{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:19:16Z","timestamp":1765484356486,"version":"3.37.3"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62072212"],"award-info":[{"award-number":["62072212"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Development Project of Jilin Province of China","award":["20220508125RC","20230201065GX"],"award-info":[{"award-number":["20220508125RC","20230201065GX"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Complex Intell. Syst."],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Body fluid biomarkers are very important, because they can be detected in a non-invasive or minimally invasive way. The discovery of secreted proteins in human body fluids is an essential step toward proteomic biomarker identification for human diseases. Recently, many computational methods have been proposed to predict secreted proteins and achieved some success. However, most of them are based on a manual negative dataset, which is usually biased and therefore limits the prediction performances. In this paper, we first propose a novel positive-unlabeled learning framework to predict secreted proteins in a single body fluid. The secreted protein discovery in a single body fluid is transformed into multiple binary classifications and solved via multi-task learning. Also, an effective convolutional neural network is employed to reduce the overfitting problem. After that, we then improve this framework to predict secreted proteins in multiple body fluids simultaneously. The improved framework adopts a globally shared network to further improve the prediction performances of all body fluids. The improved framework was trained and evaluated on datasets of 17 body fluids, and the average benchmarks of 17 body fluids achieved an accuracy of 89.48%, F1 score of 56.17%, and PRAUC of 58.93%. The comparative results demonstrate that the improved framework performs much better than other state-of-the-art methods in secreted protein discovery.<\/jats:p>","DOI":"10.1007\/s40747-023-01221-1","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T07:02:56Z","timestamp":1693810976000},"page":"1319-1331","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A multi-task positive-unlabeled learning framework to predict secreted proteins in human body fluids"],"prefix":"10.1007","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-2172","authenticated-orcid":false,"given":"Kai","family":"He","sequence":"first","affiliation":[]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Xuping","family":"Xie","sequence":"additional","affiliation":[]},{"given":"Dan","family":"Shao","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"1221_CR1","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1093\/bib\/bbz160","volume":"22","author":"L Huang","year":"2021","unstructured":"Huang L, Shao D, Wang Y et al (2021) Human body-fluid proteome: quantitative profiling and computational prediction. Brief Bioinform 22:315\u2013333","journal-title":"Brief Bioinform"},{"key":"1221_CR2","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.3390\/biomedicines10071472","volume":"10","author":"G Kall\u00f3","year":"2022","unstructured":"Kall\u00f3 G, Kumar A, T\u0151zs\u00e9r J et al (2022) Chemical barrier proteins in human body fluids. Biomedicines 10:1472","journal-title":"Biomedicines"},{"key":"1221_CR3","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1373\/clinchem.2009.126706","volume":"56","author":"NL Anderson","year":"2010","unstructured":"Anderson NL (2010) The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum. Clin Chem 56:177\u2013185","journal-title":"Clin Chem"},{"key":"1221_CR4","first-page":"250","volume":"5","author":"JT Lathrop","year":"2003","unstructured":"Lathrop JT, Anderson NL, Anderson NG et al (2003) Therapeutic potential of the plasma proteome. Curr Opin Mol Ther 5:250\u2013257","journal-title":"Curr Opin Mol Ther"},{"key":"1221_CR5","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1002\/prca.200700217","volume":"1","author":"S-M Ahn","year":"2007","unstructured":"Ahn