Delivery of MERS antigen encapsulated in α-GalCer-bearing liposomes elicits stronger antigen-specific immune responses.

Alpha-Galactosylceramide (α-GalCer) effectively activates the natural killer T (NKT) cells to secrete remarkable amounts of Th1 and Th2 cytokines and therefore, acts as a potential immunoadjuvant in vaccine formulation. In the present study, we prepared α-GalCer-bearing or α-GalCer-free liposomes and loaded them with Middle East Respiratory Syndrome Coronavirus papain-like protease (α-GalCer-Lip-MERS-CoV PLpro or Lip-MERS-CoV PLpro). These formulations were injected in mice to investigate the antigen-specific humoral and cell-mediated immune responses. The immunisation with α-GalCer-Lip-MERS-CoV PLpro or Lip-MERS-CoV PLpro did not induce any notable toxicity in immunised mice. The results demonstrated that mice immunised with α-GalCer-Lip-MERS-CoV PLpro showed greater antigen-specific antibody titre, switching of IgG isotyping to IgG2a subclass and higher lymphocyte proliferation. Moreover, the splenocytes from α-GalCer-Lip-MERS-CoV PLpro immunised mice secreted greater levels of IFN-γ, IL-4, IL-2 and IL-12. Interestingly, a booster dose induced stronger memory immune responses in mice previously immunised with α-GalCer-Lip-MERS-CoV PLpro. In summary, α-GalCer-Lip-MERS-CoV PLpro may prove to be a promising vaccine formulation to protect the individuals against MERS-CoV infection.

Introduction to the special issue on managing software processes using soft computing techniques.

The coronavirus outbreak dramatically changed the work culture in the software industry. Most software practitioners began working remotely, which significantly revolutionized the traditional software processes landscape. Software development organizations have begun thinking about automating software processes to cope with the challenges raised by remote work. This special issue presents papers describing soft computing solutions for improving traditional software processes and capabilities. This editorial introduces the accepted papers and reflects on their contributions.

Comparing the Impact of Road Networks on COVID-19 Severity between Delta and Omicron Variants: A Study Based on Greater Sydney (Australia) Suburbs.

The Omicron and Delta variants of COVID-19 have recently become the most dominant virus strains worldwide. A recent study on the Delta variant found that a suburban road network provides a reliable proxy for human mobility to explore COVID-19 severity. This study first examines the impact of road networks on COVID-19 severity for the Omicron variant using the infection and road connections data from Greater Sydney, Australia. We then compare the findings of this study with a recent study that used the infection data of the Delta variant for the same region. In analysing the road network, we used four centrality measures (degree, closeness, betweenness and eigenvector) and the coreness measure. We developed two multiple linear regression models for Delta and Omicron variants using the same set of independent and dependent variables. Only eigenvector is a statistically significant predictor for COVID-19 severity for the Omicron variant. On the other hand, both degree and eigenvector are statistically significant predictors for the Delta variant, as found in a recent study considered for comparison. We further found a statistical difference (p < 0.05) between the R-squared values for these two multiple linear regression models. Our findings point to an important difference in the transmission nature of Delta and Omicron variants, which could provide practical insights into understanding their infectious nature and developing appropriate control strategies accordingly.

Encapsulation of MERS antigen into α-GalCer-bearing-liposomes elicits stronger effector and memory immune responses in immunocompetent and leukopenic mice.

Objectives: Here, we prepared a liposome-based vaccine formulation containing Middle East Respiratory Syndrome Coronavirus papain-like protease (MERS-CoV-PLpro). Methods: A persistent leukopenic condition was induced in mice by injecting cyclophosphamide (CYP) three days before each dose of immunization. Mice were immunized on days 0, 14 and 21 with α-GalCer-bearing MERS-CoV PLpro-encapsulated DPPC-liposomes (α-GalCer-MERS-PLpro-liposomes or MERS-CoV PLpo-encapsulated DPPC-liposomes (MERS-PLpro-liposomes), whereas the antigen emulsified in Alum (MERS-PLpro-Alum) was taken as a control. On day 26, the blood was taken from the immunized mice to analyze IgG titer, whereas the splenocytes were used to analyze the lymphocyte proliferation and the level of cytokines. In order to assess the memory immune response, mice were given a booster dose after 150 days of the last immunization. Results: The higher levels of MERS-CoV-PLpro-specific antibody titer, IgG2a and lymphocyte proliferation were noticed in mice immunized with α-GalCer-MERS-PLpro-liposomes. Besides, the splenocytes from mice immunized with α-GalCer-MERS-PLpro-liposomes produced larger amounts of IFN-γ as compared to the splenocytes from MERS-PLpro-liposomes or MERS- PLpro-Alum immunized mice. Importantly, an efficient antigen-specific memory immune response was observed in α-GalCer-MERS-PLpro-liposomes immunized mice. Conclusions: These findings suggest that α-GalCer-MERS-PLpro-liposomes may substantiate to be a successful vaccine formulation against MERS-CoV infection, particularly in immunocompromised individuals.

Suburban Road Networks to Explore COVID-19 Vulnerability and Severity.

