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Mapping Context-Dependent Dimensions of Human-Data Viz Interaction
No full textThis paper attempts to identify and characterize some context-dependent dimensions of Human-Data Visualization Interaction that are crucial to estimate the complexity of data-driven decision making. These dimensions are only partly related to off-line considerations such as the kind of charts, the data represented, and the like, and are mapped with operationalization constructs for their characterization and assessment. A what-if scenario in an industrial company is the starting point to reflect upon living constraints, such as the level of expertise in visual analytics of managers (the so-called Visual Information Literacy), the strategy that drives the decision process, and the flexibility and adaptability of the technology design to the data characterizing the decisions and both the previous aspects. How can we relate these three aspects for a better estimate of the data-driven decision-making flaws and complexity? Some hypotheses are proposed here
Targeted plasma proteomics uncover proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders
No full textKIF5A (Kinesin family member 5A) is a motor protein that functions as a key component of the axonal transport machinery. Variants in KIF5A are linked to several neurodegenerative diseases, mainly spastic paraplegia type 10 (SPG10), Charcot-Marie-Tooth disease type 2 (CMT2), and amyotrophic lateral sclerosis (ALS). These diseases share motor neuron involvement but vary significantly in clinical presentation, severity, and progression. KIF5A variants are mainly categorized into N-terminal variants associated with SPG10/CMT2 and C-terminal variants linked to ALS. This study utilized a multiplex NULISA targeted platform to analyze plasma proteome from KIF5A-linked SPG10 and ALS individuals and compare them to healthy controls. Our results revealed distinct proteomic signatures, with significant alterations in proteins related to synaptic function and inflammation. Notably, neurofilament light polypeptide, a biomarker for neurodegenerative diseases, was elevated in KIF5A ALS but not in SPG1..
Anterior Chamber Inflammation and Descemet Membrane Endothelial Keratoplasty: An Anterior Segment-OCT-Based Analysis
No full textPurpose: To assess anterior chamber (AC) subclinical inflammation using a noninvasive method in patients undergoing Descemet membrane endothelial keratoplasty (DMEK). Design: Retrospective interventional case series. Participants: This study included 83 eyes from 73 patients who underwent DMEK surgery and 15 control eyes from 15 healthy individuals. Methods: The number of hyperreflective dots representing AC cells and optical density ratio (aqueous-to-air relative intensity [ARI] index) for flare quantification were calculated from anterior segment-OCT images. Aqueous-to-air relative intensity index and AC cells were calculated preoperatively and postoperatively at 1 week (T1), 1 month (T2), and 3 months (T3) after DMEK surgery. Baseline values were compared with a healthy control group. Main Outcome Measures: Anterior chamber cell count and ARI index over time; association with postoperative posterior stromal ripples (PSRs) and rebubbling. Results: Baseline ARI index was significantly higher in the DMEK group compared with controls, whereas no significant difference in AC cell count was observed. Anterior chamber cell count increased postoperatively from a median of 1.1 cells (0.6–2.1) at baseline to 3.5 (1.7–5.3) at T1 (P < 0.001), to 1.7 (1.1–3.0) at T2 (P = 0.03), and to 2.1 (1.1–4.2) at T3 (P = 0.01). The ARI index also increased from a median of 98.3 (84.1–121.9) at baseline to 142.8 (119.8–221.3) at T1 (P < 0.001) and 114.4 (101.7–140.7) at T2 (P < 0.001). Higher ARI at T1 was weakly associated with postoperative PSR (odds ratio [OR] = 1.63; 95% confidence interval [CI], 1.00–2.67; P = 0.048), whereas postoperative PSR were strongly associated with rebubbling (OR = 26.00; 95% CI, 3.20–211.18; P = 0.002). Conclusions: Anterior segment-OCT enables noninvasive detection of subclinical inflammation after DMEK surgery. The presence of markers of inflammation can increase the risk of early postoperative complications. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article
Codatorialità e contratto di rete
No full textLe reti d’impresa come mercati interni del lavoro. – Il “dogma” dell’unicità del datore di lavoro. – Il lavoro nelle reti d’impresa “codificate”. L’art. 30 del d.lgs. n. 276/2003. – Il ruolo della contrattazione collettiv
