bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of Multiple GWAS Results Identifies Metabolic Pathways Associated with Resistance to A. flavus Infection and Aflatoxin Accumulation in Maize
Authors: Warburton Marilyn L. , Jeffers Dan , Smith Jessie Spencer , Scapim Carlos , Uhdre Renan , Thrash Adam , Williams William Paul
Published: October 2022

Aflatoxins are carcinogenic secondary metabolites produced by several species of Aspergillus, including Aspergillus flavus, an important ear rot pathogen in maize. Most commercial corn hybrids are susceptible to infection by A. flavus, and aflatoxin contaminated grain causes economic damage to farmers. The creation of inbred lines resistant to Aspergillus fungal infection or the accumulation of aflatoxins would be aided by knowing the pertinent alleles and metabolites associated with resistance in corn lines. Multiple Quantitative Trait Loci (QTL) and association mapping studies have uncovered several dozen potential genes, but each with a small effect on resistance. Metabolic pathway analysis, using the Pathway Association Study Tool (PAST), was performed on aflatoxin accumulation resistance using data from four Genome-wide Association Studies (GWAS). The present research compares the outputs of these pathway analyses and seeks common metabolic mechanisms underlying each. Genes, pathways, metabolites, and mechanisms highlighted here can contribute to improving phenotypic selection of resistant lines via measurement of more specific and highly heritable resistance-related traits and genetic gain via marker assisted or genomic selection with multiple SNPs linked to resistance-related pathways.
A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA
Authors: Kaji Ryuji , Miyashiro Ai , Sato Nori , Furumoto Taiki , Takeuchi Toshiaki , Miyamoto Ryosuke , Kohda Tomoko , Izumi Yuishin , Kozaki Shunji
Published: October 2022

All the currently used type A botulinum neurotoxins for clinical uses are of subtype A1. We compared the efficacy and safety for the first time head-to-head between a novel botulinum toxin A2NTX prepared from subtype A2 and onabotulinumtoxinA (BOTOX) derived from A1 for post-stroke spasticity. We assessed the modified Ashworth scale (MAS) of the ankle joint, the mobility scores of Functional Independence Measure (FIM), and the grip power of the unaffected hand before and after injecting 300 units of BOTOX or A2NTX into calf muscles. The procedure was done in a blinded manner for the patient, the injecting physician, and the examiner. Stroke patients with chronic spastic hemiparesis (15 for A2NTX and 16 for BOTOX) were enrolled, and 11 for A2NTX and 13 for BOTOX (MAS of ankle; > or = 2) were entered for the MAS study. Area-under-curves of changes in MAS (primary outcome) were greater for A2NTX by day 30 (p = 0.044), and were similar by day 60. FIM was significantly improved in the A2NTX group (p = 0.005), but not in the BOTOX group by day 60. The hand grip of the unaffected limb was significantly decreased in the BOTOX-injected group (p = 0.002), but was unaffected in the A2NTX-injected group by day 60, suggesting there was less spread of A2NTX to the upper limb than there was with BOTOX. Being a small-sized pilot investigation with an imbalance in the gender of the subjects, the present study suggested superior efficacy and safety of A2NTX, and warrants a larger scale clinical trial of A2NTX to confirm these preliminary results.
Centrifugation-Assisted Solid-Phase Extraction Coupled with UPLC-MS/MS for the Determination of Mycotoxins in ARECAE Semen and Its Processed Products
Authors: Liang Huanyan , Hou Qianyu , Zhou Yakui , Zhang Lei , Yang Meihua , Zhao Xiangsheng
Published: October 2022

Mycotoxins can occur naturally in a variety of agriculture products, including cereals, feeds, and Chinese herbal medicines (TCMs), via pre- and post-harvest contamination and are regulated worldwide. However, risk mitigation by monitoring for multiple mycotoxins remains a challenge using existing methods due to their complex matrices. A multi-toxin method for 22 mycotoxins (aflatoxin B1, B2, G1, G2, M1, M2; ochratoxin A, B, C; Fumonisin B1, B2, B3; 15-acetyldeoxynivalenol, 3-acetyldeoxynivalenol, diace-toxyscirpenol, HT-2, T-2, deepoxy-deoxynivalenol, deoxynivalenol, neosolaniol, zearalenone, and sterigmatocystin) using centrifugation-assisted solid-phase extraction (SPE) clean-up prior to ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis for Arecae Semen and its processed products was developed and validated. Several experimental parameters affecting the extraction and clean-up efficiency were systematically optimized. The results indicated good linearity in the range of 0.1–1000 μg/kg (r2 > 0.99), low limits of detection (ranging from 0.04 μg/kg to 1.5 μg/kg), acceptable precisions, and satisfactory recoveries for the selected mycotoxins. The validated method was then applied to investigate mycotoxin contamination levels in Areca catechu and its processed products. The mycotoxins frequently contaminating Areca catechu were aflatoxins (AFs), and the average contamination level and number of co-occurring mycotoxins in the Arecae Semen slices (Binlangpian) were higher than those in commercially whole Arecae Semen and Arecae Semen Tostum (Jiaobinlang). Sterigmatocystin was detected in 5 out of 30 Arecae Semen slices. None of the investigated mycotoxins were detected in Arecae pericarpium (Dafupi). The results demonstrated that centrifugation-assisted SPE coupled with UHPLC-MS/MS can be a useful tool for the analysis of multiple mycotoxins in Areca catechu and its processed products.
An Overview on Leishmaniasis in Romania: Diagnosis and Therapeutics
Authors: Daraban Bocaneti Florentina , Ivanescu Larisa Maria , Miron Liviu , Tanase Oana Irina , Dascalu Mihaela Anca
Published: October 2022

