bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison Epidemiology between Tuberculosis and COVID-19 in East Java Province, Indonesia: An Analysis of Regional Surveillance Data in 2020
Authors: Utomo Budi , Chan Chow Khuen , Mertaniasih Ni Made , Soedarsono Soedarsono , Fauziyah Shifa , Sucipto Teguh Hari , Aquaresta Febriana , Eljatin Dwinka Syafira , Adnyana I Made Dwi Mertha
Published: May 2022

Tuberculosis and COVID-19 are among the infectious diseases that constitute a public health concern. Therefore, this study aims to examine the recent epidemiology of tuberculosis and COVID-19 in East Java Province, Indonesia, in 2020. Case-based surveillance data were acquired with a retrospective design between January and December 2020 by the East Java Health Officer. The data were analyzed using Quantum Geographic Information System (QGIS) for mapping, and Microsoft Excel for recording. Furthermore, the statistical analysis (Spearman correlation test) was carried out via Statistical Package for Social Science (SPSS) applications. A total number of 38,089 confirmed cases of tuberculosis was recorded, with an incidence rate of 95.49/100,000 population, a case fatality rate (CFR) of 3.6%, and an average treatment success rate of 87.78%. COVID-19 is a new viral disease, with a total of 84,133 confirmed COVID-19 cases in East Java, with an incidence rate of 232.9/100,000 population. The highest incidence rate was found in Mojokerto city, while the lowest was found in Sampang. Furthermore, the CFR values of tuberculosis and COVID-19 were 1.4% and 6.8%, respectively. The regional survey in East Java Province showed that the incidence of tuberculosis remains high. This indicated that the search for active cases and preventive promotion was not completed. Therefore, inter-sectoral collaboration can be adapted to provide suitable tuberculosis health care.
Pathogenic Leptospira Species in Bats: Molecular Detection in a Colombian Cave
Authors: Silva-Ramos Carlos , Chala-Quintero Sandra , Faccini-Martínez Álvaro , Hidalgo Marylin , Pulido-Villamarín Adriana , Pérez-Torres Jairo , Cuervo Claudia
Published: May 2022

Leptospirosis is caused by pathogenic Leptospira spp., which can be found in nature among domestic and wild animals. In Colombia, the Macaregua cave is known for its bat richness; thus, because bats are reservoir hosts of human microbiological pathogens, we determined if the Macaregua cave bats harbored Leptospira in the wild. A total of 85 kidney samples were collected from three bat species (Carollia perspicillata, Mormoops megalophylla, and Natalus tumidirostris) to detect Leptospira spp. The 16S rRNA gene was targeted through conventional PCR and qPCR; in addition, the LipL32 gene was detected using conventional PCR. Obtained amplicons were purified and sequenced for phylogenetic analysis. The Leptospira spp. 16S rRNA gene was detected in 51.8% bat kidneys, of which 35 sequences were obtained, all clustering within the pathogenic group. Moreover, 11 sequences presented high-identity-values with Leptospiranoguchii, Leptospiraalexanderi, Leptospiraborgpetersenii, Leptospirakirschneri, and Leptospiramayottensis. From the 16S rRNALeptospira spp.-positive population samples, 28 amplified for the LipL32 gene, and 23 sequences clustered in five different phylogenetic groups. In conclusion, we detected the circulation of different groups of Leptospira spp. sequences among cave bats in the wild; some sequences were detected in more than one bat specimen from the same species, suggesting a conspecific transmission within the cave.
Performance of an Emergency Road Ambulance Service in Bhutan: Response Time, Utilization, and Outcomes
Authors: Tshokey Tshokey , Tshering Ugyen , Lhazeen Karma , Abrahamyan Arpine , Timire Collins , Gurung Bikash , Subedi Devi Charan , Wangdi Kencho , Vilas Victor Del Rio , Zachariah Rony
Published: May 2022

Background: An efficient ambulance service is a vital component of emergency medical services. We determined the emergency ambulance response and transport times and ambulance exit outcomes in Bhutan. Methods: A cross-sectional study involving real-time monitoring of emergency ambulance deployments managed by a central toll-free (112) hotline (20 October 2021 to 20 January 2022) was carried out. Results: Of 5092 ambulance deployments, 4291 (84%) were inter-facility transfers, and 801 (16%) were for emergencies. Of the latter, 703 (88%) were for non-pregnancy-related emergencies (i.e., medical, surgical, and accidents), while 98 (12%) were for pregnancy-related emergencies. The median ambulance response and patient transport times were 42 (IQR 3–271) and 41 (IQR 2–272) minutes, respectively. The median round-trip distance travelled by ambulances was 18 km (range 1–186 km). For ambulance exit outcomes that were pregnancy-related (n = 98), 89 (91%) reached the health facility successfully, 8 delivered prior to ambulance arrival at the scene or in the ambulance during transport, and 1 had no outcome record. For the remaining 703 non-pregnancy deployments, 29 (4.1%) deployments were deemed not required or refusals, and 656 (93.3%) reached the health facility successfully; 16 (2.3%) died before the ambulance’s arrival at the scene, and 2 (0.3%) were not recorded. Conclusions: This first countrywide real-time operational research showed acceptable ambulance exit outcomes. Improving ambulance response and transport times might reduce morbidities and mortalities further.
A Possible Explanation of Dark Matter and Dark Energy Involving a Vector Torsion Field
Authors: Milton Graeme W.
Published: May 2022

