bluuebunny/crossref_metadata_2025 huggingface dataset:
The Response of Thiols to Cadmium Stress in Spinach (Spinacia Oleracea L.)
Authors: Gao Ya , Li Haipu , Song Yang , Zhang Fenglin , Yang Zhaoguang
Published: July 2022

The aim of this study is to examine the thiol species for the high cadmium (Cd) tolerance of spinach and provide information for the improvement of soil utilization. The spinach was cultured in aqueous solution with concentrations of Cd ranging from 1 to 9 mg/L. The time responses of glutathione (GSH) and phytochelatins (PCs, PC2-PC4) in the tissues of spinach were monitored via HPLC–MS/MS, and the concentrations of Cd in the roots, shoots and leaves were detected by ICP–OES. Data were analyzed via one-way ANOVA and Spearman correlation to assess the relationships among the types of thiols and the changes between types of thiols and Cd. As Cd stress increased, Cd concentrations in tissues also increased. The total thiol contents responded to Cd stresses with correlations r ranging from 0.394 (root), 0.520 (shoot) to 0.771 (leaf) (p < 0.01). GSH and PC3 were dominant on most of the days under Cd stress. The correlation r between improvements in GSH and increments of Cd concentration in roots was −0.808 (p < 0.01), and r between changes in PC3 and changes in Cd concentrations in leaves was −0.503 (p < 0.01). No correlation can be found between GSH and the subtypes of PCs in shoots, but strong positive correlations within the subtypes of PCs. Thiols can be produced in different tissues of spinach, while the shoots are only a transport tissue for GSH.
Acer pseudoplatanus: A Potential Risk of Poisoning for Several Herbivore Species
Authors: Renaud Benoît , Kruse Caroline-Julia , François Anne-Christine , Grund Lisa , Bunert Carolin , Brisson Lucie , Boemer François , Gault Gilbert , Ghislain Barbara , Petitjean Thierry , Gustin Pascal , Votion Dominique-Marie
Published: July 2022

Acer pseudoplatanus is a worldwide-distributed tree which contains toxins, among them hypoglycin A (HGA). This toxin is known to be responsible for poisoning in various species, including humans, equids, Père David’s deer and two-humped camels. We hypothesized that any herbivore pasturing with A. pseudoplatanus in their vicinity may be at risk for HGA poisoning. To test this hypothesis, we surveyed the HGA exposure from A. pseudoplatanus in species not yet described as being at risk. Animals in zoological parks were the major focus, as they are at high probability to be exposed to A. pseudoplatanus in enclosures. We also searched for a toxic metabolite of HGA (i.e., methylenecyclopropylacetyl-carnitine; MCPA-carnitine) in blood and an alteration of the acylcarnitines profile in HGA-positive animals to document the potential risk of declaring clinical signs. We describe for the first instance cases of HGA poisoning in Bovidae. Two gnus (Connochaetes taurinus taurinus) exposed to A. pseudoplatanus in their enclosure presented severe clinical signs, serum HGA and MCPA-carnitine and a marked modification of the acylcarnitines profile. In this study, even though all herbivores were exposed to A. pseudoplatanus, proximal fermenters species seemed less susceptible to HGA poisoning. Therefore, a ruminal transformation of HGA is hypothesized. Additionally, we suggest a gradual alteration of the fatty acid metabolism in case of HGA poisoning and thus the existence of subclinical cases.
Lethal and Sublethal Toxicity Assessment of Cyclosporin C (a Fungal Toxin) against Plutella xylostella (L.)
Authors: Wu Jianhui , Zhang Xiaochen , Bashir Muhammad Hamid , Ali Shaukat
Published: July 2022

Secondary metabolites/toxins produced by Purpeocillium lilacinum (Hypocreales; Phiocordycipitaceae), a well-known insect pathogen, can be used for the management of different insect pests. We report the lethal and sublethal effects of cyclosporin C (a toxin produced by P. lilacinum) against a major vegetable pest, Plutella xylostella, at specific organismal (feeding rate, larval growth, adult emergence, fecundity, and adult longevity) and sub-organismal levels (changes in antioxidant and neurophysiological enzyme activities). The toxicity of cyclosporin C against different larval instars of P. xylostella increased with increasing concentrations of the toxin and the maximum percent mortality rates for different P. xylostella larval instars at different times were observed for the 300 µg/mL cyclosporin C treatment, with an average mortality rate of 100% for all larval instars. The median lethal concentrations (LC50) of cyclosporin C against the first, second, third, and fourth larval instars of P. xylostella 72 h post-treatment were 78.05, 60.42, 50.83, and 83.05 μg/mL, respectively. Different concentrations of cyclosporin C caused a reduction in the average leaf consumption and average larval weight. Different life history parameters, such as the pupation rate (%), adult emergence (%), female fecundity, and female longevity were also inhibited when different concentrations of cyclosporin C were applied topically. The cyclosporin C concentrations inhibited the activities of different detoxifying (glutathione S-transferase, carboxylesterase, and acetylcholinesterase) and antioxidant enzyme (superoxide dismutase, catalase, and peroxidase) activities of P. xylostella when compared to the control. These findings can serve as baseline information for the development of cyclosporin C as an insect control agent, although further work on mass production, formulation, and field application is still required.
Transcriptome Analysis Reveals MAPK/AMPK as a Key Regulator of the Inflammatory Response in PST Detoxification in Mytilus galloprovincialis and Argopecten irradians
Authors: Dong Chenfan , Wu Haiyan , Zheng Guanchao , Peng Jixing , Guo Mengmeng , Tan Zhijun
Published: July 2022

