bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockchain Technology: Potential Applications for Public Sector E-Procurement and Project Management
Authors: Khalfan Malik , Azizi Neda , Haass Omid , Maqsood Tayyab , Ahmed Istiaq
Published: May 2022

Project implementations normally fail due to sustainable development problems that inhibit the usage levels required to facilitate successful implementations. This paper explores the successful implementation from a Bangladesh perspective. In particular, it identifies the possible applications of Blockchain in project procurement and management, and it develops a guideline for incorporating Blockchain into project management to improve the existing project and the procurement management practices in developing countries. This is a qualitative study with an interpretivist research methodology. By adopting an interpretive approach, this study construes knowledge as that only gained through social constructions, such as language, shared meanings, documents, industry reports, reviews of academic papers, and tools; it is a changing and relative phenomenon. This study reveals that developing countries are suffering in terms of the development of projects, including poor project management, a lack of transparency, poor procurement management, etc. A total of 38 issues were identified through this study, which are the main barriers to the successful implementation of public sector projects. One of the main reasons is due to the practice of awarding the lowest bidder during the procurement process due to the current regulatory requirements. This paper found that the Oracle platform, built on Blockchain technology as a cloud-computing platform, is one of the prominent E-procurement platforms that provides both the Blockchain platform and the cloud-based applications. Therefore, after observing and analysing the platform, it is found that Blockchain technology has the capability to resolve 25 issues out of 38 identified issues.
Experimental Validation of a Double-Deck Track-Bridge System under Railway Traffic
Authors: Saramago Gabriel , Montenegro Pedro Aires , Ribeiro Diogo , Silva Artur , Santos Sergio , Calçada Rui
Published: May 2022

This article describes the experimental and numerical evaluation of the dynamic behaviour of the Cascalheira bridge, located on the Northern Line of the Portuguese railway network. The bridge has a short span formed by two filler-beam half-decks, each one accommodating a railway track. The study includes the development of a finite element numerical model in ANSYS® software, as well as in situ dynamic characterization tests of the structure, namely ambient vibration tests, for the estimation of natural frequencies, modes shapes and damping coefficients, and a dynamic test under railway traffic, particularly for the passage of the Alfa Pendular train. The damping coefficients’ estimation was performed based on the Prony method, which proved effective in situations where the classical methods (e.g., decrement logarithm) tend to fail, particularly in the case of mode shapes with closed natural frequencies, as typically happens with the first vertical bending and torsion modes. The updating of the numerical model of the bridge was carried out using an iterative methodology based on a genetic algorithm, allowing an upgrade of the agreement between the numerical and experimental modal parameters. Particular attention was given to the characterization of the ballast degradation over the longitudinal joint between the two half-decks, given its influence in the global dynamic behavior of this type of double-deck bridges. Finally, the validation of the numerical model was performed by comparing the acceleration response of the structure under traffic actions, by means of numerical dynamic analyses considering vehicle-bridge interaction and including track irregularities, with the ones obtained by the dynamic test under traffic actions. The results of the calibrated numerical model showed a better agreement with the experimental results based on the accelerations evaluated in several measurement points located in both half-decks. In the validation process the vertical stiffness of the supports, as well as the degradation of the ballast located over the longitudinal joint between half-decks, was demonstrated to be relevant for the accuracy and effectiveness of the numerical models.
Formation of Matter-Wave Droplet Lattices in Multi-Color Periodic Confinements
Authors: Pathak Maitri R. , Nath Ajay
Published: May 2022

In the paper, we introduce a new model that addresses the generation of quantum droplets (QDs) in the binary Bose–Einstein condensate (BEC) mixture with mutually symmetric spinor components loaded in multi-color optical lattices (MOLs) of commensurate wavelengths and tunable intensities. The considered MOL confinement is the combination of the four-color optical lattice with an exponential periodic trap, which includes the complete set of the Fourier harmonics. Employing the one-dimensional (1D) extended Gross–Pitäevskii equation (eGPE), we calculate the exact analytical form of the wavefunction, MF/BMF nonlinearities, and MOL trap parameters. Utilizing the exact solutions, the formation of supersolid-like spatially periodic matter-wave droplet lattices and superlattices is illustrated under the space-periodic nonlinearity management. The precise positioning of the density maxima/minima of the droplet patterns at the center of the trap and tunable Anderson-like localization are observed by tuning the symmetry and amplitude of the considered MOL trap. The stability of the obtained solution is confirmed using the Vakhitov–Kolokolov (VK) criterion.
Some Results on the Truncated Multivariate Skew-Normal Distribution
Authors: Morán-Vásquez Raúl Alejandro , Cataño Salazar Duván Humberto , Nagar Daya K.
Published: May 2022

The multivariate skew-normal distribution is useful for modeling departures from normality in data through parameters controlling skewness. Recently, several extensions of this distribution have been proposed in the statistical literature, among which the truncated multivariate skew-normal distribution is the foremost. Truncated distributions appear frequently in various theoretical and applied statistical problems. In this article, we study several properties of the truncated multivariate skew-normal distribution. We obtain distributional results through affine transformations, marginalization, and conditioning. Furthermore, the log-concavity of the joint probability density function is established.
Cognitive and Neurophysiological Models of Brain Asymmetry
Authors: Ocklenburg Sebastian , Güntürkün Onur
Published: May 2022