A simple gravitational model with torsion is studied, and it is suggested that it could explain the dark matter and dark energy in the universe. It can be reinterpreted as a model using the Einstein gravitational equations where spacetime has regions filled with a perfect fluid with negative energy (pressure) and positive mass density, other regions containing an anisotropic substance that in the rest frame (where the momentum is zero) has negative mass density and a uniaxial stress tensor, and possibly other “luminal” regions where there is no rest frame. The torsion vector field is inhomogeneous throughout spacetime, and possibly turbulent. Numerical simulations should reveal whether or not the equations are consistent with cosmological observations of dark matter and dark energy.
Polymer Dynamics of Isotropic Universe in Ashtekar and in Volume Variables
Authors: Giovannetti Eleonora , Barca Gabriele , Mandini Federico , Montani Giovanni
Published: May 2022

We analyze the semiclassical and quantum polymer dynamics of the isotropic Universe in terms of both the standard Ashtekar-Barbero-Immirzi connection and its conjugate momentum and also of the new generalized coordinate conjugate to the Universe volume. We study the properties of the resulting bouncing cosmology that emerges in both the representations and we show that the Big Bounce is an intrinsic cut-off on the cosmological dynamics only when the volume variable is implemented, while in terms of the standard connection the Universe Bounce energy density is fixed by the initial conditions on the prepared wavepacket. As a phenomenological implication, we introduce particle creation as a dissipative term and study the production of entropy in the two formulations. Then, we compare the obtained dynamics with what emerges in Loop Quantum Cosmology, where the same difference in the nature of the Big Bounce is associated to fixing a minimum area eigenvalue in a comoving or in a physical representation. We conclude that the privileged character of the Ashtekar-Barbero-Immirzi connection suggests that the natural scenario in the polymer framework is a Big Bounce that is not a Universal cut-off. However, by a parallelism between the polymer and Loop Quantum Cosmology properties of the basic operators, we also develop some considerations in favour of the viability of the μ¯ scheme of Loop Quantum Cosmology on a semiclassical level.
Antarctic Survey Telescope 3-3: Overview, System Performance and Preliminary Observations at Yaoan, Yunnan
Authors: Sun Tianrui , Li Xiaoyan , Hu Lei , Meng Kelai , Han Zijian , Hu Maokai , Li Zhengyang , Wen Haikun , Du Fujia , Yang Shihai , Gu Bozhong , Yuan Xiangyan , Li Yun , Wang Huihui , Liu Lei , Zhu Zhenxi , Huang Xuehai , Lei Chengming , Wang Lifan , Wu Xuefeng
Published: May 2022

The third Antarctic Survey Telescope array instrument at Dome A in Antarctica, the AST3-3 telescope, has been in commissioning from March 2021. We deployed AST3-3 at the Yaoan astronomical station in Yunnan Province for an automatic time-domain survey and follow-up observations with an optimised observation and protection system. The telescope system of AST3-3 is similar to that of AST3-1 and AST3-2, except that it is equipped with a 14 K × 10 K QHY411 CMOS camera. AST3-3 has a field of view of 1.65∘×1.23∘ and is currently using the g band filter. During commissioning at Yaoan, AST3-3 aims to conduct an extragalactic transient survey, coupled with prompt follow-ups of opportunity targets. In this paper, we present the architecture of the AST3-3 automatic observation system. We demonstrate the data processing of observations by representatives SN 2022eyw and GRB 210420B.
A Note on Proton Stability in the Standard Model
Authors: Koren Seth
Published: May 2022

In this short note, we describe the symmetry responsible for absolute, nonperturbative proton stability in the Standard Model. The SM with Nc colors and Ng generations has an exact, anomaly-free, generation-independent, global symmetry group U(1)B−NcL×ZNgL, which contains a subgroup of baryon plus lepton number of order 2NcNg. This disallows proton decay for Ng>1. Many well-studied models beyond the SM explicitly break this global symmetry, and the alternative deserves further attention.
Differential Pathogenesis of SARS-CoV-2 Variants of Concern in Human ACE2-Expressing Mice
Authors: Natekar Janhavi Prasad , Pathak Heather , Stone Shannon , Kumari Pratima , Sharma Shaligram , Auroni Tabassum Tasnim , Arora Komal , Rothan Hussin Alwan , Kumar Mukesh
Published: May 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current pandemic, resulting in millions of deaths worldwide. Increasingly contagious variants of concern (VoC) have fueled recurring global infection waves. A major question is the relative severity of the disease caused by previous and currently circulating variants of SARS-CoV-2. In this study, we evaluated the pathogenesis of SARS-CoV-2 variants in human ACE-2-expressing (K18-hACE2) mice. Eight-week-old K18-hACE2 mice were inoculated intranasally with a representative virus from the original B.1 lineage or from the emerging B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), or B.1.1.529 (omicron) lineages. We also infected a group of mice with the mouse-adapted SARS-CoV-2 (MA10). Our results demonstrate that B.1.1.7, B.1.351 and B.1.617.2 viruses are significantly more lethal than the B.1 strain in K18-hACE2 mice. Infection with the B.1.1.7, B.1.351, and B.1.617.2 variants resulted in significantly higher virus titers in the lungs and brain of mice compared with the B.1 virus. Interestingly, mice infected with the B.1.1.529 variant exhibited less severe clinical signs and a high survival rate. We found that B.1.1.529 replication was significantly lower in the lungs and brain of infected mice in comparison with other VoC. The transcription levels of cytokines and chemokines in the lungs of B.1- and B.1.1.529-infected mice were significantly less when compared with those challenged with other VoC. Together, our data provide insights into the pathogenesis of previous and circulating SARS-CoV-2 VoC in mice.
Discovery of a Novel Jingmenvirus in Australian Sugarcane Soldier Fly (Inopus flavus) Larvae
Authors: Colmant Agathe M. G. , Furlong Michael J. , Etebari Kayvan
Published: May 2022

