Remdesivir Reduces Mortality in Immunocompromised Patients Hospitalized for Covid-19

Background: There is limited information on effectiveness of COVID-19 therapies in immunocompromised patients, who are at higher risk of hospitalizations, complications, and mortality due to COVID-19. We examined hospital all-cause mortality for early RDV use vs. no RDV use among immunocompromised COVID-19 patients across several distinct dominant variants of concern (VOC) periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): Using the Premier Healthcare Database, we identified adults with an immunocompromised condition (cancer, solid organ and hematopoietic stem cell transplant, hematologic malignancies, primary immunodeficiencies, asplenia, bone marrow failure/aplastic anemia, severe combined immunodeficiencies or HIV), hospitalized with a primary diagnosis of COVID-19. Patients treated with RDV in first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using 1:1 preferential withinhospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Cox Proportional Hazards Model was used to examine time to 14-and 28-day mortality. Result(s): Overall (Dec'20-Apr'22), 14,169 RDV-treated patients were matched to 5,341 unique non-RDV patients. Post-matching balance was achieved with 59% being 65+ years, 40.5% with no supplementary oxygen charges, 39% received low-flow oxygen, 19% on high-flow oxygen/non-invasive ventilation and 1.5% on invasive mechanical ventilation/ECMO at baseline. During the study period, unadjusted mortality rate was significantly lower for RDV patients at 14 days (11% [95% CI: 11%-12%] vs 15% [15%-16%];p< .0001) and 28 days (18% [17%-18%];p< .0001 vs 22% [22%-23%];p< .0001) as compared to patients that did not receive RDV. After adjusting for baseline and clinical covariates, 14-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (30% lower risk), pre-delta (41%), Delta (23%), Omicron (25%)]. Similarly, 28-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (25%), pre-delta (35%), Delta (21%), Omicron (16%)] (Fig). Conclusion(s): Timely initiation of RDV in first two days of hospital admission demonstrated significant mortality reduction in immunocompromised patients hospitalized with primary diagnosis of COVID-19. RDV demonstrated consistent benefit in an immunocompromised cohort across all variant periods of the pandemic.

Remdesivir Reduces Mortality in Hospitalized Covid-19 Patients across Variant Eras

Background: Clinical management of COVID-19 based on oxygenation requirements continues to change over time as variants of concern (VOC) evolve. We examine hospital all-cause mortality for early hospital RDV use vs. no RDV use across dominant VOC periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): We examined adults with a primary discharge diagnosis of COVID-19 (ICD-10: U07.1) using the Premier Healthcare Database. Patients treated with RDV in the first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using a 1:1 preferential within-hospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Time to mortality at 14-and 28-days was examined for patients with no supplemental oxygen charges (NSOc), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) at baseline. Baseline was defined as first 2 days of hospitalization. Result(s): 164,791 RDV-treated patients were matched to 48,473 unique non-RDV patients. Post-matching balance was achieved across groups with different baseline oxygenation levels and VOC periods. In the matched weighted cohort, 35% required NSOc, 41% LFO, 21% HFO/NIV and 3% IMV/ECMO. During the overall study period (Dec'20-Apr'22), unadjusted mortality rate was significantly lower for RDV patients across all oxygenation levels at 14 days (NSOc: 5.4% vs. 7.3%, LFO: 6.4% vs. 8.8%, HFO/NIV: 16.8% vs. 19.4%, IMV/ECMO: 27.8% vs. 35.3%) and 28 days (NSOc: 8.0% vs. 9.8%, LFO: 9.8% vs. 12.3%, HFO/ NIV: 25.8% vs. 28.3%, IMV/ECMO: 41.4% vs. 50.6%). After adjusting for baseline and clinical covariates, 14-day mortality results showed that RDV significantly lower risk compared to non-RDV across all oxygenation levels at baseline [NSO (26%), LFO (28%), HFO/NIV (17%), IMV/ ECMO (27%)]. Similarly, 28-day mortality results showed that RDV significantly lower risk compared to non-RDV across all oxygenation levels at baseline [NSO (19%), LFO (21%), HFO/NIV (12%), IMV/ECMO (26%)]. This lower mortality risk associated with RDV was consistently observed across all variant periods (Figure). Conclusion(s): Timely initiation of RDV within first two days of hospital admission demonstrated significant mortality reduction in patients hospitalized for a primary diagnosis of COVID-19 across all oxygenation levels. Remdesivir demonstrated consistent benefit across all variant periods of the pandemic to-date.