Paralytic shellfish toxins (PSTs) are an increasingly important source of pollution. Bivalves, as the main transmission medium, accumulate and metabolize PSTs while protecting themselves from damage. At present, the resistance mechanism of bivalves to PSTs is unclear. In this study, Mytilus galloprovincialis and Argopecten irradians were used as experimental shellfish species for in situ monitoring. We compared the inflammatory-related gene responses of the two shellfish during PSTs exposure by using transcriptomes. The results showed that the accumulation and metabolism rate of PSTs in M. galloprovincialis was five-fold higher than that in A. irradians. The inflammatory balance mechanism of M. galloprovincialis involved the co-regulation of the MAPK-based and AMPK-based anti-inflammatory pathways. A. irradians bore a higher risk of death because it did not have the balance system, and the regulation of apoptosis-related pathways such as the PI3K-AKT signaling pathway were upregulated. Taken together, the regulation of the inflammatory balance coincides with the ability of bivalves to cope with PSTs. Inflammation is an important factor that affects the metabolic pattern of PSTs in bivalves. This study provides new evidence to support the studies on the resistance mechanism of bivalves to PSTs.
A PCR-RFLP Technique to Assess the Geographic Origin of Plasmodium falciparum Strains in Central America
Authors: Fontecha Gustavo , Escobar Denis , Ortiz Bryan , Pinto Alejandra
Published: July 2022

The elimination of malaria requires strengthening diagnosis and offering adequate and timely treatment. Imported cases of falciparum malaria represent a major challenge for pre-elimination areas, such as Central America, where chloroquine and primaquine continue to be used as first-line treatment. The pfs47 gene has been previously described as a precise molecular marker to track the geographic origin of the parasite. The aim of this study was to design a simple and low-cost technique using the polymorphic region of pfs47 to assess the geographic origin of P. falciparum strains. A PCR-RFLP technique was developed and evaluated using the MseI enzyme that proved capable of discriminating, with reasonable precision, the geographical origin of the parasites. This method could be used by national surveillance laboratories and malaria elimination programs in countries such as Honduras and Nicaragua in cases of malaria where an origin outside the Central American isthmus is suspected.
Fibrinogen-to-Albumin Ratio and Blood Urea Nitrogen-to-Albumin Ratio in COVID-19 Patients: A Systematic Review and Meta-Analysis
Authors: Ulloque-Badaracco Juan R. , Alarcon-Braga Esteban A. , Hernandez-Bustamante Enrique A. , Al-kassab-Córdova Ali , Mosquera-Rojas Melany D. , Ulloque-Badaracco Ricardo R. , Huayta-Cortez Miguel A. , Maita-Arauco Sherelym H. , Herrera-Añazco Percy , Benites-Zapata Vicente A.
Published: July 2022

Fibrinogen-to-albumin ratio (FAR) and blood urea nitrogen-to-albumin ratio (BAR) are inflammatory biomarkers that have been associated with clinical outcomes of multiple diseases. The objective of this study is to evaluate the association of these biomarkers with the severity and mortality of COVID-19 patients. A systematic search was performed in five databases. Observational studies that reported the association between FAR and BAR values with the severity and mortality of COVID-19 patients were included. Random-effects models were used for meta-analyses, and effects were expressed as Odds Ratio (OR) and their 95% confidence intervals (CI). Publication bias was assessed using the Begg test, while the quality assessment was assessed using the Newcastle Ottawa Scale. A total of 21 studies (n = 7949) were included. High FAR values were associated with a higher risk of severity (OR: 2.41; 95% CI 1.41–4.12; p < 0.001) and mortality (OR: 2.05; 95% CI 1.66–2.54; p < 0.001). High BAR values were associated with higher risk of mortality (OR: 4.63; 95% CI 2.11–10.15; p < 0.001). However, no statistically significant association was found between BAR values and the risk of severity (OR: 1.16; 95% CI 0.83–1.63; p = 0.38). High FAR and BAR values were associated with poor clinical outcomes.
Drugs for Intermittent Preventive Treatment of Malaria in Pregnancy: Current Knowledge and Way Forward
Authors: Figueroa-Romero Antia , Pons-Duran Clara , Gonzalez Raquel
Published: July 2022

Malaria infection during pregnancy is an important driver of maternal and neonatal health in endemic countries. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention at each scheduled antenatal care visit, starting at the second trimester, in areas of high and moderate transmission. However, the increased resistance to SP in some endemic areas challenges its effectiveness. Furthermore, SP is contraindicated in the first trimester of pregnancy and in HIV-infected women on co-trimoxazole prophylaxis due to potential drug–drug interactions. Thus, in recent last decades, several studies evaluated alternative drugs that could be used for IPTp. A comprehensive literature review was conducted to summarize the evidence on the efficacy and safety of antimalarial drugs being evaluated for IPTp. Chloroquine, amodiaquine, mefloquine and azithromycin as IPTp have proven to be worse tolerated than SP. Mefloquine was found to increase the risk of mother-to-child transmission of HIV. Dihydroartemisin-piperaquine currently constitutes the most promising IPTp drug alternative; it reduced the prevalence of malaria infection, and placental and clinical malaria in studies among HIV-uninfected women, and it is currently being tested in HIV-infected women. Research on effective antimalarial drugs that can be safely administered for prevention to pregnant women should be prioritized. Malaria prevention in the first trimester of gestation and tailored interventions for HIV-infected women remain key research gaps to be addressed.
Difference between Microscopic and PCR Examination Result for Malaria Diagnosis and Treatment Evaluation in Sumba Barat Daya, Indonesia
Authors: Deo Dwita Anastasia , Herningtyas Elizabeth Henny , Intansari Umi Solekhah , Perdana Taufik Mulya , Murhandarwati Elsa Herdiana , Soesatyo Marsetyawan H. N. E.
Published: July 2022

