bluuebunny/crossref_metadata_2025 huggingface dataset:
Pollination Methods and Integrated Fertilizer Influenced the Pollination Rate, Fruit Development, and Quality of Cucumis melo L. under Greenhouse Conditions
Authors: Nik Hassan Nik Zuraila , Sakimin Siti Zaharah , Jaafar Noraini Md , Ibrahim Illani Zuraihah
Published: December 2021

This study was conducted to determine the effect of pollination methods (PMs) and integrated fertilizer (IF) application on the pollination rate, yield, and fruit quality of rockmelon (Cucumis melo L. var. Reticulatus cv. Glamour). This factorial experiment was arranged in a split plot design with four replications. Two rates of IF between chemical (CF) and organic (OF) fertilizer were investigated, namely, T1 (100% CF), which served as a control, and T2 (75% CF + 25% OF). The three PMs used in this study were natural (NP), bee (BP), and human (HP) pollination. Data collection included the pollination rate, yield, postharvest quality (soluble solids content, color, firmness, sugar, and organic acid), and macronutrient content in leaf tissue. The results of this study showed that there was an interaction of the pollination rate between PM and IF; however, the number of bees that survived decreased over time. The yield quality showed an interaction between PM and IF for both the fruit diameter and weight, while no interaction between PM and IF for the organic acid and sugar contents was observed. In conclusion, T2 application combined with BP reduced CF utilization, which benefits the development of a sustainable rockmelon production system.
A Proposed Framework for Developing FMEA Method Using Pythagorean Fuzzy CODAS
Authors: Almeraz-Durán Sara , Pérez-Domínguez Luis Asunción , Luviano-Cruz David , Hernández Hernández Jesús Israel , Romero López Roberto , Valle-Rosales Delia J.
Published: December 2021

The purpose of this research article is to develop a hybridization between the Failure Mode and Effect Analysis (FMEA) method and the Combinative Distance-Based Assessment (CODAS) method under Pythagorean Fuzzy environment. The traditional FMEA procedure is based on the multiplication between the parameters of severity, occurrence, and detectability where everyone has equal relative importance; therefore, different combinations of these parameters can generate the same result creating uncertainty in the analysis. In this mode, the hybridization proposed in this research deal with relative importance of each parameter; in the fact to have a more suitable combination which consider the level of knowledge of the experts in the assessment. Finally, a numerical case was carried out concerning the public transportation service to validate our proposal; the results show that 31 failure modes and potential risks can be evaluated using user perceptions, a dominant with high level of knowledge about the public transportation service and an apprentice or common user, as team of experts and exploiting the subjectivity of the information in a mathematical model. Also, we compare the results with a variation of the proposed model with the multi-criteria method multi-objective optimization method by relationship analysis (MOORA); it was observed that the convergence of the failure modes depends on the nature of the mathematical model even under the same conditions at the start.
Deep Convolutional Symmetric Encoder—Decoder Neural Networks to Predict Students’ Visual Attention
Authors: Hachaj Tomasz , Stolińska Anna , Andrzejewska Magdalena , Czerski Piotr
Published: December 2021

Prediction of visual attention is a new and challenging subject, and to the best of our knowledge, there are not many pieces of research devoted to the anticipation of students’ cognition when solving tests. The aim of this paper is to propose, implement, and evaluate a machine learning method that is capable of predicting saliency maps of students who participate in a learning task in the form of quizzes based on quiz questionnaire images. Our proposal utilizes several deep encoder–decoder symmetric schemas which are trained on a large set of saliency maps generated with eye tracking technology. Eye tracking data were acquired from students, who solved various tasks in the sciences and natural sciences (computer science, mathematics, physics, and biology). The proposed deep convolutional encoder–decoder network is capable of producing accurate predictions of students’ visual attention when solving quizzes. Our evaluation showed that predictions are moderately positively correlated with actual data with a coefficient of 0.547 ± 0.109. It achieved better results in terms of correlation with real saliency maps than state-of-the-art methods. Visual analyses of the saliency maps obtained also correspond with our experience and expectations in this field. Both source codes and data from our research can be downloaded in order to reproduce our results.
Some New Simpson’s-Formula-Type Inequalities for Twice-Differentiable Convex Functions via Generalized Fractional Operators
Authors: Ali Muhammad Aamir , Kara Hasan , Tariboon Jessada , Asawasamrit Suphawat , Budak Hüseyin , Hezenci Fatih
Published: December 2021

From the past to the present, various works have been dedicated to Simpson’s inequality for differentiable convex functions. Simpson-type inequalities for twice-differentiable functions have been the subject of some research. In this paper, we establish a new generalized fractional integral identity involving twice-differentiable functions, then we use this result to prove some new Simpson’s-formula-type inequalities for twice-differentiable convex functions. Furthermore, we examine a few special cases of newly established inequalities and obtain several new and old Simpson’s-formula-type inequalities. These types of analytic inequalities, as well as the methodologies for solving them, have applications in a wide range of fields where symmetry is crucial.
Complex Dynamics of a Model with R&D Competition
Authors: Ferrara Massimiliano , Ciano Tiziana , Gangemi Mariangela , Guerrini Luca
Published: December 2021

