{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41063917", "kind": "science-record", "revision": 4, "content_hash": "sha256:a5a976ba736cf8aae29152f8ab51b2f5ae9aafcb2d3c0c4422d3294b2eb9fd24", "created_at": "2026-11-01T20:31:07Z", "updated_at": "2026-11-01T22:57:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "401-Gene Signature of Myocardial Dysfunction in Human Heart Failure: A Transcriptomic Analysis.", "doi": "10.7759/cureus.91745", "pmid": "41063917", "authors": ["Kiki J Estes-Schmalzl", "Amy J Marcano-Reik", "Kristin M Lefebvre"], "journal": "Cureus", "year": 2025, "abstract": "Background Heart failure is a complex clinical syndrome characterized by the molecular remodeling of myocardial tissue that significantly impacts global health outcomes. Transcriptomic analysis offers powerful tools to identify disease-specific gene expression signatures and potential therapeutic targets. Methods We analyzed publicly available gene expression data from the Gene Expression Omnibus (GEO) dataset GSE57345, comprising 313 left ventricular tissue samples (295 controls, 18 heart failure) profiled using Affymetrix Human Gene 1.1 ST Arrays (Thermo Fisher Scientific, Waltham, Massachusetts, United States). Differential expression analysis was performed using limma with Benjamini-Hochberg multiple testing correction. Results We identified 401 significantly differentially expressed genes (adjusted p<0.05) between heart failure and control samples. The molecular signature showed balanced dysregulation with 198 genes upregulated and 203 genes downregulated in heart failure. Pathway analysis revealed significant enrichment in mitochondrial dysfunction, immune activation, and extracellular matrix remodeling pathways. Top dysregulated genes included AIDC1, SECA1, PVRL2, PLD1, and KTR3CL3, with high statistical significance (p<1×10⁻⁶) despite modest fold changes characteristic of complex disease pathophysiology. Cross-validation with established heart failure signatures showed significant overlap (31.7% concordance), confirming biological relevance. Conclusions This 401-gene transcriptomic signature provides insights into heart failure molecular mechanisms and represents a potential resource for biomarker development and therapeutic target identification. The balanced pattern of gene dysregulation reflects the comprehensive transcriptional remodeling underlying cardiac dysfunction and supports precision medicine approaches for heart failure diagnosis and treatment stratification.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis was performed using the limma package (version 3.54.0) [18] in R statistical software version 4.5.0 (R Foundation for Statistical Computing, Vienna, Austria) [19].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41063917", "locator": "sections[2] \"Materials and methods\" paragraph 8", "quote": "Differential expression analysis was performed using the limma package (version 3.54.0) [18] in R statistical software version 4.5.0 (R Foundation for Statistical Computing, Vienna, Austria) [19]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Primary data are publicly accessible through the GEO dataset GSE57345 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57345). Analysis code and processed results are available upon reasonable request from the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41063917", "locator": "sections[2] \"Materials and methods\" paragraph 16", "quote": "Primary data are publicly accessible through the GEO dataset GSE57345 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57345). Analysis code and processed results are available upon reasonable request from the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 401 significantly differentially expressed genes between heart failure and control samples.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "We identified 401 significantly differentially expressed genes (adjusted p<0.05) between heart failure and control samples."}, "evidence": [{"asset": "source:pmid:41063917", "locator": "sections[0] \"Abstract\" paragraph 6", "quote": "We identified 401 significantly differentially expressed genes (adjusted p<0.05) between heart failure and control samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 401 significantly differentially expressed genes between heart failure and control samples.", "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:41063917"], "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:GSE57345"], "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:GSE57345"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41063917", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7759/cureus.91745", "sha256": "sha256:f3229fb331092ecc54e5c82e40c6e9cce28df272acaad9f0a350671652b52c37", "bytes": 51993, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7759/cureus.91745", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12502992", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE57345", "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=GSE57345", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE57345", "version": null, "note": "Primary data are publicly accessible through the GEO dataset GSE57345 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57345). Analysis code and processed results are available upon reasonable request from the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Primary data are publicly accessible through the GEO dataset GSE57345 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57345). 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:41063917", "data:geo:GSE57345"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE57345"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:02:39Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11623, "completion_tokens": 801, "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:41063917", "type": "paper", "label": "pmid:41063917"}, {"id": "source:pmid:41063917", "type": "manuscript", "label": "PMID 41063917 full text"}, {"id": "data:geo:GSE57345", "type": "dataset", "label": "GEO GSE57345"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41063917", "type": "paper", "label": "pmid:41063917"}, {"id": "source:pmid:41063917", "type": "manuscript", "label": "PMID 41063917 full text"}, {"id": "data:geo:GSE57345", "type": "dataset", "label": "GEO GSE57345"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41063917", "type": "extraction", "used": ["source:pmid:41063917"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE57345", "type": "accession_resolution", "used": ["data:geo:GSE57345"], "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:41063917", "parent_hash": "sha256:d02a2129eccdd7508d14c9594d1cb6823ae81d4967d8e66df74a1bf91884f05a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE57345 licence not read", "asset:data:geo:GSE57345 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": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["5 controls, 18 heart failure) profiled using Affymetrix Human Gene 1.1 ST Arrays (Thermo Fisher Scie", "eserve RNA integrity prior to extraction and microarray processing. 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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. 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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}}}