Asymmetry is an inherent characteristic of brain organization in both humans and other vertebrate species, and is evident at the behavioral, neurophysiological, and structural levels. Brain asymmetry underlies the organization of several cognitive systems, such as emotion, communication, and spatial processing. Despite this ubiquity of asymmetries in the vertebrate brain, we are only beginning to understand the complex neuronal mechanisms underlying the interaction between hemispheric asymmetries and cognitive systems. Unfortunately, despite the vast number of empirical studies on brain asymmetries, theoretical models that aim to provide mechanistic explanations of hemispheric asymmetries are sparse in the field. Therefore, this Special Issue aims to highlight empirically based mechanistic models of brain asymmetry. Overall, six theoretical and four empirical articles were published in the Special Issue, covering a wide range of topics, from human handedness to auditory laterality in bats. Two key challenges for theoretical models of brain asymmetry are the integration of increasingly complex molecular data into testable models, and the creation of theoretical models that are robust and testable across different species.
Characterization of Engineering-Suitable Optical Fiber Sensors Packaged with Glass Fiber-Reinforced Polymers
Authors: Jiao Tong , Pu Chuhong , Xing Wenjing , Lv Tao , Li Yuan , Wang Huaping , He Jianping
Published: May 2022

Glass fiber-reinforced polymer- (GFRP-) packaged optical fiber (OF) sensors are considered a promising engineering-suitable sensor for structural health monitoring. To date, some critical characteristics of the GFRP-packaged OF (GFRP-OF) sensors have not yet been thoroughly studied. This study aimed to systematically characterize the properties of the GFRP-OF sensors. Firstly, we proposed a dimension optimization method for GFRP-OF sensors by strain transfer theory, which is based on a symmetrical three-layered cylindrical model. Then, we experimentally investigated the properties of the GFRP-packaged fiber Bragg grating sensor and GFRP-packaged distributed optical fiber sensor, including their mechanical properties, strain/temperature sensing performance, fatigue resistance, and corrosion resistance. The experimental results showed that the shear bearing capacity of GFRP-OF sensors was more than 120 times larger than that of the other three coated OF sensors, indicating that GFRP dramatically enhanced the robustness of the OF sensor. The GFRP–OF sensors also feature excellent strain and temperature sensing performance with high linearity and repeatability. The results also demonstrated that the GFRP–OF sensors have good fatigue properties with absolute fluctuations of strain sensitivity coefficients throughout the fatigue cycles within 0.02 pm/με; repeatability error did not exceed 0.5%, and nonlinear errors were less than 2%. A case study presented in the last section also illustrates the effectiveness of the GFRP-OF sensor in a field application.
Finely Modulated LDPE/PS Blends via Synergistic Compatibilization with SEBS-g-MAH and OMMT
Authors: Zhu Nianqing , Gao Xinxing , Liang Jilei , Wang Yan , Hou Rongjie , Ni Zhongbing
Published: May 2022

Melt blending is an effective way to prepare new composite materials, but most polymers are incompatible. In order to reduce the interfacial tension and obtain fine and stable morphology with internal symmetric micro-textures, suitable compatibilizers should be added to the blend. The two immiscible polymers, low-density polyethylene (LDPE) and polystyrene (PS), were compatibilized by styrene/ethylene/butylene/styrene block copolymers grafted with maleic anhydride (SEBS-g-MAH) and organomontmorillonite (OMMT). The scanning electron microscope results indicated that the size of the PS phase decreased with increasing the content of SEBS-g-MAH. By introducing OMMT into LDPE/PS/SEBS-g-MAH composites, the compatibility of composites was further improved. The rheological analysis and Cole–Cole plot analysis indicated that the addition of SEBS-g-MAH and OMMT increased the interaction between the two phases. The tensile strength, elongation at break, and impact strength of the LDPE/PS/SEBS-g-MAH (70/30/7, wt%) composite increased by 64%, 255%, and 380%, respectively, compared with the LDPE/PS (70/30, wt%) composite. A small amount of OMMT could synergistically compatibilize the LDPE/PS composite with SEBS-g-MAH. After adding 0.3% OMMT into the LDPE/PS/SEBS-g-MAH system, the tensile strength, elongation at break, and impact strength of the composite were further increased to 18.57 MPa, 71.87%, and 33.28 kJ/m2, respectively.
An Improved EDAS Method for the Multi-Attribute Decision Making Based on the Dynamic Expectation Level of Decision Makers
Authors: Peng Dan , Wang Jie , Liu Donghai , Liu Zaiming
Published: May 2022

The improved evaluation based on the distance from average solution (EDAS) of the interval-valued intuitionistic trapezoidal fuzzy set is proposed. At first, we propose a new distance between interval-valued intuitionistic trapezoidal fuzzy numbers according to their interval endpoints and centroid point, and its properties are also discussed. Furthermore, we apply the proposed distance measure to calculate the expectation level of the emergency plan, and the optimal dynamic expectation level of the emergency plan is obtained by solving the programming model. Then, we improve the EDAS method based on the dynamic expectation level of the decision makers and apply it to calculate the optimal emergency plan. Finally, a numerical example about flood disaster rescue is given to verify the feasibility and effectiveness of the proposed method, which is also compared with the existing methods.
Impact of Soil Pollution on Melliferous Plants
Authors: Bărbulescu Alina , Barbeș Lucica , Dumitriu Cristian Ştefan
Published: May 2022

