Most vaccines require multiple doses, the first to induce recognition and antibody production and subsequent doses to boost the primary response and achieve optimal protection. We show that properly prioritizing the administration of first and second doses can shift the epidemic threshold, separating the disease-free from the endemic state and potentially preventing widespread outbreaks. Assuming homogeneous mixing, we prove that at a low vaccination rate, the best strategy is to give absolute priority to first doses. In contrast, for high vaccination rates, we propose a scheduling that outperforms a first-come first-served approach. We identify the threshold that separates these two scenarios and derive the optimal prioritization scheme and interdose interval. Agent-based simulations on real and synthetic contact networks validate our findings. We provide specific guidelines for effective resource allocation, showing that adjusting the timing between the primer and booster significantly impacts epidemic outcomes and can determine whether the disease persists or disappears.

Background and Objective: Hepatoblastoma is the most common pediatric liver cancer and represents a serious clinical challenge as no effective therapies have yet been found for advanced states and relapses of the disease. Methods: In this work, we use a well-established agent-based model of the immune response now equipped with anti-cancer therapy response to study the evolution of the disease and the role of the immune system in its containment. Results: We simulate the course of hepatoblastoma over three years in a population of virtual patients, successfully mimicking clinical mortality and symptom onset rates, as well as observations on the main tumor transcriptomic subtypes. Conclusions: The capacity of the introduced framework to reproduce clinical data and the heterogeneity of hepatoblastoma, combined with the possibility of observing the dynamics of cellular entities at the microscopic scale and the key chemical signals involved in disease progression, makes the model a promising resource for future research on in silico trials.

Personalized medicine strategies are gaining momentum nowadays, enabling the introduction of targeted treatments based on individual differences that can lead to greater therapeutic efficacy by reducing adverse effects. Despite its crucial role, studying the contribution of the immune system (IS) in this context is difficult because of the intricate interplay between host, pathogen, therapy, and other external stimuli. To address this problem, a multidisciplinary approach involving in silico models can be of great help. In this perspective, we will discuss the use of a well-established agent-based model of the immune response, C-ImmSim, to study the relationship between long-lasting diseases and the combined effects of IS, drug therapies and exogenous factors such as physical activity and dietary habits.

The Critical Node Detection Problem (CNDP) consists in finding the set of nodes, defined critical, whose removal maximally degrades the graph. In this work we focus on finding the set of critical nodes whose removal minimizes the pairwise connectivity of a direct graph (digraph). Such problem has been proved to be NP-hard, thus we need efficient heuristics to detect critical nodes in real-world applications. We aim at understanding which is the best heuristic we can apply to identify critical nodes in practice, i.e., taking into account time constrains and real-world networks. We present an in-depth analysis of several heuristics we ran on both real-world and on synthetic graphs. We define and evaluate two different strategies for each heuristic: standard and iterative. Our main findings show that an algorithm recently proposed to solve the CNDP and that can be used as heuristic for the general case provides the best results in real-world graphs, and it is also the fastest. However, there are few exceptions that are thoroughly analyzed and discussed. We show that among the heuristics we analyzed, few of them cannot be applied to very large graphs, when the iterative strategy is used, due to their time complexity. Finally, we suggest possible directions to further improve the heuristic providing the best results.

The importance of the immune system (IS) in tuberculosis (TB) drug development is often underestimated because of the intricate nature of experiments and the specialized knowledge needed. In vitro and animal studies fall short in replicating the intricate reactions of the human IS to drugs and infections. In this study, we present our initial efforts in employing an in silico approach to comprehend how an individual’s IS impacts the efficacy of therapy, particularly in managing mycobacterium tuberculosis (Mtb) infection and minimizing the risk of relapse. We employed a well-established agent-based IS simulator called C-IMMSIM. We conducted simulations to investigate the long-term outcomes of TB disease in a virtual cohort infected with Mtb over a 50-year period. Our simulations revealed that individuals with competent IS showed a high success rate in containing Mtb infection. Furthermore, to better understand the dynamic interactions between Mtb and the IS, we deliberately introduced specific IS deficiencies, thus successfully inducing short-term relapses and mortality. These results confirm the model’s ability to elucidate the mechanisms underlying the interactions between Mtb and the IS.

