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Early antiproteinuric effect of voclosporin in patients with lupus nephritis in a real-life setting: preliminary results from the VoRLiSS (Voclosporin in Real Life Setting Study) experience
No full textObjective: To assess efficacy of voclosporin from a retrospective, observational, clinical-practice-based, nationwide multicentre study of patients with lupus nephritis (LN).
Methods: Patients with biopsy-proven LN were enrolled from November 2023 to April 2025 from tertiary Rheumatology and Nephrology Italian Centres. Those with uncontrolled arterial hypertension and eGFR < 30 ml/min/1.73m2 were excluded. Patients received oral 23.7 mg voclosporin BID, and MMF 1 g BID. Glucocorticoid schedule followed existing recommendations for LN management. Clinical and serological data were collected at SLE diagnosis, voclosporin initiation, and after 6, 12, 24, and 48 weeks. Complete Renal Response (CRR) was defined as eGFR ≥60ml/min/1.73m2, <20% eGFR decrease from baseline, 24-h proteinuria <0.5 g/day, no rescue therapy, prednisone ≤5 mg/day, and Partial Renal Response (PRR) as a 50% decrease of 24 h-proteinuria and <20% eGFR decrease.
Results: Forty-two patients from 14 Centers were enrolled, 26 females (61.9%), mean age 43.1 ± 11.9 years, follow-up 6.6 ± 5.1 months. 31.5% of patients achieved CRR or PRR at 6 weeks, 68.9% at 12 weeks, 83.3% at 24 weeks, and 91.6% at 48 weeks of follow-up. A significant decrease in 24-h proteinuria was observed at 6 weeks (p= 0.006) and at all subsequent time points. A mild eGFR decrease was observed at 6 (p= 0.008) and 24 weeks (p= 0.01), but not at 48 weeks. Significant decrease was also observed in anti-dsDNA positivity at 6 (p= 0.0016) and 12 weeks (p= 0.0009), and in SLEDAI-2K after 24 (p= 0.008) and 48 weeks (p= 0.05).
Conclusions: Voclosporin may provide a valuable therapeutic option in LN management, achieving early 24 h-proteinuria response consistent with clinical trial data.Objective To assess efficacy of voclosporin (VCL) from a retrospective, observational, clinical-practice-based, nationwide multicentre study of patients with LN. Methods Patients with biopsy-proven LN were enrolled from November 2023 to April 2025 from tertiary Rheumatology and Nephrology Italian Centres. Those with uncontrolled arterial hypertension and eGFR<30ml/min/1.73m2 were excluded. Patients received oral 23.7mg VCL BID and MMF 1g BID. Glucocorticoid schedule followed existing recommendations for LN management. Clinical and serological data were collected at SLE diagnosis, VCL initiation and after 6, 12, 24 and 48weeks. Complete renal response (CRR) was defined as eGFR≥60ml/min/1.73m2, <20% eGFR decrease from baseline, 24-h proteinuria <0.5g/day, no rescue therapy, prednisone ≤5mg/day and partial renal response (PRR) as a 50% decrease of 24h proteinuria and <20% eGFR decrease. Results Forty-two patients from 14 centres were enrolled, 26 females (61.9%), mean age 43.1±11.9years, follow-up 6.6±5.1months. A total of 31.5% of patients achieved CRR or PRR at 6weeks, 68.9% at 12weeks, 83.3% at 24weeks and 91.6% at 48weeks of follow-up. A significant decrease in 24-h proteinuria was observed at 6weeks (P=0.006) and at all subsequent time points. A mild eGFR decrease was observed at 6 (P=0.008) and 24weeks (P=0.01), but not at 48weeks. Significant decrease was also observed in anti-dsDNA positivity at 6 (P=0.0016) and 12weeks (P=0.0009), and in SLEDAI-2K after 24 (P=0.008) and 48weeks (P=0.05). Conclusions VCL may provide a valuable therapeutic option in LN management, achieving early 24h-proteinuria response consistent with clinical trial data
Seasonal and Cross-Shore Characterization of Sediments Along the Ferrara Coastal Area (NW Adriatic Sea, Italy)
No full textThis study provides a seasonal and cross-shore characterization of sediments along the Ferrara coastal area (Italy). Four sites (Goro, Volano, Estensi, and Spina) were investigated through an integrated approach including textural and geochemical analyses. Surface sediments were sampled seasonally from summer 2023 to summer 2024 and analyzed to determine granulometry, major oxides composition, carbonate content, and potentially toxic element (PTE) contents. Results revealed that both grain-size and geochemistry vary seasonally and along the cross-shore profile, reflecting the combined effects of hydrodynamic forcing, sediment transport, and fluvial inputs. Elevated contents of Ce, Cr, La, V, and Zr were detected at various sites, seasons, and geomorphological zones. In some cases, the environmental quality indices applied allowed the sediments to be classified as polluted. Furthermore, some exceedances of the legal limits for Cr and V contents were observed at Goro and Volano. These pollution levels are attributable to the presence of PTE-bearing minerals originating from the source basins (geogenic sources). Overall, the results highlight the interplay between hydrodynamics and sediment provenance, emphasizing the dominance of geogenic contributions along the northern Adriatic coast, providing updated geochemical data for future monitoring and environmental management of coastal systems