This study aims at providing bee products and derivatives of medicinal plant consumers with a multifaceted perspective on mineral elements occurring in the soils of two forest zones in the vicinity of North Dobrogea (Romania) by (1) analyzing the pollution levels of the soils at three sites (denoted by DS, PH, and ST) in the study region, using different indicators; (2) providing the results of the transfer of metals from the soil to Sambucus nigra L. (SnL), Hypericum perforatum (Hp), and Tilia tomentosa (Tt). The statistical analysis of the series collected at these locations shows no difference between the elements’ concentrations (as a whole). Still, the values of the geo-accumulation index (Igeo) classify the soils as being soils that are moderately to highly contaminated with Cd (and not contaminated with Cu, Mn, or Zn) with respect to the European background values. The cumulative indices—the degree of contamination (DC), the pollution load index (PLI), the Nemerow integrated pollution index (NIPI), and the potential ecological risk index (PERI) indicated the highest contamination in DS (which is a tourist area). To assess the accumulation of different metals in plants, the enrichment factors (EF) were computed. In over 75% of cases, EF was above 1, indicating a high degree of enrichment with different metals. The highest values were those for Cu (41.10 in DS for SnL), and Cd (12.85 in DS for Tt). The results showed that there were different degrees of accumulation between microelements and trace elements in the plants. Tt acted as a bioaccumulator for almost all of the studied elements (K, Mg, Na, Fe, Mn, Cu, Zn, and Cd).
COVID-19 Lockdowns—Effect on Concentration of Pharmaceuticals and Illicit Drugs in Two Major Croatian Rivers
Authors: Stipaničev Draženka , Repec Siniša , Vucić Matej , Lovrić Mario , Klobučar Göran
Published: May 2022

In order to prevent the spread of COVID-19, contingency measures in the form of lockdowns were implemented all over the world, including in Croatia. The aim of this study was to detect if those severe, imposed restrictions of social interactions reflected on the water quality of rivers receiving wastewaters from urban areas. A total of 18 different pharmaceuticals (PhACs) and illicit drugs (IDrgs), as well as their metabolites, were measured for 16 months (January 2020–April 2021) in 12 different locations at in the Sava and Drava Rivers, Croatia, using UHPLC coupled to LCMS. This period encompassed two major Covid lockdowns (March–May 2020 and October 2020–March 2021). Several PhACs more than halved in river water mass flow during the lockdowns. The results of this study confirm that Covid lockdowns caused lower cumulative concentrations and mass flow of measured PhACs/IDrgs in the Sava and Drava Rivers. This was not influenced by the increased use of drugs for the treatment of the COVID-19, like antibiotics and steroidal anti-inflammatory drugs. The decreases in measured PhACs/IDrgs concentrations and mass flows were more pronounced during the first lockdown, which was stricter than the second.
Towards the Development of Standardized Bioassays for Corals: Acute Toxicity of the UV Filter Benzophenone-3 to Scleractinian Coral Larvae
Authors: Miller Ingo B. , Moeller Mareen , Kellermann Matthias Y. , Nietzer Samuel , Di Mauro Valentina , Kamyab Elham , Pawlowski Sascha , Petersen-Thiery Mechtild , Schupp Peter J.
Published: May 2022

Coral reefs have been declining globally at a historically unprecedented rate. Ultraviolet (UV) filters used in sunscreens may contribute to this decline at local scales, which has already led to bans on various organic UV filters in some regions. However, the underlying studies for these bans demonstrated significant flaws in the experimental design due to a lack of validated and standardized testing methods for corals. This study aimed to investigate options for the development of a standard acute toxicity test for the larval stage of scleractinian corals. Planula larvae of two brooding (Leptastrea purpurea and Tubastraea faulkneri) and two spawning (Acropora digitifera and A. millepora) species were exposed to the organic UV filter benzophenone-3 (BP3) for 48 h under static conditions. We observed interspecific variations in toxicity, with A. digitifera being the most sensitive (LC50 = 0.75 µg L−1) and T. faulkneri the least sensitive (LC50 = 2951.24 µg L−1) species. Inhibition of settlement was found to be a useful endpoint leading to an EC50 of 1.84 µg L−1 in L. purpurea larvae. Although the analytical challenges of measuring lipophilic substances in small volume test setups remain, the here applied test design and selected endpoints are suitable for further validation and subsequent standardization.
Effects of Two Toxin-Producing Harmful Algae, Alexandrium catenella and Dinophysis acuminata (Dinophyceae), on Activity and Mortality of Larval Shellfish
Authors: Pease Sarah K. D. , Brosnahan Michael L. , Sanderson Marta P. , Smith Juliette L.
Published: May 2022

Harmful algal bloom (HAB) species Alexandrium catenella and Dinophysis acuminata are associated with paralytic shellfish poisoning (PSP) and diarrhetic shellfish poisoning (DSP) in humans, respectively. While PSP and DSP have been studied extensively, less is known about the effects of these HAB species or their associated toxins on shellfish. This study investigated A. catenella and D. acuminata toxicity in a larval oyster (Crassostrea virginica) bioassay. Larval activity and mortality were examined through 96-h laboratory exposures to live HAB cells (10–1000 cells/mL), cell lysates (1000 cells/mL equivalents), and purified toxins (10,000 cells/mL equivalents). Exposure to 1000 cells/mL live or lysed D. acuminata caused larval mortality (21.9 ± 7.0%, 10.2 ± 4.0%, respectively) while exposure to any tested cell concentration of live A. catenella, but not lysate, caused swimming arrest and/or mortality in >50% of larvae. Exposure to high concentrations of saxitoxin (STX) or okadaic acid (OA), toxins traditionally associated with PSP and DSP, respectively, had no effect on larval activity or mortality. In contrast, pectenotoxin-2 (PTX2) caused rapid larval mortality (49.6 ± 5.8% by 48 h) and completely immobilized larval oysters. The results indicate that the toxic effects of A. catenella and D. acuminata on shellfish are not linked to the primary toxins associated with PSP and DSP in humans, and that PTX2 is acutely toxic to larval oysters.
A Case Report of Secondary Syphilis Co-Infected with Measles: A Diagnostic Dilemma with Fever and Rash
Authors: Imad Hisham Ahmed , Lakanavisid Ploi , Pisutsan Phimphan , Trerattanavong Kentaro , Ngamprasertchai Thundon , Matsee Wasin , Piyaphanee Watcharapong , Leaungwutiwong Pornsawan , Nguitragool Wang , Nakayama Emi E. , Shioda Tatsuo
Published: May 2022

