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Jeffrey Gudin,1 Seferina Mavroudi,2,3 Aigli Korfiati,3 Konstantinos Theofilatos,3 Derek Dietze,4 Peter Hurwitz5 1Rutgers New Jersey Medical School, Newark, NJ, USA; 2Department of Nursing, School of Health Rehabilitation Sciences, University of Patras, Pátrai, Greece; 3InSyBio Ltd, Winchester, UK; 4Metrics for Learning LLC, Queen Creek, Arizona, USA; 5Clarity Science LLC, Narragansett, Rhode Island, USACorrespondence: Peter HurwitzClarity Science LLC, 750 Boston Neck Road, Suite 11, Narragansett, RI 02882, USATel +1917 757 0521Fax +1855-891-8303Email peterh@claritysciences.orgPurpose: Chronic pain is a life changing condition, and non-opioid treatments have been lately introduced to overcome the addictive nature of opioid therapies and their side effects. In the present study, we explore the potential of machine learning methods to discriminate chronic pain patients into ones who will benefit from such a treatment and ones who will not, aiming to personalize their treatment.Patients and Methods: In the current study, data from the OPERA study were used, with 631 chronic pain patients answering the Brief Pain Inventory (BPI) validated questionnaire along with supplemental questions before and after a follow-up period. A novel machine learning approach combining multi-objective optimization and support vector regression was used to build prediction models which can predict, using responses in the baseline, the four different outcomes of the study: total drugs change, total interference change, total severity change, and total complaints change. Data were split to training (504 patients) and testing (127 patients) sets and all results are measured on the independent test set.Results: The machine learning models extracted in the present study significantly overcame other state of the art machine learning methods which were deployed for comparative purposes. The experimental results indicated that the machine learning models can predict the outcomes of this study with considerably high accuracy (AUC 73.8– 87.2%) and this allowed their incorporation in a decision support system for the selection of the treatment of chronic pain patients.Conclusion: Results of this study revealed the potential of machine learning for an individualized medicine application for chronic pain therapies. Topical analgesics treatment were proven to be, in general, beneficial but carefully selecting with the suggested individualized medicine decision support system was able to decrease by approximately 10% the patients which would have been subscribed with topical analgesics without having benefits from it.Keywords: individualized medicine, pain therapy, non-opioid treatment, machine learning, predictive analytics, regression, multi-objective optimization, support vector regression

OBJECTIVE:: Adipose tissue is now considered as an endocrine and secretory organ, and some adipocyte factors are thought to play a major role in the induction of insulin resistance in skeletal muscle. Here we tested the hypothesis that the crosstalk between fat and muscle involves activation of inhibitor ?B Kinase (IKK) in the myocytes. MEASUREMENTS:: Adipocyte-conditioned culture medium was added to the muscle cells overnight, or human fat and muscle cells were kept in co-culture. Insulin signalling was subsequently analysed in the myocytes. Involvement of IKK was assessed using I229, a highly specific inhibitor of the IKK complex. RESULTS:: Adipocyte-conditioned medium strongly inhibited insulin-induced serine phosphorylation of Akt in myocytes with a rapid parallel activation of the nuclear factor ?B pathway in these cells. Conditioned medium lacking the perturbation of insulin signalling did not activate NF-?B. Insulin signalling to Akt was completely abrogated under co-culture conditions. The IKK inhibitor I229 did not affect protein expression of Akt, but fully restored insulin action in myocytes subjected to co-culture. CONCLUSION:: These data show that the release of fat cell factors may rapidly induce insulin resistance in human skeletal muscle cells. This process appears to be mediated by an IKK/NF-?B dependent pathway. We suggest that inhibitors of IKK would be of use to counteract the negative crosstalk between fat and muscle.International Journal of Obesity (2004) 28, 985-992. doi:10.1038/sj.ijo.0802701 Published online 22 June 2004 [ABSTRACT FROM AUTHOR]