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1.
J Med Internet Res ; 24(7): e38584, 2022 07 06.
Article in English | MEDLINE | ID: covidwho-1933490

ABSTRACT

BACKGROUND: Multiple types of biomedical associations of knowledge graphs, including COVID-19-related ones, are constructed based on co-occurring biomedical entities retrieved from recent literature. However, the applications derived from these raw graphs (eg, association predictions among genes, drugs, and diseases) have a high probability of false-positive predictions as co-occurrences in the literature do not always mean there is a true biomedical association between two entities. OBJECTIVE: Data quality plays an important role in training deep neural network models; however, most of the current work in this area has been focused on improving a model's performance with the assumption that the preprocessed data are clean. Here, we studied how to remove noise from raw knowledge graphs with limited labeled information. METHODS: The proposed framework used generative-based deep neural networks to generate a graph that can distinguish the unknown associations in the raw training graph. Two generative adversarial network models, NetGAN and Cross-Entropy Low-rank Logits (CELL), were adopted for the edge classification (ie, link prediction), leveraging unlabeled link information based on a real knowledge graph built from LitCovid and Pubtator. RESULTS: The performance of link prediction, especially in the extreme case of training data versus test data at a ratio of 1:9, demonstrated that the proposed method still achieved favorable results (area under the receiver operating characteristic curve >0.8 for the synthetic data set and 0.7 for the real data set), despite the limited amount of testing data available. CONCLUSIONS: Our preliminary findings showed the proposed framework achieved promising results for removing noise during data preprocessing of the biomedical knowledge graph, potentially improving the performance of downstream applications by providing cleaner data.


Subject(s)
COVID-19 , Humans , Knowledge , Neural Networks, Computer , Pattern Recognition, Automated , ROC Curve
2.
J Inflamm Res ; 15: 2181-2198, 2022.
Article in English | MEDLINE | ID: covidwho-1779836

ABSTRACT

The COVID-19 pandemic has caused devastating loss of life and a healthcare crisis worldwide. SARS-CoV-2 is the causative pathogen of COVID-19 and is transmitted mainly through the respiratory tract, where the virus infects host cells by binding to the ACE2 receptor. SARS-CoV-2 infection is associated with acute pneumonia, but neuropsychiatric symptoms and different brain injuries are also present. The possible routes by which SARS-CoV-2 invades the brain are unclear, as are the mechanisms underlying brain injuries with the resultant neuropsychiatric symptoms in patients with COVID-19. Ferroptosis is a unique iron-dependent form of non-apoptotic cell death, characterized by lipid peroxidation with high levels of glutathione consumption. Ferroptosis plays a primary role in various acute and chronic brain diseases, but to date, ferroptosis in COVID-19-related brain injuries has not been explored. This review discusses the mechanisms of ferroptosis and recent evidence suggesting a potential pathogenic role for ferroptosis in COVID-19-related brain injury. Furthermore, the possible routes through which SARS-CoV-2 could invade the brain are also discussed. Discoveries in these areas will open possibilities for treatment strategies to prevent or reduce brain-related complications of COVID-19.

3.
Artif Intell Rev ; 55(3): 1887-1913, 2022.
Article in English | MEDLINE | ID: covidwho-1750743

ABSTRACT

Exploring efficiency approaches to solve the problems of decision making under uncertainty is a mainstream direction. This article explores the rough approximation of the uncertainty information with Pythagorean fuzzy information on multi-granularity space over two universes combined with grey relational analysis. Based on grey relational analysis, we present a new approach to calculate the relative degree or the attribute weight with Pythagorean fuzzy set and give a new descriptions for membership degree and non-membership. Then, this paper proposes a multi-granulation rough sets combined with Pythagorean fuzzy set, including optimistic multi-granulation Pythagorean fuzzy rough set, pessimistic multi-granulation Pythagorean fuzzy rough set and variable precision Pythagorean fuzzy rough set. Several basic properties for the established models are investigated in detail. Meanwhile, we present an approach to solving the multiple-criteria group decision making problems with fuzzy information based on the proposed model. Eventually, a case study of psychological evaluation of health care workers in COVID-19 show the principle of the established model and is utilized to verify the availability. The main contributions have three aspects. The first contribution of an approach of calculating the attribute weight is presented based on Grey Relational Analysis and gives a new perspective for the Pythagorean fuzzy set. Then, this paper proposes a mutli-granulation rough set model with Pythagorean fuzzy set over two universes. Finally, we apply the proposed model to solving the psychological evaluation problems.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325137

ABSTRACT

Background: Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive impact on human health. Due to the absence of antiviral medicine for COVID-19 thus far, it is desperately need to develop the effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, hoping to produce clinical efficacy and decrease the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Baidu Jieduan granule in curing COVID-19. Methods: /design: This multicenter, open-label randomized controlled trial is conducted 300 cases with COVID-19. The patients will be randomly (1:1) divided into treatment group or control group. All cases will receive standard therapy at the same time. The experiment group will receive Baidu Jieduan granule treatment twice a day for 14 days. The outcomes are assessed at baseline and at 3, 5, 7, 14 days after treatment initiation. The primary outcome is the rate of symptom (fever, fatigue, and coughing) recovery. Adverse events (AEs) will be monitored throughout the trial. Discussion: The study will provide a high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan granule in treatment of moderate COVID-19, and also enrich the theory and practice of TCM in treating COVID-19. Trial registration : Chinese Clinical Trial Registry, ChiCTR2000029869. Registered on 15 February 2020

