Archivio Istituzionale della Ricerca- Università del Piemonte Orientale
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Università negativa: la realizzazione della filosofia.
No full textSaggio introduttivo alla nuova edizione del testo di R. Curcio e M. Rostagno, Università negativa. Trento 1967-1968
Immaginari razziali in Italia dagli anni Venti a oggi
No full textRaccolta di saggi sulla costruzione, l'incidenza e la decostruzione degli immaginari razziali nelle produzioni culturali e nei discorsi politici italiani dagli anni Venti del Novecento a oggi
Comparative Effectiveness of Switching From First‐Generation Basal Insulins to Either Glargine 300 U/mL or Degludec 100 U/mL in Children and Adolescents With Type 1 Diabetes: Results From the ISPED CARD Clinical Registry
Get PDFBackground: To assess the real-world effectiveness of switching from first-generation basal insulins (1BIs) to either glargine U300 (Gla-300) or degludec U100 (Deg-100) in children and adolescents with type 1 diabetes (T1D), using data from the Italian ISPED CARD clinical registry. Materials and Methods: This multicenter retrospective observational study included 1063 pediatric patients with T1D from 22 diabetes centers across Italy who switched from 1BI to either Gla-300 (64.6%) or Deg-100 (35.4%) between 2021 and 2023. Propensity score matching (PSM) was applied to create comparable groups (n = 353 per group). Primary endpoint was the change in HbA1c at 6 months. Secondary endpoints included fasting blood glucose (FBG), standardized body mass index (BMI/SDS), and insulin doses at 6 and 12 months. Longitudinal models for repeated measures were used to assess treatment effectiveness. Results: Both groups showed significant and clinically relevant reductions in HbA1c at 6 months from ~ 8.7% to ~ 7.4% (−1.3 percentage points), maintained at 12 months, with no significant differences between groups. FBG also decreased significantly in both groups, slightly favoring Deg-100, but without statistical significance between groups. BMI/SDS remained stable. Gla-300 was associated with a slight increase in basal insulin dose over 12 months, while Deg-100 showed a temporary reduction at 6 months. A significant reduction in short-acting insulin dose (−0.03 U/kg) was observed in both groups. Conclusion: Switching from 1BI to either Gla-300 or Deg-100 significantly improves glycemic control in pediatric T1D patients without weight gain. Although both insulins showed comparable effectiveness, differences in titration patterns highlight the need for individualized treatment strategies and improved clinician education in insulin optimization. Safety outcomes, particularly hypoglycemia, could not be assessed
Protein diversity, type 2 diabetes, and effect modifiers: a multi-country prospective study
No full textBackground Dietary diversity may affect type 2 diabetes (T2D) but no studies have examined protein diversity by source. We examined five diversity scores and the 10-year risk of T2D and effect modification. Methods A prospective study of 10 363 incident T2D cases and a representative sub-cohort of 13 937 individuals sampled from a cohort of 340 234 participants in eight European countries (1993-2007). Five diversity scores were derived from self-reported diet data (gr/day): diversity of food groups (range: 0-5); and diversity within subtype of vegetables (0-4); meat/alternatives (0-6); animal-protein (0-8); and plant-protein sources (0-5). Country-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained by using Prentice-weighted Cox regression and combined by using mixed-effects models. Models were stratified by sex (male/female) and obesity status (body mass index ≥ 30 kg/m2; waist circumference ≥ 88 cm for females and ≥102 cm for males). Results Daily intake of five food groups (versus up to three) was linked to lower T2D incidence overall [HR 0.86 (95% CI 0.75, 0.98)], in females [0.86 (0.77, 0.96)], and in people without central obesity [0.79 (0.70, 0.89)]. Three or more subtypes of plant protein were inversely associated with T2D overall [0.78 (0.65, 0.98)], in females [0.75 (0.62, 0.90)] and people without central obesity [0.82 (0.68, 1.00)]. Additionally, consuming three subtypes of vegetables was inversely associated with T2D overall [0.90 (0.83, 0.98)] and in males [0.85 (0.73, 0.99)]. Conclusion Diabetes prevention may benefit not only from a diet consisting of five different food groups, but also from a diet that is diverse in plant-protein sources, with specific benefits for female Europeans and those without central obesity
Impact of comprehensive genomic profiling and molecular tumour board on costs and access to tailored therapies: real-world observational study
