Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model

The aim of this study was to visualize the tumor propagation and surrounding mucosal field in radiography-based 3D model for advanced stage HNSCC and combine it with HPV genotyping and miRNA expression characterization of the visualized area. 25 patients with T1-3 clinical stage HNSCC were enrolled in mapping biopsy sampling. Biopsy samples were evaluated for HPV positivity and miR-21-5p, miR-143, miR-155, miR-221-5p expression in Digital Droplet PCR system. Significant miRNA expression differences of HPV positive tumor tissue biopsies were found for miR-21-5p, miR-143 and miR-221-5p compared to the HPV negative tumor biopsy series. Peritumoral mucosa showed patchy pattern alterations of miR-21-5p and miR-155 in HPV positive cases, while gradual change of miR-21-5p and miR-221-5p was seen in HPV negative tumors. In our study we found differences of the miRNA expression patterns among the HPV positive and negative tumorous tissues as well as the surrounding mucosal fields. The CT based 3D models of the cancer field and surrounding mucosal surface can be utilized to improve proper preoperative planning. Complex evaluation of HNSCC tissue organization field can elucidate the clinical and molecular differentiation of HPV positive and negative cases, and enhance effective organ saving therapeutic strategies

Tipping phenomena in typical dynamical systems subjected to parameter drift

Tipping phenomena, i.e. dramatic changes in the possible long-term performance of deterministic systems subjected to parameter drift, are of current interest but have not yet been explored in cases with chaotic internal dynamics. Based on the example of a paradigmatic low-dimensional dissipative system subjected to different scenarios of parameter drifts of non-negligible rates, we show that a number of novel types of tippings can be observed due to the topological complexity underlying general systems. Tippings from and into several coexisting attractors are possible, and one can find fractality-induced tipping, the consequence of the fractality of the scenario-dependent basins of attractions, as well as tipping into a chaotic attractor. Tipping from or through an extended chaotic attractor might lead to random tipping into coexisting regular attractors, and rate-induced tippings appear not abruptly as phase transitions, rather they show up gradually when the rate of the parameter drift is increased. Since chaotic systems of arbitrary time-dependence call for ensemble methods, we argue for a probabilistic approach and propose the use of tipping probabilities as a measure of tipping. We numerically determine these quantities and their parameter dependence for all tipping forms discussed