bluuebunny/crossref_metadata_2025 huggingface dataset:
Copulas Arisen from Degradation-Based Time-to-Failure Models
Authors: Alshagrawi Lolwa , Kayid Mohamed
Published: April 2022

There are a variety of degradation models in the literature, each with a certain effect of random variation around the mean degradation path on the time-to-failure of the device being degraded. To assess the dependence that the random variation around the mean degradation path exerts on the resulting time-to-failure, this paper presents copula functions for time-to-failure-based degradation models with respect to two well-known degradation models, namely, the multiplicative degradation model and the additive degradation model. The implied copula functions for the case of the multiplicative degradation model have explicit forms. The implied copula functions are proved to be symmetric in the case of deterministic effect of degradation on failure, but the copulas obtained when failure is affected uncertainly by degradation are asymmetric. Necessary and sufficient conditions for the implicit copula functions to be symmetric are given.
Rough-Set-Theory-Based Classification with Optimized k-Means Discretization
Authors: Dwiputranto Teguh Handjojo , Setiawan Noor Akhmad , Adji Teguh Bharata
Published: April 2022

The discretization of continuous attributes in a dataset is an essential step before the Rough-Set-Theory (RST)-based classification process is applied. There are many methods for discretization, but not many of them have linked the RST instruments from the beginning of the discretization process. The objective of this research is to propose a method to improve the accuracy and reliability of the RST-based classifier model by involving RST instruments at the beginning of the discretization process. In the proposed method, a k-means-based discretization method optimized with a genetic algorithm (GA) was introduced. Four datasets taken from UCI were selected to test the performance of the proposed method. The evaluation of the proposed discretization technique for RST-based classification is performed by comparing it to other discretization methods, i.e., equal-frequency and entropy-based. The performance comparison among these methods is measured by the number of bins and rules generated and by its accuracy, precision, and recall. A Friedman test continued with post hoc analysis is also applied to measure the significance of the difference in performance. The experimental results indicate that, in general, the performance of the proposed discretization method is significantly better than the other compared methods.
Geotextiles—A Versatile Tool for Environmental Sensitive Applications in Geotechnical Engineering
Authors: Tanasă Fulga , Nechifor Mărioara , Ignat Mauruşa-Elena , Teacă Carmen-Alice
Published: April 2022

Geotextiles, a group of high-performance materials, have grown during the last decades into needful auxiliaries when it comes to infrastructure, soil, construction, agriculture and environmental applications. Although geotextiles made of synthetic fibers (geosynthetics) are considered a modern achievement, the basic concept dates back to ancient times when textiles consisting of locally available natural fibers were employed to increase the stability of roads and soils. In recent decades, considering the growing interest in environmental protection and sustainable development based on using renewable resources and the recovery and recycling of waste of various origins, the use of natural fibers-based geotextiles is a viable alternative, despite their limited-life service owing to their biodegradability. In addition to this feature, their low cost, good mechanical properties and large-scale accessibility recommend them for geo-engineering applications, environmental sensitive applications in geotechnical engineering, such as land improvements and soil erosion control. This paper focuses on geotextiles as a versatile tool in environmental applications given their high theoretic and practical relevance as substantiated by recent literature reports. Natural and synthetic geotextiles are presented herein, as well as their features that recommend them for geo-engineering. Insights on the main types of applications of geotextiles are also included, along with a wide variety of materials employed to perform specific functions.
Different Prognostic Values of Dual-Time-Point FDG PET/CT Imaging Features According to Treatment Modality in Patients with Non-Small Cell Lung Cancer
Authors: Jang Su Jin , Lee Jeong Won , Lee Ji-Hyun , Jo In Young , Lee Sang Mi
Published: April 2022

This study was aimed to investigate whether dual-time-point F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging features had different prognostic values according to the treatment modality in patients with non-small cell lung cancer (NSCLC). We retrospectively reviewed 121 NSCLC patients with surgical resection (surgery group) and 69 NSCLC patients with chemotherapy and/or radiotherapy (CRT group), who underwent pretreatment dual-time-point FDG PET/CT. The maximum standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUV histogram entropy of primary cancer, and the percent changes in these parameters (Δparameters) were measured. In multivariate analysis, MTV, TLG, and entropy on both early and delayed PET/CT scans were significantly associated with progression-free survival (PFS) in the surgery group, but all Δparameters failed to show a significant association. In the CRT group, TLG on the early PET, maximum SUV on the delayed PET, ΔMTV, and ΔTLG were significant independent predictors for PFS. In the surgery group, patients with high values of MTV, TLG, and entropy had worse survival, whereas, in the CRT group, patients with high values of ΔMTV and ΔTLG had better survival. Dual-time-point FDG PET/CT parameters showed different prognostic values between the surgery and CRT groups of NSCLC patients.
Dose Reduction and Diagnostic Performance of Tin Filter–Based Spectral Shaping CT in Patients with Colorectal Cancer
Authors: Kimura Koichiro , Fujioka Tomoyuki , Mori Mio , Adachi Takuya , Hiraishi Takumi , Hada Hiroto , Ishikawa Toshiaki , Tateishi Ukihide
Published: April 2022