S-M, Simpson RJ (2007) Body fluid proteomics: prospects for biomarker discovery. Proteom Clin Appl 1:1004\u20131015","journal-title":"Proteom Clin Appl"},{"key":"1221_CR6","doi-asserted-by":"publisher","first-page":"549","DOI":"10.21873\/cgp.20280","volume":"18","author":"Y Li","year":"2021","unstructured":"Li Y, Xun D, Li L et al (2021) Deep dive on the proteome of human body fluids: a valuable data resource for biomarker discovery. Cancer Genom Proteom 18:549\u2013568","journal-title":"Cancer Genom Proteom"},{"key":"1221_CR7","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jprot.2016.08.009","volume":"153","author":"\u00c9 Cs\u0151sz","year":"2017","unstructured":"Cs\u0151sz \u00c9, Kall\u00f3 G, M\u00e1rkus B, De\u00e1k E, Csutak A, T\u0151zs\u00e9r J (2017) Quantitative body fluid proteomics in medicine\u2014a focus on minimal invasiveness. J Proteom 153:30\u201343. https:\/\/doi.org\/10.1016\/j.jprot.2016.08.009","journal-title":"J Proteom"},{"issue":"1","key":"1221_CR8","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12943-022-01526-8","volume":"21","author":"Z Ding","year":"2022","unstructured":"Ding Z, Wang N, Ji N, Chen Z-S (2022) Proteomics technologies for cancer liquid biopsies. Mol Cancer 21(1):53. https:\/\/doi.org\/10.1186\/s12943-022-01526-8","journal-title":"Mol Cancer"},{"issue":"1","key":"1221_CR9","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4103\/0972-2327.48845","volume":"12","author":"A Venugopal","year":"2009","unstructured":"Venugopal A, Chaerkady R, Pandey A (2009) Application of mass spectrometry-based proteomics for biomarker discovery in neurological disorders. Ann Indian Acad Neurol 12(1):3. https:\/\/doi.org\/10.4103\/0972-2327.48845","journal-title":"Ann Indian Acad Neurol"},{"key":"1221_CR10","doi-asserted-by":"publisher","first-page":"3531","DOI":"10.1002\/pmic.200401335","volume":"5","author":"B Muthusamy","year":"2005","unstructured":"Muthusamy B, Hanumanthu G, Suresh S et al (2005) Plasma Proteome Database as a resource for proteomics research. Proteomics 5:3531\u20133536","journal-title":"Proteomics"},{"key":"1221_CR11","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1093\/nar\/gkn849","volume":"37","author":"SJ Li","year":"2009","unstructured":"Li SJ, Peng M, Li H et al (2009) Sys-BodyFluid: a systematical database for human body fluid proteome research. Nucleic Acids Res 37:907\u2013912","journal-title":"Nucleic Acids Res"},{"key":"1221_CR12","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1093\/nar\/gkt1251","volume":"42","author":"V Nanjappa","year":"2014","unstructured":"Nanjappa V, Thomas JK, Marimuthu A et al (2014) Plasma Proteome Database as a resource for proteomics research: 2014 update. Nucleic Acids Res 42:959\u2013965","journal-title":"Nucleic Acids Res"},{"key":"1221_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/database\/baab065","volume":"2021","author":"D Shao","year":"2021","unstructured":"Shao D, Huang L, Wang Y et al (2021) HBFP: a new repository for human body fluid proteome. Database 2021:1\u201314","journal-title":"Database"},{"key":"1221_CR14","doi-asserted-by":"crossref","unstructured":"Geng Y, Jin L, Tang G et al (2022) LiqBioer: a manually curated database of cancer biomarkers in body fluid. Database 2022","DOI":"10.1093\/database\/baac077"},{"key":"1221_CR15","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1093\/bioinformatics\/btn418","volume":"24","author":"J Cui","year":"2008","unstructured":"Cui J, Liu Q, Puett D et al (2008) Computational prediction of human proteins that can be secreted into the bloodstream. Bioinformatics 24:2370\u20132375","journal-title":"Bioinformatics"},{"key":"1221_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-11-250","volume":"11","author":"Q Liu","year":"2010","unstructured":"Liu Q, Cui J, Yang Q et al (2010) In-silico prediction of blood-secretory human proteins using a ranking algorithm. BMC Bioinform 11:1\u20138","journal-title":"BMC Bioinform"},{"issue":"2","key":"1221_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016875","volume":"6","author":"CS