bluuebunny/crossref_metadata_2025 huggingface dataset:
The Various Effects of Technology Trade on the Sustainable Market Value of Firms in OECD Countries
Authors: Lee Hyunchul , Lee Kyungtag , Lee Jong Ha
Published: November 2021

This study explores the various effects of technology trade on the sustainable market value of firms in 36 OECD member countries using panel data estimations. To proxy technology trade activities, our study uses the technology export and import growths of intellectual property rights (IPRs). We suggest that technology imports, proxied by IPR imports, increase the market value of firms in our sample countries. The net technology imports (exports) are also positively (negatively) associated with the sustainable value of the firms. We use panel data regression to analyze the specific effects of the trade (i.e., imports and exports) of technology assets, proxied by IPRs, on the market value of firms proxied by country benchmark composite stock returns in 36 OECD member countries. For robustness, our study uses an instrumental variable estimation to check for the possible effects of endogeneity biases for the baseline results. System dynamic panel regressions further examine the effect of the dependent variable’s persistence. We find evidence of nonlinear effects for IPR exports and net IPR trade on the sustainable market value of firms. The positive effect of technology imports on the market value of firms is stronger at the lower and middle levels of the distribution of the firm value of stock returns, and this suggest heterogenous effects of technology trade across the quantiles. Overall, the empirical findings from our panel study suggest that the positive effects of technology trade for the market value of firms are due to the effect of its imports rather than exports.
Climate Change Concerns of Saudi Arabian Farmers: The Drivers and Their Role in Perceived Capacity Building Needs for Adaptation
Authors: Alotaibi Bader Alhafi , Abbas Azhar , Ullah Raza , Nayak Roshan K. , Azeem Muhammad I. , Kassem Hazem S.
Published: November 2021

Climate change is a serious threat to the sustainability of global agriculture and food supply that necessitates taking appropriate action for building resilient food production systems and preserving rural economies. In this regard, farmers’ beliefs and concerns about the effects of climate change on agriculture may influence their adoption of adaptation and mitigation practices to address this emerging issue. This work was undertaken to evaluate farmers’ level of concern about climate change in the Jazan province of Saudi Arabia. The study also explored the role of various socioeconomic indicators in shaping farmers’ concerns and highlights various capacity-building initiatives that can be applied at the community level for effective adaptation. Ordered logistic regression was used to study the relationship between farmers’ level of concern and their need for capacity-building initiatives to tackle climate change. Results indicated that insect infestation is the farmers’ top concern, followed by higher crop-diseases incidence and drought. Regression analysis revealed that farmers’ income is a major factor that reduces their concern for insect infestation and crop disease while increases concern for drought. Credit access and information availability have a mixed impact on the farmers’ concern level. Capacity-building initiatives deemed necessary included establishing frequent contacts with extension personnel, timely warnings on droughts and other natural hazards, the training of farmers and extension workers, easy credit facilities, improvement in rural infrastructure and creation of awareness to address specific concern stimulus.
Some Critical Reflections on the Measurement of Social Sustainability and Well-Being in Complex Societies
Authors: Arcagni Alberto , Fattore Marco , Maggino Filomena , Vittadini Giorgio
Published: November 2021

The aim of this discussion paper is to raise awareness of the conceptual and practical limits of mainstream practices in social measurement and to suggest possible directions for social indicator construction, in view of effectively supporting policies for social sustainability and well-being promotion. We start with a review of the epistemological issues raised by the measurement of social phenomena, investigate the notion of social complexity, and discuss the critical link between it and measurement. We then suggest that social indicators should be primarily designed to build structural syntheses of the data, unfolding the patterns and stylizing the complexity of social phenomena, rather than computed pursuing numerical precision, through hardly interpretable aggregated measures. This calls for tools and algorithms capable of rendering structural information, preserving the essential traits of complexity and overcoming the limitations of classical aggregation procedures. We provide some examples along this line, using real data pertaining to regional well-being in OECD countries.
From Fibre to Fashion: Understanding the Value of Sustainability in Global Cotton Textile and Apparel Value Chains
Authors: Mellick Zoe , Payne Alice , Buys Laurie
Published: November 2021

Current sustainability frameworks and tools to assess and track social and environmental impacts of textile and apparel (such as life cycle analysis) along the chain, although important, provide a narrow focus on metrics (such as a reduction in inputs) or on economic value. This paper proposes a tailored method which combines value chain thinking with qualitative value mapping techniques to identify what sustainable value means and to whom, who benefits both in and beyond the chain (such as wider society, the environment, local communities), as well as opportunities to create sustainable value in the future. Results from interviews with stakeholders of a single connected cotton value chain demonstrate that this approach can identify sustainable value propositions specific to different actors in the chain, temperature-test whether stakeholders are willing to pay a premium price for sustainability efforts, and identify novel sustainable value opportunities that disrupt the chain. In addition to extending knowledge around sustainability in the textile and apparel industry, our contribution also lies in the development of a tailored tool which can be adapted and used for other value chains.
Motives for Thermal Tourism: An Application to North and Central Portugal
Authors: Brandão Filipa , Liberato Dália , Teixeira Ana Sofia , Liberato Pedro
Published: November 2021