Microscopic examination is the backbone of malaria diagnosis and treatment evaluation in Indonesia. This test has limited ability to detect malaria at low parasite density. Inversely, nested polymerase chain reaction (PCR) can detect parasites at a density below the microscopic examination’s detection limit. The objective of this study is to compare microscopic and PCR results when being used to identify malaria in suspected patients and patients who underwent dihydroartemisinin–piperaquine (DHP) therapy in the last 3–8 weeks with or without symptoms in Sumba Barat Daya, Nusa Tenggara Timur, Indonesia. Recruitment was conducted between April 2019 and February 2020. Blood samples were then taken for microscopic and PCR examinations. Participants (n = 409) were divided into three groups: suspected malaria (42.5%), post-DHP therapy with fever (4.9%), and post-DHP therapy without fever (52.6%). Microscopic examination found five cases of P. falciparum + P. vivax infection, while PCR found 346 cases. All microscopic examinations turned negative in the post-DHP-therapy group. Conversely, PCR result from the same group yielded 29 negative results. Overall, our study showed that microscopic examination and PCR generated different results in detecting Plasmodium species, especially in patients with mixed infection and in patients who recently underwent DHP therapy.
The Role of AGN in Luminous Infrared Galaxies from the Multiwavelength Perspective
Authors: U Vivian
Published: July 2022

Galaxy mergers provide a mechanism for galaxies to effectively funnel gas and materials toward their nuclei and fuel the central starbursts and accretion of supermassive black holes. In turn, the active nuclei drive galactic-scale outflows that subsequently impact the evolution of the host galaxies. The details of this transformative process as they pertain to the supermassive black holes remain ambiguous, partially due to the central obscuration commonly found in the dust-reddened merger hosts, and also because there are relatively few laboratories in the nearby universe where the process can be studied in depth. This review highlights the current state of the literature on the role of accreting supermassive black holes in local luminous infrared galaxies as seen from various windows within the electromagnetic spectrum. Specifically, we discuss the multiwavelength signatures of the active nucleus, its associated feeding and feedback processes, and the implications of multiple supermassive black holes found in nearby interacting galaxy systems for galaxy evolution from the observational perspective. We conclude with a future outlook on how the topic of active nuclei in low- and high-redshift galaxy mergers will benefit from the advent of next-generation observing facilities with unparalleled resolving power and sensitivity in the coming decade.
Stringy Signals from Large-Angle Correlations in the Cosmic Microwave Background?
Authors: Sanchis-Lozano Miguel-Angel
Published: July 2022

We interpret the lack of large-angle temperature correlations and the even-odd parity imbalance observed in the cosmic microwave background (CMB) by COBE, WMAP and Planck satellite missions as a possible stringy signal ultimately stemming from a composite inflaton field (e.g., a fermionic condensate). Based on causality arguments and a Fourier analysis of the angular two-point correlation function, two infrared cutoffs kmineven,odd (satisfying kmineven≃2kminodd) are introduced to the CMB power spectrum associated, respectively, with periodic and antiperiodic boundary conditions of the fermionic constituents (echoing the Neveu–Schwarz–Ramond model in superstring theory), without resorting to any particular model.
Identification of Critical Genes and Pathways for Influenza A Virus Infections via Bioinformatics Analysis
Authors: Chen Gao , Li Haoyue , Hao Mingzhao , Li Xiaolei , Dong Yizhi , Zhang Yue , Liu Xiping , Lu Cheng , Zhao Jing
Published: July 2022

Influenza A virus (IAV) requires the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only reveals molecular pathways exploited by the virus or triggered by the immune system but also provides further targets for antiviral drug development. To uncover critical pathways and potential targets of influenza infection, we assembled a large amount of data from 8 RNA sequencing studies of IAV infection for integrative network analysis. Weighted gene co-expression network analysis (WGCNA) was performed to investigate modules and genes correlated with the time course of infection and/or multiplicity of infection (MOI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and pathways of the genes in 5 significant modules. Top hub genes were identified using the cytoHubba plugin in the protein interaction network. The correlation between expression levels of 7 top hub genes and time course or MOI was displayed and validated, including BCL2L13, PLSCR1, ARID5A, LMO2, NDRG4, HAP1, and CARD10. Dysregulated expression of these genes potently impacted the development of IAV infection through modulating IAV-related biological processes and pathways. This study provides further insights into the underlying molecular mechanisms and potential targets in IAV infection.
Cross-Species Analysis of Innate Immune Antagonism by Cytomegalovirus IE1 Protein
Authors: Rothemund Franziska , Scherer Myriam , Schilling Eva-Maria , Schweininger Johannes , Muller Yves A. , Stamminger Thomas
Published: July 2022

