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The Santolina chamaecyparissus complex includes 13 species of dwarf aromatic evergreen shrubs from the western Mediterranean Basin. Five native species occurring in Italy are currently accepted. Four of them are endemic to relatively restricted areas in the peninsula, whereas S. corsica Jord. & Fourr. is endemic to Corsica and Sardinia. The taxonomic treatments of Italian Santolina have been changing significantly in the past, probably due to the misinterpretation of naturalised populations of S. chamaecyparissus, a widely cultivated pentaploid species, which occasionally escapes from cultivation through agamospermy or vegetative propagation. In this study, we carried out the first quantitative morphometric and comparative niche analyses concerning the four species endemic to continental Italy (S. etrusca, S. ligustica, S. neapolitana, and S. pinnata). Morphometric analyses (PCoA, Random Forest, and univariate analyses) show that these species can be easily distinguished by combinations of character states, whereas niche analyses (Schoener’s D and similarity test) suggest that they occur in distinct climatic conditions. Based on our results, we fully confirm the taxonomic distinctiveness of these species. An updated identification key, including all Santolina species occurring in Italy, is presented.

Background: Patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (mBC) generally receive hormonal therapy (HT) combined with CDK4/6 inhibitors (CDK4/6i). Despite this treatment, resistance mechanisms to CDK4/6i emerge and the majority of these patients experience disease progression (PD). This highlight the necessity to uncover the resistance mechanism to CDK4/6i through the identification of specific biomarkers. The primary objective is to assess the accuracy and feasibility of a novel multi-gene target panel NGS assay on circulating tumor DNA (ctDNA) to detect molecular alterations of AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53 genes in women with BC undergoing HT plus CDK4/6i treatment. Secondarily, the study aims to explore the relationship between genomic profiling and clinical outcomes. Materials and Methods: Plasma samples were collected from 16 patients diagnosed with advanced/locally advanced HR+/HER2- BC at 2 time points: T0 (baseline) and at T1 (3 months after CDK4/6i treatment). Starting from 2 mL of plasma, ctDNA was isolated and libraries were set up using the Plasma-SeqSensei (PQS)® Breast Cancer IVD Kit, sequenced on Nextseq 550 and analyzed using the Plasma-SeqSensei™ IVD Software®. Results: Among the five patients who presented PD, three had PIK3CA mutations and, of these, two showed a higher mutant allele frequency (MAF) at T1. In three patients with stable disease and in eight patients with partial response, the MAF of the detected alterations decreased dramatically or disappeared during CDK4/6i treatment. Conclusions: Based on our findings, the liquid biopsy analysis using the PQS panel seems to be both feasible and accurate, demonstrating a strong sensitivity in detecting mutations. This exploratory analysis of the clinical outcome associated to the mutational status of patients highlights the potential of molecular analysis on liquid biopsy for disease monitoring, although further validation with a larger patient cohort is necessary to confirm these preliminary observations.

Background: Fibro-calcific aortic valve disease (FCAVD) is a progressive disorder characterized by the thickening and calcification of the aortic valve, eventually leading to aortic stenosis. Adiponectin and leptin, known for their anti-inflammatory and proinflammatory properties, respectively, have been implicated in cardiovascular diseases, but their associations with FCAVD are controversial. This meta-analysis aims to evaluate the relationships between adiponectin and leptin levels and FCAVD, particularly in patients with severe aortic stenosis (AS). Methods: A systematic search was conducted across the PubMed, Scopus, and Web of Science databases to identify studies on adiponectin and leptin levels in FCAVD. The methodological quality of each study was assessed using the Newcastle–Ottawa Scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and publication bias was evaluated using Egger’s test and funnel plots. Results: Out of 191 articles identified, 10 studies involving 2360 patients (989 with FCAVD and 1371 controls) were included. The analysis suggested trends in the associations of lower adiponectin levels (SMD = −0.143, 95% CI: −0.344, 0.057, p = 0.161) and higher leptin levels (SMD = 0.175, 95% CI: −0.045, 0.395, p = 0.119) with FCAVD. The association remained a trend for low adiponectin but showed a significant correlation with high leptin in severe AS patients (SMD = 0.29, 95% CI: 0.036, 0.543, p = 0.025). Conclusion: This meta-analysis indicates a potential association between elevated leptin levels and severe aortic stenosis, while the relationship with adiponectin levels remains inconclusive. These findings highlight the need for further and dedicated research to clarify the roles of these adipokines in the pathogenesis of FCAVD and their potential roles as biomarkers for disease progression.

