{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:06:09Z","timestamp":1740107169055,"version":"3.37.3"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T00:00:00Z","timestamp":1717804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T00:00:00Z","timestamp":1717804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002386","name":"Cairo University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002386","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Dermatol Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) with its etiology not yet fully understood. Interleukin (IL)-35 is an inhibitory cytokine that belongs to the IL-12 family. Elevated IL-35 in the plasma and the tumor microenvironment increases tumorigenesis and indicates poor prognosis in different types of malignancies. The objective of this study is to estimate the expression levels of IL-35 in tissue and serum of MF patients versus healthy controls. This case-control study included 35 patients with patch, plaque, and tumor MF as well as 30 healthy controls. Patients were fully assessed, and serum samples and lesional skin biopsies were taken prior to starting treatment. The IL-35 levels were measured in both serum and tissue biopsies by ELISA technique. Both tissue and serum IL-35 levels were significantly higher in MF patients than in controls (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and tissue IL-35 was significantly higher than serum IL-35 in MF patients (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Tissue IL-35 was significantly higher in female patients and patients with recurrent MF compared to male patients and those without recurrent disease (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Since both tissue and serum IL-35 levels are increased in MF, IL-35 is suggested to have a possible role in MF pathogenesis. IL-35 can be a useful diagnostic marker for MF. Tissue IL-35 can also be an indicator of disease recurrence.<\/jats:p>","DOI":"10.1007\/s00403-024-03115-9","type":"journal-article","created":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T07:02:10Z","timestamp":1717830130000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estimation of the tissue and serum levels of IL-35 in Mycosis fungoides: a case-control study"],"prefix":"10.1007","volume":"316","author":[{"given":"Maha Fathy","family":"Elmasry","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmine Ahmed","family":"Obaid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solwan Ibrahim","family":"El-Samanoudy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeinab Ahmed","family":"Nour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally Sameh","family":"Doss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,8]]},"reference":[{"key":"3115_CR1","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1182\/blood-2009-11-251926","volume":"116","author":"JJ Campbell","year":"2010","unstructured":"Campbell JJ, Clark RA, Watanabe R, Kupper TS (2010) S\u00e9zary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood 116:767\u2013771. https:\/\/doi.org\/10.1182\/blood-2009-11-251926","journal-title":"Blood"},{"key":"3115_CR2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s11864-020-00809-w","volume":"22","author":"H Kamijo","year":"2021","unstructured":"Kamijo H, Miyagaki T (2021) Mycosis Fungoides and S\u00e9zary Syndrome: updates and review of current therapy. Curr Treat Options Oncol 22:10. https:\/\/doi.org\/10.1007\/s11864-020-00809-w","journal-title":"Curr Treat Options Oncol"},{"key":"3115_CR3","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.beha.2019.06.004","volume":"32","author":"XU