bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Frequency Shift in Transmission of Asymmetric Pulse in Optical Medium
Authors: Zhang Yusheng , Huang Lin , Zhang Bin , Chen Daru , Cui Yudong
Published: April 2022

Linear and nonlinear effects often induce a pulse self-frequency shift as it propagates along with an optical medium. Here, we theoretically investigate the transmission dynamics of asymmetric pulses propagating along with an optical medium in the temporal and spectral domains. Due to the asymmetric nonlinear phase-shift effect in the optical medium, the peak wavelength of asymmetric pulses exhibits a redshift or a blueshift in the spectral domain, while it slows down or speeds up in the temporal domain. Our results show that the peak wavelength shift initiated by a temporal or spectral asymmetric pulse depends not only on the pulse intensity, but also on the initial pulse chirp and dispersion of optical medium. We find that the peak wavelength shift of the asymmetric pulse increases with the pulse intensity and the initial pulse chirp, together with the spectrum width. The temporal and frequency shifts of the asymmetric pulses are found to be sensitive to the asymmetry ratio as well. These excellent properties may lead to the realization of a self-frequency shift-based tunable light source by launching asymmetric pulses into an optical medium.
Hadamard–Mercer, Dragomir–Agarwal–Mercer, and Pachpatte–Mercer Type Fractional Inclusions for Convex Functions with an Exponential Kernel and Their Applications
Authors: Sahoo Soubhagya Kumar , Agarwal Ravi P. , Mohammed Pshtiwan Othman , Kodamasingh Bibhakar , Nonlaopon Kamsing , Abualnaja Khadijah M.
Published: April 2022

Many scholars have recently become interested in establishing integral inequalities using various known fractional operators. Fractional calculus has grown in popularity as a result of its capacity to quickly solve real-world problems. First, we establish new fractional inequalities of the Hadamard–Mercer, Pachpatte–Mercer, and Dragomir–Agarwal–Mercer types containing an exponential kernel. In this regard, the inequality proved by Jensen and Mercer plays a major role in our main results. Integral inequalities involving convexity have a wide range of applications in several domains of mathematics where symmetry is important. Both convexity and symmetry are closely linked with each other; when working on one of the topics, you can apply what you have learned to the other. We consider a new identity for differentiable mappings and present its companion bound for the Dragomir–Agarwal–Mercer type inequality employing a convex function. Applications involving matrices are presented. Finally, we conclude our article and discuss its future scope.
A Review of Hermite–Hadamard Inequality for α-Type Real-Valued Convex Functions
Authors: Almutairi Ohud , Kılıçman Adem
Published: April 2022

Inequalities play important roles not only in mathematics but also in other fields, such as economics and engineering. Even though many results are published as Hermite–Hadamard (H-H)-type inequalities, new researchers to these fields often find it difficult to understand them. Thus, some important discoverers, such as the formulations of H-H-type inequalities of α-type real-valued convex functions, along with various classes of convexity through differentiable mappings and for fractional integrals, are presented. Some well-known examples from the previous literature are used as illustrations. In the many above-mentioned inequalities, the symmetrical behavior arises spontaneously.
Reviewing the Content of European Countries’ Official Tourism Websites: A Neo/Post-Fordist Perspective
Authors: Liasidou Sotiroula
Published: April 2022

The content of the EU28 Destination Management Organisations’ (DMOs’) official tourism websites is studied to understand how each country is promoting its online position and image, and whether this is compatible with the new forms of neo/post-Fordism consumption. The research incorporates critical discourse analysis (CDA) as a method to analyse the content of the websites for tourism promotion. Today, destinations struggle to portray a unique image in terms of their natural, historical and cultural characteristics and to be ahead of the competition. This paper aims to bring together the 27 EU member states and the United Kingdom’s (EU28) DMOs’ official tourism websites and review their content. The study uses Critical Discourse Analysis (CDA) with the aim of identifying the EU member states’ written web communication with potential visitors and to understand how each country is represented on the web in relation to neo/post-Fordism. The results of the study suggest that the EU28 are positioned online with website content to urge travellers to visit their country and gain constructive experiences within the remits of neo/post-Fordist characteristics. The paper follows an original approach in using CDA of EU28 official website online content in relation to neo/post-Fordist remits of production.
Esculetin and Fucoidan Attenuate Autophagy and Apoptosis Induced by Zinc Oxide Nanoparticles through Modulating Reactive Astrocyte and Proinflammatory Cytokines in the Rat Brain
Authors: Song Woo-Ju , Kim Jeongtae , Shin Taekyun , Jeong Myeong-Seon , Kim Kil-Nam , Yun Jang-Hyuk , Wie Myung-Bok
Published: April 2022

We examined the protective effects of esculetin and fucoidan against the neurotoxicity of ZnO NPs in rats. Ninety rats were divided into nine groups and pre-treated with esculetin or fucoidan 1 h before ZnO NP administration on a daily basis for 2 weeks. Serum and brain homogenates were examined by enzyme-linked immunosorbent assay (ELISA), and neurons, microglia, and astrocytes in the hippocampal region were examined with immunohistochemical analysis. The serum levels of interleukin-1-beta (IL-1β), 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were altered in the ZnO NP treatment groups. Brain IL-1β and TNF-α levels were elevated after ZnO NP administration, and these effects were inhibited by esculetin and fucoidan. SOD, 8-OHdG, and acetylcholinesterase (AChE) levels in the brain were decreased after ZnO NP administration. The brain levels of beclin-1 and caspase-3 were elevated after ZnO NP treatment, and these effects were significantly ameliorated by esculetin and fucoidan. The number of reactive astrocytes measured by counting glial fibrillary acidic protein (GFAP)-positive cells, but not microglia, increased following ZnO NP treatment, and esculetin and fucoidan ameliorated the changes. Esculetin and fucoidan may be beneficial for preventing ZnO NP-mediated autophagy and apoptosis by the modulation of reactive astrocyte and proinflammatory cytokines in the rat brain.
Experimental Study on the Detection of Hazardous Chemicals Using Alternative Sensors in the Water Environment
Authors: Nam Su-Han , Ku Tae-Geom , Park Ye-Lim , Kwon Jae-Hyun , Huh Do-Sung , Kim Young-Do
Published: April 2022

