{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41272316", "kind": "science-record", "revision": 4, "content_hash": "sha256:8c62b53e195b5a041385ce9aadd19781c52a98563cc16114d60cf7404969caac", "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": "LETM2 regulates mitochondrial function and autophagy in diabetic foot ulcers: implications for oxidative stress and therapeutic targeting.", "doi": "10.1007/s10142-025-01748-1", "pmid": "41272316", "authors": ["Nan Su", "Jiwei Wang", "Zhiwei Xue", "Shujie Peng", "Wenchen Xing", "Haoyong Jin", "Jiangli Zhao", "Yanya He", "Jiaqi Shi", "Wenbo Li", "Qijian Wei", "Bin Huang", "Chao Li", "Xinyu Wang", "Pei Liu", "Ning Yang"], "journal": "Functional & integrative genomics", "year": 2025, "abstract": "Background A major complication of diabetes, diabetic foot ulcers (DFU), has been linked to mitochondrial dysfunction and oxidative stress. Here, we performed analysis of RNA sequencing data from publicly available databases, including single-cell assays, to identify dysregulated genes associated with these processes in DFU and the specific cell types involved. Methods Analysis of transcriptome sequencing was performed on GSE134431 and GSE80178 datasets from the GEO database to identify differentially expressed mitochondrial-related genes (DE-MRGs) in DFU samples relative to controls. LASSO and SVM-RFE algorithms were used to identify critical genes, and functional enrichment analyses were conducted to identify associated pathways. Results were validated in a cohort of DFU samples and controls processed at our institution, and single-cell RNA sequencing data from GSE245703 was used to determine expression of candidate genes in endothelial cells from DFU relative to non-DFU samples. SiRNA knockdown of one candidate gene, LETM2, was performed in human umbilical vein endothelial cells (HUVECs) exposed to H2O2 as a model system for oxidative stress. Results LETM2 emerged as key gene significantly associated with DFU from our integrated analysis of the DFU RNA sequencing datasets. Single-cell RNA sequencing data revealed increased expression of LETM2 in endothelial cells from DFU samples compared to controls. Transcriptome sequencing of RNA from HUVECs with LETM2 knockdown under oxidative stress conditions revealed corelated expression with other genes involved in mitochondrial function. HUVECs with LETM2 knockdown furthermore showed impaired mitochondrial fission and mitophagy, as well as decreased cell viability and increased apoptosis in vitro. Conclusions These findings indicate a role for LETM2 in preserving mitochondrial function in HUVECs under oxidative stress and underscore its potential as a therapeutic target for mitigating mitochondrial dysfunction in diabetic complications such as DFU.", "claims": [{"id": "claim-method", "statement": "A dual-algorithm strategy combining LASSO regression and SVM-RFE was employed to identify characteristic genes related to DFU from the GSE134431 and GSE80178 datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41272316", "locator": "sections[23] \"Identification of DFU-related characteristic differentially expressed mitochondrial-related genes (DE-MRGs)\" paragraph 2", "quote": "A dual-algorithm strategy combining LASSO regression and SVM-RFE was employed to identify characteristic genes related to DFU from the GSE134431 and GSE80178 datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41272316", "locator": "sections[33] \"Data availability\" paragraph 2", "quote": "Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "LETM2 emerged as a key gene associated with DFU, with increased endothelial-cell expression in DFU and a protective role in mitochondrial function under oxidative stress.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41272316", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "LETM2 emerged as key gene significantly associated with DFU from our integrated analysis of the DFU RNA sequencing datasets."}, {"asset": "source:pmid:41272316", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Single-cell RNA sequencing data revealed increased expression of LETM2 in endothelial cells from DFU samples compared to controls."}, {"asset": "source:pmid:41272316", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "HUVECs with LETM2 knockdown furthermore showed impaired mitochondrial fission and mitophagy, as well as decreased cell viability and increased apoptosis in vitro."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "LETM2 emerged as a key gene associated with DFU, with increased endothelial-cell expression in DFU and a protective role in mitochondrial function under oxidative stress.", "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:41272316"], "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:GSE134431"], "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:GSE134431"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41272316", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s10142-025-01748-1", "sha256": "sha256:f90c9e11094f8facb5a096743e6085a83afe7d38d0e0cd5a67b2476c3e39c10e", "bytes": 71137, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s10142-025-01748-1", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12638387", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE134431", "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=GSE134431", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE134431", "version": null, "note": "Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3946485", "GSM3946486", "GSM3946487", "GSM3946488", "GSM3946489", "GSM3946490", "GSM3946491", "GSM3946492", "GSM3946493", "GSM3946494", "GSM3946495", "GSM3946496", "GSM3946497", "GSM3946498", "GSM3946499", "GSM3946500", "GSM3946501", "GSM3946502", "GSM3946503", "GSM3946504", "GSM3946505"], "sample_count": 21, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Deregulated immune signature orchestrated by FOXM1 impairs human diabetic wound healing", "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:GSE245703", "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=GSE245703", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE245703", "version": null, "note": "Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM7847134", "GSM7847135", "GSM7847136", "GSM7847137", "GSM7847138", "GSM7847139", "GSM7847140", "GSM7847141", "GSM7847142", "GSM7847143", "GSM7847144", "GSM7847145"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "20301", "taxon": "Homo sapiens", "title": "Single Cell Analysis of Gene expression profile as single cell level of chronic diabetic foot ulcers and chronic non-diabetic foot ulcer Foot