Archivio istituzionale della ricerca - Università dell'Insubria
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    Low-grade persistent poliovirus infection in long-term polio survivors diagnosed with post-polio syndrome: diagnostic and clinical implications

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    Despite extensive research, the pathogenesis of Post-Polio Syndrome (PPS) remains unclear. We investigated 251 participants from Northern Italy: long-term polio survivors with PPS, long-term polio survivors with stable polio, family members of both groups, subjects with neurological disorders other than poliomyelitis, and healthy controls. This study investigated whether persistent viral activity or the existence of viral reservoirs contributes to causing PPS. Poliovirus (PV) genomes and proteins were detected in 87.2% of PPS cases versus 12.0% of stable polio cases and 3.5% of control family members, but not in pathologic and healthy controls. Among PPS patients, the highly concordant detection of PV strains in both peripheral blood leukocytes and cerebrospinal fluid (CSF) suggests the presence of an ongoing low-grade infection. Conversely, the very low detection rate in family members indicates the minimal transmissibility of these PV variants. Molecular analysis of the detected PV strains revealed mutations across most genome regions, likely leading to defects in virus replication. Furthermore, in cell cultures, PPS-derived PV strains induced the release of inflammatory mediators (IL6, IL8, MCP1) that may play a pathogenic role. These findings have several clinical implications. First, the presence of mutated PV forms in blood leukocytes and CSF could serve as a diagnostic marker for PPS. Second, the persistent virus infection suggests that antiviral treatments might help reduce PPS progression. Furthermore, advanced genome sequencing techniques hold potential for distinguishing vaccine-derived from wild-type PV strains, thereby refining our understanding of PPS and the full spectrum of polio disorders

    Long-Term Stability of Ethyl Glucuronide in Hair: A 10-Year Retrospective Analysis of 909 Samples by LC–MS/MS

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    Monitoring long-term alcohol consumption is critical in forensic and public health contexts. Hair analysis of ethyl glucuronide (EtG), a direct metabolite of ethanol, has become a standard method for detecting chronic alcohol use. While the reliability of EtG hair testing is well established for short- and medium-term analyses, its stability in hair stored over extended periods has not been comprehensively evaluated. This limitation is especially relevant in retrospective investigations, postmortem evaluations, and long-term epidemiological studies, where archived samples may be analyzed years after collection. In this study, we assessed the long-term stability of EtG in human hair stored for up to 10 years. A total of 909 samples originally analyzed between 2013 and 2022 were re-tested in 2023 using a previously published and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. When the results of the old and the new analyses were compared, EtG concentrations showed no significant degradation over time, with more than 80% of the samples displaying matching values when analytical uncertainty was considered. Only a small fraction of samples (4.4%) dropped below the commonly used interpretive threshold for chronic alcohol use (30 pg/mg) after 10 years of storage. These findings provide robust evidence that EtG remains chemically stable in hair under standard storage conditions over a decade, confirming the reliability of archived samples for assessing alcohol use history and expanding the utility of EtG analysis in long-term toxicological and forensic investigations. The demonstrated stability strengthens confidence in hair as a matrix for retrospective substance use evaluation across scientific disciplines

    From therapy to cancer prevention using HRD testing on high grade ovarian cancer patients

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    Approximately half of high-grade ovarian cancers are characterized by genetic and epigenetic alterations of genes involved in homologous recombination (HRR), most commonly BRCA1 and BRCA2. HRR defects identified by tests of genomic instability confer PARP-inhibitors sensitivity in ovarian cancers. Commercial tests that combine tumor BRCA testing with a genomic instability score (HRD test) are available in clinical practice. We seek to determine the performance of three different HRD tests to improve therapy management and prevention of ovarian cancer. Tumor samples from 50 patients with high grade ovarian cancers were investigated for tumoral BRCA status, genomic instability and BRCA1 promoter methylation for treatment purposes. Patients with ovarian cancer that tested positive for BRCA variants and/or genomic instability defect, were referred to the Cancer Genetics Service for germline testing. A positive HRD status was observed in 54% of cases and pathogenic variants of BRCA genes were identified in 41% of cases presenting genomic instability. BRCA1 methylation assay revealed promoter hypermethylation in 20% of ovarian cancers that tested positive for HRD and negative for BRCA1/2 variants. Among 26 women referred to cancer genetic counselling, 10 carried germline variants in HRR genes. HRD status determined eligibility for PARP inhibitor treatment in all but two ovarian cancers. This study outlined that determining genomic instability helps identify inherited ovarian cancers. HRD testing, crucial for making high-ovarian cancer treatment choices, must be linked to an established path of cancer genetic counselling and management of individuals at high cancer risk

    Conservation of a threatened marginal population of Cistus albidus of Lake Garda (Italy)

