{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40727465", "kind": "science-record", "revision": 3, "content_hash": "sha256:ea999bcc17798c89715acc7354181d2436970cc86d6ea3ab80244c582b31c7b4", "created_at": "2026-11-01T20:30:50Z", "updated_at": "2026-11-01T22:14:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "ISLR as a Cuproptosis-Related Predictor and Therapeutic Target in Heart Failure: A Multi-Omics and Bioinformatics Approach.", "doi": "10.2147/JIR.S490041", "pmid": "40727465", "authors": ["Kai Huang", "Sufan Ding", "Xiangyang Xu", "Chuyi Wang", "Lin Han"], "journal": "Journal of inflammation research", "year": 2025, "abstract": "Background: The purpose of this study was to investigate the potential correlation between Cuproptosis, a newly recognized form of programmed cell death, and heart failure (HF), using an integrative multi-omics analysis.\nMethods: All the datasets were downloaded from GEO database. Cuproptosis-related genes (CRGs) were acquired from FerrDb V2 database. Differentially expressed CRGs were obtained in heart failure dataset (GSE57338). Cuproptosis subtypes were identified from HF samples in GSE57338 based on CRGs. CIBERSORT and GSVA analysis were used to explore the immune and pathway characteristics among Cuproptosis subtypes. WGCNA was used to determined the genes related to Cuproptosis subtypes and HF phenotype. The Cuproptosis-related predictive gene in heart failure were defined by machine learning and subjected to external validation. CTD database and molecular docking were applied to seek for the chemicals binding to the selected gene.\nResults: In the study, it was found that a total of 21 CRGs exhibited dysregulated expression in individuals with heart failure (HF). Furthermore, two distinct subtypes of Cuproptosis were identified. One hundred and three genes (related to Cuproptosis subtypes and HF phenotype) were put into machine learning algorithms and 6 predictive genes were filtered (HMOX2, MTSS1L, ISLR, GRB14, ARRDC3, and MEIS1). Notably, ISLR was found to be upregulated in both dilated cardiomyopathy and ischemic cardiomyopathy. Additionally, the efficacy of Pirinixic acid in providing heart protection against HF induced by pressure overload was demonstrated.\nConclusion: We identified six cuproptosis-related biomarkers (HMOX2, MTSS1L, ISLR, GRB14, ARRDC3, and MEIS1) in HF. Notably, ISLR was upregulated in HF. The PPARα agonist Pirinixic acid demonstrated therapeutic potential by downregulating ISLR expression, thereby attenuating pressure overload-induced cardiac dysfunction.", "claims": [{"id": "claim-method", "statement": "Student’s t-test was used to evaluate differences between two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40727465", "locator": "sections[13] \"Statistical Analysis\" paragraph 2", "quote": "Student’s t-test was used to evaluate differences between two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All human transcriptomic data used in this study (GSE57338, GSE120895, GSE203160, GSE161470) were obtained from the publicly accessible Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40727465", "locator": "sections[26] \"Ethical Statement\" paragraph 2", "quote": "All human transcriptomic data used in this study (GSE57338, GSE120895, GSE203160, GSE161470) were obtained from the publicly accessible Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified six cuproptosis-related biomarkers (HMOX2, MTSS1L, ISLR, GRB14, ARRDC3, and MEIS1) in HF.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40727465", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We identified six cuproptosis-related biomarkers (HMOX2, MTSS1L, ISLR, GRB14, ARRDC3, and MEIS1) in HF."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We identified six cuproptosis-related biomarkers (HMOX2, MTSS1L, ISLR, GRB14, ARRDC3, and MEIS1) in HF.", "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:40727465"], "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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"expressible": true, "required_operations": ["spearman_rho"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: spearman."}, "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": ["GSE57338", "GSE120895", "GSE203160", "GSE161470"], "resolved_accessions": ["GSE57338", "GSE120895", "GSE203160", "GSE161470"], "statements": ["All human transcriptomic data used in this study (GSE57338, GSE120895, GSE203160, GSE161470) were obtained from the publicly accessible Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE57338, GSE120895, GSE203160, GSE161470 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["spearman_rho"], "assets": ["source:pmid:40727465", "data:geo:GSE120895"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE120895"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:58:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13233, "completion_tokens": 2765, "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:40727465", "type": "paper", "label": "pmid:40727465"}, {"id": "source:pmid:40727465", "type": "manuscript", "label": "PMID 40727465 full text"}, {"id": "data:geo:GSE120895", "type": "dataset", "label": "GEO GSE120895"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40727465", "type": "paper", "label": "pmid:40727465"}, {"id": "source:pmid:40727465", "type": "manuscript", "label": "PMID 40727465 full text"}, {"id": "data:geo:GSE120895", "type": "dataset", "label": "GEO GSE120895"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40727465", "type": "extraction", "used": ["source:pmid:40727465"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE120895", "type": "accession_resolution", "used": ["data:geo:GSE120895"], "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:40727465", "parent_hash": "sha256:884145d595233f72a9fd5bdaad60274e64832555af58d0f1c346a9dc0a593cb1", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE120895 licence not read", "asset:data:geo:GSE120895 not downloaded", "asset:data:geo:GSE161470 licence not read", "asset:data:geo:GSE161470 not downloaded", "asset:data:geo:GSE203160 licence not read", "asset:data:geo:GSE203160 not downloaded", "asset:data:geo:GSE57338 licence not read", "asset:data:geo:GSE57338 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["3). Single Cell Analysis of Predictive Genes Single-cell RNA-seq profiling was conducted on GSE161470, encomp"], "order_basis": "paper_text_order:4975", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ell Analysis of Predictive Genes Single-cell RNA-seq profiling was conducted on GSE161470, encomp"], "order_basis": "paper_text_order:4987", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ssion of six hub genes was also validated by qPCR (Figure S5G). Nomogram to Distinguish HF Sam"], "order_basis": "paper_text_order:5790", "id": "assay:3"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["spearman_rho"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Spearman rank correlation"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]},"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":"2026-11-04T03:10:33+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}}}