Health and wellness tourism should be particularly valued in the post-pandemic phase. It has the potential to be a strategic product that enhances the population’s well-being and quality of life, on social, physical, and environmental levels. Different proposals for specialized experiences that complement what the destination offers allow to position regions as health and wellness destinations. Thermal tourism should thus be encouraged as a specific product designed on the innovation and diversification observed in the related services and the benefits recognized for all ages. Considering the relevance of thermal springs and thermal tourists for the image, positioning, and development of touristic destinations, this research aims to identify the specific motivations of tourists that attract them to the practice of thermal tourism, to understand how the benefits for which thermal tourists search and their sociodemographic profile influence the motivations of tourists, and how those motivations determine the characteristics of travel. This research was developed on the North and Centre of Portugal for their relevance in the context of thermal springs and related touristic activities. To achieve the research objectives, a questionnaire survey was conducted among thermal tourists, through a non-probability by convenience sampling, using bivariate tests, such as Pearson’s chi-squared test, one-way ANOVA, and t-Student test. The results highlight that most respondents practiced thermal tourism due to leisure and relaxation benefits, such as the escape from daily stress, spend time with family, and being “pampered”; relaxation is the most valued motivation, followed by the search for psychological and physical well-being. The research found relations between the benefits expected by thermal tourists and their travel characteristics, such as the composition of the group, the general travel motivation, the chosen thermal destination, and the number of nights spent at the location. In thermal tourism, new challenges emerge, demanding the development of strategies, products, and services that respond to the needs of specific market sections.
Realizing the Need for Digital Transformation of Stakeholder Management: A Systematic Review in the Construction Industry
Authors: Prebanić Kristijan Robert , Vukomanović Mladen
Published: November 2021

The construction industry is among the least digitized industries, and the lack of innovation in construction project management practices has led to decreases in productivity. The European Directives for Public Procurement are pushing the entire construction supply chain towards more radical digital transformations over the next years, and project managers are left with the difficult task to harness ICT for the involvement and management of project stakeholders. Digitalization of various processes and practices used to manage stakeholders in construction projects is still low, and part of this problem lies in weak systematization of ICT systems which support these practices. Thus, this paper provides a systematic review of how digitalization and digital transformation affect the way stakeholders behave, engage, and communicate in projects. Following the PRISMA methodology, 73 sources from the literature were chosen for the final analysis. Results are presented through descriptive and qualitative content analysis. Six research topics were identified and thoroughly analyzed. Results show that BIM, social network analysis, and web-based applications as means to digitalize stakeholder management are more mature than social media and VR/AR. An important finding is the need to reengineer and digitally transform processes in construction projects and construction firms to enable further digitalization and effectiveness of digital technologies. Suggestions for further studies follow this line of thought.
Shaping a View on the Influence of Technologies on Sustainable Tourism
Authors: Loureiro Sandra Maria Correia , Nascimento Jorge
Published: November 2021

To date, tourism is the fastest growing industry globally, but one of the least developed in terms of environmentally sustainable practices. However, only a small portion of documents elaborate on how the introduction of new technologies can impact a more sustainable development route for tourism. This study’s objective is to provide an overview on literature state-of-the-art related to sustainable tourism and technological innovations, offering insights for further advancing this domain. We employ a bibliometric analysis and a comprehensive review of 139 articles, collected from Web of Science and Scopus databases, for the purpose of: (i) exploring and discussing the most relevant contributions in the publication network: (ii) highlighting key issues and emerging topics; (iii) uncovering open questions for the future. Our findings reveal contradictory views on the risks and benefits of technology adoption. Artificial intelligence, internet of things, circular economy, big data, augmented and virtual reality emerge as major trends. Five work streams are identified and described, leading to a broader perspective on how technology can shape the future of sustainable tourism. Relevant theoretical and managerial implications are derived. Finally, a research agenda is proposed as guidance for future studies addressing the outcomes of digital disruption on sustainable tourism.
Optimised Selection of Water Supply and Irrigation Sources—A Case Study on Surface and Underground Water, Desalination, and Wastewater Reuse in a Sahelian Coastal Arid Region
Authors: Diogo António Freire , Resende Ricardo Alves , Oliveira António Luís
Published: November 2021

