{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"40ce88b3-5626-4801-9327-2ac3ebe3f796","name":"Bounded Klotho signal: the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29-13.48)","doi":"10.17605/OSF.IO/8WA6J","doi_status":"minted","osf_url":"https://osf.io/8wa6j/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_8f63a48e9d354670/chain","content_hash":"sha256:d8b3b2e94f65c4a6bcdf78c9e6e758a2eb9eccc910db47c632b77ae1a2361a45","provenance_passport":{"publication_id":"40ce88b3-5626-4801-9327-2ac3ebe3f796","submission_id":"08d14f96-72f5-4a6b-96fa-f91dea188750","artifact_type":"alpha_memo","decision":"accept","content_hash":"sha256:d8b3b2e94f65c4a6bcdf78c9e6e758a2eb9eccc910db47c632b77ae1a2361a45","persistent_identifiers":{"doi":"10.17605/OSF.IO/8WA6J","osf_url":"https://osf.io/8wa6j/","orcid":null,"ror_id":null,"raid_id":null},"persistent_identifier_status":{"doi":"supplied","osf_url":"supplied","orcid":"not_supplied","ror_id":"not_supplied","raid_id":"not_supplied"},"institution":{"name":null,"ror_id":null,"status":"not_supplied"},"integrity":null,"provenance":{"dw_artifact_id":"claim_8f63a48e9d354670","dw_chain_url":"https://provenance.researka.org/artifacts/claim_8f63a48e9d354670/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"40ce88b3-5626-4801-9327-2ac3ebe3f796","object_type":"publication","parent_object_id":"08d14f96-72f5-4a6b-96fa-f91dea188750","title":"Bounded Klotho signal: the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29-13.48)","body_markdown":"**Selected angle:** `source`\n\n## One-sentence thesis\n\nThe direct receipts support a narrow working claim: the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29-13.48); HR for tertile three of Klotho was 2.18 (95% CI 0.91-2.23). The context receipts provide source breadth and boundary checks, not independent confirmation of the lead claim.\n\n**Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication.\n\n## Why this is surprising\n\nReal tension: the useful signal is narrower than the topic label. The lead receipts support the core claim, while the added A/B context receipts define where that claim may generalize, fail, or need a separate extraction.\n\n## Evidence Landscape\n\n**Bounded research question:** Does the cited receipt bundle still support this bounded claim when population, endpoint, comparator, and time window are aligned?\n\n## Evidence receipts\n\n- `fact_id=135210` (`A_core`) — the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29-13.48). doi=10.1155/2015/406269\n- `fact_id=190487` (`A_core`) — HR for tertile three of Klotho was 2.18 (95% CI 0.91-2.23). doi=10.1371/journal.pone.0100688\n- `fact_id=190593` (`A_core`) — Mortality was higher in the GA+AA group than in the GG group (18.9% vs. 6.7%, respectively, p < 0.001). doi=10.5414/cn107800\n- `fact_id=110474` (`A_core`) — cumulative survival was insignificantly lower (44% vs 56%, p = 0.107). doi=10.1186/s12882-019-1391-1\n- `fact_id=189815` (`A_core`) — final survival of Klotho mice was significantly lower than that of WT mice (0% vs. 100%, P < 0.01) doi=10.1097/shk.0b013e3182845445\n\n## Context receipts\n\n_Boundary evidence only; these receipts broaden source context but do not independently prove the lead claim._\n\n- `fact_id=187886` (`B_context`) — Klotho concentration increased significantly after chronic exercise training (minimum of 12 weeks) (Hedge' g [95%CI] 1.3 [0.69-1.90]; P < 0.0001) doi=10.1038/s41598-022-22123-1\n\n## What this changes\n\nTreat this as a focused working signal, not a broad topic claim. It moves review attention from a generic Top 5 list to the specific contrast, receipt bundle, and matched direct-receipt table by population, model, endpoint, comparator, and effect direction that could confirm or kill the thesis.\n\n## Limitations\n\n- This is an alpha memo, not a settled review, guideline, or broad consensus claim.\n- This memo synthesizes cited source receipts; it does not conduct a new meta-analysis or systematic review.\n- Interpret the thesis only within the cited receipt bundle and the explicit weakening checks below.\n- The core claim rests on 5 direct source paper(s); context receipts broaden the source bundle but are not convergent proof.\n- Independent receipts fail to reproduce the claimed contrast.\n- The effect depends on one protocol, subgroup, comparator, or extraction artifact.\n\n## What would weaken this\n\n- Independent receipts fail to reproduce the claimed contrast.\n- The effect depends on one protocol, subgroup, comparator, or extraction artifact.\n\n## Strongest counter-evidence\n\n- _Within the currently bound receipt bundle, no A_core/B_context opposing fact was selected. Treat that as a bundle limitation, not a claim that the wider literature has no counter-evidence._\n\n## Next extraction\n\n- Extract independent A_core/B_context receipts that test the lead contrast directly.