bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation-Based Development of Gradient Woven Fabrics for Biomimetic Implants to Restore Tendons and Ligaments
Authors: Lang Tobias Georg , Nuß Dominik , Gereke Thomas , Hoffmann Gerald , Wöltje Michael , Aibibu Dilbar , Cherif Chokri
Published: June 2022

Tendons and ligaments are complex tissues that are necessary for human movement. Injuries occur very commonly and treatment quite often requires implants. Such implants must be adapted to the biological and structural composition of human tendons and ligaments. Thus, the objective is to realize graded, biomimetic tendon and ligament implants that are long-term resorbable. First, basic woven fabrics are fabricated from biocompatible silk fibroin yarns. Starting from the basic fabrics, gradient fabrics, with three different weave zones, are then developed and produced. In addition, fabrics with variable width and lateral warp yarn offset are fabricated on the basis of open reed weaving (ORW) technology on a modified shuttle narrow weaving loom. Meso-scale finite element models are developed in order to support the design of the gradient weaves. First, TexGen software is used to create a close to reality fabric geometry. Models are then converted into beam element models using a Python script. Results of real and virtual tensile tests show a clear relationship between the crimp of the warp yarns in the fabric structures and the resulting elongations. The additional ORW yarn system influences the stiffness. The tensile behavior of experiments and simulation agree very well, so the models are suitable for further development of woven implants.
Atypical Cognitive Impairment and Recovery in Two Colorectal Cancer Patients
Authors: Lee Hui Su , Jo Hwan Ho , Kim Ko Woon , Shin Byoung-Soo , Kang Hyun Goo
Published: June 2022

Cognitive impairment in cancer patients can be caused by various factors; in approximately 30% of cancer patients, the symptoms appear before starting treatment. Paraneoplastic limbic encephalitis (PLE) is a rare disease associated with an autoimmune response, and is characterized by memory loss, depression, and personality changes; it is one of the potential causes of cognitive dysfunction in cancer patients. Two patients were previously diagnosed with mild cognitive impairment and maintained clinical stability; after suffering a rapid change in personality and sudden cognitive decline, colorectal cancer was diagnosed within a few months. The patients did not meet the diagnostic criteria for PLE in several tests. The symptoms improved after the underlying cancer was treated, and the patients returned to their previous stable state. Sudden cognitive impairment may appear as an early cancer symptom, and PLE is considered an atypical cause for these symptoms. However, in patients with unexplained PLE-like symptoms who do not meet the diagnostic criteria for PLE, probable etiologies to be considered are the gut–brain connection, CD8+ T-cell-mediated limbic encephalitis, and somatic mutations in dementia-related genes. Currently, few studies have investigated these symptoms, and further research will offer significant therapeutic strategies for cognitive impairment in cancer patients.
Dynamic Contrast Enhanced Study in Multiparametric Examination of the Prostate—Can We Make Better Use of It?
Authors: Guljaš Silva , Benšić Mirta , Krivdić Dupan Zdravka , Pavlović Oliver , Krajina Vinko , Pavoković Deni , Šmit Takač Petra , Hranić Matija , Salha Tamer
Published: June 2022

We sought to investigate whether quantitative parameters from a dynamic contrast-enhanced study can be used to differentiate cancer from normal tissue and to determine a cut-off value of specific parameters that can predict malignancy more accurately, compared to the obturator internus muscle as a reference tissue. This retrospective study included 56 patients with biopsy proven prostate cancer (PCa) after multiparametric magnetic resonance imaging (mpMRI), with a total of 70 lesions; 39 were located in the peripheral zone, and 31 in the transition zone. The quantitative parameters for all patients were calculated in the detected lesion, morphologically normal prostate tissue and the obturator internus muscle. Increase in the Ktrans value was determined in lesion-to-muscle ratio by 3.974368, which is a cut-off value to differentiate between prostate cancer and normal prostate tissue, with specificity of 72.86% and sensitivity of 91.43%. We introduced a model to detect prostate cancer that combines Ktrans lesion-to-muscle ratio value and iAUC lesion-to-muscle ratio value, which is of higher accuracy compared to individual variables. Based on this model, we identified the optimal cut-off value with 100% sensitivity and 64.28% specificity. The use of quantitative DCE pharmacokinetic parameters compared to the obturator internus muscle as reference tissue leads to higher diagnostic accuracy for prostate cancer detection.
Visual Evaluation of Ultrafast MRI in the Assessment of Residual Breast Cancer after Neoadjuvant Systemic Therapy: A Preliminary Study Association with Subtype
Authors: Honda Maya , Kataoka Masako , Iima Mami , Ota Rie , Ohashi Akane , Kishimoto Ayami Ohno , Miyake Kanae Kawai , Nickel Marcel Dominik , Yamada Yosuke , Toi Masakazu , Nakamoto Yuji
Published: June 2022

