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YEAST DERIVATIVES FOR PRECISION OENOLOGY: EMERGING AND SUSTAINABLE APPLICATION FOR WINE PRODUCTION (WINNY)
No full textYeast derivative products (YDPs) have become widely employed in modern oenology, being used as tools to enhance fermentation kinetics, improve wine stability, and modulate sensory properties. Despite their increasing application, the mechanisms underlying their action remain only partially understood, and their use in winemaking is often based on empirical knowledge rather than on a comprehensive understanding of their chemical and functional characteristics. This PhD research represents the first systematic study in which an in-depth chemical characterization was performed on such a large number of YDPs, providing an unprecedented overview of their composition. Furthermore, it constitutes the first work in which these derivatives were tested across such a broad spectrum of enological trials. In particular, the attention was focused on (I) alcoholic and malolactic fermentations, (II) tartaric, protein and color stabilization, (III) and impact on aging of sparkling wine.
The innovative approach of this thesis lied in the combination of a detailed analytical characterization with an extensive experimental evaluation, which together allow for the establishment of correlations between the chemical composition of YDPs and their oenological effects. Innovative techniques such as atomic force microscopy (AFM) and nuclear magnetic resonance (NMR) were also applied for the first time on YDPs. The results highlighted the strong variability among different commercial products, not only in terms of composition (i.e., proteins, polysaccharides, amino acids, glutathione, cysteine) but also regarding their capacity to influence fermentation kinetics, colloidal stability, antioxidant properties, protein haze formation, tartaric stabilization, and color preservation. This variability underscores the importance of considering the specific characteristics of each product, whose behavior depend not only on its intrinsic characteristics, but also on the wine matrix in which the product is employed.
The findings provided new insights into how YDPs interact with the wine matrix, clarifying some aspects of their behavior while also revealing the complexity and multifactorial nature of their effects. By analyzing and comparing their performance in different winemaking contexts, this research implements the knowledge on YDPs and on the correlation between their characteristics and the oenological functions they can better exploit thus helping industries and oenologists in selecting the most suitable derivative according to the desired technological or sensory objective. In addition, the results contribute to a better understanding of the potential of YDPs as alternatives to traditional fining and stabilization agents, with particular relevance in the context of sustainable and precision oenology. Overall, this thesis demonstrated that the functionality of YDPs could not be dissociated from their chemical composition. It also showed that their potential in winemaking extends beyond their current applications, opening new perspectives for their rational use. The comprehensive dataset generated in this study lays the groundwork for further investigations into the mechanisms of action of YDPs, which remain incompletely understood but hold considerable promise for future innovation in the wine industry
Towards a shared diagnostic approach for pediatric short stature: a Delphi consensus of the Italian Society of Pediatrics and the Italian Society for Pediatric Endocrinology and Diabetology
No full textBackground: Short stature is a common reason for referral in pediatric practice, but significant variability exists in diagnostic approaches and referral criteria. Therefore, the aim of this consensus was to improve the management of children with short stature through the knowledge and expertise of various Italian centers through a Delphi-consensus process. Methods: A multidisciplinary scientific board of 11 experts and 1 patient advocate were involved in a consensus process and used the Delphi method. The scientific board identified 4 key domains regarding short stature: clinical evaluation, biochemical assessment, imaging and genetic investigation. Two literature searches were conducted. The first search aimed to identify international guidelines and consensus on the diagnosis of short stature in children. The second search sought to retrieve clinical studies focusing on the four domains. The results of the literature searches were evaluated by the scientific board and a total of 14 statements were drafted and submitted to a panel of 39 pediatricians and pediatric endocrinologists using a two-round Delphi method conducted between February and March 2025. Consensus was defined as ≥ 80% agreement or disagreement (scores 7–9 or scores 1–3 on a 9-point Likert scale). Results: In the first Delphi round, 34 out of 39 experts responded (response rate 87%), and consensus was reached on 11 out of 14 statements. The remaining 3 statements were revised by the scientific board and re-submitted. In the second round, 34 of 34 eligible experts responded (100%), and consensus was achieved for one additional statement. Overall, a strong agreement was reached for 12 out of 14 statements. Conclusion: This consensus provides valuable insights and recommendations to guide pediatricians in approaching a child with short stature. By addressing clinical, biochemical, imaging and genetic domains this consensus provides a model of growth monitoring that may result in early detection and appropriate management of children with short stature
