Inhibiting Cardiac Autophagy Suppresses Zika Virus Replication

alexandrossfakianakis shared this article with you from Inoreader Inhibiting Cardiac Autophagy Suppresses Zika Virus Replication via Journal of Medical Virology Abstract Zika Virus (ZIKV) infection is a global threat. Other than the congenital neurological disorders it causes, ZIKV infection has been reported to induce cardiac complications. However, the precise treatment plans are unclear. Thus, illustrating the pathogenic mechanism of ZIKV in the heart is critical to providing effective prevention and treatment of ZIKV infection. The mechanism of autophagy has been reported recently in Dengue virus infection. Whether or not autophagy participates in ZIKV infection and its role remains unrevealed. This study successfully established the in vitro cardiomyocytes and in vivo mouse models of ZIKV infection to investigate the involvement of autophagy in ZIKV infection. The results showed that ZIKV infection is both time and gradient-dependent. The key autophagy protein, LC3B, increased remarkably after ZIKV infection. Meanwhile, autophagic flux was detected by immunofluorescence. Applying autophagy inhibitors decreased the LC3B levels. F urthermore, the number of viral copies was quantified to evaluate the influence of autophagy during infection. We found that autophagy was actively involved in the ZIKV infection and the inhibition of autophagy could effectively reduce the viral copies, suggesting a potential intervention strategy for reducing ZIKV infection and the undesired complications caused by ZIKV. This article is protected by copyright. All rights reserved. View on Web

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Needle‐free injection system delivery of ZyCoV‐D DNA vaccine demonstrated improved immunogenicity and protective efficacy in Rhesus macaques against SARS‐CoV‐2

alexandrossfakianakis shared this article with you from Inoreader Needle‐free injection system delivery of ZyCoV‐D DNA vaccine demonstrated improved immunogenicity and protective efficacy in Rhesus macaques against SARS‐CoV‐2 via Journal of Medical Virology Abstract The apprehension of needles related to injection site pain, risk of transmitting the blood borne pathogens and effective mass immunization have led to the development of needle free injection system (NFIS). Here, we evaluated the efficacy of the NFIS and needle injection system (NIS) for the delivery and immunogenicity of DNA vaccine candidate ZyCOV-D in Rhesus macaques against SARS-CoV-2 infection. Briefly, twenty rhesus macaques were divided into five groups (4 animals each) i.e., I (1 mg dose by NIS), II (2mg dose by NIS), III [1mg dose by NFIS], IV (2mg dose by NFIS) and V (phosphate-buffer saline). The macaques were immunized with the vaccine candidates/PBS intradermally on day 0, 28 and 56. Subsequently, the animals were challenged with live SARS-CoV-2 after 15 weeks of the first immunization. Blood, nasal swab, throat swab, and bronchoalveolar lavage fluid specimens were collected on 0, 1, 3, 5 and 7 days post infection from each animal to determine immune response and vira l clearance. Amongst all the five groups, 2mg dose by NFIS elicited significant titers of IgG and neutralizing antibody after immunization with enhancement in their titers post virus challenge. Besides this, it also induced increased lymphocyte proliferation and cytokine response. The minimal viral load post-SARS-CoV-2 challenge and significant immune response in the immunized animals demonstrated efficiency of NFIS in delivering 2mg ZyCOV-D vaccine candidate. This article is protected by copyright. All rights reserved. View on Web

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Complete genome analyses of G12P[8] rotavirus strains from hospitalized children

alexandrossfakianakis shared this article with you from Inoreader Complete genome analyses of G12P[8] rotavirus strains from hospitalized children in Surabaya, Indonesia, 2017–2018 via Journal of Medical Virology ABSTRACT Rotavirus A (RVA) is a major viral cause of acute gastroenteritis worldwide. G12 RVA strains have emerged globally since 2007. There has been no report of the whole genome sequences of G12 RVAs in Indonesia. We performed the complete genome analysis by the next-generation sequencing of five G12 strains from hospitalized children with acute gastroenteritis in Surabaya from 2017–2018. All five G12 strains were Wa-like strains (G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) and were clustered into lineage-III of VP7 gene phylogenetic tree. STM430 sample was observed as a mixed-infection between G12 and G1 strains: G12/G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. A phylogenetic tree analysis revealed that all five Indonesian G12 strains (SOEP379, STM371, STM413, STM430, and STM433) were genetically close to each other in all 11 genome segments with 98.0-100% nucleotide identities, except VP3 and NSP4 of STM430, suggesting that these strains have originated from a similar ancestral G12 RVA. The VP3 and NSP4 genome segments of STM430-G12P[8] were separated phylogenetically from those of the other four G12 strains, probably due to intra-genotype reassortment between the G12 and G1 Wa-like strains. The change from G12P[6] lineage-II in 2007 to G12P[8] lineage-III 2017–2018 suggests the evolution and diversity of G12 RVAs in Indonesia over the past approximately 10 years. This article is protected by copyright. All rights reserved. View on Web