The human cytomegalovirus (CMV) immediate early 1 (IE1) protein has evolved as a multifunctional antagonist of intrinsic and innate immune mechanisms. In addition, this protein serves as a transactivator and potential genome maintenance protein. Recently, the crystal structures of the human and rat CMV IE1 (hIE1, rIE1) core domain were solved. Despite low sequence identity, the respective structures display a highly similar, all alpha-helical fold with distinct variations. To elucidate which activities of IE1 are either species-specific or conserved, this study aimed at a comparative analysis of hIE1 and rIE1 functions. To facilitate the quantitative evaluation of interactions between IE1 and cellular proteins, a sensitive NanoBRET assay was established. This confirmed the species-specific interaction of IE1 with the cellular restriction factor promyelocytic leukemia protein (PML) and with the DNA replication factor flap endonuclease 1 (FEN1). To characterize the respective binding surfaces, helix exchange mutants were generated by swapping hIE1 helices with the corresponding rIE1 helices. Interestingly, while all mutants were defective for PML binding, loss of FEN1 interaction was confined to the exchange of helices 1 and 2, suggesting that FEN1 binds to the stalk region of IE1. Furthermore, our data reveal that both hIE1 and rIE1 antagonize human STAT2; however, distinct regions of the respective viral proteins mediated the interaction. Finally, while PML, FEN1, and STAT2 binding were conserved between primate and rodent proteins, we detected that rIE1 lacks a chromatin tethering function suggesting that this activity is dispensable for rat CMV. In conclusion, our study revealed conserved and distinct functions of primate and rodent IE1 proteins, further supporting the concept that IE1 proteins underwent a narrow co-evolution with their respective hosts to maximize their efficacy in antagonizing innate immune mechanisms and supporting viral replication.
Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study
Authors: Moreno-Torres Víctor , de Mendoza Carmen , Mellor-Pita Susana , Martínez-Urbistondo María , Durán-del Campo Pedro , Tutor-Ureta Pablo , Vázquez-Comendador José-Manuel , Calderón-Parra Jorge , Múñez-Rubio Elena , Ramos-Martínez Antonio , Fernández-Cruz Ana , Castejón Raquel , Vargas-Nuñez Juan-Antonio
Published: July 2022

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren’s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet’s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78–1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04–1.07), heart failure (OR = 1.67, 95% CI 1.10–2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05–1.59) and liver disease (OR = 1.97, 95% CI 1.13–3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.
Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models
Authors: Gunder Laura C. , Blaine-Sauer Simon , Johnson Hillary R. , Shin Myeong-Kyun , Auyeung Andrew S. , Zhang Wei , Leverson Glen E. , Ward-Shaw Ella T. , King Renee E. , McGregor Stephanie M. , Matkowskyj Kristina A. , Lambert Paul F. , Carchman Evie H.
Published: July 2022

The artemisinin family of compounds is cytopathic in certain cancer cell lines that are positive for human papillomaviruses (HPV) and can potentially drive the regression of dysplastic lesions. We evaluated the efficacy of topical dihydroartemisinin (DHA) on cervical dysplasia and anal dysplasia in two papillomavirus mouse models: K14E6/E7 transgenic mice, which express HPV16 oncogenes; and immunodeficient NOD/SCID gamma (NSG) mice infected with Mus musculus papillomavirus (MmuPV1). Mice started treatment with DHA at 25 weeks of age (K14E6/E7) or 20 weeks post infection (MmuPV1-infected), when the majority of mice are known to have papillomavirus-induced low- to high-grade dysplasia. Mice were treated with or without topical DHA at the cervix or anus and with or without topical treatment with the chemical carcinogen 7,12 dimethylbenz(a)anthracene (DMBA) at the anus of in transgenic mice to induce neoplastic progression. Mice were monitored for overt tumor growth, and tissue was harvested after 20 weeks of treatment and scored for severity of histological disease. For MmuPV1-infected mice, anogenital lavages were taken to monitor for viral clearance. Tissues were also evaluated for viral gene expression at the RNA and/or protein levels. Treatment with topical DHA did not reduce dysplasia in the anogenital tract in either papillomavirus-induced mouse model and did not prevent progression to anal cancer in the DMBA-treated K14E6/E7 mice.
Evolutionary Dynamics of Foot and Mouth Disease Virus Serotype A and Its Endemic Sub-Lineage A/ASIA/Iran-05/SIS-13 in Pakistan
Authors: Naqvi Syeda Sumera , Bostan Nazish , Fukai Katsuhiko , Ali Qurban , Morioka Kazuki , Nishi Tatsuya , Abubakar Muhammad , Ahmed Zaheer , Sattar Sadia , Javed Sundus , Tariq Aamira , Sadiq Asma
Published: July 2022

