{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38198162", "kind": "science-record", "revision": 4, "content_hash": "sha256:de03120fb06f8698c36610edf742137c671acecbccbca226cc36a926c4cc4d8b", "created_at": "2026-11-01T19:20:07Z", "updated_at": "2026-11-01T22:53:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Novel diagnostic biomarkers of oxidative stress, ferroptosis, immune infiltration characteristics and experimental validation in ischemic stroke.", "doi": "10.18632/aging.205415", "pmid": "38198162", "authors": ["Kaisheng Yuan", "Xiao Jin", "Xiaocong Mo", "Ruiqi Zeng", "Xu Zhang", "Qiufang Chen", "Ling Jin"], "journal": "Aging", "year": 2024, "abstract": "Ischemic stroke (IS) is a prominent type of cerebrovascular disease leading to death and disability in an aging society and is closely related to oxidative stress. Gene expression profiling (GSE222551) was derived from Gene Expression Omnibus (GEO), and 1934 oxidative stress (OS) genes were obtained from the GeneCards database. Subsequently, we identified 149 differentially expressed genes related to OS (DEOSGs). Finally, PTGS2, FOS, and RYR1 were identified as diagnostic markers of IS. Moreover, GSE16561 was used to validate the DEOSGs. Two diagnostic genes (PTGS2 and FOS) were significantly highly expressed, while RYR1 was significantly lowly expressed in the IS group. Remarkably, immune infiltration characteristics of these three genes were analyzed, and we found that PTGS2, FOS, and RYR1 were mainly correlated with Mast cells activated, Neutrophils, and Plasma cells, respectively. Next, we intersected three DEOSGs with the ferroptosis gene set, the findings revealed that only PTGS2 was a differentially expressed gene of ferroptosis. High PTGS2 expression levels in the infarcted cortex of middle cerebral artery occlusion (MCAO) rats were confirmed by immunofluorescence (IF), western blotting (WB), and Immunohistochemistry (IHC). Inhibition of PTGS2 clearly improved the neurological outcome of rats by decreasing infarct volume, neurological problems, and modified neurological severity scores following IS compared with the controls. The protective effect of silencing PTGS2 may be related to anti-oxidative stress and ferroptosis. In conclusion, this work may provide a new perspective for the research of IS, and further research based on PTGS2 may be a breakthrough.", "claims": [{"id": "claim-method", "statement": "The analysis of differentially expressed genes was executed by the “limma” package with the criteria of the adjusted P-value <0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38198162", "locator": "sections[3] \"Data collection and processing\" paragraph 2", "quote": "The analysis of differentially expressed genes was executed by the “limma” package with the criteria of the adjusted P-value <0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) in this study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38198162", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "The datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) in this study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using limma analysis of GSE22255, the study identified 1,766 differentially expressed genes and 149 differentially expressed oxidative-stress genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38198162", "locator": "sections[21] \"Identification of DEGs and DEOSGs\" paragraph 2", "quote": "The analysis of differentially expressed genes (DGEs) (GSE22255) was performed by the “limma” package. A total of 1766 DEGs were obtained."}, {"asset": "source:pmid:38198162", "locator": "sections[21] \"Identification of DEGs and DEOSGs\" paragraph 2", "quote": "Among the DEGs and OS genes, there were 149 overlapping items between DEGs and OS genes (Figure 2C). Here, we selected the 149 DEOSGs overlapping for subsequent researches."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using limma analysis of GSE22255, the study identified 1,766 differentially expressed genes and 149 differentially expressed oxidative-stress genes.", "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:38198162"], "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:GSE16561"], "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:GSE16561"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38198162", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.18632/aging.205415", "sha256": 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"access_statement_verbatim": "The datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) in this study.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM554014", "GSM554015", "GSM554016", "GSM554017", "GSM554018", "GSM554019", "GSM554020", "GSM554021", "GSM554022", "GSM554023", "GSM554024", "GSM554025", "GSM554026", "GSM554027", "GSM554028", "GSM554029", "GSM554030", "GSM554031", "GSM554032", "GSM554033", "GSM554034", "GSM554035", "GSM554036", "GSM554037", "GSM554038", "GSM554039", "GSM554040", "GSM554041", "GSM554042", "GSM554043", "GSM554044", "GSM554045", "GSM554046", "GSM554047", "GSM554048", "GSM554049", "GSM554050", "GSM554051", "GSM554052", "GSM554053"], "sample_count": 40, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Blood genomic expression profile for ischemic stroke (IS)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE22255", "GSE16561"], "resolved_accessions": ["GSE22255", "GSE16561"], "statements": ["The datasets were downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) in this study."], "basis": "The paper names GSE22255, GSE16561 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:38198162", "data:geo:GSE16561"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE16561"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:04:38Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13264, "completion_tokens": 1428, "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:38198162", "type": "paper", "label": "pmid:38198162"}, {"id": "source:pmid:38198162", "type": "manuscript", "label": "PMID 38198162 full text"}, {"id": "data:geo:GSE16561", "type": "dataset", "label": "GEO GSE16561"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38198162", "type": "paper", "label": "pmid:38198162"}, {"id": "source:pmid:38198162", "type": "manuscript", "label": "PMID 38198162 full text"}, {"id": "data:geo:GSE16561", "type": "dataset", "label": "GEO GSE16561"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38198162", "type": "extraction", "used": ["source:pmid:38198162"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE16561", "type": "accession_resolution", "used": ["data:geo:GSE16561"], "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:38198162", "parent_hash": "sha256:2094d3399c9914121d64e417af20acbb34928898d9e013576a5c2364c1c98a51", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE16561 licence not read", "asset:data:geo:GSE16561 not downloaded", "asset:data:geo:GSE22255 licence not read", "asset:data:geo:GSE22255 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["x of middle cerebral artery occlusion (MCAO) rats were confirmed by immunofluorescence (IF), wester", "x of middle cerebral artery occlusion (MCAO) rats were confirmed by immunofluorescence (IF), w", "clearly improved the neurological outcome of rats by decreasing infarct volume, neurological p", "tudy, healthy adult male Sprague-Dawley (SD) rats weighing between 220–250 g were provided by"], "order_basis": "paper_text_order:1250", "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": ["luorescence (IF), western blotting (WB), and Immunohistochemistry (IHC). Inhibition of PTGS2 clearly improved", "tery occlusion (MCAO) rats were confirmed by immunofluorescence (IF), western blotting (WB), and Immunohisto", "ern blotting (WB), and Immunohistochemistry (IHC). Inhibition of PTGS2 clearly improved the n"], "order_basis": "paper_text_order:1273", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["s were confirmed by immunofluorescence (IF), western blotting (WB), and Immunohistochemistry (IHC). Inhibi"], "order_basis": "paper_text_order:1298", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["in cortex of newborn rats (24 hours old) and cultured in humidified incubator as previously depicted", "penicillin (100 U/mL). The neuron cells were cultured in 37°C humidified incubator containing 5% CO2", "t, neuron cells were firstly washed and then cultured in glucose-free DMEM in humidified hypoxic incu", "The negative control was neuron cells which cultured in normoxia. Statistical analysis Differences w"], "order_basis": "paper_text_order:2511", "id": "assay:4"}, {"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 analysis of differentially expressed genes was executed by the “limma” package with the criteria of the adjusted P-value <0.05."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]},"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":"2026-11-04T04:17:07+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}}}