Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted.     

Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives

Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.     

Local Therapies and Modulation of Tumor Surrounding Stroma in Malignant Pleural Mesothelioma: A Translational Approach

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.     

Rethinking Global-Regulation: world’s law meets artificial intelligence

This article takes a critical look at Machine Translation of legal text, especially global legislation, through the discussion of Global-Regulation, a state of the art online search engine of the world’s legislation in English. Part 2 explains the rationale for an online platform such as Global-Regulation. Part 3 provides a brief account of the history of the development of machine translation, and it describes some of the limits of the use of statistical machine translation for translating legal texts. Part 4 describes Neural Machine Translation (NMT), which is a new generation of machine translation systems. Finally, Parts 5 and 6 outline the ‘big sky’ thoughts on future directions for Global-Regulation.     

The ANNS approach to DEM reconstruction

This research has 6 fundamental aims: (i) to present a modified version of Taylor's interpolation, one that is more effective and faster than the original; (ii) outline the capability of artificial neural networks (ANNs) to perform an optimal functional approximation of the digital elevation model reconstruction from a satellite map, using a small and independent sample of Global Positioning System observations; (iii) demonstrate experimentally how ANNs outperform the traditional and most used algorithm for the height interpolation (Taylor's interpolation); (iv) introduce a new ANN, the Conic Net, able to outperform the results of the classic and more known multilayer perceptron; (v) determine that Conic Nets, even when using Taylor's modified interpolation as input features, are able to optimally approximate the heights with one order of magnitude more than the original satellite map; and (vi) make evident the possibility to interpolate the DEM heights through an ANN, which learns a data set of known points.     

Simulating protection rackets: a case study of the Sicilian Mafia

Protection racketeering groups are powerful, deeply entrenched in multiple societies across the globe, and they harm the societies and economies in which they operate in multiple ways. These reasons make their dynamics important to understand and an objective of both scientific and application-oriented interest. Legal and social norm-based approaches arguably play significant roles in influencing protection racket dynamics. We propose an agent-based simulation model, the Palermo Scenario, to enrich our understanding of these influences and to test the effect of different policies on protection racket dynamics. Our model integrates the legal and the social norm-based approaches and uses a complex normative agent architecture that enables the analysis of both agents’ behaviours and mental normative representations driving behaviour. We demonstrate the usefulness of the model and the benefits of using this complex normative architecture through a case study of the Sicilian Mafia.