{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:12:31Z","timestamp":1790651551474,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Russian Federation Government","award":["075-15-2022-1095"],"award-info":[{"award-number":["075-15-2022-1095"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alterations in function of hypoxanthine guanine phosphoribosyl transferase (HPRT), one of the major enzymes involved in purine nucleotide exchange, lead to overproduction of uric acid and produce various symptoms of Lesch-Nyhan syndrome (LNS). One of the hallmarks of LNS is maximal expression of HPRT in the central nervous system with the highest activity of this enzyme in the midbrain and basal ganglia. However, the nature of neurological symptoms has yet to be clarified in details. Here, we studied whether HPRT1 deficiency changes mitochondrial energy metabolism and redox balance in murine neurons from the cortex and midbrain. We found that HPRT1 deficiency inhibits complex I-dependent mitochondrial respiration resulting in increased levels of mitochondrial NADH, reduction of the mitochondrial membrane potential, and increased rate of reactive oxygen species (ROS) production in mitochondria and cytosol. However, increased ROS production did not induce oxidative stress and did not decrease the level of endogenous antioxidant glutathione (GSH). Thus, disruption of mitochondrial energy metabolism but not oxidative stress could play a role of potential trigger of brain pathology in LNS.<\/jats:p>","DOI":"10.1007\/s12035-023-03266-2","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T16:25:35Z","timestamp":1676996735000},"page":"3147-3157","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["HPRT1 Deficiency Induces Alteration of Mitochondrial Energy Metabolism in the Brain"],"prefix":"10.1007","volume":"60","author":[{"given":"Andrey Y.","family":"Vinokurov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav O.","family":"Soldatov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia S.","family":"Seregina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina I.","family":"Dolgikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel A.","family":"Tagunov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey V.","family":"Dunaev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Y.","family":"Skorkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey V.","family":"Deykin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-7235","authenticated-orcid":false,"given":"Andrey Y.","family":"Abramov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"3266_CR1","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1146\/annurev.bi.40.070171.004115","volume":"40","author":"AW Murray","year":"1971","unstructured":"Murray AW (1971) The biological significance of purine salvage. Annu Rev Biochem 40:811\u2013826. https:\/\/doi.org\/10.1146\/annurev.bi.40.070171.004115","journal-title":"Annu Rev Biochem"},{"issue":"3","key":"3266_CR2","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/BF00220062","volume":"90","author":"DG Sculley","year":"1992","unstructured":"Sculley DG, Dawson PA, Emmerson BT, Gordon RB (1992) A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Hum Genet 90(3):195\u2013207. https:\/\/doi.org\/10.1007\/BF00220062","journal-title":"Hum Genet"},{"issue":"2","key":"3266_CR3","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1097\/YCO.0000000000000388","volume":"31","author":"JC Harris","year":"2018","unstructured":"Harris JC (2018) Lesch-Nyhan syndrome and its variants: examining the behavioral and neurocognitive phenotype. Curr Opin Psychiatry 31(2):96\u2013102. https:\/\/doi.org\/10.1097\/YCO.0000000000000388","journal-title":"Curr Opin Psychiatry"},{"key":"3266_CR4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1750-1172-2-48","volume":"2","author":"RJ Torres","year":"2007","unstructured":"Torres RJ, Puig JG (2007) Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. Orphanet J Rare Dis 2:48. https:\/\/doi.org\/10.1186\/1750-1172-2-48","journal-title":"Orphanet J Rare Dis"},{"key":"3266_CR5","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/0002-9343(64)90104-4","volume":"36","author":"M Lesch","year":"1964","unstructured":"Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36:561\u2013570. https:\/\/doi.org\/10.1016\/0002-9343(64)90104-4","journal-title":"Am J Med"},{"key":"3266_CR6","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1203\/00006450-197205000-00004","volume":"6","author":"JC Crawhall","year":"1972","unstructured":"Crawhall