In Australia, soldier flies are major pests of sugarcane, and they can cause significant yield losses in some areas, possibly due to the virus’ transmission to the plants. We sequenced fly larvae salivary glands and identified a novel jingmenvirus, putatively named Inopus flavus jingmenvirus 1 (IFJV1). Phylogenetic trees confirmed that IFJV1 groups with insect-associated jingmenviruses, newly identified flavivirus-like viruses with a segmented genome. After the design and the validation of molecular detection systems for IFJV1, larval homogenates were passaged on insect and vertebrate cells, but IFJV1 could only be detected in the first two passages in insect cells and not at all in vertebrate cells. Despite this lack of consistent replication in laboratory models, this virus does replicate in its host Inopus flavus, as sequenced, small RNA from the larvae matched the IFJV1 sequences. Moreover, they were found to be predominantly 21 nucleotides long and map to the whole sequences on both strands, which is typical of an actively replicating virus. This discovery confirms the worldwide presence of jingmenviruses which, until now, had only been detected on four continents. However, the study of IFJV1 tropism and the possible pathogenicity to its host or the sugarcane it parasitizes requires the development of a stable replication model.
Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo
Authors: Li Yuexiang , Liu Miaomiao , Yan Yunzheng , Wang Zhuang , Dai Qingsong , Yang Xiaotong , Guo Xiaojia , Li Wei , Chen Xingjuan , Cao Ruiyuan , Zhong Wu
Published: May 2022

Enterovirus infections can cause hand, foot, and mouth disease (HFDM), aseptic meningitis, encephalitis, myocarditis, and acute flaccid myelitis, leading to death of infants and young children. However, no specific antiviral drug is currently available for the treatment of this type of infection. The Unites States and United Kingdom health authorities recently approved a new antiviral drug, molnupiravir, for the treatment of COVID-19. In this study, we reported that molnupiravir (EIDD-2801) and its active form, EIDD-1931, have broad-spectrum anti-enterovirus potential. Our data showed that EIDD-1931 could significantly reduce the production of EV-A71 progeny virus and the expression of EV-A71 viral protein at non-cytotoxic concentrations. The results of the time-of-addition assay suggest that EIDD-1931 acts at the post-entry step, which is in accordance with its antiviral mechanism. The intraperitoneal administration of EIDD-1931 and EIDD-2801 protected 1-day-old ICR suckling mice from lethal EV-A71 challenge by reducing the viral load in various tissues of the infected mice. The pharmacokinetics analysis indicated that the plasma drug concentration overwhelmed the EC50 for enteroviruses, suggesting the clinical potential of molnupiravir against enteroviruses. Thus, molnupiravir along with its active form, EIDD-1931, may be a promising drug candidate against enterovirus infections.
New Targets for Antiviral Therapy: Inhibitory Receptors and Immune Checkpoints on Myeloid Cells
Authors: Liu Yanni , Nicklin Paul , He Yuan
Published: May 2022

Immune homeostasis is achieved by balancing the activating and inhibitory signal transduction pathways mediated via cell surface receptors. Activation allows the host to mount an immune response to endogenous and exogenous antigens; suppressive modulation via inhibitory signaling protects the host from excessive inflammatory damage. The checkpoint regulation of myeloid cells during immune homeostasis raised their profile as important cellular targets for treating allergy, cancer and infectious disease. This review focuses on the structure and signaling of inhibitory receptors on myeloid cells, with particular attention placed on how the interplay between viruses and these receptors regulates antiviral immunity. The status of targeting inhibitory receptors on myeloid cells as a new therapeutic approach for antiviral treatment will be analyzed.
Secretory Profile of Adipose-Tissue-Derived Mesenchymal Stem Cells from Cats with Calicivirus-Positive Severe Chronic Gingivostomatitis
Authors: Villatoro Antonio J. , Martín-Astorga María del Carmen , Alcoholado Cristina , Kazantseva Liliya , Cárdenas Casimiro , Fariñas Fernando , Becerra José , Visser Rick
Published: May 2022

The feline calicivirus (FCV) causes infections in cats all over the world and seems to be related to a broad variety of clinical presentations, such as feline chronic gingivostomatitis (FCGS), a severe oral pathology in cats. Although its etiopathogeny is largely unknown, FCV infection is likely to be a main predisposing factor for developing this pathology. During recent years, new strategies for treating FCGS have been proposed, based on the use of mesenchymal stem cells (MSC) and their regenerative and immunomodulatory properties. The main mechanism of action of MSC seems to be paracrine, due to the secretion of many biomolecules with different biological functions (secretome). Currently, several pathologies in humans have been shown to be related to functional alterations of the patient’s MSCs. However, the possible roles that altered MSCs might have in different diseases, including virus-mediated diseases, remain unknown. We have recently demonstrated that the exosomes produced by the adipose-tissue-derived MSCs (fAd-MSCs) from cats suffering from FCV-positive severe and refractory FCGS showed altered protein contents. Based on these findings, the goal of this work was to analyze the proteomic profile of the secretome produced by feline adipose-tissue-derived MSCs (fAd-MSCs) from FCV-positive patients with FCGS, in order to identify differences between them and to increase our knowledge of the etiopathogenesis of this disease. We used high-resolution mass spectrometry and functional enrichment analysis with Gene Ontology to compare the secretomes produced by the fAd-MSCs of healthy and calicivirus-positive FCGS cats. We found that the fAd-MSCs from cats with FCGS had an increased expression of pro-inflammatory cytokines and an altered proteomic profile compared to the secretome produced by cells from healthy cats. These findings help us gain insight on the roles of MSCs and their possible relation to FCGS, and may be useful for selecting specific biomarkers and for identifying new therapeutic targets.
Evolution of Phage Tail Sheath Protein
Authors: Evseev Peter , Shneider Mikhail , Miroshnikov Konstantin
Published: May 2022

