{ "map_id": "NOP_EMPIRICAL_REFERENCE_MAP_V0_2", "schema_version": "0.2.0", "created_utc_date": "2026-11-12", "scope": "Observable-to-source and observable-to-tool traceability. No participant dataset or empirical model fit is created by this map.", "correspondence": "Every map row has one stable observable identity, source locator, measurement context and destination field. Different endpoint assays use separately declared datasets even when their destination field name is the same. Invertible coordinate representation is conditional on admitted paired positive assays and retained references; causal correspondence requires separate predictions and experiments.", "status_definitions": { "measured": "The source reports acquisition of this observable. 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(2011), PMID 21294852", "url": "https://pubmed.ncbi.nlm.nih.gov/21294852/", "type": "primary_crossover_study", "inspection": "Primary abstract inspected; full text not retrieved.", "doi": "10.1111/j.1748-1716.2011.02262.x" }, { "id": "DEBEVEC_2012", "citation": "Debevec et al. (2012), PMID 21735214", "url": "https://pubmed.ncbi.nlm.nih.gov/21735214/", "type": "primary_controlled_study", "inspection": "Primary abstract inspected; full text not retrieved.", "doi": "10.1007/s00421-011-2060-7" }, { "id": "KHALIFE_2021", "citation": "Khalife et al. (2021), Frontiers in Physiology 12, 744074", "url": "https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.744074/full", "type": "primary_postoperative_trial", "inspection": "Full text inspected. Raw data offered through authors.", "doi": "10.3389/fphys.2021.744074" }, { "id": "KHALIFE_2024", "citation": "Khalife et al. (2024), Journal of Anesthesia, Analgesia and Critical Care 4, 43", "url": "https://link.springer.com/article/10.1186/s44158-024-00179-x", "type": "primary_post_hoc_trial_report", "inspection": "Full text inspected. Data available on reasonable request.", "doi": "10.1186/s44158-024-00179-x" }, { "id": "CHANDEL_1998", "citation": "Chandel et al. (1998), PNAS 95, 11715–11720", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC21706/", "type": "primary_cell_mechanism", "inspection": "Primary abstract and indexed full-text excerpts inspected." }, { "id": "JAAKKOLA_2001", "citation": "Jaakkola et al. (2001), Science, PMID 11292861", "url": "https://pubmed.ncbi.nlm.nih.gov/11292861/", "type": "primary_molecular_mechanism", "inspection": "Primary abstract retrieved." }, { "id": "KOBAYASHI_2016", "citation": "Kobayashi et al. (2016), JCI 126, 1926–1938", "url": "https://www.jci.org/articles/view/83551", "type": "primary_mouse_genetic_mechanism", "inspection": "Full text inspected." }, { "id": "ARBOR_K006_H", "citation": "Arbor Assays, K006-H1 manufacturer protocol and sample-preparation guidance", "url": "https://www.arborassays.com/questions/how-do-i-prepare-my-samples-for-gsh-measurement/", "type": "manufacturer_assay_documentation", "inspection": "Current manufacturer guidance inspected; historical study processing must be confirmed independently.", "pdf_url": "https://www.arborassays.com/documentation/inserts/K006-H.pdf" }, { "id": "BALESTRA_2006", "citation": "Balestra et al. (2006), Journal of Applied Physiology 100, 512–518", "url": "https://pubmed.ncbi.nlm.nih.gov/16239610/", "doi": "10.1152/japplphysiol.00964.2005", "type": "primary_human_experiment", "inspection": "Primary abstract inspected; full text not retrieved." }, { "id": "KERAMIDAS_2012", "citation": "Keramidas et al. 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No participant file received.", "raw_participant_data_received": false, "public_material": "Tables 1–3, Figure 1, methods.", "source_id": "KHALIFE_2021", "locator": "Data availability; Statistical analysis" }, "K24_RAW": { "description": "Available from corresponding author on reasonable request; no participant file received.", "raw_participant_data_received": false, "public_material": "Article tables, figures and methods.", "source_id": "KHALIFE_2024", "locator": "Availability of data and materials" }, "ABSTRACT_ONLY": { "description": "Primary abstract inspected. 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Participant-level paired files and assay metadata have not been obtained.", "tool_field": "ros", "binding": "conditional", "metadata_paths": [ "ros.unit", "ros.compartment", "ros.assay" ], "role": "observable", "import_ready": false, "notes": "Oxidant-assay signal; raw pairing and calibration required. No total-ROS concentration claim.", "source_flag_ids": [] }, { "id": "D17_GSH", "study_id": "DONATI_2017", "observable": "Reported glutathione", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Immunoassays; Table 4; Figure 2b", "method": "Arbor Assays K006-H1 colorimetric kit", "unit": "µM", "normalization": "Table 4 raw scale; Figure 2 subject baseline=100%", "compartment": "serum", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "scavenger", "binding": "conditional", "metadata_paths": [ "scavenger.unit", "scavenger.compartment", "scavenger.assay" ], "role": "observable", "import_ready": false, "notes": "A denotes this specified assay. Total antioxidant capacity has not been measured.", "source_flag_ids": [ "GSH_PROCESSING_MODE", "D17_ESTIMAND" ] }, { "id": "D17_GSH_MODE", "study_id": "DONATI_2017", "observable": "Reduced-versus-total glutathione processing", "status": "unresolved", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Immunoassays; Abbreviations; manufacturer