bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Synthetic Biology in the Bioeconomy of Non-Food-Competing Biofuels
Authors: Fantinel Antônio Luiz , Margis Rogério , Talamini Edson , Dewes Homero
Published: May 2022

Despite the acknowledged relevance of renewable energy sources, biofuel production supported by food-related agriculture has faced severe criticism. One way to minimize the considered negative impacts is the use of sources of non-food biomass or wastes. Synthetic biology (SB) embraces a promising complex of technologies for biofuel production from non-edible and sustainable raw materials. Therefore, it is pertinent to identify the global evolution of investments, concepts, and techniques underlying the field in support of policy formulations for sustainable bioenergy production. We mapped the SB scientific knowledge related to biofuels using software that combines information visualization methods, bibliometrics, and data mining algorithms. The United States and China have been the leading countries in developing SB technologies. The Technical University of Denmark and Tsinghua University are institutions with higher centrality and have played prominent roles besides UC Los Angeles and Delft University Technology. We identified six knowledge clusters under the terms: versatile sugar dehydrogenase, redox balance principle, sesquiterpene production, Saccharomyces cerevisiae, recombinant xylose-fermenting strain, and Clostridium saccharoperbutylacetonicum N1-4. The emerging trends refer to specific microorganisms, processes, and products. Yarrowia lipolytica, Oleaginous yeast, E. coli, Klebsiella pneumoniae, Phaeodactylum tricornutum, and Microalgae are the most prominent microorganisms, mainly from the year 2016 onward. Anaerobic digestion, synthetic promoters, and genetic analysis appear as the most relevant platforms of new processes. Improved biofuels, bioethanol, and N-butanol are at the frontier of the development of SB-derived products. Synthetic biology is a dynamic interdisciplinary field in environmentally friendly bioenergy production pushed by growing social concerns and the emergent bioeconomy.
Supporting Newsrooms with Journalistic Knowledge Graph Platforms: Current State and Future Directions
Authors: Gallofré Ocaña Marc , Opdahl Andreas
Published: May 2022

Increasing competition and loss of revenues force newsrooms to explore new digital solutions. The new solutions employ artificial intelligence and big data techniques such as machine learning and knowledge graphs to manage and support the knowledge work needed in all stages of news production. The result is an emerging type of intelligent information system we have called the Journalistic Knowledge Platform (JKP). In this paper, we analyse for the first time knowledge graph-based JKPs in research and practice. We focus on their current state, challenges, opportunities and future directions. Our analysis is based on 14 platforms reported in research carried out in collaboration with news organisations and industry partners and our experiences with developing knowledge graph-based JKPs along with an industry partner. We found that: (a) the most central contribution of JKPs so far is to automate metadata annotation and monitoring tasks; (b) they also increasingly contribute to improving background information and content analysis, speeding-up newsroom workflows and providing newsworthy insights; (c) future JKPs need better mechanisms to extract information from textual and multimedia news items; (d) JKPs can provide a digitalisation path towards reduced production costs and improved information quality while adapting the current workflows of newsrooms to new forms of journalism and readers’ demands.
Web-Based Application for Biomedical Image Registry, Analysis, and Translation (BiRAT)
Authors: Pemmaraju Rahul , Minahan Robert , Wang Elise , Schadl Kornel , Daldrup-Link Heike , Habte Frezghi
Published: May 2022

Imaging has become an invaluable tool in preclinical research for its capability to non-invasively detect and monitor disease and assess treatment response. With the increased use of preclinical imaging, large volumes of image data are being generated requiring critical data management tools. Due to proprietary issues and continuous technology development, preclinical images, unlike DICOM-based images, are often stored in an unstructured data file in company-specific proprietary formats. This limits the available DICOM-based image management database to be effectively used for preclinical applications. A centralized image registry and management tool is essential for advances in preclinical imaging research. Specifically, such tools may have a high impact in generating large image datasets for the evolving artificial intelligence applications and performing retrospective analyses of previously acquired images. In this study, a web-based server application is developed to address some of these issues. The application is designed to reflect the actual experimentation workflow maintaining detailed records of both individual images and experimental data relevant to specific studies and/or projects. The application also includes a web-based 3D/4D image viewer to easily and quickly view and evaluate images. This paper briefly describes the initial implementation of the web-based application.
Tumor Diagnosis and Treatment: Imaging Assessment
Authors: Crimì Filippo , Vernuccio Federica , Cabrelle Giulio , Zanon Chiara , Pepe Alessia , Quaia Emilio
Published: May 2022

At present, oncologic imaging is crucial for clinical decision-making [...]
Water-Rock Interaction Processes: A Local Scale Study on Arsenic Sources and Release Mechanisms from a Volcanic Rock Matrix
Authors: Parrone Daniele , Ghergo Stefano , Preziosi Elisabetta , Casentini Barbara
Published: May 2022

