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    Rationale and study protocol of the MAMELI Cohort study (Mapping the Methylation of repetitive elements to track the Exposome effects on health: the city of Legnano as a Living lab)

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    The concept of the exposome encompasses all the factors influencing human health throughout the life course. The exposome induces epigenetic changes, such as DNA methylation, which influence gene expression and impact overall health. Several recent studies have explored how repetitive elements (REs) in the genome can be activated in response to environmental stimuli. However, most of these investigations have assumed that altered RE methylation is always detrimental to individual health. The MAMELI project proposes an alternative hypothesis: that some REs are plastic entities capable of responding physiologically to environmental stimuli without compromising genome stability. This hypothesis suggests that the ability of DNA to adapt to environmental triggers could be monitored and used as an indicator of health resilience. To test this hypothesis, the MAMELI project will enroll 6,200 participants from the city of Legnano (Italy) and will be conducted in three main phases: i) A total of 200 healthy participants will undergo DNA methylation analysis through third-generation sequencing at two time points: T0 (baseline) and T1 (6 months after T0). This phase aims to identify a set of REs ("differential REs") whose methylation changes in response to the exposome without affecting genome stability; ii) This phase will include 2,700 subjects (the original 200 participants from the discovery phase plus 2,500 additional subjects). The goal will be to develop a predictive algorithm (the MAMELI algorithm) that links the exposome to RE methylation status, creating a "RE methylation signature" reflecting the environmental impact on DNA methylation; iii) In this phase, the MAMELI algorithm will be applied to a separate cohort of 3,500 participants to compare the measured RE methylation signature with values predicted by the algorithm. Additionally, an intervention study will be embedded within the cohort to assess the reversibility of RE methylation following lifestyle changes. The MAMELI project offers a novel perspective in the field of epigenetics and environmental health, demonstrating how the epigenome can act as a sensor for environmental changes and how this interaction can be harnessed for disease prevention. If validated, the MAMELI algorithm could become a powerful tool for identifying individuals at risk and developing personalized interventions to improve global health outcomes

    Rare Bacteria and Uncommon Organismsin Chronic Bacterial Prostatitis

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    Introduction: Currently,non-pathogenic bacteria, suchas Gram-positive microorganisms,have been discov-ered as the causative agents of chronic bacte-rial prostatitis (CBP) and non-culturable organisms on standardmedia but detectable using molecular techniques, have beenimplicated in chronic prostatitis syndromes. In this paper, weinvestigate the incidence and the nature of uncommon organismsfound in cultured material from CBP patients.Materials and methods: We have reviewed bacterial isolatesfrom urine, prostatic secretions, urethral smear, and total ejaculatefrom confirmed CBP cases from March 2008 to March 2021.Most of these (472) were assessed from Meares–Stamey’s “fourglass” and Nickels’ “two glass” tests (358 and 114, respectively).Urethral smear and total ejaculate samples from subjects witha history of epididymitis and concomitant urethritis (32 and 94,respectively) were additionally evaluated.Results: The majority of the five hundred and seventy-eightcultures developed bacterial isolates from common pathogens.In a small number of cases (41/7.09%), were found unusualpathogens (namely, Morganella morganii, Acinetobacter bau-mannii, Streptococcus species (mitis oralis, milleri, parasan-guinis, salivarius, and anginosus), Haemophilus parainfluenzae,Raoultella planticola, Klebsiella oxyto-ca, Serratia marcescens,Brevundimonas diminuta, Enterobacter aerogenes, Pseu-domonas oryzihabitans, Gemella morbillorum, Citrobacterfreundii, Citrobacter koseri, and Oligella urethralis). In almosthalf of these cases (20/41), the pathogens were found inpolymicrobial isolates.Conclusion: Unusual organisms and rare bacteria are iden-tified more frequently in current studies than in the past. Thereason for this epidemiological shift is virtually unknown; how-ever, these “rare” pathogens may represent temporal trends inbacterial colonization of the prostate due to in-creasing bacte-rial resistance worldwide

    Comparison of the Environmental Impact of Similar Prefabricated Industrial Structures Made of Precast Concrete or Steel

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    Environmental sustainability is assuming a growing role in the strategic plans of several countries worldwide. In order to switch to more sustainable solutions in the construction field, many researchers and efforts are focusing on the material level, mainly concerning solutions aimed at partially or fully replacing the most impacting components with alternative or recycled solutions characterised by a lower carbon footprint or a higher durability, in view of a life-cycle assessment. Alongside these positive efforts, another instrument to reduce the environmental impact of construction materials, often less tackled by researchers, is reduction of environmental impact by smart structural design. This concept is analysed in the present paper by comparing the environmental impact of similar single-storey supermarket industrial facilities, designed under the same conditions though with different prefabrication technologies: precast concrete and steel. Having at disposal the global bill of materials employed for the superstructure of the precast concrete buildings without cladding and finishes, and after simulated design of a similar steel carpentry building under the same geometric and load conditions, the comparison was carried out based on several environmental impact indicators certified by material producers through Environmental Product Declarations (EPDs). The results allow to evaluate and compare the impact of the structural solutions in the stages of material supply and manufacturing (A1-A3). The analysis demonstrates that, despite using materials with high footprint, the precast solution allows a relevant global reduction of all the environmental indicators, thanks to the structural optimisation allowed by the use of such materials in combination with advanced batching and moulding technologies, and the steel solution turns out being significantly more impacting

    Enhancing upconversion with space–time entanglement: from twin photons to twin-beams

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    We investigate the use of entangled photons generated by parametric downconversion to improve the efficiency of second harmonic generation (SHG). Using a fully three-dimensional model for the nonlinear interactions, we obtain quantitative predictions of the efficiency of quantum-enhanced SHG and identify the critical parameters to optimize the process. By a careful control of the spatial and temporal degrees of freedom, we demonstrate a robust quantum advantage, extending to illumination fluxes well above the limits traditionally considered in the literature. Our analysis offers valuable insights into the ongoing debate on quantum-enhanced two-photon processes and helps establish their usefulness in applications

    Il Faculty Development basato sull’Action Learning Approach

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    Uno degli approcci più e"caci per stimolare l’innovazione didattica nelle università è la creazione di gruppi di lavoro tra docenti che condividono esperienze, difficoltà e strategie adottate in aula. Il lavoro di gruppo tra docenti non è solo un modo per condividere pratiche, ma anche uno strumento per costruire competenze e sviluppare innovazioni. La collaborazione tra colleghi permette di unire diverse prospettive e competenze, trasformando idee individuali in progetti comuni che possono essere testati, analizzati e, se e"caci, condivisi su più ampia scala

    Understanding Artificial Intelligence in Chess: The RubiChess Case Study

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    Software chess engines and advanced solutions based on Artificial Intelligence (AI) are changing the historical game of chess. Several AI-based chess engines are now available as closed or open software solutions with unique characteristics and game abilities. However, these AI-based engines are very complex to analyze from a functional point-of-view, and a deep study of their source code is not often enough to understand the advantages and disadvantages of their game approach. In this paper, we adopted a two-fold approach to study the behavior of a well-known AI-based chess engine called RubiChess. From one side, we studied the RubiChess architecture to understand its main game strategies and adopted algorithms. On the other side, we simulated a set of matches played against other AI chess engines, and we evaluated these matches (in different conditions) by using statistical tests and data visualization to determine the properties that made RubiChess unique. For example, the simulations highlight that RubiChess performs better as a white player and during "slow" games. This gives engine developers and players important insights into how RubiChess plays

    Replacing fishmeal with an insect meal blend: implications for intestinal microbiota in European seabass.

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    In this study, we investigated the effects of an insect meal (IM) blend containing larvae of Hermetia illucens and Tenebrio molitor on the gut microbiota of European seabass (Dicentrarchus labrax), a key species in Mediterranean marine aquaculture. This research stands out by examining a combination of IMs rather than a single source, thereby addressing an underexplored area in the current literature. In a feeding trial that lasted 75 days, European seabass were fed three different diets: a commercial-like control diet and two experimental diets containing partial replacement of FM with IM (25 % and 50 %). The experimental diets showed no adverse effects on feed intake or overall fish health. Analysis of the microbiota revealed significant changes in gut microbial communities, with a trend towards increased bacterial richness and diversity in fish fed IM. Beta diversity analysis showed that the mucosa-associated microbial communities were stable across diets, while the digesta associated microbiota showed notable shifts in the IM25 and IM50 groups, suggesting that the transient microbiota is more sensitive to dietary changes. The study also found an enrichment of beneficial bacterial genera, particularly Bacillus and Paenibacillus, in fish fed IM. These genera, known for their chitinolytic activity, have likely adapted to the increased chitin content in IM diets. Oceanobacillus (Bacillaceae) and Brevibacterium (Brevibacteriaceae) were more abundant in the digesta of fish from the IM25 and IM50 groups, but not in the mucosa. Their presence indicates that they react more strongly to changes in diet than to a stable mucosal environment. Overall, the study highlights the potential of an IM-based diet to support fish health and growth while promoting a favorable gut microbiota

    Predictors and Patterns of Recurrence in Vulvar Cancer

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    Objective: To identify prognostic factors predicting recurrence in vulvar cancer patients undergoing surgery. Methods: We retrospectively evaluated data from consecutive patients with vulvar cancer treated between 2002 and 2024 in 2 Italian centers. Basic descriptive statistics and multivariable analysis were used to create predictive models for patient outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using a Cox proportional hazards model. Results: The study included 283 patients diagnosed with vulvar cancer (239 with squamous cell carcinoma). The most frequent stages were stage I (50.9%) and stage III (30.4%). After a median follow-up of 27 months, 91 (32.2%) recurrences were observed, of which 20% were local, 6% were regional, and 6% were distant. The five-year DFS and OS were 46% and 60%, respectively. Multivariate analysis identified the presence of positive lymph nodes (hazard ratio [HR]: 3.54, 95% confidence interval [CI]: 1.04-12.08), age (HR: 1.02, 95% CI: 1-1.04), FIGO stage II (HR: 3.12, 95% CI: 1.24-7.87), and FIGO stage IV (HR: 3.85, 95% CI: 1.19-12.43) as factors associated with worse DFS. Positive nodes (HR: 2.64, 95% CI: 1.2-5.8) and tumor diameter > 4 cm (HR: 1.89, 95% CI: 1.05-3.42) were associated with OS. FIGO stage > I was predictive of regional and distant recurrences, but no factor was found to correlate with local recurrence. Conclusions: FIGO stage > I was predictive of regional and distant recurrences, while no factors influencing local recurrence were identified. Positive nodes, age, and FIGO stage > I correlated with DFS, whereas tumor diameter > 4 cm and positive nodes influenced OS

    External validation of the annual recurrence risk model for tailored surveillance strategy in patients with cervical cancer

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    Objective: The annual recurrence risk model (ARRM), developed by the Surveillance in Cervical Cancer consortium and endorsed by the European Society of Gynecological Oncology, predicts the annual risk of cervical cancer recurrence. However, it lacks an external validation, which we aimed to address in the current retrospective study. Methods: We included patients with pathology confirmed T1a to T2b cervical cancers who underwent radical surgery at the European Institute of Oncology, Milan from January 2010 to December 2022. Using the ARRM risk calculator, patients were assigned a score from 0 to 100 points, which allowed classification into 5 risk groups (0, 1-25, 26-50, 51-75, and 76-100 points). Differences in 5-year disease-free survival were evaluated through log-rank tests with pairwise comparisons. Annual risk of recurrence was calculated using conditional survival analysis. Results: Overall, 411 patients with cervical cancers were included: 0 (0.0%) scored 0 points, 149 (36.3%) scored 1 to 25 points, 224 (54.5%) scored 26 to 50 points, 37 (9.0%) scored 51 to 75 points, and 1 (0.2%) scored 76 to 100 points. The patient from 76 to 100 points was excluded from further analyses. The 5-year disease-free survival rates were 96.3% (95% CI 90.0 to 98.6), 85.7% (95% CI 80.1% to 89.9%), and 66.6% (95% CI 47.3% to 80.2%) in groups 1 to 25, 26 to 50, and 51 to 75 points, respectively (p < .01). Compared with 26 to 50 and 51 to 75 points, the annual risk of recurrence was lower in the 1 to 25 points group, at around 1% from year 1 to 5. Conclusions: The ARRM tool confirmed its validity in stratifying cervical cancer into groups with significantly different disease-free survival rates in an independent large population from a tertiary center. The annual risk of recurrence should be carefully considered when tailoring follow-up, always taking into account the patient's perspective

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