Hong","year":"2011","unstructured":"Hong CS, Cui J, Ni Z et al (2011) A computational method for prediction of excretory proteins and application to identification of gastric cancer markers in urine. PLoS One 6(2):e16875","journal-title":"PLoS One"},{"key":"1221_CR18","doi-asserted-by":"publisher","first-page":"80211","DOI":"10.1371\/journal.pone.0080211","volume":"8","author":"J Wang","year":"2013","unstructured":"Wang J, Liang Y, Wang Y et al (2013) Computational prediction of human salivary proteins from blood circulation and application to diagnostic biomarker identification. PLoS One 8:80211","journal-title":"PLoS One"},{"key":"1221_CR19","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1109\/TNB.2015.2395143","volume":"14","author":"Y Sun","year":"2015","unstructured":"Sun Y, Du W, Zhou C et al (2015) A computational method for prediction of saliva-secretory proteins and its application to identification of head and neck cancer biomarkers for salivary diagnosis. IEEE Trans Nanobiosci 14:167\u2013174","journal-title":"IEEE Trans Nanobiosci"},{"key":"1221_CR20","doi-asserted-by":"crossref","unstructured":"Wang Y, Du W, Liang Y et al (2016) PUEPro: a computational pipeline for prediction of urine excretory proteins. In: Advanced data mining and applications. Springer, Gold Coast, pp. 714\u2013725","DOI":"10.1007\/978-3-319-49586-6_51"},{"key":"1221_CR21","doi-asserted-by":"crossref","unstructured":"Shao D, Huang L, Wang Y et al (2019) Computational prediction of human body-fluid protein. In: IEEE international conference on bioinformatics and biomedicine. IEEE, San Diego, pp 2735\u20132740","DOI":"10.1109\/BIBM47256.2019.8982951"},{"key":"1221_CR22","doi-asserted-by":"publisher","first-page":"22989","DOI":"10.1371\/journal.pone.0022989","volume":"6","author":"L-L Hu","year":"2011","unstructured":"Hu L-L, Huang T, Cai Y-D et al (2011) Prediction of body fluids where proteins are secreted into based on protein interaction network. PLoS One 6:22989","journal-title":"PLoS One"},{"key":"1221_CR23","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/s11390-021-0851-9","volume":"36","author":"W Du","year":"2021","unstructured":"Du W, Sun Y, Bao H-M et al (2021) DeepHBSP: a deep learning framework for predicting human blood-secretory proteins using transfer learning. J Comput Sci Technol 36:234\u2013247","journal-title":"J Comput Sci Technol"},{"key":"1221_CR24","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.3390\/math10142490","volume":"10","author":"L Huang","year":"2022","unstructured":"Huang L, Qu Y, He K et al (2022) DenSec: secreted protein prediction in cerebrospinal fluid based on DenseNet and transformer. Mathematics 10:2490","journal-title":"Mathematics"},{"key":"1221_CR25","doi-asserted-by":"publisher","first-page":"10152562","DOI":"10.3390\/math10152562","volume":"10","author":"K He","year":"2022","unstructured":"He K, Wang Y, Xie X et al (2022) MultiSec: multi-task deep learning improves secreted protein discovery in human body fluids. Mathematics 10:10152562","journal-title":"Mathematics"},{"key":"1221_CR26","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1093\/bioinformatics\/btab545","volume":"38","author":"D Shao","year":"2021","unstructured":"Shao D, Huang L, Wang Y et al (2021) DeepSec: a deep learning framework for secreted protein discovery in human body fluids. Bioinformatics 38:228\u2013235","journal-title":"Bioinformatics"},{"issue":"8","key":"1221_CR27","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.3390\/molecules28083617","volume":"28","author":"K He","year":"2023","unstructured":"He K, Wang Y, Xie X, Shao D (2023) Prediction of proteins in cerebrospinal fluid and application to glioma biomarker identification. Molecules 28(8):3617. https:\/\/doi.org\/10.3390\/molecules28083617","journal-title":"Molecules"},{"key":"1221_CR28","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/nar\/gkr284","volume":"39","author":"HB Rao","year":"2011","unstructured":"Rao HB, Zhu F, Yang GB et al (2011) Update of PROFEAT: a web server for computing