Arsenic is a potentially toxic element (PTE) that is widely present in groundwater, with concentrations often exceeding the WHO drinking water guideline value (10.0 μg/L), entailing a prominent risk to human health due to long-term exposure. We investigated its origin in groundwater in a study area located north of Rome (Italy) in a volcanic-sedimentary aquifer. Some possible mineralogical sources and main mechanisms governing As mobilization from a representative volcanic tuff have been investigated via laboratory experiments, such as selective sequential extraction and dissolution tests mimicking different release conditions. Arsenic in groundwater ranges from 0.2 to 50.6 μg/L. It does not exhibit a defined spatial distribution, and it shows positive correlations with other PTEs typical of a volcanic environment, such as F, U, and V. Various potential As-bearing phases, such as zeolites, iron oxyhydroxides, calcite, and pyrite are present in the tuff samples. Arsenic in the rocks shows concentrations in the range of 17–41 mg/kg and is mostly associated with a minor fraction of the rock constituted by FeOOH, in particular, low crystalline, containing up to 70% of total As. Secondary fractions include specifically adsorbed As, As-coprecipitated or bound to calcite and linked to sulfides. Results show that As in groundwater mainly originates from water-rock interaction processes. The release of As into groundwater most likely occurs through desorption phenomena in the presence of specific exchangers and, although locally, via the reductive dissolution of Fe oxy-hydroxides.
Role of Nrf2 Nucleus Translocation in Beauvericin-Induced Cell Damage in Rat Hepatocytes
Authors: Shi Jiabin , Wang Yaling , Xu Wenlin , Cai Guodong , Zou Hui , Yuan Yan , Gu Jianhong , Liu Zongping , Bian Jianchun
Published: May 2022

Beauvericin (BEA), a food-borne mycotoxin metabolite derived from the fungus Beauveria Bassiana, is proven to exhibit high hepatotoxicity. However, the molecular mechanism underlying BEA-induced liver damage is not fully understood. Herein, the effect of Nrf2 nuclear translocation-induced by BEA in hepatocytes was investigated. CCK8 solution was used to determine the appropriate concentrations of BEA (0, 1, 1.5 and 2 μmol/L), and BRL3A cells were then exposed to different concentrations of BEA for 12 h. Our results reveal that BEA exposure is associated with high cytotoxicity, lowered cell viability, damaged cellular morphology, and increased apoptosis rate. BEA could lead to oxidative damage through the overproduction of ROS and unbalanced redox, trigger the activation of Nrf2 signaling pathway and Nrf2 nuclear translocation for transcriptional activation of downstream antioxidative genes. Additionally, BEA treatment upregulated the expression of autophagy-related proteins (LC3, p62, Beclin1, and ATG5) indicating a correlation between Nrf2 activation and autophagy, which warrants further studies. Furthermore, ML385, an Nrf2 inhibitor, partially ameliorated BEA-induced cell injury while CDDO, an Nrf2 activator, aggravated liver damage. The present study emphasizes the role of Nrf2 nuclear translocation in BEA-induced oxidative stress associated with the hepatotoxic nature of BEA.
Whole-Transcriptome Analysis of Non-Coding RNA Alteration in Porcine Alveolar Macrophage Exposed to Aflatoxin B1
Authors: Chao Huhe , Ma Haohai , Sun Jiadong , Yuan Shuai , Dong Peiyu , Zhao Aihong , Li Lan , Shen Wei , Zhang Xifeng
Published: May 2022

Aflatoxin B1 (AFB1) is a type of mycotoxin produced by the fungi Aspergillus flavus and Aspergillus parasiticus and is commonly found in cereals, oils and foodstuffs. In order to understand the toxic effects of AFB1 exposure on Porcine alveolar macrophages (3D4/2 cell), the 3D4/2 cells were exposed to 40 μg/mL AFB1 for 24 h in vitro, and several methods were used for analysis. Edu and TUNEL analysis showed that the proliferation of 3D4/2 cells was significantly inhibited and the apoptosis of 3D4/2 cells was significantly induced after AFB1 exposure compared with that of the control group. Whole-transcriptome analysis was performed to reveal the non-coding RNA alteration in 3D4/2 cells after AFB1 exposure. It was found that the expression of cell-cycle-related and apoptosis-related genes was altered after AFB1 exposure, and lncRNAs and miRNAs were also significantly different among the experimental groups. In particular, AFB1 exposure affected the expression of lncRNAs associated with cellular senescence signaling pathways, such as MSTRG.24315 and MSTRG.80767, as well as related genes, Cxcl8 and Gadd45g. In addition, AFB1 exposure affected the expression of miRNAs associated with immune-related genes, such as miR-181a, miR-331-3p and miR-342, as well as immune-related genes Nfkb1 and Rras2. Moreover, the regulation networks between mRNA-miRNAs and mRNA-lncRNAs were confirmed by the results of RT-qPCR and immunofluorescence. In conclusion, our results here demonstrate that AFB1 exposure impaired proliferation of 3D4/2 cells via the non-coding RNA-mediated pathway.
Can Botulinum Toxin-A Contribute to Reconstructing the Physiological Homeostasis of the Masticatory Complex in Short-Faced Patients during Occlusal Therapy? A Prospective Pilot Study
Authors: Li Xin , Feng Xiaoyan , Li Juan , Bao Xinyu , Xu Jinghong , Lin Jun
Published: May 2022

