48 research outputs found

    A mobile voice search client for European Portuguese

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    The generalization of speech technology availability notable in simple mobility scenarios, such as searching the Internet using the user´s voice or “voice search”, has increased user awareness of the usefulness of this human-computer interaction modality. In this paper, we present a mobile voice search client that accepts a generic spo ken query and presents the search engine’s result page using European Portuguese.info:eu-repo/semantics/publishedVersio

    Casa de la Lhéngua: A set of language resources and natural language processing tools for Mirandese

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    This paper describes the efforts for the construction of Language Resources and NLP tools for Mirandese, a minority language spoken in North-eastern Portugal, now available on a community-led portal, Casa de la Lhéngua. The resources were developed in the context of a collaborative citizenship project led by Microsoft, in the context of the creation of the first TTS system for Mirandese. Development efforts encompassed the compilation of a corpus with over 1M tokens, the construction of a GTP system, syllable-division, inflection and a Part-of-Speech (POS) tagger modules, leading to the creation of an inflected lexicon of about 200.000 entries with phonetic transcription, detailed POS tagging, syllable division, and stress mark-up. Alongside these tasks, which were made easier through the adaptation and reuse of existing tools for closely related languages, a casting for voice talents among the speaking community was conducted and the first speech database for speech synthesis was recorded for Mirandese. These resources were combined to fulfil the requirements of a well-tested statistical parameter synthesis model, leading to an intelligible voice font. These language resources are available freely at Casa de la Lhéngua, aiming at promoting the development of real-life applications and fostering linguistic research on Mirandese.info:eu-repo/semantics/publishedVersio

    The regulatory mechanisms of NG2/CSPG4 expression

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    Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2. These regulatory factors crucially determine NG2-mediated cellular processes such as glial scar formation in the central nervous system (CNS) or tumor growth and metastasis. Therefore, they are potential targets for the establishment of novel NG2-based therapeutic strategies in the treatment of CNS injuries, cancer and other conditions of these types

    Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma

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    Background: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). Methods: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. Results: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0 - 16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (>25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). Conclusions: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC

    Can metabolic plasticity be a cause for cancer? Warburg–Waddington legacy revisited

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    Fermentation of glucose to lactate in the presence of sufficient oxygen, known as aerobic glycolysis or Warburg effect, is a universal phenotype of cancer cells. Understanding its origin and role in cellular immortalization and transformation has attracted considerable attention in the recent past. Intriguingly, while we now know that Warburg effect is essential for tumor growth and development, it is thought to arise because of genetic and/or epigenetic changes. In contrast to the above, we propose that Warburg effect can also arise due to normal biochemical fluctuations, independent of genetic and epigenetic changes. Cells that have acquired Warburg effect proliferate rapidly to give rise to a population of heterogeneous progenitors of cancer cells. Such cells also generate more lactate and alter the fitness landscape. This dynamic fitness landscape facilitates evolution of cancer cells from its progenitors, in a fashion analogous to Darwinian evolution. Thus, sporadic cancer can also occur first by the acquisition of Warburg effect, then followed by mutation and selection. The idea proposed here circumvents the inherent difficulties associated with the current understanding of tumorigenesis, and is also consistent with many experimental and epidemiological observations. We discuss this model in the context of epigenetics as originally enunciated by Waddington

    Chronic histiocytic intervillositis with trophoblast necrosis is a risk factor associated with placental infection from coronavirus disease 2019 (COVID-19) and intrauterine maternal-fetal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in live-born and stillborn infants

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    Context.—The number of neonates with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is increasing, and in a few there are reports of intrauterine infection. Objective.—To characterize the placental pathology findings in a preselected cohort of neonates infected by transplacental transmission arising from maternal infection with SARS-CoV-2, and to identify pathology risk factors for placental and fetal infection. Design.—Case-based retrospective analysis by a multinational group of 19 perinatal specialists of the placental pathology findings from 2 cohorts of infants delivered to mothers testing positive for SARS-CoV-2: live-born neonates infected via transplacental transmission who tested positive for SARS-CoV-2 after delivery and had SARS-CoV-2 identified in cells of the placental fetal compartment by molecular pathology, and stillborn infants with syncytiotrophoblast positive for SARS-CoV-2. Results.—In placentas from all 6 live-born neonates acquiring SARS-CoV-2 via transplacental transmission, the syncytiotrophoblast was positive for coronavirus using immunohistochemistry, RNA in situ hybridization, or both. All 6 placentas had chronic histiocytic intervillositis and necrosis of the syncytiotrophoblast. The 5 stillborn/ terminated infants had placental pathology findings that were similar, including SARS-CoV-2 infection of the syncytiotrophoblast, chronic histiocytic intervillositis, and syncytiotrophoblast necrosis. Conclusions.—Chronic histiocytic intervillositis together with syncytiotrophoblast necrosis accompanies SARS-CoV-2 infection of syncytiotrophoblast in live-born and stillborn infants. The coexistence of these 2 findings in all placentas from live-born infants acquiring their infection prior to delivery indicates that they constitute a pathology risk factor for transplacental fetal infection. Potential mechanisms of infection of the placenta and fetus with SARSCoV-2, and potential future studies, are discussed

    Hofbauer Cells and COVID-19 in Pregnancy Molecular Pathology Analysis of Villous Macrophages, Endothelial Cells, and Placental Findings From 22 Placentas Infected by SARS-CoV-2 With and Without Fetal Transmission

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    Context.-SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown. Objective.-To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants. Design.-Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2- infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells. Results.-Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. Conclusions.-SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement. (Arch Pathol Lab Med. 2021;145:1328-1340 ; doi: 10.5858/arpa.2021-0296-SA)OV
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