N-Acylaminoethyltetrahydroquinolines: A new class of melatonin receptor ligands with in vivo activity on glioblastoma
No full textTetrahydroquinoline (THQ) derivatives bearing an N-acylaminoethyl side chain were investigated as a new class of potent melatonergic ligands offering opportunities for a versatile modulation of binding and pharmacological properties. These compounds were designed from N-anilinoethylamide ligands by formal closure of the N-substituent into an additional fused ring. Molecular modelling studies, including alchemical simulations, allowed to rationalize configurational and conformational aspects of ligand activity and supported the role of the THQ nucleus in the MT2 receptor selectivity observed for these compounds when compared to N-anilinoethylamide counterparts. The moderate stereoselectivity generated by substituents in position 2 of the THQ ring or at the β-position of the ethylamide chain could be ascribed to the conformational enrichment of ligand poses fitting the receptor binding site observed for the eutomer. Replacement of the methoxy group with bulkier substituents was investigated to differentially modulate intrinsic activity at the MT1 and MT2 receptor subtypes. Mixed activity, with MT1 agonist and MT2 antagonist profile, could be achieved by insertion of a 7-(2-hydroxyethoxy) group, as already observed for compound 5-HEAT. UCM1400 (4d) was more potent than 5-HEAT and emerged as a promising pharmacological tool for targeting glioblastoma. The compound exhibited in vitro antiproliferative activity on human glioma cell lines and was effective in vivo, reducing tumor growth in a U87MG orthotopic xenograft mouse model. These findings support the development of subtype-selective modulators of melatonin receptors as a promising new avenue for cancer therapy
Upstream migration of the invasive blue crab in the Po River, Italy, highlights the vulnerability of freshwater ecosystems
No full textThe Atlantic blue crab (Callinectes sapidus) is one of the most rapidly expanding invaders in the Mediterranean Sea, where it has established populations across all coastal and estuarine habitats. While its impacts in these environments are well documented, little is known about its occurrence and ecological role in inland waters. This study provides the first evidence of significant upstream migration of blue crabs along the Po River and nearby branches (Northern Italy), beyond typical coastal habitat distributions. Blue crab occurrences were based on 50 validated geo-referenced records collected between 2022 and 2025 through fishermen reports. Environmental variables and blue crab upstream distance were analyzed to explore possible drivers of this migration. The potential trophic interactions between blue crab and riverine fish species were also examined through a systematic literature review. The findings revealed that upstream dispersal reached distances of more than 160 km from the sea, primarily driven by adult males. No clear correlation was found between upstream distance reached by blue crab and water temperature, conductivity, dissolved oxygen, or river discharge, suggesting that ecological dynamics, rather than abiotic filtering, likely drive inland expansion. The literature review highlighted only a few documented trophic interactions in European freshwaters, although potential predation by invasive fish species and competition with native fauna may occur. These results underscore the urgent need for targeted monitoring and research to evaluate the ecological consequences of blue crab invasion in freshwater systems, particularly regarding its potential impacts on biodiversity, food web dynamics, and ecosystem functioning
Un filosofo e un filologo in dialogo. Edizione e commento del carteggio tra Giorgio Fano e Sebastiano Timpanaro (1949-1963)
No full textIl carteggio inedito tra il filosofo neoidealista Giorgio Fano e il filologo classico Sebastiano Timpanaro, comprende l’arco cronologico 1949-1963, anno di morte di Fano e consta di 112 lettere: 51 di Fano e 61 di Timpanaro. Il carteggio è conservato nel fondo Timpanaro jr. della Scuola Normale Superiore di Pisa (scatola 13) e nel fondo della famiglia Fano a Pesaro (scatolone AA4, BB1, BB13 e BB14).