Chemical accidents in rivers may be triggered by natural or anthropogenic causes and refer to the flow of large quantities of hazardous chemicals into rivers. In South Korea, domestic water is sourced from large rivers, such as the Nakdong River. However, owing to rapid industrialization, industrial facilities have become heavily concentrated in the middle and upper reaches of the Nakdong River. Therefore, severe problems could arise if harmful chemicals are leaked from industrial facilities into the river, and this contaminated river water is supplied to cities. Quantitative evaluation based on instrumental analysis during chemical accidents and prediction research based on modeling is actively being conducted however, research on the initial response is insufficient. Therefore, in this study, the variations in pH and EC were analyzed according to their chemical concentrations for seven chemicals. These seven chemicals are designated accident-preparedness substances that frequently cause chemical spills in South Korea. Additionally, we evaluated the possibility of identifying unknown substances by comparing the variations in pH and EC and statistics while diluting unknown substances. Thus, the potential of pH and EC as alternative indicators for detecting and identifying chemicals was evaluated in this study. NaF, NH4HF2, NaCN, and NH4OH were classified by comparing their spatial distributions in a pH-EC relation curve. However, H2SO4, HCl, and SOCl2 showed similar spatial distributions in the pH-EC curves and were difficult to identify. The results of this study provide information for chemical detection and identification using alternative sensors that permit easy and rapid field measurements in the event of a chemical spill and could be used as preliminary data for rapidly responding to accidents.
High Cell Density Cultivation Process for the Expression of Botulinum Neurotoxin a Receptor Binding Domain
Authors: Ben David Alon , Papir Yoel , Hazan Ophir , Redelman Moses , Diamant Eran , Barnea Ada , Torgeman Amram , Zichel Ran
Published: April 2022

The receptor-binding domain of botulinum neurotoxin (HC fragment), is a promising botulism vaccine candidate. In the current study, fermentation strategies were evaluated to upscale HC fragment expression. A simple translation of the growth conditions from shake flasks to a batch fermentation process resulted in limited culture growth and protein expression (OD of 11 and volumetric protein yields of 123 mg/L). Conducting fed-batch fermentation with rich media and continuous nutrient supplementation significantly improved culture growth (OD of 40.3) and protein expression (1093 mg/L). A further increase in HC fragment yield was achieved by high cell density cultivation (HCDC). The bacterium was grown in a defined medium and with a combined bolus/continuous feed of nutrients to maintain desired oxygen levels and prevent acetate accumulation. The final OD of the process was 260, and the volumetric yield of the HC fragment was 2065 mg/L, which reflects improvement by an order of magnitude. Purified HC fragments, produced by HCDC, exhibited typical biochemical and protective characteristics in mice. Taken together, the advancements achieved in this study promote large-scale production of the HC fragment in E. coli for use in anti-botulism vaccines.
Toxinologic and Pharmacological Investigation of Venomous Arthropods
Authors: Rádis-Baptista Gandhi , Konno Katsuhiro
Published: April 2022

Arthropods comprise the largest group of living animals, including thousands of species that inhabit marine and terrestrial niches in the biosphere [...]
Effectiveness and Safety of Intracavernosal IncobotulinumtoxinA (Xeomin®) 100 U as an Add-on Therapy to Standard Pharmacological Treatment for Difficult-to-Treat Erectile Dysfunction: A Case Series
Authors: Giuliano Francois , Denys Pierre , Joussain Charles
Published: April 2022

Registered pharmacological treatments are insufficiently effective for erectile dysfunction (ED) in around 30% of affected men. Intracavernosal injection (ICI) of ona- and abobotulinumtoxinA can reduce ED in insufficient responders. We aimed to assess the safety and effectiveness of incobotulinumtoxinA ICI as an add-on therapy to phosphodiesterase-type 5 inhibitors (PDE5-Is) or prostaglandinE1 ICIs (PGE1 ICIs) to treat ED that did not respond sufficiently to this treatment alone. We retrospectively analyzed data from 66 men with difficult to treat ED treated with single or repeated incobotulinumtoxinA 100U ICI as an add-on therapy. Response rate (increase in International Index of Erectile Function-Erectile Function domain score ≥ the minimum clinically important difference) was 52% (median (1st–3rd quartile) 43.5 (34–71) days post-incobotulinumtoxinA ICI). ED etiology (except spinal cord injury) and severity did not influence effectiveness. Only a clinically significant response to the 1st injection predicted a request for a 2nd injection (OR = 5.6, 95%, CI 1.6–19.4). Three men reported mild penile pain during the injection. These results provide preliminary evidence for the effectiveness and safety of incobotulinumtoxinA ICI as an add-on therapy to treat ED that is insufficiently responsive to standard care and provides support for the multicenter randomized clinical trial NCT05196308.
Serum P-Cresyl Sulfate Level Is an Independent Marker of Peripheral Arterial Stiffness as Assessed Using Brachial-Ankle Pulse Wave Velocity in Patients with Non-Dialysis Chronic Kidney Disease Stage 3 to 5
Authors: Chang Yu-Chi , Lin Yu-Li , Lai Yu-Hsien , Wang Chih-Hsien , Hsu Bang-Gee
Published: April 2022

