bluuebunny/crossref_metadata_2025 huggingface dataset:
Prebiotic Route to Thymine from Formamide—A Combined Experimental–Theoretical Study
Authors: Petera Lukáš , Mrazikova Klaudia , Nejdl Lukas , Zemankova Kristyna , Vaculovicova Marketa , Pastorek Adam , Civis Svatopluk , Kubelik Petr , Heays Alan , Cassone Giuseppe , Sponer Jiri , Ferus Martin , Sponer Judit
Published: April 2021

Synthesis of RNA nucleobases from formamide is one of the recurring topics of prebiotic chemistry research. Earlier reports suggest that thymine, the substitute for uracil in DNA, may also be synthesized from formamide in the presence of catalysts enabling conversion of formamide to formaldehyde. In the current paper, we show that to a lesser extent conversion of uracil to thymine may occur even in the absence of catalysts. This is enabled by the presence of formic acid in the reaction mixture that forms as the hydrolysis product of formamide. Under the reaction conditions of our study, the disproportionation of formic acid may produce formaldehyde that hydroxymethylates uracil in the first step of the conversion process. The experiments are supplemented by quantum chemical modeling of the reaction pathway, supporting the plausibility of the mechanism suggested by Saladino and coworkers.
Human Pleural Fluid and Human Serum Albumin Modulate the Behavior of a Hypervirulent and Multidrug-Resistant (MDR) Acinetobacter baumannii Representative Strain
Authors: Pimentel Camila , Le Casin , Tuttobene Marisel R. , Subils Tomas , Martinez Jasmine , Sieira Rodrigo , Papp-Wallace Krisztina M. , Keppetipola Niroshika , Bonomo Robert A. , Actis Luis A. , Tolmasky Marcelo E. , Ramirez Maria Soledad
Published: April 2021

Acinetobacter baumannii is a nosocomial pathogen capable of causing serious infections associated with high rates of morbidity and mortality. Due to its antimicrobial drug resistance profile, A. baumannii is categorized as an urgent priority pathogen by the Centers for Disease Control and Prevention in the United States and a priority group 1 critical microorganism by the World Health Organization. Understanding how A. baumannii adapts to different host environments may provide critical insights into strategically targeting this pathogen with novel antimicrobial and biological therapeutics. Exposure to human fluids was previously shown to alter the gene expression profile of a highly drug-susceptible A. baumannii strain A118 leading to persistence and survival of this pathogen. Herein, we explore the impact of human pleural fluid (HPF) and human serum albumin (HSA) on the gene expression profile of a highly multi-drug-resistant strain of A. baumannii AB5075. Differential expression was observed for ~30 genes, whose products are involved in quorum sensing, quorum quenching, iron acquisition, fatty acid metabolism, biofilm formation, secretion systems, and type IV pilus formation. Phenotypic and further transcriptomic analysis using quantitative RT-PCR confirmed RNA-seq data and demonstrated a distinctive role of HSA as the molecule involved in A. baumannii’s response.
Triple Atresia, Triple Threat? An Unusual Constellation of Primary Surgical Abnormalities
Authors: Jackson Raef , Francis Carmen , Awad Karim , Folaranmi Semiu E.
Published: April 2021

We present a case series of two patients with tracheo-oesophageal fistula with oesophageal atresia (TOF/OA), duodenal atresia (DA) and ano-rectal malformation (ARM). This constellation of abnormalities, dubbed triple atresia (TA), is a rare combination with few described cases in the literature. Here we describe our management of these cases, as well as the results of our literature review. Both of our cases had staged surgical procedures and were initially managed with thoracotomy for repair of TOF/OA on day two of life. They subsequently underwent laparotomy for management of their abdominal pathology at day five and seven of life. Both have survived the neonatal period and are awaiting definitive surgery for ARM. Literature review yielded seven cases of TA involving a TOF, DA, and ARM. Four patients underwent staged repair, while three patients underwent repair of TOF/OA, DA and colostomy for ARM at the same time. Of these three patients, two died, representing 22% of the overall cohort. Triple atresia remains a rare subset of patients suspected to have VACTERL association, however mortality may be significantly higher. Our data would suggest a staged approach to be optimal for long term survival.
Real-World Failure Prevention Framework for Manufacturing Facilities Using Text Data
Authors: Park Jonghyuk , Choi Eunyoung , Choi Yerim
Published: April 2021

In recent years, manufacturing companies have been continuously engaging in research for the full implementation of smart factories, with many studies on methods to prevent facility failures that directly affect the productivity of the manufacturing sites. However, most studies have only analyzed sensor signals rather than text manually typed by operators. In addition, existing studies have not proposed an actual application system considering the manufacturing site environment but only presented a model that predicts the status or failure of the facility. Therefore, in this paper, we propose a real-world failure prevention framework that alerts the operator by providing a list of possible failure categories based on a failure pattern database before the operator starts work. The failure pattern database is constructed by analyzing and categorizing manually entered text to provide more detailed information. The performance of the proposed framework was evaluated utilizing actual manufacturing data based on scenarios that can occur in a real-world manufacturing site. The performance evaluation experiments demonstrated that the proposed framework could prevent facility failures and enhance the productivity and efficiency of the shop floor.
Optimal Surplus-Dependent Reinsurance under Regime-Switching in a Brownian Risk Model
Authors: Eisenberg Julia , Fabrykowski Lukas , Schmeck Maren Diane
Published: April 2021