This paper presents a general conceptual procedure and an economic, sustainable, resilient, and integrated solution for the water supply and landscape irrigation of a large touristic complex projected in an arid to semi-arid southwest coastal region of the island of Santiago in Cape Verde, in the Western African Sahel. It is assumed that underground water can be explored, but at a minimum level to avoid aquifers depletion or any eventual saline intrusion, and that surface water can be mobilised with the construction of a dam. Other important sources of water that were identified, assessed, and compared include treated wastewater produced in the complex, which can be reused for irrigation after undergoing tertiary treatment, and desalinated sea water, which requires the construction of a desalination plant. The devised procedure includes the definition of all feasible alternatives by a deterministic complete enumeration, and the selection of the optimised solution that may be determined by a single objective cost function to be minimised, as well as by a multi-criteria decision-making process that considers a conventional 1–5 score to be maximised. Beyond the cost, four additional criteria are considered and scored for each solution, namely, Environmental Sustainability, Water Quality, Resilience, and Local Integration, and for the relative weighting between criteria a weighted sum model is assumed. For the parameters and cost models used, the best solution that was found considers that the landscape irrigation is performed with surface water and reused wastewater, and that the water distribution network is supplied with underground and desalinated water. Other solutions more or less close can be selected based on different scores or different decision maker weighting preferences.
An Agent-Based Model for 5G Technology Diffusion in Urban Societies: Simulating Two Development Scenarios
Authors: Hutajulu Sahat , Dhewanto Wawan , Prasetio Eko Agus
Published: November 2021

Although 5G has been deployed in several countries, stakeholders are still hesitant to adopt the technology. Massive investment and collaboration become prerequisites for this technology to be successfully implemented and bring the most benefit. This research discusses the diffusion of 5G technology to personal end-users and industries and simulates the collaboration model. The simulation analyzes key essential indicators for stakeholders, such as the number of adopters, diffusion time, and total revenue. This study follows the pragmatism philosophy and abductive approach, integrating qualitative and quantitative research, resulting in the diffusion model. The qualitative data was obtained through focus groups and semi-structured interviews with key sources, while quantitative data from 437 people were gathered through a questionnaire. The simulation resulted in a 34% improvement in diffusion time, leading to faster investment return for industry players. This study offers an alternative paradigm compared to the diffusion of innovation theory, especially for new technology distribution. Finally, this research suggests that 5G stakeholders adopt the proposed collaboration strategy to achieve better business indicators.
How Does the Social Support Affect Refugees’ Life Satisfaction in Turkey? Stress as a Mediator, Social Aids and Coronavirus Anxiety as Moderators
Authors: Ekmen Eymen , Koçak Orhan , Solmaz Umut , Kopuz Koray , Younis Mustafa Z. , Orman Deniz
Published: November 2021

The number of refugees has increased exponentially due to international crises, wars, and political pressures in recent years worldwide. Turkey hosts the largest refugee population in the world with 3,672,646 Syrian refugees. This study aimed to examine the relationship among refugees’ stress, life satisfaction, social support, coronavirus anxiety, and social aids they get during the COVID-19 process. We hypothesized that stress, social aids, and coronavirus anxiety could play a role in the relationship between life satisfaction, stress, and social support. A cross-sectional survey was used to collect data from 628 Syrian refugees via an online questionnaire in Turkey. Confirmatory factor, correlation, and multiple regression analyses were conducted. In addition, the moderator and mediator role of variables tested using the 95% bias-corrected confidence interval from 5000 resamples was generated by the bias-corrected bootstrapping method. The study results show that stress partially mediated the relationship between family support and life satisfaction and between friend support and life satisfaction. In addition, coronavirus anxiety had a moderating effect on the relationship between family support and stress and friend support and stress. Finally, social aids moderated the relationship between stress and life satisfaction. In conclusion, the role of social aids, stress, and coronavirus anxiety in the relationship between social support, stress, and life satisfaction has been revealed.
Participation of Local People in the Payment for Forest Environmental Services Program: A Case Study in Central Vietnam
Authors: Ngoc Hoang Phan Bich , Fujiwara Takahiro , Iwanaga Seiji , Sato Noriko
Published: November 2021

In 2010, Vietnam implemented the payment for forest environmental services (PFES) program that was expected to bring additional income to local people and improve the efficiency of forest protection. However, factors affecting the motivation to participate in PFES have rarely been examined. The objectives of this study were to (1) identify factors that influence local people’s participation in PFES, (2) examine how local people participating in the PFES program were involved in decision-making in the Thua Thien Hue Province, and (3) assess PFES impact on local people. We conducted a field survey of 32 households at the study site. We found no difference in the access to PFES between poor and non-poor households. Participation in PFES was considered a reward for labor work in forests and a means to compensate for the legal rights of participants. Local people could participate at many stages of PFES implementation; however, they were only passive spectators with regards to PFES management. Two-thirds of the participants did not participate in decision-making regarding PFES distribution. We conclude that the efficiency of future PFES programs may be increased by enabling and stimulating the participants to take a more active part in the process of PFES management and distribution.
Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization
Authors: Cârcu-Dobrin Melania , Hancu Gabriel , Papp Lajos Attila , Fülöp Ibolya , Kelemen Hajnal
Published: November 2021