protocol", "method": "Study-specific reduction, blocking and subtraction steps not supplied", "unit": null, "normalization": "unresolved", "compartment": "serum", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "metadata.scavenger.assay", "binding": "metadata_only", "metadata_paths": [ "scavenger.assay" ], "role": "assay_identity", "import_ready": false, "notes": "Retain paper label; request contemporaneous kit/lab procedure before choosing molecular species.", "source_flag_ids": [ "GSH_PROCESSING_MODE" ] }, { "id": "D17_PAO2", "study_id": "DONATI_2017", "observable": "Arterial oxygen partial pressure", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Table 1", "method": "Arterial blood-gas measurement; analyzer model not stated", "unit": "mmHg", "normalization": "absolute", "compartment": "arterial blood", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "oxygen", "binding": "conditional", "metadata_paths": [ "oxygen_read.kind", "oxygen_read.unit", "oxygen_read.compartment", "oxygen_read.assay" ], "role": "observable", "import_ready": false, "notes": "Use arterial_po2. Convert to kPa under an explicitly recorded convention and retain original mmHg. Match redox-subset subject IDs.", "source_flag_ids": [] }, { "id": "D17_FIO2", "study_id": "DONATI_2017", "observable": "Nominal inspired oxygen fraction", "status": "computed", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Interventions", "method": "Protocol-setting representation; actual gas/ventilator log required", "unit": "fraction", "normalization": "nominal setting; hyperoxia=1; return=individual baseline", "compartment": "inspired gas", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "fio2", "binding": "conditional", "metadata_paths": [], "role": "protocol", "import_ready": false, "notes": "Protocol setting is distinct from measured delivered oxygen.", "source_flag_ids": [ "D17_RETURN" ] }, { "id": "D17_PRESSURE", "study_id": "DONATI_2017", "observable": "Absolute ambient pressure", "status": "unresolved", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Interventions", "method": "Normobaric setting; measured atmospheric pressure not reported", "unit": "kPa", "normalization": "absolute", "compartment": "ambient atmosphere", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "pressure_kpa", "binding": "missing_required_context", "metadata_paths": [], "role": "protocol", "import_ready": false, "notes": "The word normobaric does not provide an individual pressure measurement.", "source_flag_ids": [] }, { "id": "D17_EPO", "study_id": "DONATI_2017", "observable": "Erythropoietin concentration", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Table 2", "method": "Serum EPO assay; platform not specified", "unit": "IU/L", "normalization": "absolute; Table 2 median/IQR", "compartment": "serum", "sampling_schedule_id": "D17_HEMATOLOGY", "sampling_time": "08:00 on study day and 24/48 h later.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "endpoint", "binding": "linked_outcome_required", "metadata_paths": [ "endpoint.unit", "endpoint.compartment", "endpoint.assay" ], "role": "observable", "import_ready": false, "notes": "Different draw schedule: use explicit linked outcome times. Do not attach 24/48 h EPO to a redox row as a simultaneous assay.", "source_flag_ids": [ "D17_EPO_TIMING", "D17_EPO_ESTIMAND" ] }, { "id": "D17_RETIC", "study_id": "DONATI_2017", "observable": "Reticulocyte concentration", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Table 2", "method": "Hematology measurement; analyzer not stated", "unit": "10^3/mm^3", "normalization": "absolute", "compartment": "blood", "sampling_schedule_id": "D17_HEMATOLOGY", "sampling_time": "08:00 on study day and 24/48 h later.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_retic", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Optional endpoint in a separately declared, correctly timed dataset; current auxiliary field is retained without inference.", "source_flag_ids": [] }, { "id": "D17_HB", "study_id": "DONATI_2017", "observable": "Hemoglobin concentration", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Table 2", "method": "Hematology measurement; analyzer not stated", "unit": "g/dL", "normalization": "absolute", "compartment": "blood", "sampling_schedule_id": "D17_HEMATOLOGY", "sampling_time": "08:00 on study day and 24/48 h later.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_hb", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Optional endpoint in a separately declared, correctly timed dataset; current auxiliary field is retained without inference.", "source_flag_ids": [] }, { "id": "D17_HCT", "study_id": "DONATI_2017", "observable": "Hematocrit", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Table 2", "method": "Hematology measurement; analyzer not stated", "unit": "%", "normalization": "absolute", "compartment": "blood", "sampling_schedule_id": "D17_HEMATOLOGY", "sampling_time": "08:00 on study day and 24/48 h later.