The paper analyzes a two-stage oligopoly game of semi-collusion in production described by a system with a symmetric structure. We examine the local stability of a Nash equilibrium and the presence of bifurcations. We discover that the model is capable of exhibiting extremely complicated dynamic behaviors.
An Asymmetric Bimodal Double Regression Model
Authors: Gómez Yolanda M. , Gallardo Diego I. , Venegas Osvaldo , Magalhães Tiago M.
Published: December 2021

In this paper, we introduce an extension of the sinh Cauchy distribution including a double regression model for both the quantile and scale parameters. This model can assume different shapes: unimodal or bimodal, symmetric or asymmetric. We discuss some properties of the model and perform a simulation study in order to assess the performance of the maximum likelihood estimators in finite samples. A real data application is also presented.
Improved Opposition-Based Particle Swarm Optimization Algorithm for Global Optimization
Authors: Ul Hassan Nafees , Bangyal Waqas Haider , Ali Khan M. Sadiq , Nisar Kashif , Ag. Ibrahim Ag. Asri , Rawat Danda B.
Published: December 2021

Particle Swarm Optimization (PSO) has been widely used to solve various types of optimization problems. An efficient algorithm must have symmetry of information between participating entities. Enhancing algorithm efficiency relative to the symmetric concept is a critical challenge in the field of information security. PSO also becomes trapped into local optima similarly to other nature-inspired algorithms. The literature depicts that in order to solve pre-mature convergence for PSO algorithms, researchers have adopted various parameters such as population initialization and inertia weight that can provide excellent results with respect to real world problems. This study proposed two newly improved variants of PSO termed Threefry with opposition-based PSO ranked inertia weight (ORIW-PSO-TF) and Philox with opposition-based PSO ranked inertia weight (ORIW-PSO-P) (ORIW-PSO-P). In the proposed variants, we incorporated three novel modifications: (1) pseudo-random sequence Threefry and Philox utilization for the initialization of population; (2) increased population diversity opposition-based learning is used; and (3) a novel introduction of opposition-based rank-based inertia weight to amplify the execution of standard PSO for the acceleration of the convergence speed. The proposed variants are examined on sixteen bench mark test functions and compared with conventional approaches. Similarly, statistical tests are also applied on the simulation results in order to obtain an accurate level of significance. Both proposed variants show highest performance on the stated benchmark functions over the standard approaches. In addition to this, the proposed variants ORIW-PSO-P and ORIW-PSO-P have been examined with respect to training of the artificial neural network (ANN). We have performed experiments using fifteen benchmark datasets obtained and applied from the repository of UCI. Simulation results have shown that the training of an ANN with ORIW-PSO-P and ORIW-PSO-P algorithms provides the best results than compared to traditional methodologies. All the observations from our simulations conclude that the proposed ASOA is superior to conventional optimizers. In addition, the results of our study predict how the proposed opposition-based method profoundly impacts diversity and convergence.
A Comprehensive Commercialization Framework for Nanocomposites Utilizing a Model-Based Systems Engineering Approach
Authors: Kirmse Sebastian , Cloutier Robert J. , Hsiao Kuang-Ting
Published: December 2021

Nanocomposites provide outstanding benefits and possibilities compared to traditional composites but struggle to make it into the market due to the complexity and large number of associated challenges involved in, as well as lack of standards for, nanocomposite commercialization. This article proposes a commercialization framework utilizing market analysis and systems engineering to support the commercialization process of such high technologies. The article demonstrates the importance and usefulness of utilizing Model-Based Systems Engineering throughout the commercialization process of nanocomposite technologies when combining it with the Lean LaunchPad approach and an engineering analysis. The framework was validated using a qualitative research method with a case study approach. Applying this framework to a nanocomposite, called ZT-CFRP technology, showed tremendous impacts on the commercialization process, such as reduced market and technological uncertainties, which limits the commercialization risk and increases the chance for capital funding. Furthermore, utilizing the framework helped to decrease the commercialization time and cost due to the use of a lean engineering analysis. This framework is intended to assist advanced material-based companies, material scientists, researchers and entrepreneurs in academia and the industry during the commercialization process by minimizing uncertainties and risks, while focusing resources to reduce time-to-market and development costs.
Intelligent Interference Management in UAV-Based HetNets
Authors: Singh Simran , Kumbhar Abhaykumar , Güvenç İsmail , Sichitiu Mihail L.
Published: December 2021

Unmanned aerial vehicles (UAVs) can play a key role in meeting certain demands of cellular networks. UAVs can be used not only as user equipment (UE) in cellular networks but also as mobile base stations (BSs) wherein they can either augment conventional BSs by adapting their position to serve the changing traffic and connectivity demands or temporarily replace BSs that are damaged due to natural disasters. The flexibility of UAVs allows them to provide coverage to UEs in hot-spots, at cell-edges, in coverage holes, or regions with scarce cellular infrastructure. In this work, we study how UAV locations and other cellular parameters may be optimized in such scenarios to maximize the spectral efficiency (SE) of the network. We compare the performance of machine learning (ML) techniques with conventional optimization approaches. We found that, on an average, a double deep Q learning approach can achieve 93.46% of the optimal median SE and 95.83% of the optimal mean SE. A simple greedy approach, which tunes the parameters of each BS and UAV independently, performed very well in all the cases that we tested. These computationally efficient approaches can be utilized to enhance the network performance in existing cellular networks.
Correction: Yuan et al. Sub-Micromolar Methylmercury Exposure Promotes Premature Differentiation of Murine Embryonic Neural Precursor at the Expense of Their Proliferation. Toxics 2018, 6, 61
Authors: Yuan Xiaoyang , Wang Jing , Chan Hing
Published: December 2021