The purpose of this study was to investigate the diagnostic performance of ultrafast DCE (UF-DCE) MRI after the completion of neoadjuvant systemic therapy (NST) in breast cancer. In this study, MR examinations of 55 post-NST breast cancers were retrospectively analyzed. Residual tumor sizes were measured in the 20th phase of UF-DCE MRI, early and delayed phases of conventional DCE MRI, and high spatial-resolution CE MRI (UF, early, delayed, and HR, respectively). The diagnostic performance for the detection of residual invasive cancer was calculated by ROC analysis. The size difference between MRI and pathological findings was analyzed using the Wilcoxon signed-rank test with the Bonferroni correction. The overall AUC was highest for UF (0.86 and 0.88 for readers 1 and 2, respectively). The difference in imaging and pathological sizes for UF (5.7 ± 8.2 mm) was significantly smaller than those for early, delayed, and HR (p < 0.01). For luminal subtype breast cancer, the size difference was significantly smaller for UF and early than for delayed (p < 0.01). UF-DCE MRI demonstrated higher AUC and specificity for the more accurate detection of residual cancer and the visualization of tumor extent than conventional DCE MRI.
Copper Monitoring in Vineyard Soils of Central Italy Subjected to Three Antifungal Treatments, and Effects of Sub-Lethal Copper Doses on the Earthworm Eisenia fetida
Authors: De Bernardi Arianna , Marini Enrica , Casucci Cristiano , Tiano Luca , Marcheggiani Fabio , Vischetti Costantino
Published: June 2022

The extensive employment of copper-based fungicides has increased copper concentration in vineyard soils. The present study’s objectives were to monitor copper concentration in two vineyard soils during two cropping seasons and study the ecotoxicological effects on the earthworm Eisenia fetida. Total, soluble, and bioavailable copper fractions were measured at the end of two cropping seasons and different depths in two vineyards of central Italy, characterised by three anticryptogamic control methods: copper compounds, chitosan, and combined treatments of them. A laboratory experiment to assess the effects on Eisenia fetida was conducted with soil samples collected in the vineyards with a mean copper concentration of 60 mg/kg and two higher concentrations of 90 and 150 mg/kg. Results showed low levels of total copper concentration in the first 20 cm of soils, regardless of antifungal treatment, highlighting prudent management of the vineyards under study, but the soluble fractions showed a significant increase in all samples during the two cropping seasons. At the dose of 150 mg/kg, earthworms suffer during the first two days, showing weight loss and DNA damage, but they are able to recover until day 28, showing no permanent harm at this copper concentration in soil.
Environmental Chemicals: Integrative Approach to Human Biomonitoring and Health Effects
Authors: Fernandes Virgínia Cruz , Pestana Diogo
Published: June 2022

In recent decades, citizen awareness of toxic chemicals has been a topic of interest, particularly concerning national and international policy decision makers, expert/scientific platforms, and health protection organizations (WHO, UNEP, CDC, EFSA, IPEN, etc [...]
Suicidal Behavior and Its Relationship with Postmortem Forensic Toxicological Findings
Authors: Collados-Ros Aurelia , Torres-Sánchez Carmen , Pérez-Cárceles María Dolores , Luna Aurelio , Legaz Isabel
Published: June 2022

