bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Botulinum Toxin Injection on EMG Activity and Bite Force in Masticatory Muscle Disorder: A Randomized Clinical Trial
Authors: Sitnikova Victoria , Kämppi Antti , Teronen Olli , Kemppainen Pentti
Published: August 2022

Botulinum toxin type A (BoNT-A) is increasingly used in treating masticatory muscle pain disorder; however, safe doses and reinjection intervals still need to be established. The purpose of this randomized clinical trial was to evaluate the degree and duration of the impairment of masticatory muscle performance. Fifty-seven subjects were randomly divided into two groups: one of which received BoNT-A first (n = 28) while the other received saline first (n = 29), with the cross-over being in week 16, and a total follow-up period of 32 weeks. A total dose of 50 U of BoNT-A was injected in the masseter and temporal muscles bilaterally. Electromyographic (EMG) activity and bite forces were assessed. A significant reduction in EMG activity was observed up to week 18 (p ≤ 001), with total recovery at week 33. A significant reduction in maximum bite force was observed up to week 11 (p ≤ 005), with total recovery at week 25. In conclusion, when treating masticatory muscle pain disorder with 50 U of BoNT-A, a reinjection interval of 33 weeks can be considered safe since the recovery of muscle function occurs by that time.
A Deacetylase CqSIRT1 Promotes WSSV Infection by Binding to Viral Envelope Proteins in Cherax quadricarinatus
Authors: Zheng Shucheng , Meng Fanjuan , Li Dongli , Liu Lingke , Ge Di , Wang Qing , Liu Haipeng
Published: August 2022

Sirtuin 1 (SIRT1), a member of the class III lysine deacetylases, exhibits powerful functional diversity in physiological processes and disease occurrences. However, the potential molecular mechanism underlying the role of SIRT1 during viral infection in crustaceans is poorly understood. Herein, SIRT1 was functionally characterized from the red claw crayfish Cherax quadricarinatus, which possesses typically conserved deacetylase domains and strong evolutionary relationships across various species. Moreover, gene knockdown of CqSIRT1 in crayfish haematopoietic tissue (Hpt) cell culture inhibited white spot syndrome virus (WSSV) late envelope gene vp28 transcription. In contrast, enhancement of deacetylase activity using a pharmacological activator promoted the replication of WSSV. Mechanically, CqSIRT1 was co-localized with viral envelope protein VP28 in the nuclei of Hpt cells and directly bound to VP28 with protein pulldown and co-immunoprecipitation assays. Furthermore, CqSIRT1 also interacted with another two viral envelope proteins, VP24 and VP26. To the best of our knowledge, this is the first report that WSSV structural proteins are linked to lysine deacetylases, providing a better understanding of the role of CqSIRT1 during WSSV infection and novel insights into the basic mechanism underlying the function of lysine deacetylases in crustaceans.
Construction of Attenuated Strains for Red-Spotted Grouper Nervous Necrosis Virus (RGNNV) via Reverse Genetic System
Authors: Lei Yingying , Xiong Yu , Tao Dagang , Wang Tao , Chen Tianlun , Du Xufei , Cao Gang , Tu Jiagang , Dai Jinxia
Published: August 2022

The nervous necrosis virus (NNV) mainly attacks the central nervous system of fish to cause viral nervous necrosis, which is an acute and serious prevalent disease in fish. Among different genotypes of NNV, red-spotted grouper nervous necrosis virus (RGNNV) is the most widely reported, with the highest number of susceptible species. To better understand the pathogenicity of RGNNV, we first developed a reverse genetic system for recombinant RGNNV rescue using B7GG and striped snakehead (SSN-1) cells. Furthermore, we constructed attenuated RGNNV strains rRGNNV-B2-M1 and rRGNNV-B2-M2 with the loss of B2 protein expression, which grew slower and induced less Mx1 expression than that of wild-type RGNNV. Moreover, rRGNNV-B2-M1 and rRGNNV-B2-M2 were less virulent than the wild-type RGNNV. Our study provides a potential tool for further research on the viral protein function, virulence pathogenesis, and vaccine development of RGNNV, which is also a template for the rescue of other fish viruses.
SARS-CoV-2 in a Mink Farm in Italy: Case Description, Molecular and Serological Diagnosis by Comparing Different Tests
Authors: Moreno Ana , Lelli Davide , Trogu Tiziana , Lavazza Antonio , Barbieri Ilaria , Boniotti MariaBeatrice , Pezzoni Giulia , Salogni Cristian , Giovannini Stefano , Alborali Giovanni , Bellini Silvia , Boldini Massimo , Farioli Marco , Ruocco Luigi , Bessi Olivia , Maroni Ponti Andrea , Di Bartolo Ilaria , De Sabato Luca , Vaccari Gabriele , Belli Gabriele , Margutti Alberto , Giorgi Maurilio
Published: August 2022