structural and physicochemical features of proteins and peptides from amino acid sequence. Nucleic Acids Res 39:385\u2013390","journal-title":"Nucleic Acids Res"},{"key":"1221_CR29","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1093\/nar\/gky1049","volume":"47","author":"A Bateman","year":"2019","unstructured":"Bateman A (2019) UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res 47:506\u2013515","journal-title":"Nucleic Acids Res"},{"key":"1221_CR30","doi-asserted-by":"publisher","first-page":"9054","DOI":"10.3390\/ijms22169054","volume":"22","author":"W Du","year":"2021","unstructured":"Du W, Zhao X, Sun Y et al (2021) SecProCT: in silico prediction of human secretory proteins based on capsule network and transformer. Int J Mol Sci 22:9054","journal-title":"Int J Mol Sci"},{"key":"1221_CR31","doi-asserted-by":"crossref","unstructured":"Xu Y, Xu C, Xu C et al (2017) Multi-positive and unlabeled learning. In: Proceedings of the twenty-sixth international joint conference on artificial intelligence. In: International joint conferences on artificial intelligence organization, Melbourne, pp 3182\u20133188","DOI":"10.24963\/ijcai.2017\/444"},{"key":"1221_CR32","doi-asserted-by":"crossref","unstructured":"Jaskie K, Spanias A (2019) Positive and unlabeled learning algorithms and applications: a survey. In: 10th International conference on information, intelligence, systems and applications. IEEE, Patras, pp 1\u20138","DOI":"10.1109\/IISA.2019.8900698"},{"key":"1221_CR33","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1007\/s10994-020-05877-5","volume":"109","author":"J Bekker","year":"2020","unstructured":"Bekker J, Davis J (2020) Learning from positive and unlabeled data: a survey. Mach Learn 109:719\u2013760 arXiv:1811.04820","journal-title":"Mach Learn"},{"key":"1221_CR34","first-page":"1","volume":"23","author":"F Li","year":"2022","unstructured":"Li F, Dong S, Leier A et al (2022) Positive-unlabeled learning in bioinformatics and computational biology: a brief review. Brief Bioinform 23:1\u201313","journal-title":"Brief Bioinform"},{"key":"1221_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/bib\/bbaa058","volume":"22","author":"H Wei","year":"2021","unstructured":"Wei H, Xu Y, Liu B (2021) iPiDi-PUL: identifying Piwi-interacting RNA-disease associations based on positive unlabeled learning. Brief Bioinform 22:1\u201311","journal-title":"Brief Bioinform"},{"key":"1221_CR36","doi-asserted-by":"publisher","first-page":"5586","DOI":"10.1109\/TKDE.2021.3070203","volume":"34","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Yang Q (2022) A survey on multi-task learning. IEEE Trans Knowl Data Eng 34:5586\u20135609","journal-title":"IEEE Trans Knowl Data Eng"},{"key":"1221_CR37","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nature14539","volume":"521","author":"Y LeCun","year":"2015","unstructured":"LeCun Y, Bengio Y, Hinton G (2015) Deep learning. Nature 521:436\u2013444","journal-title":"Nature"},{"key":"1221_CR38","doi-asserted-by":"crossref","unstructured":"Kalchbrenner N, Grefenstette E, Blunsom P (2014) A convolutional neural network for modelling sentences. In: Proceedings of the 52nd annual meeting of the association for computational linguistics. Association for Computational Linguistics, Baltimore, pp 655\u2013665","DOI":"10.3115\/v1\/P14-1062"},{"key":"1221_CR39","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1093\/bioinformatics\/btq003","volume":"26","author":"Y Huang","year":"2010","unstructured":"Huang Y, Niu B, Gao Y et al (2010) CD-HIT Suite: a web server for clustering and comparing biological sequences. Bioinformatics 26:680\u2013682","journal-title":"Bioinformatics"},{"key":"1221_CR40","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1093\/nar\/gky995","volume":"47","author":"S El-Gebali","year":"2019","unstructured":"El-Gebali S, Mistry J, Bateman A et al (2019) The Pfam protein families database in 2019. Nucleic Acids Res 47:427\u2013432","journal-title":"Nucleic Acids Res"},{"key":"1221_CR41","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","volume":"25","author":"S