In the original article [...]
High Thyroid Cancer Incidence Rate in a Community near a Landfill: A Descriptive Epidemiological Assessment
Authors: van Gerwen Maaike , Gold Brandon , Alsen Mathilda , Khan Mohemmed N. , Petrick Lauren , Genden Eric
Published: December 2021

Background: to investigate the high thyroid cancer incidence rate of Staten Island and to disentangle the effects of potential environmental exposure from a landfill from screening. Methods: age-adjusted thyroid cancer incidence rates obtained from the New York State Public Access Cancer Epidemiology Data for New York State (NYS) excluding New York City (NYC) and the five NYC boroughs, including Staten Island, were mapped over time (1995–2018), investigated per age group and by percentage of localized thyroid cancer. Changes in trends were assessed using joinpoint. Contaminants of concern on Staten Island were assessed for carcinogenic and endocrine disruptive properties. Results: a more pronounced thyroid cancer incidence rate increase, without a difference in age distribution and similar percentages of localized thyroid cancer, was found in Staten Island compared to its demographic equivalent (NYS excluding NYC). Multiple contaminants of concern with carcinogenic and endocrine disrupting properties (e.g., cadmium, lead) were identified in air, water and sediment samples. Conclusion: investigations into the effects of increased/sustained environmental exposures are needed in chronically exposed populations to identify potential mechanisms of action of certain pollutants.
A Generic LC-HRMS Screening Method for Marine and Freshwater Phycotoxins in Fish, Shellfish, Water, and Supplements
Authors: Klijnstra Mirjam D. , Faassen Elisabeth J. , Gerssen Arjen
Published: December 2021

Phycotoxins occur in various marine and freshwater environments, and can accumulate in edible species such as fish, crabs, and shellfish. Human exposure to these toxins can take place, for instance, through consumption of contaminated species or supplements and through the ingestion of contaminated water. Symptoms of phycotoxin intoxication include paralysis, diarrhea, and amnesia. When the cause of an intoxication cannot directly be found, a screening method is required to identify the causative toxin. In this work, such a screening method was developed and validated for marine and freshwater phycotoxins in different matrices: fish, shellfish, water, and food supplements. Two LC methods were developed: one for hydrophilic and one for lipophilic phycotoxins. Sample extracts were measured in full scan mode with an Orbitrap high resolution mass spectrometer. Additionally, a database was created to process the data. The method was successfully validated for most matrices, and in addition, regulated lipophilic phycotoxins, domoic acid, and some paralytic shellfish poisoning toxins could be quantified in shellfish. The method showed limitations for hydrophilic phycotoxins in sea water and for lipophilic phycotoxins in food supplements. The developed method is a screening method; in order to confirm suspected compounds, comparison with a standard or an additional analysis such as NMR is required.
Prevalence, Enterotoxigenic Potential and Antimicrobial Resistance of Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus (MRSA) Isolated from Algerian Ready to Eat Foods
Authors: Mekhloufi Omar Amine , Chieffi Daniele , Hammoudi Abdelhamid , Bensefia Sid Ahmed , Fanelli Francesca , Fusco Vincenzina
Published: December 2021

Staphylococcus aureus causes a foodborne intoxication due to the production of enterotoxins and shows antimicrobial resistance, as in the case of methicillin-resistant strains (MRSA). Herein, we analyzed 207 ready-to-eat foods collected in Algeria, reporting a S. aureus prevalence of 23.2% (48/207) and respective loads of coagulase positive staphylococci (CPS) ranging from 1.00 ± 0.5 to 5.11 ± 0.24 Log CFU/g. The 48 S. aureus isolates were widely characterized by staphylococcal enterotoxin gene (SEg)-typing and 16S-23S rDNA intergenic spacer region (ISR)-PCR, as well as by detecting tst and mecA genes, genetic determinants of toxic shock syndrome toxin-1 and methicillin resistance, respectively. We found that the S. aureus isolates belonged to seven different SEg-types harboring the following combinations of genes: (1) selW, selX; (2) egc (seG, seI, seM, seN, seO), selW, selX; (3) seA, seH, seK, seQ, selW, selX; (4) seB, selW, selX; (5) seD, selJ, seR, selW, selX; (6) seH, selW, selX, selY; and (7) seA, egc, selW, selX, while among these, 2.1% and 4.2% were tst- and mecA- (staphylococcal chromosomal cassette mec-type IV) positive, respectively. Selected strains belonging to the 12 detected ISR-types were resistant towards antimicrobials including benzylpenicillin, ofloxacin, erythromycin, lincomycin, tetracyclin, kanamycin, oxacillin, and cefoxitin; 8.3% (1/12) were confirmed as MRSA and 16.7% (2/12) were multidrug resistant. The present study shows the heterogeneity of the S. aureus population in Algerian ready-to-eat foods as for their toxigenic potential and antimicrobial resistance, shedding the light on the quality and safety related to the consume of ready-to-eat foods in Algeria.
New Strategies for the Reduction of Uremic Toxins: How Much More We Know
Authors: Rocchetti Maria Teresa
Published: December 2021

