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Objectives To calculate the shrinkage of the neck muscles and dosimetric changes and to clarify the necessity of covering part of the muscle in neck node region delineation for patients with nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy. Methods In total, 44 patients with NPC were enrolled. Distances between the lateral border of the neck muscles and longitudinal midline were measured on every selected slice. This process was repeated three times, and the mean values of the three distances of planning computed tomography (CT) images and repeated CT images were adopted (labeled d1 and d2). The mean value of the differences between d1 and d2 was regarded as the medial shrinkage of the neck muscles. The initial clinical target volume of cervical lymph nodes (CTV‐n) was shifted medially with the value of shrinkage, yielding a new CTV‐n. Doses that covered 95% of the planning tumor volume (PTV) (D95), 99% of the PTV (D99), mean dose (Dmean), and maximum dose (Dmax) were used to calculate the dosimetric variation between the initial and new CTV‐n. Comparisons were performed using the paired samples t test. Results The median d1 was 3.81 cm (range: 1.19‐8.20 cm), and the median d2 was 3.68 cm (range: 0.94‐9.59 cm), with a statistically significant difference (P

To reduce carbon emissions, using more solar energy is a feasible solution. Many meteorological-based models can estimate global downward solar radiation (DSR), but they are with limited applications due to the point-based estimation and low temporal resolution. Satellite remote sensing-based models can estimate DSR with better spatial coverage. However, most previous models are restricted to estimate clear-sky or monthly scale DSR at several sites, limiting the solar energy monitoring of nationwide scale. In this study, using high spatiotemporal resolution Geostationary Operational Environmental Satellites (GOES)-16 satellite data, an iterative random forest (RF) model was developed to estimate and map half-hourly DSR at 1-km spatial resolution over the Continental United States (CONUS). The results show that the iterative RF model performed better than multiple linear regression (MLR) and traditional RF models. The accuracy of estimating half-hourly DSR is that R2 = 0.95, root-mean-square-error (RMSE) = 66.92 W/m2, and mean-bias-error (MBE) = 0.06 W/m2. Half-hourly and daily DSR with spatial resolution 1-km over the CONUS were mapped. The GOES-16 estimated DSR showed the similar spatial patterns with the results from the Clouds and the Earth's Radiant Energy System (CERES) DSR product. This study demonstrated the potential of GOES-16 data for mapping DSR over the CONUS, and hence can be further used in solar energy related applications.

In this study, a novel photovoltaic cell based on the Ti3C2Tx MXene/n-type silicon (n-Si) Schottky junction is developed by a simple solution-processed method of drop-casting the Ti3C2Tx MXene ethanol suspension onto the surface of n-Si wafers and the subsequent natural drying in air. The demonstration device with a simple configuration of Ag (top electrode)/Ti3C2Tx/n-Si/In:Ga (back electrode) delivers a power conversion efficiency (PCE) of 5.70% with a short-circuit current density (Jsc) of 20.68 mA cm−2, open-circuit voltage (Voc) of 0.530 V and fill factor (FF) of 52.0% under AM 1.5G illumination. After treating the MXene layer with the SnCl2 aqueous solution, an improved PCE to 6.95% (Jsc: 23.04 mA cm−2; Voc: 0.536 V; FF: 56.2%) can be achieved because of the reduced light reflection, improved quality of junction and electrical contact, as well as the increased carrier lifetime/suppressed carrier recombination. Given the simple device configuration, facile preparation and huge potential for performance improvement, this work is believed to provide valuable exploration of developing novel solar cells.

The adverse environmental impact associated with producing animal foods (e.g. chick, pork, beef, and fish) presents an opportunity for insect foods to meet the rising global demand for meat product...

Endoleaks may be present in up to 25% of patients after endovascular abdominal aortic aneurysm repair (EVAR) and there is no clear consensus on valuable biomarkers to determine endoleak presence. The aim of this study was to examine the potential value of plasma tumor necrosis factor-α converting enzyme (TACE) and Notch1 concentrations in determining endoleak presence after EVAR.A total of 110 patients with abdominal aortic aneurysm who underwent EVAR were enrolled in our study, and plasma TACE and Notch1 concentrations were measured prior to and 6 months after EVAR. Logistic regression was performed to assess the association of postoperative plasma TACE and Notch1 concentrations with endoleak after adjusting for potential confounders. The ability of plasma TACE and Notch1 concentrations to determine endoleak presence was assessed using receiver operating characteristic curves and area under the curve (AUC).Twenty-four patients developed endoleaks 6 months after EVAR. Both postoperative plasma TACE and Notch1 concentrations were higher in patients with endoleak than in those without endoleak (2376.4 ± 28.1 pg/ml vs. 2094.1 ± 27.3 pg/ml, P0.01; 218.6 ± 1.9 pg/ml vs. 195.0 ± 2.1 pg/ml, P0.01, respectively). The AUCs from receiver operating characteristic curve analysis of plasma TACE and Notch1 concentrations in determining endoleak presence were 0.844 (95% CI 0.771 to 0.918, P0.01) and 0.860 (95% CI 0.791 to 0.930, P0.01), respectively. Combining the detection of plasma Notch1 and TACE concentrations could improve the accuracy in determining endoleak presence (AUC 0.930, 95% CI 0.883 to 0.978, P0.01). The predicted probability cutoff of 0.22 yielded a sensitivity of 95.8% and a specificity of 82.6% for endoleak presence.Plasma TACE and Notch1 levels can discriminate patients with and without endoleak 6 months after EVAR, and have a potential role in screening patients requiring computed tomography angiography.