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_hct", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Optional endpoint in a separately declared, correctly timed dataset; current auxiliary field is retained without inference.", "source_flag_ids": [] }, { "id": "D17_NITRITE_NITRATE", "study_id": "DONATI_2017", "observable": "Nitrite/nitrate", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Immunoassays; Table 4", "method": "Arbor Assays K023-H1 colorimetric kit", "unit": "µM", "normalization": "absolute", "compartment": "plasma", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.nitrite_nitrate", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "NO-production marker retained as its assayed analytes.", "source_flag_ids": [] }, { "id": "D17_TVD_SMALL", "study_id": "DONATI_2017", "observable": "Small-vessel total density", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "mm/mm^2", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_tvd_small", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_PVD_SMALL", "study_id": "DONATI_2017", "observable": "Small-vessel perfused density", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "mm/mm^2", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_pvd_small", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_TVD_MEDIUM", "study_id": "DONATI_2017", "observable": "Medium-vessel total density", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "mm/mm^2", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_tvd_medium", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_PVD_MEDIUM", "study_id": "DONATI_2017", "observable": "Medium-vessel perfused density", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "mm/mm^2", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_pvd_medium", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_DEBACKER", "study_id": "DONATI_2017", "observable": "De Backer score", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "n/mm", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_debacker", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_MFI", "study_id": "DONATI_2017", "observable": "Small-vessel microcirculatory flow index", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "AU", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_mfi", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_PPV", "study_id": "DONATI_2017", "observable": "Small-vessel perfused proportion", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "%", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_ppv", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_FHI", "study_id": "DONATI_2017", "observable": "Small-vessel flow heterogeneity index", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "AU", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_fhi", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_BFV", "study_id": "DONATI_2017", "observable": "Blood flow velocity", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Sublingual SDF videomicroscopy and AVA analysis", "unit": "µm/s", "normalization": "absolute", "compartment": "sublingual microcirculation", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_bfv", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Retain vessel class and site; these measures do not establish renal oxygen pressure.", "source_flag_ids": [] }, { "id": "D17_MICRO_EARLY_TVD", "study_id": "DONATI_2017", "observable": "Early small-vessel total vessel density change", "status": "computed", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Results: Effects on the sublingual microcirculation", "method": "Same-site SDF video comparison", "unit": "% of switch baseline", "normalization": "separate baseline for each switch", "compartment": "sublingual microcirculation; small vessels ≤20 µm", "sampling_schedule_id": "D17_MICRO_EARLY", "sampling_time": "Before/2 min after exposure onset and before/2 min after return; same sublingual site observed continuously.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.microvascular_switch_tvd", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Source results report baseline-relative change for this specified small-vessel measure. Retain the switch-specific baseline and event identity.", "source_flag_ids": [] }, { "id": "D17_MICRO_EARLY_PVD", "study_id": "DONATI_2017", "observable": "Early small-vessel perfused vessel density change", "status": "computed", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Results: Effects on the sublingual microcirculation; Figure 1", "method": "Same-site SDF video comparison", "unit": "% of switch baseline", "normalization": "separate baseline for each switch", "compartment": "sublingual microcirculation; small vessels ≤20 µm", "sampling_schedule_id": "D17_MICRO_EARLY", "sampling_time": "Before/2 min after exposure onset and before/2 min after return; same sublingual site observed continuously.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.microvascular_switch_pvd", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Source results report baseline-relative change for this specified small-vessel measure. Retain the switch-specific baseline and event identity.", "source_flag_ids": [] }, { "id": "D17_MICRO_EARLY_PPV", "study_id": "DONATI_2017", "observable": "Early small-vessel proportion of perfused vessels change", "status": "computed", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Results: Effects on the sublingual microcirculation; Figure 1", "method": "Same-site SDF video comparison", "unit": "% of switch baseline", "normalization": "separate baseline for each switch", "compartment": "sublingual microcirculation; small vessels ≤20 µm", "sampling_schedule_id": "D17_MICRO_EARLY", "sampling_time": "Before/2 min after exposure onset and before/2 min after return; same sublingual site observed continuously.