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    Liver transplantation for non-resectable colorectal liver metastasis

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    Il 50% dei pazienti con adenocarcinoma del colon-retto svilupperà metastasi epatiche durante la malattia. Sfortunatamente solo il 20% potrà essere candidato a resezione. I pazienti trattati esclusivamente con chemioterapia o con trattamenti locoregionali hanno una sopravvivenza a 5 anni del 20%, mentre nei pazienti sottoposti a resezione la sopravvivenza a 5 anni è del 50-60%. Recentemente, alcuni studi hanno esplorato la possibilità del trapianto di fegato nei pazienti affetti da metastasi epatiche non-resecabili con risultati incoraggianti. Si tratta di uno studio pilota, in pazienti affetti da metastasi giudicate non resecabili, in assenza di recidiva del tumore primitivo e di malattia extraepatica, in risposta alla chemioterapia per un periodo di 3 mesi. I pazienti potranno essere sottoposti a trapianto di fegato con organi interi o parziali. Tra l’aprile 2021 ed il settembre 2024, 11 pazienti sono stati sottoposti a trapianto per metastasi. L’età mediana al trapianto era di 61 anni. Nel 54% dei casi il tumore primitivo era nel colon sinistro. L’intervallo mediano tra rimozione del primitivo e trapianto di fegato è stato di 13 mesi. Il motivo del trapianto di fegato è stato: metastasi non-resecabili “upfront” in 8 casi (73%) mentre nei restanti 3 casi (27%) non-resecabili dopo pregressa epatectomia. Tre pazienti (27%) hanno presentato una complicanza con CCI di 20,9 ed un paziente (9%) è deceduto. Dopo un follow-up mediano di 15 mesi, il 50% ha sviluppato una recidiva. La sopravvivenza globale mediana è di 18 mesi, mentre la DFS di 10 mesi. Questa è un’analisi preliminare del nostro protocollo di trapianto per metastasi non-resecabili. I risultati confermano la validità del trapianto nell’ambito delle metastasi non-resecabili, è necessario un campione più ampio ed un follow-up più lungo per poter identificare i fattori prognostici di recidiva e stratificare meglio i diversi sottogruppi di pazienti che beneficiano maggiormente di tale procedura.Fifty percent of patients with colorectal adenocarcinoma will develop liver metastasis during the disease. Unfortunately, only 20% could be considered for surgical resection. Patients who undergo exclusively chemotherapy or locoregional treatments experience a 5 years-survival of 20%, while patients treated with liver resection have a 5 years-survival of 50-60%. Recently, some studies have explored the possibility of liver transplantation in patients with non-resectable colorectal liver metastasis with no extra-hepatic disease with encouraging results. This is a pilot, prospective, single-arm study in patients with non-resectable colorectal liver metastasis with no primary tumor recurrence and extra-hepatic disease with response to chemotherapy for at least 3 months. Patients can receive either a whole graft or partial grafts. Between April 2021 and September 2024, 11 patients underwent liver transplantation for non-resectable colorectal liver metastasis at our institution. Median age at transplantation was 61 years. Fifty-four percent of patients had primary tumor located in left colon. Median time between colorectal resection and transplantation was 13 months. Indication for liver transplantation was upfront non-resectable liver metastasis in 8 patients (73%), while in the remaining 3 cases (27%) non-resectability was considered after previous liver resections. Three patients (27%) reported a post-operative complication with a CCI score of 20,9. One patient died within 90-days. After a median follow-up of 15 months, 50% of the patients developed a recurrence. Median over-all survival was 18 months while median disease-free survival was 10 months. This study is a preliminary analysis of our ongoing protocol of liver transplantation in patients with non-resectable colorectal liver metastasis. Our results confirm liver transplantation as a valid treatment in this setting, however a larger pool of patients and a longer follow-up are needed in order to identify prognostic factors of disease recurrence and better stratify which subgroups of patients benefit more from this procedure

    Application of functional imaging techniques PSMA-PET and WB-DWI-MRI in newly diagnosed multiple myeloma: comparison of different methods and standardization of therapy response assessment.