Leishmaniasis, a vector-borne disease considered to be one of the twenty neglected diseases by the World Health Organization, represents one of the public health concerns in endemic countries. In humans, as well as in animal counterparts, the infection can evolve with different clinical localizations, such as those that are cutaneous, mucocutaneous and visceral. Romania has been traditionally considered a nonendemic country for Leishmania species infection and has had sporadic positive human cases; however, the climate change recorded in recent decades has created potentially optimal conditions for the preponderant vectors of Phlebotomus spp., which has lately been identified in various parts of country. Moreover, with people and dogs (the prevailing hosts) traveling in endemic countries, the disease was imported and diagnosed in both species, and became a medical concern. In this review, we focused on the: (1) epidemiological data of leishmaniasis cases, both in humans and animals, reported by Romania; (2) diagnostic tools available for confirmation since there is a lack of gold-standard laboratory methods for human and dog patients; and (3) conventional antileishmanial therapy.
First Molecular Detection of Pathogens Leptospira in Common Rodent Captured in North Algeria Urban Areas
Authors: Lekhal Lila , Harran Elena , Aragon Anaïs , Groud Karine , Le Guyader Marine , Kaidi Rachid , Khelef Djamel , Djelouadji Zouheira
Published: October 2022

Leptospirosis is an anthropozoonosis disease of worldwide distribution caused by mobile spirochetes of the genus Leptospira and rodents, mainly rats, are described as its primary reservoir. In Algeria, there is limited data about the prevalence of Leptospira spp. in humans and animals, as well as Leptospira carriage in wild rodents. The study aimed to highlight the importance of rodents as a reservoir of Leptospira bacterium in Blida city in Algeria by detecting and identifying circulating Leptospira species in the rodent population. A total of 101 rodents, 95 Rattus Norvegicus, 5 Rattus Rattus, and 1 Mus Musculus were captured and tested for pathogenic Leptospira spp. byreal-time PCR targeting the Leptospira 16S rRNA (rrs) gene, revealing a total prevalence of 40.6%, 95% IC [30.9–50.8%]. Positive samples were subjected to species-specific real-time PCR assays targeting L. interrogans, L. noguchii, L. borgpetersenii, and L. kirschneri for species identification. However, positive samples for which Leptospira-species could not be determined were subjected to conventional PCR targeting the partial 16S rRNA (rrs) gene, and amplified DNA was subjected to sequencing. Leptospira spp. was detected in 36 kidney, 16 urine, and three lung specimens. L. interrogans was identified in 39 rodents and L. borpetersenii in one rodent; however, one rodent with renal carriage could not be typed due to poor DNA quality. This study provides the first description of pathogenic Leptospira spp. in wild rodents in Algeria. These findings suggest a high potential risk of leptospirosis transmission from rodents to humans and animals in Algeria and therefore imply the adoption of prophylactic measures. In addition, further studies, including different animals and rodent species, should be conducted to clarify the epidemiology of this disease in Algeria.
Existing Policies/Guidelines on the Environmental Dimension of Antimicrobial Resistance in India: An Insight into the Key Facets through Review and SWOT Analysis
Authors: Debnath Falguni , Chakraborty Debjit , Giri Sandip , Saha Shatabdi , Pyne Soume , Chakraverty Raja , Majumdar Agniva , Deb Alok Kumar , Diwan Vishal , Bhatia Rajesh , Dutta Shanta
Published: October 2022

Background: Antimicrobial resistance (AMR) is a multidimensional phenomenon. The environment acts as a mixing pot of drug-resistant bacteria from many sources such as pharmaceutical, biomedical, veterinary, and agricultural sectors. In this study, we analysed the existing AMR-related policies/guidelines/legislations in India in the above domains and how the current practices are being guided by them. Methods: We used a convergent parallel mix method design. Quantitative data were collected through a review of policies/guidelines/legislations in the said domains and analysed using the SWOT tool parallelly supported by key informant interviews of domain-specific stakeholders. Results: Altogether, 19 existing AMR policies/guidelines/legislations were identified. The existence of few policies/guidelines in each domain indicated the evolving environment for policy interventions. However, the lack of capacity among farmers, inadequate provision for structured capacity building, high cost of alternatives to antimicrobials, and lack of provision of incentivisation in case of crop failure were identified as the major weaknesses prevalent across the domains. Opportunities for policy refinements/the introduction of new policies are ample. However, easy access to antimicrobials and injudicious use imposes threats to AMR containment in all sectors. Conclusions: Despite having a few policies for the containment of AMR, their implementation witnesses challenge due to the lack of collaborative approaches, the existence of policies disjointed from ground reality, infrastructural issues, and the lack of capacity and resources.
Clinical Features Related to Severity and Mortality among COVID-19 Patients in a Pre-Vaccine Period in Luanda, Angola
Authors: Sebastião Cruz S. , Cogle Adis , Teixeira Alice D’Alva , Cândido Ana Micolo , Tchoni Chissengo , Amorim Maria João , Loureiro N’gueza , Parimbelli Paolo , Penha-Gonçalves Carlos , Demengeot Jocelyne , Sacomboio Euclides , Mendes Manuela , Arrais Margarete , Morais Joana , Vasconcelos Jocelyne Neto de , Brito Miguel
Published: October 2022

