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SpectraSage unveils specific proteolytic patterns of 20S on mono-ubiquitylated Tau proteoforms involved in neurodegeneration
No full textThe ubiquitin proteasome system is a critical regulator of proteostasis and shows altered activity and composition in neurodegenerative diseases affecting both the brain (e.g., Alzheimer's disease) and the retina/optic nerve (e.g., age-related macular degeneration, glaucoma). A common feature of neurodegeneration is the progressive accumulation of amyloidogenic proteins such as beta-amyloid and tau protein (MAPT gene). There is compelling evidence that the aggregation propensity of tau protein is regulated by post-synthetic modifications including phosphorylation and ubiquitylation. These alterations are gaining increasing pathological relevance not only for brain tauopathies but also for the retinal/optic nerve degenerative diseases. In this regard, site-specific mono-ubiquitylated (Ub) tau proteoforms, have been recently identified in neurodegenerative brains. In this work, the cleavage patterns of the uncapped 20S proteasome acting on mono-Ub regio-isomers of tauK18, which covers the 4RD domain, have been unveiled by using SpectraSage, a novel proteomics software conceived for the MS1 identification of complex branched peptide and here introduced for the first time. Ub position was found to affect regio-isomers susceptibility to proteolysis and unexpectedly long Ub-tauK18 branched peptides have been identified, proving distinct catalytic preferences. These findings show that the 20S digests mono-Ub proteins through specific enzymatic mechanisms and the implications of the latter on neurodegeneration are discussed
«Dialogo di madre con il proprio feto». Andrea Zanzotto e la natura leopardiana
No full textL’articolo è dedicato ad alcuni momenti significativi dell’incontro-scontro poetico e ideologico tra Andrea Zanzotto e Giacomo Leopardi; nella fattispecie, sono stati presi in esame i testi in cui Zanzotto si è confrontato con l’immaginario leopardiano della natura madre e matrigna. Nella nostra indagine abbiamo privilegiato un approccio intertestuale che combinasse primo piano e campo largo, per far sì che l’analisi del testo e la ricostruzione della visione del mondo dei due poeti si illuminassero vicendevolmente.This article is devoted to some of the most significant aspects of the poetic and ideological confrontation between Andrea Zanzotto and Giacomo Leopardi; in particular, the study examined the texts in which Zanzotto confronted Leopardi’s imagery of mother and stepmother nature. The research has taken intertextual approach, combining textual analysis with the reconstruction of the two poets’ worldviews.L’article est consacré aux aspects significatifs du rapport poétique et idéologique entre Andrea Zanzotto et Giacomo Leopardi ; en particulier, nous avons examiné les textes dans lesquels Zanzotto s’est confronté à l’imagerie de la nature maternelle et marâtre de Leopardi. Dans notre recherche, nous avons privilégié une approche intertextuelle, combinant l’analyse du texte avec la reconstruction de la vision du monde des deux poètes
The Role of Staging Laparoscopy in Stage IV Gastric Cancer Patients
No full textIntroduction: Evidence regarding staging laparoscopy (SL) for clinical metastatic (cM+) gastric cancer (GC) patients is limited. Recently, an Italian Gastric Cancer Research Group (GIRCG) study showed SL changed peritoneal status in over 20% of cases. This study aimed to evaluate SL's role in cM+ patients and refine its indications. Methods: Clinical data of cM+ GC patients who underwent SL between 2010 and 2022 at nine GIRCG centers were retrospectively analyzed. The primary outcome was SL's yield, defined as peritoneal status changed by SL over all SLs. Results: Among 182 cM+ patients who received SL, 38 (20.9%) had SL-findings changing peritoneal status. Notably, 10.1% of cases with preoperative signs of carcinomatosis had no peritoneal disease, while 46.3% with extraperitoneal disease alone had peritoneal carcinomatosis (PC) at SL. Thirty-one patients (17.0%) underwent R0 resection: 17 (54.8%) with PC, 3 (9.7%) with liver metastases, 4 (12.9%) with PC and nodal metastases, 2 (6.4%) with lung, and 1 (3.2%) with bone metastases. Seventeen patients with suspected preoperative PC underwent curative treatment: 9 had peritoneal disease ruled out by SL, while the other 8 had limited PC, allowing R0 resection. Logistic regression revealed an inverse correlation between diffuse histotype and absence of PC at SL in patients with peritoneal involvement at imaging (p = 0.02). Conclusion: SL aids in directing cM+ GC patients to appropriate treatment, with a 20.9% yield. For those with peritoneal involvement at imaging, SL helps identify candidates for curative treatment. In patients with extraperitoneal disease, SL should be considered to assess potential radical strategies
Uncertainty-Aware Deep Ensembles for Confident Customer Churn Prediction with Rejection Option