Chirality is a property of asymmetry which determines the pharmacokinetic and pharmacological profiles of optically active pharmaceuticals. Verapamil (VER), a calcium channel blocker phenylalkylamine derivative used in the treatment of cardio-vascular diseases, is a chiral compound, marketed as a racemate, although differences between the pharmacokinetic and pharmacological attributes of the enantiomers have been reported. The aim of our study was to develop a new chiral separation method for VER enantiomers by capillary electrophoresis (CE) using cyclodextrins (CDs) as chiral selectors (CSs). After an initial screening, using different native and derivatized CDs, at four pH levels, heptakis 2,3,6-tri-O-methyl-β-CD (TM-β-CD), a neutral derivatized CD, was identified as the optimum CS. For method optimization, a preliminary univariate approach was applied to characterize the influence of analytical parameters on the separation followed by a Box–Behnken experimental design to establish the optimal separation conditions. Chiral separation of enantiomers was achieved with a resolution of 1.58 in approximately 4 min; the migration order was R-VER followed by S-VER. The method analytical performance was evaluated in terms of precision, linearity, accuracy, and robustness (applying a Plackett–Burnam experimental design). The developed method was applied for the determination of VER enantiomers in pharmaceuticals. Finally, a computer modelling of VER–CD complexes was used to describe host–guest chiral recognition.
Effects of Energy Dissipation and Deformation Function on the Entanglement, Photon Statistics and Quantum Fisher Information of Three-Level Atom in Photon-Added Coherent States for Morse Potential
Authors: Abdel-Khalek Sayed , Khalil Eied M. , Alotaibi Hammad , Abo-Dahab Sayed M. , Mahmoud Emad E. , Higazy Mahmoud , Marin Marin
Published: November 2021

The present research paper considers a three-level atom (3LA) that interacts with a field mode primarily in a photon-added coherent state of Morse potential (PACSMP). The dynamics of entanglement, the photon statistics, and the quantum Fisher information are investigated. The statistics of field photons are discussed by evaluating the Mandel parameter. We check the influence of the energy dissipation and intensity-dependent function. Finally, we detect the relationship between the entanglement, the field’s nonclassical characteristics, and atomic quantum Fisher information throughout the evolution of time. The findings illustrate the important role of the number of added photons and CSMP in affecting the entanglement’s time evolution, the quantum Fisher information, and the Mandel parameter. Based on the obtained results, we reached significant physical phenomena, including the sudden birth and death of the nonlocal correlation between atom-Morse potential field structures.
Detection of Username Enumeration Attack on SSH Protocol: Machine Learning Approach
Authors: Agghey Abel Z. , Mwinuka Lunodzo J. , Pandhare Sanket M. , Dida Mussa A. , Ndibwile Jema D.
Published: November 2021

Over the last two decades (2000–2020), the Internet has rapidly evolved, resulting in symmetrical and asymmetrical Internet consumption patterns and billions of users worldwide. With the immense rise of the Internet, attacks and malicious behaviors pose a huge threat to our computing environment. Brute-force attack is among the most prominent and commonly used attacks, achieved out using password-attack tools, a wordlist dictionary, and a usernames list—obtained through a so-called an enumeration attack. In this paper, we investigate username enumeration attack detection on SSH protocol by using machine-learning classifiers. We apply four asymmetrical classifiers on our generated dataset collected from a closed-environment network to build machine-learning-based models for attack detection. The use of several machine-learners offers a wider investigation spectrum of the classifiers’ ability in attack detection. Additionally, we investigate how beneficial it is to include or exclude network ports information as features-set in the process of learning. We evaluated and compared the performances of machine-learning models for both cases. The models used are k-nearest neighbor (K-NN), naïve Bayes (NB), random forest (RF) and decision tree (DT) with and without ports information. Our results show that machine-learning approaches to detect SSH username enumeration attacks were quite successful, with KNN having an accuracy of 99.93%, NB 95.70%, RF 99.92%, and DT 99.88%. Furthermore, the results improve when using ports information.
Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation
Authors: Smith Thomas B. , Nicholson Michael L. , Hosgood Sarah A.
Published: November 2021

Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best to deliver these preservation methods or improve organ quality has not yet been conclusively defined. This review summarises the promising advances in machine perfusion science in recent years, which have the potential to further improve early graft function and prolong graft survival.
Real Valued Functions for the BFKL Eigenvalue
Authors: Joubat Mohammad , Prygarin Alex
Published: November 2021

