{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST001098","ANALYSIS_ID":"AN001786","VERSION":"1","CREATED_ON":"November 25, 2018, 11:32 am"},

"PROJECT":{"PROJECT_TITLE":"Metabolomics of Metabolic Risk in Patients Taking Atypical Antipsychotics","PROJECT_TYPE":"NMR and GC fatty acid analysis","PROJECT_SUMMARY":"STUDY OBJECTIVE Patients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomics variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk. DESIGN Metabolomics analysis. PARTICIPANTS Ninety-four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin. Twenty age- and sex-matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index range of the patients with schizophrenia to account for metabolite concentration differences attributable to body mass index. MEASUREMENTS AND MAIN RESULTS Existing serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance (NMR) and gas chromatography (GC) methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 (interquartile range 41.0-52.0) years. Using a false discovery rate threshold of <25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one-carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward having higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2). CONCLUSION These results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle-aged adult patients with schizophrenia by fasting insulin concentration. This article is protected by copyright. All rights reserved. As published in Pharmacotherapy. 2018 Jun;38(6):638-650.","INSTITUTE":"University of Michigan","LAST_NAME":"Stringer","FIRST_NAME":"Kathleen","ADDRESS":"428 Church St","EMAIL":"stringek@umich.edu","PHONE":"734-647-4775","FUNDING_SOURCE":"Funding for this work was supported in part by grants from the following centers: the University of Michigan Claude D. Pepper Older Americans Independence Center (National Institute on Aging [NIA] grantAGA024824); the University of Michigan’s Nutrition Obesity Research Center (grant DK089503) and Weight Management Program, and the Michigan Regional Comprehensive Metabolomics Resource Core (grant DK097153),the Michigan Center for Diabetes Translational Research(grant P30DK092926), and the A. Alfred Taubman Medical Institute and the Robert C. and Veronica Atkins Foundation. This work was also supported in part by a metabolomics supplement to a grant from the National Institute of Mental Health (NIMH; grant MH082784; Dr. Ellingrod). Dr. Stringer’s effort is supported in part by a grant from the National Institute of General Medical Sciences (NIGMS; grant GM111400). Dr. Rothberg’s effort is supported in part by DK089503.","PUBLICATIONS":"Pharmacotherapy. 2018 Jun;38(6):638-650"},

"STUDY":{"STUDY_TITLE":"Metabolomics of Metabolic Risk in Patients Taking Atypical Antipsychotics (part II)","STUDY_SUMMARY":"STUDY OBJECTIVE Patients with schizophrenia are known to have higher rates of metabolic disease than the general population. Contributing factors likely include lifestyle and atypical antipsychotic (AAP) use, but the underlying mechanisms are unknown. The objective of this study was to identify metabolomics variability in adult patients with schizophrenia who were taking AAPs and grouped by fasting insulin concentration, our surrogate marker for metabolic risk. DESIGN Metabolomics analysis. PARTICIPANTS Ninety-four adult patients with schizophrenia who were taking an AAP for at least 6 months, with no changes in their antipsychotic regimen for the previous 8 weeks, and who did not require treatment with insulin. Twenty age- and sex-matched nonobese (10 subjects) and obese (10 subjects) controls without cardiovascular disease or mental health diagnoses were used to match the body mass index range of the patients with schizophrenia to account for metabolite concentration differences attributable to body mass index. MEASUREMENTS AND MAIN RESULTS Existing serum samples were used to identify aqueous metabolites (to differentiate fasting insulin concentration quartiles) and fatty acids with quantitative nuclear magnetic resonance (NMR) and gas chromatography (GC) methods, respectively. To exclude metabolites from our pathway mapping analysis that were due to variability in weight, we also subjected serum samples from the nonobese and obese controls to the same analyses. Patients with schizophrenia had a median age of 47.0 (interquartile range 41.0-52.0) years. Using a false discovery rate threshold of <25%, 10 metabolites, not attributable to weight, differentiated insulin concentration quartiles in patients with schizophrenia and identified variability in one-carbon metabolism between groups. Patients with higher fasting insulin concentrations (quartiles 3 and 4) also trended toward having higher levels of saturated fatty acids compared with patients with lower fasting insulin concentrations (quartiles 1 and 2). CONCLUSION These results illustrate the utility of metabolomics to identify pathways underlying variable fasting insulin concentration in patients with schizophrenia. Importantly, no significant difference in AAP exposure was observed among groups, suggesting that current antipsychotic use may not be a primary factor that differentiates middle-aged adult patients with schizophrenia by fasting insulin concentration. This article is protected by copyright. All rights reserved. As published in Pharmacotherapy. 2018 Jun;38(6):638-650.","INSTITUTE":"University of Michigan","LAST_NAME":"Stringer","FIRST_NAME":"Kathleen","ADDRESS":"428 Church St","EMAIL":"kmwiese@umich.edu","PHONE":"7346474775"},

