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1.
Enfermedades infecciosas y microbiologia clinica (English ed.) ; 41(1):29-32, 2023.
Article in English | ScienceDirect | ID: covidwho-2165250

ABSTRACT

Introduction COVID-19 is a worldwide public health threat. Diagnosis by RT-PCR has been employed as the standard method to confirm viral infection. Sample pooling testing can optimize the resources by reducing the workload and reagents shortage, and be useful in laboratories and countries with limited resources. This study aims to evaluate SARS-CoV-2 detection by sample pooling testing in comparison with individual sample testing. Materials and methods We created 210 pools out of 245 samples, varying from 4 to 10 samples per pool, each containing a positive sample. We conducted detection of SARS-CoV-2-specific RdRp/E target sites. Results Pooling of three samples for SARS-CoV-2 detection might be an efficient strategy to perform without losing RT-PCR sensitivity. Conclusions Considering the positivity rate in Dominican Republic and that larger sample pools have higher probabilities of obtaining false negative results, the optimal sample size to perform a pooling strategy shall be three samples. Resumen Introducción La COVID-19 es una amenaza de salud pública mundial. La RT-PCR es el método estándar para confirmar la infección. La estrategia de pruebas de muestras agrupadas puede reducir la carga de trabajo y la escasez de reactivos, y ser útil en países con escasos recursos. Evaluamos la detección del SARS-CoV-2 mediante esta estrategia en comparación con pruebas individuales. Materiales y métodos Creamos 210 grupos de 245 muestras, de 4 a 10 muestras por grupo, cada uno con una muestra positiva. Realizamos extracción de ARN y qRT-PCR para detectar la presencia de la diana RdRp/E. Resultados La combinación de hasta 3 muestras para la detección del SARS-CoV-2 podría ser una estrategia eficaz sin perder la sensibilidad. Conclusiones Considerando la tasa de positividad en República Dominicana y que los grupos con más muestras tienen mayor probabilidad de obtener resultados falsos negativos, el tamaño óptimo para realizar esta estrategia es de 3 muestras.

2.
Global Media Journal ; 20(54):1-6, 2022.
Article in English | ProQuest Central | ID: covidwho-2164720

ABSTRACT

Internet memes can be shared from one virtual social networking site to another. The natural selection of behavior and operant conditioning is a joint product in the evolutionary system of learning. The unique feature of Internet memes is that they are 'half-baked joke', internet users need to understand with their conscious (person's awareness). Internet memes are highly visual and intersexual;they are not only still images, but they also consist videos, GIF (Graphic Interchange Format), editorial cartoons, animated image or songs clip with image or punch line or aphorism quotes, catchphrases of movies or statement without added text [3, 4].

3.
Frontiers in Molecular Biosciences ; 9, 2022.
Article in English | Web of Science | ID: covidwho-2163057

ABSTRACT

Notably, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a tight relationship with the immune system. Human resistance to COVID-19 infection comprises two stages. The first stage is immune defense, while the second stage is extensive inflammation. This process is further divided into innate and adaptive immunity during the immune defense phase. These two stages involve various immune cells, including CD4(+) T cells, CD8(+) T cells, monocytes, dendritic cells, B cells, and natural killer cells. Various immune cells are involved and make up the complex and unique immune system response to COVID-19, providing characteristics that set it apart from other respiratory infectious diseases. In the present study, we identified cell markers for differentiating COVID-19 from common inflammatory responses, non-COVID-19 severe respiratory diseases, and healthy populations based on single-cell profiling of the gene expression of six immune cell types by using Boruta and mRMR feature selection methods. Some features such as IFI44L in B cells, S100A8 in monocytes, and NCR2 in natural killer cells are involved in the innate immune response of COVID-19. Other features such as ZFP36L2 in CD4(+) T cells can regulate the inflammatory process of COVID-19. Subsequently, the IFS method was used to determine the best feature subsets and classifiers in the six immune cell types for two classification algorithms. Furthermore, we established the quantitative rules used to distinguish the disease status. The results of this study can provide theoretical support for a more in-depth investigation of COVID-19 pathogenesis and intervention strategies.