p-Cresyl sulfate (PCS) is a uremic toxin that causes cardiovascular injury and progression in patients with chronic kidney disease (CKD). Peripheral arterial stiffness (PAS) as measured using the brachial-ankle pulse wave velocity (baPWV) is considered a valuable predictor of cardiovascular event risk in the general population. The study investigated the correlation between serum PCS levels and PAS (baPWV > 18.0 m/s) in 160 patients with stage 3–5 CKD. Liquid chromatography–mass spectrometry was used to assay serum PCS levels. PAS was detected in 54 patients (33.8%), and it was linked to older age, a higher prevalence of hypertension, higher systolic and diastolic blood pressure, higher serum calcium–phosphorus product and PCS levels, and lower height and body weight. Multivariable logistic regression analysis for independent factors associated with PAS illustrated that, in addition to age and diastolic blood pressure, serum PCS levels exhibited an odds ratio (OR) of 1.098 (95% confidence interval = 1.029–1.171, p = 0.005). These findings demonstrated that serum PCS levels were associated with PAS among patients with stage 3–5 CKD.
Detection of Enterotoxigenic Psychrotrophic Presumptive Bacillus cereus and Cereulide Producers in Food Products and Ingredients
Authors: Jovanovic Jelena , Tretiak Svitlana , Begyn Katrien , Rajkovic Andreja
Published: April 2022

In the last decade, foodborne outbreaks and individual cases caused by bacterial toxins showed an increasing trend. The major contributors are enterotoxins and cereulide produced by Bacillus cereus, which can cause a diarrheal and emetic form of the disease, respectively. These diseases usually induce relatively mild symptoms; however, fatal cases have been reported. With the aim to detected potential toxin producers that are able to grow at refrigerator temperatures and subsequently produce cereulide, we screened the prevalence of enterotoxin and cereulide toxin gene carriers and the psychrotrophic capacity of presumptive B. cereus obtained from 250 food products (cereal products, including rice and seeds/pulses, dairy-based products, dried vegetables, mixed food, herbs, and spices). Of tested food products, 226/250 (90.4%) contained presumptive B. cereus, which communities were further tested for the presence of nheA, hblA, cytK-1, and ces genes. Food products were mainly contaminated with the nheA B. cereus carriers (77.9%), followed by hblA (64.8%), ces (23.2%), and cytK-1 (4.4%). Toxigenic B. cereus communities were further subjected to refrigerated (4 and 7 °C) and mild abuse temperatures (10 °C). Overall, 77% (94/121), 86% (104/121), and 100% (121/121) were able to grow at 4, 7, and 10 °C, respectively. Enterotoxin and cereulide potential producers were detected in 81% of psychrotrophic presumptive B. cereus. Toxin encoding genes nheA, hblA, and ces gene were found in 77.2, 55, and 11.7% of tested samples, respectively. None of the psychrotrophic presumptive B. cereus were carriers of the cytotoxin K-1 encoding gene (cytK-1). Nearly half of emetic psychrotrophic B. cereus were able to produce cereulide in optimal conditions. At 4 °C none of the examined psychrotrophs produced cereulide. The results of this research highlight the high prevalence of B. cereus and the omnipresence of toxin gene harboring presumptive B. cereus that can grow at refrigerator temperatures, with a focus on cereulide producers.
The Initial-Final Mass Relation of White Dwarfs: A Tool to Calibrate the Third Dredge-Up
Authors: Marigo Paola
Published: April 2022

The initial mass-final mass relationship (IFMR) of white dwarfs (WD) represents a crucial benchmark for stellar evolution models, especially for the efficiency of mixing episodes and mass loss during the asymptotic giant branch (AGB) phase. In this study, we argue that this relation offers the opportunity to constrain the third dredge-up (3DU), with important consequences for chemical yields. The results are discussed in light of recent studies that have identified a kink in the IFMR for initial masses close to 2M⊙. Adopting a physically-sound approach in which the efficiency λ of the 3DU varies as a function of core and envelope masses, we calibrate λ in solar-metallicity TP-AGB models in order to reproduce the final masses of their WD progeny, over the range of initial masses 0.9≤Mi/M⊙≤6. In particular, we find that in low-mass stars with 1.4≲Mi/M⊙≲2.0 the efficiency is small, λ≤0.3, it steeply rises to about λ≃0.65 in intermediate-mass stars with 2.0≤Mi/M⊙≤4.0, and then it drops in massive TP-AGB stars with 4.0≲Mi/M⊙≲6.0. Our study also suggests that a second kink may show up in the IFMR at the transition between the most massive carbon stars and those that are dominated by hot-bottom burning.
Nonsingular Black Holes in 4D Einstein–Gauss–Bonnet Gravity
Authors: Kumar Arun , Baboolal Dharmanand , Ghosh Sushant G.
Published: April 2022

Recently, several methods have been proposed to regularize a D→4 limit of Einstein–Gauss–Bonnet (EGB), leading to nontrivial gravitational dynamics in 4D. We present an exact nonsingular black hole solution in the 4D EGB gravity coupled to non-linear electrodynamics and analyze their thermodynamic properties to calculate precise expressions for the black hole mass, temperature, and entropy. Because of the magnetic charge, the thermodynamic quantities are corrected, and the Hawking–Page phase transition is achievable with diverges of the heat capacity at a larger critical radius r=r+C in comparison to the 5D counterpart where the temperature is maximum. Thus, we have a black hole with Cauchy and event horizons, and its evaporation leads to a thermodynamically stable extremal black hole remnant with vanishing temperature, and its size is larger than the 5D counterpart. The entropy does not satisfy the usual exact horizon Bekenstein–Hawking area law of general relativity with a logarithmic area correction term.
General Deflections in Deflected AMSB
Authors: Wang Fei , Zhang Ying-Kai
Published: April 2022

The (extra)ordinary gauge mediation extension of deflected AMSB scenarios can be interesting because it can accommodate together the deflection in the Kahler potential and the superpotential. We derive the analytical expressions for soft SUSY breaking parameters in such EOGM extension of deflected AMSB scenarios with the presence of both types of deflections. The Landau pole and proton decay constraints are also discussed.
New Insights in the Occurrence of Venous Thromboembolism in Critically Ill Patients with COVID-19—A Large Postmortem and Clinical Analysis
Authors: Heinrich Fabian , Roedl Kevin , Jarczak Dominik , Goebels Hanna-Lisa , Heinemann Axel , Schäfer Ulrich , Ludwig Frank , Bachmann Martin , Bein Berthold , Weber Christian Friedrich , Sydow Karsten , Bota Marc , Paschen Hans-Richard , de Weerth Andreas , Veit Carsten , Detsch Oliver , Brand Philipp-Alexander , Kluge Stefan , Ondruschka Benjamin , Wichmann Dominic
Published: April 2022

Critically ill COVID-19 patients are at high risk for venous thromboembolism (VTE), namely deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and death. The optimal anticoagulation strategy in critically ill patients with COVID-19 remains unknown. This study investigated the ante mortem incidence as well as postmortem prevalence of VTE, the factors predictive of VTE, and the impact of changed anticoagulation practice on patient survival. We conducted a consecutive retrospective analysis of postmortem COVID-19 (n = 64) and non-COVID-19 (n = 67) patients, as well as ante mortem COVID-19 (n = 170) patients admitted to the University Medical Center Hamburg-Eppendorf (Hamburg, Germany). Baseline patient characteristics, parameters related to the intensive care unit (ICU) stay, and the clinical and autoptic presence of VTE were evaluated and statistically compared between groups. The occurrence of VTE in critically ill COVID-19 patients is confirmed in both ante mortem (17%) and postmortem (38%) cohorts. Accordingly, comparing the postmortem prevalence of VTE between age- and sex-matched COVID-19 (43%) and non-COVID-19 (0%) cohorts, we found the statistically significant increased prevalence of VTE in critically ill COVID-19 cohorts (p = 0.001). A change in anticoagulation practice was associated with the statistically significant prolongation of survival time (HR: 2.55, [95% CI 1.41–4.61], p = 0.01) and a reduction in VTE occurrence (54% vs. 25%; p = 0.02). In summary, in the autopsy as well as clinical cohort of critically ill patients with COVID-19, we found that VTE was a frequent finding. A change in anticoagulation practice was associated with a statistically significantly prolonged survival time.
Tumors and Cytomegalovirus: An Intimate Interplay
Authors: Herbein Georges
Published: April 2022

Human cytomegalovirus (HCMV) is a herpesvirus that alternates lytic and latent infection, infecting between 40 and 95% of the population worldwide, usually without symptoms. During its lytic cycle, HCMV can result in fever, asthenia, and, in some cases, can lead to severe symptoms such as hepatitis, pneumonitis, meningitis, retinitis, and severe cytomegalovirus disease, especially in immunocompromised individuals. Usually, the host immune response keeps the virus in a latent stage, although HCMV can reactivate in an inflammatory context, which could result in sequential lytic/latent viral cycles during the lifetime and thereby participate in the HCMV genomic diversity in humans and the high level of HCMV intrahost genomic variability. The oncomodulatory role of HCMV has been reported, where the virus will favor the development and spread of cancerous cells. Recently, an oncogenic role of HCMV has been highlighted in which the virus will directly transform primary cells and might therefore be defined as the eighth human oncovirus. In light of these new findings, it is critical to understand the role of the immune landscape, including the tumor microenvironment present in HCMV-harboring tumors. Finally, the oncomodulatory/oncogenic potential of HCMV could lead to the development of novel adapted therapeutic approaches against HCMV, especially since immunotherapy has revolutionized cancer therapeutic strategies and new therapeutic approaches are actively needed, particularly to fight tumors of poor prognosis.
Expression Profile of Human Renal Mesangial Cells Is Altered by Infection with Pathogenic Puumala Orthohantavirus
Authors: Nusshag Christian , Boegelein Lukas , Schreiber Pamela , Essbauer Sandra , Osberghaus Anja , Zeier Martin , Krautkrämer Ellen
Published: April 2022

Acute kidney injury (AKI) with proteinuria is a hallmark of infections with Eurasian orthohantaviruses. Different kidney cells are identified as target cells of hantaviruses. Mesangial cells may play a central role in the pathogenesis of AKI by regulation of inflammatory mediators and signaling cascades. Therefore, we examined the characteristics of hantavirus infection on human renal mesangial cells (HRMCs). Receptor expression and infection with pathogenic Puumala virus (PUUV) and low-pathogenic Tula virus (TULV) were explored. To analyze changes in protein expression in infected mesangial cells, we performed a proteome profiler assay analyzing 38 markers of kidney damage. We compared the proteome profile of in vitro-infected HRMCs with the profile detected in urine samples of 11 patients with acute hantavirus infection. We observed effective productive infection of HRMCs with pathogenic PUUV, but only poor abortive infection for low-pathogenic TULV. PUUV infection resulted in the deregulation of proteases, adhesion proteins, and cytokines associated with renal damage. The urinary proteome profile of hantavirus patients demonstrated also massive changes, which in part correspond to the alterations observed in the in vitro infection of HRMCs. The direct infection of mesangial cells may induce a local environment of signal mediators that contributes to AKI in hantavirus infection.
Development of Dog Vaccination Strategies to Maintain Herd Immunity against Rabies
Authors: Lugelo Ahmed , Hampson Katie , Ferguson Elaine A. , Czupryna Anna , Bigambo Machunde , Duamor Christian Tetteh , Kazwala Rudovick , Johnson Paul C. D. , Lankester Felix
Published: April 2022

Human rabies can be prevented through mass dog vaccination campaigns; however, in rabies endemic countries, pulsed central point campaigns do not always achieve the recommended coverage of 70%. This study describes the development of a novel approach to sustain high coverage based on decentralized and continuous vaccination delivery. A rabies vaccination campaign was conducted across 12 wards in the Mara region, Tanzania to test this approach. Household surveys were used to obtain data on vaccination coverage as well as factors influencing dog vaccination. A total 17,571 dogs were vaccinated, 2654 using routine central point delivery and 14,917 dogs using one of three strategies of decentralized continuous vaccination. One month after the first vaccination campaign, coverage in areas receiving decentralized vaccinations was higher (64.1, 95% Confidence Intervals (CIs) 62.1–66%) than in areas receiving pulsed vaccinations (35.9%, 95% CIs 32.6–39.5%). Follow-up surveys 10 months later showed that vaccination coverage in areas receiving decentralized vaccinations remained on average over 60% (60.7%, 95% CIs 58.5–62.8%) and much higher than in villages receiving pulsed vaccinations where coverage was on average 32.1% (95% CIs 28.8–35.6%). We conclude that decentralized continuous dog vaccination strategies have the potential to improve vaccination coverage and maintain herd immunity against rabies.
Distinctive High Expression of Antiretroviral APOBEC3 Protein in Mouse Germinal Center B Cells
Authors: Tsukimoto Shota , Hakata Yoshiyuki , Tsuji-Kawahara Sachiyo , Enya Takuji , Tsukamoto Tetsuo , Mizuno Seiya , Takahashi Satoru , Nakao Shinichi , Miyazawa Masaaki
Published: April 2022

Tissue and subcellular localization and its changes upon cell activation of virus-restricting APOBEC3 at protein levels are important to understanding physiological functions of this cytidine deaminase, but have not been thoroughly analyzed in vivo. To precisely follow the possible activation-induced changes in expression levels of APOBEC3 protein in different mouse tissues and cell populations, genome editing was utilized to establish knock-in mice that express APOBEC3 protein with an in-frame FLAG tag. Flow cytometry and immunohistochemical analyses were performed prior to and after an immunological stimulation. Cultured B cells expressed higher levels of APOBEC3 protein than T cells. All differentiation and activation stages of freshly prepared B cells expressed significant levels of APOBEC3 protein, but germinal center cells possessed the highest levels of APOBEC3 protein localized in their cytoplasm. Upon immunological stimulation with sheep red blood cells in vivo, germinal center cells with high levels of APOBEC3 protein expression increased in their number, but FLAG-specific fluorescence intensity in each cell did not change. T cells, even those in germinal centers, did not express significant levels of APOBEC3 protein. Thus, mouse APOBEC3 protein is expressed at distinctively high levels in germinal center B cells. Antigenic stimulation did not affect expression levels of cellular APOBEC3 protein despite increased numbers of germinal center cells.
Two Consecutive Prolines in the Fusion Peptide of Murine β-Coronavirus Spike Protein Predominantly Determine Fusogenicity and May Be Essential but Not Sufficient to Cause Demyelination
Authors: Safiriyu Abass Alao , Singh Manmeet , Kishore Abhinoy , Mulchandani Vaishali , Maity Dibyajyoti , Behera Amrutamaya , Sinha Bidisha , Pal Debnath , Das Sarma Jayasri
Published: April 2022

Combined in silico, in vitro, and in vivo comparative studies between isogenic-recombinant Mouse-Hepatitis-Virus-RSA59 and its proline deletion mutant, revealed a remarkable contribution of centrally located two consecutive prolines (PP) from Spike protein fusion peptide (FP) in enhancing virus fusogenic and hepato-neuropathogenic potential. To deepen our understanding of the underlying factors, we extend our studies to a non-fusogenic parental virus strain RSMHV2 (P) with a single proline in the FP and its proline inserted mutant, RSMHV2 (PP). Comparative in vitro and in vivo studies between virus strains RSA59(PP), RSMHV2 (P), and RSMHV2 (PP) in the FP demonstrate that the insertion of one proline significantly resulted in enhancing the virus fusogenicity, spread, and consecutive neuropathogenesis. Computational studies suggest that the central PP in Spike FP induces a locally ordered, compact, and rigid structure of the Spike protein in RSMHV2 (PP) compared to RSMHV2 (P), but globally the Spike S2-domain is akin to the parental strain RSA59(PP), the latter being the most flexible showing two potential wells in the energy landscape as observed from the molecular dynamics studies. The critical location of two central prolines of the FP is essential for fusogenicity and pathogenesis making it a potential site for designing antiviral.
Development and Evaluation of Molecular Pen-Side Assays without Prior RNA Extraction for Peste des Petits Ruminants (PPR) and Foot and Mouth Disease (FMD)
Authors: Edge David , Mahapatra Mana , Strachan Shona , Turton James , Waters Ryan , Benfield Camilla , Nazareth Nathan , Njeumi Felix , Nazareth Nelson , Parida Satya
Published: April 2022

Animal diseases such as peste des petits ruminants (PPR) and foot and mouth disease (FMD) cause significant economic losses in endemic countries and fast, accurate in-field diagnostics would assist with surveillance and outbreak control. The detection of these pathogens is usually performed at reference laboratories, tested using assays that are recommended by The World Organisation for Animal Health (OIE), leading to delays in pathogen detection. This study seeks to demonstrate a proof-of-concept approach for a molecular diagnostic assay that is compatible with material direct from nasal swab sampling, without the need for a prior nucleic acid extraction step, that could potentially be applied at pen-side for both PPR and FMD. The use of such a rapid, low-cost assay without the need for a cold chain could permit testing capacity to be established in remote, resource limited areas and support the surveillance activities necessary to meet the goal of eradication of PPR by 2030. Two individual assays were developed that detect > 99% of PPR and FMD sequences available in GenBank, demonstrating pan-serotype FMD and pan-lineage PPR assays. The ability for the BioGene XF reagent that was used in this study to lyse FMD and PPR viruses and amplify their nucleic acids in the presence of unprocessed nasal swab eluate was evaluated. The reagent was shown to be capable of detecting the viral RNA present in nasal swabs collected from naïve and infected target animals. A study was performed comparing the relative specificity and sensitivity of the new assays to the reference assays. The study used nasal swabs collected from animals before and after infection (12 cattle infected with FMDV and 5 goats infected with PPRV) and both PPR and FMD viral RNA were successfully detected two to four days post-infection in all animals using either the XF or reference assay reagents. These data suggest that the assays are at least as sensitive as the reference assays and support the need for further studies in a field setting.
Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs
Authors: Tong Haonan , Chen Hao , Williams Cranos M.
Published: April 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that caused the coronavirus disease 2019 (COVID-19) pandemic. Though previous studies have suggested that SARS-CoV-2 cellular tropism depends on the host-cell-expressed proteins, whether transcriptional regulation controls SARS-CoV-2 tropism factors in human lung cells remains unclear. In this study, we used computational approaches to identify transcription factors (TFs) regulating SARS-CoV-2 tropism for different types of lung cells. We constructed transcriptional regulatory networks (TRNs) controlling SARS-CoV-2 tropism factors for healthy donors and COVID-19 patients using lung single-cell RNA-sequencing (scRNA-seq) data. Through differential network analysis, we found that the altered regulatory role of TFs in the same cell types of healthy and SARS-CoV-2-infected networks may be partially responsible for differential tropism factor expression. In addition, we identified the TFs with high centralities from each cell type and proposed currently available drugs that target these TFs as potential candidates for the treatment of SARS-CoV-2 infection. Altogether, our work provides valuable cell-type-specific TRN models for understanding the transcriptional regulation and gene expression of SARS-CoV-2 tropism factors.
Comment on Wang et al. Development of a Novel Double Antibody Sandwich ELISA for Quantitative Detection of Porcine Deltacoronavirus Antigen. Viruses 2021, 13, 2403
Authors: Li Ming , Zhang Chi , Yu Tianfei
Published: April 2022

We were interested in reading an article published by Wang et al. [...]
Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity
Authors: Hadj Hassine Ikbel , Ben M’hadheb Manel , Menéndez-Arias Luis
Published: April 2022

In RNA viruses, a small increase in their mutation rates can be sufficient to exceed their threshold of viability. Lethal mutagenesis is a therapeutic strategy based on the use of mutagens, driving viral populations to extinction. Extinction catastrophe can be experimentally induced by promutagenic nucleosides in cell culture models. The loss of HIV infectivity has been observed after passage in 5-hydroxydeoxycytidine or 5,6-dihydro-5-aza-2′-deoxycytidine while producing a two-fold increase in the viral mutation frequency. Among approved nucleoside analogs, experiments with polioviruses and other RNA viruses suggested that ribavirin can be mutagenic, although its mechanism of action is not clear. Favipiravir and molnupiravir exert an antiviral effect through lethal mutagenesis. Both drugs are broad-spectrum antiviral agents active against RNA viruses. Favipiravir incorporates into viral RNA, affecting the G→A and C→U transition rates. Molnupiravir (a prodrug of β-d-N4-hydroxycytidine) has been recently approved for the treatment of SARS-CoV-2 infection. Its triphosphate derivative can be incorporated into viral RNA and extended by the coronavirus RNA polymerase. Incorrect base pairing and inefficient extension by the polymerase promote mutagenesis by increasing the G→A and C→U transition frequencies. Despite having remarkable antiviral action and resilience to drug resistance, carcinogenic risks and genotoxicity are important concerns limiting their extended use in antiviral therapy.
Human Norovirus Induces Aquaporin 1 Production by Activating NF-κB Signaling Pathway
Authors: Zhang Mudan , Zhang Binman , Chen Rui , Li Miaomiao , Zheng Zifeng , Xu Wanfu , Zhang Yifan , Gong Sitang , Hu Qinxue
Published: April 2022

