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Optimizing Endovascular Aortic Repair With Carbon Dioxide: A Systematic Review Toward Zero Contrast Use
No full text: Background: Endovascular Aneurysm Repair (EVAR) is a proven, safe, and effective treatment; however, its application may be limited by the potential adverse effects of iodinated contrast medium (ICM), which can exacerbate renal function and may be contraindicated in patients with renal insufficiency. Purpose: This review aims to provide an overview of "zero-iodine contrast EVAR," which uses CO2 exclusively, as a strategy to mitigate the risk of acute kidney injury (AKI) associated with ICM. Research design: A systematic literature review was conducted in PubMed, Embase, and Cochrane databases following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify EVAR cases performed using carbon dioxide. The Medical Subject Headings (MeSH) terms used were "endovascular repair AND abdominal aortic aneurysm AND contrast medium" and "endovascular repair AND abdominal aortic aneurysm AND carbon dioxide," with inclusion criteria limited to articles in English published until December 2024. Results: The literature search yielded 1167 papers. After removing duplicates, titles and abstracts were screened, and 68 papers underwent full-text review. A total of 16 studies were included in the analysis, encompassing 1625 patients. Of these, 837 patients underwent EVAR with ICM, and 788 patients underwent EVAR with CO2. Of these, 510 patients were treated with EVAR using CO2 exclusively. Conclusions: Although this method still faces inherent limitations due to the physicochemical characteristics of CO2, its use, when combined with additional technical precautions, enables the achievement of zero-contrast results in standard EVAR procedures
Corporate governance e dinamica assembleare: Riflessioni e opportunità legate alla digitalizzazione
No full textLo scopo della presente ricerca è quello di fornire una panoramica sullo stato dell’arte dell’assemblea dei soci virtuale in Italia e di analizzare, al contempo, mediante la ricostruzione delle dinamiche assembleari, il punto di vista degli azionisti e delle società italiane sulle modalità di svolgimento delle assemblee
A step toward diagnostic reference levels for male varicocele embolization: dosimetric comparison across two generations of angiographic systems
No full textPurpose: Percutaneous endovascular embolization (PVE) of male varicocele is a widely adopted procedure performed in healthy young patients with long life expectancy. Dose-optimization systems are therefore essential to minimize procedural radiation risks. We aimed to investigate the effect of a recently implemented dose-reduction technology on dosimetric parameters and its potential implication in the definition of diagnostic reference levels (DRLs). Materials and Methods: A consecutive series of 113 patients (23.3 ± 9.1 yrs) submitted to PVE between January 2020 and December 2024 were retrospectively reviewed. Two groups based on the angiographic system used, 50 patients treated using the Philips Allura Xper FD20 and 63 patients using the newer Philips Azurion Clarity IQ technology, were compared in terms of demographic, procedural, and dosimetric data. Results: Despite similar fluoroscopy and procedure times, the recently implemented angiographic technology demonstrated a significant reduction in dose area product (DAP) and reference air kerma (Ka.ref) values (4394.5 vs 20,709 mGy·cm2 and 20.35 vs 83.6 mGy; p < 0.001, respectively) with a percentage reduction of approximately 71.15% and 64.41%, respectively. Subpopulation analyses showed significant dose reductions in younger patient population (< 18 years) and in high-grade varicoceles (grades III/IV), with similar fluoroscopy times. Conclusion: The use of advanced dose-optimization technologies, together with standardized protocols and appropriate operator training, leads to a significant reduction in radiation exposure during PVE, particularly in younger patients. These single-center, retrospective results provide preliminary data that may support the future introduction of procedure-specific DRLs for this routinely and widely performed interventional radiology procedure
RILEVANZA PROGNOSTICA DEI MARCATORI MORFOLOGICI DEL CARCINOMA SQUAMOCELLULARE
No full textIl carcinoma squamocellulare della lingua rappresenta la più comune e aggressiva neoplasia maligna del
cavo orale, caratterizzata da elevata eterogeneità biologica e marcata propensione alla metastatizzazione
linfonodale. In questo studio sono stati analizzati i principali marcatori morfologici istopatologici associati
alla prognosi, con l’obiettivo di individuare indicatori utili per una più accurata stratificazione del rischio.