We consider known expressions for the eigenvalue of the Balitsky-Fadin-Kuraev-Lipatov (BFKL) equation in N=4 super Yang-Mills theory as a real valued function of two variables. We define new real valued functions of two complex conjugate variables that have a definite complexity analogous to the weight of the nested harmonic sums. We argue that those functions span a general space of functions for the BFKL eigenvalue at any order of the perturbation theory.
Understanding Spatial Distribution of Retirement Villages: An Analysis of the Greater Brisbane Region
Authors: Xia Bo , E Jiaxuan , Chen Qing , Buys Laurie , Yigitcanlar Tan , Susilawati Connie
Published: November 2021

The nature of the increasingly ageing populations of developed countries places residential issues of these populations at the heart of urban policy. Retirement villages as housing options for older adults in Australia has been growing steadily in recent years; however, there have been a dearth of geographical studies looking into the distribution of existing retirement villages at the regional level. This study aims to reveal the geographical distributions and cluster patterns of retirement villages in the Greater Brisbane Region of Australia to better understand and serve the living requirements of current and potential retirement village residents. The geovisualization method was adopted to visually explore the distribution patterns of retirement villages. The Global Moran’s I and Local Moran’s I measures were employed to analyze the spatial correlation and the clusters of retirement villages in the study region. The study revealed that distribution of retirement villages was not random (z-score = 7.11; p < 0.001), but clustered in nature and included hotspot patterns, especially along the coastline and Brisbane River areas. Moreover, for-profit and not-for-profit retirement villages have different distribution patterns and adopted significantly different tenure agreements. In the study region, the spatial distribution of retirement villages aligns with the aggregation trend of older residents. The findings of this study disclosed the spatial distribution patterns of retirement villages and will provide developers and policymakers with geographically referenced data for the choice of new development sites to meet the market demand of potential customers, forming aged-friendly development strategies, and eventually leading to improved quality of life for older Australians.
Deciphering the Role of Humoral and Cellular Immune Responses in Different COVID-19 Vaccines—A Comparison of Vaccine Candidate Genes in Roborovski Dwarf Hamsters
Authors: Trimpert Jakob , Herwig Susanne , Stein Julia , Vladimirova Daria , Adler Julia M. , Abdelgawad Azza , Firsching Theresa C. , Thoma Tizia , Sehouli Jalid , Osterrieder Klaus , Gruber Achim D. , Sawitzki Birgit , Sander Leif Erik , Cichon Günter
Published: November 2021

With the exception of inactivated vaccines, all SARS-CoV-2 vaccines currently used for clinical application focus on the spike envelope glycoprotein as a virus-specific antigen. Compared to other SARS-CoV-2 genes, mutations in the spike protein gene are more rapidly selected and spread within the population, which carries the risk of impairing the efficacy of spike-based vaccines. It is unclear to what extent the loss of neutralizing antibody epitopes can be compensated by cellular immune responses, and whether the use of other SARS-CoV-2 antigens might cause a more diverse immune response and better long-term protection, particularly in light of the continued evolution towards new SARS-CoV-2 variants. To address this question, we explored immunogenicity and protective effects of adenoviral vectors encoding either the full-length spike protein (S), the nucleocapsid protein (N), the receptor binding domain (RBD) or a hybrid construct of RBD and the membrane protein (M) in a highly susceptible COVID-19 hamster model. All adenoviral vaccines provided life-saving protection against SARS-CoV-2-infection. The most efficient protection was achieved after exposure to full-length spike. However, the nucleocapsid protein, which triggered a robust T-cell response but did not facilitate the formation of neutralizing antibodies, controlled early virus replication efficiently and prevented severe pneumonia. Although the full-length spike protein is an excellent target for vaccines, it does not appear to be the only option for future vaccine design.
Stress Induced Transcription Factors Transactivate the Herpes Simplex Virus 1 Infected Cell Protein 27 (ICP27) Transcriptional Enhancer
Authors: Ostler Jeffery B. , Jones Clinton
Published: November 2021