This work explores microcombustion technologies enhanced by plasma-assisted combustion, focusing on a novel simulation model for a Y-shaped device with a non-premixed hydrogen-air mixture. The simulation integrates the ZDPlasKin toolbox to determine plasma-produced species concentrations to Particle-In-Cell with Monte Carlo Collision analysis for momentum and power density effects. The study details an FE-DBD plasma actuator operating under a sinusoidal voltage from 150 to 325 V peak-to-peak and a 162.5 V DC bias. At potentials below 250 V, no hydrogen dissociation occurs. The equivalence ratio fitting curve for radical species is incorporated into the plasma domain, ensuring local composition accuracy. Among the main radical species produced, H reaches a maximum mass fraction of 8% and OH reaches 1%. For an equivalence ratio of 0.5, the maximum temperature reached 2238 K due to kinetic and joule heating contributions. With plasma actuation with radicals in play, the temperature increased to 2832 K, and with complete plasma actuation, it further rose to 2918.45 K. Without plasma actuation, the temperature remained at 300 K, reflecting ambient conditions and no combustion phenomena. At lower equivalence ratios, temperatures in the plasma area consistently remained around 2900 K. With reduced thermal power, the flame region decreased, and at Φ = 0.1, the hot region was confined primarily to the plasma area, indicating a potential blow-off limit. The model aligns with experimental data and introduces relevant functionalities for modeling plasma interactions within microcombustors, providing a foundation for future validation and numerical models in plasma-assisted microcombustion applications.

Background: Art therapy has a long history of applications in cognitive and motor rehabilitation. More recently, a growing body of scientific literature has highlighted the potential of virtual reality in neurorehabilitation, though it has focused more on the technology itself than on the principles adopted in digital scenarios. Methods: This study is a single-blind randomized controlled trial conducted on 40 patients with stroke, comparing conventional therapy (physical therapy for the upper and lower limbs, for posture and balance, cognitive therapy, occupational therapy, speech therapy, and specific therapy for swallowing, bowel, and bladder dysfunctions) to a protocol in which the upper limb physical therapy was substituted with art therapy administered by means of virtual reality exploiting the so-called Michelangelo effect. Results: After 12 sessions, patients in the virtual art therapy group showed a significantly greater improvement in independence in activities of daily living, as assessed by the Barthel Index (interaction of time and group: p = 0.001). Significant differences were also found in terms of upper limb muscle strength (Manual Muscle Test, p < 0.01) and reduction in spasticity (Ashworth scale, p = 0.007) in favor of the experimental group. In the virtual art therapy group, the effectiveness of the intervention was significantly correlated with patient participation (Pittsburgh Rehabilitation Participation Scale: R = 0.41), patient satisfaction (R = 0.60), and the perceived utility of the intervention by the therapist (R = 0.43). Conclusions: These findings support the efficacy of virtual art therapy leveraging the Michelangelo effect. Further studies should also focus on cognitive domains that could benefit from this type of approach.

