Optimizing mRNA vaccines and virusmediated CAR T-cell therapy for immuno-oncology: Synthetic tools for gene modification

With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest. Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A highthroughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail. The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.

Effect of Azovudine on Hepatic and Renal Function in Patients with COVID-19：a Case Series Study

Background Azovudine is a widely used antiviral drug for COVID-19 in China，but published trials on its effect on hepaticand renal function are extremely scarce. Objective To explore the changes of in hepatic and renal function in patients with COVID-19 infection after using Azovudine，so as to provide a reference for thesafe use of Azovudine in patients with renal insufficiency. Methods Inpatients ina tertiary general hospitalwho used Azovudine for COVID-19 from December 26，2022 to December 31，2022 were consecutively included in the retrospective study and divided into the normal group，mild injury group，moderate injury group，severe injury group，and end-stage groupaccording to estimated glomerularrate（eGFR）levels. The changes of biochemical parametersof liver and kidney including alanine aminotransferase（ALT），aspartate aminotransferase（AST），alkaline phosphatase （ALP），albumin（ALB），total bilirubin（TB），serum creatinine （Scr），eGFR were observed in each group；the formula D_FR=D_NL×［1-F_k （1-K_f）］ was used to correct the maintenance dose of Azivudine in patients with eGFR<60 mL·min-1·（1.73 m2）-1. The patients were divided into the corrected group and uncorrected group according to whether they were administered according to this formula，the biochemical parameters of liver and kidney were compared between the two groups. Results Among 322 patients who used Azovudine，190 patients met the inclusion and exclusion criteria. After grouping by the level of eGFR，there were statistically significant differences in the distribution of age，COVID-19 severity，peak procalcitonin（PCT）values，antihypertensive drugs，loop diuretics and Azovudine maintenance dose in each group（P<0.05）；there were 73 cases（38.4%） with elevated ALT level after Azovudine treatment，and 68 cases（93.2%） with elevated ALT level within one time of the upper normal limit；eGFR decreased in 58 cases（30.5%），of which 7 cases（12.1%） dropped to the next renal function grade；regardless of the grade of renal injury，there were no deterioration in eGFR，ALT，AST，TB，ALP and albumin after the use of conventional dose or corrected dose of Azivudine（P>0.05）；because the patients with moderate and severe renal injury were dose-corrected with Azivudine，the safety of this population was not compared if the dose was not corrected. Conclusion The use of Azivudine is prone to cause the elevation of ALT level and the decrease of eGFR，but the injury with clinical significance is 2.6% and 3.7%，respectively；there was no aggravation of liver and kidney injury in patients with moderate and severe kidney injury after using the corrected dose of Azivudine，however，this conclusion needs to be confirmed in a multicenter randomized controlled study with a large sample. © 2023 Chinese General Practice. All rights reserved.

Clinical significance of serum interleukin 6 in elderly patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant and its correlation with underlying diseases.

