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1.
22nd COTA International Conference of Transportation Professionals, CICTP 2022 ; : 887-898, 2022.
Article in English | Scopus | ID: covidwho-2062366

ABSTRACT

The outbreak of COVID-19 and the unprecedented policies issued by the government have compelled citizens to reshape their daily travel behavior. Questionnaires were designed to obtain three main related indicators of socio-economic and demographic characteristics, primary travel purposes and patterns, and factors influencing mode choice to explore the impact of the pandemic on travel behavior and mode preferences of urban residents. By applying the online survey method with Snowball sampling techniques, a total of 591 valid questionnaire responses from Hong Kong residents were received in the designated time period. Then, the non-parametric test methods (e.g., McNemar-Bowker test and Mann-Whitney U test) were employed to implement the statistical analysis. Traffic administrators can use the survey findings to adjust current policies or delineate new policies to align with the passenger travel behavior. This will ensure more fluid and safer transportation. © ASCE.

2.
Data Analysis and Knowledge Discovery ; 6(1):55-68, 2022.
Article in Chinese | Scopus | ID: covidwho-1893357

ABSTRACT

[Objective] This paper tries to measure the netizens' trust in government microblogs during public health emergencies, and then explores reasons for the changes. [Methods] First, we calculated the trust from the comments on government microblogs with the comment objects, the topic similarity between comments and microblogs, as well as their sentiments. Then, we added the numbers of likes and forwards/retweets to decide the comprehensive trust of the netizens toward the government microblogs. [Results] We examined out model with microblog data on COVID-19 and found that topics related to industrial and government efforts fighting the pandemic enhanced the trust in government microblogs. There were great differences in the development trends and reasons of the trust in government microblogs from different fields. [Limitations] We only used the events and the microbloggers as the objects of comments. [Conclusions] The proposed model could help government agencies improve decision making, public trust, and lead online opinion during public health emergencies. © 2022, Chinese Academy of Sciences. All rights reserved.

3.
Journal of Industrial and Management Optimization ; 0(0):16, 2022.
Article in English | English Web of Science | ID: covidwho-1884492

ABSTRACT

A painful lesson got from pandemic COVID-19 is that preventive healthcare service is of utmost importance to governments since it can make massive savings on healthcare expenditure and promote the welfare of the society. Recognizing the importance of preventive healthcare, this research aims to present a methodology for designing a network of preventive healthcare facilities in order to prevent diseases early. The problem is formulated as a bilevel non-linear integer programming model. The upper level is a facility location and capacity planning problem under a limited budget, while the lower level is a user choice problem that determines the allocation of clients to facilities. A genetic algorithm (GA) is developed to solve the upper level problem and a method of successive averages (MSA) is adopted to solve the lower level problem. The model and algorithm is applied to analyze an illustrative case in the Sioux Falls transport network and a number of interesting results and managerial insights are provided. It shows that solutions to medium-scale instances can be obtained in a reasonable time and the marginal benefit of investment is decreasing.

4.
Topics in Antiviral Medicine ; 30(1 SUPPL):180, 2022.
Article in English | EMBASE | ID: covidwho-1880232

ABSTRACT

Background: Molnupiravir (MOV), the orally administered prodrug of the antiviral ribonucleoside analogue, N-hydroxycytidine (NHC) has received emergency use authorization for treatment of COVID-19. NHC inhibits viral replication by introduction of random transition errors across the viral genome, resulting in non-infectious virus. In the Phase II/III (MOVe-OUT) study, non-hospitalized participants received MOV or placebo (PBO) for 5 days and followed to Day 29. Viral RNA was sequenced to determine the rate, distribution and type of viral errors observed. Methods: SARS-CoV-2 RNA isolated from nasopharyngeal swabs was quantified by RT-PCR followed by complete genome NGS using the Ion AmpliSeq SARS-CoV-2 Research panel and Ion Torrent sequencing. To distinguish between nucleotide errors resulting from the mechanism of action of MOV and those potentially associated with reduced susceptibility to NHC, two different analyses were used. To measure impact of MOV on accumulation of low-frequency errors in the viral quasispecies, nucleotide variants were identified using VarScan 2.4 mutation caller with 0.4% minimum variant allele frequency cut-off. Resistance-associated changes were identified as amino acid substitutions occurring in D3 or D5 samples from ≥2 participants with a frequency of ≥5% of NGS reads. Phenotypic analysis of selected amino acid substitutions was performed using a replicon model. Results: NGS results showed a relationship between the number of random errors across the viral genome with increasing MOV dose. By Day 5 the mean number of viral genome errors were 21, 83, 129 and 223 in the PBO, 200, 400 and 800 mg groups, respectively. Among the sequence changes observed, the majority were transitions errors, consistent with MOV's mechanism of action. After MOV treatment, few treatment-emergent amino acid substitutions were identified in the viral replicase genes. These included nsp12 (T731I) and nsp14 (A220S/T/V, V466I, S503L/P);none associated with loss of susceptibility to MOV. Changes in spike protein in both PBO and MOV groups were at sites previously described in circulating variants. Conclusion: Consistent with the mechanism of action, MOV treatment resulted in a dose-dependent increase in transition errors across the SARS-CoV-2 genome. No resistance-associated mutations were identified in the viral replicase and no evidence that MOV treatment selected for unique mutations in spike protein not previously observed in circulating variants.

5.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338085

ABSTRACT

We present spatial-CITE-seq for high-plex protein and whole transcriptome co-mapping, which was firstly demonstrated for profiling 189 proteins and transcriptome in multiple mouse tissue types. It was then applied to human tissues to measure 273 proteins and transcriptome that revealed spatially distinct germinal center reaction in tonsil and early immune activation in skin at the COVID-19 mRNA vaccine injection site. Spatial-CITE-seq may find a range of applications in biomedical research.

6.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-334725

ABSTRACT

With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two V H H nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of a5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants. ONE-SENTENCE SUMMARY: Dromedary camel ( Camelus dromedarius ) V H H phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.

7.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333539

ABSTRACT

While vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here, inhibitors of spike (S) mediated cell entry were identified in a high throughput screen of an approved drugs library with SARS-S and MERS-S pseudotyped particle entry assays. We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry. This work should contribute to the development of effective treatments against the initial stage of viral infection, thus reducing viral burden in COVID-19 patients. Abstract figure:

8.
34th Australasian Joint Conference on Artificial Intelligence, AI 2021 ; 13151 LNAI:254-266, 2022.
Article in English | Scopus | ID: covidwho-1782717

ABSTRACT

Fast and accurate traffic load prediction is a pivotal component of the Intelligent Transport System. It will reduce time spent by commuters and save our environment from vehicle emissions. During the COVID-19 pandemic, people prefer to use private transportation;thus predicting the traffic load becomes more critical. In these years, researchers have developed some traffic load prediction models and have applied these models successfully on data from the US, China or Europe. However, none of these models has been applied to traffic data in Australia. Considering that Australia bears different political, geographical, and climate conditions from other countries, these models may not be suitable to predict the traffic load in Australia. In this paper, we investigate this problem and proposes a multi-modal method that is capable of using Australia-specific data to assist traffic load prediction. Specifically, we use daily social media data together with traffic data to predict the traffic load. We illustrate a protocol to pre-process raw traffic and social media data and then propose a multi-modal model, namely DM2T, which accurately make time-series prediction by using both time-series data and other media data. We validate the effectiveness of our proposed method by a case study on Brisbane city. The result shows that with the help of Australia-specific social media data, our proposed method can make more accurate traffic load prediction for Brisbane than conventional methods. © 2022, Springer Nature Switzerland AG.

9.
CHI Conference on Human Factors in Computing Systems ; 2021.
Article in English | Web of Science | ID: covidwho-1759469

ABSTRACT

Online exams have become widely used to evaluate students' performance in mastering knowledge in recent years, especially during the pandemic of COVID-19. However, it is challenging to conduct proctoring for online exams due to the lack of face-to-face interaction. Also, prior research has shown that online exams are more vulnerable to various cheating behaviors, which can damage their credibility. This paper presents a novel visual analytics approach to facilitate the proctoring of online exams by analyzing the exam video records and mouse movement data of each student. Specifically, we detect and visualize suspected head and mouse movements of students in three levels of detail, which provides course instructors and teachers with convenient, efficient and reliable proctoring for online exams. Our extensive evaluations, including usage scenarios, a carefully-designed user study and expert interviews, demonstrate the effectiveness and usability of our approach.

10.
Non-conventional in English | National Technical Information Service, Grey literature | ID: grc-753531

ABSTRACT

The first step of SARS-CoV-2 infection is binding of the spike proteins receptor binding domain to the host cells ACE2 receptor on the plasma membrane. Here, we have generated a versatile imaging probe using recombinant Spike receptor binding domain conjugated to fluorescent quantum dots (QDs). This probe is capable of engaging in energy transfer quenching with ACE2-conjugated gold nanoparticles to enable monitoring of the binding event in solution. Neutralizing antibodies and recombinant human ACE2 blocked quenching, demonstrating a specific binding interaction. In cells transfected with ACE2-GFP, we observed immediate binding of the probe on the cell surface followed by endocytosis. Neutralizing antibodies and ACE2-Fc fully prevented binding and endocytosis with low nanomolar potency. Importantly, we will be able to use this QD nanoparticle probe to identify and validate inhibitors of the SARS-CoV-2 Spike and ACE2 receptor binding in human cells. This work enables facile, rapid, and high-throughput cell-based screening of inhibitors for coronavirus Spike-mediated cell recognition and entry.

11.
MEDLINE; 2022.
Preprint in English | MEDLINE | ID: ppcovidwho-329653

ABSTRACT

Neutralizing antibodies targeting the SARS-CoV-2 spike protein have shown a great preventative/therapeutic potential. Here, we report a rapid and efficient strategy for the development and design of SARS-CoV-2 neutralizing humanized nanobody constructs with sub-nanomolar affinities and nanomolar potencies. CryoEM-based structural analysis of the nanobodies in complex with spike revealed two distinct binding modes. The most potent nanobody, RBD-1-2G(NCATS-BL8125), tolerates the N501Y RBD mutation and remains capable of neutralizing the B.1.1.7 (Alpha) variant. Molecular dynamics simulations provide a structural basis for understanding the neutralization process of nanobodies exclusively focused on the spike-ACE2 interface with and without the N501Y mutation on RBD. A primary human airway air-lung interface (ALI) ex vivo model showed that RBD-1-2G-Fc antibody treatment was effective at reducing viral burden following WA1 and B.1.1.7 SARS-CoV-2 infections. Therefore, this presented strategy will serve as a tool to mitigate the threat of emerging SARS-CoV-2 variants.

12.
2021 IEEE International Conference on Systems, Man, and Cybernetics, SMC 2021 ; : 3200-3205, 2021.
Article in English | Scopus | ID: covidwho-1699528

ABSTRACT

The COVID-19 outbreak a pandemic, which poses a serious threat to global public health and lead to a tsunami of online social media. Individuals frequently express their views, opinions and emotions about the events of the pandemic on Twitter, Facebook, etc. Many researches try to analyze the sentiment of the COVID-19-related content from these social networks. However, they have rarely focused on the vaccine. In this paper, we study the COVID-19 vaccine topic from Twitter. Specifically, all the tweets related to COVID-19 vaccine from December 15th, 2020 to February 10th, 2021 are collected by using the Twitter API, then the unsupervised learning VADER model is used to judge the emotion categories (positive, neutral, negative) and calculate the sentiment value of the dataset. Based on the interaction between users, a communication topological network is constructed and the emotional direction is explored. We find that people had different sentiments between Chinese vaccine and those in other countries. The sentiment value might be affected by the number of daily news cases and deaths, the nature of key issues in the communication network. And revealing that the key nodes in the social network can produce emotional contagion to other nodes. © 2021 IEEE.

13.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326773

ABSTRACT

The cell entry of SARS-CoV-2 has emerged as an attractive drug development target. We previously reported that the entry of SARS-CoV-2 depends on the cell surface heparan sulfate proteoglycan (HSPG) and the cortex actin, which can be targeted by therapeutic agents identified by conventional drug repurposing screens. However, this drug identification strategy requires laborious library screening, which is time-consuming and often limited number of compounds can be screened. As an alternative approach, we developed and trained a graph convolutional network (GCN)-based classification model using information extracted from experimentally identified HSPG and actin inhibitors. This method allowed us to virtually screen 170,000 compounds, resulting in ∼2000 potential hits. A hit confirmation assay with the uptake of a fluorescently labeled HSPG cargo further shortlisted 256 active compounds. Among them, 16 compounds had modest to strong inhibitory activities against the entry of SARS-CoV-2 pseudotyped particles into Vero E6 cells. These results establish a GCN-based virtual screen workflow for rapid identification of new small molecule inhibitors against validated drug targets.