Martinez","year":"2019","unstructured":"Martinez XU, Di Raimondo C, Abdulla FR, Zain J, Rosen ST, Querfeld C (2019) Leukaemic variants of cutaneous T-cell lymphoma: erythrodermic mycosis fungoides and S\u00e9zary syndrome. Best Pract Res Clin Haematol 32:239\u2013252. https:\/\/doi.org\/10.1016\/j.beha.2019.06.004","journal-title":"Best Pract Res Clin Haematol"},{"key":"3115_CR4","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.semcancer.2021.12.003","volume":"86","author":"K Patil","year":"2022","unstructured":"Patil K, Kuttikrishnan S, Khan AQ, Ahmad F, Alam M, Buddenkotte J, Ahmad A, Steinhoff M, Uddin S (2022) Molecular pathogenesis of cutaneous T cell lymphoma: role of chemokines, cytokines, and dysregulated signaling pathways. Semin Cancer Biol 86:382\u2013399. https:\/\/doi.org\/10.1016\/j.semcancer.2021.12.003","journal-title":"Semin Cancer Biol"},{"key":"3115_CR5","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1089\/jir.2021.0147","volume":"41","author":"C Ye","year":"2021","unstructured":"Ye C, Yano H, Workman CJ, Vignali DAA (2021) Interleukin-35: structure, function and its impact on Immune-Related diseases. J Interf Cytokine Res 41:391\u2013406. https:\/\/doi.org\/10.1089\/jir.2021.0147","journal-title":"J Interf Cytokine Res"},{"key":"3115_CR6","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1002\/jcb.29441","volume":"121","author":"Z Yazdani","year":"2020","unstructured":"Yazdani Z, Rafiei A, Golpour M, Zafari P, Moonesi M, Ghaffari S (2020) IL-35, a double\u2010edged sword in cancer. J Cell Biochem 121:2064\u20132076. https:\/\/doi.org\/10.1002\/jcb.29441","journal-title":"J Cell Biochem"},{"key":"3115_CR7","doi-asserted-by":"publisher","first-page":"6272","DOI":"10.1158\/1078-0432.CCR-11-0060","volume":"17","author":"R Nishino","year":"2011","unstructured":"Nishino R, Takano A, Oshita H, Ishikawa N, Akiyama H, Ito H, Nakayama H, Miyagi Y, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y (2011) Identification of Epstein-Barr Virus\u2013Induced Gene 3 as a Novel serum and tissue biomarker and a therapeutic target for Lung Cancer. Clin Cancer Res 17:6272\u20136286. https:\/\/doi.org\/10.1158\/1078-0432.CCR-11-0060","journal-title":"Clin Cancer Res"},{"key":"3115_CR8","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.immuni.2016.01.013","volume":"44","author":"ME Turnis","year":"2016","unstructured":"Turnis ME, Sawant DV, Szymczak-Workman AL, Andrews LP, Delgoffe GM, Yano H, Beres AJ, Vogel P, Workman CJ, Vignali DAA (2016) Interleukin-35 limits Anti-tumor Immunity. Immunity 44:316\u2013329. https:\/\/doi.org\/10.1016\/j.immuni.2016.01.013","journal-title":"Immunity"},{"key":"3115_CR9","doi-asserted-by":"publisher","first-page":"2780","DOI":"10.3390\/cells10102780","volume":"10","author":"A Pileri","year":"2021","unstructured":"Pileri A, Guglielmo A, Grandi V, Violetti SA, Fanoni D, Fava P, Agostinelli C, Berti E, Quaglino P, Pimpinelli N (2021) The Microenvironment\u2019s role in Mycosis Fungoides and S\u00e9zary Syndrome: from progression to therapeutic implications. Cells 10:2780. https:\/\/doi.org\/10.3390\/cells10102780","journal-title":"Cells"},{"key":"3115_CR10","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s00281-016-0594-9","volume":"39","author":"T Krejsgaard","year":"2017","unstructured":"Krejsgaard T, Lindahl LM, Mongan NP, Wasik MA, Litvinov IV, Iversen L, Langhoff E, Woetmann A, Odum N (2017) Malignant inflammation in cutaneous T-cell lymphoma\u2014a hostile takeover. Semin Immunopathol 39:269\u2013282. https:\/\/doi.org\/10.1007\/s00281-016-0594-9","journal-title":"Semin Immunopathol"},{"key":"3115_CR11","doi-asserted-by":"publisher","first-page":"491","DOI":"10.3109\/10428194.2010.517877","volume":"52","author":"MB