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    Il Mieloma Multiplo (MM) è una neoplasia ematologica caratterizzata dalla presenza di interessamento scheletrico in circa l’80% dei casi alla diagnosi e nella pressoché totalità delle forme ricadute/refrattarie. La [18F]FDG-PET/TC è una tecnica di imaging funzionale largamente impiegata nella valutazione delle lesioni focali, malattia midollare diffusa, malattia paramidollare e extramidollare nel MM; rappresenta, inoltre, la metodica di scelta per la valutazione della risposta strumentale al trattamento. Nonostante la sua elevata sensibilità (85-90%), l’incidenza di falsi negativi è di circa il 10-15%, possibilmente per ridotta espressione di esochinasi-2 nelle plasmacellule patologiche. L’utilizzo di tecniche innovative, o di radiotraccianti alternativi, potrebbe consentire di superare tale limite. In questo progetto, è stato esplorato il ruolo delle metodiche DWI-WB-MRI e Ga-PSMA-PET/CT nel mieloma multiplo di nuova diagnosi (NDMM), confrontate con il gold standard FDG-PET/CT. Nella prima parte dello studio, 50 pazienti affetti da NDMM, arruolati dal novembre 2021 all’aprile 2024, hanno ricevuto valutazione basale con PSMA-PET e FDG-PET; 38/50 pazienti hanno mostrato concordanza tra le due metodiche, mentre in 11/12 casi discordanti la FDG-PET era positiva, a fronte di PSMA-PET negativa. La FDG-PET è risultata superiore alla PSMA-PET nel rivelare le lesioni focali (93% vs 31%) e la malattia midollare diffusa. Nella seconda parte dello studio, che ha coinvolto 124 pazienti arruolati da ottobre 2022 a luglio 2024, la WB-MRI, confrontata con il gold standard FDG-PET, ha dimostrato superiorità nell’identificazione delle lesioni focali e paramidollari (81% vs. 58%, p=0.002) e della malattia midollare diffusa (p=0.019) rispetto a FDG-PET. Infine, abbiamo partecipato a una sub-analisi dello studio FORTE (Fase II), da cui è emerso come la CMR, definita con FDG-PET secondo i criteri di Deauville, correli con una migliore PFS (HR 0.4, p=0,0065), confermando il suo valore prognostico. Tali risultati suggeriscono, inoltre, l’impiego dei criteri di Deauville per uniformare i risultati FDG-PET tra diversi centri.Multiple Myeloma (MM) is a hematologic malignancy characterized by skeletal involvement in about 80% of cases at diagnosis and nearly all relapsed/refractory cases. Positron Emission Tomography/Computed Tomography (PET/CT) with [18F]-Fluorodeoxyglucose ([18F]FDG) is widely used for detecting skeletal lesions, diffuse bone marrow disease, and extramedullary involvement, offering high sensitivity (85-90%) in identifying active lesions. However, false negatives occur in 10-15% of cases, likely due to reduced expression of hexokinase 2 in malignant plasma cells. Innovative imaging techniques or alternative radiotracers could address this issue. In this project, two alternative imaging techniques were explored for newly diagnosed multiple myeloma (NDMM) compared with the gold standard FDG-PET/CT: whole-body magnetic resonance imaging with diffusion-weighted sequences (DWI-WB-MRI) and Ga-PSMA-PET/CT. In the first part of the study, 50 NDMM patients were prospectively enrolled from November 2021 to April 2024 to received both FDG-PET and PSMA-PET at baseline; 38/50 pts showed concordant results between FDG-PET and PSMA-PET, whereas 11/12 discordant cases showed positive FDG-PET and negative PSMA-PET. FDG-PET detected 93% of focal lesions, whereas PSMA-PET detected 31%. FDG-PET also outperformed PSMA-PET in detecting bone marrow involvement. In the second part of the study, involving 124 patients enrolled from October 2022 to July 2024, we compared WB-MRI with FDG-PET at diagnosis and pre maintenance time points. WB-MRI showed superior identification of focal lesions and paramedullary lesions (81% vs. 58%, p=0.002). It also performed better than FDG-PET in detecting diffuse bone marrow disease (p=0.019). Finally, in the present PhD project we partecipated in a sub-analysis of the FORTE trial (Phase II), which showed that CMR, achieved by 109 enrolled NDMM patients and defined by FDG-PET according to Deauville criteria, correlated with improved progression-free survival (HR 0.4, p=0.0065), confirming its role in assessing treatment response and prognostic significance. The study suggests using Deauville criteria for consistent interpretation across centers