Routine CT examinations are crucial in colorectal cancer patients (CCPs); however, the high frequency of radiation exposure is a significant concern. This study investigated the radiation dose, image quality, and diagnostic performance of tin filter-based spectral shaping chest–abdominal–pelvic (CAP) CT for CCPs. We reviewed 44 CCPs who underwent single-phase enhanced tin-filtered 100 kV (TF100kV) and standard 120 kV (ST120kV) CAP CT on separate days. Radiation metrics including the volume CT dose index (CTDIvol), dose-length product (DLP), and effective dose (ED) were calculated for both protocols. Two radiologists assessed the presence of the following lesions: lung metastasis, liver metastasis, lymph node metastasis, peritoneal dissemination, and bone metastasis. The area under the receiver operating characteristic curve (AUC) was calculated for the diagnostic performance of each protocol. Radiation metrics of the TF100kV protocol were significantly lower than those of the ST120kV protocol (CDTIvol 1.60 ± 0.31 mGy vs. 14.4 ± 2.50, p < 0.0001; DLP 107.1 (95.9–125.5) mGy·cm vs. 996.7 (886.2–1144.3), p < 0.0001; ED 1.93 (1.73–2.26) mSv vs. 17.9 (16.0–20.6), p < 0.0001, respectively). TF100kV protocol achieved comparable diagnostic performance to that of the ST120kV protocol (AUC for lung metastasis: 1.00 vs. 0.94; liver metastasis: 0.88 vs. 0.83, respectively). TF100kV protocol could substantially reduce the radiation dose by 89% compared to that with the ST120kV protocol while maintaining good diagnostic performance in CCPs.
Detailed Speciation of Non-Methane Volatile Organic Compounds in Exhaust Emissions from Diesel and Gasoline Euro 5 Vehicles Using Online and Offline Measurements
Authors: Marques Baptiste , Kostenidou Evangelia , Valiente Alvaro Martinez , Vansevenant Boris , Sarica Thibaud , Fine Ludovic , Temime-Roussel Brice , Tassel Patrick , Perret Pascal , Liu Yao , Sartelet Karine , Ferronato Corinne , D’Anna Barbara
Published: April 2022

The characterization of vehicle exhaust emissions of volatile organic compounds (VOCs) is essential to estimate their impact on the formation of secondary organic aerosol (SOA) and, more generally, air quality. This paper revises and updates non-methane volatile organic compounds (NMVOCs) tailpipe emissions of three Euro 5 vehicles during Artemis cold urban (CU) and motorway (MW) cycles. Positive matrix factorization (PMF) analysis is carried out for the first time on proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS) datasets of vehicular emission. Statistical analysis helped to associate the emitted VOCs to specific driving conditions, such as the start of the vehicles, the activation of the catalysts, or to specific engine combustion regimes. Merged PTR-ToF-MS and automated thermal desorption gas chromatography mass spectrometer (ATD-GC-MS) datasets provided an exhaustive description of the NMVOC emission factors (EFs) of the vehicles, thus helping to identify and quantify up to 147 individual compounds. In general, emissions during the CU cycle exceed those during the MW cycle. The gasoline direct injection (GDI) vehicle exhibits the highest EF during both CU and MW cycles (252 and 15 mg/km), followed by the port-fuel injection (PFI) vehicle (24 and 0.4 mg/km), and finally the diesel vehicle (15 and 3 mg/km). For all vehicles, emissions are dominated by unburnt fuel and incomplete combustion products. Diesel emissions are mostly represented by oxygenated compounds (65%) and aliphatic hydrocarbons (23%) up to C22, while GDI and PFI exhaust emissions are composed of monoaromatics (68%) and alkanes (15%). Intermediate volatility organic compounds (IVOCs) range from 2.7 to 13% of the emissions, comprising essentially linear alkanes for the diesel vehicle, while naphthalene accounts up to 42% of the IVOC fraction for the gasoline vehicles. This work demonstrates that PMF analysis of PTR-ToF-MS datasets and GC-MS analysis of vehicular emissions provide a revised and deep characterization of vehicular emissions to enrich current emission inventories.
Cyanotoxins in Bloom: Ever-Increasing Occurrence and Global Distribution of Freshwater Cyanotoxins from Planktic and Benthic Cyanobacteria
Authors: Kaloudis Triantafyllos , Hiskia Anastasia , Triantis Theodoros M.
Published: April 2022

Toxic cyanobacteria in freshwater bodies constitute a major threat to public health and aquatic ecosystems [...]
Anti-Neurotoxins from Micrurus mipartitus in the Development of Coral Snake Antivenoms
Authors: Cardona-Ruda Ana , Rey-Suárez Paola , Núñez Vitelbina
Published: April 2022