Sheath proteins comprise a part of the contractile molecular machinery present in bacteriophages with myoviral morphology, contractile injection systems, and the type VI secretion system (T6SS) found in many Gram-negative bacteria. Previous research on sheath proteins has demonstrated that they share common structural features, even though they vary in their size and primary sequence. In this study, 112 contractile phage tail sheath proteins (TShP) representing different groups of bacteriophages and archaeal viruses with myoviral morphology have been modelled with the novel machine learning software, AlphaFold 2. The obtained structures have been analysed and conserved and variable protein parts and domains have been identified. The common core domain of all studied sheath proteins, including viral and T6SS proteins, comprised both N-terminal and C-terminal parts, whereas the other parts consisted of one or several moderately conserved domains, presumably added during phage evolution. The conserved core appears to be responsible for interaction with the tail tube protein and assembly of the phage tail. Additional domains may have evolved to maintain the stability of the virion or for adsorption to the host cell. Evolutionary relations between TShPs representing distinct viral groups have been proposed using a phylogenetic analysis based on overall structural similarity and other analyses.
Adequacy of Hemodialysis Serves as an Independent Predictor of Humoral Response to ChAdOx1 Prime-Boost Vaccination in Hemodialysis Patients
Authors: Chen Chun-Yu , Liu Kuan-Ting , Shih Shin-Ru , Ye Jung-Jr , Chen Yih-Ting , Hsu Cheng-Kai , Pan Heng-Chih , Hsu Heng-Jung , Sun Chiao-Yin , Lee Chin-Chan , Wu Chun-Ying , Lai Chi-Chun , Wu I-Wen
Published: May 2022

Background: Immune response assessed by the quantification of neutralizing antibodies (nAbs) and predictors associated with immunogenicity after the prime-boost ChAdOx1 (Oxford–AstraZeneca) COVID-19 vaccine in hemodialysis (HD) patients remains unclear. Methods: This prospective study enrolled 174 HD patients and 67 healthy subjects to evaluate antibodies against the spike protein 1 and receptor-binding domain of severe acute respiratory syndrome coronavirus type 2 after prime-booster vaccination, by using enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict 50% neutralization titer (NT50). The correlation between HD parameters and NT50 was analyzed. Results: NT50 was lower in HD patients compared with healthy controls after the prime-boost dose (p < 0.001). The geometric mean titer ratios were higher in first-dose seronegative than in the seropositive subgroup in HD patients and healthy controls (6.96 vs. 2.36, p = 0.002, and 9.28 vs. 1.26, p = 0.011, respectively). After two doses of ChAdOx1, one-way ANOVA showed that Ca × P was positively associated with NT50 (p trend = 0.043) and multiple linear regression showed the similar results (p = 0.021). Kt/V (a quantification of dialysis adequacy) (OR = 20.295, p = 0.005) could independently predict seroconversion (NT50 ≥ 35.13 IU/mL). Conclusion: Adequacy of hemodialysis could independently predict seroconversion in HD subjects vaccinated with prime-boost doses of ChAdOx1.
Recombination between the Fostera MLV-like Strain and the Strain Belonging to Lineage 1 of Porcine Reproductive and Respiratory Syndrome Virus in Korea
Authors: Shin Go-Eun , Park Ji-Young , Lee Kyoung-Ki , Ku Bok-Kyung , Park Choi-Kyu , Jeoung Hye-Young
Published: May 2022

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry worldwide. In Korea, Fostera PRRS commercial modified live virus (MLV) vaccines have been used since 2014 to control the PRRSV infection. In this study, two PRRSV-2 strains (20D160-1 and 21R2-63-1) were successfully isolated, and their complete genomic sequences were determined. Genetic analysis showed that the two isolates have recombination events between the P129-like strain derived from the Fostera PRRS MLV vaccine and the strain of lineage 1. The 20D160-1 indicated that partial ORF2 to partial ORF4 of the minor parental KNU-1902-like strain, which belongs to Korean lineage C (Kor C) of lineage 1, was inserted into the major parental P129-like strain. The 21R2-63-1 revealed that partial ORF1b of the P129-like strain was inserted into the backbone of the NADC30-like strain. This study is the first to report natural recombinant strains between Fostera PRRS MLV-like strain and the field strain in Korea. These results may have significant implications for MLV evolution and the understanding of PRRSV genetic diversity, while highlighting the need for continuous surveillance of PRRSV.
Trans-Encapsidation of Foot-and-Mouth Disease Virus Genomes Facilitates Escape from Neutralizing Antibodies
Authors: Childs Kay , Jackson Ben , Harvey Yongjie , Seago Julian
Published: May 2022

Foot-and-mouth disease is an economically devastating disease of livestock caused by foot-and-mouth disease virus (FMDV). Vaccination is the most effective control measure in place to limit the spread of the disease; however, the success of vaccination campaigns is hampered by the antigenic diversity of FMDV and the rapid rate at which new strains emerge that escape pre-existing immunity. FMDV has seven distinct serotypes, and within each serotype are multiple strains that often induce little cross-protective immunity. The diversity of FMDV is a consequence of the high error rate of the RNA-dependent RNA polymerase, accompanied by extensive recombination between genomes during co-infection. Since multiple serotypes and strains co-circulate in regions where FMDV is endemic, co-infection is common, providing the conditions for recombination, and also for other events such as trans-encapsidation in which the genome of one virus is packaged into the capsid of the co-infecting virus. Here, we demonstrate that the co-infection of cells with two FMDVs of different serotypes results in trans-encapsidation of both viral genomes. Crucially, this facilitates the infection of new cells in the presence of neutralizing antibodies that recognize the capsid that is encoded by the packaged genome.
Single-Domain Antibodies as Therapeutics for Respiratory RNA Virus Infections
Authors: Huang Keke , Ying Tianlei , Wu Yanling
Published: May 2022