Suicide affects all sociodemographic levels, age groups, and populations worldwide. The factors that can increase the risk of suicidal tendencies are widely studied. The aim of this study was to analyze the types and combinations of toxics found in fatal suicide victims with different suicide mechanisms. A total of 355 autopsies were retrospectively studied, and 26 toxics were determined and related to mechanisms of suicide. Hanging (55%), drug overdose (22.7%), and jumping from a height (17.8%) were most represented suicide mechanisms with positive toxicology. Hanging was the most represented in men (50.3%; p = 0.019), while jumping from a height was more represented in women (29.7%, p = 0.028). Drugs of abuse were the most frequent toxics found in men (55.5%; p < 0.001), while medicines were the most frequent type found in women (70.3%, p < 0.001). Alcohol, nordiazepam, cocaine, and venlafaxine were the most consumed toxics. Benzodiazepines and venlafaxine were found in suicides involving drug overdose, hanging, and jumping from a height. In conclusion, most suicides were associated with drug abuse in men. Hanging was more represented in men and jumping from a height in women. Alcohol was present in combination with other toxics and medicines. The toxicological analysis is fundamental to understanding consumption patterns and establishing strategies and protocols for detecting and preventing suicide.
Operational Gaps in Implementing the COVID-19 Case Investigation and Contact Tracing in Madhesh Province of Nepal, May–July 2021
Authors: Thakur Nishant , Vogt Florian , Satyanarayana Srinath , Nair Divya , Garu Krishna , Subedee Koshal Chandra , Mandal Shrawan Kumar , Pokhrel Amrit , Gautam Dipendra , Paudel Krishna Prasad
Published: June 2022

In Nepal, case investigation and contact tracing (CICT) was adopted as an important public health measure to reduce COVID-19 transmission. In this study, we assessed the performance of CICT in Madhesh Province of Nepal against national benchmarks, using routine programmatic data reported by district CICT teams. Between May and July 2021, 17,943 COVID-19 cases were declared in the province, among which case investigation was performed for 30% (95% CI: 29.6–31.0%) within 24 h (against 80% benchmark). As a result of case investigations, 6067 contacts were identified (3 contacts per 10 cases), of which 40% were traced and tested for SARS-CoV-2 infection (against 100% benchmark). About 60% of the contacts tested positive. At most 14% (95% CI: 13.1% to 14.9%) of traced contacts underwent a 14-day follow-up assessment (against 100% benchmark). We found the performance of the CICT program in Madhesh Province to be sub-optimal and call for corrective measures to strengthen CICT in the province and the country at large. Similar studies with wider geographical scope and longer time frames are needed to identify and address deficiencies in data recording and reporting systems for COVID-19, in low- and middle-income countries like Nepal and others.
COVID-19 Amongst Travelers at Points of Entry in Nepal: Screening, Testing, Diagnosis and Isolation Practices
Authors: Subedee Koshal Chandra , Paudel Krishna Prasad , Khogali Mohammed , Pokhrel Amrit , Chinnakali Palanivel , Thakur Nishant , Timsina Deepak , Gautam Rabin , Rahman Anisur , Mandal Shrawan Kumar , Adhikari Mahendra Dhose , Harries Anthony D.
Published: June 2022

WHO recommends surveillance for COVID-19 among travelers at Points of Entry (POE) to countries. At 13 selected POE at the Nepal-India border, between March 2021 and July 2021, we describe the screening, testing, diagnosis and isolation practices of COVID-19 amongst travelers. Those who stayed in India or elsewhere for > one day and those who did not have a negative RT-PCR result within the last 72 h of travel were tested for COVID-19 with rapid antigen diagnostic tests. Daily surveillance reports maintained at POE were used for analysis. Of 337,338 travelers screened, 69,886 (21%) were tested and 3907 (6%) were diagnosed with COVID-19. The proportions tested averaged 15% during April-May when screened numbers were high and increased to 35% in July when screened numbers had decreased. The proportions diagnosed positive peaked at 10% in April-May, but decreased to below 1% in June and July. Testing coverage varied from 0–99% in the different POE. Most COVID-19 cases were Nepalese, male, <60 years of age, migrant workers and presented with fever. Of COVID-19 cases, 32% had home-based isolation, 64% underwent community-based isolation and the remainder either went to hospital or returned to India. In conclusion, about one fifth of travelers overall were tested, with coverage varying considerably over time and among different POE. Strengthening surveillance processes at POE is needed.
Microbiological Characterisation of Community-Acquired Urinary Tract Infections in Bagamoyo, Tanzania: A Prospective Study
Authors: Schmider Joseph , Bühler Nina , Mkwatta Hasina , Lechleiter Anna , Mlaganile Tarsis , Utzinger Jürg , Mzee Tutu , Kazimoto Theckla , Becker Sören
Published: June 2022

