Elucidating the role of matrix porosity and rigidity in glioblastoma type IV progression

The highly infiltrating nature of glioma cells is the major cause for the poor prognosis of brain malignancies. Motility, proliferation, and gene expression of cells in natural and synthetic gels have been analyzed by several authors, yet quantitative studies elucidating the role of matrix porosity and rigidity in the development of whole malignant masses are missing. Here, an experimental\u2010computational framework is introduced to analyze the behavior of U87\u2010MG cells and spheroids in compact hyaluronic acid gels (HA), replicating the brain parenchyma; and fibrous collagen gels (COL), resembling the organized structures of the brain. Experimentally it was observed that individual U87\u2010MG cells in COL assumed an elongated morphology within a few hours post inclusion (p.i.) and travelled longer distances than in HA. As spheroids, U87\u2010MG cells rapidly dispersed into COL resulting in infiltrating regions as large as tumor cores ( 48600 \u3bcm, at 8 days p.i.). Conversely, cells in HA originated smaller and denser infiltrating regions ( 48300 \u3bcm, at 8 days p.i.). Notably, COL tumor core size was only 20% larger than in HA, at longer time points. Computationally, by introducing for the first time the effects of matrix heterogeneity in our numerical simulations, the results confirmed that matrix porosity and its spatial organization are key factors in priming the infiltrating potential of these malignant cells. The experimental\u2010numerical synergy can be used to predict the behavior of neoplastic masses under diverse conditions and the efficacy of combination therapies simultaneously aiming at killing cancer cells and modulating the tumor microenvironment

The role of cell lysis and matrix deposition in tumor growth modeling

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Mechanics of growing tumors: impact of modeling assumptions and boundary conditions on reliability of numerical results

A new computational model based on porous media mechanics has been recently developed for prediction of tumor growth [1]. The tumor mass is modeled as a four-phase system consisting of a solid phase, the extracellular matrix (ECM), and three immiscible fluid phases: the interstitial fluid (IF); the tumor cells (TC) and the healthy cells (HC) (TC and HC are modeled as adhesive fluids). Being the tumor growth strongly influenced by nutrients availability, the diffusion of oxygen coming from the nearby existing vessels is also considered. The mathematical model – governed by mass balance equations of phases and species and by the linear momentum balance equation of the solid scaffold (ECM) – has been discretized in space by finite elements and in the time domain by finite differences, and implemented in Cast3M (FE code of the French Atomic Agency). When in 2011 we started working on this model we introduced two simplifying assumptions: i) a unique pressure was considered for both cell populations (pTC = pHC) and ii) the ECM was assumed rigid. Then, the introduction of relevant constitutive relationships for the pressure difference among each pair of fluid phases (these are based on relative wettability of fluids and fluid–fluid interfacial tensions, see [2]) has allowed for relaxation of the first hypothesis and for a more realistic modeling of cell adhesion and invasion [3]. More recently also the second hypothesis has been relaxed and ECM deformability and its impact on tumor growth can be properly taken into account [4]. Our final aim is to develop a numerical tool which can be a complement for in vivo and in vitro experimental tests and help scientists in better understanding physical interaction between tumor and its surrounding. Hence, we will present our recent efforts to extensively validate the model, the impact of modeling assumptions and boundary conditions on reliability of numerical results, and some perspectives of enhancement of the model

A mechanism contributing to subsidence above gas reservoirs

This paper aims to demonstrate that capillary effects and structural collapse can not be ruled out as significant factors in the development of subsidence occurring above gas fields. These phenomena provide sound explanations for continuing surface settlements when reservoir pore pressures stabilize and for additional settlements occurring even after the end of gas production. Conventional subsidence models fail to simulate this settlement behavior. Capillary effects also explain the lower rock compressibilities observed in gas-bearing strata as compared to the values obtained in the laboratory from fully saturated samples. Taking into account these aspects, the observed subsidence above a reservoir in the North Adriatic basin, Italy, is studied in detail

Interstitial lung disease in patients with antisynthetase syndrome: a retrospective case series study

Purpose: Antisynthetase syndrome (ASS) is a rare systemic autoimmune condition associated to the presence of anti-aminoacyl-tRNA synthetase antibodies. Interstitial lung disease (ILD) is the most prevalent manifestation of ASS and is a major determinant of morbidity and mortality. The aim of this study was to describe the radiological characteristics of patients with ASS-associated-ILD in our institution. Materials and methods: Medical records from 2014 to 2020 were retrospectively reviewed and patients with a diagnosis of ASS and evidence of ILD on HRCT were included. HRCT images were reviewed by two thoracic radiologists in consensus. Five HRCT patterns were defined: cellular non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP), mixed NSIP/OP pattern, acute interstitial pneumonia (AIP) pattern and fibrotic pattern. Descriptive statistics was calculated for all variables. Results: Twenty-two patients with ASS who met inclusion criteria were included. The disease presented with the typical triad of ASS in 45% of patients, 55% had ILD only at the onset. Cellular NSIP was present in 27% of patients, OP in 23%, mixed NSIP/OP in 9%, AIP in 18% and a fibrotic pattern in 23%. Conclusion: HRCT findings in ASS-associated ILD are often non-specific; nevertheless, it is important to consider this diagnosis, especially in patients presenting with acute onset of symptoms

