{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41139197", "kind": "science-record", "revision": 4, "content_hash": "sha256:a79148b62725c88cd661ccf88d9d6231b610deba9c8e358a82f149fd117da574", "created_at": "2026-11-01T20:31:11Z", "updated_at": "2026-11-01T22:57:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mitochondria-associated endoplasmic reticulum membrane (MAM)-associated calpains system in preeclampsia.", "doi": "10.1186/s12884-025-08244-1", "pmid": "41139197", "authors": ["Cui Zhang", "Jingjing Jiang", "Hongfang Kong", "Xuyuan Ma", "Hong Xin"], "journal": "BMC pregnancy and childbirth", "year": 2025, "abstract": "BACKGROUND: Preeclampsia (PE) is a multisystem disorder characterized primarily by hypertension and proteinuria after 20 weeks of gestation, significantly impacting maternal and fetal health. The etiology remains unclear, but it is primarily attributed to placental dysfunction leading to systemic vascular endothelial damage and inflammatory responses. Mitochondria-associated endoplasmic reticulum membranes (MAMs) influence mitochondrial and endoplasmic reticulum (ER) function by regulating calcium homeostasis, autophagy, and apoptosis. In PE, mitochondrial dysfunction and ER stress have been widely observed. However, detailed investigations into the specific mechanisms and roles of MAMs in PE remain limited. Thus, this study aimed to investigate how MAM-associated biomarkers affect PE.\nMETHODS: The study involved 31 women with early-onset PE, 30 with late-onset PE, and 54 healthy controls matched for gestational age. Placental morphology and MAM structure in both PE and control tissues were assessed using Hematoxylin-Eosin (HE) staining and electron microscopy (EM). Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment. Real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to validate biomarker expression in PE placentas. Calpain-1, calpain-2, and calpastatin expression levels were evaluated using Immunofluorescence and Western blotting techniques.\nRESULTS: The results showed early-onset PE (EOPE) had higher abnormal pregnancy history, fetal growth restriction, systolic/diastolic ratio, and lower placental growth factor than late-onset PE (LOPE) and controls. Both PE types had fewer placental villi, but EOPE showed more severe ultrastructural changes in mitochondria-associated membranes. Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01). Immunofluorescence and Western blotting showed calpain-1 and calpastatin were decreased in EOPE, while calpain-2 was reduced in both PE types, with calpain-1 increased in LOPE.\nCONCLUSIONS: EOPE is characterized by placental dysfunction, with increased MAM contact observed in PE placentas.The calpain-calpastatin system may be involved in placental dysfunction in PE, with calpain-2 downregulation observed in both PE subtypes and calpain-1 dysregulation differing between EOPE and LOPE. These changes are accompanied by increased MAM contacts in PE placentas, suggesting a potential link between MAM structural abnormalities and calpain system dysregulation, with calpain-2 levels potentially associated with disease severity.", "claims": [{"id": "claim-method", "statement": "Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41139197", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data is provided within the manuscript or supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41139197", "locator": "sections[22] \"Data availability\" paragraph 2", "quote": "Data is provided within the manuscript or supplementary information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01).", "kind": "quantitative", "target": {"value": 0.01, "unit": "p-value", "tolerance": null, "source": "Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01)."}, "evidence": [{"asset": "source:pmid:41139197", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Bioinformatics identified CAST as potential MAM biomarkers, and its expression was significantly downregulated in PE samples (P < 0.01).", "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:41139197"], "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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In PE, mitochondrial dysfunction and ER str"], "order_basis": "paper_text_order:591", "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": ["rse transcriptase-polymerase chain reaction (RT-qPCR) was used to validate biomarker expression i", "transcriptase-polymerase chain reaction (RT-qPCR) was used to validate biomarker expression i"], "order_basis": "paper_text_order:1578", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tatin expression levels were evaluated using Immunofluorescence and Western blotting techniques. RESULTS: Th", "ntly downregulated in PE samples (P < 0.01). Immunofluorescence and Western blotting showed calpain-1 and ca", "(PBS), and part was fixed in 4% formalin for immunofluorescence and hematoxylin-eosin (HE) staining analysis"], "order_basis": "paper_text_order:1723", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["were evaluated using Immunofluorescence and Western blotting techniques. RESULTS: The results showed earl", "E samples (P < 0.01). Immunofluorescence and Western blotting showed calpain-1 and calpastatin were decrea", "remaining samples were stored at − 80 °C for Western blotting. Additionally, a 1 mm × 1 mm tissue sample w"], "order_basis": "paper_text_order:1747", "id": "assay:4"}, {"role": "analysis", "definition_id": "machine_learning", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["train_classifier", "cross_validate", "roc_auc"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets (GSE190971, GSE24129) identified MAMs-related genes (MAMs-RGs) and candidate biomarkers through weighted gene co-expression network analysis (WGCNA), machine learning algorithms (Least absolute shrinkage and selection operator, Support Vector Machine Recursive Feature Elimination), and functional enrichment."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. 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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}}}