JC, Henderson JF, Kelley WN (1972) Diagnosis and treatment of the Lesch-Nyhan syndrome. Pediatr Res 6:504\u2013513. https:\/\/doi.org\/10.1203\/00006450-197205000-00004","journal-title":"Pediatr Res"},{"key":"3266_CR7","first-page":"1141","volume-title":"The metabolic basis of inherited disease","author":"WN Kelley","year":"1983","unstructured":"Kelley WN, Wyngaarden JB (1983) Clinical syndromes associated with hypoxanthine phosphoribosyltransferase deficiency. In: Stanbury JB et al (eds) The metabolic basis of inherited disease, 5th edn. McGraw-Hill, New York, pp 1141\u20131142","edition":"5"},{"key":"3266_CR8","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1146\/annurev.ge.19.120185.001015","volume":"19","author":"JT Stout","year":"1985","unstructured":"Stout JT, Caskey CT (1985) HPRT: gene structure, expression, and mutation. Ann Rev Genet 19:127\u2013148. https:\/\/doi.org\/10.1146\/annurev.ge.19.120185.001015","journal-title":"Ann Rev Genet"},{"issue":"19","key":"3266_CR9","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1056\/NEJM198111053051902","volume":"305","author":"LLoyd KG, Hornykiewicz O, Davidson","year":"1981","unstructured":"LLoyd KG, Hornykiewicz O, Davidson L, Shannak K, Farley I, Goldstein M, Shibuya M, et al (1981) Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome. N Engl J Med 305(19):1106\u20131111. https:\/\/doi.org\/10.1056\/NEJM198111053051902","journal-title":"N Engl J Med"},{"key":"3266_CR10","doi-asserted-by":"publisher","unstructured":"Yang Y, Zhou Y, Cheng S Sun JL, Yao H, Ma L (2016) Effect of uric acid on mitochondrial function and oxidative stress in hepatocytes. Genetics and Molecular Research 15(2). https:\/\/doi.org\/10.4238\/gmr.15028644.","DOI":"10.4238\/gmr.15028644"},{"issue":"8","key":"3266_CR11","doi-asserted-by":"publisher","first-page":"100510","DOI":"10.1016\/j.jhepr.2022.100510","volume":"4","author":"PR Angelova","year":"2022","unstructured":"Angelova PR, Kerbert AJC, Habtesion A, Hall A, Abramov AY, Jalan R (2022) Hyperammonemia induces mitochondrial dysfunction and neuronal cell death. JHEP Reports. 4(8):100510. https:\/\/doi.org\/10.1016\/j.jhepr.2022.100510","journal-title":"JHEP Reports."},{"issue":"4","key":"3266_CR12","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3897\/rrpharmacology.4.32209","volume":"4","author":"VA Kalmykov","year":"2018","unstructured":"Kalmykov VA, Kusov PA, Yablonskaia MI, Korshunov E, Korshunova D, Kubekina MV, Silaeva Y (2018) New personalized genetic mouse model of Lesch-Nyhan syndrome for pharmacology and gene therapy. Res Results Pharmacol 4(4):97\u2013104. https:\/\/doi.org\/10.3897\/rrpharmacology.4.32209","journal-title":"Res Results Pharmacol"},{"issue":"7","key":"3266_CR13","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1248\/bpb.b15-01046","volume":"39","author":"T Watanabe","year":"2016","unstructured":"Watanabe T, Tomioka NH, Watanabe S, Suzuki Y, Tsuchiya M, Hosoyamada M (2016) The mechanism of false in vitro elevation of uric acid level in mouse blood. Biol Pharm Bull 39(7):1081\u20131084. https:\/\/doi.org\/10.1248\/bpb.b15-01046","journal-title":"Biol Pharm Bull"},{"issue":"2","key":"3266_CR14","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/0003-2697(68)90309-6","volume":"22","author":"GF Domagk","year":"1968","unstructured":"Domagk GF, Schlicke HH (1968) A colorimetric method using uricase and peroxidase for the determination of uric acid. Anal Biochem 22(2):219\u2013224. https:\/\/doi.org\/10.1016\/0003-2697(68)90309-6","journal-title":"Anal Biochem"},{"issue":"4","key":"3266_CR15","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1111\/jnc.15239","volume":"157","author":"XP Cheng","year":"2020","unstructured":"Cheng XP, Vinokurov AY, Zherebtsov EA, Stelmashchuk OA, Angelova PR, Esteras N, Abramov AY (2020) Variability of mitochondrial energy balance across brain regions. J Neurochem 157(4):1234\u20131243. https:\/\/doi.org\/10.1111\/jnc.15239","journal-title":"J Neurochem"},{"issue":"8","key":"3266_CR16","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1042\/BCJ20200042","volume":"477","author":"AY Baev","year":"2020","unstructured":"Baev AY, Angelova PR, Abramov AY (2020) Inorganic polyphosphate is produced and hydrolyzed in F0F1-ATP synthase of mammalian mitochondria. Biochem J 477(8):1515\u20131524. https:\/\/doi.org\/10.1042\/BCJ20200042","journal-title":"Biochem J"},{"key":"3266_CR17","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/bs.mcb.2019.10.003","volume":"155","author":"N