BACKGROUND: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. METHODS: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov ( NCT04651790 ). FINDINGS: The recruitment of participants occurred between November 27 (th) , 2020, until January 9 (th) , 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. INTERPRETATION: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens. FUNDING: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

Background Levodopa‐carbidopa intestinal gel (LCIG) is an established treatment for improving motor and some non‐motor symptoms (NMS) in patients with advanced Parkinson's disease (PD). Prospective long‐term data in routine clinical practice are limited. Objective Assess LCIG effectiveness and safety in patients with advanced PD after 12 months during real‐world routine clinical practice. Methods Duodopa/Duopa in patients with advanced Parkinson's disease—a global observational study evaluating long‐term effectiveness (DUOGLOBE) (NCT02611713) is an ongoing, prospective, multinational, observational study of LCIG‐naïve patients treated as part of routine clinical practice; 3 years of follow‐up are planned. The primary outcome is the change in patient‐reported off time. Other assessments include the Unified Dyskinesia Rating Scale (UDysRS), Non‐Motor Symptoms Scale (NMSS), Parkinson's Disease Sleep scale (PDSS‐2), Epworth Sleepiness Scale (ESS), health‐related quality of life (HR‐QoL), caregiver burden, and serious adverse events (SAEs). Outcomes from baseline to month (M) 12 are presented. Results In this 12‐month follow‐up, patients (N = 195) had baseline characteristics similar to other LCIG studies. Significant improvements (mean change to M12) were observed in off time (−3.9 ± 3.6 hr/day, P

Neuropathic pain is a devastating disease and exists tolerance to current available analgesics. MicroRNAs were reported to be involved in the regulation of neuropathic pain, but the biological role of miR-216a-5p in neuropathic pain remains unclear. In this study, we constructed a CCI rat model of neuropathic pain. Our results showed that the expression of miR-216a-5p was downregulated in CCI rats, and mechanical allodynia and thermal hyperalgesia in CCI rats were improved by miR-216a-5p overexpression, suggesting that miR-216a-5p overexpression alleviated neuropathic pain. Moreover, ELISA showed that miR-216a-5p overexpression inhibited concentration and mRNA expression of IL-6, TNF-α and IL-1β as well as suppressed microglial infiltration, indicating that miR-216a-5p overexpression inhibited neuroinflammation. Besides, we found that miR-216a-5p upregulation inactivated the Wnt/β-catenin signaling pathway. Furthermore, KDM3A was the downstream target of miR-216a-5p and KDM3A knockdown attenuated neuropathic pain. Finally, through rescue assay, we found that KDM3A countervailed miR-216a-5p mediated regulation of neuropathic pain via the Wnt/β-catenin signaling pathway. To sum up, our study confirmed that miR-216a-5p alleviated neuropathic pain in rats by targeting KDM3A and inactivating the Wnt/β-catenin signaling pathway, which may open a new and useful way for treatment of neuropathic pain.

In the research and application of images, people are often only interested in the foreground or specific area of the image, so it is necessary to extract the specific area from the image, and image segmentation technology is the key to solving this problem. Aiming at the complex background and the color image with unclear target contour as the target image to be segmented, this paper first uses the texture and color of the image as the feature vector, and proposes an image segmentation algorithm based on SVM. The experimental results show that the segmentation accuracy is 91.23%. Secondly, in order to improve the accuracy of segmentation, the SVM algorithm is improved. The improved SVM algorithm is based on the grid search method to optimize the parameters C and g in the SVM. At the same time, the HIS color channel is added to the feature vector to obtain more Excellent SVM image segmentation model. Finally, the color image segmentation is verified and compared with the standard SVM algorithm. The experimental results show that the accuracy rate of the improved SVM algorithm reaches 97.263%, which improves the segmentation efficiency. It is verified that the improved model proposed in this paper can effectively segment complex color images.

We analyse the determinants of RMB as an international reserve currency and the impact of joining the Special Drawing Rights (SDR) on the currency swap agreements between China and other countries....

This work was intended to explore the effect of circ-0005519 on the apoptosis of bronchial epithelial cells in children with severe asthma and its molecular mechanism. To this end, asthma’s inflammatory environment was simulated by using 1 mg/L lipopolysaccharide (LPS) to induce human bronchial epithelial 16HBE cells, which were considered the 16HBE model cells. After transfection, these 16HBE model cells were divided into following groups: control group, model+si-NC group, model+si-circ-0005519 group, model+miR-NC group, model+miR-625-5p group, model+si-circ-0005519+anti-miR-NC group, and model+si-circ-0005519+anti-miR-625-5p group. A series of experiments were then carried out, including RT-qPCR assay for testing circ-0005519 and miR-625-5p expressions, flow cytometry assay for analyzing cell apoptosis, western blot for testing protein expression, ELISA assay for detecting IL-6. TNF-α, IL-13, IL-8 expression, and dual-luciferase reporter confirm the targeted functions of circ-0005519 to miR-625-5p. The results displayed highly expressed circ-0005519 and lowly expressed miR-625-5p in 16HBE model cells induced by lipopolysaccharide. Furthermore, we also found increases in apoptosis, Bax expression, and levels of IL-6, TNF-α, IL-13, and IL-8, as well as a decrease in Bcl-2 expression. Additionally, our data revealed that silencing circ-0005519 or overexpressing miR-625-5p would affect these 16HBE model cells, including decreases in apoptosis, Bax expression, and levels of IL-6, TNF-α, IL-13, and IL-8, as well as an increase in Bcl-2 expression. The targeted binding function of circ-0005519 to miR-625-5p was also confirmed, in which interference miR-625-5p would weaken the influences of silencing circ-0005519 on 16HBE cells. These results suggested that silencing circ-0005519 could inhibit apoptosis of lipopolysaccharide-induced bronchial epithelial cells via targeted binding functions to miR-625-5p.

