{"publication_id":"054f72de-a886-4506-a529-11d92344f009","content_hash":"sha256:0b8eec7084df48cfcdfd0f940d669e121eae847e31c36324d04ef97b4789e950","nodes":[{"id":"054f72de-a886-4506-a529-11d92344f009","type":"publication","title":"Adjacent Evidence Brief: Telomere Cancer Effects — full paper"},{"id":"claim_1","type":"claim","text":"This synthesis tests the thesis that evidence for Telomere Cancer Effects is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation."},{"id":"claim_2","type":"claim","text":"Evidence-honesty note: The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_3","type":"claim","text":"This paper synthesizes evidence on telomere cancer effects across 25 included source papers and 826 high-confidence extracted claims."},{"id":"claim_4","type":"claim","text":"The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 24 adjacent clinical sources, and 1 mechanistic or model-system source, with 3 cross-study disagreements across the evidence base."},{"id":"claim_5","type":"claim","text":"Positive study-level signals are summarized in the frailty outcome class; null signals are summarized in the immune and inflammation and mechanism outcome classes; negative signals are summarized in the dosing and pharmacokinetics outcome class; mixed or heterogeneous signals are summarized in the contextual adjacent evidence, mortality and survival, and longevity outcome classes. The paper therefore reports a source-directness and outcome-class map rather than a pooled effect."},{"id":"claim_6","type":"claim","text":"The conclusion is narrower: the retained evidence maps associations, mechanisms, and candidate endpoints for follow-up; it does not establish clinical benefit, therapeutic actionability, or anti-aging efficacy."},{"id":"claim_7","type":"claim","text":"For Telomere Cancer Effects, what does the retained evidence show about prognostic or risk-marker associations, causal or mechanistic evidence, treatment or intervention relevance across prognostic and survival-marker evidence, treatment or intervention-response evidence, causal-risk and Mendelian-randomization evidence, and are those outcome-class source-level signals directionally consistent enough for clinical actionability once unclear direction coding, adjacent/contextual source roles, and directness limits are considered?"},{"id":"claim_8","type":"claim","text":"This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-telomere_cancer_effects-v06-DAILY-2026-06-28T00-39-28Z`."},{"id":"claim_9","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text."},{"id":"claim_10","type":"claim","text":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification."},{"id":"claim_11","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, dosing and pharmacokinetics, frailty, immune and inflammation, longevity, mechanism, mortality and survival); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_12","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_13","type":"claim","text":"Source directness breakdown: 0/25 retained sources directly address the stated topic and aging-relevant hard endpoints; 25/25 are adjacent, contextual, review-level, or mechanistic and are used only to bound interpretation. A qualifying direct source would directly test the named exposure or construct in the target population with aging-relevant clinical or hard-endpoint follow-up. Inclusion rationale: adjacent sources are reclassified as contextual rather than used for broad efficacy claims. Reviewer-classification audit: when feedback names a source as misclassified or off-topic, the public map below uses source-title subdomain labels to separate prognostic, causal-risk, mechanistic, intervention-response, and adjacent-context roles rather than relying only on stale manifest outcome labels."},{"id":"claim_14","type":"claim","text":"Alhareeri 2020: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_15","type":"claim","text":"Jaeger 2024: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_16","type":"claim","text":"Markozannes 2022: outcome=Immune and Inflammation; direction=null; directness=review; tier=B2."},{"id":"claim_17","type":"claim","text":"Li 2026: outcome=Contextual Adjacent Evidence; direction=positive; directness=indirect; tier=B2."},{"id":"claim_18","type":"claim","text":"Davidson-Swinton 2026: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_19","type":"claim","text":"Langsenlehner 2026: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_20","type":"claim","text":"Gil-Korilis 2026: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_21","type":"claim","text":"Cheng 2026: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_22","type":"claim","text":"Bhat 2023: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_23","type":"claim","text":"Brown 2026: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_24","type":"claim","text":"Chen 2023: outcome=Contextual Adjacent Evidence; direction=null; directness=review; tier=B2."},{"id":"claim_25","type":"claim","text":"Alqaisi 2026: outcome=Contextual Adjacent Evidence; direction=null; directness=review; tier=B2."},{"id":"claim_26","type":"claim","text":"Wan 2023: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_27","type":"claim","text":"Genetta 2026: outcome=Contextual Adjacent Evidence; direction=null; directness=indirect; tier=B2."},{"id":"claim_28","type":"claim","text":"Andreikos 2024: outcome=Contextual Adjacent Evidence; direction=unclear; directness=review; tier=B2."},{"id":"claim_29","type":"claim","text":"Song 2022: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_30","type":"claim","text":"Aierken 2026: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"source_1","type":"source","study":"Shorter telomere length as a prognostic marker for survival and recurrence in breast cancer: a systematic review and meta-analysis","year":2025,"doi":"10.37349/etat.2025.1002289","url":"https://doi.org/10.37349/etat.2025.1002289","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_2","type":"source","study":"Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study","year":2020,"doi":"10.1186/s13058-020-01368-6","url":"https://doi.org/10.1186/s13058-020-01368-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_3","type":"source","study":"A Natural Astragalus-Based Nutritional Supplement Lengthens Telomeres in a Middle-Aged Population: A Randomized, Double-Blind, Placebo-Controlled Study","year":2024,"doi":"10.3390/nu16172963","url":"https://doi.org/10.3390/nu16172963","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_4","type":"source","study":"The association of epigenetic age acceleration with internal smoking dose, risk of lung cancer, and all-cause mortality in cigarette smokers: the Multiethnic Cohort study","year":2026,"doi":"10.1186/s13148-026-02137-6","url":"https://doi.org/10.1186/s13148-026-02137-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_5","type":"source","study":"Systematic review of Mendelian randomization studies on risk of cancer","year":2022,"doi":"10.1186/s12916-022-02246-y","url":"https://doi.org/10.1186/s12916-022-02246-y","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_6","type":"source","study":"Aging and increased cancer risk: exploring the potential of LE8 score to mitigate