Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis

Although the expression of the stem/progenitor cell marker cytokeratin-19 (CK-19) has been associated with the worst clinical prognosis among all HCC subclasses, it is yet unknown whether its presence in HCC is the result of clonal expansion of hepatic progenitor cells (HPCs) or of de-differentiation of mature hepatocytes towards a progenitor-like cell phenotype. We addressed this question by using two rat models of hepatocarcinogenesis: the Resistant-Hepatocyte (R-H) and the Choline-methionine deficient (CMD) models. Our data indicate that the expression of CK-19 is not the result of a clonal expansion of HPCs (oval cells in rodents), but rather of a further step of preneoplastic hepatocytes towards a less differentiated phenotype and a more aggressive behavior. Indeed, although HCCs were positive for CK-19, very early preneoplastic foci (EPFs) were completely negative for this marker. While a few weeks later the vast majority of preneoplastic nodules remained CK-19 negative, a minority became positive, suggesting that CK-19 expression is the result of de-differentiation of a subset of EPFs, rather than a marker of stem/progenitor cells. Moreover, the gene expression profile of CK-19-negative EPFs clustered together with CK-19-positive nodules, but was clearly distinct from CK-19 negative nodules and oval cells. Conclusion: i) CK-19-positive cells are not involved in the early clonal expansion observed in rat hepatocarcinogenesis; ii) CK-19 expression arises in preneoplastic hepatocyte lesions undergoing malignant transformation; iii) CK-19 positivity in HCCs does not necessarily reflect the cell of origin of the tumor, but rather the plasticity of preneoplastic cells during the tumorigenic proces

Random walks and search in time-varying networks

The random walk process underlies the description of a large number of real world phenomena. Here we provide the study of random walk processes in time varying networks in the regime of time-scale mixing; i.e. when the network connectivity pattern and the random walk process dynamics are unfolding on the same time scale. We consider a model for time varying networks created from the activity potential of the nodes, and derive solutions of the asymptotic behavior of random walks and the mean first passage time in undirected and directed networks. Our findings show striking differences with respect to the well known results obtained in quenched and annealed networks, emphasizing the effects of dynamical connectivity patterns in the definition of proper strategies for search, retrieval and diffusion processes in time-varying network

Exposure to Endocrine Disruptors and Nuclear Receptors Gene Expression in Infertile and Fertile Men from Italian Areas with Different Environmental Features

Internal levels of selected endocrine disruptors (EDs) (i.e., perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), di-2-ethylhexyl-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and bisphenol A (BPA)) were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas. PFOS and PFOA levels were also evaluated in seminal plasma. In peripheral blood mononuclear cells (PBMCs) of same subjects, gene expression levels of a panel of nuclear receptors (NRs), namely estrogen receptor α (ERα) estrogen receptor β (ERβ), androgen receptor (AR), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptor γ (PPARγ) and pregnane X receptor (PXR) were also assessed. Infertile men from the metropolitan area had significantly higher levels of BPA and gene expression of all NRs, except PPARγ, compared to subjects from other areas. Subjects from urban areas had significantly higher levels of MEHP, whereas subjects from rural area had higher levels of PFOA in both blood and seminal plasma. Interestingly, ERα, ERβ, AR, PXR and AhR expression is directly correlated with BPA and inversely correlated with PFOA serum levels. Our study indicates the relevance of the living environment when investigating the exposure to specific EDs. Moreover, the NRs panel in PBMCs demonstrated to be a potential biomarker of effect to assess the EDs impact on reproductive health

Oncoplastic conservative surgery for breast cancer: long-term outcomes of our first ten years experience

The main goal of oncoplastic breast surgery (OBS) is to optimize cosmetic outcomes and reduce patient morbidity, while still providing an oncologically-safe surgical outcome and extending the target population of conservative surgery. Although the growing number of reported experiences with oncoplastic surgery, few studies account for the long-term outcomes