Karpova","year":"2011","unstructured":"Karpova MB, Fujii K, Jenni D, Dummer R, Urosevic-Maiwald M (2011) Evaluation of lymphangiogenic markers in S\u00e9zary syndrome. Leuk Lymphoma 52:491\u2013501. https:\/\/doi.org\/10.3109\/10428194.2010.517877","journal-title":"Leuk Lymphoma"},{"key":"3115_CR12","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1002\/ijc.31382","volume":"143","author":"M Teymouri","year":"2018","unstructured":"Teymouri M, Pirro M, Fallarino F, Gargaro M, Sahebkar A (2018) IL-35, a hallmark of immune\u2010regulation in cancer progression, chronic infections and inflammatory diseases. Int J Cancer 143:2105\u20132115. https:\/\/doi.org\/10.1002\/ijc.31382","journal-title":"Int J Cancer"},{"key":"3115_CR13","doi-asserted-by":"publisher","first-page":"651","DOI":"10.7150\/ijbs.7.651","volume":"7","author":"BF Zamarron","year":"2011","unstructured":"Zamarron BF, Chen W (2011) Dual Roles of Immune Cells and their factors in Cancer Development and Progression. Int J Biol Sci 7:651\u2013658. https:\/\/doi.org\/10.7150\/ijbs.7.651","journal-title":"Int J Biol Sci"},{"key":"3115_CR14","doi-asserted-by":"publisher","unstructured":"Uzhachenko RV, Shanker A (2019) CD8\u2009+\u2009T lymphocyte and NK Cell Network: Circuitry in the cytotoxic domain of immunity. Front Immunol 10. https:\/\/doi.org\/10.3389\/fimmu.2019.01906","DOI":"10.3389\/fimmu.2019.01906"},{"key":"3115_CR15","doi-asserted-by":"publisher","first-page":"205031212110690","DOI":"10.1177\/20503121211069012","volume":"10","author":"B Mirlekar","year":"2022","unstructured":"Mirlekar B (2022) Tumor promoting roles of IL-10, TGF-\u03b2, IL-4, and IL-35: its implications in cancer immunotherapy. SAGE Open Med 10:205031212110690. https:\/\/doi.org\/10.1177\/20503121211069012","journal-title":"SAGE Open Med"},{"key":"3115_CR16","doi-asserted-by":"publisher","unstructured":"Larousserie F, Kebe D, Huynh T, Audebourg A, Tamburini J, Terris B, Devergne O (2019) Evidence for IL-35 expression in diffuse large B-Cell lymphoma and impact on the patient\u2019s prognosis. Front Oncol 9. https:\/\/doi.org\/10.3389\/fonc.2019.00563","DOI":"10.3389\/fonc.2019.00563"},{"key":"3115_CR17","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.humimm.2015.09.020","volume":"76","author":"J Wang","year":"2015","unstructured":"Wang J, Tao Q, Wang H, Wang Z, Wu F, Pan Y, Tao L, Xiong S, Wang Y, Zhai Z (2015) Elevated IL-35 in bone marrow of the patients with acute myeloid leukemia. Hum Immunol 76:681\u2013686. https:\/\/doi.org\/10.1016\/j.humimm.2015.09.020","journal-title":"Hum Immunol"},{"key":"3115_CR18","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1097\/MPH.0000000000001667","volume":"42","author":"H Solati","year":"2020","unstructured":"Solati H, Zareinejad M, Ghavami A, Ghasemi Z, Amirghofran Z (2020) IL-35 and IL-18 serum levels in children with Acute Lymphoblastic Leukemia: the relationship with prognostic factors. J Pediatr Hematol Oncol 42:281\u2013286. https:\/\/doi.org\/10.1097\/MPH.0000000000001667","journal-title":"J Pediatr Hematol Oncol"},{"key":"3115_CR19","first-page":"1806","volume":"6","author":"J-C Zeng","year":"2013","unstructured":"Zeng J-C, Zhang Z, Li T-Y, Liang Y-F, Wang H-M, Bao J-J, Zhang J-A, Wang W-D, Xiang W-Y, Kong B, Wang Z-Y, Wu B-H, Chen X-D, He L, Zhang S, Wang C-Y, Xu J-F (2013) Assessing the role of IL-35 in colorectal cancer progression and prognosis. Int J Clin Exp Pathol 6:1806\u20131816","journal-title":"Int J Clin Exp Pathol"},{"key":"3115_CR20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.humimm.2013.09.018","volume":"75","author":"P