Overcoming Engineering Challenges to Enable Commercial-Scale mRNA Vaccine Manufacturing

Increasing production capacity may necessitate the facility to cater for higher hazardous area category (e.g., H-Occupancy) design features, such as specialized building construction and potential blast zones. [...]an assessment should cover: * Quantification of flammable material use for production steps, including buffer preparation and LNP storage * Equipment and facility cleaning strategies that contribute to the facility flammable materials inventory * Impact of HVAC design to avoid hazardous atmospheres (e.g., full fresh air), use of local exhaust ventilation (LEV) or fume hoods * Solvent distribution methods (e.g., closed solvent delivery and waste removal systems) * Location of solvent bulk storage outside of the processing area/ facility, and piping in what is necessary plus removing spent solvent in a timely manner (e.g., piped transfer to a waste tank for removal by a specialist contractor). At present, the process cannot be fully single-use, so thought needs to be put into the cleaning and sterilization processes, plus the analytical support infrastructure needed for reusable product-contact surfaces. [...]it is recommended that for each mRNA project, consideration is given to the following aspects to determine the link between the equipment available and the facility design: * Need for custom/proprietary equipment * Independent production rooms with "through-wall" buffer transfer through iris ports in from logistics corridor (Buffer Prep/Hold) * Room electrical classification needs versus process step. * Equipment selection versus electrical and fire code requirements * Benefits and limitations of implementing single-use technologies, given that the process will be hybrid (with stainless steel). [...]the limited capacity for outsourcing of supporting functions, such as facility environmental monitoring or product sterility testing, should be considered during concept design.

The evolution of consumers' demand for hotels under the public health crisis: opinion mining from online reviews

This research aims to grasp the evolution of consumer demand and improve the resilience of the hotel industry under the public health crisis (COVID-19). Online reviews of 7,679 hotels in 10 cities were collected from Ctrip, China's major online hotel platform. Then, we applied opinion mining and time evolution to mine the change in consumer demand before, during, and after the COVID-19 pandemic. Findings show that some consumer demands (e.g. epidemic safety) will change during the outbreak period. However, during the nonoutbreak period, users were more concerned about their own check-in experience (e.g. hotel facilities, front desk services). This article provides new ideas for identifying the dynamic value of online reviews. We suggest that businesses focus on ensuring hotel safety during the crisis period. The results contribute essential theoretical and practical significance to the hotel industry's crisis management during public health crises.

Consumers' fear regarding food security in Slovenia during the first wave of COVID-19 crisis

The various crises are having a significant impact on the entire food sector and are changing the attitudes of Europeans as well as policies on the importance of food security and sustainably produced quality and safe food for consumer health. The paper focuses on the consumer's fear of food security for the time of the first wave of COVID-19 and the associated concern for food security in the future and the changes in consumer behaviour. The online survey in Slovenia was conducted in June 2020 using a "snowball" method. The sample included 490 individuals. The results showed that both measured forms of fear (i) fear over food security during the first wave of COVID-19 crisis, and (ii) fear over food security in the future were statistically significant, moderately strong and positively associated with almost all forms of self-perceived behaviour change caused by the COVID-19 crisis. The respondents focused more on buying locally produced and processed food, food stockpiling and decreasing food waste. Only minor changes were expressed with regards to their food purchasing channels, with the elderly, the highly educated and those who classified themselves in a higher social class buying more often directly from farmers. In the future, the results of this research should be compared with other countries and the impact of an individual's economic situation and the impact of promotional campaigns on agricultural products on changing consumer behaviour should also be analysed in more detail.

Getting a Nose for Vaccines

According to expert opinion, the incorporation of effective adjuvants that can trigger both mucosal and systemic immune responses are necessary for noninvasive vaccine delivery, and a more extensive understanding of mucosal immunity is required (4). To overcome these potential issues, it has been suggested by some experts that gelling agents, such as polymers, included in the formulation could increase the residence time of the vaccine in the nasal passage (5). Another potential intranasal candidate from Altimmune is no longer in development as a result of inadequate immune response in healthy volunteers (8).

