{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T06:38:47Z","timestamp":1722062327080},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cheminform"],"abstract":"Abstract<\/jats:title>BBPs have the potential to facilitate the delivery of drugs to the brain, opening up new avenues for the development of treatments targeting diseases of the central nervous system (CNS). The obstacle faced in central nervous system disorders stems from the formidable task of traversing the blood\u2013brain barrier (BBB) for pharmaceutical agents. Nearly 98% of small molecule-based drugs and nearly 100% of large molecule-based drugs encounter difficulties in successfully penetrating the BBB. This importance leads to identification of these peptides, can help in healthcare systems. In this study, we proposed an improved intelligent computational model BBB-PEP-Prediction for identification of BBB peptides. Position and statistical moments based features have been computed for acquired benchmark dataset. Four types of ensembles such as bagging, boosting, stacking and blending have been utilized in the methodology section. Bagging employed Random Forest (RF) and Extra Trees (ET), Boosting utilizes XGBoost (XGB) and Light Gradient Boosting Machine (LGBM). Stacking uses ET and XGB as base learners, blending exploited LGBM and RF as base learners, while Logistic Regression (LR) has been applied as Meta learner for stacking and blending. Three classifiers such as LGBM, XGB and ET have been optimized by using Randomized search CV. Four types of testing such as self-consistency, independent set, cross-validation with 5 and 10 folds and jackknife test have been employed. Evaluation metrics such as Accuracy (ACC), Specificity (SPE), Sensitivity (SEN), Mathew\u2019s correlation coefficient (MCC) have been utilized. The stacking of classifiers has shown best results in almost each testing. The stacking results for independent set testing exhibits accuracy, specificity, sensitivity and MCC score of 0.824, 0.911, 0.831 and 0.663 respectively. The proposed model BBB-PEP-Prediction shown superlative performance as compared to previous benchmark studies. The proposed system helps in future research and research community for in-silico identification of BBB peptides.<\/jats:p>","DOI":"10.1186\/s13321-023-00773-1","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T06:01:51Z","timestamp":1700287311000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["BBB-PEP-prediction: improved computational model for identification of blood\u2013brain barrier peptides using blending position relative composition specific features and ensemble modeling"],"prefix":"10.1186","volume":"15","author":[{"given":"Ansar","family":"Naseem","sequence":"first","affiliation":[]},{"given":"Fahad","family":"Alturise","sequence":"additional","affiliation":[]},{"given":"Tamim","family":"Alkhalifah","sequence":"additional","affiliation":[]},{"given":"Yaser Daanial","family":"Khan","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,11,18]]},"reference":[{"key":"773_CR1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00050.2017","author":"MD Sweeney","year":"2018","unstructured":"Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV (2018) Blood-brain barrier: from physiology to disease and back. Physiol Rev. https:\/\/doi.org\/10.1152\/physrev.00050.2017","journal-title":"Physiol Rev"},{"issue":"1","key":"773_CR2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","volume":"37","author":"NJ Abbott","year":"2010","unstructured":"Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood\u2013brain barrier. Neurobiol Dis 37(1):13\u201325","journal-title":"Neurobiol Dis"},{"issue":"5","key":"773_CR3","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3109\/09687688.2014.937468","volume":"31","author":"M Tajes","year":"2014","unstructured":"Tajes M et al (2014) The blood-brain barrier: structure, function and therapeutic approaches to cross it. Mol Membr Biol 31(5):152\u2013167","journal-title":"Mol Membr Biol"},{"issue":"1","key":"773_CR4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrn1824","volume":"7","author":"NJ Abbott","year":"2006","unstructured":"Abbott NJ, R\u00f6nnb\u00e4ck L, Hansson E (2006) Astrocyte\u2013endothelial interactions at the blood\u2013brain barrier. Nat Rev Neurosci 7(1):41\u201353","journal-title":"Nat Rev Neurosci"},{"issue":"5093","key":"773_CR5","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.8420006","volume":"259","author":"PM Friden","year":"1993","unstructured":"Friden PM et al (1993) Blood-brain barrier penetration and in vivo activity of an NGF conjugate. Science 259(5093):373\u2013377","journal-title":"Science"},{"issue":"3","key":"773_CR6","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","volume":"14","author":"MD Sweeney","year":"2018","unstructured":"Sweeney MD, Sagare AP, Zlokovic BV (2018) Blood\u2013brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 14(3):133\u2013150","journal-title":"Nat Rev Neurol"},{"key":"773_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.02.009","author":"J Chambers","year":"2012","unstructured":"Chambers J (2012) Delivery of therapeutics to the central nervous system. Adv Drug Deliv Rev. https:\/\/doi.org\/10.1016\/j.addr.2012.02.009","journal-title":"Adv Drug Deliv Rev"},{"key":"773_CR8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1602\/neurorx.2.1.3","volume":"2","author":"WM Pardridge","year":"2005","unstructured":"Pardridge WM (2005) The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2:3\u201314","journal-title":"NeuroRx"},{"issue":"1","key":"773_CR9","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1021\/acs.jcim.0c01115","volume":"61","author":"R Dai","year":"2021","unstructured":"Dai R et al (2021) BBPpred: sequence-based prediction of blood-brain barrier peptides with feature representation learning and logistic regression. J Chem Inf Model 61(1):525\u2013534","journal-title":"J Chem Inf Model"},{"issue":"8","key":"773_CR10","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.3390\/pharmaceutics13081237","volume":"13","author":"V Kumar","year":"2021","unstructured":"Kumar V, Patiyal S, Dhall A, Sharma N, Raghava GPS (2021) B3pred: a random-forest-based method for predicting and designing blood\u2013brain barrier penetrating peptides. Pharmaceutics 13(8):1237","journal-title":"Pharmaceutics"},{"key":"773_CR11","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.845747","author":"X Chen","year":"2022","unstructured":"Chen X et al (2022) BBPpredict: a web service for identifying blood-brain barrier penetrating peptides. Front Genet. https:\/\/doi.org\/10.3389\/fgene.2022.845747","journal-title":"Front Genet"},{"key":"773_CR12","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1007\/s00429-011-0375-0","volume":"217","author":"S Van Dorpe","year":"2012","unstructured":"Van Dorpe S et al (2012) Brainpeps: the blood\u2013brain barrier peptide database. Brain Struct Funct 217:687\u2013718","journal-title":"Brain Struct Funct"},{"key":"773_CR13","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1007\/s00429-021-02341-5","volume":"226","author":"V Kumar","year":"2021","unstructured":"Kumar V et al (2021) B3Pdb: an archive of blood\u2013brain barrier-penetrating peptides. Brain Struct Funct 226:2489\u20132495","journal-title":"Brain Struct Funct"},{"issue":"2","key":"773_CR14","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1109\/TCBB.2019.2919025","volume":"18","author":"M Awais","year":"2019","unstructured":"Awais M, Hussain W, Khan YD, Rasool N, Khan SA, Chou K-C (2019) iPhosH-PseAAC: identify phosphohistidine sites in proteins by blending statistical moments and position relative features according to the Chou\u2019s 5-step rule and general pseudo amino acid composition. IEEE\/ACM Trans Comput Biol Bioinform 18(2):596\u2013610","journal-title":"IEEE\/ACM Trans Comput Biol Bioinform"},{"issue":"11","key":"773_CR15","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.3390\/diagnostics13111940","volume":"13","author":"AH Butt","year":"2023","unstructured":"Butt AH, Alkhalifah T, Alturise F, Khan YD (2023) Ensemble learning for hormone binding protein prediction: a promising approach for early diagnosis of thyroid hormone disorders in serum. Diagnostics 