{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:32:52Z","timestamp":1792290772832,"version":"4.4.0"},"reference-count":59,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University in Lublin","doi-asserted-by":"publisher","award":["DS394"],"award-info":[{"award-number":["DS394"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic sclerosis (SSc), a predominantly female-affected systemic autoimmune disease, requires tailored treatment strategies contingent on organ involvement and symptom severity. Given SSc\u2019s inflammatory nature, the involvement of the kynurenine pathway (KP) in its pathophysiology is underexplored. Our study aimed to investigate sex-related differences in KP activation among SSc patients and assess the impact of angiotensin-converting enzyme (ACE) inhibitors and estimated glomerular filtration rate (eGFR) on KP metabolite concentrations. We enrolled 48 SSc patients and 53 healthy controls, quantifying KP metabolites (tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA)) in serum via high-performance liquid chromatography. Separate multivariate analyses of covariance (MANCOVAs) for women and men were performed to ascertain mean differences between patients and healthy controls while correcting for age. For our secondary objective, we conducted a MANCOVA to explore disparities in ACE inhibitor users and non-users among patients, with BMI correction. Our findings revealed decreased TRP concentrations but increased KYNA\/TRP ratio and KYN\/TRP ratio in both male and female SSc patients compared to their respective controls. Unlike women, SSc males exhibited higher KYN concentrations and decreased KYNA\/KYN ratio relative to their controls. Additionally, SSc patients using ACE inhibitors had higher serum KYNA levels than non-users. Notably, we established a significant correlation between eGFR and KYNA in SSc patients. These results indicate differential KP activation in male and female SSc patients, with males demonstrating heightened KP activation. While ACE inhibitors may influence the KP in SSc patients, further research is necessary to comprehensively understand their impact on symptoms and prognosis in the context of these KP alterations.<\/jats:p>","DOI":"10.3390\/ijms25073842","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:42:30Z","timestamp":1711892550000},"page":"3842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Different Kynurenine Pathway Dysregulation in Systemic Sclerosis in Men and Women"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2400-591X","authenticated-orcid":false,"given":"Monika","family":"Turska-Koz\u0142owska","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, The John Paul II Catholic University of Lublin, Konstantynow 1H, 20-708 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4119-971X","authenticated-orcid":false,"given":"Bruno","family":"Pedraz-Petrozzi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, J5, 68159 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7993-1654","authenticated-orcid":false,"given":"Piotr","family":"Paluszkiewicz","sequence":"additional","affiliation":[{"name":"Department of General, Oncological and Metabolic Surgery, Institute of Hematology and Transfusion Medicine, Indiry Gandhi 14, 02-778 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4476-4080","authenticated-orcid":false,"given":"Jolanta","family":"Parada-Turska","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1093\/rheumatology\/keab190","article-title":"Incidence and Prevalence of Systemic Sclerosis Globally: A Comprehensive Systematic Review and Meta-Analysis","volume":"60","author":"Bairkdar","year":"2021","journal-title":"Rheumatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15002","DOI":"10.1038\/nrdp.2015.2","article-title":"Systemic Sclerosis","volume":"1","author":"Allanore","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1136\/annrheumdis-2013-204424","article-title":"2013 Classification Criteria for Systemic Sclerosis: An American College of Rheumatology\/European League against Rheumatism Collaborative Initiative","volume":"72","author":"Khanna","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41380-019-0414-4","article-title":"The Kynurenine Pathway: A Finger in Every Pie","volume":"25","author":"Savitz","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"L617","DOI":"10.1152\/ajplung.00177.2023","article-title":"Kynurenine Pathway Metabolism Evolves with Development of Preclinical and Scleroderma-Associated Pulmonary Arterial Hypertension","volume":"325","author":"Simpson","year":"2023","journal-title":"Am. J. Physiol.\u2014Lung Cell Mol. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Morales-Gonz\u00e1lez, V., Galeano-S\u00e1nchez, D., Covaleda-Vargas, J.E., Rodriguez, Y., Monsalve, D.M., Pardo-Rodriguez, D., Cala, M.P., Acosta-Ampudia, Y., and Ram\u00edrez-Santana, C. (2023). Metabolic Fingerprinting of Systemic Sclerosis: A Systematic Review. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1215039"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"B\u00f6gl, T., Mlynek, F., Himmelsbach, M., Sepp, N., Buchberger, W., and Geroldinger-Simi\u0107, M. (2022). Plasma Metabolomic Profiling Reveals Four Possibly Disrupted Mechanisms in Systemic Sclerosis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030607"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1093\/brain\/awp074","article-title":"Kynurenine Pathway Inhibition Reduces Central Nervous System Inflammation in a Model of Human African Trypanosomiasis","volume":"132","author":"Rodgers","year":"2009","journal-title":"Brain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0049-0172(73)90022-X","article-title":"Tryptophan Metabolism in Man (with Special Reference to Rheumatoid Arthritis and Scleroderma)","volume":"2","author":"Houpt","year":"1973","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/art.1780070606","article-title":"Tryptophan Metabolism in Rheumatic Disease","volume":"7","author":"Pinals","year":"1964","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/BF00595531","article-title":"Tryptophan to Niacin Pathway in Scleroderma and in Dermatomyositis","volume":"246","author":"Binazzi","year":"1973","journal-title":"Arch. Dermatol. Forsch."},{"key":"ref_12","first-page":"134","article-title":"Tryptophan Metabolism \u201cvia\u201d Nicotimic Acid in Patients with Scleroderma","volume":"30","author":"Muggeo","year":"1976","journal-title":"Acta Vitaminol. Enzym."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Poormasjedi-Meibod, M.-S., Hartwell, R., Kilani, R.T., and Ghahary, A. (2014). Anti-Scarring Properties of Different Tryptophan Derivatives. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091955"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/jid.2013.303","article-title":"Kynurenine Increases Matrix Metalloproteinase-1 and -3 Expression in Cultured Dermal Fibroblasts and Improves Scarring in Vivo","volume":"134","author":"Li","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"964","DOI":"10.36849\/JDD.6197","article-title":"A Randomized, Double-Blind, Active- and Placebo-Controlled Trial Evaluating a Novel Topical Treatment for Keloid Scars","volume":"20","author":"Nestor","year":"2021","journal-title":"J. Drugs Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.xphs.2018.01.023","article-title":"The Safety and Tolerability of Topically Delivered Kynurenic Acid in Humans. A Phase 1 Randomized Double-Blind Clinical Trial","volume":"107","author":"Papp","year":"2018","journal-title":"J. Pharm. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105309","DOI":"10.1016\/j.jbspin.2021.105309","article-title":"Serotonin and Systemic Sclerosis. An Emerging Player in Pathogenesis","volume":"89","author":"Sagonas","year":"2022","journal-title":"Jt. Bone Spine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"204","DOI":"10.5301\/jsrd.5000209","article-title":"Gender Differences in Systemic Sclerosis: Relationship to Clinical Features, Serologic Status and Outcomes","volume":"1","author":"Peoples","year":"2016","journal-title":"J. Scleroderma Relat. Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102494","DOI":"10.1016\/j.autrev.2020.102494","article-title":"Gender-Related Differences in Systemic Sclerosis","volume":"19","author":"Hughes","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e002971","DOI":"10.1136\/rmdopen-2022-002971","article-title":"Step Forward in Early Recognition of Systemic Sclerosis: Data from the Leiden CCISS Cohort","volume":"9","author":"Liem","year":"2023","journal-title":"RMD Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3899\/jrheum.210794","article-title":"Sex-Related Differences in Systemic Sclerosis: A Multicenter Cross-Sectional Study From the National Registry of the Italian Society for Rheumatology","volume":"49","author":"Giuggioli","year":"2022","journal-title":"J. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S0140-6736(22)01692-0","article-title":"Systemic Sclerosis","volume":"401","author":"Volkmann","year":"2023","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"530","DOI":"10.12968\/hmed.2019.80.9.530","article-title":"Systemic Sclerosis","volume":"80","author":"Hughes","year":"2019","journal-title":"Br. J. Hosp. Med."},{"key":"ref_24","first-page":"269","article-title":"Decreased Serum Tryptophan and Elevated Neopterin Levels in Systemic Sclerosis","volume":"13","author":"Szerafin","year":"1995","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bengtsson, A.A., Trygg, J., Wuttge, D.M., Sturfelt, G., Theander, E., Donten, M., Moritz, T., Sennbro, C.