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A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation. National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented. The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.

[Display omitted] •Investigate the interactions between quality advertising and market research tactics.•Explain the variation in arrangements for product-consumer related information transmission.•The retailer prefers to postpone the market research decision after manufacturer's movement.•Either information decision sequence could become manufacturer's preferred scenario. Two-way asymmetric information frequently hampers performances of manufacturer-retailer distribution channel members. Typically, the manufacturer is better informed about the quality of his product than the retailer while the latter knows more about her consumers’ preference for product quality than the manufacturer. Bridging these information gaps can enable more profitable channel (wholesale and retail) pricing decisions. Specifically, once the manufacturer knows his product quality, he can at some cost advertise it to the downstream retailer and her consumers. Similarly, the retailer can decide to conduct market research at some cost to more precisely determine her consumers’ preference for product quality and share her finding with the manufacturer. In this paper, the authors examine the strategic impacts of two alternative timings of these information gap-filling decisions: In the “Upfront Market Research” (UMR) scenario, the retailer moves first with her market research decision and then the manufacturer makes his product quality advertising decision. Alternatively, in the “Upfront Quality Advertising” (UQA) scenario, the manufacturer first decides about product quality advertising and then the retailer proceeds with her market research decision. This paper analytically investigates and compares the strategic impacts of the UMR and UQA scenarios on the firms’ equilibrium information strategies and payoffs in a two-way asymmetric information setting for the first time. The authors find that the retailer is always better off in the UQA than the UMR scenario while the manufacturer can find either UMR or UQA decision sequence more beneficial depending on the relative costs of market research and product quality advertising. The analyses offer new insights and guidelines for more efficient and profitable information acquisition and coordination in bilateral manufacturer-retailer channels.

Loss of CD20 is a major obstacle for the retreatment of relapsed/refractory diffuse large B cell lymphoma (DLBCL) with Rituximab-associated regimens. Histone deacetylation causes gene silencing and inhibits CD20 expression. Chidamide is a novel inhibitor for histone deacetylases (HDACs). We hypothesize that Chidamide could overcome Rituximab-mediated down-regulation of CD20 and facilitate Rituximab-induced killing. In this study, we determine the mechanism of synergy of Chidamide with Rituximab in DLBCL using in vitro and in vivo models. We found that the levels of CD20 protein surface expression on five DLBCL cell lines were significantly and positively correlated with the sensitivities of cells to Rituximab. Treatment with Rituximab significantly reduced CD20 surface expression at the protein levels. RNA sequencing showed that Chidamide significantly increased expression of more than 2000 transcriptomes in DLBCL cells, around 1000 transcriptomes belong to the cell membrane and cell periphery pathways, including MS4A1. Chidamide significantly increased CD20 surface expression in DLBCL cell lines. Combination with Chidamide significantly synergized Rituximab-induced cell death in vitro and significantly inhibited tumour growth in DLBCL-bearing xenograft mice. A patient with relapsed/refractory DLBCL achieved a complete response after three cycles combined treatment with Chidamide and Rituximab. In conclusion, our data demonstrate for the first time that inhibition of HDACs by Chidamide significantly enhanced Rituximab-induced tumour growth inhibition in vitro and in vivo. We propose that CD20 surface expression should be used clinically to evaluate treatment response in patients with DLBCL. Chidamide is a promising sensitizer for the retreatment of DLBCL with Rituximab.

We aimed to compare the cardiovascular events and mortality in patients who underwent either physician-oriented or patient-oriented kidney replacement therapy (KRT) conversion due to discontinuation of peritoneal dialysis (PD). Patients with end-stage kidney disease who were receiving PD and required a switch to an alternative KRT were included. They were divided into physician-oriented group or patient-oriented group based on the decision-making process. Logistic regression analysis was used to explore the influencing factors related to KRT conversion in PD patients. The association of physician-oriented or patient-oriented KRT conversion with outcomes after the conversion was assessed by using Cox proportional hazards models. A total of 257 PD patients were included in the study. The median age at catheterization was 35 years. 69.6% of the participants were male. The median duration of PD was 20 months. 162 participants had patient-oriented KRT conversion, while 95 had physician-oriented KRT conversion. Younger patients, those with higher education levels, higher income, and no diabetes were more likely to have patient-oriented KRT conversion. Over a median follow-up of 39 months, 40 patients experienced cardiovascular events and 16 patients died. Physician-oriented KRT conversion increased nearly 3.8-fold and 4.0-fold risk of cardiovascular events and death, respectively. After adjusting for confounders, physician-oriented KRT conversion remained about a 3-fold risk of cardiovascular events. Compared to patient-oriented KRT conversion, PD patients who underwent physician-oriented conversion had higher risks of cardiovascular events and all-cause mortality. Factors included age at catheterization, education level, annual household income, and history of diabetes mellitus.

