An intelligent management of integrated biomedical data for digital health via Network Medicine and its application to different human diseases

Personalized medicine aims to tailor the health care to each person’s unique signature leading to better distinguish an individual patient from the others with similar clinical manifestation. Many different biomedical data types contribute to define this patient’s unique signature, such as omics data produced trough next generation sequencing technologies. The integration of single-omics data, in a sequential or simultaneous manner, could help to understand the interplay of the different molecules thus helping to bridge the gap between genotype and phenotype. To this end, Network Medicine offers a promising formalism for multi-omics data integration by providing a holistic approach that look at the whole system at once rather than focusing on the single entities. This thesis regards the integration of various omics data following two different procedures within the framework of Network Medicine: A procedural multi-omics data integration, where a single omics was first selected to perform the main analysis, and then the other omics were used in cascade to molecularly characterize the results obtained in the main analysis. A parallel multi-omics data integration, where the result was given by the intersection of the results of each single-omics. The procedural multi-omics data integration was leveraged to study Colorectal and Breast Cancer. In the Colorectal Cancer case study, we defined the molecular signatures of a new subgroup of Colorectal Cancer possibly eligible for immune-checkpoint inhibitors therapy. Moreover, in the Breast Cancer case study we defined 11 prognostic biomarkers specific for the Basal-like subtype of Breast Cancer. Instead, the parallel multi-omics data integration was exploited to study COVID-19 and Chronic Obstructive Pulmonary Disease. In the COVID-19 case study, we defined a pool of drugs potentially repurposable for COVID-19. Whereas, in the Chronic Obstructive Pulmonary Disease case study, we discovered a group of differentially expressed and methylated genes that have a considerable biological specificity and could be related to the inflammatory pathological mechanism of Chronic Obstructive Pulmonary Disease

Clinical Multigene Panel Sequencing Identifies Distinct Mutational Association Patterns in Metastatic Colorectal Cancer

Extensive molecular characterization of human colorectal cancer (CRC) via Next Generation Sequencing (NGS) indicated that genetic or epigenetic dysregulation of a relevant, but limited, number of molecular pathways typically occurs in this tumor. The molecular picture of the disease is significantly complicated by the frequent occurrence of individually rare genetic aberrations, which expand tumor heterogeneity. Inter- and intratumor molecular heterogeneity is very likely responsible for the remarkable individual variability in the response to conventional and target-driven first-line therapies, in metastatic CRC (mCRC) patients, whose median overall survival remains unsatisfactory. Implementation of an extensive molecular characterization of mCRC in the clinical routine does not yet appear feasible on a large scale, while multigene panel sequencing of most commonly mutated oncogene/oncosuppressor hotspots is more easily achievable. Here, we report that clinical multigene panel sequencing performed for anti-EGFR therapy predictive purposes in 639 formalin-fixed paraffin-embedded (FFPE) mCRC specimens revealed previously unknown pairwise mutation associations and a high proportion of cases carrying actionable gene mutations. Most importantly, a simple principal component analysis directed the delineation of a new molecular stratification of mCRC patients in eight groups characterized by non-random, specific mutational association patterns (MAPs), aggregating samples with similar biology. These data were validated on a The Cancer Genome Atlas (TCGA) CRC dataset. The proposed stratification may provide great opportunities to direct more informed therapeutic decisions in the majority of mCRC cases

COVID-19 and atrial fibrillation: Intercepting lines

Almost 20% of COVID-19 patients have a history of atrial fibrillation (AF), but also a new-onset AF represents a frequent complication in COVID-19. Clinical evidence demonstrates that COVID-19, by promoting the evolution of a prothrombotic state, increases the susceptibility to arrhythmic events during the infective stages and presumably during post-recovery. AF itself is the most frequent form of arrhythmia and is associated with substantial morbidity and mortality. One of the molecular factors involved in COVID-19-related AF episodes is the angiotensin-converting enzyme (ACE) 2 availability. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 to enter and infect multiple cells. Atrial ACE2 internalization after binding to SARS-CoV-2 results in a raise of angiotensin (Ang) II, and in a suppression of cardioprotective Ang(1–7) formation, and thereby promoting cardiac hypertrophy, fibrosis and oxidative stress. Furthermore, several pharmacological agents used in COVID-19 patients may have a higher risk of inducing electrophysiological changes and cardiac dysfunction. Azithromycin, lopinavir/ritonavir, ibrutinib, and remdesivir, used in the treatment of COVID-19, may predispose to an increased risk of cardiac arrhythmia. In this review, putative mechanisms involved in COVID-19-related AF episodes and the cardiovascular safety profile of drugs used for the treatment of COVID-19 are summarized

The conservation project in polarity of the multidimensional survey. The need for critical discussion drafting of operating protocols. Modernity and tradition: the wooden caisson in the great hall of the Economic School in Naples

