Derivation Web

source_ad39ec4973274d0c

by researka:v2 · 2026-06-24 05:56:25.779828+04:00

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Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. 50/53 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.", "type": "claim"}, {"id": "claim_2", "text": "Functional surrogates in older adults carry prognostic weight well beyond lipid numbers — for example, gait speed near 0.8 m/s has been tied to frailty risk (Studenski 2011), and an annual decline of 0.05 m/s is typical in aging cohorts (Bohannon 1997) — making statin effects on physical function a longevity-relevant, not merely symptomatic, question.", "type": "claim"}, {"id": "claim_3", "text": "Additional corpus sources included animal/preclinical evidence; we conducted an AI-assisted structured evidence synthesis across 53 curated references, with every claim traced to a numbered source and tensions between mechanistic, observational, and randomized evidence explicitly logged rather than smoothed over (Pintea 2026; Lv 2025).", "type": "claim"}, {"id": "claim_4", "text": "Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.", "type": "claim"}, {"id": "claim_5", "text": "This synthesis evaluates evidence on Statins longevity across 53 included source papers and 3220 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, indirect interventional hard-endpoint evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty.", "type": "claim"}, {"id": "claim_6", "text": "The corpus contains 3 direct clinical sources, 49 adjacent clinical sources, and 1 mechanistic or model-system source. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.", "type": "claim"}, {"id": "claim_7", "text": "The thesis is: Across 53 curated reference papers, the evidence base for Statins shows a context-dependent profile. Positive signals appear in: contextual other, longevity. Null findings dominate: contextual other, safety comorbidity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Statins 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. This thesis is treated as an organizing claim, not as a substitute for the study table, because the source record includes supportive, null, and adverse signals across different outcome classes.", "type": "claim"}, {"id": "claim_8", "text": "This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.", "type": "claim"}, {"id": "claim_9", "text": "The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.", "type": "claim"}, {"id": "claim_10", "text": "Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.", "type": "claim"}, {"id": "claim_11", "text": "Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.", "type": "claim"}, {"id": "claim_12", "text": "The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.", "type": "claim"}, {"id": "claim_13", "text": "For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.", "type": "claim"}, {"id": "claim_14", "text": "Additional corpus sources included animal/preclinical evidence; the background evidence for Statins longevity is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Qian 2026, Fernando 2025, Zheng 2025 are interpreted separately from mechanistic studies such as Lv 2025, because these evidence roles answer different questions about aging biology and clinical translation.", "type": "claim"}, {"id": "claim_15", "text": "The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.", "type": "claim"}, {"id": "claim_16", "text": "Across the retained sources, positive signals cluster around the contextual adjacent evidence, longevity, immune and inflammation outcome classes; null signals around the contextual adjacent evidence, safety and comorbidity, longevity outcome classes; and negative or adverse signals around no dominant outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "type": "claim"}, {"id": "claim_17", "text": "The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.", "type": "claim"}, {"id": "claim_18", "text": "The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.", "type": "claim"}, {"id": "claim_19", "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.", "type": "claim"}, {"id": "claim_20", "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.", "type": "claim"}, {"id": "claim_21", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, immune and inflammation, longevity, mortality and survival, muscle function, safety, safety and comorbidity, 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.", "type": "claim"}, {"id": "claim_22", "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.", "type": "claim"}, {"id": "claim_23", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_24", "text": "| Contextual Adjacent Evidence | n=29; claims=1274 | no extracted directional signal in 22/29 sources | 1 direct; 12 indirect; 3 protocol; 13 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_25", "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.", "type": "claim"}, {"id": "claim_26", "text": "Contextual Adjacent Evidence: n=29; claims=1274; no extracted directional signal in 22/29 sources | directness: 1 direct; 12 indirect; 13 review; 3 protocol; main limitation: directionally