Coronavirus, uses the Angiotensin Converting Enzyme-2 Receptor to enter airway cells. Viral endocytosis is mediated by several factors, including clathrin, the adaptor protein-2 complex (AP2) and the adaptor-associated kinase-1 (AAK1). 2 According to a recent report, 3 COVID-19, the disease caused by SARS-CoV-2, is characterized by three clinical patterns: no symptoms, mild to moderate disease, severe pneumonia requiring admission to Intensive Care Unit (ICU) in up to 31% of the patients. 3 Thus far, there is no specific therapy for COVID-19 infection. No benefit of lopinavir-ritonavir treatment resulted in a recent trial. 4 Hydroxychloroquine, currently used in view of its "in vitro" observed effect of reduction of viral replication, seems unsatisfactory. 5 Elevated proinflammatory cytokine/chemokine responses seem associated with respiratory failure. 3 Recently, tocilizumab, an interleukin-6 inhibitor, was reported as effective in patients with severe COVID-19 pneumonia. 6 Baricitinib, another inhibitor of cytokine-release, seems an interesting anti-inflammatory drug. It is a Janus kinase inhibitor (anti-JAK) licensed for the treatment of rheumatoid arthritis (RA) with good efficacy and safety records. 7 Moreover it seems to have anti-viral effects by its affinity for AP2-associated protein AAK1, reducing SARS-CoV-2 endocytosis. 8 On this basis, we assessed the safety of baricitinib therapy combined with lopinavir-ritonavir in moderate COVID-19 pneumonia patients and we evaluated its clinical impact.All consecutive hospitalized patients (March 16th −30th) with moderate COVID-19 pneumonia, older than 18 years, were treated for 2 weeks with baricitinib tablets 4 mg/day added to ritonavir-lopinavir therapy. The last consecutive patients with moderate COVID-19 pneumonia receiving standard of care therapy (lopinavir/ritonavir tablets 250 mg/bid and hydroxychloroquine 400 mg/day/orally for 2 weeks) admitted before the date of the first baricitinib-treated patient served as controls. Antibiotics were scheduled only in the case of suspected bacterial infection.Inclusion criteria were: a. SARS-Co-V2 positivity in the nasal/oral swabs; b. presence of at least 3 of the following symptoms: fever, cough, myalgia, fatigue; c. evidence of radiological pneumonia . After discharge, patients treated with baricitinib were planned to be followed for additional 6 weeks. Exclusion criteria: history of thrombophlebitis (TP), latent tuberculosis infection (QuantiFERON Plus-test positivity, Qiagen, Germany 9 ), pregnancy and lactation.Mild to moderate COVID-19 disease definition: presence of bilateral pneumonia with or without ground glass opacity and in absence of consolidation, not requiring intubation at enrollment; arterial oxygen saturation (SpO2) > 92% at room-air, and ratio arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO2) 10 0-30 0 mmHg. Parameters daily accessed were: fever, pulmonary function, Modified Early Warning Score (MEWS), 10 pulse rate, blood pressure. After the initial execution, r...

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We focus on the study of conversational recommendation in the context of multi-type dialogs, where the bots can proactively and naturally lead a conversation from a nonrecommendation dialog (e.g., QA) to a recommendation dialog, taking into account user's interests and feedback. To facilitate the study of this task, we create a human-to-human Chinese dialog dataset DuRecDial (about 10k dialogs, 156k utterances), which contains multiple sequential dialogs for every pair of a recommendation seeker (user) and a recommender (bot). In each dialog, the recommender proactively leads a multi-type dialog to approach recommendation targets and then makes multiple recommendations with rich interaction behavior. This dataset allows us to systematically investigate different parts of the overall problem, e.g., how to naturally lead a dialog, how to interact with users for recommendation. Finally we establish baseline results on DuRecDial for future studies. 1 * This work was done at Baidu.

BackgroundThe objective of this study is to perform a meta-analysis to evaluate the associations between the BRAFV600E mutation status and aggressive clinicopathological features and poor prognostic factors in papillary thyroid cancer.MethodsA literature search was performed within the PubMed, MEDLINE, Web of Science databases, and EMBASE databases using the Medical Subject Headings and keywords from January 2003 to July 2015. Individual study-specific odds ratios and confidence intervals were calculated, as were the Mantel-Haenszel pooled odds ratios for the combined studies.ResultsSixty-three studies of 20,764 patients were included in the final analysis. Compared with wild-type BRAF, the BRAFV600E mutation was associated with aggressive clinicopathological factors, including extrathyroidal extension, higher TNM stage, lymph node metastasis, and recurrence, and was associated with reduced overall survival; however, there was no significant association between the presence of BRAF mutation and distant metastasis.ConclusionsBRAF mutations are closely associated with aggressive clinicopathological characteristics and poorer prognosis in papillary thyroid cancer. Accordingly, aggressive treatment should be considered for papillary thyroid cancer patients with BRAF mutation.

A controlled evaluation was made of the efficacy of copper-silver ionization in eradicating Legionella pneumophila from a hospital water supply. Copper-silver ionization units were installed on the hot water recirculation line of one building with water fixtures positive for Legionella species. Another building with the same water supply served as a control. Legionella species persisted within the system when copper and silver concentrations were < 0.3 and < 0.03 ppm, respectively. When copper and silver concentrations were > 0.4 and > 0.04 ppm, respectively, there was a significant decrease in Legionella species colonization, but the percentage of water fixtures positive for organisms was unchanged in the control building. When the ionization unit was inactivated, water fixtures continued to be free of Legionella species for 2 additional months. Copper-silver ionization can eradicate L. pneumophila in a water distribution system. The advantages of copper-silver ionization include relatively low cost, straightforward installation, easy maintenance, nontoxic by-products and the presence of a disinfecting residual.

Mesoporous thin films of TiO 2 doped with silver can undergo spectacular microstructural modifications upon laser scanning at visible wavelengths through the excitation of a localized surface plasmon resonance in Ag nanoparticles (NPs). The latter can result in competitive physicochemical mechanisms, leading either to the shrinkage or to the growth of NPs depending on the exposure conditions. Contrary to intuition, we provide evidence that the speed of the laser scan controls the size of NPs as follows: low speeds lead to silver oxidation and a decrease in the NP size, whereas high speeds induce rapid temperature rises and a spectacular growth of NPs. Both regimes are separated by a speed threshold that depends on extrinsic and intrinsic parameters such as laser power, beam diameter, and initial size of Ag NPs. We propose here a comprehensive model based on a set of coupled differential equations describing the transformations of silver under laser excitation between the Ag 0 , Ag + , and metallic NP states, which provides a convincing physicochemical explanation of the experimental findings. This study constitutes a significant advance in the understanding of oxidation−reduction processes involved during laser exposure of metallic NPs and opens new directions to control their growth rate and their final size.

Controlling plasmonic systems with nanometre resolution in transparent films and their colors over large non-planar areas is a key issue for spreading their use in various industrial fields. Using light to direct self-organization mechanisms provides high-speed and flexible processes to meet this challenge. Here, we describe a route for the laser-induced self-organization of metallic nanostructures in 3D. Going beyond the production of planar nanopatterns, we demonstrate that ultrafast laser-induced excitation combined with non-linear feedback mechanisms in a nanocomposite thin film can lead to 3D self-organized nanostructured films. The process, which can be extended to complex layered composite systems, produces highly uniform large-area nanopatterns. We show that 3D self-organization originates from the simultaneous excitation of independent optical modes at different depths in the film and is activated by the plasmon-induced charge separation and thermally-induced NP growth mechanisms. This laser color marking technique enables multiplexed optical image encoding and the generated nanostructured Ag NPs:TiO 2 films offer great promise for applications in solar energy harvesting, photocatalysis or photochromic devices. KeywordsUltrafast photonics; Laser-induced self-organization; Nanostructured thin film; plasmonic nanomaterials; plasmonic colors Controlling metallic nanostructures over large non-planar areas with high flexibility and speed is of strategic importance for developing industrial applications of plasmonic systems.

Background: Interleukin-6 (IL-6), a proinflammatory cytokine, has been reported to be associated with disease severity and mortality in patients with coronavirus disease 2019 (COVID-19). Yet, dynamic changes in IL-6 levels and their prognostic value as an indicator of lung injury in COVID-19 patients have not been fully elucidated. Objective: To validate whether IL-6 levels are associated with disease severity and mortality and to investigate whether dynamic changes in IL-6 levels might be a predictive factor for lung injury in COVID-19 patients. Methods: This retrospective, single-center study included 728 adult COVID-19 patients and used data extracted from electronic medical records for analyses. Results: The mortality rate was higher in the elevated IL-6 group than in the normal IL-6 group (0.16 vs 5%). Cox proportional hazards and logistic regression analyses for survival (adjusted hazard ratio, 10.39; 95% confidence interval [CI], 1.09-99.23; p = 0.042) and disease severity (adjusted odds ratio, 3.56; 95% CI, 2.06-6.19; p < 0.001) revealed similar trends. Curve-fitting analyses indicated that patient computed tomography (CT) scores peaked on days 22 and 24. An initial decline in IL-6 levels on day 16 was followed by resurgence to a peak, nearly in tandem with the CT scores. Conclusion: Increased IL-6 level may be an independent risk factor for disease severity and in-hospital mortality and dynamic IL-6 changes may serve as a potential predictor for lung injury in Chinese COVID-19 patients. These findings may guide future treatment of COVID-19 patients.