Following acute infection, herpes simplex virus 1 (HSV-1) establishes lifelong latency in neurons, including sensory neurons within trigeminal ganglia. During latency, lytic cycle viral gene expression is silenced. However, stressful stimuli can trigger reactivation from latency. The viral tegument protein, VP-16, transactivates all immediate early (IE) promoters during productive infection. Conversely, cellular factors are expected to trigger viral gene expression during early stages of reactivation from latency and in non-neuronal cells that do not support high levels of productive infection. The glucocorticoid receptor (GR), synthetic corticosteroid dexamethasone, and certain stress-induced transcription factors cooperatively transactivate infected cell protein 0 (ICP0) and ICP4 promoters. Since ICP27 protein expression is required for productive infection, we hypothesized that the ICP27 promoter is transactivated by stress-induced transcription factors. New studies have demonstrated that ICP27 enhancer sequences were transactivated by GR and Krüppel-like factor 15 (KLF15). Mutation of a consensus Sp1 binding site within ICP27 enhancer sequences impaired transactivation by GR and KLF15. Chromatin immunoprecipitation studies have demonstrated that GR and KLF15 occupy ICP27 promoter sequences during productive infection. Cells transfected with an ICP27 enhancer fragment revealed the GR and KLF15 occupancy of ICP27 enhancer sequences required the intact Sp1 binding site. Notably, GR and KLF15 form a feed-forward transcription loop in response to stress, suggesting these cellular factors promote viral replication following stressful stimuli.
Improving Therapeutic Vaccination against Hepatitis B—Insights from Preclinical Models of Immune Therapy against Persistent Hepatitis B Virus Infection
Authors: Knolle Percy A. , Huang Li-Rung , Kosinska Anna , Wohlleber Dirk , Protzer Ulrike
Published: November 2021

Chronic hepatitis B affects more than 250 million individuals worldwide, putting them at risk of developing liver cirrhosis and liver cancer. While antiviral immune responses are key to eliminating hepatitis B virus (HBV) infections, insufficient antiviral immunity characterized by failure to eliminate HBV-infected hepatocytes is associated with chronic hepatitis B. Prophylactic vaccination against hepatitis B successfully established protective immunity against infection with the hepatitis B virus and has been instrumental in controlling hepatitis B. However, prophylactic vaccination schemes have not been successful in mounting protective immunity to eliminate HBV infections in patients with chronic hepatitis B. Here, we discuss the current knowledge on the development and efficacy of therapeutic vaccination strategies against chronic hepatitis B with particular emphasis on the pathogenetic understanding of dysfunctional anti-viral immunity. We explore the development of additional immune stimulation measures within tissues, in particular activation of immunogenic myeloid cell populations, and their use for combination with therapeutic vaccination strategies to improve the efficacy of therapeutic vaccination against chronic hepatitis B.
Production and Characterization of Nucleocapsid and RBD Cocktail Antigens of SARS-CoV-2 in Nicotiana benthamiana Plant as a Vaccine Candidate against COVID-19
Authors: Mamedov Tarlan , Yuksel Damla , Ilgın Merve , Gürbüzaslan Irem , Gulec Burcu , Mammadova Gulshan , Ozdarendeli Aykut , Yetiskin Hazel , Kaplan Busra , Islam Pavel Shaikh Terkis , Uygut Muhammet Ali , Hasanova Gulnara
Published: November 2021

The COVID-19 pandemic has put global public health at high risk, rapidly spreading around the world. Although several COVID-19 vaccines are available for mass immunization, the world still urgently needs highly effective, reliable, cost-effective, and safe SARS-CoV-2 coronavirus vaccines, as well as antiviral and therapeutic drugs, to control the COVID-19 pandemic given the emerging variant strains of the virus. Recently, we successfully produced receptor-binding domain (RBD) variants in the Nicotiana benthamiana plant as promising vaccine candidates against COVID-19 and demonstrated that mice immunized with these antigens elicited a high titer of RBD-specific antibodies with potent neutralizing activity against SARS-CoV-2. In this study, we engineered the nucleocapsid (N) protein and co-expressed it with RBD of SARS-CoV-2 in Nicotiana benthamiana plant to produce an antigen cocktail. The purification yields were about 22 or 24 mg of pure protein/kg of plant biomass for N or N+RBD antigens, respectively. The purified plant produced N protein was recognized by N protein-specific monoclonal and polyclonal antibodies demonstrating specific reactivity of mAb to plant-produced N protein. In this study, for the first time, we report the co-expression of RBD with N protein to produce a cocktail antigen of SARS-CoV-2, which elicited high-titer antibodies with potent neutralizing activity against SARS-CoV-2. Thus, obtained data support that a plant-produced antigen cocktail, developed in this study, is a promising vaccine candidate against COVID-19.
Immunomodulatory Strategies for Parapoxvirus: Current Status and Future Approaches for the Development of Vaccines against Orf Virus Infection
Authors: Bukar Alhaji Modu , Jesse Faez Firdaus Abdullah , Abdullah Che Azurahanim Che , Noordin Mustapha M. , Lawan Zaharaddeen , Mangga Hassana Kyari , Balakrishnan Krishnan Nair , Azmi Mohd-Lila Mohd
Published: November 2021

