Derivation Web

source_0ad306f2bfa14cdf

by researka:v2 · 2026-06-26 09:16:27.965560+04:00

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The conclusion therefore does not support broad causal, clinical, or policy claims.", "type": "claim"}, {"id": "claim_2", "text": "This synthesis tests the thesis that evidence for Cardiovascular Subgroups is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation.", "type": "claim"}, {"id": "claim_3", "text": "Cardiovascular disease in older adults carries disproportionate mortality, with adults aged ≥65 accounting for over 80% of CVD-related deaths in the United States (Sun 2026), and frailty, sarcopenic obesity, and cardiometabolic syndrome have each emerged as candidate modifiers of cardiovascular risk trajectories in this population (Zhang 2025; Zhao 2025; Chen 2026a).", "type": "claim"}, {"id": "claim_4", "text": "We conducted an AI-assisted structured evidence synthesis with a per-source audit trail, screening 64 curated reference papers across cardiometabolic, longevity, frailty, muscle-function, and contextual-other outcomes, and we explicitly preserved the direct/indirect/review/protocol/mechanistic design label of each source rather than collapsing them.", "type": "claim"}, {"id": "claim_5", "text": "Methodologically, the synthesis is dominated by indirect, review, and protocol-level evidence with comparatively few direct RCTs, and the available human data do not yet adjudicate whether subgroup-specific signals (e. For example, the adverse detraining effects in Zheng 2025 versus the null influenza-vaccine cardiovascular subgroup effects in Nielsen 2026) reflect genuine heterogeneity versus design-driven noise.", "type": "claim"}, {"id": "claim_6", "text": "Aging remains the dominant driver of chronic disease burden in high-income health systems, and cardiovascular subgroups sit at the centre of that question because cardiovascular events are both common and tightly coupled to functional decline in later life. The clinical stake is straightforward: most years lived with multimorbidity accumulate after age 65, and the question of whether interventions targeting aging biology can extend healthspan has been proposed as a route to compressing that morbidity (Sun 2026). Evidence suggests that adults aged 65 and over carry a disproportionate share of cardiovascular mortality, with U.S. figures indicating that this group accounts for over 80% of cardiovascular-disease-related deaths, framing the urgency of any healthspan-oriented strategy. Why now is a matter of timing rather than novelty: existing cardiovascular drug classes have decades of safety data, several recent trials have begun enrolling older or frail participants explicitly, and regulatory pathways for function- and event-based endpoints are mature enough to be repurposed for aging indications. The cardiovascular subgroups question, in short, is whether an already-prescribed cardiovascular therapy can be repositioned to slow the upstream biology of aging rather than only its downstream manifestations.", "type": "claim"}, {"id": "claim_7", "text": "The geroscience hypothesis argues that targeting the molecular hallmarks of aging may yield larger and more synchronised gains across organ systems than the current strategy of treating each chronic disease in isolation. Within that frame, cardiovascular subgroups are attractive because the cardiovascular system is both measurable (through blood pressure, lipids, vascular function, and hard events) and mechanistically entangled with pathways implicated in aging biology such as inflammation, metabolic regulation, and fibrosis. A practical appeal is that several candidate agents are already licensed for cardiovascular or metabolic indications, so the choice between repurposing and novel development can in principle be answered through pragmatic trials in cardiovascular subgroups rather than de novo drug development. Whether the geroscience bet actually translates into clinical cardiovascular benefit remains uncertain, however, because trials designed around aging biology endpoints have only recently entered the cardiovascular subgroups pipeline. The cardiovascular subgroups anti-aging case, as currently constituted, therefore rests on a mix of mechanistic plausibility and indirect human evidence rather than on dedicated trials.", "type": "claim"}, {"id": "claim_8", "text": "source-grounded cardiovascular subgroups in this evidence base span multiple drug classes, including sodium-glucose cotransporter 2 inhibitors, cholesteryl ester transfer protein inhibitors, influenza vaccination strategies, and antithrombotic regimens. SGLT2 inhibitors have an established cardiometabolic regulatory history and are being examined in older adults with cardiovascular disease (Minami 2025), while the CETP inhibitor obicetrapib has been studied at the 10 mg daily dose in the BROADWAY trial programme with secondary mechanistic readouts (Davidson 2025). Influenza vaccination has a different access pathway: high-dose versus standard-dose formulations are being compared for severe cardiovascular outcomes in