This study described a SARS-CoV-2 infection in minks on an Italian farm. Surveillance was performed based on clinical examination and a collection of 1879 swabs and 74 sera from dead and live animals. The farm was placed under surveillance for 4.5 months, from the end of July 2020, when a man working on the farm tested positive by RT-PCR, till mid-December 2020 when all the animals were sacrificed. Clinical examination revealed no clinical signs or increased mortality rates attributable to SARS-CoV-2, while diagnostic tests detected only four weak PCR-positive samples, but 100% of sera were positive for SARS-CoV-2 anti-S antibodies. The phylogenetic analysis of two SARS-CoV-2 sequences from two minks and the sequence of the worker showed that they belonged to different clades. It could be therefore assumed that two distinct introductions of the virus occurred on the farm, and that the first introduction probably occurred before the start of the surveillance period. From the data collected, and especially from the detection of specific antibodies through the combination of different tests, it can be postulated that syndromic surveillance combined with genome detection by PCR may not be sufficient to achieve a diagnosis in asymptomatic animals. In particular, the serological approach, especially when using tests directed towards the S protein, may be useful for improving the traceability of virus circulation in similar environments.
Antibody-Dependent Enhancement: ″Evil″ Antibodies Favorable for Viral Infections
Authors: Yang Xiaoke , Zhang Xin , Zhao Xiaotian , Yuan Mengqi , Zhang Kehui , Dai Jingwen , Guan Xiangyu , Qiu Hua-Ji , Li Yongfeng
Published: August 2022

The pandemics caused by emerging viruses such as severe acute respiratory syndrome coronavirus 2 result in severe disruptions to public health. Vaccines and antibody drugs play essential roles in the control and prevention of emerging infectious diseases. However, in contrast with the neutralizing antibodies (NAbs), sub- or non-NAbs may facilitate the virus to enter the cells and enhance viral infection, which is termed antibody-dependent enhancement (ADE). The ADE of most virus infections is mediated by the Fc receptors (FcRs) expressed on the myeloid cells, while others are developed by other mechanisms, such as complement receptor-mediated ADE. In this review, we comprehensively analyzed the characteristics of the viruses inducing FcRs-mediated ADE and the new molecular mechanisms of ADE involved in the virus entry, immune response, and transcription modulation, which will provide insights into viral pathogenicity and the development of safer vaccines and effective antibody drugs against the emerging viruses inducing ADE.
Long-Term Infection and Pathogenesis in a Novel Mouse Model of Human Respiratory Syncytial Virus
Authors: Xiong Rui , Fu Rui , Wu Yong , Wu Xi , Cao Yuan , Qu Zhe , Yang Yanwei , Liu Susu , Huo Guitao , Wang Sanlong , Huang Weijin , Lyu Jianjun , Zhu Xiang , Liang Chunnan , Peng Yihong , Wang Youchun , Fan Changfa
Published: August 2022

Intensive efforts have been made to develop models of hRSV infection or disease using various animals. However, the limitations such as semi-permissiveness and short duration of infection have impeded their applications in both the pathogenesis of hRSV and therapeutics development. Here, we present a mouse model based on a Rag2 gene knockout using CRISPR/Cas9 technology. Rag2−/− mice sustained high viral loads upon intranasal inoculation with hRSV. The average peak titer rapidly reached 1 × 109.8 copies/g and 1c106 TCID50 in nasal cavity, as well as 1 × 108 copies/g and 1 × 105 TCID50 in the lungs up to 5 weeks. Mild interstitial pneumonia, severe bronchopneumonia, elevated cytokines and NK cells were seen in Rag2−/− mice. A humanized monoclonal antibody showed strong antiviral activity in this animal model, implying that Rag2−/− mice that support long-term stable infection are a useful tool for studying the transmission and pathogenesis of human RSV, as well as evaluating therapeutics.
Outbreak of Middle East Respiratory Syndrome Coronavirus in Camels and Probable Spillover Infection to Humans in Kenya
Authors: Ngere Isaac , Hunsperger Elizabeth A. , Tong Suxiang , Oyugi Julius , Jaoko Walter , Harcourt Jennifer L. , Thornburg Natalie J. , Oyas Harry , Muturi Mathew , Osoro Eric M. , Gachohi John , Ombok Cynthia , Dawa Jeanette , Tao Ying , Zhang Jing , Mwasi Lydia , Ochieng Caroline , Mwatondo Athman , Bodha Boku , Langat Daniel , Herman-Roloff Amy , Njenga M. Kariuki , Widdowson Marc-Alain , Munyua Peninah M.
Published: August 2022

The majority of Kenya’s > 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0–24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April–September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya.
PEDV: Insights and Advances into Types, Function, Structure, and Receptor Recognition
Authors: Lin Feng , Zhang Huanyu , Li Linquan , Yang Yang , Zou Xiaodong , Chen Jiahuan , Tang Xiaochun
Published: August 2022

Porcine epidemic diarrhea virus (PEDV) has been endemic in most parts of the world since its emergence in the 1970s. It infects the small intestine and intestinal villous cells, spreads rapidly, and causes infectious intestinal disease characterized by vomiting, diarrhea, and dehydration, leading to high mortality in newborn piglets and causing massive economic losses to the pig industry. The entry of PEDV into cells is mediated by the binding of its spike protein (S protein) to a host cell receptor. Here, we review the structure of PEDV, its strains, and the structure and function of the S protein shared by coronaviruses, and summarize the progress of research on possible host cell receptors since the discovery of PEDV.
Elevated NETs and Calprotectin Levels after ChAdOx1 nCoV-19 Vaccination Correlate with the Severity of Side Effects
Authors: Hetland Geir , Fagerhol Magne Kristoffer , Wiedmann Markus Karl Hermann , Søraas Arne Vasli Lund , Mirlashari Mohammad Reza , Nissen-Meyer Lise Sofie Haug , Istre Mette Stausland , Holme Pål Andre , Schultz Nina Haagenrud
Published: August 2022

