{ "document_id": "fresh-bethgelab-298331", "source_sha256": "b7eff773bb1f99e0ec70566688feff4ba5a0189784a14a115bf01994215833e7", "kind": "ku", "status": "generated", "result": { "schema_version": "1.0", "title": "A six-month periodic fasting reduces microalbuminuria and improves metabolic control in patients with type 2 diabetes and diabetic nephropathy: a randomized controlled study", "abstract_sha256": "", "mode": "sequential", "model": "trained", "config": { "mode": "sequential", "chunk_words": 500, "context_words": 0, "previous_units": 10, "canonicalize": false, "minhash_permutations": 16, "canonicalization_max_tokens": 4096, "parse_retries": 0 }, "knowledge_units": [ { "chunk_index": 0, "context_summary": "A randomized controlled study evaluated the effects of a six-month fasting-mimicking diet versus a Mediterranean diet on patients with type 2 diabetes and diabetic nephropathy. The intervention significantly reduced microalbuminuria and improved metabolic markers like HOMA-IR and suPAR in the fasting-mimicking group. However, these improvements were not sustained at the three-month follow-up, potentially due to a lack of change in dicarbonyl detoxification and DNA-damage markers.", "entities": [ { "name": "A six-month periodic fasting reduces microalbuminuria and improves metabolic control in patients with type 2 diabetes and diabetic nephropathy: a randomized controlled study", "entity_id": "a_six_month_periodic_fasting_reduces_microalbuminuria_and_improves_metabolic_control_in_patients_with_type_2_diabetes_and_diabetic_nephropathy_a_randomized_controlled_study", "entity_type": "event", "aliases": [], "attributes": { "study_type": "randomized controlled study", "duration": "6 months", "follow_up": "3 months" }, "relationships": [ { "predicate": "conducted_by", "target": "Alba Sulaj", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Stefan Kopf", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Ekaterina Von Rauchhaupt", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Elisabeth Kliemank", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Maik Brune", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Zoltan Kender", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Hannelore Bartl", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Fabiola Garcia Cortizo", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Katarina Klepac", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Zhe Han", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Varun Kumar", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Valter Longo", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Aurelio Teleman", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Jürgen G Okun", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Jakob Morgenstern", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Thomas Fleming", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Julia Szendroedi", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Stephan Herzig", "attributes": {}, "target_id": null }, { "predicate": "conducted_by", "target": "Peter P Nawroth", "attributes": {}, "target_id": null } ] }, { "name": "fasting-mimicking diet", "entity_id": "fasting_mimicking_diet", "entity_type": "method", "aliases": [], "attributes": { "abbreviation": "FMD", "sample_size": 21 }, "relationships": [ { "predicate": "assigned_to", "target": "patients with type 2 diabetes and diabetic nephropathy", "attributes": {}, "target_id": null }, { "predicate": "resulted_in_change_in_acr", "target": "110.3mg/g (95% CI 99.2, 121.5mg/g; P=0.45)", "attributes": {}, "target_id": null }, { "predicate": "resulted_in_change_in_acr_microalbuminuria", "target": "-30.3mg/g (95% CI -35.7, -24.9mg/g; P≤0.05)", "attributes": {}, "target_id": null }, { "predicate": "resulted_in_change_in_acr_macroalbuminuria", "target": "434.0mg/g (95% CI 404.7, 463.4mg/g; P=0.23)", "attributes": {}, "target_id": null }, { "predicate": "resulted_in_change_in_homa_ir", "target": "-3,8 (95% CI -5,6, -2.0; P≤0.05)", "attributes": {}, "target_id": null }, { "predicate": "resulted_in_change_in_supar", "target": "-156.6pg/ml (95% CI -172.9, -140.4pg/ml; P≤0.05)", "attributes": {}, "target_id": null }, { "predicate": "resulted_in_no_change_in", "target": "markers of dicarbonyl detoxification or DNA-damage/repair", "attributes": {}, "target_id": null } ] }, { "name": "Mediterranean diet", "entity_id": "mediterranean_diet", "entity_type": "method", "aliases": [], "attributes": { "sample_size": 19 }, "relationships": [ { "predicate": "assigned_to", "target": "patients with type 2 diabetes and diabetic nephropathy", "attributes": {}, "target_id": null } ] }, { "name": "patients with type 2 diabetes and diabetic nephropathy", "entity_id": "patients_with_type_2_diabetes_and_diabetic_nephropathy", "entity_type": "other", "aliases": [], "attributes": { "total_sample_size": 40, "hba1c": "7.8±0.2% [62.1±2.3 mmol/mol]", "condition": "increased albumin-to-creatinine ratio (ACR)", "model_entity_type": "population" }, "relationships": [ { "predicate": "randomized_to", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null }, { "predicate": "randomized_to", "target": "Mediterranean diet", "attributes": {}, "target_id": null } ] }, { "name": "albuminuria", "entity_id": "albuminuria", "entity_type": "measurement", "aliases": [], "attributes": { "subtypes": [ "microalbuminuria", "macroalbuminuria" ] }, "relationships": [ { "predicate": "reduced_by", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null }, { "predicate": "relapse_at_follow_up_explained_by", "target": "lack of changes in markers of dicarbonyl detoxification and DNA-damage/repair", "attributes": {}, "target_id": null } ] }, { "name": "HOMA-IR", "entity_id": "homa_ir", "entity_type": "measurement", "aliases": [], "attributes": { "description": "insulin resistance marker" }, "relationships": [ { "predicate": "reduced_by", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null }, { "predicate": "sustained_reduction_at_follow_up", "target": "-1.9 [95% CI -3.7, -0.1], P≤0.05", "attributes": {}, "target_id": null } ] }, { "name": "suPAR", "entity_id": "supar", "entity_type": "measurement", "aliases": [], "attributes": { "description": "senescence marker" }, "relationships": [ { "predicate": "reduced_by", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "markers of dicarbonyl detoxification", "entity_id": "markers_of_dicarbonyl_detoxification", "entity_type": "measurement", "aliases": [], "attributes": { "components": [ "MG-H1", "glyoxalase-1", "hydroxyacetone" ] }, "relationships": [ { "predicate": "no_change_observed_in", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "DNA-damage/repair", "entity_id": "dna_damage_repair", "entity_type": "measurement", "aliases": [], "attributes": { "marker": "(yH2Ax)" }, "relationships": [ { "predicate": "no_change_observed_in", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "lipid oxidation", "entity_id": "lipid_oxidation", "entity_type": "measurement", "aliases": [], "attributes": { "marker": "acylcarnitines" }, "relationships": [ { "predicate": "change_in_profile_related_to", "target": "patient responsiveness to ACR improvement", "attributes": {}, "target_id": null } ] }, { "name": "diabetic nephropathy", "entity_id": "diabetic_nephropathy", "entity_type": "other", "aliases": [], "attributes": { "prevalence": "The most common cause of terminal kidney disease ", "model_entity_type": "condition" }, "relationships": [ { "predicate": "therapeutic_options_limited_to", "target": "control of glycemia, lipidemia and blood pressure", "attributes": {}, "target_id": null }, { "predicate": "nephroprotection_exerted_by", "target": "sodium-glucose cotransporter-2 (SGLT2) inhibitors", "attributes": {}, "target_id": null }, { "predicate": "nephroprotection_exerted_by", "target": "ACE inhibitors", "attributes": {}, "target_id": null } ] }, { "name": "sodium-glucose cotransporter-2 (SGLT2) inhibitors", "entity_id": "sodium_glucose_cotransporter_2_sglt2_inhibitors", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "treatment" }, "relationships": [ { "predicate": "exert_nephroprotection_in", "target": "diabetic nephropathy", "attributes": {}, "target_id": null }, { "predicate": "renal_benefits_not_explained_by", "target": "modest improvements in glycemic, blood pressure and lipid control", "attributes": {}, "target_id": null } ] }, { "name": "ACE inhibitors", "entity_id": "ace_inhibitors", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "treatment" }, "relationships": [ { "predicate": "exert_nephroprotection_in", "target": "diabetic nephropathy", "attributes": {}, "target_id": null } ] } ], "source": { "chunk_index": 0, "start_word": 0, "end_word": 493, "word_count": 493, "sha256": "e46273c5dcc068c6e94680280cec983098372c485a7786046a95e278ea16ecbf", "sentence_minhash": [ 6510041791773535, 211045936105277080, 12309405932600981, 201948566748835051, 31941388625203915, 99098051124777616, 110722415692105071, 84916492449827032, 164501479184262938, 2607707833378508, 6226213327830117, 95656761971753031, 21933493368060407, 906306679132868, 192943377640405015, 658790404649858 ] }, "extraction_warnings": [ "normalized unsupported entity type 'population' for 'patients with type 2 diabetes and diabetic nephropathy'", "normalized unsupported entity type 'condition' for 'diabetic nephropathy'", "normalized unsupported entity type 'treatment' for 'sodium-glucose cotransporter-2 (SGLT2) inhibitors'", "normalized unsupported entity type 'treatment' for 'ACE inhibitors'" ] }, { "chunk_index": 1, "context_summary": "The study investigates the impact of a periodic fasting-mimicking diet on albumin-to-creatinine ratio and metabolic markers in patients with type 2 diabetes. It highlights the role of