{"publication_id":"825b123b-8868-470c-9e7e-9196adde37c5","content_hash":"sha256:361af0f178a616d030624ca7fc8fd2bb47f9c638155b0edecd128406742ab0a3","nodes":[{"id":"825b123b-8868-470c-9e7e-9196adde37c5","type":"publication","title":"Hypothesis-Generating Brief: ABT-263 — full paper"},{"id":"claim_1","type":"claim","text":"This paper synthesizes evidence on ABT-263 across 33 accepted source papers and 1290 high-confidence extracted claims."},{"id":"claim_2","type":"claim","text":"The evidence profile contains 1 direct clinical source, 26 adjacent clinical sources, and 6 mechanistic or model-system sources, with 46 cross-study disagreements across the evidence base."},{"id":"claim_3","type":"claim","text":"Positive study-level signals are summarized in the immune and inflammation, longevity, contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, mechanism, immune and inflammation outcome classes, and negative signals in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect."},{"id":"claim_4","type":"claim","text":"The conclusion is that ABT-263 remains a bounded geroscience case: the retained clinical and mechanistic evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim."},{"id":"claim_5","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-senolytics-v06-DAILY-2026-06-25T00-24-59Z`."},{"id":"claim_6","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_7","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_8","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, immune and inflammation, longevity, mechanism, skeletal, fracture, and bone); 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_9","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_10","type":"claim","text":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim."},{"id":"claim_11","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_12","type":"claim","text":"| Contextual Adjacent Evidence | n=14; claims=822 | no extracted directional signal in 11/14 sources | 10 indirect; 1 protocol; 3 review | limited corpus depth in this outcome class |"},{"id":"claim_13","type":"claim","text":"This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate."},{"id":"claim_14","type":"claim","text":"14 included sources were assigned to this outcome class. Directional coding: null=11, positive=1, unclear=2. Directness coding: indirect=10, protocol=1, review=3."},{"id":"claim_15","type":"claim","text":"2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: review=2."},{"id":"claim_16","type":"claim","text":"Evidence for this outcome class is represented in the structured results table, but the retained narrative paragraphs were more strongly assigned to adjacent outcome classes. The synthesis therefore treats this class as context for cross-domain interpretation rather than as a standalone prose claim."},{"id":"claim_17","type":"claim","text":"4 included sources were assigned to this outcome class. Directional coding: null=4. Directness coding: mechanistic=4."},{"id":"claim_18","type":"claim","text":"3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=3."},{"id":"claim_19","type":"claim","text":"3 included sources were assigned to this outcome class. Directional coding: mixed=1, null=2. Directness coding: direct=1, indirect=2."},{"id":"claim_20","type":"claim","text":"1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1."},{"id":"claim_21","type":"claim","text":"Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim."},{"id":"claim_22","type":"claim","text":"The curated corpus is heavily skewed toward preclinical and indirect interventional hard-endpoint evidence, and the headline conclusions cannot be re-anchored to long-term, hard-outcome human RCTs. Several trials frequently invoked in the senolytic literature, including extension studies of dasatinib+quercetin in diabetic kidney disease, the SToMP-AD cerebrospinal-fluid penetration study, and the SToMP-AD phase 1 feasibility work, are represented only as protocols or as reports in which the field-relevant clinical endpoints are not powered to confirm or refute efficacy. Consequently, any synthesis-level claim of clinical benefit is built on a thin spine of direct human evidence and a thick base of mechanistic or surrogate work, and the gap between mechanistic plausibility and clinic-ready demonstration cannot be closed from this corpus alone."},{"id":"claim_23","type":"claim","text":"Several outcome classes rest on a single source, and that single-source status is itself a within-corpus generalization risk that should be foregrounded. The directness asymmetry is also informative: Farr 2024 is the only source coded direct, while the surrounding directness=indirect and directness=mechanistic sources share no common endpoint definition, so a corroborating indirect signal cannot substitute for a missing direct one."},{"id":"claim_24","type":"claim","text":"The populations enrolled in the direct and indirect human evidence are narrow, and the external-validity envelope is correspondingly tight. Shimizu 2025 randomized middle-aged humans to an Agrimonia pilosa extract. Outside these specific disease phenotypes, ages, and sex strata, the corpus offers no direct human signal: healthy community-dwelling older men, younger adults, and pediatric or non-European populations are absent. A substantial fraction of the supporting evidence is animal-only, including Falahatgaroshibi 2026 (male young Wistar rats, 10 and 30 mg/kg). Translational relevance to humans remains uncertain."},{"id":"claim_25","type":"claim","text":"Finally, the mechanism-to-clinic gap is itself a corpus-level limitation that no individual RoB column can encode. The result is a corpus in which a coherent mechanistic story is told, but the clinically relevant dose, schedule, target population, and hard outcome remain undefined, and any cross-domain inference from mechanistic or surrogate sources onto a clinical recommendation must be treated as hypothesis-generating rather than evidence-supported."},{"id":"claim_26","type":"claim","text":"For ABT-263, the final interpretation is deliberately tiered: the retained clinical and mechanistic evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging."},{"id":"claim_27","type":"claim","text":"This synthesis maps 33 included sources on Senolytics across 8 outcome classes and 46 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit."},{"id":"claim_28","type":"claim","text":"Across 33 curated reference papers, the evidence base for senolytics shows a context-dependent profile. Positive signals appear in: immune inflammation, longevity. Null findings dominate: contextual other, mechanism. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The senolytics anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established."},{"id":"claim_29","type":"claim","text":"Additional corpus sources included animal/preclinical evidence; the strongest unresolved contrast is the null vs positive between Mahoney 2025 and Schweiger 2025 on contextual adjacent evidence (severity 4/5), which defines the boundary condition future studies must test rather than smooth over."},{"id":"claim_30","type":"claim","text":"This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary."},{"id":"source_1","type":"source","study":"Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability","year":2023,"doi":"10.1016/j.ebiom.2023.104481","url":"https://doi.org/10.1016/j.ebiom.2023.104481","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_2","type":"source","study":"The Senolytic Drug Navitoclax Protects the Brain After Experimental Ischemic Stroke","year":2026,"doi":"10.3390/ph19030431","url":"https://doi.org/10.3390/ph19030431","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":"Senolytic reduction of senescent cells mitigates atrial arrhythmia vulnerability in aging rabbits","year":2026,"doi":"10.1016/j.hrthm.2026.01.007","url":"https://doi.org/10.1016/j.hrthm.2026.01.007","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":"Senolytic Treatment With Fisetin Reverses Age‐Related Endothelial Dysfunction Partially Mediated by SASP Factor CXCL12","year":2026,"doi":"10.1111/acel.70500","url":"https://doi.org/10.1111/acel.70500","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":"Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age","year":2023,"doi":"10.1111/acel.13767","url":"https://doi.org/10.1111/acel.13767","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_6","type":"source","study":"Senolytic-loaded asymmetric wound dressing for targeted senescent cell clearance in diabetic wound healing","year":2025,"doi":"10.1016/j.mtbio.2025.102741","url":"https://doi.org/10.1016/j.mtbio.2025.102741","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":"Comparative analysis of senolytic drugs reveals mitochondrial determinants of efficacy and resistance","year":2026,"doi":"10.1038/s43587-025-01057-z","url":"https://doi.org/10.1038/s43587-025-01057-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_8","type":"source","study":"Supramolecular delivery of senolytics enables targeted anti-senescence therapy and accelerated fracture healing","year":2026,"doi":"10.1186/s12951-026-04138-2","url":"https://doi.org/10.1186/s12951-026-04138-2","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_9","type":"source","study":"Reevaluating the senolytic activity of a GLS1 inhibitor and an anti-PD-1 antibody: toward greater reproducibility and methodological rigor","year":2026,"doi":"10.1038/s44319-026-00740-5","url":"https://doi.org/10.1038/s44319-026-00740-5","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":"Is exercise a senolytic medicine? A systematic review","year":2020,"doi":"10.1111/acel.13294","url":"https://doi.org/10.1111/acel.13294","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_11","type":"source","study":"DEL‐1 is an Endogenous Senolytic Protein that Inhibits Senescence‐Associated Bone Loss","year":2026,"doi":"10.1002/advs.202509263","url":"https://doi.org/10.1002/advs.202509263","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":"Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice","year":2026,"doi":"10.1038/s41413-026-00526-4","url":"https://doi.org/10.1038/s41413-026-00526-4","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":"Synergistic targeting of senolytic and senomorphic action with dual-engineered biomimetic macrophage nanovesicles for mitigating osteoarthritis","year":2026,"doi":"10.1016/j.bioactmat.2025.11.047","url":"https://doi.org/10.1016/j.bioactmat.2025.11.047","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":"Senolytics alleviate cyclophosphamide-induced premature ovarian insufficiency by eliminating senescent cells","year":2026,"doi":"10.4081/ejh.2026.4537","url":"https://doi.org/10.4081/ejh.2026.4537","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":"Senolytic‐Resistant Senescent Cells Have a Distinct SASP Profile and Functional Impact: The Path to Developing Senosensitizers","year":2025,"doi":"10.1111/acel.70358","url":"https://doi.org/10.1111/acel.70358","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":"Preliminary Data on the Senolytic Effects of Agrimonia pilosa Ledeb. Extract Containing Agrimols for Immunosenescence in Middle-Aged Humans: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Study","year":2025,"doi":"10.3390/nu17040667","url":"https://doi.org/10.3390/nu17040667","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_17","type":"source","study":"Senolytic Treatment With Dasatinib and Quercetin Reshapes Influenza‐Specific CD8 T Cell Responses During Infection in Aged, Vaccinated Mice","year":2025,"doi":"10.1111/acel.70345","url":"https://doi.org/10.1111/acel.70345","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_18","type":"source","study":"Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.","year":2024,"doi":"10.1038/s41591-024-03096-2","url":"https://doi.org/10.1038/s41591-024-03096-2","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_19","type":"source","study":"Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in elderly patients: Study protocol for a multicenter, randomized, adaptive allocation clinical trial","year":2024,"doi":"10.1186/s13063-024-08474-2","url":"https://doi.org/10.1186/s13063-024-08474-2","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_20","type":"source","study":"Synergistic senolytic–regenerative therapy significantly extends healthspan and