The importance of uremic toxin (UTx) removal in chronic kidney disease (CKD) is an emerging topic in the literature, widely recognized over time as a strategy to slow-down the disease progression towards end-stage renal disease and, consequentely, the occurence of deleterious effects on cardiovascular (CV) system [...]
Botulinum Toxin Therapy: A Series of Clinical Studies on Patients with Spasmodic Dysphonia in Japan
Authors: Hyodo Masamitsu , Asano Kento , Nagao Asuka , Hirose Kahori , Nakahira Maya , Yanagida Saori , Nishizawa Noriko
Published: December 2021

Spasmodic dysphonia (SD) is a rare voice disorder caused by involuntary and intermittent spasms of the laryngeal muscles. Both diagnosis and treatment have been controversial. Therefore, a series of clinical studies has recently been conducted in Japan. A nationwide epidemiological survey revealed that adductor SD predominated (90–95% of all cases; 3.5–7.0/100,000), principally among young women in their 20s and 30s. To facilitate early diagnosis, we created diagnostic criteria for SD and a severity grading system. The diagnostic criteria include the principal and accompanying symptoms, clinical findings during phonation, the treatment response, and the differential diagnoses. The severity grade is determined using a combination of subjective and objective assessments. Botulinum toxin (BT) injection is the treatment of choice; however, there have been few high-quality clinical studies and BT has been used off-label. We conducted a placebo-controlled, randomized, double-blinded clinical trial of BT therapy; this was effective and safe. BT treatment is now funded by the Japanese medical insurance scheme. Studies thus far have facilitated early diagnosis and appropriate therapy; they have fostered patient awareness of SD.
On the Geometric Approach to the Boundary Problem in Supergravity
Authors: Andrianopoli Laura , Ravera Lucrezia
Published: December 2021

We review the geometric superspace approach to the boundary problem in supergravity, retracing the geometric construction of four-dimensional supergravity Lagrangians in the presence of a non-trivial boundary of spacetime. We first focus on pure N=1 and N=2 theories with negative cosmological constant. Here, the supersymmetry invariance of the action requires the addition of topological (boundary) contributions which generalize at the supersymmetric level the Euler-Gauss-Bonnet term. Moreover, one finds that the boundary values of the super field-strengths are dynamically fixed to constant values, corresponding to the vanishing of the OSp(N|4)-covariant supercurvatures at the boundary. We then consider the case of vanishing cosmological constant where, in the presence of a non-trivial boundary, the inclusion of boundary terms involving additional fields, which behave as auxiliary fields for the bulk theory, allows to restore supersymmetry. In all the cases listed above, the full, supersymmetric Lagrangian can be recast in a MacDowell-Mansouri(-like) form. We then report on the application of the results to specific problems regarding cases where the boundary is located asymptotically, relevant for a holographic analysis.
Dynamical Analysis and Cosmological Evolution in Weyl Integrable Gravity
Authors: Paliathanasis Andronikos
Published: December 2021

We investigate the cosmological evolution for the physical parameters in Weyl integrable gravity in a Friedmann–Lemaître–Robertson–Walker universe with zero spatial curvature. For the matter component, we assume that it is an ideal gas, and of the Chaplygin gas, from the Weyl integrable gravity a scalar field is introduced by a geometric approach which provides an interaction with the matter component.We calculate the stationary points for the field equations and we study their stability properties. Furthermore, we solve the inverse problem for the case of an ideal gas and prove that the gravitational field equations can follow from the variation of a Lagrangian function. Finally, variational symmetries are applied for the construction of analytic and exact solutions.
Effect of the Cubic Torus Topology on Cosmological Perturbations
Authors: Eingorn Maxim , Canay Ezgi , Metcalf Jacob M. , Brilenkov Maksym , Zhuk Alexander
Published: December 2021

We study the effect of the cubic torus topology of the Universe on scalar cosmological perturbations which define the gravitational potential. We obtain three alternative forms of the solution for both the gravitational potential produced by point-like masses, and the corresponding force. The first solution includes the expansion of delta-functions into Fourier series, exploiting periodic boundary conditions. The second one is composed of summed solutions of the Helmholtz equation for the original mass and its images. Each of these summed solutions is the Yukawa potential. In the third formula, we express the Yukawa potentials via Ewald sums. We show that for the present Universe, both the bare summation of Yukawa potentials and the Yukawa-Ewald sums require smaller numbers of terms to yield the numerical values of the potential and the force up to desired accuracy. Nevertheless, the Yukawa formula is yet preferable owing to its much simpler structure.
1S0 Pairing Gaps, Chemical Potentials and Entrainment Matrix in Superfluid Neutron-Star Cores for the Brussels–Montreal Functionals
Authors: Allard Valentin , Chamel Nicolas
Published: December 2021

Temperature and velocity-dependent 1S0 pairing gaps, chemical potentials and entrainment matrix in dense homogeneous neutron–proton superfluid mixtures constituting the outer core of neutron stars, are determined fully self-consistently by solving numerically the time-dependent Hartree–Fock–Bogoliubov equations over the whole range of temperatures and flow velocities for which superfluidity can exist. Calculations have been made for npeμ in beta-equilibrium using the Brussels–Montreal functional BSk24. The accuracy of various approximations is assessed and the physical meaning of the different velocities and momentum densities appearing in the theory is clarified. Together with the unified equation of state published earlier, the present results provide consistent microscopic inputs for modeling superfluid neutron-star cores.
Identification of Hepatitis E Virus Genotypes 3 and 7 in Israel: A Public Health Concern?
Authors: Shirazi Rachel , Pozzi Paolo , Gozlan Yael , Wax Marina , Lustig Yaniv , Linial Michal , Mendelson Ella , Bardenstein Svetlana , Mor Orna
Published: December 2021