Objective To investigate the clinical significance of serum interleukin 6 (IL-6) in elderly patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant and its correlation with underlying diseases. Methods A total of 22 elderly patients (80 years old) infected with omicron variant, who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Apr. to Jun. 2022 and tested positive for SARS-CoV-2 RNA, were included. The level of serum IL-6 was measured by flow cytometry, and the level of serum C reactive protein (CRP) was measured by immunonephelometry. Patients were divided into pneumonia group (16 cases) and non-pneumonia group (6 cases) according to the imaging examination results, and were divided into severe group (severe and critical type, 5 cases) and non-severe group (mild and normal type, 17 cases) according to the condition. Binary logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the correlation between serum IL-6 and CRP levels and the severity of the disease and whether it would progress to pneumonia. Meanwhile, the relationships between underlying diseases and serum IL-6 level were explored. Results Among the 22 patients, 6 were mild, 11 were normal, 3 were severe, and 2 were critical. The baseline serum IL-6 level in the pneumonia group was significantly higher than that in the non-pneumonia group (20.16+/-12.36pg/mL vs 5.42+/-1.57 pg/mL, P=0.009), and there was no significant difference in baseline serum CRP level between the 2 groups (P0.05). There were no significant differences in baseline serum IL-6 or CRP levels between the severe group and the non-severe group (both P0.05). Logistic regression analysis showed that the baseline serum IL-6 and CRP might be related to pneumonia after infection with omicron variant (odds ratio OR=2.407, 95% confidence interval CI0.915-6.328;OR=1.030, 95% CI 0.952-1.114). ROC curve analysis showed that the area under curve values of serum IL-6 and CRP in predicting the progression to pneumonia were 0.969 (95% CI 0.900-1.000) and 0.656 (95% CI 0.380-0.932), respectively, with statistical significance (Z=2.154, P=0.030). There were no significant differences in the baseline serum IL-6 level or proportions of severe patients or pneumonia patients among patients with or without hypertension, diabetes mellitus, coronary heart disease, chronic kidney disease or chronic obstructive pulmonary disease (all P0.05). The baseline serum IL-6 levels of the omicron variant infected elderly patients with 1, 2, and 3 or more underlying diseases were 12.50 (9.15, 21.75), 23.55 (9.63, 50.10), and 10.90 (5.20, 18.88) pg/mL, respectively, with no statistical significance (P0.05). Conclusion For omicron variant infected patients, serum IL-6 level is significantly increased in patients with pneumonia manifestations and is correlated with disease progression. Serum IL-6 level is of great guiding significance to judge disease progression and evaluate efficacy and prognosis of elderly coronavirus disease 2019 patients.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Clinical significance of serum interleukin 6 in elderly patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant and its correlation with underlying diseases

Objective To investigate the clinical significance of serum interleukin 6 (IL-6) in elderly patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant and its correlation with underlying diseases. Methods A total of 22 elderly patients (>80 years old) infected with omicron variant, who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Apr. to Jun. 2022 and tested positive for SARS-CoV-2 RNA, were included. The level of serum IL-6 was measured by flow cytometry, and the level of serum C reactive protein (CRP) was measured by immunonephelometry. Patients were divided into pneumonia group (16 cases) and non-pneumonia group (6 cases) according to the imaging examination results, and were divided into severe group (severe and critical type, 5 cases) and non-severe group (mild and normal type, 17 cases) according to the condition. Binary logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the correlation between serum IL-6 and CRP levels and the severity of the disease and whether it would progress to pneumonia. Meanwhile, the relationships between underlying diseases and serum IL-6 level were explored. Results Among the 22 patients, 6 were mild, 11 were normal, 3 were severe, and 2 were critical. The baseline serum IL-6 level in the pneumonia group was significantly higher than that in the non-pneumonia group ([20.16+/-12.36]pg/mL vs [5.42+/-1.57] pg/mL, P=0.009), and there was no significant difference in baseline serum CRP level between the 2 groups (P>0.05). There were no significant differences in baseline serum IL-6 or CRP levels between the severe group and the non-severe group (both P>0.05). Logistic regression analysis showed that the baseline serum IL-6 and CRP might be related to pneumonia after infection with omicron variant (odds ratio [OR]=2.407, 95% confidence interval [CI]0.915-6.328;OR=1.030, 95% CI 0.952-1.114). ROC curve analysis showed that the area under curve values of serum IL-6 and CRP in predicting the progression to pneumonia were 0.969 (95% CI 0.900-1.000) and 0.656 (95% CI 0.380-0.932), respectively, with statistical significance (Z=2.154, P=0.030). There were no significant differences in the baseline serum IL-6 level or proportions of severe patients or pneumonia patients among patients with or without hypertension, diabetes mellitus, coronary heart disease, chronic kidney disease or chronic obstructive pulmonary disease (all P>0.05). The baseline serum IL-6 levels of the omicron variant infected elderly patients with 1, 2, and 3 or more underlying diseases were 12.50 (9.15, 21.75), 23.55 (9.63, 50.10), and 10.90 (5.20, 18.88) pg/mL, respectively, with no statistical significance (P>0.05). Conclusion For omicron variant infected patients, serum IL-6 level is significantly increased in patients with pneumonia manifestations and is correlated with disease progression. Serum IL-6 level is of great guiding significance to judge disease progression and evaluate efficacy and prognosis of elderly coronavirus disease 2019 patients.Copyright © 2022, Second Military Medical University Press. All rights reserved.

A Potential Therapeutic Target Underling Binge Alcohol-Triggered Spontaneous Arrhythmia Onset in the Aged Heart

Background: Aging and binge alcohol abuse are both known as independent risk factors for both atrial and ventricular arrhythmias. With the COVID-19 pandemic, increased social isolation has significantly increased alcohol consumption worldwide. Older adults are a high-risk drinking group and alcohol significantly enhances the risk of arrhythmia onset. Yet, how alcohol (a secondary stressor) drives spontaneous atrial and ventricular arrhythmia onset in the aged heart (a primary stressor) remains unclear. Objective(s): We recently reported the stress-response kinase c-jun N-terminal kinase 2 (JNK2) underlies alcohol-enhanced atrial arrhythmia vulnerability (pacing-induced) in healthy young hearts. Here, we reveal a critical role of JNK2 in alcohol-driven arrhythmia onset in the aged heart in vivo. Method(s): Ambulatory ECGs were recorded using wireless telemeters in binge alcohol-exposed aged (24 months) and young mice (2 months). Spontaneous premature atrial and ventricular contractions (PACs, PVCs), atrial and ventricular tachycardia (AT, VT) were quantified as previously described. The role of JNK2 in triggered arrhythmic activities was assessed using a well-evaluated JNK2-specific inhibitor and our unique cardiac-specific MKK7D and MKK7D-JNK2dn mouse models with tamoxifen inducible overexpression of constitutively active MKK7 (a JNK upstream activator) or co-expression of MKK7D and inactive dominant negative JNK2 (JNK2dn). Result(s): We found that binge alcohol exposure in aged mice (n=14) led to spontaneous PACs/PVCs (75% of the mice), and AT/VT episodes (50%) along with a 21% mortality rate. However, alcohol-exposed young (n=5) and non-alcohol-exposed aged mice (n=11) were absent of any spontaneous arrhythmic activities or premature death. Intriguingly, JNK2-specific inhibition in vivo abolished those alcohol-associated triggered activities and mortality in aged mice. The causative role of JNK2 in triggered arrhythmias and premature death was further supported by the high frequency of spontaneous PACs/PVCs and nonsustained AT/VT episodes along with a 50% mortality rate in MKK7D mice (n=10), which was strikingly alleviated in MKK7D-JNK2dn mice (n=5) with cardiac-specific JNK2 competitive inhibition. Conclusion(s): Our findings are the first to reveal that stress kinase JNK2 underlies binge alcohol-evoked atrial and ventricular arrhythmia initiation in aged mice. Modulating JNK2 could be a novel therapeutic strategy to treat and/or prevent binge drinking-evoked cardiac arrhythmias.Copyright © 2023

Role of toll-like receptors in the pathogenesis of COVID-19: Current and future perspectives

The coronavirus disease 2019 (COVID-19) pandemic underlines a persistent threat of respiratory tract infectious diseases and warrants preparedness for a rapid response. At present, COVID-19 has had a serious social impact and imposed a heavy global burden on public health. The exact pathogenesis of COVID-19 has not been fully elucidated. Since the outbreak of COVID-19, a renewed attention has been brought to Toll-like receptors (TLRs). Available data and new findings have demonstrated that the interaction of human TLRs and SARS-CoV-2 is a vital mediator of COVID-19 immunopathogenesis. TLRs such as TLR2, 4, 7 and 8 are potentially important in viral combat and activation of immunity in patients with COVID-19. Therapeutics targeting TLRs are currently considered promising options against the pandemic. A number of TLR-targeting immunotherapeutics are now being investigated in preclinical studies and different phases of clinical trials. In addition, innovative vaccines based on TLRs under development could be a promising approach for building a new generation of vaccines to solve the current challenges. In this review, we summarize recent progress in the role of TLRs in COVID-19, focusing the new candidate drugs targeting TLRs, the current technology and potential paths forward for employing TLR agonists as vaccine adjuvants.Copyright © 2023 The Scandinavian Foundation for Immunology.

Interpersonal-function topoi in Chinese central government's work report (2020) as epidemic (counter-)crisis discourse

Using Systemic Functional Grammar and conceptual framework in the argumentation-oriented approach to discourse, this study analyzes Chinese central government's " Report on the Work of the Government" in 2020 (henceforth the Report) to explore the "interpersonal-function topoi" in the political discourse. The Report was delivered and issued against the backdrop of the surging covid-19 epidemic. This study first calculated the frequency of mood, modality and persons in the Report. The statistics were qualitatively analyzed in relation to various topoi-imagery of the crisis vis-a-vis representing the agency-reflected in the interpersonal metafunction of the language in the Report. These topoi play a vital role in winning popular support for the Chinese central government's anti-epidemic measures and mobilizing the widest public into actions against the covid-19 pandemic. The analysis demonstrates how the analysis of interpersonal metafunction from an argumentation-oriented perspective can shed light on dealing with crisis discourse, especially in the pandemic settings.

Computer-Aided System for COVID-19 Using Semi-supervised-based Ensemble Learning and Reinforcement Learning

Coronavirus Disease 2019(COVID-19) has shocked the world with its rapid spread and enormous threat to life and has continued up to the present. In this paper, a computer-aided system is proposed to detect infections and predict the disease progression of COVID-19. A high-quality CT scan database labeled with time-stamps and clinicopathologic variables is constructed to provide data support. To our knowledge, it is the only database with time relevance in the community. An object detection model is then trained to annotate infected regions. Using those regions, we detect the infections using a model with semi-supervised-based ensemble learning and predict the disease progression depending on reinforcement learning. We achieve an mAP of 0.92 for object detection. The accuracy for detecting infections is 98.46%, with a sensitivity of 97.68%, a specificity of 99.24%, and an AUC of 0.987. Significantly, the accuracy of predicting disease progression is 90.32% according to the timeline. It is a state-of-the-art result and can be used for clinical usage. © 2022 IEEE.

Displaced workers and the pandemic recession

Workers displaced during the pandemic recession experienced better earnings and employment outcomes than workers displaced during previous recessions. A sharp recovery in aggregate labor market conditions after the pandemic recession accounts for these better outcomes. The industry and occupation composition of displaced workers, the prevalence of recalls, and increased take-up of unemployment insurance benefits are unlikely explanations. © 2023 Elsevier B.V.

Application of chest low-dose CT screening of Corona Virus Disease 2019 with a third-generation dual-source scanner.

