{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:04:02Z","timestamp":1770066242696,"version":"3.49.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cancer is one of the most widespread diseases around the world with millions of new patients each year. Bladder cancer is one of the most prevalent types of cancer affecting all individuals alike with no obvious \u201cprototypical patient\u201d. The current standard treatment for BC follows a routine weekly Bacillus Calmette-Gu\u00e9rin (BCG) immunotherapy-based therapy protocol which is applied to all patients alike. The clinical outcomes associated with BCG treatment vary significantly among patients due to the biological and clinical complexity of the interaction between the immune system, treatments, and cancer cells. In this study, we take advantage of the patient\u2019s socio-demographics to offer a personalized mathematical model that describes the clinical dynamics associated with BCG-based treatment. To this end, we adopt a well-established BCG treatment model and integrate a machine learning component to temporally adjust and reconfigure key parameters within the model thus promoting its personalization. Using real clinical data, we show that our personalized model favorably compares with the original one in predicting the number of cancer cells at the end of the treatment, with<jats:inline-formula><jats:alternatives><jats:tex-math>$$14.8\\%$$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mrow><mml:mn>14.8<\/mml:mn><mml:mo>%<\/mml:mo><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula>improvement, on average.<\/jats:p>","DOI":"10.1038\/s41598-023-45581-7","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T16:02:49Z","timestamp":1698768169000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mathematical modeling of BCG-based bladder cancer treatment using socio-demographics"],"prefix":"10.1038","volume":"13","author":[{"given":"Elizaveta","family":"Savchenko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel","family":"Rosenfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Bunimovich-Mendrazitsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"45581_CR1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1097\/CM9.0000000000001474","volume":"134","author":"W Cao","year":"2021","unstructured":"Cao, W. et al. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020. Chin. Med. J. 134, 783\u2013791 (2021).","journal-title":"Chin. Med. J."},{"key":"45581_CR2","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray, F. et al. Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394\u2013424 (2018).","journal-title":"CA Cancer J. Clin."},{"key":"45581_CR3","volume":"7","author":"M Mohammadian","year":"2020","unstructured":"Mohammadian, M. et al. Recent patterns of bladder cancer incidence and mortality: A global overview. World Cancer Res. J. 7, e1464 (2020).","journal-title":"World Cancer Res. J."},{"key":"45581_CR4","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1093\/carcin\/bgi310","volume":"27","author":"MA Knowles","year":"2006","unstructured":"Knowles, M. A. Molecular subtypes of bladder cancer: Jekyll and hyde or chalk and cheese?. Carcinogenesis 27, 361\u2013373 (2006).","journal-title":"Carcinogenesis"},{"key":"45581_CR5","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1016\/S0140-6736(03)13580-5","volume":"361","author":"C Vale","year":"2003","unstructured":"Vale, C. Neoadjuvant chemotherapy in invasive bladder cancer: A systematic review and meta-analysis. Lancet 361, 1927\u20131934 (2003).","journal-title":"Lancet"},{"key":"45581_CR6","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.eursup.2008.04.006","volume":"7","author":"G Urdaneta","year":"2008","unstructured":"Urdaneta, G., Solsona, E. & Palou, J. Intravesical chemotherapy and BCG for the treatment of bladder cancer: Evidence and opinion. Eur. Urol. Suppl. 7, 542\u2013547 (2008).","journal-title":"Eur. Urol. Suppl."},{"key":"45581_CR7","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/S0022-5347(17)58737-6","volume":"116","author":"A Morales","year":"1976","unstructured":"Morales, A., Eidinger, D. & Bruce, A. Intracavity Bacillus Calmette-Gu\u00e9rin in the treatment of superficial bladder tumors. J. Urol. 116, 180\u2013183 (1976).","journal-title":"J. Urol."},{"key":"45581_CR8","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1200\/JCO.1988.6.9.1450","volume":"6","author":"HW Herr","year":"1988","unstructured":"Herr, H. W. et al. Bacillus Calmette-Gu\u00e9rin therapy alters the progression of superficial bladder cancer. J. Clin. Oncol. 6, 1450\u20131455 (1988).","journal-title":"J. Clin. Oncol."},{"key":"45581_CR9","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nrurol.2014.15","volume":"11","author":"G Redelman-Sidi","year":"2014","unstructured":"Redelman-Sidi, G., Glickman, M. & Bochner, B. The mechanism of action of BCG therapy for bladder cancer\u2014A current perspective. Nat. Rev. Urol. 11, 153\u2013162 (2014).","journal-title":"Nat. Rev. Urol."},{"key":"45581_CR10","first-page":"341","volume":"26","author":"MP Simons","year":"2008","unstructured":"Simons, M. P., O\u2019Donnell, M. A. & Griffith, T. S. Role of neutrophils in BCG immunotherapy for bladder cancer. Urol. Oncol. Semin. Orig. Investig. 26, 341\u2013345 (2008).","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"45581_CR11","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1515\/ijnsns-2018-0181","volume":"20","author":"E Guzev","year":"2019","unstructured":"Guzev, E., Halachmi, S. & Bunimovich-Mendrazitsky, S. Additional extension of the mathematical model for BCG immunotherapy of bladder cancer and its validation by auxiliary tool. Int. J. Nonlinear Sci. Numer. Simul. 20, 675\u2013689 (2019).","journal-title":"Int. J. Nonlinear Sci. Numer. Simul."},{"key":"45581_CR12","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.jtbi.2007.04.003","volume":"247","author":"F Castiglione","year":"2007","unstructured":"Castiglione, F. & Piccoli, B. Cancer immunotherapy, mathematical modeling and optimal control. J. Theor. Biol. 247, 723\u2013732 (2007).","journal-title":"J. Theor. Biol."},{"key":"45581_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100382","volume":"2","author":"H Mi","year":"2021","unstructured":"Mi, H. et al. Predictive models of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer using nuclear morphology and tissue architecture. Cell Rep. Med. 2, 100382 (2021).","journal-title":"Cell Rep. Med."},{"key":"45581_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0210976","volume":"14","author":"Z Hasnain","year":"2019","unstructured":"Hasnain, Z. et al. Machine learning models for predicting post-cystectomy recurrence and survival in bladder cancer patients. PLoS One 14, 1\u201315 (2019).","journal-title":"PLoS One"},{"key":"45581_CR15","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nrc2808","volume":"10","author":"HM Byrne","year":"2010","unstructured":"Byrne, H. M. Dissecting cancer through mathematics: From the cell to the animal model. Nat. Rev. Cancer 10, 221\u2013230 (2010).","journal-title":"Nat. Rev. Cancer"},{"key":"45581_CR16","doi-asserted-by":"crossref","unstructured":"Lazebnik, T., Weitman, C. & Kaminka, G.\u00a0A. Generic purpose pharmacokinetics-pharmacodynamics mathematical model for nanomedicine targeted drug delivery: Mouse model. bioRxiv (2022).","DOI":"10.1101\/2022.07.13.499855"},{"key":"45581_CR17","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/BF02460644","volume":"56","author":"VA Kuznetsov","year":"1994","unstructured":"Kuznetsov, V. A., Makalkin, I. A., Taylor, M. A. & Perelson, A. S. Nonlinear dynamics of immunogenic tumours: Parameter estimation and global bifurcation analysis. Bull. Math. Biol. 56, 295\u2013321 (1994).","journal-title":"Bull. Math. Biol."