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Le riforme della Chiesa nel secolo XI tra sistemi in conflitto e processi di ricomposizione
No full textThe essay moves among the interpretations that have settled in medievalist historiography. It oscillates between the lexicon of the Reformation and that of the investiture contest, while recently it has been referred to as the revolution of the 11th century
Patients' Global Impression of Change (PGIC) Score Compared to Monthly Migraine Days to Evaluate Treatment Persistence With Anti-CGRP Monoclonal Antibodies
No full textThis study assessed whether continued treatment with anti-CGRP monoclonal antibodies (mAbs) is driven more by reductions in monthly migraine days (MMDs) or patients' global impression of change (PGIC), a patient-reported outcome. Among 169 patients treated with anti-CGRP mAbs, 21.3% discontinued due to ineffectiveness. PGIC responders (≥ 5) at month 12 were 69.8%, whereas MMD responders (≥ 50% reduction) were 59.2%. Both were significantly associated with discontinuation (PGIC: χ2 = 33.474, φ = 0.445; MMD: χ2 = 29.884, φ = 0.421; p < 0.0001). PGIC showed a stronger correlation with discontinuation (rpb = 0.541) than MMD reduction (rpb = 0.470). These findings highlight PGIC as strongly associated with treatment response, supporting the need for PROMs in evaluating migraine treatment effectiveness
Does the Uterine Injection Site Matter for the Pelvic Sentinel Lymph Node Mapping? A Systematic Review and Meta-Analysis
No full text: Background and Objectives: To summarize the evidence on in vivo uterine pelvic lymphatic drainage. Materials and Methods: A literature search was performed in multiple electronic databases from inception to December 2024. We included all the studies that compared two different uterine injection sites in the mapping of pelvic sentinel lymph nodes by injecting two different tracers into two distinct injection sites. The primary outcomes included the concordance and discordance rates in the mapped pelvic sentinel lymph nodes between the pairs of injection sites. The secondary outcomes were the detection rates per injection site and tracer. Four reviewers independently reviewed the records for inclusion, assessed the risk of bias, and extracted the data. Pooled concordance, discordance, and detection rates with 95% confidence intervals (CIs) were estimated using the random effects model. Heterogeneity was quantified using the I2 tests. Results: Out of 2512 records, we included 4 studies (172 patients and 344 hemipelves). Three studies injected the cervix with the technetium-99m and the uterine corpus with methylene blue; one study injected the cervix with indocyanine green and the utero-ovarian ligament with methylene blue. Both tracers/injection sites successfully identified a sentinel lymph node in 132 hemipelves (132/344; 38.4%), identifying the same sentinel lymph node in 116 cases (116/132; 87.9%). The pooled concordance rate per hemipelvis was 91.8% (95% CI 0.665-1.000; I2 = 92%; chi2p-value < 0.01). Two different sentinel lymph nodes were identified in the remaining 16 hemipelves, with a pooled hemipelvis discordance rate of 8.2% (95% CI 0.000-0.335; I2 = 92%; chi2p-value < 0.01). The cervix and technetium-99m were the injection site and tracer with the highest pooled detection rate. Conclusions: Different uterine injection sites appear to share a common pelvic lymphatic pathway and sentinel lymph node in most cases, consistent with the current practice in endometrial cancer. Future research will confirm whether cervical injections might be proposed for pelvic sentinel lymph node mapping in all gynecological cancers
NON-INDIGENOUS PESTS: ENTRY PATHWAYS, INTRODUCTION HOTSPOTS, AND RISK ASSESSMENT IN THE EUROPEAN UNION
No full textGli organismi dannosi per le piante rappresentano una minaccia significativa per l'agricoltura globale, gli ecosistemi naturali e la biodiversità, causando gravi danni ecologici ed economici. Questa tesi si propone di identificare le regioni ad alto rischio di introduzione di questi organismi (hotspot), analizzare i principali fattori ambientali e antropici che li determinano e sviluppare nuovi strumenti per la valutazione del rischio.
Tramite una revisione sistematica della letteratura sono stati esaminati i metodi di identificazione di hotspot, evidenziando il potenziale dei modelli Bayesiani per l'analisi dei dati spaziali. È stato compilato un dataset contenente 278 introduzioni di organismi nell'Unione Europea (UE) tra il 1999 e il 2019, fornendo informazioni chiave a livello spaziale e temporale. La modellizzazione spaziale gerarchica Bayesiana ha rivelato che temperatura, precipitazioni e densità della popolazione umana influenzano significativamente le introduzioni di organismi, sottolineando anche l'importanza della componente spaziale. Le aree ad alto rischio sono state individuate nell'Europa meridionale e nei principali snodi commerciali.