Background: Hepatitis E (HEV) is an emerging cause of viral hepatitis worldwide. Swine carrying hepatitis E genotype 3 (HEV-3) are responsible for the majority of chronic viral hepatitis cases in developed countries. Recently, genotype 7 (HEV-7), isolated from a dromedary camel in the United Arab Emirates, was also associated with chronic viral hepatitis in a transplant recipient. In Israel, chronic HEV infection has not yet been reported, although HEV seroprevalence in humans is ~10%. Camels and swine are >65% seropositive. Here we report on the isolation and characterization of HEV from local camels and swine. Methods: Sera from camels (n = 142), feces from swine (n = 18) and blood from patients suspected of hepatitis E (n = 101) were collected during 2017–2020 and used to detect and characterize HEV sequences. Results: HEV-3 isolated from local swine and the camel-derived HEV-7 sequence were highly similar to HEV-3f and HEV-7 sequences (88.2% and 86.4%, respectively) related to viral hepatitis. The deduced amino acid sequences of both isolates were also highly conserved (>98%). Two patients were HEV-RNA positive; acute HEV-1 infection could be confirmed in one of them. Discussion: The absence of any reported HEV-3 and HEV-7 infection in humans remains puzzling, especially considering the reported seroprevalence rates, the similarity between HEV sequences related to chronic hepatitis and the HEV genotypes identified in swine and camels in Israel.
History of Arbovirus Research in the Czech Republic
Authors: Hubálek Zdenek
Published: December 2021

The aim of this review is to follow the history of studies on endemiv arboviruses and the diseases they cause which were detected in the Czech lands (Bohemia, Moravia and Silesia (i.e., the Czech Republic)). The viruses involve tick-borne encephalitis, West Nile and Usutu flaviviruses; the Sindbis alphavirus; Ťahyňa, Batai, Lednice and Sedlec bunyaviruses; the Uukuniemi phlebovirus; and the Tribeč orbivirus. Arboviruses temporarily imported from abroad to the Czech Republic have been omitted. This brief historical review includes a bibliography of all relevant papers.
Gammaherpesvirus Infections in Cattle in Europe
Authors: Rosato Giuliana , Ruiz Subira Andres , Al-Saadi Mohammed , Michalopoulou Eleni , Verin Ranieri , Dettwiler Martina , Nordgren Heli , Chiers Koen , Groβmann Ernst , Köhler Kernt , Suntz Michael , Stewart James P. , Kipar Anja
Published: December 2021

The genus Macavirus, subfamily Gammaherpesvirinae, comprises ungulate viruses that infect domestic and wild ruminants and swine. They cause asymptomatic latent infections in reservoir hosts and malignant catarrhal fever in susceptible species. Lung, spleen, bronchial lymph node, and tongue were collected from 448 cattle (348 necropsied, 100 slaughtered) in Switzerland, United Kingdom, Finland, Belgium, and Germany to determine their infection with bovine herpesvirus-6 (BoHV-6) and gammaherpesviruses of other ruminants, i.e., ovine herpesvirus-1 and -2, caprine herpesvirus-2, and bison lymphotropic herpesvirus, using quantitative PCR. Only BoHV-6 was detected, with an overall frequency of 32%, ranging between 22% and 42% in the different countries. Infection was detected across all ages, from one day after birth, and was positively correlated with age. There was no evidence of an association with specific disease processes. In positive animals, BoHV-6 was detected in all organs with high frequency, consistently in the lungs or spleen. Viral loads varied substantially. In BoHV-6-positive gravid cows, organs of fetuses tested negative for infection, indicating that the virus is not vertically transmitted. Our results confirm previous data indicating that BoHV-6 is a commensal of domestic cattle not associated with disease processes and confirm that infections with other macaviruses are rare and sporadic.
Interactions between the Prophage 919TP and Its Vibrio cholerae Host: Implications of gmd Mutation for Phage Resistance, Cell Auto-Aggregation, and Motility
Authors: Li Na , Zeng Yigang , Hu Bijie , Zhu Tongyu , Svenningsen Sine Lo , Middelboe Mathias , Tan Demeng
Published: December 2021

Prophage 919TP is widely distributed among Vibrio cholera and is induced to produce free φ919TP phage particles. However, the interactions between prophage φ919TP, the induced phage particle, and its host remain unknown. In particular, phage resistance mechanisms and potential fitness trade-offs, resulting from phage resistance, are unresolved. In this study, we examined a prophage 919TP-deleted variant of V. cholerae and its interaction with a modified lytic variant of the induced prophage (φ919TP cI-). Specifically, the phage-resistant mutant was isolated by challenging a prophage-deleted variant with lytic phage φ919TP cI-. Further, the comparative genomic analysis of wild-type and φ919TP cI--resistant mutant predicted that phage φ919TP cI- selects for phage-resistant mutants harboring a mutation in key steps of lipopolysaccharide (LPS) O-antigen biosynthesis, causing a single-base-pair deletion in gene gmd. Our study showed that the gmd-mediated O-antigen defect can cause pleiotropic phenotypes, e.g., cell autoaggregation and reduced swarming motility, emphasizing the role of phage-driven diversification in V. cholerae. The developed approach assists in the identification of genetic determinants of host specificity and is used to explore the molecular mechanism underlying phage-host interactions. Our findings contribute to the understanding of prophage-facilitated horizontal gene transfer and emphasize the potential for developing new strategies to optimize the use of phages in bacterial pathogen control.
Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles
Authors: Chongchai Aitthiphon , Waramit Sajee , Wongwichai Tunchanok , Kampangtip Jirawan , Phitak Thanyaluck , Kongtawelert Prachya , Hajitou Amin , Suwan Keittisak , Pothacharoen Peraphan
Published: December 2021