Fever and rash as manifestations of infection by microorganisms are collectively known as febrile exanthem. Since viruses are more frequently associated with fever and rash, these symptoms are thus impetuously termed viral exanthem. However, bacteria represent a frequently overlooked infectious etiology causing rash in humans. In addition, certain microbes may exhibit pathognomonic features that erupt during illness and facilitate clinical diagnosis. Conversely, coinfections often obscure the clinical characteristics of the primary disease and further challenge clinicians attempting to reach a diagnosis. We retrospectively looked at de-identified clinical data of a patient who presented to the Hospital for Tropical Diseases in Bangkok in July 2019 with complaints of fever and rash. The case involved a 35-year-old who presented with a 3-day history of fever, respiratory symptoms, myalgia, conjunctivitis, diarrhea, and a generalized maculopapular rash. On examination, the patient was febrile, tachycardic, and tachypneic, with a mean arterial pressure of 95 mmHg. A differential white blood cell count showed: leukocytes, 5800/µL; neutrophils, 4408/µL; lymphocytes, 406/µL; and platelets, 155,000/µL. Striking findings involving the integumentary system included Koplik’s spots and generalized maculopapular rash. Further serology revealed positive immunoglobulin (Ig)M and IgG for both measles and rubella virus, including reactive serology for Treponema pallidum. Here we describe the clinical course and management of this patient.
Belatacept as a Treatment Option in Patients with Severe BK Polyomavirus Infection and High Immunological Risk—Walking a Tightrope between Viral Control and Prevention of Rejection
Authors: Jehn Ulrich , Siam Sami , Wiening Vanessa , Pavenstädt Hermann , Reuter Stefan
Published: May 2022

Balancing the immune system with immunosuppressive treatment is essential in kidney transplant recipients to avoid allograft rejection on the one hand and infectious complications on the other. BK polyomavirus nephropathy (BKPyVAN) is a viral complication that seriously threatens kidney allograft survival. Therefore, the main treatment strategy is to reduce immunosuppression, but this is associated with an increased rejection risk. Belatacept is an immunosuppressant that acts by blocking the CD80/86-CD28 co-stimulatory pathway of effector T-cells with marked effects on the humoral response. However, when compared with calcineurin-inhibitors (CNI), the cellular rejection rate is higher. With this in mind, we hypothesized that belatacept could be used as rescue therapy in severely BKPyV-affected patients with high immunological risk. We present three cases of patients with BKPyVAN-associated complications and donor-specific antibodies (DSA) and one patient who developed T-cell-mediated rejection after a reduction in immunosuppression in response to BKPyVAN. Patients were switched to a belatacept-based immunosuppressive regimen and showed significantly improved viral control and stabilized graft function. The cases presented here suggest that belatacept is a potential treatment option in the complicated situation of refractory BKPyV infection in patients with high immunological risk.
SARS-CoV-2 Lineage A.27: New Data from African Countries and Dynamics in the Context of the COVID-19 Pandemic
Authors: Chouikha Anissa , Lagare Adamou , Ghedira Kais , Diallo Amadou , Njouom Richard , Sankhe Safietou , Derrar Fawzi , Victoir Kathleen , Dellagi Koussay , Triki Henda , Diagne Moussa Moise
Published: May 2022

SARS-CoV-2 is constantly evolving with lineages emerging and others eclipsing. Some lineages have an important epidemiological impact and are known as variants of interest (VOIs), variants under monitoring (VUMs) or variants of concern (VOCs). Lineage A.27 was first defined as a VUM since it holds mutations of concern. Here, we report additional lineage A.27 data and sequences from five African countries and describe the molecular characteristics, and the genetic history of this lineage worldwide. Based on the new sequences investigated, the most recent ancestor (tMRCA) of lineage A.27 was estimated to be from April 2020 from Niger. It then spread to Europe and other parts of the world with a peak observed between February and April 2021. The detection rate of A.27 then decreased with only a few cases reported during summer 2021. The phylogenetic analysis revealed many sub-lineages. Among them, one was defined by the substitution Q677H in the spike (S) gene, one was defined by the substitution D358N in the nucleoprotein (N) gene and one was defined by the substitution A2143V in the ORF1b gene. This work highlights the importance of molecular characterization and the timely submission of sequences to correctly describe the circulation of particular strains in order to be proactive in monitoring the pandemic.
RETRACTED: Jiang, H.; Mei, Y.-F. SARS–CoV–2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro. Viruses 2021, 13, 2056
Authors: Jiang Hui , Mei Ya-Fang
Published: May 2022

The published article [...]
Characterization of a Novel Reassortant Epizootic Hemorrhagic Disease Virus Serotype 6 Strain Isolated from Diseased White-Tailed Deer (Odocoileus virginianus) on a Florida Farm
Authors: Rodrigues Thaís C. S. , Viadanna Pedro H. O. , Subramaniam Kuttichantran , Hawkins Ian K. , Jeon Albert B. , Loeb Julia C. , Krauer Juan M. C. , Lednicky John A. , Wisely Samantha M. , Waltzek Thomas B.
Published: May 2022