Esteras","year":"2020","unstructured":"Esteras N, Adjobo-Hermans MJW, Abramov AY, Koopman WJH (2020) Visualization of mitochondrial membrane potential in mammalian cells. In Methods in Cell Biology 155:221\u2013245. https:\/\/doi.org\/10.1016\/bs.mcb.2019.10.003","journal-title":"In Methods in Cell Biology"},{"key":"3266_CR18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/978-1-0716-0896-8_2","volume":"2202","author":"PR Angelova","year":"2021","unstructured":"Angelova PR, Dinkova-Kostova AT, Abramov AY (2021) Assessment of ROS production in the mitochondria of live cells. In Reactive Oxygen Species: Methods and Protocols, Methods in Molecular Biology 2202:33\u201342. https:\/\/doi.org\/10.1007\/978-1-0716-0896-8_2","journal-title":"In Reactive Oxygen Species: Methods and Protocols, Methods in Molecular Biology"},{"key":"3266_CR19","doi-asserted-by":"publisher","unstructured":"Vinokurov AY, Dremin VV, Piavchenko GA, Stelmashchuk OA, Angelova PR, Abramov AY (2021) Assessment of mitochondrial membrane potential and NADH redox state in acute brain slices. In: Weissig, V., Edeas, M. (eds) Mitochondrial Medicine. Methods in Molecular Biology, vol 2276. Springer, New York, NY. https:\/\/doi.org\/10.1007\/978-1-0716-1266-8_14","DOI":"10.1007\/978-1-0716-1266-8_14"},{"key":"3266_CR20","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1093\/brain\/awq015","volume":"133","author":"AY Abramov","year":"2010","unstructured":"Abramov AY, Smulders-Sriniasan KDM, Acin-Perez R, Enriquez JA, Lightowlers RN, Duchen MR (2010) Mechanism of neurodegeneration of neurons with mitochondrial DNA mutations. Brain 133:797\u2013807. https:\/\/doi.org\/10.1093\/brain\/awq015","journal-title":"Brain"},{"issue":"6","key":"3266_CR21","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1042\/BST20191042","volume":"47","author":"AY Abramov","year":"2019","unstructured":"Abramov AY, Angelova PR (2019) Cellular mechanisms of complex I-associated pathology. Biochem Soc Trans 47(6):1963\u20131969. https:\/\/doi.org\/10.1042\/BST20191042","journal-title":"Biochem Soc Trans"},{"issue":"5","key":"3266_CR22","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1002\/1873-3468.12964","volume":"592","author":"PR Angelova","year":"2018","unstructured":"Angelova PR, Abramov AY (2018) Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Letter 592(5):692\u2013702. https:\/\/doi.org\/10.1002\/1873-3468.12964","journal-title":"FEBS Letter"},{"key":"3266_CR23","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.freeradbiomed.2021.08.014","volume":"174","author":"AY Vinokurov","year":"2021","unstructured":"Vinokurov AY, Stelmashuk OA, Ukolova PA, Zherebtsov EA, Abramov AY (2021) Brain region specificity in reactive oxygen species production and maintenance of redox balance. Free Radical Biol Med 174:195\u2013201. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2021.08.014","journal-title":"Free Radical Biol Med"},{"issue":"5","key":"3266_CR24","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1515\/hsz-2015-0295","volume":"397","author":"N Esteras","year":"2016","unstructured":"Esteras N, Dinkova-Kostova AT, Abramov AY (2016) Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function. Biol Chem 397(5):383\u2013400. https:\/\/doi.org\/10.1515\/hsz-2015-0295","journal-title":"Biol Chem"},{"key":"3266_CR25","doi-asserted-by":"publisher","first-page":"535686","DOI":"10.1155\/2015\/535686","volume":"2015","author":"M Cristobal-Garcia","year":"2015","unstructured":"Cristobal-Garcia M, Garcia-Arroyo FE, Tapia E, Osorio H, Arellano-Buendia AS, Madero M, Rodriguez-Iturbe B et al (2015) Renal oxidative stress induced by long-term hyperuricemia alters mitochondrial function and maintains systemic hypertension. Oxidative Med Cell Longevity. 2015:535686. https:\/\/doi.org\/10.1155\/2015\/535686","journal-title":"Oxidative Med Cell Longevity."},{"key":"3266_CR26","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1159\/000345509","volume":"121","author":"LG Sanchez-Lozada","year":"2012","unstructured":"Sanchez-Lozada LG, Lanaspa MA, Cristobal-Carcia M (2012) Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations. Nephron Exp Nephrol 121:e71-78. https:\/\/doi.org\/10.1159\/000345509","journal-title":"Nephron Exp Nephrol"},{"key":"3266_CR27","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.freeradbiomed.2016.06.005","volume":"100","author":"PR Angelova","year":"2016","unstructured":"Angelova PR, Abramov AY (2016) Functional role of mitochondrial reactive oxygen species in physiology. Free Radic Biol Med 100:81\u201385. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2016.06.005","journal-title":"Free Radic Biol Med"},{"issue":"5","key":"3266_CR28","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1523\/JNEUROSCI.4468-06.2007","volume":"27","author":"AY Abramov","year":"2007","unstructured":"Abramov AY, Scorziello A, Duchen MR (2007) Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation. J Neurosci 27(5):1129\u20131138. https:\/\/doi.org\/10.1523\/JNEUROSCI.4468-06.2007","journal-title":"J Neurosci"},{"key":"3266_CR29","doi-asserted-by":"publisher","first-page":"101882","DOI":"10.1016\/j.redox.2021.101882","volume":"41","author":"M Bortolotti","year":"2021","unstructured":"Bortolotti M, Polito L, Battelli MG, Bolognesi A (2021) Xanthine oxidoreductase: one enzyme for multiple physiological tasks. Redox Biology. 41:101882. https:\/\/doi.org\/10.1016\/j.redox.2021.101882","journal-title":"Redox Biology."},{"key":"3266_CR30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.neurobiolaging.2018.10.031","volume":"75","author":"RG Cutler","year":"2019","unstructured":"Cutler RG, Camandola S, Feldman NH, Yoon JS, Haran JB, Arguelles S, Mattson MP (2019) Uric acid enhances longevity and endurance and protects the brain against ischemia. Neurobiol Aging 75:159\u2013168. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2018.10.031","journal-title":"Neurobiol Aging"},{"key":"3266_CR31","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s11011-009-9134-9","volume":"24","author":"V Micheli","year":"2009","unstructured":"Micheli V, Jacomelli G, Di Marcello F et al (2009) NAD metabolism in HPRT-deficient mice. Metab Brain Dis 24:311\u2013319. https:\/\/doi.org\/10.1007\/s11011-009-9134-9","journal-title":"Metab Brain Dis"},{"key":"3266_CR32","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.bbagen.2009.08.002","volume":"3","author":"AY Abramov","year":"1800","unstructured":"Abramov AY (1800) Duchen MR (2010) Impaired mitochondrial bioenergetics determines glutamate-induced delayed calcium deregulation in neurons. Biochim Biophys Acta 3:297\u2013304. https:\/\/doi.org\/10.1016\/j.bbagen.2009.08.002","journal-title":"Biochim Biophys Acta"},{"issue":"4","key":"3266_CR33","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1634\/stemcells.22-4-635","volume":"22","author":"A Urbach","year":"2004","unstructured":"Urbach A, Schuldiner M, Benvenisty N (2004) Modeling for Lesch-Nyhan disease by gene targeting in human embryonic stem cells. Stem Cells 22(4):635\u2013641. https:\/\/doi.org\/10.1634\/stemcells.22-4-635","journal-title":"Stem Cells"},{"key":"3266_CR34","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/2211-5463.12453","volume":"8","author":"V Kalmykov","year":"2018","unstructured":"Kalmykov V, Kusov P, Deikin A (2018) Bioinformatic analysis of a transgenic personalized murine model of Lesch-Nyhan syndrome. FEBS Open Bio. 8:23\u2013015-Wed. https:\/\/doi.org\/10.1002\/2211-5463.12453","journal-title":"FEBS Open Bio."},{"issue":"10","key":"3266_CR35","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1093\/hmg\/5.10.1607","volume":"5","author":"SJ Engle","year":"1996","unstructured":"Engle SJ, Womer DE, Davies PM, Boivin G, Sahota A, Simmonds HA, Stambrook PJ, Tischfield JA (1996) HPRT-APRT-deficient mice are not a model for Lesch-Nyhan syndrome. Hum Mol Genet 5(10):1607\u20131610. https:\/\/doi.org\/10.1093\/hmg\/5.10.1607","journal-title":"Hum Mol Genet"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-023-03266-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-023-03266-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-023-03266-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T16:20:38Z","timestamp":1682180438000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-023-03266-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["3266"],"URL":"https:\/\/doi.org\/10.1007\/s12035-023-03266-2","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,21]]},"assertion":[{"value":"22 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the animal procedures were conducted according to the ARRIVE guidelines and approved by the institutional ethical committee of Orel State University (No. 18 dated 21.02.2020) in compliance with Russian Federation legislation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from all individual participants and authors involved in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"We confirm that consent to publish has been received from all participants involved in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}