Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Predicting Demands of COVID-19 Prevention and Control Materials via Co-Evolutionary Transfer Learning.

The novel coronavirus pneumonia (COVID-19) has created great demands for medical resources. Determining these demands timely and accurately is critically important for the prevention and control of the pandemic. However, even if the infection rate has been estimated, the demands of many medical materials are still difficult to estimate due to their complex relationships with the infection rate and insufficient historical data. To alleviate the difficulties, we propose a co-evolutionary transfer learning (CETL) method for predicting the demands of a set of medical materials, which is important in COVID-19 prevention and control. CETL reuses material demand knowledge not only from other epidemics, such as severe acute respiratory syndrome (SARS) and bird flu but also from natural and manmade disasters. The knowledge or data of these related tasks can also be relatively few and imbalanced. In CETL, each prediction task is implemented by a fuzzy deep contractive autoencoder (CAE), and all prediction networks are cooperatively evolved, simultaneously using intrapopulation evolution to learn task-specific knowledge in each domain and using interpopulation evolution to learn common knowledge shared across the domains. Experimental results show that CETL achieves high prediction accuracies compared to selected state-of-the-art transfer learning and multitask learning models on datasets during two stages of COVID-19 spreading in China.

Digital health literacy and well-being among university students: Mediating roles of fear of COVID-19, information satisfaction, and internet information search.

Background: Digital health literacy (DHL) enables healthy decisions, improves protective behaviors and adherence to COVID-19 measures, especially during the era of the "infodemic", and enhances psychological well-being. Objective: We aimed to explore the mediating roles of fear of COVID-19, information satisfaction, and the importance of online information searching on the association between DHL and well-being. Methods: A cross-sectional web-based survey was conducted among 1631 Taiwanese university students, aged 18 years and above, from June 2021 to March 2022. The collected data include sociodemographic characteristics (sex, age, social status, and financial satisfaction), the importance of online information searching, information satisfaction, fear of COVID-19, DHL, and well-being. A linear regression model was utilized to investigate factors associated with well-being, followed by a pathway analysis to assess the direct and indirect relationship between DHL and well-being. Results: The scores of DHL and overall well-being were 3.1 ± 0.4 and 74.4 ± 19.7, respectively. Social status (B = 2.40, 95% confidence interval (CI) 1.73-3.07, p < 0.001), DHL (B 0.29, 95% CI 0.10-0.49, p < 0.001), importance of online information searching (B = 0.78, 95% CI 0.38-1.17, p < 0.001), and information satisfaction (B = 3.59, 95% CI 2.22-4.94, p < 0.001) were positively associated with well-being, whereas higher fear of COVID-19 scores (B = -0.38, 95% CI -0.55-(-0.21), p < 0.001) and female (B = -2.99, 95% CI -5.02-0.6, p = 0.004) were associated with lower well-being, when compared with lower fear scores and male, respectively. Fear of COVID-19 (B = 0.03, 95% CI 0.016-0.04, p < 0.001), importance of online information searching (B = 0.03, 95% CI 0.01-0.05, p = 0.005), and information satisfaction (B = 0.05, 95% CI 0.023-0.067, p < 0.001) were significantly mediated the relationship between DHL and well-being. Conclusion: Higher DHL scores show direct and indirect associations with higher well-being scores. Fear, importance of online information searching, and information satisfaction significantly contributed to the association.

Links between COVID-19 and Parkinson's disease/Alzheimer's disease: reciprocal impacts, medical care strategies and underlying mechanisms.

The impact of coronavirus disease 2019 (COVID-19) pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest. However, there are still many issues of concern to be clarified. Therefore, we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson's disease (PD) and Alzheimer's disease (AD). We summarize the impact of COVID-19 infection on symptom severity, disease progression, and mortality rate of PD and AD, and discuss whether COVID-19 infection could trigger PD and AD. In addition, the susceptibility to and the prognosis of COVID-19 in PD patients and AD patients are also included. In order to achieve better management of PD and AD patients, modifications of care strategies, specific drug therapies, and vaccines during the pandemic are also listed. At last, mechanisms underlying the link of COVID-19 with PD and AD are reviewed.