La ricerca portatata avanti nei tre anni ha avuto come obiettivo quello di mettere in luce un carteggio inedito con una figura considerata dalla critica come “minore”, ma che si dimostra invece importante nella fase di messa in discussione di Timpanaro alla corrente dell’idealismo italiano. Inoltre, il mio lavoro vuole inserirsi nel contesto di promozione di edizione dei carteggi ancora inediti di Timpanaro, come figura centrale della cultura del Novecento italiano.The unpublished correspondence between the neo-idealist philosopher Giorgio Fano and the classical philologist Sebastiano Timpanaro covers the period 1949-1963, the year of Fano's death, and consists of 112 letters: 51 from Fano and 61 from Timpanaro. The correspondence is preserved in the Timpanaro Jr. collection at the Scuola Normale Superiore in Pisa (box 13) and in the Fano family collection in Pesaro (boxes AA4, BB1, BB13 and BB14).
The research carried out over the three years aimed to highlight unpublished correspondence with a figure considered by critics to be “minor”, n the phase of Timpanaro's questioning of the current of Italian idealism. Furthermore, my work aims to contribute to the promotion of the publication of Timpanaro's still unpublished correspondence, as a central figure in 20th-century Italian culture
University students’ sense-making of the asymptotic behavior of functions
No full textMy research focuses on the study of university students’ solving processes, specifically concerning the asymptotic behavior of functions. As highlighted in the literature, the learning process about the concept of asymptotic behavior has not been extensively investigated, particularly in relation to growth at infinity. Existing studies have mainly addressed asymptotes, emphasizing the difficulties students encounter in dealing with these notions (Katalenić et al., 2020; Katalenić et al., 2023; Mpofu & Pournara, 2018; Mpofu & Mudaly, 2020). More broadly, research in mathematics education has examined students’ discourse, especially at the university level, in connection with challenges in coordinating different realizations of the same mathematical concept and in learning the concept of function (Güçler, 2016; Nachlieli & Tabach, 2012; Ryve et al., 2013).
Within this field, our study aims to address the gap concerning students’ sense-making of asymptotic behavior. We focus on how students engage with unfamiliar tasks, analyzing their verbal and non-verbal communication as well as the approaches they adopt. The research is framed within commognitive theory (Sfard, 2008; Lavie, Steiner & Sfard, 2019), locally integrated (Prediger, Bikner-Ahsbahs & Arzarello, 2008) with the notion of resistance (Wertsch, 1998) and with Jeannotte and Kieran’s model (2017) of mathematical reasoning. Integrating resistance into the commognitive framework makes it possible to connect with the constraints described in the precedent-search-space (Lavie et al., 2019) and to gain deeper insight into students’ approaches when facing unfamiliar mathematical tasks. It also allows us to explore how the use of routines relates to the overcoming—or persistence—of resistance.
The study was carried out in two phases: a preliminary phase, based on a mixed-methods approach (Johnson & Onwuegbuzie, 2004), and a main study designed through task-based interviews following Goldin’s approach (2012). Participants were university students from engineering and mathematics faculties. The tasks drew on contexts familiar to students, such as the intersection of functions, but differed from those typically encountered in school or university settings, as they aimed to explore the concept of asymptotic behavior without explicitly referring to it.