Molecular Docking and Dynamics of Phytochemicals From Chinese Herbs With SARS-CoV-2 RdRp

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing coronavirus disease 2019 (COVID-19) pandemic. Ancient Chinese herbal formulas are effective for diseases caused by viral infection, and their effects on COVID-19 are currently being examined. To directly evaluate the role of Chinese herbs in inhibiting replication of SARS-CoV-2, we investigated how the phytochemicals from Chinese herbs interact with the viral RNA-dependent RNA polymerase (RdRP). Total 1025 compounds were screened, and then 181compounds were selected for molecular docking analysis. Four phytochemicals licorice glycoside E, diisooctyl phthalate, (-)-medicocarpin, and glycyroside showed good binding affinity with RdRp. The best complex licorice glycoside E/RdRp forms 3 hydrogen bonds, 4 hydrophobic interactions, 1 pair of Pi-cation/stacking, and 4 salt bridges. Furthermore, docking complexes licorice glycoside E/RdRp and diisooctyl phthalate/RdRp were optimized by molecular dynamics simulation to obtain the stable conformation. These studies indicate that they are promising as antivirals against SARS-CoV-2.Copyright © The Author(s) 2022.

Fast In Situ Inactivation of Pathogens in Tubes by Plasma

During the COVID-19 pandemic, the prevailing method for inactivating samples used in nucleic acid detection is a time-consuming process that involves heating the samples in a thermostatic water bath at 56 <inline-formula> <tex-math notation="LaTeX">$

An Analysis of Public Service Satisfaction of Tourists at Scenic Spots: The Case of Xiamen City

The outbreak of the COVID-19 epidemic has greatly hindered the development of the tourism industry. It is urgent for the city to improve the quality of public service in scenic spots, so as to attract more tourists and achieve sustainable development. With a literature review and reference to some guidance, the evaluation indicator system of public service satisfaction of scenic spots was constructed based on the analytic hierarchy process. Then, we distributed two questionnaires to complete the study. The first is the expert questionnaire for the evaluation indicator system. We used YAAHP software to process the questionnaire data and calculated the weight of each indicator, which provided a basis for the following analysis. The second is the questionnaire distributed to tourists of Xiamen. Then, we used the fuzzy comprehensive evaluation method to analyze the satisfaction of public services in scenic spots. The outcomes show that tourists are overall satisfied with the public services of scenic spots in Xiamen. However, there are still some problems, such as lagging information service, inadequate security, and supervision in the scenic spot. Therefore, the city and scenic spots should improve the level of smart tourism service, strengthen the construction of hardware and software facilities, and focus on the protection of tourists' rights and interests. © 2023 by the authors.

Time-varying jumps in China crude oil futures market impacted by COVID-19 pandemic

China crude oil futures market launched in 2018 has become the third-largest global crude oil exchange, indicating its important role in global crude oil markets. Understanding the time-varying jumps of the newly RMB denominated crude oil futures market is not only for the benefit of the market participants in risk management and hedging, but also for the reference of policy-makers in formulating regulation policies, market pricing and financializing energy markets. However, the literature on time-varying jumps in China crude oil futures market is quite scarce compared with existed literature. In this regard, we attempt to study time-varying jumping behaviors of China crude oil futures market impacted by discrete random events, and analyze the sensitivity of jump intensity, jump size and its variance to market volatility and historical volatility, applying the constant and time-varying intensity jump models, based on the daily returns of China crude oil futures market from March 26, 2018 to August 31, 2021. Further, we compare the differential jumps of China crude oil futures market impacted by COVID-19 pandemic. The empirical results have shown that significant time-varying jumping behaviors appear in China crude oil futures market and take on discrete jumping form. The jump intensity is persistent and sensitive to historical volatility of the market. Meanwhile, jump intensity and jump size increase suffered by great public health emergency, and negative jump size arises with high probability. However, the variance of jump size is little sensitive to historical volatility of the market. These findings suggest that the time-varying jumps, especially negative jumps, should be considered for decision-makers and market participants associated with China crude oil futures market. © 2023 Elsevier Ltd

[Related factors of negative conversion time of nucleic acid in children with COVID-19].

Objective: To explore the related factors of negative conversion time (NCT) of nucleic acid in children with COVID-19. Methods: A retrospective cohort study was conducted. A total of 225 children who were diagnosed with COVID-19 and admitted to Changxing Branch of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 3rd to May 31st 2022 were enrolled in the study. The infection age, gender, viral load, basic disease, clinical symptoms and information of accompanying caregivers were retrospectively analyzed. According to age, the children were divided into<3 years of age group and 3-<18 years of age group. According to the viral nucleic acid test results, the children were divided into positive accompanying caregiver group and negative accompanying caregiver group. Comparisons between groups were performed using Mann-Whitney U test or Chi-square test. Multivariate Logistic regression analysis was used to analyze the related factors of NCT of nucleic acid in children with COVID-19. Results: Among the 225 patients (120 boys and 105 girls) of age 2.8 (1.3, 6.2) years, 119 children <3 years and 106 children 3-<18 years of age, 19 cases were diagnosed with moderate COVID-19, and the other 206 cases were diagnosed with mild COVID-19. There were 141 patients in the positive accompanying caregiver group and 84 patients in the negative accompanying caregiver group.Patients 3-<18 years of age had a shorter NCT (5 (3, 7) vs.7 (4, 9) d, Z=-4.17, P<0.001) compared with patients <3 years of age. Patients in the negative accompanying caregiver group had a shorter NCT (5 (3, 7) vs.6 (4, 9) d,Z=-2.89,P=0.004) compared with patients in the positive accompanying caregiver group. Multivariate Logistic regression analysis showed that anorexia was associated with NCT of nucleic acid (OR=3.74,95%CI 1.69-8.31, P=0.001). Conclusion: Accompanying caregiver with positive nucleic acid test may prolong NCT of nucleic acid, and decreased appetite may be associated with prolonged NCT of nucleic acid in children with COVID-19.

Dynamic Incentive Mechanism Design for COVID-19 Social Distancing

As countries enter the endemic phase of COVID-19, people's risk of exposure to the virus is greater than ever. There is a need to make more informed decisions in our daily lives on avoiding crowded places. Crowd monitoring systems typically require costly infrastructure. We propose a crowdsourced crowd monitoring platform which leverages user inputs to generate crowd counts and forecast location crowdedness. A key challenge for crowd-sourcing is a lack of incentive for users to contribute. We propose a Reinforcement Learning based dynamic incentive mechanism to optimally allocate rewards to encourage user participation.

Longest k-tuple Common Sub-Strings

We focus on a new problem that is formulated to find a longest k-tuple of common sub-strings (abbr. k-CSSs) of two or more strings. We present a suffix tree based algorithm for this problem, which can find a longest k-CSS of m strings in O(kmn-{k}) time and O(kmn) space where n is the length sum of the m strings. This algorithm can be used to approximate the longest k-CSS problem to a performance ratio frac{1}{epsilon} in O(kmn-{lceilepsilon krceil}) time for epsilonin(0,1]. Since the algorithm has the space complexity in linear order of n, it will show advantage in comparing particularly long strings. This algorithm proves that the problem that asks to find a longest gapped pattern of non-constant number of strings is polynomial time solvable if the gap number is restricted constant, although the problem without any restriction on the gap number was proved NP-Hard. Using a C++ tool that is reliant on the algorithm, we performed experiments of finding longest 2-CSSs, 3-CSSs and 5-CSSs of 2 14 COVID-19 S-proteins. Under the help of longest 2-CSSs and 3-CSSs of COVID-19 S-proteins, we identified the mutation sites in the S-proteins of two COVID-19 variants Delta and Omicron. The algorithm based tool is available for downloading at https://github.com/lytt0/k-CSS. © 2022 IEEE.

Longest k-tuple Common Sub-Strings

We focus on a new problem that is formulated to find a longest k-tuple of common sub-strings (abbr. k-CSSs) of two or more strings. We present a suffix tree based algorithm for this problem, which can find a longest k-CSS of m strings in O(kmn-{k}) time and O(kmn) space where n is the length sum of the m strings. This algorithm can be used to approximate the longest k-CSS problem to a performance ratio frac{1}{epsilon} in O(kmn-{lceilepsilon krceil}) time for epsilonin(0,1]. Since the algorithm has the space complexity in linear order of n, it will show advantage in comparing particularly long strings. This algorithm proves that the problem that asks to find a longest gapped pattern of non-constant number of strings is polynomial time solvable if the gap number is restricted constant, although the problem without any restriction on the gap number was proved NP-Hard. Using a C++ tool that is reliant on the algorithm, we performed experiments of finding longest 2-CSSs, 3-CSSs and 5-CSSs of 2 14 COVID-19 S-proteins. Under the help of longest 2-CSSs and 3-CSSs of COVID-19 S-proteins, we identified the mutation sites in the S-proteins of two COVID-19 variants Delta and Omicron. The algorithm based tool is available for downloading at https://github.com/lytt0/k-CSS. © 2022 IEEE.

In vitro diagnostics industry in china: Current status and development strategies

In vitro diagnostics plays an important role in the process of disease diagnosis and treatment, which is referred to as the doctor's eye. In the context of the unprecedented increase in people's attention to life and health caused by the COVID-19 pandemic, in vitro diagnostics has showed an explosive growth as an important part of the health industry. For the field of in vitro diagnostics, the developing status of the world and China was summarized. Particularly, the market situation, competition landscape, and national-made situation were analyzed. The problems in the current stage of in-vitro diagnostics industry in China were analyzed, and then the corresponding suggestions and countermeasures were put forward from some aspects, including making a breakthrough in original innovation, strengthening the guarantee of funds, building a complete industrial chain, and strengthening personnel training. © 2022, China Biotechnology Press. All rights reserved.

An immobilization-based, loop-mediated isothermal amplification device for nucleic acid detection of SARS-CoV-2 N gene

Confronting the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), simple, fast and specific non-laboratory SARS-CoV-2 diagnostic tests are urgently required. However, the current nucleic acid assays generally rely on the diagnostic laboratory, trained staff and specialized equipment for execution and analysis, presenting clear limitations in the field detection. Here, we describe a portable and reliable immobilization-based loop-mediated isothermal amplification (LAMP) device which is mobile, without the requirement of any complicated instrument and appropriate for high-throughput testing. This device was constructed by utilizing the interaction between a carboxyl-tagged primer and an amino-tagged substrate, and capable of catching the target sequence in SARS-CoV-2 produced via the immobilization-based LAMP. In this study, the immobilization conditions and immobilized primer structure were explored and optimized. With this proposed device, the analysis result can be obtained rapidly in 30 min with excellent specificity, even if the template is extracted from a complex sample containing pharyngeal swab or human blood. In addition, the device can be applied to detect the nucleic acid of SARS-CoV-2 and various other pathogens, showing attractive potential for rapid and high-throughput detection at airports, railway stations, cold-chain transportations, community hospitals and so on. Therefore, we believe that the immobilization-based LAMP device is an advanced approach to developing a portable, specific, low-cost and high-throughput diagnostic platform.