Urinary tract infections (UTIs) are among the most common infections in sub-Saharan Africa, but microbiological data to guide treatment decisions are limited. Hence, we investigated the bacterial aetiology and corresponding antimicrobial susceptibility patterns in outpatients with UTIs in Bagamoyo, Tanzania. Urine samples from symptomatic individuals were subjected to microbiological examinations for bacterial species identification using conventional methods and disc diffusion-based resistance testing. Subsequently, urine samples were transferred to Germany for confirmatory diagnostics using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and automated resistance testing. Overall, 104 out of 270 (38.5%) individuals had a positive urine culture and 119 putative pathogens were identified. The most frequently detected bacteria were Escherichia coli (23%), Klebsiella spp. (7%), Enterobacter cloacae complex (3%) and Staphylococcus aureus (2%). E. coli isolates showed high resistance against cotrimoxazole (76%), ampicillin (74%), piperacillin (74%) and fluoroquinolones (37%), but widespread susceptibility to meropenem (100%), fosfomycin (98%), piperacillin/tazobactam (97%) and amoxicillin/clavulanic acid (82%). The agreement between E. coli susceptibility testing results in Tanzania and Germany was ≥95%, except for piperacillin/tazobactam (89%) and ciprofloxacin (84%). Given the considerable resistance to frequently prescribed antibiotics, such as cotrimoxazole and fluoroquinolones, future research should explore the potential of oral alternatives (e.g., fosfomycin) for the treatment of UTIs in Tanzania.
Spatio-Temporal Responses of Precipitation to Urbanization with Google Earth Engine: A Case Study for Lagos, Nigeria
Authors: Molla Alamin , Di Liping , Guo Liying , Zhang Chen , Chen Fei
Published: June 2022

Lagos, Nigeria, is considered a rapidly growing urban hub. This study focuses on an urban development characterization with remote sensing-based variables for Lagos as well as understanding spatio-temporal precipitation responses to the changing intensity of urban development. Initially, a harmonic analysis showed an increase in yearly precipitation of about 3 mm from 1992 to 2018 for the lower bound of the fitted curve and about 2 mm for the upper bound. The yearly total precipitation revealed no significant trend based on the Mann–Kendall trend test. Subsequent analyses first involved characterizing urbanization based on nighttime light and population density data and then combined them together for the final analysis. Each time, the study area was subdivided into four zones: Zone 0, Zone 1, Zone 2, and Zone 3, which refer to non-urbanized, low-urbanized, mid-urbanized, and highly urbanized regions, respectively. The results from the Google Earth Engine-based analysis uncovered that only Zone 1 has a statistical monotonic increasing precipitation trend (Tau 0.29) with a 0.03 significance level when the combined criteria were applied. There is about a 200 mm precipitation increase in Zone 1. Insignificant patterns for the other three zones (Zone 2, Zone 3, and Zone 4) indicate that these trends are not consistent, they might change over time, and fluctuate heavily.
Antibody Response Induced by BNT162b2 and mRNA-1273 Vaccines against the SARS-CoV-2 in a Cohort of Healthcare Workers
Authors: Delgado Juan F. , Berenguer-Llergo Antoni , Julià Germà , Navarro Gema , Espasa Mateu , Rodríguez Sara , Sánchez Noemí , Van Den Eynde Eva , Navarro Marta , Calvet Joan , Gratacós Jordi , Serrano Rosa M. , Peña Pilar , Amengual María J.
Published: June 2022

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.
Recombination in Coronaviruses, with a Focus on SARS-CoV-2
Authors: Focosi Daniele , Maggi Fabrizio
Published: June 2022

Recombination is a common evolutionary tool for RNA viruses, and coronaviruses are no exception. We review here the evidence for recombination in SARS-CoV-2 and reconcile nomenclature for recombinants, discuss their origin and fitness, and speculate how recombinants could make a difference in the future of the COVID-19 pandemics.
Serum Neutralizing and Enhancing Effects on African Swine Fever Virus Infectivity in Adherent Pig PBMC
Authors: Canter Jessica A. , Aponte Theresa , Ramirez-Medina Elizabeth , Pruitt Sarah , Gladue Douglas P. , Borca Manuel V. , Zhu James J.
Published: June 2022