Results from the preliminary phase indicated that the use of different visual mediators influenced students’ responses and performance (Gambini, Viola & Ferretti, 2024). These results were confirmed in the main study, which further revealed that the presence of multiple realizations often triggered the emergence of resistance (Viola, under review). Moreover, the results suggest that the characteristics of routines are closely connected to whether resistance is overcome: overcoming resistance appeared to be associated with greater flexibility and applicability (Viola & Gambini, under review). Finally, by analyzing the different approaches adopted by students in relation to the aspects of mathematical reasoning, it was possible to examine how they substantiated their reasoning, highlighting the link between substantiation, the overcoming of resistance, and the absence of a predominant aspect of mathematical reasoning (Viola et al., submitted).La mia ricerca si concentra sullo studio dei processi di risoluzione degli studenti universitari, in particolare riguardo al comportamento asintotico delle funzioni. Come evidenziato in letteratura, il processo di apprendimento relativo al concetto di comportamento asintotico non è stato indagato in modo approfondito, soprattutto in relazione alla crescita all’infinito. Gli studi esistenti si sono principalmente concentrati sulle asintoti, sottolineando le difficoltà incontrate dagli studenti nel trattare queste nozioni (Katalenić et al., 2020; Katalenić et al., 2023; Mpofu & Pournara, 2018; Mpofu & Mudaly, 2020). Più in generale, la ricerca in didattica della matematica ha esaminato il discorso degli studenti, soprattutto a livello universitario, in relazione alle difficoltà nel coordinare differenti realizzazioni dello stesso concetto matematico e nell’apprendimento del concetto di funzione (Güçler, 2016; Nachlieli & Tabach, 2012; Ryve et al., 2013).
All’interno di questo campo, il nostro studio si propone di colmare il vuoto relativo al senso che gli studenti attribuiscono al comportamento asintotico. Ci concentriamo su come gli studenti affrontano compiti non familiari, analizzando la loro comunicazione verbale e non verbale, così come gli approcci che adottano. La ricerca è inquadrata nella teoria commognitiva (Sfard, 2008; Lavie, Steiner & Sfard, 2019), integrata localmente (Prediger, Bikner-Ahsbahs & Arzarello, 2008) con la nozione di resistenza (Wertsch, 1998) e con il modello di ragionamento matematico di Jeannotte e Kieran (2017). Integrare la resistenza nel quadro commognitivo permette di collegarsi ai vincoli descritti nel precedent-search-space (Lavie et al., 2019) e di ottenere una comprensione più approfondita degli approcci degli studenti di fronte a compiti matematici non familiari. Consente inoltre di esplorare come l’uso delle routine si relazioni al superamento – o alla persistenza – della resistenza.
Lo studio è stato condotto in due fasi: una fase preliminare, basata su un approccio a metodi misti (Johnson & Onwuegbuzie, 2004), e uno studio principale progettato attraverso interviste basate su compiti secondo l’approccio di Goldin (2012). I partecipanti erano studenti universitari delle facoltà di ingegneria e matematica. I compiti si basavano su contesti familiari agli studenti, come l’intersezione di funzioni, ma differivano da quelli tipicamente incontrati a scuola o all’università, poiché miravano a esplorare il concetto di comportamento asintotico senza farvi riferimento esplicito.