heterogeneous.", "type": "claim"}, {"id": "claim_27", "text": "Quantitative signals across the class are heterogeneous. These source-traced numerics populate the evidence synthesis and indicate that adverse-event, functional, and lipid endpoints each carry statistically detectable variation without converging on a unified cardiometabolic direction.", "type": "claim"}, {"id": "claim_28", "text": "Mechanistically, the cardiometabolic class triangulates three distinct causal substrates. In a clinical observational cohort, Alqasrawi 2025 frames statin tolerability as a pharmacogenomic problem, with adverse-event incidence modulated by SLCO1B1- and CYP3A4-related variants (Alqasrawi 2025). Mechanistic human data from Spiegeleer 2025 implicate concomitant-medication burden, suggesting that gait-speed decrements in statin users may reflect polypharmacy rather than statin monotherapy (Spiegeleer 2025). Preclinical and clinical lipid-pathway evidence in Masood 2026 positions PPAR-α agonism as an alternative triglyceride-lowering route, indirectly testing whether the cardiometabolic benefits traditionally attributed to statins can be recapitulated by a mechanistically adjacent agent (Masood 2026). Together, these substrates frame cardiometabolic change as a function of lipid handling, drug clearance genetics, and concomitant exposures rather than a single longevity pathway.", "type": "claim"}, {"id": "claim_29", "text": "Within-corpus tensions surface chiefly through disagreement over whether statin exposure is harmful, neutral, or beneficial on cardiometabolic surrogates. Alqasrawi 2025 reports mixed adverse-event signals with effect direction marked unclear and individual p-values spanning P = 0.0730 to P < 0.0001, indicating that some adverse outcomes track robustly with statin exposure while others do not (Alqasrawi 2025). The integrating thesis that Statins presents a context-dependent profile is consistent with these source-level disagreements: positive, null, and adverse signals coexist across the cardiometabolic class, and no single source resolves the direction of effect on longevity-relevant cardiometabolic endpoints.", "type": "claim"}, {"id": "claim_30", "text": "The contextual other evidence class is the dominant outcome category in the corpus and aggregates 53 curated reference papers spanning Alzheimer's disease, lipid variability, migraine, cirrhotic portal hypertension, thoracic aortic aneurysm growth, colorectal cancer prognosis, traumatic brain injury recovery, schizophrenia, pancreatic ductal adenocarcinoma, and LDL-C pharmacogenetics. In a clinical RCT design, Aebi 2025 frames the STREAM non-inferiority trial of statin discontinuation in multimorbid older adults without cardiovascular disease, with a primary composite of major CV events and a protocol-level signal at P = 0.04. A mechanistic/biomarker RCT is reported by Zheng 2025, where the EPISODE trial evaluates PCSK9 inhibition on a background of stable statin therapy (rosuvastatin or atorvastatin) for at least 4 weeks in calcific aortic valve stenosis.", "type": "claim"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s40246-025-00753-6", "effect": "not extracted", "endpoint": "not extracted", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Pharmacogenomic insights into atorvastatin and rosuvastatin adverse effects: a prospective observational study in the UAE’s multiethnic population", "type": "source", "url": "https://doi.org/10.1186/s40246-025-00753-6", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s12876-025-04398-6", "effect": "not extracted", "endpoint": "not extracted", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1186/s12876-025-04398-6", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1177/13872877261424220", "effect": "not extracted", "endpoint": "not extracted", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Alzheimer's disease in patients prescribed statins: A real-world data analysis of U.S. patient health records", "type": "source", "url": "https://doi.org/10.1177/13872877261424220", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s11357-025-01682-x", "effect": "not extracted", "endpoint": "not extracted", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The association between statins and gait speed reserve in older adults: effects of concomitant medication", "type": "source", "url": "https://doi.org/10.1007/s11357-025-01682-x", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/bcp.70493", "effect": "not extracted", "endpoint": "not extracted", "id": "source_5", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "APOE genotype and the effect of statins on lipid outcomes: A meta‐analysis", "type": "source", "url": "https://doi.org/10.1002/bcp.70493", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1371/journal.pone.0323749", "effect": "not extracted", "endpoint": "not extracted", "id": "source_6", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Impact of statins as immune-modulatory agents on inflammatory markers in adults with chronic diseases: A systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1371/journal.pone.0323749", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1155/cdr/6684099", "effect": "not