The seismic performance of a steel tubular bridge pier in a five-span continuous girder bridge system was evaluated through dynamic non-linear time-history analysis under strong ground motions. The seismic performance of the hollow steel tubular (HST) and partially concrete-filled steel tubular (PCFST) bridge piers was assessed with different eccentricities of superstructure. Considering the variation of ground classification under rare earthquakes, six seismic waves were input. The analytical results indicate that the eccentricity of superstructure has little effect on the maximum displacement response of the HST bridge piers and the PCFST bridge piers under ground motion excitations in the longitudinal (LG) direction; however, under the ground motion excitations in the transverse (TR) direction, the maximum displacement response of the bridge piers increases when the eccentricity (e/H) increases from 0 to 0.2, which implies that eccentricity affects the seismic response of the two types of piers. Both in the LG direction and TR direction, the HST piers have reached their yield strengths; stress concentration and local buckling were observed around the plastic hinge zone and the load bearing capacity decreases. Although the PCFST piers entered the elasto-plastic range, the expansion of local buckling deformation of the steel tubular column has been restrained by the concrete in-fill. According to the simulated results, the PCFST pier exhibits high ductility and bearing capacity, which can improve the seismic performance of the bridge system.

Rationale: Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full ...

This study examines how the team norm of information exchange and team information processing affects team performance. Data were collected from 354 project teams from software development companies in Thailand. Structural Equation Modelling (SEM) was conducted to test the proposed hypotheses. The results of the study revealed that team norms of information exchange (TNM) has a significant relationship with team information processing (PRO). Team information processing positively influences team performance (TPM). Software development organisations could adopt such norms and this team process to improve software development projects performance and recognise team processes, which is essential for long-term sustainability and competitiveness.

The interictal discharges of temporal lobe epilepsy (TLE) can be unilateral or bilateral. In addition, the ictal electroencephalogram (EEG) showed the discharges also tend to spread to the contralateral brain in TLE. The factors influencing unilateral and bilateral interictal discharges in TLE as well as ictal diffusion patterns in scalp EEG during onset of seizure were evaluated in the present study. This was a retrospective analysis of 129 patients with TLE. Cases were classified into unilateral and bilateral discharge groups based on interictal discharge patterns in the EEG. Differences between the two groups in age, gender, disease duration, seizure frequency, magnetic resonance imaging (MRI) findings, origin of TLE, antiepileptic drug (AED) administration, and ictal diffusion patterns during seizures were statistically analyzed. In addition, the differences in ictal diffusion patterns between left and right TLE were statistically analyzed. Statistically significant differences were not observed in gender, disease duration, seizure frequency, MRI findings, administration of AEDs, and ictal diffusion patterns between interictal unilateral and bilateral discharge groups but with statistically significant differences in age and side of origin of the TLE. In addition, whether the EEG-recorded diffusion pattern was confined to the same hemisphere or spread to both hemispheres was investigated and shown statistically significant differences between the left and right temporal lobes. Age and side of origin of TLE affects the TLE interictal discharge patterns. Older patients are more prone to bilateral discharges. Bilateral discharges are more common in right TLE, and the onset of EEG more likely to bilateral diffusion in right TLE.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fatal interstitial lung disease characterized by abnormal transition and proliferation of fibroblasts. The uncontrolled transition of fibroblasts, commonly known as myofibroblasts, are the principal source of the enormous extracellular matrix (ECM) depositing in lung parenchyma, leading to gradual failure of gas exchange and mortality of the patients. However, up to now, rare effective therapeutic strategies have been developed to blockade fibroblast-to-myofibroblast transition (FMT) in IPF. Method: We illustrated that the lungs originated from IPF patients and mice with pulmonary fibrosis are characterized by the overexpression of sushi-repeat-containing protein, X-linked 2 (SRPX2). Further functionality studies identified the pivotal role of SRPX2 in FMT. Mechanistically, SRPX2 was involved in a TGFβR1/SMAD3/SRPX2/AP1/SMAD7 positive feedback loop. Specifically, SRPX2 was upregulated by TGF-β1 in a TGFβR1/SMAD3-dependent manner, after which SRPX2 in turn repressed the expression of AP1, subsequently minimized SMAD7 expression, through which it reduced the formation of inhibitory complex with TGFβR1 and enhanced SMAD signaling pathway to promote FMT and exacerbate pulmonary fibrosis. Notably, intratracheal administration of siRNA-loaded liposomes could effectively suppress the expression of Srpx2 in the lung and remarkably protect mice against BLM-induced pulmonary fibrosis, concomitant with a significant reduction of FMT. Results: Accordingly, these data indicate that Srpx2 plays an essential role in the pathogenesis of pulmonary fibrosis and suggests the strategy aiming at silencing Srpx2 could be a promising therapeutic approach against pulmonary fibrosis in clinical settings.

Based on femtosecond laser ablated processing, one-dimensional arrays with different line spacings were fabricated on titanium disulfide (TiS2) nanosheet. Optical modulated measurements with these devices were demonstrated. Photo-induced complex conductivity changes of the TiS2 nanosheet devices were studied by an optical-pump THz-probe (OPTP) measurement system. For the 700 μm line spacing device, the optically introduced modulation depth (MD) reached up to 70%. Our experimental results have demonstrated the ultrafast dynamics and photoconductivity for the TiS2 nanosheet devices in the THz frequency range. TiS2 nanosheet based devices would be suitable as the photoelectric modulators of THz wave.

The progression of Alzheimer’s disease (AD) is a continuous process in cognitive and biomarker changes, with only a fraction of mild cognitive impairment (MCI) patients eventually advancing to AD. ...

Simulating changes in the value of ecosystem services caused by land use changes in large cities under multiple scenarios is of great significance for cities to formulate land use policies and improve ecosystem services. Take Shijiazhuang, which is in the process of rapid urbanization, as an example. Based on the remote sensing image data and statistical yearbook of 1988, 1998, 2008, and 2018 as the basic data to analyze and estimate the 30 years of land use and ecosystem service value changes in Shijiazhuang. According to this, the CA-Markov model was used to simulate the land use change in Shijiazhuang under three scenarios in 2030 and estimate the value of ecosystem services under each scenario, using grid tools to visually express the spatial distribution of ecosystem service values and the degree of agglomeration under three scenarios. The results indicate that the most obvious feature of land use change in Shijiazhuang from 1988 to 2018 was that the farmland area decreased year by year, the built-up expanded rapidly, the farmland area decreased by 86,874.75 hm2 in 30 years, and the built-up increased by 154,711.90 hm2. In 1988, 1998, 2008, and 2018, the ecosystem service value of Shijiazhuang was 32.578 billion yuan, 32.799 billion yuan, 29.944 billion yuan, and 31.251 billion yuan respectively. In 2030, under three scenarios of natural development, farmland protection, and ecological protection, the value of ecosystem services is 331.111 billion yuan, 33.670 billion yuan, and 33.891 billion yuan in order. The hot spots are mainly concentrated in the northwest and southwest of Shijiazhuang, and cold spots are concentrated in the eastern cities, counties, and districts. Based on changes in land use brought about by urban expansion, simulating the value of ecosystem services under multiple scenarios in the future, providing scientific guidance for building urban ecological networks, and realizing sustainable urban ecological development.

Purpose The purpose of this paper is to examine the effect of team learning processes (information acquisition, information processing and information storage and retrieval) on team performance in software development projects and to assess the effect of ethical leadership and its influence on these processes. Design/methodology/approach The authors examined 354 software development project teams in Thailand. A quantitative study was conducted through a Web-based survey, with structural equation modelling used to test the hypotheses. Findings The results of this study revealed that ethical leadership is positively correlated with the team learning processes of information acquisition, information processing and information storage and retrieval. However, only information processing and information storage and retrieval are positively related to team performance. The results indicate that ethical leadership has a positive direct effect on team performance. The results also show that the positive relationship between ethical leadership and team performance is partially mediated by team learning processes, namely, information processing and information storage and retrieval. Research limitations/implications This study highlights the importance of ethical leadership and guides managers towards considering the characteristics of both ethical leadership and team learning processes for enhancing team performance in software development projects. Originality/value This is the first study to the best of authors’ knowledge to examine the role of team learning processes in mediating the relationship between ethical leadership and team performance, particularly concerning software development projects. The present research contributes to the literature on team performance management, emphasising the manner in which ethical leadership can result in team learning and team performance. The findings of this study can be used to encourage organisations to develop ethical leadership behaviours and team learning processes in software development projects.

Targeting the SARS-CoV-2 main protease Vaccines are an important tool in the fight against COVID-19, but developing antiviral drugs is also a high priority, especially with the rise of variants that may partially evade vaccines. The viral protein main protease is required for cleaving precursor polyproteins into functional viral proteins. This essential function makes it a key drug target. Qiao et al. designed 32 inhibitors based on either boceprevir or telaprevir, both of which are protease inhibitors approved to treat hepatitis C virus. Six compounds protected cells from viral infection with high potency, and two of these were selected for in vivo studies based on pharmokinetic experiments. Both showed strong antiviral activity in a mouse model. Science, this issue p. 1374, Designed SARS-CoV-2 Mpro (main protease) inhibitors display excellent antiviral activity both in vitro and in a transgenic mouse model., The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either boceprevir or telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro, with 50% inhibitory concentration values ranging from 7.6 to 748.5 nM. The cocrystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a transgenic mouse model of SARS-CoV-2 infection, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.

Complexity of emergency procedures have direct impacts on the accomplishment of tasks in metro system. In order to ensure the efficient operation of automated metro in emergency scenarios, it is necessary to understand the potential relationship between system change and emergency procedures. To solve this problem, an evaluation method for emergency procedures is proposed. Firstly, on the basis of investigation, interview and empirical analysis of different types of automated metro lines, combined with Team-Cognitive Work Analysis(CWA) method and network theory, the team emergency task network is established. Then four characteristic indexes, i.e. degree, average shortest path length, agglomeration coefficient and overall network efficiency, are selected as the analysis metrics of emergency task network complexity. The complexity of different emergency procedures under grades of automation(GOA) 4 and same emergency procedure under GOA1-GOA4 are comprehensively analyzed. The research results reveal that no matter what level of automation system, the more nodes and communication between nodes, the larger network scale is, which will lead to the emergency procedures more complicated, and vice versa. The driver’s behavior plays a decisive role in the variation of communicating frequencies.

Train-induced vibration exhibits a potential dynamic impact on historic buildings and especially on those with high historical and cultural value. Under the long-term reciprocating load of train vibrations, structural fatigue damage can occur, and thus, a significant problem involves effectively evaluating and mitigating vibration impact on historic buildings while developing a rail transit system. In the present study, train-induced vibration impact and dynamic behavior of Probhutaratna pagoda in the suburb of Beijing, which has a history of approximately 1000 years, was investigated. To examine the dynamic behavior of the Probhutaratna pagoda and determine the weakest position in its architectural damage under train loads, its dynamic characteristics were measured. The free vibration modes were identified based on the dynamic measurement results. Subsequently, a finite element (FE) model of the Probhutaratna pagoda was constructed and the models and train-induced structural responses were compared with measured results. Finally, the structural dynamic responses to moving train loads were analyzed in detail. The results indicate the following conclusions. (1) The dominant frequency of the ambient vibration is below 4 Hz, and the dominant frequency of the train-induced vibration is between 8 and 16 Hz. (2) The first, second, and third order natural frequencies are 1, 3.25, and 6 Hz, respectively, in the west-east direction, and are 1, 3.25, and 6.25 Hz, respectively, in the north-south direction. (3) The two weakest locations (A and B) of the Probhutaratna pagoda are observed at the spire bottom and west gate of the first floor. At location A, the maximum principal stress reached 243.6 N/m2 and the corresponding maximum tensile strain reached 3.74×10−7.

As an important feature of dispatching team task in operating control center (OCC), task complexity has a significant impact on the team performance and operational safety of the whole metro system. However, the existing concepts and methods for individual tasks cannot be fully applied to the research of the dispatching team task of OCC. In view of the research status, this work analyzed the characteristics of the dispatching team task complexity (TTC) in OCC and developed a network-based model of dispatching team task. Based on the team task network model, a three-dimension conceptual model of TTC for dispatching team task in OCC was finally constructed in the paper using an induction method. Three kinds of emergency tasks also verified the effectiveness of the proposed three-dimension conceptual model.

Background Studies have shown that liver fluke infections may be associated with kidney injury and that Helicobacter pylori (Hp) may be involved in the pathogenesis of kidney diseases. However, no studies have reported the relationship between co-infection with Clonorchis sinensis (Cs) and Hp and renal function. The aim of this study was to examine the relationship between co-infection with Cs and Hp and estimated glomerular filtration rate (eGFR) in a general population, and gender-related differences were also investigated. Methods In the cross-sectional study, 4122 subjects from the Health Examination Center of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine from January 2017 to December 2018 were enrolled. All participants underwent stool examination for the diagnosis of Cs infection and 13C-urea breath test (UBT) for the diagnosis of Hp infection. Participants were categorized into four groups: (1) co-infection with Cs and Hp group comprising 207 cases (Hp(+) + Cs(+) group), (2) Cs infection group comprising 1392 cases (Hp(−) + Cs(+)group), (3) Hp infection group comprising 275 cases (Hp(+) + Cs(−) group), and (4) non-infection group comprising 2248 cases (Hp(−) + Cs(−) group). Multiple linear regression analysis was performed to evaluate the relationship between co-infection with Cs and Hp and eGFR. Results Hp infection without Cs infection was present in 6.67% (275/4122) of subjects, while Cs infection without Hp infection was present in 33.77% (1392/4122) of subjects. Co-infection with Hp and Cs were present in 5.02% (207/4122) of subjects. Median age of the participants was 43 years (IQR 35–51). Most of the participants were male (2955/4122, 71.69%). Median eGFR was 96.61 ml/min/1.73 m2 (IQR 85.05–106.24). Co-infection with Cs and Hp was negatively associated with eGFR after full adjusting (β = − 1.89, 95% CI: − 3.33 to − 0.45, p = 0.01). The relationship remained significant in females (β = − 9.37, 95% CI: − 11.60 to − 7.1, p Conclusion Our findings suggest that co-infection with Cs and Hp may be associated with reduced renal function in females, but not in males.

Jie Xia,1– 4,* Lina Sun,5,* Suqin Xu,1– 4 Qiu Xiang,1– 4 Jianping Zhao,1– 4 Weining Xiong,1– 4 Yongjian Xu,1– 4 Shuyuan Chu1– 4,6 1Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of China; 2Wuhan Clinical Medical Research Center for Chronic Airway Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of China; 3Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of China; 4Key Site of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 6Laboratory of Respiratory Disease, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuyuan Chu; Jie XiaDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan, People’s Republic of ChinaTel +8613978345180; +8627-83665520Email emilyyuanchu@163.com; xiajhzu1215@126.comPurpose: Patients with chronic obstructive pulmonary disease (COPD) would have a poor prognosis if they were not continuously managed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. We aim to develop a model to classify whether COPD patients have been continuously managed according to GOLD in the previous year.Methods: The Managed group were COPD patients from a prospectivecohort from November 2017 to November 2019, who have been continuously managed according to GOLD for 1 year. The Control group were COPD patients who were not continuously managed according to GOLD. They were from a retrospective cohort from October 2016 to October 2017 in the same hospitals as the Managed group. A synthetic minority over-sampling technique (SMOTE) algorithm was used to up-sample the Managed group in a training dataset. Features for classification were selected using a support vector machine recursive feature elimination (SVM-RFE) algorithm. The classification model was developed using LibSVM, and its performance was assessed on the testing dataset.Results: The final analysis included 15 subjects in the Managed group and 191 in the Control group. SVM-RFE selects nine features including smoking history, post-bronchodilator (post-)FVC before management, and those after 1-year follow-up (BMI, moderate and severe AECOPD frequency in previous 12 months, mMRC score, post-FEV1, post-FEV1%pred, post-FVC, and post-FEV1/FVC). For our model, positive predictive value is 66.7%, F1 score is 0.978, and AUC is 0.987.Conclusion: SVM classifier combined with SVM-REF feature selection algorithm could achieve good classification between COPD patients who are or are not continuously managed. This model could be applied in clinical practice to help doctors make decisions and enhance COPD patients’ compliance with standard treatment.Keywords: COPD, GOLD, continuous management, support vector machine

For heterojunction semiconductor photoelectrodes, efficient charge separation is localized in the junction-induced electric field region and charge transfer follows a band-to-band charge-transfer pathway. Here, we found that polaron states at the heterojunction interface have a function of storing and transferring electrons. As a successful demonstration, we verified that the polaron states (Ti3+OH) on TiO2 are not passivated when used to create a CdS/TiO2 heterojunction and function as an efficient pathway for massively capturing, storing, and transferring the electrons from conduction bands of both TiO2 and CdS, thus effectively enhancing the charge separation efficiency of the heterojunction photoanode. The electron throughput of polaron states remains a positive correlation with polaron state density. Interfacial electron transfer through the TiO2 surface polaron states has great potential application in the development of high-performance heterojunction devices based on TiO2.

Cross-channel integration (CCI) has been adopted by firms to improve firm performance. However, the underlying mechanism by which CCI enhances firm performance remains unclear. To address this gap, we apply knowledge-based view and propose that CCI may affect firm innovation, thereby influencing firm performance. Specifically, we consider that exploratory innovation and exploitative innovation play the mediating roles between CCI and firm performance. In addition, the study explores the moderating effects of electronic commerce (EC) type (i.e., self-own website and third-party platform). We propose if CCI’s effects differ in terms of EC type. Survey-based samples of 338 EC firms and structural equation modeling are employed to examine the research model. The results show that CCI can influence firm performance through the mediating role of exploitative innovation but not exploratory innovation. In addition, CCI has a stronger effect on firm innovation in third-party platform than in self-own website. This paper also discusses about the theoretical contributions and practical implications of the study.

Coronavirus disease 2019 (COVID-19) emerged in December 2019 and has spread globally. Diabetics are at increased risk of infections caused by a variety of pathogens including viruses. The present research aims to describe clinical characteristics and outcomes of COVID-19 patients with diabetes.A retrospective multicenter study of COVID-19 patients with diabetes was conducted in four hospitals in Wuhan, Shanghai, and Anhui Province. Reverse transcription polymerase chain reaction or next-generation sequencing was carried out to confirm the existence of severe acute respiratory syndrome coronavirus 2 from respiratory specimens.A total of 54 diabetics (10.36%) were recruited from among 521 COVID-19 patients, with a median age of 63 (interquartile range, 52-70) years. Among them, 51 had been previously diagnosed with diabetes and 3 had been newly diagnosed based on glycosylated hemoglobin over 6.5%. For COVID-19, 47 of the 54 patients had an exposure history. Fever (47/54, 87.04%), dry cough (36/54, 66.67%), and expectoration (21/53, 39.62%) were among the top three symptoms. Lung infiltration was bilateral (46/52, 88.46%) and multilobe (47/52, 90.38%), and ground-glass opacity (36/37, 97.30%) was the most common pattern in radiological images. Moreover, COVID-19 patients with diabetes were prone to be classified as severe or critical cases (46.30%, 25/54) and had complications such as acute lung injury, acute respiratory distress syndrome, and acute kidney injury. The proportions of intensive care unit (ICU) admissions and deaths among the COVID-19 diabetics were 14.81% (8/54) and 12.96% (7/54), respectively.With older age, diabetics diagnosed as having COVID-19 were prone to develop into severe cases and exhibited a high rate of ICU admission and mortality.背景: 2019年12月新型冠状病毒肺炎出现并迅速在全球爆发。糖尿病患者更易于感染包括病毒在内的各种病原体。本研究旨在描述合并糖尿病的新冠肺炎患者的临床特征及预后。 方法: 在武汉市金银潭医院、上海瑞金医院、上海同仁医院及安徽省铜陵医院共4家单位开展多中心回顾性临床研究。采用RT-PCR 或NGS检测呼吸道标本中SARS-Covid-2病毒。 结果: 521位新冠肺炎患者中54位患有糖尿病, 中位年龄63岁(四分位间距52-70), 其中51位患者既往已诊断糖尿病, 3位因糖化血红蛋白超过6.5%新诊断为糖尿病。47位患者有新冠病毒暴露史。发热(47/54,87.04%)、干咳(36/54, 66.67%)、咳痰(21/53, 39.62%) 为主要常见症状。双肺(46/52, 88.46%)、多肺叶浸润(47/52, 90.38%)、磨玻璃影(36/37, 97.30%)为常见影像学改变。合并糖尿病的新冠患者更多发展为重症或危重症型, 也往往合并急性肺损伤、急性呼吸窘迫综合征及急性肾损伤等并发症。这类人群中14.81%(8/54)需入住重症监护病房(ICU)治疗, 12.96%(7/54)最终死亡。 结论: 年龄较大的合并糖尿病的新冠肺炎患者易于发展为重症类型, 有较高的ICU入住及死亡率。.

Accurate short-term traffic flow prediction is an important basis of intelligent transportation systems (ITS) such as transportation operations and urban planning applications. However, due to the lack of complete directly measured data on urban traffic flow, existing studies cannot adequately mine the dynamic spatial-temporal correlations characterizing traffic flows in urban road networks. Electronic registration identification (ERI), which is an emerging technology for uniquely identifying a vehicle, can help collect the travel records of all vehicles. This inspires us to employ ERI big data for traffic flow prediction. In this paper, we propose a dynamic spatial-temporal feature optimization method with ERI big data for short-term traffic flow prediction based on a gradient–boosted regression tree, called DSTO-GBRT. Firstly, the framework of DSTO-GBRT is built. Secondly, we analyze the dynamic spatial-temporal correlations among the current prediction point and upstream correlative points using the Pearson correlation coefficient (PCC). Thirdly, to eliminate the linear correlations among features, we exploit principal component analysis (PCA) to optimize the original training data and obtain optimized training data. In the experiment, real-world ERI big data from Chongqing are employed for the proposed DSTO-GBRT method. Compared with ST-GBRT, ARIMA, DSTO-BPNN and DSTO-SVM, the results demonstrate that DSTO-GBRT can provide timely and adaptive prediction even in rush hour, when traffic conditions change rapidly. Furthermore, compared with DSO-GBRT and DTO-GBRT, the results show that the proposed DSTO-GBRT method is more accurate.

Purpose To predict the risk of developing severe pneumonia among mild novel coronavirus pneumonia (mNCP) patients on admission. Methods A retrospective cohort study was conducted at three hospitals in Shanghai and Wuhan from January 2020 to February 2020. Real-time polymerasechain-reaction assays were used to detect COVID-19. A total of 529 patients diagnosed with NCP were recruited from three hospitals and classified by four severity types during hospitalization following the standards of the Chinese Diagnosis and Treatment of Pneumonia Caused by New Coronavirus Infection (eighth version). Patients were excluded if admitted by ICU on admission (n=92, on a general ward while meeting the condition of severe or critical type on admission (n=25), or there was insufficient clinical information (n=64). In sum, 348 patients with mNCP were finally included, and 68 developed severe pneumonia. Results mNCP severity prognostic index values were calculated based on multivariate logistic regression: history of diabetes (OR 2.064, 95% CI 1.010-4.683; p=0.043), time from symptom onset to admission ≥7 days (OR 1.945, 95% CI 1.054-3.587; p=0.033), lymphocyte count ≤0.8 (OR 1.816, 95% CI 1.008-3.274; p=0.047), myoglobin ≥90 mg/L (OR 2.496, 95% CI 1.235-5.047; p=0.011), and D-dimer ≥0.5 mg/L (OR 2.740, 95% CI 1.395-5.380; p=0.003). This model showed a c-statistics of 0.747, with sensitivity and specificity 0.764 and 0.644, respectively, under cutoff of 165. Conclusion We designed a clinical predictive tool for risk of severe pneumonia among mNCP patients to provided guidance for medicines. Further studies are required for external validation.

Purpose Nasopharyngeal carcinoma (NPC) is more common among women in Southeast Asia. An important issue is whether it is safe for them to bear children after treatment and when it is safe to do so. We conducted this study to explore the relation between fertility and prognosis in child-bearing women with NPC. Patients and methods Child-bearing women were defined as young women between the ages of 18 and 30. A total of 127 eligible child-bearing NPC patients were identified from December 2003 to December 2014. The patients were divided into two groups, depending on whether or not they had post-therapeutic births. The Kaplan-Meier method was used for survival analyses. The Log rank test was used to compare two survival curves and the independent significances of different prognostic factors were assessed by Cox proportional hazards regression analysis. Results The 5-year overall survival (OS) and disease-free survival (DFS) in the Childbirth group were significantly higher than those in the Non-Childbirth group (100% vs 88.8%, P = 0.026 and 100% vs 77.5%, P = 0.007, respectively). In the Childbirth group, no difference was found in the 5-year DFS between different birth interval times, from 1 to 5 years after treatment. The clinical stage was identified as the risk factor of OS (HR = 101.725, 95% CI: 2.160-4790.910, P = 0.019), and consequent childbirth after treatment was associated with favorable DFS (HR = 0.148, 95% CI: 0.034-0.643, P = 0.011). Conclusion Post-therapeutic birth did not increase the mortality risk of child-bearing women with NPC. There was no significant correlation between the subsequent birth time window after treatment and the prognosis.

Adjuvant chemotherapy improves overall survival (OS) following stereotactic body radiotherapy (SBRT) in patients with early stage non-small cell lung cancer and tumors ≥four cm. Here, we aim to evaluate its role following SBRT in older patients. Patients70 years diagnosed with clinical stages I-II NSCLC, (N0 disease), who received SBRT, were identified using the National Cancer Database (n = 7042). The Kaplan-Meier method was used to estimate OS, and the log-rank test was used to compare distributions by treatment strategy overall and within clinical stages I and II. There were 3533 female patients (50.2%), and 6074 (86.3%) had stage I disease. Among stage I patients, 643 (10.6%) received adjuvant chemotherapy, compared to 372 stage II patients (38.4%). Median OS was better with SBRT in patients with stage I disease (25.4 vs. 20.3 months; p .001); while patients with stage II NSCLC had better OS with SBRT + chemotherapy (20.2 vs. 14.2 months; p .001). On multivariate analysis, patients with stage I NSCLC who received SBRT alone had better overall survival (HR: 0.79; 95% CI, 0.73, 0.87). SBRT alone was associated with an increased risk of death in patients with stage II disease (HR: 1.34; 95% CI, 1.15, 1.55). Patients with tumors ≥4 cm had better OS with SBRT + chemotherapy (18.5 vs. 15.5 months; p = .003), while patients with tumors4 cm did better with SBRT (median OS of 24.1 vs. 20.3 months; p .001). In70 years old patients with tumors ≥4 cm, adjuvant chemotherapy following SBRT was associated with improved OS.