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    The population of Cistus albidus of Lake Garda (N-Italy), present at the northernmost margin of its range, is endangered by urban development and extreme climate events. Since this species has been continuously declining for over 200 years, conservation actions are necessary to prevent its extinction. To identify the best sites for an assisted colonisation of the species in the area, we carried out experiments posing 120 plantlets grown from seeds from the natural population in each of 5 sites within a 20 km range from the natural population. Environmental, demographic and meteorological parameters were monitored for 8 years at each site to evaluate the response to our intervention. Demographic changes occurred at different rates, reflecting the effect of environmental factors on new plants establishment and survival; the final survival rate of reintroduced plants was 45.3%. Unlike winter temperature, summer drought had a strong negative impact on plant survival. Inter-population comparison suggests a formerly wider distribution of the species, and bodes well for the survival of the newly created populations. Differentiating between ecological factors influencing growth and those regulating reproductive biology and success of new generations will help to improve long-term fitness and viability in assisted colonisation projects

    Il destino dei luoghi turistici all'incrocio tra immagine, racconto e realtà

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    La geografia della comunicazione e la geografia del turismo sono intrinsecamente correlate, poiché la comunicazione svolge un ruolo fondamentale nel plasmare le percezioni, le esperienze e i flussi del turismo. La rappresentazione mediatica, le tecnologie di comunicazione e le pratiche comunicative influenzano, come è noto (Albanese, 2017b), le geografie del turismo. I media digitali ricoprono un ruolo di primo piano nel costruire immagini e narrazioni di luoghi turistici. La pubblicità turistica, le guide di viaggio, i programmi televisivi e le piattaforme online presentano rappresentazioni di destinazioni che influenzano i desideri e le scelte dei turisti

    Abductor digiti minimi opponensplasty and flexor digitorum superficialis opposition transfer: What are the main indications? A literature review

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    Thumb hypoplasia is a rare deformity of the hand. Type II and IIIA are the main indications for opponensplasty, together with thumbs with a residual weak opposition after pollicization. Our study operates a review of the current literature to establish which opponensplasty technique is the most appropriate for each patient. We conducted a systematic search using PubMed, Embase, and Web of Science databases. The keywords used were “thumb hypoplasia,” AND “opponensplasty,” “abductor digiti minimi opponensplasty,” “thumb hypoplasia,” AND “abductor digiti minimi,” “opponensplasty,” AND “hypoplasia,” “flexor superficialis opponensplasty,” “flexor digitorum superficialis opponensplasty.” A minimum of 1 year of follow-up was required for inclusion. A total of 222 studies were recovered, of which only 9 articles satisfied our inclusion criteria. From the results obtained, the choice between abductor digiti minimi opponensplasty and flexor digitorum superficialis transfer should depend on the severity of the deformity and the main goal that should be achieved. Children with type IIIA hypoplasia characterized by more unstable joints should undergo flexor digitorum superficialis transfer to restore joint stability. On the contrary, when the instability is not of great concern, abductor digiti minimi opponensplasty, which aims at better defining the thenar eminence and restoring a better global hand function, should be preferred

    UNVEILING THE HIDDEN REPERTOIRE OF GLIOBLASTOMA TUMOR ANTIGENS BY GENETIC MODOFICATION OF TUMOR CELLS WITH THE MHC CLASS II TRANSACTIVATOR CIITA

