{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40787256", "kind": "science-record", "revision": 4, "content_hash": "sha256:d1379dfcf13faa32d534ef4ca9c943a14f89f7c6497a30552f26f158ebbc53ad", "created_at": "2026-11-01T20:30:52Z", "updated_at": "2026-11-01T22:56:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Unveiling the Temporal Dynamics and Molecular Regulation Profiles of Neutrophil Extracellular Traps Following Spinal Cord Injury.", "doi": "10.2147/JIR.S530446", "pmid": "40787256", "authors": ["Jinze Li", "Chao Chang", "Yanqiu Li", "Shengyu Cui", "Jun Bai", "Can Zhang", "Xinyu Wang", "Kang Li", "Fengzeng Jian"], "journal": "Journal of inflammation research", "year": 2025, "abstract": "Background: Spinal cord injury (SCI) initiates secondary inflammatory processes that exacerbate tissue damage, with neutrophil extracellular traps (NETs) playing a significant role in amplifying these cascades. This study aimed to explore the temporal dynamics and key regulatory genes of NET formation in SCI to identify therapeutic targets.\nMethods: We integrated two transcriptomic datasets from the GEO database to identify differentially expressed NETs-related genes (NRGs) in SCI. WGCNA identified SCI-related modules, while GSVA assessed NET formation dynamics. Publicly available single-cell RNA sequencing data from the GEO database determined cell-specific expression patterns of key NRGs. Findings were validated through immunofluorescence, Western blot, and qPCR in a mouse SCI model. Regulatory networks were constructed, and potential therapeutic compounds were predicted using DSigDB and molecular docking.\nResults: We identified seven key NRGs (Casp1, Ccl3, Fcgr2b, Itgam, Itgb2, Tlr2, Tlr4) in SCI. GSVA revealed peak NET score at day 1 post-injury, with attenuation at days 3 and 7. Single-cell transcriptome analysis demonstrated predominant expression of these key genes in neutrophils during the acute phase, most prominently at 1 day post-injury, which coincides with the most pronounced neutrophil infiltration. Immunofluorescence and Western blot analyses confirmed significantly elevated NET formation at 1 day post-SCI. qPCR verified the expression of all key NRGs. Regulatory network analysis identified CHD1 as an important transcription factor governing NET formation, while miRNA-mRNA network construction revealed sophisticated post-transcriptional regulation mechanisms. Drug prediction analysis identified atorvastatin as a promising therapeutic candidate with strong binding affinity to multiple key NET-related proteins.\nConclusion: Our study provides insights into the temporal dynamics and molecular mechanisms of NET formation after SCI, identifying potential therapeutic targets to mitigate neutrophil-mediated secondary injury and improve functional outcomes.", "claims": [{"id": "claim-method", "statement": "The limma package was utilized to conduct differential expression analysis, comparing the SCI-1d, SCI-3d, and SCI-7d groups against the Sham group.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40787256", "locator": "sections[4] \"Data Processing and the Identification of NETs-Related DEGs\" paragraph 2", "quote": "The limma package was utilized to conduct differential expression analysis, comparing the SCI-1d, SCI-3d, and SCI-7d groups against the Sham group."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data generated in this study are publicly available in the Gene Expression Omnibus (GEO) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40787256", "locator": "sections[32] \"Data Sharing Statement\" paragraph 2", "quote": "The data generated in this study are publicly available in the Gene Expression Omnibus (GEO) database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Twenty-two differentially expressed NETs-related genes were shared across all three post-SCI time points.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40787256", "locator": "sections[19] \"Identification of Differentially Expressed NETs-Related Genes in SCI\" paragraph 4", "quote": "The Venn diagram analysis revealed 22 shared DENRGs that were consistently differentially expressed across all three time points (1d, 3d, and 7d) post-SCI (Figure 1G)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Twenty-two differentially expressed NETs-related genes were shared across all three post-SCI time points.", "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:40787256"], "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. 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Publicly available single-cell RNA sequencing data from the GEO database determined cell-s", "rapeutic targets. Methods: We integrated two transcriptomic datasets from the GEO database to identify d", "ith attenuation at days 3 and 7. Single-cell transcriptome analysis demonstrated predominant expression", "tomic analysis. Importantly, our single-cell RNA sequencing data demonstrated that these genes are predo"], "order_basis": "paper_text_order:455", "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": ["of key NRGs. Findings were validated through immunofluorescence, Western blot, and qPCR in a mouse SCI model", "the most pronounced neutrophil infiltration. 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Immunofluorescence and Western blot analyses confirmed significantly elevated NE", "munofluorescence analysis (n = 6 per group), Western blot analysis (n = 3 per group), qPCR analysis (n"], "order_basis": "paper_text_order:837", "id": "assay:3"}, {"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": ["hrough immunofluorescence, Western blot, and qPCR in a mouse SCI model. Regulatory networks we", "ly elevated NET formation at 1 day post-SCI. qPCR verified the expression of all key NRGs. Reg", "p), Western blot analysis (n = 3 per group), qPCR analysis (n = 6 per group), and in vitro neu", "mental Validation of Key Genes Expression by qPCR To validate the expression of key NETs-relat"], "order_basis": "paper_text_order:855", "id": "assay:4"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["unofluorescence, Western blot, and qPCR in a mouse SCI model. Regulatory networks were construc", "estricted access to nutrition and hydration. Mice were group-housed (4–5 mice per cage) in standard", "reated neutrophils (p < 0.05) (n = 6). (C–I) In vivo qPCR validation of key NRGs in spinal cord t"], "order_basis": "paper_text_order:865", "id": "assay:5"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["profile of peripheral blood samples from SCI patients were extracted for validation. The results showed", "in the gene expression profile of peripheral blood samples from SCI patients were extracted for validation.", "Validation of eight hub genes in peripheral blood samples from SCI patients compared to healthy controls. B"], "order_basis": "paper_text_order:9981", "id": "assay:6"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The limma package was utilized to conduct differential expression analysis, comparing the SCI-1d, SCI-3d, and SCI-7d groups against the Sham group."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T00:30:49+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. 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}}}