Over the years, infectious diseases with high morbidity and mortality disrupted human healthcare systems and devastated economies globally. Respiratory viruses, especially emerging or re-emerging RNA viruses, including influenza and human coronavirus, are the main pathogens of acute respiratory diseases that cause epidemics or even global pandemics. Importantly, due to the rapid mutation of viruses, there are few effective drugs and vaccines for the treatment and prevention of these RNA virus infections. Of note, a class of antibodies derived from camelid and shark, named nanobody or single-domain antibody (sdAb), was characterized by smaller size, lower production costs, more accessible binding epitopes, and inhalable properties, which have advantages in the treatment of respiratory diseases compared to conventional antibodies. Currently, a number of sdAbs have been developed against various respiratory RNA viruses and demonstrated potent therapeutic efficacy in mouse models. Here, we review the current status of the development of antiviral sdAb and discuss their potential as therapeutics for respiratory RNA viral diseases.
Simian Varicella Virus Pathogenesis in Skin during Varicella and Zoster
Authors: Mahalingam Ravi , Feia Brittany , Coleman Colin , Anupindi Kusala , Saravanan Pratush , Luthens Amalia , Bustillos Amalia , Das Arpita , de Haro Eileen , Doyle-Meyers Lara , Looper Jayme , Bubak Andrew N. , Niemeyer Christy S. , Palmer Brent , Nagel Maria A. , Traina-Dorge Vicki
Published: May 2022

Primary simian varicella virus (SVV) infection and reactivation in nonhuman primates is a valuable animal model in the study of varicella zoster virus disease [varicella (chickenpox) and herpes zoster (shingles)]. To understand SVV pathogenesis in skin, we inoculated 10 rhesus macaques with SVV, resulting in varicella rash. After the establishment of latency, eight of the monkeys were immunosuppressed using tacrolimus with or without irradiation and prednisone and two monkeys were not immunosuppressed. Zoster rash developed in all immunosuppressed monkeys and in one non-immunosuppressed monkey. Five monkeys had recurrent zoster. During varicella and zoster, SVV DNA in skin scrapings ranged from 50 to 107 copies/100 ng of total DNA and 2–127 copies/100 ng of total DNA, respectively. Detection of SVV DNA in blood during varicella was more frequent and abundant compared to that of zoster. During varicella and zoster, SVV antigens colocalized with neurons expressing β-III tubulin in epidermis, hair follicles, and sweat glands, suggesting axonal transport of the virus. Together, we have demonstrated that both SVV DNA and antigens can be detected in skin lesions during varicella and zoster, providing the basis for further studies on SVV skin pathogenesis, including immune responses and mechanisms of peripheral spread.
Time Trend in SARS-CoV-2 Seropositivity, Surveillance Detection- and Infection Fatality Ratio until Spring 2021 in the Tirschenreuth County—Results from a Population-Based Longitudinal Study in Germany
Authors: Einhauser Sebastian , Peterhoff David , Beileke Stephanie , Günther Felix , Niller Hans-Helmut , Steininger Philipp , Knöll Antje , Korn Klaus , Berr Melanie , Schütz Anja , Wiegrebe Simon , Stark Klaus J. , Gessner André , Burkhardt Ralph , Kabesch Michael , Schedl Holger , Küchenhoff Helmut , Pfahlberg Annette B. , Heid Iris M. , Gefeller Olaf , Überla Klaus , Wagner Ralf
Published: May 2022

Herein, we provide results from a prospective population-based longitudinal follow-up (FU) SARS-CoV-2 serosurveillance study in Tirschenreuth, the county which was hit hardest in Germany in spring 2020 and early 2021. Of 4203 individuals aged 14 years or older enrolled at baseline (BL, June 2020), 3546 participated at FU1 (November 2020) and 3391 at FU2 (April 2021). Key metrics comprising standardized seroprevalence, surveillance detection ratio (SDR), infection fatality ratio (IFR) and success of the vaccination campaign were derived using the Roche N- and S-Elecsys anti-SARS-CoV-2 test together with a self-administered questionnaire. N-seropositivity at BL was 9.2% (1st wave). While we observed a low new seropositivity between BL and FU1 (0.9%), the combined 2nd and 3rd wave accounted for 6.1% new N-seropositives between FU1 and FU2 (ever seropositives at FU2: 15.4%). The SDR decreased from 5.4 (BL) to 1.1 (FU2) highlighting the success of massively increased testing in the population. The IFR based on a combination of serology and registration data resulted in 3.3% between November 2020 and April 2021 compared to 2.3% until June 2020. Although IFRs were consistently higher at FU2 compared to BL across age-groups, highest among individuals aged 70+ (18.3% versus 10.7%, respectively), observed differences were within statistical uncertainty bounds. While municipalities with senior care homes showed a higher IFR at BL (3.0% with senior care home vs. 0.7% w/o), this effect diminished at FU2 (3.4% vs. 2.9%). In April 2021 (FU2), vaccination rate in the elderly was high (>77.4%, age-group 80+).
A Thorough Synthesis of Phage Therapy Unit Activity in Poland—Its History, Milestones and International Recognition
Authors: Żaczek Maciej , Górski Andrzej , Weber-Dąbrowska Beata , Letkiewicz Sławomir , Fortuna Wojciech , Rogóż Paweł , Pasternak Edyta , Międzybrodzki Ryszard
Published: May 2022

