Archivio istituzionale della ricerca - Università dell'Insubria
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Retinal biomarkers for early Alzheimer’s detection: a systematic review of optical coherence tomography (OCT) findings
Full text linkObjective: Retinal biomarkers accessible via non-invasive optical coherence tomography (OCT) could facilitate early detection of Alzheimer's disease (AD), complementing current invasive or costly diagnostic methods. This review evaluates the evidence for spectral-domain OCT (SD-OCT) and OCT angiography (OCT-A) in identifying retinal changes associated with preclinical and early AD. Methods and analysis: We conducted a systematic review registered in PROSPERO and aligned with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. PubMed/MEDLINE was searched up to April 2025, complemented by reference list screening and citation tracking. Eligible studies assessed SD-OCT and/or OCT-A in biomarker-defined preclinical or early AD, mild cognitive impairment or mild AD. Data were synthesised narratively by disease stage, and methodological quality was appraised with the Newcastle-Ottawa Scale. Results: 22 studies met inclusion criteria. Reported alterations included thinning of the peripapillary retinal nerve fibre layer and retinal ganglion cell layer, macular and choroidal thickness changes and microvascular alterations on OCT-A. However, findings were heterogeneous: some studies observed early thickening or increased vascular density, possibly reflecting inflammatory or compensatory mechanisms, while others reported thinning and rarefaction more consistent with neurodegeneration. Most studies were of moderate quality, limited by small sample sizes, cross-sectional designs and incomplete control for ocular/systemic confounders. Conclusion: SD-OCT and OCT-A hold promise as candidate biomarkers of early AD, but current evidence remains variable, non-specific and methodologically constrained. Further research is needed to standardise imaging protocols, validate findings in biomarker-confirmed longitudinal cohorts and compare OCT-based measures across dementia subtypes. Integration with other biomarkers (eg, plasma or metabolomics) may improve diagnostic specificity and support translation of OCT/OCT-A into clinical practice. Prospero registration number: CRD42024600456
IL-1-Beta and TNF-Alpha in Gingival Crevicular Fluid of Patients with Orthodontic Aligners and Application of Vibrations with Sonic Toothbrush: A Pilot Study
No full textIntroduction: Non-invasive methods to modulate orthodontic tooth movement have gained interest, particularly those targeting inflammatory mediators such as IL-1β and TNF-α, which regulate osteoclast and osteoblast activity. High-frequency vibrations (HFV), including those delivered by sonic toothbrushes, have been proposed to influence these biological responses. The aim of the study is to assess whether sonic vibrations affect IL-1β and TNF levels in patients undergoing clear aligner therapy. Materials and Methods: Twenty Invisalign® patients were evaluated. For each patient, one tooth received HFV via a 285 Hz sonic toothbrush (experimental), while the contralateral served as a control. Gingival crevicular fluid was sampled at baseline (T0), after one week without HFV (T1), and after one week with HFV (T2). Cytokines were measured by ELISA. Because data were non-normally distributed, non-parametric tests were applied. Results: No significant differences across T0–T2 were found within the HFV group. At T2, IL-1β levels were significantly lower in the HFV group (mean: 23.04; SD: ± 20.18) than in controls (mean: 44.44; SD: ± 47.14), which showed an IL-1β increase with orthodontic force alone. TNF-α levels remained near the ELISA detection limit. Conclusions: Sonic vibrations combined with clear aligners appear to reduce IL-1β secretion and local inflammation without adverse effects. Sonic toothbrushes provide a simple HFV delivery method, though larger studies are needed to confirm these findings
A strategic framework for zinc oxide electrochemical synthesis using design of experiments
Full text linkElectrochemical methods have gained increasing attention for the synthesis of micro- and nanostructured materials such as zinc oxide (ZnO). Traditionally, the development of such syntheses has relied on the One Variable At a Time (OVAT) approach, which systematically changes a single parameter while keeping others constant. However, this method provides only a limited understanding of the multidimensional experimental space. In contrast, a Design of Experiments (DoE) strategy offers a more efficient and statistically robust framework for identifying optimal synthesis conditions. In this work, we propose the application of a Full Factorial Design combined with Response Surface Methodology (RSM) to optimize for the first time the electrochemical synthesis of ZnO structures. The synthetic strategy integrates a hybrid electrochemical–Thermal process: sacrificial zinc electrolysis in a 30 mM sodium hydrogen carbonate solution, followed by thermal annealing that is typically employed in sol–gel methods to gain a final control over stoichiometry and morphology. ZnO microrods (ZnO MRs) were synthesized under galvanostatic conditions using benzalkonium chloride as a cationic surfactant and stabilizer. Its concentration (0.001–0.5 M) and the applied current density (2–20 mA/cm2) were selected as the key variables. A two-factor, three-level Central Composite Design (CCD) was implemented to investigate their combined effects on the electrosynthesis yield and ZnO length. The predictive model derived from the chemometric analysis was successfully validated, demonstrating the method’s potential for rational and efficient optimization of nano- and micromaterial electrosynthesis. Moreover, the proposed model was also validated on a scaled-up system, proving effective not only for laboratory-scale optimization but also for guiding process development toward industrial applications, where control, reproducibility, and efficiency are critical