The physiological homeostasis of the masticatory complex in short-faced patients is too robust to be disintegrated and reconstructed due to the powerful masseter muscle. This study innovatively introduced the botulinum toxin-A (BTX-A) into the field of dental occlusal treatment, providing a novel and minimally invasive therapy perspective for the two major clinical problems in these patients (low treatment efficiency and high rates of complications). In total, 10 adult patients with skeletal low angle seeking occlusal treatment (age: 27.0 ± 6.1 years; 4 males and 6 females) were administered 30–50 U of BTX-A in each masseter muscle and evaluated before and 3 months after injection based on cone-beam computed tomography (CBCT). We found a significant reduction in the thickness of the masseter muscle (MMT) (p < 0.0001). With regards to occlusion, we found a significant increase in the height of the maxillary second molar (U7-PP) (p < 0.05) with significantly flattened occlusal curves (the curve of Spee [COS] (p < 0.01), and the curve of Wilson [COW] (p < 0.05)). Furthermore, the variations in the temporomandibular joint exhibited a significant reduction in the anterior joint space (AJS) (p < 0.05) and superior joint space (SJS) (p < 0.05). In addition, the correlation analysis of the masticatory complex provided the basis for the following multiple regression equation: MMT = 10.08 − 0.11 COW + 2.73 AJS. The findings from our pilot study indicate that BTX-A, as a new adjuvant treatment attempt of occlusal therapy for short-faced patients, can provide a more favorable muscular environment for subsequent occlusal therapy through the adjustment of the biting force and may contribute to the reconstruction of healthier homeostasis of the masticatory complex. However, further research is required to establish the reliability and validity of these findings.
Mycotoxin Analysis of Grain via Dust Sampling: Review, Recent Advances and the Way Forward: The Contribution of the MycoKey Project
Authors: Ciasca Biancamaria , De Saeger Sarah , De Boevre Marthe , Reichel Mareike , Pascale Michelangelo , Logrieco Antonio F. , Lattanzio Veronica M. T.
Published: May 2022

The sampling protocols for the official control of the levels of mycotoxins in foodstuffs are very costly and time-consuming. More efforts are needed to implement alternative sampling plans able to support official control, or to adapt the current ones. The aim of the research carried out within the European Horizon 2020 MycoKey project was to evaluate the applicability at industrial scale of the dust sampling approach to detect multiple mycotoxins in grains. To this end, two trials were performed on an EU industrial site: (i) control of the unloading of wheat from train wagons; (ii) control of the unloading of wheat from trucks. In line with previous studies, the MycoKey results indicated that dust sampling and mycotoxin analysis represent a fitness for purpose approach for non–destructive and rapid identification of wheat commodities compliant to the maximum permitted levels. Based on reviewed and newly generated results, this article discusses potential applications and limits of the dust sampling methodology, identifying future research needs.
Progress in the Simulation and Modelling of Coherent Radio Pulses from Ultra High-Energy Cosmic Particles
Authors: Alvarez-Muñiz Jaime , Zas Enrique
Published: May 2022

In the last decade, many experiments have been planned, designed or constructed to detect Ultra High Energy showers produced by cosmic rays or neutrinos using the radio technique. This technique consists in detecting short radio pulses emitted by the showers. When the detected wavelengths are longer than typical shower length scales, the pulses are coherent. Radio emission can be simulated by adding up the contributions of all the particle showers in a coherent way. The first program to use this approach was based on an algorithm developed more than thirty years ago and referred to as “ZHS”. Since then, much progress has been obtained using the ZHS algorithm with different simulation programs to investigate pulses from showers in dense homogeneous media and the atmosphere, applying it to different experimental initiatives, and developing extensions to address different emission mechanisms or special circumstances. We here review this work, primarily led by the authors in collaboration with other scientists, illustrating the connections between different articles, and giving a pedagogical approach to most of the work.
NK Cells in Protection from HIV Infection
Authors: Bernard Nicole F. , Alsulami Khlood , Pavey Erik , Dupuy Franck P.
Published: May 2022

Some people, known as HIV-exposed seronegative (HESN) individuals, remain uninfected despite high levels of exposure to HIV. Understanding the mechanisms underlying their apparent resistance to HIV infection may inform strategies designed to protect against HIV infection. Natural Killer (NK) cells are innate immune cells whose activation state depends on the integration of activating and inhibitory signals arising from cell surface receptors interacting with their ligands on neighboring cells. Inhibitory NK cell receptors use a subset of major histocompatibility (MHC) class I antigens as ligands. This interaction educates NK cells, priming them to respond to cells with reduced MHC class I antigen expression levels as occurs on HIV-infected cells. NK cells can interact with both autologous HIV-infected cells and allogeneic cells bearing MHC antigens seen as non self by educated NK cells. NK cells are rapidly activated upon interacting with HIV-infected or allogenic cells to elicit anti-viral activity that blocks HIV spread to new target cells, suppresses HIV replication, and kills HIV-infected cells before HIV reservoirs can be seeded and infection can be established. In this manuscript, we will review the epidemiological and functional evidence for a role for NK cells in protection from HIV infection.
Memory CD8 T Cells Protect against Cytomegalovirus Disease by Formation of Nodular Inflammatory Foci Preventing Intra-Tissue Virus Spread
Authors: Holtappels Rafaela , Podlech Jürgen , Freitag Kirsten , Lemmermann Niels A. , Reddehase Matthias J.
Published: May 2022