Orf virus (ORFV), the prototype species of the parapoxvirus genus, is the causative agent of contagious ecthyma, an extremely devastating skin disease of sheep, goats, and humans that causes enormous economic losses in livestock production. ORFV is known for its ability to repeatedly infect both previously infected and vaccinated sheep due to several immunomodulatory genes encoded by the virus that temporarily suppress host immunity. Therefore, the development of novel, safe and effective vaccines against ORFV infection is an important priority. Although, the commercially licensed live-attenuated vaccines have provided partial protection against ORFV infections, the attenuated viruses have been associated with major safety concerns. In addition to safety issues, the persistent reinfection of vaccinated animals warrants the need to investigate several factors that may affect vaccine efficacy. Perhaps, the reason for the failure of the vaccine is due to the long-term adaptation of the virus in tissue culture. In recent years, the development of vaccines against ORFV infection has achieved great success due to technological advances in recombinant DNA technologies, which have opened a pathway for the development of vaccine candidates that elicit robust immunity. In this review, we present current knowledge on immune responses elicited by ORFV, with particular attention to the effects of the viral immunomodulators on the host immune system. We also discuss the implications of strain variation for the development of rational vaccines. Finally, the review will also aim to demonstrate future strategies for the development of safe and efficient vaccines against ORFV infections.
Complicated Long Term Vaccine Induced Thrombotic Immune Thrombocytopenia—A Case Report
Authors: Günther Albrecht , Brämer Dirk , Pletz Mathias W. , Kamradt Thomas , Baumgart Sabine , Mayer Thomas E. , Baier Michael , Autsch Angelina , Mawrin Christian , Schönborn Linda , Greinacher Andreas , Thiele Thomas
Published: November 2021

Background and Objectives: Vaccine induced thrombotic thrombocytopenia (VITT) may occur after COVID-19 vaccination with recombinant adenoviral vector-based vaccines. VITT can present as cerebral sinus and venous thrombosis (CSVT), often complicated by intracranial hemorrhage. Today it is unclear, how long symptomatic VITT can persist. Here, we report the complicated long-term course of a VITT patient with extremely high titers of pathogenic anti-platelet factor 4 (PF4)-IgG antibodies. Methods: Clinical and laboratory findings are presented, including the course of platelet counts, D-Dimer levels, clinical presentation, imaging, SARS-CoV-2-serological and immunological, platelet activating anti-PF4-IgG, as well as autopsy findings. Results: The patient presented with extended superior sagittal sinus thrombosis with accompanying bifrontal intracerebral hemorrhage. Repeated treatment with intravenous immune globuline (IVIG) resolved recurrent episodes of thrombocytopenia. Moreover, the patient’s serum remained strongly positive for platelet-activating anti-PF4-IgG over three months. After a period of clinical stabilization, the patient suffered a recurrent and fatal intracranial hemorrhage. Conclusions: Complicated VITT with extremely high anti-PF4-IgG titers over three months can induce recurrent thrombocytopenia despite treatment with IVIG and anticoagulation. Plasma exchange, immunoadsorption, and /or immunosuppressive treatment may be considered in complicated VITT to reduce extraordinarily high levels of anti-PF4-IgG. Long-term therapy in such cases must take the individual bleeding risk and CSVT risk into account.
The Importance of RNA-Based Vaccines in the Fight against COVID-19: An Overview
Authors: Machado Bruna Aparecida Souza , Hodel Katharine Valéria Saraiva , Fonseca Larissa Moraes dos Santos , Mascarenhas Luís Alberto Brêda , Andrade Leone Peter Correia da Silva , Rocha Vinícius Pinto Costa , Soares Milena Botelho Pereira , Berglund Peter , Duthie Malcolm S. , Reed Steven G. , Badaró Roberto
Published: November 2021

In recent years, vaccine development using ribonucleic acid (RNA) has become the most promising and studied approach to produce safe and effective new vaccines, not only for prophylaxis but also as a treatment. The use of messenger RNA (mRNA) as an immunogenic has several advantages to vaccine development compared to other platforms, such as lower coast, the absence of cell cultures, and the possibility to combine different targets. During the COVID-19 pandemic, the use of mRNA as a vaccine became more relevant; two out of the four most widely applied vaccines against COVID-19 in the world are based on this platform. However, even though it presents advantages for vaccine application, mRNA technology faces several pivotal challenges to improve mRNA stability, delivery, and the potential to generate the related protein needed to induce a humoral- and T-cell-mediated immune response. The application of mRNA to vaccine development emerged as a powerful tool to fight against cancer and non-infectious and infectious diseases, for example, and represents a relevant research field for future decades. Based on these advantages, this review emphasizes mRNA and self-amplifying RNA (saRNA) for vaccine development, mainly to fight against COVID-19, together with the challenges related to this approach.
CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology
Authors: DeMarco Jennifer K. , Royal Joshua M. , Severson William E. , Gabbard Jon D. , Hume Steve , Morton Josh , Swope Kelsi , Simpson Carrie A. , Shepherd John W. , Bratcher Barry , Palmer Kenneth E. , Pogue Gregory P.
Published: November 2021