Jin","year":"2014","unstructured":"Jin P, Ren H, Sun W, Xin W, Zhang H, Hao J (2014) Circulating IL-35 in pancreatic ductal adenocarcinoma patients. Hum Immunol 75:29\u201333. https:\/\/doi.org\/10.1016\/j.humimm.2013.09.018","journal-title":"Hum Immunol"},{"key":"3115_CR21","doi-asserted-by":"publisher","first-page":"2845","DOI":"10.7314\/APJCP.2015.16.7.2845","volume":"16","author":"Y-G Fan","year":"2015","unstructured":"Fan Y-G, Zhai J-M, Wang W, Feng B, Yao G-L, An Y-H, Zeng C (2015) IL-35 over-expression is Associated with Genesis of Gastric Cancer. Asian Pac J Cancer Prev 16:2845\u20132849. https:\/\/doi.org\/10.7314\/APJCP.2015.16.7.2845","journal-title":"Asian Pac J Cancer Prev"},{"key":"3115_CR22","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1111\/ajco.13403","volume":"17","author":"J Gu","year":"2021","unstructured":"Gu J, Wang X, Wang L, Zhou L, Tang M, Li P, Wu X, Chen M, Zhang Y (2021) Serum level of interleukin-35 as a potential prognostic factor for gastric cancer. Asia Pac J Clin Oncol 17:52\u201359. https:\/\/doi.org\/10.1111\/ajco.13403","journal-title":"Asia Pac J Clin Oncol"},{"key":"3115_CR23","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2019.10208","author":"J Zhu","year":"2019","unstructured":"Zhu J, Yang X, Wang Y, Zhang H, Guo Z (2019) Interleukin\u201335 is associated with the tumorigenesis and progression of prostate cancer. Oncol Lett. https:\/\/doi.org\/10.3892\/ol.2019.10208","journal-title":"Oncol Lett"},{"key":"3115_CR24","first-page":"2255","volume":"8","author":"G Chen","year":"2016","unstructured":"Chen G, Liang Y, Guan X, Chen H, Liu Q, Lin B, Chen C, Huang M, Chen J, Wu W, Liang Y, Zhou K, Zeng J (2016) Circulating low IL-23: IL-35 cytokine ratio promotes progression associated with poor prognosisin breast cancer. Am J Transl Res 8:2255\u20132264","journal-title":"Am J Transl Res"},{"key":"3115_CR25","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1111\/cts.12891","volume":"14","author":"T Zhang","year":"2021","unstructured":"Zhang T, Nie J, Liu X, Han Z, Ding N, Gai K, Liu Y, Chen L, Guo C (2021) Correlation analysis among the level of IL-35, Microvessel Density, Lymphatic Vessel density, and prognosis in non\u2010small cell Lung Cancer. Clin Transl Sci 14:389\u2013394. https:\/\/doi.org\/10.1111\/cts.12891","journal-title":"Clin Transl Sci"},{"key":"3115_CR26","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/cei.13535","volume":"203","author":"X Liu","year":"2021","unstructured":"Liu X, Ren H, Guo H, Wang W, Zhao N (2021) Interleukin-35 has a tumor-promoting role in hepatocellular carcinoma. Clin Exp Immunol 203:219\u2013229. https:\/\/doi.org\/10.1111\/cei.13535","journal-title":"Clin Exp Immunol"},{"key":"3115_CR27","doi-asserted-by":"publisher","unstructured":"Liu K, Huang A, Nie J, Tan J, Xing S, Qu Y, Jiang K (2021) IL-35 regulates the function of Immune cells in Tumor Microenvironment. Front Immunol 12. https:\/\/doi.org\/10.3389\/fimmu.2021.683332","DOI":"10.3389\/fimmu.2021.683332"},{"key":"3115_CR28","doi-asserted-by":"publisher","unstructured":"Yang L, Shao X, Jia S, Zhang Q, Jin Z (2019) Interleukin-35 dampens CD8\u2009+\u2009T cells activity in patients with non-viral Hepatitis-Related Hepatocellular Carcinoma. Front Immunol 10. https:\/\/doi.org\/10.3389\/fimmu.2019.01032","DOI":"10.3389\/fimmu.2019.01032"},{"key":"3115_CR29","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1002\/jnr.20881","volume":"84","author":"MJ Polanczyk","year":"2006","unstructured":"Polanczyk MJ, Hopke C, Vandenbark AA, Offner H (2006) Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of treg cells, and enhanced expression of the PD-1 