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Content-aware approach for improving biomedical image analysis: an interdisciplinary study series
Biomedicine is a highly interdisciplinary research area at the interface of sciences, anatomy, physiology, and medicine. In the last decade, biomedical studies have been greatly enhanced by the introduction of new technologies and techniques for automated quantitative imaging, thus considerably advancing the possibility to investigate biological phenomena through image analysis. However, the effectiveness of this interdisciplinary approach is bounded by the limited knowledge that a biologist and a computer scientist, by professional training, have of each other’s fields. The possible solution to make up for both these lacks lies in training biologists to make them interdisciplinary researchers able to develop dedicated image processing and analysis tools by exploiting a content-aware approach.
The aim of this Thesis is to show the effectiveness of a content-aware approach to automated quantitative imaging, by its application to different biomedical studies, with the secondary desirable purpose of motivating researchers to invest in interdisciplinarity. Such content-aware approach has been applied firstly to the phenomization of tumour cell response to stress by confocal fluorescent imaging, and secondly, to the texture analysis of trabecular bone microarchitecture in micro-CT scans. Third, this approach served the characterization of new 3-D multicellular spheroids of human stem cells, and the investigation of the role of the Nogo-A protein in tooth innervation. Finally, the content-aware approach also prompted to the development of two novel methods for local image analysis and colocalization quantification.
In conclusion, the content-aware approach has proved its benefit through building new approaches that have improved the quality of image analysis, strengthening the statistical significance to allow unveiling biological phenomena. Hopefully, this Thesis will contribute to inspire researchers to striving hard for pursuing interdisciplinarity
Kissing stenting of aortic bifurcation for aorto-iliac obstructive disease: a comparison between bare metal stents and covered stents
INTRODUCTION
Aim of this multicentric study:to compare the short-and mid-term results of bare metal stents(BMS)and covered stents(CS)in the Kissing Stent(KS)technique.
METHODS
Patients undertaking a KS with BMS or CS between January 2017-August 2021 included. Morphological features of plaques were classified as per the extension of calcifications and thrombosis. Every endpoint and outcome was compared in relation to BMS or CS. All patients included received dual anti-platelets DAPT)for at least one month.
RESULTS
Thirty-four patients enrolled,17 treated with BMS and 17 with CS. Average age 66 years. The 80% of patients were part of TASC C-D categories. DAPT was administered to 82.4%(28/34)of patients with a mean duration of 4.4±1.6 months. Mean follow-up 32.1±17.8 months. Technical Success was 100%. Immediate Clinical Success was reached in 29 cases(85.3%). Immediate and 30-day Clinical Success was higher in CS(64.7% vs 100%, p=.01). Overall Clinical Success at 1-year follow-up was 91.2%,and resulted significantly higher in CS(82.4% vs 100%,p .04). Overall Primary Patency,Assisted Patency,and Secondary Patency at 30 days were 97.1%,97.1%,and 100%,without differences between BMS and CS(94.1% vs 100%,94.1% vs 100%,and 100% vs 100%;p =.7). Two cases(5.9%)of thrombosis were registered,and both occurred within 3 months after the procedure and both in the BMS,without statistical differences with the CS group(11.8% vs 0%,p .48). Both cases of thrombosis occurred in patients who were not treated with dual antiplatelet therapy(33.3% vs 0%,p .027). Survival statistically differed only at the mean follow-up in favour of CS(70.6% and 100%,p .04).
CONCLUSIONS
The endovascular approach is currently safe and effective in the treatment of AIOD,and KS offers excellent results in particular if performed with CS; however,no statistically significant differences emerged between the two types of stents in terms of patency,reintervention,and complications. DAPT seems to warrant the best results in terms of patency,although there is still no consensus about the ideal duration of administration
Design and characterization of polymorphs and co-crystals of organic molecular semiconductors
In the last decades, organic semiconductors have attracted attention due to their possible employment in solution-processed optoelectronic and electronic devices. One of the advantages of solution processing is the possibility to process into flexible substrates at low cost. Organic molecular materials tend to form polymorphs, which can exhibit very different properties. In most cases, the control of the crystal structure is decisive to maximize the performance of the final device. Although organic electronics have progressed a lot, n-type organic semiconductors still lag behind p-type, presenting challenges such as air instability and poor solubility.
NDI derivatives are promising candidates for applications in organic electronics due to their characteristics. Recently, the structure-properties relationship and the polymorphism of these molecules have gained attention.