hyperglycemia, dicarbonyl stress, and DNA damage in diabetic kidney disease progression. The research design involves a randomized, controlled, open study at the University Hospital in Heidelberg, which includes specific inclusion criteria and monitoring protocols. ", "entities": [ { "name": "diabetic kidney disease", "entity_id": "diabetic_kidney_disease", "entity_type": "other", "aliases": [], "attributes": { "progression_status": "slowable once established", "remission_therapy_status": "lacking", "model_entity_type": "condition" }, "relationships": [ { "predicate": "caused_by", "target": "hyperglycemia", "attributes": {}, "target_id": null }, { "predicate": "associated_with", "target": "dicarbonyl stress", "attributes": {}, "target_id": null }, { "predicate": "associated_with", "target": "AGE", "attributes": {}, "target_id": null } ] }, { "name": "hyperglycemia", "entity_id": "hyperglycemia", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "condition" }, "relationships": [ { "predicate": "causes_decline_in", "target": "renal function", "attributes": {}, "target_id": null }, { "predicate": "activates", "target": "sorbitol pathway", "attributes": {}, "target_id": null }, { "predicate": "activates", "target": "hexosamine pathway", "attributes": {}, "target_id": null }, { "predicate": "increases", "target": "oxidative stress", "attributes": {}, "target_id": null } ] }, { "name": "oxidative stress", "entity_id": "oxidative_stress", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "biological_process" }, "relationships": [ { "predicate": "results_in", "target": "fibrosis", "attributes": {}, "target_id": null } ] }, { "name": "dicarbonyl stress", "entity_id": "dicarbonyl_stress", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "biological_process" }, "relationships": [ { "predicate": "implicated_in", "target": "diabetic complications", "attributes": {}, "target_id": null }, { "predicate": "implicated_in", "target": "diabetic kidney disease", "attributes": {}, "target_id": null } ] }, { "name": "AGE", "entity_id": "age", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "biological_process" }, "relationships": [ { "predicate": "implicated_in", "target": "diabetic complications", "attributes": {}, "target_id": null }, { "predicate": "implicated_in", "target": "diabetic kidney disease", "attributes": {}, "target_id": null } ] }, { "name": "DNA-damage", "entity_id": "dna_damage", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "biological_process" }, "relationships": [ { "predicate": "described_in", "target": "type 2 diabetes", "attributes": {}, "target_id": null } ] }, { "name": "periodic fasting", "entity_id": "periodic_fasting", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "intervention" }, "relationships": [ { "predicate": "reduces", "target": "oxidative damage", "attributes": {}, "target_id": null }, { "predicate": "reduces", "target": "inflammation", "attributes": {}, "target_id": null }, { "predicate": "supports", "target": "cellular protection", "attributes": {}, "target_id": null }, { "predicate": "might_activate", "target": "lipolysis", "attributes": {}, "target_id": null } ] }, { "name": "SGLT-2 inhibitors", "entity_id": "sglt_2_inhibitors", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "medication" }, "relationships": [ { "predicate": "postulated_benefit_mechanism", "target": "enhanced ketogenesis", "attributes": {}, "target_id": null }, { "predicate": "shifts_fuel_metabolism_from", "target": "glucose oxidation", "attributes": {}, "target_id": null }, { "predicate": "shifts_fuel_metabolism_to", "target": "fat", "attributes": {}, "target_id": null }, { "predicate": "shifts_energy_metabolism_to", "target": "ketolysis", "attributes": {}, "target_id": null } ] }, { "name": "periodic fasting-mimicking diet", "entity_id": "periodic_fasting_mimicking_diet", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "intervention" }, "relationships": [ { "predicate": "aim_to_reduce", "target": "ACR", "attributes": {}, "target_id": null }, { "predicate": "aim_to_relate_to_changes_in", "target": "markers of dicarbonyl detoxification", "attributes": {}, "target_id": null }, { "predicate": "aim_to_relate_to_changes_in", "target": "fatty acid oxidation", "attributes": {}, "target_id": null }, { "predicate": "aim_to_relate_to_changes_in", "target": "DNA-damage/repair", "attributes": {}, "target_id": null }, { "predicate": "aim_to_relate_to_changes_in", "target": "senescence", "attributes": {}, "target_id": null } ] }, { "name": "University Hospital of Heidelberg", "entity_id": "university_hospital_of_heidelberg", "entity_type": "organization", "aliases": [], "attributes": { "department": "Clinics of Endocrinology, Diabetology, Metabolism and Clinical Chemistry" }, "relationships": [ { "predicate": "conducted_study_at", "target": "randomized controlled open study", "attributes": {}, "target_id": null }, { "predicate": "approved_study_procedures", "target": "Ethic-Nr. S-682/2016", "attributes": {}, "target_id": null } ] }, { "name": "randomized controlled open study", "entity_id": "randomized_controlled_open_study", "entity_type": "event", "aliases": [], "attributes": { "registration_id": "DRKS00014287", "registration_body": "German Clinical Trial Register (DRKS) " }, "relationships": [ { "predicate": "recruited_patients_with", "target": "type 2 diabetes", "attributes": {}, "target_id": null }, { "predicate": "recruited_patients_with", "target": "good glycemic and blood pressure control", "attributes": {}, "target_id": null }, { "predicate": "recruited_patients_with", "target": "increased albumin-to-creatinine ratio", "attributes": {}, "target_id": null }, { "predicate": "adherence_assessed_by", "target": "dietary protocols", "attributes": {}, "target_id": null }, { "predicate": "adherence_assessed_by", "target": "measurement of ketone bodies", "attributes": {}, "target_id": null } ] }, { "name": "albumin-to-creatinine ratio", "entity_id": "albumin_to_creatinine_ratio", "entity_type": "measurement", "aliases": [], "attributes": { "abbreviation": "ACR", "assessment_guideline": "KDIGO guidelines" }, "relationships": [ { "predicate": "assessed_from", "target": "two consecutive spot urine samples", "attributes": {}, "target_id": null } ] }, { "name": "American Diabetes Association", "entity_id": "american_diabetes_association", "entity_type": "organization", "aliases": [], "attributes": {}, "relationships": [ { "predicate": "provided_recommendations_for", "target": "individual dietary counseling", "attributes": {}, "target_id": null } ] } ], "source": { "chunk_index": 1, "start_word": 493, "end_word": 987, "word_count": 494, "sha256": "3ccf13bd243f38dd2c5b30e398ee2fd220ea214699f1caa9ce7a147a59705b05", "sentence_minhash": [ 103524869278618013, 7605519510423274, 14512286676696481, 61919449716151556, 133839408494452977, 62667647458868521, 23718652799488495, 83575544965282909, 130591936822558120, 243945572124720763, 10770288728711951, 95656761971753031, 38129318889309710, 906306679132868, 73860429008392155, 4555549854558376 ] }, "extraction_warnings": [ "normalized unsupported entity type 'condition' for 'diabetic kidney disease'", "normalized unsupported entity type 'condition' for 'hyperglycemia'", "normalized unsupported entity type 'biological_process' for 'oxidative stress'", "normalized unsupported entity type 'biological_process' for 'dicarbonyl stress'", "normalized unsupported entity type 'biological_process' for 'AGE'", "normalized unsupported entity type 'biological_process' for 'DNA-damage'", "normalized unsupported entity type 'intervention' for 'periodic fasting'", "normalized unsupported entity type 'medication' for 'SGLT-2 inhibitors'", "normalized unsupported entity type 'intervention' for 'periodic fasting-mimicking diet'" ] }, { "chunk_index": 2, "context_summary": "The study utilized a stratified randomization procedure based on BMI and HbA1c to assign participants to either a fasting-mimicking diet or a Mediterranean diet. The intervention consisted of five consecutive days with specific dietary guidelines each month, during which the insulin dosage and oral antidiabetic medications were adjusted during the fasting period. Monitoring included self-reported blood sugar levels, blood pressure, and physical activity, with blood chemistry analysis performed at the University Hospital in Heidelberg. ", "entities": [ { "name": "Randomizer Version 2.0.3", "entity_id": "randomizer_version_2_0_3", "entity_type": "method", "aliases": [], "attributes": { "owner": "Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz", "function": "stratified computed randomization" }, "relationships": [ { "predicate": "stratified_by", "target": "BMI", "attributes": { "cut_off": "30.0 kg/m²" }, "target_id": null }, { "predicate": "stratified_by", "target": "HbA1c", "attributes": { "cut_off": "7.0%" }, "target_id": null } ] }, { "name": "Fasting-Mimicking Diet (FMD)", "entity_id": "fasting_mimicking_diet_fmd", "entity_type": "method", "aliases": [], "attributes": { "type": "plant-based", "duration": "5 consecutive days each month", "cycle_gap": "about 25 days", "day_1_energy": "4600 kJ", "day_1_macronutrients": "11% protein, 46% fat, 43% carbohydrates", "day_2_to_5_energy": "3000 kJ", "day_2_to_5_macronutrients": "9% protein, 44% fat, 47% carbohydrate" }, "relationships": [ { "predicate": "mimics", "target": "fasting-like effects on glucose and ketone bodies", "attributes": {}, "target_id": null }, { "predicate": "requires_insulin_adjustment", "target": "discontinue short-acting insulin, reduce long-acting insulin by 50%", "attributes": {}, "target_id": null }, { "predicate": "requires_medication_discontinuation", "target": "oral antidiabetic therapy", "attributes": {}, "target_id": null } ] }, { "name": "Mediterranean Diet (M-Diet)", "entity_id": "mediterranean_diet_m_diet", "entity_type": "method", "aliases": [], "attributes": { "duration": "5 consecutive days each month", "cycle_gap": "about 25 days", "caloric_change": "no change compared to pre-study diet", "adaptation_standard": "Mediterranean Diet Score (MDS)" }, "relationships": [ { "predicate": "assigned_to", "target": "control group", "attributes": {}, "target_id": null } ] }, { "name": "Glycemic Monitoring", "entity_id": "glycemic_monitoring", "entity_type": "method", "aliases": [], "attributes": { "frequency": "at least 4 measurements daily", "types": "fasting and 2-hour postprandial", "device": "Accu-Check Guide, Roche", "reporting_platform": "24-hour telephone platform" }, "relationships": [ { "predicate": "triggers_medication_reduction", "target": "antihyperglycemic medication", "attributes": { "condition": "Reducing blood sugar levels by more than 20% in a fasting state " }, "target_id": null } ] }, { "name": "Antihypertensive Medication Adjustment", "entity_id": "antihypertensive_medication_adjustment", "entity_type": "method", "aliases": [], "attributes": { "condition": "hypotension", "systolic_threshold": "lower than 100 mmHg", "diastolic_threshold": "lower than 60 mmHg" }, "relationships": [ { "predicate": "action", "target": "medication reduced", "attributes": {}, "target_id": null } ] }, { "name": "SF-12 Questionnaire", "entity_id": "sf_12_questionnaire", "entity_type": "measurement", "aliases": [], "attributes": { "items": 12, "purpose": "Assess the quality of life in relation to health and physical well-being. " }, "relationships": [] }, { "name": "Patient Health Questionnaire (PHQ)", "entity_id": "patient_health_questionnaire_phq", "entity_type": "measurement", "aliases": [], "attributes": { "purpose": "evaluate somatic and depression symptoms" }, "relationships": [] }, { "name": "Central Laboratory of the University Hospital of Heidelberg", "entity_id": "central_laboratory_of_the_university_hospital_of_heidelberg", "entity_type": "place", "aliases": [], "attributes": { "function": "blood sample processing", "conditions": "standardized" }, "relationships": [ { "predicate": "measures", "target": "Beta-hydroxybutyrate", "attributes": {}, "target_id": null } ] }, { "name": "Beta-hydroxybutyrate", "entity_id": "beta_hydroxybutyrate", "entity_type": "measurement", "aliases": [], "attributes": { "measurement_device": "StatStrip glucose/ketone measurement system, by Nova Biomedical ", "sample_type": "venous blood" }, "relationships": [ { "predicate": "measured_at", "target": "each visit", "attributes": {}, "target_id": null } ] } ], "source": { "chunk_index": 2, "start_word": 987, "end_word": 1439, "word_count": 452, "sha256": "5470261db13a29a53beed762cbe5a0102549c991fec870ca5448ea4d18d6edf1", "sentence_minhash": [ 78394354238995921, 18551641988871988, 298143106562491488, 61919449716151556, 50154285776315358, 62667647458868521, 22742697865333914, 83575544965282909, 64333332902950267, 9462436175016187, 10770288728711951, 95656761971753031, 79488634481212582, 906306679132868, 161357415568664162, 3126852891561233 ] }, "extraction_warnings": [] }, { "chunk_index": 3, "context_summary": "The study defined primary and secondary endpoints, including ACR changes and metabolic markers, and detailed the statistical methods and power calculations. A sample size of 40 was determined to detect a 30% reduction in ACR, with 38 patients completing three cycles and 33 completing the full study. Analysis was conducted on an intention-to-treat basis using ANCOVA and hierarchical testing in R.", "entities": [ { "name": "Primary endpoint", "entity_id": "primary_endpoint", "entity_type": "measurement", "aliases": [], "attributes": { "definition": "absolute difference of change of ACR from baseline to after six diet cycles between FMD and M-Diet group" }, "relationships": [ { "predicate": "includes_subgroup_analysis", "target": "micro-versus macroalbuminuria levels at baseline", "attributes": {}, "target_id": null } ] }, { "name": "Secondary endpoints", "entity_id": "secondary_endpoints", "entity_type": "measurement", "aliases": [], "attributes": { "components": [ "absolute difference of change of ACR after three diet cycles", "absolute difference of change after three and after six diet cycles of HOMA-IR", "plasma MG-H1", "plasma MG", "Glo-1 activity", "expression of pGlo-1 in WBC", "hydroxyacetone in RBC", "plasma AC profile", "yH2Ax expression in WBC", "soluble urokinase plasminogen activator receptor (suPAR)" ] }, "relationships": [ { "predicate": "uses_hierarchical_test", "target": "multiple testing adjustment", "attributes": {}, "target_id": null } ] }, { "name": "Power Calculation", "entity_id": "power_calculation", "entity_type": "method", "aliases": [], "attributes": { "clinically_relevant_reduction": "30%", "required_sample_size": 34, "assumed_standard_deviation": "30%", "significance_level": "alpha=5%", "power": "at least 80%", "estimated_dropout_rate": "15%", "final_sample_size": 40, "software": "PASS 16.0.12" }, "relationships": [] }, { "name": "Statistical Analysis", "entity_id": "statistical_analysis", "entity_type": "method", "aliases": [], "attributes": { "population": "intention-to-treat", "missing_value_handling": "not imputed", "analysis_type": "available-case analysis", "comparison_method": "ANCOVA was adjusted to account for age, gender, weight loss, and the initial value. ", "software": "R (version 3.6.1 2019-07-05)", "visualization_tools": "R core packages, tiduverse, pheatmap, GraphPad Prism version 5.00" }, "relationships": [] }, { "name": "Patient characteristics", "entity_id": "patient_characteristics", "entity_type": "event", "aliases": [], "attributes": { "study_period": "March 2018 to May 2020", "total_randomized": 41, "fmd_group_size": 21, "m_diet_group_size": 20, "discontinued_m_diet": 1, "discontinued_reason": "erysipelas", "completed_three_cycles": 38, "completion_rate_three_cycles": "95%", "completed_study": 33, "completion_rate_study": "83%", "follow_up_count": 31, "follow_up_rate": "78%", "follow_up_time": "112±31 days" }, "relationships": [] } ], "source": { "chunk_index": 3, "start_word": 1439, "end_word": 1932, "word_count": 493, "sha256": "0635085d24fe345380e5f09e70331157570e5370693183d6494a604ae7ea3ce8", "sentence_minhash": [ 143470254565919416, 60625189416255572, 13745959893517690, 148613333131239159, 31941388625203915, 62667647458868521, 99359698575653691, 40361113771795953, 166844233492045914, 9462436175016187, 42389510456722272, 95656761971753031, 38129318889309710, 906306679132868, 29116561381011342, 489599467541456454 ] }, "extraction_warnings": [] }, { "chunk_index": 4, "context_summary": "The study attributes participant withdrawal to Covid-19 pandemic restrictions and notes comparable baseline anthropometric and metabolic measures between groups. The fasting-mimicking diet (FMD) significantly reduced albumin-to-creatinine ratio (ACR) in patients with microalbuminuria after three and six cycles, while showing no significant difference in the macroalbuminuria subgroup. FMD also improved urea levels, cystatin C-based eGFR, suPAR, and HbA1c compared to the Mediterranean diet, though fasting plasma glucose and lipid levels remained unchanged.", "entities": [ { "name": "Covid-19 pandemic restrictions", "entity_id": "covid_19_pandemic_restrictions", "entity_type": "event", "aliases": [], "attributes": { "impact": "The main reason for a break after the third dietary cycle and during the follow-up period was " }, "relationships": [ { "predicate": "caused_withdrawal_from", "target": "study", "attributes": {}, "target_id": null } ] }, { "name": "Fasting-Mimicking Diet (FMD)", "entity_id": "fasting_mimicking_diet_fmd", "entity_type": "method", "aliases": [], "attributes": { "intervention_type": "dietary" }, "relationships": [ { "predicate": "reduced_acr_in_microalbuminuria_group_after_3_cycles", "target": "37% reduction", "attributes": { "difference_of_change": "-23.7mg/g", "p_value": "≤0.05" }, "target_id": null }, { "predicate": "reduced_acr_in_microalbuminuria_group_after_6_cycles", "target": "54% reduction", "attributes": { "difference_of_change": "-30.3mg/g", "p_value": "≤0.05" }, "target_id": null }, { "predicate": "reduced_urea_after_3_cycles", "target": "-11.8mg/dl", "attributes": { "p_value": "≤0.01" }, "target_id": null }, { "predicate": "reduced_urea_after_6_cycles", "target": "-17.9mg/dl", "attributes": { "p_value": "≤0.05" }, "target_id": null }, { "predicate": "reduced_decline_in_egfr_after_6_cycles", "target": "8.3ml/min/1,73m²", "attributes": { "p_value": "≤0.05" }, "target_id": null }, { "predicate": "reduced_supar_after_3_cycles", "target": "-214.8pg/ml", "attributes": { "p_value": "≤0.05" }, "target_id": null }, { "predicate": "reduced_supar_after_6_cycles", "target": "-156.6pg/ml", "attributes": { "p_value": "≤0.05" }, "target_id": null }, { "predicate": "reduced_hba1c_after_6_cycles", "target": "17% reduction", "attributes": { "difference_of_change": "-1.1%", "p_value": "≤0.05" }, "target_id": null }, { "predicate": "reduced_homa_ir_after_6_cycles", "target": "60% reduction", "attributes": { "difference_of_change": "-3.8", "p_value": "≤0.05", "population": "non-insulin treated participants" }, "target_id": null } ] }, { "name": "Mediterranean Diet (M-Diet)", "entity_id": "mediterranean_diet_m_diet", "entity_type": "method", "aliases": [], "attributes": { "intervention_type": "dietary" }, "relationships": [ { "predicate": "compared_to_in_acr_change_all_patients_6_cycles", "target": "110.3mg/g", "attributes": { "p_value": "0.45" }, "target_id": null }, { "predicate": "compared_to_in_acr_change_macroalbuminuria_6_cycles", "target": "434.0mg/g", "attributes": { "p_value": "0.23" }, "target_id": null }, { "predicate": "compared_to_in_acr_change_all_patients_3_cycles", "target": "-62.5mg/g", "attributes": { "p_value": "0.45" }, "target_id": null }, { "predicate": "compared_to_in_acr_change_macroalbuminuria_3_cycles", "target": "-176.2mg/g", "attributes": { "p_value": "0.47" }, "target_id": null }, { "predicate": "compared_to_in_egfr_change_3_cycles", "target": "2.4ml/min/1,73m²", "attributes": { "p_value": "0.06" }, "target_id": null } ] }, { "name": "Albumin-to-Creatinine Ratio (ACR)", "entity_id": "albumin_to_creatinine_ratio_acr", "entity_type": "measurement", "aliases": [], "attributes": { "subgroups": "all patients, microalbuminuria, macroalbuminuria" }, "relationships": [ { "predicate": "difference_of_change_all_patients_6_cycles", "target": "110.3mg/g", "attributes": { "p_value": "0.45" }, "target_id": null }, { "predicate": "difference_of_change_microalbuminuria_6_cycles", "target": "-30.3mg/g", "attributes": { "p_value": "≤0.05" }, "target_id": null }, { "predicate": "difference_of_change_macroalbuminuria_6_cycles", "target": "434.0mg/g", "attributes": { "p_value": "0.23" }, "target_id": null }, { "predicate": "difference_of_change_all_patients_3_cycles", "target": "-62.5mg/g", "attributes": { "p_value": "0.45" }, "target_id": null }, { "predicate": "difference_of_change_microalbuminuria_3_cycles", "target": "-23.7mg/g", "attributes": { "p_value": "≤0.05" }, "target_id": null }, { "predicate": "difference_of_change_macroalbuminuria_3_cycles", "target": "-176.2mg/g", "attributes": { "p_value": "0.47" }, "target_id": null } ] }, { "name": "eGFR based on cystatin C", "entity_id": "egfr_based_on_cystatin_c", "entity_type": "measurement", "aliases": [], "attributes": { "unit": "ml/min/1,73m²" }, "relationships": [ { "predicate": "difference_of_change_after_6_cycles", "target": "8.3ml/min/1,73m²", "attributes": { "p_value": "≤0.05" }, "target_id": null }, { "predicate": "difference_of_change_after_3_cycles", "target": "2.4ml/min/1,73m²", "attributes": { "p_value": "0.06" }, "target_id": null } ] }, { "name": "HbA1c", "entity_id": "hba1c", "entity_type": "measurement", "aliases": [], "attributes": { "unit": "%" }, "relationships": [ { "predicate": "reduction_after_6_cycles", "target": "17%", "attributes": { "difference_of_change": "-1.1%", "p_value": "≤0.05" }, "target_id": null }, { "predicate": "change_after_3_cycles", "target": "no change", "attributes": {}, "target_id": null } ] }, { "name": "Fasting Plasma Glucose (FPG)", "entity_id": "fasting_plasma_glucose_fpg", "entity_type": "measurement", "aliases": [], "attributes": {}, "relationships": [ { "predicate": "change_after_6_cycles", "target": "comparable and did not change between study groups", "attributes": {}, "target_id": null } ] }, { "name": "Lipid levels (LDL, HDL, Triglycerides)", "entity_id": "lipid_levels_ldl_hdl_triglycerides", "entity_type": "measurement", "aliases": [], "attributes": {}, "relationships": [ { "predicate": "change_throughout_study", "target": "no change observed in FMD group compared to M-Diet group and baseline", "attributes": {}, "target_id": null } ] } ], "source": { "chunk_index": 4, "start_word": 1932, "end_word": 2387, "word_count": 455, "sha256": "e1d37a9a844d3015c7d18e20b7f3373ad64aa9a97ed85d08a19568155cf6265d", "sentence_minhash": [ 6919897742352966, 60625189416255572, 40863640610520970, 22894168227513268, 117184690827267154, 39127440086368283, 99359698575653691, 341714292460901511, 149650309763788182, 2607707833378508, 104535835787444099, 95656761971753031, 38129318889309710, 906306679132868, 98254322503569589, 240807075185782334 ] }, "extraction_warnings": [] }, { "chunk_index": 5, "context_summary": "The fasting-mimicking diet group experienced significantly greater weight loss than the Mediterranean diet group over six cycles, though body composition remained unchanged. Responders to the diet showed distinct acetylcarnitine levels and lower baseline ACR, while metabolic improvements like HOMA-IR reduction were sustained at follow-up. No significant changes were observed in dicarbonyl stress markers or DNA damage indicators.", "entities": [ { "name": "Fasting-Mimicking Diet (FMD) group", "entity_id": "fasting_mimicking_diet_fmd_group", "entity_type": "other", "aliases": [], "attributes": { "weight_loss_3_cycles": "-5.6kg (-5.9%)", "weight_loss_6_cycles": "-7.2kg (-7.5%)", "male_proportion": "71%", "model_entity_type": "group" }, "relationships": [ { "predicate": "compared_to", "target": "Mediterranean Diet (M-diet) group", "attributes": { "weight_loss_3_cycles_diff": "significant", "weight_loss_6_cycles_diff": "significant" }, "target_id": null }, { "predicate": "showed_no_change_in", "target": "body composition", "attributes": { "adjustment": "adjusted for weight loss" }, "target_id": null } ] }, { "name": "Mediterranean Diet (M-diet) group", "entity_id": "mediterranean_diet_m_diet_group", "entity_type": "other", "aliases": [], "attributes": { "weight_loss_3_cycles": "-0.7kg (-0.8%)", "weight_loss_6_cycles": "-1.1kg (-1.2%)", "male_proportion": "74%", "model_entity_type": "group" }, "relationships": [ { "predicate": "showed_no_change_in", "target": "body composition", "attributes": { "adjustment": "adjusted for weight loss" }, "target_id": null } ] }, { "name": "FMD responders", "entity_id": "fmd_responders", "entity_type": "other", "aliases": [], "attributes": { "definition": "at least 30% improvement in ACR", "baseline_acr": "85.7mg/g", "acetylcarnitine_change": "increased after three diet cycles", "model_entity_type": "subgroup" }, "relationships": [ { "predicate": "compared_to", "target": "FMD non-responders", "attributes": { "baseline_acr_diff": "significant" }, "target_id": null }, { "predicate": "showed_no_difference_in", "target": "anthropometric and metabolic parameters", "attributes": {}, "target_id": null }, { "predicate": "showed_no_difference_in", "target": "medication at baseline and throughout study", "attributes": {}, "target_id": null } ] }, { "name": "FMD non-responders", "entity_id": "fmd_non_responders", "entity_type": "other", "aliases": [], "attributes": { "baseline_acr": "271mg/g", "model_entity_type": "subgroup" }, "relationships": [] }, { "name": "M-Diet responders", "entity_id": "m_diet_responders", "entity_type": "other", "aliases": [], "attributes": { "baseline_acr": "55.5mg/g", "model_entity_type": "subgroup" }, "relationships": [] }, { "name": "M-Diet non-responders", "entity_id": "m_diet_non_responders", "entity_type": "other", "aliases": [], "attributes": { "baseline_acr": "563.0mg/g", "model_entity_type": "subgroup" }, "relationships": [] }, { "name": "plasma MG-H1", "entity_id": "plasma_mg_h1", "entity_type": "other", "aliases": [], "attributes": { "reduction_3_cycles": "62%", "model_entity_type": "biomarker" }, "relationships": [ { "predicate": "not_associated_with", "target": "change in ACR", "attributes": {}, "target_id": null } ] }, { "name": "HOMA-IR", "entity_id": "homa_ir", "entity_type": "other", "aliases": [], "attributes": { "follow_up_change": "-1.9 [-3.7, -0.1]", "follow_up_significance": "P≤0.05", "model_entity_type": "biomarker" }, "relationships": [ { "predicate": "sustained_at", "target": "follow-up", "attributes": {}, "target_id": null } ] }, { "name": "body weight", "entity_id": "body_weight", "entity_type": "measurement", "aliases": [], "attributes": { "follow_up_change": "no change compared to baseline" }, "relationships": [] }, { "name": "antihyperglycemic medication", "entity_id": "antihyperglycemic_medication", "entity_type": "other", "aliases": [], "attributes": { "follow_up_status": "increased for all but three FMD participants", "model_entity_type": "treatment" }, "relationships": [] } ], "source": { "chunk_index": 5, "start_word": 2387, "end_word": 2864, "word_count": 477, "sha256": "ac7403a5bc713946b85e663e8b2362b98033e2fc0998eaeb4af1e7a98ef0e4c9", "sentence_minhash": [ 123739674064968645, 76987600409896885, 153262400589127199, 10004148275772588, 31941388625203915, 62667647458868521, 89633613770379075, 85390325476433150, 34383880606747972, 2607707833378508, 104535835787444099, 95656761971753031, 38129318889309710, 906306679132868, 95169533629451962, 109206766937244242 ] }, "extraction_warnings": [ "normalized unsupported entity type 'group' for 'Fasting-Mimicking Diet (FMD) group'", "normalized unsupported entity type 'group' for 'Mediterranean Diet (M-diet) group'", "normalized unsupported entity type 'subgroup' for 'FMD responders'", "normalized unsupported entity type 'subgroup' for 'FMD non-responders'", "normalized unsupported entity type 'subgroup' for 'M-Diet responders'", "normalized unsupported entity type 'subgroup' for 'M-Diet non-responders'", "normalized unsupported entity type 'biomarker' for 'plasma MG-H1'", "normalized unsupported entity type 'biomarker' for 'HOMA-IR'", "normalized unsupported entity type 'treatment' for 'antihyperglycemic medication'" ] }, { "chunk_index": 6, "context_summary": "The fasting-mimicking diet was well tolerated with no severe adverse effects and comparable hypoglycemic rates to the Mediterranean diet. The intervention allowed for significant reductions in antihyperglycemic and antihypertensive medications in the FMD group, while the M-Diet group required medication increases. Blood ketones increased three-fold in the FMD group, while the M-Diet group maintained high compliance scores.", "entities": [ { "name": "fasting-mimicking diet", "entity_id": "fasting_mimicking_diet", "entity_type": "method", "aliases": [], "attributes": { "tolerability": "well tolerated", "adverse_effect_rate": "71% to 95% reported no effects", "common_symptoms": "weakness, muscle pain, dizziness, headache", "severe_adverse_effects": "none reported" }, "relationships": [ { "predicate": "causes_ketone_increase", "target": "blood ketones", "attributes": { "fold_increase": "3-fold", "p_value": "P≤0.001" }, "target_id": null }, { "predicate": "enables_medication_reduction", "target": "antihyperglycemic medication", "attributes": { "reduction_rate_3_cycles": "57%", "reduction_rate_6_cycles": "67%" }, "target_id": null }, { "predicate": "enables_medication_reduction", "target": "antihypertensive medication", "attributes": { "reduction_rate_3_cycles": "10%", "reduction_rate_6_cycles": "10%" }, "target_id": null } ] }, { "name": "mediterranean diet", "entity_id": "mediterranean_diet", "entity_type": "method", "aliases": [], "attributes": { "compliance_score": "6.1 MDS" }, "relationships": [ { "predicate": "requires_medication_increase", "target": "antihyperglycemic medication", "attributes": { "increase_rate_3_cycles": "5%", "increase_rate_6_cycles": "21%" }, "target_id": null }, { "predicate": "requires_medication_increase", "target": "antihypertensive medication", "attributes": { "increase_rate_3_cycles": "5%", "increase_rate_6_cycles": "10%" }, "target_id": null } ] }, { "name": "blood ketones", "entity_id": "blood_ketones", "entity_type": "measurement", "aliases": [], "attributes": { "fmd_3_cycles": "0.50 mmol [0.32, 0.68]", "fmd_6_cycles": "0.50 mmol [0.25, 0.75]" }, "relationships": [ { "predicate": "increased_by", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "hypoglycemic episodes", "entity_id": "hypoglycemic_episodes", "entity_type": "event", "aliases": [], "attributes": { "fmd_grade_1": "10%", "m_diet_grade_1": "11%", "fmd_grade_2": "5%", "m_diet_grade_2": "11%" }, "relationships": [ { "predicate": "comparable_between", "target": "fasting-mimicking diet and mediterranean diet", "attributes": {}, "target_id": null } ] }, { "name": "albumin-to-creatinine ratio", "entity_id": "albumin_to_creatinine_ratio", "entity_type": "measurement", "aliases": [], "attributes": {}, "relationships": [ { "predicate": "reversed_to_baseline_at_follow_up", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "MG-H1 plasma levels", "entity_id": "mg_h1_plasma_levels", "entity_type": "measurement", "aliases": [], "attributes": {}, "relationships": [ { "predicate": "reversed_to_baseline_at_follow_up", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null }, { "predicate": "transient_reduction_observed", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "suPAR", "entity_id": "supar", "entity_type": "measurement", "aliases": [], "attributes": {}, "relationships": [ { "predicate": "transient_reduction_observed", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "HOMA-IR", "entity_id": "homa_ir", "entity_type": "measurement", "aliases": [], "attributes": {}, "relationships": [ { "predicate": "sustained_improvement_observed", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] } ], "source": { "chunk_index": 6, "start_word": 2864, "end_word": 3363, "word_count": 499, "sha256": "d7704b202ad10d8b841117183b3a73ade4e887ce7803ccd67b62181f560ab0e2", "sentence_minhash": [ 228487063155910791, 18551641988871988, 153262400589127199, 61919449716151556, 439990425904285965, 99436724310786061, 134854053530791596, 84916492449827032, 149650309763788182, 316267458192039586, 128047967744972732, 95656761971753031, 38129318889309710, 906306679132868, 161357415568664162, 187819574551997385 ] }, "extraction_warnings": [] }, { "chunk_index": 7, "context_summary": "FMD-induced reductions in microalbuminuria were reversed after refeeding and did not affect patients with macroalbuminuria, unlike SGLT-2 inhibitors. Improved metabolic control was achieved through reduced medication requirements, though weight loss and glycemic control alone do not fully explain the antialbuminuric effect. Responders were distinguished by specific acylcarnitine and amino acid profiles, with glycine potentially offering renal protection.", "entities": [ { "name": "fasting-mimicking diet", "entity_id": "fasting_mimicking_diet", "entity_type": "method", "aliases": [], "attributes": { "effect_on_microalbuminuria": "reduces ACR levels", "effect_on_macroalbuminuria": "no change in ACR levels", "effect_on_medication": "Significant reduction in the use of medications to lower blood sugar and blood pressure. ", "effect_on_metabolic_control": "improved", "effect_on_albuminuria_persistence": "not sustained after refeeding" }, "relationships": [ { "predicate": "comparable_to", "target": "SGLT-2 inhibitors", "attributes": { "context": "reduction in microalbuminuria" }, "target_id": null }, { "predicate": "contrasted_with", "target": "SGLT-2 inhibitors", "attributes": { "context": "lack of effect in macroalbuminuria" }, "target_id": null } ] }, { "name": "SGLT-2 inhibitors", "entity_id": "sglt_2_inhibitors", "entity_type": "method", "aliases": [], "attributes": { "effect_on_microalbuminuria": "reduces ACR levels", "effect_on_macroalbuminuria": "reduces ACR levels" }, "relationships": [] }, { "name": "microalbuminuria", "entity_id": "microalbuminuria", "entity_type": "other", "aliases": [], "attributes": { "pathogenesis": "pathogenic events targeting vasculature, glomerulus, and tubular cells", "model_entity_type": "condition" }, "relationships": [ { "predicate": "affected_by", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "macroalbuminuria", "entity_id": "macroalbuminuria", "entity_type": "other", "aliases": [], "attributes": { "pathogenesis": "Fibrosis and loss of the normal structure of the kidneys have been observed. ", "model_entity_type": "condition" }, "relationships": [ { "predicate": "not_affected_by", "target": "fasting-mimicking diet", "attributes": {}, "target_id": null } ] }, { "name": "acetylcarnitine", "entity_id": "acetylcarnitine", "entity_type": "measurement", "aliases": [], "attributes": { "source": "Strong activation of lipolysis during a prolonged fasting period ", "role": "marker of high compliance or substrate for renal metabolism" }, "relationships": [ { "predicate": "discriminates", "target": "FMD responders and non-responders", "attributes": {}, "target_id": null } ] }, { "name": "glycine", "entity_id": "glycine", "entity_type": "measurement", "aliases": [], "attributes": { "source": "increased concentration in responders", "protective_effect": "protects against renal tubular injury" }, "relationships": [ { "predicate": "discriminates", "target": "FMD responders and non-responders", "attributes": {}, "target_id": null }, { "predicate": "potentially_enhances", "target": "Glo-1 activity", "attributes": {}, "target_id": null } ] }, { "name": "Glo-1 activity", "entity_id": "glo_1_activity", "entity_type": "measurement", "aliases": [], "attributes": { "status_in_study": "no change observed in WBC" }, "relationships": [ { "predicate": "potentially_enhanced_by", "target": "glycine", "attributes": {}, "target_id": null } ] }, { "name": "ketogenesis", "entity_id": "ketogenesis", "entity_type": "other", "aliases": [], "attributes": { "role": "orchestrates nephroprotective effects of SGLT-2 inhibitors", "mechanism": "shifts energy metabolism to ketolysis", "model_entity_type": "biological_process" }, "relationships": [ { "predicate": "induced_by", "target": "SGLT-2 inhibitors", "attributes": {}, "target_id": null } ] }, { "name": "fatty acid oxidation", "entity_id": "fatty_acid_oxidation", "entity_type": "other", "aliases": [], "attributes": { "role": "nephroprotective effect", "model_entity_type": "biological_process" }, "relationships": [ { "predicate": "explained_by", "target": "kidney metabolism reliance on lipolysis and ketone bodies", "attributes": {}, "target_id": null } ] } ], "source": { "chunk_index": 7, "start_word": 3363, "end_word": 3841, "word_count": 478, "sha256": "8c2e53af3f854057bb85e4f6276b64f7bcff92197731782168ab54778ab415ec", "sentence_minhash": [ 14279474218976588, 18551641988871988, 12309405932600981, 78327297244480524, 117184690827267154, 276121774265279552, 23718652799488495, 83575544965282909, 96635883400075078, 341344229639597412, 19416574622547768, 95656761971753031, 38129318889309710, 906306679132868, 95169533629451962, 109206766937244242 ] }, "extraction_warnings": [ "normalized unsupported entity type 'condition' for 'microalbuminuria'", "normalized unsupported entity type 'condition' for 'macroalbuminuria'", "normalized unsupported entity type 'biological_process' for 'ketogenesis'", "normalized unsupported entity type 'biological_process' for 'fatty acid oxidation'" ] }, { "chunk_index": 8, "context_summary": "The study found that fasting-mimicking diet did not activate key dicarbonyl detoxification pathways or repair DNA damage, potentially explaining the rapid return of albuminuria after the intervention. The lack of change in methylglyoxal and hydroxyacetone suggests that metabolic shifts were more complex than simple caloric restriction. The study highlights the clinical importance of fasting in type 2 diabetes while noting limitations such as the isocaloric control diet and the need for longer intervention periods.", "entities": [ { "name": "plasma methylglyoxal", "entity_id": "plasma_methylglyoxal", "entity_type": "measurement", "aliases": [], "attributes": { "change_status": "no change" }, "relationships": [ { "predicate": "evidenced_by", "target": "lack of increase in Glo-1 activity or pGlo-1 expression in WBC", "attributes": {}, "target_id": null } ] }, { "name": "dicarbonyl detoxification", "entity_id": "dicarbonyl_detoxification", "entity_type": "other", "aliases": [], "attributes": { "improvement_status": "no improvement", "model_entity_type": "biological_process" }, "relationships": [ { "predicate": "evidenced_by", "target": "lack of increase in Glo-1 activity or pGlo-1 expression in WBC", "attributes": {}, "target_id": null } ] }, { "name": "Glo-1 