ChAdOx1 nCoV-19 vaccination has been associated with the rare side effect; vaccine-induced immune thrombotic thrombocytopenia (VITT). The mechanism of thrombosis in VITT is associated with high levels of neutrophil extracellular traps (NETs). The present study examines whether key markers for NETosis, such as H3-NETs and calprotectin, as well as syndecan-1 for endotheliopathy, can be used as prognostic factors to predict the severity of complications associated with ChAdOx1 vaccination. Five patients with VITT, 10 with prolonged symptoms and cutaneous hemorrhages but without VITT, and 15 with only brief and mild symptoms after the vaccination were examined. Levels of H3-NETs and calprotectin in the vaccinated individuals were markedly increased in VITT patients compared to vaccinees with milder vaccination-associated symptoms, and a strong correlation (r ≥ 0.745, p < 0.001) was found with severity of vaccination side effects. Syndecan-1 levels were also positively correlated (r = 0.590, p < 0.001) in vaccinees to side effects after ChAdOx1 nCoV-19 vaccination. We hypothesize that the inflammatory markers NETs and calprotectin may be used as confirmatory tests in diagnosing VITT.
Intensity of Humoral Immune Responses, Adverse Reactions, and Post-Vaccination Morbidity after Adenovirus Vector-Based and mRNA Anti-COVID-19 Vaccines
Authors: Voulgaridi Ioanna , Sarrou Styliani , Dadouli Aikaterini , Peristeri Athanasia-Marina , Nasika Asimina , Onoufriadis Ilias , Kyritsi Maria A. , Anagnostopoulos Lemonia , Theodoridou Aikaterini , Avakian Ioanna , Pappa Dimitra , Konstantinou Adamos-Konstantinos , Papadamou Georgia , Mouchtouri Varvara A. , Petinaki Efi , Speletas Matthaios , Hadjichristodoulou Christos
Published: August 2022

The aim of the study was to compare mRNA vaccine BNT162b2 with adenovirus vector- based vaccines in terms of presence of adverse reactions, immunogenicity, and protection against COVID-19. A total of 270 individuals were enrolled, of which 135 were vaccinated with adenovirus vector-based vaccines and compared with 135 age- and sex-matched participants who received the BNT162b2 mRNA vaccine. Serum sampling was performed on all participants on days 21, 42, 90, and 180 following the first dose, to evaluate anti-spike IgG and IgA responses. Antibodies were quantified by chemiluminescent microplate and ELISA assays. We demonstrate that both mRNA and adenovirus vector-based vaccines caused mild side-effects and were effective in inducing adequate antibody responses against SARS-CoV-2, although BNT162b2 was superior concerning the intensity of antibody responses and protection against severe COVID-19. Moreover, we identify that IgG and IgA responses depended primarily on both history of previous COVID-19 infection and vaccination platform used, with individuals immunized with a single-dose vaccine having lower antibody titers over time. Lastly, all vaccine platforms had limited side-effects, with the most frequent pain at the injection site. Our results provide useful information regarding antibody responses after vaccination with different vaccine platforms, which can be useful for public health vaccination strategies.
Are Fear of COVID-19 and Vaccine Hesitancy Associated with COVID-19 Vaccine Uptake? A Population-Based Online Survey in Nigeria
Authors: Chutiyami Muhammad , Salihu Dauda , Bello Umar Muhammad , Winser Stanley John , Gambo Amina Abdullahi , Sabo Hadiza , Kolo Adam Mustapha , Jalo Hussaina Abubakar , Muhammad Abdullahi Salisu , Mahmud Fatima Ado , Adeleye Khadijat Kofoworola , Azubuike Onyinye Mary , Bukola Ibitoye Mary , Kannan Priya
Published: August 2022

This study examined the association between COVID-19 and fear of contracting COVID-19 and reasons for vaccination refusal. A population-based online survey was conducted via social media in Nigeria using the Fear of COVID-19 scale and items related to vaccination refusal/hesitancy items. Individuals aged 13 years and older were invited to participate. Data were analysed using binary logistic regression to calculate odds ratios (ORs) and associated 95% confidence intervals (CIs) at a p-value of less than 0.05. The study enrolled 577 individuals with a mean age of 31.86 years, 70% of whom were male and 27.7% of whom had received at least one dose of the vaccine against COVID-19. None of the variables on the Fear of COVID-19 scale significantly predicted vaccine uptake in multivariate analysis. However, individuals who were fearful of COVID-19 were more likely to be vaccinated in bivariate analysis (OR: 1.7, 95% CI: 1.06–2.63). The most significant factors among the vaccination refusal items associated with COVID-19 vaccination were doubts about vaccination (adjusted OR: 2.56, 95% CI: 1.57–4.17) and misconceptions about vaccine safety/efficacy (adjusted OR: 2.15, 95% CI: 1.24–3.71). These results suggest that uptake of the vaccine against COVID-19 in Nigeria can be predicted by factors associated with vaccination refusal, but not by fear of COVID-19. To contain the pandemic COVID-19 in Nigeria, efforts should be made to educate people about the efficacy of the vaccine and to increase their confidence in vaccination.
Cervical Staphylococcus aureus Infection after Receiving the Third Dose of COVID-19 Vaccination: A Case Report
Authors: Li Tao , Zhang Hongqi , Wang Yuxiang , Wang Yunjia , Gao Qile , Tang Mingxing , Liu Shaohua , Zhang Gengming , Guo Chaofeng
Published: August 2022