},{"key":"45581_CR18","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/S0022-5347(05)66518-4","volume":"165","author":"JC Kim","year":"2001","unstructured":"Kim, J. C. & Steinberg, G. D. The limits of Bacillus Calmette-Gu\u00e9rin for carcinoma in situ of the bladder. J. Urol. 165, 745\u2013756 (2001).","journal-title":"J. Urol."},{"key":"45581_CR19","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s002850050127","volume":"37","author":"D Kirschner","year":"1998","unstructured":"Kirschner, D. & Panetta, J. C. Modeling immunotherapy of the tumor-immune interaction. J. Math. Biol. 37, 235\u2013252 (1998).","journal-title":"J. Math. Biol."},{"key":"45581_CR20","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/BF02460591","volume":"58","author":"JC Panetta","year":"1996","unstructured":"Panetta, J. C. A mathematical model of periodically pulsed chemotherapy: Tumor recurrence and metastasis in a competitive environment. Bull. Math. Biol. 58, 425\u2013447 (1996).","journal-title":"Bull. Math. Biol."},{"key":"45581_CR21","doi-asserted-by":"publisher","first-page":"7950","DOI":"10.1158\/0008-5472.CAN-05-0564","volume":"65","author":"LG De Pillis","year":"2005","unstructured":"De Pillis, L. G., Radunskaya, A. E. & Wiseman, C. L. A validated mathematical model of cell-mediated immune response to tumor growth. Cancer Res. 65, 7950\u20137958 (2005).","journal-title":"Cancer Res."},{"key":"45581_CR22","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.compbiomed.2014.12.022","volume":"58","author":"S Bunimovich-Mendrazitsky","year":"2014","unstructured":"Bunimovich-Mendrazitsky, S., Pisarev, V. & Kashdan, E. Modeling and simulation of a low-grade urinary bladder carcinoma. Comput. Biol. Med. 58, 118\u2013129 (2014).","journal-title":"Comput. Biol. Med."},{"key":"45581_CR23","doi-asserted-by":"publisher","first-page":"529","DOI":"10.3934\/mbe.2011.8.529","volume":"8","author":"S Bunimovich-Mendrazitsky","year":"2011","unstructured":"Bunimovich-Mendrazitsky, S. & Goltser, Y. Use of quasi-normal form to examine stability of tumor-free equilibrium in a mathematical model of BCG treatment of bladder cancer. Math. Biosci. Eng. 8, 529\u2013547 (2011).","journal-title":"Math. Biosci. Eng."},{"key":"45581_CR24","doi-asserted-by":"publisher","first-page":"5346","DOI":"10.3934\/mbe.2019267","volume":"16","author":"O Nave","year":"2019","unstructured":"Nave, O., Hareli, S., Elbaz, M., Iluz, I. H. & Bunimovich-Mendrazitsky, S. BCG and IL-2 model for bladder cancer treatment with fast and slow dynamics based on SPVF method-stability analysis. Math. Biosci. Eng. 16, 5346\u20135379 (2019).","journal-title":"Math. Biosci. Eng."},{"key":"45581_CR25","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1007\/s11538-007-9195-z","volume":"69","author":"S Bunimovich-Mendrazitsky","year":"2007","unstructured":"Bunimovich-Mendrazitsky, S., Shochat, E. & Stone, L. Mathematical model of BCG immunotherapy in superficial bladder cancer. Bull. Math. Biol. 69, 1847\u20131870 (2007).","journal-title":"Bull. Math. Biol."},{"key":"45581_CR26","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.3390\/math11051192","volume":"11","author":"A Yaniv-Rosenfeld","year":"2023","unstructured":"Yaniv-Rosenfeld, A., Savchenko, E., Rosenfeld, A. & Lazebnik, T. Scheduling BCG and IL-2 injections for bladder cancer immunotherapy treatment. Mathematics 11, 1192 (2023).","journal-title":"Mathematics"},{"key":"45581_CR27","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.3390\/cells11152372","volume":"15","author":"T Lazebnik","year":"2022","unstructured":"Lazebnik, T. Cell-level spatio-temporal model for a Bacillus Calmette-Gu\u00e9rin-based immunotherapy treatment protocol of superficial bladder cancer. Cells 15, 2372 (2022).","journal-title":"Cells"},{"key":"45581_CR28","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002707","volume":"9","author":"E Yl\u00f6sm\u00e4ki","year":"2021","unstructured":"Yl\u00f6sm\u00e4ki, E. et al. Novel personalized cancer vaccine platform based on Bacillus Calmette-Guerin. J. Immunother. Cancer 9, e002707 (2021).","journal-title":"J. Immunother. Cancer"},{"key":"45581_CR29","volume-title":"Mathematical and Computational Oncology","author":"T Lazebnik","year":"2021","unstructured":"Lazebnik, T. & Bunimovich-Mendrazitsky, S. Improved geometric configuration for the bladder cancer BCG-based immunotherapy treatment model. In Mathematical and Computational Oncology (eds Bebis, G. et al.) (ISMCO, 2021)."},{"key":"45581_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0056327","volume":"8","author":"CA Rentsch","year":"2013","unstructured":"Rentsch, C. A. et al. BCG-mediated bladder cancer immunotherapy: Identifying determinants of treatment response using a calibrated mathematical model. PLoS One 8, 1\u20136 (2013).","journal-title":"PLoS One"},{"key":"45581_CR31","first-page":"1059","volume":"13","author":"KE Starkov","year":"2016","unstructured":"Starkov, K. E. & Bunimovich-Mendrazitsky, S. Dynamical properties and tumor clearance conditions for a nine-dimensional model of bladder cancer immunotherapy. Am. Inst. Math. Sci. 13, 1059\u20131075 (2016).","journal-title":"Am. Inst. Math. Sci."},{"key":"45581_CR32","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/imammb\/dqv007","volume":"33","author":"S Bunimovich-Mendrazitsky","year":"2015","unstructured":"Bunimovich-Mendrazitsky, S., Halachmi, S. & Kronik, N. Improving Bacillus Calmette Guerin (BCG) immunotherapy for bladder cancer by adding interleukin-2 (IL-2): A mathematical model. Math. Med. Biol. 33, 159\u2013188 (2015).","journal-title":"Math. Med. Biol."},{"key":"45581_CR33","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1002\/path.5306","volume":"249","author":"D Song","year":"2019","unstructured":"Song, D. et al. Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches. J. Pathol. 249, 151\u2013165 (2019).","journal-title":"J. Pathol."},{"key":"45581_CR34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000362","volume":"5","author":"S Eikenberry","year":"2009","unstructured":"Eikenberry, S., Thalhauser, C. & Kuang, Y. Tumor-immune interaction, surgical treatment, and cancer recurrence in a mathematical model of melanoma. PLoS Comput. Biol. 5, e1000362 (2009).","journal-title":"PLoS Comput. Biol."},{"key":"45581_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.biosystems.2020.104319","volume":"200","author":"T Lazebnik","year":"2021","unstructured":"Lazebnik, T., Bunimovich-Mendrazitsky, S. & Haroni, N. PDE based geometry model for BCG immunotherapy of bladder cancer. Biosystems 200, 104319 (2021).","journal-title":"Biosystems"},{"key":"45581_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/imammb\/21.1.1","volume":"21","author":"A Matzavinos","year":"2004","unstructured":"Matzavinos, A., Chaplain, M. A. & Kuznetsov, V. A. Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour. Math. Med. Biol. 21, 1\u201334 (2004).","journal-title":"Math. Med. Biol."},{"key":"45581_CR37","doi-asserted-by":"publisher","first-page":"9653873","DOI":"10.1155\/2018\/9653873","volume":"2018","author":"L Shaikhet","year":"2018","unstructured":"Shaikhet, L. & Bunimovich-Mendrazitsky, S. Stability analysis of delayed immune response BCG infection in bladder cancer treatment model by stochastic perturbations. Comput. Math. Methods Med. 2018, 9653873 (2018).","journal-title":"Comput. Math. Methods Med."