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    Il glioblastoma (GBM) è uno dei tumori cerebrali più aggressivi e mortali, noto per la sua capacità di eludere il sistema immunitario del corpo e resistere ai trattamenti tradizionali. Per affrontare questa sfida, abbiamo esplorato un nuovo approccio di immunoterapia utilizzando il MHC classe II transattivatore (CIITA) per aiutare il sistema immunitario a riconoscere e mirare cellule GBM in modo più efficace. In questo studio, abbiamo modificato tre diverse linee cellulari murine GBM (GL261, CT-2A e SB28) per esprimere CIITA. Questa modificazione ha significativamente indotto e/o aumentato i livelli di molecole MHC-II e MHC-I sulle loro superfici, che sono cruciali per la presentazione al sistema immunitario delle proteine (antigeni) associate ai tumori. Con questi antigeni diventando più visibili, le cellule T del sistema immunitario, comprese sia le cellule T aiutanti (CD4+) che killer (CD8+), potrebbero meglio identificare e attaccare il tumore. in vitro proliferazione ha ulteriormente confermato che l'espressione CIITA non ha influenzato il tasso di crescita delle cellule tumorali, indicando che eventuali cambiamenti nel comportamento del tumore sarebbe dovuto solo alla risposta immunitaria piuttosto che alterazioni nelle cellule stesse. Abbiamo poi valutato questa strategia nei topi utilizzando diverse combinazioni di vaccini GL261-CIITA e sfide. Questo studio si concentra sui topi che sono stati inizialmente vaccinati con le cellule GL261-CIITA modificate e successivamente sfidato con le cellule tumorali aggressive SB28. Sorprendentemente, il 75% dei topi vaccinati ha completamente respinto le cellule tumorali e il restante 25% ha mostrato una crescita del tumore ridotta rispetto ai topi non vaccinati. L'analisi di immunoistochimica (IHC) ha rivelato una forte risposta immunitaria, con chiare indicazioni di infiltrati di cellule T che prendono attivamente di mira il tumore. Per comprendere meglio la protezione in questi topi, specialmente nel contesto di sfide eterogenee, abbiamo impiegato la spettrometria di massa per identificare i peptidi specifici che sono presentati dalle cellule tumorali modificate. Curiosamente, molti di questi peptidi erano condivisi tra le tre linee cellulari e erano anche simili a quelli trovati nelle cellule umane GBM, suggerendo il potenziale traslazionale del nostro approccio alle impostazioni cliniche. Questa maggiore presentazione di antigene da parte delle cellule modificate con CIITA potrebbe servire come base per un nuovo vaccino ad ampio spettro contro il GBM. I nostri risultati suggeriscono anche che aumentare la capacità del sistema immunitario di riconoscere e rispondere alle cellule GBM utilizzando CIITA può innescare una potente risposta anti-tumorale. Questa strategia non solo aiuta a combattere il tumore iniziale, ma suggerisce anche la possibilità di una protezione incrociata contro diversi tipi di GBM.Glioblastoma (GBM) is one of the most aggressive and deadly brain tumors, known for its ability to evade the body's immune system and resist traditional treatments. To tackle this challenge, we have explored a new immunotherapy approach using the MHC class II transactivator (CIITA) to help the immune system to recognize and target GBM cells more effectively. In this study, we have modified three different murine GBM cell lines (GL261, CT-2A, and SB28) to express CIITA. This modification has significantly induced and/or increased the levels of MHC-II and MHC-I molecules on their surfaces, which are crucial for presenting tumor-associated proteins (antigens) to the immune system. With these antigens becoming more visible, the immune system's T cells, including both helper (CD4+) and killer (CD8+) T cells, could better identify and attack the tumor. in vitro proliferation assays has further confirmed that CIITA expression did not affect the growth rate of the tumor cells, indicating that any changes in tumor behavior would solely be due to the immune response rather than alterations in the cells themselves. We then have evaluated this strategy in mice using different combinations of GL261-CIITA vaccinations and challenges. This study focuses on mice that were initially vaccinated with the modified GL261-CIITA cells and later challenged with aggressive SB28 tumor cells. Remarkably, 75% of the vaccinated mice has completely rejected the tumor cells, and the remaining 25% has showed reduced tumor growth compared to non-vaccinated mice. Immunohistochemistry (IHC) analysis has revealed a strong immune response, with clear indications of T-cell infiltrates actively targeting the tumor. To further understand the protection in these mice, especially in the context of heterogeneous challenges, we have employed mass spectrometry to identify the specific peptides that are presented by the modified tumor cells. Interestingly, many of these peptides were shared among the three cell lines and were also similar to those found in human GBM cells, suggesting the translational potential of our approach to clinical settings. This increased antigen presentation by CIITA-modified cells could serve as the foundation for a new, broad-spectrum GBM vaccine. Our findings also suggests that boosting the immune system's ability to recognize and respond to GBM cells using CIITA can trigger a powerful anti-tumor response. This strategy not only helps in fighting off the initial tumor but also suggests potential for cross-protection against different types of GBM

    SOFTENG 2025 The Eleventh International Conference on Advances and Trends in Software Engineering

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    The Eleventh International Conference on Advances and Trends in Software Engineering (SOFTENG 2025), held between May 18-22, 2025 in Nice, France, continued a series of events focusing on the challenging aspects for software development and deployment, across the whole life-cycle. Software engineering exhibits challenging dimensions in the light of new applications, devices and services. Mobility, user-centric development, smart-devices, e-services, ambient environments, e-health and wearable/implantable devices pose specific challenges for specifying software requirements and developing reliable and safe software. Specific software interfaces, agile organization and software dependability require particular approaches for software security, maintainability, and sustainability. We welcomed academic, research and industry contributions. The conference had the following tracks: - Challenges for dedicated software, platforms, and tools - Software testing and validation - Software requirements - Maintenance and life-cycle management We take here the opportunity to warmly thank all the members of the SOFTENG 2025 technical program committee, as well as all the reviewers. The creation of such a high quality conference program would not have been possible without their involvement. We also kindly thank all the authors who dedicated much of their time and effort to contribute to SOFTENG 2025. We truly believe that, thanks to all these efforts, the final conference program consisted of top quality contributions. We also thank the members of the SOFTENG 2025 organizing committee for their help in handling the logistics and for their work that made this professional meeting a success. We hope that SOFTENG 2025 was a successful international forum for the exchange of ideas and results between academia and industry and to promote further progress in the field of software engineering. We also hope that Nice provided a pleasant environment during the conference and everyone saved some time to enjoy the historic charm of the city

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