risk","year":2026,"doi":"10.1038/s41514-026-00352-2","url":"https://doi.org/10.1038/s41514-026-00352-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_7","type":"source","study":"Lymphoid malignancy and clonality in the POT1-mediated long telomere syndrome ∗","year":2026,"doi":"10.1182/blood.2025031287","url":"https://doi.org/10.1182/blood.2025031287","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_8","type":"source","study":"Leukocyte telomere attrition following radiotherapy in prostate cancer: a prospective study","year":2026,"doi":"10.1038/s41598-026-36205-x","url":"https://doi.org/10.1038/s41598-026-36205-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_9","type":"source","study":"Effect of Traditional Korean Medicine Oncotherapy on the Survival, Quality of Life, and Telomere Length: A Prospective Cohort Study","year":2023,"doi":"10.1177/15347354231154267","url":"https://doi.org/10.1177/15347354231154267","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_10","type":"source","study":"Unraveling the telomere-mitochondrial axis in colorectal cancer: Results from a prospectively followed cohort","year":2026,"doi":"10.1186/s10020-026-01423-6","url":"https://doi.org/10.1186/s10020-026-01423-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_11","type":"source","study":"Integrative Analysis of Telomere‐Related Genes Reveals Prognostic Signatures in Laryngeal Cancer","year":2026,"doi":"10.1155/ijog/5301600","url":"https://doi.org/10.1155/ijog/5301600","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_12","type":"source","study":"Leukocyte Telomere Length Variants Are Independently Associated with Survival of Patients with Colorectal Cancer","year":2026,"doi":"10.3390/cancers18030490","url":"https://doi.org/10.3390/cancers18030490","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_13","type":"source","study":"DNA methylation‐based telomere length is associated with HIV infection, physical frailty, cancer, and all‐cause mortality","year":2024,"doi":"10.1111/acel.14174","url":"https://doi.org/10.1111/acel.14174","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_14","type":"source","study":"Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India","year":2023,"doi":"10.1186/s12885-023-11387-z","url":"https://doi.org/10.1186/s12885-023-11387-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_15","type":"source","study":"SMARCAL1 is a targetable synthetic lethal therapeutic vulnerability in ATRX-deficient gliomas that use alternative lengthening of telomeres","year":2026,"doi":"10.1093/neuonc/noaf300","url":"https://doi.org/10.1093/neuonc/noaf300","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_16","type":"source","study":"Association between genetically determined telomere length and health‐related outcomes: A systematic review and meta‐analysis of Mendelian randomization studies","year":2023,"doi":"10.1111/acel.13874","url":"https://doi.org/10.1111/acel.13874","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_17","type":"source","study":"Telomerase Activity in Melanoma: Impact on Cancer Cell Proliferation Kinetics, Tumor Progression, and Clinical Therapeutic Strategies—A Scoping Review","year":2026,"doi":"10.3390/curroncol33020074","url":"https://doi.org/10.3390/curroncol33020074","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_18","type":"source","study":"ZEB1 Promotes Alternate Lengthening of Telomeres at Multiple Levels","year":2026,"doi":"10.3390/cancers18030499","url":"https://doi.org/10.3390/cancers18030499","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_19","type":"source","study":"Mendelian randomization study on the causal relationship between leukocyte telomere length and prostate cancer","year":2023,"doi":"10.1371/journal.pone.0286219","url":"https://doi.org/10.1371/journal.pone.0286219","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_20","type":"source","study":"The Association between Telomere Length and Head and Neck Cancer Risk: A Systematic Review and Meta-Analysis","year":2024,"doi":"10.3390/ijms25169000","url":"https://doi.org/10.3390/ijms25169000","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_21","type":"source","study":"Association Between Telomere Length and Skin Cancer and Aging: A Mendelian Randomization Analysis","year":2022,"doi":"10.3389/fgene.2022.931785","url":"https://doi.org/10.3389/fgene.2022.931785","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_22","type":"source","study":"Integrative Bulk and Single-Cell Transcriptome Profiling of Telomere-Related Genes Reveals a Robust Prognostic Signature and Immunotherapeutic Landscape in Neuroblastoma","year":2026,"doi":"10.7150/jca.129718","url":"https://doi.org/10.7150/jca.129718","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_23","type":"source","study":"Telomere-driven dysfunctional changes in gynecological cancers: mechanistic insights, biomarker 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source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_28","type":"source","study":"**Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_29","type":"source","study":"**Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"}],"edges":[{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_1","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_2","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_3","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_4","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_5","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_6","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_7","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_8","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_9","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_10","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_11","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_12","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_13","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_14","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_15","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_16","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_17","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_18","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_19","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_20","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_21","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_22","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_23","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_24","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_25","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_26","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_27","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_28","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_29","type":"contains_claim"},{"from":"054f72de-a886-4506-a529-11d92344f009","to":"claim_30","type":"contains_claim"}],"screening":{"identified":25,"screened":25,"excluded":0,"included":25,"included_or_retained":25,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"25 candidate receipts retained after source retrieval, deduplication, and topic filtering. 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