Introduction: Vaccination is one of the most effective ways to control the COVID-19 pandemic. However, as the number of people vaccinated against COVID-19 continues to increase, there are more reports on the safety of vaccines. So far, there have been no reported cases of spinal infection associated with COVID-19 vaccination. Recently, we admitted a patient who developed cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine when the symptoms of cold did not completely disappear. Case presentation: The patient was a 70-year-old man who received the third injection of COVID-19 vaccine when the cold symptoms were not completely gone. On the day after the injection, the patient developed severe neck and shoulder pain, accompanied by numbness and fatigue in the limbs. MRI examination of the cervical spine on day 6 after vaccination showed no obvious signs of infection. The patient had progressive weakness in the extremities. On the ninth day after vaccination, the patient developed paralysis of both lower limbs and significant sensory loss. Cervical abscess and cervical spinal cord injury were considered for cervical CT and MRI examination on the 15th day after vaccination. We used an anterior approach to remove as much of the lesion as possible. Staphylococcus aureus was detected and antibiotic treatment was continued after surgery. The patient’s pain symptoms were significantly relieved, which prevented the abscess from further pressing the spinal cord and provided possible conditions for the recovery of neurological function in the later stage. Conclusion: This case is the first reported cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine with low immunity. This case raises awareness of this rare but potentially life-threatening adverse reaction, and reminds people to hold off when their immune system is weakened.
Association between Stroke Risk and Influenza Vaccination in Patients with Gout: A Nationwide Population-Based Study
Authors: Chen Chun-Chao , Chou Kuan-Ting , Liu Ju-Chi , Chiu Chun-Chih , Yang Tsung-Yeh , Lin Cheng-Hsin , Fang Yu-Ann , Jian William , Lei Meng-Huan , Yeh Hsien-Tang , Hsu Min-Huei , Hao Wen-Rui
Published: August 2022

The risk of stroke in patients with gout is high. The effect of vaccines in lowering the stroke risk in patients with gout remains unclear. We retrospectively analyzed 23,949 patients with gout (age ≥ 55 years) from the National Health Insurance Research Database over a 12-year period. The patients were divided into vaccinated (n = 11,649) and unvaccinated groups (n = 12,300). Overall, the vaccinated group had significantly lower risks of all stroke, hemorrhagic stroke, and ischemic stroke than the unvaccinated group (adjusted hazard ratio [aHR], 0.59 and 95% confidence interval [CI], 0.55–0.63; aHR, 0.60 and 95% CI, 0.49–0.73; and aHR, 0.60 and 95% CI, 0.55–0.65, respectively). The association appeared to be dose-dependent for both hemorrhagic and ischemic stroke (hemorrhagic stroke: aHR, 0.81 and 95% CI, 0.61–1.08; aHR, 0.80 and 95% CI, 0.62–1.02; and aHR, 0.37 and 95% CI, 0.28–0.48; ischemic stroke: aHR, 0.83 and 95% CI, 0.74–0.94; aHR, 0.73 and 95% CI, 0.65–0.81; and aHR, 0.42 and 95% CI, 0.38–0.47 for patients vaccinated 1, 2 or 3, and ≥4 times, respectively, during the follow-up period). Patients with a history of atrial fibrillation did not have a lower risk of hemorrhagic stroke even after receiving four vaccinations (aHR, 0.59; 95% CI, 0.25–1.38). Influenza vaccination was associated with a lower risk of all stroke in people with gout, and the association appeared to be dose-dependent.
High Seroprevalence of SARS-CoV-2 IgG and RNA among Asymptomatic Blood Donors in Makkah Region, Saudi Arabia
Authors: Alzabeedi Kamal H. , Makhlof Raafat T. M. , Bakri Rowaida A. , Ewis Ashraf A. , Alhamdi Heba W. , Habeebullah Turki M. A. , Khogeer Asim A. , Mulla Eman A. A. , Roshan Safiah A. M. , Qabbani Fadel H. , Hafez Fayez H. , Alqurashi Rehab G. , Babalghaith Muhammad O. , Ghouth Ahmad A. , Alhazmi Mohammed H. , Fallatah Othman M. , Badahdah Saeed A. , Endergiri Duaa I. A. , Albarakati Boshra M. , Abdelwahab Sayed F.
Published: August 2022

The gold-standard approach for diagnosing and confirming Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection is reverse transcription-polymerase chain reaction (RT-PCR). This method, however, is inefficient in detecting previous or dormant viral infections. The presence of antigen-specific antibodies is the fingerprint and cardinal sign for diagnosis and determination of exposure to infectious agents including Corona virus disease-2019 (COVID-19). This cross-sectional study examined the presence of SARS-CoV-2 spike-specific immunoglobulin G (IgG) among asymptomatic blood donors in Makkah region. A total of 4368 asymptomatic blood donors were enrolled. They were screened for spike-specific IgG using ELISA and COVID-19 RNA by real-time PCR. COVID-19 IgG was detected among 2248 subjects (51.5%) while COVID-19-RNA was detected among 473 (10.8%) subjects. The IgG frequency was significantly higher among males and non-Saudi residents (p < 0.001 each) with no significant variation in IgG positivity among blood donors with different blood groups. In addition, COVID-19 RNA frequency was significantly higher among donors below 40-years old (p = 0.047, χ2 = 3.95), and non-Saudi residents (p = 0.001, χ2 = 304.5). The COVID-19 IgG levels were significantly higher among the RNA-positive donors (p = 001), and non-Saudi residents (p = 0.041), with no variations with age or blood group (p > 0.05). This study reveals a very high prevalence of COVID-19 IgG and RNA among asymptomatic blood donors in Makkah, Saudi Arabia indicating a high exposure rate of the general population to COVID-19; particularly foreign residents. It sheds light on the spread on COVID-19 among apparently healthy individuals at the beginning of the pandemic and could help in designing various control measures to minimize viral spread.
Effectiveness of Booster Dose of Anti SARS-CoV-2 BNT162b2 in Cirrhosis: Longitudinal Evaluation of Humoral and Cellular Response
Authors: Giambra Vincenzo , Piazzolla Annarita Valeria , Cocomazzi Giovanna , Squillante Maria Maddalena , De Santis Elisabetta , Totti Beatrice , Cavorsi Chiara , Giuliani Francesco , Serra Nicola , Mangia Alessandra
Published: August 2022