Background: Infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with clinical features of diverse severity. Few studies investigated the severity and mortality predictors of coronavirus disease 2019 (COVID-19) in Africa. Herein, we investigated the clinical features of severity and mortality among COVID-19 patients in Luanda, Angola. Methods: This multicenter cohort study involved 101 COVID-19 patients, between December 2020 and April 2021, with clinical and laboratory data collected. Analysis was done using independent-sample t-tests and Chi-square tests. The results were deemed significant when p < 0.05. Results: The mean age of patients was 51 years (ranging from 18 to 80 years) and 60.4% were male. Fever (46%), cough (47%), gastrointestinal symptoms (26.7%), and asthenia (26.7%), were the most common symptoms. About 64.4% of the patients presented coexistent disorders, including hypertension (42%), diabetes (17%), and chronic renal diseases (6%). About 23% were non-severe, 77% were severe, and 10% died during hospitalization. Variations in the concentration of neutrophil, urea, creatinine, c-reactive protein, sodium, creatine kinase, and chloride were independently associated with severity and/or mortality (p < 0.05). Conclusion: Several factors contributed to the severity and mortality among COVID-19 patients in Angola. Further studies related to clinical features should be carried out to help clinical decision-making and follow-up of COVID-19 patients in Angola.
On the Birth of the Universe and Time
Authors: Gorobey Natalia , Lukyanenko Alexander , Goltsev Alexander V.
Published: October 2022

A theory of the initial state of the universe is proposed within the framework of the Euclidean quantum theory of gravity. The theory is based on a quantum representation in which the action functional is implemented as an operator on the space of wave functionals depending on the 4D space metric and matter fields. The initial construction object is the eigenvalue of the action operator in the area of the origin of the universe with the given values of the 3D metric and matter fields on the boundary. The wave function of the initial state is plotted as an exponential of this eigenvalue, after a Wick rotation in the complex plane of the radial variable of the Euclidean 4D space. An estimate of the initial radius of the universe is proposed.
Influence of Extragalactic Magnetic Fields on Extragalactic Cascade Gamma-Ray Emission
Authors: Uryson Anna
Published: October 2022

We discuss the influence of extragalactic magnetic fields on the intensity of gamma-ray emission produced in electromagnetic cascades from ultra-high energy cosmic rays propagating in extragalactic space. Both cosmic rays and cascade particles propagate mostly out of galaxies, galactic clusters, and large-scale structures, as their relative volume is small. Therefore, their magnetic fields weakly affect emission produced in cascades. Yet, estimates of this influence can be useful in searching for dark matter particles when components of extragalactic gamma-ray background should be known, including cascade gamma-ray emission. To study magnetic field influence on cascade emission, we calculated cosmic particle propagation in fields of ~10−6 and 10−12 G (the former is typical inside galaxies and clusters and the latter is common in voids and outside galaxies and clusters). The calculated spectra of cascade gamma-ray emissions are similar in the range of ~107–109 eV, so analyzing cascade emission in this range it is not necessary to specify models of an extragalactic magnetic field.
Nonsingular Phantom Cosmology in Five-Dimensional f(R, T) Gravity
Authors: Sahoo Rakesh Ranjan , Mahanta Kamal Lochan , Ray Saibal
Published: October 2022

We obtain exact solutions to the field equations for five-dimensional locally rotationally symmetric (LRS) Bianchi type-I spacetime in the f(R,T) theory of gravity, where specifically, the following three cases are considered: (i) f(R,T)=μ(R+T), (ii) f(R,T)=Rμ+RTμ2, and (iii) f(R,T)=R+μR2+μT, where R and T, respectively, are the Ricci scalar and trace of the energy–momentum tensor. It is found that the equation of state (EOS) parameter w is governed by the parameter μ involved in the f(R,T) expressions. We fine-tune the parameter μ to obtain the effect of phantom energy in the model. However, we also restrict this parameter to obtain a stable model of the universe.
Isolation and Characterization of Lytic Bacteriophages Active against Clinical Strains of E. coli and Development of a Phage Antimicrobial Cocktail
Authors: Alexyuk Pavel , Bogoyavlenskiy Andrey , Alexyuk Madina , Akanova Kuralay , Moldakhanov Yergali , Berezin Vladimir
Published: October 2022

Pathogenic E. coli cause urinary tract, soft tissue and central nervous system infections, sepsis, etc. Lytic bacteriophages can be used to combat such infections. We investigated six lytic E. coli bacteriophages isolated from wastewater. Transmission electron microscopy and whole genome sequencing showed that the isolated bacteriophages are tailed phages of the Caudoviricetes class. One-step growth curves revealed that their latent period of reproduction is 20–30 min, and the average value of the burst size is 117–155. During co-cultivation with various E. coli strains, the phages completely suppressed bacterial host culture growth within the first 4 h at MOIs 10−7 to 10−3. The host range lysed by each bacteriophage varied from six to two bacterial strains out of nine used in the study. The cocktail formed from the isolated bacteriophages possessed the ability to completely suppress the growth of all the E. coli strains used in the study within 6 h and maintain its lytic activity for 8 months of storage. All the isolated bacteriophages may be useful in fighting pathogenic E. coli strains and in the development of phage cocktails with a long storage period and high efficiency in the treatment of bacterial infections.
Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
Authors: Pi Keng-Shuo , Bortolotti Daria , Sang Yurou , Schiuma Giovanna , Beltrami Silvia , Rizzo Sabrina , Bortoluzzi Alessandra , Baldi Eleonora , Creagh A. Louise , Haynes Charles A. , Rizzo Roberta , Straus Suzana K.
Published: October 2022

