{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002569","ANALYSIS_ID":"AN004233","VERSION":"1","CREATED_ON":"April 19, 2023, 3:54 pm"},

"PROJECT":{"PROJECT_TITLE":"Remodeling of lipid landscape in high fat fed very-long chain acyl-CoA dehydrogenase null mice favors pro-arrhythmic polyunsaturated fatty acids and their downstream metabolites","PROJECT_SUMMARY":"Very-long chain acyl-CoA dehydrogenase (VLCAD) catalyses mitochondrial fatty acid β-oxidation (FAO). Inherited VLCAD deficiency (VLCADD) predisposes to neonatal arrhythmias whose pathophysiology is still not understood. We hypothesized that VLCADD results in global disruption of cardiac complex lipid homeostasis, which may set conditions predisposing to arrhythmia. To test this, we assessed the cardiac lipidome and related molecular markers in seven-month-old VLCAD-/- mice, which mimic to some extent the human cardiac phenotype. Mice were sacrificed in the fed or fasted state after receiving for two weeks a chow or a high-fat diet (HFD), the latter condition being known to worsen symptoms in human VLCADD. Compared to their littermate counterparts, HFD/fasted VLCAD-/- mouse hearts displayed the following lipid alterations: (1) Lower LC, but higher VLC-acylcarnitines accumulation, (2) higher levels of arachidonic acid (AA) and lower docosahexaenoic acid (DHA) contents in glycerophospholipids (GPLs), as well as (3) corresponding changes in pro-arrhythmogenic AA-derived isoprostanes and thromboxane B2 (higher), and anti-arrythmogenic DHA-derived neuroprostanes (lower). These changes were associated with remodeling in the expression of gene or protein markers of (1) PL remodeling: higher calcium-dependent phospholipase A2 and lysophosphatidylcholine-acyltransferase 2, (2) calcium handling perturbations: higher SERCA2a and phospholamban, but lower RyR2, and (3) endoplasmic reticulum stress: higher CHOP and GRP78. Altogether, these results highlight global lipid dyshomeostasis beyond FAO in VLCAD-/- mouse hearts, which may set conditions predisposing the hearts to calcium mishandling and endoplasmic reticulum stress and thereby may contribute to the pathogenesis of arrhythmias in VLCADD in mice as well as in humans.","INSTITUTE":"Montreal Heart Institute","LAST_NAME":"Forest","FIRST_NAME":"Anik","ADDRESS":"5000 Bélanger Street","EMAIL":"metabolomique.icm@mhi-rc.org","PHONE":"5143763330 ext 2133"},

"STUDY":{"STUDY_TITLE":"Lipidomic analysis in very-long chain acyl-CoA dehydrogenase null mice","STUDY_SUMMARY":"Compared to their littermate counterparts, HFD/fasted VLCAD-/- mouse hearts displayed higher VLC-acylcarnitines accumulation, higher levels of arachidonic acid (AA) and lower docosahexaenoic acid (DHA) contents in glycerophospholipids (GPLs).","INSTITUTE":"Montreal Heart Institute","LAST_NAME":"Forest","FIRST_NAME":"Anik","ADDRESS":"5000 Bélanger Street","EMAIL":"metabolomique.icm@mhi-rc.org","PHONE":"5143763330 ext 2133"},

"SUBJECT":{"SUBJECT_TYPE":"Mammal","SUBJECT_SPECIES":"Mus musculus","TAXONOMY_ID":"10090","GENDER":"Male"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"5687",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5687 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5688",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5688 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5689",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5689 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5690",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5690 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5691",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5691 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5692",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5692 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5693",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5693 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5694",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5694 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5695",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5695 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5696",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5696 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5697",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5697 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5698",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5698 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5699",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5699 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5700",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5700 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5701",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5701 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5702",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5702 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5703",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5703 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5704",
"Factors":{"Diet":"Standard diet","Nutritional status":"Fed","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5704 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5959",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5959 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5961",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5961 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5962",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5962 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5963",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5963 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5964",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5964 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5965",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5965 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5966",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5966 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5967",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5967 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5968",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5968 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5969",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD +/+"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5969 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5970",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5970 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5971",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5971 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5972",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5972 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5973",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5973 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5974",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5974 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5975",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5975 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5976",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5976 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5977",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5977 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5978",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5978 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5979",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5979 VLC04C pos.mzML"}
},
{
"Subject ID":"-",
"Sample ID":"5980",
"Factors":{"Diet":"High Fat diet","Nutritional status":"Fasted","Genotype":"VLCAD -/-"},
"Additional sample data":{"RAW_FILE_NAME":"300719 5980 VLC04C pos.mzML"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Mice were sacrificed under anesthesia using ketamine (100mg/ml) and xylazine (20mg/ml). Immediately after mouse sacrifice, hearts were rapidly excised, snap-frozen with liquid nitrogen, and then stored at -80°C.","SAMPLE_TYPE":"Heart","STORAGE_CONDITIONS":"-80℃","COLLECTION_TUBE_TEMP":"-80"},