Evaluating the appropriateness of penile prosthesis in non-organic erectile dysfunction and premature ejaculation: a Delphi consensus among penile implant surgeons
No full textBackground Non-organic erectile dysfunction (ED) and premature ejaculation (PE) are common conditions for which European Association of Urology guidelines lack specific recommendations on penile prosthesis implantation (PPI). Aim To establish expert consensus on the role of PPI in non-organic ED and PE using the Delphi method. Methods A panel of 24 international penile implant surgeons with significant experience in PPI participated in a 3-round Delphi consensus between February and May 2025. Participants were mainly European-based (Italy, n=16; Turkey, n=4; United Kingdom, n=2; Spain, n=1; Germany, n=1). Two online questionnaire rounds were followed by a final virtual meeting. Topics included diagnostics, treatment hierarchy, indications for PPI, ethical concerns, surgical risks, patient satisfaction, partner’s involvement, and follow-up strategies. Consensus was defined as ≥75% agreement or disagreement on Likert-scale items. Outcomes Expert consensus was reached on all 53 items, including the ones regarding the appropriateness of PPI in non-organic ED and PE. Results Experts agreed on the importance of thorough psychosexological assessment, standardized diagnostic tools, and exhausting conservative treatments before considering PPI in non-organic ED. Seventy-five percent supported PPI as a last-resort option in non-organic ED, provided psychological evaluation and informed consent protocols are in place. In contrast, the panel rejected PPI as a treatment for pure PE due to insufficient evidence and lack of clinical experience. Emphasis was placed on ethical safeguards, long-term follow-up, and partner involvement in decision-making. Clinical Implications These findings suggest that, under strict conditions, PPI may have a role in treatment-resistant non-organic ED but not in pure PE. Strengths and Limitations Limitations include the inherent subjectivity of the Delphi methodology and the restricted representativeness of the panel, which was mainly European-based and composed exclusively of urologists specializing in penile implants. Conclusion Selective use of PPI in non-organic ED is supported by expert consensus, while its use in pure PE is not; updated guidelines and further research are warranted
Uncovering patterns in skin and gut microbiota of rainbow trout (Oncorhynchus mykiss): insights from machine learning and feeding trials with sustainable aquafeeds based on yellow mealworm (Tenebrio molitor).
No full textDefeasible Reasoning in Description Logics with Prototype Descriptions
No full textDefeasible reasoning has always been a central interest of researchers in the fields of Artificial Intelligence (AI) and Multi-Agent Systems (MAS). In fact, this kind of reasoning is central to dealing with conflicting knowledge or beliefs that agents may hold without causing inconsistencies. In the context of languages for Knowledge Representation, many formal approaches have been proposed specifically in Description Logics (DLs) to deal with this phenomenon. With a perspective towards human-centred and agentive AI and building on the DL paradigm we pursue an approach informed by results coming from fields such as linguistics, philosophy and cognitive science. A central problem in the general area of defeasible DLs is to give a principled solution to the question of where preferences originate from in order to provide a notion of defeasibility. To address this issue, a core aspect of our approach is to compute preferences from the knowledge presented in a knowledge base (with standard semantics) itself. We thus present a non-monotonic DL based on a combination of ideas from prototype theory, weighted DLs (aka ‘tooth logic’), and earlier work on justifiable exceptions. A central ingredient in the new framework is the notion of a prototype description, i.e. weighted characterisations of concepts based on the typical features of its members. We show that through such descriptions it is possible to compute a typicality score which allows to define a preference order over models, useful to solve conflicts across exceptional instances. We define two principle ways of computing such preferences, discuss some core semantic properties and finally outline a translation into Answer Set Programming
La tutela degli interessi individuali negli accessi domiciliari
No full textL’indagine condotta ha l’obiettivo di verificare se il legislatore nazionale, con la modifica apportata all’art. 12, co. 1, l. 212/2000, sia riuscito a rimediare a quanto riscontrato dalla Corte EDU nelle due recenti sentenze Italgomme e Agrisud, ovvero alla non conformità all’art. 8, CEDU, della disciplina nazionale delle attività di indagine fiscale consistenti in accesi, ispezioni e verifiche presso i locali adibiti ad attività commerciali o professionali. Sempre in quest’ottica viene esaminata anche la proposta normativa di iniziativa parlamentare intervenuta sull’argomento, nonché il rapporto tra l’esigenza di tutela degli interessi individuali coinvolti negli accessi domiciliari e la disciplina statutaria dei vizi istruttori.The investigation aims to verify whether the national legislator, with the amendment made to Article 12, paragraph 1, Law 212/2000, has succeeded in remedying the findings of the European Court of Human Rights in the two recent Italgomme and Agrisud judgments, namely the non-compliance with Article 8 of the ECHR of the national regulations governing tax investigation activities consisting of access, inspections, and audits at premises used for commercial or professional activities. In this context, the parliamentary initiative on the subject is also examined, as well as the relationship between the need to protect the individual interests involved in home searches and the statutory regulation of procedural defects