No full textCustomer churn prediction is an important problem in business intelligence, especially in industries where keeping customers is both difficult and expensive. Many existing models can predict churn accurately but do not show how confident they are in their results, which can cause costly or incorrect decisions. To solve this issue, this paper introduces an Uncertainty-Aware Ensemble (UA-Ensemble) framework that predicts churn while also estimating confidence levels. The model combines five neural network types, including attention-based LSTMs, Bayesian networks, and Monte Carlo Dropout, to measure both aleatoric and epistemic uncertainty. A cost-aware rejection rule is used to avoid unreliable predictions. Experiments on large banking, e-commerce, and telecom datasets reached 94.2% accuracy and reduced intervention costs by 18.3% compared to baseline models. The proposed approach outperforms traditional machine learning and deep learning methods, proving effective and trustworthy for business decision-making across various industries
Knowledge, Attitudes, and Practices in Neonatal Diabetes Mellitus Management: the JEnious-NeOnatal-DIabetes (JENODI) Survey
No full textIntroductionWe aimed to explore the knowledge, attitude, and management of neonatal diabetes mellitus (NDM) among members of the International Society for Pediatric and Adolescent Diabetes (ISPAD).MethodsMembers of the society were invited to complete an online questionnaire posted on the ISPAD website.ResultsWe received 108 responses from 45 different countries. Of these, 103 were involved in NDM management. 87.9% of participants would start insulin at diagnosis, and 11% would prefer sulfonylurea (SU); 54.6% would start with an insulin pump, and 80.6% would use continuous glucose monitoring. Genetic testing was suggested by 97.2% (50.9% when diagnosis occurs up to 6 months, 15.7% up to 9 months, and 30.6% up to 12 months of age), while 79.6% routinely request it in clinical practice. Of the participants, 96.3% consider genetic testing necessary to identify children who can be treated with SU, and 26.9% would try SU before testing/obtaining results. Only 37% received specific training on NDM, while 44.5% felt less confident in managing patients with NDM. Incidence in the country of practice, participant's age, years of experience in the field, number of patients registered in the clinic, and number of patients with NDM followed up were associated with differences in answers.ConclusionsThis survey offers the possibility of informing health providers about the awareness of different aspects of NDM management. Our results provide the opportunity to compare various aspects of diagnosis and treatment of NDM in different geographic areas. Continuous education is needed to boost physicians' confidence in managing patients with this rare form of diabetes
"Connessioni Narrative. Note su telegrafia e telefono nei racconti di Ella Cheever Thayer e Mark Twain"
No full textIl contributo analizza il ruolo delle tecnologie di comunicazione di fine Ottocento, in particolare telegrafo e telefono, nel genere del racconto, a partire da testi di Ella Cheever Thayer e Mark Twain. L’analisi mostra come la mediazione tecnologica delle relazioni sentimentali, messa in scena in queste narrazioni, anticipi in modo inconsapevole alcune delle principali problematiche dell’era digitale, richiamando parallelismi con il fenomeno contemporaneo degli incontri online
Turning waste into substrates enhance rooftop tomato production through microbial mediation
No full textUrban agriculture is emerging as a valuable strategy to mitigate the challenges posed by rapid urbanisation and global population growth. Among its forms, productive rooftops stand out as a sustainable solution, enabling food production, organic waste recycling, and the creation of green spaces by repurposing underutilized roofs. Leveraging
natural resources, including plant-associated microbiomes, offers further potential to sustainably improve productivity and food quality. However, microbial communities inhabiting different organic amendments, such as compost and biochar (BC), remain poorly studied despite their relevance in shaping plant–substrate interactions.
The Madreenroof project, conducted on the rooftop of the Instituto de Ciencias Agrarias (ICA-CSIC) in the city of Madrid, aimed at investigating how different organic biomasses (i.e., spent coffee grounds, coffee silverskin, and seaweeds) composted with or without BC affect substrate properties, microbial communities, and tomato productivity. A commercial peat-based substrate was used as a benchmark.
Our results showed that feedstock type was the primary factor influencing substrate chemical and physical properties, and thus microbial communities. While BC addition improved compost quality, its role in shaping microbial communities was less pronounced than that of the feedstock. Alternative substrates exhibited higher phosphorus
concentrations, pH, and electrical conductivity than peat. Microbial analysis revealed that bacterial diversity was higher in alternative substrates, yet their overall taxonomic structure remained relatively consistent across treatments, indicating functional redundancy. Notably, we identified distinct microbial communities associated with each
feedstock. Communities enriched in the composted seaweed biomass substrate were significantly and positively correlated with increased tomato yield.