Cytomegaloviruses (CMVs) are controlled by innate and adaptive immune responses in an immunocompetent host while causing multiple organ diseases in an immunocompromised host. A risk group of high clinical relevance comprises transiently immunocompromised recipients of hematopoietic cell transplantation (HCT) in the “window of risk” between eradicative therapy of hematopoietic malignancies and complete reconstitution of the immune system. Cellular immunotherapy by adoptive transfer of CMV-specific CD8 T cells is an option to prevent CMV disease by controlling a primary or reactivated infection. While experimental models have revealed a viral epitope-specific antiviral function of cognate CD8 T cells, the site at which control is exerted remained unidentified. The observation that remarkably few transferred cells protect all organs may indicate an early blockade of virus dissemination from a primary site of productive infection to various target organs. Alternatively, it could indicate clonal expansion of a few transferred CD8 T cells for preventing intra-tissue virus spread after successful initial organ colonization. Our data in the mouse model of murine CMV infection provide evidence in support of the second hypothesis. We show that transferred cells vigorously proliferate to prevent virus spread, and thus viral histopathology, by confining and eventually resolving tissue infection within nodular inflammatory foci.
HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score
Authors: Arentoft Alyssa , Troxell Katie , Alvarez Karen , Aghvinian Maral , Rivera Mindt Monica , Cherner Mariana , Van Dyk Kathleen , Razani Jill , Roxas Michaela , Gavilanes Melissa
Published: May 2022

This literature review summarizes the existing research examining the CNS penetration effectiveness (CPE) score and neurocognitive outcomes (i.e., neuropsychological assessment and neurocognitive screening) in HIV+ individuals. Despite the effectiveness of Combined Antiretroviral Therapy (CART) in reducing mortality and morbidity in HIV and controlling viral replication, HIV often persists in the Central Nervous System (CNS), and rates of neurocognitive impairment remain higher than predicted in the post-CART era. The CPE score was developed to rank antiretroviral regimens on their ability to penetrate the CNS and potency in inhibiting the virus, and it has been examined in relation to neurocognitive functioning for over a decade. Based on the results of 23 studies, we conclude that CPE is not as strongly associated with neurocognitive outcomes as initially hypothesized, although higher CPE ARV regimens may be associated with modest, improved outcomes in global neurocognitive functioning, and to a lesser extent attention/working memory and learning/memory. Conclusions, however, are limited by the heterogeneity in study design and methods, and the lack of a more recent CPE metric update. It is recommended that future research in this area employ comprehensive, standardized neuropsychological test batteries and examine domain-level performance, and use the newer 2010 CPE metric, although an updated CPE ranking is urgently needed.
Transmission of Grapevine Red Blotch Virus by Spissistilus festinus [Say, 1830] (Hemiptera: Membracidae) between Free-Living Vines and Vitis vinifera ‘Cabernet Franc’
Authors: Hoyle Victoria , Flasco Madison T. , Choi Jiyeong , Cieniewicz Elizabeth J. , McLane Heather , Perry Keith , Dangl Gerald , Rwahnih Maher Al , Heck Michelle , Loeb Greg , Fuchs Marc F.
Published: May 2022

Grapevine red blotch disease emerged within the past decade, disrupting North American vine stock production and vineyard profitability. Our understanding of how grapevine red blotch virus (GRBV), the causal agent of the disease, interacts with its Vitis hosts and insect vector, Spissistilus festinus, is limited. Here, we studied the capabilities of S. festinus to transmit GRBV from and to free-living vines, identified as first-generation hybrids of V. californica and V. vinifera ‘Sauvignon blanc’ (Vcal hybrids), and to and from V. vinifera ‘Cabernet franc’ (Vvin Cf) vines. The transmission rate of GRBV was high from infected Vcal hybrid vines to healthy Vcal hybrid vines (77%, 10 of 13) and from infected Vvin Cf vines to healthy Vcal hybrid vines (100%, 3 of 3). In contrast, the transmission rate of GRBV was low from infected Vcal hybrid vines to healthy Vvin Cf vines (15%, 2 of 13), and from infected Vvin Cf vines to healthy Vvin Cf vines (19%, 5 of 27). No association was found between transmission rates and GRBV titer in donor vines used in transmission assays, but the virus titer was higher in the recipient leaves of Vcal hybrid vines compared with recipient leaves of Vvin Cf vines. The transmission of GRBV from infected Vcal hybrid vines was also determined to be trans-stadial. Altogether, our findings revealed that free-living vines can be a source for the GRBV inoculum that is transmissible by S. festinus to other free-living vines and a wine grape cultivar, illustrating the interconnected roles of the two virus hosts in riparian areas and commercial vineyards, respectively, for virus spread. These new insights into red blotch disease epidemiology will inform the implementation of disease management strategies.
Novel Vaccines and Drugs That Target the Surface Glycoproteins of Influenza Viruses, RSV, Parainfluenza Viruses, and SARS-CoV-2
Authors: Russell Charles J. , Govorkova Elena A.
Published: May 2022

Newly emerging and seasonal respiratory viruses have a great impact on public health[...]
Low Susceptibility of Rubella Virus in First-Trimester Trophoblast Cell Lines
Authors: Pham Ngan Thi Kim , Trinh Quang Duy , Takada Kazuhide , Komine-Aizawa Shihoko , Hayakawa Satoshi
Published: May 2022

