{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40589609", "kind": "science-record", "revision": 3, "content_hash": "sha256:2ffea62eae182ea240a130f744e0cffff8577d3c06e891c1c2a7a777c4315a17", "created_at": "2026-11-01T20:30:40Z", "updated_at": "2026-11-01T22:14:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploration and Validation of Key Genes and Immune Infiltration in Alcoholic Hepatitis.", "doi": "10.2147/JIR.S514515", "pmid": "40589609", "authors": ["Yingna Mei", "Yitao Zheng", "Xingfen Zhang", "Ting Hu", "Xiaoqing Zheng", "Cui Zhang", "Qinzhi Deng"], "journal": "Journal of inflammation research", "year": 2025, "abstract": "Objective: Apart from alcohol abstinence and glucocorticoids, there is still no effective treatment to improve alcoholic hepatitis, and the specific mechanism of its pathogenesis is still unclear.\nMethods: We screened the differential genes in GEO alcoholic hepatitis database by differential analysis and screened the eQTL genes that have causal relationship with alcoholic hepatitis by Mendelian randomization analysis. The intersection of differential genes and eQTL genes was used to obtain candidate genes. The candidate genes were then screened out by machine learning, and their expression was further verified in clinical patients and mice with alcoholic hepatitis. Based on key genes, pathway analysis via single-gene GSEA analysis and immune microenvironment analysis via ssGSEA analysis were conducted to explore the relationship between key genes and immune microenvironment. Finally, regulatory relationship between key genes and immune cells was explored based on cell experiments.\nResults: Based on the GEO Alcoholic hepatitis database (GSE28619 and GSE142530) and Mendelian randomization of eQTL genes, we obtained 17 candidate genes. We then obtained two key genes (CXCL8 and CTNNA1) through lasso and random forest tree algorithms. CXCL8 and CTNNA1 were highly expressed in the alcoholic hepatitis group, which were verified in clinical patients and mice. Through single-gene GSEA analysis, two key genes were identified to be enriched in the antigen presentation pathway. At the same time, the alcoholic hepatitis group had obvious immune infiltration disorder, and two key genes were correlated with immune environment via correlation analysis. B cells and NKT cells exhibited the highest correlation with key genes. In alcoholic hepatitis mice, liver infiltration of B cells and NKT cells was verified. Through cell experiments, ethanol exposure increased CTNNA1 and CXCL8 expression in NKT and B cells, enhancing inflammatory cytokine release and suppressing IgG production, respectively. Silencing CXCL8 and CTNNA1 reversed these effects.\nConclusion: These results suggested that CXCL8 and CTNNA1 were potential biomarkers for alcoholic hepatitis, and might be new targets for the treatment of alcoholic hepatitis.", "claims": [{"id": "claim-method", "statement": "Using Pearson correlation analysis test the relationship between the key genes and immune microenvironment.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40589609", "locator": "sections[11] \"Comparison of the Immune Microenvironment Between AH and Normal Groups\" paragraph 2", "quote": "Using Pearson correlation analysis test the relationship between the key genes and immune microenvironment."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE28619 (15 AH vs 7 control), GSE142530 (13 AH vs 16 control) and GSE155907 (5 AH vs 4 control) datasets were downloaded from the Gene Expression Omnibus database, and sequenced using the GPL570, GLP11154 and GPL21290 platforms.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40589609", "locator": "sections[3] \"Data Acquisition\" paragraph 2", "quote": "The GSE28619 (15 AH vs 7 control), GSE142530 (13 AH vs 16 control) and GSE155907 (5 AH vs 4 control) datasets were downloaded from the Gene Expression Omnibus database, and sequenced using the GPL570, GLP11154 and GPL21290 platforms."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Two key genes, CXCL8 and CTNNA1, were obtained through lasso and random forest tree algorithms.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40589609", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We then obtained two key genes (CXCL8 and CTNNA1) through lasso and random forest tree algorithms."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Two key genes, CXCL8 and CTNNA1, were obtained through lasso and random forest tree algorithms.", "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:40589609"], "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:GSE142530"], "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:GSE142530"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40589609", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/JIR.S514515", "sha256": 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"platform": "11154", "taxon": "Homo sapiens", "title": "Integrated Multi-Omics Analysis Reveals Glucose Metabolic Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE155907", "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=GSE155907", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE155907", "version": null, "note": "The GSE28619 (15 AH vs 7 control), GSE142530 (13 AH vs 16 control) and GSE155907 (5 AH vs 4 control) datasets were downloaded from the Gene Expression Omnibus database, and sequenced using the GPL570, GLP11154 and GPL21290 platforms.", "structure": {"repository": "GEO", 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pearson_r"], "assets": ["source:pmid:40589609", "data:geo:GSE142530"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE142530"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:55:14Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 11504, "completion_tokens": 1375, "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:40589609", "type": "paper", "label": "pmid:40589609"}, {"id": "source:pmid:40589609", "type": "manuscript", "label": "PMID 40589609 full text"}, {"id": "data:geo:GSE142530", "type": "dataset", "label": "GEO GSE142530"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40589609", "type": "paper", "label": "pmid:40589609"}, {"id": "source:pmid:40589609", "type": "manuscript", "label": "PMID 40589609 full text"}, {"id": "data:geo:GSE142530", "type": "dataset", "label": "GEO GSE142530"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40589609", "type": "extraction", "used": ["source:pmid:40589609"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE142530", "type": "accession_resolution", "used": ["data:geo:GSE142530"], "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:40589609", "parent_hash": "sha256:da2479d8078d82042a009abd1a7a515e4fe58dd74cdb40e499bb77831edd03ba", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE142530 licence not read", "asset:data:geo:GSE142530 not downloaded", "asset:data:geo:GSE155907 licence not read", "asset:data:geo:GSE155907 not downloaded", "asset:data:geo:GSE28619 licence not read", "asset:data:geo:GSE28619 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": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["purchased from FUHENG BIOLOGY (FH1258). Two cell lines were cultured in 1640 medium supplemented with 10% fetal b", "FUHENG BIOLOGY (FH1258). Two cell lines were cultured in 1640 medium supplemented with 10% fetal bovi"], "order_basis": "paper_text_order:4045", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["as treated for 24h.28 After that, cells were transfected with siRNAs (siCXCL8 and siCTNNA1) (General", "for subsequent experiments. The sequence of siRNA primers was shown in Table 1.Table 1Sequence"], "order_basis": "paper_text_order:4399", "id": "assay:2"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["c Hepatitis Patients and Mice We applied the Elisa assay to evaluate CXCL8 and CTNNA1 levels in"], "order_basis": "paper_text_order:5109", "id": "assay:3"}, {"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": ["ssfully constructed. CXCL8 was not expressed in mice. It has been reported that CXCL2 in mice cou", "sed in mice. It has been reported that CXCL2 in mice could replace CXCL8 in humans.29 Thus, we ap", "evaluated the expression of CXCL2 and CTNNA1 in mice liver. CTNNA1 and CXCL2 levels were increase"], "order_basis": "paper_text_order:6414", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["replace CXCL8 in humans.29 Thus, we applied immunohistochemical staining to evaluated the expression of CXCL"], "order_basis": "paper_text_order:6514", "id": "assay:5"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Using Pearson correlation analysis test the relationship between the key genes and immune microenvironment."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]},"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. 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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. 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}}}