Models of networks play a major role in explaining and reproducing empirically observed patterns. Suitable models can be used to randomize an observed network while preserving some of its features, or to generate synthetic graphs whose properties may be tuned upon the characteristics of a given population. In the present paper, we introduce the Fitness-Corrected Block Model, an adjustable-density variation of the well-known Degree-Corrected Block Model, and we show that the proposed construction yields a maximum entropy model. When the network is sparse, we derive an analytical expression for the degree distribution of the model that depends on just the constraints and the chosen fitness-distribution. Our model is perfectly suited to define maximum-entropy data-driven spatial social networks, where each block identifies vertices having similar position (e.g., residence) and age, and where the expected block-to-block adjacency matrix can be inferred from the available data. In this case, the sparse-regime approximation coincides with a phenomenological model where the probability of a link binding two individuals is directly proportional to their sociability and to the typical cohesion of their age-groups, whereas it decays as an inverse-power of their geographic distance. We support our analytical findings through simulations of a stylized urban area.

The geographic distribution of the population on a region is a significant ingredient in shaping the spatial and temporal evolution of an epidemic outbreak. Heterogeneity in the population density directly impacts the local relative risk: the chances that a specific area is reached by the contagion depend on its local density and connectedness to the rest of the region. We consider an SIR epidemic spreading in an urban territory subdivided into tiles (i.e., census blocks) of given population and demographic profile. We use the relative attack rate and the first infection time of a tile to quantify local severity and timing: how much and how fast the outbreak will impact any given area. Assuming that the contact rate of any two individuals depends on their household distance, we identify a suitably defined geographical centrality that measures the average connectedness of an area as an efficient indicator for local riskiness. We simulate the epidemic under different assumptions regarding the socio-demographic factors that influence interaction patterns, providing empirical evidence of the effectiveness and soundness of the proposed centrality measure.

Tor is an open source software that allows accessing various kinds of resources, known as hidden services, while guaranteeing sender and receiver anonymity. Tor relies on a free, worldwide, overlay network, managed by volunteers, that works according to the principles of onion routing in which messages are encapsulated in layers of encryption, analogous to layers of an onion. The Tor Web is the set of web resources that exist on the Tor network, and Tor websites are part of the so-called dark web. Recent research works have evaluated Tor security, its evolution over time, and its thematic organization. Nevertheless, limited information is available about the structure of the graph defined by the network of Tor websites, not to be mistaken with the network of nodes that supports the onion routing. The limited number of entry points that can be used to crawl the network, makes the study of this graph far from being simple. In the present paper we analyze two graph representations of the Tor Web and the relationship between contents and structural features, considering three crawling datasets collected over a five-month time frame. Among other findings, we show that Tor consists of a tiny strongly connected component, in which link directories play a central role, and of a multitude of services that can (only) be reached from there. From this viewpoint, the graph appears inefficient. Nevertheless, if we only consider mutual connections, a more efficient subgraph emerges, that is, probably, the backbone of social interactions in Tor.