Il lavoro ha incluso una coorte di pazienti sottoposti a trattamento chirurgico, valutati mediante analisi
istologica dettagliata dei parametri tumorali – tra cui pattern di invasione, profondità di invasione,
infiltrazione perineurale e risposta linfonodale – e successive analisi statistiche multivariate. È stato inoltre
sviluppato un modello prognostico integrato per predire il rischio di recidiva e la sopravvivenza specifica di
malattia.
I risultati evidenziano che alcuni marcatori morfologici presentano un significativo impatto prognostico
indipendente e possono migliorare la capacità predittiva del sistema TNM tradizionale. Questi dati
supportano l’importanza di una caratterizzazione morfologica approfondita nel percorso diagnostico del
carcinoma squamocellulare della lingua e suggeriscono possibili direzioni per futuri approcci di medicina
personalizzata.Tongue squamous cell carcinoma is the most common and clinically aggressive malignancy of the oral
cavity, characterized by marked biological heterogeneity and early lymphatic spread. This study investigated
key histopathological morphological markers associated with prognosis, with the aim of identifying reliable
indicators for improved risk stratification.
A cohort of surgically treated patients was evaluated through detailed histological assessment of tumor
parameters—including pattern of invasion, depth of invasion, perineural invasion, and lymph node
involvement—followed by multivariate statistical analyses. An integrated prognostic model was developed
to predict recurrence risk and disease-specific survival.
The results show that several morphological markers possess significant independent prognostic value and
enhance the predictive accuracy of the traditional TNM system. These findings highlight the importance of
comprehensive morphological characterization in the diagnostic workflow of tongue squamous cell
carcinoma and point toward potential applications in future personalized medical strategies
A Novel Framework for Heat Stress Risk Assessment and Mitigation in Real and Typological Historical Public Open Spaces Under Climate Change Scenarios
Full text linkClimate change is altering the use of public open spaces in historical urban environments, compounded by urban heat island effects. Especially considering urban squares, rising temperatures increase health risks for outdoor users, particularly for vulnerable individuals (by, e.g., age and fragility). Rapid risk assessment under current and future climate scenarios can exploit integrated simulations to support the process, considering both real-world environments and Built Environment Typologies (BETs), which represent the recurring morphological, constructive, and material features of such urban squares. Simulation-based approaches can also support the assessment of mitigation strategies considering sustainability, reversibility, visual integration, and compatibility with the heritage. This work proposes a framework for simulation-based heat risk assessment of outdoor users under current and future (2050 and 2080) overheating scenarios and considers pre- and post-mitigation conditions of urban squares. Outdoor temperature conditions are simulated using ENVI-met, enabling the multiscale assessment of users’ heat stress and thresholds in exposure timings before critical dehydration. The approach is applied to two Italian historical urban squares in Bari and Naples, and to their associated BETs. The results highlight the framework’s capabilities in addressing the impact of climate scenarios and pre-/post-mitigation conditions, considering the local and global conditions of the urban squares. Moreover, the observed similarities between POSs and their corresponding BETs demonstrate that these archetypes can support preliminary risk assessments, providing decision makers with a rapid overview before adapting analyses and mitigation strategies to the specific characteristics of each urban square
Histological-based characterization of ovarian developmental stages in blue crab (Callinectes sapidus) within the spawning season in the central western Adriatic Sea