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.microvascular_switch_ppv", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Source results report baseline-relative change for this specified small-vessel measure. Retain the switch-specific baseline and event identity.", "source_flag_ids": [] }, { "id": "D17_STO2", "study_id": "DONATI_2017", "observable": "Microvascular oxygen saturation", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Thenar NIRS with vascular occlusion test", "unit": "%", "normalization": "reported NIRS quantity", "compartment": "thenar eminence", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_sto2", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Saturation and its slopes are distinct from tissue pO2; signed slopes remain auxiliary fields.", "source_flag_ids": [] }, { "id": "D17_STO2_DOWN", "study_id": "DONATI_2017", "observable": "Occlusion desaturation slope", "status": "computed", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Thenar NIRS with vascular occlusion test", "unit": "%/min", "normalization": "reported NIRS quantity", "compartment": "thenar eminence", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_sto2_down", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Calculated by the source from measured assay/signal data. Saturation and its slopes are distinct from tissue pO2; signed slopes remain auxiliary fields.", "source_flag_ids": [] }, { "id": "D17_STO2_UP", "study_id": "DONATI_2017", "observable": "Reperfusion saturation slope", "status": "computed", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Thenar NIRS with vascular occlusion test", "unit": "%/min", "normalization": "reported NIRS quantity", "compartment": "thenar eminence", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_sto2_up", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Calculated by the source from measured assay/signal data. Saturation and its slopes are distinct from tissue pO2; signed slopes remain auxiliary fields.", "source_flag_ids": [] }, { "id": "D17_STO2_AUC", "study_id": "DONATI_2017", "observable": "Hyperemic saturation area", "status": "computed", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Thenar NIRS with vascular occlusion test", "unit": "%·min", "normalization": "reported NIRS quantity", "compartment": "thenar eminence", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_sto2_auc", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Calculated by the source from measured assay/signal data. Saturation and its slopes are distinct from tissue pO2; signed slopes remain auxiliary fields.", "source_flag_ids": [] }, { "id": "D17_THI", "study_id": "DONATI_2017", "observable": "Tissue hemoglobin index", "status": "measured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Microcirculation assessment; Table 3", "method": "Thenar NIRS with vascular occlusion test", "unit": "AU", "normalization": "reported NIRS quantity", "compartment": "thenar eminence", "sampling_schedule_id": "D17_REDOX", "sampling_time": "t0 before exposure; t1 at the end of 2 h hyperoxia; t2 2 h after return to individual baseline FiO2.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.d17_thi", "binding": "extra_field_only", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Saturation and its slopes are distinct from tissue pO2; signed slopes remain auxiliary fields.", "source_flag_ids": [] }, { "id": "D17_CAPACITY", "study_id": "DONATI_2017", "observable": "Total antioxidant scavenging capacity", "status": "unmeasured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Immunoassays", "method": "No direct assay reported", "unit": null, "normalization": "none", "compartment": "not measured", "sampling_schedule_id": "UNSPECIFIED", "sampling_time": "No empirical sampling schedule supplied.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "scavenger", "binding": "no_import", "metadata_paths": [ "scavenger.unit", "scavenger.compartment", "scavenger.assay" ], "role": "observable", "import_ready": false, "notes": "Keep absent; no substitution from circulating GSH, arterial gas or EPO.", "source_flag_ids": [] }, { "id": "D17_HIF1", "study_id": "DONATI_2017", "observable": "HIF-1α activity/abundance", "status": "unmeasured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Immunoassays", "method": "No direct assay reported", "unit": null, "normalization": "none", "compartment": "not measured", "sampling_schedule_id": "UNSPECIFIED", "sampling_time": "No empirical sampling schedule supplied.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "endpoint", "binding": "no_import", "metadata_paths": [ "endpoint.unit", "endpoint.compartment", "endpoint.assay" ], "role": "observable", "import_ready": false, "notes": "Keep absent; no substitution from circulating GSH, arterial gas or EPO.", "source_flag_ids": [] }, { "id": "D17_HIF2", "study_id": "DONATI_2017", "observable": "Renal HIF-2α activity/abundance", "status": "unmeasured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Immunoassays", "method": "No direct assay reported", "unit": null, "normalization": "none", "compartment": "not measured", "sampling_schedule_id": "UNSPECIFIED", "sampling_time": "No empirical sampling schedule supplied.