{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T21:08:59Z","timestamp":1753736939021,"version":"3.37.3"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["FPU17\/00627","FPU17\/05346"],"award-info":[{"award-number":["FPU17\/00627","FPU17\/05346"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014180","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["LE082-18","LE051-18","LE135-19","LE096-20"],"award-info":[{"award-number":["LE082-18","LE051-18","LE135-19","LE096-20"]}],"id":[{"id":"10.13039\/501100014180","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["AGL2016-79813-C2-1R\/2R","AGL2016-79813-C2-1R\/2R","RYC-2015-18368","AGL2016-79813-C2-1R\/2R"],"award-info":[{"award-number":["AGL2016-79813-C2-1R\/2R","AGL2016-79813-C2-1R\/2R","RYC-2015-18368","AGL2016-79813-C2-1R\/2R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The control of gastrointestinal nematodes in livestock is becoming increasingly difficult due to the limited number of available drugs and the rapid development of anthelmintic resistance. Therefore, it is imperative to develop new anthelmintics that are effective against nematodes. Under this context, we tested the potential toxicity of three compounds in mice and their potential anthelmintic efficacy in Mongolian gerbils infected with <jats:italic>Haemonchus contortus<\/jats:italic>. The compounds were selected from previous in vitro experiments: two diamine (AAD-1 and AAD-2) and one benzimidazole (2aBZ) derivatives. 2aBZ was also selected to test its efficacy in sheep. In Mongolian gerbils, the benzimidazole reduced the percentage of pre-adults present in the stomach of gerbils by 95% at a dose of 200\u00a0mg\/kg. In sheep, there was a 99% reduction in the number of eggs shed in faeces after 7\u00a0days at a dose of 120\u00a0mg\/kg and a 95% reduction in the number of worm adults present in the abomasum. In conclusion, 2aBZ could be considered a promising candidate for the treatment of helminth infections in small ruminants.<\/jats:p>","DOI":"10.1038\/s41598-022-17112-3","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T10:04:36Z","timestamp":1659089076000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel compound shows in vivo anthelmintic activity in gerbils and sheep infected by Haemonchus contortus"],"prefix":"10.1038","volume":"12","author":[{"given":"Elora","family":"Valderas-Garc\u00eda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nerea","family":"Escala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"\u00c1lvarez-Bard\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Castilla-G\u00f3mez de Ag\u00fcero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Cambra-Pellej\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Gonz\u00e1lez del Palacio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Vallejo Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"de la Vega","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"San Feliciano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"del Olmo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Mart\u00ednez-Valladares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Bala\u00f1a-Fouce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"17112_CR1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.cvfa.2019.12.005","volume":"36","author":"AM Zajac","year":"2020","unstructured":"Zajac, A. M. & Garza, J. Biology, epidemiology, and control of gastrointestinal nematodes of small ruminants. Vet. Clin. Food Anim. Pract. 36, 73\u201387 (2020).","journal-title":"Vet. Clin. Food Anim. Pract."},{"key":"17112_CR2","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.3390\/ani12101238","volume":"12","author":"KJ Flay","year":"2022","unstructured":"Flay, K. J., Hill, F. I. & Muguiro, D. H. A review: Haemonchus contortus infection in pasture-based sheep production systems, with a focus on the pathogenesis of anemia and changes in haematological parameters. Animals 12, 1238 (2022).","journal-title":"Animals"},{"key":"17112_CR3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cvfa.2019.12.001","volume":"36","author":"RM Kaplan","year":"2020","unstructured":"Kaplan, R. M. Biology, epidemiology, diagnosis, and management of anthelmintic resistance in gastrointestinal nematodes of livestock. Vet. Clin. North Am. Food. Anim. Pract. 36, 17\u201330 (2020).","journal-title":"Vet. Clin. North Am. Food. Anim. Pract."},{"key":"17112_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2020.105103","volume":"182","author":"J Charlier","year":"2020","unstructured":"Charlier, J. et al. Initial assessment of the economic burden of major parasitic helminth infections to the ruminant livestock industry in Europe. Prev. Vet. Med. 182, 105103 (2020).","journal-title":"Prev. Vet. Med."