Full text linkThe Atlantic blue crab (Callinectes sapidus Rathbun, 1896) is a euryhaline and eurythermal species native to the Atlantic coasts of the Americas. Although its widespread distribution across the Mediterranean basin is well documented, information on its reproductive patterns remains limited. This study focused on the combination of both macroscopic and histologic characterization of ovarian developmental stages in female blue crabs along the north-central Italian Adriatic coast, within the spawning period. Samples were collected off the coast of Ancona, in collaboration with local fishermen, between September and November 2023. For each specimen, sex and biometric parameters were recorded to determine the sex ratio, while size distribution and gonadosomatic index (GSI) were calculated for female specimens. Ovary samples and eggs sponge were collected to determine the ovarian developmental stage and fecundity respectively. Results showed females as the dominant sex throughout the sampling period, with males being extremely rare. The collapse of female catches in early November, alongside the consistent presence of ovigerous females and the strong female-biased sex ratio, identified this area as a spawning ground. These findings align with reproductive patterns observed in the species’ native range and other Mediterranean areas. Moreover, GSI values and fecundity indexes associated with macroscopic and histological examination of ovarian stages suggested that the end of the reproductive season corresponded to mid-November
Matrix-valued AutoRegressive (MAR) models in gretl
No full textThis paper describes the first version of the MAR package, designed to estimate Matrix-valued Auto-Regressive (MAR) models in gretl. The current version of the package estimates the MAR(1) model via two techniques: Least Squares Estimation (LSE) and Maximum Likelihood Estimation (MLE). It provides standard estimation output in gretl formats, including estimated coefficients, standard errors, t-statistics, p-values, and some basic regression statistics. The package also calculates and displays the impulse response functions. For ease of use, the package includes a simple Graphical User Interface (GUI), while offering full functionality via the gretl scripting language. Two examples, one using real data and the other using simulated data, illustrate its relevance in economic modeling
Insights Into Late-Onset Rheumatoid Arthritis (LORA): Characteristics (Clinical and Imaging), Comorbidities, and Therapeutic Targets
No full textLate-onset rheumatoid arthritis (LORA) is defined as rheumatoid arthritis (RA) manifesting after the age of 65 years, although the terminology remains somewhat ambiguous. With the advent of a super-aging society and extended life expectancies, a significant increase in the incidence of LORA is anticipated. In comparison to young-onset RA (YORA), LORA is predominantly characterized by a higher incidence of acute onset, augmented disease activity and constitutional symptoms, a propensity for systemic manifestations, increased erythrocyte sedimentation rate at disease onset, reduced seropositivity, a predilection for involvement of large and proximal joints with symptoms resembling polymyalgia rheumatica, a higher frequency of erosive disease, and a more evenly distributed gender ratio. Elderly individuals, particularly those with multimorbidity and on multiple medications (polypharmacy), are at an elevated risk of developing geriatric syndromes, including sarcopenia and frailty. The response to TNF inhibitors in elderly individuals with RA is generally comparable to that in younger patients, though it may be slightly diminished. The duration of the disease appears to have a more pronounced impact on outcomes than the patient's age. For the management of LORA, it is critical to adopt a patient-specific approach. Non-frail LORA patients who are otherwise aging healthily should receive aggressive treat-to-target management. Conversely, in pre-frail and frail patients, the therapeutic focus should be on averting the progression of irreversible geriatric conditions. The confluence of multimorbidity, polypharmacy, and geriatric syndromes in this patient population necessitates a tailored therapeutic approach to maintain patient autonomy and functional status
rePLAY - reInterpretare il Progetto di Architettura Attraverso le Lenti del Gioco
No full textLa tesi, afferente alla progettazione architettonica, propone di rileggere il progetto di architettura attraverso il gioco come dispositivo operativo capace di tenere insieme regola e libertà, coerenza e apertura.
L’ipotesi centrale è che considerare l’architettura come un campo di gioco permetta di generare spazi empatici e inclusivi, che invitano all’azione e all’appropriazione spontanea. Il tema non è “che cos’è il gioco in architettura”, ma “come si progetta con il gioco”, tentando di definire come un progetto possa essere guidato operativamente dal gioco.
Gioco e architettura condividono l’uso di regole che lasciano spazio a eccezioni e reinterpretazioni. È proprio nell’oscillazione tra prescrizione e apertura - tra game e play - che lo spazio si rende “giocabile”: leggibile e sicuro, ma permeabile a usi imprevisti e a forme di cooperazione spontanea. Si sposta il baricentro progettuale dal controllo degli esiti al controllo delle condizioni, predisponendo opzioni di apertura che permettono allo spazio di crescere e trasformarsi insieme ai suoi utenti.