In this paper, we consider a company that wishes to determine the optimal reinsurance strategy minimising the total expected discounted amount of capital injections needed to prevent the ruin. The company’s surplus process is assumed to follow a Brownian motion with drift, and the reinsurance price is modelled by a continuous-time Markov chain with two states. The presence of regime-switching substantially complicates the optimal reinsurance problem, as the surplus-independent strategies turn out to be suboptimal. We develop a recursive approach that allows to represent a solution to the corresponding Hamilton–Jacobi–Bellman (HJB) equation and the corresponding reinsurance strategy as the unique limits of the sequence of solutions to ordinary differential equations and their first- and second-order derivatives. Via Ito’s formula, we prove the constructed function to be the value function. Two examples illustrate the recursive procedure along with a numerical approach yielding the direct solution to the HJB equation.
Hybrid Task Coordination Using Multi-Hop Communication in Volunteer Computing-Based VANETs
Authors: Waheed Abdul , Shah Munam Ali , Khan Abid , Maple Carsten , Ullah Ikram
Published: April 2021

Computation offloading is a process that provides computing services to vehicles with computation sensitive jobs. Volunteer Computing-Based Vehicular Ad-hoc Networking (VCBV) is envisioned as a promising solution to perform task executions in vehicular networks using an emerging concept known as vehicle-as-a-resource (VaaR). In VCBV systems, offloading is the primary technique used for the execution of delay-sensitive applications which rely on surplus resource utilization. To leverage the surplus resources arising in periods of traffic congestion, we propose a hybrid VCBV task coordination model which performs the resource utilization for task execution in a multi-hop fashion. We propose an algorithm for the determination of boundary relay vehicles to minimize the requirement of placement for multiple road-side units (RSUs). We propose algorithms for primary and secondary task coordination using hybrid VCBV. Extensive simulations show that the hybrid technique for task coordination can increase the system utility, while the latency constraints are addressed.
Statistical and Machine Learning Models for Classification of Human Wear and Delivery Days in Accelerometry Data
Authors: Moore Ryan , Archer Kristin R. , Choi Leena
Published: April 2021

Accelerometers are increasingly being used in biomedical research, but the analysis of accelerometry data is often complicated by both the massive size of the datasets and the collection of unwanted data from the process of delivery to study participants. Current methods for removing delivery data involve arduous manual review of dense datasets. We aimed to develop models for the classification of days in accelerometry data as activity from human wear or the delivery process. These models can be used to automate the cleaning of accelerometry datasets that are adulterated with activity from delivery. We developed statistical and machine learning models for the classification of accelerometry data in a supervised learning context using a large human activity and delivery labeled accelerometry dataset. Model performances were assessed and compared using Monte Carlo cross-validation. We found that a hybrid convolutional recurrent neural network performed best in the classification task with an F1 score of 0.960 but simpler models such as logistic regression and random forest also had excellent performance with F1 scores of 0.951 and 0.957, respectively. The best performing models and related data processing techniques are made publicly available in the R package, Physical Activity.
Wearable Sensor-Based Real-Time Gait Detection: A Systematic Review
Authors: Prasanth Hari , Caban Miroslav , Keller Urs , Courtine Grégoire , Ijspeert Auke , Vallery Heike , von Zitzewitz Joachim
Published: April 2021

Gait analysis has traditionally been carried out in a laboratory environment using expensive equipment, but, recently, reliable, affordable, and wearable sensors have enabled integration into clinical applications as well as use during activities of daily living. Real-time gait analysis is key to the development of gait rehabilitation techniques and assistive devices such as neuroprostheses. This article presents a systematic review of wearable sensors and techniques used in real-time gait analysis, and their application to pathological gait. From four major scientific databases, we identified 1262 articles of which 113 were analyzed in full-text. We found that heel strike and toe off are the most sought-after gait events. Inertial measurement units (IMU) are the most widely used wearable sensors and the shank and foot are the preferred placements. Insole pressure sensors are the most common sensors for ground-truth validation for IMU-based gait detection. Rule-based techniques relying on threshold or peak detection are the most widely used gait detection method. The heterogeneity of evaluation criteria prevented quantitative performance comparison of all methods. Although most studies predicted that the proposed methods would work on pathological gait, less than one third were validated on such data. Clinical applications of gait detection algorithms were considered, and we recommend a combination of IMU and rule-based methods as an optimal solution.
Non-Contact Monitoring of Human Vital Signs Using FMCW Millimeter Wave Radar in the 120 GHz Band
Authors: Lv Wenjie , He Wangdong , Lin Xipeng , Miao Jungang
Published: April 2021