Association of Digital Health Literacy with Future Anxiety as Mediated by Information Satisfaction and Fear of COVID-19: A Pathway Analysis among Taiwanese Students.

Digital Health Literacy (DHL) helps online users with navigating the infodemic and co-existing conspiracy beliefs to avoid mental distress and maintain well-being. We aimed to investigate the association between DHL and future anxiety (FA); and examine the potential mediation roles of information satisfaction and fear of COVID-19 (F-CoV). A web-based cross-sectional survey was carried out among 1631 Taiwanese university students aged 18 years and above from June 2021 to March 2022. Data collected were socio-demographic characteristics (sex, age, social status, university location), information satisfaction, F-CoV, DHL and FA (using Future Dark scale). The linear regression model was used to explore factors associated with FA. The pathway analysis was further used to evaluate the direct and indirect relationship between DHL and FA. A higher score of DHL (B = -0.21; 95% CI, -0.37, -0.06; p = 0.006), and information satisfaction (B = -0.16; 95% CI, -0.24, -0.08; p < 0.001) were associated with a lower FA score, whereas a higher F-CoV score was associated with a higher FA score (B = 0.43; 95% CI, 0.36, 0.50; p < 0.001). DHL showed the direct impact (B = -0.1; 95% CI, -0.17, -0.04; p = 0.002) and indirect impact on FA as mediated by information satisfaction (B = -0.04; 95% CI, -0.06, -0.01; p = 0.002) and F-CoV (B = -0.06, 95% CI, -0.08, -0.04; p < 0.001). Strategic approaches to promote DHL, information satisfaction, lower F-CoV are suggested to reduce FA among students.

Antibody-mediated autoimmune encephalitis evaluated by 18F-DPA714 PET/MRI

SARS-CoV-2 vaccine has considered being the most effective method to prevent SARS-CoV-2 infection. The safety and effectiveness of the SARS-CoV-2 vaccine has been confirmed. However, in very rare cases, autoimmune neurological diseases may occur. In this article, we report three rare cases of autoimmune encephalitis with definite auto-antibody after SARS-CoV-2 vaccination. They all have good prognosis after treatment. In addition, we first use 18F-DPA-714 PET/MRI to evaluate microglia activation in our patients. We found that 18F-DPA-714 PET/MRI may be a powerful tool for quantitative analysis of neuroinflammation in patients of autoimmune encephalitis. Finally, although rare complications may happen after vaccination, we still consider the benefits of vaccination far outweigh the risks. People without contraindications should be vaccinated without delay to prevent infection in current outbreak situation.

Antibody-mediated autoimmune encephalitis evaluated by 18F-DPA714 PET/MRI.

SARS-CoV-2 vaccine has considered being the most effective method to prevent SARS-CoV-2 infection. The safety and effectiveness of the SARS-CoV-2 vaccine has been confirmed. However, in very rare cases, autoimmune neurological diseases may occur. In this article, we report three rare cases of autoimmune encephalitis with definite auto-antibody after SARS-CoV-2 vaccination. They all have good prognosis after treatment. In addition, we first use 18F-DPA-714 PET/MRI to evaluate microglia activation in our patients. We found that 18F-DPA-714 PET/MRI may be a powerful tool for quantitative analysis of neuroinflammation in patients of autoimmune encephalitis. Finally, although rare complications may happen after vaccination, we still consider the benefits of vaccination far outweigh the risks. People without contraindications should be vaccinated without delay to prevent infection in current outbreak situation.

Identifying potential pharmacological targets and mechanisms of vitamin D for hepatocellular carcinoma and COVID-19.

Coronavirus disease 2019 (COVID-19) is a severe pandemic that has posed an unprecedented challenge to public health worldwide. Hepatocellular carcinoma (HCC) is a common digestive system malignancy, with high aggressiveness and poor prognosis. HCC patients may be vulnerable to COVID-19. Since the anti-inflammatory, immunomodulatory and antiviral effects of vitamin D, we aimed to investigate the possible therapeutic effects and underlying action mechanisms of vitamin D in COVID-19 and HCC in this study. By using a range of bioinformatics and network pharmacology analyses, we identified many COVID-19/HCC target genes and analyzed their prognostic significance in HCC patients. Further, a risk score model with good predictive performance was developed to evaluate the prognosis of HCC patients with COVID-19 based on these target genes. Moreover, we identified seven possible pharmacological targets of vitamin D against COVID-19/HCC, including HMOX1, MB, TLR4, ALB, TTR, ACTA1 and RBP4. And we revealed the biological functions, signaling pathways and TF-miRNA coregulatory network of vitamin D in COVID-19/HCC. The enrichment analysis revealed that vitamin D could help in treating COVID-19/HCC effects through regulation of immune response, epithelial structure maintenance, regulation of chemokine and cytokine production involved in immune response and anti-inflammatory action. Finally, the molecular docking analyses were performed and showed that vitamin D possessed effective binding activity in COVID-19. Overall, we revealed the possible molecular mechanisms and pharmacological targets of vitamin D for treating COVID-19/HCC for the first time. But these findings need to be further validated in actual HCC patients with COVID-19 and need further investigation to confirm.

Artificial stem cells mediated inflammation-tropic delivery of antiviral drugs for pneumonia treatment.

BACKGROUND: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity. METHODS: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo. RESULTS: MPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently. CONCLUSION: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.

COVID-19-related fear, stress and depression in school principals: impacts of symptoms like COVID-19, information confusion, health-related activity limitations, working hours, sense of coherence and health literacy.

BACKGROUND: School principals have been reported to have a higher prevalence of burnout and psychological problems than their colleagues. During the pandemic, extra workload and pressure from unprecedented situations potentially cause fear, stress and depression. Therefore, we aimed to explore associated factors of stress, fear of COVID-19 (F-CoV-19S) and depressive symptoms among school principals. METHODS: A cross-sectional online survey was conducted in Taiwan from 23 June to 16 July 2021. Data of 413 school principals were collected, including socio-demographic factors, COVID-19-related factors, work-related information, health status, sense of coherence (SoC), health literacy (HL), F-CoV-19S, stress and depression. Multiple linear and logistic regression models were utilized to explore associations. RESULTS: School principals with symptoms like COVID-19 (S-COVID-19-S), or with health-related activity limitations had a higher score of stress (B = 0.92; p = .039) (B = 1.52; p < .001) and a higher depression likelihood (OR = 3.38; p < .001) (OR = 3.06; p < .001), whereas those with a better SoC had a lower stress score (B = -1.39; p < .001) and a lower depression likelihood (OR = 0.76; p = .020). School principals confusing about COVID-19-related information had a higher score of stress (B = 2.47; p < .001) and fear (B = 3.77; p < .001). The longer working time was associated with a higher fear score (B = 1.69; p = .006). Additionally, school principals with a higher HL score had a lower stress score (B = -1.76; p < .001), a lower fear score (B = -1.85; p < .001) and a lower depression likelihood (OR = 0.53; p = .043). CONCLUSIONS: Health-related activity limitations, S-COVID-19-S, COVID-19-related information confusion and longer working hours were positively associated with at least one mental health problem (e.g. stress, fear and depression), whereas better SoC and HL showed the benefits to mitigate fear, stress and depressive symptoms in school principals. Our study provides evidence for appropriate strategies to improve principals' mental health during the pandemic.Key messages:School principals with health-related activity limitations or with symptoms like COVID-19 were more likely to be stressed and depressed.Higher levels of stress and fear were observed in school principals who confused about COVID-19-related information, and who had longer working time than before the pandemic.Better sense of coherence and higher health literacy could potentially mitigate the fear, stress and depressive symptoms in school principals.

Osmotic Processor for Enabling Sensitive and Rapid Biomarker Detection via Lateral Flow Assays.

Urine is an attractive biospecimen for in vitro diagnostics, and urine-based lateral flow assays are low-cost devices suitable for point-of-care testing, particularly in low-resource settings. However, some of the lateral flow assays exhibit limited diagnostic utility because the urinary biomarker concentration is significantly lower than the assay detection limit, which compromises the sensitivity. To address the challenge, we developed an osmotic processor that statically and spontaneously concentrated biomarkers. The specimen in the device interfaces with the aqueous polymer solution via a dialysis membrane. The polymer solution induces an osmotic pressure difference that extracts water from the specimen, while the membrane retains the biomarkers. The evaluation demonstrated that osmosis induced by various water-soluble polymers efficiently extracted water from the specimens, ca. 5-15 ml/h. The osmotic processor concentrated the specimens to improve the lateral flow assays' detection limits for the model analytes-human chorionic gonadotropin and SARS-CoV-2 nucleocapsid protein. After the treatment via the osmotic processor, the lateral flow assays detected the corresponding biomarkers in the concentrated specimens. The test band intensities of the assays with the concentrated specimens were very similar to the reference assays with 100-fold concentrations. The mass spectrometry analysis estimated the SARS-CoV-2 nucleocapsid protein concentration increased ca. 200-fold after the osmosis. With its simplicity and flexibility, this device demonstrates a great potential to be utilized in conjunction with the existing lateral flow assays for enabling highly sensitive detection of dilute target analytes in urine.

Canadian perspectives of digital mental health supports: Findings from a national survey conducted during the COVID-19 pandemic.

Objectives: The impact of the COVID-19 pandemic on population mental health has highlighted the potential for digital mental health to support the needs of those requiring care. This study sought to understand the digital mental health experiences and priorities of Canadians affected by mental health conditions (i.e. seekers, patients, and care partners). Methods: A national cross-sectional electronic survey of Canadians was administered through a market research firm's survey panel. Seekers, patients, and care partners were asked about their digital mental health experiences (e.g. uptake, barriers to access) and priorities. Survey responses were summarized using descriptive statistics. Results: Overall, 1003 participants completed the survey. 70.2% of participants routinely use digital mental health supports to support themselves or those they care for; however, only 28.6% of participants are satisfied with the available digital mental health supports. Most participants (73.3%) have encountered some barriers when accessing digital mental health supports. Awareness of digital mental health supports was a top barrier identified by participants. The top digital mental health priorities consisted of digital mental health curation, navigation, and a digital mental health passport. Conclusions: Most participants use digital mental health supports for themselves or others, however, many are unaware of digital mental health supports available. Efforts to improve navigating access to digital and in-person mental health services are seen as a top priority, highlighting the need to enable seekers, patients, and care partners to find the appropriate support and make decisions on how to best improve their mental health.

Advanced Genetic Methodologies in Tracking Evolution and Spread of SARS-CoV-2.

A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. Here, we describe genetic methods to trace the evolution route and probe the transmission dynamics of this virus.

Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms.

Aging is a natural process, which plays a critical role in the pathogenesis of a variety of diseases, i.e., aging-related diseases, such as diabetes, osteoarthritis, Alzheimer disease, cardiovascular diseases, cancers, obesity and other metabolic abnormalities. Metformin, the most widely used antidiabetic drug, has been reported to delay aging and display protective effect on attenuating progression of various aging-related diseases by impacting key hallmark events of aging, including dysregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, altered intercellular communication, telomere attrition, genomic instability, epigenetic alterations, stem cell exhaustion and cellular senescence. In this review, we provide updated information and knowledge on applications of metformin in prevention and treatment of aging and aging-related diseases. We focus our discussions on the roles and underlying mechanisms of metformin in modulating aging and treating aging-related diseases.