Rispetto allo stato dell’arte, la ricerca introduce una definizione operativa di “giocabilità” come qualità relazionale e mette a punto una tassonomia di casi studio per estrapolare un alfabeto di regolarità trasferibili; le scelte progettuali vengono tradotte in tattiche concrete che generano libertà d'uso senza sacrificare la coerenza della cornice architettonica.
La fase sperimentale si è svolta con SOUxAncona (laboratori per bambini dagli 8 ai 12 anni), agendo da ponte tra teoria e pratica. Le tattiche sono state verificate sul campo con veri “esperti di gioco”, invertendo la prospettiva e trasformando l’architettura in un gioco serio, validando le assunzioni elaborate.
Il lavoro culmina in un “Handbook di progettazione giocosa”, che racchiude strategie ludiche e linee operative per progettisti e non solo. “rePLAY” invita a concepire l’architettura come risorsa civica e infrastruttura di relazioni: uno spazio che moltiplica le possibilità, restando aperto a esiti futuri resi possibili, e non imposti, dal progetto.The thesis, relating to architectural design, proposes to reinterpret the architectural project through play as an operational device capable of holding together rule and freedom, coherence and openness.
The central hypothesis is that considering architecture as a play allows the generation of empathetic and inclusive spaces, which invite action and spontaneous appropriation. The theme is not "what is play in architecture", but "how do you design with play", trying to define how a project can be operationally guided by play.
Play and architecture share the use of rules that leave room for exceptions and reinterpretations. It is precisely in the oscillation between prescription and openness - between game and play - that space becomes "playable": readable and safe, but permeable to unexpected uses and forms of spontaneous cooperation. The design center of gravity shifts from the control of outcomes to the control of conditions, providing opening options that allow the space to grow and transform together with its users.
Compared to the state of the art, the research introduces an operational definition of "playability" as a relational quality and develops a taxonomy of case studies to extrapolate an alphabet of transferable regularities; The design choices are translated into concrete tactics that generate freedom of use without sacrificing the coherence of the architectural frame.
The experimental phase took place with SOUxAncona (workshops for children aged 8 to 12), acting as a bridge between theory and practice. The tactics were tested on the field with real "play experts", inverting the perspective and transforming the architecture into a serious play, validating the assumptions elaborated.
The work culminates in a "Handbook of playful design", which contains playful strategies and operational lines for designers and others. "rePLAY" invites us to conceive architecture as a civic resource and infrastructure of relationships: a space that multiplies possibilities, remaining open to future outcomes made possible - and not imposed - by the project
Structural Determinants of Kv7.2 Channel Function and Variant-Induced Dysfunction: Insights from Molecular Dynamics Simulations
No full textI canali del potassio voltaggio–dipendenti della famiglia Kv7 (KCNQ) sono sensibili a perturbazioni anche sottili a livello della porta di attivazione del poro (activation gate, AG) e del filtro di selettività (selectivity filter, SF). Questa tesi utilizza simulazioni di dinamica molecolare (MD) all-atomo per analizzare come quattro varianti clinicamente identificate di KCNQ2 rimodellano il gating e la permeazione: tre varianti gain-of-function (GoF) nella porzione distale dell’elica S6 (G313S, A317T, L318V) e una variante loss-of-function (LoF) nell’elica del poro (A265V). A partire da modelli di poro chiuso e aperto basati su strutture crio-EM, inseriti in membrane esplicitamente solvatate, combiniamo simulazioni di equilibrio e sotto voltaggio, insieme a un confronto tra diversi force field, per calcolare caratteristiche strutturali quali la geometria del poro, l’idratazione della cavità centrale (central cavity, CC), le microstati del filtro di selettività e l’accoppiamento tra porta e filtro, e per metterle in relazione con i fenotipi delle varianti. Per le varianti GoF in S6, le simulazioni di equilibrio mostrano un allentamento consistente della porta di attivazione nel modello chiuso, in particolare a livello delle caratteristiche costrizioni S314/L318, e una persistente idratazione della cavità centrale, mentre il modello aperto rimane sostanzialmente invariato. Questi cambiamenti razionalizzano i fenotipi sperimentali, caratterizzati da una maggiore probabilità di apertura a singolo