In the first part of this thesis, NDI-C6 thermal behavior was extensively explored which revealed two different behaviors depending on the annealing process. This study allowed to define the stability ranking of the NDI-C6 bulk forms and to determine the crystal structure of Form γ at 54°C. Additionally, the polymorphic and thermal behavior of thin films of NDI-C6 was also explored. It was possible to isolate pure Form α, Form β, Form γ and a new metastable Form ε. It was also possible to determine the stability ranking of the phases in thin films. OFETs were fabricated having different polymorphs as active layer, unfortunately the performance was not ideal.
During the second part of this thesis, core-chlorinated NDIs with fluoroalkyl chains were studied. Initially, the focus was on the polymorphism of CF3-NDI that revealed a solvate form with a very interesting molecular arrangement suggesting the possibility to form charge transfer co-crystals. In the last part of the thesis, the synthesis and characterization of CT co-crystal with different NDI derivatives, and acceptor and as donor BTBT and ditBu-BTBT were explored
Relationship between phenotype and environment in marine calcifying organisms: exploring growth and shell properties of different mollusks species in past and modern scenario
Coastal ecosystems represent an inestimable source of biodiversity, being among the most productive areas on the planet. Despite the great ecological and economic value of those environments, many threats endanger the species living in this ecosystem, like the rapid warming and the sea acidification, among many other. Benthic calcifying organisms (e.g. mollusks, corals and echinoderms) in particular, are among the most exposed to those hazards. These organisms use calcium carbonate as a structural and protective material through the biomineralization process, biologically controlled by the organism, but nevertheless, strongly influenced by the environmental surroundings. Evaluating how a changing environment can influence the process of biomineralization is critical to understand how those species of great ecological and economic importance will face the ongoing climate change.
This thesis investigates the mechanism of biomineralization in different mollusks’ species of the Adriatic Sea, providing detailed descriptions of shells skeletal, biometric and growth parameters. Applying a multidisciplinary and multi-scale research approach, the influence of external environmental factors on the process of shell formation has been investigated. To achieve this purpose analysis were conducted both on current populations and on fossil remain, which allows to investigate ecological responses to past climate transitions. Mollusks’ shells in fact are one of the best tools to understand climate change in the past, present and future, since they record the environmental conditions prevailed during their life, reflected on the geochemical properties, microstructure and growth of the shell. This approach allowed to overcome the time scale limit imposed by field and laboratory survey, and better understand species long term adaptive response to changing environment, a crucial issue to define proper conservation and management strategies.
Furthermore, the investigation of fossil record of mollusks assemblages offered the opportunity to evaluate the long-term biotic response to anthropogenic stressors in the north Adriatic Sea
From sacrifice to prayer. The destruction of the Second Temple in Jerusalem and the cultic transformations of the Jewish religion
La distruzione del Secondo Tempio di Gerusalemme nel 70 e.v. rappresenta un momento cruciale nell’evoluzione storica e teologica della religione giudaica. Prima della catastrofe, l’intero sistema cultuale si fondava sulle ritualità sacrificali, che si concentravano esclusivamente nel santuario gerosolimitano. Con la caduta di quest’ultimo e il venir meno delle sue prassi, il giudaismo dovette ripensare totalmente la propria religiosità, la quale andò gradualmente a imperniarsi sulla preghiera e su atti di devozione non cruenti, in una prospettiva più aperta, mobile e orizzontale. Pertanto, questa ricerca si pone lo scopo di analizzare, in una prospettiva fortemente votata all’antropologia, alla storia e alla sociologia della religione, il senso profondo di tale trasformazione. A questo fine, è stato studiato il culto sacrificale e liturgico giudaico precedente e successivo al 70 e.v., indagando in particolare alcuni aspetti specifici, quali la spazialità sacra, la gestualità rituale e l’uso della musica. In questo modo, è stato possibile delineare alcune logiche fondamentali che costituiscono la struttura dell’intero sistema religioso. Confrontando quelle del periodo del Secondo Tempio con quelle posteriori a esso, è dunque emersa una certa linearità, ma anche una forte discontinuità nella percezione del sacro e dei suoi rituali, fornendo così una nuova interpretazione del significato di una trasformazione di così vasta portata.The destruction of the Second Temple in Jerusalem in 70 CE represents a crucial moment in the historical and theological evolution of the Jewish religion. Before the catastrophe, the entire cultic system was based on sacrifices, which were concentrated solely in the Temple. With the fall of the latter and the demise of its practices, Judaism had to completely rethink its religion, which gradually became centered on prayer and non-bloody acts of devotion, in a more open, mobile, and horizontal way. Therefore, this research aims to analyze, from a perspective strongly rooted in the anthropology, history, and sociology of religion, the profound meaning of this transformation. To this purpose, the Jewish sacrificial and liturgical cult before and after 70 CE was studied, especially investigating certain specific aspects, such as sacred spatiality, ritual gestures, and the use of music. In this way, it has been possible to outline some fundamental logics that constitute the structure of the entire religious system. Comparing those of the Second Temple period with those after it, a certain linearity emerged, but also a strong discontinuity in the perception of the sacred and its rituals, thus providing a new interpretation of the meaning of such a major transformation