Get PDFObjective There is limited evidence on the economic implications of assessing patients' access to personalised treatments through Comprehensive Genomic Profiling (CGP) and Molecular Tumour Board (MTB), prompting the need to analyse their impact on the cost of the cancer diagnostic journey (from hospital admission to MTB evaluation) and accessibility to personalised therapies. Design Retrospective observational cohort. Setting Patients discussed from April 2020 to September 2021 by the institutional MTB operating at Fondazione IRCCS Istituto Nazionale Tumori of Milan, an Italian centre of excellence in oncology pertaining to the national health system. Participants 676 patients focused on: non-small cell lung cancer (NSCLC), cholangiocarcinoma (CCA), pancreatic carcinoma (PC) and gastro-oesophageal carcinoma (GEC). We defined two different scenarios: (1) patients tested with small Next-Generation Sequencing (NGS) panels (≤60 biomarkers) vs (2) patients tested with comprehensive panels (>60 biomarkers). Main outcomes and measures We measured (1) patients' eligibility to personalised therapies based on genomic data obtained using targeted somatic NGS panels, (2) MTB cost and the overall diagnostic journey cost and (3) the cost to find a patient eligible to access personalised treatments. Results Tumour profiling with comprehensive NGS panels improved patients' eligibility to personalised therapies compared with small panels (NSCLC: 39% comprehensive panel vs 37% small panel; CCA: 43% vs 17%; PC: 35% vs 3%; GEC: 40% vs 0%). The overall diagnostic journey cost per patient was between 3.2K and 7.4K (NSCLC: 7.4K comprehensive panel vs 6.4K small panel; CCA: 4.9K vs 3.7K; PC: 5.8K vs 4.5K; GEC: 4.2K vs 3.2K). MTB discussion accounted for only 2-3% of the diagnostic journey cost per patient (around 113€/patient). The cost to find patient eligible for personalised treatments varied significantly according to panel size and tumour setting (NSCLC: 5K comprehensive panel vs 2.8K small panel; CCA: 4.4K vs 4.4K; PC: 5.5K vs 27K; GEC: 5.2K vs not measurable since none of the patients analysed with small NGS panels were eligible). Conclusions and relevance MTB discussion of genomic data obtained with NGS comprehensive panels significantly increases patient eligibility to targeted therapies and optimise the cost to find a patient eligible to personalised treatments, mainly for CCA, PC and GEC patients
Search for charged lepton flavor violating and boson decays in proton-proton collisions at
No full textA nationwide forensic case-series of femicides in Italy – Part 2: Clues to its epidemiology, prediction and prevention
Get PDFFemicides are grievous, but little is known about risk factors and preventive measures. We present the results of a study conducted across 27 Italian Forensic Institutes. We analyzed 1,238 cases of female homicide and, adopting the definition of femicide as the murder due to the failure to recognize women's right to self-determination, we identified 410 cases as femicides and 395 as non-femicides Current partners were identified as aggressors in a much larger proportion of femicide cases (241 femicides vs. 145 non-femicides; odds ratio (OR) of femicide 2.46, 95 % CI 1.85–3.27), such association being more pronounced for ex-partners (102 vs. 11; OR 11.56, 95 % CI 6.10–21.92). Sharp weapons showed a higher frequency in femicides (168 vs. 140; OR 1.26, 95 % CI 0.95–1.68). Femicides were more often associated with bodies found in vehicles (31 vs. 9; OR 3.50, 95 % CI 1.64–7.45) and outdoor (68 vs. 43; OR 1.62, 95 % CI 1.08–2.45). There was an indication of femicides being more frequently associated with overkilling (87/323 vs. 71/324; OR 1.24, 95 % CI 0.88–1.76) and even more with lesions located in erogenous zones (94/316 vs. 70/325; OR 1.38, 95 % CI: 0.97–1.95). However, the strongest (though statistically imprecise) association emerged for overkilling in erogenous zones (12/398 vs. 6/389; OR 1.95, 95 % CI: 0.72–5.25). The number of lesions showed a nonlinear association with femicide likelihood. These findings offer forensic indicators that could contribute in predicting and potentially prevent femicide occurrence in a Western population such as the Italian one
Search for New Physics in Jet Multiplicity Patterns of Multilepton Events at (Formula presented)
No full textA first search for beyond the standard model physics in jet multiplicity patterns of multilepton events is presented, using a data sample corresponding to an integrated luminosity of (Formula presented) of 13 TeV proton-proton collisions recorded by the CMS detector at the LHC. The search uses observed jet multiplicity distributions in one-, two-, and four-lepton events to explore possible enhancements in jet production rate in three-lepton events with and without bottom quarks. The data are found to be consistent with the standard model expectation. The results are interpreted in terms of supersymmetric production of electroweak chargino-neutralino superpartners with cascade decays terminating in prompt hadronic (Formula presented)-parity violating interactions
MiR-22/GLUT1 Axis Induces Metabolic Reprogramming and Sorafenib Resistance in Hepatocellular Carcinoma.