extracted", "endpoint": "not extracted", "id": "source_7", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "A Meta-Analysis of the Incidence of Adverse Reactions of Statins in Various Diseases", "type": "source", "url": "https://doi.org/10.1155/cdr/6684099", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1007/s00423-026-04011-8", "effect": "not extracted", "endpoint": "not extracted", "id": "source_8", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Pre-morbid statin use and mortality in trauma: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1007/s00423-026-04011-8", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1002/clc.70204", "effect": "not extracted", "endpoint": "not extracted", "id": "source_9", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Comparative Effectiveness of Cholesteryl Ester Transfer Protein (CETP) Inhibitors on Lipid Profiles in Adults With Hyperlipidemia: A Comprehensive Systematic Review and Frequentist Network Meta‐Analysis of Randomized Controlled Trials", "type": "source", "url": "https://doi.org/10.1002/clc.70204", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s10194-025-01957-w", "effect": "not extracted", "endpoint": "not extracted", "id": "source_10", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Exploring the association between statins use or HMG-CoA reductase inhibition and migraine: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1186/s10194-025-01957-w", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.eclinm.2026.103798", "effect": "not extracted", "endpoint": "not extracted", "id": "source_11", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation", "type": "source", "url": "https://doi.org/10.1016/j.eclinm.2026.103798", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s13643-026-03186-x", "effect": "not extracted", "endpoint": "not extracted", "id": "source_12", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Pemafibrate for hypertriglyceridemia: a meta-analysis of randomized controlled trials evaluating efficacy and safety outcomes", "type": "source", "url": "https://doi.org/10.1186/s13643-026-03186-x", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fmed.2025.1640270", "effect": "not extracted", "endpoint": "not extracted", "id": "source_13", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Comparative effectiveness of statins for chronic obstructive pulmonary disease patients with pulmonary hypertension: systematic review and network meta-analysis", "type": "source", "url": "https://doi.org/10.3389/fmed.2025.1640270", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s12325-025-03429-8", "effect": "not extracted", "endpoint": "not extracted", "id": "source_14", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "LDL-C Goal Attainment with Fixed-Dose Ezetimibe and Atorvastatin Versus High-Dose Atorvastatin in Chinese Patients: Subgroup Analysis of a Randomized Trial", "type": "source", "url": "https://doi.org/10.1007/s12325-025-03429-8", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fcvm.2025.1612095", "effect": "not extracted", "endpoint": "not extracted", "id": "source_15", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effectiveness of combining PCSK9 inhibitors with statins on major adverse cardiovascular events and lipid levels in patients after percutaneous coronary intervention: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.3389/fcvm.2025.1612095", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3349/ymj.2024.0476", "effect": "not extracted", "endpoint": "not extracted", "id": "source_16", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Prognostic Implication of LDL-C Variability and Its Association with Lipid-Lowering Strategies: Insights from the RACING and LODESTAR Trials", "type": "source", "url": "https://doi.org/10.3349/ymj.2024.0476", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3390/medicina61091563", "effect": "not extracted", "endpoint": "not extracted", "id": "source_17", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Impact of Statin Use on Sepsis Mortality: A Systematic Review and Meta-Analysis", "type": "source", "url": "https://doi.org/10.3390/medicina61091563", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1002/cre2.70364", "effect": "not extracted", "endpoint": "not extracted", "id": "source_18", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Adjunctive Use of Locally Delivered Statins in Periodontal Therapy and Pre‐Implant Bone Regeneration: A Systematic Review and Meta‐Analysis", "type": "source", "url": "https://doi.org/10.1002/cre2.70364", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/clc.70170", "effect": "not extracted", "endpoint": "not extracted", "id": "source_19", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effect of Statin Intensity on Cardiovascular Outcomes and Survival Following Coronary Artery Bypass Grafting", "type": "source", "url": "https://doi.org/10.1002/clc.70170", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.5144/0256-4947.2025.112", "effect": "not extracted", "endpoint": "not extracted", "id": "source_20", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "High-dose