A non-contact heartbeat/respiratory rate monitoring system was designed using narrow beam millimeter wave radar. Equipped with a special low sidelobe and small-sized antenna lens at the front end of the receiving and transmitting antennas in the 120 GHz band of frequency-modulated continuous-wave (FMCW) system, this sensor system realizes the narrow beam control of radar, reduces the interference caused by the reflection of other objects in the measurement background, improves the signal-to-clutter ratio (SCR) of the intermediate frequency signal (IF), and reduces the complexity of the subsequent signal processing. In order to solve the problem that the accuracy of heart rate is easy to be interfered with by respiratory harmonics, an adaptive notch filter was applied to filter respiratory harmonics. Meanwhile, the heart rate obtained by fast Fourier transform (FFT) was modified by using the ratio of adjacent elements, which helped to improve the accuracy of heart rate detection. The experimental results show that when the monitoring system is 1 m away from the human body, the probability of respiratory rate detection error within ±2 times for eight volunteers can reach 90.48%, and the detection accuracy of the heart rate can reach 90.54%. Finally, short-term heart rate measurement was realized by means of improved empirical mode decomposition and fast independent component analysis algorithm.
Multi-Dimension and Multi-Feature Hybrid Learning Network for Classifying the Sub Pathological Type of Lung Nodules through LDCT
Authors: Fan Jiacheng , Bao Jianying , Xu Jianlin , Mo Jinqiu
Published: April 2021

In order to develop appropriate treatment and rehabilitation plans with regard to different subpathological types (PILs and IAs) of lung nodules, it is important to diagnose them through low-dose spiral computed tomography (LDCT) during routine screening before surgery. Based on the characteristics of different subpathological lung nodules expressed from LDCT images, we propose a multi-dimension and multi-feature hybrid learning neural network in this paper. Our network consists of a 2D network part and a 3D network part. The feature vectors extracted from the 2D network and 3D network are further learned by XGBoost. Through this formation, the network can better integrate the feature information from the 2D and 3D networks. The main learning block of the network is a residual block combined with attention mechanism. This learning block enables the network to learn better from multiple features and pay more attention to the key feature map among all the feature maps in different channels. We conduct experiments on our dataset collected from a cooperating hospital. The results show that the accuracy, sensitivity and specificity of our network are 83%, 86%, 80%, respectively It is feasible to use this network to classify the subpathological type of lung nodule through routine screening.
Monitoring Physical Activity with a Wearable Sensor in Patients with COPD during In-Hospital Pulmonary Rehabilitation Program: A Pilot Study
Authors: Rutkowski Sebastian , Buekers Joren , Rutkowska Anna , Cieślik Błażej , Szczegielniak Jan
Published: April 2021

Accelerometers have become a standard method of monitoring physical activity in everyday life by measuring acceleration in one, two, or three axes. These devices provide reliable and objective measurements of the duration and intensity of physical activity. We aimed to investigate whether patients undertake physical activity during non-supervised days during stationary rehabilitation and whether patients adhere to the rigor of 24 h monitoring. The second objective was to analyze the strengths and weaknesses of such kinds of sensors. The research enrolled 13 randomly selected patients, qualified for in-patient, 3 week, high-intensity, 5 times a week pulmonary rehabilitation. The SenseWear armband was used for the assessment of physical activity. Participants wore the device 24 h a day for the next 4 days (Friday–Monday). The analysis of the number of steps per day, the time spent lying as well as undertaking moderate or vigorous physical activity (>3 metabolic equivalents of task (METs)), and the energy expenditure expressed in kcal showed no statistically significant difference between the training days and the days off. It seems beneficial to use available physical activity sensors in patients with chronic obstructive pulmonary disease (COPD); measurable parameters provide feedback that may increase the patient’s motivation to be active to achieve health benefits.
Cross-Layer Optimization for Heterogeneous MU-MIMO/OFDMA Networks
Authors: Lee Kyu-haeng , Kim Daehee
Published: April 2021

To enable the full benefits from MU-MIMO (Multiuser-Multiple Input Multiple Output) and OFDMA (Orthogonal Frequency Division Multiple Access) to be achieved, the optimal use of these two technologies for a given set of network resources has been investigated in a rich body of literature. However, most of these studies have focused either on maximizing the performance of only one of these schemes, or have considered both but only for single-hop networks, in which the effect of the interference between nodes is relatively limited, thus causing the network performance to be overestimated. In addition, the heterogeneity of the nodes has not been sufficiently considered, and in particular, the joint use of OFDMA and MU-MIMO has been assumed to be always available at all nodes. In this paper, we propose a cross-layer optimization framework that considers both OFDMA and MU-MIMO for heterogeneous wireless networks. Not only does our model assume that the nodes have different capabilities, in terms of bandwidth and the number of antennas, but it also supports practical use cases in which nodes can support either OFDMA or MU-MIMO, or both at the same time. Our optimization model carefully takes into account the interactions between the key elements of the physical layer to the network layer. In addition, we consider multi-hop networks, and capture the complicated interference relationships between nodes as well as multi-path routing via multi-user transmissions. We formulate the proposed model as a Mixed Integer Linear Programming (MILP) problem, and initially model the case in which each node can selectively use either OFDMA or MU-MIMO; we then extend this to scenarios in which they are jointly used. As a case study, we apply the proposed model to sum-rate maximization and max–min fair allocation, and verify through MATLAB numerical evaluations that it can take appropriate advantage of each technology for a given set of network resources. Based on the optimization results, we also observe that when the two technologies are jointly used, more multi-user transmissions are enabled thanks to flexible resource allocation, meaning that greater use of the link capacity is achieved.
Protecting Children, Empowering Birth Parents: New Approaches in Family Justice
Authors: Cox Pamela , McPherson Susan , Blumenfeld Frances
Published: April 2021