13(11):1940","journal-title":"Diagnostics"},{"key":"773_CR16","doi-asserted-by":"publisher","first-page":"104623","DOI":"10.1016\/j.chemolab.2022.104623","volume":"228","author":"S Ahmed","year":"2022","unstructured":"Ahmed S, Arif M, Kabir M, Khan K, Khan YD (2022) PredAoDP: accurate identification of antioxidant proteins by fusing different descriptors based on evolutionary information with support vector machine. Chemom Intell Lab Syst 228:104623","journal-title":"Chemom Intell Lab Syst"},{"key":"773_CR17","doi-asserted-by":"publisher","DOI":"10.1177\/20552076231180739","author":"G Perveen","year":"2023","unstructured":"Perveen G, Alturise F, Alkhalifah T, Daanial Khan Y (2023) Hemolytic-Pred: a machine learning-based predictor for hemolytic proteins using position and composition-based features. Digit Health. https:\/\/doi.org\/10.1177\/20552076231180739","journal-title":"Digit Health"},{"issue":"9","key":"773_CR18","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.2174\/1574893615999200424085947","volume":"15","author":"YD Khan","year":"2020","unstructured":"Khan YD, Alzahrani E, Alghamdi W, Ullah MZ (2020) Sequence-based identification of allergen proteins developed by integration of PseAAC and statistical moments via 5-step rule. Curr Bioinforma 15(9):1046\u20131055","journal-title":"Curr Bioinforma"},{"issue":"2","key":"773_CR19","doi-asserted-by":"publisher","first-page":"124","DOI":"10.2174\/1389202920666190325162307","volume":"20","author":"A Ehsan","year":"2019","unstructured":"Ehsan A, Mahmood MK, Khan YD, Barukab OM, Khan SA, Chou K-C (2019) iHyd-PseAAC (EPSV): identifying hydroxylation sites in proteins by extracting enhanced position and sequence variant feature via Chou\u2019s 5-step rule and general pseudo amino acid composition. Curr Genomics 20(2):124\u2013133","journal-title":"Curr Genomics"},{"issue":"8","key":"773_CR20","doi-asserted-by":"publisher","first-page":"797","DOI":"10.2174\/1386207323666200428115449","volume":"23","author":"W Hussain","year":"2020","unstructured":"Hussain W, Rasool N, Khan YD (2020) A sequence-based predictor of Zika virus proteins developed by integration of PseAAC and statistical moments. Comb Chem High Throughput Screen 23(8):797\u2013804","journal-title":"Comb Chem High Throughput Screen"},{"key":"773_CR21","doi-asserted-by":"publisher","first-page":"e11581","DOI":"10.7717\/peerj.11581","volume":"9","author":"YD Khan","year":"2021","unstructured":"Khan YD, Khan NS, Naseer S, Butt AH (2021) iSUMOK-PseAAC: prediction of lysine sumoylation sites using statistical moments and Chou\u2019s PseAAC. PeerJ 9:e11581","journal-title":"PeerJ"},{"issue":"3","key":"773_CR22","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1007\/s10989-019-09931-2","volume":"26","author":"AH Butt","year":"2020","unstructured":"Butt AH, Khan YD (2020) Prediction of S-sulfenylation sites using statistical moments based features via CHOU\u2019S 5-step rule. Int J Pept Res Ther 26(3):1291\u20131301","journal-title":"Int J Pept Res Ther"},{"key":"773_CR23","doi-asserted-by":"publisher","first-page":"9520","DOI":"10.1109\/ACCESS.2019.2962002","volume":"8","author":"AH Butt","year":"2019","unstructured":"Butt AH, Khan YD (2019) CanLect-Pred: a cancer therapeutics tool for prediction of target cancerlectins using experiential annotated proteomic sequences. IEEE Access 8:9520\u20139531","journal-title":"IEEE Access"},{"key":"773_CR24","doi-asserted-by":"crossref","unstructured":"AA Shah, YD Khan. SulfoTyr-PseAAC: a machine learning framework to identify sulfotyrosine sites. In 2022 International Conference on Information Science and Communications Technologies (ICISCT), IEEE, 2022, pp. 1\u20135.","DOI":"10.1109\/ICISCT55600.2022.10146792"},{"issue":"5","key":"773_CR25","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1109\/TCBB.2020.2968441","volume":"18","author":"MA Akmal","year":"2020","unstructured":"Akmal MA, Hussain W, Rasool N, Khan YD, Khan SA, Chou K-C (2020) Using Chou\u2019s 5-steps rule to predict O-linked serine glycosylation sites by blending position relative features and statistical moment. IEEE\/ACM Trans Comput Biol Bioinform 