We report an outbreak of a novel reassortant epizootic hemorrhagic disease virus serotype 6 (EHDV-6) in white-tailed deer (WTD) on a Florida farm in 2019. At necropsy, most animals exhibited hemorrhagic lesions in the lung and heart, and congestion in the lung, liver, and spleen. Histopathology revealed multi-organ hemorrhage and congestion, and renal tubular necrosis. Tissues were screened by RT-qPCR and all animals tested positive for EHDV. Tissues were processed for virus isolation and next-generation sequencing was performed on cDNA libraries generated from the RNA extracts of cultures displaying cytopathic effects. Six isolates yielded nearly identical complete genome sequences of a novel U.S. EHDV-6 strain. Genetic and phylogenetic analyses revealed the novel strain to be most closely related to a reassortant EHDV-6 strain isolated from cattle in Trinidad and both strains received segment 4 from an Australian EHDV-2 strain. The novel U.S. EHDV-6 strain is unique in that it acquired segment 8 from an Australian EHDV-8 strain. An RNAscope® in situ hybridization assay was developed against the novel U.S. EHDV-6 strain and labeling was detected within lesions of the heart, kidney, liver, and lung. These data support the novel U.S. reassortant EHDV-6 strain as the cause of disease in the farmed WTD.
Exposure Route Influences Disease Severity in the COVID-19 Cynomolgus Macaque Model
Authors: Bixler Sandra L. , Stefan Christopher P. , Jay Alexandra N. , Rossi Franco D. , Ricks Keersten M. , Shoemaker Charles J. , Moreau Alicia M. , Zeng Xiankun , Hooper Jay W. , Dyer David N. , Frick Ondraya M. , Koehler Jeffrey W. , Kearney Brian J. , DiPinto Nina , Liu Jun , Tostenson Samantha D. , Clements Tamara L. , Smith Jeffrey M. , Johnson Joshua A. , Berrier Kerry L. , Esham Heather L. , Delp Korey L. , Coyne Susan R. , Bloomfield Holly A. , Kuehnert Paul A. , Akers Kristen , Gibson Kathleen M. , Minogue Timothy D. , Nalca Aysegul , Pitt Margaret L. M.
Published: May 2022

The emergence of SARS-CoV-2 and the subsequent pandemic has highlighted the need for animal models that faithfully replicate the salient features of COVID-19 disease in humans. These models are necessary for the rapid selection, testing, and evaluation of potential medical countermeasures. Here, we performed a direct comparison of two distinct routes of SARS-CoV-2 exposure—combined intratracheal/intranasal and small particle aerosol—in two nonhuman primate species, rhesus and cynomolgus macaques. While all four experimental groups displayed very few outward clinical signs, evidence of mild to moderate respiratory disease was present on radiographs and at necropsy. Cynomolgus macaques exposed via the aerosol route also developed the most consistent fever responses and had the most severe respiratory disease and pathology. This study demonstrates that while all four models produced suitable representations of mild COVID-like illness, aerosol exposure of cynomolgus macaques to SARS-CoV-2 produced the most severe disease, which may provide additional clinical endpoints for evaluating therapeutics and vaccines.
Studies of Infection and Experimental Reactivation by Recombinant VZV with Mutations in Virally-Encoded Small Non-Coding RNA
Authors: Bisht Punam , Das Biswajit , Borodianskiy-Shteinberg Tatiana , Kinchington Paul R. , Goldstein Ronald S.
Published: May 2022

Locked-nucleotide analog antagonists (LNAA) to four varicella zoster virus small non-coding RNA (VZVsncRNA 10–13) derived from the mRNA of the open reading frame (ORF) 61 gene individually reduce VZV replication in epithelial cells and fibroblasts. To study the potential roles VZVsncRNA 10–13 have in neuronal infection we generated two recombinant VZV; one in which 8 nucleotides were changed in VZVsncRNA10 without altering the encoded residues of ORF61 (VZVsnc10MUT) and a second containing a 12-nucleotide deletion of the sequence common to VZVsncRNA12 and 13, located in the ORF61 mRNA leader sequence (VZVsnc12-13DEL). Both were developed from a VZV BAC with a green fluorescent protein (GFP) reporter fused to the N terminal of the capsid protein encoded by ORF23. The growth of both mutant VZV in epithelial cells and fibroblasts was similar to that of the parental recombinant virus. Both mutants established productive infections and experimental latency in neurons derived from human embryonic stem cells (hESC). However, neurons that were latently infected with both VZV mutant viruses showed impaired ability to reactivate when given stimuli that successfully reactivated the parental virus. These results suggest that these VZVsncRNA may have a role in VZV latency maintenance and/or reactivation. The extension of these studies and confirmation of such roles could potentially inform the development of a non-reactivating, live VZV vaccine.
Immunosuppressive Tumor Microenvironment and Immunotherapy of Epstein–Barr Virus-Associated Malignancies
Authors: Zheng Xueyi , Huang Yuhua , Li Kai , Luo Rongzhen , Cai Muyan , Yun Jingping
Published: May 2022

The Epstein–Barr virus (EBV) can cause different types of cancer in human beings when the virus infects different cell types with various latent patterns. EBV shapes a distinct and immunosuppressive tumor microenvironment (TME) to its benefit by influencing and interacting with different components in the TME. Different EBV-associated malignancies adopt similar but slightly specific immunosuppressive mechanisms by encoding different EBV products to escape both innate and adaptive immune responses. Strategies reversing the immunosuppressive TME of EBV-associated malignancies have been under evaluation in clinical practice. As the interactions among EBV, tumor cells, and TME are intricate, in this review, we mainly discuss the epidemiology of EBV, the life cycle of EBV, the cellular and molecular composition of TME, and a landscape of different EBV-associated malignancies and immunotherapy by targeting the TME.
COVID-19 Vaccine Hesitancy and Vaccination Coverage in India: An Exploratory Analysis
Authors: Dhalaria Pritu , Arora Himanshu , Singh Ajeet Kumar , Mathur Mansi , S. Ajai Kumar
Published: May 2022