"TREATMENT":{"TREATMENT_SUMMARY":"VLCAD-/- males (129svJ X C57BL/6J genetic background) were crossed with C57Bl/6J females to generate heterozygous VLCAD+/- mice. Coupling of heterozygous mice then produced VLCAD-/- mice and control littermate counterparts (VLCAD+/+). All animals were genotyped as previously described. Mice were housed in a specific pathogen-free facility under a 12-h light/dark cycle at constant temperature and with access to water and food ad libitum. At 7-month of age, mice were fed for 2 weeks with either a chow diet (Harlan no. 2018; 3.1 kcal/g) or a high-fat diet (Harlan Teklab no. 3584; 5.4kcal/g) ad libitum. Mice were sacrificed in fed state for the CD group (CD/fed condition) or after fasting for 24 hours for the HFD group (HFD/fasted condition. Percent calories from carbohydrates, lipids and proteins were 58/18/24 for the CD and 26.6/58.4/15 for the HFD."},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Total lipids were extracted from 40mg of pulverized hearts under liquid nitrogen using in methyl tert-butyl ether (MTBE) and ethyl acetate after spiking with the following internal standards lysophosphatidylcholine (LPC) 13:0, phosphatidylcholine (PC) 19:0/19:0, PC14:0/14:0, phosphatidylserine (PS) 12:0/12:0, phosphatidylglycerol (PG) 15:0/15:0 and phosphatidylethanolamine (PE) 17:0/17:0). Supernatants were evaporated using a Speed Vacuum concentrator overnight, dissolved in methanol/chloroform (2:1) and aliquots (50 µL) were stored at -80ºC until use.","SAMPLEPREP_PROTOCOL_FILENAME":"Sample preparation protocol of untargeted lipidomic analysis","PROCESSING_STORAGE_CONDITIONS":"-80℃"},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Agilent 1290 Infinity","COLUMN_NAME":"Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,1.8um)","SOLVENT_A":"100% water; 0.2% formic acid; 10 mM ammonium formate","SOLVENT_B":"55% ethanol,/35% acetonitrile/10% MTBE, 55:35:10; 0.2% formic acid; 10 mM ammonium formate","FLOW_GRADIENT":"0–2 min, 50% B; 2–11 min, 50–85% B; 11–33 min, 85–94% B; 33–35 min, 94–98% B, 35–38 min; 98–99.5% B; 38–82 min, 98–99.5% B; 82–83 min, 99.5–50% B, plus an equilibration of 8 min","FLOW_RATE":"0.45 ml/min","COLUMN_TEMPERATURE":"40","METHODS_FILENAME":"LC-MS and data processing protocol of untargeted lipidomic analysis"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"Agilent 6530 QTOF","INSTRUMENT_TYPE":"QTOF","MS_TYPE":"ESI","ION_MODE":"POSITIVE","MS_COMMENTS":"MS data processing was achieved using the Mass Hunter Qualitative Analysis software package (version B.07) for peak picking and a bioinformatic script that we have developed and encoded in both Perl and R languages to enable optimal MS data alignment, filtering of presence, normalisation, batch effect correction, and missing data imputation. The resulting final dataset list reproducible high quality MS signals referred as features with their mass-over-charge (m/z), corrected signal intensity, and retention time (RT). Feature identity (ID) was as following: ionization mode:mass@RT.","MS_RESULTS_FILE":"ST002569_AN004233_Results.txt UNITS:Counts Has m/z:Yes Has RT:Yes RT units:Minutes"},

"MS_METABOLITE_DATA":{
"Units":"Counts",

"Data":[{"Metabolite":"CAR 14:1_A","5687":"3595114.641","5688":"2392021.839","5689":"1122086.887","5690":"1516658.072","5691":"3525954.687","5692":"904645.7864","5693":"596364.4229","5694":"1229107.127","5695":"1410888.662","5696":"287373.8696","5697":"267595.3583","5698":"430875.7969","5699":"329473.8115","5700":"245025.721","5701":"206525.4298","5702":"470747.4827","5703":"217097.8213","5704":"639508.2887","5959":"937177.6753","5961":"1532823.574","5962":"1208765.326","5963":"297264.1999","5964":"437005.2486","5965":"1867787.995","5966":"2736922.102","5967":"1151029.893","5968":"1219674.299","5969":"850600.8602","5970":"707386.416","5971":"444365.8066","5972":"1023798.241","5973":"840523.3505","5974":"184646.3771","5975":"148065.5717","5976":"396788.9689","5977":"261513.5471","5978":"421853.9888","5979":"285702.0158","5980":"264306.1865"},{"Metabolite":"CAR 14:0","5687":"8545630.867","5688":"15418433.59","5689":"4800403.473","5690":"6318481.226","5691":"14602010.08","5692":"6919084.627","5693":"5771146.244","5694":"4881757.241","5695":"7231917.539","5696":"2140681.89","5697":"2734810.174","5698":"2485221.32","5699":"2895866.04","5700":"2096221.511","5701":"1341311.682","5702":"2943362.439","5703":"1447616.878","5704":"2829533.229","5959":"4223290.024","5961":"11017235.43","5962":"6139243.99","5963":"1695732.398","5964":"1605279.815","5965":"12559629.51","5966":"12061304.01","5967":"6751241.557","5968":"3788939.49","5969":"2868443.729","5970":"4722733.27","5971":"5256301.48","5972":"8281283.528","5973":"6657337.839","5974":"2218256.261","5975":"1600764.077","5976":"2204552.669","5977":"2275025.311","5978":"3587157.871","5979":"2346409.383","5980":"2259375.539"},{"Metabolite":"CAR 14:1_B","5687":"587805.3674","5688":"2898218.135","5689":"445761.6229","5690":"656542.8911","5691":"2205162.126","5692":"861228.6","5693":"728198.7584","5694":"522092.8554","5695":"618046.6531","5696":"229008.5094","5697":"267823.156","5698":"62238.05922","5699":"260273.3571","5700":"213509.6301","5701":"77284.09437","5702":"276507.2381","5703":"154230.151","5704":"301001.6502","5959":"351795.4002","5961":"757701.4776","5962":"443052.7856","5963":"120323.772","5964":"103903.5596","5965":"1244210.861","5966":"1429339.584","5967":"630960.294","5968":"348159.2372","5969":"219727.3875","5970":"313223.9351","5971":"246304.3155","5972":"722005.3823","5973":"622335.9384","5974":"112250.4007","5975":"79064.6707","5976":"244657.1221","5977":"139663.013","5978":"370793.4206","5979":"114751.1514","5980":"87210.43422"},{"Metabolite":"CAR 14:2","5687":"1034988.222","5688":"1043428.879","5689":"554115.2803","5690":"1068086.6","5691":"1618573.453","5692":"452580.1334","5693":"407886.473","5694":"657718.5278","5695":"875867.646","5696":"248905.8778","5697":"203678.9499","5698":"313216.0637","5699":"258225.7725","5700":"234835.7863","5701":"132911.7614","5702":"306909.3824","5703":"149338.5744","5704":"340992.3526","5959":"260194.5695","5961":"386537.9182","5962":"533063.6563","5963":"156016.2261","5964":"411013.9605","5965":"336777.3373","5966":"489978.4082","5967":"486426.5204","5968":"483238.4431","5969":"311083.0755","5970":"260121.1861","5971":"128804.1975","5972":"325963.2926","5973":"358217.3594","5974":"133997.2202","5975":"95018.74742","5976":"160612.6599","5977":"181735.4908","5978":"233362.093","5979":"152083.6135","5980":"123916.8042"},{"Metabolite":"CAR 16:1","5687":"5917918.478","5688":"17207618.78","5689":"6109688.197","5690":"5702318.269","5691":"18141288.49","5692":"7984543.737","5693":"6466013.798","5694":"5120537.611","5695":"9436741.031","5696":"2710130.818","5697":"3223423.409","5698":"3793852.533","5699":"3272099.186","5700":"2510159.784","5701":"1568081.796","5702":"3954394.118","5703":"1807132.608","5704":"5969721.229","5959":"4223029.049","5961":"14614206.42","5962":"6233570.276","5963":"1611445.055","5964":"1937477.208","5965":"15235978.72","5966":"19055940.24","5967":"8802940.691","5968":"4124377.343","5969":"2976429.115","5970":"6487258.267","5971":"5416084.195","5972":"11810325.23","5973":"7947922.811","5974":"2344430.553","5975":"2530023.555","5976":"4324251.816","5977":"3508170.725","5978":"5073275.591","5979":"4311286.979","5980":"3530491.23"},{"Metabolite":"CAR 18:1(OH)","5687":"1313001.206","5688":"5044388.341","5689":"587000.4065","5690":"781171.6097","5691":"5148143.034","5692":"4296346.815","5693":"3613851.125","5694":"2338813.892","5695":"3170959.389","5696":"535199.2618","5697":"307580.7607","5698":"484763.5621","5699":"377959.7577","5700":"180459.5688","5701":"302386.3665","5702":"478598.5909","5703":"300555.6741","5704":"518382.3963","5959":"684864.8714","5961":"1811287.136","5962":"804577.8354","5963":"206213.8647","5964":"318263.4011","5965":"1644531.777","5966":"4653279.287","5967":"863217.9428","5968":"835379.3055","5969":"643106.4054","5970":"1180233.724","5971":"1306140.487","5972":"1667279.3","5973":"1105806.681","5974":"214826.3407","5975":"233240.072","5976":"534992.6368","5977":"310591.8795","5978":"736818.4413","5979":"560860.9479","5980":"497426.2214"},{"Metabolite":"CAR 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}

}