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive deterioration and loss of articular cartilage. There is currently no treatment to reverse the onset of OA. Thus, we developed a targeted delivery strategy to transfer genes into primary human chondrocytes as a proof-of-concept study. We displayed a chondrocyte-affinity peptide (CAP) on the pIII minor coat protein of the M13 filamentous bacteriophage (phage)-based particle carrying a mammalian transgene cassette under cytomegalovirus CMV promoter and inverted terminal repeats (ITRs) cis elements of adeno-associated virus serotype 2 (AAV-2). Primary human articular chondrocytes (HACs) were used as an in vitro model, and the selectivity and binding properties of the CAP ligand in relation to the pathogenic conditions of HACs were characterized. We found that the CAP ligand is highly selective toward pathogenic HACs. Furthermore, the stability, cytotoxicity, and gene delivery efficacy of the CAP-displaying phage (CAP.Phage) were evaluated. We found that the phage particle is stable under a wide range of temperatures and pH values, while showing no cytotoxicity to HACs. Importantly, the CAP.Phage particle, carrying a secreted luciferase (Lucia) reporter gene, efficiently and selectively delivered transgene expression to HACs. In summary, it was found that the CAP ligand preferably binds to pathogenic chondrocytes, and the CAP.Phage particle successfully targets and delivers transgene to HACs.
Constraint of Base Pairing on HDV Genome Evolution
Authors: Nagata Saki , Kiyohara Ryoji , Toh Hiroyuki
Published: December 2021

The hepatitis delta virus is a single-stranded circular RNA virus, which is characterized by high self-complementarity. About 70% of the genome sequences can form base-pairs with internal nucleotides. There are many studies on the evolution of the hepatitis delta virus. However, the secondary structure has not been taken into account in these studies. In this study, we developed a method to examine the effect of base pairing as a constraint on the nucleotide substitutions during the evolution of the hepatitis delta virus. The method revealed that the base pairing can reduce the evolutionary rate in the non-coding region of the virus. In addition, it is suggested that the non-coding nucleotides without base pairing may be under some constraint, and that the intensity of the constraint is weaker than that by the base pairing but stronger than that on the synonymous site.
Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections
Authors: Huber Silke , Massri Mariam , Grasse Marco , Fleischer Verena , Kellnerová Sára , Harpf Verena , Knabl Ludwig , Knabl Ludwig , Heiner Tatjana , Kummann Moritz , Neurauter Magdalena , Rambach Günter , Speth Cornelia , Würzner Reinhard
Published: December 2021

Overactivation of the complement system has been characterized in severe COVID-19 cases. Complement components are known to trigger NETosis via the coagulation cascade and have also been reported in human tracheobronchial epithelial cells. In this longitudinal study, we investigated systemic and local complement activation and NETosis in COVID-19 patients that underwent mechanical ventilation. Results confirmed significantly higher baseline levels of serum C5a (24.5 ± 39.0 ng/mL) and TCC (11.03 ± 8.52 µg/mL) in patients compared to healthy controls (p < 0.01 and p < 0.0001, respectively). Furthermore, systemic NETosis was significantly augmented in patients (5.87 (±3.71) × 106 neutrophils/mL) compared to healthy controls (0.82 (±0.74) × 106 neutrophils/mL) (p < 0.0001). In tracheal fluid, baseline TCC levels but not C5a and NETosis, were significantly higher in patients. Kinetic studies of systemic complement activation revealed markedly higher levels of TCC and CRP in nonsurvivors compared to survivors. In contrast, kinetic studies showed decreased local NETosis in tracheal fluid but comparable local complement activation in nonsurvivors compared to survivors. Systemic TCC and NETosis were significantly correlated with inflammation and coagulation markers. We propose that a ratio comprising systemic inflammation, complement activation, and chest X-ray score could be rendered as a predictive parameter of patient outcome in severe SARS-CoV-2 infections.
Identification of a Novel Geminivirus in Fraxinus rhynchophylla in Korea
Authors: Lal Aamir , Kim Yong-Ho , Vo Thuy Thi Bich , Wira Sanjaya I Gusti Ngurah Prabu , Ho Phuong Thi , Byun Hee-Seong , Choi Hong-Soo , Kil Eui-Joon , Lee Sukchan
Published: December 2021