Fast cardiac magnetic resonance (CMR) protocol for biventricular functional assessment and tissue characterisation
No full textBackground: Clinical use of cardiovascular magnetic resonance (CMR), reference tool for cardiac function and myocardial tissue assessment, is frequently limited by long acquisition times. This study aimed to compare conventional “standard protocol” (ASSET bSSFP cine plus 2D single-segment PSIR LGE) with novel “fast protocol” incorporating deep-learning reconstruction (Sonic DL bSSFP cine and 2D multisegment PSIR LGE with AIR Recon DL), focusing on image quality, functional measurements, myocardial characterisation, and overall scan duration. Methods and results: One-hundred consecutive patients with known or suspected myocardial disease underwent both protocols. Participants were predominantly male (78%), mean age 52 ± 16 years, mean BMI 25.0 ± 4.3 kg/m2. Clinical indications included arrhythmias (26%), hypertrophic cardiomyopathy (19%), and coronary artery disease (13%). Cine image quality was comparable between ASSET bSSFP and Sonic DL bSSFP (Likert score 4.59 vs 4.56, p = 0.682), with no differences in ventricular size, function, or left ventricle mass. However, Sonic DL cine markedly shortened acquisition time for long-axis and short-axis stacks (38 vs 61 s and 125 vs 227 s respectively, both p < 0.001). Similarly, 2D-MS PS LGE preserved diagnostic quality (Likert score 4.60 vs 4.51) while reducing acquisition time for long-axis and short-axis stacks (25 vs 77 s and 78 vs 302 s respectively, both p < 0.001). The “fast” protocol reduced total scan time by nearly 60%, enabling comprehensive CMR completion in under 10 min. Conclusions: A deep learning-based “fast” CMR protocol significantly reduces scan time without compromising volumetric accuracy or image quality, resulting a feasible option for routine clinical practice
New NDM-producing and blaKPC-2 harbouring Klebsiella pneumoniae ST6668 (CC147) clone in Milan, Northern Italy
No full textUsing AI to Train Prospective Primary School Teachers to Teach AI
No full textOur work investigates the use of LLMs (Large Language
Models) as training tools for prospective primary school teachers in the
field of mathematics education and artificial intelligence (AI) literacy.
Building on previous classroom experience of introducing AI concepts
through unplugged activities, this preliminary study explores whether
LLMs can simulate students, particularly those with learning difficulties,
to support teacher preparation also in inclusive contexts. Two models,
ChatGPT-5 and Perplexity Pro, were tested using role-play prompts
designed to generate responses resembling those of real pupils. The
results indicate that while the mistakes made by the artificial students
do not completely overlap those observed in actual classrooms, the simu-
lations still provide valuable insights for teacher reflection. In particular,
the experiments highlighted challenges related to negation, set represen-
tation, and the didactic contract, with the artificial students sometimes
reproducing behaviors documented in mathematical education research,
such as anxiety-driven overgeneralization. These findings suggest that
LLMs can serve as a useful resource for developing teacher awareness
of potential learning difficulties and for designing strategies to address
them. In the future, testing can be extended to a larger number of mod-
els and tasks, and simulations can be compared with a larger amount of
empirical data from students with formally diagnosed learning disorders,
particularly dyscalculia
First molecular detection and genotyping of Enterocytozoon bieneusi (Microsporidia) in fattening pigs from Italy
No full textBackground: Enterocytozoon bieneusi is the most reported microsporidian species in humans worldwide, with high
prevalences also documented in animals, particularly pigs.
Due to limited information on E. bieneusi in Italian livestock,
this cross-sectional observational study aimed to investigate its prevalence, genetic diversity, and associated risk
factors in pigs. For this purpose, 440 faecal samples were collected from pigs raised on 22 intensive farms in northern
Italy during two sampling sessions, corresponding to the beginning and the end of the fattening cycle. A nested
PCR protocol was performed to amplify the internal transcribed spacer region (ITS), followed by DNA sequencing
for genotype identification. Moreover, several risk factors were evaluated as predictors of E. bieneusi positivity using
generalised linear models.