We recently published an article about myelin oligodendrocyte glycoprotein-independent rubella infection of keratinocytes in vitro, in which first-trimester trophoblast cells were shown as rubella virus (RuV)-resistant. Given an incident rate as high as 90% of congenital rubella syndrome in the first eight weeks of pregnancy, the RuV infection of first-trimester trophoblasts is considered key to opening the gate to transplacental transmission mechanisms. Therefore, with this study, we aimed to verify the susceptibility/resistance of first-trimester trophoblast cell lines, HTR-8/SVneo and Swan.71, against RuV. Cells cultured on multi-well plates were challenged with a RuV clinical strain at a multiplicity of infection from 5 to 10 for 3 h. The infectivity was investigated by immunofluorescence (IF) assay and flow cytometry (FCM) analysis. Supernatants collected during the post-infection period were used to determine virus-progeny production. The scattered signaling of RuV infection of these cells was noted by IF assay, and the FCM analysis showed an average of 4–5% of gated cells infected with RuV. In addition, a small but significant production of virus progeny was also observed. In conclusion, by employing appropriate approaches, we determined the low infectivity of RuV in first-trimester trophoblast cell lines but not resistance as in our previous report.
CREB3 Plays an Important Role in HPSE-Facilitated HSV-1 Release in Human Corneal Epithelial Cells
Authors: Yadavalli Tejabhiram , Sharma Pankaj , Wu David , Kapoor Divya , Shukla Deepak
Published: May 2022

Herpes simplex virus type-1 (HSV-1) exploits several host factors to enhance its replication and release from infected cells. It induces the production of host enzyme heparanase (HPSE) to aid in egress. While the mechanism by which HPSE assists in viral release is well-characterized, other host factors that are recruited along with HPSE for viral release are less well understood. In this study, we identify cyclic-AMP-responsive element-binding protein3 (CREB3) as a key player in HPSE-facilitated HSV-1 egress. When CREB3 is transiently upregulated in human corneal epithelial cells, HSV-1 release from the infected cells is correspondingly enhanced. This activity is linked to HPSE expression such that HPSE-transfected corneal epithelial (HCE) cells more highly express CREB3 than wild-type cells while the cells knocked out for HPSE show very little CREB3 expression. CREB3-transfected HCE cells showed significantly higher export of HPSE upon infection than wild-type cells. Our data suggests that coat protein complex II (COPII), which mediates HPSE trafficking, is also upregulated via a CREB3-dependent pathway during HSV-1 infection. Finally, the co-transfection of CREB3 and HPSE in HCE cells shows the highest viral release compared to either treatment alone, establishing CREB3 as a key player in HPSE-facilitated HSV-1 egress.
Identification of NP Protein-Specific B-Cell Epitopes for H9N2 Subtype of Avian Influenza Virus
Authors: Huang Xiangyu , Huang Jingwen , Yin Guihu , Cai Yiqin , Chen Mengli , Hu Jianing , Feng Xiuli
Published: May 2022

Avian Influenza (AI) caused by the H9N2 subtype of the avian influenza virus (AIV) poses a serious threat to both the poultry industry and to public health safety. NP is one of the major structural proteins in influenza viruses. B-cell determinants located on NP proteins have attracted increasing attention. In this study, based on the NP sequence of the H9N2 (A/chicken/Shandong/LY1/2017) strain, the truncated NP gene (71 AA–243 AA) was cloned and prokaryotically expressed in a pET-28a (+) vector. BALB/c mice were immunized with a purified recombinant of an NP protein to prepare a monoclonal antibody against NP proteins. The prokaryotic expression of four overlapping fragments, NP-N-96, NP-C-103, NP-C-54 and NP-C-49, were used to recognize an antigenic epitope of the NP protein. The results show that, after cell fusion, one hybridoma cell clone secreted the antibody specific to the NP protein, following screening with ELISA and indirect immunofluorescence, which is named the 4F5 monoclonal antibody (mAb). Western blotting on the overlapping fragments showed that the 230FQTAAQRA237 motif was identified as the minimal motif recognized by 4F5mAb, which was represented as the linear B-cell epitope of the NP protein. Homology analysis of this epitope shows that it was highly conserved in 18 AIVs analyzed in this study, and the epitope prediction results indicate that the epitope may be located on the surface of the NP protein. These results provide a strong experimental basis for studying the function of the NP protein of the H9N2 AIV and also strong technical support for the development of a universal assay based on an anti-NP monoclonal antibody.
Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron
Authors: Gerges Daniela , Kapps Sebastian , Hernández-Carralero Esperanza , Freire Raimundo , Aiad Monika , Schmidt Sophie , Winnicki Wolfgang , Reiter Thomas , Pajenda Sahra , Schmidt Alice , Sunder-Plassmann Gere , Wagner Ludwig
Published: May 2022

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.
Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds
Authors: Schmitz Katharina S. , Lange Mona V. , Gommers Lennert , Handrejk Kim , Porter Danielle P. , Alabi Christopher A. , Moscona Anne , Porotto Matteo , de Vries Rory D. , de Swart Rik L.
Published: May 2022

Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic interventions are complicated by the long incubation time of measles, resulting in a narrow treatment window. At present, the only available WHO-advised option is treatment with intravenous immunoglobulins, although this is not approved as standard of care. Antivirals against measles may contribute to intervention strategies to limit the impact of future outbreaks. Here, we review previously described antivirals and antiviral assays, evaluate the antiviral efficacy of a number of compounds to inhibit MV dissemination in vitro, and discuss potential application in specific target populations. We conclude that broadly reactive antivirals could strengthen existing intervention strategies to limit the impact of measles outbreaks.
Gastrointestinal Involvement in SARS-CoV-2 Infection
Authors: Chen Tsung-Hsien , Hsu Ming-Tse , Lee Ming-Yang , Chou Chu-Kuang
Published: May 2022

SARS-CoV-2 has evolved into a virus that primarily results in mild or asymptomatic disease, making its transmission more challenging to control. In addition to the respiratory tract, SARS-CoV-2 also infects the digestive tract. Some gastrointestinal symptoms occur with or before respiratory symptoms in patients with COVID-19. Respiratory infections are known to cause intestinal immune impairment and gastrointestinal symptoms. When the intestine is inflamed, cytokines affect the lung immune response and inflammation through blood circulation. The gastrointestinal microbiome may be a modifiable factor in determining the risk of SARS-CoV-2 infection and disease severity. The development of oral SARS-CoV-2 vaccine candidates and the maintenance of gut microbiota profiles may contribute to the early control of COVID-19 outbreaks. To this end, this review summarizes information on the gastrointestinal complications caused by SARS-CoV-2, SARS-CoV-2 infection, the gastrointestinal–lung axis immune response, potential control strategies for oral vaccine candidates and maintaining intestinal microbiota homeostasis.
Evolution Characterization and Pathogenicity of a Porcine Reproductive and Respiratory Syndrome Virus Isolate from a Pig Farm in Shandong Province, China
Authors: Xu Yulin , Ji Xiaojing , Fu Chunyu , Hu Dong , Pang Heng , Wang Tingting , Li Chuangang , Wang Gang , Peng Jun
Published: May 2022

In recent years, porcine reproductive and respiratory syndrome virus (PRRSV) strains have been experiencing extensive recombination in Chinese swine farms. This recombination usually happens in NADC30/34 strains and highly pathogenic (HP) PRRSV strains. This study identified a new PRRSV isolate that shared 99% and 99.1% nucleotide identity with CH-1a and CH-1R at the genomic level, respectively. After purification by viral plaque assay, this isolate was named PRRSV CSR1801. The isolate did not experience any recombination with other PRRSV strains common in swine herd epidemics in China, which means it still maintains the stable features of the classical PRRSV strain and did not easily recombine with other PRRSV strains. Further analysis of the pathogenicity of the PRRSV isolate CSR1801 was performed in piglets. The results indicated that none of the inoculated piglets showed the typical clinical manifestations of PRRS, which presented with runny noses, rough back hair, rectal temperatures always below 40.5 °C, and no deaths. Additionally, no obvious histopathological lesions such as severe interstitial pneumonia could be observed in the lungs of the piglets. Hence, the PRRSV isolate CSR1801 should be classified as a classical-like PRRSV strain. This classical PRRSV strain showed genetic stability and maintained low pathogenicity. This study may provide new clues for further understanding the genetic evolution and pathogenicity of PRRSV and may also be an important reference for the prevention and control of PRRS in swine farms.
Poly(A)-Binding Protein Cytoplasmic 1 Inhibits Porcine Epidemic Diarrhea Virus Replication by Interacting with Nucleocapsid Protein
Authors: Wu Tingting , Wei Xiaona , Zheng Shumei , She Gaoli , Han Zhenling , Xu Zhichao , Cao Yongchang , Xue Chunyi
Published: May 2022

Porcine epidemic diarrhea virus (PEDV) is the etiological agent of porcine epidemic diarrhea (PED) characterized by vomit, watery diarrhea, dehydration and high mortality. Outbreaks of highly pathogenic variant strains of PEDV have resulted in extreme economic losses to the swine industry all over the world. The study of host–virus interaction can help to better understand the viral pathogenicity. Many studies have shown that poly(A)-binding proteins are involved in the replication process of various viruses. Here, we found that the infection of PEDV downregulated the expression of poly(A)-binding protein cytoplasmic 1 (PABPC1) at the later infection stage in Vero cells. The overexpression of PABPC1 inhibited the proliferation of PEDV at transcription and translation level, and siRNA-mediated depletion of PABPC1 promoted the replication of PEDV. Furthermore, mass spectrometry analysis and immunoprecipitation assay confirmed that PABPC1 interacted with the nucleocapsid (N) protein of PEDV. Confocal microscopy revealed the co-localizations of PABPC1 with N protein in the cytoplasm. Taken together, these results demonstrate the antiviral effect of PABPC1 against PEDV replication by interacting with N protein, which increases understanding of the interaction between PEDV and host.
Immunogenicity and Reactogenicity of the Booster Dose of COVID-19 Vaccines and Related Factors: A Panel Study from the General Population in Serbia
Authors: Stosic Maja , Milic Marija , Markovic Milos , Kelic Ivana , Bukumiric Zoran , Veljkovic Marko , Kisic Tepavcevic Darija , Saponjic Vladan , Plavsa Dragana , Jovanovic Sofija , Jovanovic Verica
Published: May 2022