A Novel Prognostic Signature for Survival Prediction and Immune Implication Based on SARS-CoV-2-Related Genes in Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) is a common aggressive malignancy of the urinary system. COVID-19, a highly infectious and severe disease caused by SARS-CoV-2, has become a significant challenge for global public health. Cancer patients have been reported to be more vulnerable to SARS-CoV-2 infection and have a higher risk for serious complications than the general population. However, the correlation between KIRC and COVID-19 remains incompletely elucidated. In this study, we comprehensively investigated the expression and prognostic significance of 333 SARS-CoV-2 infection-related genes in KIRC using the TCGA dataset and identified 31 SARS-CoV-2-related differently expressed genes between KIRC and normal renal tissues. Based on these genes, we constructed and validated a 5-gene prognostic signature (including ACADM, CENPF, KDELC1, PLOD2, and TRMT1) to distinguish low- and high-risk KIRC patients of poor survival in TCGA and E-MTAB-1980 cohorts. Gene set enrichment analysis (GSEA) showed that some inflammatory/immune-related pathways were significantly enriched in the high-risk group. The ESTIMATE analysis indicated that patients in the high-risk group had higher stromal and immune cell scores, therefore lower tumor purity. Moreover, they presented higher proportions of macrophages M0, regulatory T cells (Tregs), and T follicular helper cells and higher expression of immune checkpoints CTLA-4, LAG-3, TIGIT, and PDCD1 than low-risk patients. Besides, we also developed a nomogram to expand clinical applicability, which exhibits excellent predictive accuracy for survival. In conclusion, we identified a novel prognostic signature and nomogram based on SARS-CoV-2-related genes as reliable prognostic predictors for KIRC patients and provided potential therapeutic targets for KIRC and COVID-19.

Effective Antiviral Activity of the Tyrosine Kinase Inhibitor Sunitinib Malate against Zika Virus.

INTRODUCTION: Zika virus (ZIKV), a mosquito-borne flavivirus, causes the outbreaks of Latin America in 2015 - 2016, with the incidence of neurological complications. Sunitinib malate, an orally bioavailable malate salt of the tyrosine kinase inhibitor, is suggested as a broad-spectrum antiviral agent against emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. MATERIALS AND METHODS: This study investigated the antiviral efficacy and antiviral mechanisms of sunitinib malate against ZIKV infection using cytopathic effect reduction, virus yield, and time-of-addition assays. RESULTS: Sunitinib malate concentration-dependently reduced ZIKV-induced cytopathic effect, the expression of viral proteins, and ZIKV yield in supernatant with 50% inhibitory concentration (IC50) value of 0.015 µM, and the selectivity index of greater than 100 against ZIKV infection, respectively. Sunitinib malate had multiple antiviral actions during entry and post-entry stages of ZIKV replication. Sunitinib malate treatment at entry stage significantly reduced the levels of ZIKV RNA replication with the reduction of (+) RNA to (-) RNA ratio and the production of new intracellular infectious particles in infected cells. The treatment at post-entry stage caused a concentration-dependent increase in the levels of ZIKV (+) RNA and (-) RNA in infected cells, along with enlarging the ratio of (+) RNA to (-) RNA, but caused a pointed increase in the titer of intracellular infectious particles by 0.01 and 0.1 µM, and a substantial decrease in the titer of intracellular infectious particles by 1 µM. CONCLUSION: The study discovered the antiviral actions of sunitinib malate against ZIKV infection, demonstrating a repurposed, host-targeted approach to identify potential antiviral drugs for treating emerging and global viral diseases.

The incidence and duration of COVID-19 vaccine-related reactive lymphadenopathy on 18F-FDG PET-CT.

OBJECTIVES: Reactive axillary lymph nodes (ALN) may occur post-COVID-19 vaccination. This may be confused with malignant nodal metastases on oncological imaging. We aimed to determine the reactive ALN incidence and duration on 18F-fluorodeoxyglucose positron emission tomography - computed tomography (18F-FDG PET-CT), and its relationship with gender, age and vaccine type. METHODS: A retrospective study was performed. Two-hundred and four eligible patients had 18F-FDG PET-CT between 01 January 2021 and 31 March 2021, post-vaccination with Pfizer-BioNTech or Oxford-AstraZeneca vaccine. Image analysis was performed on dedicated workstations. SPSS was used for statistical analysis. RESULTS: Thirty-six per cent of patients had reactive ALN until 10 weeks post-vaccination; reducing in frequency and intensity with time. Women were more likely to have reactive ALN compared with men. The frequency and intensity were higher in patients aged <65 years compared with those aged ≥65 years. However, no difference was found between both vaccine types in our study cohort. CONCLUSIONS: Physicians' awareness of COVID-19 vaccine-related reactive ALN on 18F-FDG PET-CT is important to avoid inappropriate upstaging of cancers.