{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41299729", "kind": "science-record", "revision": 3, "content_hash": "sha256:b49c14b8d19f3559efc44a991ec011f6d0482c3138ce51e3efd2de376e002a5e", "created_at": "2026-11-01T20:31:19Z", "updated_at": "2026-11-01T22:15:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptomic exploration combined with experimental validation: uncovering the potential value of biomarkers related to ammonia-induced cell death in hepatic ischemia-reperfusion injury.", "doi": "10.1186/s40001-025-03450-1", "pmid": "41299729", "authors": ["Runyu Zhuang", "Junhao Xiao", "Benliang Mao", "Yong Yan", "Wei Yuan", "Fan Wu", "Bailin Wang"], "journal": "European journal of medical research", "year": 2025, "abstract": "BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) represents the leading cause of postoperative liver dysfunction and failure. Ammonia-induced cell death (ACD), defined by lysosomal and mitochondrial disruption due to intracellular ammonia accumulation, appears to contribute to the pathogenesis of HIRI.\nMETHODS: Transcriptomic datasets GSE151648 and GSE12720 were retrieved from the Gene Expression Omnibus (GEO), and 467 ACD-related genes were compiled from published reports. Differential expression analysis combined with Weighted Gene Co-expression Network Analysis (WGCNA) was applied to identify candidate genes and assess their functional relevance. Biomarkers closely associated with HIRI were subsequently determined through protein-protein interaction (PPI) network construction, machine learning approaches, and expression validation. A nomogram was then established based on these biomarkers, followed by Gene Set Enrichment Analysis (GSEA), immune infiltration profiling, and network prediction. Furthermore, single-cell analysis was employed to investigate the expression of biomarkers across different cell types. Finally, liver tissues from HIRI mouse models were examined to confirm biomarker expression.\nRESULTS: A total of 586 differentially expressed genes intersected with 762 key module genes, yielding 39 candidates primarily enriched in inflammatory signaling pathways. Among these, LCP1, SLC16A3, and RGS2 emerged as biomarkers, each markedly upregulated in HIRI samples. The biomarker-based nomogram demonstrated robust diagnostic accuracy. Enrichment analyses indicated that the biomarkers were closely related to immune and metabolic pathways. Consistently, immune cell infiltration and immune functions were elevated in HIRI samples and correlated significantly with biomarker expression. Concurrently, single-cell analysis revealed that all three biomarkers were expressed within mononuclear phagocytes, with their expression levels exhibiting significant differences between the HIRI group and the control group. Moreover, multiple miRNAs and lncRNAs were predicted to interact with the identified biomarkers. Validation in HIRI mouse liver tissues confirmed consistency with transcriptomic findings.\nCONCLUSION: LCP1, SLC16A3, and RGS2 have been identified as biomarkers of HIRI. The study advances understanding of ACD-related genes signatures in HIRI and provides a foundation for future mechanistic research and therapeutic development.", "claims": [{"id": "claim-method", "statement": "Intergroup comparisons were assessed with the Wilcoxon test, applying a significance threshold of P < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41299729", "locator": "sections[16] \"Statistical analysis\" paragraph 2", "quote": "Intergroup comparisons were assessed with the Wilcoxon test, applying a significance threshold of P < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset(s) supporting the conclusions of this article is(are) available in the [GEO] at [https://www.ncbi.nlm.nih.gov/gds] with accession numbers (GSE151648，GSE171539 and GSE12720), [MSigDB] at [https://www.gsea-msigdb.org/gsea/msigdb].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41299729", "locator": "sections[35] \"Data availability\" paragraph 2", "quote": "The dataset(s) supporting the conclusions of this article is(are) available in the [GEO] at [https://www.ncbi.nlm.nih.gov/gds] with accession numbers (GSE151648，GSE171539 and GSE12720), [MSigDB] at [https://www.gsea-msigdb.org/gsea/msigdb]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "LCP1, SLC16A3, and RGS2 have been identified as biomarkers of HIRI.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41299729", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "LCP1, SLC16A3, and RGS2 have been identified as biomarkers of HIRI."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "LCP1, SLC16A3, and RGS2 have been identified as biomarkers of HIRI.", "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:41299729"], "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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Finally, liver tissues from HIRI mouse models were examined to confirm biomarker ex", "he identified biomarkers. Validation in HIRI mouse liver tissues confirmed consistency with tra"], "order_basis": "paper_text_order:1313", "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": ["nerated in Cytoscape software (v3.10.2). For RT-qPCR validation, group differences in biomarker e", "ated in Cytoscape software (v3.10.2). 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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}}}