African swine fever virus (ASFV) causes hemorrhagic fever with mortality rates of up to 100% in domestic pigs. Currently, there are no commercial vaccines for the disease. Only some live-attenuated viruses have been able to protect pigs from ASFV infection. The immune mechanisms involved in the protection are unclear. Immune sera can neutralize ASFV but incompletely. The mechanisms involved are not fully understood. Currently, there is no standardized protocol for ASFV neutralization assays. In this study, a flow cytometry-based ASFV neutralization assay was developed and tested in pig adherent PBMC using a virulent ASFV containing a fluorescent protein gene as a substrate for neutralization. As with previous studies, the percentage of infected macrophages was approximately five time higher than that of infected monocytes, and nearly all infected cells displayed no staining with anti-CD16 antibodies. Sera from naïve pigs and pigs immunized with a live-attenuated ASFV and fully protected against parental virus were used in the assay. The sera displayed incomplete neutralization with MOI-dependent neutralizing efficacies. Extracellular, but not intracellular, virions suspended in naïve serum were more infectious than those in the culture medium, as reported for some enveloped viruses, suggesting a novel mechanism of ASFV infection in macrophages. Both the intracellular and extracellular virions could not be completely neutralized.
Structural Plasticity and Immune Evasion of SARS-CoV-2 Spike Variants
Authors: Ghimire Dibya , Han Yang , Lu Maolin
Published: June 2022

The global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly affected every human life and overloaded the health care system worldwide. Limited therapeutic options combined with the consecutive waves of the infection and emergence of novel SARS-CoV-2 variants, especially variants of concern (VOCs), have prolonged the COVID-19 pandemic and challenged its control. The Spike (S) protein on the surface of SARS-CoV-2 is the primary target exposed to the host and essential for virus entry into cells. The parental (Wuhan-Hu-1 or USA/WA1 strain) S protein is the virus-specific component of currently implemented vaccines. However, S is most prone to mutations, potentially shifting the dynamics of virus-host interactions by affecting S conformational/structural profiles. Scientists have rapidly resolved atomic structures of S VOCs and elucidated molecular details of these mutations, which can inform the design of S-directed novel therapeutics and broadly protective vaccines. Here, we discuss recent findings on S-associated virus transmissibility and immune evasion of SARS-CoV-2 VOCs and experimental approaches used to profile these properties. We summarize the structural studies that document the structural flexibility/plasticity of S VOCs and the potential roles of accumulated mutations on S structures and functions. We focus on the molecular interpretation of structures of the S variants and its insights into the molecular mechanism underlying antibody evasion and host cell-receptor binding.
High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19
Authors: Cords Leon , Knapp Maximilian , Woost Robin , Schulte Sophia , Kummer Silke , Ackermann Christin , Beisel Claudia , Peine Sven , Johansson Alexandra Märta , Kwok William Wai-Hung , Günther Thomas , Fischer Nicole , Wittner Melanie , Addo Marylyn Martina , Huber Samuel , Schulze zur Wiesch Julian
Published: June 2022

Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145–164) epitope-specific CD4+ T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class II DRB1*11:01 Tetramer analysis. We detected a high and stable SARS-CoV-2 membrane-specific CD4+ T-cell response in both patients, with higher frequencies of virus-specific CD4+ T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4+ T-cell memory phenotype in the B-cell-depleted patient that was skewed towards late differentiated memory T-cells, as well as reduced frequencies of SARS-CoV-2-specific CD4+ T-cells with CD45RA− CXCR5+ PD-1+ circulating T follicular helper cell (cTFH) phenotype. Furthermore, we observed a delayed contraction of CD127− virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4+ T-cells of the patient, but were associated with the inflammation markers IL-6 and CRP. Our findings indicate that, despite B-cell depletion and a lack of B-cell—T-cell interaction, a robust virus-specific CD4+ T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection.
Mechanism of Viral Suppression among HIV Elite Controllers and Long-Term Nonprogressors in Nigeria and South Africa
Authors: Ahmed Rahaman Ademolu , Adekoya Khalid Olajide , Onwuamah Chika Kingsley , Oboh Bolanle Olufunmilayo , Iyer Smita Swaminathan , Oluwatosin Ayomide Samuel , Audu Rosemary Ajuma , Ezechi Oliver Chukwujekwu
Published: June 2022