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Machine learning‐driven blood transcriptome‐based discovery of SARS‐CoV‐2 specific severity biomarkers

alexandrossfakianakis shared this article with you from Inoreader Machine learning‐driven blood transcriptome‐based discovery of SARS‐CoV‐2 specific severity biomarkers via Journal of Medical Virology ABSTRACT The COVID-19 pandemic, caused by rapidly evolving variants of SARS-CoV-2, continues to be a global health threat. SARS-CoV-2 infection symptoms often intersect with other nonsevere respiratory infections, making early diagnosis challenging. There is an urgent need for early diagnostic and prognostic biomarkers to predict severity and reduce mortality when a sudden outbreak occurs. This study implemented a novel approach of integrating bioinformatics and machine learning algorithms over publicly available clinical COVID-19 transcriptome datasets. The robust seven-gene biomarker identified through this analysis can not only discriminate SARS-CoV-2 associated acute respiratory illness (ARI) from other types of ARIs but also can discriminate severe COVID-19 patients from nonsevere COVID-19 patients. Validation of the 7-gene biomarker in an independent blood transcriptome dataset of longitudinal analysis of COVID-19 patients across various stages of the disease showed that the dysregul ation of the identified biomarkers during severe disease is restored during recovery, showing their prognostic potential. The blood biomarkers identified in this study can serve as potential diagnostic candidates and help reduce COVID-19-associated mortality. This article is protected by copyright. All rights reserved. View on Web

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Association between exposure to combustion-related air pollution and multiple sclerosis risk

alexandrossfakianakis shared this article with you from Inoreader Association between exposure to combustion-related air pollution and multiple sclerosis risk via International Journal of Epidemiology - Advance Access Abstract Background Smoking and occupational pulmonary irritants contribute to multiple sclerosis (MS) development. We aimed to study the association between ambient air pollution and MS risk and potential interaction with the human leukocyte antigen (HLA)-DRB1*15:01 allele. Methods Exposure to combustion-related air pollution was estimated as outdoor levels of nitrogen oxides (NOx) at the participants' residence locations, by spatially resolved dispersion modelling for the years 1990–18. Using two population-based case-control studies (6635 cases, 8880 controls), NOx levels were associated with MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Interaction between high NOx levels and the HLA-DRB1*15:01 allele regarding MS risk was calculated by the attributable proportion due to interaction (AP). In addition, a register study was performed comprising al l MS cases in Sweden who had received their diagnosis between 1993 and 2018 (n = 22 173), with 10 controls per case randomly selected from the National Population register. Results Residential air pollution was associated with MS risk. NOx levels (3-year average) exceeding the 90th percentile (24.6 µg/m3) were associated with an OR of 1.37 (95% CI 1.10–1.76) compared with levels below the 25th percentile (5.9 µg/m3), with a trend of increasing risk of MS with increasing levels of NOx (P <0.0001). A synergistic effect was observed between high NOx levels (exceeding the lower quartile among controls) and the HLA-DRB1*15:01 allele regarding MS risk (AP 0.26, 95% CI 0.13–0.29). Conclusions Our findings indicate that moderate levels of combustion-related ambient air pollution may play a role in MS development. View on Web

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A comprehensive evaluation of an animal model for Helicobacter pylori‐associated stomach cancer: Fact and controversy

alexandrossfakianakis shared this article with you from Inoreader A comprehensive evaluation of an animal model for Helicobacter pylori‐associated stomach cancer: Fact and controversy via Helicobacter Abstract Even though Helicobacter pylori infection was the most causative factor of gastric cancer, numerous in vivo studies failed to induce gastric cancer using H. pylori infection only. The utilization of established animal studies in cancer research is crucial as they aim to investigate the coincidental association between suspected oncogenes and pathogenesis as well as generate models for the development and testing of potential treatments. The methods to establish gastric cancer using infected animal models remain limited, diverse in methods, and showed different results. This study investigates the differences in animal models, which highlight different pathological results in gaster by literature research. Electronic databases searched were performed in PubMed, Science Direct, and Cochrane, without a period filter. A total of 135 articles were used in this study after a full-text assessment was conducted. The most frequent animal models used for gastric ca ncer were Mice, while Mongolian gerbils and Transgenic mice were the most susceptible model for gastric cancer associated with H. pylori infection. Additionally, transgenic mice showed that the susceptibility to gastric cancer progression was due to genetic and epigenetic factors. These studies showed that in Mongolian gerbil models, H. pylori could function as a single agent to trigger stomach cancer. However, most gastric cancer susceptibilities were not solely relying on H. pylori infection, and numerous factors are involved in cancer progression. Further study using Mongolian gerbils and Transgenic mice is crucial to conduct and establish the best models for gastric cancer associated H. pylori. View on Web

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Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway

alexandrossfakianakis shared this article with you from Inoreader <i>Porphyromonas gingivalis</i> bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 12 January 2023; doi:10.1038/s41368-022-00215-y Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway View on Web