A number of studies have suggested that human herpesvirus 6A (HHV-6A) may play a role in multiple sclerosis (MS). Three possible hypotheses have been investigated: (1) U24 from HHV-6A (U24-6A) mimics myelin basic protein (MBP) through analogous phosphorylation and interaction with Fyn-SH3; (2) U24-6A affects endocytic recycling by binding human neural precursor cell (NPC) expressed developmentally down-regulated protein 4-like WW3* domain (hNedd4L-WW3*); and (3) MS patients who express Killer Cell Immunoglobulin Like Receptor 2DL2 (KIR2DL2) on natural killer (NK) cells are more susceptible to HHV-6 infection. In this contribution, we examined the validity of these propositions by investigating the interactions of U24 from HHV-6B (U24-6B), a variant less commonly linked to MS, with Fyn-SH3 and hNedd4L-WW3* using heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) titrations and isothermal titration calorimetry (ITC). In addition, the importance of phosphorylation and the specific role of U24 in NK cell activation in MS patients were examined. Overall, the findings allowed us to shed light into the models linking HHV-6 to MS and the involvement of U24.
SARS-CoV-2 Morphometry Analysis and Prediction of Real Virus Levels Based on Full Recurrent Neural Network Using TEM Images
Authors: Taha Bakr Ahmed , Mashhadany Yousif Al , Al-Jumaily Abdulmajeed H. J. , Zan Mohd Saiful Dzulkefly Bin , Arsad Norhana
Published: October 2022

The SARS-CoV-2 virus is responsible for the rapid global spread of the COVID-19 disease. As a result, it is critical to understand and collect primary data on the virus, infection epidemiology, and treatment. Despite the speed with which the virus was detected, studies of its cell biology and architecture at the ultrastructural level are still in their infancy. Therefore, we investigated and analyzed the viral morphometry of SARS-CoV-2 to extract important key points of the virus’s characteristics. Then, we proposed a prediction model to identify the real virus levels based on the optimization of a full recurrent neural network (RNN) using transmission electron microscopy (TEM) images. Consequently, identification of virus levels depends on the size of the morphometry of the area (width, height, circularity, roundness, aspect ratio, and solidity). The results of our model were an error score of training network performance 3.216 × 10−11 at 639 epoch, regression of −1.6 × 10−9, momentum gain (Mu) 1 × 10−9, and gradient value of 9.6852 × 10−8, which represent a network with a high ability to predict virus levels. The fully automated system enables virologists to take a high-accuracy approach to virus diagnosis, prevention of mutations, and life cycle and improvement of diagnostic reagents and drugs, adding a point of view to the advancement of medical virology.
Comparison of Biosafety and Diagnostic Utility of Biosample Collection Cards
Authors: Keck Hanna , Eschbaumer Michael , Beer Martin , Hoffmann Bernd
Published: October 2022

Six different biosample collection cards, often collectively referred to as FTA (Flinders Technology Associates) cards, were compared for their ability to inactivate viruses and stabilize viral nucleic acid for molecular testing. The cards were tested with bluetongue virus, foot-and-mouth disease virus (FMDV), small ruminant morbillivirus (peste des petits ruminants virus), and lumpy skin disease virus (LSDV), encompassing non-enveloped and enveloped representatives of viruses with double-stranded and single-stranded RNA genomes, as well as an enveloped DNA virus. The cards were loaded with virus-containing cell culture supernatant and tested after one day, one week, and one month. The inactivation of the RNA viruses was successful for the majority of the cards and filters. Most of them completely inactivated the viruses within one day or one week at the latest, but the inactivation of LSDV presented a greater challenge. Three of the six cards inactivated LSDV within one day, but the others did not achieve this even after an incubation period of 30 days. Differences between the cards were also evident in the stabilization of nucleic acid. The amount of detectable viral genome on the cards remained approximately constant for all viruses and cards over an incubation period of one month. With some cards, however, a bigger loss of detectable nucleic acid compared with a directly extracted sample was observed. Using FMDV, it was confirmed that the material applied to the cards was sufficiently conserved to allow detailed molecular characterization by sequencing. Furthermore, it was possible to successfully recover infectious FMDV by chemical transfection from some cards, confirming the preservation of full-length RNAs.
In Vitro Evaluation of Anti-Rotaviral Activity and Intestinal Toxicity of a Phytotherapeutic Prototype of Achyrocline bogotensis (Kunth) DC.
Authors: Ramírez María-Camila , Méndez Kelly , Castelblanco-Mora Alicia , Quijano Sandra , Ulloa Juan
Published: October 2022