5.
Antioxidants (Basel) ; 10(10)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1480546

ABSTRACT

To investigate the effects of tannins (TA) on porcine oocyte in vitro maturation (IVM), different concentrations of TA (0, 1, 10 and 100 µg/mL) were supplemented with a maturation medium and the COCs and subsequent embryonic development were examined. The results showed that 10 µg/mL TA significantly improved the cumulus expansion index (CEI), cumulus-expansion-related genes (PTGS1, PTGS2, PTX-3, TNFAIP6 and HAS2) expression and blastocyst formation rates after parthenogenetic activation (PA), in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) compared to the control groups, but not oocyte nuclear maturation. Nevertheless, 10 µg/mL TA dramatically enhanced the mRNA expression of oocyte-development-related genes (BMP15, GDF9, CDC2 and CYCLIN B1), GSH, ATP, SOD1, PGC1α, BMP15, GDF9 and CDC2 levels and reduced intracellular ROS level in porcine oocytes. These results indicated that porcine oocyte cytoplasmic maturation was improved by 10 µg/mL TA treatment during IVM. In contrast, a high concentration of TA (100 µg/mL) significantly decreased the CEI and PTGS1, PTGS2, PTX-3 and HAS2 mRNA expressions in cumulus cells, and reduced oocyte nuclear maturation and the total cell numbers/blastocyst. In general, these data showed that 10 µg/mL TA supplementation has beneficial effects on oocyte cytoplasmic maturation and subsequent embryonic development in pigs.

6.
Dev Cogn Neurosci ; 52: 101020, 2021 12.
Article in English | MEDLINE | ID: covidwho-1469834

ABSTRACT

The ongoing Chinese Color Nest Project (CCNP) was established to create normative charts for brain structure and function across the human lifespan, and link age-related changes in brain imaging measures to psychological assessments of behavior, cognition, and emotion using an accelerated longitudinal design. In the initial stage, CCNP aims to recruit 1520 healthy individuals (6-90 years), which comprises three phases: developing (devCCNP: 6-18 years, N = 480), maturing (matCCNP: 20-60 years, N = 560) and aging (ageCCNP: 60-84 years, N = 480). In this paper, we present an overview of the devCCNP, including study design, participants, data collection and preliminary findings. The devCCNP has acquired data with three repeated measurements from 2013 to 2017 in Southwest University, Chongqing, China (CCNP-SWU, N = 201). It has been accumulating baseline data since July 2018 and the second wave data since September 2020 in Chinese Academy of Sciences, Beijing, China (CCNP-CAS, N = 168). Each participant in devCCNP was followed up for 2.5 years at 1.25-year intervals. The devCCNP obtained longitudinal neuroimaging, biophysical, social, behavioral and cognitive data via MRI, parent- and self-reported questionnaires, behavioral assessments, and computer tasks. Additionally, data were collected on children's learning, daily life and emotional states during the COVID-19 pandemic in 2020. We address data harmonization across the two sites and demonstrated its promise of characterizing the growth curves for the overall brain morphometry using multi-center longitudinal data. CCNP data will be shared via the National Science Data Bank and requests for further information on collaboration and data sharing are encouraged.


Subject(s)
COVID-19 , Pandemics , Brain , Humans , Longitudinal Studies , Neuroimaging , SARS-CoV-2
7.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Article in English | MEDLINE | ID: covidwho-1428995

ABSTRACT

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.


Subject(s)
Aminohydrolases/genetics , COVID-19/genetics , Formate-Tetrahydrofolate Ligase/genetics , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Multienzyme Complexes/genetics , Pandemics , Aminohydrolases/antagonists & inhibitors , Animals , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Cell Line , Chiroptera/genetics , Chiroptera/virology , Formate-Tetrahydrofolate Ligase/antagonists & inhibitors , Humans , Methylenetetrahydrofolate Dehydrogenase (NADP)/antagonists & inhibitors , Minor Histocompatibility Antigens , Multienzyme Complexes/antagonists & inhibitors , RNA Viruses/genetics , SARS-CoV-2/pathogenicity , Virus Replication/genetics
8.
Trials ; 22(1): 476, 2021 Jul 22.
Article in English | MEDLINE | ID: covidwho-1322945

