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pmid:41484064
SOX4-STAT6-MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance.
Cell death & disease · 2026 doi:10.1038/s41419-025-08394-2
Paper
partial
Experiment
partial
Data
partial
Analysis
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Execution
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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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Complete file
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"{\"parent_value\":0,\"unit\":\"\",\"evidence\":\"\",\"target_result\":\"The source text states the main finding qualitatively: the SOX4–STAT6–MTHFD2 axis is a critical driver of hepatocellular carcinoma progression and therapeutic resistance. It gives no headline numerical result for this registered target.\",\"number_stated\":false}", "reading": {"parent_value": 0, "unit": "", "evidence": "", "target_result": "The source text states the main finding qualitatively: the SOX4–STAT6–MTHFD2 axis is a critical driver of hepatocellular carcinoma progression and therapeutic resistance. It gives no headline numerical result for this registered target.", "number_stated": false, "source_locator": null}, "recorded_at": "2026-10-31T15:27:38.150352+00:00"}, {"provider": "minimax_alt", "model": "MiniMax-M3", "prompt_version": "replication-target-v2", "prompt_hash": "c6eab4bb2890ea2663fc1423d4dec92b3d14a05bd3f80395a9038f0340b26fe8", "source_hash": "d62027b0c50c992cec31d53810239315a085be219622fa088690b4ee6a866866", "raw_response": "<think>We need answer JSON only. Need identify single numerical result headline main finding for registered target. Source is abstract + methods, no quantitative headline result perhaps Y641, P <0.05, 62 etc. User asks numerical result replication target reproduce, paper states for registered target. We need determine perhaps target result absent because source text doesn't state a headline numerical finding. Need not mistake cohort 62 or residue 641 as main finding result. The abstract mostly qualitative. Registered target: headline numerical result paper states for main finding. There is no headline numerical result. So number_stated false, parent_value 0, unit \"\", evidence \"\", target_result what text states instead. Need JSON valid. target_result concise describe main finding from text, perhaps \"The SOX4–STAT6–MTHFD2 axis drives HCC progression and treatment resistance; SOX4/STAT6 regulate MTHFD2, NADPH production and nucleotide biosynthesis, and targeting STAT6 or MTHFD2 suppresses tumor growth in TKI-resistant patient-derived xenograft models.\" They insist if no number, say in target_result what text does state instead. We should exact? No requirement exact quote for target_result in false case, likely okay paraphrase? \"Never invent source.\" Better quote exact clauses? The output target_result could say paper states main finding qualitatively. Evidence must empty. We must ensure no other numbers.\n\nCould there be a number intended as 641 Y641? \"single numerical result that a replication of registered target has to reproduce\" Registered target broad \"headline numerical result the paper states for its main finding.\" This supplied text likely excerpt lacking results section; no headline number. The answer false. Need only JSON object. Let's formulate target_result perhaps exact source wording from abstract, preserving enough: \"The SOX4–STAT6–MTHFD2 axis is a critical driver of HCC progression and therapeutic resistance; elevated axis activity is associated with resistance to immunotherapy or TKIs, and targeting STAT6 or MTHFD2 suppresses tumor growth in TKIs-resistant patient-derived xenograft models.\" That's paraphrase but source grounded. Maybe exact contiguous quote can go there though evidence empty. User says evidence empty in false case. target_result \"The text states that...\" Fine.\n\nNeed parent_value number 0, unit empty, evidence empty, boolean false.</think>\n\n{\"parent_value\":0,\"unit\":\"\",\"evidence\":\"\",\"target_result\":\"The paper states that the SOX4–STAT6–MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance, with elevated axis activity associated with resistance to immunotherapy or TKIs and targeting STAT6 or MTHFD2 suppressing tumor growth in TKI-resistant patient-derived xenograft models.