{"data":{"pmid":"41354084","pmcid":"PMC12682394","source":"europe_pmc_fulltext","retrieved_at":"2026-11-01T13:58:31Z","text_hash":"02cdab857e48bffcc1f38e8bb2630dc6d7173e300e4ff2753678ed2a82486775","characters":72614,"coverage":"whole_body","truncated":false,"cut":[],"roles_basis":"title","section_count":53,"table_count":764,"sections":[{"index":0,"title":"Abstract","role":"front","chars":2455,"table_count":0},{"index":1,"title":"def-list","role":"other","chars":879,"table_count":0},{"index":2,"title":"Introduction","role":"front","chars":3430,"table_count":0},{"index":3,"title":"Materials and Methods","role":"methods","chars":21,"table_count":0},{"index":4,"title":"Data Collection for Bioinformatics Analyses","role":"data","chars":43,"table_count":0},{"index":5,"title":"Primary Bioinformatics Cohort (TCGA)","role":"data","chars":545,"table_count":0},{"index":6,"title":"Tumor Heterogeneity and Immune Cell Analyses (TCGA and CGGA)","role":"other","chars":249,"table_count":0},{"index":7,"title":"Ivy Glioblastoma Atlas","role":"other","chars":389,"table_count":0},{"index":8,"title":"Single\u2010Cell Sequencing (GEO)","role":"methods","chars":395,"table_count":0},{"index":9,"title":"Figure\u2013Data Source Map","role":"data","chars":5418,"table_count":2},{"index":10,"title":"Transcriptome, Proteomics, and Single\u2010Cell Sequencing Data Processing","role":"methods","chars":2045,"table_count":0},{"index":11,"title":"Gene Set Enrichment Analysis (GSEA)","role":"methods","chars":605,"table_count":0},{"index":12,"title":"Twelve\u2010Cell State and CIBERSORT Analyses","role":"other","chars":909,"table_count":0},{"index":13,"title":"Tissue Microarray and Immunohistochemistry","role":"methods","chars":1058,"table_count":0},{"index":14,"title":"Scoring of the Immunohistochemistry","role":"methods","chars":1016,"table_count":0},{"index":15,"title":"Spatial Transcriptome Data","role":"other","chars":780,"table_count":0},{"index":16,"title":"Protein\u2013Protein Interaction Curation and Prioritization","role":"other","chars":647,"table_count":0},{"index":17,"title":"Drug Sensitivity Inference by pRRophetic","role":"results","chars":1136,"table_count":0},{"index":18,"title":"Immunotherapy Biomarkers and IPS Modeling","role":"methods","chars":725,"table_count":0},{"index":19,"title":"Nomogram Construction","role":"other","chars":1458,"table_count":0},{"index":20,"title":"Results","role":"other","chars":7,"table_count":0},{"index":21,"title":"Result 1: Dual Expression Roles of TMEM106A in Cancer: Elevated Expression in Glioma","role":"results","chars":1112,"table_count":0},{"index":22,"title":"Result 2: Differential Analyses Between Normal and Tumor Tissues Reveal the Essential Roles of TMEM106A and TMEM106C in Gliomas, Particularly Within the IDH\u2010Wildtype Subtype","role":"results","chars":1018,"table_count":0},{"index":23,"title":"Result 3: High TMEM106A and TMEM106C Expression Serves as a Prognostic Indicator in Gliomas, Particularly Within the IDH\u2010Wildtype Subtype","role":"results","chars":1002,"table_count":0},{"index":24,"title":"Result 4: TMEM106A Emerges as an Independent Prognostic Factor Associated With Aggressive Glioma Behavior, Especially in IDH\u2010Wildtype Astrocytomas","role":"results","chars":1383,"table_count":0},{"index":25,"title":"Result 5: Immunohistochemistry Confirms TMEM106A Upregulation in IDH\u2010Wildtype Gliomas","role":"methods","chars":2148,"table_count":0},{"index":26,"title":"Result 6: High TMEM106A Expression Correlates With pro\u2010Inflammatory and Tumorigenic Signatures","role":"results","chars":2869,"table_count":0},{"index":27,"title":"Result 7: From mRNA TMEM106A\u2010High Gliomas Show Increased Myeloid and Granulocytes","role":"results","chars":2721,"table_count":0},{"index":28,"title":"Result 8: Single\u2010Cell RNA\u2010Seq Reveals TMEM106A Enrichment in Myeloid Series","role":"results","chars":1324,"table_count":0},{"index":29,"title":"Result 9: TMEM106A Shows Modest Associations With Macrophage Polarization Signatures","role":"results","chars":1799,"table_count":0},{"index":30,"title":"Result 10: Spatial Stratification of TMEM106A in Glioma: Mapping Expression to Immune Profiles and Clinical Nomograms","role":"results","chars":3356,"table_count":0},{"index":31,"title":"Result 11: TMEM106A\u2010High IDH\u2010Wt Gliomas Exhibit Broad Predicted Drug Sensitivity","role":"results","chars":1183,"table_count":0},{"index":32,"title":"Result 12: TMEM106A\u2010High Associates With Higher Immunophenoscore (IPS) Under PD\u20101\u2013Positive Contexts, Especially in IDH\u2010Wildtype Astrocytoma","role":"results","chars":1178,"table_count":0},{"index":33,"title":"Discussion","role":"discussion","chars":10,"table_count":0},{"index":34,"title":"TMEM106A as an Independent Prognostic Marker in Glioma: Context\u2010Dependent Biology Divergent From Other Cancers","role":"other","chars":2272,"table_count":1},{"index":35,"title":"TMEM106A as a Macrophage\u2010Enriched Microenvironmental Readout in Glioma","role":"other","chars":2360,"table_count":0},{"index":36,"title":"Inflammatory and Oncogenic Programs in TMEM106A\u2010High Tumors: IL\u20106\/JAK\/STAT3, TNF\u2010\u03b1\/NF\u2010\u03baB, EMT, and Angiogenesis","role":"other","chars":2368,"table_count":0},{"index":37,"title":"Translational Outlook: TMEM106A As a Microenvironmental Biomarker for Risk Stratification and PD\u20101\u2013Axis Nomination in IDH\u2010Wildtype Glioma","role":"other","chars":2582,"table_count":0},{"index":38,"title":"Limitations","role":"other","chars":1956,"table_count":0},{"index":39,"title":"Conclusion","role":"discussion","chars":787,"table_count":0},{"index":40,"title":"Author Contributions","role":"back","chars":475,"table_count":0},{"index":41,"title":"Funding","role":"back","chars":424,"table_count":0},{"index":42,"title":"Ethics Statement","role":"other","chars":381,"table_count":0},{"index":43,"title":"Consent","role":"back","chars":201,"table_count":0},{"index":44,"title":"Conflicts of Interest","role":"other","chars":66,"table_count":0},{"index":45,"title":"Supporting information","role":"back","chars":272,"table_count":0},{"index":46,"title":"(untitled)","role":"other","chars":246,"table_count":0},{"index":47,"title":"Data Availability Statement","role":"data","chars":666,"table_count":0},{"index":48,"title":"References","role":"other","chars":10,"table_count":0},{"index":49,"title":"References","role":"other","chars":8214,"table_count":0},{"index":50,"title":"Associated Data","role":"back","chars":15,"table_count":0},{"index":51,"title":"Supplementary Materials","role":"methods","chars":273,"table_count":0},{"index":52,"title":"Data Availability Statement","role":"data","chars":666,"table_count":0}]},"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":"2026-11-04T03:30:54+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\u2019s 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}}}