lifespan","year":2026,"doi":"10.1186/s12967-026-08221-y","url":"https://doi.org/10.1186/s12967-026-08221-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":"primary"},{"id":"source_21","type":"source","study":"Natural senolytic activity of Rhodiola rosea extract alleviates age-associated phenotypes via paraptosis","year":2026,"doi":"10.1016/j.isci.2026.115607","url":"https://doi.org/10.1016/j.isci.2026.115607","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":"Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease (SToMP-AD): A Pilot Clinical Trial","year":2022,"doi":"10.14283/jpad.2021.62","url":"https://doi.org/10.14283/jpad.2021.62","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":"Effect of Natural Senolytic Agents & NLRP3 Inhibitors on Osteoarthritis","year":2024,"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":"review-level"},{"id":"source_24","type":"source","study":"Senolytic Treatment Reduces Acute and Chronic Lung Inflammation in an Aged Mouse Model of Influenza","year":2026,"doi":"10.1111/acel.70480","url":"https://doi.org/10.1111/acel.70480","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_25","type":"source","study":"Protocol for a pilot clinical trial of the senolytic drug combination Dasatinib Plus Quercetin to mitigate age-related health and cognitive decline in mental disorders","year":2025,"doi":"10.12688/f1000research.151963.2","url":"https://doi.org/10.12688/f1000research.151963.2","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_26","type":"source","study":"Senolytic effects of exercise in human muscles require acute inflammation.","year":2024,"doi":"10.18632/aging.205827","url":"https://doi.org/10.18632/aging.205827","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_27","type":"source","study":"Senolytic treatment with fisetin reverses age-related endothelial dysfunction partially mediated by SASP factor CXCL12","year":2025,"doi":"10.1101/2025.08.13.670216","url":"https://doi.org/10.1101/2025.08.13.670216","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_28","type":"source","study":"Senolytic Intervention Improves Cognition, Metabolism, and Adiposity in Female APP NL-F/NL-F Mice","year":2023,"doi":"10.1101/2023.12.12.571277","url":"https://doi.org/10.1101/2023.12.12.571277","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_29","type":"source","study":"Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial.","year":2023,"doi":"10.1038/s41591-023-02543-w","url":"https://doi.org/10.1038/s41591-023-02543-w","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_30","type":"source","study":"Senolytic-Resistant Senescent Cells Have a Distinct SASP Profile and Functional Impact: The Path to Developing Senosensitizers","year":2025,"doi":"10.1101/2025.08.27.672709","url":"https://doi.org/10.1101/2025.08.27.672709","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_31","type":"source","study":"Effect of senolytic drugs in young female mice chemically induced to estropause","year":2024,"doi":"10.1101/2024.05.22.595355","url":"https://doi.org/10.1101/2024.05.22.595355","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_32","type":"source","study":"Senolytic and senomorphic secondary metabolites as therapeutic agents in Drosophila melanogaster models of Parkinson’s disease","year":2023,"doi":"10.3389/fneur.2023.1271941","url":"https://doi.org/10.3389/fneur.2023.1271941","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_33","type":"source","study":"Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study","year":2019,"doi":"10.1016/j.ebiom.2018.12.052","url":"https://doi.org/10.1016/j.ebiom.2018.12.052","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_34","type":"source","study":"**Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.","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_35","type":"source","study":"**Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct 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_36","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_37","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"},{"id":"source_38","type":"source","study":"Effect of Natural Senolytic 2024","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":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_1","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_2","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_3","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_4","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_5","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_6","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_7","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_8","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_9","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_10","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_11","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_12","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_13","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_14","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_15","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_16","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_17","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_18","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_19","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_20","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_21","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_22","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_23","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_24","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_25","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_26","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_27","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_28","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_29","type":"contains_claim"},{"from":"825b123b-8868-470c-9e7e-9196adde37c5","to":"claim_30","type":"contains_claim"}],"screening":{"identified":33,"screened":33,"excluded":0,"included":33,"included_or_retained":33,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"33 candidate receipts retained after source retrieval, deduplication, and topic filtering. 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