Objective: To investigate the application value of third-generation dual-source CT(3-G DSCT) low-dose scan mode combined with iterative reconstruction technology in the screening of COVID-19 and to evaluate the radiation dose. Method(s): One hundred and twenty patients suspected of COVID-19 from December 2019 to February 2020 were retrospectively analysed and randomly divided into two groups (test group and conventional group, 60 patients in each). The parameters for test group included 3-G DSCT, Turbo Flash scan mode, CARE kV, with reference 90 kV, pitch 2.0, and ADMIRE algorithm, while those parameters for conventional group included the 128-slice CT, conventional spiral scan mode, 120 kV, pitch 1.2, and FBP algorithm. The CT values of aorta, spinal posterior muscle, and subcutaneous fat, the aortic noise, signal-to-noise ratio (SNR), and contrast noise ratio (CNR) were compared to evaluate the image quality between two groups. Two experienced doctors scored the image quality using a double-blind method, and compared the CT dose index volume (CTDIvol), dose-length product (DLP), and effective dose (E) of the two groups. Result(s): The CT value of the aorta and spinal posterior muscle and the aortic SNR in the test group were (45.38+/-4.77), (53.41+/-8.44) HU, and 2.82+/-0.59, and significantly higher than those in the conventional group [(39.68+/-6.26), (42.66+/-6.32) HU, 2.58+/-0.61, t=5.608, 7.897, 2.162, P<0.05]. The aortic noise, CNR and subjective scores between the two groups had no significant difference( P>0.05). The CTDIvol, DLP, and E in the test group were (3.09+/-1.02) mGy, (107.57+/-32.81) mGy*cm, (1.51+/-0.46) mSv, significantly lower than those in the conventional group [(7.00+/-1.80) mGy, (261.65+/-73.93) mGy*cm, (3.66+/-1.03) mSv;t=-14.680, -14.756, -14.756, P<0.05]. Conclusion(s): In the screening of COVID-19, using low-dose scanning mode of 3-G DSCT combined with iterative reconstruction technology would provide diagnostic quality images and meanwhile effectively reduce the radiation dose and improve the SNR of the image.Copyright © 2020 by the Chinese Medical Association.

Multicenter post-marketing clinical evaluation on the clinical performance of the five domestic fast nucleic acid detection reagents for 2019-nCoV.

Objective This multicenter clinical evaluation analyzed the clinical performance of five fast nucleic acid detection systems for 2019-nCoV. Methods Clinical performance of the five fast nucleic acid detection reagents approved in China was evaluated in the present study. Fifty-seven throat swabs samples from COVID-19 patients and fifteen throat swabs samples from healthy people were collected from the First Affiliated Hospital of Zhejiang University school of Medicine, Tongji Hospital of Tongji Medical College of HUST, and National Institute of Viral Disease Control and Prevention of CDC to evaluate the positive coincidence rate, negative coincidence rate, total coincidence rate, the detection time and retest rate as well as the relation between positive intensity and positive coincidence rate of the five fast nucleic acid detection systems in November 2020. Results The positive coincidence rates of the five kits were 92.59% (50/54), 83.64% (46/55), 98.25% (56/57), 94.44% (51/54) and 98.18% (54/55);and the negative coincidence rates were 93.33% (14/15), 93.33% (14/15), 86.67% (13/15), 100% (14/14) and 93.33% (14/15);and the total coincidence rates were 92.75% (64/69), 85.71% (60/70), 95.83% (69/72), 94.20% (65/69) and 97.14% (68/70), respectively. The positive coincidence rate of the five kits reached 100% for the strong-positive (90/90) and medium-positive samples (84/84), but only 82.18% (83/101) for weak-positive samples (cycle threshold value>33), and the retest rate of two kits were 15.28% (11/72) and 12.50% (9/72), which were both higher than 10%. Total time from sample extraction to amplification was between 32.33-65.33 minutes for these five kits. Conclusion The five fast nucleic acid detection reagents have good performance and can be used as a supplement to routine nucleic acid detection reagents.Copyright © 2022 Chinese Journal of Laboratory Medicine. All rights reserved.

Foreign Bodies Detector Based on DETR for High-Resolution X-Ray Images of Textiles

Foreign bodies (FBs) detection for X-ray images of textiles is a novel and challenging task. To solve the problem of poor performance of anchor-based detectors for FBs detection, we propose a feature-enhanced object detection framework with transformer (FE-DETR). Based on the split-attention of residual split-attention network (ResNeSt), we add convolutional block attention module (CBAM) between residual blocks and replace the $3\times $ 3 convolutional layer of the last residual block with deformable convolution network (DCN) to adapt FBs with different scales. Then, we propose a multiscale feature encoding (MSFE) module to solve the feature dispersion caused by deep convolution. Meanwhile, the transformer module is selected as the prediction head of the detector. During training, several heuristic strategies are used to further optimize the performance of FE-DETR. In addition, we construct a benchmark dataset for the textile FBs detection task. With end-to-end training, FE-DETR achieves higher performance than the baseline and mainstream state-of-the-art methods, with mean average precision (mAP) = 0.74, average precision (AP) = 0.992, average recall (AR) = 0.971, and $F1$ -score = 0.987. This article has been applied to the production line of medical protective clothing during the Corona Virus Disease 2019 (COVID-19) period and has yielded impressive results in actual production. © 1963-2012 IEEE.