Background: LC has been associated with hyporesponsiveness to several vaccines. Nonetheless, no data on complete serological and B- and T-cell immune response are currently available. Aims: To assess, in comparison with healthy controls of the same age and gender, both humoral and cellular immunoresponses of patients with LC after two or three doses of the mRNA Pfizer-BioNTech vaccine against SARS-CoV-2 and to investigate clinical features associated with non-response. Material and methods: 179 patients with LC of CTP class A in 93.3% and viral etiology in 70.1% of cases were longitudinally evaluated starting from the day before the first dose to 4 weeks after the booster dose. Their antibody responses were compared to those of healthcare workers without co-morbidities. In a subgroup of 40 patients, B- and T-cell responses were also compared to controls. Results: At d31, d90 and d180 after BNT162b2 vaccine, no detectable SARS-CoV-2 IgG response was observed in 5.9%, 3.9% and 7.2% of LC patients as compared to 0 controls (p < 0.03). A delay in B-cell and lack of prompt T-cell response compared to healthcare workers was also registered. A significant correlation between antibody titers and cellular response was observed. A MELD score > 8 was the only independent predictor of poor d31 response (p = 0.028). Conclusions: Our results suggest that cirrhotic patients have a slower and in <10% suboptimal immune response to SARS-CoV-2 vaccination. Rates of breakthrough infections were comparable between cirrhotics and controls. The booster dose was critical in inducing both humoral and cellular responses comparable to controls.
In Vitro Evaluation and Mitigation of Niclosamide’s Liabilities as a COVID-19 Treatment
Authors: Wotring Jesse W. , McCarty Sean M. , Shafiq Khadija , Zhang Charles J. , Nguyen Theophilus , Meyer Sophia R. , Fursmidt Reid , Mirabelli Carmen , Clasby Martin C. , Wobus Christiane E. , O’Meara Matthew J. , Sexton Jonathan Z.
Published: August 2022

Niclosamide, an FDA-approved oral anthelmintic drug, has broad biological activity including anticancer, antibacterial, and antiviral properties. Niclosamide has also been identified as a potent inhibitor of SARS-CoV-2 infection in vitro, generating interest in its use for the treatment or prevention of COVID-19. Unfortunately, there are several potential issues with using niclosamide for COVID-19, including low bioavailability, significant polypharmacology, high cellular toxicity, and unknown efficacy against emerging SARS-CoV-2 variants of concern. In this study, we used high-content imaging-based immunofluorescence assays in two different cell models to assess these limitations and evaluate the potential for using niclosamide as a COVID-19 antiviral. We show that despite promising preliminary reports, the antiviral efficacy of niclosamide overlaps with its cytotoxicity giving it a poor in vitro selectivity index for anti-SARS-CoV-2 inhibition. We also show that niclosamide has significantly variable potency against the different SARS-CoV-2 variants of concern and is most potent against variants with enhanced cell-to-cell spread including the B.1.1.7 (alpha) variant. Finally, we report the activity of 33 niclosamide analogs, several of which have reduced cytotoxicity and increased potency relative to niclosamide. A preliminary structure–activity relationship analysis reveals dependence on a protonophore for antiviral efficacy, which implicates nonspecific endolysosomal neutralization as a dominant mechanism of action. Further single-cell morphological profiling suggests niclosamide also inhibits viral entry and cell-to-cell spread by syncytia. Altogether, our results suggest that niclosamide is not an ideal candidate for the treatment of COVID-19, but that there is potential for developing improved analogs with higher clinical translational potential in the future.
Cost Effectiveness of Quadrivalent Versus Trivalent Inactivated Influenza Vaccines for the Portuguese Elderly Population
Authors: Tavares Diana , Mouriño Helena , Rodríguez Cristina Antón , Saborido Carlos Martín
Published: August 2022

Background: quadrivalent inactivated vaccine (QIV) has replaced trivalent inactivated vaccine (TIV). In Portugal, TIV is free of charge for risk groups, including older adults (≥65 years old). In its turn, QIV—which provides broader protection as it includes an additional lineage B strain—was introduced in Portugal in October 2018; only since the 2019/20 influenza season has it been provided free of charge for risk groups. This study evaluates the cost effectiveness of switching from TIV to QIV, from the National Health Service perspective, in the Portuguese elderly mainland population. Methods: A decision tree model was developed to compare TIV and QIV, based on Portuguese hospitalization data for the 2015/16 influenza season. The primary health economic outcome under consideration was the incremental cost-effectiveness ratio (ICER). In addition, one-way sensitivity analysis and probabilistic sensitivity analysis were performed. Results: the high cost of QIV (approximately three times the cost of TIV) would lead to a total increment of EUR 5,283,047, and the resulting ICER would be EUR 26,403,007/QALY, above the usual willingness-to-pay threshold. Conclusions: from the National Health Service perspective, our findings reveal that QIV is not cost effective for the Portuguese elderly population due to the high cost. If the QIV costs were the same as the TIV, then QIV would be cost effective.
Cross-Sectional Study of University Students’ Attitudes to ‘On Campus’ Delivery of COVID-19, MenACWY and MMR Vaccines and Future-Proofing Vaccine Roll-Out Strategies
Authors: Webb Adam , Gogoi Mayuri , Weidman Sarah , Woolf Katherine , Zavala Maria , Ladhani Shamez N. , Pareek Manish , Gies Lieve , Bayliss Christopher D.
Published: August 2022