The paper focuses on the multidisciplinary study of the coffered ceiling wooden, existing in the Great Hall of the School of Economics of Naples. One of the rare examples of wooden work carried out in Italy in the twentieth century, designed by Roberto Pane, master of Italian architecture and academia.. The multidisciplinary and multidimensional approach has involved researchers and academics active in remote sensing and 3D modeling (Argenziano P.), in the conservation and restoration (Saverio Carillo, Petillo Pasquale, Luca Ferri), in lighting and colorimetry (Sibilio Sergio, Falconetti Pasquale).. The direct and instrumental survey, from 3D modeling to videoendoscopy, from the characterization of materials and coatings, the work has allowed us to understand the material composition of the coffered ceiling and its manufacturing technology in a non-invasive approach. This protocol will be useful for a possible conservation work of the coffered ceiling in question and also provides a scientific protocol for the analytical study of coffered wood of any size and timing

Technical and architectural integration of a solar cooling system in a historical building

Solar heating and cooling technology is a plant engineering technique which uses hot water of solar collectors for building air conditioning during both winter and summer. Recently the interest for this technology has grown constantly especially due to the fact that it allows to reduce carbon dioxide emissions, save energy, and assure a local supply of energy thus more reliable. A critical point of discussion begins when solar collectors are installed in historical buildings because the protrusion formed by solar panels and mounting structures transforms the shape of the building, thereby altering its architectural aspects. In these cases, respect for historical heritage, protection of the landscape and the employment of renewable energy must be conciliated. As a consequence the design of the installation must be performed in order find out a good balance between technical and aesthetical requests. In this paper a solar heating and cooling plant designed for the Architecture Faculty of Second University of Naples with the aim to promote solar cooling and heating installations that facilitate the discovery of visual integrations and good compromises between technical and architectonic features is depicted in detail

Technical and architectural integration of a solar cooling system in a historical building

Solar heating and cooling technology is a plant engineering technique which uses hot water of solar collectors for building air conditioning during both winter and summer. Recently the interest for this technology has grown constantly especially due to the fact that it allows to reduce carbon dioxide emissions, save energy, and assure a local supply of energy thus more reliable. A critical point of discussion begins when solar collectors are installed in historical buildings because the protrusion formed by solar panels and mounting structures transforms the shape of the building, thereby altering its architectural aspects. In these cases, respect for historical heritage, protection of the landscape and the employment of renewable energy must be conciliated. As a consequence the design of the installation must be performed in order find out a good balance between technical and aesthetical requests. In this paper a solar heating and cooling plant designed for the Architecture Faculty of Second University of Naples with the aim to promote solar cooling and heating installations that facilitate the discovery of visual integrations and good compromises between technical and architectonic features is depicted in detail

A Transcriptome- and Interactome-Based Analysis Identifies Repurposable Drugs for Human Breast Cancer Subtypes

Breast cancer (BC) is a heterogeneous and complex disease characterized by different subtypes with distinct morphologies and clinical implications and for which new and effective treatment options are urgently demanded. The computational approaches recently developed for drug repurposing provide a very promising opportunity to offer tools that efficiently screen potential novel medical indications for various drugs that are already approved and used in clinical practice. Here, we started with disease-associated genes that were identified through a transcriptome-based analysis, which we used to predict potential repurposable drugs for various breast cancer subtypes by using an algorithm that we developed for drug repurposing called SAveRUNNER. Our findings were also in silico validated by performing a gene set enrichment analysis, which confirmed that most of the predicted repurposable drugs may have a potential treatment effect against breast cancer pathophenotypes

A Transcriptome- and Interactome-Based Analysis Identifies Repurposable Drugs for Human Breast Cancer Subtypes

Breast cancer (BC) is a heterogeneous and complex disease characterized by different subtypes with distinct morphologies and clinical implications and for which new and effective treatment options are urgently demanded. The computational approaches recently developed for drug repurposing provide a very promising opportunity to offer tools that efficiently screen potential novel medical indications for various drugs that are already approved and used in clinical practice. Here, we started with disease-associated genes that were identified through a transcriptome-based analysis, which we used to predict potential repurposable drugs for various breast cancer subtypes by using an algorithm that we developed for drug repurposing called SAveRUNNER. Our findings were also in silico validated by performing a gene set enrichment analysis, which confirmed that most of the predicted repurposable drugs may have a potential treatment effect against breast cancer pathophenotypes

Effectiveness of light pipes in Italy

"Development of daylight exploitation products has been accelerated during last decade thanks to an increasing demand for an improvement in environmental conditions for living and a need for energy saving. Among these products, the light-pipes, which bring natural light indoors where sunlight cannot reach without generating excessive heat, are gaining more and more interest.. In this paper a review of the commercially available tubular light transportation systems, for Europe and USA, has been carried out.. In addition first experimental results of a tubular system application in a low-energy house (Leaf House) under climatic conditions of North Italy have been reported..