Analisi di mobillità pedonale mediante dati di telefonia georeferenziati

Al fine di organizzare al meglio le città del futuro occorrono nuovi strumenti in grado di analizzare e comprendere il comportamento delle persone nelle aree urbane. In questo elaborato viene illustrata la costruzione di un modello teorico relativo alla mobilità pedonale nella città di Venezia a partire dall'analisi di dati di telefonia mobile, rilevati nella giornata del 26 Febbraio 2017. Vengono in seguito mostrate le differenti fasi necessarie alla realizzazione del modello a partire dall'elaborazione preliminare dei data set a disposizione e focalizzando poi l'attenzione sugli algoritmi di georeferenziazione disponibili in letteratura. Una volta ultimata l'analisi dati, vengono esposti i concetti teorici che stanno alla base del modello realizzato ponendo l'accento sul carattere stocastico del fenomeno osservato si rivolge lo sguardo al risultato ottenuto portando alla luce le verifiche a cui viene sottoposto e le criticità che emergono nell'affrontare questo studio

Dynamical Boolean Modeling of Immunogenic Cell Death

International audienceAs opposed to the standard tolerogenic apoptosis, immunogenic cell death (ICD) constitutes a type of cellular demise that elicits an adaptive immune response. ICD has been characterized in malignant cells following cytotoxic interventions, such as chemotherapy or radiotherapy. Briefly, ICD of cancer cells releases some stress/danger signals that attract and activate dendritic cells (DCs). The latter can then engulf and cross-present tumor antigens to T lymphocytes, thus priming a cancer-specific immunity. This series of reactions works as a positive feedback loop where the antitumor immunity further improves the therapeutic efficacy by targeting cancer cells spared by the cytotoxic agent. However, not all chemotherapeutic drugs currently approved for cancer treatment are able to stimulate bona fide ICD: some commonly used agents, such as cisplatin or 5-fluorouracil, are unable to activate all features of ICD. Therefore, a better characterization of the process could help identify some gene or protein candidates to target pharmacologically and suggest combinations of drugs that would favor/increase antitumor immune response. To this end, we have built a mathematical model of the major cell types that intervene in ICD, namely cancer cells, DCs, CD8+ and CD4+ T cells. Our model not only integrates intracellular mechanisms within each individual cell entity, but also incorporates intercellular communications between them. The resulting cell population model recapitulates key features of the dynamics of ICD after an initial treatment, in particular the time-dependent size of the different cell types. The model is based on a discrete Boolean formalism and is simulated by means of a software tool, UPMaBoSS, which performs stochastic simulations with continuous time, considering the dynamics of the system at the cell population level with appropriate timing of events, and accounting for death and division of each cell type. With this model, the time scales of some of the processes involved in ICD, which are challenging to measure experimentally, have been predicted. In addition, our model analysis led to the identification of actionable targets for boosting ICD-induced antitumor response. All computational analyses and results are compiled in interactive notebooks which cover the presentation of the network structure, model simulations, and parameter sensitivity analyses

Advancement in the Oropharyngeal Primary Unknown Cancer Diagnostic and Current Treatments Pathway: A Narrative Review

Objective: The objective of this article is to define a correct diagnostic pathway for oropharyngeal cancer of unknown primary (OPCUP) identification. Background: OPCUP represents one of the most frequent causes of neck metastases onset without the identification of the primary tumor. Therefore, there is a high percentage of late or missing diagnoses, resulting in treatment delay or in a wrong therapeutic process. The up-to-date diagnostic procedures can help us to begin therapies at the right time. Methods: This is a review of the latest articles about diagnostic pathways in the OPCUP. A selection of the references was carried out in PubMed, EMBASE, Cochrane, and CENTRAL electronic databases. Conclusion: The oropharynx represents the most common site of primary unknown head and neck cancer (HNCUP). Recent epidemiologic data reported an increasing incidence of HNCUP related to human papilloma virus positive squamous cell carcinoma. Positron emission tomography combined with computerized tomography scanning or magnetic resonance imaging allows for improving the detection of primary unknown tumors and distant and locoregional metastases. Finally, the introduction of the trans-oral robotic surgical approach has introduced a new role of surgery in the HNCUP diagnosis and treatment. Hence, the new technological improvement allows reaching in most HNCUP patients an early diagnosis, achieving targeted management and better treatment outcomes, as well as decreasing toxicity and the side effects of treatment options

Surgical Treatment for Advanced Oropharyngeal Cancer: A Narrative Review

Background and Objectives: to describe current scientific knowledge regarding the treatment options in advanced oropharyngeal cancer. The standard care for advanced oropharyngeal cancer (OPSCC) has been chemoradiotherapy, although surgical approaches followed by adjuvant treatment have been proposed. The best therapy for each patient should be decided by an interdisciplinary tumour-board. Different strategies should be considered for the specific patient’s treatment: surgery, chemotherapy and radiation therapy or combinations of them. The treatment choice is influenced by tumour variability and prognostic factors, but it also depends on cancer extension, extranodal extension, nervous invasion, human papilloma virus (HPV) presence, making the decisional algorithm not always clear. HPV-related OPSCC is strongly associated with a favourable overall survival (OS) and disease-free survival rate (DSS); by contrast, HPV-negative OPSCC often flags a worse prognosis. Consequently, the American Joint Committee on Cancer (AJCC) differentiates OPSCC treatment and prognosis based on HPV status. Methods: we carried out a review of current scientific literature to analyze the different indications and limitations of surgical treatment options in OPSCC stage III and IV. Conclusion: robotic surgery or open approaches with reconstructive flaps can be considered in advanced stages, resulting in the de-intensification of subsequent systemic therapy and fewer related side effects. Furthermore, in the event of the primary failure of systemic therapy or disease recurrence, the surgical approach constitutes an additional therapeutic option which lengthens patient survival functions

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

International audienceCholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract