{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33235459", "kind": "science-record", "revision": 8, "content_hash": "sha256:b300a74560ab616dab6b6ced9cd0a9a50b25e6b699d41a06d33870ee94fa8408", "created_at": "2026-11-01T15:41:17Z", "updated_at": "2026-11-01T22:45:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of MSX1 as a Key Candidate for Progestin Resistance in Endometrial Cancer.", "doi": "10.2147/OTT.S271494", "pmid": "33235459", "authors": ["Linlin Yang", "Yunxia Cui", "Ting Huang", "Xiao Sun", "Yudong Wang"], "journal": "OncoTargets and therapy", "year": 2020, "abstract": "PURPOSE: Progestin resistance is a critical obstacle for endometrial conservative therapy. Therefore, studies to acquire a more comprehensive understanding of the mechanisms are urgent. However, the pivotal molecules are still unexplored.\nMATERIALS AND METHODS: We downloaded GSE121367 from the GEO database. The \"limma\" R language package was applied to identify differentially expressed genes (DEGs). We conducted Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). Protein-protein interaction was constructed by STRING and visualized in Cytoscape. The tumor immune microenvironment was explored by the TISIDB database. Methylation validation and overall survival analysis were conducted by the TCGA database. In addition, the upstream modulators of hub genes were predicted by miRTarBase and Network Analyst databases. The expression levels of candidate genes were validated by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemical assay (IHC). Cell growth, clone formation, migration, invasion, and wound healing assays were studied to explore the role of MSX1 in progestin resistance in vitro.\nRESULTS: A total of 3,282 DEGs were identified and they were mostly enriched in the cell adhesion pathway. We screened out ten hub genes whose genomic alteration rates were low based on the current endometrial carcinoma sample sets. Has-miR-335-5p, has-miR-124-3p, MAZ, and TFDP1 were the most prominent upstream regulators. The methylation status of CDH1, JAG1, EPCAM, and MSX1 was decreased, corresponding to their high protein expression, which also predicted better overall survival. The homeobox protein of MSX1 showed significant tissue specificity and better prognostic value and its knockdown inhibited epithelial-mesenchymal transitions (EMT) and enhanced progesterone efficacy.\nCONCLUSION: Our study identified that the gene of MSX1 promised to be the specific indicator and therapeutic target for progestin resistance. This would shed new light on the underlying biological mechanism to overcome progestin resistance of endometrial cancer.", "claims": [{"id": "claim-data-access", "statement": "All data analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33235459", "locator": "sections[32] \"Data Sharing Statement\" paragraph 2", "quote": "All data analyzed during this study are included in this published article."