Plantar fasciitis is one of the most common causes of foot pain; in 35% of cases, it is also associated with bone edema of the heel. The aim of this study was to investigate the relationship between bone edema and the outcomes of temperature-controlled high-energy adjustable multi-mode emission laser (THEAL) and/or exercises in patients with plantar fasciitis. A prospective randomized clinical trial was designed, in which 48 patients suffering from plantar fasciitis, with or without bone edema, were treated with temperature-controlled high-energy adjustable multi-mode emission laser and exercises (the laser group) or with exercises only (the control group). The patients were evaluated at recruitment (T0) and at 2 (T1) and 6 months (T2), monitoring pain (with the Visual Analogue Scale), functionality (with the Foot Function Index), perception of improvement (with the Roles and Maudsley Score), and fascia thickness (with ultrasound examination). In both groups, there was a significant improvement in pain, functional recovery, perception of remission, and a reduction in plantar fascia thickness at T1 and T2. The laser group presented statistically better values at T2 for the Roles and Maudsley Score (z: 2.21; 0.027). The regression analysis showed that a greater reduction in fascia thickness occurred in the laser group (p-value: 0.047). In conclusion, the two conservative treatments were effective in patients suffering from plantar fasciitis, even in the presence of bone edema, but with lesser results.

Abstract. Background. To evaluate the effectiveness and safety of cabazitaxel in castration-resistant prostate cancer patients aged ≥80 years, we performed a retrospective study on a sample of patients from 11 Italian cancer centers. Materials and methods. Fifty-seven patients aged ≥80 years were treated with cabazitaxel after previous failure with docetaxel; 39 completed a comprehensive geriatric assessment questionnaire (34 fit and 5 vulnerable) and 8 patients (14%) had an Eastern Cooperative Oncology Group performance status (PS) ≥2, while most had a PS of 0–1 (86%). Cabazitaxel was administered at a dose of 25 mg/m2 in 30 (52%) patients and 20 mg/m2 or adapted schedules in 27 (48%) patients. These schedules were adopted mainly in patients ≥85 years (75%), with a PS ≥2 (87.5%), and those classified as vulnerable (100%). Results. The duration of treatment was 4.8 months and was comparable in all subgroups; disease control rate was reported in 36 patients (63%); prostate-specific antigen response was recorded in 18 patients (31.5%). Median overall survival was 13.1 months regardless of age (

Abstract The Berry curvature provides a powerful tool to unify several branches of science through their geometrical aspect: topology, energy bands, spin and vector fields. While quantum defects–phase vortices and skyrmions–have been in the spotlight, as rotational entities in condensates, superfluids and optics, their dynamics in multi-component fields remain little explored. Here we use two-component microcavity polaritons to imprint a dynamical pseudospin texture in the form of a double full Bloch beam, a conformal continuous vortex beyond unitary skyrmions. The Berry curvature plays a key role to link various quantum spaces available to describe such textures. It explains for instance the ultrafast spiraling in real space of two singular vortex cores, providing in particular a simple expression–also involving the complex Rabi frequency–for their intricate velocity. Such Berry connections open new perspectives for understanding and controlling highly-structured quantum objects, including strongly asymmetric cases or even higher multi-component fields.

In the past few years, artificial intelligence (AI) has been increasingly used to create tools that can enhance workflow in medicine. In particular, neuro-oncology has benefited from the use of AI and especially machine learning (ML) and radiogenomics, which are subfields of AI. ML can be used to develop algorithms that dynamically learn from available medical data in order to automatically do specific tasks. On the other hand, radiogenomics can identify relationships between tumor genetics and imaging features, thus possibly giving new insights into the pathophysiology of tumors. Therefore, ML and radiogenomics could help treatment tailoring, which is crucial in personalized neuro-oncology. The aim of this review is to illustrate current and possible future applications of ML and radiomics in neuro-oncology.