Viruses represent the primary etiologic agents (70–80%) of acute diarrheal disease (ADD), and rotavirus (RV) is the most relevant one. Currently, four rotavirus vaccines are available. However, these vaccines do not protect against emerging viral strains or are not available in low-income countries. To date, there are no approved drugs available against rotavirus infection. In this study, we evaluated the in vitro anti-rotaviral activity and intestinal toxicity of a phytotherapeutic prototype obtained from Achyrocline bogotensis (Kunth) DC. (PPAb); medicinal plant that contains compounds that inhibit the rotavirus replication cycle. Virucidal and viral yield reduction effects exerted by the PPAb were evaluated by immunocytochemistry and flow cytometry. Furthermore, the toxic impact of the PPAb was evaluated in polarized human intestinal epithelial C2BBe1 cells in terms of cytotoxicity, loss of cytoplasmic membrane asymmetry, and DNA fragmentation by MTT and fluorometry. PPAb concentrations under 0.49 mg/mL exerted significant virucidal and viral yield reduction activities, and concentrations under 16 mg/mL neither reduced cell viability, produced DNA fragmentation, nor compromised the C2BBe1cell membrane stability after 24-h incubation. Based on these results, the evaluated phytotherapeutic prototype of Achyrocline bogotensis might be considered as a promising alternative to treat ADD caused by rotavirus.
Interplay between the Lung Microbiome, Pulmonary Immunity and Viral Reservoirs in People Living with HIV under Antiretroviral Therapy
Authors: Wang Zihui , Jenabian Mohammad-Ali , Alexandrova Yulia , Pagliuzza Amélie , Olivenstein Ron , Samarani Suzanne , Chomont Nicolas , Kembel Steven W. , Costiniuk Cecilia T.
Published: October 2022

Pulmonary dysbiosis may predispose people living with HIV (PLWH) to chronic lung disease. Herein, we assessed whether intrapulmonary HIV reservoir size and immune disruption are associated with reduced bacterial lung diversity in PLWH. Bacterial DNA was extracted and PCR-amplified from cell-free bronchoalveolar lavage (BAL) fluid from 28 PLWH and 9 HIV-negative controls. Amplicon sequence variant (ASV) relative abundances and taxonomic identities were analyzed using joint species distribution modeling. HIV-DNA was quantified from blood and pulmonary CD4+ T-cells using ultra-sensitive qPCR. Immunophenotyping of BAL T-cells was performed using flow cytometry. Lung microbiome diversity was lower in smokers than non-smokers and microbiome composition was more variable in PLWH than HIV-negative individuals. Frequencies of effector memory BAL CD4+ and CD8+ T-cells positively correlated with abundance of several bacterial families while frequencies of BAL activated CD4+ T-cells negatively correlated with abundance of most lung bacterial families. Higher HIV-DNA levels in blood, but not in BAL, as well as frequencies of senescent CD4+ T-cells were associated with reduced bacterial diversity. These findings suggest that HIV infection may weaken the relationship between the lung microbiome and smoking status. Viral reservoir and immune activation levels may impact the lung microbiome, predisposing PLWH to pulmonary comorbidities.
RSV Replication, Transmission, and Disease Are Influenced by the RSV G Protein
Authors: Bergeron Harrison C. , Tripp Ralph A.
Published: October 2022

It is important to understand the features affecting virus replication, fitness, and transmissibility as they contribute to the outcome of infection and affect disease intervention approaches. Respiratory syncytial virus (RSV) is a major contributor to respiratory disease, particularly in the infant and elderly populations. Although first described over 60 years ago, there are no approved vaccines and there are limited specific antiviral treatments due in part to our incomplete understanding of the features affecting RSV replication, immunity, and disease. RSV studies have typically focused on using continuous cell lines and conventional RSV strains to establish vaccine development and various antiviral countermeasures. This review outlines how the RSV G protein influences viral features, including replication, transmission, and disease, and how understanding the role of the G protein can improve the understanding of preclinical studies.
Geographic Range Overlap Rather than Phylogenetic Distance Explains Rabies Virus Transmission among Closely Related Bat Species
Authors: Jacquot Maude , Wallace Megan A. , Streicker Daniel G. , Biek Roman
Published: October 2022

The cross-species transmission (CST) of pathogens can have dramatic consequences, as highlighted by recent disease emergence events affecting human, animal and plant health. Understanding the ecological and evolutionary factors that increase the likelihood of disease agents infecting and establishing in a novel host is therefore an important research area. Previous work across different pathogens, including rabies virus (RABV), found that increased evolutionary distance between hosts reduces the frequency of cross-species transmission and of permanent host shifts. However, whether this effect of host relatedness still holds for transmission among recently diverged hosts is not well understood. We aimed to ask if high host relatedness can still increase the probability of a host shift between more recently diverged hosts, and the importance of this effect relative to ecological predictors. We first addressed this question by quantifying the CST frequency of RABV between North American bat species within the genus Myotis, using a multi-decade data set containing 128 nucleoprotein (N) RABV sequences from ten host species. We compared RABV CST frequency within Myotis to the rates of CST between nine genera of North American bat species. We then examined whether host relatedness or host range overlap better explains the frequency of CST seen between Myotis species. We found that at the within genus scale, host range overlap, rather than host relatedness best explains the frequency of CST events. Moreover, we found evidence of CST occurring among a higher proportion of species, and CST more frequently resulting in sustained transmission in the novel host in the Myotis dataset compared to the multi-genus dataset. Our results suggest that among recently diverged species, the ability to infect a novel host is no longer restricted by physiological barriers but instead is limited by physical contact. Our results improve predictions of where future CST events for RABV might occur and clarify the relationship between host divergence and pathogen emergence.
A South American Mouse Morbillivirus Provides Insight into a Clade of Rodent-Borne Morbilliviruses
Authors: Debat Humberto J.
Published: October 2022

