{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37821869", "kind": "science-record", "revision": 4, "content_hash": "sha256:83bf907e3db547fe57f99e62dd192e3271cb78c22b181d937b4ee19879c1afe8", "created_at": "2026-11-01T19:02:41Z", "updated_at": "2026-11-01T22:10:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Ferroptosis-related potential biomarkers and immunocyte characteristics in Chronic Thromboembolic Pulmonary Hypertension via bioinformatics analysis.", "doi": "10.1186/s12872-023-03511-5", "pmid": "37821869", "authors": ["Jiangpeng Lin", "Shuangfeng Lin", "Yuzhuo Zhang", "Weihua Liu"], "journal": "BMC cardiovascular disorders", "year": 2023, "abstract": "BACKGROUND: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a form of pulmonary hypertension with a high mortality rate. A new type of iron-mediated cell death is Ferroptosis, which is characterized by the accumulation of lethal iron ions and lipid peroxidation leading to mitochondrial atrophy and increased mitochondrial membrane density. Now, there is a lack of Ferroptosis-related biomarkers (FRBs) associated with pathogenic process of CTEPH.\nMETHODS: The differentially expressed genes (DEGs) of CTEPH were obtained by GEO2R. Genes related to Ferroptosis were obtained from FerrDb database. The intersection of Ferroptosis and DEGs results in FRBs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed in Database for Annotation, Visualization and Integrated Discovery (DAVID) database. The optimal potential biomarkers for CTEPH were analyzed by least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) machine learning. The four hub genes were verified from the Gene Expression Omnibus (GEO) dataset GSE188938. Immune infiltration was analyzed by CIBERSORT. SPSS software was used to analyze the Spearman rank correlation between FRBs identified and infiltration-related immune cells, and p < 0.05 was considered as statistically significant.\nRESULTS: In this study, potential genetic biomarkers associated with Ferroptosis in CTEPH were investigated and explored their role in immune infiltration. In total, we identified 17 differentially expressed Ferroptosis-associated genes by GEOquery package. The key FRBs including ARRDC3, HMOX1, BRD4, and YWHAE were screened using Lasso and SVM-RFE machine learning methods.Through gene set GSE188938 verification, only upregulation of gene ARRDC3 showed statistical difference. In addition, immune infiltration analysis using the CIBERSORT algorithm revealed the infiltration of Eosinophils and Neutrophils in CTEPH samples was less than that in the control group. And correlation analysis revealed that ARRDC3 was positively correlated with T cells follicular helper (r = 0.554, p = 0.017) and negatively correlated with Neutrophils (r = -0.47, p = 0.049).\nCONCLUSIONS: In conclusion, ARRDC3 upregulation with different immune cell infiltration were involved in the development of CTEPH. ARRDC3 might a potential Ferroptosis-related biomarker for CTEPH treatment. This study provided a new insight into pathogenesis CTEPH.", "claims": [{"id": "claim-method", "statement": "SPSS software was used to analyze the Spearman rank correlation between FRBs identified and the level of related immune cells.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37821869", "locator": "sections[9] \"Correlation analysis between diagnostic biomarkers and infiltration-related immune cells\" paragraph 2", "quote": "SPSS software was used to analyze the Spearman rank correlation between FRBs identified and the level of related immune cells."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37821869", "locator": "sections[24] \"Availability of data and materials\" paragraph 2", "quote": "The data used to support the findings of this study are available from Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ARRDC3 was significantly upregulated in CTEPH, was positively correlated with T cells follicular helper, and was negatively correlated with neutrophils.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37821869", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Through gene set GSE188938 verification, only upregulation of gene ARRDC3 showed statistical difference."}, {"asset": "source:pmid:37821869", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "And correlation analysis revealed that ARRDC3 was positively correlated with T cells follicular helper (r = 0.554, p = 0.017) and negatively correlated with Neutrophils (r = -0.47, p = 0.049)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ARRDC3 was significantly upregulated in CTEPH, was positively correlated with T cells follicular helper, and was negatively correlated with neutrophils.", "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:37821869"], "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:GSE130391"], "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:GSE130391"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37821869", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12872-023-03511-5", "sha256": 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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":"2026-11-04T03:51:29+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. 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