    On vehicular communications in 5G dynamic environments

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    The goal of autonomous driving systems is to reach the highest possible level of autonomy, where no human intervention would be required. Achieving this level will rely heavily on Vehicle-to-Everything (V2X) communications. Focusing on the physical (PHY) layer of 5G-based communications, Line-of-Sight (LOS) identification is essential for V2X communications. In V2X systems, LOS paths typically offer the most robust and reliable signals, so as recognizing LOS conditions may lead to improved communication quality, with less signal fading and fewer errors, especially if compared to Non LOS (NLOS) scenarios, where buildings, vehicles, or terrain may obstruct signals. In this Thesis dissertation, a Matlab-based 5G NR DL simulator is used in order to test a developed approach for automatically identifying the channel status conditions of several gNBs-UEs links, by exploiting the collected CSI-RSRP measurements. In dense networks requiring reliable and low latency communications, such as the vehicular networks, managing HandOvers (HOs) becomes of paramount importance. In particular, a phenomenon that deteriorates the QoS and Quality of Experience (QoE) perceived by the UEs is represented by the Unnecessary HOs (UHOs). In this Thesis dissertation, an approach for UHOs mitigation in a 5G NR dynamic environment is proposed. Finally, even focusing on physical aspects of vehicular communication-oriented environments, nowadays, Integrated Sensing and Communication (ISAC) is one of the most exploited technologies for wireless communications thanks to its potential to reduce hardware costs and improve spectral efficiency. In this Thesis dissertation, an approach for the minimization of the resource allocated to the vehicular UEs for the UpLink (UL) transmission of the data extracted from a target is proposed. The goal is to allow the serving Base Station (BS) to receive the necessary information to manage the vehicular network in time to take the required actions

    "What are we supposed to do while we are waiting?": vernacular geographies of the "Balkan Route" in Trieste

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    Since 2018, the Italian border city of Trieste has become a key segment in the informal migration corridor of the so-called "Balkan Route." Despite rising anti-migration rhetoric from local and national authorities, a solidarity network of formal and informal actors has been active in the city since 2019. By 2022-2023, increased migrant arrivals, inadequate transfers to other cities, and a lack of proper accommodation created a dire situation. Asylum seekers in Trieste became trapped in prolonged periods of stuckness, deprived of shelter and healthcare, leading to their segregation into specific areas of the city where informal social and political practices emerged. This project examines migrants' everyday life at the border through a “vernacular” approach, focusing on the co-construction and negotiation of knowledge in spaces marked by marginality and segregation. The study is based on ethnographic fieldwork in Trieste (2022-2023) and interviews with around 50 participants, and it explores three key elements: urban grammars, material traces, and theories of time. The thesis posits that “vernacular actors” contribute to the co-construction of these spaces, participating in both collective political organisation and practices of place-making. I argue that “vernacular spaces” are spaces in translation, which make it possible, albeit in a limited and fragmented way, for marginalised subjects to crystallise their experiences of “wait” onto space and to negotiate collective political subjectivities through the construction of a “bordered” space and referent for their struggles, which turns tactics into strategies of resistance