"SUBJECT":{"SUBJECT_TYPE":"Human","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606","AGE_OR_AGE_RANGE":"30-60 years old","WEIGHT_OR_WEIGHT_RANGE":"52.3-176.6 kg","GENDER":"Male and female","HUMAN_MEDICATIONS":"To be included in the study all participants had to be taking an atypical (second-generation) antipsychotic","HUMAN_INCLUSION_CRITERIA":"DSM IV diagnosis of a schizophrenia spectrum diagnosis who had been taking an atypical antipsychotic for at least 6 months, with no changes in antipsychotic regimen for 8 weeks preceding the baseline visit. Twenty age and sex matched obese and nonobese participants without mental health diagnoses were included to match the BMI range of the patients with schizophrenia as BMI controls.","HUMAN_EXCLUSION_CRITERIA":"Current use of insulin, diagnosis of diabetes mellitus type 2 prior to antipsychotic exposure, active substance abuse diagnosis"},
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"Sample ID":"Q005",
"Factors":{"Treatment":"Obese control"},
"Additional sample data":{"BMI":"35.9","Fasting Insulin (mU/mL)":"19.1"}
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{
"Subject ID":"-",
"Sample ID":"Q025",
"Factors":{"Treatment":"Obese control"},
"Additional sample data":{"BMI":"32.0","Fasting Insulin (mU/mL)":"11.0"}
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{
"Subject ID":"-",
"Sample ID":"Q077",
"Factors":{"Treatment":"Obese control"},
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"Factors":{"Treatment":"Obese control"},
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"Factors":{"Treatment":"Obese control"},
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"Factors":{"Treatment":"Obese control"},
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"Factors":{"Treatment":"Obese control"},
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"Factors":{"Treatment":"Obese control"},
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"Factors":{"Treatment":"Obese control"},
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{
"Subject ID":"-",
"Sample ID":"CCMB_04",
"Factors":{"Treatment":"Non-obese control"},
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{
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"Factors":{"Treatment":"Non-obese control"},
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"Factors":{"Treatment":"Non-obese control"},
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{
"Subject ID":"-",
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"Factors":{"Treatment":"Non-obese control"},
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V019",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"30.3","Fasting Insulin (mU/mL)":"10.1"}
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"Subject ID":"-",
"Sample ID":"V023",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V029",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"33.9","Fasting Insulin (mU/mL)":"20.7"}
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"Subject ID":"-",
"Sample ID":"V032",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"40.1","Fasting Insulin (mU/mL)":"47.4"}
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"Subject ID":"-",
"Sample ID":"V033",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"38.7","Fasting Insulin (mU/mL)":"20.6"}
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"Subject ID":"-",
"Sample ID":"V034",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V035",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V037",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Sample ID":"V041",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V045",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V046",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V047",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V055",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
"Sample ID":"V056",
"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"27.7","Fasting Insulin (mU/mL)":"7.7"}
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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{
"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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"Subject ID":"-",
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"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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{