Human norovirus (HuNoV) is one of the major pathogens of acute nonbacterial gastroenteritis. Due to the lack of a robust and reproducible in vitro culture system and an appropriate animal model, the mechanism underlying HuNoV-caused diarrhea remains unknown. In the current study, we found that HuNoV transfection induced the expression of aquaporin 1 (AQP1), which was further confirmed in the context of virus infection, whereas the enterovirus EV71 (enterovirus 71) did not have such an effect. We further revealed that VP1, the major capsid protein of HuNoV, was crucial in promoting AQP1 expression. Mechanistically, HuNoV induces AQP1 production through the NF-κB signaling pathway via inducing the expression, phosphorylation and nuclear translocation of p65. By using a model of human intestinal epithelial barrier (IEB), we demonstrated that HuNoV and VP1-mediated enhancement of small molecule permeability is associated with the AQP1 channel. Collectively, we revealed that HuNoV induced the production of AQP1 by activating the NF-κB signaling pathway. The findings in this study provide a basis for further understanding the significance of HuNoV-induced AQP1 expression and the potential mechanism underlying HuNoV-caused diarrhea.
Synonymous Codon Usage Analysis of Three Narcissus Potyviruses
Authors: He Zhen , Ding Shiwen , Guo Jiyuan , Qin Lang , Xu Xiaowei
Published: April 2022

Narcissus degeneration virus (NDV), narcissus late season yellows virus (NLSYV) and narcissus yellow stripe virus (NYSV), which belong to the genus Potyvirus of the family Potyviridae, cause significant losses in the ornamental value and quality of narcissus. Several previous studies have explored the genetic diversity and evolution rate of narcissus viruses, but the analysis of the synonymous codons of the narcissus viruses is still unclear. Herein, the coat protein (CP) of three viruses is used to analyze the viruses’ phylogeny and codon usage pattern. Phylogenetic analysis showed that NYSV, NDV and NLSYV isolates were divided into five, three and five clusters, respectively, and these clusters seemed to reflect the geographic distribution. The effective number of codon (ENC) values indicated a weak codon usage bias in the CP coding region of the three narcissus viruses. ENC-plot and neutrality analysis showed that the codon usage bias of the three narcissus viruses is all mainly influenced by natural selection compared with the mutation pressure. The three narcissus viruses shared the same best optimal codon (CCA) and the synonymous codon prefers to use codons ending with A/U, compared to C/G. Our study shows the codon analysis of different viruses on the same host for the first time, which indicates the importance of the evolutionary-based design to control these viruses.
COVID-19 Vaccine Hesitancy among Arab Americans
Authors: Kheil Mira H. , Jain Deepti , Jomaa Jamil , Askar Brandon , Alcodray Yasmeen , Wahbi Shatha , Brikho Salar , Kadouh Ali , Harajli Deanna , Jawad Zain N. , Fehmi Ziad , Elhage Malaak , Tawil Tala , Fehmi Omar , Alzouhayli Suma J. , Ujayli Deema , Suleiman Noor , Kazziha Omar , Saleh Rawan , Abada Evi , Shallal Anita , Kim Seongho , Kumar Vijaya Arun , Zervos Marcus , Cote Michele L. , Ali-Fehmi Rouba
Published: April 2022

(1) Background: Coronavirus disease-2019 (COVID-19) vaccines have a significant impact on reducing morbidity and mortality from infection. However, vaccine hesitancy remains an obstacle in combating the pandemic. The Arab American (AA) population is understudied; thus, we aimed to explore COVID-19 attitudes within this community. (2) Methods: This was a cross-sectional study. An anonymous online survey was distributed to members of different AA associations and to the community through the snowball method. (3) Results: A total of 1746 participants completed the survey. A total of 92% of respondents reported having received at least one dose of a COVID-19 vaccine. A total of 73% reported willingness to receive a booster, and 72% plan to give their children the vaccine. On multivariate analysis, respondents were more likely to be vaccine-hesitant if they were hesitant about receiving any vaccine in general. They were less likely to be vaccine-hesitant if they were immigrants, over the age of 40, up to date on their general vaccination and if they believed that COVID-19 vaccines are safe and effective in preventing an infection. The belief that all vaccines are effective at preventing diseases was also associated with lower hesitancy. (4) Conclusions: This sample of AAs have higher vaccination rates and are more willing to vaccinate their children against COVID-19 when compared to the rest of the population. However, a reemergence of hesitancy might be arising towards the boosters.
Prolonged Protective Immunity Induced by Mild SARS-CoV-2 Infection of K18-hACE2 Mice
Authors: Bar-On Liat , Aftalion Moshe , Makdasi Efi , Gur David , Alcalay Ron , Cohen Hila , Beth-Din Adi , Rosenfeld Ronit , Achdout Hagit , Bar-Haim Erez , Falach Reut , Chitlaru Theodor , Cohen Ofer
Published: April 2022

Longevity of the immune response following viral exposure is an essential aspect of SARS-CoV-2 infection. Mild SARS-CoV-2 infection of K18-hACE2 mice was implemented for evaluating the mounting and longevity of a specific memory immune response. We show that the infection of K18-hACE2 mice induced robust humoral and cellular immunity (systemic and local), which persisted for at least six months. Virus-specific T cells and neutralizing antibody titers decreased over time, yet their levels were sufficient to provide sterile immunity against lethal rechallenge six months post-primary infection. The study substantiates the role of naturally induced immunity against SARS-CoV-2 infection for preventing recurring morbidity.
The Immunomodulatory Functions of Various CpG Oligodeoxynucleotideson CEF Cells and H9N2 Subtype Avian Influenza Virus Vaccination
Authors: Li Chenfei , Huang Xiangyu , Cai Jiaxi , Lu Anran , Hao Shanshan , Zhang Ze , Sun Haifeng , Feng Xiuli
Published: April 2022

