Scientific reports
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This study aimed to identify potential predictive factors for the survival of advanced lung adenocarcinoma patients undergoing pemetrexed maintenance therapy. 122 advanced lung adenocarcinoma patients who received pemetrexed maintenance therapy were retrospectively analyzed. Kaplan-Meier method with Log-rank test was used for survival analysis. Univariate and multivariate Cox regression were performed to evaluate prognostic factors for overall survival (OS) and progression-free survival (PFS). ⋯ PD-L1 expression was an independent prognostic factor for both PFS and OS times (PFS: HR, 0.175; P = 0.001; OS: HR, 0.107; P = 0.036). Bivariate correlation showed a significant positive correlation between PD-L1 expression and PFS (correlation coefficient R = 0.485, P < 0.001). High PD-L1 expression could be a potential effective predictor for favorable survival of advanced lung adenocarcinoma patients undergoing pemetrexed maintenance therapy.
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In spite of many compounds identified as antifibrotic in preclinical studies, pulmonary fibrosis remains a life-threatening condition for which highly effective treatment is still lacking. Towards improving the success-rate of bench-to-bedside translation, we investigated in vivo µCT-derived biomarkers to repeatedly quantify experimental silica-induced pulmonary fibrosis and assessed clinically relevant readouts up to several months after silicosis induction. Mice were oropharyngeally instilled with crystalline silica or saline and longitudinally monitored with respiratory-gated-high-resolution µCT to evaluate disease onset and progress using scan-derived biomarkers. ⋯ The volume of healthy, aerated lung first dropped then increased, corresponding to an acute inflammatory response followed by recovery into lower elevated aerated lung volume. Imaging results were confirmed by a significantly decreased Tiffeneau index, increased neutrophilic inflammation, increased IL-13, MCP-1, MIP-2 and TNF-α concentration in bronchoalveolar lavage fluid, increased collagen content and fibrotic nodules. µCT-derived biomarkers enable longitudinal evaluation of early onset inflammation and non-resolving pulmonary fibrosis as well as lung volumes in a sensitive and non-invasive manner. This approach and model of non-resolving lung fibrosis provides quantitative assessment of disease progression and stabilization over weeks and months, essential towards evaluation of fibrotic disease burden and antifibrotic therapy evaluation in preclinical studies.
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The temporal structure of sound such as in music and speech increases the efficiency of auditory processing by providing listeners with a predictable context. Musical meter is a good example of a sound structure that is temporally organized in a hierarchical manner, with recent studies showing that meter optimizes neural processing, particularly for sounds located at a higher metrical position or strong beat. Whereas enhanced cortical auditory processing at times of high metric strength has been studied, there is to date no direct evidence showing metrical modulation of subcortical processing. ⋯ Results show that neural encoding of the fundamental frequency of the vowel was enhanced at the strong beat, and also that the neural consistency of the vowel was the highest at the strong beat. When comparing musicians to non-musicians, musicians were found, at the strong beat, to selectively enhance the behaviorally relevant component of the speech sound, namely the formant frequency of the transient part. Our findings indicate that the meter of sound influences subcortical processing, and this metrical modulation differs depending on musical expertise.
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The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify the risk factors associated with its progression. ⋯ The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases.
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SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. ⋯ In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.