Our paper examines the key determinants of COVID-19 vaccination coverage in India and presents an analytical framework to probe whether vaccine hesitancy, socioeconomic factors and multi-dimensional deprivations (MPI) play a role in determining COVID-19 vaccination uptake. Our exploratory analysis reveals that COVID-19 vaccine hesitancy has a negative and statistically significant impact on COVID-19 vaccination coverage. A percentage increase in vaccine hesitancy can lead to a decline in vaccination coverage by 30 percent. Similarly, an increase in the proportion of people living in multi-dimensional poverty reduces the COVID-19 vaccination coverage. A unit increase in MPI or proportion of people living in acute poverty leads to a mean decline in vaccination coverage by 50 percent. It implies that an increase in socioeconomic deprivation negatively impacts health outcomes, including vaccination coverage. We additionally demonstrated that gender plays a significant role in determining how access to digital technologies such as the internet impacts vaccine coverage and hesitancy. We found that, as males’ access to the internet increases, vaccination coverage also increases. This may be attributed to India’s reliance on digital tools (COWIN, AAROGYA SETU, Imphal, India) to allocate and register for COVID-19 vaccines and the associated digital divide (males have greater digital excess than females). Conversely, females’ access to the internet is statistically significant and inversely associated with coverage. This can be attributed to higher vaccine hesitancy among the female population and lower utilization of health services by females.
Anti-SARS-CoV-2S Antibody Levels in Healthcare Workers 10 Months after the Administration of Two BNT162b2 Vaccine Doses in View of Demographic Characteristic and Previous COVID-19 Infection
Authors: Wolszczak-Biedrzycka Blanka , Bieńkowska Anna , Zaborowska Joanna Ewa , Smolińska-Fijołek Elwira , Biedrzycki Grzegorz , Dorf Justyna
Published: May 2022

Antibody levels that confer full protection against SARS-CoV-2 infection after the administration of different vaccine brands as well as the factors influencing the humoral immune response have been analyzed extensively ever since the vaccination program was launched in late 2020. The aim of this study was to determine anti-SARS-CoV-2S antibody titers in 100 healthcare workers 10 months after the administration of two BNT162b2 vaccine doses, and to investigate the influence of demographic characteristics, the presence of comorbidities and history of COVID-19 infection. The results were compared with antibody levels that were determined eight months after the administration of two BNT162b2 vaccine doses in our previous study. Antibody levels in venous blood serum were measured by the ECLIA method with the use of the Roche Cobas e411 analyzer. In all tested subjects, antibody titers remained high 10 months after vaccination, particularly in recovered COVID-19 patients, and only a minor decrease was observed relative to the values noted two months earlier.
New-Onset Acute Kidney Disease Post COVID-19 Vaccination
Authors: Li Yebei , Rao Meiying , Xu Gaosi
Published: May 2022

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an exceptional setback to the global economy and health. Vaccination is one of the most effective interventions to markedly decrease severe illness and death from COVID-19. In recent years, there have been increasingly more reports of new acute kidney injury (AKI) after COVID-19 vaccination. Podocyte injury, IgA nephropathy, vasculitis, tubulointerstitial injury, and thrombotic microangiopathy appear to be the main pathological phenotypes. Nonetheless, whether the link between the COVID-19 vaccine and acute kidney disease (AKD) is causal or coincidental remains to be verified. Here, we generalize some hypotheses for the emergence of AKD and its pathogenesis in response to certain COVID-19 vaccines. In fact, the enormous benefits of mass vaccination against COVID-19 in preventing COVID-19 morbidity and mortality cannot be denied. The purpose of this review is to assist in the clinical assessment and management of AKD following COVID-19 vaccination.
Increased Receptor Affinity and Reduced Recognition by Specific Antibodies Contribute to Immune Escape of SARS-CoV-2 Variant Omicron
Authors: Vogt Anne-Cathrine S. , Augusto Gilles , Martina Byron , Chang Xinyue , Nasrallah Gheyath , Speiser Daniel E. , Vogel Monique , Bachmann Martin F. , Mohsen Mona O.
Published: May 2022

In this report, we mechanistically reveal how the Variant of Concern (VOC) SARS-CoV-2 Omicron (B.1.1.529) escapes neutralizing antibody responses, by physio-chemical characterization of this variant in comparison to the wild-type Wuhan and the Delta variant (B.1.617.2). Convalescent sera, as well as sera obtained from participants who received two or three doses of mRNA vaccines (Moderna-mRNA-1273® or Pfizer-BNT162b2®), were used for comparison in this study. Our data demonstrate that both Delta, as well as Omicron variants, exhibit a higher affinity for the receptor ACE2, facilitating infection and causing antibody escape by receptor affinity (affinity escape), due to the reduced ability of antibodies to compete with RBD-receptor interaction and virus neutralization. In contrast, only Omicron but not the Delta variant escaped antibody recognition, most likely because only Omicron exhibits the mutation at E484A, a position associated with reduced recognition, resulting in further reduced neutralization (specificity escape). Nevertheless, the immunizations with RNA-based vaccines resulted in marked viral neutralization in vitro for all strains, compatible with the fact that Omicron is still largely susceptible to vaccination-induced antibodies, despite affinity- and specificity escape.
Adverse Events and Safety Profile of the COVID-19 Vaccines in Adolescents: Safety Monitoring for Adverse Events Using Real-World Data
Authors: Lee Chae Won , Sa Soonok , Hong Myunghee , Kim Jihyun , Shim Sung Ryul , Han Hyun Wook
Published: May 2022

A COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) has recently been authorized for adolescents in the US. However, the impact of adverse events on adolescents after vaccination has not been fully investigated. To assess the safety of the COVID-19 vaccine in adolescents, the incidence of adverse events (AEs) in adolescents and adults was compared after vaccination. We included 6304 adolescents (68.14 per 100,000 people) who reported adverse events using vaccine adverse event reporting system (VAERS) data from 10 May 2021 to 30 September 2021. The mean age was 13.6 ± 1.1 years and women (52.7%) outnumbered men. We analyzed severe and common adverse events in response to the COVID-19 vaccine among 6304 adolescents (68.14 per 100,000 people; 52% female; mean age, 13.6 ± 1.1 years). The risk of myocarditis or pericarditis among adolescents was significantly higher in men than in women (OR = 6.61, 95% CI = 4.43 to 9.88; p < 0.001), with a higher frequency after the second dose of the vaccine (OR = 8.52, 95% CI = 5.79 to 12.54; p < 0.001). In addition, severe adverse events such as multisystem inflammatory syndromes, where the incidence rate per 100,000 people was 0.11 (n = 10), and the relative risk was 244.3 (95% CI = 31.27 to 1908.38; p < 0.001), were significantly higher in adolescents than in adults. The risk of the inflammatory response to the COVID-19 vaccine, including myocarditis, pericarditis, or multisystem inflammatory syndromes, was significantly higher in men than in women, with a higher frequency in adolescents than in adults. The inflammation-related AEs may require close monitoring and management in adolescents.
Innovative Therapies Targeting the Virus and the Host for Treating Chronic Hepatitis B Virus Infection: From Bench to Bedside
Authors: Akbar Sheikh Mohammad Fazle , Al Mahtab Mamun , Khan Sakirul , Yoshida Osamu , Aguilar Julio Cesar , Gerardo Guillen Nieto , Hiasa Yoichi
Published: May 2022

Chronic hepatitis B (CHB) is a highly complicated pathological process in which the disease is initiated by the hepatitis B virus (HBV); however, host immune responses are primarily responsible for variable extents of liver damage. If the patients with CHB remain untreated, many CHB patients will eventually develop complications like cirrhosis of the liver (LC) and hepatocellular carcinoma (HCC). In 2019, an estimated 882,000 patients died due to HBV-related complications worldwide. Accordingly, several drugs with antiviral properties have been used to treat CHB patients during the last four decades. However, the treatment outcome is not satisfactory because viral suppression is not usually related to the containment of progressive liver damage. Although proper reconstruction of host immunity is essential in CHB patients, as of today, there is no acceptable immune therapeutic protocol for them. These realities have exposed new, novel, and innovative therapeutic regimens for the management of CHB patients. This review will update the scope and limitation of the different innovative antiviral and immune therapeutic approaches for restoring effective host immunity and containing the virus in CHB patients to block progression to LC and HCC.
Analysis of the Effectiveness of Measures on the COVID-19 Vaccination Rate in Hong Kong
Authors: Chu Yui-Ki , Chung Pui-Hong , Pang Fei-Chau
Published: May 2022

Background: The World Health Organization has set a target of at least 70% of the global population being vaccinated by the middle of 2022. There are only 17 countries that achieved a 70% vaccination rate (VR). This study aims to analyze the effectiveness of public policies to increase the COVID-19 VR. Methods: vaccination figures of all eligible population groups in Hong Kong from 22 February 2021 to 23 January 2022, were extracted for analysis. Weekly acceleration in the VR (AVR) was calculated as a measure of policy effectiveness. A total of 13 identified measures were classified into four policy categories: eligibility, accessibility, incentives, and restrictions. Age-weighted AVR (AWAVR) was compared by age group and policy presence vs. absence using Mann–Whitney U tests. Results: the AWAVR means across age groups ranged from −1.26% to +0.23% (p = 0.12) for eligibility; accessibility ranged from +0.18% to +1.51% (p < 0.0001); incentives ranged from +0.11% to +0.68% (p < 0.0001); and restrictions ranged from +0.02% to +1.25% (p < 0.0001). Conclusions: policies targeting accessibility, incentives, and restrictions are effective at increasing the VR. These results may serve as a policy reference.
High Prevalence of Non-Vaccinated Oncogenic Human Papillomavirus Genotypes in High-Grade Squamous Intraepithelial Lesions of the Cervix: Thought-Provoking Results of a Detailed HPV Genotype Analysis
Authors: Rideg Orsolya , Dergez Tímea , Farkas Kornélia , Kovács Krisztina , Kálmán Endre , Tornóczky Tamás , Oszter Angéla
Published: May 2022

