2,049 research outputs found

    Emerging topics in Brexit debate on Twitter around the deadlines a probabilistic topic modelling approach

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    The present study is focused on the online debate relating to the Brexit process, three years and half since the historical referendum that has sanctioned the divide of the United Kingdom from the European Union. In our analysis we consider a corpus of approximately 33 million Brexit related tweets, shared on Twitter for 58 weeks, spanning from 31 December 2019 to 9 February 2020. Due to its great accessibility to data, Twitter constitutes a convenient data source to monitor and evaluate a wide variety of topics. In addition, Twitter’s marked orientation towards news and the dissemination of information makes this microblogging network more connected to politics compared to other platforms. Through static and dynamic topic modelling techniques, we were able to identify the topics that have attracted the most attention from Twitters users and to characterise their temporal evolution. The topics retrieved by the static model highlight the major events of the Brexit process while the dynamic analysis recovered the persistent themes of discussion and debate over the entire period

    Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies

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    BackgroundThymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies.Main bodyStarting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin.Short conclusionThe newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer

    LA SIEROLOGIA TIPO-SPECIFICA PER HERPES SYMPLEX TIPO 2 NELLA GESTIONE DEI PAZIENTI HIV POSITIVI

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    none8noVedi allegato.Pauri, P.; Balercia, M.; Barchiesi, F.; Butini, L.; Costantini, A.; Del Gobbo, R.; Marinelli, K.; Tomassini, T.Pauri, P.; Balercia, M.; Barchiesi, Francesco; Butini, L.; Costantini, Andrea; Del Gobbo, R.; Marinelli, K.; Tomassini, T

    Epigenetic effects of chromatin remodeling agents on organotypic cultures

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    Background: Tumor epigenetic defects are of increasing relevance to clinical practice, because they are 'druggable' targets for cancer therapy using chromatin-remodeling agents (CRAs). New evidences highlight the importance of the microenvironment on the epigenome regulation and the need to use culture models able to preserve tissue morphology, to better understand the action of CRAs. Methods & methods: We studied the epigenetic response induced by culturing and CRAs in a preclinical model, preserving ex vivo the original tissue microenvironment and morphology, assessing different epigenetic signatures. Our overall findings suggest that culturing and CRAs cause heterogeneous effects on the genes methylation; CRAs affect the global DNA methylation and can trigger an active DNA demethylation; the culture induces alterations in the histone deacetylase expression. Conclusion: Despite the limited number of cases, these findings can be considered a proof of concept of the possibility to test CRAs epigenetic effects on ex vivo tissues maintained in their native tissue architecture

    The oncofetal protein IMP3: a novel grading tool and predictor of poor clinical outcome in human gliomas

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    Morphologic criteria illustrated in WHO guidelines are the most significant prognostic factor in human gliomas, but novel biomarkers are needed to identify patients with a poorer outcome. The present study examined the expression of the oncofetal protein IMP3 in a series of 135 patients affected by high-grade (grade III and IV) gliomas, correlating the results with proliferative activity, molecular parameters, and clinical and follow-up data. Overall, IMP3 expression was higher in glioblastomas (68%) than in grade III tumors (20%, P < 0.0001), and IMP3-positive high-grade gliomas showed a shorter overall and disease-free survival than negative ones (P = 0.0002 and P = 0.006, resp.). IMP3 expression was significantly associated with the absence of mutations of IDH1 gene (P = 0.0001) and with the unmethylated phenotype of MGMT in high-grade gliomas (P = 0.004). High Ki67 levels were correlated with better prognosis in glioblastomas but IMP3 expression was not correlated with the proliferation index. These findings confirm the role of IMP3 as a marker of poor outcome, also in consideration of its association with IDH1 wild-type phenotype and MGMT unmethylated status. The data suggest that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas

    Cartographies of the Body in Pandemic Times

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    As Fox and Alldred (2020) note, culture/nature dualism has supplied post-Enlightenment philosophers, scientists and social scientists with a neat way to set limits on the respective Cartographies of the Body in Pandemic Times Saúde em Redes. 2022; 8 (3) 494 concerns of the social and natural sciences (see also Barad, 2007; Braidotti, 2013; Fullagar et al., 2019). This dualism has also enabled the creation of distinctions between “modern” (read “civilised”) and “traditional” (read “primitive”) bodies and ways of being-in-the-world. Yet, when critically exploring issues of embodiment, the influence of the built environment on well-being, climate transitions and/or the ongoing Covid-19 pandemic such distinctions start to become problematic, as eloquently argued in the last three decades by feminist, post-human, newmaterialist and political ecological –among others– debates and propositions. Giving continuity to an ongoing dialogue started in 2018 between scholars and activists from Latin America and Europe, we organized the online seminar “Re-assembling the nature-culture-body nexus: practices and epistemologies”. In this two-parts online event was explored how the interrelated domains of health, physical activity, and education can look like from perspectives that de-stabilise established ontological boundaries between nature, culture, the body, and their relationship. This paper is the transcription of the second session, called “Cartographies of the body in pandemic times”, and present the dialogues between Alice del Gobbo, Carla Panico, Gianluca De Fazio, Alexandre Fernandez Vaz and Eduardo Galak, researchers from Brazil, Italy Portugal and Argentina

    Combined Large Cell Neuroendocrine Carcinomas of the Lung: Integrative Molecular Analysis Identifies Subtypes with Potential Therapeutic Implications

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    Simple Summary In this manuscript, we offer an integrated molecular analysis of 44 combined large cell neuroendocrine carcinomas (CoLCNECs) in order to deepen the knowledge about these rare histotypes and to clarify their relationship with lung cancers. In the present state of research, molecular studies are still scant, consisting of small and heterogeneous cohorts, and the genomic landscape is poorly characterized. This study shows that CoLCNECs constitute a standalone group of neuroendocrine neoplasm, with three different molecular profiles, two of which overlap with pure LCNEC or adenocarcinoma. CoLCNECs can be considered an independent histologic category with specific genomic and transcriptomic features, different and therefore not comparable to other lung cancers. Indeed, in addition to a histological re-evaluation of lung cancer classification, our study may help to develop a new diagnostic approach for novel and personalized treatments in CoLCNECs. Background: Combined large cell neuroendocrine carcinoma (CoLCNEC) is given by the association of LCNEC with adeno or squamous or any non-neuroendocrine carcinoma. Molecular bases of CoLCNEC pathogenesis are scant and no standardized therapies are defined. Methods: 44 CoLCNECs: 26 with adenocarcinoma (CoADC), 7 with squamous cell carcinoma (CoSQC), 3 with small cell carcinoma (CoSCLC), 4 with atypical carcinoid (CoAC) and 4 napsin-A positive LCNEC (NapA+), were assessed for alterations in 409 genes and transcriptomic profiling of 20,815 genes. Results: Genes altered included TP53 (n = 30), RB1 (n = 14) and KRAS (n = 13). Targetable alterations included six KRAS G12C mutations and ALK-EML4 fusion gene. Comparison of CoLCNEC transcriptomes with 86 lung cancers of pure histology (8 AC, 19 ADC, 19 LCNEC, 11 SCLC and 29 SQC) identified CoLCNEC as a separate entity of neuroendocrine tumours with three different molecular profiles, two of which showed a non-neuroendocrine lineage. Hypomethylation, activation of MAPK signalling and association to immunotherapy signature specifically characterized each of three CoLCNEC molecular clusters. Prognostic stratification was also provided. Conclusions: CoLCNECs are an independent histologic category. Our findings support the extension of routine evaluation of KRAS mutations, fusion genes and immune-related markers to offer new perspectives in the therapeutic management of CoLCNEC

    Invasive pleural malignant mesothelioma with rib destruction and concurrent osteosarcoma in a dog

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    A 7-year-old Dachshund was clinically examined because of a 10-day history of lameness in the left hind limb. On the basis of radiological and cytological findings, an osteosarcoma of the left acetabular region was suspected. The dog underwent a hemipelvectomy and osteosarcoma was diagnosed by subsequent histopathological examination. An immovable subcutaneous mass was noted on the left chest wall during the physical examination and non-septic neutrophilic inflammation was diagnosed by cytology. Forty days later, the dog showed signs of respiratory distress with an in-diameter increase of the subcutaneous mass up to 4 cm. Thoracic radiography and ultrasonography revealed pleural effusion and a lytic process in the fourth left rib. Furthermore, ultrasound examination revealed a mixed echogenic mobile structure with a diameter of around 2 cm floating within the pleural fluid of the left hemithorax close to the pericardium. The dog underwent surgery for an en bloc resection of the subcutaneous mass together with the fourth rib and the parietal pleura. Moreover, the left altered lung lobe, corresponding to the mobile structure detected by ultrasound, was removed. Based on cytological, histopathological, and immunohistochemical examinations, an invasive epithelioid pleural malignant mesothelioma was diagnosed

    Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

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    This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered
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