Altschul","year":"1997","unstructured":"Altschul S (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389\u20133402","journal-title":"Nucleic Acids Res"},{"key":"1221_CR42","unstructured":"Kingma DP, Ba JL (2015) Adam: a method for stochastic optimization. In: International conference on learning representations. OpenReview.net, San Diego"},{"issue":"5","key":"1221_CR43","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1093\/jalm\/jfab004","volume":"6","author":"M Chen","year":"2021","unstructured":"Chen M, Ren AH, Prassas I et al (2021) Plasma protein profiling by proximity extension assay technology reveals novel biomarkers of traumatic brain injury\u2013a pilot study. J Appl Lab Med 6(5):1165\u20131178. https:\/\/doi.org\/10.1093\/jalm\/jfab004","journal-title":"J Appl Lab Med"},{"issue":"4","key":"1221_CR44","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/proteomes9040047","volume":"9","author":"L-AC Andersen","year":"2021","unstructured":"Andersen L-AC, Palstr\u00f8m NB, Diederichsen A et al (2021) Determining plasma protein variation parameters as a prerequisite for biomarker studies\u2014a TMT-based LC-MSMS proteome investigation. Proteomes 9(4):47. https:\/\/doi.org\/10.3390\/proteomes9040047","journal-title":"Proteomes"},{"key":"1221_CR45","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.patrec.2013.06.010","volume":"37","author":"F Mordelet","year":"2014","unstructured":"Mordelet F, Vert JP (2014) A bagging SVM to learn from positive and unlabeled examples. Pattern Recognit Lett 37:201\u2013209 arXiv:1010.0772","journal-title":"Pattern Recognit Lett"},{"key":"1221_CR46","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1039\/C9AN01704F","volume":"145","author":"T Dong","year":"2020","unstructured":"Dong T, Santos S, Yang Z et al (2020) Sputum and salivary protein biomarkers and point-of-care biosensors for the management of COPD. Analyst 145:1583\u20131604","journal-title":"Analyst"},{"key":"1221_CR47","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.3390\/cancers12061629","volume":"12","author":"V El-Khoury","year":"2020","unstructured":"El-Khoury V, Schritz A, Kim S-Y et al (2020) Identification of a blood-based protein biomarker panel for lung cancer detection. Cancers 12:1629","journal-title":"Cancers"},{"key":"1221_CR48","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s40364-022-00425-w","volume":"10","author":"K Waury","year":"2022","unstructured":"Waury K, Willemse EAJ, Vanmechelen E et al (2022) Bioinformatics tools and data resources for assay development of fluid protein biomarkers. Biomark Res 10:83","journal-title":"Biomark Res"},{"key":"1221_CR49","doi-asserted-by":"publisher","first-page":"4917","DOI":"10.3390\/ijms23094917","volume":"23","author":"JE Rodrigues","year":"2022","unstructured":"Rodrigues JE, Martinho A, Santa C et al (2022) Systematic review and meta-analysis of mass spectrometry proteomics applied to human peripheral fluids to assess potential biomarkers of schizophrenia. Int J Mol Sci 23:4917","journal-title":"Int J Mol Sci"}],"container-title":["Complex &amp; Intelligent Systems"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40747-023-01221-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40747-023-01221-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40747-023-01221-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T22:34:20Z","timestamp":1707604460000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40747-023-01221-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,4]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["1221"],"URL":"https:\/\/doi.org\/10.1007\/s40747-023-01221-1","relation":{},"ISSN":["2199-4536","2198-6053"],"issn-type":[{"type":"print","value":"2199-4536"},{"type":"electronic","value":"2198-6053"}],"subject":[],"published":{"date-parts":[[2023,9,4]]},"assertion":[{"value":"31 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 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":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}