activity", "entity_id": "glo_1_activity", "entity_type": "measurement", "aliases": [], "attributes": { "change_status": "no increase" }, "relationships": [ { "predicate": "measured_in", "target": "WBC", "attributes": {}, "target_id": null } ] }, { "name": "pGlo-1 expression", "entity_id": "pglo_1_expression", "entity_type": "measurement", "aliases": [], "attributes": { "change_status": "no increase" }, "relationships": [ { "predicate": "measured_in", "target": "WBC", "attributes": {}, "target_id": null } ] }, { "name": "hydroxyacetone", "entity_id": "hydroxyacetone", "entity_type": "measurement", "aliases": [], "attributes": { "change_status": "no change" }, "relationships": [ { "predicate": "reflects", "target": "alternative MG detoxification pathways", "attributes": {}, "target_id": null }, { "predicate": "measured_in", "target": "RBC", "attributes": {}, "target_id": null } ] }, { "name": "aldo-keto reductase", "entity_id": "aldo_keto_reductase", "entity_type": "other", "aliases": [], "attributes": { "model_entity_type": "enzyme" }, "relationships": [ { "predicate": "part_of", "target": "alternative MG detoxification pathways", "attributes": {}, "target_id": null } ] }, { "name": "DNA-damage/repair", "entity_id": "dna_damage_repair", "entity_type": "other", "aliases": [], "attributes": { "reconstitution_status": "no reconstitution", "model_entity_type": "biological_process" }, "relationships": [ { "predicate": "potential_explanation_for", "target": "rapid increase of ACR after termination of FMD", "attributes": {}, "target_id": null } ] }, { "name": "suPAR", "entity_id": "supar", "entity_type": "measurement", "aliases": [], "attributes": { "change_status": "fast increase after FMD" }, "relationships": [ { "predicate": "marker_of", "target": "accelerated aging and senescence", "attributes": {}, "target_id": null }, { "predicate": "supports_explanation_for", "target": "rapid increase of ACR after termination of FMD", "attributes": {}, "target_id": null } ] }, { "name": "Fasting-Mimicking Diet (FMD)", "entity_id": "fasting_mimicking_diet_fmd", "entity_type": "method", "aliases": [], "attributes": { "duration_requirement": "A longer treatment period may be necessary to reverse the kidney damage. " }, "relationships": [ { "predicate": "did_not_activate", "target": "defense pathways to control nephropathy", "attributes": {}, "target_id": null }, { "predicate": "showed_different_response_in", "target": "MG-H1 reduction after three but not after six cycles", "attributes": {}, "target_id": null } ] }, { "name": "MG-H1 reduction", "entity_id": "mg_h1_reduction", "entity_type": "measurement", "aliases": [], "attributes": { "response_pattern": "Different depending on three, but not on six, FMD cycles. " }, "relationships": [ { "predicate": "suggests", "target": "sustained redirection of metabolism during FMD", "attributes": {}, "target_id": null }, { "predicate": "unlikely_due_to", "target": "reduced energy intake during FMD", "attributes": {}, "target_id": null } ] }, { "name": "randomized controlled design", "entity_id": "randomized_controlled_design", "entity_type": "method", "aliases": [], "attributes": { "novelty": "first time exploring clinical importance of fasting in type 2 diabetes patients" }, "relationships": [] }, { "name": "hypoglycemia", "entity_id": "hypoglycemia", "entity_type": "event", "aliases": [], "attributes": { "severity": "no episodes of severe" }, "relationships": [] }, { "name": "hypotension", "entity_id": "hypotension", "entity_type": "event", "aliases": [], "attributes": { "severity": "no episodes of severe" }, "relationships": [] }, { "name": "isocaloric diet", "entity_id": "isocaloric_diet", "entity_type": "method", "aliases": [], "attributes": { "group": "control group" }, "relationships": [ { "predicate": "contrasts_with", "target": "caloric restriction of the FMD", "attributes": {}, "target_id": null }, { "predicate": "showed", "target": "mild weight loss", "attributes": {}, "target_id": null } ] }, { "name": "weight loss", "entity_id": "weight_loss", "entity_type": "measurement", "aliases": [], "attributes": { "FMD_group_status": "higher and significant compared to baseline and control group" }, "relationships": [ { "predicate": "persistent_at", "target": "refeeding (one week after FMD)", "attributes": {}, "target_id": null }, { "predicate": "less_likely_to_affect", "target": "reduction of albuminuria", "attributes": {}, "target_id": null } ] }, { "name": "glycemia", "entity_id": "glycemia", "entity_type": "measurement", "aliases": [], "attributes": { "control_status": "strictly controlled" }, "relationships": [ { "predicate": "comparable_between", "target": "study groups throughout the study", "attributes": {}, "target_id": null } ] }, { "name": "blood pressure", "entity_id": "blood_pressure", "entity_type": "measurement", "aliases": [], "attributes": { "control_status": "strictly controlled" }, "relationships": [ { "predicate": "comparable_between", "target": "study groups throughout the study", "attributes": {}, "target_id": null } ] }, { "name": "albuminuria", "entity_id": "albuminuria", "entity_type": "measurement", "aliases": [], "attributes": { "overall_group_change": "no significant change after FMD treatment" }, "relationships": [ { "predicate": "significant_reduction_in", "target": "subgroup analysis of patients with microalbuminuria", "attributes": {}, "target_id": null }, { "predicate": "baseline_levels_predict", "target": "development of diabetic nephropathy in type 2 diabetes", "attributes": {}, "target_id": null } ] } ], "source": { "chunk_index": 8, "start_word": 3841, "end_word": 4333, "word_count": 492, "sha256": "08156e3519dadfe820ed0612bab0b444df52b71928cb959c74ffbc6573a9d23b", "sentence_minhash": [ 147519523736366927, 1306423125707224, 153262400589127199, 125075598868273132, 26384097017582652, 99436724310786061, 23718652799488495, 85390325476433150, 96635883400075078, 17444917348060025, 67831053780325945, 53801230756016856, 38129318889309710, 906306679132868, 95169533629451962, 285412106277652386 ] }, "extraction_warnings": [ "normalized unsupported entity type 'biological_process' for 'dicarbonyl detoxification'", "normalized unsupported entity type 'enzyme' for 'aldo-keto reductase'", "normalized unsupported entity type 'biological_process' for 'DNA-damage/repair'" ] }, { "chunk_index": 9, "context_summary": "The study acknowledges limitations including a small sample size and the absence of kidney biopsies to assess renal cell metabolism. It concludes that fasting-mimicking diet cycles can be integrated into clinical practice to reduce albuminuria and improve metabolic control in type 2 diabetes patients. The lack of change in dicarbonyl detoxification and DNA-damage markers suggests that longer intervention periods may be necessary to prevent albuminuria relapse.", "entities": [ { "name": "small sample size", "entity_id": "small_sample_size", "entity_type": "other", "aliases": [], "attributes": { "impact": "may play a role in study results", "model_entity_type": "limitation" }, "relationships": [ { "predicate": "requires_future_study_in", "target": "larger cohorts", "attributes": {}, "target_id": null } ] }, { "name": "fasting-mimicking diet (FMD)", "entity_id": "fasting_mimicking_diet_fmd", "entity_type": "method", "aliases": [], "attributes": { "status": "proof-of-concept-study" }, "relationships": [ { "predicate": "integrated_into", "target": "clinical practice", "attributes": {}, "target_id": null }, { "predicate": "complementary_to", "target": "current guidelines", "attributes": {}, "target_id": null }, { "predicate": "leads_to_reduction_in", "target": "ACR in type 2 diabetes patients with microalbuminuria", "attributes": {}, "target_id": null }, { "predicate": "leads_to_improvement_in", "target": "glycemic and blood pressure control", "attributes": {}, "target_id": null }, { "predicate": "leads_to_sustained_reduction_in", "target": "insulin resistance", "attributes": { "condition": "adjusted for weight loss" }, "target_id": null } ] }, { "name": "dicarbonyl detoxification and DNA-damage/repair markers", "entity_id": "dicarbonyl_detoxification_and_dna_damage_repair_markers", "entity_type": "measurement", "aliases": [], "attributes": { "change_status": "lack of changes" }, "relationships": [ { "predicate": "explains", "target": "relapse of albuminuria after six FMD cycles", "attributes": {}, "target_id": null }, { "predicate": "suggests_need_for", "target": "longer intervention periods", "attributes": {}, "target_id": null } ] }, { "name": "markers of incomplete lipid oxidation", "entity_id": "markers_of_incomplete_lipid_oxidation", "entity_type": "measurement", "aliases": [], "attributes": { "effect_status": "distinct effects" }, "relationships": [ { "predicate": "observed_in", "target": "patients showing improvement of albuminuria", "attributes": {}, "target_id": null }, { "predicate": "may_help_develop", "target": "new therapeutic strategies", "attributes": {}, "target_id": null } ] }, { "name": "kidney biopsies", "entity_id": "kidney_biopsies", "entity_type": "other", "aliases": [], "attributes": { "collection_status": "not collected", "model_entity_type": "procedure" }, "relationships": [ { "predicate": "limits_exploration_of", "target": "renal cell metabolism", "attributes": {}, "target_id": null } ] } ], "source": { "chunk_index": 9, "start_word": 4333, "end_word": 4701, "word_count": 368, "sha256": "0271f0dbe51e1cd1447c560755caaba3232fe41cbdfc9f6cbf72b3d916959a18", "sentence_minhash": [ 147519523736366927, 1306423125707224, 263266681512727230, 37498130448765965, 60043449279178472, 99436724310786061, 134854053530791596, 47615437990415314, 266927695903760850, 67885135535576213, 141479479946104613, 95656761971753031, 38129318889309710, 906306679132868, 320556702413602850, 285412106277652386 ] }, "extraction_warnings": [ "normalized unsupported entity type 'limitation' for 'small sample size'", "normalized unsupported entity type 'procedure' for 'kidney biopsies'" ] } ], "canonical_entities": [] }, "chunks_expected": 10, "chunks_generated": 10, "failed_chunks": [], "repair": { "accepted_windows": 14, "rolled_back": false, "original_context_sha256": "76fb6df8c7578596f214fb7c08a6456f931936b4da84e1969e8f9299392a7231", "final_context_sha256": "b348c26c21176f2a345b4d9b538d1f99fae726ff5b64941b7d02a0cbac48d230", "critical_values": { "passed": true, "checks": { "numbers": true, "quantities": true, "formulas": true, "mathematical_variables": true, "operators": true }, "before": { "numbers": [ "2", "2", "6", "3", "21", "2", "110.3", "95", "99.2", "121.5", "0.45", "-30.3", "95", "-35.7", "-24.9", "0.05", "434", "95", "404.7", "463.4", "0.23", "-3", "8", "95", "-5", "6", "-2", "0.05", "95", "-172.9", "0.05", "19", "2", "2", "4E+1", "7.8", "0.2", "62.1", "2.3", "-1.9", "95", "-3.7", "-0.1", "0.05", "1", "2", "2", "2", "2", "2", "682", "2016", "2", "3E+1", "2", "7", "5", "25", "4.6E+3", "11", "46", "43", "3E+3", "9", "44", "47", "5E+1", "5", "25", "4", "2", "24", "2E+1", "1E+2", "6E+1", "12", "12", "4E+1", "3E+1", "38", "33", "1", "1", "3E+1", "34", "3E+1", "5", "8E+1", "15", "4E+1", "2019", "7", "5", "5", "2018", "2.02E+3", "41", "21", "2E+1", "1", "38", "95", "33", "83", "31", "78", "112", "31", "19", "19", "37", "-23.7", "0.05", "54", "-30.3", "0.05", "-11.8", "0.01", "-17.9", "0.05", "1", "73", "2", "0.05", "0.05", "0.05", "17", "-1.1", "0.05", "6E+1", "-3.8", "0.05", "110.3", "0.45", "434", "0.23", "-62.5", "0.45", "-176.2", "0.47", "1", "73", "2", "0.06", "110.3", "0.45", "-30.3", "0.05", "434", "0.23", "-62.5", "0.45", "-23.7", "0.05", "-176.2", "0.47", "1", "73", "2", "1", "73", "2", "0.05", "1", "73", "2", "0.06", "17", "-1.1", "0.05", "-5.6", "-5.9", "-7.2", "-7.5", "71", "-0.7", "-0.8", "-1.1", "-1.2", "74", "3E+1", "85.7", "271", "55.5", "563", "62", "-1.9", "-3.7", "-0.1", "0.05", "71", "95", "3", "0.001", "57", "67", "1E+1", "1E+1", "6.1", "5", "21", "5", "1E+1", "0.5", "0.32", "0.68", "0.5", "0.25", "0.75", "1E+1", "11", "5", "11", "2", "2", "2", "2", "1", "1", "2", "2", "2", "1", "1", "1", "1", "1", "1", "2", "2", "2", "2" ], "quantities": [ [ "110.3", "mg/g" ], [ "95", "%" ], [ "121.5", "mg/g" ], [ "-30.3", "mg/g" ], [ "95", "%" ], [ "-24.9", "mg/g" ], [ "434", "mg/g" ], [ "95", "%" ], [ "463.4", "mg/g" ], [ "95", "%" ], [ "95", "%" ], [ "0.2", "%" ], [ "2.3", "mmol/mol" ], [ "95", "%" ], [ "3E+1", "kg/m" ], [ "7", "%" ], [ "4.6E+3", "kJ" ], [ "11", "%" ], [ "46", "%" ], [ "43", "%" ], [ "3E+3", "kJ" ], [ "9", "%" ], [ "44", "%" ], [ "47", "%" ], [ "5E+1", "%" ], [ "2E+1", "%" ], [ "3E+1", "%" ], [ "3E+1", "%" ], [ "3E+1", "%" ], [ "5", "%" ], [ "8E+1", "%" ], [ "15", "%" ], [ "95", "%" ], [ "83", "%" ], [ "78", "%" ], [ "37", "%" ], [ "-23.7", "mg/g" ], [ "54", "%" ], [ "-30.3", "mg/g" ], [ "-11.8", "mg" ], [ "-17.9", "mg" ], [ "73", "m^2" ], [ "17", "%" ], [ "-1.1", "%" ], [ "6E+1", "%" ], [ "110.3", "mg/g" ], [ "434", "mg/g" ], [ "-62.5", "mg/g" ], [ "-176.2", "mg/g" ], [ "73", "m^2" ], [ "110.3", "mg/g" ], [ "-30.3", "mg/g" ], [ "434", "mg/g" ], [ "-62.5", "mg/g" ], [ "-23.7", "mg/g" ], [ "-176.2", "mg/g" ], [ "73", "m^2" ], [ "73", "m^2" ], [ "73", "m^2" ], [ "17", "%" ], [ "-1.1", "%" ], [ "-5.6", "kg" ], [ "-5.9", "%" ], [ "-7.2", "kg" ], [ "-7.5", "%" ], [ "71", "%" ], [ "-0.7", "kg" ], [ "-0.8", "%" ], [ "-1.1", "kg" ], [ "-1.2", "%" ], [ "74", "%" ], [ "3E+1", "%" ], [ "85.7", "mg/g" ], [ "271", "mg/g" ], [ "55.5", "mg/g" ], [ "563", "mg/g" ], [ "62", "%" ], [ "71", "%" ], [ "95", "%" ], [ "57", "%" ], [ "67", "%" ], [ "1E+1", "%" ], [ "1E+1", "%" ], [ "5", "%" ], [ "21", "%" ], [ "5", "%" ], [ "1E+1", "%" ], [ "0.5", "mmol" ], [ "0.5", "mmol" ], [ "1E+1", "%" ], [ "11", "%" ], [ "5", "%" ], [ "11", "%" ] ], "formulas": [ "P=0.23", "P=0.45", "P≤0.001", "P≤0.05", "P≤0.05", "P≤0.05", "P≤0.05", "P≤0.05", "R(version3.60.12019to7to5)", "S-682/2016", "a=5", "chemical:DRKS00014287", "chemical:H1", "chemical:H1", "chemical:H1", "chemical:H1", "chemical:H1", "chemical:H1", "chemical:SGLT2", "chemical:SGLT2", "g(95%CI-35.7,-24.9mg/g;P≤0.05)", "g(95%CI404.7,463.4mg/g;P=0.23)", "g(95%CI99.2,121.5mg/g;P=0.45)", "m^2", "m^2", "m^2", "m^2", "m^2", "m^2" ], "mathematical_variables": [ "D_group_status", "c_change", "c_options_limited_to", "c_threshold", "c_threshold", "d_3_cycles", "d_6_cycles", "d_acr_in_microalbuminuria_group_after_3_cycles", "d_acr_in_microalbuminuria_group_after_6_cycles", "d_at", "d_at", "d_benefit_mechanism", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_decline_in_egfr_after_6_cycles", "d_different_response_in", "d_dropout_rate", "d_from", "d_grade_1", "d_grade_2", "d_group_size", "d_hba1c_after_6_cycles", "d_homa_ir_after_6_cycles", "d_improvement_observed", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in_change_in_acr", "d_in_change_in_acr_macroalbuminuria", "d_in_change_in_acr_microalbuminuria", "d_in_change_in_homa_ir", "d_in_change_in_supar", "d_in_no_change_in", "d_increase", "d_into", "d_m_diet", "d_no_change_in", "d_no_change_in", "d_no_difference_in", "d_no_difference_in", "d_not_activate", "d_patients_with", "d_patients_with", "d_patients_with", "d_reason", "d_recommendations_for", "d_reduction_at_follow_up", "d_sample_size", "d_standard_deviation", "d_study", "d_study_at", "d_study_procedures", "d_supar_after_3_cycles", "d_supar_after_6_cycles", "d_three_cycles", "d_to", "d_to", "d_to", "d_to", "d_to", "d_to", "d_to", "d_to_baseline_at_follow_up", "d_to_baseline_at_follow_up", "d_to_in_acr_change_all_patients_3_cycles", "d_to_in_acr_change_all_patients_6_cycles", "d_to_in_acr_change_macroalbuminuria_3_cycles", "d_to_in_acr_change_macroalbuminuria_6_cycles", "d_to_in_egfr_change_3_cycles", "d_urea_after_3_cycles", "d_urea_after_6_cycles", "d_with", "d_with", "d_with", "d_withdrawal_from", "e_acr", "e_acr", "e_acr", "e_acr", "e_acr_diff", "e_adverse_effects", "e_after_3_cycles", "e_after_6_cycles", "e_assessed_by", "e_assessed_by", "e_at_follow_up_explained_by", "e_between", "e_between", "e_between", "e_change", "e_effect", "e_effect_rate", "e_gap", "e_gap", "e_in_profile_related_to", "e_level", "e_levels_predict", "e_of_change", "e_of_change", "e_of_change", "e_of_change", "e_of_change", "e_of_change_after_3_cycles", "e_of_change_after_6_cycles", "e_of_change_all_patients_3_cycles", "e_of_change_all_patients_6_cycles", "e_of_change_macroalbuminuria_3_cycles", "e_of_change_macroalbuminuria_6_cycles", "e_of_change_microalbuminuria_3_cycles", "e_of_change_microalbuminuria_6_cycles", "e_pattern", "e_proportion", "e_proportion", "e_rate_3_cycles", "e_rate_3_cycles", "e_rate_6_cycles", "e_rate_6_cycles", "e_score", "e_size", "e_size", "e_status", "e_status", "e_status", "e_status", "e_status", "e_status", "e_throughout_study", "e_to", "e_type", "g_platform", "g_value_handling", "l_benefits_not_explained_by", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_explanation_for", "l_group_change", "l_process", "l_process", "l_process", "l_process", "l_process", "l_process", "l_process", "l_process", "l_randomized", "l_sample_size", "l_sample_size", "l_status", "l_status", "m_diet_grade_1", "m_diet_grade_2", "m_diet_group_size", "m_to_reduce", "m_to_relate_to_changes_in", "m_to_relate_to_changes_in", "m_to_relate_to_changes_in", "m_to_relate_to_changes_in", "n_3_cycles", "n_after_6_cycles", "n_body", "n_exerted_by", "n_exerted_by", "n_id", "n_method", "n_rate_3_cycles", "n_rate_3_cycles", "n_rate_6_cycles", "n_rate_6_cycles", "n_rate_study", "n_rate_three_cycles", "n_requirement", "n_standard", "n_status", "n_status", "n_status", "n_symptoms", "n_therapy_status", "n_tools", "n_type", "n_type", "o_change_observed_in", "o_change_observed_in", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "r_of", "s_decline_in", "s_energy_metabolism_to", "s_explanation_for", "s_exploration_of", "s_fuel_metabolism_from", "s_fuel_metabolism_to", "s_future_study_in", "s_hierarchical_test", "s_in", "s_in_study", "s_insulin_adjustment", "s_ketone_increase", "s_likely_to_affect", "s_medication_discontinuation", "s_medication_increase", "s_medication_increase", "s_medication_reduction", "s_medication_reduction", "s_medication_reduction", "s_need_for", "s_subgroup_analysis", "s_to_improvement_in", "s_to_reduction_in", "s_to_sustained_reduction_in", "s_type", "s_with", "t_activate", "t_affected_by", "t_associated_with", "t_at", "t_device", "t_guideline", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_loss_3_cycles", "t_loss_3_cycles", "t_loss_3_cycles_diff", "t_loss_6_cycles", "t_loss_6_cycles", "t_loss_6_cycles_diff", "t_nephroprotection_in", "t_nephroprotection_in", "t_of", "t_off", "t_off", "t_on_albuminuria_persistence", "t_on_macroalbuminuria", "t_on_macroalbuminuria", "t_on_medication", "t_on_metabolic_control", "t_on_microalbuminuria", "t_on_microalbuminuria", "t_reduction_in", "t_reduction_observed", "t_reduction_observed", "t_status", "t_status", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "w_up", "w_up_change", "w_up_change", "w_up_count", "w_up_rate", "w_up_significance", "w_up_status", "w_up_time", "y_1_energy", "y_1_macronutrients", "y_2_to_5_energy", "y_2_to_5_macronutrients", "y_due_to", "y_enhanced_by", "y_enhances", "y_help_develop", "y_period", "y_relevant_reduction", "y_to", "y_type" ], "operators": [ "=", "≤", "=", "≤", "≤", "±", "±", "≤", "=", "±", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤" ] }, "after": { "numbers": [ "2", "2", "6", "3", "21", "2", "110.3", "95", "99.2", "121.5", "0.45", "-30.3", "95", "-35.7", "-24.9", "0.05", "434", "95", "404.7", "463.4", "0.23", "-3", "8", "95", "-5", "6", "-2", "0.05", "95", "-172.9", "0.05", "19", "2", "2", "4E+1", "7.8", "0.2", "62.1", "2.3", "-1.9", "95", "-3.7", "-0.1", "0.05", "1", "2", "2", "2", "2", "2", "682", "2016", "2", "3E+1", "2", "7", "5", "25", "4.6E+3", "11", "46", "43", "3E+3", "9", "44", "47", "5E+1", "5", "25", "4", "2", "24", "2E+1", "1E+2", "6E+1", "12", "12", "4E+1", "3E+1", "38", "33", "1", "1", "3E+1", "34", "3E+1", "5", "8E+1", "15", "4E+1", "2019", "7", "5", "5", "2018", "2.02E+3", "41", "21", "2E+1", "1", "38", "95", "33", "83", "31", "78", "112", "31", "19", "19", "37", "-23.7", "0.05", "54", "-30.3", "0.05", "-11.8", "0.01", "-17.9", "0.05", "1", "73", "2", "0.05", "0.05", "0.05", "17", "-1.1", "0.05", "6E+1", "-3.8", "0.05", "110.3", "0.45", "434", "0.23", "-62.5", "0.45", "-176.2", "0.47", "1", "73", "2", "0.06", "110.3", "0.45", "-30.3", "0.05", "434", "0.23", "-62.5", "0.45", "-23.7", "0.05", "-176.2", "0.47", "1", "73", "2", "1", "73", "2", "0.05", "1", "73", "2", "0.06", "17", "-1.1", "0.05", "-5.6", "-5.9", "-7.2", "-7.5", "71", "-0.7", "-0.8", "-1.1", "-1.2", "74", "3E+1", "85.7", "271", "55.5", "563", "62", "-1.9", "-3.7", "-0.1", "0.05", "71", "95", "3", "0.001", "57", "67", "1E+1", "1E+1", "6.1", "5", "21", "5", "1E+1", "0.5", "0.32", "0.68", "0.5", "0.25", "0.75", "1E+1", "11", "5", "11", "2", "2", "2", "2", "1", "1", "2", "2", "2", "1", "1", "1", "1", "1", "1", "2", "2", "2", "2" ], "quantities": [ [ "110.3", "mg/g" ], [ "95", "%" ], [ "121.5", "mg/g" ], [ "-30.3", "mg/g" ], [ "95", "%" ], [ "-24.9", "mg/g" ], [ "434", "mg/g" ], [ "95", "%" ], [ "463.4", "mg/g" ], [ "95", "%" ], [ "95", "%" ], [ "0.2", "%" ], [ "2.3", "mmol/mol" ], [ "95", "%" ], [ "3E+1", "kg/m" ], [ "7", "%" ], [ "4.6E+3", "kJ" ], [ "11", "%" ], [ "46", "%" ], [ "43", "%" ], [ "3E+3", "kJ" ], [ "9", "%" ], [ "44", "%" ], [ "47", "%" ], [ "5E+1", "%" ], [ "2E+1", "%" ], [ "3E+1", "%" ], [ "3E+1", "%" ], [ "3E+1", "%" ], [ "5", "%" ], [ "8E+1", "%" ], [ "15", "%" ], [ "95", "%" ], [ "83", "%" ], [ "78", "%" ], [ "37", "%" ], [ "-23.7", "mg/g" ], [ "54", "%" ], [ "-30.3", "mg/g" ], [ "-11.8", "mg" ], [ "-17.9", "mg" ], [ "73", "m^2" ], [ "17", "%" ], [ "-1.1", "%" ], [ "6E+1", "%" ], [ "110.3", "mg/g" ], [ "434", "mg/g" ], [ "-62.5", "mg/g" ], [ "-176.2", "mg/g" ], [ "73", "m^2" ], [ "110.3", "mg/g" ], [ "-30.3", "mg/g" ], [ "434", "mg/g" ], [ "-62.5", "mg/g" ], [ "-23.7", "mg/g" ], [ "-176.2", "mg/g" ], [ "73", "m^2" ], [ "73", "m^2" ], [ "73", "m^2" ], [ "17", "%" ], [ "-1.1", "%" ], [ "-5.6", "kg" ], [ "-5.9", "%" ], [ "-7.2", "kg" ], [ "-7.5", "%" ], [ "71", "%" ], [ "-0.7", "kg" ], [ "-0.8", "%" ], [ "-1.1", "kg" ], [ "-1.2", "%" ], [ "74", "%" ], [ "3E+1", "%" ], [ "85.7", "mg/g" ], [ "271", "mg/g" ], [ "55.5", "mg/g" ], [ "563", "mg/g" ], [ "62", "%" ], [ "71", "%" ], [ "95", "%" ], [ "57", "%" ], [ "67", "%" ], [ "1E+1", "%" ], [ "1E+1", "%" ], [ "5", "%" ], [ "21", "%" ], [ "5", "%" ], [ "1E+1", "%" ], [ "0.5", "mmol" ], [ "0.5", "mmol" ], [ "1E+1", "%" ], [ "11", "%" ], [ "5", "%" ], [ "11", "%" ] ], "formulas": [ "P=0.23", "P=0.45", "P≤0.001", "P≤0.05", "P≤0.05", "P≤0.05", "P≤0.05", "P≤0.05", "R(version3.60.12019to7to5)", "S-682/2016", "a=5", "chemical:DRKS00014287", "chemical:H1", "chemical:H1", "chemical:H1", "chemical:H1", "chemical:H1", "chemical:H1", "chemical:SGLT2", "chemical:SGLT2", "g(95%CI-35.7,-24.9mg/g;P≤0.05)", "g(95%CI404.7,463.4mg/g;P=0.23)", "g(95%CI99.2,121.5mg/g;P=0.45)", "m^2", "m^2", "m^2", "m^2", "m^2", "m^2" ], "mathematical_variables": [ "D_group_status", "c_change", "c_options_limited_to", "c_threshold", "c_threshold", "d_3_cycles", "d_6_cycles", "d_acr_in_microalbuminuria_group_after_3_cycles", "d_acr_in_microalbuminuria_group_after_6_cycles", "d_at", "d_at", "d_benefit_mechanism", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_by", "d_decline_in_egfr_after_6_cycles", "d_different_response_in", "d_dropout_rate", "d_from", "d_grade_1", "d_grade_2", "d_group_size", "d_hba1c_after_6_cycles", "d_homa_ir_after_6_cycles", "d_improvement_observed", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in", "d_in_change_in_acr", "d_in_change_in_acr_macroalbuminuria", "d_in_change_in_acr_microalbuminuria", "d_in_change_in_homa_ir", "d_in_change_in_supar", "d_in_no_change_in", "d_increase", "d_into", "d_m_diet", "d_no_change_in", "d_no_change_in", "d_no_difference_in", "d_no_difference_in", "d_not_activate", "d_patients_with", "d_patients_with", "d_patients_with", "d_reason", "d_recommendations_for", "d_reduction_at_follow_up", "d_sample_size", "d_standard_deviation", "d_study", "d_study_at", "d_study_procedures", "d_supar_after_3_cycles", "d_supar_after_6_cycles", "d_three_cycles", "d_to", "d_to", "d_to", "d_to", "d_to", "d_to", "d_to", "d_to_baseline_at_follow_up", "d_to_baseline_at_follow_up", "d_to_in_acr_change_all_patients_3_cycles", "d_to_in_acr_change_all_patients_6_cycles", "d_to_in_acr_change_macroalbuminuria_3_cycles", "d_to_in_acr_change_macroalbuminuria_6_cycles", "d_to_in_egfr_change_3_cycles", "d_urea_after_3_cycles", "d_urea_after_6_cycles", "d_with", "d_with", "d_with", "d_withdrawal_from", "e_acr", "e_acr", "e_acr", "e_acr", "e_acr_diff", "e_adverse_effects", "e_after_3_cycles", "e_after_6_cycles", "e_assessed_by", "e_assessed_by", "e_at_follow_up_explained_by", "e_between", "e_between", "e_between", "e_change", "e_effect", "e_effect_rate", "e_gap", "e_gap", "e_in_profile_related_to", "e_level", "e_levels_predict", "e_of_change", "e_of_change", "e_of_change", "e_of_change", "e_of_change", "e_of_change_after_3_cycles", "e_of_change_after_6_cycles", "e_of_change_all_patients_3_cycles", "e_of_change_all_patients_6_cycles", "e_of_change_macroalbuminuria_3_cycles", "e_of_change_macroalbuminuria_6_cycles", "e_of_change_microalbuminuria_3_cycles", "e_of_change_microalbuminuria_6_cycles", "e_pattern", "e_proportion", "e_proportion", "e_rate_3_cycles", "e_rate_3_cycles", "e_rate_6_cycles", "e_rate_6_cycles", "e_score", "e_size", "e_size", "e_status", "e_status", "e_status", "e_status", "e_status", "e_status", "e_throughout_study", "e_to", "e_type", "g_platform", "g_value_handling", "l_benefits_not_explained_by", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_entity_type", "l_explanation_for", "l_group_change", "l_process", "l_process", "l_process", "l_process", "l_process", "l_process", "l_process", "l_process", "l_randomized", "l_sample_size", "l_sample_size", "l_status", "l_status", "m_diet_grade_1", "m_diet_grade_2", "m_diet_group_size", "m_to_reduce", "m_to_relate_to_changes_in", "m_to_relate_to_changes_in", "m_to_relate_to_changes_in", "m_to_relate_to_changes_in", "n_3_cycles", "n_after_6_cycles", "n_body", "n_exerted_by", "n_exerted_by", "n_id", "n_method", "n_rate_3_cycles", "n_rate_3_cycles", "n_rate_6_cycles", "n_rate_6_cycles", "n_rate_study", "n_rate_three_cycles", "n_requirement", "n_standard", "n_status", "n_status", "n_status", "n_symptoms", "n_therapy_status", "n_tools", "n_type", "n_type", "o_change_observed_in", "o_change_observed_in", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "p_value", "r_of", "s_decline_in", "s_energy_metabolism_to", "s_explanation_for", "s_exploration_of", "s_fuel_metabolism_from", "s_fuel_metabolism_to", "s_future_study_in", "s_hierarchical_test", "s_in", "s_in_study", "s_insulin_adjustment", "s_ketone_increase", "s_likely_to_affect", "s_medication_discontinuation", "s_medication_increase", "s_medication_increase", "s_medication_reduction", "s_medication_reduction", "s_medication_reduction", "s_need_for", "s_subgroup_analysis", "s_to_improvement_in", "s_to_reduction_in", "s_to_sustained_reduction_in", "s_type", "s_with", "t_activate", "t_affected_by", "t_associated_with", "t_at", "t_device", "t_guideline", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_id", "t_loss_3_cycles", "t_loss_3_cycles", "t_loss_3_cycles_diff", "t_loss_6_cycles", "t_loss_6_cycles", "t_loss_6_cycles_diff", "t_nephroprotection_in", "t_nephroprotection_in", "t_of", "t_off", "t_off", "t_on_albuminuria_persistence", "t_on_macroalbuminuria", "t_on_macroalbuminuria", "t_on_medication", "t_on_metabolic_control", "t_on_microalbuminuria", "t_on_microalbuminuria", "t_reduction_in", "t_reduction_observed", "t_reduction_observed", "t_status", "t_status", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "t_summary", "w_up", "w_up_change", "w_up_change", "w_up_count", "w_up_rate", "w_up_significance", "w_up_status", "w_up_time", "y_1_energy", "y_1_macronutrients", "y_2_to_5_energy", "y_2_to_5_macronutrients", "y_due_to", "y_enhanced_by", "y_enhances", "y_help_develop", "y_period", "y_relevant_reduction", "y_to", "y_type" ], "operators": [ "=", "≤", "=", "≤", "≤", "±", "±", "≤", "=", "±", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤", "≤" ] }, "numeric_content_present": true, "formula_content_present": true, "exact_text_unchanged": false, "interpretation": "Conservative preservation filter; changed signatures require review and can include harmless reordering or equivalent unit/algebra conversions" } }, "condition": "gemma12_r128_ku500_bt", "source_metadata": { "title": "A six-month periodic fasting reduces microalbuminuria and improves metabolic control in patients with type 2 diabetes and diabetic nephropathy: a randomized controlled study", "authors": [ "Alba Sulaj", "Stefan Kopf", "Ekaterina Von Rauchhaupt", "Elisabeth Kliemank", "Maik Brune", "Zoltan Kender", "Hannelore Bartl", "Fabiola Garcia Cortizo", "Katarina Klepac", "Zhe Han", "Varun Kumar", "Valter Longo", "Aurelio Teleman", "Jürgen G Okun", "Jakob Morgenstern", "Thomas Fleming", "Julia Szendroedi", "Stephan Herzig", "Peter P Nawroth" ], "doi": "", "year": "", "openalex_id": "", "origin": "Existing disjoint 20-paper benchmark cohort", "metadata_added_for_attribution_only": true, "metadata_not_used_to_change_QA_context": true } }