"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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{
"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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{
"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
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{
"Subject ID":"-",
"Sample ID":"V198",
"Factors":{"Treatment":"Schizophrenia dx"},
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{
"Subject ID":"-",
"Sample ID":"V202",
"Factors":{"Treatment":"Schizophrenia dx"},
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{
"Subject ID":"-",
"Sample ID":"V205",
"Factors":{"Treatment":"Schizophrenia dx"},
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{
"Subject ID":"-",
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"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"30.3","Fasting Insulin (mU/mL)":"13.9"}
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{
"Subject ID":"-",
"Sample ID":"V212",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"31.2","Fasting Insulin (mU/mL)":"16.5"}
},
{
"Subject ID":"-",
"Sample ID":"V214",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"26.2","Fasting Insulin (mU/mL)":"9.2"}
},
{
"Subject ID":"-",
"Sample ID":"V215",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"25.9","Fasting Insulin (mU/mL)":"9.3"}
},
{
"Subject ID":"-",
"Sample ID":"V216",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"27.1","Fasting Insulin (mU/mL)":"9.2"}
},
{
"Subject ID":"-",
"Sample ID":"V221",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"33.5","Fasting Insulin (mU/mL)":"23.4"}
},
{
"Subject ID":"-",
"Sample ID":"V223",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"23.6","Fasting Insulin (mU/mL)":"9.8"}
},
{
"Subject ID":"-",
"Sample ID":"V224",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"29.8","Fasting Insulin (mU/mL)":"15.8"}
},
{
"Subject ID":"-",
"Sample ID":"V225",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"20.0","Fasting Insulin (mU/mL)":"7.0"}
},
{
"Subject ID":"-",
"Sample ID":"V228",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"20.9","Fasting Insulin (mU/mL)":"10.0"}
},
{
"Subject ID":"-",
"Sample ID":"V232",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"40.1","Fasting Insulin (mU/mL)":"39.9"}
},
{
"Subject ID":"-",
"Sample ID":"V241",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"34.9","Fasting Insulin (mU/mL)":"35.9"}
},
{
"Subject ID":"-",
"Sample ID":"V249",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"51.6","Fasting Insulin (mU/mL)":"15.1"}
},
{
"Subject ID":"-",
"Sample ID":"V250",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"27.6","Fasting Insulin (mU/mL)":"16.1"}
},
{
"Subject ID":"-",
"Sample ID":"V252",
"Factors":{"Treatment":"Schizophrenia dx"},
"Additional sample data":{"BMI":"27.3","Fasting Insulin (mU/mL)":"22.7"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Fasting blood samples were collected via venipuncture into an additive-free vial and allowed to coagulate at room temperature for 30 minutes. They were then centrifuged for 15 minutes at 2500 rcf to obtain serum. Samples were frozen and -80C, thawed once for sample processing related to the parent study, then kept at -80C until processing for NMR and GC assays","SAMPLE_TYPE":"Blood (serum)","STORAGE_CONDITIONS":"-80℃","COLLECTION_VIALS":"Additive-free vacuatiner"},

"TREATMENT":{"TREATMENT_SUMMARY":"N/A (observational study)"},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Serum samples were subjected to a 1:1 methanol:choloroform extraction, then dried with a speedvac. Prior to fatty acid analysis, the lipid fractions were resuspended and purified by TLC prior to GC analysis. This is described in more detail in the attached document, with sample prep summaries for the NMR component of this study included as well.","SAMPLEPREP_PROTOCOL_ID":"EllingrodSamplePrepProtocol","EXTRACTION_METHOD":"1:1 methanol:chloroform","SAMPLE_RESUSPENSION":"hexane","SAMPLE_SPIKING":"C17:0 methyl ester"},

"CHROMATOGRAPHY":{"CHROMATOGRAPHY_TYPE":"GC","INSTRUMENT_NAME":"Agilent 6890N","COLUMN_NAME":"Unspecified"},

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

"MS":{"MS_COMMENTS":"-","INSTRUMENT_NAME":"-","INSTRUMENT_TYPE":"-","MS_TYPE":"Other","ION_MODE":"UNSPECIFIED"},

"MS_METABOLITE_DATA":{
"Units":"nmol",

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}