4.
BioMed Research International ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-2162052

ABSTRACT

Background. Lung squamous cell carcinoma (LUSC) has poor survival prognosis and few clinical treatment options. We urgently need to explore new therapeutic drugs in clinical practice. Cepharanthine (CEP) has been shown to have anticancer effects in several tumors, but the mechanism of CEP in treating LUSC has not been reported. Methods. SwissTargetPrediction, PharmMapper, and GeneCards were used to identify targets of CEP and LUSC. Further topological analysis was used to obtain hub genes via Cytoscape. Molecular docking was carried out to verify the combination of CEP with hub targets. Based on bioinformatics, we first analyzed the expression and survival of hub targets in LUSC and further analyzed the correlation between hub targets and cancer stemness, immune cell infiltration, and tumor mutation burden (TMB). Results. A total of 41 targets were identified. Further topological analysis identified 6 hub genes: AURKA, CCNA2, CCNE1, CDK1, CHEK1, and PLK1. Molecular docking analysis showed that CEP had stable binding to all these 6 target proteins. In-depth bioinformatics analysis of these 6 targets showed that high expression of these targets were positively correlated with cancer stemness index and negatively correlated with tumor infiltrating immune cells. In immune subtype analysis, the expressions of these targets were significantly decreased in inflammatory tumors. In addition, we also found that the expressions of these targets were positively correlated with TMB. Conclusion. Based on multidisciplinary analysis, we preliminarily identified potential targets of CEP for LUSC treatment and suggested that CEP may play a role in regulating LUSC stemness.

5.
13th International Conference on Information and Communication Technology Convergence, ICTC 2022 ; 2022-October:664-667, 2022.
Article in English | Scopus | ID: covidwho-2161413

ABSTRACT

Viral escape analysis has become significantly important area of research due to an unpredictable nature of frequent gene mutations in viruses. Mutation in genes of virus is posing frequent threats to humanity from time to time as the drug or vaccines developed for virus becomes less effective against the mutated viruses. In this study, we proposed a novel method for identifying significant mutational viral sequences from non-significant mutational sequences using the escape mutant information of the SARS-COV-2 viral sequences with supervised transformer based binary classification technique. With our novel approach, we achieved model classification;validation and test accuracy of 0.983, 0.9014 respectively on the split size of 0.7-0.15-0.15 used for train, validation, and test dataset respectively. The developed model would be helpful for computationally identifying the significant mutational sequences without in-vivo experiments. © 2022 IEEE.

6.
Human Gene ; 35:201135, 2023.
Article in English | ScienceDirect | ID: covidwho-2158925

ABSTRACT

COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. Patients infected with SARS-CoV-2 exhibit heterogeneous symptoms that pose pragmatic hurdles for implementing appropriate therapy and management of the COVID-19 patients and their post-COVID complications. Thus, understanding the impact of infection severity at the molecular level in the host is vital to understand the host response and accordingly it's precise management. In the current study, we performed a comparative transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis employing Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1224 significantly upregulated genes (logFC≥ 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC≤ −1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) revealed the upregulation of anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc.;while, downregulation of lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. Conclusively, these findings provide insight into the enhanced susceptibility of severe COVID-19 patients to other health comorbidities including non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. owing to the activation of biological processes, pathways and molecular functions associated with them. We anticipate this study will facilitate the researchers in finding efficient therapeutic targets and eventually the clinicians in management of COVID-19 patients and post-COVID-19 effects in them.

7.
Advances in Virus Research, Vol. 112 ; 112:1-29, 2022.
Article in English | Web of Science | ID: covidwho-2156882

ABSTRACT

Reverse genetics is the prospective analysis of how genotype determines phenotype. In a typical experiment, a researcher alters a viral genome, then observes the phenotypic outcome. Among RNA viruses, this approach was first applied to positive-strand RNA viruses in the mid-1970s and over nearly 50 years has become a powerful and widely used approach for dissecting the mechanisms of viral replication and pathogenesis. During this time the global health importance of two virus groups, flaviviruses (genus Flavivirus, family Flaviviridae) and betacoronaviruses (genus Betacoronavirus, subfamily Orthocoronavirinae, family Coronaviridae), have dramatically increased, yet these viruses have genomes that are technically challenging to manipulate. As a result, several new techniques have been developed to overcome these challenges. Here I briefly review key historical aspects of positive-strand RNA virus reverse genetics, describe some recent reverse genetic innovations, particularly as applied to flaviviruses and coronaviruses, and discuss their benefits and limitations within the larger context of rigorous genetic analysis.