    Identifying key genetic drivers in multiple myeloma progression using AI-driven bioinformatics and synthetic data augmentation

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    The progression of multiple myeloma (MM) from precursor conditions, such as monoclonal gammopathy of undetermined significance (MGUS), is driven by a complex network of genomic and molecular alterations. This thesis integrates traditional bioinformatics with advanced artificial intelligence (AI) and machine learning (ML) models to identify key genomic drivers of disease progression. Specifically, deep learning is applied to the publicly available GSE6477 dataset using generative adversarial networks (GANs), artificial neural networks (ANNs), support vector machines (SVMs), and XGBoost, alongside statistical tools like GEO2R and platforms such as STRING, Cytoscape, Enrichr, and KMplotter. These methods help identify gene signatures involved in the transition from a healthy state to MGUS and from MGUS to MM. Reverse-engineering gene expression networks and applying feature selection techniques, including principal component analysis (PCA) and random forests, enabled the identification of significant genes at each stage of disease progression. To address challenges such as class imbalance and data scarcity, synthetic data generation using GANs improved the robustness of prognostic models by generating realistic samples, validated through Euclidean distance and Pearson correlation to ensure biological fidelity. Key findings include identifying gene networks strongly associated with MM progression, validated through enrichment and survival analyses using KMplotter. AI/ML models, particularly those enhanced by synthetic data, showed improved generalizability across patient cohorts, suggesting potential broader applications beyond the GSE6477 dataset. This research provides insights into the molecular mechanisms underlying MM progression, which may aid in developing targeted therapies. Moreover, combining traditional bioinformatics with ML techniques demonstrates a powerful approach for deciphering gene interactions in complex diseases like MM. Future work should focus on translating these findings into clinical practice to enhance patient outcomes through personalized medicin

    The editorial policies of production, valorization and circulation of contemporary Italian documentary film: the case of “Cinema of the Real”.

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    Il progetto di ricerca si concentra sull'analisi dell'industria documentaristica italiana contemporanea a partire dal caso del “Cinema del Reale”. Tra fenomeno e tendenza, si tratta di una forma cinematografica che mette insieme lo sguardo documentario tipico della tradizione realista italiana con le esigenze narrative del cinema di finzione. Gli autori del “Cinema del Reale” utilizzano tutto il potenziale del mezzo cinematografico per indagare e interrogare la realtà, facendone emergere verità sottili e non immediatamente intellegibili. Tra questi possiamo citare Gianfranco Rosi, Roberto Minervini, Michelangelo Frammartino, Pietro Marcello, Alice Rohrwacher, Alessandro Comodin e molti altri. Si configura quindi un cinema d’autore libero e stilisticamente variegato, che si trova spesso a confrontarsi con le mille sfaccettature dell’Italia odierna. La ricerca si pone perciò l’obiettivo di indagare, attingendo al campo dei Media Industry Studies, quelle che sono le politiche editoriali dei player coinvolti nella filiera finanziaria, produttiva e distributiva del documentario italiano in relazione alle nuove produzioni riconducibili all’etichetta del “Cinema del Reale”. Tra gli strumenti metodologici adottati abbiamo l’uso di interviste in profondità, l’elaborazione di una classificazione dei modelli produttivi e distributivi esistenti e l’analisi di specifici casi studio. Sarà quindi possibile ricostruire una storia dell’industria del documentario italiano nell’ultimo ventennio, metterne in luce le problematiche rimaste irrisolte, analizzare quali sono stati gli impatti su di essa generati dagli interventi ministeriali che si sono succeduti, a partire dal Decreto Urbani del 2004 fino a giungere alla più recente Legge Cinema (Franceschini) del 2016, oltre che ragionare su quali possano essere le prospettive future del documentario italiano.This research project focuses on the analysis of the contemporary Italian documentary industry from the case of “Cinema of the Real”. Between phenomenon and trend, this is a film form that combines the documentary gaze typical of the Italian realist tradition with the narrative needs of fiction cinema. The authors of the “Cinema of the Real” use the full potential of the film medium to investigate and interrogate reality, bringing out subtle truths that are not immediately intelligible. Among them we can mention Gianfranco Rosi, Roberto Minervini, Michelangelo Frammartino, Pietro Marcello, Alice Rohrwacher, Alessandro Comodin and many others. Thus, a free and stylistically variagated auteur cinema is configured, which is often confronted with the thousand facets of today's Italy. The research therefore aims to investigate, drawing on the field of Media Industry Studies, what are the editorial policies of the players involved in the financial, production and distribution chain of the Italian documentary in relation to the new productions ascribable to the label of “Cinema of the Real.” Among the methodological tools adopted we have the use of in-depth interviews, the elaboration of a classification of existing production and distribution models and the analysis of specific case studies. It will thus be possible to reconstruct a history of the Italian documentary industry over the last two decades, highlight its remaining unresolved issues, analyze what impacts have been generated on it by the ministerial interventions that have followed one another, starting from the 2004 Decreto Urbani up to the most recent Legge Cinema (Franceschini) of 2016, as well as to reason about the prospects of the Italian documentary