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. Participant-level paired files and assay metadata have not been obtained.", "tool_field": "endpoint", "binding": "no_import", "metadata_paths": [ "endpoint.unit", "endpoint.compartment", "endpoint.assay" ], "role": "observable", "import_ready": false, "notes": "Keep absent; no substitution from circulating GSH, arterial gas or EPO.", "source_flag_ids": [] }, { "id": "D17_TISSUE_PO2", "study_id": "DONATI_2017", "observable": "Renal tissue oxygen partial pressure", "status": "unmeasured", "source_url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "source_locator": "Methods: Measurements; Immunoassays", "method": "No direct assay reported", "unit": null, "normalization": "none", "compartment": "not measured", "sampling_schedule_id": "UNSPECIFIED", "sampling_time": "No empirical sampling schedule supplied.", "data_access_id": "D17_RAW", "data_access": "The article states that supporting data are available from the corresponding author on reasonable request. 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Participant-level paired files and assay metadata have not been obtained.", "tool_field": "extra_fields.gssg", "binding": "no_import", "metadata_paths": [], "role": "observable", "import_ready": false, "notes": "Keep absent; no substitution from circulating GSH, arterial gas or EPO.", "source_flag_ids": [] }, { "id": "F21_GSH", "study_id": "FRATANTONIO_2021", "observable": "Intracellular reduced glutathione", "status": "measured", "source_url": "https://www.mdpi.com/1422-0067/22/1/458", "source_locator": "Section 5.3; Figure 4", "method": "Deproteinized cell lysate; DTNB/Ellman assay; GSH standard; Bradford protein", "unit": "nmol/mg protein", "normalization": "protein-normalized; reconcile Figure 4 baseline scale", "compartment": "PBMC cell lysate", "sampling_schedule_id": "F21_RECOVERY", "sampling_time": "Pre-exposure baseline; 0.5, 3 and 24 h after 1 h exposure.", "data_access_id": "F21_RAW", "data_access": "Data available from authors on request; participant-level records not received.", "tool_field": "scavenger", "binding": "conditional", "metadata_paths": [ "scavenger.unit", "scavenger.compartment", "scavenger.assay" ], "role": "observable", "import_ready": false, "notes": "Assay run in triplicate; technical replicates do not increase participant count.", "source_flag_ids": [ "F21_GSH_LABEL", "F21_BASELINE_SCALE" ] }, { "id": "F21_HIF1", "study_id": "FRATANTONIO_2021", "observable": "HIF-1α nuclear protein", "status": "measured", "source_url": "https://www.mdpi.com/1422-0067/22/1/458", "source_locator": "Section 5.2; Figure 1", "method": "Nuclear-lysate immunoblot; Lamin B control included", "unit": "fold relative to baseline", "normalization": "baseline=1; published group mean±SEM", "compartment": "PBMC nucleus", "sampling_schedule_id": "F21_RECOVERY", "sampling_time": "Pre-exposure baseline; 0.5, 3 and 24 h after 1 h exposure.", "data_access_id": "F21_RAW", "data_access": "Data available from authors on request; participant-level records not received.", "tool_field": "endpoint", "binding": "conditional", "metadata_paths": [ "endpoint.unit", "endpoint.compartment", "endpoint.assay" ], "role": "observable", "import_ready": false, "notes": "One assay identity per endpoint dataset. 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Raw band quantification and normalization records needed.", "source_flag_ids": [ "F21_TIME" ] }, { "id": "F21_NFKB", "study_id": "FRATANTONIO_2021", "observable": "NF-κB p65 nuclear protein", "status": "measured", "source_url": "https://www.mdpi.com/1422-0067/22/1/458", "source_locator": "Section 5.2; Figure 3", "method": "Nuclear-lysate immunoblot; Lamin B control included", "unit": "fold relative to baseline", "normalization": "baseline=1; published group mean±SEM", "compartment": "PBMC nucleus", "sampling_schedule_id": "F21_RECOVERY", "sampling_time": "Pre-exposure baseline; 0.5, 3 and 24 h after 1 h exposure.", "data_access_id": "F21_RAW", "data_access": "Data available from authors on request; participant-level records not received.", "tool_field": "endpoint", "binding": "conditional", "metadata_paths": [ "endpoint.unit", "endpoint.compartment", "endpoint.assay" ], "role": "observable", "import_ready": false, "notes": "One assay identity per endpoint dataset. 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Raw count units and definition needed for import. Signed percentage change is an auxiliary outcome; import of positive raw reticulocyte counts as an endpoint requires the raw baseline and units.", "source_flag_ids": [ "K24_SCALE" ] }, { "id": "K24_EPO", "study_id": "KHALIFE_2024", "observable": "Erythropoietin", "status": "unmeasured", "source_url": "https://link.springer.com/article/10.1186/s44158-024-00179-x", "source_locator": "Methods: Parameters collected; Discussion", "method": "No EPO assay reported", "unit": null, "normalization": "none", "compartment": "not measured", "sampling_schedule_id": "UNSPECIFIED", "sampling_time": "No empirical sampling schedule supplied.", "data_access_id": "K24_RAW", "data_access": "Available from corresponding author on reasonable request; no participant file received.", "tool_field": "endpoint", "binding": "no_import", "metadata_paths": [ "endpoint.unit", "endpoint.compartment", "endpoint.assay" ], "role": "observable", "import_ready": false, "notes": "Reticulocyte response does not supply an EPO measurement.", "source_flag_ids": [] }, { "id": "TOOL_R", "study_id": "NOP_TOOL_V0_2", "observable": "Normalized oxidant-assay read", "status": "computed", "source_url": null, "source_locator": "nop_audit.py::_derive; 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A later outcome requires its own timed linked source record; no cross-time attachment is inferred.", "source_flag_ids": [] }, { "id": "TOOL_RETURN", "study_id": "NOP_TOOL_V0_2", "observable": "Oxygen-return