Foot and mouth disease (FMD) causes severe economic losses to the livestock industry of endemic countries, including Pakistan. Pakistan is part of the endemic pool 3 for foot and mouth disease viruses (FMDV), characterized by co-circulating O, A, and Asia 1 serotypes, as designated by the world reference laboratory for FMD (WRL-FMD). FMDV serotype A lineage ASIA/Iran-05 is widespread in buffalos and cattle populations and was first reported in Pakistan in 2006. This lineage has a high turnover, with as many as 10 sub-lineages reported from Pakistan over the years. In this study, we reconstructed the evolutionary, demographic, and spatial history of serotype A and one of its sub-lineages, A/ASIA/Iran-05/SIS-13, prevalent in Pakistan. We sequenced nearly complete genomes of three isolates belonging to sub-lineage A/ASIA/Iran-05/SIS-13. We estimated recombination patterns and natural selection acting on the serotype A genomes. Source and transmission routes in Pakistan were inferred, and the clustering pattern of isolates of the SIS-13 sub-lineage were mapped on a tree. We hereby report nearly complete genome sequences of isolates belonging to sub-lineage A/ASIA/Iran-05/SIS-13, along with purported recombinant genomes, and highlight that complete coding sequences can better elucidate the endemic history and evolutionary pressures acting on long-term co-circulating FMDV strains.
Beyond Amyloid Fibers: Accumulation, Biological Relevance, and Regulation of Higher-Order Prion Architectures
Authors: Naeimi Wesley R. , Serio Tricia R.
Published: July 2022

The formation of amyloid fibers is associated with a diverse range of disease and phenotypic states. These amyloid fibers often assemble into multi-protofibril, high-order architectures in vivo and in vitro. Prion propagation in yeast, an amyloid-based process, represents an attractive model to explore the link between these aggregation states and the biological consequences of amyloid dynamics. Here, we integrate the current state of knowledge, highlight opportunities for further insight, and draw parallels to more complex systems in vitro. Evidence suggests that high-order fibril architectures are present ex vivo from disease relevant environments and under permissive conditions in vivo in yeast, including but not limited to those leading to prion formation or instability. The biological significance of these latter amyloid architectures or how they may be regulated is, however, complicated by inconsistent experimental conditions and analytical methods, although the Hsp70 chaperone Ssa1/2 is likely involved. Transition between assembly states could form a mechanistic basis to explain some confounding observations surrounding prion regulation but is limited by a lack of unified methodology to biophysically compare these assembly states. Future exciting experimental entryways may offer opportunities for further insight.
Collaborative Referral Model to Achieve Hepatitis C Micro-Elimination in Methadone Maintenance Treatment Patients during the COVID-19 Pandemic
Authors: Tai Chi-Ming , Huang Chun-Kai , Changchien Te-Chang , Lin Po-Chun , Wang Deng-Wu , Chang Ting-Ting , Chan Hsue-Wei , Chen Tzu-Haw , Tseng Cheng-Hao , Chen Chih-Cheng , Tsai Chia-Ta , Sie Yu-Ting , Yen Yung-Chieh , Yu Ming-Lung
Published: July 2022

Although hepatitis C virus (HCV) prevails in patients receiving methadone maintenance treatment (MMT), most do not receive anti-HCV therapy. This single-center observational study aimed to achieve HCV micro-elimination at an MMT center during the COVID-19 pandemic using a collaborative referral model, which comprised a referral-for-diagnosis stage (January 2020 to August 2020) and an on-site-diagnosis stage (September 2020 to January 2021). A multidisciplinary team was established and all MMT center patients were enrolled. HCV micro-elimination was defined as >90% of HCV-infected patients diagnosed and >80% of HCV-viremic patients treated. A total of 305 MMT patients, including 275 (90.2%) anti-HCV seropositive patients, were enrolled. Among 189 HCV-infected patients needing referral, the accumulative percentage receiving HCV RNA testing increased from 93 (49.2%) at referral-for-diagnosis stage to 168 (88.9%) at on-site-diagnosis stage. Among 138 HCV-viremic patients, the accumulative percentage receiving direct-acting antiviral (DAA) therapy increased from 77 (55.8%) at referral-for-diagnosis stage to 129 (93.5%) at on-site-diagnosis stage. We achieved an HCV RNA testing rate of 92.4% (254/275), an HCV treatment rate of 95.8% (203/212) and a sustained virological response rate of 94.1% (191/203). The collaborative referral model is highly effective in HCV RNA testing and HCV treatment uptake among MMT patients, achieving HCV micro-elimination.
Adenovirus 36 Infection in People Living with HIV—An Epidemiological Study of Seroprevalence and Associations with Cardiovascular Risk Factors
Authors: Sapuła Mariusz , Suchacz Magdalena , Kozłowska Joanna , Cybula Aneta , Siwak Ewa , Krankowska Dagny , Wiercińska-Drapało Alicja
Published: July 2022