    The ocular surface, a target for One Health indicators: the mirror of microbial interactions between pets and owners and an indicator of air pollution

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    One Health aims at tackling health issues with a comprehensive approach, encompassing human, animal and environmental health. Relationships between human health and the health of wildlife or livestock animals have been explored, however very few studies focus on the relationship between owner and companion animal. Evidence of pathogen sharing, including antimicrobial-resistant pathogens, between companion animal and owner highlights the existence and the importance of both pathogenic and non-pathogenic microbial exchanges and calls for a One Health approach to study the microbiomes. Outdoor air pollutants are known to have a negative impact on the ocular surface, however, their impact on the ocular surface microbiome, hosted by the conjunctiva, is not yet known. The conjunctiva has the particularity of being the only mucosa of the body directly exposed to the external environment. For this reason, it could act as a sentinel of the body identifying these interactions. The goal of this research was to apply a One Health approach to the study of the ocular surface microbiome, by combining several disciplines to investigate microbiome similarities between pet and owner, and the impact of pollutant exposure on the ocular surface. The research entails the implementation of a pipeline for the sampling, processing, and sequencing of the ocular surface microbiome in dogs and owners. 15 dogs and their owners were included in the study. Dog and owner microbiomes were found to be similar in overall composition, harboring the same main phyla and families, albeit dogs having a significantly more diverse microbiome. Pairs cohabiting with other pets had an ocular surface microbiome composition significantly more similar than the ones who did not. This is the first research evaluating ocular surface microbiome interactions between pet and owner. The ocular surface is proposed as a valuable indicator of pathogenic and non-pathogenic microbial exchanges, and pollution exposure

    Statistical delimitation of biological species based on genetic and spatial data

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    The delimitation of biological species, i.e., deciding which individuals belong to the same species and whether and how many different species are represented in a data set, is key to the conservation of biodiversity. In the presence of spatial patterns of genetic differentiation, delimitation methods based on genetic data might overestimate the number of species in a dataset. This work tackles this problem in two settings. When individuals are divided into two putative groups, methods that model the relationship between genetic and geographic dissimilarity are used to test whether the two groups belong to the same species. Existing approaches based on partial Mantel testing and regression on distances are explored and new ones are proposed. A modelling challenge is connected to the fact that dissimilarities are not independent. All methodologies are compared through an extensive simulation study involving SLiM and GSpace, two different software packages that can simulate spatially-explicit genetic data at an individual level. A proposed version of the partial Mantel test that uses jackknife instead of permutations is found to provide fairly good power while controlling for the type I error rate in all simulated scenarios. In a setting where no putative grouping is available, existing model-based clustering algorithms (sNMF and TESS3) are integrated with distance-based approaches for the estimation of the number of species in the dataset. Further considered approaches use null models to calibrate tests for the presence of more than one species in the dataset. In particular, a weighted null model is developed that can capture spatial patterns of genetic differentiation. When calibrated with this null model, a test statistic proposed to adapt the ΔK method to TESS3 is found to display promising type I error and power properties on SLiM data

