{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41270284", "kind": "science-record", "revision": 4, "content_hash": "sha256:d0c55fdfe5a1a79566e895c70b8e689f9140030902d77dce2248bb2f9732762d", "created_at": "2026-11-01T20:31:18Z", "updated_at": "2026-11-01T22:57:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Serum miRNA-based diagnostic models for endometriosis: from discovery to validation.", "doi": "10.1093/humrep/deaf221", "pmid": "41270284", "authors": ["Antonella Ravaggi", "Cosetta Bergamaschi", "Jacopo Conforti", "Giuseppe Ciravolo", "Laura Zanotti", "Aline S C Fabricio", "Massimo Gion", "Elia Cappelletto", "Antonette E Leon", "Diego Oreste Rossetti", "Cesare Romagnolo", "Stefano Calza", "Eliana Bignotti", "Franco Odicino"], "journal": "Human reproduction (Oxford, England)", "year": 2025, "abstract": "STUDY QUESTION: Can a serum miRNA signature serve as a potential diagnostic biomarker for endometriosis (END)?\nSUMMARY ANSWER: A miRNA-based diagnostic model demonstrated an accuracy of 65.8% in distinguishing END patients from control subjects (CTR), demonstrating good sensitivity but limited specificity.\nWHAT IS KNOWN ALREADY: Existing research has examined the potential utility of circulating miRNAs as biomarkers for END diagnosis, revealing their differential expression between women with END and CTR. Nevertheless, the findings remain conflicting, and at present, neither a single miRNA nor a panel of them has yet been established as a reliable diagnostic test in clinical practice for the management of END.\nSTUDY DESIGN, SIZE, DURATION: We previously reported different miRNA expression patterns in serum samples from 67 END patients and 60 CTR by high-throughput RT-qPCR. In this multicenter study, a total of 364 patients with pathology-confirmed diagnosis of END or a benign non-END gynecological condition were retrospectively selected from a biobank or prospectively enrolled. The aims of the present study were to analyze, in the entire cohort of patients, a set of 23 potential diagnostic miRNAs via RT-qPCR and to create models capable of diagnosing END through cross-validated machine learning algorithms.\nPARTICIPANTS/MATERIALS, SETTING, METHODS: Total RNA was extracted from serum samples collected before surgical treatment and miRNAs were evaluated by RT-qPCR. Diagnostic models were developed using both the Random Forest and Logistic Regression algorithms. The performance assessment of the various models was derived from internal validation, using repeated cross-validation.\nMAIN RESULTS AND THE ROLE OF CHANCE: The most effective diagnostic model was constructed with 11 miRNAs: miR-140-3p, miR-181a-5p, miR-192-5p, miR-22-3p, miR-29a-3p, miR-30b-5p, miR-338-3p, miR-340-5p, miR-342-3p, miR-486-5p, and miR-652-3p. The diagnostic efficacy of the model was defined by an AUC of 70.4%, a sensitivity of 75.6%, a specificity of 53.5%, and an accuracy of 65.8%. The model that used six miRNAs (miR-192-5p, miR-30b-5p, miR-335-5p, miR-338-3p, miR-486-5p, miR-652-3p) was the best at identifying deep infiltrating endometriosis compared to the control group, with an AUC of 80.4% and an accuracy of 75.9%. A lower accuracy was achieved by the model differentiating ovarian endometrioma (OMA) from CTR (AUC = 65.8%; accuracy = 62.4%).\nLARGE SCALE DATA: miRNA expression profiles have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession numbers GSE279435.\nLIMITATIONS, REASONS FOR CAUTION: Despite the internal cross-validation, the models still need to be tested on larger cohorts of prospectively enrolled patients across several centers to enhance their accuracy and robustness. This testing will also facilitate monitoring the model in a real-world setting, potentially integrating the miRNA-based model with other diagnostic tools, such as ultrasound.\nWIDER IMPLICATIONS OF THE FINDINGS: If proven effective in larger cohorts, this model could serve as a tool for the diagnosis of END, thereby enhancing early identification and clinical care of this disease. Moreover, given its low false negative rate, the miRNA-based model may be useful as a screening tool to help identify patients who are likely to have END but warrant further evaluation to confirm END diagnosis.\nSTUDY FUNDING/COMPETING INTEREST(S): This research was financed by the Italian Ministry of Health, grant number \"LOMBARDIA ENDO-2021-12371946\", project title: FREEDOM TRIAL. The authors disclose no conflicts of interest.