-J., Torell, F., and Lood, C. (2016). Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sj\u00f6gren\u2019s Syndrome and Systemic Sclerosis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159384"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.clim.2018.12.009","article-title":"Elevated Kynurenine Levels in Diffuse Cutaneous and Anti-RNA Polymerase III Positive Systemic Sclerosis","volume":"199","author":"Campochiaro","year":"2019","journal-title":"Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"21912","DOI":"10.1038\/s41598-020-78951-6","article-title":"Serum Metabolites as Biomarkers in Systemic Sclerosis-Associated Interstitial Lung Disease","volume":"10","author":"Meier","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Smolenska, Z., Zabielska-Kaczorowska, M., Wojteczek, A., Kutryb-Zajac, B., and Zdrojewski, Z. (2020). Metabolic Pattern of Systemic Sclerosis: Association of Changes in Plasma Concentrations of Amino Acid-Related Compounds with Disease Presentation. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.585161"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155587","DOI":"10.1016\/j.metabol.2023.155587","article-title":"Serum Metabolomic Profiling Reveals Potential Biomarkers in Systemic Sclerosis","volume":"144","author":"Guo","year":"2023","journal-title":"Metabolism"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s10238-022-00962-6","article-title":"Role of Kinurenic Acid in the Systemic Sclerosis Renal Involvement","volume":"23","author":"Pellicano","year":"2022","journal-title":"Clin. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/978-3-319-67577-0_9","article-title":"Tryptophan Catabolism and Cancer Immunotherapy Targeting IDO Mediated Immune Suppression","volume":"Volume 1036","author":"Kalinski","year":"2017","journal-title":"Tumor Immune Microenvironment in Cancer Progression and Cancer Therapy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.tips.2023.04.006","article-title":"Modulation of T Cells by Tryptophan Metabolites in the Kynurenine Pathway","volume":"44","author":"Stone","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"941","DOI":"10.4049\/jimmunol.2300442","article-title":"TDO2-Overexpressed Dendritic Cells Possess Tolerogenicity and Ameliorate Collagen-Induced Arthritis by Modulating the Th17\/Regulatory T Cell Balance","volume":"212","author":"Jia","year":"2024","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Klaessens, S., Stroobant, V., De Plaen, E., and Van den Eynde, B.J. (2022). Systemic Tryptophan Homeostasis. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.897929"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1124\/mol.115.100412","article-title":"GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids l-Tryptophan and l-Phenylalanine","volume":"88","author":"Liu","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1080\/10799893.2016.1247861","article-title":"Discovery and Pharmacological Effects of a Novel GPR142 Antagonist","volume":"37","author":"Murakoshi","year":"2017","journal-title":"J. Recept. Signal Transduct."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e006728","DOI":"10.1136\/jitc-2023-006728","article-title":"Tryptophan Depletion Sensitizes the AHR Pathway by Increasing AHR Expression and GCN2\/LAT1-Mediated Kynurenine Uptake, and Potentiates Induction of Regulatory T Lymphocytes","volume":"11","author":"Solvay","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103185","DOI":"10.1016\/j.autrev.2022.103185","article-title":"T Cell Abnormalities in Systemic Sclerosis","volume":"21","author":"Jin","year":"2022","journal-title":"Autoimmun. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0167-5699(99)01520-0","article-title":"Tryptophan Catabolism and T-Cell Tolerance: Immunosuppression by Starvation?","volume":"20","author":"Mellor","year":"1999","journal-title":"Immunol. Today"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature10491","article-title":"An Endogenous Tumour-Promoting Ligand of the Human Aryl Hydrocarbon Receptor","volume":"478","author":"Opitz","year":"2011","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/s12276-023-01028-7","article-title":"Immune Regulation through Tryptophan Metabolism","volume":"55","author":"Seo","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106886","DOI":"10.1016\/j.intimp.2020.106886","article-title":"Aryl Hydrocarbon Receptor Signaling Activation in Systemic Sclerosis Attenuates Collagen Production and Is a Potential Antifibrotic Target","volume":"88","author":"Shi","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"109764","DOI":"10.1016\/j.intimp.2023.109764","article-title":"UVA1 Irradiation Attenuates Collagen Production via Ficz\/AhR\/MAPK Signaling Activation in Scleroderma","volume":"116","author":"Shi","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/toxsci\/kfq024","article-title":"Kynurenic Acid Is a Potent Endogenous Aryl Hydrocarbon Receptor Ligand That Synergistically Induces Interleukin-6 in the Presence of Inflammatory Signaling","volume":"115","author":"DiNatale","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.pharmthera.2012.07.010","article-title":"Drug Transport by Organic Anion Transporters (OATs)","volume":"136","author":"Burckhardt","year":"2012","journal-title":"Pharm. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1038\/s41598-017-04949-2","article-title":"Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in Vivo Handling of Uremic Toxins and Solutes","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1365-2982.2007.00989.x","article-title":"Kynurenic Acid Inhibits Intestinal Hypermotility and Xanthine Oxidase Activity during Experimental Colon Obstruction in Dogs","volume":"20","author":"Kaszaki","year":"2008","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1365-2982.2009.01390.x","article-title":"N-Methyl-D-Aspartate Receptor Antagonism Decreases Motility and Inflammatory Activation in the Early Phase of Acute Experimental Colitis in the Rat","volume":"22","author":"Varga","year":"2010","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez Ortega, D., Ugalde Mu\u00f1iz, P.E., Blanco Ayala, T., V\u00e1zquez Cervantes, G.I., Lugo Huitr\u00f3n, R., Pineda, B., Gonz\u00e1lez Esquivel, D.F., P\u00e9rez de la Cruz, G., Pedraza Chaverr\u00ed, J., and S\u00e1nchez Chapul, L. (2021). On the Antioxidant Properties of L-Kynurenine: An Efficient ROS Scavenger and Enhancer of Rat Brain Antioxidant Defense. Antioxidants, 11.","DOI":"10.3390\/antiox11010031"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.ntt.2011.07.002","article-title":"On the Antioxidant Properties of Kynurenic Acid: Free Radical Scavenging Activity and Inhibition of Oxidative Stress","volume":"33","author":"Maldonado","year":"2011","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17559","DOI":"10.1038\/s41598-017-17979-7","article-title":"Inhibition of Human Kynurenine Aminotransferase Isozymes by Estrogen and Its Derivatives","volume":"7","author":"Jayawickrama","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/S0021-9258(18)69404-9","article-title":"Estrogen-Enzyme Interactions: Inhibition and Protection of Kynurenine Transaminase by the Sulfate Esters of Diethylstilbestrol, Estradiol, and Estrone","volume":"235","author":"Mason","year":"1960","journal-title":"JBC"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"IJTR.S40332","DOI":"10.4137\/IJTR.S40332","article-title":"Progesterone Alters Kynurenine Pathway Activation in IFN-\u03b3-Activated Macrophages\u2014Relevance for Neuroinflammatory Diseases","volume":"9","author":"Lim","year":"2016","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00296-020-04720-3","article-title":"Incidence, Prevalence and Mortality of Systemic Sclerosis in Italy: A Nationwide Population-Based Study Using Administrative Health Data","volume":"41","author":"Ciaffi","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1007\/s10067-020-05522-5","article-title":"Prevalence and Clinical Associations with Premature Ovarian Insufficiency, Early Menopause, and Low Ovarian Reserve in Systemic Sclerosis","volume":"40","author":"Jutiviboonsuk","year":"2021","journal-title":"Clin. Rheumatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.jchromb.2010.01.006","article-title":"Optimization of Zn2+-Containing Mobile Phase for Simultaneous Determination of Kynurenine, Kynurenic Acid and Tryptophan in Human Plasma by High Performance Liquid Chromatography","volume":"878","author":"Zhao","year":"2010","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1056\/NEJMoa2102953","article-title":"New Creatinine- and Cystatin C\u2013Based Equations to Estimate GFR without Race","volume":"385","author":"Inker","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1080\/09658211.2013.763984","article-title":"Effect Sizes in Memory Research","volume":"21","author":"Morris","year":"2013","journal-title":"Memory"},{"key":"ref_59","unstructured":"University of Cambridge (2020, February 21). Rules of Thumb on Magnitudes of Effect Sizes. Available online: http:\/\/imaging.mrc-cbu.cam.ac.uk\/statswiki\/FAQ\/effectSize."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3842\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:21:01Z","timestamp":1760106061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3842"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":59,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25073842"],"URL":"https:\/\/doi.org\/10.3390\/ijms25073842","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,29]]}}}