This Special Issue presents insights from new interdisciplinary research in the family justice field [...]
Video-Assisted Thoracic Surgery for Late Recurrence of Congenital Diaphragmatic Hernia
Authors: Brochier Walther , Rezai Maryam Monfared , Mahieu Julien
Published: April 2021

Congenital diaphragmatic hernia (CDH) is often diagnosed and treated in the perinatal period. Recurrence is a known complication that may very rarely occur years after the operation. We report here the case of a patient who had an operation for a CDH at birth that then recurred in adulthood. Given the risk of complications and the symptomatology of the patient, we decided to treat the patient surgically. We successfully performed a video-assisted thoracic surgery (VATS) procedure during which we reduced the hernia and closed the breach. Given the recurrent nature of the hernia, we decided to reinforce the repair with a mesh.
Review of Battery Management Systems (BMS) Development and Industrial Standards
Authors: Gabbar Hossam , Othman Ahmed , Abdussami Muhammad
Published: April 2021

The evolving global landscape for electrical distribution and use created a need area for energy storage systems (ESS), making them among the fastest growing electrical power system products. A key element in any energy storage system is the capability to monitor, control, and optimize performance of an individual or multiple battery modules in an energy storage system and the ability to control the disconnection of the module(s) from the system in the event of abnormal conditions. This management scheme is known as “battery management system (BMS)”, which is one of the essential units in electrical equipment. BMS reacts with external events, as well with as an internal event. It is used to improve the battery performance with proper safety measures within a system. Therefore, a safe BMS is the prerequisite for operating an electrical system. This report analyzes the details of BMS for electric transportation and large-scale (stationary) energy storage. The analysis includes different aspects of BMS covering testing, component, functionalities, topology, operation, architecture, and BMS safety aspects. Additionally, current related standards and codes related to BMS are also reviewed. The report investigates BMS safety aspects, battery technology, regulation needs, and offer recommendations. It further studies current gaps in respect to the safety requirements and performance requirements of BMS by focusing mainly on the electric transportation and stationary application. The report further provides a framework for developing a new standard on BMS, especially on BMS safety and operational risk. In conclusion, four main areas of (1) BMS construction, (2) Operation Parameters, (3) BMS Integration, and (4) Installation for improvement of BMS safety and performance are identified, and detailed recommendations were provided for each area. It is recommended that a technical review of the BMS be performed for transportation electrification and large-scale (stationary) applications. A comprehensive evaluation of the components, architectures, and safety risks applicable to BMS operation is also presented.
An Easy Procedure to Quantify Anticoagulant Rodenticides and Pharmaceutical Active Compounds in Soils
Authors: Acosta-Dacal Andrea , Rial-Berriel Cristian , Díaz-Díaz Ricardo , Bernal-Suárez María , Zumbado Manuel , Henríquez-Hernández Luis , Luzardo Octavio
Published: April 2021

A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction was validated for the extraction of seven coumarin anticoagulant rodenticides (ARs) and 36 pharmaceutical active compounds (PhACs) residues in soil samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). The aim of this work was to develop a method for the monitoring of these compounds in agricultural lands as well as in forensic applications for the determination of ARs poisoning. As far as is known, this is the first time that a QuEChERS-based method is used for the extraction of ARs in soil, as well as on such a quantity of PhACs. A matrix effect study was carried out on samples of soil devoted to agriculture in the midland area of the Canary Islands (clay loam type). It was in house validated (accuracy, precision, and linearity) at seven spiked levels between 0.5 and 50 ng g−1. The limits of quantification (LOQ) ranged between 0.5 and 50.0 ng g−1 and the limits of detection (LOD) ranged from 0.024 to 6.25 ng g−1. The method was then successfully used for both the determination of the target analytes in the soils from the agricultural plots that had been irrigated with regenerated water, and in the soil collected from underneath wild bird carcasses (which had been the subject of forensic investigation).
The Trans-Planckian Censorship Conjecture in Different Frameworks of Viable Inflation
Authors: Sanna Bruno , Sebastiani Lorenzo
Published: April 2021

We review the recently proposed Trans-Planckian Censorship Conjecture (TCC) that stems from the trans-Planckian problem of cosmological perturbations. We analyze the implications and constraints that the TCC introduces in different frameworks of viable inflation. We revisit the case of slow-roll scalar field inflation and we investigate the cases of slow-roll f(R) and f(R,ϕ)-gravity. Finally, we consider the conjecture in the context of constant-roll scalar field inflation.
A Gravitational-Wave Perspective on Neutron-Star Seismology
Authors: Andersson Nils
Published: April 2021