costimulatory pathway. J Neurosci Res 84:370\u2013378. https:\/\/doi.org\/10.1002\/jnr.20881","journal-title":"J Neurosci Res"},{"key":"3115_CR30","doi-asserted-by":"publisher","first-page":"736","DOI":"10.3390\/cancers7020736","volume":"7","author":"R Upadhyay","year":"2015","unstructured":"Upadhyay R, Hammerich L, Peng P, Brown B, Merad M, Brody J (2015) Lymphoma: Immune Evasion Strategies. Cancers (Basel) 7:736\u2013762. https:\/\/doi.org\/10.3390\/cancers7020736","journal-title":"Cancers (Basel)"},{"key":"3115_CR31","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.jdermsci.2016.05.004","volume":"83","author":"S Furudate","year":"2016","unstructured":"Furudate S, Fujimura T, Kakizaki A, Hidaka T, Asano M, Aiba S (2016) Tumor-associated M2 macrophages in mycosis fungoides acquire immunomodulatory function by interferon alpha and interferon gamma. J Dermatol Sci 83:182\u2013189. https:\/\/doi.org\/10.1016\/j.jdermsci.2016.05.004","journal-title":"J Dermatol Sci"},{"key":"3115_CR32","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/s41416-019-0444-3","volume":"120","author":"L Heim","year":"2019","unstructured":"Heim L, Kachler K, Siegmund R, Trufa DI, Mittler S, Geppert C-I, Friedrich J, Rieker RJ, Sirbu H, Finotto S (2019) Increased expression of the immunosuppressive interleukin-35 in patients with non-small cell lung cancer. Br J Cancer 120:903\u2013912. https:\/\/doi.org\/10.1038\/s41416-019-0444-3","journal-title":"Br J Cancer"},{"key":"3115_CR33","doi-asserted-by":"publisher","first-page":"13401","DOI":"10.3390\/ijms232113401","volume":"23","author":"A Filippelli","year":"2022","unstructured":"Filippelli A, Del Gaudio C, Simonis V, Ciccone V, Spini A, Donnini S (2022) Scoping review on platelets and Tumor angiogenesis: do we need more evidence or Better Analysis? Int J Mol Sci 23:13401. https:\/\/doi.org\/10.3390\/ijms232113401","journal-title":"Int J Mol Sci"},{"key":"3115_CR34","doi-asserted-by":"publisher","first-page":"174","DOI":"10.4103\/jewd.jewd_10_21","volume":"18","author":"R Youssef","year":"2021","unstructured":"Youssef R, Hay R, Aboulghate A, Ibrahim N, Hegazy A, Sayed K (2021) Mycosis fungoides and metabolic syndrome: a hospital-based case-control study. J Egypt Women\u2019s Dermatol Soc 18:174. https:\/\/doi.org\/10.4103\/jewd.jewd_10_21","journal-title":"J Egypt Women\u2019s Dermatol Soc"},{"key":"3115_CR35","doi-asserted-by":"publisher","first-page":"100219","DOI":"10.1016\/j.xjidi.2023.100219","volume":"3","author":"CM Johnson","year":"2023","unstructured":"Johnson CM, Talluru SM, Bubic B, Colbert M, Kumar P, Tsai H, Varadhan R, Rozati S (2023) Association of Cardiovascular Disease in patients with Mycosis Fungoides and S\u00e9zary Syndrome compared to a Matched Control Cohort. JID Innov 3:100219. https:\/\/doi.org\/10.1016\/j.xjidi.2023.100219","journal-title":"JID Innov"}],"container-title":["Archives of Dermatological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00403-024-03115-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00403-024-03115-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00403-024-03115-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T20:27:32Z","timestamp":1725913652000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00403-024-03115-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,8]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["3115"],"URL":"https:\/\/doi.org\/10.1007\/s00403-024-03115-9","relation":{},"ISSN":["1432-069X"],"issn-type":[{"type":"electronic","value":"1432-069X"}],"subject":[],"published":{"date-parts":[[2024,6,8]]},"assertion":[{"value":"6 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"349"}}