},{"key":"17112_CR5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1756-3305-6-1","volume":"6","author":"F Roeber","year":"2013","unstructured":"Roeber, F., Jex, A. R. & Gasser, R. B. Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for explor ing epidemiology and drug resistance: An Australian perspective. Parasites Vect. 6, 1\u201313 (2013).","journal-title":"Parasites Vect."},{"key":"17112_CR6","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1515\/acve-2017-0013","volume":"67","author":"M Abongwa","year":"2017","unstructured":"Abongwa, M., Martin, R. J. & Robertson, A. P. A brief review on the mode of action of antinematodal drugs. Acta Vet. 67, 137\u2013152 (2017).","journal-title":"Acta Vet."},{"key":"17112_CR7","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-011-2753-1","author":"M Mart\u00ednez-Valladares","year":"2012","unstructured":"Mart\u00ednez-Valladares, M. et al. Characterization of a multidrug resistant Teladorsagia circumcincta isolate from Spain. Parasitol. Res. https:\/\/doi.org\/10.1007\/s00436-011-2753-1 (2012).","journal-title":"Parasitol. Res."},{"key":"17112_CR8","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.vetpar.2012.03.036","volume":"189","author":"E Papadopoulos","year":"2012","unstructured":"Papadopoulos, E., Gallidis, E. & Ptochos, S. Anthelmintic resistance in sheep in Europe: A selected review. Vet. Parasitol. 189, 85\u201388 (2012).","journal-title":"Vet. Parasitol."},{"key":"17112_CR9","first-page":"484","volume":"3","author":"ER Morgan","year":"2013","unstructured":"Morgan, E. R. et al. Global change and helminth infections in grazing ruminants in Europe: Impacts, trends and sustainable solutions. Agric. 3, 484\u2013502 (2013).","journal-title":"Agric."},{"key":"17112_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1051\/parasite\/2020062","volume":"27","author":"HR Vineer","year":"2020","unstructured":"Vineer, H. R. et al. Increasing importance of anthelmintic resistance in European livestock: Creation and meta-analysis of an open database. Parasite 27, 69 (2020).","journal-title":"Parasite"},{"key":"17112_CR11","doi-asserted-by":"publisher","first-page":"3091","DOI":"10.20546\/ijcmas.2018.702.372","volume":"7","author":"DB Bhinsara","year":"2018","unstructured":"Bhinsara, D. B. et al. Benzimidazole resistance: An overview. Int J Curr Microbiol App Sci. 7, 3091\u20133104 (2018).","journal-title":"Int J Curr Microbiol App Sci."},{"key":"17112_CR12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S0001-706X(01)00144-9","volume":"80","author":"H Zahner","year":"2001","unstructured":"Zahner, H., Taubert, A., Harder, A. & Von Samson-Himmelstjerna, G. Effects of Bay 44\u20134400, a new cyclodepsipeptide, on developing stages of filariae (Acanthocheilonema viteae, Brugia malayi, Litomosoides sigmodontis) in the rodent Mastomys coucha. Acta Trop. 80, 19\u201328 (2001).","journal-title":"Acta Trop."},{"key":"17112_CR13","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1007\/s00436-008-1080-7","volume":"103","author":"R Kaminsky","year":"2008","unstructured":"Kaminsky, R. et al. Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate. Parasitol. Res. 103, 931\u2013939 (2008).","journal-title":"Parasitol. Res."},{"key":"17112_CR14","doi-asserted-by":"publisher","unstructured":"Woods, D. J. et al. Discovery, Mode of Action, and Commercialization of Derquantel. in Parasitic Helminths: Targets, Screens, Drugs and Vaccines 297\u2013307 (Wiley-VCH, 2012). https:\/\/doi.org\/10.1002\/9783527652969.ch18.","DOI":"10.1002\/9783527652969.ch18"},{"key":"17112_CR15","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ijpddr.2020.07.001","volume":"14","author":"SA Nixon","year":"2020","unstructured":"Nixon, S. A. et al. Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics. Int. J. Parasitol. Drugs Drug Resist. 14, 8\u201316 (2020).","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"17112_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2021.109496","volume":"296","author":"E Valderas-Garc\u00eda","year":"2021","unstructured":"Valderas-Garc\u00eda, E. et al. Anthelmintic activity of aminoalcohol and diamine derivatives against the gastrointestinal nematode Teladorsagia circumcincta. Vet. Parasitol. 296, 109496 (2021).","journal-title":"Vet. Parasitol."},{"key":"17112_CR17","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.drudis.2019.12.007","volume":"25","author":"M Zaj\u00ed\u010dkov\u00e1","year":"2020","unstructured":"Zaj\u00ed\u010dkov\u00e1, M., Nguyen, L. T., Sk\u00e1lov\u00e1, L., Raisov\u00e1 Stuchl\u00edkov\u00e1, L. & Matou\u0161kov\u00e1, P. Anthelmintics in the future: Current trends in the discovery and development of new drugs against gastrointestinal nematodes. Drug Discov. Today 25, 430\u2013437 (2020).","journal-title":"Drug Discov. Today"},{"key":"17112_CR18","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1645\/14-703.1","volume":"101","author":"TG Geary","year":"2015","unstructured":"Geary, T. G., Sakanari, J. A. & Caffrey, C. R. Anthelmintic drug discovery: Into the future. J. Parasitol. 