We provide a bird’s-eye view of neutron-star seismology, which aims to probe the extreme physics associated with these objects, in the context of gravitational-wave astronomy. Focussing on the fundamental mode of oscillation, which is an efficient gravitational-wave emitter, we consider the seismology aspects of a number of astrophysically relevant scenarios, ranging from transients (like pulsar glitches and magnetar flares), to the dynamics of tides in inspiralling compact binaries and the eventual merged object and instabilities acting in isolated, rapidly rotating, neutron stars. The aim is not to provide a thorough review, but rather to introduce (some of) the key ideas and highlight issues that need further attention.
Nuclear Matrix Elements for Heavy Ion Sequential Double Charge Exchange Reactions
Authors: Lenske Horst , Bellone Jessica , Colonna Maria , Gambacurta Danilo
Published: April 2021

The theoretical approach to a sequential heavy ion double charge exchange reaction is presented. A brief introduction into the formal theory of second-order nuclear reactions and their application to Double Single Charge Exchange (DSCE) reactions by distorted wave theory is given, thereby completing the theoretical background to our recent work. Formally, the DSCE reaction amplitudes are shown to be separable into superpositions of distortion factors, accounting for initial and final state ion–ion interactions, and nuclear matrix elements. A broad space is given to the construction of nuclear DSCE response functions on the basis of polarization propagator theory. The nuclear response tensors resemble the nuclear matrix elements of 2νββ decay in structure but contain in general a considerable more complex multipole and spin structure. The QRPA theory is used to derive explicit expressions for nuclear matrix elements (NMEs). The differences between the NME of the first and the second interaction vertexes in a DSCE reaction is elucidated. Reduction schemes for the transition form factors are discussed by investigating the closure approximation and the momentum structure of form factors. DSCE unit strength cross sections are derived.
Chimeric Protein IPath® with Chelating Activity Improves Atlantic Salmon’s Immunity against Infectious Diseases
Authors: Valenzuela-Muñoz Valentina , Benavente Bárbara P. , Casuso Antonio , Leal Yeny , Gallardo-Escárate Cristian
Published: April 2021

Infection processes displayed by pathogens require the acquisition of essential inorganic nutrients and trace elements from the host to survive and proliferate. Without a doubt, iron is a crucial trace metal for all living organisms and also a pivotal component in the host–parasite interactions. In particular, the host reduces the iron available to face the infectious disease, increasing iron transport proteins’ expression and activating the heme synthesis and degradation pathways. Moreover, recent findings have suggested that iron metabolism modulation in fish promotes the immune response by reducing cellular iron toxicity. We hypothesized that recombinant proteins related to iron metabolism could modulate the fish’s immune system through iron metabolism and iron-responsive genes. Here a chimeric iron transport protein (IPath®) was bioinformatically designed and then expressed in a recombinant bacterial system. The IPath® protein showed a significant chelating activity under in vitro conditions and biological activity. Taking this evidence, a vaccine candidate based on IPath® was evaluated in Atlantic salmon challenged with three different fish pathogens. Experimental trials were conducted using two fish groups: one immunized with IPath® and another injected with adjutant as the control group. After 400 accumulated thermal units (ATUs), two different infection trials were performed. In the first one, fish were infected with the bacterium Aeromonas salmonicida, and in a second trial, fish were exposed to the ectoparasite Caligus rogercresseyi and subsequently infected with the intracellular bacterium Piscirickettsia salmonis. Fish immunized with IPath® showed a significant delay in the mortality curve in response to A. salmonicida and P. salmonis infections. However, no significant differences between infected and control fish groups were observed at the end of the experiment. Notably, sea lice burden reduction was observed in vaccinated Atlantic salmon. Transcriptional analysis evidenced a high modulation of iron-homeostasis-related genes in fish vaccinated with IPath® compared to the control group during the infection. Moreover, increasing expression of Atlantic salmon IgT was associated with IPath® immunization. This study provides evidence that the IPath® protein could be used as an antigen or booster in commercial fish vaccines, improving the immune response against relevant pathogens for salmon aquaculture.
Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A “Leaky” Vaccine with Debatable Efficacy and Safety
Authors: Zhou Lei , Ge Xinna , Yang Hanchun
Published: April 2021

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most economically important diseases, that has significantly impacted the global pork industry for over three decades, since it was first recognized in the United States in the late 1980s. Attributed to the PRRSV extensive genetic and antigenic variation and rapid mutability and evolution, nearly worldwide epidemics have been sustained by a set of emerging and re-emerging virus strains. Since the first modified live virus (MLV) vaccine was commercially available, it has been widely used for more than 20 years, for preventing and controlling PRRS. On the one hand, MLV can induce a protective immune response against homologous viruses by lightening the clinical signs of pigs and reducing the virus transmission in the affected herd, as well as helping to cost-effectively increase the production performance on pig farms affected by heterologous viruses. On the other hand, MLV can still replicate in the host, inducing viremia and virus shedding, and it fails to confer sterilizing immunity against PRRSV infection, that may accelerate viral mutation or recombination to adapt the host and to escape from the immune response, raising the risk of reversion to virulence. The unsatisfied heterologous cross-protection and safety issue of MLV are two debatable characterizations, which raise the concerns that whether it is necessary or valuable to use this leaky vaccine to protect the field viruses with a high probability of being heterologous. To provide better insights into the immune protection and safety related to MLV, recent advances and opinions on PRRSV attenuation, protection efficacy, immunosuppression, recombination, and reversion to virulence are reviewed here, hoping to give a more comprehensive recognition on MLV and to motivate scientific inspiration on novel strategies and approaches of developing the next generation of PRRS vaccine.
Vaccine Quality Is a Key Factor to Determine Thermal Stability of Commercial Newcastle Disease (ND)Vaccines
Authors: Osman Nabila , Goovaerts Danny , Sultan Serageldeen , Salt Jeremy , Grund Christian
Published: April 2021