Morbilliviruses are negative-sense single-stranded monosegmented RNA viruses in the family Paramyxoviridae (order Mononegavirales). Morbilliviruses infect diverse mammals including humans, dogs, cats, small ruminants, seals, and cetaceans, which serve as natural hosts. Here, I report the identification and characterization of novel viruses detected in public RNAseq datasets of South American long-haired and olive field mice. The divergent viruses dubbed Ratón oliváceo morbillivirus (RoMV) detected in renal samples from mice collected from Chile and Argentina are characterized by an unusually large genome including long intergenic regions and the presence of an accessory protein between the F and H genes redounding in a genome architecture consisting in 3′-N-P/V/C-M-F-hp-H-L-5′. Structural and functional annotation, genetic distance, and evolutionary insights suggest that RoMV is a member of a novel species within genus Morbillivirus tentatively named as South American mouse morbillivirus. Phylogenetic analysis suggests that this mouse morbillivirus is closely related to and clusters into a monophyletic group of novel rodent-borne morbilliviruses. This subclade of divergent viruses expands the host range, redefines the genomic organization and provides insights on the evolutionary history of genus Morbillivirus.
Towards a Functional Cure for Hepatitis B Virus: A 2022 Update on New Antiviral Strategies
Authors: Degasperi Elisabetta , Anolli Maria Paola , Lampertico Pietro
Published: October 2022

Chronic infection with hepatitis B virus (HBV) represents one of the main causes of the development of cirrhosis and its complications. Treatment with potent third-generation nucleos(t)ide analogues (NUCs) results in >99% HBV DNA undetectability, and prevents fibrosis progression and liver-related complications. However, NUCs are not able to induce the so-called functional cure, which is hepatitis B surface antigen (HBsAg) loss and anti-HBs seroconversion. Consequently, NUC treatment is currently intended as being long-term or lifelong, resulting in the need for clinical monitoring and potentially suffering from compliance issues. Consequently, drug development in HBV has the goal of developing new agents in order to achieve a functional cure for HBV. Currently, the three main strategies include the following: inhibition of viral replication, inhibition of viral antigens, and immune modulation. This review summarizes the most recent updates concerning HBV compounds among these three main classes.
Identification of Key Genes Involved in Resistance to Early Stage of BmNPV Infection in Silkworms
Authors: Yu Linyuan , Cao Yeqing , Ge Sicheng , Xu Anying , Qian Heying , Li Gang
Published: October 2022

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the most serious pathogens restricting the sustainable development of the sericulture industry. Currently, there is no effective treatment for BmNPV infection in silkworms, and the mechanism underlying BmNPV resistance in silkworms is also not clear. In this study, comparative transcriptome analyses were carried out in midguts of two silkworm varieties, namely BaiyuN, which is a resistance variety, and Baiyu, which is a susceptible variety, at five different time points (i.e., 0, 1, 3, 6, and 9 h) post-BmNPV infection to detect the early-stage transcriptional changes in these silkworms. In total, 1911 and 1577 differentially expressed genes (DEGs) were identified in the Baiyu and BaiyuN varieties, respectively, involving a total of 48 metabolic pathways. Of these pathways, eight were shared by the Baiyu and BaiyuN varieties in response to BmNPV infection. Notably, four genes (i.e., BGIBMGA08815, BGIBMGA003935, BGIBMGA003571, BGIBMGA010059) were upregulated in the Baiyu variety while downregulated in the BaiyuN variety. The inhibited expression of these four genes in the resistant variety highlighted their potential roles in the resistance of early-stage viral replication. Thus, our study provided a new avenue for the further study of the mechanism underlying BmNPV infection in silkworms and the potential treatment of BmNPV infection.
Estimating the Effectiveness of Shielding during Pregnancy against SARS-CoV-2 in New York City during the First Year of the COVID-19 Pandemic
Authors: Chen Siyu , Murphy Elisabeth A. , Pendergrass Angeline G. , Sukhu Ashley C. , Eng Dorothy , Jurkiewicz Magdalena , Mohammed Iman , Rand Sophie , White Lisa J. , Hupert Nathaniel , Yang Yawei J.
Published: October 2022

Pregnant patients have increased morbidity and mortality in the setting of SARS-CoV-2 infection. The exposure of pregnant patients in New York City to SARS-CoV-2 is not well understood due to early lack of access to testing and the presence of asymptomatic COVID-19 infections. Before the availability of vaccinations, preventative (shielding) measures, including but not limited to wearing a mask and quarantining at home to limit contact, were recommended for pregnant patients. Using universal testing data from 2196 patients who gave birth from April through December 2020 from one institution in New York City, and in comparison, with infection data of the general population in New York City, we estimated the exposure and real-world effectiveness of shielding in pregnant patients. Our Bayesian model shows that patients already pregnant at the onset of the pandemic had a 50% decrease in exposure compared to those who became pregnant after the onset of the pandemic and to the general population.
Impact of Hypertension on COVID-19 Burden in Kidney Transplant Recipients: An Observational Cohort Study
Authors: Aguiar-Brito Isabella , de Lucena Débora D. , Veronese-Araújo Alexandre , Cristelli Marina P. , Tedesco-Silva Hélio , Medina-Pestana José O. , Rangel Érika B.
Published: October 2022