Infine, è stato sviluppato il pacchetto qPRAentry per il software R, progettato per modellare i percorsi di ingresso degli organismi, integrando dati commerciali e offrendo strumenti intuitivi per la valutazione quantitativa del rischio fitosanitario. Questa ricerca supporta strategie mirate di prevenzione, rilevamento precoce e preparazione, contribuendo alla protezione dell'agricoltura, degli ecosistemi e della biodiversità nell'UE e nel Regno Unito.Plant pests pose a significant threat to global agriculture, natural ecosystems, and biodiversity, causing severe ecological and economic damage. This thesis aimed to identify high-risk regions for pest introductions (hotspots), analyse key environmental and human factors, and develop new tools for risk assessment.
A systematic review evaluated hotspot identification methods, highlighting the potential of Bayesian models for analysing areal data. A dataset of 278 pest introductions in the European Union (EU) (1999–2019) was compiled, offering key spatial and temporal insights. Bayesian hierarchical spatial modelling revealed that temperature, precipitation, and human population density significantly influence pest introductions, also highlighting the relevance of the spatial component. High-risk areas were identified in southern Europe and major trade hubs.
Finally, the qPRAentry R package was developed to model pest entry pathways, integrating trade data and providing user-friendly tools for quantitative pest risk assessment. This research supports targeted prevention, early detection, and preparedness strategies, contributing to the protection of agriculture, ecosystems, and biodiversity in the EU and UK
THE IMPACT OF WATERLOGGING, DROUGHT, SALINITY AND MULTIPLE ABIOTIC STRESSES ON ARABIDOPSIS THALIANA: A COMPREHENSIVE PHENOTYPING AND MATABOLOMIC ANALYSIS
No full textGarantire la sicurezza alimentare è una delle principali sfide legate alla crescita della popolazione
mondiale in condizioni di cambiamento climatico. L'aumento dei livelli di salinità del suolo, i
ristagni d'acqua, la siccità, le ondate di calore e il raffreddamento tardivo minacciano gravemente le
colture e spesso, in campo, si verificano congiuntamente. Questo lavoro si propone di approfondire
l'impatto degli stress abiotici singoli e combinati a livello di crescita, biochimico e fotosintetico in
Arabidopsis thaliana (l.) studiando gli stress singoli e combinati.
I risultati della siccità, della salinità, del caldo e del freddo mostrano che i valori più bassi di QY
max sono stati registrati nelle piante sottoposte a stress da salinità, il NPQ è aumentato in caso di
stress da calore e salinità singoli e combinati, mentre il qP è diminuito in caso di stress combinato.
Coerentemente, il contenuto di MDA e H2O2 è risultato alterato in tutte le condizioni di stress, ma i
valori più elevati sono stati registrati con la sola salinità e in combinazione. La quantificazione
metabolomica targeted di glicina e GABA ha indicato che questi osmoliti non sono cambiati
significativamente sotto stress, la prolina ha invece evidenziato un impatto gerarchicamente più
forte della salinità, mentre la glicina-betaina si è ridotta principalmente nelle combinazioni di
siccità. La metabolomica untargeted accoppiata alla statistica multivariata ha evidenziato una
riprogrammazione metabolica distinta in relazione alle diverse condizioni di stress, singoli o in
combinazione, differenziando l'impatto della salinità, della siccità e della loro combinazione con
freddo e caldo. L'analisi dei patway ha rivelato che gli stress abiotici hanno influenzato in modo
significativo gli ormoni, gli aminoacidi e i derivati e i metaboliti secondari. I flavonoidi si sono
accumulati maggiormente con la siccità applicata da sola e in combinazione con il caldo e il freddo,
mentre i composti contenenti N sono diminuiti con tutti i trattamenti di stress combinati. Questi
risultati contribuiscono ad approfondire l'impatto di varie combinazioni di stress, evidenziando
gerarchicamente gli effetti specifici dello stress e sottolineando l’importanza dello studio delle
combinazioni.