    An aesthetics of vulnerability: critical approaches to Afrodescendant Portuguese literature

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    This dissertation examines the relationship between colonial vulnerability and Afrodescendant literature in Portugal. Western colonialism involved not only the exploitation of peoples and lands but also an aesthetic project that dehumanized colonized populations through stereotypes, erasing their subjectivities and histories. This colonial imagery portrayed Black subjects merely as sites of harm or dereliction, stripped of agency and any capacity for self-representation. These aesthetic ideologies reflect a racialized grammar that persists in traditional Portuguese literature and social memory. Following growing interest in the recent affirmation of Afrodescendant literature in Portugal, this study explores how six novels by Afrodescendant Portuguese authors articulate corporeal, enunciative, and memory vulnerability as sites of misappropriation. The selected novels — Luísa Semedo’s O canto da Moreia, Yara Nakahanda Monteiro’s Essa dama bate bué, Joaquim Arena’s Debaixo da nossa pele: uma viagem, and three works by Djaimilia Pereira de Almeida, specifically Luanda, Lisboa, Paraíso, Maremoto, and As Telefones — question the racial regimes of representation within the national literary canon. Grounded in Black and decolonial feminist theories, this thesis argues that these novels reclaim vulnerability from colonial frameworks, transforming it into a subversive expression against contemporary necropolitical representations. Methodologically, the study undertakes a close reading of four fictional elements — temporality, characterization, language aesthetics, and spatiality — to examine how misappropriated narratives of colonial and neoliberal injury counteract the precarity colonialism imposes on Black bodies and memories. This analysis reveals a counter-aesthetic of vulnerability, where the protagonists, despite their exposure to violence, resist passive objectification. By challenging anti-Black modern aesthetics, these novels establish ‘decolonial grammars’ that affirm the agency, inwardness, and subjectivity of Black characters within Portuguese literature, offering alternative modes of self-representation that defy and subvert colonial historicity and power

    Non-iterative numerical simulation techniques for nonlinear string vibration in musical acoustics

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    Physics-based sound synthesis of musical instruments has seen growing interest in recent years, as it allows for reproducing realistic and natural sounds while offering great flexibility and minimal storage requirements. This research falls within the scope of the NEMUS project, which is dedicated to the digital reproduction of the sound of ancient stringed instruments using physical modelling techniques. Specifically, this work focuses on the numerical simulation of nonlinear string vibration. Nonlinearities are a critical factor in accurately replicating the sound of real-world instruments. Much of the recent literature has employed energy-based methods to ensure algorithmic stability when nonlinear behaviour is present, often resulting in fully implicit schemes requiring iterative root-finding methods. While effective, these schemes are computationally expensive and introduce additional complexities. Recent developments in numerical analysis have, in some cases, enabled real-time simulation of strongly nonlinear systems using non-iterative algorithms. However, several challenges remain unresolved. This thesis aims to advance the use of finite-difference time-domain and modal methods to address nonlinearities in string vibration, which capture salient perceptual features. The emphasis is on the efficiency of the algorithms, while also developing a framework for the sound synthesis of nonlinear strings. The work begins with a comprehensive review of string models and simulation techniques, covering both historical and modern approaches. Linear models are then used as a starting point, allowing for the introduction of impedance-type boundary conditions. The research then investigates typical nonlinear effects in string vibration, such as geometric nonlinearities, collisions, and friction, using newly developed non-iterative approaches, including quadratisation-based methods for conservative forces. These techniques significantly reduce computation times, making real-time simulation feasible for most systems. However, the quality of the simulations is still highly dependent on tailored discretisation choices. The thesis concludes with two case studies that apply these methods to physical models of musical instruments

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