Get PDFThe approval of immunotherapy has revolutionized the management of hepatocellular carcinoma (HCC) patients. However, sorafenib remains a first-line therapeutic option for advanced patients and, in particular, for patients not eligible for immune checkpoint inhibitors, but its efficacy is limited by the onset of acquired resistance, highlighting the urgent need for predictive biomarkers. This study investigates the role of miR-22 in metabolic reprogramming and its potential as a biomarker in HCC. The analysis of miR-22 expression was performed in HCC patients and preclinical models by qPCR. Functional analyses in HCC cells evaluated GLUT1 as a direct miR-22 target. Cellular and metabolic assays evaluated the miR-22/GLUT1 axis's role in metabolic changes, tumor aggressiveness, and sorafenib response. Circulating miR-22 was analyzed in sorafenib-treated HCC patients and rats. MiR-22 was downregulated in HCCs and associated with aggressive tumor features. Functionally, miR-22 modulated the HIF1A pathway, enhanced survival in stressful conditions, promoted a glycolytic shift, and enhanced cancer cell plasticity and sorafenib resistance via GLUT1 targeting. In addition, high serum miR-22 levels were associated with sorafenib resistance in HCC patients and rats. GLUT1 inhibition sensitized low miR-22-expressing HCC cells to sorafenib in preclinical models. These findings suggest that circulating miR-22 deserves attention as a predictive biomarker of sorafenib response. GLUT1 inhibition may represent a therapeutic strategy to combine with sorafenib, particularly in patients exhibiting high circulating miR-22 levels
Evaluation of the 4Kscore Test in Relation to Subsequent Risk of Aggressive Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition
No full textBACKGROUND: PSA is central to referrals for prostate biopsy but has low specificity for aggressive prostate cancer. This study evaluates the 4Kscore (OPKO Diagnostics) versus total PSA in predicting short- and long-term risks of aggressive prostate cancer. METHODS: Baseline blood samples from 1,658 men diagnosed with prostate cancer (median diagnosis time = 8.6 years) and 1,658 matched controls in the European Prospective Investigation into Cancer and Nutrition were analyzed. Discrimination for the 4Kscore and total PSA was assessed using the AUC with 95% confidence intervals (CI) via bootstrapping. RESULTS: For high-grade tumors, AUCs were 0.69 (95% CI, 0.66-0.72) for the 4Kscore and 0.75 (95% CI, 0.73-0.78) for total PSA. For advanced-stage disease, AUCs were 0.71 (95% CI, 0.66-0.75) for the 4Kscore and 0.77 (95% CI, 0.73-0.80) for total PSA. Similar findings were observed for other aggressive cancer endpoints. Among men with PSA >2 ng/mL, the 4Kscore had better discrimination than PSA for overall prostate cancer, high-grade disease, and prostate cancer death but only in men <60 years at recruitment. CONCLUSIONS: In this large European study, the 4Kscore did not significantly improve the prediction of clinically significant prostate cancer compared with total PSA, except in younger men with elevated PSA. IMPACT: The findings underscore the limited utility of the 4Kscore in improving medium- to longer-term risk prediction over PSA, with potential benefits restricted to younger men with elevated PSA