In Colombia, the genus Micrurus includes 30 species, of which M. mipartitus and M. dumerilii are the most widely distributed. Micrurus causes less than 3% of the approximately 5000 cases of snakebite per year. The elapid envenomation caused by the snakes from the Micrurus genus, are characterized by the severity of their clinical manifestations, due to the venom neurotoxic components such as three-finger toxins (3FTx) and phospholipases (PLA2). The treatment for snakebites is the administration of specific antivenoms, however, some of them have limitations in their neutralizing ability. A strategy proposed to improve antivenoms is to produce antibodies against the main components of the venom. The aim of this work was to produce an antivenom, using an immunization protocol including the main 3FTx and PLA2 responsible for M. mipartitus lethality. The antibody titers were determined by ELISA in rabbits’ serum. The immunized animals elicited a response against toxins and whole venom. The Immunoglobulin G (IgGs) obtained were able to neutralize the lethal effect of their homologous toxins. A combination of antivenom from M. mipartitus with antitoxins improved their neutralizing ability. In the same way, a mixture of anti 3FTx and PLA2 protected the mice from a 1.5 median lethal dose (LD50) of M. mipartitus venom. The results showed that this might be a way to improve antibody titers specificity against the relevant toxins in M. mipartitus venom and indicated that there is a possibility to develop and use recombinant 3FTx and PLA2 toxins as immunogens to produce antivenoms. Additionally, this represents an alternative to reduce the amount of venom used in anti-coral antivenom production.
Lipopolysaccharide from the Cyanobacterium Geitlerinema sp. Induces Neutrophil Infiltration and Lung Inflammation
Authors: Swartzendruber Julie A. , Del Toro Rosalinda Monroy , Incrocci Ryan , Seangmany Nessa , Gurr Joshua R. , Mayer Alejandro M. S. , Williams Philip G. , Swanson-Mungerson Michelle
Published: April 2022

Glucocorticoid-resistant asthma, which predominates with neutrophils instead of eosinophils, is an increasing health concern. One potential source for the induction of neutrophil-predominant asthma is aerosolized lipopolysaccharide (LPS). Cyanobacteria have recently caused significant tidal blooms, and aerosolized cyanobacterial LPS has been detected near the cyanobacterial overgrowth. We hypothesized that cyanobacterial LPS contributes to lung inflammation by increasing factors that promote lung inflammation and neutrophil recruitment. To test this hypothesis, c57Bl/6 mice were exposed intranasally to LPS from the cyanobacterium member, Geitlerinema sp., in vivo to assess neutrophil infiltration and the production of pro-inflammatory cytokines and chemokines from the bronchoalveolar fluid by ELISA. Additionally, we exposed the airway epithelial cell line, A549, to Geitlerinema sp. LPS in vitro to confirm that airway epithelial cells were stimulated by this LPS to increase cytokine production and the expression of the adhesion molecule, ICAM-1. Our data demonstrate that Geitlerinema sp. LPS induces lung neutrophil infiltration, the production of pro-inflammatory cytokines such as Interleukin (IL)-6, Tumor necrosis factor-alpha, and Interferongamma as well as the chemokines IL-8 and RANTES. Additionally, we demonstrate that Geitlerinema sp. LPS directly activates airway epithelial cells to produce pro-inflammatory cytokines and the adhesion molecule, Intercellular Adhesion Molecule-1 (ICAM-1), in vitro using the airway epithelial cell line, A549. Based on our findings that use Geitlerinema sp. LPS as a model system, the data indicate that cyanobacteria LPS may contribute to the development of glucocorticoid-resistant asthma seen near water sources that contain high levels of cyanobacteria.
Anatomical Proposal for Botulinum Neurotoxin Injection for Glabellar Frown Lines
Authors: Yi Kyu-Ho , Lee Ji-Hyun , Hu Hye-Won , Kim Hee-Jin
Published: April 2022

Botulinum neurotoxin injection for treating glabellar frown lines is a commonly used method; however, side effects, such as ptosis and samurai eyebrow, have been reported due to a lack of comprehensive anatomical knowledge. The anatomical factors important for the injection of the botulinum neurotoxin into the corrugator supercilii muscle has been reviewed in this study. Current understanding on the localization of the botulinum neurotoxin injection point from newer anatomy examination was evaluated. We observed that for the glabellar-frown-line-related muscles, the injection point could be more accurately demarcated. We propose the injection method and the best possible injection sites for the corrugator supercilii muscle. We propose the optimal injection sites using external anatomical landmarks for the frequently injected muscles of the face to accelerate effective glabellar frown line removal. Moreover, these instructions would support a more accurate procedure without adverse events.
An Imported Case of Afebrile Plasmodium falciparum Malaria Infection from Tanzania in a Returning Traveler to the Republic of Korea following an Earlier COVID-19 Infection
Authors: Lee Chaeryoung , Hong Sung Kwan , Kim Jong Hun
Published: April 2022

Malaria is well-known as one of the most common causes of fever among travelers returning from endemic areas such as tropical African countries. However, afebrile Plasmodium falciparum malaria has rarely been reported in a returning traveler with no prior history of malaria infection. Here, we report an imported case of afebrile P. falciparum malaria infection from Tanzania in a returning traveler to the Republic of Korea, following an earlier COVID-19 infection without previous history of malaria infection. Our case suggests the hypothesis that severe symptoms of P. falciparum malaria infection might be prevented by cross- immunity from previous COVID-19 infection.
Superconducting Phases in Neutron Star Cores
Authors: Wood Toby S. , Graber Vanessa
Published: April 2022

Using a phenomenological Ginzburg–Landau model that includes entrainment, we identify the possible ground states for the neutron and proton condensates in the core of a neutron star, as a function of magnetic field strength. Combining analytical and numerical techniques, we find that much of the outer core is likely to be a “type-1.5” superconductor (instead of a type-II superconductor as often assumed), in which magnetic flux is distributed inhomogeneously, with bundles of magnetic fluxtubes separated by flux-free Meissner regions. We provide an approximate criterion to determine the transition between this type-1.5 phase and the type-I region in the inner core. We also show that bundles of fluxtubes can coexist with non-superconducting regions, but only in a small part of the parameter space.
Ultraviolet Finiteness or Asymptotic Safety in Higher Derivative Gravitational Theories
Authors: Rachwał Lesław
Published: April 2022