},{"key":"45581_CR38","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/S0022-5347(05)68633-8","volume":"162","author":"C Durek","year":"1999","unstructured":"Durek, C. et al. Bacillus-Calmette-Guerin (BCG) and 3d tumors: An in vitro model for the study of adhesion and invasion. J. Urol. 162, 600\u2013605 (1999).","journal-title":"J. Urol."},{"key":"45581_CR39","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12911-022-01877-8","volume":"22","author":"T Lazebnik","year":"2022","unstructured":"Lazebnik, T., Bahouth, Z., Bunimovich-Mendrazitsky, S. & Halachmi, S. Predicting acute kidney injury following open partial nephrectomy treatment using sat-pruned explainable machine learning model. BMC Med. Inform. Decis. Making 22, 133 (2022).","journal-title":"BMC Med. Inform. Decis. Making"},{"key":"45581_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.xops.2022.100258","volume":"3","author":"YA Veturi","year":"2023","unstructured":"Veturi, Y. A. et al. SynthEye: Investigating the impact of synthetic data on artificial intelligence-assisted gene diagnosis of inherited retinal disease. Ophthalmol. Sci. 3, 100258 (2023).","journal-title":"Ophthalmol. Sci."},{"key":"45581_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/ITT.S202006","volume":"13","author":"S Guallar-Garrido","year":"2020","unstructured":"Guallar-Garrido, S. & Julian, E. Bacillus Calmette-Guerin (BCG) therapy for bladder cancer: An update. Immunotargets Ther. 13, 1\u201311 (2020).","journal-title":"Immunotargets Ther."},{"key":"45581_CR42","first-page":"1188","volume":"16","author":"J Lee","year":"2015","unstructured":"Lee, J., Won, K. K., Hyun, C. S., Jimi, H. & Ho, P. S. Systematic review and meta-analysis of studies evaluating diagnostic test accuracy: A practical review for clinical researchers-part ii. statistical methods of meta-analysis. KJR 16, 1188\u20131196 (2015).","journal-title":"KJR"},{"key":"45581_CR43","first-page":"105","volume-title":"Extended Finite State Machine","author":"VS Alagar","year":"2011","unstructured":"Alagar, V. S. & Periyasamy, K. Extended Finite State Machine 105\u2013128 (Springer, 2011)."},{"key":"45581_CR44","unstructured":"Kohavi, R. A study of cross validation and bootstrap for accuracy estimation and model select. In International Joint Conference on Artificial Intelligence (1995)."},{"key":"45581_CR45","doi-asserted-by":"crossref","unstructured":"Savchenko, E., Rosenfeld, A. & Bunimovich-Mendrazitsky, S. Optimizing SMS reminder campaigns for pre- and post-diagnosis cancer check-ups using socio-demographics: An in-silco investigation into bladder cancer. arXiv (2023).","DOI":"10.1016\/j.seps.2024.102047"},{"key":"45581_CR46","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1090\/qam\/10667","volume":"2","author":"HB Curry","year":"1944","unstructured":"Curry, H. B. The method of steepest descent for non-linear minimization problems. Q. Appl. Math. 2, 258\u2013261 (1944).","journal-title":"Q. Appl. Math."},{"key":"45581_CR47","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1137\/S1064827599350320","volume":"22","author":"DW Zingg","year":"2000","unstructured":"Zingg, D. W. Comparison of high-accuracy finite-difference methods for linear wave propagation. SIAM J. Sci. Comput. 22, 476\u2013502 (2000).","journal-title":"SIAM J. Sci. Comput."},{"key":"45581_CR48","unstructured":"Ruder, S. An overview of gradient descent optimization algorithms. arXiv (2016)."