Delation as a procedural instrument to combat public corruption
La corrupción pública se ha incrementado con la globalización, generando una crisis de investigación que reduce la eficiencia del proceso penal para perseguir y sancionarla. En ese contexto, se plantea que la delación ha estado presente desde época romana, pasando por la Inquisición y época contemporánea, y constituye una herramienta procesal moderna con la cual se busca fortalecer la prevención y persecución de dicho delito. Así pues, se examina los antecedentes, mecanismos y efectos de la delación, el uso del whistleblower y la posición jurídica del delator, así como los aspectos procesales relacionados con la delación en la investigación, la práctica probatoria y los recursos de apelación y casación. Finalmente, se concluye que la colaboración del arrepentido requiere de corroboración y ser sometida a contradicción para que su valor incriminatorio sea empleado en la condena de los delitos.Public corruption has increased with globalization, generating an investigation crisis that reduces the efficiency of the criminal process to prosecute and punish it. In this context, it is proposed that the delation has been present since Roman times, passing through the Inquisition and contemporary times, and constitutes a modern procedural tool with which it seeks to strengthen the prevention and prosecution of such crime. Thus, it examines the background, mechanisms and effects of the delation, the use of the whistleblower and the legal position of the informant, as well as the procedural aspects related to the denunciation in the investigation, the evidentiary practice and the resources of appeal and cassation. Finally, it is concluded that the collaboration of the whistleblower requires corroboration and to be submitted to contradiction for its incriminating value to be used in the conviction of the crimes
Modelling and classification with quantile-based distributions
In this work, we explore and demonstrate the potential for modeling and classification using quantile-based distributions, which are random variables defined by their quantile function.
In the first part we formalize a least squares estimation framework for the class of linear quantile functions, leading to unbiased and asymptotically normal estimators. Among the distributions with a linear quantile function, we focus on the flattened generalized logistic distribution (fgld), which offers a wide range of distributional shapes. A novel naïve-Bayes classifier is proposed that utilizes the fgld estimated via least squares, and through simulations and applications, we demonstrate its competitiveness against state-of-the-art alternatives.
In the second part we consider the Bayesian estimation of quantile-based distributions. We introduce a factor model with independent latent variables, which are distributed according to the fgld. Similar to the independent factor analysis model, this approach accommodates flexible factor distributions while using fewer parameters. The model is presented within a Bayesian framework, an MCMC algorithm for its estimation is developed, and its effectiveness is illustrated with data coming from the European Social Survey.
The third part focuses on depth functions, which extend the concept of quantiles to multivariate data by imposing a center-outward ordering in the multivariate space. We investigate the recently introduced integrated rank-weighted (IRW) depth function, which is based on the distribution of random spherical projections of the multivariate data. This depth function proves to be computationally efficient and to increase its flexibility we propose different methods to explicitly model the projected univariate distributions. Its usefulness is shown in classification tasks: the maximum depth classifier based on the IRW depth is proven to be asymptotically optimal under certain conditions, and classifiers based on the IRW depth are shown to perform well in simulated and real data experiments
Investigation of plant genetic-microbiome interactions in different plant species
The rhizosphere, i.e. the soil surrounding the plant roots, and endosphere, i.e. the microbial communities within the plant organs harbors microbes known to influence root and plant physiological processes. An important question is to what extent plant species, genotypes and environmental conditions affect bacterial and fungal communities.
The objectives of the first research study were to unravel and compare the rhizospheric microbiota of grape in two independent vineyards using 16S and ITS amplicon sequencing, evaluate location and varietal effects, and test the correlation between bioavailable copper levels and other soil parameters with microbiota composition and diversity. Our results showed that the microbial alpha diversity based on Shannon index differed significantly between vineyards while it did not differ between two grape cultivars.
In the second study, we were focusing on different wheat species and genotypes such as Bread Wheat, Wild Emmer Wheat, Domesticated Emmer Wheat, Durum Wheat Landraces, Durum Wheat cultivars, T. monococcum and triticale in two fields located in Bologna and Foggia. The objectives of this research experiment were to elucidate and compare the rhizospheric and endophytic microbiota of 30 diverse wheat genotypes in two different fields using 16S amplicon sequencing. Our results showed that the microbial alpha diversity based on Shannon index differed significantly between fields of Bologna and Foggia, in which Bologna had a higher diversity in respect to Foggia for both rhizospheric and endophytic communities. Using Shannon index there was significant differences, for instance, between Durum Emmer Wheat and Wild Emmer Wheat in Bologna, and between Bread Wheat and Durum Wheat Landraces in Foggia. Our results contribute to understand the role of wheat species and genotype and the filed management on the root-microbe-soil interactions in the perspective of understanding their impact on crop systems sustainability
Governing algorithms in the big data era for balancing new digital rights - designing GDPR compliant and trustworthy XAI systems
This thesis investigates the legal, ethical, technical, and psychological issues of general data processing and artificial intelligence practices and the explainability of AI systems. It consists of two main parts.
In the initial section, we provide a comprehensive overview of the big data processing ecosystem and the main challenges we face today. We then evaluate the GDPR’s data privacy framework in the European Union. The Trustworthy AI Framework proposed by the EU’s High-Level Expert Group on AI (AI HLEG) is examined in detail. The ethical principles for the foundation and realization of Trustworthy AI are analyzed along with the assessment list prepared by the AI HLEG. Then, we list the main big data challenges the European researchers and institutions identified and provide a literature review on the technical and organizational measures to address these challenges. A quantitative analysis is conducted on the identified big data challenges and the measures to address them, which leads to practical recommendations for better data processing and AI practices in the EU.
In the subsequent part, we concentrate on the explainability of AI systems. We clarify the terminology and list the goals aimed at the explainability of AI systems. We identify the reasons for the explainability-accuracy trade-off and how we can address it. We conduct a comparative cognitive analysis between human reasoning and machine-generated explanations with the aim of understanding how explainable AI can contribute to human reasoning. We then focus on the technical and legal responses to remedy the explainability problem. In this part, GDPR’s right to explanation framework and safeguards are analyzed in-depth with their contribution to the realization of Trustworthy AI. Then, we analyze the explanation techniques applicable at different stages of machine learning and propose several recommendations in chronological order to develop GDPR-compliant and Trustworthy XAI systems
Methylmercury and polycyclic aromatic hydrocarbons in Mediterranean seafood: a molecular anthropological perspective
Seafood carries several contaminants, among which mercury and polycyclic aromatic hydrocarbons are those that cause major concern. Evidence exists that human populations are exposed to these environmental chemicals since ancient times, which may have driven the positive selection of specific genetic polymorphisms related to chemicals toxicokinetic. Both mercury and polycyclic aromatic hydrocarbons are able to cause DNA methylation changes in humans. Some Mediterranean populations may be particularly exposed to these contaminants, being the Mediterranean Sea at a high-risk for contamination by toxic compounds, and because of their traditionally high consumption of locally caught seafood. Starting from these premises the present thesis aims to contribute to the understanding of the molecular impact of seafood consumption on the biology of the Mediterranean population. To this end the work has been divided into four main parts: (1) the development and meta-analysis of a georeferenced database on polycyclic aromatic hydrocarbons in Mediterranean seafood aimed at identifying geographical patterns of contamination and trends that could be related to the biology of the marine organisms, to the physico-chemical properties of each hydrocarbon and to the oceanographic characteristic of the Mediterranean; (2) the development and validation of a food frequency questionnaire to estimate the intake of mercury through seafood consumption among a population living in a geographic area that is usually considered a contamination hotspot; (3) the creation of a biobank made of biological samples from members of several Italian communities together with information on their dietary habits, lifestyle and general health; (4) a review of the literature on the genetic component of individual susceptibility to methylmercury and polycyclic aromatic hydrocarbons exposure in humans, to the effects that these pollutants have on human DNA methylation, and to the evidence that Mediterranean coastal communities represent an informative case study to investigate the potential molecular impact of these chemicals