Background: The immune response to adenoviral COVID-19 vaccines is affected by the interval between doses. The optimal interval is unknown.Aim: We aim to explore in-silico the effect of the interval between vaccine administrations on immunogenicity and to analyze the contribution of pre-existing levels of antibodies, plasma cells, and memory B and T lymphocytes.Methods: We used a stochastic agent-based immune simulation platform to simulate two-dose and three-dose vaccination protocols with an adenoviral vaccine. We identified the model's parameters fitting anti-Spike antibody levels from individuals immunized with the COVID-19 vaccine AstraZeneca (ChAdOx1-S, Vaxzevria). We used several statistical methods, such as principal component analysis and binary classification, to analyze the correlation between pre-existing levels of antibodies, plasma cells, and memory B and T cells to the magnitude of the antibody response following a booster dose.Results and conclusions: We find that the magnitude of the antibody response to a booster depends on the number of pre-existing memory B cells, which, in turn, is highly correlated to the number of T helper cells and plasma cells, and the antibody titers. Pre-existing memory T cytotoxic cells and antibodies directly influence antigen availability hence limiting the magnitude of the immune response. The optimal immunogenicity of the third dose is achieved over a large time window, spanning from 6 to 16 months after the second dose. Interestingly, after any vaccine dose, individuals can be classified into two groups, sustainers and decayers, that differ in the kinetics of decline of their antibody titers due to differences in long-lived plasma cells. This suggests that the decayers may benefit from a tailored boosting schedule with a shorter interval to avoid the temporary loss of serological immunity.

Network-based epidemic models that account for heterogeneous contact patterns are extensively used to predict and control the diffusion of infectious diseases. We use census and survey data to reconstruct a geo-referenced and age-stratified synthetic urban population connected by stable social relations. We consider two kinds of interactions, distinguishing daily (household) contacts from other frequent contacts. Moreover, we allow any couple of individuals to have rare fortuitous interactions. We simulate the epidemic diffusion on a synthetic urban network for a typical medium-sized Italian city and characterize the outbreak speed, pervasiveness, and predictability in terms of the socio-demographic and geographic features of the host population. Introducing age-structured contact patterns results in faster and more pervasive outbreaks, while assuming that the interaction frequency decays with distance has only negligible effects. Preliminary evidence shows the existence of patterns of hierarchical spatial diffusion in urban areas, with two regimes for epidemic spread in low- and high-density regions.

Defining accurate and flexible models for real-world networks of human beings is instrumental to understand the observed properties of phenomena taking place across those networks and to support computer simulations of dynamic processes of interest for several areas of research - including computational epidemiology, which is recently high on the agenda. In this paper we present a flexible model to generate age-stratified and geo-referenced synthetic social networks on the basis of widely available aggregated demographic data and, possibly, of estimated age-based social mixing patterns. Using the Italian city of Florence as a case study, we characterize our network model under selected configurations and we show its potential as a building block for the simulation of infections' propagation. A fully operational and parametric implementation of our model is released as open-source.

The COVID-19 pandemic triggered a global research effort to define and assess timely and effective containment policies. Understanding the role that specific venues play in the dynamics of epidemic spread is critical to guide the implementation of fine-grained non-pharmaceutical interventions (NPIs). In this paper, we present a new model of context-dependent interactions that integrates information about the surrounding territory and the social fabric. Building on this model, we developed an open-source data-driven simulator of the patterns of fruition of specific gathering places that can be easily configured to project and compare multiple scenarios. We focused on the greatest park of the City of Florence, Italy, to provide experimental evidence that our simulator produces contact graphs with unique, realistic features, and that gaining control of the mechanisms that govern interactions at the local scale allows to unveil and possibly control non-trivial aspects of the epidemic.

The definition of suitable generative models for synthetic yet realistic social networks is a widely studied problem in the literature. By not being tied to any real data, random graph models cannot capture all the subtleties of real networks and are inadequate for many practical contexts--including areas of research, such as computational epidemiology, which are recently high on the agenda. At the same time, the so-called contact networks describe interactions, rather than relationships, and are strongly dependent on the application and on the size and quality of the sample data used to infer them. To fill the gap between these two approaches, we present a data-driven model for urban social networks, implemented and released as open source software. By using just widely available aggregated demographic and social-mixing data, we are able to create, for a territory of interest, an age-stratified and geo-referenced synthetic population whose individuals are connected by "strong ties" of two types: Intra-household (e.g., kinship) or friendship. While household links are entirely data-driven, we propose a parametric probabilistic model for friendship, based on the assumption that distances and age differences play a role, and that not all individuals are equally sociable. The demographic and geographic factors governing the structure of the obtained network under different configurations, are thoroughly studied through extensive simulations focused on three Italian cities of different size.