We present and discuss well known conditions for ultraviolet finiteness and asymptotic safety. The requirements for complete absence of ultraviolet divergences in quantum field theories and existence of a non-trivial fixed point for renormalization group flow in the ultraviolet regime are compared based on the example of a six-derivative quantum gravitational theory in d=4 spacetime dimensions. In this model, it is possible for the first time to have fully UV-finite quantum theory without adding matter or special symmetry, but by inclusion of additional terms cubic in curvatures. We comment on similarities and some apparent differences between the two approaches, but we show that they are both compatible to each other. Finally, we motivate the claim that actually asymptotic safety needs UV-finite models for providing explicit form of the ultraviolet limit of Wilsonian effective actions describing special situations at fixed points.
Polyadic Analogs of Direct Product
Authors: Duplij Steven
Published: April 2022

We propose a generalization of the external direct product concept to polyadic algebraic structures which introduces novel properties in two ways: the arity of the product can differ from that of the constituents, and the elements from different multipliers can be “entangled” such that the product is no longer componentwise. The main property which we want to preserve is associativity, which is gained by using the associativity quiver technique, which was provided previously. For polyadic semigroups and groups we introduce two external products: (1) the iterated direct product, which is componentwise but can have an arity that is different from the multipliers and (2) the hetero product (power), which is noncomponentwise and constructed by analogy with the heteromorphism concept introduced earlier. We show in which cases the product of polyadic groups can itself be a polyadic group. In the same way, the external product of polyadic rings and fields is generalized. The most exotic case is the external product of polyadic fields, which can be a polyadic field (as opposed to the binary fields), in which all multipliers are zeroless fields. Many illustrative concrete examples are presented.
Modeling of Magnetospheres of Terrestrial Exoplanets in the Habitable Zone around G-Type Stars
Authors: Belenkaya Elena S. , Alexeev Igor I. , Blokhina Marina S.
Published: April 2022

Using a paraboloid model of an Earth-like exoplanetary magnetospheric magnetic field, developed from a model of the Earth, we investigate the magnetospheric structure of planets located in the habitable zone around G-type stars. Different directions of the stellar wind magnetic field are considered and the corresponding variations in the magnetospheric structure are obtained. It is shown that the exoplanetary environment significantly depends on stellar wind magnetic field orientation and that the parameters of magnetospheric current systems depend on the distance to the stand-off magnetopause point.
Outbreaks of Avipoxvirus Clade E in Vaccinated Broiler Breeders with Exacerbated Beak Injuries and Sex Differences in Severity
Authors: Chacón Ruy D. , Astolfi-Ferreira Claudete S. , Pereira Patrícia C. , Assayag Mario S. , Campos-Salazar Antony B. , De la Torre David , Sá Lilian R. M. de , Almeida Sonia R. Yokomizo de , Rici Rose Elí Grassi , Ferreira Antonio J. Piantino
Published: April 2022

Avipoxvirus affects chickens and wild birds, and it is characterized by lesions on the nonfeathered parts of the body (the cutaneous form), or necrotic lesions in the upper respiratory tract (the diphtheritic form). In poultry farming, avian pox is usually controlled by live attenuated vaccines. However, there have been many reports of outbreaks, even in flocks of vaccinated birds. In the present study, different outbreaks of the emerging clade E avipoxvirus were detected in commercial breeder flocks of chickens vaccinated against fowlpox virus in Southeast Brazil. Clinical manifestations of these outbreaks included a marked prevalence of moderate to severe progressive lesions in the beaks of affected birds, especially in roosters with increased mortality (up to 8.48%). Also, a reduced hatchability (up to 20.77% fewer hatching eggs) was observed in these flocks. Analysis of clinical samples through light and transmission electron microscopy revealed the presence of Bollinger bodies and poxvirus particles in epithelial cells and affecting chondrocytes. PCR, sequencing, and phylogenetic analysis of major core protein (P4b) and DNA polymerase (pol) genes identified this virus as clade E avipoxvirus. We also developed qPCR assays for open reading frames (ORFs) 49, 114, and 159 to detect and quantify this emergent virus. These results show the arrival and initial spread of this pathogen in the poultry industry, which was associated with harmful outbreaks and exacerbated clinical manifestations in vaccinated commercial breeder flocks. This study also highlights the relevance of permanent vigilance and the need to improve sanitary and vaccination programs.
Alpha-Fetoprotein (AFP) and AFP-L3 Is Most Useful in Detection of Recurrence of Hepatocellular Carcinoma in Patients after Tumor Ablation and with Low AFP Level
Authors: Force Madison , Park Grace , Chalikonda Divya , Roth Christopher , Cohen Micah , Halegoua-DeMarzio Dina , Hann Hie-Won
Published: April 2022