8.
Journal of Pure and Applied Microbiology ; 16(4):2619-2630, 2022.
Article in English | Web of Science | ID: covidwho-2156009

ABSTRACT

The coronavirus disease (COVID-19) pandemic has expanded the use of chlorhexidine digluconate, a biocide frequently used in hospitals, to inhibit the spread of infection. Genes responsible for resistance against the quaternary ammonium compound qac in Staphylococcus aureus isolates have been shown to confer tolerance to a number of biocidal chemicals, including chlorhexidine. The aim of this study was to determine the occurrence of antiseptic resistance genes (qacA/B and qacC) in clinical isolates of methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). The study also aimed to investigate the association between the presence of the mecA, qacA/B, and qacC genes in MRSA isolates and the susceptibility of the isolates to chlorhexidine to evaluate its future use in the Theodor Bilharz Research Institute (TBRI) hospital, following the Centers for Disease Control and Prevention recommendations for patients with MRSA. S. aureus isolates (n = 100) were collected from inpatients and outpatients at TBRI. A minimal inhibitory concentration of chlorhexidine was also detected. Polymerase chain reaction was used to detect the mecA, qacA/B, and qacC genes. The results revealed that 84% of S. aureus isolates were MRSA. MRSA (61.9%) and MSSA (68.8%) isolates were susceptible to chlorhexidine. The qacA/B gene was more dominant, being detected in 34%, while qacC was detected in only 5% of S. aureus isolates. All S. aureus isolates with reduced susceptibility to chlorhexidine harbored either the qacA/B or qacC genes. The clinical use of chlorhexidine may continue to increase, emphasizing the significance of continuous caution underlining the emergence of new clones with reduced susceptibility and avoiding antiseptic misuse.

9.
Health Affairs ; 41(12):1763-4, 2022.
Article in English | ProQuest Central | ID: covidwho-2154309

ABSTRACT

Population health strategies tend to focus on individuals' behaviors, genes, or health care access, yet it is well established that socioecological conditions are fundamental to health and strongly influenced by policy. In the Us, health and other policies continue to be shaped by the country's unique legacy of racial and economic segregation. Policy reform must be at the center of population health. This requires communities to have power. We present theoretical and empirical research linking community power and health, and we share an example of our work in which communities organized to hold policy makers accountable for advancing health equity in the distribution of parks. We call this a democratic approach to health improvement and discuss how population health, whether part of public health, philanthropy, or health care, needs to focus on community power and include funding for power-building organizations. We conclude that achieving health equity requires enhancing the quality of democracy.

10.
2022 IEEE Biomedical Circuits and Systems Conference, BioCAS 2022 ; : 510-514, 2022.
Article in English | Scopus | ID: covidwho-2152430

ABSTRACT

The sheer amount of genomic sequencing data generated daily that requires time-sensitive processing for downstream analysis calls for accelerating the bioinformatics pipelines. Previous studies mainly have attempted accelerating the alignment stage, leaving the other pipeline stages as performance bottlenecks. In this work, we propose the first FPGA-based framework dubbed FAST to accelerate the stages that deal with sequence trimming, in particular adapter and primer removal. FAST supports a comprehensive set of functionalities and is convenient to use by operating on standard genomics data formats. The proposed framework is fully configurable and supports variety of runtime settings. It surpasses the state-of-the-art widely-used adapter trimmer (fastp) by 4.7×-29.4× speed-up, with 10.1×-54.9 less energy, respectively. For clipping primers, which with current existing tool (iVar) accounts for ∼50% of SARS-CoV-2 analysis pipeline, FAST achieves up to 62× speed-up in trimming the virus sequences with a low FPGA resource utilization of 12%. © 2022 IEEE.

11.
Front Immunol ; 13: 984553, 2022.
Article in English | MEDLINE | ID: covidwho-2142012

ABSTRACT

SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) respectively, from three different groups including individuals with moderate (nM), or severe disease with (vS) or without (nS) detectable plasma viral load. Whole transcriptome analysis demonstrated that all seven immune cell subsets were associated with disease severity regardless of cell type. Supervised clustering analysis demonstrated that mDCs and pDCs gene signatures could distinguish disease severity. Notably, transcriptional signatures of the vS group were enriched in pathways related to DNA repair, E2F targets, and G2M checkpoints; in contrast, transcriptional signatures of the nM group were enriched in interferon responses. Moreover, we observed an impaired induction of interferon responses accompanied by imbalanced cell-intrinsic immune sensing and an excessive inflammatory response in patients with severe disease (nS and vS). In sum, our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in COVID-19 patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Viremia , Immunity, Innate , Interferons/metabolism
12.
Front Immunol ; 13: 918817, 2022.
Article in English | MEDLINE | ID: covidwho-2141935

ABSTRACT

Most transcriptomic studies of SARS-CoV-2 infection have focused on differentially expressed genes, which do not necessarily reveal the genes mediating the transcriptomic changes. In contrast, exploiting curated biological network, our PathExt tool identifies central genes from the differentially active paths mediating global transcriptomic response. Here we apply PathExt to multiple cell line infection models of SARS-CoV-2 and other viruses, as well as to COVID-19 patient-derived PBMCs. The central genes mediating SARS-CoV-2 response in cell lines were uniquely enriched for ATP metabolic process, G1/S transition, leukocyte activation and migration. In contrast, PBMC response reveals dysregulated cell-cycle processes. In PBMC, the most frequently central genes are associated with COVID-19 severity. Importantly, relative to differential genes, PathExt-identified genes show greater concordance with several benchmark anti-COVID-19 target gene sets. We propose six novel anti-SARS-CoV-2 targets ADCY2, ADSL, OCRL, TIAM1, PBK, and BUB1, and potential drugs targeting these genes, such as Bemcentinib, Phthalocyanine, and Conivaptan.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/drug therapy , COVID-19/genetics , Cell Line , Humans , Leukocytes, Mononuclear , Transcriptome
13.
Heliyon ; 8(11): e11724, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2130936

ABSTRACT

There is emerging evidence that age-dependent differences in susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlate with stronger innate immune response in the upper respiratory tract in children compared to adults. The efficient induction of interferon (IFN) alpha and beta (α and ß) signaling, and interferon-stimulated genes (ISGs) is fundamental to the host antiviral response. In-silico transcriptomic analyses was conducted to determine the expression levels of IFN α/ß pathway genes as well as 524 human ISGs in upper and lower airways of children and adults at baseline and post respiratory infections including coronavirus disease 2019 (COVID-19). To validate our in-silico analysis, we conducted qRT-PCR to measure ISGs levels in children and adult's nasal epithelial samples. At baseline, children had significantly higher levels of IFN α/ß and ISGs genes compared to adults. More distinction was also seen in bronchial compared to nasal basal levels. Children nasal epithelial cells exhibited superior antiviral IFN α/ß and associated ISGs response following ex-vivo poly (I:C) treatment model, and in clinical samples of SARS-CoV-2 infected patients. This was also confirmed in nasal epithelial samples using qRT-PCR validation. No gender-based difference in type I IFN levels across both age groups were observed. Understanding the biological basis for children resistance against severe COVID-19 is a challenge that has substantial clinical importance. More mechanistic studies are needed to carefully quantify how much of early IFN levels is needed to bypass the viral evasion mechanism and prevent its further replication and dissemination to lower airways and the rest of the body.

14.
Revista Cientifica Multidisciplinar RECIMA21 ; 3(8), 2022.
Article in Portuguese | CAB Abstracts | ID: covidwho-2146697

ABSTRACT

The objective of this work was to obtain the perception of the population about: (1) the importance of immunization;(2) knowledge of methodologies (genetic manipulation) used for vaccine production;(3) acceptance of the vaccine against COVID-19. To this end, an online questionnaire produced via Google Forms was made available. This form was disseminated in various virtual environments such as academic and social media. Over six months, 353 responses were obtained. In this survey, responses were obtained from participants residing in 14 states in Brazil. Considering the investigation about vaccines, the results showed that most (90.6%) have already been vaccinated, as well as their families, and understand the importance of immunization. The techniques of genetic manipulation are complex and more widespread in the scientific environment, so it was observed that a large part of the interviewed population does not have an opinion on the subject. The research showed that because of the state of calamity caused by the pandemic, people had urgency in immunization, even with distrust in aspects such as efficiency. Currently, it is clear that vaccination does not prevent infection with the virus, but minimizes the damage caused by the infection. Data from the Ministry of Health show that the number of cases and deaths has reduced by more than 40%, showing once again the effectiveness and necessity of immunization of the population.

15.
Istanbul Tip Fakultesi Dergisi ; 85(3):344-354, 2022.
Article in English | Scopus | ID: covidwho-2146254

ABSTRACT

Objective: In the research conducted during the ongoing pandemic period, it has been determined that IRF7, TBK1, IFNAR1, IFNAR2, and TLR3 immunity genes play an important role in the predisposition to SARS-CoV-2 infection. However, there is no information about variants of these genes in the Turkish population. The aim of this study was to determine the variants specific to the our study’s population in these genes that predispose to infections and to compare them with other populations. Materials and Methods: The variants in the exonic and flanking intronic regions of these five genes were analysed in in-house whole-exome sequencing data of 139 unrelated non-anonymous individuals. The allele frequencies of variants were compared with other population datasets. The DysGeNet database was used to determine human diseases associated with these genes. Results: In our population, gene variants were detected including 28 in IRF7, 16 in TBK1, 18 in IFNAR1, 19 in IFNAR2, and 9 in TLR3. The allele frequencies of variants were compared with other populations. Of these variants, 9 were determined to be novel, previously unreported variants. It was shown that these genes are mainly involved in cancer and infectious diseases, especially viral infections according to the DisGeNET database. Conclusion: The determination of immunity gene variants specific to our population and the variability of allele frequencies among populations suggest that it may cause differences in immune response, especially to SARS-CoV-2 infection. In this study, preliminary information was obtained for studies that will investigate the relationship between the clinical manifestations of infectious diseases and immunity gene variants. ©PMA.

16.
Journal of Hainan Medical University ; 27(1):1-5, 2021.
Article in Chinese | GIM | ID: covidwho-2145379

ABSTRACT

Objective:To investigate the changes of Mg2+ levels in serum and peripheral blood mononuclear cells (PB-MCs) of patients with COVID-19 and its effects on the functions of CD8+ T lymphocytes and NK cells.

17.
Journal of Hainan Medical University ; 26(19):1446-1454, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-2145375

ABSTRACT

Objective: To clarify potential annti-inflammatory molecular mechanism and signal pathway of XuanBaiChengQi(XBCQ) Decoction in treatment on COVID-19.

18.
Jundishapur Journal of Microbiology ; 15(1):1706-1718, 2022.
Article in English | GIM | ID: covidwho-2125226

ABSTRACT

Background and Objective: Despite of the COVID-19 pathogenesis and severity of the infection still completely unclear, but the human's genetic variation in gene participate in SARS-COV2 infectivity, inflammation and immunity response might have a great association with severity of clinical out-comes of nCoV-2019 disease. This study evaluates the impact of CD14-159 and IL4 genotypes on the severity of SARS-COV2 infection. Materials and method: This research have been done with one hundred individuals from Al-Qadisiyah governorate in Iraq, whom infected with SARA-COV2. The patients have been divided into three subgroups according to severity of clinical symptoms;mild, moderate and severe groups. RFLP-PCR technique has been worked out to specify genes polymorphisms.

19.
Protein Expression and Purification ; 201, 2023.
Article in English | Web of Science | ID: covidwho-2122740

ABSTRACT

Heterologous expression systems have been used as a powerful experimental strategy to study the function of many proteins, particularly ion transporters. For this experiment, it is fundamental to prepare an expression vector encoding a protein of interest. However, we encountered problems in vector preparation of the voltage sensor domain (VSD) of murine sperm-specific Na+/H+ exchanger (sNHE) due to its severe toxicity to bacteria. We overcame the problems by insertion of an amber stop codon or a synthetic intron into the coding sequence of the VSD in the expression vectors. Both methods allowed us to express the protein of interest in HEK293 cells (combined with a stop codon suppression system for amber codon). The VSD of mouse sNHE generates voltage-dependent outward ionic currents, which is a probable cause of toxicity to bacteria. We propose these two strategies as practical solutions to study the function of any protein toxic to bacteria.

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