Physical activity habits, well-being, and quality of life during COVID-19 preventive isolation in Bogota, Colombia

The Covid-19 pandemic forced the world population to incorporate prevention activities into their daily lives to preserve people's physical health. In Colombia, the national government, through resolutions and decrees, regulated quarantine and preventive isolation in order not to saturate health services and intensive care units, which were not prepared to respond to the disease. In this sense, this article analyzed the habits of physical activity, well-being, and quality of life in preventive isolation - Covid-19 in Bogota, Colombia. A cross-sectional descriptive quantitative study was conducted on a sample of 1,775 people with an average age of 43.5+or-25.5 years, of which 50.9% (n=903) corresponded to women and 49.1% (n=872) to men. It was found that due to the confinement the consumption of coffee and alcoholic beverages increased, as well as a decrease in physical activity. In addition, manifestations of anxiety, depression and feelings of loneliness were identified, which directly affected people's well-being and quality of life. It is expected that this type of research will contribute to the understanding of the impact of the contingency measures taken by the different nations to curb Covid-19 infections on people's health.

Establishment and application of triple PCR method for CPV, CCoV and CRV

Canine parvovirus (CPV), canine coronavirus (CCoV) and canine rotavirus (CRV) are the three main causative viruses of diarrhea in dogs with similar clinical symptoms;thereby it is necessary to establish a high effective molecular detection method for differentiating the above pathogens. By optimizing the primer concentration and annealing temperature, a triple PCR method was established for simultaneous detection of CPV, CCoV and CRV, and then the specificity, sensitivity and repeatability of the method were tested. The results showed that the target fragments of CPV VP2 gene (253 bp), CCoV ORF-1b gene (379 bp) and CRV VP6 gene (852 bp) could be accurately amplified by the triple PCR method with high specificity, the detection limits of CPV, CCOV and CRV were 6.44x10-1 pg/L, 8.72x10-1 pg/L and 8.35x10-1 pg/L respectively with high sensitivity, and the method had good stability. Using this triple PCR method, 135 canine diarrhea fecal samples collected in Chengdu region from 2019 to 2020 were detected, and compared with those of single PCR method. The detection rates of CPV, CCoV and CRV were 16.30%, 20.74% and 4.44%, respectively, and the total infection rate was 51.11% (65/135) with 20.00% (13/65) co-infection rate. The detection results were consistent with three single PCR methods. In conclusion, CPV/CCoV/CRV triple PCR method successfully established in this paper can be applied as an effective molecular method to detection of related pathogens and to the epidemiological investigation.

What's Next for C0VID-19 Vaccines and Variants?

Telma Lery Janssen EMEA therapeutic area lead for infectious diseases and vaccines at Johnson & Johnson, explains that the company's COVID-19 vaccine candidate (also known as Ad26.COV2.S, Ad26COVS1, VAC31518, JNJ-78436735, or Ad26-S.PP) is a monovalent, recombinant, inactivated/non-infective adenovirus vector (similar to a cold virus), which contains a transgene that codes for the coronavirus spike (S) protein. The vaccine technology, AdVac, is based on the development and production of adenovirus vectors (gene carriers). Adenovirus vectors (gene carriers) are genetically altered forms of an adenovirus and lack the DNA needed to replicate. Some of the main differences between a COVID-19 oral tablet vaccine from injectable COVID-19 vaccines, according to Tucker, include: * Immune responses are triggered in the mucosa and the serum with a COVID-19 oral tablet vaccine (based on preclinical and clinical testing), unlike the existing vaccines that are serum-only. * Ease of distribution and vaccination with a COVID-19 oral tablet vaccine, which eliminates the need for special accommodations to transport injectable vaccines that require cold chain infrastructure as well as the need for trained professionals to administer vaccines.

Cellular and Gene Therapies Face a Manufacturing Capacity Crunch

The long-term trend is for development of allogeneic cellular and gene therapies, involving batched manufacturing of products to be used for treatment of multiple patients (1). There is potential for a significant shortage of manufacturing capacity-measured as total volume of bioreactors in use-particularly at commercial scales, similar to a decade or more ago when there was widespread expectation of a severe shortage of capacity for mainstream recombinant products. [...]reflecting the primitive state of much cellular/gene therapies bioprocessing, only 16% each cited, "Our commercial manufacturing will or does use only closed systems, aseptic transfers/connections, etc." and "Anticipate no problems with meeting good manufacturing practice (GMP) requirements."

Exploring the influence of self-efficacy and autonomy on outdoor recreation behaviors during the COVID-19 pandemic

Outdoor Recreation (OR) provides the benefits of physical activity and traditional leisure placed in an outdoor environment. Motivation, self-efficacy, and autonomy can increase depending on the physical and social environment. This study explored the relationship between self-efficacy and autonomy on OR behaviors and identified barriers and facilitators to OR during the COVID-19 pandemic. Survey information was collected from 995 U.S. adults (93.6% white, 64.0% female) regarding OR behaviors, changes in OR during COVID-19, and OR self-perceptions. Significant positive correlations existed between autonomy and self-efficacy (r = 0.138, p < 0.01), and self-efficacy and pre/post pandemic OR behaviors 2020 (r = 0.158, p < 0.01), (r = 0.129, p < 0.01) respectively. Qualitative data implied barriers and facilitators to OR as: social, mental health, and increased or changed OR/physical activity. Implications from this research are beneficial to OR and health professionals to promote overall physical and mental well-being for OR participants.

Viral modernity? Epidemics, infodemics, and the ‘bioinformational' paradigm

Viral modernity is a concept based upon the nature of viruses, the ancient and critical role they play in evolution and culture, and the basic application to understanding the role of information and forms of bioinformation in the social world. The concept draws a close association between viral biology on the one hand, and information science on the other – it is an illustration and prime example of bioinformationalism that brings together two of the most powerful forces that now drive cultural evolution. The concept of viral modernity applies to viral technologies, codes and ecosystems in information, publishing, education and emerging knowledge (journal) systems. This paper traces the relationship between epidemics, quarantine, and public health management and outlines elements of viral-digital philosophy (VDP) based on the fusion of living and technological systems. We discuss Covid-19 as a ‘bioinformationalist' response that represents historically unprecedented level of sharing information from the sequencing of the genome to testing for a vaccination. Finally, we look at the US response to Covid-19 through the lens of infodemics and post-truth. The paper is followed by three open reviews, which further refine its conclusions as they relate to (educational) philosophy and the notion of the virus as Pharmakon.

Applications of Multi-omics Approaches for Food and Nutritional Security

Food systems are constantly changing to accommodate the advancement of societies. Increased challenges, including the World Wars, natural disasters, and the COVID-19 pandemic, have stimulated the improvement of the economics, quantity, and quality of food around the globe. Food security was introduced to alleviate and eradicate hunger and poverty with an aim to provide access to enough food and calories to everybody all the time. In society, this was translated to an increase in food rich in carbohydrates but not specifically all the nutrients and minerals required for healthy growth and development. Agriculturally, this has resulted in a rise in large-scale production of starch and filling food that can be used as staples worldwide. While hunger is not a problem in most countries, malnutrition is rampant on many levels. There are several cohorts of people suffering from metabolic disorders related to an imbalance in nutrients, including diabetes, obesity, and anemia, amongst others. The introduction of nutritional security is to ensure that everybody has access to nutrients from all food groups;this means proteins, carbohydrates, fibers, vitamins, and minerals. Rapid development in omics research has resulted in high-throughput techniques that can profile the makeup of crops, environmental samples, food, and human biofluids. Genomics, transcriptomics, proteomics, and metabolomics all explain how the different systems behave. Multi-omics is the assembly of all the complex data recorded to explain what is happening at a macroscale. This chapter provides an overview of the most up-to-date applications of multi-omics in food and nutrition security. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023.

Uncovering the interplay between hypertension and the inflammatory response for the patient affected by COVID-19 via mathematical modeling and computer-based analysis

We explore here the systems-based regulatory mechanisms that determine human blood pressure patterns. This in the context of the reported negative association between hypertension and COVID-19 disease. We are particularly interested in the key role that plays angiotensin converting enzyme 2 (ACE2), one of the first identified receptors that enable the entry of the SARS-CoV-2 virus into a cell. Taking into account the two main systems involved in the regulation of blood pressure, that is, the Renin-Angiotensin system and the Kallikrein-Kinin system, we follow a Bottom-Up systems biology modeling approach in order to built the discrete Boolean model of the gene regulatory network that underlies both the typical hypertensive phenotype and the hypotensive/normotensive phenotype. These phenotypes correspond to the dynamic attractors of the regulatory network modeled on the basis of publicly available experimental information. Our model recovers the observed phenotypes and shows the key role played by the inflammatory response in the emergence of hypertension. Source code go to the next url: https://github.com/cxro-cc/red_ras_kks © 2023, EasyChair. All rights reserved.