Background: COVID-19 severity is determined by cardiometabolic risk factors, which can be further aggravated by chronic immunosuppression in kidney transplant recipients (KTRs). We aimed to verify the main risk factors related to hypertension (HTN) that contribute to COVID-19 progression and mortality in that population. Methods: Retrospective analysis of 300 KTRs from March 2020 to August 2020 in a single center. We compared the main outcomes between HTN (n = 225) and non-HTN (n = 75), including admission to the intensive care unit (ICU), development of acute kidney injury (AKI), need for invasive mechanical ventilation or oxygen, and mortality. Results: Of the patients in the study, 57.3% were male, 61.3% were white, the mean age was 52.5 years, and 75% had HTN. Pre-existing HTN was independently associated with higher rates of mortality (32.9%, OR = 1.96, p = 0.036), transfer to the ICU (50.7%, OR = 1.94, p = 0.017), and AKI with hemodialysis (HD) requirement (40.4%, OR = 2.15, p = 0.011). In the hypertensive group, age, diabetes mellitus, heart disease, smoking, glycemic control before admission, C-reactive protein, lactate dehydrogenase, lymphocytes, and D-dimer were significantly associated with COVID-19 progression and mortality. Both lower basal and previous estimated glomerular filtration rates posed KTRs with HTN at greater risk for HD requirement. Conclusions: Therefore, the early identification of factors that predict COVID-19 progression and mortality in KTRs affected by COVID-19 contributes to therapeutic decisions, patient flow management, and allocation of resources.
Recombinant Virus-like Particles of Human Parvovirus B19 with the Internal Location of VP1 Unique Region Produced by Hansenula polymorpha
Authors: Shao Shuai , Wang Qingqing , Jin Yuqin , Zhang Xuefeng , Liu Zhaoming , Chen Shi , Wu Hailan , Yang Sensen , Tang Fang , Su Jiguo , Liang Yu , Zhang Jing , Li Qiming
Published: October 2022

Human parvovirus B19 (HPV B19) is pathogenic to human, which can cause fifth disease, transient aplastic crisis, arthritis, myocarditis, autoimmune disorders, hydrops fetalis, and so on. Currently, no approved vaccines or antiviral drugs are available against HPV B19, and thus the development of effective vaccines is needed. The capsid of HPV B19 is composed of two types of proteins, i.e., the major capsid protein VP2 and the minor protein VP1. Previous experimental studies have shown that the dominant immune responses against HPV B19 are elicited by VP1, especially the unique region on the N-terminus of VP1. It has been found that VP2 alone or VP2 and VP1 together can assemble into virus-like particle (VLP). The VLP structure formed by VP2 has been resolved, however, the location of VP1 in the capsid, especially the location of VP1 unique region with strong immunogenicity, is still not clear. In the present work, using the Hansenula polymorpha expression system developed by our laboratory, two kinds of recombinant HPV B19 VLPs were expressed, i.e., the VLP co-assembled by VP1 and VP2 (VP1/VP2 VLP) and the VLP whose VP1 content was improved (VP1h/VP2 VLP). The expression, purity, and morphology of these two VLPs were characterized, and then their immunogenic properties were investigated and compared with those of the VLP containing VP2 alone (VP2 VLP) previously developed by our group. Furthermore, the location of the VP1 unique region in the VLPs was determined by using the immunogold electron microscopy (IGEM). Our experimental results show that the VP1h/VP2 VLP elicits a stronger neutralization against the HPV B19 than VP2 and VP1/VP2 VLPs, which implies that the increase of VP1 content significantly improves the level of neutralizing antibodies. In addition, the IGEM observations suggest that the unique region of VP1 may be located inside the recombinant VLP. The VLPs recombinantly expressed by our Hansenula polymorpha system may serve as a promising candidate immunogen for HPV B19 vaccine development.
Evaluation of the Perceptions, Attitudes and Practices among Greek Non-Professional Athletes Visiting a Public Hospital during March 2022, towards COVID-19 Vaccination and Its Consequences on Sports Training and Sports Activity
Authors: Marinos Georgios , Lamprinos Dimitrios , Georgakopoulos Panagiotis , Kavoukidis Nikiforos , Oikonomou Evangelos , Zoumpoulis Georgios , Siasos Gerasimos , Schizas Dimitrios , Nikolopoulos Alexandros , Botonis Petros G. , Damaskos Christos , Rachiotis Georgios , Lagiou Pagona , Orfanos Philippos
Published: October 2022