Generation and characterization of a novel transgenic line expressing human alpha-synuclein in the zebrafish nervous system as a new complementary model of Parkinson's Disease
No full textLa Malattia di Parkinson (MP) è il disordine neurodegenerativo a sintomatologia motoria più diffuso al mondo. Le principali caratteristiche neuropatologiche della MP sono la perdita di neuroni dopaminergici nel sistema nigrostriatale e la presenza di corpi di Lewy (CL) e neuriti di Lewy (NL), inclusioni proteiche insolubili composte principalmente da aggregati fibrillari di α-sinucleina (αSyn). Analisi post-mortem sul cervello dei pazienti affetti da MP e demenza con CL (DCL) hanno mostrato che la quantità di depositi di αSyn negli aggregati sinaptici è molto più alta rispetto a quella contenuta nei CL, mentre evidenze sperimentali di malattie a CL suggeriscono che αSyn danneggi prima i terminali neuronali, innescando una degenerazione retrograda fino alla morte cellulare. Recenti studi hanno mostrato che Synapsina III (Syn III) si lega agli aggregati di αSyn e aumenta significativamente nei cervelli post-mortem di pazienti con MP sporadica e DCL. Pertanto, modelli che replichino l'interazione patologica tra αSyn e Syn III potrebbero essere cruciali per studiare le basi molecolari di queste malattie. Negli ultimi anni, zebrafish (Danio rerio) è emerso come modello utile per studiare i meccanismi molecolari dei disturbi neurologici, inclusa la MP. Tuttavia, nessuno dei modelli zebrafish transgenici per αSyn sviluppati finora replica completamente tutte le principali caratteristiche patologiche della MP. L'obiettivo del mio progetto di tesi è stato creare un modello transgenico di zebrafish che ricapitoli la co-patologia di Syn III e αSyn, per investigare i meccanismi alla base la loro interazione e migliorare la nostra comprensione della fisiopatologia della MP. In particolare, il mio obiettivo è stato generare due linee transgeniche stabili di zebrafish che esprimessero nel sistema nervoso le due proteine: una esprimente Syn III umana con un tag GFP C-terminale, e l'altra con espressione di αSyn umana full-length con un tag mCherry N-terminale. Ho prima stabilito la linea transgenica per Syn III umana. La cassetta genomica di Syn III umana è stata progettata per esprimere una proteina di fusione costituita da Syn IIIa e GFP all’N-terminale, sotto il controllo del promotore neuronale endogeno elavl3/HuC, utilizzando il sistema di transgenesi Tol2. A causa dell'elevata omologia di sequenza e funzione tra la Syn III di zebrafish e il suo omologo umano, l'espressione della proteina di fusione è stata possibile solo in forma transitoria, in quanto ha causato un'elevata mortalità e anomalie morfologiche negli embrioni entro due giorni dalla fecondazione. In parallelo, è stata invece possibile la generazione di una linea stabile di zebrafish transgenica per αSyn umana con tag mCherry all’estremità N-terminale. Questa linea, definita Tg(elavl3:mCherry-hsa.SNCA), mostra l’espressione di αSyn umana con il tag mCherry N-terminale sotto il controllo del promotore endogeno pan-neuronale elavl3/HuC. Gli embrioni allo stadio di cinque giorni dopo la fecondazione presentano già diverse caratteristiche fenotipiche tipiche della MP, come accumulo di αSyn aggregata, diminuzione dei terminali catecolaminergici, deficit nella motilità di base e segni di ansia. Questi cambiamenti sono stati accompagnati dall'accumulo di Synapsina III e Synapsina II, nonché da disfunzioni dei processi autofagici. Gli studi sugli esemplari adulti Tg(elavl3:mCherry-hsa.SNCA), hanno dimostrato alterazioni comportamentali con ansia e una marcata riduzione della capacità motoria rispetto ai controlli non esprimenti αSyn umana. Complessivamente, questi risultati suggeriscono che la linea Tg(elavl3:mCherry-hsa.SNCA) rappresenta un modello innovativo e complementare per studiare la base biologica della MP e il primo modello stabile di zebrafish che esprime αSyn umana che ricapitola le principali caratteristiche della MP dallo stadio larvale.Parkinson's Disease (PD) is the most common neurodegenerative disorder with motor symptoms worldwide. The main neuropathological features of PD are the loss of dopaminergic neurons in the nigrostriatal system and the presence of Lewy bodies (LBs) and Lewy neurites (LNs), insoluble protein inclusions composed primarily of fibrillar aggregates of α-synuclein (αSyn). Post-mortem analyses of the brains of patients with PD and