Recreational travel behavior and COVID-19: insights from expected utility and the theory of planned behavior

Understanding what factors play a role in people's decisions to travel during a pandemic is important to public health officials and to stakeholders in the travel and tourism industry in the United States (US) and worldwide. This study examines factors influencing people's decisions to cancel/postpone recreational travel within the US amidst the COVID-19 pandemic. Our conceptual framework extends the Expected Utility model, commonly used in economics to model decisions under risk and uncertainty, to incorporate subjective norms and perceived behavioral control from the Theory of Planned Behavior. Our results suggest that risk perceptions, subjective norms, and concerns over transmitting COVID-19 to others play a significant role in the decision to cancel and postpone recreational travel. Results also suggest that perceived behavioral control may be less relevant to travel decisions when traveling involves elevated health risks.

Establishment of a duplex fluorescent quantitative PCR assay for detection of Porcine circovirus type 2 and type 3

To establish a method for simultaneous detection of porcine circovirus type 2 (PCV2) and porcine circovirus type 3 (PCV3), specific primers and TaqMan probes were designed after sequence alignment according to the specific sequences of PCV2 Cap gene and PCV3 Cap gene on GenBank. By optimizing the reaction conditions, a duplex fluorescence quantitative PCR detection method for simultaneous detection of porcine circovirus type 2 and 3 was established, and the specificity, sensitivity, and reproducibility were tested. Specificity test results showed that in addition to the positive test results for PCV2 and PCV3, tests for PRRSV, CSFV, PPV, PRV, PEDV, and TGEV were all negative with no cross-reaction, indicating its good specificity. Sensitivity test results showed that the minimum detection limit for detection of PCV2 and PCV3 can both reach 10 copies.L-1, indicating its high sensitivity. The coefficient of variation within and between groups of this method was less than 2%, indicating its good stability. A total of 181 pork and whole blood samples collected from Zhejiang Province were tested using the detection method established in this article and the standard common fluorescent PCR detection method. The results showed that the positive rate of PCV2 was 50.83% (92/181), the positive rate of PCV3 was 37.57% (68/181), and the co-infection rate of PCV2 and PCV3 was 12.15% (22/181). The above detection results of ordinary fluorescent PCR were 50.28% (91/181), 36.46% (66/181), and the co-infection rate was 11.60% (21/181). The coincidence rates of the two methods for PCV2 and PCV3 can reach 98.91% and 97.06%, and the coincidence rate for PCV2 and PCV3 mixed infection were 95.45%. In summary, the duplex fluorescence quantitative PCR detection method established in this experiment can distinguish PCV2 and PCV3 rapidly, which can be used for pathogen detection and epidemiological investigation.

Silent superbug killers in a river near you how factory farms contaminate public water courses on three continents

Water downstream from factory farms harbours an invisible threat to people's health which could eclipse the COVID-19 crisis. The threat? Antibiotic Resistance Genes (ARGs) which are driving antimicrobial resistance the world's superbug crisis - projected to kill up to 10 million people annually by 2050. This publication reports the presence of ARGs in animal waste discharged from industrial farms into public waterways or onto soil (or crops) in four countries. Gauge community impact and sentiment regarding the issue was also highlighted. The water and sediment from public water courses connected to effluent discharges from 6-10 pig farms were tested in each of four countries (Canada, Spain, Thailand and the USA).

Effects of Porcine deltacoronavirus on the transduction pathway of the innate immune signal

Porcine deltacoronavirus (PDCOV) is a new type of pig intestinal coronavirus, which targets pig small intestinal epithelial cells to cause severe enteritis. After infecting the host, PDCoV finishes its proliferation in the host cell by antagonism or escape the innate immune signaling transduction pathway. In order to understand the action mechanism of PDCOV 0n the congenital immune signal transduction pathways, this paper reviews the effects of PDCOV on RLR, Jak-STAT, MAPK and mitochondrial signaling pathway to clarify the relationship between PDCOV and host innate immune signaling transduction pathways in order to provide help for the prevention and treatment of PDCOV infection.

Modular Processes and Facilities Enable Flexible Vaccine Manufacturing

The COVID-19 pandemic has accelerated the need for modular designs to rapidly expand vaccine production capacity. Speed to market An established benefit of modular facilities is that they are constructed off-site and then delivered to the site where they will be put into use. CRB's SlateXpace was introduced in September 2020 as a "suitebased" modular facility design for cell and gene therapy. Modular systems enable the manufacturer to produce regionally on the required scale and thus to react flexibly to the current situation and local requirements," says Kappeler.

