Khalifa University

About: Khalifa University is a education organization based out in Abu Dhabi, United Arab Emirates. It is known for research contribution in the topics: Computer science & Adsorption. The organization has 3752 authors who have published 10909 publications receiving 141629 citations.

Immune Checkpoints in Circulating and Tumor-Infiltrating CD4+ T Cell Subsets in Colorectal Cancer Patients.

Abstract: Blockade of inhibitory immune checkpoints (ICs) is a promising therapeutic approach; however, it has shown limited success in some cancers including colorectal cancer (CRC). The tumor microenvironment (TME) is largely responsible for response to therapy, and its constituents may provide robust biomarkers for successful immunotherapeutic approaches. In this study, we performed phenotypical characterization and critical analyses of key inhibitory ICs and T regulatory cell (Treg)-related markers on CD4+ T cell subsets in CRC patients, and compared with normal colon tissues and peripheral blood from the same patients. We also investigated correlations between the levels of different CD4+ T cell subsets and the clinicopathologic features including disease stage and tumor budding. We found a significant increase in the levels of CD4+FoxP3+Helios+ T cells, which represent potentially highly immunosuppressive Tregs, in the CRC TME. Additionally, tumor-infiltrating CD4+ T cells upregulated programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), T cell immunoglobulin and mucin domain-3 (TIM-3) and lymphocyte-activation gene 3 (LAG-3). We also characterized the expression of PD-1, CTLA-4, TIM-3, and LAG-3 on different CD4+FoxP3−/+Helios−/+ T cell subsets. Interestingly, we found that CTLA-4, TIM-3, and LAG-3 were mainly co-expressed on FoxP3+Helios+ Tregs in the TME. Additionally, FoxP3high Tregs expressed higher levels of Helios, CTLA-4 and TIM-3 than FoxP3low T cells. These results highlight the significance of Tregs in the CRC TME and suggest that Tregs may hamper response to IC blockade in CRC patients, but effects of different IC inhibition regimes on Treg levels or activity warrants further investigations. We also found that CD4+CTLA-4+ T cells in circulation are increased in patients with advanced disease stage. This study simultaneously provides important insights into the differential levels of CD4+ T cell subpopulations and IC expression in CRC TME, compared to periphery and associations with clinicopathologic features, which could be used as potential biomarkers for CRC progression and response to therapy.

Using Zebrafish for Investigating the Molecular Mechanisms of Drug-Induced Cardiotoxicity

Abstract: Over the last decade, the zebrafish (Danio rerio) has emerged as a model organism for cardiovascular research. Zebrafish have several advantages over mammalian models. For instance, the experimental cost of using zebrafish is comparatively low; the embryos are transparent, develop externally, and have high fecundity making them suitable for large-scale genetic screening. More recently, zebrafish embryos have been used for the screening of a variety of toxic agents, particularly for cardiotoxicity testing. Zebrafish has been shown to exhibit physiological responses that are similar to mammals after exposure to medicinal drugs including xenobiotics, hormones, cancer drugs, and also environmental pollutants, including pesticides and heavy metals. In this review, we provided a summary for recent studies that have used zebrafish to investigate the molecular mechanisms of drug-induced cardiotoxicity. More specifically, we focused on the techniques that were exploited by us and others for cardiovascular toxicity assessment and described several microscopic imaging and analysis protocols that are being used for the estimation of a variety of cardiac hemodynamic parameters.

Isocitrate dehydrogenase (IDH) status prediction in histopathology images of gliomas using deep learning.

Abstract: Mutations in isocitrate dehydrogenase genes IDH1 and IDH2 are frequently found in diffuse and anaplastic astrocytic and oligodendroglial tumours as well as in secondary glioblastomas. As IDH is a very important prognostic, diagnostic and therapeutic biomarker for glioma, it is of paramount importance to determine its mutational status. The haematoxylin and eosin (H&E) staining is a valuable tool in precision oncology as it guides histopathology-based diagnosis and proceeding patient’s treatment. However, H&E staining alone does not determine the IDH mutational status of a tumour. Deep learning methods applied to MRI data have been demonstrated to be a useful tool in IDH status prediction, however the effectiveness of deep learning on H&E slides in the clinical setting has not been investigated so far. Furthermore, the performance of deep learning methods in medical imaging has been practically limited by small sample sizes currently available. Here we propose a data augmentation method based on the Generative Adversarial Networks (GAN) deep learning methodology, to improve the prediction performance of IDH mutational status using H&E slides. The H&E slides were acquired from 266 grade II-IV glioma patients from a mixture of public and private databases, including 130 IDH-wildtype and 136 IDH-mutant patients. A baseline deep learning model without data augmentation achieved an accuracy of 0.794 (AUC = 0.920). With GAN-based data augmentation, the accuracy of the IDH mutational status prediction was improved to 0.853 (AUC = 0.927) when the 3,000 GAN generated training samples were added to the original training set (24,000 samples). By integrating also patients’ age into the model, the accuracy improved further to 0.882 (AUC = 0.931). Our findings show that deep learning methodology, enhanced by GAN data augmentation, can support physicians in gliomas’ IDH status prediction.

The impact of long term freezing on the mechanical properties of porcine aortic tissue.

Abstract: Background Preservation of the native artery׳s functionality can be important in both clinical and experimental applications. Although, simple cryopreservation techniques offer an attractive solution to this problem, the extent to which freezing affects the tissue׳s properties is widely debated. Earlier assessments of the mechanical properties post-freezing have been limited by one or more of the following: small sample numbers, uncontrolled inter-specimen/animal variability, failure to account for the impact of potential errors in thickness measurements, short storage times and uniaxial test methods. Material and methods Biaxial mechanical tests were performed on porcine aortic samples (n=89) extracted from superior, middle and inferior regions of five aortas, stored in isotonic saline at −20°C for 1 day, 1 week, 1, 6 and 12 months, thawed and retested. The sample׳s weight and thickness were also measured pre and post-freezing. A total of 178 tests were performed and elastic modulus was assessed by calculating the slope of the Cauchy stress–stretch curve at the low and high stretch regions in both the circumferential (θ) and longitudinal (L) directions. Results The weight of the samples increased post-freezing. However, in general, no significant difference was found between the elastic modulus of porcine aortic tissue before and after freezing at −20°C and was unaffected by storage time. Although more accurate measuring instruments are warranted to confirm this finding, minor changes to the elastic modulus as a result of freezing were negatively correlated with regional variances i.e. changes in the elastic modulus decreased from the superior to the inferior region. Conclusions These results indicate that for applications which require preservation of the gross mechanical properties, storing the tissue at −20 °C in isotonic saline, for an extended period of time, is acceptable.