Wounds", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE80178", "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=GSE80178", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE80178", "version": null, "note": "Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2114231", "GSM2114232", "GSM2114233", "GSM2114234", "GSM2114235", "GSM2114236", "GSM2114237", "GSM2114238", "GSM2114239", "GSM2114240", "GSM2114241", "GSM2114242"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "16686", "taxon": "Homo sapiens", "title": "Genomic Profiling of Diabetic Foot Ulcers Identifies miR-15b-5p as a Major Regulator that Leads to Suboptimal Inflammatory Response and Diminished DNA Repair Mechanisms", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE134431 not downloaded", "asset:data:geo:GSE134431 licence not read", "asset:data:geo:GSE245703 not downloaded", "asset:data:geo:GSE245703 licence not read", "asset:data:geo:GSE80178 not downloaded", "asset:data:geo:GSE80178 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "A dual-algorithm strategy combining LASSO regression and SVM-RFE was employed to identify characteristic genes related to DFU from the GSE134431 and GSE80178 datasets."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "analysis of variance"}}, {"id": "method-3", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "principal component analysis"}}, {"id": "method-4", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "Limma"}}, {"id": "method-5", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "pathway enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": true, "required_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: support_vector_machine."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE134431", "GSE80178", "GSE245703"], "resolved_accessions": ["GSE134431", "GSE80178", "GSE245703"], "statements": ["Datasets and other files generated, analyzed, or used during this study are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE134431, GSE80178, GSE245703 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "assets": ["source:pmid:41272316", "data:geo:GSE134431"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE134431"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:06:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 18340, "completion_tokens": 1671, "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:41272316", "type": "paper", "label": "pmid:41272316"}, {"id": "source:pmid:41272316", "type": "manuscript", "label": "PMID 41272316 full text"}, {"id": "data:geo:GSE134431", "type": "dataset", "label": "GEO GSE134431"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41272316", "type": "paper", "label": "pmid:41272316"}, {"id": "source:pmid:41272316", "type": "manuscript", "label": "PMID 41272316 full text"}, {"id": "data:geo:GSE134431", "type": "dataset", "label": "GEO GSE134431"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41272316", "type": "extraction", "used": ["source:pmid:41272316"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE134431", "type": "accession_resolution", "used": ["data:geo:GSE134431"], "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:41272316", "parent_hash": "sha256:8375b8daaf8a419cd322b30723388c34ee685969405c7d4352fbf03cb408251b", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE134431 licence not read", "asset:data:geo:GSE134431 not downloaded", "asset:data:geo:GSE245703 licence not read", "asset:data:geo:GSE245703 not downloaded", "asset:data:geo:GSE80178 licence not read", "asset:data:geo:GSE80178 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": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ative stress. Here, we performed analysis of RNA sequencing data from publicly available databases, incl", "rocessed at our institution, and single-cell RNA sequencing data from GSE245703 was used to determine ex", "DFU from our integrated analysis of the DFU RNA sequencing datasets. Single-cell RNA sequencing data re", "the DFU RNA sequencing datasets. Single-cell RNA sequencing data revealed increased expression of LETM2"], "order_basis": "paper_text_order:265", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d controls processed at our institution, and single-cell RNA sequencing data from GSE245703 was used to determine ex", "analysis of the DFU RNA sequencing datasets. Single-cell RNA sequencing data revealed increased expression of LETM2", "analysis of the LETM2 expression profile Raw single-cell RNA-seq data underwent the following quality control", "from DFU samples A comprehensive analysis of single-cell RNA sequencing data from 5 DFU and 7 non-diabetic ulcer sam"], "order_basis": "paper_text_order:933", "id": "assay:2"}, {"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": ["from DFU relative to non-DFU samples. SiRNA knockdown of one candidate gene, LETM2, was performed", "ome sequencing of RNA from HUVECs with LETM2 knockdown under oxidative stress conditions revealed c", "in mitochondrial function. HUVECs with LETM2 knockdown furthermore showed impaired mitochondrial fi", "cells from DFU relative to non-DFU samples. SiRNA knockdown of one candidate gene, LETM2, was"], "order_basis": "paper_text_order:1092", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ll as decreased cell viability and increased apoptosis in vitro. Conclusions These findings indicat", "species (ROS) production, inflammation, and apoptosis, which together impair wound healing (Fang e"], "order_basis": "paper_text_order:1847", "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": ["VECs with 300 µM hydrogen peroxide for 48 h. Immunofluorescence and cytoskeletal staining revealed significa"], "order_basis": "paper_text_order:12853", "id": "assay:5"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["rked increase in LETM2 expression (Fig. 3E). Western blot and qPCR analyses confirmed that LETM2 expre"], "order_basis": "paper_text_order:13007", "id": "assay:6"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["LETM2 expression (Fig. 3E). Western blot and qPCR analyses confirmed that LETM2 expression was"], "order_basis": "paper_text_order:13024", "id": "assay:7"}, {"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": ["A dual-algorithm strategy combining LASSO regression and SVM-RFE was employed to identify characteristic genes related to DFU from the GSE134431 and GSE80178 datasets."], "order_basis": "consumes_earlier_output", "id": "assay:8"}]},"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. 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":"2026-11-04T02:52:13+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. 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}}}