These findings highlight the dual role of organic substrates in directly influencing plant growth through their physicochemical traits and indirectly through microbiome modulation. Selecting appropriate organic materials not only boosts rooftop vegetable production but also enriches urban microbial diversity in otherwise underexploited
spaces
La rinunzia abdicativa alla proprietà nel sistema della pubblicità immobiliare
No full textIl contributo esamina il tema della rinunzia abdicativa alla proprietà immobiliare per studiarne criticamente i riflessi sul piano della pubblicità immobiliare, indagando, in particolare, gli effetti per i quali la trascrizione è prevista dall'art. 2643 c.c. (ai fini, almeno a prima lettura, dell'art. 2644 c.c.), l'applicabilità alla rinunzia del principio di continuità delle trascrizioni (art. 2650 c.c.) e le modalità attraverso le quali la trascrizione deve essere effettuata, anche tenuto conto della natura riflessa - e, secondo l'opinione prevalente, originaria - dell'acquisto in capo allo Stato del bene immobile oggetto di rinunzia. Sullo sfondo dell'indagine si colloca l'importante presa di posizione delle Sezioni Unite della Corte di Cassazione dell'agosto 2025 in favore dell'ammissibilità della rinunzia immobiliare e dell'esclusione di qualsiasi profilo di sindacabilità dell'atto, da parte del giudice, sul piano della sua validità
Assessment of IBM-FRS total score and specific functional domains in a large cohort of inclusion body myositis patients
No full textInclusion body myositis (IBM) is an acquired myopathy of older adults, associated with progressive weakness and functional limitations. The inclusion body myositis functional rating score (IBM-FRS) is a reliable tool for the assessment of disease severity, but poor data are available on its correlation with clinical features. In this cross-sectional, retrospective multicenter study, we analyzed IBM-FRS total score (TS) and its items in a cohort of 147 IBM patients, considering 4 functional domains (FD) (dysphagia, upper limb function, daily living and independence, lower limb function). We analyzed TS and FD values' correlations with demographic and clinical variables (onset, loss of walking ability, non-invasive ventilation, percutaneous gastrostomy-PEG) as well as between each FD and the remaining TS. Lower, hence worse, scores in the dysphagia domain (FD1) correlated with female gender (p < 0.01), dysphagia as presenting symptom (p < 0.01), and PEG use (p < 0.0001), but interestingly without correlation with time variables IBM-FRS total score or other domains. This may define a distinct phenotype with different onset and outcome. Worse scores in the upper and lower limb and daily living domains (FD2-FD4) were strongly associated with loss of ambulation, higher age at baseline, and longer disease duration (p < 0.001). We identified a cutoff value of 28/40, allowing to differentiate patients with less disease burden, potentially able to show better response in future clinical trials. Our study enriches the literature by correlating IBM-FRS total scores and its items with patient characteristics, offering important implications for clinical management, subgroup analysis, and future trials design
Bewegliche Grenzen: die “Osterweiterung” der deutschsprachigen Literatur als kritische Herausforderung / Confini mobili: la “svolta orientale” della letteratura tedescofona come sfida critica
No full textQuesto numero di «links» presenta una sezione monografica dedicata al fenomeno del cosiddetto Eastern Turn o della Osterweiterung della letteratura di lingua tedesca: concetti che, negli ultimi quindici anni, hanno animato le riflessioni critiche intorno alla presenza, sempre più rilevante, di autrici e autori di origine “est-europea” nel panorama letterario contemporaneo. La rinnovata attualità e urgenza delle riflessioni prodotte da questa letteratura, che hanno mostrato come le categorie di “est” e “ovest” non siano mai innocue, ma costantemente rinegoziate da dinamiche politiche, culturali e memoriali, costituiscono l’orizzonte in cui si muovono i saggi qui raccolti, che rendono evidente la centralità di queste scritture per comprendere l’Europa di oggi: un continente attraversato da nuove linee di frattura e da mappe culturali in continua trasformazione, in cui la letteratura diventa luogo di negoziazione tra memorie traumatiche, identità ibride e sperimentazioni estetiche. In quest’ottica, la sezione monografica qui presentata non vuole offrire uno stato dell’arte, bensì proporsi come strumento critico per indagare come la letteratura di lingua tedesca a “estensione orientale” continui a interrogare i confini – geografici, identitari, memoriali – dell’Europa contemporanea, proiettandoli verso
nuove cartografie culturali