University students are a critical group for vaccination programmes against COVID-19, meningococcal disease (MenACWY) and measles, mumps and rubella (MMR). We aimed to evaluate risk factors for vaccine hesitancy and views about on-campus vaccine delivery among university students. Data were obtained through a cross-sectional anonymous online questionnaire study of undergraduate students in June 2021 and analysed by univariate and multivariate tests to detect associations. Complete data were obtained from 827 participants (7.6% response-rate). Self-reporting of COVID-19 vaccine status indicated uptake by two-thirds (64%; 527/827), willing for 23% (194/827), refusal by 5% (40/827) and uncertain results for 8% (66/827). Hesitancy for COVID-19 vaccines was 5% (40/761). COVID-19 vaccine hesitancy was associated with Black ethnicity (aOR, 7.01, 95% CI, 1.8–27.3) and concerns about vaccine side-effects (aOR, 1.72; 95% CI, 1.23–2.39). Uncertainty about vaccine status was frequently observed for MMR (11%) and MenACWY (26%) vaccines. Campus-associated COVID-19 vaccine campaigns were favoured by UK-based students (definitely, 45%; somewhat, 16%) and UK-based international students (definitely, 62%; somewhat, 12%). Limitations of this study were use of use of a cross-sectional approach, self-selection of the response cohort, slight biases in the demographics and a strict definition of vaccine hesitancy. Vaccine hesitancy and uncertainty about vaccine status are concerns for effective vaccine programmes. Extending capabilities of digital platforms for accessing vaccine information and sector-wide implementation of on-campus vaccine delivery are strategies for improving vaccine uptake among students. Future studies of vaccine hesitancy among students should aim to extend our observations to student populations in a wider range of university settings and with broader definitions of vaccine hesitancy.
CCL28 Enhances HSV-2 gB-Specific Th1-Polarized Immune Responses against Lethal Vaginal Challenge in Mice
Authors: Yan Yan , Hu Kai , Fu Ming , Deng Xu , Guan Xinmeng , Luo Sukun , Zhang Mudan , Liu Yalan , Hu Qinxue
Published: August 2022

Plasmid DNA (pDNA) represents a promising “genetic vaccine platform” capable of overcoming major histocompatibility complex barriers. We previously demonstrated that low-to-moderate doses of mucosae-associated epithelial chemokine (MEC or CCL28) as an immunomodulatory adjuvant can trigger effective and long-lasting systemic and mucosal HSV-2 gD-specific immune responses, whereas mice immunized with gD in combination with high-dose CCL28 showed toxicity and lost their immunoprotective effects after lethal HSV-2 challenge. The exact causes underlying high-dose, CCL28-induced lesions remain unknown. In an intramuscularly immunized mouse model, we investigated the immune-enhancement mechanisms of low-dose CCL28 as a molecular adjuvant combined with the relatively weak immunogen HSV-2 gB. Compared with the plasmid gB antigen group, we found that a low-dose of plasmid CCL28 (pCCL28) codelivered with pgB induced increased levels of gB-specific serum IgG and vaginal fluid IgA, serum neutralizing antibodies (NAb), Th1-polarized IgG2a, and cytokine IL-2 (>5-fold). Furthermore, low-dose pCCL28 codelivery with pgB enhanced CCL28/CCR10-axis responsive CCR10− plus CCR10+ B-cell (~1.2-fold) and DC pools (~4-fold) in the spleen, CCR10− plus CCR10+ T-cell pools (~2-fold) in mesenteric lymph nodes (MLNs), and the levels of IgA-ASCs in colorectal mucosal tissues, leading to an improved protective effect against a lethal dose of HSV-2 challenge. Findings in this study provide a basis for the development of CCL28-adjuvant vaccines against viral mucosal infections.
Did Italy Really Need Compulsory Vaccination against COVID-19 for Healthcare Workers? Results of a Survey in a Centre for Maternal and Child Health
Authors: Peruch Michela , Toscani Paola , Grassi Nicoletta , Zamagni Giulia , Monasta Lorenzo , Radaelli Davide , Livieri Tommaso , Manfredi Alessandro , D’Errico Stefano
Published: August 2022

Since its early spread, the COVID-19 pandemic has become a health threat globally. Due to their crucial role in the pandemic, Italy declared compulsory vaccination for healthcare workers. Vaccine hesitancy was observed among the healthcare workers and an ethical debate arose about Italian legal statement D.L. n. 44/2021. In this article, we present the results of a survey performed in an Italian center for maternal and infant care and assess the attitudes towards the COVID-19 pandemic and the mandatory COVID-19 vaccination of healthcare workers. Since March 2022, 91.5% of healthcare workers have been vaccinated with an additional dose. Only 2.3% of the respondents refused to take vaccination: the reasons behind this refusal were distrust, doubts over safety, and lack of information. Despite the high rate of response to vaccination, 17.7% of HCWs did not agree with its mandatory nature. In addition, 5.4% stated that they agreed to be vaccinated exclusively because of the sanctions provided for by the legislation. In conclusion, adequate vaccination coverage has been achieved in the hospital under consideration. However, it is still very important to continue to persuade HCWs of vaccine efficacy and safety, considering their social role.
Dew Evaporation Amount and Its Influencing Factors in an Urban Ecosystem in Northeastern China
Authors: Xu Yingying , Jia Chenzhuo , Liu Hongzhao
Published: August 2022