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:33235459"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33235459", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/OTT.S271494", "sha256": "sha256:93c39d3e3f7f64d03a645b1aa55576357cb6b0c06ee30b8b2685cd77bda607f9", "bytes": 51313, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/OTT.S271494", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7679365", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:33235459:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:13d19fd3e68b70821e463b01660a33861283752358c484a8d3bc98037779c1d6", "bytes": 1163, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#t0001", "version": null, "note": "The Related Databases and Their Functions in This Study", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 13, "column_count": 2}, "table": {"label": "Table 1", "caption": "The Related Databases and Their Functions in This Study", "rows": [["Databases", "Functions"], ["Gene Expression Omnibus (GEO)", "Extraction of gene expression microarray data"], ["The Cancer Genome Atlas (TCGA) database", "Extraction of gene expression data and survival data"], ["The Database for Annotation, Visualization, and Integrated Discovery (DAVID)", "Gene functional annotation"], ["Metascape", "Pathway enrichment analysis"], ["Search Tool for the Retrieval of Interacting Genes (STRING)", "Functional interactions between proteins"], ["Gene Expression Profiling Interactive Analysis (GEPIA)", "Hub genes expression analysis and survival analysis"], ["cBioPortal for Cancer Genomics", "Mutation and DNA copy-number alterations analysis"], ["UALCAN", "Evaluate gene expression and epigenetic regulation"], ["Human Protein Atlas database (HPA)", "Protein expression detection"], ["TISIDB database", "Explore immune microenvironment"], ["miRTarBase database", "Detect related miRNAs"], ["Network Analyst", "Predict transcriptional factors"]], "row_count": 13, "column_count": 2, "numeric_cells": 0, "header_rows": 1, "locator": "section[8]/table-wrap[1]#t0001"}}, {"id": "asset:table:pmid:33235459:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ae4878f260492b15899fea101dd9cadb329f5e4b22f5b9e645b6026b9751797c", "bytes": 2042, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[2]#t0002", "version": null, "note": "Sequences of Primers Used for Amplification of Target Genes", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 37, "column_count": 2}, "table": {"label": "Table 2", "caption": "Sequences of Primers Used for Amplification of Target Genes", "rows": [["Gene", "Primer Nucleotide Sequence"], ["CDH1", "Forward: 5ʹ-GAACGCATTGCCACATACAC-3’"], ["", "Reverse: 5ʹ-TGGTGTAAGCGATGGCGGCA-3"], ["EPCAM", "Forward: 5′-AATCGTCAATGCCAGTGTACTT-3′"], ["", "Reverse: 5′-TCTCATCGCAGTCAGGATCATAA-3′"], ["MSX1", "Forward: 5′-CCTCTTTGCTCCCTGAGTTCA-3′"], ["", "Reverse: 5′-GGGACTCTTCCAGCCACTTTTT-3′"], ["KRT19", "Forward: 5ʹ-GCGAGCTAGAGGTGAAGATC-3’"], ["", "Reverse: 5ʹ-CGGAAGTCATCTGCAGCCA-3’"], ["OAS1", "Forward: 5′-CGTGTTTCCGCATGCAAAT-3′"], ["", "Reverse: 5′-ACCTCGGAAGCACCTTTCCT-3′"], ["JAG1", "Forward: 5ʹ-ATCGTGCTGCCTTTCAGTTT-3′"], ["", "Reverse: 5ʹ-GATCATGCCCGAGTGAGAA-3′"], ["TBX1", "Forward: 5ʹ-CTGACCAATAACCTGCTGGATGA-3′"], ["", "Reverse: 5ʹ-GGCTGATATCTGTGCATGGAGTT-3′"], ["DAB2", "Forward: 5ʹ-GTAGAAACAAGTGCAACCAATGG-3’"], ["", "Reverse: 5ʹ-GCCTTTGAACCTTGCTAAGAGA-3’"], ["E-cadherin", "Forward: 5′-CGAGAGCTACACGTTCACGG-3′"], ["", "Reverse: 5′-GGGTGTCGAGGGAAAAATAGG-3′"], ["N-cadherin", "Forward: 5′-TGCGGTACAGTGTAACTGGG-3′"], ["", "Reverse: 5′-GAAACCGGGCTATCTGCTCG-3′"], ["Vimentin", "Forward: 5′-TGCCGTTGAAGCTGCTAACTA-3′"], ["", "Reverse: 5′-CCAGAGGGAGTGAATCCAGATTA-3′"], ["Snail", "Forward: 5′-ACTGCAACAAGGAATACCTCAG-3′"], ["", "Reverse: 5′-GCACTGGTACTTCTTGACATCTG-3′"], ["Twist", "Forward: 5′-ATTCAAAGAAACAGGGCGTGG-3′"], ["", "Reverse: 5′-CCTTTCAGTGGCTGATTGGC-3′"], ["MMP9", "Forward: 5′-TTGACAGCGACAAGAAGTGG-3′"], ["", "Reverse: 