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been shown to provide some additional detection of 6–8% of cases compared to ultrasound alone; however, this also increases false-positive results. This is because AFP can be elevated not only in the setting of HCC, but also in chronic hepatitis, liver cirrhosis, or ALT flare in CHB, which limits the specificity of AFP. AFP-L3 is a subfraction of AFP that is produced by malignant hepatocytes. The ratio of AFP-L3 to total AFP is reported as a percentage, and over 10% AFP-L3 is consistent with a diagnosis of HCC. Here, we review five cases of patients with CHB, cirrhosis, and HCC, and their levels of AFP and the AFP-L3% at various stages of disease including ALT flare, cirrhosis, initial diagnosis of HCC, and recurrence of HCC. These cases emphasize the utility of AFP-L3% in identifying early, new or recurrent HCC prior to the presence of imaging findings.
Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection
Authors: Philippens Ingrid H. C. H. M. , Böszörményi Kinga P. , Wubben Jacqueline A. M. , Fagrouch Zahra C. , van Driel Nikki , Mayenburg Amber Q. , Lozovagia Diana , Roos Eva , Schurink Bernadette , Bugiani Marianna , Bontrop Ronald E. , Middeldorp Jinte , Bogers Willy M. , de Geus-Oei Lioe-Fee , Langermans Jan A. M. , Verschoor Ernst J. , Stammes Marieke A. , Verstrepen Babs E.
Published: April 2022

SARS-CoV-2 causes acute respiratory disease, but many patients also experience neurological complications. Neuropathological changes with pronounced neuroinflammation have been described in individuals after lethal COVID-19, as well as in the CSF of hospitalized patients with neurological complications. To assess whether neuropathological changes can occur after a SARS-CoV-2 infection, leading to mild-to-moderate disease, we investigated the brains of four rhesus and four cynomolgus macaques after pulmonary disease and without overt clinical symptoms. Postmortem analysis demonstrated the infiltration of T-cells and activated microglia in the parenchyma of all infected animals, even in the absence of viral antigen or RNA. Moreover, intracellular α-synuclein aggregates were found in the brains of both macaque species. The heterogeneity of these manifestations in the brains indicates the virus’ neuropathological potential and should be considered a warning for long-term health risks, following SARS-CoV-2 infection.
Human Cytomegalovirus Infection Elicits Global Changes in Host Transcription by RNA Polymerases I, II, and III
Authors: Ball Christopher B. , Parida Mrutyunjaya , Li Ming , Spector Benjamin M. , Suarez Gustavo A. , Meier Jeffery L. , Price David H.
Published: April 2022

How human cytomegalovirus (HCMV) infection impacts the transcription of the host genome remains incompletely understood. Here, we examine the global consequences of infection of primary human foreskin fibroblasts (HFFs) on transcription by RNA polymerase I, II, and III over the course of a lytic infection using PRO-Seq. The expected rapid induction of innate immune response genes is observed with specific subsets of genes exhibiting dissimilar expression kinetics. We find minimal effects on Pol II initiation, but increased rates of the release of paused Pol II into productive elongation are detected by 24 h postinfection and pronounced at late times postinfection. Pol I transcription increases during infection and we provide evidence for a potential Pol I elongation control mechanism. Pol III transcription of tRNA genes is dramatically altered, with many induced and some repressed. All effects are partially dependent on viral genome replication, suggesting a link to viral mRNA levels and/or a viral early–late or late gene product. Changes in tRNA transcription are connected to distinct alterations in the chromatin state around tRNA genes, which were probed with high-resolution DFF-ChIP. Additionally, evidence is provided that the Pol III PIC stably contacts an upstream −1 nucleosome. Finally, we compared and contrasted our HCMV data with results from published experiments with HSV-1, EBV, KSHV, and MHV68. We report disparate effects on Pol II transcription and potentially similar effects on Pol III transcription.
Longitudinal Survey of Coronavirus Circulation and Diversity in Insectivorous Bat Colonies in Zimbabwe
Authors: Chidoti Vimbiso , De Nys Hélène , Pinarello Valérie , Mashura Getrude , Missé Dorothée , Guerrini Laure , Pfukenyi Davies , Cappelle Julien , Chiweshe Ngoni , Ayouba Ahidjo , Matope Gift , Peeters Martine , Gori Elizabeth , Bourgarel Mathieu , Liégeois Florian
Published: April 2022

Background: Studies have linked bats to outbreaks of viral diseases in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. Methods: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat–human interactions: Magweto cave and Chirundu farm. A total of 1732 and 1866 individual bat fecal samples were collected, respectively. Coronaviruses and bat species were amplified using PCR systems. Results: Analysis of the coronavirus sequences revealed a high genetic diversity, and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site and 16.5% and 38.9% at Magweto site for insectivorous bats and Macronycteris gigas, respectively. Conclusions: The higher risk of bat coronavirus exposure for humans was found in December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe.
How Do Point Mutations Enhancing the Basic Character of the RBDs of SARS-CoV-2 Variants Affect Their Transmissibility and Infectivity Capacities?
Authors: Barre Annick , Klonjkowski Bernard , Benoist Hervé , Rougé Pierre
Published: April 2022