The year 2020 marked 15 years of the Phage Therapy Unit in Poland, the inception of which took place just one year after Poland’s accession to the European Union (2004). At first sight, it is hard to find any connection between these two events, but in fact joining the European Union entailed the need to adapt the regulatory provisions concerning experimental treatment in humans to those that were in force in the European Union. These changes were a solid foundation for the first phage therapy center in the European Union to start its activity. As the number of centers conducting phage therapy in Europe and in the world constantly and rapidly grows, we want to grasp the opportunity to take a closer look at the over 15-year operation of our site by analyzing its origins, legal aspects at the local and international levels and the impressive number and diversity of cases that have been investigated and treated during this time. This article is a continuation of our work published in 2020 summarizing a 100-year history of the development of phage research in Poland.
Association of the p75NTR Ser205Leu Polymorphism with Asymptomatic HTLV-1 Infection
Authors: Queiroz Maria Alice Freitas , Lopes Felipe Teixeira , Botelho Bruno José Sarmento , Torres Maria Karoliny da Silva , Amoras Ednelza da Graça Silva , Costa Carlos A. da , Sousa Maísa Silva , Ishak Ricardo , Vallinoto Antonio Carlos Rosário
Published: May 2022

Genetic variations in components of the immune response seem to be an important factor that contributes to the manifestation of symptoms of some diseases related to HTLV-1 infection. Nerve growth factor (NGF) and the p75 neurotrophin receptor (p75NTR) are related to the maintenance of neurons and the activation of the immune response. In this study, we evaluated the association of the NGF -198C/T, NGF Ala35Val, and p75NTR Ser205Leu polymorphisms with HTLV-1 infection and plasma cytokine levels in 166 samples from individuals infected with HTLV-1 (59 symptomatic and 107 asymptomatic). The genotyping and quantification of the proviral load were performed by real-time PCR, and cytokine levels were measured by ELISA. The NGF -198C/T and NGF Ala35Val polymorphisms were not associated with HTLV-1 infection. The frequency of the Ser/Leu genotype of p75NTR Ser205Leu was more frequent in the control group (p = 0.0385), and the Ser/Leu genotype and allele Leu were more frequent among the asymptomatic (p < 0.05), especially with respect to the HTLV-1-associated myelopathy (HAM) group (p < 0.05). The symptomatic showed a higher proviral load and higher TNF-α and IL-10 levels (p < 0.05). Asymptomatic carriers of the Ser/Leu genotype (p = 0.0797) had lower levels of proviral load and higher levels of TNF-α (p = 0.0507). Based on the results obtained, we conclude that the p75NTR Ser205Leu polymorphism may be associated with reduced susceptibility to HTLV-1 infection, a lower risk of developing symptoms, including HAM, and better infection control.
Comparative Evaluation of Three Commercial Quantitative Real-Time PCRs Used in Japan for Bovine Leukemia Virus
Authors: Yoneyama Syuji , Kobayashi Sota , Matsunaga Towa , Tonosaki Kaoru , Leng Dongze , Sakai Yusuke , Yamada Shinji , Kimura Atsushi , Ichijo Toshihiro , Hikono Hirokazu , Murakami Kenji
Published: May 2022

Bovine leukemia virus (BLV) is an oncogenic virus belonging to the genus Deltaretrovirus and is the causative agent of enzootic bovine leukosis. Proviral load (PVL) determined by real-time quantitative PCR (qPCR) is now widely used as an indicator of not only BLV infection, but also BLV disease progression. To interpret PVLs determined by different qPCRs used in Japan, we compared a chimeric cycling probe-based qPCR, CY415, targeting the BLV tax region; a TaqMan probe-based qPCR, RC202, targeting the BLV pol region; and a TaqMan probe-based qPCR, CoCoMo, targeting the BLV long terminal repeat (LTR) region. Whole-blood samples collected from 317 naturally BLV-infected cattle (165 Holstein–Friesian and 152 Japanese Black) and tumor tissue samples collected from 32 cattle at a meat inspection center were used. The PVLs determined by each qPCR were strongly correlated. However, the PVL and the proportion of BLV-infected cells determined by RC202 or CoCoMo were significantly higher than those determined by CY415. Genetic analysis of three tumor tissue samples revealed that LTR region mutations or a deletion affected the PVL determined by CoCoMo. These results suggest that the TaqMan-based RC202 or CoCoMo qPCR is better than CY415 for BLV PVL analysis. However, qPCR target region mutations were not rare in tumors and could hamper PVL analysis by using qPCR.
Discovery and Genomic Function of a Novel Rice Dwarf-Associated Bunya-like Virus
Authors: Wang Dan , Fu Shuai , Wu Hongyue , Cao Mengji , Liu Li , Zhou Xueping , Wu Jianxiang
Published: May 2022

