{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41019433", "kind": "science-record", "revision": 3, "content_hash": "sha256:ce0daeae8710dd2d6c1677f9567257cf9109109b8a1b76aa84e6e7cc7d1f63cb", "created_at": "2026-11-01T20:31:05Z", "updated_at": "2026-11-01T22:14:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of aging-related genes and immune infiltration landscape in ischemic cardiomyopathy.", "doi": "10.3389/fcvm.2025.1653314", "pmid": "41019433", "authors": ["Zhichao Wu", "Liang Du", "Xunfu Zhang", "Chengyu Jin", "Jinshan Ma"], "journal": "Frontiers in cardiovascular medicine", "year": 2025, "abstract": "Background: Ischemic cardiomyopathy (ICM), which arises from obstructive coronary artery diseases, is a leading cause of heart failure. Aging is a major risk factor for cardiovascular diseases, yet its connection to ICM remains unclear. This study aimed to investigate the role of aging-related gene expression in the context of ICM.\nMethods: Human microarray data (GSE116250) were retrieved from the GEO database and aging-related differentially expressed genes (ARDEGs) were identified using the Aging Atlas database. Functional enrichment and protein-protein interaction (PPI) network analyses were performed to elucidate the functions and interactions of these ARDEGs, leading to the identification of hub genes. The immune infiltration landscape in ICM was further characterized. Subsequently, integrated regulatory networks involving the hub genes were constructed through microRNA-mRNA-transcription factor interaction and GeneMANIA analyses, while their biological functions were inferred via gene set enrichment analysis (GSEA). The predictive value of the hub genes was validated using receiver operating characteristic (ROC) analysis based on both the identification dataset (GSE116250) and an independent validation cohort (GSE1145) Finally,the expression patterns of these genes were verified by RT-qPCR on mouse disease model.\nResults: A total of 50 ARDEGs (42 upregulated and 8 downregulated) were identified,which are primarily involved in the response to inflammation. Ten types of immune cells showed significant alterations in the ICM heart tissues. Among these cells, CD56dim NK cells exhibited extensive and significant correlations with other immune cells. JUN was identified as a key transcription factor regulating the top five hub ARDEGs: TNF, PTGS2, IL6, IL1B, and CXCL8. ROC analysis demonstrated that TNF, CXCL8, and IL6 serve as potential biomarkers for ICM, and the combination of the three markers further improved the predictive value. RT-qPCR analysis subsequently confirmed the upregulation of these hub inflammatory ARDEGs in mouse heart tissues.\nConclusion: Aging-related genes play a significant role in ICM and targeting these genes may pave the way for ICM diagnostic and therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "Comparisons between the two groups were performed by using T-test analysis in GraphPad Prism (9.5.0).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41019433", "locator": "sections[16] \"Statistical analysis\" paragraph 2", "quote": "Comparisons between the two groups were performed by using T-test analysis in GraphPad Prism (9.5.0)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE116250 and GSE1145.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41019433", "locator": "sections[30] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE116250 and GSE1145."}], "state": "complete"}, {"id": "claim-target-result", "statement": "As expected, compared to the control group, the expression levels of Il6, Tnf, and IL1b were significantly upregulated in the MI group (P < 0.05, Figures 8D–F).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "As expected, compared to the control group, the expression levels of Il6, Tnf, and IL1b were significantly upregulated in the MI group (P < 0.05, Figures 8D–F)."}, "evidence": [{"asset": "source:pmid:41019433", "locator": "sections[25] \"Expression validation of hub ARDEGs in mouse MI model\" paragraph 2", "quote": "As expected, compared to the control group, the expression levels of Il6, Tnf, and IL1b were significantly upregulated in the MI group (P < 0.05, Figures 8D–F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "As expected, compared to the control group, the expression levels of Il6, Tnf, and IL1b were significantly upregulated in the MI group (P < 0.05, Figures 8D–F).", "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:41019433"], "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:GSE1145"], "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:GSE1145"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41019433", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2025.1653314", "sha256": "sha256:89c9359f7b3f72e569714cd138ab443bfeb8b62d4fbb878df78e4127febf432c", "bytes": 60972, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2025.1653314", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12461871", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1145", "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=GSE1145", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1145", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE116250 and GSE1145.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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This data can be found here: Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE116250 and GSE1145.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pearson_r"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pearson."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE116250", "GSE1145"], "resolved_accessions": ["GSE116250", "GSE1145"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE116250 and GSE1145."], "basis": "The paper names GSE116250, GSE1145 in Gene Expression Omnibus (GEO) repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pearson_r"], "assets": ["source:pmid:41019433", "data:geo:GSE1145"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE1145"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:02:19Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16676, "completion_tokens": 2312, "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:41019433", "type": "paper", "label": "pmid:41019433"}, {"id": "source:pmid:41019433", "type": "manuscript", "label": "PMID 41019433 full text"}, {"id": "data:geo:GSE1145", "type": "dataset", "label": "GEO GSE1145"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41019433", "type": "paper", "label": "pmid:41019433"}, {"id": "source:pmid:41019433", "type": "manuscript", "label": "PMID 41019433 full text"}, {"id": "data:geo:GSE1145", "type": "dataset", "label": "GEO GSE1145"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41019433", "type": "extraction", "used": ["source:pmid:41019433"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE1145", "type": "accession_resolution", "used": ["data:geo:GSE1145"], "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:41019433", "parent_hash": "sha256:4ae1d956331b5891cfd2d491ac3671289a6b425358a81157a6a377a30c56f1b1", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE1145 licence not read", "asset:data:geo:GSE1145 not downloaded", "asset:data:geo:GSE116250 licence not read", "asset:data:geo:GSE116250 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ession in the context of ICM. Methods: Human microarray data (GSE116250) were retrieved from the GEO"], "order_basis": "paper_text_order:412", "id": "assay:1"}, {"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": ["ion patterns of these genes were verified by RT-qPCR on mouse disease model. Results: A total of", "rkers further improved the predictive value. RT-qPCR analysis subsequently confirmed the upregula", "patterns of these genes were verified by RT-qPCR on mouse disease model. Results: A total of", "rs further improved the predictive value. RT-qPCR analysis subsequently confirmed the upregula"], "order_basis": "paper_text_order:1372", "id": "assay:2"}, {"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": ["s of these genes were verified by RT-qPCR on mouse disease model. Results: A total of 50 ARDEGs", "gulation of these hub inflammatory ARDEGs in mouse heart tissues. Conclusion: Aging-related gen", "aged male C57BL/6 mice (12 months old). The mice were obtained from the animal center of Xinjiang", "spital of Xinjiang Autonomous Region. 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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}}}