The spread of SARS-CoV-2 variants in the population depends on their ability to anchor the ACE2 receptor in the host cells. Differences in the electrostatic potentials of the spike protein RBD (electropositive/basic) and ACE2 receptor (electronegative/acidic) play a key role in both the rapprochement and the recognition of the coronavirus by the cell receptors. Accordingly, point mutations that result in an increase in electropositively charged residues, e.g., arginine and lysine, especially in the RBD of spike proteins in the SARS-CoV-2 variants, could contribute to their spreading capacity by favoring their recognition by the electronegatively charged ACE2 receptors. All SARS-CoV-2 variants that have been recognized as being highly transmissible, such as the kappa (κ), delta (δ) and omicron (o) variants, which display an enhanced electropositive character in their RBDs associated with a higher number of lysine- or arginine-generating point mutations. Lysine and arginine residues also participate in the enhanced RBD–ACE2 binding affinity of the omicron variant, by creating additional salt bridges with aspartic and glutamic acid residues from ACE2. However, the effects of lysine- and arginine-generating point mutations on infectivity is more contrasted, since the overall binding affinity of omicron RBD for ACE2 apparently results from some epistasis among the whole set of point mutations.
An Approach to Quantifying the Interaction between Behavioral and Transmission Clusters
Authors: Salazar-Vizcaya Luisa , Kusejko Katharina , Günthard Huldrych F. , Böni Jürg , Metzner Karin J. , Braun Dominique L. , Nicca Dunja , Bernasconi Enos , Calmy Alexandra , Darling Katharine E. A. , Wandeler Gilles , Kouyos Roger D. , Rauch Andri ,   the Swiss HIV Cohort Study
Published: April 2022

We hypothesize that patterns of sexual behavior play a role in the conformation of transmission networks, i.e., the way you behave might influence whom you have sex with. If that was the case, behavioral grouping might in turn correlate with, and potentially predict transmission networking, e.g., proximity in a viral phylogeny. We rigorously present an intuitive approach to address this hypothesis by quantifying mapped interactions between groups defined by similarities in sexual behavior along a virus phylogeny while discussing power and sample size considerations. Data from the Swiss HIV Cohort Study on condom use and hepatitis C virus (HCV) sequences served as proof-of-concept. In this case, a strict inclusion criteria contrasting with low HCV prevalence hindered our possibilities to identify significant relationships. This manuscript serves as guide for studies aimed at characterizing interactions between behavioral patterns and transmission networks. Large transmission networks such as those of HIV or COVID-19 are prime candidates for applying this methodological approach.
Combining a Universal Capture Ligand and Pan-Serotype Monoclonal Antibody to Develop a Pan-Serotype Lateral Flow Strip Test for Foot-and-Mouth Disease Virus Detection
Authors: Yang Ming , Zhmendak Dmytro , Mioulet Valerie , King Donald P. , Burman Alison , Nfon Charles K.
Published: April 2022

Foot-and-mouth disease virus (FMDV) causes FMD, a highly contagious disease of cloven-hoofed animals including cattle, goats, pigs and sheep. Rapid detection of FMDV is critical to limit the devastating economic losses due to FMD. Current laboratory methods for FMDV detection such as virus isolation, real-time reverse transcription PCR and antigen detection enzyme-linked immunosorbent assay (AgELISA) are labor-intensive, requiring trained personnel and specialized equipment. We present the development and validation of a pan-serotype lateral flow strip test (LFST) that uses recombinant bovine integrin αvβ6 as a universal capture ligand and a pan-serotype monoclonal antibody (mAb) to detect FMDV. The LFST detected all seven FMDV serotypes, where the diagnostic sensitivity was comparable to the AgELISA, and the diagnostic specificity was 100% without cross-reactivity to other viruses causing vesicular disease in livestock. This rapid test will be useful for on-site FMDV detection, as well as in laboratories in endemic countries where laboratory resources are limited.
Hepatitis B Co-Infection Has Limited Impact on Liver Stiffness Regression in Chronic Hepatitis C Patients Treated with Direct-Acting Antivirals
Authors: Hsu Cheng-Er , Liu Yen-Chun , Cheng Ya-Ting , Jeng Wen-Juei , Chien Rong-Nan , Lin Chun-Yen , Tai Dar-In , Sheen I-Shyan
Published: April 2022

Introduction: High sustained virological response (SVR) rate (>95%) and liver stiffness regression can be achieved with direct acting antivirals treatment (DAA) in patients with chronic hepatitis C virus (CHC) infection. Reactivation of hepatitis B virus (HBV) was reported during DAA treatment in patients co-infected with HBV, although its impact on liver stiffness remains unknown. This study aims to investigate whether the liver stiffness (LSM) regression is different between HBV/HCV co-infected and mono-HCV-infected patients. Materials and Methods: CHC patients with/without HBV co-infection who received DAA treatment and achieved SVR12 between March 2015 and December 2019 in Chang Gung Memorial Hospital, Linkou branch were prospectively enrolled. LSM was assessed by transient elastography (TE, Fibroscan) at baseline and after SVR. Propensity score matching (PSM) at 3:1 ratio, adjusted for age, gender, pre-DAA alanine aminotransferase (ALT), platelet count, and LSM, between CHC with and without HBV co-infection, was performed before further analysis. Results: Among 906 CHC patients enrolled, 52 (5.7%) patients had HBV/HCV co-infection. Patients with HBV/HCV co-infection were of younger age (61.8 vs. 63.2, p = 0.31), with a higher proportion of males (53.8% vs. 38.9%, p = 0.03), and lower pretreatment LSM level (8.15 vs. 10.2 kPa, p = 0.09), while other features were comparable. After PSM, patients with HBV/HCV co-infection had insignificantly lower LSM regression compared to mono-HCV-infected patients (−0.85 kPa vs. −1.65 kPa, p = 0.250). Conclusions: The co-infection of HBV among CHC patients has limited impact on liver stiffness regression after successful DAA treatment.
Benefits of Inactivated Vaccine and Viral Vector Vaccine Immunization on COVID-19 Infection in Kidney Transplant Recipients
Authors: Sutharattanapong Napun , Thotsiri Sansanee , Kantachuvesiri Surasak , Wiwattanathum Punlop
Published: April 2022