Bunyaviruses cause diseases in vertebrates, arthropods, and plants. Here, we used high-throughput RNA-seq to identify a bunya-like virus in rice plants showing the dwarfing symptom, which was tentatively named rice dwarf-associated bunya-like virus (RDaBV). The RDaBV genome consists of L, M, and S segments. The L segment has 6562 nt, and encodes an RdRp with a conserved Bunya_RdRp super family domain. The M segment has 1667 nt and encodes a nonstructural protein (NS). The complementary strand of the 1120 nt S segment encodes a nucleocapsid protein (N), while its viral strand encodes a small nonstructural protein (NSs). The amino acid (aa) sequence identities of RdRp, NS, and N between RDaBV and viruses from the family Discoviridae were the highest. Surprisingly, the RDaBV NSs protein did not match any viral proteins. Phylogenetic analysis based on RdRp indicated that RDaBV is evolutionarily close to viruses in the family Discoviridae. The PVX-expressed system indicated that RDaBV N and NS may be symptom determinants of RDaBV. Our movement complementation and callose staining experiment results confirmed that RDaBV NSs is a viral movement protein in plants, while an agro-infiltration experiment found that RDaBV NS is an RNA silencing suppressor. Thus, we determined that RDaBV is a novel rice-infecting bunya-like virus.
Heterologous Prime-Boost Immunization with DNA Vaccine and Modified Recombinant Proteins Enhances Immune Response against Trueperella pyogenes in Mice
Authors: Huang Ting , Zhao Kelei , Song Xuhao , Song Tao , Wang Xinrong , Zhang Xiuyue , Yue Bisong , Chu Yiwen
Published: May 2022

Trueperella pyogenes (T. pyogenes) is a crucial opportunistic pathogen normally causing mastitis, abscesses and pneumonia in economically important ruminants. Although only one commercial vaccine of T. pyogenes is currently obtainable, its immunoprotective effect is limited. Pyolysin (PLO) is the most predominant virulence factor highly expressed in T. pyogenes and is an excellent target for the development of novel vaccines against T. pyogenes. In this study, we designed a heterologous prime-boost vaccination scheme combining a DNA vaccine pVAX1-PLO and a subunit vaccine His-PLO to maximize host responses in mice. Humoral and cellular immune responses and protective effects were evaluated in mice to compare the immunogenicity induced by different immunization schemes. Compared to the PBS-control group, in vivo immunization results showed that better immune responses of mice immunized with the pVAX1-PLO plasmids and His-PLO proteins were induced. The residual bacterial burdens from the liver and peritoneal fluid were remarkably decreased in the immunized mice compared with the PBS group. Notably, the heterologous prime-boost vaccination groups significantly enhanced host humoral and cellular immune responses and protected mice from different virulent T. pyogenes strains infection. Conclusively, this study provides a favorable strategy for the further development of next-generation vaccines against T. pyogenes infections.
Success of Current COVID-19 Vaccine Strategies vs. the Epitope Topology of SARS-CoV-2 Spike Protein-Receptor Binding Domain (RBD): A Computational Study of RBD Topology to Guide Future Vaccine Design
Authors: Addala Santhinissi , Vissapragada Madhuri , Aggunna Madhumita , Mukala Niharikha , Lanka Manisha , Gampa Shyamkumar , Sodasani Manikanta , Chintalapati Jahnavi , Kamidi Akhila , Veeranna Ravindra P. , Yedidi Ravikiran S.
Published: May 2022

Coronavirus disease-2019 (COVID-19) is a pandemic with a high morbidity rate occurring over recent years. COVID-19 is caused by the severe acute respiratory syndrome causing coronavirus type-2 (SARS-CoV-2). COVID-19 not only challenged mankind but also gave scope to the evolution of various vaccine design technologies. Although these vaccines protected and saved many lives, with the emerging viral strains, some of the strains may pose a threat to the currently existing vaccine design that is primarily based on the wild type spike protein of SARS-CoV-2. To evaluate the risk involved from such mutant viral strains, we performed a systematic in silico amino acid substitution of critical residues in the receptor binding domain (RBD) of the spike protein. Our molecular modeling analysis revealed significant topological changes in the RBD of spike protein suggesting that they could potentially contribute to the loss of antigen specificity for the currently existing therapeutic antibodies/vaccines, thus posing a challenge to the current vaccine strategies that are based on wild type viral spike protein epitopes. The structural deviations discussed in this article should be considered carefully in the future vaccine design.
The Benefits of Vaccination against SARS-CoV-2 during Pregnancy in Favor of the Mother/Newborn Dyad
Authors: Popescu Daniela-Eugenia , Cîtu Cosmin , Jura Ana Maria Cristina , Lungu Nicoleta , Navolan Dan , Craina Marius , Semenescu Alin , Gorun Florin , Jura Mihai-Andrei , Belengeanu Valerica , Boia Marioara
Published: May 2022

When the first vaccines against SARS-CoV-2 emerged, pregnant women were excluded from clinical trials, so vaccine recommendations were initially adjourned, with late initiation for this populational category. The present study aims to quantify the serum and breastmilk values of SARS-CoV-2 spike protein antibodies in both the mother and her newborn after complete vaccination during pregnancy. Ninety-one vaccinated patients were included, some of whom presented COVID-19 infection during pregnancy. In the delivery room, venous blood was collected from the mother and umbilical cord blood from her offspring. All samples were processed using the ECLIA (electrochemiluminescence) method. Breastmilk was collected and tested during the third postnatal day. The highest maternal serum values were 19,523 U/mL (detection limit > 0.8 U/mL) and in breastmilk, 206.7 U/mL. Every single newborn had antibody values higher than 0, with a mean serum value (M = 5288.37, SD = 5661.49) significantly higher than 0, t(90) = 8.91, p < 0.001. Consequently, this study intents to emphasize the importance of vaccination against SARS-CoV-2 during pregnancy. This double kind of neonatal protection, attained by placental and breastmilk transfer, can be accomplished by encouraging vaccination, breastfeeding, bonding, and providing maternal empowerment to participate in her infant’s care.
Neurocognitive Profile of the Post-COVID Condition in Adults in Catalonia—A Mixed Method Prospective Cohort and Nested Case–Control Study: Study Protocol
Authors: Dacosta-Aguayo Rosalia , Lamonja-Vicente Noemí , Chacón Carla , Carrasco-Ribelles Lucia Amalía , Montero-Alia Pilar , Costa-Garrido Anna , García-Sierra Rosa , López-Lifante Victor M. , Moreno-Gabriel Eduard , Massanella Marta , Puig Josep , Muñoz-Moreno Jose A. , Mateu Lourdes , Prats Anna , Rodríguez Carmina , Mataró Maria , Prado Julia G. , Martínez-Cáceres Eva , Violán Concepción , Torán-Monserrat Pere
Published: May 2022