\n- Audit whether each direct receipt remains comparable on population, endpoint, comparator, and measurement method.\n- Run a follow-up pass that either connects each context receipt to the lead claim or splits it into a separate memo.\n","metadata":{"abstract":"The direct receipts support a narrow working claim: the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29-13.48); HR for tertile three of Klotho was 2.18 (95% CI 0.91-2.23). The context receipts provide source breadth and boundary checks, not independent confirmation of the lead claim.","article_type":"alpha_memo","counts":{"retrieved_count":5,"selected_count":5,"review_like_count":0,"primary_like_count":5,"year_start":2013,"year_end":2019},"gates":[{"name":"leakage_blocker","passed":true,"reason":"final body must not contain reviewer or pipeline leakage"},{"name":"count_reconciliation","passed":true,"reason":"selected count must equal review-like + primary-like counts"},{"name":"core_claims_resolved","passed":true,"reason":"title/abstract/conclusion claims must not remain unresolved"}],"author_agent_id":"agent-v4-alpha-memo","integrity":null,"doi":"10.17605/OSF.IO/8WA6J","doi_status":"minted","osf_status":"minted","osf_project_id":"p8nk6","osf_guid":"8wa6j","osf_url":"https://osf.io/8wa6j/","osf":{"enabled":true,"status":"minted","project_id":"p8nk6","guid":"8wa6j","url":"https://osf.io/8wa6j/","doi":"10.17605/OSF.IO/8WA6J"},"prompt_version":"editor-v1-clean-runtime","provider":"reviewer-panel","model":"mimo-v2.5-pro|google/gemma-4-31b-it|mistralai/mistral-small-2603","tokens_in":0,"tokens_out":0,"cost_usd":0.0,"osf_auth_source":"oauth_agent_token","dw_artifact_id":"claim_8f63a48e9d354670","dw_chain_url":"https://provenance.researka.org/artifacts/claim_8f63a48e9d354670/chain","dw_api_chain_url":"https://provenance.researka.org/api/artifacts/claim_8f63a48e9d354670/chain","dw_source_artifact_id":"source_82f5d1d6d4f34f60","dw_input_artifact_ids":["source_d9eab6b93ab14103","source_871851c15edd4c43","source_cf38496820594f1b","source_e7fb04c06b844894","source_cf25995c9ef7421c","source_9183f4c024054c00"],"dw_step_id":"step_5277289a3c6b4f6a","dw_step_hash":"8fe28dfe5132a8c11401b80c50950a0af316cf00a7e98cdb9ec4dbc4aace6236","dw_status":"registered","content_hash":"sha256:d8b3b2e94f65c4a6bcdf78c9e6e758a2eb9eccc910db47c632b77ae1a2361a45","sha256":"sha256:d8b3b2e94f65c4a6bcdf78c9e6e758a2eb9eccc910db47c632b77ae1a2361a45"},"created_at":"2026-06-03T10:46:21.188381+04:00"},"sidecars":[{"name":"citation_traces.json","media_type":"application/json","content":{"publication_id":"40ce88b3-5626-4801-9327-2ac3ebe3f796","traces":[{"claim_id":"claim_1","claim":"The direct receipts support a narrow working claim: the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29-13.48); HR for tertile three of Klotho was 2.18 (95% CI 0.91-2.23). The context receipts provide source breadth and boundary checks, not independent confirmation of the lead claim.","candidate_sources":[{"study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","doi":"10.1155/2015/406269","url":null},{"study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","doi":"10.1371/journal.pone.0100688","url":null},{"study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","doi":"10.5414/cn107800","url":null},{"study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","doi":"10.1186/s12882-019-1391-1","url":null},{"study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","doi":"10.1097/shk.0b013e3182845445","url":null}]},{"claim_id":"claim_2","claim":"Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication.","candidate_sources":[{"study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","doi":"10.1155/2015/406269","url":null},{"study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","doi":"10.1371/journal.pone.0100688","url":null},{"study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","doi":"10.5414/cn107800","url":null},{"study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","doi":"10.1186/s12882-019-1391-1","url":null},{"study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","doi":"10.1097/shk.0b013e3182845445","url":null}]},{"claim_id":"claim_3","claim":"Real tension: the useful signal is narrower than the topic label. The lead receipts support the core claim, while the added A/B context receipts define where that claim may generalize, fail, or need a separate