Research Progress of Non-viral Vector Delivery System for mRNA Vaccines

With the outbreak of COVID-19, the world urgently needs a large number of effective vaccines to deal with this disaster. mRNA vaccines are safe and have short development cycle, which can fill the gap between epidemic diseases and vaccine shortages. So mRNA has become one of the most potential vaccines at present and has attracted attention in the field of infectious diseases and tumors. Technological innovation has greatly improved the shortcomings of mRNA, such as instability and low translation efficiency. However, delivering mRNA to target cells safely and efficiently is still a major challenge that hinders the progress in mRNA research. Hopefully, delivery systems have put forward many effective solutions. This review focuses on the non-viral vector delivery system for mRNA vaccine delivery in vivo, and the application of mRNA in infectious disease and tumor vaccine, in order to provide reference for research and development of mRNA vaccines. © 2022, China Biotechnology Press. All rights reserved.

Posttraumatic stress symptom trajectories of Chinese university students during the first eight months of the COVID-19 pandemic and their association with cognitive reappraisal, expressive suppression, and posttraumatic growth

Objective: To identify the moderating effects of cognitive reappraisal (CR) and expressive suppression (ES) on the relationship between posttraumatic stress (PTS) symptoms and posttraumatic growth (PTG) in university students. Methods: The survey included 1 987 Chinese university students who completed questionnaires on PTS symptoms in February 2020, with three follow-up surveys at two-month intervals until August 2020. We assessed CR and ES at February 2020 and PTG at August 2020. Growth mixture modeling was used to classify the PTS symptom trajectories. Multinomial logistic regression was used to recognize the predictors of class membership. The relationships among PTS symptoms, CR, ES, and PTG were examined using multi-group path analysis. Results: Sex, SARS-CoV-2 infection of a family member or friend, number of siblings, CR, and ES were significantly associated with PTS symptoms. Three latent classes were identified: 'Increasing PTS' (n=205, 10.0%) who had rapid deterioration of PTS symptoms, 'Moderate PTS' (n=149, 8.0%) who had a high level of PTS symptoms at the beginning and slightly increasing, and 'Persistent Minimal PTS' (n=1 633, 82.0%), who had slow resolution of PTS symptoms over time. Male, SARS-CoV-2 infection of a family member or friend, and having a lower CR and a higher ES, were more likely to have 'Increasing PTS'. PTS at February 2020 predicted PTG only in 'Increasing PTS' class, and both CR and ES had moderating effects on the conversion between them. Conclusions: Most students recovered from posttraumatic stress of COVID-19 pandemic, but a small proportion expeienced increasing PTS symptoms, and those with this condition may benefit from emotional regulation intervention.

Birds of a Feather Flock Together: Generating Pornographic and Gambling Domain Names Based on Character Composition Similarity

Cybercriminals often register many pornographic or gambling domains (known as abusive domains) with similar character compositions in bulk to reduce their investment in buying domains and make it easier for clients to remember and spread them. Therefore, this study combines the ideas of text similarity and text generation and proposes an abusive domain generation model based on GRU for rapidly generating new abusive domain names from known ones. Additionally, we develop a two-layer detection system for pornography and gambling domains using fastText and CNN models to obtain an abusive domain dataset for model training and validation. In the end, our detection system identifies pornographic and gambling domains with 99% precision while balancing correctness and speed. By inputting 40,000 random keywords into the abusive domain generation model, we obtained 130,220 online domains that served web pages, of which about 66% were pornographic or gambling domains. The results show that by exploiting cybercriminals' behaviors in registering abusive domain names, such as bulk registration of similar domain names, we can prospectively acquire a large number of new abusive domains based on known ones. This study demonstrates that predicting new abusive domains not only expands the domain blacklist but also allows researchers to target the generated suspicious domains and dispose of them in time before they show abusive behavior.