Dew is an important water input and promotes plant growth. Dew condenses on plant leaves at night, and a portion of this dew returns to the atmosphere through evaporation. The amount of dew that evaporates is not equal to the amount of condensation; however, the dew evaporation process has not received enough attention. By monitoring the dew condensation and evaporation processes associated with four typical shrubs (Syringa, Hemiptelea, Buxus, and Cornus) in northeast China, we found that dew condensation started approximately 30 min after sunset, finished approximately 30 min before sunrise, and then turned to the evaporation phase. Dew had completely depleted approximately 4 h after sunrise. The dew evaporation period was negatively correlated with the wind speed (p < 0.01) and positively correlated with temperature, solar radiation, and relative humidity (RH) (p < 0.01). The average evaporation periods of Syringa, Buxus, Cornus, and Hemiptelea were 282 ± 21 min, 255 ± 26 min, 242 ± 22 min, and 229 ± 17 min, respectively. The daily evaporation amounts in May and September reached the minimum and maximum values, respectively, and the evaporation intensity of dew was positively correlated with RH (p < 0.01). There was no significant difference in the daily evaporation amounts of Syringa, Hemiptelea, Buxus, or Cornus (p > 0.05), and the annual evaporation amounts of these four plants were 17.05 mm/y, 16.38 mm/y, 21.94 mm/y, and 16.15 mm/y, respectively. The microstructure of leaves affected both the rate and amount of evaporation. Dew evaporated faster on hydrophilic leaves, and leaves with high trichome and stomatal densities had lower proportions of the dew evaporation amount to the condensation amount. The proportions of the dew evaporation amount to the condensation amount derived for Syringa, Hemiptelea, Buxus, and Cornus were 60.38%, 46.07%, 57.24%, and 52.81%, respectively. This study supplements our understanding of dew evaporation amounts, providing information that was missing in the near-surface hydrological cycle and aiding in the assessment of the ecological significance of dew to plants.
Spatiotemporal Evaluation of Blue and Green Water in Xinjiang River Basin Based on SWAT Model
Authors: Zhang Xudong , Jiang Cong , Huang Junzhe , Ni Zhenyu , Sun Jizhou , Li Zuzhong , Wen Tianfu
Published: August 2022

Poyang Lake is the largest freshwater lake in China. As an important tributary of Poyang Lake, Xinjiang River has an important influence on the water ecology and water resources of the Poyang Lake basin. Based on the hydrological simulation of the SWAT (Soil and Water Assessment Tool) model, the spatiotemporal distribution and evaluation of the blue and green water during the period (1982–2016) in the basin were explored by the Mann–Kendall test, precipitation anomaly percentage, and scenario simulation. It is found that the SWAT model presents a satisfactory performance in runoff simulation of the basin. The multi-year average blue water in the Xinjiang River basin is 1138 mm, and the green water is 829 mm, with a green water coefficient of 0.42. The amount of blue water in wet years is about 1.5 times that in normal years and 2.4 times that in dry years. Compared with the green water, the blue water of the basin is more sensitive to the variations in precipitation. In spatial distribution, the blue and green water in the middle of the basin is obviously more than those in other parts of the basin. During the study period, the blue water in the basin shows a slight decreasing trend, and the green water shows a significant decreasing trend. It is also found that climatic factors have a greater influence on the trend of blue and green water than land use, and the decrease in precipitation is the dominant cause for the trend of blue and green water.
Evaluation of TIGGE Precipitation Forecast and Its Applicability in Streamflow Predictions over a Mountain River Basin, China
Authors: Xiang Yiheng , Peng Tao , Gao Qi , Shen Tieyuan , Qi Haixia
Published: August 2022

The number of numerical weather prediction (NWP) models is on the rise, and they are commonly used for ensemble precipitation forecast (EPF) and ensemble streamflow prediction (ESP). This study evaluated the reliabilities of two well-behaved NWP centers in the Observing System Research and Predictability Experiment (THORPEX) Interactive Grand Global Ensemble (TIGGE), the European Centre for Medium-Range Weather Forecasts (ECMWF) and the National Centers for Environmental Prediction (NCEP), in EPF and ESP over a mountain river basin in China. This evaluation was carried out based on both deterministic and probabilistic metrics at a daily temporal scale. The effectiveness of two postprocessing methods, the Generator-based Postprocessing (GPP) method, and the Bayesian Model Averaging (BMA) method were also investigated for EPF and ESP. Results showed that: (1) The ECMWF shows better performances than NCEP in both EPF and ESP in terms of evaluation indexes and representation of the hydrograph. (2) The GPP method performs better than BMA in improving both EPF and ESP performances, and the improvements are more significant for the NCEP with worse raw performances. (3) Both ECMWF and NCEP have good potential for both EPF and ESP. By using the GPP method, there are desirable EPF performances for both ECMWF and NCEP at all 7 lead days, as well as highly skillful ECMWF ESP for 1~5 lead days and average moderate skillful NCEP ESP for all 7 lead days. The results of this study can provide a reference for the applications of TIGGE over mountain river basins.
Flash Flood Susceptibility Mapping in Sinai, Egypt Using Hydromorphic Data, Principal Component Analysis and Logistic Regression
Authors: El-Rawy Mustafa , Elsadek Wael M. , De Smedt Florimond
Published: August 2022