comparison", "status": "computed", "source_url": null, "source_locator": "nop_audit.py::_derive", "method": "Compare declared oxygen-read intervals", "unit": "categorical", "normalization": "same run baseline", "compartment": "declared oxygen-read compartment", "sampling_schedule_id": "ADMITTED_ROWS", "sampling_time": "Each admitted sample and its declared baseline; preserve source row, occurrence and time.", "data_access_id": "TOOL_DERIVED", "data_access": "Defined computation; empirical execution requires admitted participant records.", "tool_field": "oxygen_comparison", "binding": "defined_computation", "metadata_paths": [], "role": "comparison", "import_ready": false, "notes": "Interval overlap gives compatibility; equality of entered values is a read-level fact.", "source_flag_ids": [] }, { "id": "TOOL_MEMORY", "study_id": "NOP_TOOL_V0_2", "observable": "Return with retained assay difference", "status": "computed", "source_url": null, "source_locator": "nop_audit.py::_derive", "method": "Combine oxygen comparison with r/a interval status", "unit": "categorical", "normalization": "same run baseline", "compartment": "declared measurement context", "sampling_schedule_id": "ADMITTED_ROWS", "sampling_time": "Each admitted sample and its declared baseline; preserve source row, occurrence and time.", "data_access_id": "TOOL_DERIVED", "data_access": "Defined computation; empirical execution requires admitted participant records.", "tool_field": "relationship", "binding": "defined_computation", "metadata_paths": [], "role": "comparison", "import_ready": false, "notes": "Descriptive witness from admitted records; no recovery of unrecorded events.", "source_flag_ids": [] }, { "id": "TOOL_RETENTION", "study_id": "NOP_TOOL_V0_2", "observable": "Sampled adaptation retention", "status": "unresolved", "source_url": null, "source_locator": "model.py::adapt; Formal Note", "method": "lambda=exp(-Delta/tau) under declared first-order law", "unit": "dimensionless", "normalization": "model parameter", "compartment": "unassigned biological state", "sampling_schedule_id": "UNSPECIFIED", "sampling_time": "No empirical sampling schedule supplied.", "data_access_id": "TOOL_DERIVED", "data_access": "Defined computation; empirical execution requires admitted participant records.", "tool_field": "model.retention", "binding": "unfitted_model", "metadata_paths": [], "role": "parameter", "import_ready": false, "notes": "No human kinetic parameter fitted.", "source_flag_ids": [] } ], "source_corrections": [ { "id": "FIO2_140", "sources": [ "FRATANTONIO_2021", "NOP_REVIEW_2023" ], "locator": "F21 Section 5.1/Discussion; review Section 5", "issue": "140% or FiO2=1.4 shorthand", "resolution": "Pure oxygen has FiO2=1; retain absolute pressure separately.", "state": "RESOLVED_REPRESENTATION" }, { "id": "F21_PRESSURE_UNIT", "sources": [ "FRATANTONIO_2021" ], "locator": "Section 5.1 versus Discussion", "issue": "bar and ATA labels both used", "resolution": "Retain original labels; obtain chamber log before numerical pressure conversion.", "state": "OPEN" }, { "id": "F21_TIME", "sources": [ "FRATANTONIO_2021" ], "locator": "Section 5.1/Figures 1–5 versus Discussion", "issue": "3 h versus 4 h", "resolution": "Use 3 h as methods-defined nominal schedule; confirm actual draw times.", "state": "METHODS_PREFERRED_RAW_OPEN" }, { "id": "F21_GSH_LABEL", "sources": [ "FRATANTONIO_2021" ], "locator": "Section 2.4 heading versus Section 5.3/Figure 4", "issue": "Plasma total heading versus intracellular reduced assay", "resolution": "Bind to PBMC intracellular reduced GSH described by methods.", "state": "METHODS_PREFERRED" }, { "id": "F21_BASELINE_SCALE", "sources": [ "FRATANTONIO_2021" ], "locator": "Figures 4–5 captions versus Section 5.5", "issue": "Captions say baseline set at 10; methods say 100% and use fold/percentage changes", "resolution": "Preserve published labels; use raw values and declared normalization, not digitized baseline assumptions.", "state": "OPEN" }, { "id": "F21_HIF_100", "sources": [ "FRATANTONIO_2021", "NOP_REVIEW_2023" ], "locator": "F21 Section 2.1/Figure 1b", "issue": "Compressed wording can erase early HIF response at 100%", "resolution": "Retain early smaller HIF-1α rise; no significant HIF change belongs to hyperbaric arm.", "state": "PRIMARY_RETAINED" }, { "id": "GSH_PROCESSING_MODE", "sources": [ "DONATI_2017", "ARBOR_K006_H" ], "locator": "D17 Immunoassays/Abbreviations; manufacturer sample preparation", "issue": "Paper calls GSH reduced but does not specify total/GSSG separation branch", "resolution": "Use reported GSH label and µM; historical processing remains open. Current manufacturer instructions cannot retrospectively identify study procedure.", "state": "OPEN" }, { "id": "D17_ESTIMAND", "sources": [ "DONATI_2017" ], "locator": "Table 4 versus Figure 2/NO, ROS and GSH", "issue": "Absolute GSH time test differs from normalized within-subject comparison", "resolution": "Retain absolute overall-time p=0.114 separately from normalized t2-versus-t1 comparison.", "state": "DISTINCT_ESTIMANDS" }, { "id": "D17_RETURN", "sources": [ "DONATI_2017", "NOP_REVIEW_2023" ], "locator": "D17 Methods versus review Table 1", "issue": "Review table says ambient-air return", "resolution": "Return was individual baseline FiO2; do not set to 0.21.", "state": "PRIMARY_RETAINED" }, { "id": "D17_REDOX_TIME", "sources": [ "DONATI_2017", "NOP_REVIEW_2023" ], "locator": "D17 