The coronavirus virus disease 2019 (COVID-19) pandemic has impacted the global healthcare system. In Thailand, the first and most available vaccines were inactivated and viral vector vaccines. We reported the impact of those vaccines in preventing severe disease and death in kidney transplant recipients. This retrospective study comprised 45 kidney transplant recipients with COVID-19 infection, classified by vaccination status. Outcomes of interest were death, pneumonia, and allograft dysfunction. There were 23 patients in vaccinated group and 22 patients in unvaccinated group. All baseline characteristics were similar except mean age was older in vaccinated group, 55 vs. 48 years. Total 11 patients (24%) died (13% vaccinated vs. 36% unvaccinated RR, 0.56; 95% CI, 0.29–0.83; p = 0.03). Multivariate analysis showed that vaccination significantly decrease mortality (odds ratio, 0.54; 95% CI, 0.10–0.94; p = 0.03). Pneumonia developed equally in both groups (70%). There was a trend toward less oxygen requirement as well as ventilator requirement in vaccinated group. The rate of allograft dysfunction was similar (47%). Inactivated and viral vector COVID-19 vaccines have beneficial effect on mortality reduction in kidney transplant recipients. Even partial vaccination can exert some protection against death. However, full vaccination should be encouraged to achieve better prevention.
Spatial Patterns of COVID-19 Vaccination Coverage by Social Vulnerability Index and Designated COVID-19 Vaccine Sites in Texas
Authors: Mofleh Dania , Almohamad Maha , Osaghae Ikponmwosa , Bempah Sandra , Zhang Qianzi , Tortolero Guillermo , Ebeidat Ahmad , Ramphul Ryan , Sharma Shreela V.
Published: April 2022

Equitable access to the COVID-19 vaccine remains a public health priority. This study explores the association between ZIP Code–Tabulation Area level Social Vulnerability Indices (SVI) and COVID-19 vaccine coverage in Texas. A mixed-effects, multivariable, random-intercept negative binomial model was used to explore the association between ZIP Code–Tabulation Area level SVI and COVID-19 vaccination coverage stratified by the availability of a designated vaccine access site. Lower COVID-19 vaccine coverage was observed in ZIP codes with the highest overall SVIs (adjusted mean difference (aMD) = −13, 95% CI, −23.8 to −2.1, p < 0.01), socioeconomic characteristics theme (aMD = −16.6, 95% CI, −27.3 to −5.7, p = 0.01) and housing and transportation theme (aMD = −18.3, 95% CI, −29.6 to −7.1, p < 0.01) compared with the ZIP codes with the lowest SVI scores. The vaccine coverage was lower in ZIP Code–Tabulation Areas with higher median percentages of Hispanics (aMD = −3.3, 95% CI, −6.5 to −0.1, p = 0.04) and Blacks (aMD = −3.7, 95% CI, −6.4 to −1, p = 0.01). SVI negatively impacted COVID-19 vaccine coverage in Texas. Access to vaccine sites did not address disparities related to vaccine coverage among minority populations. These findings are relevant to guide the distribution of COVID-19 vaccines in regions with similar demographic and geospatial characteristics.
Severe Acute Myocarditis after the Third (Booster) Dose of mRNA COVID-19 Vaccination
Authors: Mengesha Bethlehem , Asenov Asen G. , Hirsh-Raccah Bruria , Amir Offer , Pappo Orit , Asleh Rabea
Published: April 2022

Vaccination with mRNA vaccines against coronavirus disease 2019 (COVID-19) has been associated with a risk of developing myocarditis and pericarditis, with an estimated standardized incidence ratio of myocarditis being 5.34 (95% CI, 4.48 to 6.40) as compared to the expected incidence based on historical data according to a large national study in Israel. Most cases of myocarditis in vaccine recipients occur in young males, particularly following the second dose, and the presentation is usually mild. Recently, the third (booster) dose has been shown to reduce confirmed infections and severe illness even against common variants of the virus. In Israel, over 4.4 million citizens (more than 45% of the population) have been vaccinated with the third dose of Pfizer-BioNTech vaccine BNT162b2. Herein, we report the first case of a histologically confirmed severe myocarditis following the third dose of BNT162b2 COVID-19 vaccine.
Influenza and Other Prophylactic Vaccination Coverage in Polish Adult Patients Undergoing Allergen Immunotherapy—A Survey Study among Patients and Physicians
Authors: Czerwińska Ewa , Nittner-Marszalska Marita , Zaryczański Janusz , Gąszczyk Grzegorz , Mastalerz-Migas Agnieszka , Szenborn Leszek
Published: April 2022