14.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326746

ABSTRACT

Lethal COVID-19 is associated with respiratory failure that is thought to be caused by acute respiratory distress syndrome (ARDS) secondary to pulmonary infection. To date, the cellular pathogenesis has been inferred from studies describing the expression of ACE2, a transmembrane protein required for SARS-CoV-2 infection, and detection of viral RNA or protein in infected humans, model animals, and cultured cells. To functionally test the cellular mechanisms of COVID-19, we generated hACE2fl animals in which human ACE2 (hACE2) is expressed from the mouse Ace2 locus in a manner that permits cell-specific, Cre-mediated loss of function. hACE2fl animals developed lethal weight loss and hypoxemia within 7 days of exposure to SARS-CoV-2 that was associated with pulmonary infiltrates, intravascular thrombosis and patchy viral infection of lung epithelial cells. Deletion of hACE2 in lung epithelial cells prevented viral infection of the lung, but not weight loss, hypoxemia or death. Inhalation of SARS-CoV-2 by hACE2fl animals resulted in early infection of sustentacular cells with subsequent infection of neurons in the neighboring olfactory bulb and cerebral cortex—events that did not require lung epithelial cell infection. Pharmacologic ablation of the olfactory epithelium or Foxg1Cre mediated deletion of hACE2 in olfactory epithelial cells and neurons prevented lethality and neuronal infection following SARS-CoV-2 infection. Conversely, transgenic expression of hACE2 specifically in olfactory epithelial cells and neurons in Foxg1Cre;LSL-hACE2 mice was sufficient to confer neuronal infection associated with respiratory failure and death. These studies establish mouse loss and gain of function genetic models with which to genetically dissect viral-host interactions and demonstrate that lethal disease due to respiratory failure may arise from extrapulmonary infection of the olfactory epithelium and brain. Future therapeutic efforts focused on preventing olfactory epithelial infection may be an effective means of protecting against severe COVID-19.

15.
Frontiers in Physics ; 10:5, 2022.
Article in English | Web of Science | ID: covidwho-1686526

ABSTRACT

We present an R package developed to quantify coronavirus disease 2019 (COVID-19) importation risk. Quantifying and visualizing the importation risk of COVID-19 from inbound travelers is urgent and imperative to trigger public health responses, especially in the early stages of the COVID-19 pandemic and emergence of new SARS-CoV-2 variants. We provide a general modeling framework to estimate COVID-19 importation risk using estimated pre-symptomatic prevalence of infection and air traffic data from the multi-origin places. We use Hong Kong as a case study to illustrate how our modeling framework can estimate the COVID-19 importation risk into Hong Kong from cities in Mainland China in real time. This R package can be used as a complementary component of the pandemic surveillance system to monitor spread in the next pandemic.

16.
3rd International Conference on Computing and Data Science, CONF-CDS 2021 ; 1513 CCIS:185-192, 2021.
Article in English | Scopus | ID: covidwho-1680664

ABSTRACT

In this paper, the SEIR model is modified. According to the characteristics of COVID-19, a new room of people under quarantine is added, and the incubation period infection rate is introduced. We define the disease-free equilibrium and prove the stability of the equilibrium. Local stability is proved by examinating Characteristic polynomial, and global stability is proved by constructing Lyapunov Function. In addition, the effect of the epidemic prevention measures are evaluated by numerical simulation. The research shows that the post exposure infection rate and quarantine rate are the most crucial parameters of this disease. © 2021, Springer Nature Singapore Pte Ltd.