Role of surgeons in the medical model of treating patients infected with COVID-19 in makeshift hospitals.

Since the outbreak of Corona Virus Disease 2019 (COVID-19) in December 2019, the number of new confirmed cases in Wuhan has been increasing, and medical resources are in short supply. Under this grim situation, makeshift hospitals have been used to treat patients with mild symptoms and achieved the largest capacity. Under the model of concentrated admission in makeshift hospitals with limited medical resources, the frontline surgeons adopt strict disease observation and treatment strategies, actively carry out psychological counseling for patients, and organize multidisciplinary teams to deal with chronic and emergency surgical diseases of patients with COVID-19. Combined with their own clinical practices, the authors summarize a series of clinical experiences for the treatment of patients with COVID-19.Copyright © 2020 by the Chinese Medical Association.

Viruses as biomaterials

Viruses lacking the capacity to infect mammals exhibit minimal toxicity, good biocompatibility, and well-defined structures. As self-organized biomolecular assemblies, they can be produced from standard biological techniques on a large scale at a low cost. Genetic, chemical, self-assembly, and mineralization techniques have been applied to allow them to display functional peptides or proteins, encapsulate therapeutic drugs and genes, assemble with other materials, and be conjugated with bioactive molecules, enabling them to bear different biochemical properties. So far, a variety of viruses (infecting bacteria, plants, or animals), as well as their particle variants, have been used as biomaterials to advance human disease prevention, diagnosis, and treatment. Specifically, the virus-based biomaterials can serve as multifunctional nanocarriers for targeted therapy, antimicrobial agents for infectious disease treatment, hierarchically structured scaffolds for guiding cellular differentiation and promoting tissue regeneration, versatile platforms for ultrasensitive disease detection, tissue-targeting probes for precision bioimaging, and effective vaccines and immunotherapeutic agents for tackling challenging diseases. This review provides an in-depth discussion of these exciting applications. It also gives an overview of the viruses from materials science perspectives and attempts to correlate the structures, properties, processing, and performance of virus-based biomaterials. It describes the use of virus-based biomaterials for preventing and treating COVID-19 and discusses the challenges and future directions of virus-based biomaterials research. It summarizes the progressive clinical trials of using viruses in humans. With the impressive progress made in the exciting field of virus-based biomaterials, it is clear that viruses are playing key roles in advancing important areas in biomedicine such as early detection and prevention, drug delivery, infectious disease treatment, cancer therapy, nanomedicine, and regenerative medicine. © 2023 Elsevier B.V.

A Staging Prediction Model for COVID-19 Pandemic under Strong Public Health Interventions

With the extensive implementation of the strong public health interventions in China, many models proposed to predict COVID-19 epidemic are no longer applicable to the current epidemic development. In this paper, a COVID-19 prediction method is proposed based on a staging SEITR model with consideration of strong public health interventions in China. The method simulates preventive and control measures such as mass nucleic acid testing and quarantine of close contacts by introducing the role of Isolates and the transformation of Exposed to Isolated. The experimental evaluation uses real epidemic data from six cities including Nanjing, Yangzhou, and etc. The accuracy of prediction for total number of infections reaches 95.8% with the data of the first 15 days of the outbreak. In addition, the prediction accuracy of the end of the pandemic is 95.07%. These show that the proposed method can effectively predict the course of the epidemic and it is practical for relevant departments to formulate reasonable prevention and control measures. © 2022 IEEE.

Multicenter post-marketing clinical evaluation on the clinical performance of the five domestic fast nucleic acid detection reagents for 2019-nCoV

Objective This multicenter clinical evaluation analyzed the clinical performance of five fast nucleic acid detection systems for 2019-nCoV. Methods Clinical performance of the five fast nucleic acid detection reagents approved in China was evaluated in the present study. Fifty-seven throat swabs samples from COVID-19 patients and fifteen throat swabs samples from healthy people were collected from the First Affiliated Hospital of Zhejiang University school of Medicine, Tongji Hospital of Tongji Medical College of HUST, and National Institute of Viral Disease Control and Prevention of CDC to evaluate the positive coincidence rate, negative coincidence rate, total coincidence rate, the detection time and retest rate as well as the relation between positive intensity and positive coincidence rate of the five fast nucleic acid detection systems in November 2020. Results The positive coincidence rates of the five kits were 92.59% (50/54), 83.64% (46/55), 98.25% (56/57), 94.44% (51/54) and 98.18% (54/55);and the negative coincidence rates were 93.33% (14/15), 93.33% (14/15), 86.67% (13/15), 100% (14/14) and 93.33% (14/15);and the total coincidence rates were 92.75% (64/69), 85.71% (60/70), 95.83% (69/72), 94.20% (65/69) and 97.14% (68/70), respectively. The positive coincidence rate of the five kits reached 100% for the strong-positive (90/90) and medium-positive samples (84/84), but only 82.18% (83/101) for weak-positive samples (cycle threshold value>33), and the retest rate of two kits were 15.28% (11/72) and 12.50% (9/72), which were both higher than 10%. Total time from sample extraction to amplification was between 32.33-65.33 minutes for these five kits. Conclusion The five fast nucleic acid detection reagents have good performance and can be used as a supplement to routine nucleic acid detection reagents.

Dynamic lead–lag relationship between Chinese carbon emission trading and stock markets under exogenous shocks

Using the non-parametric thermal optimal path method, we investigate the dynamic lead–lag relationship between carbon emission trading and stock markets in China, and further consider the impact of different types of exogenous shocks on the lead–lag relationship. The empirical results show that the stock market leads the carbon market on most trading days, and the relationship reverses when the mean values of carbon market return are significantly smaller than zero. In addition, the lead–lag relationships when the carbon market leads the high energy-consuming stock market sectors are more obvious. We also find that there exist significant heterogeneous effects of different types of exogenous shocks on the lead–lag relationship between the two markets, including government policy, the Sino-US trade war and the Covid-19 outbreak. These findings have the potential to help regulators understand the interrelationship between components of the financial market, and be of great value for investors to optimize portfolio allocation by incorporating carbon assets into the portfolio. © 2023 Elsevier Inc.

Geospatial Network Analysis and Origin-Destination Clustering of Bike-Sharing Activities during the COVID-19 Pandemic

Bike-sharing data are an important data source to study urban mobility in the context of the coronavirus disease 2019 (COVID-19). However, studies that focus on different bike-sharing activities including both riding and rebalancing are sparse. This limits the comprehensiveness of the analysis of the impact of the pandemic on bike-sharing. In this study, we combine geospatial network analysis and origin-destination (OD) clustering methods to explore the spatiotemporal change patterns hidden in the bike-sharing data during the pandemic. Different from previous research that mostly focuses on the analysis of riding behaviors, we also extract and analyze the rebalancing data of a bike-sharing system. In this study, we propose a framework including three components: (1) a geospatial network analysis component for a statistical and spatiotemporal description of the overall riding flows and behaviors, (2) an origin-destination clustering component that compensates the network analysis by identifying large flow groups in which individual edges start from and end at nearby stations, and (3) a rebalancing data analysis component for the understanding of the rebalancing patterns during the pandemic. We test our framework using bike-sharing data collected in New York City. The results show that the spatial distribution of the main riding flows changed significantly in the pandemic compared to pre-pandemic time. For example, many riding trips seemed to expand the purposes of riding for work-home commuting to more leisure activities. Furthermore, we found that the changes in the riding flow patterns led to changes in the spatiotemporal distributions of bike rebalancing, such as the shifting of the rebalancing peak time and the increased ratio between the number of rebalancing and the total number of rides. Policy implications are also discussed based on our findings.