older adults with diabetes (Nielsen 2026), and the regulatory history of these vaccines means the cardiovascular subgroups case can be tested without the long safety runway required for novel small molecules. Within antiplatelet and antithrombotic care, extended follow-up of the ASPREE cohort has evaluated aspirin for primary prevention in adults aged 70 years and over (Wolfe 2025). The cardiovascular subgroups rationale, then, is partly that the infrastructure and labelling for these agents already exist, which may shorten the path from hypothesis to actionable prescribing.", "type": "claim"}, {"id": "claim_9", "text": "Several unresolved questions remain at the centre of the cardiovascular subgroups debate. First, the translation from mechanistic signal to functional and hard-outcome benefit is uncertain: the same intervention can move a surrogate biomarker while leaving clinical cardiovascular events unchanged, and Ioannidis 2005 cautions against treating surrogate endpoints as proxies for hard-outcome validity. Second, treatment effects appear to differ across subgroups, with frailty status emerging as a recurring modifier of cardiovascular benefit, and sarcopenia-related cohorts in this source set reporting elevated cardiovascular risk and mortality (Zhang 2025). Third, tradeoffs between benefit and harm, including bleeding, polypharmacy burden, and drug–drug interactions, are not uniformly characterised in older or multimorbid cardiovascular subgroups populations (Lee 2026). Fourth, follow-up durations in many of the included trials and reviews are short relative to the lifespan arc that an aging-targeted cardiovascular subgroups strategy would need to address, and dose–response relationships remain poorly mapped in frail subgroups. Whether cardiovascular subgroups effects can be sustained, or amplified, with longer follow-up remains uncertain.", "type": "claim"}, {"id": "claim_10", "text": "The background evidence for cardiovascular subgroups is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Salerno 2026, Riquelme-Hernandez 2026, Wang 2026 are interpreted separately from mechanistic studies such as Ghosh 2026, because these evidence roles answer different questions about aging biology and clinical translation.", "type": "claim"}, {"id": "claim_11", "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_12", "text": "Across the retained sources, positive signals cluster around the cardiometabolic outcome class; null signals around the contextual adjacent evidence, cardiometabolic, dosing and pharmacokinetics outcome classes; and negative or adverse signals around the longevity and cardiometabolic outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "type": "claim"}, {"id": "claim_13", "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_14", "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_15", "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_16", "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_17", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, frailty, immune and inflammation, longevity, mechanism, mortality and survival, muscle function, safety, safety and comorbidity); 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_18", "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_19", "text": "Source-label disambiguation note: citation label Chen (2026a) maps to one retained manifest receipt (Longevity; direction=mixed; directness=indirect; title: The Relationship between Sarcopenia and All-Cause and Cardiovascular Mortality Risk among Middle-Aged and Older Adults across Stages 0–3 of Cardiovascular-Kidney-Metabolic Syndrome: Evidence from NHANES and CHARLS); citation label Chen (2026b) maps to one retained manifest receipt (Longevity; direction=unclear; directness=indirect; title: Resting Heart Rate as a Non-Cardiovascular Mortality Marker in Young Adults: A Population-Based Cohort Study); citation label Ward (2026) maps to one retained manifest receipt (Immune and Inflammation; direction=null; directness=indirect; title: Targeting inflammation in cardiometabolic disease: Icosapent ethyl modulates monocyte‐derived macrophages isolated from patients with cardiovascular disease with or without type 2 diabetes); citation label Filev (2026) maps to one retained manifest receipt (Immune and Inflammation; direction=unclear; directness=indirect; title: Association of Acute-Phase IL-6 and SAA with Cardiovascular Events and Mortality Six Years After COVID-19 Infection: An Observational Cohort Study).", "type": "claim"}, {"id": "claim_20", "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_21", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_22", "text": "| Cardiovascular Subgroups / Contextual Adjacent Evidence | n=21; claims=1250 | significant source statistic in 16/21 sources; receipt-level direction coded null | 3 direct; 7 indirect; 3 protocol; 8 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_23", "text": "| Cardiovascular Subgroups / Dosing and Pharmacokinetics | n=2; claims=187 | significant source statistic in 1/2 sources; receipt-level direction coded null | 2 indirect | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_24", "text": "| Cardiovascular Subgroups / Mechanism | n=1; claims=77 | significant source statistic in 1/1 sources; receipt-level direction coded null | 1 mechanistic | single-source slice; hypothesis-generating |", "type": "claim"}, {"id": "claim_25", "text": "Aging and geroscience context: 24 sources; significant source statistic in 19/24 sources; receipt-level direction coded null.", "type": "claim"}, {"id": "claim_26", "text": "Infectious-disease and immunology context: 3 sources; significant source statistic in 1/3 sources; receipt-level direction coded null.", "type": "claim"}, {"id": "claim_27", "text": "Contextual Adjacent Evidence: n=21; claims=1250; no extracted directional signal in 14/21 sources | directness: 3 direct; 7 indirect; 8 review; 3 protocol; main limitation: directionally heterogeneous.", "type": "claim"}, {"id": "claim_28", "text": "The cardiometabolic class carries the bulk of the evidence base, anchored by four protocol/RCT bundles, six systematic reviews or meta-analyses, and four observational cohort bundles. Durstenfeld 2026 is an RCT protocol — the EPIC-HIV trial — enrolling adults at least 40 years old with treated and virally suppressed HIV plus at least one cardiovascular risk factor (source Durstenfeld 2026). Grazuleviciene 2026 is an RCT protocol for an ambient air and noise pollution cardiovascular lifestyle intervention in Lithuania (source Grazuleviciene 2026). Wolfe 2025 reports extended follow-up of the ASPREE trial (NCT01038583) in adults aged ≥70 years (≥65 for US minorities) without prior cardiovascular events, dementia, or independence-limiting physical disability (source Wolfe 2025). Together these four direct studies set the clinical-RCT boundary within which the surrounding indirect and review evidence is interpreted.", "type": "claim"}, {"id": "claim_29", "text": "Within-corpus tensions are extensive and must be kept within their evidence class. Directness is a non-trivial boundary: the three direct RCT protocols (Wang 2026, Durstenfeld 2026, Grazuleviciene 2026) should be interpreted separately from the indirect cohort and review evidence that surrounds them, and we therefore do not collapse them into the same effect-direction tally as Erdogan 2025 or Wolfe 2025. The disagreement between You 2026 and Delaney 2025 (negative in frail OSA adults versus positive systolic-blood-pressure reduction with strawberry intake in older adults) is a direct directional conflict best read as context-dependent rather than as a uniform class effect. We therefore refrain from a single composite direction label for the cardiometabolic class and instead present direction stratified by exposure, population, and follow-up (see the evidence synthesis for the per-study endpoint evidence).", "type": "claim"}, {"id": "claim_30", "text": "The contextual other outcome class spans the largest share of the curated corpus and includes review-level syntheses, observational cohorts, and ongoing trial protocols that situate cardiovascular subgroups within broader geriatric and cardiometabolic risk frameworks. The clinical RCT and observational substrate underlying this finding is augmented by Etayo-Urtasun 2025, which conducted a systematic review and meta-analysis of exercise effects on autonomic cardiovascular function in older adults and reported a root mean square of successive differences (RMSSD) effect size of SMD 0.636 (95% CI 0.014–1.258; P = 0.045), with additional cohort signal at P = 0.027, P = 0.093, P = 0.013, P = 0.006, P = 0.227, P = 0.188, and P = 0.003.", "type": "claim"}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fspor.2026.1708003", "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": "Isotemporal substitution of sedentary time with physical activity for cardiovascular health in older adults: a systematic review", "type": "source", "url": "https://doi.org/10.3389/fspor.2026.1708003", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1080/15502783.2026.2675444", "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": "Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1080/15502783.2026.2675444", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1001/jamainternmed.2025.7286", "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": "High-Dose vs Standard-Dose Influenza Vaccine in Older Adults With Diabetes", "type": "source", "url": "https://doi.org/10.1001/jamainternmed.2025.7286", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1016/j.jnha.2025.100714", "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": "Effects of detraining on cardiovascular risk factors in older adults: A systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1016/j.jnha.2025.100714", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.tjpad.2025.100394", "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": "Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease", "type": "source", "url": "https://doi.org/10.1016/j.tjpad.2025.100394", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1111/jgs.70143", "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": "SGLT2 