Results: In the first session, the positive samples were 197 out of 220 (89.5%); in the second, the positive samples
were 82 out of 220 (37.3%). Overall, 279 out of 440 pig faecal samples (63.4%) were positive for E. bieneusi. In the
multivariate analysis, age and faecal soiling of the animal’s body were significant risk factors (p-value < 0.05), with
younger animals and those with a high degree of faecal soiling showing higher prevalences. All identified ITS
sequences clustered within Group 1, which comprises the main genotypes with zoonotic potential.
Conclusions: This study demonstrates a high prevalence of E. bieneusi in Italian pigs, albeit in a single production
category, supporting their role as natural reservoirs. Further research is needed to assess the parasite’s presence in
other pig categories, humans, environmental matrices, and food products to clarify its public health significance
FUNCTIONAL CHARACTERIZATION OF THE INTERACTION BETWEENP. AERUGINOSA AND DENDRITIC CELLS TRIGGERING THE DIFFERENTIATION OF PATHOGENIC TH1/17 CELLS IN CYSTIC FIBROSIS.
No full textLa fibrosi cistica (CF) è una malattia genetica caratterizzata da una risposta infiammatoria cronica ed eccessiva a infezioni polmonari persistenti, prevalentemente causate da Pseudomonas aeruginosa (Pa). Nonostante l’ambiente polmonare ostile generato dalla disfunzione del CFTR, Pa è in grado promuovere una costante attivazione del sistema immunitario innato e adattativo. Infatti, oltre al ruolo pro-infiammatorio dannoso di neutrofili e macrofagi, i linfociti Th1/17 co-produttori di IFN-γ/IL-17 sembrano avere un ruolo patogenico cardine nella CF. Nonostante ciò, la connessione tra l’infezione di Pa e la generazione dei linfociti co-produttori di IFNγ/IL-17 non è mai stata caratterizzata.
A tal fine, abbiamo analizzato e isolato i subset di linfociti T da campioni di sangue e polmone di pazienti con CF e di pazienti non-CF mediante citofluorimetria, ed è stato analizzato il profilo trascrittomico dei subset isolati tramite RNA-Seq. La loro attività patogenica è stata valutata utilizzando co-colture di cellule epiteliali polmonari tramite immunofluorescenza e dosaggio delle citochine. Inoltre, è stata utilizzata una libreria di isolati clinici di P. aeruginosa per valutare la risposta infiammatoria mediata da Pa, e un saggio di antigen-specificity per indagare se Pa inducesse direttamente il trans-differenziamento dei linfociti protettivi cTh17 in patogenici co-produttori di IFNγ/IL-17.
I nostri dati dimostrano che i subsets patogenici (Th1/17+ e pTh17) sono significativamente e selettivamente arricchiti nei polmoni dei pazienti CF cronicamente infetti da Pa, al contrario i Th1 e cTh17 protettivi sono significativamente ridotti. L’analisi comparativa dei dati di trascrittomica ha rivelato un profilo molecolare distinto e specifico subset patogenici infiltranti il polmone. Inoltre, i linfociti patogenici Th1/17+ e pTh17, ma non i protettivi cTh17, inducono un danno epiteliale diretto in vitro. Rispetto al ceppo di laboratorio PAO1, i ceppi clinici di Pa inducono il rilascio significativamente maggiore di IL-1β e IL-23 dalle cellule dendritiche, correlate al differenziamento dei subset patogenici. Inoltre, il trans-differenziamento dei linfociti patogenici co-produttori di IFN-γ/IL-17 dai linfociti cTh17 è notevolmente promosso dai ceppi clinici di Pa, senza differenze tra ceppi precoci e tardivi. Nel corso del trans-differenziamento, i linfociti co-produttori di IFN-γ/IL-17 aumentano l’espressione dei fattori di trascrizione CEBP-δ e PPAR-γ, coerentemente con i risultati dall’analisi trascrittomica.
