1,340 research outputs found

    Developing a risk assessment score for patients with cancer during the coronavirus disease 2019 pandemic

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    The novel coronavirus (CoV) pandemic is a serious threat for patients with cancer, who have an immunocompromised status and are considered at high risk of infections. Data on the novel CoV respiratory disease (coronavirus disease 2019 [COVID-19]) in patients with cancer are still limited. Unlike other common viruses, CoVs have not been shown to cause a more severe disease in immunocompromised subjects. Along with direct viral pathogenicity, in some individuals, CoV infection triggers an uncontrolled aberrant inflammatory response, leading to lung tissue damage. In patients with cancer treated with immunotherapy (e.g. immune checkpoint inhibitors), COVID-19 may therefore represent a serious threat. After a thorough review of the literature on CoV pathogenesis and cancer, we selected several shared features to define which patients can be considered at higher risk of COVID-19. We combined these clinical and laboratory variables, with the aim of developing a score to weight the risk of COVID-19 in patients with cancer

    A metanalysis on cabozantinib and bone metastases: True story or commercial gimmick?

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    Is it true that cabozantinib should be the preferred option treating patients with bone metastases? Are there any reliable comparisons between this drug and other standard options in this subgroup? To address the issue, we performed a systematic review and metanalysis of randomized trials with cabozantinib, to assess its effectiveness, in terms of overall survival, according to the presence of bone metastases. We included (a) randomized controlled trials; (b) any solid tumors and therapeutic line; and (c) overall survival data available according to the site of disease. Cabozantinib improved overall survival both for the group with bone metastases, with risk of death decreased by 53% (hazard ratio, 0.47; 95% confidence interval, 0.26–0.87; P=0.02) and for the group without bone metastases, decreasing the risk of death by 44% (hazard ratio, 0.56; 95% confidence interval, 0.40–0.79; P=0.001) over the standard of care. The difference was not significantly different between the two groups. Despite cabozantinib can be undoubtedly listed as a good therapeutic option for cancer patients with bone metastases, it seems that its preclinical profile against bone remodeling does not translate into an actual clinical relevance, preventing from considering the presence of bone metastases as principal criterion for the choice of this drug

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    Different roles for the acyl chain and the amine leaving group in the substrate selectivity of N-Acylethanolamine acid amidase

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    N-acylethanolamine acid amidase (NAAA) is an N-terminal nucleophile (Ntn) hydrolase that catalyses the intracellular deactivation of the endogenous analgesic and anti-inflammatory agent palmitoylethanolamide (PEA). NAAA inhibitors counteract this process and exert marked therapeutic effects in animal models of pain, inflammation and neurodegeneration. While it is known that NAAA preferentially hydrolyses saturated fatty acid ethanolamides (FAEs), a detailed profile of the relationship between catalytic efficiency and fatty acid-chain length is still lacking. In this report, we combined enzymatic and molecular modelling approaches to determine the effects of acyl chain and polar head modifications on substrate recognition and hydrolysis by NAAA. The results show that, in both saturated and monounsaturated FAEs, the catalytic efficiency is strictly dependent upon fatty acyl chain length, whereas there is a wider tolerance for modifications of the polar heads. This relationship reflects the relative stability of enzyme-substrate complexes in molecular dynamics simulations

    Towards a Conceptualization of Sociomaterial Entanglement

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    In knowledge representation, socio-technical systems can be modeled as multiagent systems in which the local knowledge of each individual agent can be seen as a context. In this paper we propose formal ontologies as a means to describe the assumptions driving the construction of contexts as local theories and to enable interoperability among them. In particular, we present two alternative conceptualizations of the notion of sociomateriality (and entanglement), which is central in the recent debates on socio-technical systems in the social sciences, namely critical and agential realism. We thus start by providing a model of entanglement according to the critical realist view, representing it as a property of objects that are essentially dependent on different modules of an already given ontology. We refine then our treatment by proposing a taxonomy of sociomaterial entanglements that distinguishes between ontological and epistemological entanglement. In the final section, we discuss the second perspective, which is more challenging form the point of view of knowledge representation, and we show that the very distinction of information into modules can be at least in principle built out of the assumption of an entangled reality

    Non-volatile voltage control of in-plane and out-of-plane magnetization in polycrystalline Ni films on ferroelectric PMN-PT (001)pcsubstrates

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    We identify room-temperature converse magnetoelectric effects (CMEs) that are non-volatile by using a single-crystal substrate of PMN-PT (001)pc (pc denotes pseudocubic) to impart voltage-driven strain to a polycrystalline film of Ni. An appropriate magnetic-field history enhances the magnetoelectric coefficient to a near-record peak of ∼10-6 s m-1 and permits electrically driven magnetization reversal of substantial net magnetization. In zero magnetic field, electrically driven ferroelectric domain switching produces large changes of in-plane magnetization that are non-volatile. Microscopically, these changes are accompanied by the creation and destruction of magnetic stripe domains, implying the electrical control of perpendicular magnetic anisotropy. Moreover, the stripe direction can be rotated by a magnetic field or an electric field, the latter yielding the first example of electrically driven rotatable magnetic anisotropy. The observed CMEs are associated with repeatable ferroelectric domain switching that yields a memory effect. This memory effect is well known for PMN-PT (110)pc but not PMN-PT (001)pc. Given that close control of the applied field is not required as for PMN-PT (110)pc, this memory effect could lead the way to magnetoelectric memories based on PMN-PT (001)pc membranes that switch at low voltage

    Humoral and cellular response to BoHV-1 in buffalo and cattle treated with an inactivated marker vaccine

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    The study is aimed at assessing and comparing the immune response to BoHV-1 elicited by an inactivated marker vaccine in buffaloes and cattle. Vaccination did not produced any local or general reactions in buffaloes. Seroneutralizing antibodies and cellular response by IFN-γ- test have been detected in buffaloes and cattle after a prime/ booster vaccination strategy. Humoral and cellular responses were significantly higher in cattle than in buffaloes. Data pointed out the possibility to use the marker vaccine in buffaloes. However, further studies must be planned to assess the immune pressure of marker vaccines in terms of IBR eradicative attitude in infected buffalo herds

    Giant and reversible extrinsic magnetocaloric effects in La0.7Ca0.3MnO3 films due to strain

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    Large thermal changes driven by a magnetic field have been proposed for environmentally friendly energy efficient refrigeration, but only a few materials which suffer hysteresis show these giant magnetocaloric effects. Here we create giant and reversible extrinsic magnetocaloric effects in epitaxial films of the ferromagnetic manganite La0.7Ca0.3MnO3 using strain mediated feedback from BaTiO3 substrates near a first-order structural phase transition. Our findings should inspire the discovery of giant magnetocaloric effects in a wide range of magnetic materials, and the parallel development of nanostructured bulk samples for practical applications.Comment: 32 pages, 1 Table, 5 figures, supplementary informatio

    Knowledge Graph Embedding for Ecotoxicological Effect Prediction

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    Exploring the effects a chemical compound has on a species takes a considerable experimental effort. Appropriate methods for estimating and suggesting new effects can dramatically reduce the work needed to be done by a laboratory. In this paper we explore the suitability of using a knowledge graph embedding approach for ecotoxicological effect prediction. A knowledge graph has been constructed from publicly available data sets, including a species taxonomy and chemical classification and similarity. The publicly available effect data is integrated to the knowledge graph using ontology alignment techniques. Our experimental results show that the knowledge graph based approach improves the selected baselines
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