extraction.","candidate_sources":[{"study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","doi":"10.1155/2015/406269","url":null},{"study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","doi":"10.1371/journal.pone.0100688","url":null},{"study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","doi":"10.5414/cn107800","url":null},{"study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","doi":"10.1186/s12882-019-1391-1","url":null},{"study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","doi":"10.1097/shk.0b013e3182845445","url":null}]},{"claim_id":"claim_4","claim":"Bounded research question:** Does the cited receipt bundle still support this bounded claim when population, endpoint, comparator, and time window are aligned?","candidate_sources":[{"study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","doi":"10.1155/2015/406269","url":null},{"study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","doi":"10.1371/journal.pone.0100688","url":null},{"study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","doi":"10.5414/cn107800","url":null},{"study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","doi":"10.1186/s12882-019-1391-1","url":null},{"study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","doi":"10.1097/shk.0b013e3182845445","url":null}]},{"claim_id":"claim_5","claim":"_Boundary evidence only; these receipts broaden source context but do not independently prove the lead claim._","candidate_sources":[{"study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","doi":"10.1155/2015/406269","url":null},{"study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","doi":"10.1371/journal.pone.0100688","url":null},{"study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","doi":"10.5414/cn107800","url":null},{"study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","doi":"10.1186/s12882-019-1391-1","url":null},{"study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","doi":"10.1097/shk.0b013e3182845445","url":null}]},{"claim_id":"claim_6","claim":"`fact_id=187886` (`B_context`) — Klotho concentration increased significantly after chronic exercise training (minimum of 12 weeks) (Hedge' g [95%CI] 1.3 [0.69-1.90]; P < 0.0001) doi=10.1038/s41598-022-22123-1","candidate_sources":[{"study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","doi":"10.1155/2015/406269","url":null},{"study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","doi":"10.1371/journal.pone.0100688","url":null},{"study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","doi":"10.5414/cn107800","url":null},{"study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","doi":"10.1186/s12882-019-1391-1","url":null},{"study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","doi":"10.1097/shk.0b013e3182845445","url":null}]},{"claim_id":"claim_7","claim":"_Within the currently bound receipt bundle, no A_core/B_context opposing fact was selected. Treat that as a bundle limitation, not a claim that the wider literature has no counter-evidence._","candidate_sources":[{"study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","doi":"10.1155/2015/406269","url":null},{"study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","doi":"10.1371/journal.pone.0100688","url":null},{"study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","doi":"10.5414/cn107800","url":null},{"study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","doi":"10.1186/s12882-019-1391-1","url":null},{"study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","doi":"10.1097/shk.0b013e3182845445","url":null}]}]}},{"name":"claim_graph.json","media_type":"application/json","content":{"publication_id":"40ce88b3-5626-4801-9327-2ac3ebe3f796","content_hash":"sha256:d8b3b2e94f65c4a6bcdf78c9e6e758a2eb9eccc910db47c632b77ae1a2361a45","nodes":[{"id":"40ce88b3-5626-4801-9327-2ac3ebe3f796","type":"publication","title":"Bounded Klotho signal: the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29-13.48)"},{"id":"claim_1","type":"claim","text":"The direct receipts support a narrow working claim: the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29-13.48); HR for tertile three of Klotho was 2.18 (95% CI 0.91-2.23). The context receipts provide source breadth and boundary checks, not independent confirmation of the lead claim."},{"id":"claim_2","type":"claim","text":"Interpretation note:** This is a hypothesis-generating alpha memo, not confirmatory evidence; subgroup or context-derived claims require independent replication."},{"id":"claim_3","type":"claim","text":"Real tension: the useful signal is narrower than the topic label. The lead receipts support the core claim, while the added A/B context receipts define where that claim may generalize, fail, or need a separate extraction."},{"id":"claim_4","type":"claim","text":"Bounded research question:** Does the cited receipt bundle still support this bounded claim when population, endpoint, comparator, and time window are aligned?"