Nel complesso, i nostri risultati indicano che i ceppi clinici di Pa promuovono la generazione dei linfociti co-produttori di IFN-γ/IL-17 patogenici, inducendo inoltre una riprogrammazione trascrittomica. Decifrare i meccanismi molecolari alla base della generazione dei linfociti patogenici, dipendente da Pa, potrebbe portare alla scoperta di cruciali bersagli batterici e immunologici che potrebbero essere utilizzati per lo sviluppo di nuove strategie terapeutiche più efficaci nella CF.Cystic Fibrosis (CF) is a genetic disease characterized by an exaggerated inflammatory response to persistent bacterial lung infections, predominantly caused by Pseudomonas aeruginosa (Pa). Despite the hostile environment resulting from CFTR dysfunction, Pa promotes sustained activation of both innate and adaptive immunity. While neutrophils and macrophages exert a detrimental pro-inflammatory effect, IFNγ/IL-17 co-producing Th17 lymphocytes appear to play a pivotal pathogenic role. However, the mechanisms linking Pa infection to the generation of lung-infiltrating IFNγ/IL-17 co-producing Th17 cells remain undefined.
To address this, we analysed T cell subsets in blood and lung samples from people with cystic fibrosis (pwCF) and non-CF patients by flow cytometry and we analysed the transcriptomic profile of the isolated subsets by RNA-Seq. Their pathogenic activity was evaluated using lung epithelial cell co-cultures by immunofluorescence and cytokine measurement. Furthermore, a library of Pa clinical isolates was used to assess the Pa-dependent immune response, and an antigen-dependent assay was employed to investigate whether Pa directly induced the trans-differentiation of ex vivo cTh17 into pathogenic IFNγ/IL-17 co-producing cells.
Our data revealed that pathogenic IFNγ/IL-17 co-producing cells (Th1/17+ and pTh17) were significantly enriched in the lungs of pwCF chronically infected with Pa, whereas protective Th1 and cTh17 cells were reduced. Transcriptomic comparison highlighted unique molecular signatures of lung-infiltrating pathogenic subsets. Functionally, Th1/17+ and pTh17 cells, but not cTh17 cells, mediated epithelial damage in vitro. Compared with the laboratory strain PAO1, clinical Pa isolates induced stronger release of IL-1β and IL-23 from dendritic cells, promoting IFNγ/IL-17 co-producing T cells differentiation. Notably, the skewing of IFNγ/IL-17 co-producing cells from cTh17 was strongly driven by clinical isolates, with no significant differences between early and late isolates. During this process, IFNγ/IL-17 co-producing cells showed increased expression of the transcription factors CEBP-δ and PPAR-γ, consistent with transcriptomic data from pwCF lungs.
Altogether, our findings indicate that Pa infection of dendritic cells drives the generation of pathogenic IFNγ/IL-17 co-producing T cells, together with their transcriptional reprogramming. Understanding the molecular mechanisms of Pa-dependent generation of pathogenic T cells may uncover bacterial and immunological targets exploitable for novel therapeutic strategies in CF
PERFECT FLUIDS AND SIGMA MODELS: A MATHEMATICAL INVESTIGATION BETWEEN GENERAL RELATIVITY AND COTTON GRAVITY
No full textIn this thesis, we deal with two physics-inspired structures on Riemannian manifolds, depending
on a smooth map φ between Riemannian manifolds and several other functions and constants; they
are called Cotton φ-Perfect Fluids (C-φ-PF) and φ-static perfect fluids space-times (φ-SPFST).
The latter are special solutions of the Einstein field equations on a static space-time with matter
sources modelled by a perfect fluid and a map φ, while the former are the natural generalization of
φ-SPFSTs in the framework of a gravitational theory of recent introduction, called Cotton Gravity.
We highlight the role of the Introduction in clarifying the physical background of this work and
the expected contributions that such structures might give to Riemannian Geometry. In Chapter
1 we fix the notations and conventions and review some of the basics of Riemannian Geometry
and General Relativity.