Le piogge torrenziali improvvise, il successivo ristagno d'acqua, l'aumento dei livelli di salinità del
suolo, le ondate di calore e il raffreddamento ritardato minacciano gravemente le colture e spesso si
verificano simultaneamente. il nostro lavoro riporta i cambiamenti fisiologici e metabolomici di
Arabidopsis thaliana L. dopo un'esposizione di 3 giorni al solo ristagno d'acqua e alla combinazione
di freddo, calore e salinità. I nostri risultati hanno confermato che la compresenza di diversi stress
non agisce come la somma dei singoli stress, ma rappresenta piuttosto una nuova condizione di
stress con effetti unici sulle firme biochimiche della pianta. La produzione di ROS e la
quantificazione targeted dei marcatori di stress (glutatione, GABA, prolina e glicina) nelle foglie e
nelle radici hanno rivelato in modo coerente il maggiore impatto del ristagno idrico e delle sue
combinazioni sulla biochimica delle piante. La metabolomica untargeted e la statistica multivariata
hanno rivelato una riprogrammazione metabolica distinta nelle diverse condizioni di stress, singole
o combinate, distinguendo l'impatto del ristagno idrico combinato con il freddo, il caldo e la
salinità. Diverse classi di metaboliti secondari sono state modulate in modo specifico per ogni
tessuto, coinvolgendo terpeni, steroli, flavonoidi e derivati degli aminoacidi nelle foglie e
flavonoidi, derivati degli aminoacidi, alcaloidi e acidi grassi nelle radici. Questi risultati
contribuiscono a comprendere l'impatto gerarchico di vari stress e delle loro combinazioni,
sottolineando gli effetti specifici degli stress e le loro interazioni.
In particolare, oltre alla compromissione delle parti aeree delle piante, l'apparato radicale è
particolarmente vulnerabile a questi fattori di stress, con conseguenze sulla crescita e sulla
sopravvivenza della pianta. Nel nostro studio, abbiamo combinato la metabolomica e la
metagenomica per svelare la risposta di Arabidopsis thaliana l. in seguito all'esposizione al freddo,
al caldo, al sale e al ristagno idrico e alla loro combinazione per tre giorni, esaminando i
cambiamenti metabolici nelle radici e negli essudati radicali, nonché la struttura e la diversità dei microrganismi della rizosfera. Infine, l'approccio di integrazione dei dati di mixomics ha permesso di approfondire le loro interazioni. Nelle radici, il ristagno d'acqua ha influenzato fortemente il metabolismo rispetto ad altri singoli stress, con una modulazione verso il basso di flavonoidi, derivati degli aminoacidi, alcaloidi e acidi grassi, mostrando un effetto additivo e sinergico quando combinato con gli stress termici rispettivamente. Per quanto riguarda gli essudati radicali, i flavonoidi, i terpenoidi e gli alcaloidi sono stati le principali classi di composti interessate. mentre gli stress da freddo e da caldo da soli hanno indotto un aumento dell'accumulo, il ristagno idrico ha provocato un abbassamento dell'accumulo e sono state osservate tendenze miste negli stress combinati con il ristagno idrico. In particolare, la salinità da sola e la sua combinazione con il ristagno idrico hanno portato a una modulazione specifica dello stress. Anche se la diversità alfa e beta delle comunità microbiche è rimasta stabile, suggerendo la loro resilienza agli stress a breve termine, la modulazione di taxa specifici è stata registrata in ogni condizione di stress. Nel complesso, questi risultati contribuiscono a comprendere l'impatto gerarchico di varie combinazioni di stress, sottolineando gli effetti specifici degli stress e delle loro combinazioni a livello della rizosfera.Ensuring food security is one of the main challenges associated with global population growth under changing climate conditions. The increase in soil salinity levels, waterlogging, drought, heat waves, and delayed cooling pose serious threats to crops, often occurring simultaneously in the field. This study aims to deepen our understanding of the impact of single and combined abiotic stresses on growth, biochemical, and photosynthetic responses in Arabidopsis thaliana (L.), investigating both individual and combined stress conditions.
The results of drought, salinity, heat, and cold stress indicate that the lowest QY_max values were recorded in plants subjected to salinity stress. NPQ increased under both single and combined heat and salinity stress, while qP decreased under combined stress conditions. Consistently, MDA and H2O2 levels were altered across all stress conditions, with the highest values observed under salinity stress alone and in combination. Targeted metabolomic quantification of glycine and GABA revealed no significant changes under stress, whereas proline exhibited a hierarchically stronger impact under salinity stress, and glycine betaine primarily decreased under drought combinations.