The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our study employs a prospected cohort and nested case–control design with mixed methods, including statistical analyses, interviews, and focus groups. Our main aim is to identify biomarkers (functional and structural neural changes, inflammatory and immune status, vascular and vestibular signs and symptoms) easily applied in primary care to detect cognitive changes in post-COVID cases. The results will open up a new line of research to inform diagnostic and therapeutic decisions with special considerations for cognitive impairment in the post-COVID condition.
Pre-Impressions of the Third COVID-19 Vaccination among Medical Staff: A Text Mining-Based Survey
Authors: Mori Yoshiro , Miyatake Nobuyuki , Suzuki Hiromi , Mori Yuka , Okada Setsuo , Tanimoto Kiyotaka
Published: May 2022

The aim of this study was to investigate the pre-impressions of the third Coronavirus disease 2019 (COVID-19) vaccination among Japanese medical staff using quantitative analysis. Among 413 medical staff, 260 (60 men and 200 women) aged 40.4 ± 12.3 years were enrolled in this cross-sectional study. Pre-impressions of the third COVID-19 vaccination were analyzed using the text-mining analysis software, KH coder. Among 260 subjects, 242 (93.1%) agreed to the third vaccination, with the rate being lower among subjects in their 30s (87.3%) than those in the other age groups. The word “side effects” was characteristic of subjects in their 20s and nurses, and “pregnancy” of those in their 30s and administrative staff. Pre-impressions of the third COVID-19 vaccination varied among age groups and different professions. The results obtained provide useful information for promoting the third COVID-19 vaccination to Japanese adults.
Comparison of BNT162b2-, mRNA-1273- and Ad26.COV2.S-Elicited IgG and Neutralizing Titers against SARS-CoV-2 and Its Variants
Authors: Padhiar Nigam H. , Liu Jin-Biao , Wang Xu , Wang Xiao-Long , Bodnar Brittany H. , Khan Shazheb , Wang Peng , Khan Adil I. , Luo Jin-Jun , Hu Wen-Hui , Ho Wen-Zhe
Published: May 2022

Because the vaccine-elicited antibody and neutralizing activity against spike protein of SARS-CoV-2 are associated with protection from COVID-19, it is important to determine the levels of specific IgG and neutralization titers against SARS-CoV-2 elicited by the vaccines. While three widely used vaccine brands (Pfizer-BNT162b2, Moderna-mRNA-1273 and Johnson-Ad26.COV2.S) are effective in preventing SARS-CoV-2 infection and alleviating COVID-19 illness, they have different efficacy against COVID-19. It is unclear whether the differences are due to varying ability of the vaccines to elicit a specific IgG antibody response and neutralization activity against spike protein of the virus. In this study, we compared the plasma IgG and neutralization titers against spike proteins of wild-type SARS-CoV-2 and eight variants in healthy subjects who received the mRNA-1273, BNT162b2 or Ad26.COV2.S vaccine. We demonstrated that subjects vaccinated with Ad26.COV2.S vaccine had significantly lower levels of IgG and neutralizing titers as compared to those who received the mRNA vaccines. While the linear regression analysis showed a positive correlation between IgG levels and neutralizing activities against SARS-CoV-2 WT and the variants, there was an overall reduction in neutralizing titers against the variants in subjects across the three groups. These findings suggest that people who received one dose of Ad26.COV2.S vaccine have a more limited IgG response and lower neutralization activity against SARS-CoV-2 WT and its variants than recipients of the mRNA vaccines. Thus, monitoring the plasma or serum levels of anti-SARS-CoV-2 spike IgG titer and neutralization activity is necessary for the selection of suitable vaccines, vaccine dosage and regimens.
Factors Associated with Limited Vaccine Literacy: Lessons Learnt from COVID-19
Authors: Engelbrecht Michelle C. , Kigozi N. Gladys , Heunis J. Christo
Published: May 2022

Compared to many other developed countries, South Africa has a lower uptake of COVID-19 vaccinations. Although not widely researched, there is evidence that vaccine literacy (VL) is positively associated with vaccination uptake. Therefore, this study aimed to assess levels of VL among the adult population in South Africa, as well as to identify factors associated with limited VL. A cross-sectional, anonymous online survey was conducted during September 2021. The survey, which included the standardized Health Literacy about Vaccination in adulthood (HLVa) Scale, was widely advertised, yielding a total of 10,466 respondents. The average scores for the two HLVa sub-scales were relatively high: functional (M = 2.841, SD 0.799) and interactive-critical (M = 3.331, SD 0.559) VL. A proposed ‘limited’ VL score (score value ≤ 2.50) was observed in 40% of respondents for functional literacy and 8.2% of respondents for interactive-critical literacy. The main factors associated with limited VL included lower levels of education, lower socio-economic status, not being vaccinated against COVID-19, self-identifying as Black/African or Colored (i.e., people of mixed ethnic descent), having poorer health, and being a woman. The significant association between VL and vaccination uptake provides an impetus for policy makers such as the South African Department of Health to promote VL in the attempt to increase COVID-19 vaccination uptake.