Preoperative mFOLFIRINOX versus PAXG for stage I-III resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results of the first randomisation analysis of a randomised, open-label, 2 × 2 factorial phase 3 trial
No full textBackground Perioperative chemotherapy is a standard option for treatment of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). This study aimed to assess the superiority of PAXG (cisplatin, nab-paclitaxel, capecitabine, and gemcitabine) over mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) in this population. Methods CASSANDRA is a randomised, open-label, 2 × 2 factorial phase 3 trial, involving 17 Italian academic hospitals. Eligible patients were aged 18–75 years with pathologically confirmed resectable or borderline resectable PDAC. Randomisation was performed by a central web-based system using R-code lists with a computerised algorithm. The design adopted a 1:1 randomisation, with a block stratification by centre and carbohydrate antigen 19-9. Participants were first randomly assigned PAXG (total daily capecitabine dose of 1250 mg/m2 in a 625 mg/m2 twice a day dosage and intravenous cisplatin 30 mg/m2, nab-paclitaxel 150 mg/m2, and gemcitabine 800 mg/m2 every 14 days) or mFOLFIRINOX (intravenous fluorouracil 2400 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2, and oxaliplatin 85 mg/m2 every 14 days) for 4 months, followed by a second randomisation to 2 months of additional chemotherapy either before or after surgery. The primary endpoint was event-free survival (EFS) in the intention-to-treat population and the safety population included all patients who received at least one cycle of the assigned therapy. The results of the first randomisation are reported here. The trial, registered on ClinicalTrials.gov ( NCT04793932 ) and EudraCT (2020-003080-26 and 2024-519031-42-00), completed accrual and reached the necessary events for first randomisation primary analysis but follow-up of overall survival is ongoing. Findings Between Nov 3, 2020, and April 24, 2024, 132 eligible patients were assigned to PAXG and 128 to mFOLFIRINOX. In the PAXG group, the median age was 65 years (IQR 60–70), 68 (52%) of 132 patients were female, and 64 (48%) were male. In the mFOLFIRNOX group, the median age was 63 years (IQR 57–69), 62 (48%) of 128 patients were female, and 66 (52%) were male. All 260 patients received at least one assigned chemotherapy administration. PAXG prolonged the median EFS compared with mFOLFIRINOX (16·0 months [95% CI 12·4–19·8] vs 10·2 months [8·6–13·5]; hazard ratio 0·63 [0·47–0·84]; p=0·0018). At least one grade 3 or worse adverse event was observed in 87 (66%) of 132 patients in the PAXG group and in 78 (61%) of 128 patients in the mFOLFIRINOX group, including one fatal event. Interpretation PAXG significantly improved EFS compared with mFOLFIRINOX in resectable or borderline resectable PDAC. Preopertive PAXG could be considered a standard option for resectable or borderline resectable PDAC. Accordingly, preoperative PAXG should be considered as the standard comparator group for future trials in this setting. Funding MyEverest and Codice Viola
Ground-Glass Enhancement on Contrast-Enhanced Mammography: A CT-Inspired Qualitative Descriptor for Breast Lesion Characterization
No full textBackground: This study introduces a new qualitative enhancement descriptor for contrast-enhanced mammography (CEM), termed Ground-Glass Enhancement (GGE). The objective was to categorize breast lesions using this descriptor and evaluate its association with malignancy and markers of tumor aggressiveness. Methods: In this single-center retrospective study, 249 patients with a single enhancing lesion on CEM were included. Lesions were classified into pure Ground-Glass Enhancement (PGGE), Heterogeneous Ground-Glass Enhancement (HGGE), or Opaque Enhancement (OE) based on the degree of obscuration of the underlying parenchyma. Clinical, imaging, and pathological features were compared across groups. Multivariable logistic regression was used to identify independent predictors of malignancy. Results: Significant differences across enhancement patterns were found in lesion conspicuity, enhancement type, size, background enhancement, and patient age. OE lesions more frequently showed high conspicuity (83% vs. 62% in HGGE and 20% in PGGE) and a mass-like appearance (94% vs. 73% in HGGE and 81% in PGGE). HGGE lesions had the largest median size (25 mm, vs. 17 mm in OE and 13 mm in PGGE), and OE lesions most often exhibited minimal background enhancement (77%, vs. 50% in HGGE). In multivariable analysis, mass-like enhancement (OR = 4.59), larger size (OR = 1.27 per +5 mm), and high conspicuity (OR = 3.43) were independently associated with malignancy. Although GGE categories correlated with malignancy in univariable analysis, this was not confirmed in the adjusted model. OE lesions were significantly associated with higher Ki-67 expression (73% with Ki-67 >20%), indicating increased proliferative activity compared with PGGE (43%) and HGGE (57%). Conclusions: The GGE descriptor captures clinically relevant imaging features and may support visual stratification of breast lesions on CEM. While not an independent predictor of malignancy, it appears more closely related to markers of tumor aggressiveness