dementia with Lewy bodies (DLB) have shown that the amount of αSyn deposits in synaptic aggregates is much higher than that contained in LBs, while experimental evidence from LB diseases suggests that αSyn first damages neuronal terminals, triggering retrograde degeneration leading to cell death. Recent studies have shown that the synaptic protein Synapsin III (Syn III) binds to αSyn aggregates and is significantly increased in the post-mortem brains of patients with sporadic PD and DLB. Therefore, models that replicate the pathological interaction between αSyn and Syn III could be crucial for studying the molecular basis of these diseases. In recent years, zebrafish (Danio rerio) has emerged as a useful model for studying the molecular mechanisms of neurological disorders, including PD. However, none of the transgenic zebrafish models for αSyn developed so far fully replicate all the main pathological features of PD. The aim of my thesis project was to create a transgenic zebrafish model that recapitulates the co-pathology of Syn III and αSyn, to investigate the mechanisms underlying their interaction and to improve our understanding of the pathophysiology of PD. In particular, my goal was to generate two stable transgenic zebrafish lines expressing the two proteins in the nervous system: one expressing human Syn III with a C-terminal GFP tag, and the other with expression of full-length human αSyn with an N-terminal mCherry tag. I first established the transgenic line for human Syn III. The human Syn III genomic cassette was designed to express a fusion protein consisting of human Syn IIIa and GFP at the N-terminus, driven by endogenous neuronal elavl3/HuC promoter, using the Tol2 transgenesis system. Due to the high sequence and functional homology between zebrafish Syn III and its human orthologue, the expression of the fusion protein was only possible in a transient form, as it caused high mortality and morphological abnormalities in embryos within two days of fertilization. In parallel, it was instead possible to generate a stable transgenic zebrafish line for human αSyn with an N-terminal mCherry tag. This line, Tg(elavl3:mCherry-hsa.SNCA), shows the expression of human αSyn with the N-terminal mCherry tag under the control of the endogenous pan-neuronal elavl3/HuC promoter. Embryos at the five-day post-fertilization stage already present several phenotypic features typical of PD, such as accumulation of aggregated αSyn, decrease in catecholaminergic terminals, deficits in basal motility, and signs of anxiety. These changes were accompanied by the accumulation of endogenous Synapsin III and Synapsin II, as well as dysfunctions of autophagic flux. Studies on adult Tg(elavl3:mCherry-hsa.SNCA) specimens have shown behavioural alterations with anxiety and a marked reduction in motor capacity compared to not αSyn-expressing controls. Overall, these results suggest that the Tg(elavl3:mCherry-hsa.SNCA) line represents an innovative and complementary model for studying the biological basis of PD and the first stable zebrafish model expressing human αSyn that recapitulates the main features of PD from the larval stage
The Experience of Setting up a Vascular Access Unit in a South European Large Hospital: The Step‐by‐Step Description of the First Year of Activity
No full textClinical outcomes of Descemet Membrane Endothelial Keratoplasty (DMEK)
Full text linkIntroduzione
L’intervento di cheratoplastica endoteliale di Descemet Membrane Endothelial Keratoplasty (DMEK) è indicato per trattare disfunzioni endoteliali corneali, come nella distrofia endoteliale di Fuchs e nella cheratopatia bollosa, che causano edema corneale e riduzione dell’acuità visiva. Nonostante l’efficacia della procedura, fattori come complicanze chirurgiche, storia di chirurgia del glaucoma e età del ricevente influenzano i risultati. Questo studio mira a valutare l’impatto della supervisione chirurgica, della morfologia della cornea ospite, della localizzazione dell’incisione e della decentratura del lembo sui risultati della DMEK.
Metodi
Sono stati analizzati quattro dataset per esplorare queste variabili. Esperienza del chirurgo: confronto tra interventi supervisionati e non supervisionati (2017–2020). Ripple stromali posteriori (RSP): analisi degli effetti pre- e post-operatori dei RSP in interventi dal 2021 al 2023.Localizzazione dell’incisione: confronto tra incisioni superiori e temporali (2017–2021). Decentratura del lembo: valutazione degli esiti in casi con lembo decentrato (2022–2023).