Identification of HPV infection is usually performed on cytological specimens, despite the often transient virus types. HPV profile analysis of pathologically confirmed lesions can also be performed on formalin-fixed paraffin-embedded (FFPE) cone samples and should be taken as standard during follow-up. We compared HPV profiles of cytological and FFPE specimens of women diagnosed with HSIL. Archived PAP smears and FFPE cones from 49 patients were processed. For genotyping, the HPV Direct Flow CHIP test was used. All samples were positive. HPV profile agreement of the two sample types was 84.16–100%. Mono-infections occurred in 12.24% and 61.22% in PAP smears and FFPE specimens, respectively; while multi-infections were detected in 87.76% and 38.78%, respectively. The most abundant genotypes were HPVs 16, 31, and 51/33. Of all infections, 56.25% and 64.93% were caused by nonavalent vaccinated type (VT) HPVs; while 50.69% and 38.96% belonged to non-nonavalent VT HPVs, in PAP smears and FFPE specimens, respectively. Our results confirmed the importance of HPV genotyping of FFPE cone samples. We also confirmed a remarkable presence of non-vaccinated HPV types in HSIL cases indicating the importance of vaccine development.
COVID-19 Vaccines Confer Protection in Hospitalized Pregnant and Postpartum Women with Severe COVID-19: A Retrospective Cohort Study
Authors: de Freitas Paganoti Cristiane , Alkmin da Costa Rafaela , Papageorghiou Aris T. , da Silva Costa Fabrício , Quintana Silvana Maria , Graziela de Godoi Luciana , Adriana Jiménez Monroy Nátaly , Sacramento Rodrigues Agatha , Pulcineli Vieira Francisco Rossana
Published: May 2022

The coronavirus disease 2019 (COVID-19) pandemic has had deleterious effects among the obstetric population. Pregnant and postpartum women constitute a high-risk group for severe COVID-19. Vaccination reduces the risk of infection, but it is not known whether women who become infected despite vaccination have a milder course of disease than those who had not been vaccinated. This retrospective cohort study evaluated whether vaccination reduces the severity of COVID-19 infection, as measured by severe maternal morbidity and mortality among hospitalized pregnant and postpartum individuals. A total of 2284 pregnant and postpartum women hospitalized with severe COVID-19 were included. Those who did and who did not receive COVID-19 vaccination were compared. The rates of intensive care unit admission, intubation, and mortality were significantly lower among subjects in the vaccinated group (p < 0.001, p < 0.001 and p < 0.001, respectively). The numbers of patients who needed to be vaccinated to avoid one case of intensive care unit admission, intubation, or death due to COVID-19 were 7, 7, and 9, respectively. The COVID-19 vaccine offers protective effects against intensive care unit admission, intubation, and death in hospitalized pregnant and postpartum women with severe SARS-CoV-2-induced SARS.
Lineage 1 Porcine Reproductive and Respiratory Syndrome Virus Attenuated Live Vaccine Provides Broad Cross-Protection against Homologous and Heterologous NADC30-Like Virus Challenge in Piglets
Authors: Zhang Hongliang , Xiang Lirun , Xu Hu , Li Chao , Tang Yan-Dong , Gong Bangjun , Zhang Wenli , Zhao Jing , Song Shuaijie , Peng Jinmei , Wang Qian , An Tongqing , Cai Xuehui , Tian Zhi-Jun
Published: May 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that endangers the swine industry worldwide. Recently, lineage 1 PRRSVs, especially NADC30-like PRRSVs, have become the major endemic strains in many pig-breeding countries. Since 2016, NADC30-like PRRSV has become the predominant strain in China. Unfortunately, current commercial vaccines cannot provide sufficient protection against this strain. Here, an attenuated lineage 1 PRRSV strain, named SD-R, was obtained by passaging an NADC30-like PRRSV strain SD in Marc-145 cells for 125 passages. Four-week-old PRRSV-free piglets were vaccinated intramuscularly with 105.0TCID50 SD-R and then challenged intramuscularly (2 mL) and intranasally (2 mL) with homologous NADC30-like PRRSV SD (1 × 105.0TCID50/mL) and heterologous NADC30-like PRRSV HLJWK108-1711 (1 × 105.0TCID50/mL). The results showed that antibodies against specific PRRSVs in 5 of 5 immunized piglets were positive after a 14-day post-vaccination and did not develop fever or clinical diseases after NADC30-like PRRSV challenges. Additionally, compared with challenge control piglets, vaccinated piglets gained significantly more weight and showed much milder pathological lesions. Furthermore, the viral replication levels of the immunized group were significantly lower than those of the challenge control group. These results demonstrate that lineage 1 PRRSV SD-R is a good candidate for an efficacious vaccine, providing complete clinical protection for piglets against NADC30-like PRRSVs.
Biological Compositions of Canine Amniotic Membrane and Its Extracts and the Investigation of Corneal Wound Healing Efficacy In Vitro
Authors: Permkam Chompunut , Suriyaphol Gunnaporn , Sirisawadi Sujin , Tuntivanich Nalinee
Published: May 2022

The usage of canine amniotic membrane (cAM) is mainly of interest in veterinary ophthalmology. Topical formulations of cAM could deliver the beneficial properties of cAM without the need for surgical intervention. The present study aimed to investigate biological compositions of cAM and its extracts, including their corneal wound healing efficacy. In this study, canine amniotic membrane extract (cAME) and lyophilized canine amniotic membrane extract (cAMX) were developed. Bioactive molecules related to corneal wound healing, including hepatocyte growth factor, tissue inhibitor of metalloproteinase-1 and -2, Thrombospondin-1 and Interleukin-1 receptor antagonist were studied at both gene and protein expression levels. Cell viability and wound healing assays were investigated for the possibility of cAME and cAMX as topical applications. The results demonstrated that all of the relevant genes and proteins were detected in cAM, cAME and cAMX. Both cAME and cAMX showed wound healing properties in vitro and cAME at 1.0 mg/mL concentration appeared to have the best healing efficacy. In conclusion, cAME and cAMX generated for topical use provided promising results in the healing of corneal defects.