Measurements versus review Table 1", "issue": "Review table compresses/misstates ROS/GSH timing", "resolution": "t1=end of 2 h exposure; t2=2 h after return.", "state": "PRIMARY_RETAINED" }, { "id": "D17_EPO_TIMING", "sources": [ "DONATI_2017" ], "locator": "Methods: Interventions/Measurements", "issue": "EPO clock differs from redox clock", "resolution": "08:00 EPO draws; exposure within 10:00–14:00. Link by subject and actual timestamps.", "state": "LINKAGE_REQUIRED" }, { "id": "D17_EPO_ESTIMAND", "sources": [ "DONATI_2017" ], "locator": "Table 2", "issue": "Within-group EPO time p=0.022; interaction entry is blank/dash", "resolution": "Preserve within-group result; do not upgrade it to a reported group×time effect.", "state": "PRIMARY_RETAINED" }, { "id": "D17_HIF_SIGN", "sources": [ "DONATI_2017" ], "locator": "Discussion first mechanistic paragraph", "issue": "Printed GSH-surplus sentence says HIF inactivation; causal interpretation is internally problematic", "resolution": "Retain as unresolved mechanism wording; it does not define a signed HIF transfer function.", "state": "OPEN" }, { "id": "K11_PROTOCOL", "sources": [ "KERAMIDAS_2011", "NOP_REVIEW_2023" ], "locator": "Primary Abstract versus review Table 1/Section 5", "issue": "Review table says 2 h×7 days; review prose implies fixed air-first order", "resolution": "Primary reports counterbalanced crossover, one 2 h exposure per condition.", "state": "PRIMARY_RETAINED" }, { "id": "K21_POPULATION_TIME", "sources": [ "KHALIFE_2021", "NOP_REVIEW_2023" ], "locator": "Primary Methods/Table 2 versus review Section 5", "issue": "Review prose says abdominal surgery and days 7/9", "resolution": "DIEP breast reconstruction; 26 enrolled/22 analyzed; EPO baseline and days 2/3/4/9.", "state": "PRIMARY_RETAINED" }, { "id": "K21_CONTROL", "sources": [ "KHALIFE_2021" ], "locator": "Methods: oxygen administration", "issue": "Control arm shared perioperative oxygen exposure", "resolution": "Retain shared history and additional scheduled exposure contrast.", "state": "PRIMARY_RETAINED" }, { "id": "K24_SCALE", "sources": [ "KHALIFE_2024" ], "locator": "Results/Figure 1", "issue": "Percentage-change and greater-than-100%-of-baseline terminology are mixed", "resolution": "Request raw counts and exact transformation before importing summary percentages as measurements.", "state": "OPEN" }, { "id": "CAPACITY_IDENTITY", "sources": [ "DONATI_2017", "FRATANTONIO_2021", "NOP_REVIEW_2023" ], "locator": "Measured assays versus review Section 3.2", "issue": "GSH concentration and total scavenging capacity are distinct quantities", "resolution": "A retains its assayed identity; any capacity interpretation requires independent calibration.", "state": "BOUNDARY" }, { "id": "ISOFORM_COMPARTMENT", "sources": [ "FRATANTONIO_2021", "KAPITSINOU_2010", "KOBAYASHI_2016" ], "locator": "F21 Section 5.2; renal genetic primary studies", "issue": "PBMC HIF-1α and renal HIF-2α/EPO are different measurement jurisdictions", "resolution": "Require isoform/cell-type/organism/compartment and an independently tested link.", "state": "BOUNDARY" } ], "retained_prior_study_audit": [ { "id": "NOP_REVIEW_2023", "citation": "Salvagno et al. (2023), IJMS 24(1), 82", "url": "https://www.mdpi.com/1422-0067/24/1/82", "type": "narrative_review", "finding": "Proposes antioxidant persistence after oxygen return; explicitly leaves the ROS–HIF mechanism and exposure timing unresolved.", "tool_implication": "Retain oxygen, redox state, endpoint, and history as separate records. Use primary studies for protocol details.", "access": "Full text inspected; no original participant dataset." }, { "id": "FRATANTONIO_2021", "citation": "Fratantonio et al. (2021), IJMS 22(1), 458", "url": "https://www.mdpi.com/1422-0067/22/1/458", "type": "primary_human_pilot", "design": "12 healthy adults, four per group; one-hour oxygen exposures; baseline and 0.5/3/24-hour recovery samples.", "finding": "PBMC HIF-1alpha activation differed by exposure. The 100% arm retained an early response. GSH was measured; ROS was not directly measured.", "tool_implication": "No observed ROS/GSH ratio can be reconstructed from this study alone. Keep PBMC HIF-1alpha distinct from renal HIF-2alpha/EPO.", "source_flags": [ "Methods/figures use 3 hours; a discussion sentence says 4.", "Methods and figures describe intracellular reduced GSH; section heading says plasma total glutathione.", "Pressure is described using both bar and ATA; preserve and resolve the unit.", "The 140% shorthand requires a separate pressure field; FiO2 remains at most 1." ], "access": "Full text inspected. Data available from authors on request; no subject-level data bundled." }, { "id": "DONATI_2017", "citation": "Donati et al. (2017), BMC Anesthesiology 17, 49", "url": "https://link.springer.com/article/10.1186/s12871-017-0342-2", "type": "primary_observational_pilot", "design": "20 exposed and 20 control ICU patients, sequential nonrandomized allocation. Return to individual baseline FiO2; redox subset 12 per group.", "finding": "Transient serum ROS rise, later GSH rise, and a within-exposure-group EPO increase at 48 hours were reported.", "tool_implication": "Preserve individual baseline, serum compartment, and within-group versus between-group estimand; measure local oxygen independently.", "access": "Full text inspected. Data available on reasonable request." }, { "id": "KERAMIDAS_2011", "citation": "Keramidas et al. (2011), PMID 