Dataset Information

Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.

ABSTRACT: The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clinical, experimental, genomic, immunological and not least epidemiological studies. Only a few studies have described the development of MPNs by mathematical models, and none have addressed the role of inflammation for clonal evolution and disease progression. Herein, we aim at using mathematical modelling to substantiate the concept of chronic inflammation as an important trigger and driver of MPNs.The basics of the model describe the proliferation from stem cells to mature cells including mutations of healthy stem cells to become malignant stem cells. We include a simple inflammatory coupling coping with cell death and affecting the basic model beneath. First, we describe the system without feedbacks or regulatory interactions. Next, we introduce inflammatory feedback into the system. Finally, we include other feedbacks and regulatory interactions forming the inflammatory-MPN model. Using mathematical modeling, we add further proof to the concept that chronic inflammation may be both a trigger of clonal evolution and an important driving force for MPN disease progression. Our findings support intervention at the earliest stage of cancer development to target the malignant clone and dampen concomitant inflammation.

SUBMITTER: Andersen M

PROVIDER: S-EPMC5578482 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.

Andersen Morten M Sajid Zamra Z Pedersen Rasmus K RK Gudmand-Hoeyer Johanne J Ellervik Christina C Skov Vibe V Kjær Lasse L Pallisgaard Niels N Kruse Torben A TA Thomassen Mads M Troelsen Jesper J Hasselbalch Hans Carl HC Ottesen Johnny T JT

PloS one 20170831 8

The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clin ...[more]

PMID: 28859112

Similar Datasets

Project description:BackgroundMany people want to build good habits to become healthier, live longer, or become happier but struggle to change their behavior. Gamification can make behavior change easier by awarding points for the desired behavior and deducting points for its omission.ObjectiveIn this study, we introduced a principled mathematical method for determining how many points should be awarded or deducted for the enactment or omission of the desired behavior, depending on when and how often the person has succeeded versus failed to enact it in the past. We called this approach optimized gamification of behavior change.MethodsAs a proof of concept, we designed a chatbot that applies our optimized gamification method to help people build healthy water-drinking habits. We evaluated the effectiveness of this gamified intervention in a 40-day field experiment with 1 experimental group (n=43) that used the chatbot with optimized gamification and 2 active control groups for which the chatbot's optimized gamification feature was disabled. For the first control group (n=48), all other features were available, including verbal feedback. The second control group (n=51) received no feedback or reminders. We measured the strength of all participants' water-drinking habits before, during, and after the intervention using the Self-Report Habit Index and by asking participants on how many days of the previous week they enacted the desired habit. In addition, all participants provided daily reports on whether they enacted their water-drinking intention that day.ResultsA Poisson regression analysis revealed that, during the intervention, users who received feedback based on optimized gamification enacted the desired behavior more often (mean 14.71, SD 6.57 times) than the active (mean 11.64, SD 6.38 times; P<.001; incidence rate ratio=0.80, 95% CI 0.71-0.91) or passive (mean 11.64, SD 5.43 times; P=.001; incidence rate ratio=0.78, 95% CI 0.69-0.89) control groups. The Self-Report Habit Index score significantly increased in all conditions (P<.001 in all cases) but did not differ between the experimental and control conditions (P>.11 in all cases). After the intervention, the experimental group performed the desired behavior as often as the 2 control groups (P≥.17 in all cases).ConclusionsOur findings suggest that optimized gamification can be used to make digital behavior change interventions more effective.Trial registrationOpen Science Framework (OSF) H7JN8; https://osf.io/h7jn8.

Project description:To assess the feasibility of developing a Combined Clinical and Pharmacogenetic Predictive Test, comprised of multiple single nucleotide polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR).We genotyped SNPs that tagged the whole genome of the parents and children in the Childhood Asthma Management Program (CAMP) and implemented an algorithm using a family-based association test that ranked SNPs by statistical power. The top eight SNPs that were associated with BDR comprised the Pharmacogenetic Predictive Test. The Clinical Predictive Test was comprised of baseline forced expiratory volume in 1 s (FEV1). We evaluated these predictive tests and a Combined Clinical and Pharmacogenetic Predictive Test in three distinct populations: the children of the CAMP trial and two additional clinical trial populations of asthma. Our outcome measure was poor BDR, defined as BDR of less than 20th percentile in each population. BDR was calculated as the percent difference between the prebronchodilator and postbronchodilator (two puffs of albuterol at 180 microg/puff) FEV1 value. To assess the predictive ability of the test, the corresponding area under the receiver operating characteristic curves (AUROCs) were calculated for each population.The AUROC values for the Clinical Predictive Test alone were not significantly different from 0.50, the AUROC of a random classifier. Our Combined Clinical and Pharmacogenetic Predictive Test comprised of genetic polymorphisms in addition to FEV1 predicted poor BDR with an AUROC of 0.65 in the CAMP children (n = 422) and 0.60 (n = 475) and 0.63 (n = 235) in the two independent populations. Both the Combined Clinical and Pharmacogenetic Predictive Test and the Pharmacogenetic Predictive Test were significantly more accurate than the Clinical Predictive Test (AUROC between 0.44 and 0.55) in each of the populations.Our finding that genetic polymorphisms with a clinical trait are associated with BDR suggests that there is promise in using multiple genetic polymorphisms simultaneously to predict which asthmatics are likely to respond poorly to bronchodilators.

Dataset Information

Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.

Publications

Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets