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Artificial intelligence prognostic predictive algorithms in advanced lung cancer using pre-therapy 18F-FDG PET-CT metabolic parameters. Preliminary results.
No full textLo studio mira a definire modelli predittivi prognostici di Progression Free Survival (PFS) e di sopravvivenza globale (OS) utilizzando i parametri metabolici estratti da PET-CT [18F]-FDG pre-trattamento di pazienti con NSCLC stadio IV. Materiali e metodi: sono stati valutati retrospettivamente i dati PET-CT pre-trattamento di 51 pazienti con NSCLC in stadio IV. I volumi di interesse di tumore, linfonodi e metastasi (TNM VOI) sono stati delineati sulle scansioni PET e sono stati registrati i parametri metabolici MTV, SUVmax e SUVmean di T, N e M. È stata eseguita un'analisi di sopravvivenza utilizzando le curve di Kaplan-Meier (KM) e log-rank test. La PFS è stata valutata mediante valutazione PET-CT o TC di follow-up. Sono stati testati quattro modelli per eseguire l'analisi di sopravvivenza: CoxPH, CoxNet, Random Survival Forest (RSF) e Gboost. Il punteggio Bier integrato (IBS) e l'indice di concordanza (C-index) sono stati calcolati per ciascun modello dopo nested cross validation. L'analisi della sopravvivenza tramite KM e log-rank test è stata condotta per ciascun modello. Risultati: nessuno dei test log-rank KM ha mostrato valore p significativo nel predire la PFS o l'OS utilizzando dati quali SUVmax di T, N e M, SUVmean di T, N e M. Il modello RSF_TNM ha mostrato la migliore performance nel discriminare tra alto e basso rischio di PFS [C-index: 0,575, IBS: 0,23 e rapporto valori P significativi nel 24% dei casi]. RSF_TNM è stato il modello migliore, anche considerando l'OS: RSF_TNM, con un C-index di 0,59 con CI (intervallo di confidenza al 95%): 0,478 – 0,707, IBS di 0,236 e un rapporto P-value significativo nel 32% dei casi. Conclusioni: alcuni dei percorsi di machine learning proposti potrebbero avere il potenziale per prevedere con precisione la PFS e l'OS nei pazienti con NSCLC avanzato incorporando parametri PET metabolici dal VOI TNM.The study aims to define a prognostic Progression Survival (PFS) and Overall survival (OS) modeling framework by selecting metabolic parameters extracted from pre-treatment [18F]-FDG PET-CT of stage IV NSCLC patients. Materials and methods: we retrospectively evaluated pre-treatment PET-CT data of 51 patients undergoing Best Standard of Care. Tumor, lymph node, and metastasis volumes of interest (TNM VOI) were delineated on PET, and metabolic parameters MTV, SUVmax, and SUVmean of T, N, and M were recorded. A survival analysis was performed using Kaplan-Meier (KM) curves and log-rank tests. Follow-up PET-CT or CT evaluated the PFS. Nested cross-validation with PCC (Pearson Correlation Coefficient) >0.8 was applied for reliable results. Four models were tested in performing survival analysis: CoxPH, CoxNet, Random Survival Forest (RSF) and Gboost. The integrated Bier Score (IBS) and (Concordance-index) C-index were applied. The percentage of the significant p-value of KM curves log-rank test, was evaluated for each model. Results: None of the KM log-rank tests showed a significant p-value in predicting PFS or OS using data such as SUVmax of T, N, and M, SUVmean of T, N, and M. The highest percentage of significant p values to discriminate for high and low risk of PFS is shown by the RSF_TNM model [C-index: 0.575, IBS: 0.23, and significant P-values ratio in 24% of cases]. Even when OS was considered, the RSF_TNM was the best model in successfully stratifying high- and low-risk groups with a C-index of 0.59 with (95% confidence interval) CI: 0.478 – 0.707, IBS of 0.236 and a significant P-values ratio in 32% of cases. Conclusions: Some of the proposed machine learning pipelines may have the potential to accurately predict PFS and OS in patients with advanced NSCLC by incorporating conventional metabolic PET parameters from TNM VOI
New methodologies for the stereoselective synthesis and modification of nitrogen containing molecules
No full textThe chemistry of nitrogen-containing compounds is highly significant due to their numerous applications in various aspects of life. These compounds are fundamental to essential biomolecules that enable biological functions, such as amino acids (and consequently all proteins) and nucleic acids (DNA and RNA). Many biologically active natural and synthetic products contain nitrogen, with alkaloids and heterocycles such as piperidine, pyridine, piperazine, β-lactam, and pyrrolidine being some of the most prominent examples. Additionally, nitrogen-containing compounds serve as ligands and catalysts, further demonstrating their broad utility. For this reason, this PhD thesis focuses on the synthesis and functionalization of nitrogen-containing compounds, while also addressing sustainability issues whenever possible. The thesis is structured into distinct chapters, each dedicated to a specific project with a defined objective. Chapters 3 and 4 focus on the diastereoselective synthesis of substituted pyrrolidine scaffolds via the addition of organometallic species to chiral sulfinyl imines. Specifically, Chapter 3 describes the development of a new stereoselective synthesis of α-disubstituted β-amino acids. Chapter 4 details the design of a stereoselective synthesis for a key intermediate intended for the preparation of new Hayashi-type catalysts, in which the silyl ether moiety is replaced with a more stable alkyl ether moiety. Chapter 5 presents a new methodology based on EDA photochemistry for the enantioselective preparation of γ-amino aldehydes. Continuing the focus on photochemistry, Chapter 6 explores the possibility of improving the sustainability of a known photocatalytic α-arylation of amines by conducting the reaction in green media and recycling the metal-based photocatalyst. Finally, Chapter 7 investigates the hydrofunctionalization of allenamides to generate γ-heterosubstituted enamides, with sustainability and broad applicability as central objectives
Production, composition and sensory characterization of new flavoured oils: focus on sustainability
No full textThis research explores the integration of agri-food by-products into flavoured vegetable oils to develop innovative, sustainable, and nutritionally enhanced products. Specifically, tomato pomace, rich in lycopene, was dried using a non-thermal drying prototype to reduce moisture content, improve stability, and preserve bioactive compounds. After 110 days of storage, dried samples showed lower carotenoid degradation compared to conventional thermal drying, which can cause up to 80% immediate carotenoid loss.
Subsequently, olive oil was flavored through co-malaxation with dried tomato powders and co-milling with other by-products (orange peel, black pepper, and hemp seeds). The analysis confirmed that the non-thermal drying method preserved tocopherols, carotenoids, and bioactive compounds, contributing to a distinctive sensory profile with notes of tomato, orange, and balsamic aromas. Additionally, it masked defects like the fusty/muddy off-flavor detected in control samples.
Flavored cold-pressed hemp seed oils were also developed, offering new sensory experiences while reducing food waste. Consumer tests confirmed a preference for hemp seed oil flavored with Cannabis sativa L. essential oil (obtained from distilled exhausted inflorescences) over control samples, positioning the product as a pioneer in promoting familiarity with hemp-based foods.
A biometric approach to consumer testing revealed variations in sensory and emotional engagement while tasting flavored oils containing by-products (e.g., orange pomace, hemp essential oil). This method provided insights into both conscious and unconscious emotional responses, complementing traditional sensory analysis.
In summary, this PhD research highlights the potential of incorporating food by-products into high-value flavoured oils, supporting circular economy practices while meeting consumer demand for high-quality, sensory-rich, and sustainable food products
The virtual archive of Pomposa: the abbey and its properties. analysis and representation of geographic and climatic data.
No full textLa tesi analizza il rapporto tra uomo e ambiente vallivo nel delta padano tra IX e XII secolo, ponendo al centro dell’indagine l’abbazia di Santa Maria di Pomposa (FE). La ricerca si sviluppa intorno all’analisi della documentazione proveniente dall’archivio abbaziale, avvalendosi anche del confronto con fonti narrative, agiografiche e cartografiche coeve. Si fa inoltre sempre riferimento alla letteratura scientifica relativa alla storia ambientale del Medioevo, alla storia di Pomposa, a studi archeologici, archeobotanici e archeozoologici condotti nel territorio del delta padano medievale. I sei capitoli successivi all’introduzione, dedicata alla storiografia della storia ambientale, affrontano la storia istituzionale di Pomposa; le fonti esaminate; la dinamica interrelata delle trasformazioni idrografiche del delta e del popolamento dell’area; la gestione delle risorse acquatiche; la copertura vegetale dell’area del delta padano nel pieno Medioevo e l’organizzazione agricola. La tesi è corredata di mappe dell’area deltizia realizzate con il programma QGIS e di due appendici, dedicate rispettivamente alla localizzazione dei coltivi di Pomposa e dei toponimi ricavati dalla documentazione d’archivio. Il settimo capitolo, successivo alle conclusioni, affronta il ruolo delle Digital Humanities nella ricerca, soffermandosi in particolare sulle operazioni di schedatura e marcatura in linguaggio XML della documentazione pomposiana nel database online Fiscus e sulla costruzione di un thesaurus specifico per la documentazione medievale, finalizzato all’estrazione di dati relativi all’ambiente. Nella tesi si analizza l’interazione tra le pratiche di gestione delle risorse naturali adottate dai monaci (pesca, agricoltura, bonifica, disboscamento) e le trasformazioni ambientali, con l’obiettivo di offrire nuove prospettive sulla relazione tra sfruttamento del territorio e risposte ecologiche.This thesis examines the relationship between human communities and the wetland environment of the Po Delta region, between the IX and XII centuries, focusing on the Abbey of Santa Maria di Pomposa (Ferrara, Italy). The study is based primarily on the analysis of the abbey’s archival documentation, complemented by coeval narrative, hagiographic, and cartographic sources. It further engages with the relevant scholarly literature on medieval environmental history, the history of Pomposa, as well as archaeological, archaeobotanical, and archaeozoological investigations conducted in the region. Following an introductory chapter on the historiography of environmental history, the thesis is structured into six chapters which cover the institutional development of Pomposa, the typology of the sources employed, the interrelated dynamics of hydrographic transformations and settlement patterns, the management of aquatic resources, the reconstruction of vegetation cover during the High Middle Ages, and the agricultural use of the delta area. The research is supported by cartographic material produced with QGIS and two appendices dedicated to the localization of Pomposa’s cultivated lands and the identification of toponyms from archival sources respectively. A final chapter addresses the contribution of Digital Humanities to this research, focusing on the cataloguing and XML semantic encoding of archival documents in the Fiscus online database, and the development of a specialized thesaurus for the extraction of environmental data. The study highlights how monastic practices of resource management reshaped the ecological configuration of the Po Delta and how territorial organization evolved in continuous interaction with the environmental
Peor es nada: Social Impact Bonds, measured outcomes, and employment development in Colombia
No full textThis doctoral thesis examines Colombia’s first Social Impact Bond, Empleando Futuro, a financial instrument offering returns to investors if predefined outcomes, specifically, job placement and three to six-month retention in formal employment for at least 766 beneficiaries, primarily victims of Colombia’s armed conflict, were met. The bond used a Payment by Results model: private investors provided upfront capital, and repayment by the Colombian government, the Swiss Economic Cooperation Agency, and the Inter-American Development Bank was contingent on independently verified outcomes. Based on 14 months of ethnographic fieldwork and interviews, this research situates Empleando Futuro within Colombia’s history of international development interventions and under the growing influence of audit culture, where measurable outcomes define success. It explores the perspectives of promoters and administrators seeking efficient use of public funds and investor returns; practitioners under pressure to meet measurable targets; and beneficiaries who saw formal employment as a route out of poverty, within Colombia’s precarious labour market. Drawing on anthropological perspectives on development, quantification, and financialisation, the thesis shows how Empleando Futuro reshaped social service provision into a financial operation privileging investor interests. It did so by reducing unemployment to calculable risks and outcomes capable of generating financial value, and by normalising a logic of peor es nada (something is better than nothing), accepting outcomes that satisfy investor metrics as sufficient, even when failing to address beneficiaries’ broader employment challenges. This research contributes to anthropological understandings of financialisation in development, highlighting how social problems are transformed into investment opportunities and how financial instruments redefine what counts as positive social impact—legitimising private sector profit in development while failing to produce substantial social change
Adapted physical activity as a tool to optimize exoskeleton use in daily life for individuals with spinal cord injury
No full textSpinal cord injuries significantly affect mobility, autonomy, and quality of life, impacting approximately 85,000 individuals in Italy. Advances in robotic exoskeletons show promise for improving mobility; however, challenges persist in adapting these devices for daily use, particularly in maneuverability and functionality in home settings. Additionally, structured physical activity programs are essential for enhancing the strength, endurance, and coordination required for exoskeleton use.
This project aims to develop a physical activity program to prepare individuals with spinal cord injuries for exoskeleton use. Specific objectives include: (1) identifying barriers and facilitators to exoskeleton use; (2) examining attitudes toward physical activity in this population; and (3) designing and evaluating a home-based, adapted physical activity program.
A systematic review revealed key barriers, including financial costs, environmental adaptability, and psychological acceptance. A survey highlighted motivational and environmental factors influencing physical activity participation, emphasizing personalized support. Lastly, a study protocol was developed for the SCI-HOME-ACTIVE program, featuring supervised exercises to enhance physical conditioning over three months.
The findings highlight the need for an integrated approach combining physical training, exoskeleton technology, and healthcare support to improve mobility and independence in individuals with spinal cord injuries. The study also underscores the importance of interdisciplinary collaboration, professional training, and policy measures to promote accessible and adapted physical activity programs
Biological control of Diptera in agri-food system
No full textThis study explores sustainable biocontrol to mitigate pests which can affect Italy's agri-food system: Piophila casei Linnaeus (Diptera: Piophilidae) and Drosophila suzukii Matsumura (Diptera: Drosophilidae), which threaten cured meats and small fruits, respectively. Chapter One optimized P. casei rearing and its parasitoids, Pachycrepoideus vindemiae Rondani and Muscidifurax raptor Girault & Sanders (Hymenoptera: Pteromalidae). Three diets (infant formula, milk powder, dry ham) were tested on P. casei. Dry ham accelerated development, while infant formula increased longevity and growth. The second part assessed parasitism success (SP), degree of parasitism (DP), sex ratio (SR), development time (DT), longevity (LO) and emergence rate (ER) for the two parasitoids through laboratory trials. Both had low ER, affecting DP and SP, while SR was female-biased. The final section evaluated freezing P. casei pupae at -20°C for 14–56 days on P. vindemiae rearing. Extended storage reduced ER, increased non-attraction (NA), and caused pupal decay, affecting parasitoid quality. However, DT, LO, and F2 generation quality were unaffected when emerging from fresh pupae. Chapter Two examined P. vindemiae and M. raptor releases in a ham facility. Data included total parasitism (TP), ER, SR, and LO. While LO and SR showed no significant differences, P. vindemiae had higher TP and ER, making it the superior biocontrol candidate. Chapter Three presents a non-destructive method to detect P. casei in dry-cured ham using an electronic nose to identify infestation volatiles. Tests scaled from 1 g to 500 g and whole hams (~9 kg). PCA analysis showed 80% accuracy with 1 g, 64% with 500 g, and 60% with whole hams. Chapter Four assessed D. suzukii control in Emilia-Romagna, focusing on Ganaspis kimorum Buffington (Hymenoptera: Figitidae) release. Monitoring 20 sites (2022–2023) evaluated its impact. G. kimorum overwintered and parasitized D. suzukii in 2022 but was absent in 2023
Intercropping systems: a pathway to more sustainable and resilient camelina cultivation
No full textAgriculture in developed countries has increasingly relied on intensive practices, contributing to the degradation of soil health and biodiversity. Organic farming is considered a key model for improving the sustainability of current agricultural practices. However, sustainable strategies are needed in order to increase the use of nutrients that can only be supplied organically. Numerous studies have highlighted the significant ability of intercropping systems to increase seed yield, plant N and P acquisition, weed control, and below and aboveground biodiversity. Camelina is attracting considerable attention from both the research community and the industry due to its agronomic traits and quality characteristics. The aim of the present study evaluates the productive, quality, and environmental aspects of intercropping systems including camelina under organic farming. In the first chapter, two intercropping systems were studied: camelina-pea and camelina-lentil, in comparison to their respective monocultures. The camelina-pea intercropping system proved to be the most promising, yielding more than the combined yields of their respective monocultures on the same land area (LER>1), without compromising the pea’s yield. In the second chapter, qualitative analyses were conducted on the most promising intercropping system. Camelina in intercropping significantly increased the oil percentage (36.5%) and reduced the percentage of saturated fatty acids (SFA, 10.06%), while the pea showed no significant variations. In the final chapter, the role of microorganisms in the absorption of nitrogen and phosphorus in the intercropping system was explored. An increase in nitrogen fixation and nitrogen absorption exceeding 165% was observed compared to when the individual species are grown separately. After three years of study, camelina has proven to be suitable for intercropping with pea, offering advantages in terms of productivity, quality, and environmental impact. Further research is needed regarding genetic improvement and mechanization to make these systems more efficient and cost-effective
Metabolomics to investigate the effects of treatments on food and of food consumption on health
No full textMetabolomics has established itself as a discipline that can offer a unique point of view on how a technological treatment could impact on the charactersitics of a food. Even more, the same analytical platforms necessary for the purpose can also effectively unravel intricate interactions between such food and human health upon consumption. This PhD thesis investigates the application of metabolomics in understanding the impact of technological treatments on food and their subsequent effects on human health, utilizing 1H-NMR as the analytical platform. The study involves the development of standard operating procedures (SOPs) to ensure a fast and stable preparation of seafood samples, incorporating novel algorithms to enhance the accuracy of metabolome profiles.
To gain insight on how metabolomics can allow exploring the effects of a technological treatment on a food, we performed three sets of experiments to investigate the application of metabolomics in studying the impact of high hydrostatic pressure (HHP) treatment on seafood metabolome during storage. The first experiment employs untargeted metabolomic analysis on chill-stored rose shrimp, revealing significant post-HHP treatment metabolic alterations and mechanisms. The investigation is extended to grey mullet in the second experiment, utilizing both untargeted and targeted metabolomic analyses to account for matrix-related effects. The third experiment assesses the targeted metabolome of striped prawns, showing that HHP significantly influences metabolic pathways, positively impacting freshness and taste through alterations in related metabolites.
Shifting focus to the effects of food on humans, the study explores the impact of multistrain probiotics on cirrhosis patients using 1H-NMR. The platform reveals notable alterations in glutamine/glutamate metabolism, enhancing the patients' ammonia detoxification capacity. This research underscores the potential of metabolomics in uncovering intricate interactions between technological treatments, food, and human health, providing valuable insights for both the food industry and healthcare interventions
Hypofractionated stereotactic radiotherapy after hyperbaric oxygenation for recurrent high-grade glioma: a pilot study
No full textPurpose
The presence of hypoxic cells in high-grade glioma (HGG) is one of the main reasons of local failure after radiotherapy (RT). The use of hyperbaric oxygen therapy (HBO) could help to overcome the problem of hypoxia in poorly oxygenated regions of the tumor. We performed a pilot study to evaluate the efficacy of hypofractionated image-guided helical TomoTherapy (HT) after HBO in the treatment of recurrent HGG (rHGG).
Methods
We enrolled 15 patients (aged >18 years) with diagnosis of rHGG. A total dose of 15-25 Gy was administered in daily 5-Gy fractions for 3-5 consecutive days after daily HBO. Each fraction was delivered up to maximum of 60 minutes after HBO.
Results
Median follow-up from HBO-RT was 28.6 (range: 5.3-56.8). No patient was lost to follow-up.
Median progression-free survival (mPFS) for all patients was 3.2 months (95% CI: 1.34- 6.4 ), while 3-month, 6-month and 12 month PFS was 60% (95%CI: 31.8.4-79.7), 40% (95%CI: 16.5-
62.8) and10.0 (0.8-33.5) , respectively. Median overall survival (mOS) of HBO-RT was 11.7 months (95% CI: 7.3-29.3), while 3-month, 6-month and 12 month OS was 100% , 93.3% (61.3-99.0) and 46.7 % (21.2-68.8). No acute or late neurologic toxicity >grade 2 (CTCAE version 4.3) was observed in 86.66% of patients. Two patients developed G3 Radionecrosis.
Conclusion
HSRT combined to HBO seems effective and safe in the treatment of rHGG. One of advantages of HBO-RT is the reduced overall treatment time (3-5 consecutive days)