I risultati della fase preliminare hanno indicato che l’uso di diversi mediatori visivi influenzava le risposte e le performance degli studenti (Gambini, Viola & Ferretti, 2024). Questi risultati sono stati confermati nello studio principale, che ha ulteriormente rivelato come la presenza di multiple realizzazioni spesso innescasse l’emergere della resistenza (Viola, in revisione). Inoltre, i risultati suggeriscono che le caratteristiche delle routine sono strettamente correlate al superamento della resistenza: il superamento della resistenza sembra essere associato a una maggiore flessibilità e applicabilità (Viola & Gambini, in revisione). Infine, analizzando i diversi approcci adottati dagli studenti in relazione agli aspetti del ragionamento matematico, è stato possibile esaminare come essi giustificassero il loro ragionamento, evidenziando il legame tra giustificazione, superamento della resistenza e assenza di un aspetto predominante del ragionamento matematico (Viola et al., sottomesso)
Patient profiles and early response in patients with systemic lupus erythematosus initiating anifrolumab: interim analysis from the ongoing multicentre observational REVEAL study
No full textBackground: Anifrolumab is a type I interferon receptor antagonist approved for the treatment of systemic lupus erythematosus (SLE). However, real-world evidence on its use, especially from large, unselected cohorts, is scarce. The ongoing REVEAL study is designed to collect real-world data on anifrolumab use. The data reported here are the pre-specified 6-month interim analysis, which aims to provide a phenotypic characterisation of a large real-world cohort of patients with SLE initiating anifrolumab, and to evaluate early treatment response in routine clinical practice.
Methods: REVEAL is a 5-year, multicentre, prospective observational study conducted in 25 tertiary rheumatology centres across Italy. A pre-specified interim analysis was planned when the first 50 patients completed the first 6 months of follow-up; this analysis includes all patients who initiated anifrolumab by the data cutoff of Feb 10, 2025. Patients with SLE were consecutively enrolled on the day of their first infusion of anifrolumab, prescribed according to clinical judgement and Italian indications for use. Eligible patients were aged 18 years or older, had a clinical diagnosis of SLE fulfilling at least one set of established classification criteria valid at the time of diagnosis (1997 American College of Rheumatology [ACR], 2012 Systemic Lupus International Collaborating Clinics, or 2019 European Alliance of Associations for Rheumatology-ACR), had active disease warranting anifrolumab treatment (including compassionate use programmes), and were naive to anifrolumab. Data were collected at baseline and at 1 month, 3 months, and 6 months. The primary outcome was the number of patients reaching remission (defined according to the Definition of Remission in SLE criteria as a clinical SLEDAI-2K score of 0, physician global assessment score of <0·5 [on a 0-3 scale], with a prednisone-equivalent dose ≤5 mg per day, and stable antimalarials or immunosuppressants), Lupus Low Disease Activity State (LLDAS; defined as a SLEDAI-2K ≤4 [with no activity in major organ systems and no new disease activity], with a prednisone-equivalent dose ≤5 mg per day, and stable antimalarials or immunosuppressants), Lupus Low Disease Activity State (LLDAS; defined as a SLEDAI-2K ≤4 [with no activity in major organ systems and no new disease activity, physician global assessment ≤1·0, and a prednisone-equivalent dose ≤7·5 mg per day), and LLDAS5 (a modified version of the LLDAS with a prednisone-equivalent dose ≤5 mg per day) at 6 months. Adverse and serious adverse events were also recorded. No people with lived experience of SLE were involved in designing or conducting the study. This study is registered with ClinicalTrials.gov (NCT07215754) and with the Italian Medicines Agency (Agenzia Italiana del Farmaco; ID number 247) and recruitment is ongoing.
Findings: Between May 25, 2023, and Feb 10, 2025, 236 patients were recruited and included in this interim analysis. Of these, 219 (93%) were female, 17 (7%) were male, 218 (92%) were White, and the median age was 46·9 years (IQR 36·0-53·6). At baseline, the median SLEDAI-2K was 7 (IQR 6-9), and the main indications for anifrolumab were mucocutaneous (157 [67%]) and articular (116 [49%]) involvement. At 6 months, 37 (26%) of 140 patients reached remission, 80 (57%) reached LLDAS5 and 93 (66%) reached LLDAS. One patient was excluded from the outcome analysis due to missing physician global assessment data. 108 adverse events were recorded during the 6-month follow-up period; of these, 83 (77%) were infections. Five serious adverse events occurred, resulting in six hospitalisations.
Interpretation: This study provides the first large-scale real-world evidence of anifrolumab use in patients with SLE, supporting its clinical benefit and rapid onset of action in routine care
Industrial policy for a just structural change
No full textThe current economic and geo-political scenario requires rethinking industrial policy and diving deeper into the link between industrial policy, structural change and human development, given that governing structural transformations also means to go towards more sustainable and just societies.