We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.
Retinal Vascular Events after mRNA and Adenoviral-Vectored COVID-19 Vaccines—A Case Series
Authors: Girbardt Christian , Busch Catharina , Al-Sheikh Mayss , Gunzinger Jeanne Martine , Invernizzi Alessandro , Xhepa Alba , Unterlauft Jan Darius , Rehak Matus
Published: November 2021

Background: To describe cases of retinal vascular events shortly after administration of mRNA or adenoviral-vectored COVID-19 vaccines. Design: Retrospective, multicenter case series. Methods: Six cases of retinal vascular events shortly after receiving COVID-19 vaccines. Results: A 38-year-old, otherwise healthy male patient presented with branch retinal arterial occlusion four days after receiving his second dose of SARS-CoV-2 vaccination with Comirnaty® (BioNTech®, Mainz, Germany; Pfizer®, New York City, NY, USA). An 81-year-old female patient developed visual symptoms twelve days after the second dose of SARS-CoV-2 vaccination with Comirnaty® and was diagnosed with a combined arterial and venous occlusion in her right eye. A 40-year-old male patient noticed blurry vision five days after his first dose of SARS-CoV-2 vaccination with Comirnaty® and was diagnosed with venous stasis retinopathy in his left eye. A 67-year-old male was diagnosed with non-arteritic anterior ischemic optic neuropathy in his right eye four days after receiving the first dose of Vaxzevria® (AstraZeneca®, Cambridge, UK). A 32-year-old man presented with a sudden onset of a scotoma two days after receiving the second dose of SARS-CoV-2 vaccination with Spikevax® (Moderna, Cambridge, UK) and was diagnosed with a circumscribed nerve fiber infarction. A 21-year-old female patient developed an acute bilateral acute macular neuroretinopathy three days after receiving the first dose of SARS-CoV2-vaccine Vaxzevria® (AstraZeneca®, Cambridge, UK). Conclusion: This case series describes six cases of retinal vascular events shortly after receiving mRNA or adenoviral-vectored COVID-19 vaccines. The short time span between received vaccination and occurrence of the observed retinal vascular events raises the question of a direct correlation. Our case series adds to further reports of possible side effects with potential serious post-immunization complications of COVID-19 vaccinations.
Effects of Stepwise Adjustment of C/N during the Start-Up of Submerged Membrane Bioreactors (SMBRs) on the Aerobic Denitrification of Wastewater
Authors: Zhang Yinan , Fang Yuxin , Wang Banglong , Zhang Hangjun , Ding Jiafeng
Published: November 2021

Based on the improved high-efficiency sewage treatment performance of submerged membrane bioreactors (SMBRs), we focused on how to adjust the C/N ratio of the influent water during reactor start-up to prevent an excessive C/N ratio from causing membrane fouling. In this study, an experimental method of gradually adjusting the influent C/N ratio to quickly start the reactor was proposed, and the results showed that biofilm formation in R1 (SMBR, three influent C/N ratios of 5, 10, and 20) was approximately completed in 32 days, shorter than that (40 days) required in R2 (SMBR, influent C/N ratio of 20). Higher removal efficiencies of 76.4% for TN, 70.1% for COD, and 79.2% for NH3-N were obtained in R1 than in R2. The high-throughput sequencing results indicated that after 150 days of operation, the Shannon index of bacteria in R1 increased from 2.97 to 4.41 and the growth of Nakamurella, Ferruginibacter, and Rhodanobacter was promoted in the reactor, which indicated substantial microbial diversity in the biofilm. Therefore, gradually adjusting the influent C/N ratio could effectively enhance the nitrogen removal performance of denitrification microbial communities in SMBRs. This study offers a reliable approach for starting the SMBR-enhanced biological nutrient removal process in wastewater treatment plants by gradually adjusting the influent C/N ratio.
Electrical Interoperability Evaluating of Wireless Electric Vehicle Charging Systems Based on Impedance Space
Authors: Shi Bingkun , Yang Fuyuan , Wei Bin , Ouyang Minggao
Published: November 2021

In the commercialization process of wireless electric vehicle charging (WEVC), it is essential to ensure the interoperability between diverse WEVC systems due to the wide application of various coil configurations and compensation topologies. This paper proposes a novel electrical interoperability evaluation method based on impedance indices and corresponding feasible space in the complex plane. Firstly, the electromagnetic description of the coil system is introduced to reveal the energy flow process of WEVC system. Further, two key impedance indices and their feasible space are derived and verified. Interoperability evaluation results show that the reference devices in Chinese WEVC standard GB/T 38775.6 and GB/T 38775.7 are able to achieve the requirements of power capability. Moreover, it is necessary to reduce the duty cycle of rectifier when the battery voltage rises so as to narrow down the variation of load resistance and avoid dangerous working conditions. The proposed method can effectively evaluate the electrical interoperability of WEVC systems from different manufacturers under different power or distance levels before conducting experiments.