{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:22:21Z","timestamp":1790652141778,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["RO1EY030088"],"award-info":[{"award-number":["RO1EY030088"]}]},{"DOI":"10.13039\/501100014069","name":"Champalimaud Foundation","doi-asserted-by":"publisher","award":["award"],"award-info":[{"award-number":["award"]}],"id":[{"id":"10.13039\/501100014069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["department grant"],"award-info":[{"award-number":["department grant"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government of Portugal","award":["HMSP-ICJ\/006\/2013"],"award-info":[{"award-number":["HMSP-ICJ\/006\/2013"]}]},{"DOI":"10.13039\/100007745","name":"Massachusetts Lions Eye Research Fund","doi-asserted-by":"publisher","award":["Husain"],"award-info":[{"award-number":["Husain"]}],"id":[{"id":"10.13039\/100007745","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Plasma metabolomic profiles have been shown to be associated with age-related macular degeneration (AMD) and its severity stages. However, all studies performed to date have been cross-sectional and have not assessed progression of AMD. This prospective, longitudinal, pilot study analyzes, for the first time, the association between plasma metabolomic profiles and progression of AMD over a 3-year period. At baseline and 3 years later, subjects with AMD (n = 108 eyes) and controls (n = 45 eyes) were imaged with color fundus photos for AMD staging and tested for retinal function with dark adaptation (DA). Fasting plasma samples were also collected for metabolomic profiling. AMD progression was considered present if AMD stage at 3 years was more advanced than at baseline (n = 26 eyes, 17%). Results showed that, of the metabolites measured at baseline, eight were associated with 3-year AMD progression (p &lt; 0.01) and 19 (p &lt; 0.01) with changes in DA. Additionally, changes in the levels (i.e., between 3 years and baseline) of 6 and 17 metabolites demonstrated significant associations (p &lt; 0.01) with AMD progression and DA, respectively. In conclusion, plasma metabolomic profiles are associated with clinical and functional progression of AMD at 3 years. These findings contribute to our understanding of mechanisms of AMD progression and the identification of potential therapeutics for this blinding disease.<\/jats:p>","DOI":"10.3390\/metabo12010032","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:14:02Z","timestamp":1641518042000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Plasma Metabolomic Profiles Associated with Three-Year Progression of Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8136-4724","authenticated-orcid":false,"given":"Ines","family":"Lains","sequence":"first","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Mendez","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Nigalye","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raviv","family":"Katz","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian Paraskevi","family":"Douglas","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-1822","authenticated-orcid":false,"given":"Rachel S.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0109-9738","authenticated-orcid":false,"given":"John B.","family":"Miller","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrios G.","family":"Vavvas","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Liang","sequence":"additional","affiliation":[{"name":"Systems Genetics and Genomics Unit, Channing Division of Network Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lasky-Su","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan W.","family":"Miller","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deeba","family":"Husain","sequence":"additional","affiliation":[{"name":"Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ung, C., Lains, I., Miller, J.W., and Kim, I.K. (2021). Current Management of Age-Related Macular Degeneration. Advances in Experimental Medicine and Biology, Springer.","DOI":"10.1007\/978-3-030-66014-7_12"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11262-1","article-title":"A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration","volume":"10","author":"Handa","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1001\/jamaophthalmol.2013.2578","article-title":"Validation of a Prediction Algorithm for Progression to Advanced Macular Degeneration Subtypes","volume":"131","author":"Seddon","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/opo.12675","article-title":"Risk factors for progression of age-related macular degeneration","volume":"40","author":"Heesterbeek","year":"2020","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.preteyeres.2018.11.002","article-title":"Metabolomics in the study of retinal health and disease","volume":"69","author":"Gantner","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature11708","article-title":"Metabolic phenotyping in clinical and surgical environments","volume":"491","author":"Nicholson","year":"2012","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lains, I., Duarte, D., Barros, A., Martins, A.S., Gil, J., Miller, J.B., Marques, M., Mesquita, T., Kim, I., and Cachulo, M.L. (2017). Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177749"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ophtha.2017.08.008","article-title":"Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers","volume":"125","author":"Lains","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"La\u00edns, I., Chung, W., Kelly, R.S., Gil, J., Marques, M., Barreto, P., Murta, J.N., Kim, I.K., Vavvas, D.G., and Miller, J.B. (2019). Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts. Metabolites, 9.","DOI":"10.3390\/metabo9070127"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.ophtha.2020.06.020","article-title":"Integrating Metabolomics, Genomics, and Disease Pathways in Age-Related Macular Degeneration: The EYE-RISK Consortium","volume":"127","author":"Acar","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ophtha.2015.09.041","article-title":"Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration","volume":"123","author":"Owsley","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/j.ophtha.2017.03.061","article-title":"Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration","volume":"124","author":"Lains","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI)","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108219","DOI":"10.1016\/j.exer.2020.108219","article-title":"IL-6-induced acetylation of E2F1 aggravates oxidative damage of retinal pigment epithelial cell line","volume":"200","author":"Gong","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.preteyeres.2017.03.002","article-title":"The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD","volume":"60","author":"Datta","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.preteyeres.2008.09.001","article-title":"Mitochondrial DNA damage and its potential role in retinal degeneration","volume":"27","author":"Jarrett","year":"2008","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s10522-013-9463-2","article-title":"Role of antioxidant enzymes and small molecular weight antioxidants in the pathogenesis of age-related macular degeneration (AMD)","volume":"14","author":"Tokarz","year":"2013","journal-title":"Biogerontology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.tem.2011.08.002","article-title":"Neuroprotective actions of estradiol revisited","volume":"22","author":"Azcoitia","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3389\/fendo.2018.00066","article-title":"Gonadal Hormones and Retinal Disorders: A Review","volume":"9","author":"Nuzzi","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.steroids.2015.08.002","article-title":"The estrogenic retina: The potential contribution to healthy aging and age-related neurodegenerative diseases of the retina","volume":"103","author":"Cascio","year":"2015","journal-title":"Steroids"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2012.10.002","article-title":"PI3K\/Akt and NF-\u03baB activation following intravitreal administration of 17\u03b2-estradiol: Neuroprotection of the rat retina from light-induced apoptosis","volume":"228","author":"Mo","year":"2013","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3109\/02713683.2014.925933","article-title":"Estrogen signalling in the pathogenesis of age-related macular degeneration","volume":"40","author":"Kaarniranta","year":"2015","journal-title":"Curr. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3109\/02713683.2014.906625","article-title":"Gender Differences in Ocular Blood Flow","volume":"40","author":"Schmidl","year":"2015","journal-title":"Curr. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1001\/archopht.124.7.988","article-title":"Hormone Therapy and Age-Related Macular Degeneration: The women\u2019s health initiative sight exam study","volume":"124","author":"Haan","year":"2006","journal-title":"Arch. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chakravarthy, U., Wong, T.Y., Fletcher, A., Piault, E., Evans, C., Zlateva, G., Buggage, R., Pleil, A., and Mitchell, P. (2010). Clinical risk factors for age-related macular degeneration: A systematic review and meta-analysis. BMC Ophthalmol., 10.","DOI":"10.1186\/1471-2415-10-31"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1167\/iovs.13-13745","article-title":"Diagnostic Sensitivity and Specificity of Dark Adaptometry for Detection of Age-Related Macular Degeneration","volume":"55","author":"Jackson","year":"2014","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.ophtha.2018.09.039","article-title":"Longitudinal Study of Dark Adaptation as a Functional Outcome Measure for Age-Related Macular Degeneration","volume":"126","author":"Chen","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1097\/IAE.0000000000003152","article-title":"Baseline Predictors Associated with Three-Year Changes in Dark Adaptation in Age-related Macular Degeneration","volume":"41","author":"Lains","year":"2021","journal-title":"Retina"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mendez, K.M., Kim, J., La\u00edns, I., Nigalye, A., Katz, R., Pundik, S., Kim, I., Liang, L., Vavvas, D., and Miller, J. (2021). Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration. Metabolites, 11.","DOI":"10.3390\/metabo11030183"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kersten, E., Dammeier, S., Ajana, S., Groenewoud, J.M.M., Codrea, M., Klose, F., Lechanteur, Y.T., Fauser, S., Ueffing, M., and Delcourt, C. (2019). Metabolomics in serum of patients with non-advanced age-related macular degeneration reveals aberrations in the glutamine pathway. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218457"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cruzat, V., Rogero, M.M., Keane, K.N., Curi, R., and Newsholme, P. (2018). Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients, 10.","DOI":"10.20944\/preprints201809.0459.v1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/jcp.20339","article-title":"Molecular mechanisms of glutamine action","volume":"204","author":"Curi","year":"2005","journal-title":"J. Cell. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"528940","DOI":"10.1155\/2013\/528940","article-title":"Abnormalities in Glutamate Metabolism and Excitotoxicity in the Retinal Diseases","volume":"2013","author":"Ishikawa","year":"2013","journal-title":"Scientifica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1126\/science.7901908","article-title":"Oxidative stress, glutamate, and neurodegenerative disorders","volume":"262","author":"Coyle","year":"1993","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1167\/iovs.61.3.49","article-title":"Glucose Metabolic Characterization of Human Aqueous Humor in Relation to Wet Age-Related Macular Degeneration","volume":"61","author":"Han","year":"2020","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pundlik, S., Nigalye, A., La\u00edns, I., Mendez, K.M., Katz, R., Kim, J., Kim, I.K., Miller, J.B., Vavvas, D., and Miller, J.W. (2021). Area under the dark adaptation curve as a reliable alternate measure of dark adaptation response. Br. J. Ophthalmol., 318806.","DOI":"10.1136\/bjophthalmol-2021-318806"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/BF01062108","article-title":"Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level-time curve","volume":"6","author":"Chiou","year":"1978","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"ref_39","unstructured":"Oliphant, T.E. (2006). A Guide to NumPy, Trelgol Publishing."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1167\/tvst.6.2.3","article-title":"Automated Brightness and Contrast Adjustment of Color Fundus Photographs for the Grading of Age-Related Macular Degeneration","volume":"6","author":"Tsikata","year":"2017","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4548","DOI":"10.1167\/iovs.13-11804","article-title":"Methods and Reproducibility of Grading Optimized Digital Color Fundus Photographs in the Age-Related Eye Disease Study 2 (AREDS2 Report Number 2)","volume":"54","author":"Danis","year":"2013","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"The Age-Related Eye Disease Study Research Group (2001). The Age-Related Eye Disease Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: The Age-Related Eye Disease Study Report Number 6. Am. J. Ophthalmol., 132, 668\u2013681.","DOI":"10.1016\/S0002-9394(01)01218-1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4236\/abb.2018.98022","article-title":"A Comparison of Various Normalization Methods for LC\/MS Metabolomics Data","volume":"09","author":"Wulff","year":"2018","journal-title":"Adv. Biosci. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1158\/0008-5472.CAN-19-2567","article-title":"A Prospective Analysis of Circulating Plasma Metabolites Associated with Ovarian Cancer Risk","volume":"80","author":"Zeleznik","year":"2020","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"van den Berg, R.A., Hoefsloot, H.C.J., Westerhuis, J.A., Smilde, A.K., and van der Werf, M.J. (2006). Centering, scaling, and transformations: Improving the biological information content of metabolomics data. BMC Genom., 7.","DOI":"10.1186\/1471-2164-7-142"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/(SICI)1097-0258(19980615)17:11<1261::AID-SIM846>3.0.CO;2-Z","article-title":"Extending the simple linear regression model to account for correlated responses: An introduction to generalized estimating equations and multi-level mixed modelling","volume":"17","author":"Burton","year":"1998","journal-title":"Stat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s00439-011-1118-2","article-title":"Evaluating the effective numbers of independent tests and significant p-value thresholds in commercial genotyping arrays and public imputation reference datasets","volume":"131","author":"Li","year":"2011","journal-title":"Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1086\/383251","article-title":"A Simple Correction for Multiple Testing for Single-Nucleotide Polymorphisms in Linkage Disequilibrium with Each Other","volume":"74","author":"Nyholt","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fitzmaurice, G.M., Laird, N.M., and Ware, J.H. (2011). Linear Mixed Effect Models. Applied Longitudinal Analysis, John Wiley and Sons Inc.. [2nd ed.].","DOI":"10.1002\/9781119513469"},{"key":"ref_50","first-page":"57","article-title":"Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis","volume":"9","author":"Chong","year":"2019","journal-title":"Curr. Protoc. Bioinform."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/1\/32\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:35:54Z","timestamp":1760362554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/1\/32"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["metabo12010032"],"URL":"https:\/\/doi.org\/10.3390\/metabo12010032","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,1]]}}}