5′-GCCATTCACGTCGTCCTTAT-3′"], ["MMP2", "Forward: 5′-TCTCCTGACATTGACCTTGGC-3′"], ["", "Reverse: 5′-CAAGGTGCTGGCTGAGTAGATC-3′"], ["CCND1", "Forward:5ʹ-AAACAGATCATCCGCAAACAC-3’"], ["", "Reverse:5ʹ-GTTGGGGCTCCTCAGGTTC-3’"], ["MYC", "Forward:5ʹ-CCTGGTGCTCCATGAGGAGA-3’"], ["", "Reverse:5ʹ-TCCAGCAGAAGGTGATCCAGAC-3’"], ["GAPDH", "Forward: 5ʹ-ACCCAGAAGACTGTGGATGG-3’"], ["", "Reverse: 5ʹ-TCAGCTCAGGGATGACCTTG-3’"]], "row_count": 37, "column_count": 2, "numeric_cells": 37, "header_rows": 1, "locator": "section[8]/table-wrap[2]#t0002"}}, {"id": "asset:table:pmid:33235459:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cc731fa430280b12264472ad24804862a765fa6cdac3403605b86ca632ccd764", "bytes": 1559, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[3]#t0003", "version": null, "note": "GO and Pathway Enrichment Analysis of DEGs", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 21, "column_count": 3}, "table": {"label": "Table 3", "caption": "GO and Pathway Enrichment Analysis of DEGs", "rows": [["Category", "Term", "P-value"], ["GOTERM_BP_DIRECT", "GO:0021983~pituitary gland development", "2.52E-04"], ["GOTERM_BP_DIRECT", "GO:0043392~negative regulation of DNA binding", "2.52E-04"], ["GOTERM_BP_DIRECT", "GO:0060337~type I interferon signaling pathway", "7.45E-04"], ["GOTERM_BP_DIRECT", "GO:0010628~positive regulation of gene expression", "7.56E-04"], ["GOTERM_BP_DIRECT", "GO:0001764~neuron migration", "0.001169"], ["GOTERM_CC_DIRECT", "GO:0031225~anchored component of membrane", "0.000235"], ["GOTERM_CC_DIRECT", "GO:0005615~extracellular space", "0.000690"], ["GOTERM_CC_DIRECT", "GO:0005771~multivesicular body", "0.001670"], ["GOTERM_CC_DIRECT", "GO:0005576~extracellular region", "0.002465"], ["GOTERM_CC_DIRECT", "GO:0016324~apical plasma membrane", "0.004640"], ["GOTERM_MF_DIRECT", "GO:0046983~protein dimerization activity", "0.006223"], ["GOTERM_MF_DIRECT", "GO:0008201~heparin binding", "0.008454"], ["GOTERM_MF_DIRECT", "GO:0005112~Notch binding", "0.016286"], ["GOTERM_MF_DIRECT", "GO:0046872~metal ion binding", "0.016772"], ["GOTERM_MF_DIRECT", "GO:0005215~transporter activity", "0.023963"], ["KEGG_PATHWAY", "hsa04514:Cell adhesion molecules", "0.0046"], ["KEGG_PATHWAY", "hsa04612:Antigen processing and presentation", "0.0096"], ["KEGG_PATHWAY", "hsa05168:Herpes simplex infection", "0.0153"], ["KEGG_PATHWAY", "hsa04144:Endocytosis", "0.0166"], ["KEGG_PATHWAY", "hsa04145:Phagosome", "0.0246"]], "row_count": 21, "column_count": 3, "numeric_cells": 40, "header_rows": 1, "locator": "section[8]/table-wrap[3]#t0003"}}, {"id": "asset:table:pmid:33235459:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8b554a0c889521dd78b920760a502f1dc1d687c053c2dfd8ea3a8f981e2b2e2a", "bytes": 929, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[4]#t0004", "version": null, "note": "Upregulated Gene Sets in the IshikawaPR Cell Line", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 11, "column_count": 6}, "table": {"label": "Table 4", "caption": "Upregulated Gene Sets in the IshikawaPR Cell Line", "rows": [["Gene Sets", "Size", "ES", "NES", "NOM P-value", "FDR q-value"], ["Interferon gamma response", "196", "0.55", "2.07", "0.00", "0.00"], ["TNF-a signaling via NF-KB", "196", "0.46", "1.72", "0.00", "0.01"], ["Epithelial mesenchymal transition", "195", "0.43", "1.62", "0.00", "0.01"], ["Hypoxia", "191", "0.39", "1.47", "0.00", "0.04"], ["Complement", "193", "0.44", "1.67", "0.00", "0.01"], ["Negative