Multi-Vortex Tornado Blueprint for Disruptive Global Co-Creation (Inspired by EUvsVirus): Hackathons vs Grand Challenges

Since its burst in early 2020, the Covid-19 pandemic has deeply affected every aspect of daily life, from international trade and travelling to restrictions on an individual level, becoming a complex multi-level and highly multi-faceted problem. Due to its overarching influence and deep impact, it can be seen as one of the most disruptive Grand Challenges of our time. Different from most other lasting Grand Challenges, such as Climate Change, the pandemic exerted its influence with little ramp-up, rapidly transforming health and health systems, human lives, goods and economic flows, decision-making mechanisms, research and innovation, and many other aspects of life in a very short span of time. Grand Challenges require extraordinary efforts from society as a whole since they need holistic, effective, collaborative endeavours to solve them. One such unique orchestrated effort can be observed in the subsequent series of virtual massive EUvsVirus (https://www.euvsvirus.org/ ) events and committed collaborations (‘hackathon', ‘matchathon', ‘launchathon', ‘community', ‘EIC Covid platform', and the unparalleled ‘Academia Diffusion Experiment' [ADE], analysed in chapter "Academia Diffusion Experiment: Trailblazing the Emergence from Co-Creation” of this book). While this chapter explains ‘what' has been produced with the ADE, inspired by the EUvsVirus phenomenon, the ADE chapter describes ‘how' it has been done. Both are extremely unique in terms of content, procedure, motivation, collaboration, effects—and they attempt to trailblaze at highest level co-creation, co-evolution, and co-dreaming. Hence, situated as the last chapters of this book. This chapter will shed light on the EUvsVirus events, where over 30,000 individuals from 40 countries came together and addressed the complexity of this massive challenge in a pioneering and groundbreaking way. The chapter is focused on analysing the EUvsVirus hackathon (alongside its mentioned unique spillovers) as a tool, method, and process capable of channelling and activating individuals' and institutions' concerns, wills, and commitments into a unique orchestrated open, collaborative response to an urgent Grand Challenge, the pandemic. We are producing a multi-vortex tornado model, resembling the EUvsVirus phenomenon, its components, mechanisms, behaviour and how to replicate it to achieve such disruptive, global organisational effort of co-creation. Especially, the emergence of such collaboration in the face of such urgency leads to the assumption that there are crucial lessons to be learned from this endeavour, quite fittingly encapsulated by these words: ‘We are learning That though we weren't ready for this, We have been readied by it'. Amanda Gorman's New Year poem (https://amandagormanbooks.com/#the-hill-we-climb-and-other-poems or https://edition.cnn.com/videos/tv/2022/01/06/exp-amanda-gorman-nye-poem.cnn ) © 2023, The Author(s).

An Art-Based Inquiry into the Perception of Tourism Impacts on Their Quality of Life: The Case of Cambodian Host-Children

While host-children are vulnerable to tourism impacts, the tourism literature has neglected how these impacts affect host-children's quality of life (QOL). The concept of QOL is ambiguous, and the influence of a host-guest relationship on residents' QOL has been overlooked. This paper addresses these gaps by exploring how host-children in a developing country perceive tourism impacts on their QOL, focusing on power dynamics in a host-guest relationship. Data were collected from 94 Cambodian host-children using qualitative methods, including drawings and group interviews. The findings revealed Cambodian host-children's perceptions of tourism impacts over five life domains-material, learning opportunity, cultural pride, emotion, and child sex tourism/trafficking. Despite their perception of negative impacts, all host-children believed that tourism had improved their QOL. The paradox of QOL is explained through Bottom-up Spillover Theory incorporated with Social Exchange Theory. Practical implications for post-COVID and directions for future research are suggested.