17.
Chemistry of Materials ; : 10, 2022.
Article in English | Web of Science | ID: covidwho-1655408

ABSTRACT

There is a need for surveillance of COVID-19 to identify individuals infected with SARS-CoV-2 coronavirus. Although specific, nucleic acid testing has limitations in terms of point-of-care testing. One potential alternative is the nonstructural protease (nsp5, also known as M-pro/3CL(pro)) implicated in SARS-CoV-2 viral replication but not incorporated into virions. Here, we report a divalent substrate with a novel design, (Cys)(2)-(AA)(x)-(Asp)(3) , to interface gold colloids in the specific presence of M-pro leading to a rapid and colorimetric readout. Citrate-and tris(2-carboxyethyl)phosphine (TCEP)-AuNPs were identified as the best reporter out of the 17 ligated nanoparticles. Furthermore, we empirically determined the effects of varying cysteine valence and biological media on the sensor specificity and sensitivity. The divalent peptide was specific to M-pro , that is, there was no response when tested with other proteins or enzymes. Furthermore, the M-pro detection limits in Tris buffer and exhaled breath matrices are 12.2 and 18.9 nM, respectively, which are comparable to other reported methods (i.e., at low nanomolar concentrations) yet with a rapid and visual readout. These results from our work would provide informative rationales to design a practical and noninvasive alternative for COVID-19 diagnostic testing -the presence of viral proteases in biofluids is validated.

18.
American Journal of Pathology ; 191(10 S):S6-S6, 2021.
Article in English | Web of Science | ID: covidwho-1610071
19.
8th International Conference on Bioinformatics Research and Applications, ICBRA 2021 ; : 79-83, 2021.
Article in English | Scopus | ID: covidwho-1599324

ABSTRACT

The majority of deaths in the global epidemic of COVID-19 is caused by ALI and ARDS, in which cytokine storm caused by excessive secretion of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, in the lung plays an essential role in the development of these two lung injuries. This research is designed to establish a mice model using LPS to simulate the cytokine storm generated by SARS-CoV-2 invasion in mice, and then to administer different doses of licorice flavonoid to mice before and after the model establishment. The expression levels of cytokines (TNF-α, IL-6, IL-1β) were measured by ELISA assay and RT-qPCR assay. This experiment was designed to test the inhibitory effects of prevention and direct treatment with licorice flavonoids on cytokine storm, providing an academic basis for exploring the possibility of clinical use of licorice flavonoids in the treatment of COVID-19, or widespread use in human bodies for prevention, through a more convenient and cheaper way compared to vaccines or glucocorticoids. © 2021 ACM.

20.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-297018

ABSTRACT

Lethal COVID-19 is associated with respiratory failure that is thought to be caused by acute respiratory distress syndrome (ARDS) secondary to pulmonary infection. To date, the cellular pathogenesis has been inferred from studies describing the expression of ACE2, a transmembrane protein required for SARS-CoV-2 infection, and detection of viral RNA or protein in infected humans, model animals, and cultured cells. To functionally test the cellular mechanisms of COVID-19, we generated hACE2 fl animals in which human ACE2 (hACE2) is expressed from the mouse Ace2 locus in a manner that permits cell-specific, Cre-mediated loss of function. hACE2 fl animals developed lethal weight loss and hypoxemia within 7 days of exposure to SARS-CoV-2 that was associated with pulmonary infiltrates, intravascular thrombosis and patchy viral infection of lung epithelial cells. Deletion of hACE2 in lung epithelial cells prevented viral infection of the lung, but not weight loss, hypoxemia or death. Inhalation of SARS-CoV-2 by hACE2 fl animals resulted in early infection of sustentacular cells with subsequent infection of neurons in the neighboring olfactory bulb and cerebral cortexa" events that did not require lung epithelial cell infection. Pharmacologic ablation of the olfactory epithelium or Foxg1 Cre mediated deletion of hACE2 in olfactory epithelial cells and neurons prevented lethality and neuronal infection following SARS-CoV-2 infection. Conversely, transgenic expression of hACE2 specifically in olfactory epithelial cells and neurons in Foxg1 Cre ;LSL- hACE2 mice was sufficient to confer neuronal infection associated with respiratory failure and death. These studies establish mouse loss and gain of function genetic models with which to genetically dissect viral-host interactions and demonstrate that lethal disease due to respiratory failure may arise from extrapulmonary infection of the olfactory epithelium and brain. Future therapeutic efforts focused on preventing olfactory epithelial infection may be an effective means of protecting against severe COVID-19.

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