Vaccination against Newcastle disease (ND), a devastating viral disease of chickens, is often hampered by thermal inactivation of the live vaccines, in particular in tropical and hot climate conditions. In the past, “thermostable” vaccine strains (I-2) were proposed to overcome this problem but previous comparative studies did not include formulation-specific factors of commercial vaccines. In the current study, we aimed to verify the superior thermal stability of commercially formulated I-2 strains by comparing six commercially available ND vaccines. Subjected to 37 °C as lyophilized preparations, two vaccines containing I-2 strains were more sensitive to inactivation than a third I-2 vaccine or compared to three other vaccines based on different ND strains. However, reconstitution strains proved to have a comparable tenacity. Interestingly, all vaccines still retained a sufficient virus dose for protection (106 EID50) after 1 day at 37 °C. These results suggest that there are specific factors that influence thermal stability beyond the strain-specific characteristics. Exposing ND vaccines to elevated temperatures of 51 and 61 °C demonstrated that inactivation of all dissolved vaccines including I-2 vaccine strains occurred within 2 to 4 h. The results revealed important differences among the vaccines and emphasize the importance of the quality of a certain vaccine preparation rather than the strain it contains. These data highlight that regardless of the ND strain used for vaccine preparation, the appropriate cold chain is mandatory for keeping live ND vaccines efficiency in hot climates.
Strategies for Immunomonitoring after Vaccination and during Infection
Authors: Adam Lucille , Rosenbaum Pierre , Bonduelle Olivia , Combadière Behazine
Published: April 2021

Immunomonitoring is the study of an individual’s immune responses over the course of vaccination or infection. In the infectious context, exploring the innate and adaptive immune responses will help to investigate their contribution to viral control or toxicity. After vaccination, immunomonitoring of the correlate(s) and surrogate(s) of protection is a major asset for measuring vaccine immune efficacy. Conventional immunomonitoring methods include antibody-based technologies that are easy to use. However, promising sensitive high-throughput technologies allowed the emergence of holistic approaches. This raises the question of data integration methods and tools. These approaches allow us to increase our knowledge on immune mechanisms as well as the identification of key effectors of the immune response. However, the depiction of relevant findings requires a well-rounded consideration beforehand about the hypotheses, conception, organization and objectives of the immunomonitoring. Therefore, well-standardized and comprehensive studies fuel insight to design more efficient, rationale-based vaccines and therapeutics to fight against infectious diseases. Hence, we will illustrate this review with examples of the immunomonitoring approaches used during vaccination and the COVID-19 pandemic.
Would Parents Get Their Children Vaccinated Against SARS-CoV-2? Rate and Predictors of Vaccine Hesitancy According to a Survey over 5000 Families from Bologna, Italy
Authors: Montalti Marco , Rallo Flavia , Guaraldi Federica , Bartoli Lapo , Po Giulia , Stillo Michela , Perrone Paola , Squillace Lorena , Dallolio Laura , Pandolfi Paolo , Resi Davide , Fantini Maria Pia , Reno Chiara , Gori Davide
Published: April 2021

In the near future, COVID-19 vaccine efficacy trials in larger cohorts may offer the possibility to implement child and adolescent vaccination. The opening of the vaccination for these strata may play a key role in order to limit virus circulation, infection spreading towards the most vulnerable subjects, and plan safe school reopening. Vaccine hesitancy (VH) could limit the ability to reach the coverage threshold required to ensure herd immunity. The aim of this study was to investigate the prevalence and determinants of VH among parents/guardians toward a potentially available COVID-19 vaccination for children and adolescents. An online survey was performed in parents/guardians of children aged <18 years old, living in Bologna. Overall, 5054 questionnaires were collected. A vast majority (60.4%) of the parents/guardians were inclined to vaccinate, while 29.6% were still considering the opportunity, and 9.9% were hesitant. Highest vaccine hesitancy rates were detected in female parents/guardians of children aged 6–10 years, ≤29 years old, with low educational level, relying on information found in the web/social media, and disliking mandatory vaccination policies. Although preliminary, these data could help in designing target strategies to implement adherence to a vaccination campaign, with special regard to web-based information.
Impact of Media Coverage on Influenza Vaccine Coverage in Elderly Individuals from 2020 to 2021 in the Republic of Korea
Authors: Kwon Yunhyung , Choe Young June , Yun Jae-Won , Kim Hee Kyoung , Kim Sungnam , Chun Chaemin , Jung Yeon Haw , Kim HeeJung , Oh Hyun-kyung , Lee Yeonkyoeng , Lee Jae Young , Lee Seon Kui , Park Young-Joon
Published: April 2021