Using low cost and small size light emitting diodes (LED) as the alternative illumination source for photoacoustic (PA) imaging has many advantages, and can largely benefit the clinical translation of the emerging PA imaging technology. Here, we present our development of LED-based PA imaging integrated with B-mode ultrasound. To overcome the challenge of achieving sufficient signal-to-noise ratio by the LED light that is orders of magnitude weaker than lasers, extensive signal averaging over hundreds of pulses is performed. Facilitated by the fast response of the LED and the high-speed driving as well as the high pulse repetition rate up to 16 kHz, B-mode PA images superimposed on gray-scale ultrasound of a biological sample can be achieved in real-time with frame rate up to 500 Hz. The LED-based PA imaging could be a promising tool for several clinical applications, such as assessment of peripheral microvascular function and dynamic changes, diagnosis of inflammatory arthritis, and detection of head and neck cancer.

Molecular toxicity prediction is one of the key studies in drug design. In this paper, a deep learning network based on a two-dimension grid of molecules is proposed to predict toxicity. At first, the van der Waals force and hydrogen bond were calculated according to different descriptors of molecules, and multi-channel grids were generated, which could discover more detail and helpful molecular information for toxicity prediction. The generated grids were fed into a convolutional neural network to obtain the result. A Tox21 dataset was used for the evaluation. This dataset contains more than 12,000 molecules. It can be seen from the experiment that the proposed method performs better compared to other traditional deep learning and machine learning methods.

As a key layer for continental tight gas exploration and development in the Sichuan Basin, the Shaximiao Formation of the Middle Jurassic (J 2 S) has submitted proven reserves in the Yanting Area of the Tianfu Gas Field for two consecutive years, with huge exploration and development potential. Since the old well was tested in Member 1 of Shaximiao Formation (J 2 S 1 ) in Yanting area, many wells have obtained high-yield industrial gas flow, confirming that the fluvial sandstone reservoir contains gas. Compared with the more mature area in Jianyang Area in Tianfu Gas Field, the gas reservoir of J 2 S 1 in Yanting area is a lithologic reservoir under the same sedimentary background, with a relatively lower pressure gas reservoir and higher gas saturation. Based on core observation, scanning electron microscopy, analysis and testing, this paper studies the reservoir characteristics and main controlling factors of the sandstone of J 2 S 1 in Yanting area. The results show that: (1) It is a shallow deltaic sedimentary system controlled by southern provenance, and the underwater diversion channel sandstone is a favorable microfacies of J 2 S 1 in Yanting area; (2) The reservoir lithology is mainly fine-medium grained clastic feldspar sandstone and feldspar clastic sandstone with low content of miscellaneous base and cement; The reservoir space is residual intergranular pores, followed by intergranular dissolved pores and a small amount of intragranular dissolved pores; (3) It is dominated by Class II and III reservoirs, and the median porosity is 8.9% and the median permeability is 0.216mD, which has the characteristics of low porosity and ultra-low permeability; (4) Advantageous sand bodies, superior reservoirs and favorable source-fault-sandstone configuration relationships together control the gas filling and enrichment of J 2 S 1 in Yanting area. The research results can provide a scientific basis for the prediction of favorable reservoir distribution areas and the deployment of natural gas exploration and development schemes of J 2 S 1 in Yanting area.

By using our dual-modality system enabling simultaneous real-time ultrasound (US) and photoacoustic (PA) imaging of human peripheral joints, we explored the potential contribution of PA imaging modality to rheumatology clinic. By performing PA imaging at a single laser wavelength, the spatially distributed hemoglobin content reflecting the hyperemia in synovial tissue in metacarpophalangeal (MCP) joints of 16 patients were imaged, and compared to the results from 16 healthy controls. In addition, by performing PA imaging at two laser wavelengths, the spatially distributed hemoglobin oxygenation reflecting the hypoxia in inflammatory joints of 10 patients were imaged, and compared to the results from 10 healthy controls. The statistical analyses of the PA imaging results demonstrated significant differences (p < 0.001) in quantified hemoglobin content and oxygenation between the unequivocally arthritic joints and the normal joints. Increased hyperemia and increased hypoxia, two important physiological biomarkers of synovitis reflecting the increased metabolic demand and the relatively inadequate oxygen delivery in affected synovium, can both be objectively and non-invasively evaluated by PA imaging. The proposed dual-modality system has the potential of providing additional diagnostic information over the traditional US imaging approaches and introducing novel imaging biomarkers for diagnosis and treatment evaluation of inflammatory arthritis.