Risultati
Esperienza del chirurgo: su 89 interventi, non sono emerse differenze nella qualità visiva pre/postoperatoria tra gruppi supervisionati e no; i tassi di rebubbling erano simili (34,1% supervisionati, 33,3% non supervisionati); gli interventi non supervisionati hanno mostrato più complicanze intraoperatorie (9 vs. 2 casi) e cheratoplastiche secondarie (12,2% vs. 0%); i tessuti preparati dalle banche degli occhi hanno evidenziato tassi di rebubbling significativamente più alti rispetto a quelli preparati dai chirurghi.
Ripple stromali posteriori: su 71 casi, il recupero visivo è stato più lento e l’acuità visiva finale più bassa negli occhi con RSP preoperatori (0,3 logMAR vs. 0,1 logMAR, p=0,02); la presenza di RSP postoperatori ha aumentato significativamente il rischio di rebubbling [HR 7,1; p=0,02]; le RSP suggeriscono possibili danni strutturali irreversibili e si configurano come biomarcatori prognostici affidabili per l’adesione del lembo e il recupero visivo.
Localizzazione dell’incisione:su 187 pazienti, le incisioni superiori hanno mostrato una tendenza a un maggiore tasso di rebubbling (38,4% vs. 29,6%), sebbene non statisticamente significativa (p=0,186);le incisioni temporali più piccole (2,8 mm) hanno indotto meno astigmatismo chirurgico e facilitato la gestione nei pazienti con occhi profondi; le incisioni superiori possono essere soggette a maggiore perdita di tamponante, influenzando l’adesione del lembo.
Decentratura del lembo:in 8 casi, la decentratura non ha avuto effetti negativi sull’acuità visiva finale, che è migliorata significativamente (0,49 a 0,01 logMAR, p=0,003); l’edema periferico si è risolto entro 3–6 mesi, grazie all’attività delle cellule endoteliali.
Discussione
La supervisione chirurgica riduce le complicanze, sottolineando l’importanza di una formazione strutturata e pratica simulata. Le RSP preoperatorie si correlano a un recupero visivo ritardato e si propongono come marker prognostici utili. L’incisione temporale offre vantaggi operativi, sebbene la significatività statistica per il tasso di rebubbling rimanga non conclusiva. La decentratura del lembo non ha compromesso i risultati visivi, anche se sono necessari studi con campioni più ampi. Questi risultati evidenziano fattori chiave che influenzano il successo e il recupero della DMEK.Background and Goals
Descemet Membrane Endothelial Keratoplasty (DMEK) addresses corneal endothelial dysfunction, such as in Fuchs’ endothelial dystrophy (FED) and bullous keratopathy (BK), which cause corneal edema and vision loss. This study aims to assess how surgeon supervision, host cornea morphology, incision location, and graft decentration affect DMEK success.
Methods
Four datasets explored these variables. Surgeon experience compared supervised vs. unsupervised surgeries from 2017–2020.Posterior Stromal Ripples (PSR), examined pre- and postoperative impacts of PSR in surgeries from 2021–2023. Incision localization compared superior vs. temporal incisions from 2017–2021.Graft Decentration, evaluated outcomes of decentered grafts in surgeries from 2022–2023.
Results
Surgeon Experience: 89 surgeries analyzed showed no difference in pre/postoperative visual acuity (VA) between supervised and unsupervised groups; graft rebubbling rates were similar (34.1% supervised, 33.3% unsupervised); unsupervised surgeries had higher intraoperative complications (9 vs. 2 cases) and secondary keratoplasties (12.2% vs. 0%); and eye bank-prepared tissues showed significantly higher rebubbling rates than surgeon-prepared grafts.
Posterior Stromal Ripples (PSR):71 cases revealed delayed visual acuity (VA) recovery and lower final VA in pre-PSR eyes (0.3 logMAR vs. 0.1 logMAR, p=0.02); postoperative PSR increased rebubbling risk significantly [HR 7.1; p=0.02];PSR indicated possible irreversible structural damage and served as a prognostic biomarker for surgical outcomes.
Incision Localization: among 187 patients, superior incisions showed a higher rebubbling trend (38.4% vs. 29.6%) though not statistically significant (p=0.186); smaller temporal incisions (2.8 mm) caused less surgical-induced astigmatism (SIA) and facilitated easier handling, especially in deep-set eyes; superior incisions may experience higher pressure-related air leakage affecting graft adhesion.
Graft Decentration: 8 cases showed no adverse effect of graft decentration on final best-corrected visual acuity, which improved significantly (0.49 to 0.01 logMAR, p=0.003), while peripheral edema resolved within 3–6 months, attributed to endothelial cell activity.