Increased awareness of adverse events following immunization (AEFI) can disrupt vaccination programs. In South Korea, a report of alleged influenza vaccine-related deaths attracted significant media attention in 2020. We retrieved the vaccination coverage and AEFI data to determine their association with media coverage. Between 2015 and 2019, the vaccination coverage rate ranged between 80.5% and 83.3%; however, the vaccination coverage rate declined significantly from 2020 to 2021 to 73.6% (p < 0.0001). During the 43rd week of 2020, following a large amount of media coverage on vaccine safety issues, the number of cases with AEFI reached 60. Between 2015 and 2020, the mortality rate ratios for influenza vaccines and non-vaccines ranged between 0.1296 (95% confidence interval (CI), 0.1262–0.1331, p < 0.0001) and 0.1608 (95% CI, 0.1572–0.1644, p < 0.0001). Vaccine safety surveillance should be continued in conjunction with investigation and transparent risk communication to maintain public trust in vaccines and vaccinations.
Microparticles and Nanoparticles from Plants—The Benefits of Bioencapsulation
Authors: Schwestka Jennifer , Stoger Eva
Published: April 2021

The efficacy of drugs and vaccines depends on their stability and ability to interact with their targets in vivo. Many drugs benefit from encapsulation, which protects them from harsh conditions and allows targeted delivery and controlled release. Although many encapsulation methods are inexpensive, such as the formulation of tablets for oral delivery, others require complex procedures that add significantly to production costs and require low-temperature transport and storage, making them inaccessible in developing countries. In this review we consider the benefits of encapsulation technologies based on plants. Plant-derived biopolymers such as starch and the maize storage protein zein are already used as protective coatings, but plant cells used as production host provide natural in vivo bioencapsulation that survives passage through the stomach and releases drugs in the intestine, due to the presence of microbes that can digest the cell wall. Proteins can also be encapsulated in subcellular compartments such as protein bodies, which ensure stability and activity while often conferring additional immunomodulatory effects. Finally, we consider the incorporation of drugs and vaccines into plant-derived nanoparticles assembled from the components of viruses. These are extremely versatile, allowing the display of epitopes and targeting peptides as well as carrying cargoes of drugs and imaging molecules.
The C-Terminal Domain of Nefmut Is Dispensable for the CD8+ T Cell Immunogenicity of In Vivo Engineered Extracellular Vesicles
Authors: Chiozzini Chiara , Manfredi Francesco , Ferrantelli Flavia , Leone Patrizia , Giovannelli Andrea , Olivetta Eleonora , Federico Maurizio
Published: April 2021

Intramuscular injection of DNA vectors expressing the extracellular vesicle (EV)-anchoring protein Nefmut fused at its C-terminus to viral and tumor antigens elicit a potent, effective, and anti-tolerogenic CD8+ T cell immunity against the heterologous antigen. The immune response is induced through the production of EVs incorporating Nefmut-derivatives released by muscle cells. In the perspective of a possible translation into the clinic of the Nefmut-based vaccine platform, we aimed at increasing its safety profile by identifying the minimal part of Nefmut retaining the EV-anchoring protein property. We found that a C-terminal deletion of 29-amino acids did not affect the ability of Nefmut to associate with EVs. The EV-anchoring function was also preserved when antigens from both HPV16 (i.e., E6 and E7) and SARS-CoV-2 (i.e., S1 and S2) were fused to its C-terminus. Most important, the Nefmut C-terminal deletion did not affect levels, quality, and diffusion at distal sites of the antigen-specific CD8+ T immunity. We concluded that the C-terminal Nefmut truncation does not influence stability, EV-anchoring, and CD8+ T cell immunogenicity of the fused antigen. Hence, the C-terminal deleted Nefmut may represent a safer alternative to the full-length isoform for vaccines in humans.
Diversity in the Circulation of Influenza A(H3N2) Viruses in the Northern Hemisphere in the 2018–19 Season
Authors: Pando Rakefet , Stern Shahar , Nemet Ital , Glatman-Freedman Aharona , Sefty Hanna , Zuckerman Neta S. , Drori Yaron , Friedman Nehemya , McCauley John W. , Keinan-Boker Lital , Mendelson Ella , Daniels Rodney S. , Mandelboim Michal
Published: April 2021