\",\"number_stated\":false}", "reading": {"parent_value": 0, "unit": "", "evidence": "", "target_result": "The paper states that the SOX4–STAT6–MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance, with elevated axis activity associated with resistance to immunotherapy or TKIs and targeting STAT6 or MTHFD2 suppressing tumor growth in TKI-resistant patient-derived xenograft models.", "number_stated": false, "source_locator": null}, "recorded_at": "2026-10-31T15:27:31.161698+00:00"}], "agreement": false, "disagreements": {"target_result": {"minimax": "No headline numerical result is stated in the supplied source text; the main finding is stated qualitatively as the SOX4–STAT6–MTHFD2 axis driving HCC progression and therapeutic resistance.", "minimax_alt": "unclear", "decisive": false}, "physical_methods": {"minimax": ["co-immunoprecipitation", "immunofluorescence", "chromatin immunoprecipitation (ChIP) assays", "genetic ablation or knockdown of SOX4", "knockdown of SOX4 or STAT6", "mutation of SOX4/STAT6 binding sites within the MTHFD2 promoter", "DNA methyltransferase inhibitor treatment with 5-Aza-2’-deoxycytidine", "patient-derived xenograft models"], "minimax_alt": ["Genetic ablation or knockdown of SOX4", "treatment with the DNA methyltransferase inhibitor 5-Aza-2’-deoxycytidine", "co-immunoprecipitation", "immunofluorescence", "ChIP assays", "mutation of their binding sites within the MTHFD2 promoter", "Metabolomic profiling", "patient-derived xenograft models", "DNA methylation, ChIP-seq, and RNA-seq profiles"], "decisive": false}, "analysis_methods": {"minimax": ["Student’s t test for quantitative data", "Kaplan–Meier survival analysis", "percentile normalization of gene-expression data", "transcriptomic analysis", "metabolomic profiling"], "minimax_alt": ["GraphPad Prism 9", "Student’s t test for quantitative data", "Kaplan–Meier", "SPSS 21", "normalized as percentile gene expression for statistical analysis", "Transcriptomic analyses"], "decisive": false}, "statistical_method": {"minimax": "Student’s t test for quantitative data; overall survival was analyzed by Kaplan–Meier.", "minimax_alt": "unclear", "decisive": true}}, "agreement_basis": {"policy": "decisive_fields", "decisive_fields": ["work_type", "number_stated", "parent_value", "unit"]}, "blinded": true}, "human_critique": {"status": "not_run", "reviewer": null, "signed_at": null, "conflict_checked": false, "commentary": null}, "stages": [{"key": "target_materials", "status": "pending", "reason": null, "evidence": null}, {"key": "independent_readings", "status": "blocked", "reason": "The independent readings are incomplete or disagree; the source evidence must resolve the difference.", "evidence": {"provider_errors": []}}, {"key": "source_resolution", "status": "pending", "reason": null, "evidence": null}, {"key": "protocol_reconstruction", "status": "pending", "reason": null, "evidence": null}, {"key": "control_execution", "status": "pending", "reason": null, "evidence": null}, {"key": "control_comparison", "status": "pending", "reason": null, "evidence": null}, {"key": "publication", "status": "pending", "reason": null, "evidence": null}], "gaps": ["review.human_critique", "review.machine_critique.blocked"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "package:2e864f3a7dd740b3f97a366bb5d991ae46d379201c75668ec9288776d240f1c5", "type": "sep_package", "label": "SEP v1 package for pmid:41484064"}], "activities": [{"id": "activity:conversion:pmid:41484064", "type": "conversion", "used": ["package:2e864f3a7dd740b3f97a366bb5d991ae46d379201c75668ec9288776d240f1c5"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:minimax", "type": "model", "label": "minimax"}, {"id": "agent:minimax_alt", "type": "model", "label": "minimax_alt"}, {"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}], "source_run_id": "run-20261023T122449232913", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:41484064", "parent_hash": "sha256:30f36305ad45d8ae560d1c7c0c09065436400b045dbc40feb927be61d2405072", "fork_of": null, "generation": 2}, "gaps": ["abstract", "asset:source:pmid:41484064 not verified", "authors", "capability", "corpus_record_absent", "execution.not_run", "method", "review.human_critique", "review.machine_critique.blocked", "step:obtain_source_data blocked on data:not_downloaded", "step:run_analysis blocked on no owned computational capability is bound to this experiment", "step:run_analysis input 'materials:the source data behind the published result in pmid:41484064' does not resolve to a declared asset", "targets"]}