\nTRIAL REGISTRATION NUMBER: N/A.", "claims": [{"id": "claim-method", "statement": "Diagnostic models were constructed using two machine learning algorithms: Random Forest (RF) and Logistic Regression (LR), using default tuning parameters. The performance assessment of the various models was derived through internal validation via repeated cross-validation (5 repetitions, 5 folds).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41270284", "locator": "sections[8] \"Definition of diagnostic models\" paragraph 2", "quote": "Diagnostic models were constructed using two machine learning algorithms: Random Forest (RF) and Logistic Regression (LR), using default tuning parameters. The performance assessment of the various models was derived through internal validation via repeated cross-validation (5 repetitions, 5 folds)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw data of miRNA expression obtained by OpenArray technology have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO Series accession numbers GSE279435. The other data could be shared upon reasonable request to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41270284", "locator": "sections[20] \"Data availability\" paragraph 2", "quote": "Raw data of miRNA expression obtained by OpenArray technology have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO Series accession numbers GSE279435. The other data could be shared upon reasonable request to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The RF model based on 11 miRNAs (miR-140-3p, miR-181a-5p, miR-192-5p, miR-22-3p, miR-29a-3p, miR-30b-5p, miR-338-3p, miR-340-5p, miR-342-3p, miR-486-5p, and miR-652-3p) showed an AUC of 70.4%, a sensitivity of 75.6%, and a specificity of 53.5% in differentiating END from CTR.", "kind": "quantitative", "target": {"value": 70.4, "unit": "auc", "tolerance": null, "source": "The RF model based on 11 miRNAs (miR-140-3p, miR-181a-5p, miR-192-5p, miR-22-3p, miR-29a-3p, miR-30b-5p, miR-338-3p, miR-340-5p, miR-342-3p, miR-486-5p, and miR-652-3p) showed an AUC of 70.4%, a sensitivity of 75.6%, and a specificity of 53.5% in differentiating END from CTR."}, "evidence": [{"asset": "source:pmid:41270284", "locator": "sections[14] \"Development and internal validation of miRNA-based diagnostic models from RT-qPCR data\" paragraph 2", "quote": "The RF model based on 11 miRNAs (miR-140-3p, miR-181a-5p, miR-192-5p, miR-22-3p, miR-29a-3p, miR-30b-5p, miR-338-3p, miR-340-5p, miR-342-3p, miR-486-5p, and miR-652-3p) showed an AUC of 70.4%, a sensitivity of 75.6%, and a specificity of 53.5% in differentiating END from CTR."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The RF model based on 11 miRNAs (miR-140-3p, miR-181a-5p, miR-192-5p, miR-22-3p, miR-29a-3p, miR-30b-5p, miR-338-3p, miR-340-5p, miR-342-3p, miR-486-5p, and miR-652-3p) showed an AUC of 70.4%, a sensitivity of 75.6%, and a specificity of 53.5% in differentiating END from CTR.", "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:41270284"], "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:GSE279435"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:machine_learning_random_forest", "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:GSE279435"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:machine_learning_random_forest"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41270284", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1093/humrep/deaf221", "sha256": "sha256:adc87d5b902e02b2e0abed6beafab06d341ec1e1c73c37339042a1ab196f861f", "bytes": 36811, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1093/humrep/deaf221", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12864148", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE279435", "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=GSE279435", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE279435", "version": null, "note": "Raw data of miRNA expression obtained by OpenArray technology have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO Series accession numbers GSE279435. 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No tolerance is published because the paper states none."}], "gaps": ["method.machine_learning_random_forest"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["machine_learning_random_forest"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: random_forest."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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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}}}