101, 125\u2013133 (2015).","journal-title":"J. Parasitol."},{"key":"17112_CR19","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ijpddr.2020.07.001","volume":"14","author":"SA Nixon","year":"2020","unstructured":"Nixon, S. A. et al. Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics. Int. J. Parasitol. Drugs Drug Resist. 14, 8\u201316 (2020).","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"17112_CR20","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.ijpddr.2014.07.002","volume":"4","author":"G Panic","year":"2014","unstructured":"Panic, G., Duthaler, U., Speich, B. & Keiser, J. Repurposing drugs for the treatment and control of helminth infections | Elsevier Enhanced Reader. Int. J. Parasitol. Drugs Drugs Resist. 4, 185\u2013200 (2014).","journal-title":"Int. J. Parasitol. Drugs Drugs Resist."},{"key":"17112_CR21","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.ejps.2018.02.010","volume":"117","author":"C Fei","year":"2018","unstructured":"Fei, C. et al. Safety and clinical efficacy of tenvermectin, a novel antiparasitic 16-membered macrocyclic lactone antibiotics. Eur. J. Pharm. Sci. 117, 154\u2013160 (2018).","journal-title":"Eur. J. Pharm. Sci."},{"key":"17112_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007021","volume":"12","author":"MG Blanco","year":"2018","unstructured":"Blanco, M. G. et al. Diisopropylphenyl-imidazole (DII): A new compound that exerts anthelmintic activity through novel molecular mechanisms. PLoS Negl. Trop. Dis. 12, e0007021 (2018).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"17112_CR23","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.molstruc.2018.02.060","volume":"1161","author":"EL Guti\u00e9rrez","year":"2018","unstructured":"Guti\u00e9rrez, E. L., Souza, M. S., Diniz, L. F. & Ellena, J. Synthesis, characterization and solubility of a new anthelmintic salt: Mebendazole nitrate. J. Mol. Struct. 1161, 113\u2013121 (2018).","journal-title":"J. Mol. Struct."},{"key":"17112_CR24","doi-asserted-by":"crossref","unstructured":"Auletta, C. S. Acute, subchronic, and chronic toxicology. in Handbook of Toxicology 69\u2013126 (2001).","DOI":"10.1201\/9781420042078.ch2"},{"key":"17112_CR25","doi-asserted-by":"publisher","first-page":"492","DOI":"10.2307\/3283650","volume":"78","author":"GA Conder","year":"1992","unstructured":"Conder, G. A. et al. Growth and Development of Haemonchus contortus in Jirds, Meriones unguiculatus. Source J. Parasitol. 78, 492\u2013497 (1992).","journal-title":"Source J. Parasitol."},{"key":"17112_CR26","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/bs.apar.2016.02.013","volume":"93","author":"TG Geary","year":"2016","unstructured":"Geary, T. G. Haemonchus contortus: Applications in drug discovery. Adv. Parasitol. 93, 429\u2013463 (2016).","journal-title":"Adv. Parasitol."},{"key":"17112_CR27","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1017\/S0022149X18000408","volume":"93","author":"LT Gressler","year":"2019","unstructured":"Gressler, L. T. et al. Meriones unguiculatus infected by Haemonchus contortus: Evaluation of different experimental protocols. J. Helminthol. 93, 447\u2013452 (2019).","journal-title":"J. Helminthol."},{"key":"17112_CR28","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1615\/IntJMedMushrooms.2020036364","volume":"22","author":"AFIM de Matos","year":"2020","unstructured":"de Matos, A. F. I. M. et al. Nematocidal Effect of Oyster Culinary-Medicinal Mushroom Pleurotus ostreatus (Agaricomycetes) against Haemonchus contortus. Int. J. Med. Mushrooms. 22, 1089\u20131098 (2020).","journal-title":"Int. J. Med. Mushrooms."},{"key":"17112_CR29","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.exppara.2016.09.004","volume":"170","author":"TH Grando","year":"2016","unstructured":"Grando, T. H. et al. Melaleuca alternifolia anthelmintic activity in gerbils experimentally infected by Haemonchus contortus. Exp. Parasitol. 170, 177\u2013183 (2016).","journal-title":"Exp. Parasitol."},{"key":"17112_CR30","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1007\/s11686-021-00344-0","volume":"66","author":"LF Monta\u00f1ez-Palma","year":"2021","unstructured":"Monta\u00f1ez-Palma, L. F., T\u00e9llez-T\u00e9llez, M., de Lourdes Acosta-Urdapilleta, M., D\u00edaz-God\u00ednez, G. & Aguilar-Marcelino, L. Nematicidal activity of a hydroalcoholic extract of the edible mushroom Neolentinus ponderosus on L3 larvae of Haemonchus contortus. Acta Parasitol. 