The Republic of Serbia applied the booster dose of the following COVID-19 vaccines: BNT162b2 mRNA (Pfizer-BioNTech), Sinopharm BBIBP-CorV (Vero Cell®), Gam-COVID-Vac (Sputnik V) and ChAdOk1 nCoV-19 (AstraZeneca). We aimed to examine the immunogenicity and reactogenicity of the booster dose and identify factors related to immune response and adverse events. Panel study, conducted during August and September 2021, included 300 persons receiving the booster dose at the Institute of Public Health of Serbia. Blood samples were taken on the day of receiving the booster dose, and after 7 and 28 days. When applying homologous regimen, the average increase in anti-spike immunoglobulin G was 8782.2 (after 7 days), 1213.9 after 28 days, while 9179.5 (after 7 days) and 16,728.1 after 28 days of heterologous regimen. Sinopharm BBIBP-CorV (p < 0.001) and Sputnik V (p < 0.001), age 65 and over (p = 0.001) and currently smoking (p < 0.001) were independently associated with lower levels of anti-spike immunoglobulin G. Female sex (OR = 1.77; 95%CI = 1.01–3.12), previous COVID-19 infection (OR = 3.62; 95%CI = 1.13–11.63) and adverse events after the second dose (OR = 2.66; 95%CI = 1.33–5.32) were independently associated with intense systemic adverse events 7 days after. Booster dose significantly increased antibodies titers, especially 28 days after heterologous regimen, without a significant increase in reactogenicity.
Leaving No One Behind: Interventions and Outcomes of the COVID-19 Vaccine Maximising Uptake Programme
Authors: Berrou Ilhem , Hamilton Kathryn , Cook Clare , Armour Clare , Hughes Sian , Hancock Jude , Quigg Sally , Hajinur Huda , Srivastava Seema , Kenward Charlie , Ali Amjid , Hobbs Laura , Milani Elena , Walsh Nicola
Published: May 2022

The devastating impact of COVID-19 on individuals and communities has accelerated the development of vaccines and the deployment of ambitious vaccination programmes to reduce the risks of infection, infection transmission and symptom severity. However, many people delay or refuse to get vaccinated against COVID-19, for many complex reasons. Vaccination programmes that are tailored to address individual and communities’ COVID-19 concerns can improve vaccine uptake rates and help achieve the required herd-immunity threshold. The Maximising Uptake Programme has led to the vaccination of 7979 people from February–August 2021 in the South West of England, UK, who are at high risk of severe illness from COVID-19 and/or may not access the COVID-19 vaccines through mass vaccination centres and general practices. These include: people experiencing homelessness; non-English-speaking people; people from minority ethnic groups; refugees and asylum seekers; Gypsy, Roma, Travelers and boat people; and those who are less able to access vaccination centres, such as people with learning difficulties, serious mental illness, drug and alcohol dependence, people with physical and sensory impairment, and people with dementia. Outreach work coupled with a targeted communication and engagement campaign, co-designed with community leaders and influencers, have led to significant engagement and COVID-19 vaccine uptake among the target populations.
Vulnerability Predictors of Post-Vaccine SARS-CoV-2 Infection and Disease—Empirical Evidence from a Large Population-Based Italian Platform
Authors: Corrao Giovanni , Franchi Matteo , Cereda Danilo , Bortolan Francesco , Leoni Olivia , Borriello Catia Rosanna , Della Valle Petra Giulia , Tirani Marcello , Pavesi Giovanni , Barone Antonio , Ercolanoni Michele , Jara Jose , Galli Massimo , Bertolaso Guido
Published: May 2022

We aimed to identify individual features associated with increased risk of post-vaccine SARS-CoV-2 infection and severe COVID-19 illness. We performed a nested case–control study based on 5,350,295 citizens from Lombardy, Italy, aged ≥ 12 years who received a complete anti-COVID-19 vaccination from 17 January 2021 to 31 July 2021, and followed from 14 days after vaccine completion to 11 November 2021. Overall, 17,996 infections and 3023 severe illness cases occurred. For each case, controls were 1:1 (infection cases) or 1:10 (severe illness cases) matched for municipality of residence and date of vaccination completion. The association between selected predictors (sex, age, previous occurrence of SARS-CoV-2 infection, type of vaccine received, number of previous contacts with the Regional Health Service (RHS), and the presence of 59 diseases) and outcomes was assessed by using multivariable conditional logistic regression models. Sex, age, previous SARS-CoV-2 infection, type of vaccine and number of contacts with the RHS were associated with the risk of infection and severe illness. Moreover, higher odds of infection and severe illness were significantly associated with 14 and 34 diseases, respectively, among those investigated. These results can be helpful to clinicians and policy makers for prioritizing interventions.
Serious Underlying Medical Conditions and COVID-19 Vaccine Hesitancy: A Large Cross-Sectional Analysis from Australia
Authors: Day Daphne , Grech Lisa , Nguyen Mike , Bain Nathan , Kwok Alastair , Harris Sam , Chau Hieu , Chan Bryan , Blennerhassett Richard , Nott Louise , Hamad Nada , Tognela Annette , Hoffman David , McCartney Amelia , Webber Kate , Wong Jennifer , Underhill Craig , Sillars Brett , Winkel Antony , Savage Mark , Loe Bao Sheng , Freeman Daniel , Segelov Eva ,   on behalf of the CANVACCS, DIABVACCS and MSVACCS Investigators
Published: May 2022

