Analysis of the parametric correlation in mathematical modeling of in vitro glioblastoma evolution using copulas

Modeling and simulation are essential tools for better understanding complex biological processes, such as cancer evolution. However, the resulting mathematical models are often highly non-linear and include many parameters, which, in many cases, are difficult to estimate and present strong correlations. Therefore, a proper parametric analysis is mandatory. Following a previous work in which we modeled the in vitro evolution of Glioblastoma Multiforme (GBM) under hypoxic conditions, we analyze and solve here the problem found of parametric correlation. With this aim, we develop a methodology based on copulas to approximate the multidimensional probability density function of the correlated parameters. Once the model is defined, we analyze the experimental setting to optimize the utility of each configuration in terms of gathered information. We prove that experimental configurations with oxygen gradient and high cell concentration have the highest utility when we want to separate correlated effects in our experimental design. We demonstrate that copulas are an adequate tool to analyze highly-correlated multiparametric mathematical models such as those appearing in Biology, with the added value of providing key information for the optimal design of experiments, reducing time and cost in in vivo and in vitro experimental campaigns, like those required in microfluidic models of GBM evolution

SpheroidJ: An Open-Source Set of Tools for Spheroid Segmentation

Background and objectives: Spheroids are the most widely used 3D models for studying the effects of different micro-environmental characteristics on tumour behaviour, and for testing different preclinical and clinical treatments. In order to speed up the study of spheroids, imaging methods that automatically segment and measure spheroids are instrumental; and, several approaches for automatic segmentation of spheroid images exist in the literature. However, those methods fail to generalise to a diversity of experimental conditions. The aim of this work is the development of a set of tools for spheroid segmentation that works in a diversity of settings. Methods: In this work, we have tackled the spheroid segmentation task by first developing a generic segmentation algorithm that can be easily adapted to different scenarios. This generic algorithm has been employed to reduce the burden of annotating a dataset of images that, in turn, has been employed to train several deep learning architectures for semantic segmentation. Both our generic algorithm and the constructed deep learning models have been tested with several datasets of spheroid images where the spheroids were grown under several experimental conditions, and the images acquired using different equipment. Results: The developed generic algorithm can be particularised to different scenarios; however, those particular algorithms fail to generalise to different conditions. By contrast, the best deep learning model, constructed using the HRNet-Seg architecture, generalises properly to a diversity of scenarios. In order to facilitate the dissemination and use of our algorithms and models, we present SpheroidJ, a set of open-source tools for spheroid segmentation. Conclusions: In this work, we have developed an algorithm and trained several models for spheroid segmentation that can be employed with images acquired under different conditions. Thanks to this work, the analysis of spheroids acquired under different conditions will be more reliable and comparable; and, the developed tools will help to advance our understanding of tumour behaviour

Human dirofilariosis of buccal mucosa – First molecularly confirmed case and literature review

When presented in unusual manner, human dirofilariosis is hard to recognize and often leads to misdiagnosis and unjustified use of various medications. Herein, we report a rare case of Dirofilaria infection localized in buccal mucosa.A 45-year-old male, residing in the Central Serbia, developed striking edema of buccal mucosa followed by leucocytosis, with both neutrophylia and eosinophylia. Thirty days after first symptoms occurred, nodule was formed along the lateral edge of right maxilla. Therefore, patient underwent surgical extirpation and subsequent histopathological analysis of the specimen revealed the presence of a nematode. Based on morphological characteristics of detected parasite, the diagnosis of submucosal Dirofilaria repens-like infection was made. The diagnosis was confirmed, being the first case in the world analyzed by molecular methods.So far, only 13 such cases have been reported worldwide and our paper brings attention to rare form of this zoonosis and updates the data about human dirofilariosis in buccal mucosa

5^th, 50^th and 95^th percentile concentrations of micropollutant interpolated from literature and the corresponding drinking water guidelines: Australia [33]; USEPA [35], WHO [34] and EU[36].

<p>5^th, 50^th and 95^th percentile concentrations of micropollutant interpolated from literature and the corresponding drinking water guidelines: Australia [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125979#pone.0125979.ref033" target="_blank">33</a>]; USEPA [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125979#pone.0125979.ref035" target="_blank">35</a>], WHO [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125979#pone.0125979.ref034" target="_blank">34</a>] and EU[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125979#pone.0125979.ref036" target="_blank">36</a>].</p

Plot of volume of water treated per unit area of wetland as a function of wetland area as percent of impervious catchment for: a) Brisbane wetland at the designed hydraulic resident time (HRT = 48 h) and permanent pool depth (PPD = 250 mm), and b) Melbourne wetland at the designed hydraulic resident time (HRT = 72 h) and permanent pool depth (PPD = 250 mm).

<p>Plot of volume of water treated per unit area of wetland as a function of wetland area as percent of impervious catchment for: a) Brisbane wetland at the designed hydraulic resident time (HRT = 48 h) and permanent pool depth (PPD = 250 mm), and b) Melbourne wetland at the designed hydraulic resident time (HRT = 72 h) and permanent pool depth (PPD = 250 mm).</p

Estimated average values (±standard deviation) of different operational variable at different system areas.

<p>Estimated average values (±standard deviation) of different operational variable at different system areas.</p

Flow diagram depicting systematic review search results.

<p>Flow diagram depicting systematic review search results.</p

Proposed validation framework for WSUD stormwater harvesting systems.

<p>Proposed validation framework for WSUD stormwater harvesting systems.</p

Enabling cell recovery from 3D cell culture microfluidic devices for tumour microenvironment biomarker profiling

The tumour microenvironment (TME) has recently drawn much attention due to its profound impact on tumour development, drug resistance and patient outcome. There is an increasing interest in new therapies that target the TME. Nonetheless, most established in vitro models fail to include essential cues of the TME. Microfluidics can be used to reproduce the TME in vitro and hence provide valuable insight on tumour evolution and drug sensitivity. However, microfluidics remains far from well-established mainstream molecular and cell biology methods. Therefore, we have developed a quick and straightforward collagenase-based enzymatic method to recover cells embedded in a 3D hydrogel in a microfluidic device with no impact on cell viability. We demonstrate the validity of this method on two different cell lines in a TME microfluidic model. Cells were successfully retrieved with high viability, and we characterised the different cell death mechanisms via AMNIS image cytometry in our model

Suturas mecânicas

The authors review the use of staplers in General Surgery, mainly in Gastroenterological Surgery highlighting safety and effectiveness. They emphasize that the mechanic anastomosis are a viable technique and in some conditions, the best way to perform the anastomosis. The use of staplers makes surgery faster and easier and complications are, generally related to surgeon's experience in using them. Although its costs are higher compared to handsewn suture, it can make the patient total cost lower