Discussion
Mentorship reduces complications, emphasizing the need for structured training and wet-lab practice. PSR correlates with delayed recovery and serves as a reliable prognostic marker, suggesting its use in preoperative evaluations. The temporal incision offers operational advantages, although statistical significance in rebubbling trends remains elusive. Despite concerns, graft decentration did not impair visual outcomes, although larger studies are needed. These findings highlight nuanced factors influencing DMEK success and recovery
Promoting sustainable food systems: An empirical analysis of local Food Hub governance models and structures in 12 African settings
Full text linkAfrican food systems are increasingly challenged by climate change, market instability, globalization, urbanization, and recent global crises. Such challenges, along with a mismatch between consumers’ preferences and production opportunities, are generating vulnerabilities in the local food systems and exacerbating food insecurity and environmental problems such as land degradation, water scarcity, and loss of biodiversity. In response to these challenges, this study investigates the concept of Food Hubs as a potential adaptive governance mechanism. By analyzing and comparing information collected from 12 Food Hubs across five African countries, the research aims to uncover how local actors design and implement Food Hubs alongside the governance structures and mechanisms they adopt. Our results show that the 12 Food Hubs hold the potential to respond effectively to contemporary food system challenges, promote resilience in food systems, and enable more sustainable use of environmental resources. In particular, we point to the role played by the context in which they operate, its impact on their organizational structures, public/private stakeholders’ involvement, and the array of formalization procedures, ranging from loosely binding agreements to the implementation of ad hoc institutions. This study contributes to an in-depth understanding of Food Hub development and governance, offering both empirical insights into their role in building sustainable and adaptive food systems in the African context and a theoretical contribution to the design, development, and implementation phase of Food Hubs (and similar organizations)
The Influence of Genital Lichen Sclerosus on Sexual Health and Well-being: A Tripartite Comparative Analysis
No full textOBJECTIVES: Genital lichen sclerosus (LS) is a chronic mucocutaneous disorder causing considerable discomfort. Despite this, comprehensive comparison of LS impacts on quality of life (QoL), particularly on men's health or relative to other dermatological conditions like pemphigus, are sparse. This research aims to discern the effects of LS on sexual functionality and overall QoL, benchmarking against pemphigus patients and healthy controls. The study's intent is to broaden the understanding of sexual dysfunction, satisfaction, and psychological distress attributable to LS. MATERIALS AND METHODS: From March 2021 to September 2023, this observational multicenter study at the affiliated university hospitals involved 176 individuals, 120 females and 56 males, with LS, pemphigus, or as controls. Questionnaires employed were the Female Sexual Function Index or the International Index of Erectile Function depending upon subject's gender, the General Health Questionnaire-12, the Clinical Lichen Sclerosus Score, and Pemphigus Disease Area Index. Differences in QoL were analyzed using either the Fisher exact test or the Mann-Whitney U test, and the correlation between Clinical Lichen Sclerosus Score sexual QoL using Spearman's coefficient. RESULTS: LS patients faced more sexual health challenges than pemphigus patients and healthy people. Women with LS had difficulties with lubrication and pain, men had less satisfaction during intercourse, and all had increased psychological distress, although less than those with pemphigus. A strong link between LS severity and worse sexual QoL, especially for women, was identified. CONCLUSIONS: LS significantly affects sexual function and psychological well-being, both for men and women, reaffirming the need for comprehensive management
Characterization of a multilayer coating (Ni-P plus DLC) applied on PBF-LB AlSi10Mg components with complex geometries and lattice structures
No full textAlSi10Mg alloy lattice structures produced by Powder Bed Fusion- Laser Beam (PBF-LB) technology show high specific strength and an optimal surface/volume ratio. However, in the as-built condition they are characterized by a high roughness that may worsen their performance. To address this issue, a multilayer coating consisting of (i) electroless Ni-9%P interlayer, to compensate surface defects and optimize the surface topography, and (ii) PA-CVD hydrogenated amorphous carbon (DLC a-C:H) topcoat was deposited. The features of the coated system were evaluated by: (i) optical profilometry, (ii) FEG-SEM/EDS observations, (iii) micro/nanoscale hardness tests, and (iv) scratch test. Based on the results, the main problems related to the deposition of the Ni-P + DLC multilayer coating on the PBF-LB AlSi10Mg critical components were identified, in order to optimize the whole post-printing cycle and guarantee adequate performance of the multilayer coating