ABSTRACT

BACKGROUND: Currently, coronavirus disease-2019 (COVID-19) is continuously and rapidly circulating, resulting in serious and extensive effects on human health. Due to the absence of antiviral medicine for COVID-19 thus far, there is a desperate need to develop effective medicine. Traditional Chinese medicine (TCM) has been widely applied in the treatment of epidemic diseases in China, with the aim of achieving clinical efficacy and decreasing the use of antibiotics and glucocorticoids. The aim of this study was to evaluate the efficacy and safety of Baidu Jieduan granules in treating COVID-19. METHODS/DESIGN: This multicentre, open-label, randomized controlled trial will be conducted in 300 patients with COVID-19. The patients will be randomly (1:1) divided into a treatment group and a control group. All patients will receive standard therapy at the same time. Patients in the experimental group will receive Baidu Jieduan granule treatment twice a day for 14 days. The outcomes will be assessed at baseline and at 3, 5, 7 and 14 days after treatment initiation. The primary outcome will be the rate of symptom (fever, fatigue and coughing) recovery. Adverse events (AEs) will be monitored throughout the trial. DISCUSSION: The study will provide high-quality clinical evidence to support the efficacy and safety of Baidu Jieduan granules in the treatment of moderate COVID-19, and enrich the theory and practice of TCM in treating COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000029869 . Registered on 15 February 2020.


Subject(s)
COVID-19 , Medicine, Chinese Traditional , Antiviral Agents/therapeutic use , China , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
9.
Cell Discov ; 6(1): 76, 2020 Oct 29.
Article in English | MEDLINE | ID: covidwho-904771

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with more than 33 million patients diagnosed, taking more than a million lives. Abundant mutations were observed but the functional consequences of these mutations are largely unknown. We report the mutation spectrum, replication dynamics, and infectivity of 11 patient-derived viral isolates in diverse cell lines, including the human lung cancer cell line Calu-3. We observed 46 mutations, including 9 different mutations in the spike gene. Importantly, these viral isolates show significant and consistent variations in replication dynamics and infectivity in tested cell lines, up to a 1500-fold difference in viral titers at 24 h after infecting Calu-3 cells. Moreover, we show that the variations in viral titers among viral isolates are positively correlated with blood clotting function but inversely correlated with the amount of red blood cell and hemoglobin in patients. Therefore, we provide direct evidence that naturally occurring mutations in SARS-CoV-2 can substantially change its replication dynamics and infectivity in diverse human cell lines, with clinical implications in vivo.

10.
Trials ; 21(1): 568, 2020 Jun 24.
Article in English | MEDLINE | ID: covidwho-612407

ABSTRACT

BACKGROUND: Currently, coronavirus disease 2019 (COVID-19) is continuously and rapidly circulating, causing heavy damage on public health. No effective antiviral treatment has been proved thus far. Traditional Chinese medicine (TCM) has been widely applied in the treatment of a variety of infection diseases in China, hoping to produce clinical effects and reduce the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Shenhuang granule in treatment of severe COVID-19. METHODS/DESIGN: This multicenter, open-label randomized controlled trial is conducted in 160 participants with severe COVID-19. The participants will be randomly (1:1) divided into treatment group or control group. All participants are given standard therapy at the same time. The experiment will receive Shenhuang granule treatment twice a day for 14 days. The clinical indicators of patients will be assessed at baseline and at 3, 5, 7, and 14 days after treatment initiation. The primary outcome is 14-day clinical outcome. Adverse events will be monitored throughout the trial. DISCUSSION: This will be the first randomized controlled trial, which evaluate the effect of Shenhuang granule in patients with severe COVID-19 in China. The results of this trial may not only provide evidence-based recommendations to clinicians to treat severe COVID-19, but also enrich the theory and practice of TCM in treating infectious diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000029777. Registered on 13 February 2020.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Pneumonia, Viral/drug therapy , Randomized Controlled Trials as Topic , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Drugs, Chinese Herbal/adverse effects , Humans , Middle Aged , Outcome Assessment, Health Care , Pandemics , Research Design , SARS-CoV-2 , Young Adult
11.
Microbes Infect ; 22(6-7): 236-244, 2020.
Article in English | MEDLINE | ID: covidwho-244991

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to sweep the world, causing infection of millions and death of hundreds of thousands. The respiratory disease that it caused, COVID-19 (stands for coronavirus disease in 2019), has similar clinical symptoms with other two CoV diseases, severe acute respiratory syndrome and Middle East respiratory syndrome (SARS and MERS), of which causative viruses are SARS-CoV and MERS-CoV, respectively. These three CoVs resulting diseases also share many clinical symptoms with other respiratory diseases caused by influenza A viruses (IAVs). Since both CoVs and IAVs are general pathogens responsible for seasonal cold, in the next few months, during the changing of seasons, clinicians and public heath may have to distinguish COVID-19 pneumonia from other kinds of viral pneumonia. This is a discussion and comparison of the virus structures, transmission characteristics, clinical symptoms, diagnosis, pathological changes, treatment and prevention of the two kinds of viruses, CoVs and IAVs. It hopes to provide information for practitioners in the medical field during the epidemic season.


Subject(s)
Coronavirus Infections/diagnosis , Influenza, Human/diagnosis , Pneumonia, Viral/diagnosis , Respiratory Tract Infections/virology , Seasons , Age Factors , Animals , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Humans , Influenza A virus/pathogenicity , Influenza, Human/complications , Influenza, Human/prevention & control , Influenza, Human/transmission , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Pandemics/prevention & control , Pneumonia, Viral/complications , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Public Health , Respiratory Tract Infections/transmission , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/virology
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