Inhibitors in Older Adults With Cardiovascular Disease: A Systematic Review and Meta‐Analysis", "type": "source", "url": "https://doi.org/10.1111/jgs.70143", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3390/ijms27104375", "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": "Mortality Assessment in Patients with Cardiovascular Disease and COVID-19: A Systematic Review and Meta-Analysis", "type": "source", "url": "https://doi.org/10.3390/ijms27104375", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1038/s41598-026-35996-3", "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": "A systematic review and meta-analysis of the mechanism of action of Tai Chi on cardiovascular disease: evidence map of aerobic and mind-body exercise pathways", "type": "source", "url": "https://doi.org/10.1038/s41598-026-35996-3", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s13195-025-01808-5", "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": "Cardiovascular risk factors are associated with lower posterior-medial network functional connectivity in older adults", "type": "source", "url": "https://doi.org/10.1186/s13195-025-01808-5", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1159/000550891", "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": "The Relationship between Sarcopenia and All-Cause and Cardiovascular Mortality Risk among Middle-Aged and Older Adults across Stages 0–3 of Cardiovascular-Kidney-Metabolic Syndrome: Evidence from NHANES and CHARLS", "type": "source", "url": "https://doi.org/10.1159/000550891", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s12933-026-03148-6", "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": "Associations of triglyceride–glucose-related composite obesity indices with cardiovascular diseases and mortality: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1186/s12933-026-03148-6", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s40520-025-03080-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": "Quality of plant-based diets in relation to all-cause and cardiovascular disease mortality in US adults with sarcopenia: a population-based study", "type": "source", "url": "https://doi.org/10.1007/s40520-025-03080-x", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.14744/AnatolJCardiol.2025.5635", "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": "Sarcopenic Obesity and Cardiovascular Disease Risk and Mortality: A Systematic Review and Meta-Analysis", "type": "source", "url": "https://doi.org/10.14744/AnatolJCardiol.2025.5635", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.tjnut.2026.101363", "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": "Harnessing Clinical and Biochemical Data for Personalized Cardiovascular Risk Prediction: a Machine Learning Approach Toward Precision Nutrition", "type": "source", "url": "https://doi.org/10.1016/j.tjnut.2026.101363", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s41999-025-01354-1", "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": "Cardiovascular and glucose-lowering medication use among older adults: results from 9-year follow-up of the FINGER trial", "type": "source", "url": "https://doi.org/10.1007/s41999-025-01354-1", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s12872-026-05790-0", "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": "Association between ambient temperature and out-of-hospital cardiac arrest: a systematic review and meta-analysis", "type": "source", "url": "https://doi.org/10.1186/s12872-026-05790-0", "year": 2026}, {"comparator": 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"intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Rationale, design, and baseline characteristicss of the effect of PCSK9 inhibition on cardiovascular risk in treated HIV infection: EPIC-HIV randomized clinical trial.", "type": "source", "url": "https://doi.org/10.1016/j.ahj.2026.107400", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1016/j.cardfail.2026.02.045", "effect": "not extracted", "endpoint": "not extracted", "id": "source_64", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Acoramidis, Serum Transthyretin, and Cardiovascular Outcomes in Transthyretin Amyloid Cardiomyopathy: Insights From the ATTRibute-CM Trial.", "type": "source", "url": "https://doi.org/10.1016/j.cardfail.2026.02.045", "year": 2026}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_65", "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_66", "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_67", "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_68", "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": "10.1371/journal.pmed.0020124", "effect": "not extracted", "endpoint": "not extracted", "id": "source_69", "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": "a1bcd190-f6e6-43c4-8621-4ce37971859a", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 64, "included": 64, "included_or_retained": 64, "screened": 64, "wording": "64 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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