regulation of regulated secretory pathway", "23", "0.68", "1.73", "0.00", "0.27"], ["Chronic inflammatory response", "18", "0.69", "1.72", "0.01", "0.27"], ["Interleukin1 production", "90", "0.49", "1.69", "0.00", "0.30"], ["Interferon gamma mediated signaling pathway", "87", "0.51", "1.74", "0.00", "0.30"], ["Negative regulation of response to drug", "25", "0.63", "1.68", "0.00", "0.30"]], "row_count": 11, "column_count": 6, "numeric_cells": 50, "header_rows": 1, "locator": "section[8]/table-wrap[4]#t0004"}}, {"id": "asset:table:pmid:33235459:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e6de91159a00ff31b71840ebbc9e7e002b1a1fb61c55d46108ac89f287420a48", "bytes": 1080, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[5]#t0005", "version": null, "note": "Upregulated Gene Sets in the Ishikawa Cell Line", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 11, "column_count": 6}, "table": {"label": "Table 5", "caption": "Upregulated Gene Sets in the Ishikawa Cell Line", "rows": [["Gene Sets", "Size", "ES", "NES", "NOM P-value", "FDR q-value"], ["ATP dependent microtubule motor activity plus end directed", "26", "−0.65", "−1.76", "0.00", "0.62"], ["Mesenchymal to epithelial transition", "20", "−0.69", "−1.75", "0.00", "0.58"], ["Phospholipid catabolic process", "38", "−0.59", "−1.75", "0.00", "0.55"], ["Respiratory chain complex IV", "15", "−0.72", "−1.73", "0.01", "0.56"], ["Transcytosis", "18", "−0.69", "−1.72", "0.01", "0.52"], ["Positive regulation of protein localization to cell periphery", "60", "−0.54", "−1.69", "0.00", "0.59"], ["Negative regulation of insulin secretion", "36", "−0.55", "−1.59", "0.01", "0.66"], ["Apical junction assembly", "58", "−0.48", "−1.52", "0.01", "0.88"], ["Cell–cell adhesion via plasma membrane adhesion molecules", "253", "−0.36", "−1.39", "0.01", "0.94"], ["Plasma membrane receptor complex", "184", "−0.36", "−1.37", "0.01", "0.94"]], "row_count": 11, "column_count": 6, "numeric_cells": 50, "header_rows": 1, "locator": "section[8]/table-wrap[5]#t0005"}}, {"id": "asset:table:pmid:33235459:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e00f6221a0e75f3940eec01983cb76285f25eb99ea752038ea619feb2b0cae3e", "bytes": 1291, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[6]#t0006", "version": null, "note": "Identification of Hub Genes by cytoHubba", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 11, "column_count": 13}, "table": {"label": "Table 6", "caption": "Identification of Hub Genes by cytoHubba", "rows": [["Name", "Betweenness", "BottleNeck", "Closeness", "ClusteringCoefficient", "Degree", "DMNC", "EcCentricity", "EPC", "MCC", "MNC", "Radiality", "Stress"], ["CDH1", "7,440.58", "76", "66.299", "0.085", "27", "0.227", "0.100", "43.793", "96", "17", "11.806", "17,516"], ["JAG1", "1,707.27", "14", "52.316", "0.321", "8", "0.428", "0.100", "39.736", "26", "6", "11.457", "3,744"], ["PTGES", "510.00", "1", "38.399", "1.000", "2", "0.308", "0.082", "21.129", "2", "2", "10.558", "500"], ["EPCAM", "423.05", "6", "52.267", "0.378", "10", "0.339", "0.090", "41.186", "58", "10", "11.312", "1,750"], ["CNTNAP2", "2,582.66", "10", "38.916", "0.000", "5", "0.000", "0.100", "15.668", "5", "1", "10.609", "4,672"], ["TBX1", "1,156.20", "12", "52.016", "0.333", "7", "0.454", "0.100", "39.344", "20", "5", "11.438", "3,108"], ["MSX1", "944.50", "4", "43.892", "0.167", "4", "0.308", "0.100", "25.883", "4", "2", "11.039", "1,976"], ["KRT19", "405.98", "5", "49.634", "0.389", "9", "0.334", "0.090", "39.797", "46", "9", "11.198", "1,452"], ["OAS1", "81.05", "1", "39.275", "0.500", "8", "0.408", "0.100", "29.613", "58", "8", "10.419", "450"], ["DAB2", "751.752", "2", "45.945", "0.267", "6", "0.379", "0.112", "32.237", "10", "4", "11.191", "1,378"]], "row_count": 