As COVID-19 vaccinations became available and were proven effective in preventing serious infection, uptake amongst individuals varied, including in medically vulnerable populations. This cross-sectional multi-site study examined vaccine uptake, hesitancy, and explanatory factors amongst people with serious and/or chronic health conditions, including the impact of underlying disease on attitudes to vaccination. A 42-item survey was distributed to people with cancer, diabetes, or multiple sclerosis across ten Australian health services from 30 June to 5 October 2021. The survey evaluated sociodemographic and disease-related characteristics and incorporated three validated scales measuring vaccine hesitancy and vaccine-related beliefs generally and specific to their disease: the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale-Six. Among 4683 participants (2548 [54.4%] female, 2108 [45.0%] male, 27 [0.6%] other; mean [SD] age, 60.6 [13.3] years; 3560 [76.0%] cancer, 842 [18.0%] diabetes, and 281 [6.0%] multiple sclerosis), 3813 (81.5%) self-reported having at least one COVID-19 vaccine. Unvaccinated status was associated with younger age, female sex, lower education and income, English as a second language, and residence in regional areas. Unvaccinated participants were more likely to report greater vaccine hesitancy and more negative perceptions toward vaccines. Disease-related vaccine concerns were associated with unvaccinated status and hesitancy, including greater complacency about COVID-19 infection, and concerns relating to vaccine efficacy and impact on their disease and/or treatment. This highlights the need to develop targeted strategies and education about COVID-19 vaccination to support medically vulnerable populations and health professionals.
Impact of Vaccine and Immunity Passports in the Context of COVID-19: A Time Series Analysis in Overseas France
Authors: d’Almeida Samuel
Published: May 2022

(1) Background: By summer 2021, overseas France turned COVID-19 vaccine and immunity certificates into passports to open travel bubbles. Subsequently, its territories set French records for both COVID-19 and 6-month excess all-cause mortality. (2) Methods: Official time series were collected to compare time correlations between air traffic and COVID-19 transmission and mortality in overseas France, before and after the implementation of immunity passports. (3) Results: Air traffic initially had a reversed relationship with COVID-19, which transitioned into a leader–follower relationship with the introduction of immunity passports. Essentially, air traffic increased 16 days before COVID-19 cases increased (r = 0.61) and 26 days before deaths increased (r = 0.31) in Martinique, 26 days (r = 0.72) and 40 days (r = 0.82) before in Guadeloupe, and 29 days (r = 0.60) and 31 days (r = 0.41) before in Réunion upon introduction of immunity passports. Moreover, air traffic became as correlated as community transmission to COVID-19 mortality in Guadeloupe. (4) Conclusions: Since the introduction of immunity passports, air traffic has been pacesetting COVID-19 within one month for transmission, and within an additional two weeks for mortality in overseas France. Responding to WHO’s call for real-world evidence, this study suggests that COVID-19 passports are not commensurate with health system goals.
Co-Administration of Adjuvanted Recombinant Ov-103 and Ov-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine Onchocerca ochengi Infection Model of Human Onchocerciasis
Authors: Luu Lisa , Bah Germanus S. , Okah-Nnane Ndode Herman , Hartley Catherine S. , Glover Alexandra F. , Walsh Tessa R. , Lian Lu-Yun , Zhan Bin , Bottazzi Maria Elena , Abraham David , Petrovsky Nikolai , Bayang Nicolas , Tangwa Bernard , Ayiseh Rene Billingwe , Mbah Glory Enjong , Ekale David D. , Tanya Vincent N. , Lustigman Sara , Makepeace Benjamin L. , Graham-Brown John
Published: May 2022

Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, is a neglected tropical disease mainly of sub-Saharan Africa. Worldwide, an estimated 20.9 million individuals live with infection and a further 205 million are at risk of disease. Current control methods rely on mass drug administration of ivermectin to kill microfilariae and inhibit female worm fecundity. The identification and development of efficacious vaccines as complementary preventive tools to support ongoing elimination efforts are therefore an important objective of onchocerciasis research. We evaluated the protective effects of co-administering leading O. volvulus-derived recombinant vaccine candidates (Ov-103 and Ov-RAL-2) with subsequent natural exposure to the closely related cattle parasite Onchocerca ochengi. Over a 24-month exposure period, vaccinated calves (n = 11) were shown to acquire infection and microfilaridermia at a significantly lower rate compared to unvaccinated control animals (n = 10). Furthermore, adult female worm burdens were negatively correlated with anti-Ov-103 and Ov-RAL-2 IgG1 and IgG2 responses. Peptide arrays identified several Ov-103 and Ov-RAL-2-specific epitopes homologous to those identified as human B-cell and helper T-cell epitope candidates and by naturally-infected human subjects in previous studies. Overall, this study demonstrates co-administration of Ov-103 and Ov-RAL-2 with Montanide™ ISA 206 VG is highly immunogenic in cattle, conferring partial protection against natural challenge with O. ochengi. The strong, antigen-specific IgG1 and IgG2 responses associated with vaccine-induced protection are highly suggestive of a mixed Th1/Th2 associated antibody responses. Collectively, this evidence suggests vaccine formulations for human onchocerciasis should aim to elicit similarly balanced Th1/Th2 immune responses.