Tor hidden services allow offering and accessing various Internet resources while guaranteeing a high degree of provider and user anonymity. So far, most research work on the Tor network aimed at discovering protocol vulnerabilities to de-anonymize users and services. Other work aimed at estimating the number of available hidden services and classifying them. Something that still remains largely unknown is the structure of the graph defined by the network of Tor services. In this paper, we describe the topology of the Tor graph (aggregated at the hidden service level) measuring both global and local properties by means of well-known metrics. We consider three different snapshots obtained by extensively crawling Tor three times over a 5 months time frame. We separately study these three graphs and their shared "stable" core. In doing so, other than assessing the renowned volatility of Tor hidden services, we make it possible to distinguish time dependent and structural aspects of the Tor graph. Our findings show that, among other things, the graph of Tor hidden services presents some of the characteristics of social and surface web graphs, along with a few unique peculiarities, such as a very high percentage of nodes having no outbound links.

Network-based ranking methods (e.g. centrality analysis) have found extensive use in systems medicine for the prediction of essential proteins, for the prioritization of drug targets candidates in the treatment of several pathologies and in biomarker discovery, and for human disease genes identification. Here we propose to use critical nodes as defined by the Critical Node Problem for the analysis of key physiological and pathophysiological signaling pathways, as target candidates for treatment and management of several cancer types, neurologic and inflammatory dysfunctions, among others. We show how critical nodes allow to rank the importance of proteins in the pathways in a non-trivial way, substantially different from classical centrality measures. Such ranking takes into account the extent to which the network depends on its key players to maintain its cohesiveness and consistency, and coherently maps biologically relevant characteristics that can be critical in disease onset and treatments.

The exploration and analysis of Web graphs has flourished in the recent past, producing a large number of relevant and interesting research results. However, the unique characteristics of the Tor network demand for specific algorithms to explore and analyze it. Tor is an anonymity network that allows offering and accessing various Internet resources while guaranteeing a high degree of provider and user anonymity. So far the attention of the research community has focused on assessing the security of the Tor infrastructure. Most research work on the Tor network aimed at discovering protocol vulnerabilities to de-anonymize users and services, while little or no information is available about the topology of the Tor Web graph or the relationship between pages' content and topological structure. With our work we aim at addressing such lack of information. We describe the topology of the Tor Web graph measuring both global and local properties by means of well-known metrics that require due to the size of the network, high performance algorithms. We consider three different snapshots obtained by extensively crawling Tor three times over a 5 months time frame. Finally we present a correlation analysis of pages' semantics and topology, discussing novel insights about the Tor Web organization and its content. Our findings show that the Tor graph presents some of the character- istics of social and surface web graphs, along with a few unique peculiarities.

The amount of traffic data collected by automatic number plate reading systems constantly incrseases. It is therefore important, for law enforcement agencies, to find convenient techniques and tools to analyze such data. In this paper we propose a scalable and fully automated procedure leveraging the Apache Accumulo technology that allows an effective importing and processing of traffic data. We discuss preliminary results obtained by using our application for the analysis of a dataset containing real traffic data provided by the Italian National Police. We believe the results described here can pave the way to further interesting research on the matter.

This paper describes the efforts, pitfalls, and successes of applying unsupervised classification techniques to analyze the Trap-2017 dataset. Guided by the informative perspective on the nature of the dataset obtained through a set of specifically-written perl/bash scripts, we devised an automated clustering tool implemented in python upon openly-available scientific libraries. By applying our tool on the original raw data it is possibile to infer a set of trending behaviors for vehicles travelling over a route, yielding an instrument to classify both routes and plates. Our results show that addressing the main goal of the Trap-2017 initiative (``to identify itineraries that could imply a criminal intent'') is feasible even in the presence of an unlabelled and noisy dataset, provided that the unique characteristics of the problem are carefully considered. Albeit several optimizations for the tool are still under investigation, we believe that it may already pave the way to further research on the extraction of high-level travelling behaviors from gates transit records.