SIRT6 activation is thought to be a promising target for the treatment of many diseases, particularly cancer. Herein, we report the discovery of a series of new small-molecule SIRT6 activators. Structure-activity relationship analyses led to the identification of the most potent compound, 2-(1-benzofuran-2-yl)

Palladium diselenide (PdSe2), a stable layered material with pentagonal structure, has attracted extensive interest due to its excellent electrical and optoelectronic performance. Here, we report a reliable process to synthesize PdSe2 via chemical vapor deposition (CVD) method. Through systematic regulation of temperature in the growth process, we can tune the thickness, size, nucleation density and morphology of PdSe2 nanosheets. Field-effect transistors based on PdSe2 nanosheets exhibit n-type behavior and present a high electron mobility of 105 cm2·V−1·s−1. The electrical property of the devices after 6 months keeping in the air show little change, implying outstanding air-stability of PdSe2. In addition, PdSe2 near-infrared photodetector shows a photoresponsivity of 660 A·W−1 under 914 nm laser. These performances are better than those of most CVD-grown 2D materials, making ultrathin PdSe2 a highly qualified candidate material for next-generation optoelectronic applications.

Object tracking is a very important topic in the field of computer vision. Many sophisticated appearance models have been proposed. Among them, the trackers based on holistic appearance information provide a compact notion of the tracked object and thus are robust to appearance variations under a small amount of noise. However, in practice, the tracked objects are often corrupted by complex noises (e.g., partial occlusions, illumination variations) so that the original appearance-based trackers become less effective. This paper presents a correntropy-based robust holistic tracking algorithm to deal with various noises. Then, a half-quadratic algorithm is carefully employed to minimize the correntropy-based objective function. Based on the proposed information theoretic algorithm, we design a simple and effective template update scheme for object tracking. Experimental results on publicly available videos demonstrate that the proposed tracker outperforms other popular tracking algorithms.

To investigate the hysteretic behaviour of an eccentrically loaded partially-concrete-filled steel tubular (PCFST) bridge pier in an out-of-plane horizontal direction, a quasi-static experiment and finite element (FE) analysis of steel tubular columns were carried out. In this study, four PCFST column specimens were tested under constant eccentrically loaded and out-of-plane horizontal cyclic loading. The elasto-plastic behaviour and failure mode of these specimens were investigated. Secondly, the FE models of these four experimental PCFST columns were established, through comparisons with the experimental results, the validity of the selected elements, mesh division, the contact relationship between the concrete and the steel pipe, and the boundary conditions of FE models were verified. Thirdly, 30 FE models of PCFST bridge piers were analyzed to ascertain the effects of slenderness ratio λ, radius-thickness ratio Rt, and vertical load eccentricity ratio e/L on ultimate strength and ductility. Finally, an empirical formula was proposed to describe the ultimate strength and ductility of such bridge piers for engineering application under complicated loading conditions.

Roundabout guidance receptor 2 (ROBO2) plays an important role during early kidney development. ROBO2 is expressed in podocytes, inhibits nephrin-induced actin polymerization, down-regulates nonmuscle myosin IIA activity, and destabilizes kidney podocyte adhesion. However, the role of ROBO2 during kidney injury, particularly in mature podocytes, is not known. Herein, we report that loss of ROBO2 in podocytes [Robo2 conditional knockout (cKO) mouse] is protective from glomerular injuries. Ultrastructural analysis reveals that Robo2 cKO mice display less foot process effacement and better-preserved slit-diaphragm density compared with wild-type littermates injured by either protamine sulfate or nephrotoxic serum (NTS). The Robo2 cKO mice also develop less proteinuria after NTS injury. Further studies reveal that ROBO2 expression in podocytes is up-regulated after glomerular injury because its expression levels are higher in the glomeruli of NTS injured mice and passive Heymann membranous nephropathy rats. Moreover, the amount of ROBO2 in the glomeruli is also elevated in patients with membranous nephropathy. Finally, overexpression of ROBO2 in cultured mouse podocytes compromises cell adhesion. Taken together, these findings suggest that kidney injury increases glomerular ROBO2 expression that might compromise podocyte adhesion and, thus, loss of Robo2 in podocytes could protect from glomerular injury by enhancing podocyte adhesion that helps maintain foot process structure. Our findings also suggest that ROBO2 is a therapeutic target for podocyte injury and podocytopathy.

BackgroundThe ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile.MethodsThis is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov (NCT04651790).FindingsThe recruitment of participants occurred between November 27th, 2020, until January 9th, 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity.InterpretationImmunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens.FundingMinistry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

BackgroundCoronaVac®is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization. Previous studies reported increased levels of neutralizing antibodies and specific T cells two- and four-weeks after two doses of CoronaVac®, but the levels of neutralizing antibodies are reduced at six to eight months after two doses. Here we report the effect of a booster dose of CoronaVac®on the anti-SARS-CoV-2 immune response generated against variants of concern (VOC) Delta and Omicron in adults participating in a phase 3 clinical trial in Chile.MethodsVolunteers immunized with two doses of CoronaVac®in a four-week interval received a booster dose of the same vaccine between twenty-four and thirty weeks after the 2nd dose. Four weeks after the booster dose, neutralizing antibodies and T cell responses were measured. Neutralization capacities and T cell activation against VOC Delta and Omicron were detected at four weeks after the booster dose.FindingsWe observed a significant increase in neutralizing antibodies at four weeks after the booster dose. We also observed an increase in CD4+T cells numbers over time, reaching a peak at four weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2 specific T cells induced by the booster showed activity against VOC Delta and Omicron.InterpretationOur results show that a booster dose of CoronaVac®increases the anti-SARS-CoV-2 humoral and cellular immune responses in adults. Immunity induced by a booster dose of CoronaVac®is active against VOC, suggesting an effective protection.