The Delta variant of COVID-19 has been found to be extremely difficult to contain worldwide. The complex dynamics of human mobility and the variable intensity of local outbreaks make measuring the factors of COVID-19 transmission a challenge. The inter-suburb road connection details provide a reliable proxy of the moving options for people between suburbs for a given region. By using such data from Greater Sydney, Australia, this study explored the impact of suburban road networks on two COVID-19-related outcomes measures. The first measure is COVID-19 vulnerability, which gives a low score to a more vulnerable suburb. A suburb is more vulnerable if it has the first COVID-19 case earlier and vice versa. The second measure is COVID-19 severity, which is proportionate to the number of COVID-19-positive cases for a suburb. To analyze the suburban road network, we considered four centrality measures (degree, closeness, betweenness and eigenvector) and core-periphery structure. We found that the degree centrality measure of the suburban road network was a strong and statistically significant predictor for both COVID-19 vulnerability and severity. Closeness centrality and eigenvector centrality were also statistically significant predictors for COVID-19 vulnerability and severity, respectively. The findings of this study could provide practical insights to stakeholders and policymakers to develop timely strategies and policies to prevent and contain any highly infectious pandemics, including the Delta variant of COVID-19.

Clinical Perspectives of Multiple and Extensively Drug-Resistant Typhoid; result from a tertiary care hospital from Pakistan.

INTRODUCTION: Typhoid fever remains a problem in developing countries, including Pakistan. The emergence of multidrug-resistant and, since 2016, of extensively drug-resistant cases is a continuous challenge for health care workers. The COVID-19 pandemic is making management more difficult. METHODOLOGY: In the present study, a total of 52 confirmed cases of typhoid have been studied during 2019. Detailed clinical features, complications and, lab findings were studied. Typhoid culture and sensitivity were recorded and patients were treated accordingly. Patients were asked about risk factors to aim at informing prevention. RESULTS: Out of the 52 having blood culture positive for Salmonella Typhi 47 (90.4%) and Salmonella Paratyphi 5 (9.6%), 4 (7.7%) were sensitive to first-line (Non-resistant), 11 (21.2%) MDR and 37 (71.2%) patient were XDR. One case was resistant to azithromycin. Nausea, vomiting or, abdominal pain was present in 12 (23%), abdominal distension present in 9 (17.3%), abdominal tenderness in 8 (15.4%), hepatomegaly in 10 (19.2%) and, splenomegaly in 22 (42.3%).There were ultrasound abnormalities in 58% of patients and GI complications in 19% of patients. No significant difference was found in clinical findings and complications between resistant and non-resistant cases. Only 23-27% of patients were aware of typhoid prevention and vaccination measures. CONCLUSIONS: The increasing prevalence of resistance and higher degree of complications seen in typhoid fever raises the concern further about prevention and effective infection management in the community as well as clinical settings. Moreover, judicial use of antibiotics is much needed in developing countries like Pakistan.

How did socio-demographic status and personal attributes influence compliance to COVID-19 preventive behaviours during the early outbreak in Japan? Lessons for pandemic management.

This study focuses on how socio-demographic status and personal attributes influence self-protective behaviours during a pandemic, with protection behaviours being assessed through three perspectives - social distancing, personal protection behaviour and social responsibility awareness. The research considers a publicly available and recently collected dataset on Japanese citizens during the COVID-19 early outbreak and utilises a data analysis framework combining Classification and Regression Tree (CART), a data mining approach, and regression analysis to gain deep insights. The analysis reveals Socio-demographic attributes - sex, marital family status and having children - as having played an influential role in Japanese citizens' abiding by the COVID-19 protection behaviours. Especially women with children are noted as more conscious than their male counterparts. Work status also appears to have some impact concerning social distancing. Trust in government also appears as a significant factor. The analysis further identifies smoking behaviour as a factor characterising subjective prevention actions with non-smokers or less-frequent smokers being more compliant to the protection behaviours. Overall, the findings imply the need of public policy campaigning to account for variations in protection behaviour due to socio-demographic and personal attributes during pandemics and national emergencies.

How a Psychopharmacology Clinical Trial Site in the Seattle Area Managed Clinical Trials and Patient Care During the COVID-19 Pandemic.

OBJECTIVES: As the COVID-19 pandemic developed in March 2020 in greater Seattle, our clinical trial site faced several ethical and clinical dilemmas. We remained open to research patients including high-risk elderly patients and adapted to changing health recommendations. METHODS: Beginning March 14, 2020 we developed an in-person evaluation for potential risk of COVID-19. Included are the first 3 weeks of screening by our physicians for potential exposure to COVID-19, common symptoms, temperature, blood oxygen saturation, and heart rate. Individuals with higher risk (n = 23) were identified and managed. RESULTS: The 825 evaluations included 37 staff, 167 patients, and 152 visitors. No one needed isolation or transfer to acute care facility, staff attendance was 95%, all 33 geriatric patients continued in phase II trials, and others decreased by 5%. CONCLUSION: We share how we incorporated COVID-19 Center for Disease Control health recommendations to a clinical trial center and addition of pulse oximetry.