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A tooth‐supported titanium mesh bending and positioning module for alveolar bone augmentation and improving accuracy

alexandrossfakianakis shared this article with you from Inoreader A tooth‐supported titanium mesh bending and positioning module for alveolar bone augmentation and improving accuracy via Journal of Esthetic and Restorative Dentistry Abstract Objective Guided bone regeneration with titanium mesh is a commonly used bone augmentation technique. However, deformation and sliding may occur during the installation of titanium mesh, which may lead to poor accuracy of bone augmentation. This article presented three cases, which describe a tooth-supported titanium mesh bending and positioning module aiming to improve the precision of bone augmentation. Clinical Considerations After designing the ideal bone increment volume digitally, print out the difference bone module between the ideal and existing bone mass and one or two wings. The wings are supported by the adjacent teeth to show the ideal bone mass in the patients' mouth. Finally, the titanium mesh is bent and installed in the ideal position by the module. Conclusions A favorable outcome has been preliminarily confirmed in these cases, the average vertical bone gain was 4.16 mm and the average horizontal gain was 7.48 mm after 6 months. Using the module in the treatment of patients with bone augmentation can effectively improve the accuracy, the maximum deviation was 1.5 mm and the mean was 0.6 mm. Clinical Significance This study improves the bone augmentation technology with titanium mesh. The titanium mesh is fixed in the ideal position, which facilitates subsequent implantation and denture repair. View on Web

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Automated Detection of GlotticLaryngeal Carcinomain Laryngoscopic Images from a Multicenter Databaseusing a Convolutional Neural Network

alexandrossfakianakis shared this article with you from Inoreader Automated Detection of GlotticLaryngeal Carcinomain Laryngoscopic Images from a Multicenter Databaseusing a Convolutional Neural Network via Clinical Otolaryngology ABSTRACT OBJECTIVE Little is known about the efficacy of using artificial intelligence to identify laryngeal carcinoma from images of vocal lesions taken in different hospitals with multiple laryngoscope systems. This multicenter study aimed to establish an artificial intelligence system and provide a reliable auxiliary tool to screen for laryngeal carcinoma. Study Design Multicenter case-control study Setting Six tertiary care centers Participants Laryngoscopy images were collected from 2179 patients with vocal fold lesions. Outcome Measures An automatic detection system of laryngeal carcinoma was established and used to distinguish malignant and benign vocal lesions in 2179 laryngoscopy images acquired from 6 hospitals with 5 types of laryngoscopy systems. Pathological examination was the gold standard for identifying malignant and benign vocal lesions. Results Out of 89 cases in the malignant group, the classifier was able to correctly identify laryngeal carcinoma in 66 patients (74.16%, sensitivity). Out of 640 cases in the benign group, the classifier was able to accurately assess the laryngeal lesion in 503 cases (78.59%, specificity). Furthermore, the region-based convolutional neural network(R-CNN) classifier achieved an overall accuracy of 78.05%, with a 95.63% negative predictive and a 32.51% positive predictive value for the testing dataset. Conclusion This automatic diagnostic system has the potential to assist clinical laryngeal carcinoma diagnosis which may improve and standardize the diagnostic capacity of laryngologists using different laryngoscopes. This article is protected by copyright. All rights reserved. View on Web

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Overall and abdominal obesity and risks of all-cause and cause-specific mortality

alexandrossfakianakis shared this article with you from Inoreader Overall and abdominal obesity and risks of all-cause and cause-specific mortality in Korean adults: a pooled analysis of three population-based prospective cohorts via International Journal of Epidemiology - Advance Access Abstract Background Studies found a J-shaped association between body mass index (BMI) and mortality. However, it is unclear whether the association is driven by biases, particularly confounding by fat-free mass. Methods We conducted an individual-level pooled analysis of three cohorts of Korean adults (aged ≥ 40 years; n = 153 248). Mortality was followed up through December 2019. Anthropometric data were directly measured at baseline. Fat and fat-free mass were predicted using validated prediction models. Using Cox proportional hazards models, we estimated the associations of BMI and waist circumference (WC) with all-cause and cause-specific mortality. To account for biases, we excluded participants aged ≥ 70 years, deaths that occurred within 5 years of follow-up and ever smokers, and adjusted for fat-free mass index (FFMI). Results During the follow-up of up to 18 years, 6061 deaths were identified. We observed J-shaped association of BMI (nadir at 22–26) and monotonically positive association of WC with all-cause, cardiovascular, and cancer mortality among Korean adults without a history of cancer or cardiovascular disease. In the BMI analysis, excluding ever smokers and adjusting for FFMI attenuated the excess mortality in underweight participants and transformed the J-shaped association into a monotonically positive shape, suggesting an increased mortality at BMI > 22.0. Excluding participants aged ≥ 70 years and deaths that occurred within 5 years of follow-up did not change the results. In the WC analysis, the monotonic positive associations did not change after the control. Similar results were observed among participants with a history of cancer or cardiovascular disease. Conclusions Our data suggest that both overall and abdominal body fat are associated with increased mortality in Korean adults. View on Web

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