21294852", "url": "https://pubmed.ncbi.nlm.nih.gov/21294852/", "type": "primary_crossover_study", "design": "Ten healthy men, counterbalanced air/oxygen crossover, one two-hour exposure per condition.", "finding": "Early plasma EPO suppression after oxygen; air-condition EPO varied with time of day.", "tool_implication": "Keep contrary results and clock-matched controls in model evaluation. This acute study was not seven daily exposures.", "access": "Primary abstract inspected; full text not retrieved." }, { "id": "DEBEVEC_2012", "citation": "Debevec et al. (2012), PMID 21735214", "url": "https://pubmed.ncbi.nlm.nih.gov/21735214/", "type": "primary_controlled_study", "design": "Eighteen men; oxygen followed by mild hypoxia versus air.", "finding": "No significant between-group absolute EPO increase; early relative changes were lower after the intervention.", "tool_implication": "A larger oxygen transition does not itself establish an EPO response.", "access": "Primary abstract inspected; full text not retrieved." }, { "id": "KHALIFE_2021", "citation": "Khalife et al. (2021), Frontiers in Physiology 12, 744074", "url": "https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.744074/full", "type": "primary_postoperative_trial", "design": "DIEP breast reconstruction; 26 enrolled, 22 analyzed; repeated oxygen compared with controls sharing perioperative oxygen exposure.", "finding": "EPO increased within both groups; no significant between-group EPO, reticulocyte or hemoglobin difference.", "tool_implication": "Store control exposure history and postoperative covariates; a within-group rise does not identify an intervention effect.", "access": "Full text inspected. Raw data offered through authors." }, { "id": "KHALIFE_2024", "citation": "Khalife et al. (2024), Journal of Anesthesia, Analgesia and Critical Care 4, 43", "url": "https://link.springer.com/article/10.1186/s44158-024-00179-x", "type": "primary_post_hoc_trial_report", "design": "Post hoc report of a randomized abdominal-cancer surgery study; 33 analyzed, 16 exposed and 17 controls.", "finding": "Reticulocyte percentage change differed between groups; hemoglobin change did not. EPO was not measured.", "tool_implication": "Preserve reticulocytes as the measured outcome; retain the EPO intermediate as unmeasured.", "access": "Full text inspected. Data available on reasonable request." }, { "id": "CHANDEL_1998", "citation": "Chandel et al. (1998), PNAS 95, 11715–11720", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC21706/", "type": "primary_cell_mechanism", "finding": "Hep3B experiments linked mitochondrial function, ROS and hypoxia-induced transcription, including mitochondrial-DNA-depleted cells.", "tool_implication": "Retain source compartment and signaling direction as tested variables when transporting a mechanism into NOP.", "access": "Primary abstract and indexed full-text excerpts inspected." }, { "id": "JAAKKOLA_2001", "citation": "Jaakkola et al. (2001), Science, PMID 11292861", "url": "https://pubmed.ncbi.nlm.nih.gov/11292861/", "type": "primary_molecular_mechanism", "finding": "HIF prolyl hydroxylation regulates VHL recognition and requires molecular oxygen and iron.", "tool_implication": "Treat hydroxylation/PHD activity as a measurable mechanistic intermediate; the tool does not replace this pathway with a ratio identity.", "access": "Primary abstract retrieved." }, { "id": "KOBAYASHI_2016", "citation": "Kobayashi et al. (2016), JCI 126, 1926–1938", "url": "https://www.jci.org/articles/view/83551", "type": "primary_mouse_genetic_mechanism", "finding": "Conditional genetic experiments resolve a renal interstitial PHD/HIF-2/EPO pathway and cell-population heterogeneity.", "tool_implication": "Require organism, cell type, HIF isoform and compartment before connecting a transcription-factor assay to EPO.", "access": "Full text inspected." }, { "id": "BALESTRA_2006", "finding": "Original healthy-volunteer serum-EPO contrast after normobaric/hyperbaric exposure.", "access": "Primary abstract verified; subject-level data unavailable here." }, { "id": "KERAMIDAS_2012", "finding": "Repeated-exposure study reported lower EPO than air controls at middle/final observations.", "access": "Primary abstract verified; subject-level data unavailable here." }, { "id": "KAPITSINOU_2010", "finding": "Mouse renal Hif-2 deletion established a renal Hif-2-dependent Epo response under tested conditions.", "access": "Primary source inspected for isoform boundary." } ], "empirical_import_gate": { "DONATI_2017": "OPEN: obtain paired participant RFU/GSH/PaO2 records, actual sample/switch times, baseline IDs, assay processing and uncertainty metadata.", "FRATANTONIO_2021": "OPEN: raw values and normalization needed; ROS was unmeasured, so a paired ROS/GSH coordinate cannot be recovered from this study alone.", "general": "No between-study patient pairing; no inferred concentrations/capacities; no synthetic replacement of missing empirical fields." }, "testable_use": [ "Compare the same declared oxygen read after different preceding trajectories, with assay state and timing retained.", "Test whether measured assay state improves held-out prediction beyond current oxygen and prespecified covariates.", "Measure redox/PHD/hydroxylated-HIF/isoform-specific response and causal perturbations before assigning mechanism.", "Keep circulating EPO, reticulocytes, hemoglobin and clinical outcomes separate; preserve delays and control histories." ] }