We begin Chapter 2 by introducing the theory of Cotton Gravity and showing how it preserves the
solutions of General Relativity. We then derive the equations of C-φ-PF and show their variational
origin; the class of variations that we need to consider is such that the connection, instead of the
metric, is the fundamental entity. To obtain the main result of this chapter, a rigidity result for
a C-φ-PF under some curvature conditions which are inspired by the theory of Ricci solitons, one
needs to face a novel and specific property of Cotton Gravity, that of depending on third order
derivatives of the metric tensor. In doing so, we will unveil the special relevance that Codazzi
tensors hold in this theory, as well as the important relations between the equations of C-φ-PF
and the first integrability condition of a φ-SPFST. Inspired by some works in conformal geometry,
we then conclude this chapter by studying the obstruction to a C-φ-PF to be a φ-SPFST and
relating it to some special algebraic properties of the Weyl tensor.
In Chapter 3 we deal with φ-SPFSTs. We derive other rigidity results under new curvature condi
tions, for both manifolds with and without boundary. The proof in the two cases are surprisingly
different, but both rely on some special integral identities that make our assumptions effective. We
then prove an Obata-type theorem that characterizes the standard spheres as the only compact
manifolds supporting a closed, conformal vector field and a structure of generalized Harmonic
Einstein manifold; we apply it to deduce a rigidity result for a closed φ-SPFST for which a suitable
modification of the Schouten tensor is Codazzi and has some elementary symmetric function in its
eigenvalues which is positive and constant
Adaptive quantum dynamics with the time-dependent variational Monte Carlo method
No full textWe introduce an extension of the time-dependent variational Monte Carlo (tVMC) method that adaptively controls the expressivity of the variational quantum state during the simulation of the dynamics. This adaptive tVMC (atVMC) approach is specifically designed to enhance numerical stability when overparameterized variational ansätze lead to ill-conditioned equations of motion. Building on the concept of the local-in-time error (LITE)—a measure of the deviation between variational and exact evolution—we introduce a procedure to quantify each parameter’s contribution to reducing the LITE, using only quantities already computed in standard tVMC simulations. These relevance estimates guide the selective evolution of only the most significant parameters at each time step, while maintaining a prescribed level of accuracy. We benchmark the algorithm on quantum quenches in the one-dimensional transverse-field Ising model using both spin-Jastrow and restricted Boltzmann machine wave functions, with an emphasis on overparameterized regimes. The adaptive scheme significantly improves numerical stability and reduces the need for strong regularization, enabling reliable simulations with highly expressive variational ansätze
Rehabilitation Approach for Relative Motion Flexion Orthoses After Flexor Digitorum Profundus Zone I–II Repair: A Prospective Case Series
No full textBackground:Relative motion flexion orthoses (RMFOs) are a type of early mobilization based on the "quadriga effect." Currently, there are few published clinical outcome data and no documented treatment protocols. This study aimed to standardize our a rehabilitation protocol for early mobilization with relative motion for flexor tendon injuries within a 9-week program.Methods:A prospective study was conducted from April 2023 to June 2024, which included all patients who had undergone relative motion orthoses and rehabilitation for flexor digitorum profundus repair in zone I or II. The exclusion criteria were as follows: age younger than 18 years, more than 3 injured fingers, and lack of adherence, associated fracture, and surgical repair for more than 10 days. Final measurements at weeks 8 and 12 included total active motion; Strickland and Glogovac formula; Quick Disability of the Arm, Shoulder, and Hand questionnaire; grip strength (Jamar); and pain.Results:Ten patients underwent the RMFO protocol between April 2023 and June 2024, with at least 3 months of follow-up. Two patients were excluded from the study; the remaining patients (8) showed improvements in range of motion; Disabilities of the Arm, Shoulder, and Hand; Jamar; and visual analog scale scores. No complications such as proximal interphalangeal joint contracture, tenolysis, or rupture were reported. All patients returned to work by week 10.Conclusions:In this small prospective case report of RMFOs, we continue to increase the number of patients in the literature, and our results are compared with those of previous studies. In addition, we present our step-by-step approach to a 9-week program