Drug delivery: Experiments, mathematical modelling and machine learning

We address the problem of determining from laboratory experiments the data necessary for a proper modeling of drug delivery and efficacy in anticancer therapy. There is an inherent difficulty in extracting the necessary parameters, because the experiments often yield an insufficient quantity of information. To overcome this difficulty, we propose to combine real experiments, numerical simulation, and Machine Learning (ML) based on Artificial Neural Networks (ANN), aiming at a reliable identification of the physical model factors, e.g. the killing action of the drug. To this purpose, we exploit the employed mathematical-numerical model for tumor growth and drug delivery, together with the ANN - ML procedure, to integrate the results of the experimental tests and feed back the model itself, thus obtaining a reliable predictive tool. The procedure represents a hybrid data-driven, physics-informed approach to machine learning. The physical and mathematical model employed for the numerical simulations is without extracellular matrix (ECM) and healthy cells because of the experimental conditions we reproduce

Treatment of acute respiratory distress with ECMO Experience of the Pneumology Department of Trieste [Terapia dell'insufficienza respiratoria acuta mediante ECMO Esperienza della Pneumologia di Trieste].

Extracorporeal membrane oxygenation (ECMO) is an extracorporeal technique of which provides respiratory support oxygen to patients with severe lung disease which no longer responds to conventional intensive therapy, including invasive mechanical ventilation. ECMO in Italy is usually located in general Intensive Care Units (ICUs), and patients are not managed by the specialist Pneumologists. We show the first year results of the experience of the University Hospital of Trieste where ECMO is located in the Cardiac Surgery ICU and there is a multidisciplinary team which includes Pneumologists cooperating to the management of the patients treated with ECMO due to pulmonary diseases or severe pulmonary hypertension. From January 2010, following the pandemic influenza H1N1, were treated 8 patients for refractory acute respiratory failure (2 women and 6 men, 35 years old on average, 3 with H1N1 infection, 2 with cystic fibrosis, 1 with Wegener's disease, 1 with ARDS and 1 with pulmonary hypertension), with severely lungs disease no longer responsive to conventional intensive therapy. Out of these 8 patients in ECMO 4 died, 3 were discharged from hospital and 1 proceeded to successfully pulmonary transplantation. In Italy and in Europe, it is uncommon to find a multidisciplinary team including Pneumologist to treat patients using ECMO due to severely lungs disease. The Pneumology experience of Trieste was made possible thanks to the expertise reached managing patients with severe acute hypoxemic respiratory failure in the Intensive Respiratory Care Unit

To use or not to use corticosteroids for pneumonia? A clinician's perspective

The use of corticosteroids in the management of pneumonia is still a controversial issue. The physicians in daily clinical practice often use corticosteroids in patients with pneumonia for different reasons all over the world. As an example of real life is the frequent use of corticosteroids to treat patients with pneumonia due to H1N1 pandemic influenza in spite of WHO' statements that clearly discouraged this therapy. In fact, the literature up to august 2012 reported a total of 6,650 patients with pneumonia due to H1N1 virus infection (of whom 2,515 were ICU patients): corticosteroids were used with various dose regimen in 2404 patients (37.8%). The attitude of international guidelines on pneumonia in using steroids do not help the clinician to clearly choice when and how to treat pneumonia with steroids. However, stress doses of corticosteroids are suggested by some major guidelines on community-acquired pneumonia in case of severe episodes with sepsis. To date, there are 10 randomised controlled trials assessing the effectiveness of corticosteroids for community-acquired pneumonia globally involving 1090 participants. Most of the trials adopted stress doses of glucorticoids for 4-7 days. The evidence from these trials taken separately is weak due to limitations of the studies themselves, but a Cochrane review and a systematic review found benefit using prolonged low doses of glucocorticoids in severe community-acquired pneumonia. Moreover, such a strategy decreases vasopressor dependency and appears to be safe. Nevertheless, larger trials with more patients and clinically important end-points were claimed to provide robust evidence. Finally, infection surveillance is critical in patients treated with corticosteroids, and to prevent the rebound phenomenon, the drug should be weaned slowly