Background. With the life expectancy of people living with HIV (PLHIV) rapidly approaching that of the general population, cardiovascular health in this group is as relevant as ever. Adenovirus 36 (Adv36) is one of the few viruses suspected to be a causative factor in promoting obesity in humans, yet there is a lack of data on this infection in PLHIV. Methods. PLHIV on stable suppressive antiretroviral therapy were included in the study, with assessment of anthropometric measures, blood pressure, serum lipid levels, fasting serum glucose and insulin, non-classical serum cardiovascular risk markers related to inflammation (hsCRP, resistin, calprotectin), and anti-Adv36 antibodies during a routine check-up. Results. 91 participants were recruited, of which 26.4% were Adv36-seropositive (Adv36(+)). Compared to Adv36-seronegative (Adv36(−)) controls, Adv36(+) individuals had a lower waist circumference (Adv36(+) 89.6 ± 7.7 cm, Adv36(−) 95.5 ± 11.7 cm, p = 0.024) and a lower waist-to-hip ratio (Adv36(+) 0.88 ± 0.06, Adv36(−) 0.92 ± 0.09, p = 0.014), but this did not reach statistical significance in the multivariate analysis (p > 0.05). Adv36(+) participants were less likely to be on lipid-lowering treatment (Adv36(+) 12.5%, Adv36(−) 34.3%, p = 0.042), even after adjustment for relevant baseline characteristics (OR = 0.23, 95%CI = 0.04–0.91), but no differences in cholesterol or triglyceride levels were found. No other statistically significant associations were observed. Conclusions. We found no evidence to support the claim that past Adv36-infection is associated with an increased prevalence of cardiovascular risk factors or with elevated inflammatory markers in PLHIV. More research is needed to replicate these findings in other samples of PLHIV and to compare them with the HIV-negative population.
The Role of Lebanon in the COVID-19 Butterfly Effect: The B.1.398 Example
Authors: Nour Dalal , Rafei Rayane , Lamarca Alessandra P. , de Almeida Luiz G. P. , Osman Marwan , Ismail Mohamad Bachar , Mallat Hassan , Berry Atika , Burfin Gwendolyne , Semanas Quentin , Josset Laurence , Hassan Hamad , Dabboussi Fouad , Lina Bruno , Colson Philippe , Vasconcelos Ana Tereza R. , Hamze Monzer
Published: July 2022

In the present study, we provide a retrospective genomic surveillance of the SARS-CoV-2 pandemic in Lebanon; we newly sequence the viral genomes of 200 nasopharyngeal samples collected between July 2020 and February 2021 from patients in different regions of Lebanon and from travelers crossing the Lebanese–Syrian border, and we also analyze the Lebanese genomic dataset available at GISAID. Our results show that SARS-CoV-2 infections in Lebanon during this period were shaped by the turnovers of four dominant SARS-CoV-2 lineages, with B.1.398 being the first to thoroughly dominate. Lebanon acted as a dispersal center of B.1.398 to other countries, with intercontinental transmissions being more common than within-continent. Within the country, the district of Tripoli, which was the source of 43% of the total B.1.398 sequences in our study, was identified as being an important source of dispersal in the country. In conclusion, our findings exemplify the butterfly effect, by which a lineage that emerges in a small area can be spread around the world, and highlight the potential role of developing countries in the emergence of new variants.
Six-Month Follow-Up of Immune Responses after a Rapid Mass Vaccination against SARS-CoV-2 with BNT162b2 in the District of Schwaz/Austria
Authors: Bánki Zoltán , Seekircher Lisa , Falkensammer Barbara , Bante David , Schäfer Helena , Harthaller Teresa , Kimpel Janine , Willeit Peter , von Laer Dorothee , Borena Wegene
Published: July 2022

In response to a large outbreak of the SARS-CoV-2 Beta (B.1.351) variant in the district Schwaz, Austria, a rapid mass vaccination campaign with BNT162b2 was carried out in spring 2021, immunizing more than 70% of the adult population within one week. Subsequent analysis revealed that the mass vaccination was associated with a significant reduction in new SARS-CoV-2 infections compared to control districts. Here, we aimed to evaluate both SARS-CoV-2-specific T- and B-cell responses at 35 ± 8 and 215 ± 7 days after the second dose in 600 study subjects who participated at both time points. Overall, a robust antibody and T-cell response was measured at day 35, which waned over time. Nevertheless, all persons preserved seropositivity and T cell response could still be detected in about half of the participants at day 215. Further, antibody response correlated negatively with age; however, in persons who experienced SARS-CoV-2 infection prior to study enrolment, the serum levels of both S- and N-specific antibodies surprisingly increased with age. In contrast, there was no correlation of T cell response with age. We could not detect any sex-related difference in the immune responses. SARS-CoV-2 infections prior to study enrolment or incident infections before day 215 resulted in higher antibody levels and T cell responses at day 215 compared to study participants with no history of infection. Collectively, our data support that vaccination with BNT162b2 against COVID-19 provides a durable immune response and emphasize the usefulness of vaccination even after a natural infection.
Simultaneous Isolation and Identification of Largemouth Bass Virus and Rhabdovirus from Moribund Largemouth Bass (Micropterus salmoides)
Authors: Jin Yuqi , Bergmann Sven M. , Mai Qianyi , Yang Ying , Liu Weiqiang , Sun Dongli , Chen Yanfeng , Yu Yingying , Liu Yuhong , Cai Wenlong , Dong Hanxu , Li Hua , Yu Hui , Wu Yali , Lai Mingjian , Zeng Weiwei
Published: July 2022