Fraxinus rhynchophylla, common name ash, belongs to the family Oleaceae and is found in China, Korea, North America, the Indian subcontinent, and eastern Russia. It has been used as a traditional herbal medicine in Korea and various parts of the world due to its chemical constituents. During a field survey in March 2019, mild vein thickening (almost negligible) was observed in a few ash trees. High-throughput sequencing of libraries of total DNA from ash trees, rolling-circle amplification (RCA), and polymerase chain reaction (PCR) allowed the identification of a Fraxinus symptomless virus. This virus has five confirmed open reading frames along with a possible sixth open reading frame that encodes the movement protein and is almost 2.7 kb in size, with a nonanucleotide and stem loop structure identical to begomoviruses. In terms of its size and structure, this virus strongly resembles begomoviruses, but does not show any significant sequence identity with them. To confirm movement of the virus within the trees, different parts of infected trees were examined, and viral movement was successfully observed. No satellite molecules or DNA B were identified. Two-step PCR confirmed the virion and complementary strands during replication in both freshly collected infected samples of ash tree and Nicotiana benthamiana samples agro-inoculated with infectious clones. This taxon is so distantly grouped from other known geminiviruses that it likely represents a new geminivirus genus.
The Role of Serology Testing in the Context of Immunization Policies for COVID-19 in Latin American Countries
Authors: dos Santos Ferreira Carlos , Gómez-Dantés Hector , Junqueira Bellei Nancy , López Eduardo , Nogales Crespo Katya , O’Ryan Miguel , Villegas Julieta
Published: December 2021

This review aims to explore the role and value of serology testing in the context of COVID-19 immunization policies in Latin American countries and the barriers and challenges to the adequate use and uptake of this tool. It builds on a review of the academic literature, evidence, and existing policies, and includes a multistage process of discussion and feedback by a group of five experts. Regional and country-level evidence and resources from five focus countries—Argentina, Brazil, Chile, Colombia, and Mexico—were collected and analyzed. This review contains an overview of (1) the impact of the SARS-CoV-2 pandemic, the variants of concern and current testing strategies, (2) the introduction of COVID-19 vaccination, (3) the potential use of serology testing to support immunization initiatives, (4) the current frameworks for the use of serology testing in the region, and (5) the barriers and challenges to implementing serology testing in the context of COVID-19 immunization policies, including a discussion on the potential actions required to address these barriers and facilitate the uptake of this strategy in the region. Stakeholders can use elements of this document to guide timely decision-making, raise awareness, and inspire further studies.
Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population
Authors: Sariol Carlos A. , Serrano-Collazo Crisanta , Ortiz Edwin J. , Pantoja Petraleigh , Cruz Lorna , Arana Teresa , Atehortua Dianne , Pabon-Carrero Christina , Espino Ana M.
Published: December 2021

The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. Our data show that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After only one vaccine dose, the neutralization capacity expanded to all tested variants in pre-exposed individuals. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose did induce similar neutralizing antibodies against the Delta as against the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.
Immunogenicity and Safety of an Intradermal BNT162b2 mRNA Vaccine Booster after Two Doses of Inactivated SARS-CoV-2 Vaccine in Healthy Population
Authors: Intapiboon Porntip , Seepathomnarong Purilap , Ongarj Jomkwan , Surasombatpattana Smonrapat , Uppanisakorn Supattra , Mahasirimongkol Surakameth , Sawaengdee Waritta , Phumiamorn Supaporn , Sapsutthipas Sompong , Sangsupawanich Pasuree , Chusri Sarunyou , Pinpathomrat Nawamin
Published: December 2021

Effective vaccine coverage is urgently needed to tackle the COVID-19 pandemic. Inactivated vaccines have been introduced in many countries for emergency usage, but have only provided limited protection. Heterologous vaccination is a promising strategy to maximise vaccine immunogenicity. Here, we conducted a phase I, randomised control trial to observe the safety and immunogenicity after an intradermal boost, using a fractional dosage (1:5) of BNT162b2 mRNA vaccine in healthy participants in Songkhla, Thailand. In total, 91 volunteers who had been administered with two doses of inactivated SARS-CoV-2 (CoronaVac) were recruited into the study, and then randomised (1:1:1) to received different regimens of the third dose. An intramuscular booster with a full dose of BNT162b2 was included as a conventional control, and a half dose group was included as reciprocal comparator. Both, immediate and delayed adverse events following immunisation (AEFI) were monitored. Humoral and cellular immune responses were examined to observe the booster effects. The intradermal booster provided significantly fewer systemic side effects, from 70% down to 19.4% (p < 0.001); however, they were comparable to local reactions with the conventional intramuscular booster. In the intradermal group after receiving only one fifth of the conventional dosage, serum Anti-RBD IgG was halved compared to the full dose of an intramuscular injection. However, the neutralising function against the Delta strain remained intact. T cell responses were also less effective in the intradermal group compared to the intramuscular booster. Together, the intradermal booster, using a fractional dose of BNT162b2, can reduce systemic reactions and provides a good level and function of antibody responses compared to the conventional booster. This favourable intradermal boosting strategy provides a suitable alternative for vaccines and effective vaccine management to increase the coverage during the vaccine shortage.
Clinical Phenotype and Contagiousness of Early Breakthrough SARS-CoV-2 Infections after BNT162b2 COVID-19 mRNA Vaccine: A Parallel Cohort Study in Healthcare Workers
Authors: Trunfio Mattia , Verga Federica , Ghisetti Valeria , Burdino Elisa , Emanuele Teresa , Bonora Stefano , Di Perri Giovanni , Calcagno Andrea
Published: December 2021