canale e abbondanza di membrana conservate. I risultati risultano robusti rispetto alla scelta di diversi force field biomolecolari ampiamente utilizzati, sebbene l’entità dell’allargamento e dell’idratazione vari. Le simulazioni con differenza di potenziale transmembrana applicata mostrano che i canali mutati, in stato parzialmente aperto, supportano la permeazione ionica, mentre la struttura nativa rimane non conduttiva, in accordo con il fenotipo GoF. Il filtro di selettività visita occasionalmente conformazioni ristrette, “pinched”, associate al legame transiente di poche molecole d’acqua dietro il filtro. A differenza di quanto osservato in altri canali, tuttavia, questa disposizione non è duratura, verosimilmente a causa di caratteristiche di sequenza peculiari di Kv7.2, e il filtro preferisce conformazioni conduttive che ospitano file multi-ione senza acque intercalate. La variante A265V è stata dimostrata sperimentalmente indurre inattivazione in stato aperto nel canale Kv7.2, che in condizioni fisiologiche è considerato non inattivante. Coerentemente, le simulazioni del mutante inizializzate da una struttura con porta aperta mostrano un filtro di selettività leggermente dilatato ma più labile, che campiona in modo asimmetrico microstati non conduttivi, accompagnati da un modesto restringimento della porta distale in S6, una caratteristica di allosteria “inversa” rispetto alle varianti GoF. Complessivamente, questi risultati mettono in relazione ciascuna variante con un meccanismo supportato da caratteristiche strutturali coerenti: dilatazione della porta interna che stabilizza l’apertura per le sostituzioni GoF in S6, rispetto a una labilità centrata sul filtro di selettività con accoppiamento inverso per A265V. Questo lavoro definisce relazioni struttura–funzione a livello atomistico in Kv7.2 e offre un quadro sistematico per interpretare i fenotipi clinici e guidare strategie di modulazione mirata al poro.Voltage-gated potassium channels of the Kv7 (KCNQ) family are sensitive to subtle perturbations at the pore activation gate (AG) and the selectivity filter (SF). This dissertation uses all-atom molecular dynamics (MD) to dissect how four KCNQ2 clinical identified variant remodel gating and permeation: three gain-of-function (GoF) variants in the distal S6 helix (G313S, A317T, L318V) and one loss-of-function (LoF) variant in the pore helix (A265V). Starting from cryo-EM–based closed and open pore models embedded in explicitly solvated membranes, we leverage equilibrium and voltage-driven simulations, as well as force-field cross-checking, to calculate structural features like pore geometry, central-cavity (CC) hydration, SF microstate occupancies, and gate–filter coupling, and to correlate them with variant phenotypes. For the S6 GoF variants, equilibrium MD reveals a consistent loosening of the activation gate in the closed model, in particular at the level of S314/L318 characteristic constrictions, and persistent CC wetting, while the open model remains essentially unchanged. These changes rationalize experimental phenotypes, characterized by a higher open probability with preserved single-channel conductance and membrane abundance. The results are robust against the choice of widely used biomolecular force fields, although the extent of widening and hydration varies. Simulations with applied transmembrane voltages show that the mutated, partially open channels support ion permeation, while the native structure remains nonconducting, consistent with the GoF phyenotype. The SF occasionaly visits narrow, “pinched” conformations, associated with the transient binding of few water molecules behind the SF. At variance with other channels, however, this arrangement is not long-lasting, likely because of unique Kv7.2 sequence features, and the filter prefers conductive conformations harboring multi-ion strings without intercalated waters. The A265V variant has been shown experimentally to induce open-state inactivation in the physiologically non-inactivating Kv7.2 channel. Consistently, simulations of the mutant initiated from an open-gate structure exhibit a slightly dilated and more labile SF that asymmetrically samples non-conductive microstates, accompanied by a modest tightening at the distal S6 gate, a reverse allosteric feature with respect to the GoF variants. Altogether, these results relate each variant to a mechanism supported by consistent structural features: inner-gate dilation that stabilizes opening for GoF S6 substitutions, versus SF-centric lability with reverse coupling for A265V. The work delineates atomistic structure–function relationships in Kv7.2 and offers a systematic framework for interpreting clinical phenotypes and informing pore-targeted modulation