18(5):2045\u20132056","journal-title":"IEEE\/ACM Trans Comput Biol Bioinform"},{"issue":"2","key":"773_CR26","doi-asserted-by":"publisher","first-page":"307","DOI":"10.2166\/hydro.2021.093","volume":"23","author":"T Ravichandran","year":"2021","unstructured":"Ravichandran T, Gavahi K, Ponnambalam K, Burtea V, Mousavi SJ (2021) Ensemble-based machine learning approach for improved leak detection in water mains. J Hydroinformatics 23(2):307\u2013323","journal-title":"J Hydroinformatics"},{"issue":"20","key":"773_CR27","doi-asserted-by":"publisher","first-page":"10342","DOI":"10.3390\/app122010342","volume":"12","author":"A Mehmood","year":"2022","unstructured":"Mehmood A et al (2022) Threatening URDU language detection from tweets using machine learning. Appl Sci 12(20):10342","journal-title":"Appl Sci"},{"issue":"28","key":"773_CR28","doi-asserted-by":"publisher","first-page":"46635","DOI":"10.18632\/oncotarget.16743","volume":"8","author":"B Deslouches","year":"2017","unstructured":"Deslouches B, Di YP (2017) Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications. Oncotarget 8(28):46635","journal-title":"Oncotarget"},{"key":"773_CR29","doi-asserted-by":"publisher","first-page":"e1353","DOI":"10.7717\/peerj-cs.1353","volume":"9","author":"MS Farooq","year":"2023","unstructured":"Farooq MS, Naseem A, Rustam F, Ashraf I (2023) Fake news detection in Urdu language using machine learning. PeerJ Comput Sci 9:e1353","journal-title":"PeerJ Comput Sci"},{"key":"773_CR30","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s11269-020-02704-3","volume":"35","author":"A Mosavi","year":"2021","unstructured":"Mosavi A, Sajedi Hosseini F, Choubin B, Goodarzi M, Dineva AA, Rafiei Sardooi E (2021) Ensemble boosting and bagging based machine learning models for groundwater potential prediction. Water Resour Manag 35:23\u201337","journal-title":"Water Resour Manag"},{"key":"773_CR31","first-page":"100154","volume":"6","author":"XY Liew","year":"2021","unstructured":"Liew XY, Hameed N, Clos J (2021) An investigation of XGBoost-based algorithm for breast cancer classification. Mach Learn Appl 6:100154","journal-title":"Mach Learn Appl"},{"key":"773_CR32","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.procs.2021.12.130","volume":"197","author":"N Rahmayanti","year":"2022","unstructured":"Rahmayanti N, Pradani H, Pahlawan M, Vinarti R (2022) Comparison of machine learning algorithms to classify fetal health using cardiotocogram data. Procedia Comput Sci 197:162\u2013171","journal-title":"Procedia Comput Sci"},{"key":"773_CR33","doi-asserted-by":"publisher","first-page":"104458","DOI":"10.1016\/j.chemolab.2021.104458","volume":"220","author":"M Arif","year":"2022","unstructured":"Arif M et al (2022) StackACPred: prediction of anticancer peptides by integrating optimized multiple feature descriptors with stacked ensemble approach. Chemom Intell Lab Syst 220:104458","journal-title":"Chemom Intell Lab Syst"},{"key":"773_CR34","first-page":"1","volume":"2021","author":"A Hansrajh","year":"2021","unstructured":"Hansrajh A, Adeliyi TT, Wing J (2021) Detection of online fake news using blending ensemble learning. Sci Program 2021:1\u201310","journal-title":"Sci Program"},{"key":"773_CR35","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/2465414","author":"Z Ali","year":"2023","unstructured":"Ali Z, Alturise F, Alkhalifah T, Khan YD (2023) IGPred-HDnet: prediction of immunoglobulin proteins using graphical features and the hierarchal deep learning-based approach. Comput Intell Neurosci. https:\/\/doi.org\/10.1155\/2023\/2465414","journal-title":"Comput Intell Neurosci"},{"key":"773_CR36","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5483115","author":"O Barukab","year":"2022","unstructured":"Barukab O, Khan YD, Khan SA, Chou K-C (2022) DNAPred_Prot: identification of DNA-binding proteins using composition-and position-based features. Appl Bionics Biomech. https:\/\/doi.org\/10.1155\/2022\/5483115","journal-title":"Appl Bionics Biomech"},{"issue":"1","key":"773_CR37","doi-asserted-by":"publisher","first-page":"21767","DOI":"10.1038\/s41598-021-99083-5","volume":"11","author":"E