An application of Answer Set Programming in Distributed Architectures: ASP Microservices

We propose an approach to the definition of microservices with an Answer Set Programming (ASP) `core', where microservices are a successful abstraction for designing distributed applications as suites of independently deployable interacting components. Such ASP-based components might be employed in distributed architectures related to Cloud Computing or to the Internet of Things (IoT).Comment: In Proceedings ICLP 2020, arXiv:2009.0915

An Application of Declarative Languages in Distributed Architectures: ASP and DALI Microservices

In this paper we introduce an approach to the possible adoption of Answer Set Programming (ASP) for the definition of microservices, which are a successful abstraction for designing distributed applications as suites of independently deployable interacting components. Such ASP-based components might be employed in distributed architectures related to Cloud Computing or to the Internet of Things (IoT), where the ASP microservices might be usefully coordinated with intelligent logic-based agents. We develop a case study where we consider ASP microservices in synergy with agents defined in DALI, a well-known logic-based agent-oriented programming language developed by our research group

Mechanisms of Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma

Simple Summary Immune checkpoint inhibitors (ICIs) are now a cornerstone of systemic treatment for hepatocellular carcinoma (HCC). However, their efficacy is blunted by mechanisms of tumour resistance in many patients. This review reports on the state of the art of resistance to ICIs, focusing on HCC, with the aim to provide clear and direct information to clinicians and researchers. Growing knowledge on the mechanisms of resistance to immunotherapy can indeed guide the choice of and expand the application of novel combined treatments. Hepatocellular carcinoma (HCC) is the most common liver cancer and a relevant global health problem. Immune checkpoint inhibitors (ICIs) represent the most effective systemic treatment for HCC. However, due to primary resistance, approximately 40% of HCC patients do not achieve a disease control with ICIs. Moreover, a similar proportion will experience disease progression after an initial response caused by secondary resistance. This review describes the mechanisms of primary and secondary resistance and reports the ongoing therapeutic strategies to overcome these obstacles

Intestinal Microbiota, Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma: The Potential Role of Dysbiosis in the Hepatocarcinogenesis

Introduction: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Approximately 5–30% of HCC patients lack a readily identifiable risk factor for their cancer, and most of these cases are attributed to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)

Application of Hybrid Agents to Smart Energy Management of a Prosumer Node

We outline a solution to the problem of intelligent control of energy consumption of a smart building system by a prosumer planning agent that acts on the base of the knowledge of the system state and of a prediction of future states. Predictions are obtained by using a synthetic model of the system as obtained with a machine learning approach. We present case studies simulations implementing different instantiations of agents that control an air conditioner according to temperature set points dynamically chosen by the user. The agents are able of energy saving while trying to keep indoor temperature within a given comfort interval

Lithium limits trimethyltin-induced cytotoxicity and proinflammatory response in microglia without affecting the concurrent autophagy impairment

Trimethyltin (TMT) is a highly toxic molecule present as an environmental contaminant causing neurodegeneration particularly of the limbic system both in humans and in rodents. We recently described the occurrence of impairment in the late stages of autophagy in TMT-intoxicated astrocytes. Here we show that similarly to astrocytes also in microglia, TMT induces the precocious block of autophagy indicated by the accumulation of the autophagosome marker, microtubule associated protein light chain 3. Consistent with autophagy impairment we observe in TMT-treated microglia the accumulation of p62/SQSTM1, a protein specifically degraded through this pathway. Lithium has been proved effective in limiting neurodegenerations and, in particular, in ameliorating symptoms of TMT intoxication in rodents. In our in vitro model, lithium displays a pro-survival and anti-inflammatory action reducing both cell death and the proinflammatory response of TMT-treated microglia. In particular, lithium exerts these activities without reducing TMT-induced accumulation of light chain 3 protein. In fact, the autophagic block imposed by TMT is unaffected by lithium administration. These results are of interest as defects in the execution of autophagy are frequently observed in neurodegenerative diseases and lithium is considered a promising therapeutic agent for these pathologies. Thus, it is relevant that this cation can still maintain its pro-survival and anti-inflammatory role in conditions of autophagy bloc

A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication

The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension

Adjuvant treatment in biliary tract cancer

Biliary tract cancers (BTCs) are a heterogeneous group of malignancies with a dismal prognosis. Despite radical surgery, the five-year overall survival (OS) does not exceed 40% in the best series. Adjuvant treatments are widely used even though they have mainly been investigated in small retrospective series until recently. Available data suggest that chemotherapy with 5-fluorouracil (and relative prodrugs) or gemcitabine can reduce the risk of relapse and potentially improve patients\u2019 long-term outcome. The role of adjuvant radiotherapy seems to be confined to patients with positive surgical margins. In addition, patients with highrisk factors for relapse (nodal involvement and non-radical resection) benefit most from chemotherapy. Recent results from large randomized trials have clarified the benefit of adjuvant treatments and probably defined a new standard of care

Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial.

The search for systemic therapies for hepatocellular carcinoma has been characterized by difficulties and failures. Despite recent progresses, many issues are still to be settled. In particular, the development of drugs inhibiting different neoplastic pathways remains a priority for patients intolerant or resistant to antiangiogenic drugs. This task may be daunting, as previous failures extensively demonstrated. We aimed to identify the future perspective of postsorafenib trials analyzing the strengths and the critical points of past and currently undergoing studies, in the light of the most recent evidences in the field. We identified various points (including stratification, biomarkers, end points, radiologic criteria of response, treatment beyond radiologic progression) that should be considered by future trials to reduce the risks of failure