Vaccines against infectious diseases may raise safety concerns in patients undergoing allergen immunotherapy (AIT). The objective of our study was to investigate influenza vaccine and other selected prophylactic vaccines coverage in patients treated with AIT and the attitude of physicians towards vaccinations in this group of patients. We conducted a questionnaire-based study among patients undergoing AIT and physicians. The patients’ survey evaluated influenza and other prophylactic vaccines coverage. The physicians’ survey assessed their experience and opinions on prophylactic vaccinations during AIT. In total, 176 patients (aged 18–79 years) and 120 doctors filled the questionnaires. Patients were assigned to two groups—inhaled allergens group (n = 101) and insect venoms group (n = 68). The number of patients who received any dose (36% and 45%, p = 0.26), as well as two or more doses (17% and 22%, p = 0.43) of influenza vaccine was comparable between two groups. However, in both groups there was a significant (p < 0.0001) decrease in influenza vaccine uptake after the beginning of AIT. Patients from the inhaled allergens group declared a higher tetanus vaccine rate (41% vs. 19%, p = 0.004). The groups did not differ in the pneumococcal and tick-borne encephalitis vaccination coverage. A majority of doctors believe that prophylactic vaccinations in patients undergoing AIT are safe and effective (96% and 94%, respectively); however, as many as 87% of them identify with the need to create clear recommendations regarding vaccinating patients undergoing AIT. Prophylactic vaccine coverage is not satisfactory among Polish adult patients undergoing AIT. Polish doctors are convinced of the validity of prophylactic vaccinations during AIT.
Dermal Delivery of a SARS-CoV-2 Subunit Vaccine Induces Immunogenicity against Variants of Concern
Authors: McMillan Christopher L. D. , Azuar Armira , Choo Jovin J. Y. , Modhiran Naphak , Amarilla Alberto A. , Isaacs Ariel , Honeyman Kate E. , Cheung Stacey T. M. , Liang Benjamin , Wurm Maria J. , Pino Paco , Kint Joeri , Fernando Germain J. P. , Landsberg Michael J. , Khromykh Alexander A. , Hobson-Peters Jody , Watterson Daniel , Young Paul R. , Muller David A.
Published: April 2022

The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to disrupt essential health services in 90 percent of countries today. The spike (S) protein found on the surface of the causative agent, the SARS-CoV-2 virus, has been the prime target for current vaccine research since antibodies directed against the S protein were found to neutralize the virus. However, as new variants emerge, mutations within the spike protein have given rise to potential immune evasion of the response generated by the current generation of SARS-CoV-2 vaccines. In this study, a modified, HexaPro S protein subunit vaccine, delivered using a needle-free high-density microarray patch (HD-MAP), was investigated for its immunogenicity and virus-neutralizing abilities. Mice given two doses of the vaccine candidate generated potent antibody responses capable of neutralizing the parental SARS-CoV-2 virus as well as the variants of concern, Alpha and Delta. These results demonstrate that this alternative vaccination strategy has the potential to mitigate the effect of emerging viral variants.
Local Response and Barrier Recovery in Elderly Skin Following the Application of High-Density Microarray Patches
Authors: Iredahl Fredrik , Muller David A. , Togö Totte , Jonasson Hanna , Baker Ben , Anderson Chris D. , Henricson Joakim
Published: April 2022

The high-density microneedle array patch (HD-MAP) is a promising alternative vaccine delivery system device with broad application in disease, including SARS-CoV-2. Skin reactivity to HD-MAP applications has been extensively studied in young individuals, but not in the >65 years population, a risk group often requiring higher dose vaccines to produce protective immune responses. The primary aims of the present study were to characterise local inflammatory responses and barrier recovery to HD-MAPs in elderly skin. In twelve volunteers aged 69–84 years, HD-MAPs were applied to the forearm and deltoid regions. Measurements of transepidermal water loss (TEWL), dielectric permittivity and erythema were performed before and after HD-MAP application at t = 10 min, 30 min, 48 h, and 7 days. At all sites, TEWL (barrier damage), dielectric permittivity (superficial water);, and erythema measurements rapidly increased after HD-MAP application. After 7 days, the mean measures had recovered toward pre-application values. The fact that the degree and chronology of skin reactivity and recovery after HD-MAP was similar in elderly skin to that previously reported in younger adults suggests that the reactivity basis for physical immune enhancement observed in younger adults will also be achievable in the older population.
Transdermal Immunization with Microparticulate RSV-F Virus-like Particles Elicits Robust Immunity
Authors: D’Sa Sucheta , Braz Gomes Kimberly , Allotey-Babington Grace Lovia , Boyoglu Cemil , Kang Sang-Moo , D’Souza Martin J.
Published: April 2022

No approved vaccines against respiratory syncytial virus (RSV) infections exist to date, due to challenges arising during vaccine development. There is an unmet need to explore novel approaches and a universal strategy to prevent RSV infections. Previous studies have proven the immune efficacy of virus-like particles (VLPs) consisting of RSV fusion (F) protein, yielding a highly immunogenic RSV-F VLP subunit vaccine. In this study, RSV-F VLP (with or without MPL®) was added to a polymer mix and spray-dried, forming microparticles. The formulations were transdermally administered in C57BL/6 mice to evaluate vaccine efficacy. The transdermal delivery of RSV-F VLP + MPL® was more effective in clearing lung viral loads and preventing weight loss after RSV challenge. At the cellular level, MPL® augmented the vaccine response in microparticulate form, which was evidenced by higher serum and lung antibody titers, and lower lung viral titers in the vaccinated groups. These preliminary results validate the effectiveness of the RSV-F VLP microparticulate vaccine via the transdermal route due to its potential to trigger robust immune responses.