11, "column_count": 13, "numeric_cells": 121, "header_rows": 1, "locator": "section[8]/table-wrap[6]#t0006"}}, {"id": "asset:table:pmid:33235459:7", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ec1f964c3b4f2c87ffc197f8cbb85c23dbd2db8d5c219b3e7b09e10c7b78a6ac", "bytes": 758, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[7]#t0007", "version": null, "note": "The Information of Ten Hub Genes", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 11, "column_count": 3}, "table": {"label": "Table 7", "caption": "The Information of Ten Hub Genes", "rows": [["Gene Name", "logFC", "P-value"], ["CDH1(cadherin 1)", "−5.41", "2.16E-10"], ["JAG1(jagged 1)", "−5.44", "2.35E-10"], ["PTGES(prostaglandin E synthase)", "7.77", "2.42E-11"], ["EPCAM(epithelial cell adhesion molecule)", "−5.39", "2.66E-10"], ["CNTNAP2(contactin associated protein-like 2)", "−7.10", "1.76E-11"], ["TBX1(T-box 1)", "7.61", "2.71E-10"], ["MSX1(msh homeobox 1)", "−5.45", "5.79E-10"], ["KRT19(keratin 19)", "−6.60", "4.00E-10"], ["OAS1(2ʹ-5ʹ-oligoadenylate synthetase 1)", "5.83", "1.24E-10"], ["DAB2(disabled homolog 2, mitogen-responsive phosphoprotein)", "9.00", "3.02E-10"]], "row_count": 11, "column_count": 3, "numeric_cells": 28, "header_rows": 1, "locator": "section[8]/table-wrap[7]#t0007"}}, {"id": "asset:table:pmid:33235459:8", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a214f59d710118823c4782a5897b52a745e70f3673189087700c1212dc93ee30", "bytes": 494, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[8]#t0008", "version": null, "note": "The Main Related MicroRNAs of Hub Genes", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs 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"section[8]/table-wrap[9]#t0009", "version": null, "note": "The Main Related TFs of Hub Genes", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 13, "column_count": 3}, "table": {"label": "Table 9", "caption": "The Main Related TFs of Hub Genes", "rows": [["TFs", "Genes", "Count"], ["MAZ", "CDH1, EPCAM, KRT19, MSX1, TBX1", "5"], ["TFDP1", "CDH1, CNTNAP2, KRT19, MSX1", "4"], ["PPARG", "CDH1, EPCAM, KRT19", "3"], ["NR2F1", "CDH1, KRT19, TBX1", "3"], ["DMAP1", "CDH1, KRT19, OAS1", "3"], ["EZH2", "CDH1, MSX1, TBX1", "3"], ["ELF3", "CDH1, EPCAM, KRT19", "3"], ["CHD1", "CDH1, KRT19, PTGES", "3"], ["BCOR", "EPCAM, PTGES, TBX1", "3"], ["E2F5", "KRT19, PTGES, TBX1", "3"], ["JUND", "EPCAM, KRT19, TBX1", "3"], ["SMARCA5", "KRT19, PTGES, TBX1", "3"]], "row_count": 13, "column_count": 3, "numeric_cells": 22, "header_rows": 1, "locator": "section[8]/table-wrap[9]#t0009"}}, {"id": "asset:table:pmid:33235459:10", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:af357e7cab0e207bb89b10e34fd4143f1423b0d20a38fac750e86ebbc4cca2a3", "bytes": 474, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[10]#t0010", "version": null, "note": "IC50 Concentrations of MPA in Sensitive and Resistant Cell Lines After MXS1 Overexpression and Silencing", "structure": {"pmcid": "PMC7679365", "section_index": 8, "section_title": "Prediction of Relevant MicroRNAs and Transcriptional Factors (TFs) of