66, 969\u2013976 (2021).","journal-title":"Acta Parasitol."},{"key":"17112_CR31","doi-asserted-by":"publisher","first-page":"168","DOI":"10.2307\/3283008","volume":"76","author":"GA Conder","year":"1990","unstructured":"Conder, G. A. et al. A Novel Anthelmintic Model Utilizing Jirds, Meriones unguiculatus, Infected with Haemonchus contortus. Source J. Parasitol. 76, 168\u2013170 (1990).","journal-title":"Source J. Parasitol."},{"key":"17112_CR32","unstructured":"Dubey, A. K. & Sanyal, P. K. Benzimidazoles in a Wormy World. Vetscan 5, (2010)."},{"key":"17112_CR33","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1021\/jm701456r","volume":"51","author":"C Chassaing","year":"2008","unstructured":"Chassaing, C. et al. Highly water-soluble prodrugs of anthelmintic benzimidazole carbamates: Synthesis, pharmacodynamics, and pharmacokinetics. J. Med. Chem. 51, 1111\u20131114 (2008).","journal-title":"J. Med. Chem."},{"key":"17112_CR34","doi-asserted-by":"publisher","first-page":"3918","DOI":"10.1021\/acs.jmedchem.7b01792","volume":"61","author":"SC Zimmermann","year":"2018","unstructured":"Zimmermann, S. C. et al. N-substituted prodrugs of mebendazole provide improved aqueous solubility and oral bioavailability in mice and dogs. J. Med. Chem. 61, 3918\u20133929 (2018).","journal-title":"J. Med. Chem."},{"key":"17112_CR35","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1590\/S0104-66322011000400013","volume":"28","author":"L Fern\u00e1ndez","year":"2011","unstructured":"Fern\u00e1ndez, L., Sigal, L., Otero, L., Silber, J. J. & Santo, M. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimer. Braz. J. Chem. Eng. 28, 679\u2013689 (2011).","journal-title":"Braz. J. Chem. Eng."},{"key":"17112_CR36","doi-asserted-by":"publisher","first-page":"718","DOI":"10.5455\/javar.2020.g473","volume":"7","author":"VA Marchenko","year":"2020","unstructured":"Marchenko, V. A., Khalikov, S. S., Vasilenko, Y. A., Ilyin, M. M. & Kravchenko, I. A. Innovative anthelmintic based on mechanochemical technology and their efficacy against parasitic infection of sheeps. J. Adv. Vet. Anim. Res. 7, 718\u2013725 (2020).","journal-title":"J. Adv. Vet. Anim. Res."},{"key":"17112_CR37","doi-asserted-by":"publisher","first-page":"5764","DOI":"10.1016\/j.bmcl.2009.07.147","volume":"19","author":"E Del Olmo","year":"2009","unstructured":"Del Olmo, E. et al. Simple dihydrosphyngosine analogues with potent activity against MDR-Mycobacterium tuberculosis. Bioorgan. Med. Chem. Lett. 19, 5764\u20135768 (2009).","journal-title":"Bioorgan. Med. Chem. Lett."},{"key":"17112_CR38","first-page":"10","volume":"1\u20132","author":"J H\u00f6glund","year":"2015","unstructured":"H\u00f6glund, J. et al. Failure of ivermectin treatment in Haemonchus contortus infected-Swedish sheep flocks. Vet. Parasitol. Reg. Stud. reports 1\u20132, 10\u201315 (2015).","journal-title":"Vet. Parasitol. Reg. Stud. reports"},{"key":"17112_CR39","doi-asserted-by":"publisher","first-page":"100","DOI":"10.2307\/3284123","volume":"82","author":"GA Conder","year":"1996","unstructured":"Conder, G. A. & Johnson, S. S. Viability of infective larvae of Haemonchus contortus, Ostertagia ostertagi, and Trichostrongylus colubriformis following exsheathment by various techniques. J. Parasitol. 82, 100\u2013102 (1996).","journal-title":"J. Parasitol."},{"key":"17112_CR40","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/0304-4017(95)00806-2","volume":"58","author":"IB Wood","year":"1995","unstructured":"Wood, I. B. et al. World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition of guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine, ovine, caprine). Vet. Parasitol. 58, 181\u2013213 (1995).","journal-title":"Vet. Parasitol."},{"key":"17112_CR41","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/0304-4017(92)90141-U","volume":"44","author":"G Coles","year":"1992","unstructured":"Coles, G. et al. World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) methods for the detection of anthelmintic resistance in nematodes of veterinary importance. Vet. Parasitol. 44, 35\u201344 (1992).","journal-title":"Vet. Parasitol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-17112-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-17112-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-17112-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T04:53:52Z","timestamp":1669352032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-17112-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,29]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["17112"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-17112-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2022,7,29]]},"assertion":[{"value":"13 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13004"}}