Largemouth bass is an important commercially farmed fish in China, but the rapid expansion of its breeding has resulted in increased incidence of diseases caused by bacteria, viruses and parasites. In this study, moribund largemouth bass containing ulcer foci on body surfaces indicated the most likely pathogens were iridovirus and rhabdovirus members and this was confirmed using a combination of immunohistochemistry, cell culture, electron microscopy and conserved gene sequence analysis. We identified that these fish had been co-infected with these viruses. We observed bullet-shaped virions (100–140 nm long and 50–100 nm in diameter) along with hexagonal virions with 140 nm diameters in cell culture inoculated with tissue homogenates. The viruses were plaque purified and a comparison of the highly conserved regions of the genome of these viruses indicated that they are most similar to largemouth bass virus (LMBV) and hybrid snakehead rhabdovirus (HSHRV), respectively. Regression infection experiments indicated fish mortalities for LMBV-FS2021 and HSHRV-MS2021 were 86.7 and 11.1%, respectively. While co-infection resulted in 93.3% mortality that was significantly (p < 0.05) higher than the single infections even though the viral loads differed by >100-fold. Overall, we simultaneously isolated and identified LMBV and a HSHRV-like virus from diseased largemouth bass, and our results can provide novel ideas for the prevention and treatment of combined virus infection especially in largemouth bass.
Myocardial Infarction Following COVID-19 Vaccine Administration: Post Hoc, Ergo Propter Hoc?
Authors: Baronti Arianna , Gentile Francesco , Manetti Alice Chiara , Scatena Andrea , Pellegrini Silvia , Pucci Angela , Franzini Maria , Castiglione Vincenzo , Maiese Aniello , Giannoni Alberto , Pistello Mauro , Emdin Michele , Aquaro Giovanni Donato , Di Paolo Marco
Published: July 2022

Vaccination against coronavirus disease 2019 (COVID-19) is the safest and most effective strategy for controlling the pandemic. However, some cases of acute cardiac events following vaccine administration have been reported, including myocarditis and myocardial infarction (MI). While post-vaccine myocarditis has been widely discussed, information about post-vaccine MI is scarce and heterogenous, often lacking in histopathological and pathophysiological details. We hereby present five cases (four men, mean age 64 years, range 50–76) of sudden death secondary to MI and tightly temporally related to COVID-19 vaccination. In each case, comprehensive macro- and microscopic pathological analyses were performed, including post-mortem cardiac magnetic resonance, to ascertain the cause of death. To investigate the pathophysiological determinants of MI, toxicological and tryptase analyses were performed, yielding negative results, while the absence of anti-platelet factor 4 antibodies ruled out vaccine-induced thrombotic thrombocytopenia. Finally, genetic testing disclosed that all subjects were carriers of at least one pro-thrombotic mutation. Although the presented cases do not allow us to establish any causative relation, they should foster further research to investigate the possible link between COVID-19 vaccination, pro-thrombotic genotypes, and acute cardiovascular events.
Robust Phylodynamic Analysis of Genetic Sequencing Data from Structured Populations
Authors: Scire Jérémie , Barido-Sottani Joëlle , Kühnert Denise , Vaughan Timothy G. , Stadler Tanja
Published: July 2022

The multi-type birth–death model with sampling is a phylodynamic model which enables the quantification of past population dynamics in structured populations based on phylogenetic trees. The BEAST 2 package bdmm implements an algorithm for numerically computing the probability density of a phylogenetic tree given the population dynamic parameters under this model. In the initial release of bdmm, analyses were computationally limited to trees consisting of up to approximately 250 genetic samples. We implemented important algorithmic changes to bdmm which dramatically increased the number of genetic samples that could be analyzed and which improved the numerical robustness and efficiency of the calculations. Including more samples led to the improved precision of parameter estimates, particularly for structured models with a high number of inferred parameters. Furthermore, we report on several model extensions to bdmm, inspired by properties common to empirical datasets. We applied this improved algorithm to two partly overlapping datasets of the Influenza A virus HA sequences sampled around the world—one with 500 samples and the other with only 175—for comparison. We report and compare the global migration patterns and seasonal dynamics inferred from each dataset. In this way, we show the information that is gained by analyzing the bigger dataset, which became possible with the presented algorithmic changes to bdmm. In summary, bdmm allows for the robust, faster, and more general phylodynamic inference of larger datasets.
Characterization of a Human Sapovirus Genotype GII.3 Strain Generated by a Reverse Genetics System: VP2 Is a Minor Structural Protein of the Virion
Authors: Li Tian-Cheng , Kataoka Michiyo , Doan Yen Hai , Saito Hiroyuki , Takagi Hirotaka , Muramatsu Masamichi , Oka Tomoichiro
Published: July 2022

We devised a reverse genetics system to generate an infectious human sapovirus (HuSaV) GII.3 virus. Capped/uncapped full-length RNAs derived from HuSaV GII.3 AK11 strain generated by in vitro transcription were used to transfect HuTu80 human duodenum carcinoma cells; infectious viruses were recovered from the capped RNA-transfected cells and passaged in the cells. Genome-wide analyses indicated no nucleotide sequence change in the virus genomes in the cell-culture supernatants recovered from the transfection or those from the subsequent infection. No virus growth was detected in the uncapped RNA-transfected cells, suggesting that the 5′-cap structure is essential for the virus’ generation and replication. Two types of virus particles were purified from the cell-culture supernatant. The complete particles were 39.2-nm-dia., at 1.350 g/cm3 density; the empty particles were 42.2-nm-dia. at 1.286 g/cm3. Two proteins (58-kDa p58 and 17-kDa p17) were detected from the purified particles; their molecular weight were similar to those of VP1 (~60-kDa) and VP2 (~16-kDa) of AK11 strain deduced from their amino acids (aa) sequences. Protein p58 interacted with HuSaV GII.3-VP1-specific antiserum, suggesting that p58 is HuSaV VP1. A total of 94 (57%) aa of p17 were identified by mass spectrometry; the sequences were identical to those of VP2, indicating that the p17 is the VP2 of AK11. Our new method produced infectious HuSaVs and demonstrated that VP2 is the minor protein of the virion, suggested to be involved in the HuSaV assembly.
Finding Asymptomatic Spreaders in a COVID-19 Transmission Network by Graph Attention Networks
Authors: Liu Zeyi , Ma Yang , Cheng Qing , Liu Zhong
Published: July 2022

