Commentary on the Integration of Model Sharing and Reproducibility Analysis to Scholarly Publishing Workflow in Computational Biomechanics

© 1964-2012 IEEE.Objective: The overall goal of this paper is to demonstrate that dissemination of models and analyses for assessing the reproducibility of simulation results can be incorporated in the scientific review process in biomechanics. Methods: As part of a special issue on model sharing and reproducibility in the IEEE Transactions on Biomedical Engineering, two manuscripts on computational biomechanics were submitted: Rajagopal et al., IEEE Trans. Biomed. Eng., 2016 and Schmitz and Piovesan, IEEE Trans. Biomed. Eng., 2016. Models used in these studies were shared with the scientific reviewers and the public. In addition to the standard review of the manuscripts, the reviewers downloaded the models and performed simulations that reproduced results reported in the studies. Results: There was general agreement between simulation results of the authors and those of the reviewers. Discrepancies were resolved during the necessary revisions. The manuscripts and instructions for download and simulation were updated in response to the reviewers' feedback; changes that may otherwise have been missed if explicit model sharing and simulation reproducibility analysis was not conducted in the review process. Increased burden on the authors and the reviewers, to facilitate model sharing and to repeat simulations, were noted. Conclusion: When the authors of computational biomechanics studies provide access to models and data, the scientific reviewers can download and thoroughly explore the model, perform simulations, and evaluate simulation reproducibility beyond the traditional manuscript-only review process. Significance: Model sharing and reproducibility analysis in scholarly publishing will result in a more rigorous review process, which will enhance the quality of modeling and simulation studies and inform future users of computational models

OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity

Paclitaxel is among the most widely used anticancer drugs and is known to cause a dose-limiting peripheral neurotoxicity, the initiating mechanisms of which remain unknown. Here, we identified the murine solute carrier organic anion–transporting polypeptide B2 (OATP1B2) as a mediator of paclitaxel-induced neurotoxicity. Additionally, using established tests to assess acute and chronic paclitaxel-induced neurotoxicity, we found that genetic or pharmacologic knockout of OATP1B2 protected mice from mechanically induced allodynia, thermal hyperalgesia, and changes in digital maximal action potential amplitudes. The function of this transport system was inhibited by the tyrosine kinase inhibitor nilotinib through a noncompetitive mechanism, without compromising the anticancer properties of paclitaxel. Collectively, our findings reveal a pathway that explains the fundamental basis of paclitaxel-induced neurotoxicity, with potential implications for its therapeutic management