statins for the prevention of recurrent ischemic stroke: a systematic review and meta-analysis of randomized controlled trials", "type": "source", "url": "https://doi.org/10.5144/0256-4947.2025.112", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s12884-025-07967-5", "effect": "not extracted", "endpoint": "not extracted", "id": "source_21", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in 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"study": "Prognostic role of statins in colorectal cancer: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.3389/fonc.2026.1763323", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s13063-025-09097-x", "effect": "not extracted", "endpoint": "not extracted", "id": "source_37", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effect of atorvastatin versus no S tatin T reatment on major clinical events in A cute C ardio E mbolic stroke patients without a definite indication for statin therapy: protocol for the STACE trial", "type": "source", "url": "https://doi.org/10.1186/s13063-025-09097-x", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.22336/rjo.2025.35", "effect": "not extracted", "endpoint": "not extracted", "id": "source_38", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Assessing the Role of Statins as an Adjunctive Anti-VEGF Therapy for Clinically Significant Macular Edema (CSME) in Type 2 Diabetes Mellitus", "type": "source", "url": "https://doi.org/10.22336/rjo.2025.35", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1136/bmjopen-2024-091971", "effect": "not extracted", "endpoint": "not extracted", "id": "source_39", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effect of statins on neurological functional outcomes in critically ill adult patients with traumatic brain injury: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1136/bmjopen-2024-091971", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fendo.2025.1512670", "effect": "not extracted", "endpoint": "not 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"effect": "not extracted", "endpoint": "not extracted", "id": "source_50", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Preclinical efficacy and mechanisms of statin-loaded polymeric nanocapsules: a meta-analysis of tumor lipid metabolism inhibition", "type": "source", "url": "https://doi.org/10.1038/s41598-025-22302-w", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1016/j.jare.2024.12.020", "effect": "not extracted", "endpoint": "not extracted", "id": "source_51", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Advances in statin adverse reactions and the potential mechanisms: A systematic review", "type": "source", "url": "https://doi.org/10.1016/j.jare.2024.12.020", "year": 2024}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.2174/0115701611419387251202152013", "effect": "not extracted", "endpoint": "not extracted", "id": "source_52", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Potential Role of Statins in Infective Endocarditis: A Meta-Analysis.", "type": "source", "url": "https://doi.org/10.2174/0115701611419387251202152013", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_53", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "STREAM Trial - Biomarker", "type": "source", "url": null, "year": 2026}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_54", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_55", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "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.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_56", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "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.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_57", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "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.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_58", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "STREAM Trial Biomarker 2026", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1001/jama.2010.1923", "effect": "not extracted", "endpoint": "not extracted", "id": "source_59", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Studenski 2011", "type": "source", "url": "https://doi.org/10.1001/jama.2010.1923", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1093/ageing/26.1.15", "effect": "not extracted", "endpoint": "not extracted", "id": "source_60", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Bohannon 1997", "type": "source", "url": "https://doi.org/10.1093/ageing/26.1.15", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1371/journal.pmed.0020124", "effect": "not extracted", "endpoint": "not extracted", "id": "source_61", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Ioannidis 2005", "type": "source", "url": "https://doi.org/10.1371/journal.pmed.0020124", "year": null}], "publication_id": "e7c852f1-873a-4cb5-98d6-2f49fad6de83", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 53, "included": 53, "included_or_retained": 53, "screened": 53, "wording": "53 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}

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