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Network science offers powerful tools to model complex social systems. Most social network science research focuses on topological networks by simply considering the binary state of the links, i.e., their presence or absence. Nonetheless, complex social systems present heterogeneity in link interactions (link weight), and accounting for this heterogeneity, it is mandatory to design reliable social network models. Here, we revisit the topic of weighted social networks (WSNs). By summarizing the main notions, findings, and applications in the field of WSNs, we outline how WSN methodology may improve the modeling of several real problems in social sciences. We are convinced that WSNs may furnish ideas and insights to open interesting lines of new research in the social sciences.

Esophageal cancer (EC) is a highly aggressive tumor, and the current monitoring procedures are partially inadequate to evaluate treatment efficacy. The aim of this study was to investigate whether allelic imbalance analysis in liquid biopsy could be used as an additional tool to monitor tumor burden in EC patients. For this purpose, circulating cell-free DNA (cfDNA) from 52 patients with a locally advanced EC, which underwent neoadjuvant treatment and resection, was analyzed. Data from four representative longitudinally followed patients are also reported. Furthermore, 17 DNAs from formalin-fixed paraffin-embedded (FFPE) tumor samples were analyzed and compared to time-matched cfDNAs. To look for allelic imbalance, which is the main genetic alteration in both EC histotypes, we used a panel of five microsatellites (MSs) and three single-nucleotide polymorphisms (SNPs) near genes described as frequently altered. The Fisher exact and Mann-Whitney U tests were used to analyze categorical and continuous data, respectively. The correlation coefficient between cfDNA and FFPE-DNA was calculated with the Pearson's correlation test. We found that the selected tumor-related alterations are present in cfDNA of both adenocarcinoma (EADC) and squamous cell carcinoma (ESCC) with similar frequencies. The only exception were the MSs, one downstream and one upstream, of SMAD4 of which the loss was only observed in EADC (26 vs. 0%, P = 0.018). More interestingly, longitudinal studies disclosed that in patients with disease progression, tumor-related alterations were present in cfDNA before overt clinical or instrumental signs of relapse. In conclusion, our data indicate that the evaluation of tumor-related gene allelic imbalance in cfDNA might be a useful tool to complement the current monitoring procedures for EC patients and to guide their management.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

The HIRMA project (Hepatocarcinoma Innovative Research Markers) aims at identifying and characterizing innovative markers related to the biological role of hepatotropic viruses (HBC, HBV and HDV) in the development of hepatocellular carcinoma, which is the third leading cause of cancer death worldwide. To achieve this result 30 research and hospital centres were involved to create an Italian collaborative network able to share and manage the information regarding a population of patients and their biological samples stored in biobanks. In order to allow the collection, the management and the search of the clinical data a dedicated centralized web portal (http://www.hirma.it) has been developed

This talk is divided in two parts. In the first part, we will summarize the status of the APEmille project that will be completed by the end of the year. We will then devote the rest of the talk to the description of a new project for a multi-TeraFlop machine, apeNEXT. The interested reader will find a much more detailed discussion of all the items touched upon here in the full proposal of the project that will shortly appear on hep-lat. © 2001 Elsevier Science B.V. All rights reserved.

Calcium ions coordinate multiple cellular functions, among which the release of neurotransmitters, the gene expression, the regulation of inflammatory processes and the activation of apoptosis. The regulation of calcium metabolism involves several biochemical pathways, different sub-cellular compartments and it is strongly compromised during aging. In fact, alterations of the calcium signalling process are frequent in the neurodegenerative diseases and mainly result in the hyper-activation of the apoptotic process. To investigate molecular alterations occurring in neurodegenerative diseases, an integrative mathematical model designed to represent the calcium metabolism has been defined. The model, which is mathematically defined by ODEs system, reproduces the calcium ions functions during glutamate stimulation. In particular, a number of different situations, such as (i) the glutamatergic transmission using different impulse frequencies, (ii) the comparison between normal and excessive stimulation and (iii) the calcium homeostasis in young/aging neurons have been reproduced. In particular, the simulations of several features associated to neurodegenerative disease, especially at molecular level and with a particular focus on the apoptotic process, allow highlighting the differences occurring in calcium metabolism in normal and pathological states. Furthermore collecting the achieved simulation and sensitivity analysis results, we propose an in silico strategy for preventing the activation of the apoptotic pathway in the neurodegenerative diseases.

Cancer cells differ from their normal counterparts more in terms of regulatory networks than of specific molecules. A recently recognized hallmark of cancer is the increased uptake of nutrients, particularly glucose, associated with a higher lactate pro- duction. A common step of tumorigenesis, which influences these metabolic alterations, is the constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Fol- lowing an integrative systems biology approach, we propose a model for the in silico investigation of the PI3K/Akt pathway effects on the central metabolism. This model represents a useful tool for the computational analysis of the metabolic differences be- tween normal and pathological conditions.

Il morbillo è un importante problema di Sanità Pubblica che comporta un elevato rischio di complicanze con conseguenti eccessi di ospedalizzazione, mortalità e costi elevati. Obiettivi: Valutare incidenza, decorso clinico, complicanze e scelte terapeutiche in bambini ospedalizzati per morbillo, nonché l’impatto dell’epidemia su strutture ed operatori di una U.O.C. di Infettivologia Pediatrica con 16 p.l. Metodologia: dalle cartelle cliniche dei bambini ricoverati per morbillo presso l’U.O.C. di Pediatria Infettivologica dell’Ospedale Pausillipon di Napoli, nel corso dell’epidemia verificatasi in Campania tra gennaio e maggio 2002, sono stati raccolti, mediante una apposita griglia di rilevazione, i dati socio anagrafici, quelli relativi a decorso della malattia, eventuali complicanze, scelte terapeutiche adottate, stato immunitario del bambino e della madre, possibile fonte di contagio, motivazione al ricovero. Su 78 bambini ricoverati (38F e 40M), età media di 4,2 anni (range 0,1 14 anni), di cui 20 con età inferiore a 15 mesi, 42 hanno presentato complicanze: 27 broncopolmoniti, di cui 4 di presumibile origine virale e 23 da presumibile sovrainfezione batterica, 7 laringotracheobronchiti (croup), 4 diarrea con disidratazione, 1 otite media, 4 piastrinopenia transitoria, 2 stomatiti, 1 cistite emorragica, 1 meningoencefalite. Oltre alla terapia antibiotica e cortisonica (quando indicate), 27 bambini hanno ricevuto una singola somministrazione di Vitamina A, con decorso favorevole della malattia e nessun effetto collaterale. In soli due bambini era stata praticata la vaccinazione antimorbillo.Conclusioni: i dati confermano l’importanza della vaccinazione antimorbillo e l’opportunità di anticiparla a 6 mesi in corso di epidemia (nella quasi totalità dei casi di età ‹15 mesi la fonte di contagio è stata la malattia in fratelli e/o cugini più grandi). Dalla valutazione dei ricoveri senza complicanze emerge l’importanza della collaborazione Ospedale Territorio per evitare ricoveri incongrui, specie se in un piccolo ospedale con risorse strutturali, economiche ed umane limitate: con una corretta gestione del panico scatenato dall’epidemia il 46% dei bambini ospedalizzati poteva essere trattato a domicilio con risparmio di risorse.

18 pp. (1999).