Untargeted metabolomics coupled with multivariate statistical analysis highlighted distinct metabolic reprogramming in response to different stress conditions, differentiating the impact of salinity, drought, and their combinations with heat and cold. Pathway analysis revealed significant effects of abiotic stress on hormones, amino acids and derivatives, and secondary metabolites. Flavonoids accumulated predominantly under drought stress alone and in combination with heat and cold, while nitrogen-containing compounds decreased across all combined stress treatments. These findings enhance our understanding of the impact of various stress combinations, hierarchically distinguishing specific stress effects and emphasizing the importance of studying stress interactions.
Sudden torrential rains, subsequent waterlogging, increased soil salinity levels, heat waves, and delayed cooling severely threaten crops, often occurring simultaneously. Our study reports the physiological and metabolomic changes in Arabidopsis thaliana (L.) after three days of exposure to waterlogging alone and in combination with cold, heat, and salinity. Our results confirm that the co-occurrence of multiple stresses does not act as a mere sum of individual stress effects but rather represents a novel stress condition with unique impacts on plant biochemical signatures.
ROS production and targeted quantification of stress markers (glutathione, GABA, proline, and glycine) in leaves and roots consistently revealed the strongest impact of waterlogging and its combinations on plant biochemistry. Untargeted metabolomics and multivariate statistics identified distinct metabolic reprogramming across different single and combined stress conditions, distinguishing the effects of waterlogging combined with cold, heat, and salinity. Several classes of secondary metabolites were specifically modulated in different tissues, involving terpenes, sterols, flavonoids, and amino acid derivatives in leaves, as well as flavonoids, amino acid derivatives, alkaloids, and fatty acids in roots. These findings contribute to understanding the hierarchical impact of various stresses and their combinations, highlighting their specific effects and interactions.
In particular, beyond the impairment of aerial plant parts, the root system is highly vulnerable to these stress factors, affecting plant growth and survival. In our study, we integrated metabolomics and metagenomics to unveil the response of Arabidopsis thaliana (L.) following exposure to cold, heat, salinity, and waterlogging—both individually and in combination—for three days. We examined metabolic changes in roots and root exudates, as well as the structure and diversity of rhizosphere microorganisms. Finally, a mixomics data integration approach provided further insights into their interactions.
In roots, waterlogging exerted the strongest impact on metabolism compared to other individual stresses, leading to a downregulation of flavonoids, amino acid derivatives, alkaloids, and fatty acids. When combined with thermal stresses, an additive and synergistic effect was observed. Regarding root exudates, flavonoids, terpenoids, and alkaloids were the main compound classes affected. While cold and heat stress alone promoted accumulation, waterlogging led to a decrease, with mixed trends observed under combined waterlogging stress. Notably, salinity alone and in combination with waterlogging resulted in a specific modulation of stress responses.
Although alpha and beta diversity of microbial communities remained stable, suggesting resilience to short-term stress, the modulation of specific taxa was recorded under each stress condition. Overall, these findings enhance our understanding of the hierarchical impact of various stress combinations, highlighting their specific effects and interactions at the rhizosphere level
La trattatistica morale
No full textThe contribution traces a reasoned profile of the themes and paths of ethical prose writing in the Renaissance, with particular attention to treatises and dialogues on behavior, on love and women, on pedagogy and de institutio
Educare alla sostenibilità, promuovere il benessere. Scenari emblematici
No full textLa complessità e l’incertezza che oggi connotano le dimensioni educative e formative, in particolare dei giovani, chiamano in causa la riflessione e la pratica pedagogiche nell’interrogarsi sulle funzioni culturale e sociale anche delle istituzioni scolastiche. C’è bisogno di educare e formare le nuove generazioni in prospettiva generativa garantendo a ognuno, fin dai primi anni di vita, livelli di benessere - nelle sue molteplici dimensioni - che consentano un adeguato livello di sviluppo fisico, cognitivo, emotivo e relazionale, per rispondere ai cambiamenti in atto e per prevenire vulnerabilità e disuguaglianze.