Flash floods in the Sinai often cause significant damage to infrastructure and even loss of life. In this study, the susceptibility to flash flooding is determined using hydro-morphometric characteristics of the catchments. Basins and their hydro-morphometric features are derived from a digital elevation model from NASA Earthdata. Principal component analysis is used to identify principal components with a clear physical meaning that explains most of the variation in the data. The probability of flash flooding is estimated by logistic regression using the principal components as predictors and by fitting the model to flash flood observations. The model prediction results are cross validated. The logistic model is used to classify Sinai basins into four classes: low, moderate, high and very high susceptibility to flash flooding. The map indicating the susceptibility to flash flooding in Sinai shows that the large basins in the mountain ranges of the southern Sinai have a very high susceptibility for flash flooding, several basins in the southwest Sinai have a high or moderate susceptibility to flash flooding, some sub-basins of wadi El-Arish in the center have a high susceptibility to flash flooding, while smaller to medium-sized basins in flatter areas in the center and north usually have a moderate or low susceptibility to flash flooding. These results are consistent with observations of flash floods that occurred in different regions of the Sinai and with the findings or predictions of other studies.
Major, Trace and Rare Earth Element Distribution in Water, Suspended Particulate Matter and Stream Sediments of the Ob River Mouth
Authors: Soromotin Andrei , Moskovchenko Dmitriy , Khoroshavin Vitaliy , Prikhodko Nikolay , Puzanov Alexander , Kirillov Vladimir , Koveshnikov Mikhail , Krylova Eugenia , Krasnenko Aleksander , Pechkin Aleksander
Published: August 2022

Ongoing climatic changes are influencing the volume and composition of the river waters that enter the Arctic Basin. This hydrochemical study was conducted within the mouth of the Ob River, which is one of the world’s largest rivers, providing 15% of the Arctic Ocean’s total intake. Concentrations of suspended and dissolved elements were determined using ICP–MS and ICP–AES. As compared to the world average values, the Ob river water had higher concentrations of dissolved P, As, Cu, Zn, Pb and Sb, i.e., the elements that form soluble organo-mineral complexes. The composition of suspended matter was characterized by low concentrations of most trace elements (Cd, Cr, Co, Cu, Mo, Al, Ni, Pb, V) due to their low contents in peat soils within the river drainage basin. Concentrations of dissolved forms were many times lower than concentrations of suspended forms in Al, Fe, Mn, Zn, Cr, Co, Ti, Sc, and all rare earth elements. Total concentrations of Ni, Cu, Bi, Pb, W in the river water increased by 2.5 to 4.2 times during the summer. The effects of climate change, which can cause an increase in the discharge of solid particles from thawing permafrost, are likely to lead to an increase in the discharge of certain elements into the Ob River estuary.
“Sea Anemone”-like CeFe Oxides for High-Efficient Phosphate Removal
Authors: Tan Xiaoying , Dong Pingping , Min Hongping , Luo Jinxue , Huang Wenhai , Wang Xiaodong , Li Qingqing , Fang Qile
Published: August 2022

The excessive release of phosphorus is a prime culprit for eutrophication and algal bloom in the aquatic environment, and there is always an urgent need to develop effective methods to deal with phosphorus pollution. Ce-based oxide is a type of compelling adsorbent for phosphate removal, and a self-templating strategy is used to construct high-performance Ce-based oxides for phosphate adsorption in this study. A “sea anemone”-like CeFe cyanometallate (CM) with a 3D microstructure is fabricated to provide a precursor for synthesizing CeFe-based oxides (CeFe-CM-T) by high-temperature pyrolysis. The as-prepared CeFe-CM-T maintains the “sea anemone” morphology well and has abundant micropores/mesopores, which render its superior phosphate adsorption capacity 1~2 orders of magnitude higher than that of the commercial CeO2 and Fe3O4 materials. Moreover, CeFe-CM-T shows high selectivity for phosphate removal when it co-exists with other anions and natural organic matter and exhibits excellent recycling performance. It demonstrates that both Ce3+ and Ce4+ are reserved in the oxides, where Ce3+ serves as the main active site for phosphate capture, which forms stable Ce-PO4 compounds via a ligand-exchange mechanism. Thus, the self-templating strategy using CM as a precursor is a potential method for synthesizing porous Ce-based oxides for phosphate removal.
Efficient Removal of Organic Matter from Biotreated Coking Wastewater by Coagulation Combined with Sludge-Based Activated Carbon Adsorption
Authors: Xia Yu , Li Weijia , He Xuwen , Liu Dannuo , Sun Yichen , Chang Jie , Liu Jing
Published: August 2022

Coagulation–adsorption can be effective in the removal of the organic matters remaining in biotreated coking wastewater (BTCW), and cheap and efficient adsorbents benefit the widespread application of this technology. In this study, a sludge-based activated carbon (SAC) was prepared using zinc chloride to activate sludge pyrolysis carbon for the treatment of BTCW with coagulation as the pretreatment process. According to Brunauer-Emmett-Teller (BET) and the scanning electron microscope (SEM) analysis, the SAC exhibited a specific surface area of 710.175 m2/g and well-developed pore structure. The removal characteristics of the organic matter in BTCW were systematically studied. The results show that 76.79% of the COD in the BTCW was removed by coagulation combined with SAC adsorption, and the effluent COD was below the discharge limit (80 mg/L) (GB16171-2012), with the optimal dosages of polyaluminum chloride and SAC being 150 mg/L and 4 g/L, respectively. Compared with a commercial powdered activated carbon (PAC) (48.26%), the SAC achieved a similar COD removal efficiency (47.74%) at a higher adsorption speed. The removal efficiencies of the hydrophobic components (77.27%) and fluorescent components by SAC adsorption were higher than those by PAC adsorption. The SAC also had an excellent removal effect on complex organic compounds and colored substances in the BTCW, as revealed by UV-vis spectra analyses.