While vaccination is considered the most effective means to prevent influenza infection, its seasonal effectiveness varies, depending on the circulating influenza strains. Here, we characterized the circulation of influenza strains in October-2018 and March-2019 around the world. For this, we used nasopharyngeal samples collected from outpatient and hospitalized patients in Israel and data reported in ECDC, CDC, and WHO databases. Influenza A(H3N2) was dominant in Israel, while in Europe, Asia, and USA, A(H1N1)pdm09 virus circulated first, and then the A(H3N2) virus also appeared. Phylogenetic analysis indicated that A(H3N2) viruses circulating in Israel belonged to clade-3C.3a, while in Europe, Asia, and USA, A(H3N2) viruses belonged to subclade-3C.2a1, but were later replaced by clade-3C.3a viruses in USA. The vaccine A(H3N2) components of that year, A/Singapore/INFIMH-16-0019/2016-(H3N2)-like-viruses, belonged to clade-3C.2a1. The circulation of different influenza subtypes and clades of A(H3N2) viruses in a single season highlights the need for universal influenza vaccines.
Vaccination and Immunity toward Measles: A Serosurvey in Future Healthcare Workers
Authors: Trevisan Andrea , Mason Paola , Nicolli Annamaria , Maso Stefano , Scarpa Bruno , Moretto Angelo , Scapellato Maria Luisa
Published: April 2021

Measles is a very contagious infectious disease, and vaccination is the only medical aid to counter the spread of the infection. The aim of this study was to evaluate the influence of vaccination schedule and type of vaccine, number of doses, and sex on the immune response. In a population of Italian medical students (8497 individuals born after 1980 with certificate of vaccination and quantitative measurement of antibodies against measles), the prevalence of positive antibodies to measles and antibody titer was measured. Vaccination schedule such as number of doses and vaccine type (measles alone or combined as measles, mumps and rubella (MMR)) and sex were the variables considered to influence the immune response. The vaccination schedule depends on the year of birth: students born before 1990 were prevalently vaccinated once and with measles vaccine alone (not as MMR). One dose of vaccine induces a significantly (p < 0.0001) higher positive response and antibody titer than two doses, in particular when measles alone is used (p < 0.0001). Females have a significantly higher percentage of positive response (p = 0.0001) than males but only when the MMR formulation was used. Multiple linear regression confirms that sex significantly influences antibody titer when only MMR is used, after one (p = 0.0002) or two (p = 0.0060) doses. In conclusion, vaccination schedule and, partially, sex influence immune response to measles vaccination. Most notably, the measles vaccine alone (one dose) is more effective than one and two doses of MMR.
Effect of Information about COVID-19 Vaccine Effectiveness and Side Effects on Behavioural Intentions: Two Online Experiments
Authors: Kerr John R. , Freeman Alexandra L. J. , Marteau Theresa M. , van der Linden Sander
Published: April 2021

The success of mass COVID-19 vaccination campaigns rests on widespread uptake. However, although vaccinations provide good protection, they do not offer full immunity and while they likely reduce transmission of the virus to others, the extent of this remains uncertain. This produces a dilemma for communicators who wish to be transparent about benefits and harms and encourage continued caution in vaccinated individuals but not undermine confidence in an important public health measure. In two large pre-registered experimental studies on quota-sampled UK public participants we investigate the effects of providing transparent communication—including uncertainty—about vaccination effectiveness on decision-making. In Study 1 (n = 2097) we report that detailed information about COVID-19 vaccines, including results of clinical trials, does not have a significant impact on beliefs about the efficacy of such vaccines, concerns over side effects, or intentions to receive a vaccine. Study 2 (n = 2217) addressed concerns that highlighting the need to maintain protective behaviours (e.g., social distancing) post-vaccination may lower perceptions of vaccine efficacy and willingness to receive a vaccine. We do not find evidence of this: transparent messages did not significantly reduce perceptions of vaccine efficacy, and in some cases increased perceptions of efficacy. We again report no main effect of messages on intentions to receive a vaccine. The results of both studies suggest that transparently informing people of the limitations of vaccinations does not reduce intentions to be vaccinated but neither does it increase intentions to engage in protective behaviours post-vaccination.
Motivation to Have COVID-19 Vaccination Explained Using an Extended Protection Motivation Theory among University Students in China: The Role of Information Sources
Authors: Wang Peng-Wei , Ahorsu Daniel Kwasi , Lin Chung-Ying , Chen I-Hua , Yen Cheng-Fang , Kuo Yi-Jie , Griffiths Mark D. , Pakpour Amir H.
Published: April 2021

Background: The aims of the present study were to examine the prediction of the threat and coping appraisal utilizing an extended protection motivation theory (PMT) for the motivation to have COVID-19 vaccination and the influence of various information sources on coping appraisal among university students in China. Methods: The sample comprised 3145 students from 43 universities in China who completed an online survey including PMT constructs as well as constructs added to PMT. The PMT constructs comprised motivation to have COVID-19 vaccination, threat appraisal, and coping appraisal. The extended PMT constructs comprised knowledge about mechanisms and information sources of COVID-19 vaccination. Results: Perceived severity of COVID-19 was positively associated with motivation to have COVID-19 vaccination. Receiving information concerning COVID-19 vaccination from medical personnel was associated with greater self-efficacy, response efficacy, and knowledge, whereas receiving information concerning COVID-19 vaccination from coworkers/colleagues was associated with less response efficacy and knowledge. Receiving online information concerning COVID-19 vaccination was associated with greater response cost of vaccination efficacy and less knowledge. Conclusions: This study supported the prediction of perceived severity in the PMT for motivation to have COVID-19 vaccination among university students in China. Vaccination information sources have different effects on students’ coping appraisal of COVID-19 vaccination.