We evaluated the clinical protection of BNT162b2 mRNA vaccine in healthcare workers (HCWs) and how COVID-19 manifestations and contagiousness change as the time since first dose increases. A matched (1:2 ratio) parallel cohort study was performed. During the first three months of vaccination campaign, HCWs of the entire health district ASL Città di Torino (Turin, Italy) were classified according to SARS-CoV-2-positivity in respect of the vaccination schedule: post-first-dose (fHCWs, <12 days), partially (PHCWs, ≥12 from first dose to ≤7 days after the second), and totally vaccinated (THCWs, ≥8 days after the second dose). Age-/sex-matched unvaccinated controls were randomly selected from all the SARS-CoV-2-positivity detected in the same district and period. Previous infections were excluded. Clinical and virologic data (ORF1ab gene cycle threshold values, Ct) were recorded. In total, 6800 HCWs received at least one dose, and 55 tested positive subsequently: 20 fHCWs, 25 PHCWs, 10 THCWs. Furthermore, 21.8% of breakthrough infections were in male, with a median age of 49 years (32–56), and 51.4% occurred while SARS-CoV-2 B.1.1.7 variant was predominant. The incident relative risk was 0.13 (0.12–0.15) for PHCWs and 0.06 (0.05–0.07) for THCWs. Compared to controls (n = 110), no difference was observed in fHCWs, while PHCWs and THCWs showed higher prevalence of asymptomatic infections, fewer signs/symptoms with a milder systemic involvement, and significantly higher Ct values (PHCWs 30.3 (24.1–35.5) vs. 22.3 (19.6–30.6), p = 0.023; THCWs 35.0 (31.3–35.9) vs. 22.5 (18.2–30.6), p = 0.024). Duration of symptoms was also shorter in THCWs (5 days (3–6) vs. 9 (7–14), p = 0.028). A linear increase of 3.81 points in Ct values was observed across the groups by vaccination status (p = 0.001) after adjusting for age, sex, comorbidities, and time between COVID-19 onset and swab collection. BNT162b2 decreased the risk of PCR-confirmed infections and severe disease, and was associated with a virologic picture of lesser epidemiologic concern as soon as 12 days after the first vaccine dose.
Economic Burden of Pneumococcal Disease in Individuals Aged 15 Years and Older in the Liguria Region of Italy
Authors: Astengo Matteo , Paganino Chiara , Amicizia Daniela , Trucchi Cecilia , Tassinari Federico , Sticchi Camilla , Sticchi Laura , Orsi Andrea , Icardi Giancarlo , Piazza Maria Francesca , Di Silverio Bruno , Deb Arijita , Senese Francesca , Prandi Gian Marco , Ansaldi Filippo
Published: December 2021

Despite the availability of vaccines against Streptococcus pneumoniae, the global incidence and economic cost of pneumococcal disease (PD) among adults is still high. This retrospective cohort analysis estimated the cost of emergency department (ED) visits/hospitalizations associated with non-invasive pneumonia and invasive pneumococcal disease among individuals ≥15 years of age in the Liguria region of Italy during 2012–2018. Data from the Liguria Region Administrative Health Databases and the Ligurian Chronic Condition Data Warehouse were used, including hospital admission date, length of stay, discharge date, outpatient visits, and laboratory/imaging procedures. A ≥30-day gap between two events defined a new episode, and patients with ≥1 ED or inpatient claim for PD were identified. The total mean annual number of hospitalizations for PD was 13,450, costing ~€49 million per year. Pneumonia accounted for the majority of hospitalization costs. The median annual cost of hospitalization for all-cause pneumonia was €38,416,440 (per-capita cost: €26.78) and was €30,353,928 (per-capita cost: €20.88) for pneumococcal and unspecified pneumonia. The total number and associated costs of ED visits/hospitalizations generally increased over the study period. PD still incurs high economic costs in adults in the Liguria region of Italy.
Investigating the Influence of Vaccine Literacy, Vaccine Perception and Vaccine Hesitancy on Israeli Parents’ Acceptance of the COVID-19 Vaccine for Their Children: A Cross-Sectional Study
Authors: Gendler Yulia , Ofri Lani
Published: December 2021

Vaccination is currently the most effective strategy for combating COVID-19. COVID-19 vaccines were introduced to the adult population in Israel in early December 2020 and have been available for children aged 12–15 since June 2021. Our study aimed at assessing the influence of vaccine literacy, perception, hesitancy, and behavior on Israeli parents’ intentions to have their children vaccinated. Using an anonymous online questionnaire, we recruited 520 parents; 70.4% of the parents indicated that they would get their children vaccinated. The participants’ COVID-19 vaccination status was the only socio-demographic factor significantly associated with COVID-19 vaccination acceptability (OR = 32.89; 95%CI = [13.11, 82.54]). The most common sources of information regarding the COVID-19 vaccine were health-care providers and the Internet. Parents who intend to vaccinate their children had higher mean levels of vaccine literacy (2.99 ± 0.47 vs. 3.07 ± 0.44 respectively, p = 0.06), more positive perception of the vaccine (mean scores of 2.26 ± 0.75 vs. 3.44 ± 0.68 respectively, p < 0.001), and lower perceived vaccine hesitancy (7.53 ± 2.37 vs. 4.68 ± 2.71 respectively, p < 0.001) than parents who do not intend to do so. Vaccine behavior was measured using the 5C model of psychological antecedents. All 5C components were significantly correlated with parents’ willingness to vaccinate their children. Understanding of parents’ willingness to have their children receive the COVID-19 vaccine and the barriers to and facilitators of the vaccination is crucial, as vaccination of children aged 5–11 has recently been approved by the FDA. Providing the population with reliable information regarding the COVID-19 vaccine is an important measure in the attempt to increase COVID-19 vaccine acceptance.