining. 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At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}