CpG oligodeoxynucleotides (CpG ODN) present adjuvant activities for antigen proteins, which can induce humoral and cellular immune responses to antigens. However, the immunomodulatory functions of CpG ODNs with different sequences are very different. In this paper, six CpG ODNs with different sequences were designed based on CpG2007 as a template. Through the screening of CEF cells in vitro, the stimulating activity of CpG ODNs was determined. Then, two selected CpG ODN sequence backbones were modified by substituting the oxygen with sulfur (S-CpG) and verifying the immune activity. Next, to prove the feasibility of S-CpG as an immune potentiator, two immune models with or without white oil adjuvant were prepared in 20-day-old chicken vaccinations. The screening experiment in vitro showed that the inducing roles of CpG ODN 4 and 5 could strongly stimulate various immune-related molecular expressions. Additionally, CpG ODN 4 and 5 with sulfation modification significantly induced various cytokines’ expressions. Furthermore, CpG ODN 4 and 5 induced the strongly humoral and cellular immune responses during vaccination, in which white oil, as an adjuvant, could significantly improve the immune effect of CpG ODN. These results provide an important experimental basis for exploring the structural characteristics and vaccine immunity of CpG ODN.
Self-Reported COVID-19 Vaccine Hesitancy and Willingness to Pay: A Cross-Sectional Survey in Thailand
Authors: Mueangpoon Kulpatsorn , Inchan Chapipak , Kaewmuneechoke Panithan , Rattana Peerunda , Budsratid Supanut , Japakiya Suthasinee , Ngamchaliew Pitchayanont , Vichitkunakorn Polathep
Published: April 2022

This study aimed to estimate the prevalence and influencing factors of COVID-19 vaccine hesitancy and willingness to pay in Thailand. A descriptive cross-sectional study was conducted from 13 September 2021 to 14 January 2022. Data were collected using an online questionnaire consisting of demographic characteristics, COVID-19 vaccine hesitancy (delay in acceptance and denying vaccination), determinants of vaccine hesitancy (complacency, convenience, and confidence), and willingness to pay. The general Thai population aged ≥18 years were surveyed. Among 705 respondents, 10.4% reported hesitancy, with significant determinants being low complacency and confidence in the vaccine; low convenience was not a significant determinant. Multivariate analysis revealed vaccine hesitancy among women, those with higher education, non-healthcare workers, and those who lived in rural areas. Furthermore, 77.2% of respondents were willing to pay, with the majority willing to pay in the range of THB 501–1000 ( USD 1 = THB 33) per dose. Increased monthly income, no impact of COVID-19 on income, and time period (before mRNA vaccine availability) significantly affected willingness to pay.
Herpesvirus Vaccines
Authors: Petrini Stefano , Maple Peter
Published: April 2022

The Special Issue titled “Herpesvirus Vaccines” contains different articles and a review regarding veterinary and human herpesviruses [...]
Clinical and Laboratory Features in the Israeli Population with COVID-19 Infection after Pfizer-BioNTech mRNA Booster Vaccination
Authors: Israel Ariel , Merzon Eugene , Shenhar Yotam , Green Ilan , Golan-Cohen Avivit , Schäffer Alejandro A. , Ruppin Eytan , Vinker Shlomo , Magen Eli
Published: April 2022

Background: Immune protection following either vaccination or infection with SARS-CoV-2 decreases over time. Objective: We aim to describe clinical and sociodemographic characteristics associated with COVID-19 infection at least 14 days after booster vaccination in the Israeli population. Methods: We conducted a population-based study among adult members of Leumit Health Services (LHS) in Israel. Nasopharyngeal swabs were examined for SARS-CoV-2 by real-time RT-PCR. The hematological and biochemical parameters in the peripheral blood before booster vaccination were evaluated. Results: Between 1 February 2021 and 30 November 2021, 136,683 individuals in LHS were vaccinated with a booster (third dose) of the BNT162b2 vaccine. Of these, 1171 (0.9%) were diagnosed with COVID-19 by testing positive for SARS-CoV-2 RT-PCR at least >14 days after the booster vaccination. The COVID-19-positive group was characterized by higher rates of chronic kidney disease than the matched COVID-19-negative group (43 (3.7%) vs. 3646 (2.7%); p = 0.039). Anemia, lower peripheral blood lymphocytes, monocytes, basophils, C3 Complement, cholesterol, and prothrombin time were also associated with COVID-19 after booster vaccination. Conclusion: People with chronic kidney disease and anemia should be included in possible future annual SARS-CoV-2 vaccination recommendations.
Suspected Pituitary Apoplexy: Clinical Presentation, Diagnostic Imaging Findings and Outcome in 19 Dogs
Authors: Galli Greta , Bertolini Giovanna , Dalla Serra Giulia , Menchetti Marika
Published: April 2022

In human medicine, pituitary apoplexy (PA) is a clinical syndrome characterised by the sudden onset of neurological signs because of haemorrhage or infarction occurring within a normal or tumoral pituitary gland. The diagnosis is usually performed combining neurological signs and imaging findings. The aim of the present study is to describe the abnormal neurological signs, the diagnostic imaging findings, based on Computed Tomography (CT) and/or Magnetic Resonance Imaging (MRI), and the outcome in a population of dogs with suspected PA. Clinical cases were retrospectively reviewed. Nineteen cases of suspected PA were included. The majority of dogs showed behavioural abnormalities (11/19). Neurological signs more frequently identified were obtundation (7/19), vestibular signs (7/19) and epileptic seizures (6/19). The onset of neurological signs was per-acute in 14 out of 19 cases. Data regarding CT and MRI were available in 18 and 9 cases, respectively. Neurological signs resolved in less than 24 h in seven patients. The short-term prognosis was defined as favourable in the majority of our study population. The median survival time was of 7 months from the time of PA diagnosis. This is the first description of neurological signs, imaging findings and outcome in a large group of dogs with PA.