},{"key":"45581_CR49","doi-asserted-by":"crossref","unstructured":"Chemchem, A., Alin, F. & Krajecki, M. Combining smote sampling and machine learning for forecasting wheat yields in France. In 2019 IEEE Second International Conference on Artificial Intelligence and Knowledge Engineering (AIKE), 9\u201314 (2019).","DOI":"10.1109\/AIKE.2019.00010"},{"key":"45581_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0270318","volume":"18","author":"DL Krongauz","year":"2023","unstructured":"Krongauz, D. L. & Lazebnik, T. Collective evolution learning model for vision-based collective motion with collision avoidance. PLoS One 18, 1\u201322 (2023).","journal-title":"PLoS One"},{"key":"45581_CR51","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.rse.2007.04.002","volume":"111","author":"RE NcRoberts","year":"2007","unstructured":"NcRoberts, R. E., Tomppo, E. O., Finley, A. O. & Heikkinen, J. Estimating areal means and variances of forest attributes using the k-nearest neighbors technique and satellite imagery. Remote Sens. Environ. 111, 466\u2013480 (2007).","journal-title":"Remote Sens. Environ."},{"key":"45581_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1021\/ci0342472","volume":"44","author":"DM Hawkins","year":"2004","unstructured":"Hawkins, D. M. The problem of overfitting. J. Chem. Inf. Comput. Sci. 44, 1\u201312 (2004).","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"45581_CR53","unstructured":"Olson, R.\u00a0S. & Moore, J.\u00a0H. Tpot: A tree-based pipeline optimization tool for automating machine learning. In Workshop on Automatic Machine Learning, 66\u201374 (PMLR, 2016)."},{"key":"45581_CR54","doi-asserted-by":"publisher","DOI":"10.1142\/1988","volume-title":"Uniqueness and Nonuniqueness Criteria for Ordinary Differential Equations","author":"RP Agarwal","year":"1993","unstructured":"Agarwal, R. P. & Lakshmikantham, V. Uniqueness and Nonuniqueness Criteria for Ordinary Differential Equations (World Scientific, 1993)."},{"key":"45581_CR55","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jtbi.2011.02.008","volume":"277","author":"S Bunimovich-Mendrazitsky","year":"2011","unstructured":"Bunimovich-Mendrazitsky, S., Gluckman, J. C. & Chaskalovic, J. A mathematical model of combined Bacillus Calmette-Guerin (BCG) and interleukin (IL)-2 immunotherapy of superficial bladder cancer. J. Theor. Biol. 277, 27\u201340 (2011).","journal-title":"J. Theor. Biol."},{"key":"45581_CR56","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198502791.001.0001","volume-title":"Numerical Analysis: A Mathematical Introduction","author":"M Schatzman","year":"2002","unstructured":"Schatzman, M. Numerical Analysis: A Mathematical Introduction (Oxford University Press, 2002)."},{"key":"45581_CR57","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1017\/S030500410004072X","volume":"58","author":"P Parks","year":"1962","unstructured":"Parks, P. A new proof of the Routh\u2013Hurwitz stability criterion using the second method of Liapunov. Math. Proc. Camb. Philos. Soc. 58, 694\u2013702 (1962).","journal-title":"Math. Proc. Camb. Philos. Soc."},{"key":"45581_CR58","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1006\/jmaa.1993.1206","volume":"176","author":"N Sternberg","year":"1993","unstructured":"Sternberg, N. A Hartman\u2013Grobman theorem for a class of retarded functional differential equations. J. Math. Anal. Appl. 176, 156\u2013165 (1993).","journal-title":"J. Math. Anal. Appl."},{"key":"45581_CR59","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1515\/ijnsns-2018-0181","volume":"20","author":"E Guzev","year":"2019","unstructured":"Guzev, E., Halachmi, S. & Bunimovich-Mendrazitsky, S. Additional extension of the mathematical model for BCG immunotherapy of bladder cancer and its validation by auxiliary tool. Int. J. Nonlinear Sci. Numer. Simul. 20, 675\u2013689 (2019).","journal-title":"Int. J. Nonlinear Sci. Numer. Simul."},{"key":"45581_CR60","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2004.03.002","volume":"26","author":"M Lommatzschm","year":"2005","unstructured":"Lommatzschm, M. et al. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol. Aging 26, 115\u2013123 (2005).","journal-title":"Neurobiol. Aging"},{"key":"45581_CR61","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1111\/j.1939-1676.1992.tb00330.x","volume":"6","author":"AM Norris","year":"1992","unstructured":"Norris, A. M. et al. Canine bladder and urethral tumors: A retrospective study of 115 cases (1980\u20131985). J. Vet. Intern. Med. 6, 145\u2013153 (1992).","journal-title":"J. Vet. Intern. Med."},{"key":"45581_CR62","first-page":"47","volume":"5","author":"DW Knapp","year":"2000","unstructured":"Knapp, D. W. et al. Naturally-occurring canine transitional cell carcinoma of the urinary bladder a relevant model of human invasive bladder cancer. Urol. Oncol. Semin. Orig. Investig. 5, 47\u201359 (2000).","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"45581_CR63","first-page":"260","volume":"28","author":"J Stella","year":"2010","unstructured":"Stella, J. et al. Differential ectonucleotidase expression in human bladder cancer cell lines. Urol. Oncol. Semin. Orig. Investig. 28, 260\u2013267 (2010).","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"45581_CR64","doi-asserted-by":"crossref","unstructured":"Kalpi\u0107, D., Hlupi\u0107, N. & Lovri\u0107, M. Student\u2019s t-Tests, 1559\u20131563 (2011).","DOI":"10.1007\/978-3-642-04898-2_641"},{"key":"45581_CR65","doi-asserted-by":"publisher","DOI":"10.4135\/9781412983419","volume-title":"ANOVA: Repeated Measures","author":"ER Girden","year":"1992","unstructured":"Girden, E. R. ANOVA: Repeated Measures (Sage, 1992)."},{"key":"45581_CR66","first-page":"86","volume":"22","author":"R Nedeb","year":"2004","unstructured":"Nedeb, R. & Messing, E. M. Gender, racial and age differences in bladder cancer incidence and mortality. Urol. Oncol. Semin. Orig. Investig. 22, 86\u201392 (2004).","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"45581_CR67","doi-asserted-by":"publisher","first-page":"5751647","DOI":"10.1155\/2016\/5751647","volume":"2016","author":"S Sasikumar","year":"2016","unstructured":"Sasikumar, S. et al. Pathological characteristics of primary bladder carcinoma treated at a tertiary care hospital and changing demographics of bladder cancer in Sri Lanka. Adv. Urol. 2016, 5751647 (2016).","journal-title":"Adv. Urol."},{"key":"45581_CR68","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s11934-018-0860-6","volume":"19","author":"SK Bhanvadia","year":"2018","unstructured":"Bhanvadia, S. K. Bladder cancer survivorship. Curr. Urol. Rep. 19, 111 (2018).","journal-title":"Curr. Urol. Rep."},{"key":"45581_CR69","first-page":"203","volume":"26","author":"T Lazebnik","year":"2020","unstructured":"Lazebnik, T., Yanetz, S., Bunimovich-Mendrazitsky, S. & Haroni, N. Treatment of bladder cancer using BCG immunotherapy: PDE modeling. Partial Differ. Equ. 26, 203\u2013219 (2020).","journal-title":"Partial Differ. Equ."},{"key":"45581_CR70","doi-asserted-by":"crossref","unstructured":"Rosenfeld, A. & Kraus, S. Predicting Human Decision-Making (2018).","DOI":"10.1007\/978-3-031-01578-6"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-45581-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-45581-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-45581-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T03:59:02Z","timestamp":1730433542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-45581-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["45581"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-45581-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]},"assertion":[{"value":"25 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":"31 October 2023","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":"18754"}}