The chapter illustrates this perspective, in which the industrial policy domain enlarges, both in terms of targets and objectives and goes beyond the traditional market failure perspective, embedding strategic and meta-economic objectives. It goes beyond the mere manufacturing sector to include financial institutions, business associations, training and education institutions. At the same time the attempt is to consider possible government failures in the policy process, calling for a deeper debate on their remedies. In discussing these issues, the chapter builds a view of industrial policy as a practice that ultimately should pursue normative social goals related to equity, human development and inclusion
Targeting 3Cpro of Enterovirus D68 with Medicinal Phytocompounds Using Structure-Based Molecular Screening and Molecular Simulation Approaches to Rescue the Host Immune Response
No full textPurpose Enterovirus D68 (EV-D68) is a viral pathogen recognized for its role in inducing severe respiratory illnesses and its
link to the development of acute flaccid myelitis (AFM) in children. The 3 C protease (3Cpro) of Enterovirus D68 disrupts
TRIF, impairing NF-κB and IFN-β signaling, evading host immunity. EV-D68 also inhibits IRF7 and interferes with MDA5-
MAVS interaction, hindering RLR pathway-mediated IFN signaling.
Methods Recognizing the key role of 3Cpro in modulating host immune responses, we employed structure-based drug
design combined with molecular dynamics simulations to comprehensively screen phytochemical databases and pinpoint
promising compounds with the potential to inhibit EV-D68 3Cpro, thereby supporting immune system restoration.
Results Our analysis identified lead compounds with high docking score such as EA-5317333 (-9.268 kcal/mol) and
EA-76313109 (-8.618 kcal/mol) from East African Natural Products Database, NA-5320945 (-7.902 kcal/mol) and
NA-101630512 (-7.570 kcal/mol) from North African Natural Products Database, SA-25245604 (-8.899 kcal/mol) and
SA-9064 (-7.538 kcal/mol) from South African Natural Compounds Database, NE-5280343 (-7.845) and NE-162817590
(-7.264 kcal/mol) from North-East African Natural Products Database, TCM-71665623 (-8.324 kcal/mol) and TCM-
163019889 (-8.414 kcal/mol) from Traditional Chinese Medicines Database as lead compounds. Furthermore, the stronger
binding affinity of these lead compounds with the 3Cpro was validated by the results of molecular dynamics (MD)
simulation, binding free energy calculation and dissociation constant analysis. The selected compounds exhibited favorable
ADMET properties, including high solubility in water, strong gastrointestinal absorption, and no signs of liver toxicity,
aligning well with Lipinski’s rule of five.
Conclusion Taken together, these findings provide compelling evidence to suppor
I'm still here and my opinion matters: a scoping review on the experience of epistemic injustice among people living with dementia
No full textEpistemic injustice refers to wrongs done to individuals in their capacity as knowers, often due to prejudice or stereotypes. People living with dementia (PLWD) are particularly vulnerable to epistemic injustice due to the cognitive, emotional and social aspects of their condition and this could negatively affect their quality of life. This scoping review aims to map the available evidence on how epistemic injustice can influence the experience of PLWD. By adopting the PRISMA and Joanna Briggs Institute guidance for scoping reviews, we included peer-reviewed and grey literature in English that describe the relation between the presence of epistemic injustice (concept) and the experience of PLWD (population) across different geographical and cultural contexts (context). Searches in academic databases (Web of Science, Proquest, PubMed, Scopus and EbscoHost) and among grey literature (OpenAlex and AlmaStart Discovery Tool) were conducted in November 2024. Two independent reviewers screened abstracts and full texts. A thematic analysis of the results was carried out. We included 10 studies, of which 7 from database searches, 2 from grey literature and 1 from reference lists of included studies. There was high methodological heterogeneity but most of the included studies were theoretical reflections. PLWD can experience epistemic injustice and are often excluded from clinical interactions and academic research due to communication challenges and difficulties in obtaining informed consent. Even when included in clinical practice and research, their voices are often not valued, limiting their involvement in decisions like advance directives, reinforcing negative stereotype