{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40624500", "kind": "science-record", "revision": 4, "content_hash": "sha256:fd14aefd730bd008d4d9d1e86506aaaf076e3dd90581ad4defb72f8bfcfb32ad", "created_at": "2026-11-01T20:30:43Z", "updated_at": "2026-11-01T22:56:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Vagus nerve stimulation inhibits pyroptosis and improves outcome of cerebral ischemic stroke by upregulating osteopontin (SPP1) to disturb ASC oligomerization.", "doi": "10.1186/s12916-025-04242-4", "pmid": "40624500", "authors": ["Jun Wen", "Hao Tang", "Ling Wang", "Qinghuan Yang", "Yong Zhao", "Yu Ren", "Ting Qin", "Xuemei Li", "Jianfeng Xu", "Gongwei Jia", "Qin Yang"], "journal": "BMC medicine", "year": 2025, "abstract": "BACKGROUND: Vagus nerve stimulation (VNS) brings new hope for handling stroke. Our previous study confirmed that VNS could reduce neuronal pyroptosis and improve stroke prognosis. However, how VNS suppresses pyroptosis remains poorly understood. Osteopontin (OPN,SPP1) plays a neuroprotective role. Therefore, this study aims to determine whether vagus nerve stimulation (VNS) inhibits pyroptosis and promotes recovery from cerebral ischemic injury through osteopontin (OPN), and to elucidate the mechanisms by which OPN regulates pyroptosis.\nMETHODS: Acute ischemic stroke (AIS) patients and healthy controls were recruited. The middle cerebral artery ischemia-reperfusion (MCAO/R) model of rats in vivo, the oxygen-glucose deprivation and reperfusion (OGD/R) and lipopolysaccharide (LPS) + adenosine triphosphate (ATP) models of microglia in vitro were established. Gene analysis of GEO public dataset (GSE61616), analysis of proteomics, western blotting, Co-immunoprecipitation (Co-IP) analysis, immunofluorescence staining, ELISA, TTC staining, TUNEL staining, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and neurological function score were used to examinate expressions or concentrations of osteopontin, pyroptosis-related molecules, OPN-ASC interaction, infarct volume, neurological function, cell membrane pore, respectively.\nRESULTS: In MCAO/R rats and AIS patients, osteopontin levels were elevated. Intranasally administered recombinant osteopontin (rOPN) and VNS reduced pyroptosis and improved neurological deficits. VNS upregulated osteopontin expression in MCAO/R rats and AIS patients. Small interfering OPN RNA (siOPN) reversed effects of VNS on pyroptosis and outcome of MCAO/R injury in rats. The binding energy of OPN and ASC was -11.7 kcal/mol. LPS + ATP enhanced OPN-ASC interaction, and rOPN interfered with ASC oligomerization. Conditioned medium of microglia treated with rOPN reversed LPS + ATP-induced neruonal injury. Collectively, OPN may serve as a potential mediator through which VNS inhibits pyroptosis and improves the outcome of ischemic stroke, thereby representing a promising therapeutic target for stroke treatment.\nCONCLUSIONS: These findings suggest that VNS alleviates pyroptosis and improves the outcome of cerebral ischemic stroke by upregulating osteopontin (OPN), which interferes with ASC oligomerization.", "claims": [{"id": "claim-method", "statement": "Data normality was assessed using the Shapiro–Wilk test. For comparisons between two groups, a two-tailed unpaired Student’s t-test was applied. For comparisons involving more than two groups, one-way analysis of variance (ANOVA) was performed, followed by Tukey’s multiple comparisons test as the post-hoc analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40624500", "locator": "sections[21] \"Statistical analysis\" paragraph 2", "quote": "Data normality was assessed using the Shapiro–Wilk test. For comparisons between two groups, a two-tailed unpaired Student’s t-test was applied. For comparisons involving more than two groups, one-way analysis of variance (ANOVA) was performed, followed by Tukey’s multiple comparisons test as the post-hoc analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We would like to clarify that the proteomics dataset generated in this study is currently being used in additional unpublished studies. As such, the data are not publicly available at this stage, but are available from the corresponding author upon reasonable request and will be made publicly accessible following the publication of those subsequent studies.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40624500", "locator": "sections[41] \"notes\" paragraph 1", "quote": "We would like to clarify that the proteomics dataset generated in this study is currently being used in additional unpublished studies. As such, the data are not publicly available at this stage, but are available from the corresponding author upon reasonable request and will be made publicly accessible following the publication of those subsequent studies."}], "state": "complete"}, {"id": "claim-target-result", "statement": "These findings suggest that VNS alleviates pyroptosis and improves the outcome of cerebral ischemic stroke by upregulating osteopontin (OPN), which interferes with ASC oligomerization.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40624500", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "These findings suggest that VNS alleviates pyroptosis and improves the outcome of cerebral ischemic stroke by upregulating osteopontin (OPN), which interferes with ASC oligomerization."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "These findings suggest that VNS alleviates pyroptosis and improves the outcome of cerebral ischemic stroke by upregulating osteopontin (OPN), which interferes with ASC oligomerization.", "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:40624500"], "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:GSE61616"], "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:GSE61616"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40624500", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12916-025-04242-4", "sha256": "sha256:8524ed4f2e4fc240d0e0717a830fb40047a43b6b86ec0ff4a038845017fd0943", "bytes": 56901, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12916-025-04242-4", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12235890", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE61616", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61616", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE61616", "version": null, "note": "We would like to clarify that the proteomics dataset generated in this study is currently being used in additional unpublished studies. 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The binding energy of OPN and ASC was -11.7", "rtery ischemia-reperfusion (MCAO/R) model of rats in vivo, the oxygen-glucose deprivation and", "brane pore, respectively. RESULTS: In MCAO/R rats and AIS patients, osteopontin levels were el"], "order_basis": "paper_text_order:807", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["dataset (GSE61616), analysis of proteomics, western blotting, Co-immunoprecipitation (Co-IP) analysis, im", "roup in rats (Fig. 2A-C). ELISA analysis and western blotting showed that osteopontin concentration in ser", "ion data in the sham and MCAO/R 3 d group by Western blotting in cerebral tissue of rats (n=5). G Regional", "fication data in the TBI and AIS patients by Western blotting (n=3). M-N Representative immunofluorescence"], "order_basis": "paper_text_order:1056", "id": "assay:2"}, {"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": ["ng, Co-immunoprecipitation (Co-IP) analysis, immunofluorescence staining, ELISA, TTC staining, TUNEL stainin", "ham group in rats, respectively (Fig. 2D-F). Immunofluorescence staining analysis indicated that osteopontin", "rfusion (MCAO/R) in rats. H-I Representative immunofluorescence images depicting expression of OPN in neuron", "y Western blotting (n=3). M-N Representative immunofluorescence images depicting expression of OPN in neuron"], "order_basis": "paper_text_order:1114", "id": "assay:3"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["o-IP) analysis, immunofluorescence staining, ELISA, TTC staining, TUNEL staining, transmission", "her in the MCAO/R group in rats (Fig. 2A-C). ELISA analysis and western blotting showed that os", "n serum in the sham and MCAO/R 3 d groups by ELISA in rats (n=18). E-F OPN expression and quant", "hy control (n=20) and AIS patients (n=22) by ELISA. K-L OPN expression and quantification data"], "order_basis": "paper_text_order:1143", "id": "assay:4"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["to investigate the gene-silencing effect of siRNA targeting osteopontin (OPN). (6) Sham, MCAO/"], "order_basis": "paper_text_order:5969", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Data normality was assessed using the Shapiro–Wilk test. 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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. 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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}}}