Alzahrani","year":"2021","unstructured":"Alzahrani E, Alghamdi W, Ullah MZ, Khan YD (2021) Identification of stress response proteins through fusion of machine learning models and statistical paradigms. Sci Rep 11(1):21767","journal-title":"Sci Rep"},{"issue":"5","key":"773_CR38","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.32604\/biocell.2021.013770","volume":"45","author":"AO Almagrabi","year":"2021","unstructured":"Almagrabi AO, Khan YD, Khan SA (2021) iPhosD-PseAAC: identification of phosphoaspartate sites in proteins using statistical moments and PseAAC. Biocell 45(5):1287","journal-title":"Biocell"},{"issue":"5","key":"773_CR39","doi-asserted-by":"publisher","first-page":"396","DOI":"10.2174\/1574893614666190723114923","volume":"15","author":"S Amanat","year":"2020","unstructured":"Amanat S, Ashraf A, Hussain W, Rasool N, Khan YD (2020) Identification of lysine carboxylation sites in proteins by integrating statistical moments and position relative features via general PseAAC. Curr Bioinforma 15(5):396\u2013407","journal-title":"Curr Bioinforma"},{"issue":"4","key":"773_CR40","doi-asserted-by":"publisher","first-page":"306","DOI":"10.2174\/1389202920666190819091609","volume":"20","author":"O Barukab","year":"2019","unstructured":"Barukab O, Khan YD, Khan SA, Chou K-C (2019) iSulfoTyr-PseAAC: identify tyrosine sulfation sites by incorporating statistical moments via Chou\u2019s 5-steps rule and pseudo components. Curr Genomics 20(4):306\u2013320","journal-title":"Curr Genomics"},{"key":"773_CR41","doi-asserted-by":"publisher","first-page":"114385","DOI":"10.1016\/j.ab.2021.114385","volume":"633","author":"W Alghamdi","year":"2021","unstructured":"Alghamdi W, Alzahrani E, Ullah MZ, Khan YD (2021) 4mC-RF: improving the prediction of 4mC sites using composition and position relative features and statistical moment. Anal Biochem 633:114385","journal-title":"Anal Biochem"},{"issue":"1","key":"773_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-021-91656-8","volume":"11","author":"SJ Malebary","year":"2021","unstructured":"Malebary SJ, Khan YD (2021) Evaluating machine learning methodologies for identification of cancer driver genes. Sci Rep 11(1):1\u201313","journal-title":"Sci Rep"},{"key":"773_CR43","doi-asserted-by":"publisher","first-page":"114069","DOI":"10.1016\/j.ab.2020.114069","volume":"615","author":"S Naseer","year":"2021","unstructured":"Naseer S, Hussain W, Khan YD, Rasool N (2021) Optimization of serine phosphorylation prediction in proteins by comparing human engineered features and deep representations. Anal Biochem 615:114069","journal-title":"Anal Biochem"},{"key":"773_CR44","doi-asserted-by":"publisher","first-page":"113477","DOI":"10.1016\/j.ab.2019.113477","volume":"588","author":"YD Khan","year":"2020","unstructured":"Khan YD, Amin N, Hussain W, Rasool N, Khan SA, Chou K-C (2020) iProtease-PseAAC (2L): a two-layer predictor for identifying proteases and their types using Chou\u2019s 5-step-rule and general PseAAC. Anal Biochem 588:113477","journal-title":"Anal Biochem"}],"container-title":["Journal of Cheminformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13321-023-00773-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13321-023-00773-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13321-023-00773-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T06:18:09Z","timestamp":1700288289000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcheminf.biomedcentral.com\/articles\/10.1186\/s13321-023-00773-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,18]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["773"],"URL":"https:\/\/doi.org\/10.1186\/s13321-023-00773-1","relation":{},"ISSN":["1758-2946"],"issn-type":[{"value":"1758-2946","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,18]]},"assertion":[{"value":"7 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 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 state that they do not have any known financial or personal competing that could potentially influence the research findings presented in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"110"}}