Hub Genes", "row_count": 7, "column_count": 2}, "table": {"label": "Table 10", "caption": "IC50 Concentrations of MPA in Sensitive and Resistant Cell Lines After MXS1 Overexpression and Silencing", "rows": [["Cell Lines", "IC50 of MPA (µM)"], ["Ishikawa", "19.3±0.6"], ["Ishikawa-siMSX1", "15.5±0.9"], ["Ishikawa-exMSX1", "25.2±0.2"], ["IshikawaPR", "30.0±0.4"], ["IshikawaPR-siMSX1", "19.8±0.9"], ["IshikawaPR-exMSX1", "35.1±0.2"]], "row_count": 7, "column_count": 2, "numeric_cells": 7, "header_rows": 1, "locator": "section[8]/table-wrap[10]#t0010"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "reordered", "quote": "“Normalized data of GSE121367 was downloaded from the GEO database and further processed by the “limma” R language package to identify differentially expressed genes (DEGs) between IshikawaPR and Ishikawa cell lines.”"}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["All data analyzed during this study are included in this published article."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:33235459", "asset:table:pmid:33235459:1", "asset:table:pmid:33235459:2", "asset:table:pmid:33235459:3", "asset:table:pmid:33235459:4", "asset:table:pmid:33235459:5", "asset:table:pmid:33235459:6", "asset:table:pmid:33235459:7", "asset:table:pmid:33235459:8", "asset:table:pmid:33235459:9", "asset:table:pmid:33235459:10"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:16:59Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 39595, "completion_tokens": 1615, "cached_tokens": 512}}, "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:33235459", "type": "paper", "label": "pmid:33235459"}, {"id": "source:pmid:33235459", "type": "manuscript", "label": "PMID 33235459 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33235459", "type": "paper", "label": "pmid:33235459"}, {"id": "source:pmid:33235459", "type": "manuscript", "label": "PMID 33235459 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33235459", "type": "extraction", "used": ["source:pmid:33235459"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:33235459", "parent_hash": "sha256:efce811413dde5c9a073efce219746799ba72fd829973386e141b68f932c02de", "fork_of": null, "generation": 7}, "gaps": ["execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"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": ["ndidate genes were validated by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochem"], "order_basis": "paper_text_order:978", "id": "assay:1"}, {"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": ["ted by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemical assay (IHC). 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A siRNA targeting human MSX1 mRNA was designed by Ge"], "order_basis": "paper_text_order:1796", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["sity but were less than confluent, they were passaged by 0.02% EDTA and 0.25% trypsin resolved in"], "order_basis": "paper_text_order:3929", "id": "assay:5"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["“Normalized data of GSE121367 was downloaded from the GEO database and further processed by the “limma” R language package to identify differentially expressed genes (DEGs) between IshikawaPR and Ishikawa cell lines.”"], "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. 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":"2026-11-04T03:12:20+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}}}