Effect of Drebrin protein on the proliferation of PEDV in Vero cells

Previous studies have revealed that developmental regulated brain protein (Drebrin) is involved in cell- to-cell communication, nerve transmission, tumor metastasis, spermatogenesis and other life activities, but there are few studies on viruses. The aim of the current research was therefore, to study the function of Drebrin and its effect on the proliferation of porcine epidemic diarrhea virus (PEDV). The Drebrin gene was cloned according to the Drebrin gene sequence (XM_008015438.2) of Chlorocebus sabaeus registered by GenBank, and the phylogenetic tree was constructed to analyze its homology. The results showed that the CDS region of Vero cells Drebrin gene was 2088 bp long, encoding 695 amino acids, and was relatively conserved and had high homology with all species. To investigate the effect of Drebrin on the proliferation of PEDV in Vero cells, the eukaryotic expression vector pcDNA3.1-Drebrin-Flag was constructed. After transfection of Vero cells with different concentrations of pcDNA3.1-Drebrin-Flag, cells were infected with PEDV. Our results showed that overexpression of Drebrin in Vero cells could significantly inhibit the intracellular PEDV mRNA level and N protein expression, reduce the extracellular virus titer and inhibit the proliferation of PEDV. Further study on the interaction between Drebrin and PEDV S proteins by laser confocal technique was also performed. The results showed that Drebrin and S protein were co-located in the cytoplasm, suggesting that the two proteins may interact with each other. This study demonstrated for the first time that Drebrin can inhibit PEDV proliferation in Vero cells, laying a foundation for further research in to Drebrin function and provides a valuable information for anti-PEDV research.

Development and application of a multiplex fluorescent quantitative RT-PCR for detection of Porcine epidemic diarrhea virus, porcine coronavirus and porcine acute diarrhea syndrome coronavirus

To develop a multiplex fluorescent quantitative RT-PCR for the detection of porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV), in this study, specific primers/probes were designed based on the conserved regions of M, M and N gene sequences of PEDV, PDCoV and SADS-CoV, respectively. After optimization of the reaction conditions, a multiplex fluorescent quantitative RT-PCR for PEDV, PDCoV and SADS-CoV was established. The results of specificity assay showed that the method was positive for detection of PEDV, PDCoV and SADS-CoV, and negative for detection of porcine transmissible gastroenteritis virus, porcine rotavirus, porcine reproductive and respiratory syndrome virus, porcine pseudorabies virus, porcine circovirus type 2, porcine parvovirus, classical swine fever virus and foot-and-mouth disease virus. The results of sensitivity assay showed that the detection limit of this method for PEDV, PDCoV, and SADS-CoV plasmids standard was 1.0x101 copies/L, and had a good linear relationship with their Ct values in the range of 101 copies/L to 106 copies/L. The results of repeatability assay showed that the coefficients of variation (CVs) of intra- and inter-assay reproducibility ranged from 0.33% to 2.53%, indicating good repeatability and stability. To evaluate the effects of the developed method, 100 clinical samples collected from different parts of Henan province were used for detection of these three viruses and compared with those of single RT-PCR and standard methods. The results of multiplex fluorescent quantitative RT-PCR showed that the positive rates of PEDV, PDCoV and SADS-CoV were 38% (38/100), 14% (14/100) and 5% (5/100), respectively. There was no mixed infection. The coincidence rate with the standard detection methods of PEDV and PDCoV was 100%, and the sensitivity was higher than that of single RT-PCR. In this study, a specific, sensitive and rapid multiplex fluorescent quantitative RTPCR method was established for the first time, which could be used for the differential detection of PEDV, PDCoV and SADS-CoV, and laid a foundation for the differential diagnosis and control of porcine diarrheal diseases.

The economic implications of the COVID-19 outbreak on tourism industry: empirical evidence from Turkey

The novel coronavirus (COVID-19) pandemic has caused tremendous fear and uncertainty and affected health, economy, and social life in an unprecedented form worldwide. Yet, the level of knowledge on its economic implications is very limited. Therefore, it is of paramount importance to explain the health, social, and economic impacts of COVID-19. Because the tourism is one of the most affected industries by the pandemic, this study aims to explain the effects of COVID-19 cases and deaths, global fear, and government responses on Turkey's tourism industry. Empirical findings show that the tourism industry reacts negatively to new cases, number of deaths, and global fear measures. Also, government containment and health measures and economic supports positively affect the tourism industry. Furthermore, government stringency policies drive down the tourism industry's performance. The findings of this study provide significant implications for tourism and travel firms, policy makers, and future research.