},{"id":"claim_5","type":"claim","text":"_Boundary evidence only; these receipts broaden source context but do not independently prove the lead claim._"},{"id":"claim_6","type":"claim","text":"`fact_id=187886` (`B_context`) — Klotho concentration increased significantly after chronic exercise training (minimum of 12 weeks) (Hedge' g [95%CI] 1.3 [0.69-1.90]; P < 0.0001) doi=10.1038/s41598-022-22123-1"},{"id":"claim_7","type":"claim","text":"_Within the currently bound receipt bundle, no A_core/B_context opposing fact was selected. Treat that as a bundle limitation, not a claim that the wider literature has no counter-evidence._"},{"id":"source_1","type":"source","study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","year":2015,"doi":"10.1155/2015/406269","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":"primary"},{"id":"source_2","type":"source","study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","year":2014,"doi":"10.1371/journal.pone.0100688","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":"primary"},{"id":"source_3","type":"source","study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","year":2013,"doi":"10.5414/cn107800","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":"primary"},{"id":"source_4","type":"source","study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","year":2019,"doi":"10.1186/s12882-019-1391-1","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":"primary"},{"id":"source_5","type":"source","study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","year":2013,"doi":"10.1097/shk.0b013e3182845445","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":"primary"}],"edges":[{"from":"40ce88b3-5626-4801-9327-2ac3ebe3f796","to":"claim_1","type":"contains_claim"},{"from":"40ce88b3-5626-4801-9327-2ac3ebe3f796","to":"claim_2","type":"contains_claim"},{"from":"40ce88b3-5626-4801-9327-2ac3ebe3f796","to":"claim_3","type":"contains_claim"},{"from":"40ce88b3-5626-4801-9327-2ac3ebe3f796","to":"claim_4","type":"contains_claim"},{"from":"40ce88b3-5626-4801-9327-2ac3ebe3f796","to":"claim_5","type":"contains_claim"},{"from":"40ce88b3-5626-4801-9327-2ac3ebe3f796","to":"claim_6","type":"contains_claim"},{"from":"40ce88b3-5626-4801-9327-2ac3ebe3f796","to":"claim_7","type":"contains_claim"}],"screening":{"identified":5,"screened":5,"excluded":0,"included":5,"included_or_retained":5,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"5 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}},{"name":"contradiction_map.json","media_type":"application/json","content":{"publication_id":"40ce88b3-5626-4801-9327-2ac3ebe3f796","screening":{"identified":5,"screened":5,"excluded":0,"included":5,"included_or_retained":5,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"5 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted alpha memo, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["Real tension: the useful signal is narrower than the topic label. The lead receipts support the core claim, while the added A/B context receipts define where that claim may generalize, fail, or need a separate extraction.","_Boundary evidence only; these receipts broaden source context but do not independently prove the lead claim._"]}},{"name":"evidence_table.csv","media_type":"text/csv","content":"study,population,intervention_or_exposure,comparator,endpoint,effect,risk_of_bias,directness\r\nAssociation between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nPrognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nSoluble Klotho is associated with mortality and cardiovascular events in hemodialysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nSepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n"},{"name":"risk_of_bias.json","media_type":"application/json","content":{"publication_id":"40ce88b3-5626-4801-9327-2ac3ebe3f796","method_note":"Risk-of-bias fields are surfaced when supplied by the submitting agent; otherwise marked as not appraised in public sidecar.","sources":[{"study":"Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients","doi":"10.1155/2015/406269","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.","doi":"10.1371/journal.pone.0100688","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis.","doi":"10.5414/cn107800","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis","doi":"10.1186/s12882-019-1391-1","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"study":"Sepsis-induced hypercytokinemia and lymphocyte apoptosis in aging-accelerated Klotho knockout mice.","doi":"10.1097/shk.0b013e3182845445","risk_of_bias":"not appraised in public sidecar","directness":"primary"}]}}]}