In the COVID-19 epidemic the mildly symptomatic and asymptomatic infections generate a substantial portion of virus spread; these undetected individuals make it difficult to assess the effectiveness of preventive measures as most epidemic prevention strategies are based on the detected data. Effectively identifying the undetected infections in local transmission will be of great help in COVID-19 control. In this work, we propose an RNA virus transmission network representation model based on graph attention networks (RVTR); this model is constructed using the principle of natural language processing to learn the information of gene sequence and using a graph attention network to catch the topological character of COVID-19 transmission networks. Since SARS-CoV-2 will mutate when it spreads, our approach makes use of graph context loss function, which can reflect that the genetic sequence of infections with close spreading relation will be more similar than those with a long distance, to train our model. Our approach shows its ability to find asymptomatic spreaders both on simulated and real COVID-19 datasets and performs better when compared with other network representation and feature extraction methods.
Results of a European-Wide External Quality Assessment (EQA) Scheme for Serological Detection of Anti-SARS-CoV-2 (CoVimm)—Pitfalls of Routine Application
Authors: Kittel Maximilian , Eichner Romy , Aida Sihem , Bode Anna , Ast Volker , Kessler Anja , Neumaier Michael , Wölfel Roman , Haselmann Verena
Published: July 2022

Background: During the last two years, a variety of assays for the serological detection of antibodies to the new SARS-CoV-2 virus have been launched and used as part of standard care in many laboratories. The pace with which these tests have been introduced into routine care emphasizes the importance of quality measures for analytical methods, particularly with regard to the implications of results for clinical and epidemiologic decisions. Accuracy, reliability and comparability of analytical test results are thus essential, and here external quality assessment (EQA) is the most important quality assurance tool. It allows us to achieve harmonization of test methods as a prerequisite for a high standard of performance for laboratory and analytical techniques and their interpretation. Methods: This EQA scheme consisted of pre-characterized clinical biospecimens dedicated to the analysis of anti-SARS-CoV-2 IgG total antibodies and differentiation into spike protein-specific IgG antibodies against SARS-CoV-2 (anti-S-SARS-CoV-2) and nucleocapsid-specific IgG antibodies against SARS-CoV-2 (anti-N-SARS-CoV-2). Results: A total of 239 laboratories across Europe participated in this scheme, called CoVimm. In detail, 536 results for anti-SARS-CoV-2 IgG, 431 results for anti-S-SARS-CoV-2 IgG, and 200 results for anti-N-SARS-CoV-2 IgG were reported. Based on the pre-defined thresholds, the success rates for the determination of anti-S-SARS-CoV-2 IgG and anti-N-SARS-CoV-2 IgG were 96% and 90%, respectively. Interestingly, only 64% of the participating laboratories successfully passed the EQA scheme for the determination of total anti-SARS-CoV-2 IgG. Conclusions: This EQA revealed serious concerns regarding the reliability and appropriate use of anti-SARS-CoV-2 antibody assays in routine care. In addition to the wide heterogeneity of different assays used by participating laboratories, a lack of standardization and harmonization is also evident. This is of particular importance for reliable and clinically meaningful interpretation of test results.
Susceptibility of Type I Interferon Receptor Knock-Out Mice to Heartland Bandavirus (HRTV) Infection and Efficacy of Favipiravir and Ribavirin in the Treatment of the Mice Infected with HRTV
Authors: Fujii Hikaru , Tani Hideki , Egawa Kazutaka , Taniguchi Satoshi , Yoshikawa Tomoki , Fukushi Shuetsu , Yamada Souichi , Harada Shizuko , Kurosu Takeshi , Shimojima Masayuki , Maeki Takahiro , Lim Chang-Kweng , Takayama-Ito Mutsuyo , Komeno Takashi , Nakajima Nozomi , Furuta Yousuke , Uda Akihiko , Morikawa Shigeru , Saijo Masayuki
Published: July 2022

Heartland bandavirus (HRTV) is an emerging tick-borne virus that is distributed in the United States and that causes febrile illness with thrombocytopenia and leukocytopenia. It is genetically close to Dabie bandavirus, which is well known as severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV). The mortality rate of human HRTV infection is approximately 10%; however, neither approved anti-HRTV agents nor vaccines exist. An appropriate animal model should be developed to evaluate the efficacy of antiviral agents and vaccines against HRTV. The susceptibility of IFNAR−/− mice with HRTV infection was evaluated using subcutaneous, intraperitoneal, and retro-orbital inoculation routes. IFNAR−/− mice intraperitoneally infected with HRTV showed the most severe clinical signs, and the 50% lethal dose was 3.2 × 106 TCID50. Furthermore, to evaluate the utility of a novel lethal IFNAR−/− mice model, IFNAR−/− mice were orally administered favipiravir, ribavirin, or a solvent for 5 days immediately after a lethal dose of HRTV inoculation. The survival rates of the favipiravir-, ribavirin-, and solvent-administered mice were 100, 33, and 0%, respectively. The changes in bodyweights and HRTV RNA loads in the blood of favipiravir-treated IFNAR−/− mice were the lowest among the three groups, which suggests that favipiravir is a promising drug candidate for the treatment of patients with HRTV infection.