Abstract Statins are commonly prescribed medications widely investigated for their potential actions on the brain and mental health. Pre-clinical and clinical evidence suggests that statins may play a role in the treatment of depressive disorders, but only the latter has been systematically assessed. Thus, the physiopathological mechanisms underlying statins’ putative antidepressant or depressogenic effects have not been established. This review aims to gather available evidence from mechanistic studies to strengthen the pharmacological basis for repurposing statins in depression. We used a broad, well-validated search strategy over three major databases (Pubmed/MEDLINE, Embase, PsychINFO) to retrieve any mechanistic study investigating statins’ effects on depression. The systematic search yielded 8068 records, which were narrowed down to 77 relevant papers. The selected studies (some dealing with more than one bodily system) described several neuropsychopharmacological (44 studies), endocrine-metabolic (17 studies), cardiovascular (6 studies) and immunological (15 studies) mechanisms potentially contributing to the effects of statins on mood. Numerous articles highlighted the beneficial effect of statins on depression, particularly through positive actions on serotonergic neurotransmission, neurogenesis and neuroplasticity, hypothalamic-pituitary axis regulation and modulation of inflammation. The role of other mechanisms, especially the association between statins, lipid metabolism and worsening of depressive symptoms, appears more controversial. Overall, most mechanistic evidence supports an antidepressant activity for statins, likely mediated by a variety of intertwined processes involving several bodily systems. Further research in this area can benefit from measuring relevant biomarkers to inform the selection of patients most likely to respond to statins’ antidepressant effects while also improving our understanding of the physiopathological basis of depression.

Durante el ciclo progresista (2005-2020) Uruguay estuvo gobernado por primera vez en su historia por un partido político de centro-izquierda. El artículo examina las políticas culturales desarrolladas durante este ciclo político. Se aplica una noción crítica de política cultural que trasciende su uso limitado a la gestión del campo artístico, sin excluirlo del análisis. Sobre las políticas sectoriales se examina la emergencia de un nuevo paradigma, la ciudadanía cultural, en paralelo a la continuidad del apoyo a disciplinas artísticas de la cultura erudita. Sobre las políticas de sustrato, se abordan las implicaciones culturales de la política hacia la diferencia en lo que se denominó nueva agenda de derechos y de la valorización del capitalismo como motor del desarrollo nacional.

As part of an increasingly multicultural society issues concerning integration and relationships between ethnic groups and different communities are receiving a great deal of attention in the social and scientific debate. The skills of design can be made available as a tool to systematise this multiplicity, promoting an innovation respectful of diversity, comparison, and interaction between people and cultures. This article concerns practical product design applications, that explore the relationship between multi-cultural society and cultural accessibility. Moreover, this contribution aims to reflect on which and how methodological strategies could be implemented within a design process that focuses on an intercultural approach. A series of case studies of narrative artifacts capable of bringing different cultures together and making them recognizable to different users will be analysed with the lens proposed in the methodological overview.

Following recent social and global transformations, cultural organizations have undergone a major redefinition in their role as keepers and promoters of knowledge and heritage, developing virtuous examples and reference models for the free, open, and autonomous enjoyment of all audiences. This contribution - contextualized in a current doctoral research on the enhancement of cultural heritage, promotion of institutional and territorial identities - is presented as a reflection on the recent awareness and attention to the issues of inclusiveness and accessibility in places of culture, especially higher education institutions. Through an analytical work on numerous university case studies, focused on institutional merchandising products, it was possible to outline common attitudes and effective communication strategies that promote core values related to multiculturalism, body positivity, gender equality, women’s empowerment, and integration of ethnic minorities.

The need to restore the former industrial factories so as not to leave the buildings and the neighborhood in a state of neglect has attracted scholarly and popular attention. The following contribution aims to highlight how designers can contribute to the repurposing of buildings by paying attention to the end user and planning new experiences and activities by reading case studies of industrial conversion of production sites into cultural hubs. The company’s history, intrinsically linked to the territory, and its products, are the protagonists of the reconversion so as not to forget the past local productive culture demonstrating how it is possible to generate new and different economies from before. The case studies tell the story of the industrial conversion of companies and mines in urban and decentralized areas to get a representative look at the Italian and European territories.

BackgroundImmunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy.MethodsThe Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS.ResultsOverall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 – 10.1), while mPFS was 7.0 months (95% CI: 5.7 – 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59).ConclusionWe found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS.

Background: Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis. Objectives: Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes. Methods: In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7. Results: From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1–2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively. Conclusion: The study met its primary endpoint, showing the efficacy of enzalutamide in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites. Trial registration: ClinicalTrials.gov Identifier: NCT03103724. First Posted: 6 April 2017. First patient enrollment: 19 April 2017.