Sports have been majorly impacted by the COVID-19 pandemic. After the lockdown period, vaccination and protocols were implemented to return to normality. We aimed to assess the attitudes and practices related to COVID-19 vaccination among athletes, and to record adverse effects of vaccination, if any. A questionnaire was distributed to 1012 male and female athletes, 15+ years old, within the region of Athens. Vaccination coverage with at least one dose was 93.5%, whereas 53.9% were fully vaccinated. More than half of the participants were infected with SARS-CoV-2 at the time of the study. More than 90% of the participants, considered the vaccines as safe, effective and important for public health. Concern about potential side-effects was raised especially by women athletes (59.1% of women compared to 42.2% of men, p < 0.001). The main reasons for avoiding vaccination were fear of vaccine safety, concern about the short time period for vaccine development and testing and doubt of risk of being exposed to SARS-CoV-2 infection. The main reported side-effects were pain at the injection site, fatigue, fever and headache. Approximately two thirds of the participants reported that vaccination did not affect their training, and none reported missing participation in scheduled athletic events. Participants reported high compliance to preventive measures by themselves and fellow athletes, but low satisfaction regarding the implementation of public protocols and the flow of information provided by the authorities. Athletes of older age and those less concerned about potential side-effects were more likely to get fully vaccinated. Nevertheless, the vast majority of the athletes in our study were vaccinated for COVID-19 despite any hesitation regarding effectiveness, safety, or potential side-effects from the vaccines.
Digital Information Approach through Social Media among Gen Z and Millennials: The Global Scenario during the COVID-19 Pandemic
Authors: Blandi Lorenzo , Sabbatucci Michela , Dallagiacoma Giulia , Alberti Federica , Bertuccio Paola , Odone Anna
Published: October 2022

An infodemic represents a concern for public health, influencing the general population’s perceptions of key health issues. Misinformation is rapidly spread by social media, particularly among young generations. We used data from the WHO “Social Media and COVID-19” study, which was conducted in 24 countries worldwide on over 23,000 subjects aged 18–40 years, to explore Generation Z and Millennials’ models for health-information-seeking behaviors on social media. We summarized data on the most used sources of information, content of interest, and content sharing, as well as the sentiment toward the infodemic, through descriptive statistics and Chi-square test to verify the differences between groups. Among the survey respondents, 9475 (40.3%) were from high-income countries (HIC), 8000 (34.1%) from upper-middle-income countries (UMIC), and 6007 (25.6%) from lower-middle-income countries (LMIC). Social media were the most used sources of information to retrieve news on COVID-19 disease (about 79% in HIC, 87% in UMIC, and 90% in LIC) and the COVID-19 vaccine (about 78% in HIC and about 88% in UMIC and LIC). More than a half of the young respondents declared that they pay attention to scientific contents (about 51% in HIC, 59% in UMIC, and 55% in LMIC). Finally, most young participants reported feeling overwhelmed by the infodemic. However, this sentiment did not stop them from seeking information about COVID-19. Our findings highlight the importance of shaping public health interventions and campaigns on social media platforms and leveraging scientific contents. Public health authorities should work also on strategies to improve the digital literacy of the population as a driving force to empower them and achieve better health outcomes.
The Association of Health Literacy with Intention to Vaccinate and Vaccination Status: A Systematic Review
Authors: Siena Leonardo Maria , Isonne Claudia , Sciurti Antonio , De Blasiis Maria Roberta , Migliara Giuseppe , Marzuillo Carolina , De Vito Corrado , Villari Paolo , Baccolini Valentina
Published: October 2022

Despite health literacy (HL) being recognized as a driver of health-promoting behavior, its influence on the vaccination decision-making process remains unclear. This study summarized current evidence on the association between HL and both intention to vaccinate and vaccination status. We searched PubMed, Scopus, and Web of Science, retrieving observational studies published until January 2022 that used HL-validated tools to investigate the above associations for any vaccine. Quality was assessed using the Newcastle–Ottawa scale. Twenty-one articles were included; of these, six investigated the intention to vaccinate and the remainder vaccination status. Articles on intention looked at SARS-CoV-2 vaccination using heterogeneous HL tools and were of high/fair quality. Vaccination status, mainly for influenza or pneumococcal vaccines, was explored using various HL tools; the quality was generally high. We found inconsistent results across and within vaccine types, with no clear conclusion for either vaccination intention or status. A weak but positive association was reported between a high HL level and influenza vaccination uptake for individuals aged more than 65 years. HL did not seem to significantly influence behavior towards vaccination. Differences in the methods used might explain these results. Further research is needed to investigate the role of HL in the vaccination decision-making process.
The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design
Authors: Benest John , Rhodes Sophie , Evans Thomas G. , White Richard G.
Published: October 2022

Mathematical modelling methods and adaptive trial design are likely to be effective for optimising vaccine dose but are not yet commonly used. This may be due to uncertainty with regard to the correct choice of parametric model for dose-efficacy or dose-toxicity. Non-parametric models have previously been suggested to be potentially useful in this situation. We propose a novel approach for locating optimal vaccine dose based on the non-parametric Continuous Correlated Beta Process model and adaptive trial design. We call this the ‘Correlated Beta’ or ‘CoBe’ dose optimisation approach. We evaluated the CoBe dose optimisation approach compared to other vaccine dose optimisation approaches using a simulation study. Despite using simpler assumptions than other modelling-based methods, we found that the CoBe dose optimisation approach was able to effectively locate the maximum efficacy dose for both single and prime/boost administration vaccines. The CoBe dose optimisation approach was also effective in finding a dose that maximises vaccine efficacy and minimises vaccine-related toxicity. Further, we found that these modelling methods can benefit from the inclusion of expert knowledge, which has been difficult for previous parametric modelling methods. This work further shows that using mathematical modelling and adaptive trial design is likely to be beneficial to locating optimal vaccine dose, ensuring maximum vaccine benefit and disease burden reduction, ultimately saving lives