Emergence of influential spreaders in modified rumor models

The burst in the use of online social networks over the last decade has provided evidence that current rumor spreading models miss some fundamental ingredients in order to reproduce how information is disseminated. In particular, recent literature has revealed that these models fail to reproduce the fact that some nodes in a network have an influential role when it comes to spread a piece of information. In this work, we introduce two mechanisms with the aim of filling the gap between theoretical and experimental results. The first model introduces the assumption that spreaders are not always active whereas the second model considers the possibility that an ignorant is not interested in spreading the rumor. In both cases, results from numerical simulations show a higher adhesion to real data than classical rumor spreading models. Our results shed some light on the mechanisms underlying the spreading of information and ideas in large social systems and pave the way for more realistic diffusion models.Comment: 14 Pages, 6 figures, accepted for publication in Journal of Statistical Physic

Controlling contagion processes in activity driven networks

The vast majority of strategies aimed at controlling contagion processes on networks consider the connectivity pattern of the system either quenched or annealed. However, in the real world, many networks are highly dynamical and evolve, in time, concurrently with the contagion process. Here, we derive an analytical framework for the study of control strategies specifically devised for a class of time-varying networks, namely activity-driven networks. We develop a block variable mean-field approach that allows the derivation of the equations describing the coevolution of the contagion process and the network dynamic. We derive the critical immunization threshold and assess the effectiveness of three different control strategies. Finally, we validate the theoretical picture by simulating numerically the spreading process and control strategies in both synthetic networks and a large-scale, real-world, mobile telephone call data set

Quantifying the effect of temporal resolution on time-varying networks

Time-varying networks describe a wide array of systems whose constituents and interactions evolve over time. They are defined by an ordered stream of interactions between nodes, yet they are often represented in terms of a sequence of static networks, each aggregating all edges and nodes present in a time interval of size Δt. In this work we quantify the impact of an arbitrary Δt on the description of a dynamical process taking place upon a time-varying network. We focus on the elementary random walk, and put forth a simple mathematical framework that well describes the behavior observed on real datasets. The analytical description of the bias introduced by time integrating techniques represents a step forward in the correct characterization of dynamical processes on time-varying graphs

Damage detection via shortest-path network sampling

Large networked systems are constantly exposed to local damages and failures that can alter their functionality. The knowledge of the structure of these systems is, however, often derived through sampling strategies whose effectiveness at damage detection has not been thoroughly investigated so far. Here, we study the performance of shortest-path sampling for damage detection in large-scale networks. We define appropriate metrics to characterize the sampling process before and after the damage, providing statistical estimates for the status of nodes (damaged, not damaged). The proposed methodology is flexible and allows tuning the trade-off between the accuracy of the damage detection and the number of probes used to sample the network. We test and measure the efficiency of our approach considering both synthetic and real networks data. Remarkably, in all of the systems studied, the number of correctly identified damaged nodes exceeds the number of false positives, allowing us to uncover the damage precisely

The Twitter of Babel: Mapping World Languages through Microblogging Platforms

Large scale analysis and statistics of socio-technical systems that just a few short years ago would have required the use of consistent economic and human resources can nowadays be conveniently performed by mining the enormous amount of digital data produced by human activities. Although a characterization of several aspects of our societies is emerging from the data revolution, a number of questions concerning the reliability and the biases inherent to the big data “proxies” of social life are still open. Here, we survey worldwide linguistic indicators and trends through the analysis of a large-scale dataset of microblogging posts. We show that available data allow for the study of language geography at scales ranging from country-level aggregation to specific city neighborhoods. The high resolution and coverage of the data allows us to investigate different indicators such as the linguistic homogeneity of different countries, the touristic seasonal patterns within countries and the geographical distribution of different languages in multilingual regions. This work highlights the potential of geolocalized studies of open data sources to improve current analysis and develop indicators for major social phenomena in specific communities