Il rapporto di reciprocità tra sostenibilità e benessere, in linea con l’“Agenda ONU 2030” e il “Rapporto BES”, interpella pratiche educative e formative che promuovano, attraverso la progettazione di setting multidisciplinari e collaborativi, il riconoscimento dell’altro - persona, ambiente, casa comune - per una crescita sostenibile e inclusiva
Noise power properties of a cone-beam CT scanner with unconventional scanning geometry
No full textPurpose: This work aims at investigating, via in-silico evaluations, the noise properties of an innovative scanning geometry in cone-beam CT (CBCT): eCT. This scanning geometry substitutes each of the projections in CBCT with a series of collimated projections acquired over an oscillating scanning trajectory. The analysis focused on the impact of the number of the projections per period (PP) on the noise characteristics. Methods: In-silico eCT scanner was simulated with a GPU based Monte Carlo software. We employed two homogeneous PMMA phantoms with a diameter of 12 cm and 16 cm whose tomographic images were reconstructed via an in-house developed software. Noise properties of the reconstructed volumes were evaluated in terms of coefficient of variation (COV), non-uniformity index, noise power spectrum (NPS), and null-cone over the 3D NPS. Results: The beam narrowing at higher PP led to a significant reduction of cupping artifacts, with a non-uniformity index reducing of about 33% going from conventional CBCT to PP = 10. Oscillating scan orbits almost fully recovered missing data in conventional CBCT, with a narrowing of the null-cone in 3D NPS to below 2.5% for PP ≥ 5 compared to 11.0% in conventional CBCT at 6.5 cm from the orbit plane Conclusions: The work characterizes the noise in reconstructed 3D images in eCT, with particular focus on the NPS. The impact of the beam collimation on cupping artifacts reduction is outlined. Similarly, the missing data outlined by the null-cone is considerably narrowed in comparison to conventional CBCT, especially for portions of the FOV far from the middle-reconstructed plane
Dedicated Sheathless System Versus Sheath-Based Approach for Transradial Percutaneous Coronary Intervention: Systematic Review and Meta-Analysis
No full textBackground: Transradial access (TRA) is the preferred approach for percutaneous coronary intervention (PCI), associated with improved patient comfort, lower vascular complications and lower mortality compared to transfemoral access. However, TRA presents challenges such as radial artery spasm (RAS), radial artery occlusion (RAO), and anatomical variability that have driven the development of the sheathless approach. Objectives: This meta-analysis evaluates the efficacy and safety of a dedicated sheathless system strategy versus conventional sheath-based techniques in TRA PCI. Methods: We conducted a systematic review and meta-analysis of studies comparing sheathless and sheath-based approaches in TRA PCI, with outcomes including RAS, access site crossover, access-related bleeding, RAO, procedural success, and procedural metrics. Primary analysis was stratified by study design-randomized controlled trials (RCTs) versus observational studies (OBS)-with additional subgroup analysis based on sheath type. Data were pooled using random-effects models, and heterogeneity assessed via the I-2 statistic. Results: Eight studies (3 RCTs, 5 OBS) comprising 6380 patients were included. The sheathless approach significantly reduced RAS (OR 0.31; 95% CI: 0.10-0.97) and access site crossover (OR 0.34; 95% CI: 0.16-0.69) compared to the sheath-based approach, particularly in the conventional sheath subgroup. No significant differences were found in access-related bleeding, RAO, procedural success, or procedural metrics. Conclusions: This meta-analysis supports the sheathless system as a safe and effective alternative to sheath-based TRA PCI, reducing RAS, and crossover without increasing RAO or bleeding risk. These advantages may enhance procedural efficiency and patient comfort, especially in small radial arteries and extend its scope to newer applications
Targeting Glucosylceramide Synthase: Innovative Drug Repurposing Strategies for Lysosomal Diseases
No full textSphingolipidoses, a subgroup of lysosomal storage diseases (LSDs), are rare and debilitating disorders caused by defects in sphingolipid metabolism. Despite advancements in treatment, therapeutic options remain limited. Miglustat, a glucosylceramide synthase EC 2.4.1.80 (GCS) inhibitor, is one of the few available pharmacological treatments; however, it is associated with significant adverse effects that impact patients’ quality of life. Drug repurposing offers a promising strategy to identify new therapeutic agents from approved drugs, expanding treatment options for rare diseases with limited therapeutic alternatives. This study aims to identify potential alternative inhibitors of GCS through a drug-repurposing approach, using computational and experimental methods to assess their therapeutic potential for sphingolipidoses. A library of approved drugs was screened using advanced computational techniques, including molecular docking, molecular dynamics simulations, and metadynamics, to identify potential GCS inhibitors. Promising candidates were selected for further in vitro validation to evaluate their inhibitory activity and potential as therapeutic alternatives to Miglustat. Computational screening identified several potential GCS inhibitors, with Dapagliflozin emerging as the most promising candidate. Experimental validation confirmed its efficacy, revealing a complementary mechanism of action to Miglustat while potentially offering a more favorable side effect profile. This study underscores the utility of computational and experimental methodologies in drug repurposing for rare diseases. The identification of Dapagliflozin as a potential GCS inhibitor provides a foundation for further preclinical and clinical evaluation, supporting its potential application in the treatment of sphingolipidoses