A subgroup among people living with HIV (PLHIV) experience viral suppression, sometimes to an undetectable level in the blood and/or are able to maintain a healthy CD4+ T-cell count without the influence of antiretroviral (ARV) therapy. One out of three hundred PLHIV fall into this category, and a large sample of this group can be found in areas with a high prevalence of HIV infection such as Nigeria and South Africa. Understanding the mechanism underpinning the nonprogressive phenotype in this subgroup may provide insights into the control of the global HIV epidemic. This work provides mechanisms of the elite control and nonprogressive phenotype among PLHIV in Nigeria and South Africa and identifies research gaps that will contribute to a better understanding on HIV controllers among PLHIV.
Nucleopore Traffic Is Hindered by SARS-CoV-2 ORF6 Protein to Efficiently Suppress IFN-β and IL-6 Secretion
Authors: Gori Savellini Gianni , Anichini Gabriele , Gandolfo Claudia , Cusi Maria Grazia
Published: June 2022

A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins that are able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical outcomes. Previous reports demonstrated that the SARS-CoV-2 ORF6 protein strongly suppresses INF-β production by hindering the RIG-I, MDA-5, and MAVS signaling cascade. In the present study, we better characterized the mechanism by which the SARS-CoV-2 ORF6 counteracts IFN-β and interleukin-6 (IL-6), which plays a crucial role in the inflammation process associated with the viral infection. In the present study, we demonstrated that the SARS-CoV-2 ORF6 protein has evolved an alternative mechanism to guarantee host IFN-β and IL-6 suppression, in addition to the transcriptional control exerted on the genes. Indeed, a block in movement through the nucleopore of newly synthetized messenger RNA encoding the immune-modulatory cytokines IFN-β and IL-6 are reported here. The ORF6 accessory protein of SARS-CoV-2 displays a multifunctional activity and may represent one of the most important virulence factors. Where conventional antagonistic strategies of immune evasion—such as the suppression of specific transcription factors (e.g., IRF-3, STAT-1/2)—would not be sufficient, the SARS-CoV-2 ORF6 protein is the trump card for the virus, also blocking the movement of IFN-β and IL-6 mRNAs from nucleus to cytoplasm. Conversely, we showed that nuclear translocation of the NF-κB transcription factor is not affected by the ORF6 protein, although inhibition of its cytoplasmic activation occurred. Therefore, the ORF6 protein exerts a 360-degree inhibition of the antiviral response by blocking as many critical points as possible.
Infectious Aerosol Capture Mask as Environmental Control to Reduce Spread of Respiratory Viral Particles
Authors: Santarpia Joshua L. , Markin Nicholas W. , Herrera Vicki L. , Ackerman Daniel N. , Rivera Danielle N. , Lucero Gabriel A. , Lisco Steven J.
Published: June 2022

Negative pressure isolation of COVID-19 patients is critical to limiting the nosocomial transmission of SARS-CoV-2; however, airborne isolation rooms are limited. Alternatives to traditional isolation procedures are needed. The evaluation of an Infectious Aerosol Capture Mask (IACM) that is designed to augment the respiratory isolation of COVID-19 patients is described. Efficacy in capturing exhaled breath aerosols was evaluated using laboratory experimentation, computational fluid dynamics (CFD) and measurements of exhaled breath from COVID-19 patients and their surroundings. Laboratory aerosol experiments indicated that the mask captured at least 99% of particles. Simulations of breathing and speaking showed that all particles between 0.1 and 20 µm were captured either on the surface of the mask or in the filter. During coughing, no more than 13% of the smallest particles escaped the mask, while the remaining particles collected on the surfaces or filter. The total exhaled virus concentrations of COVID-positive patients showed a range from undetectable to 1.1 × 106 RNA copies/h of SARS-CoV-2, and no SARS-CoV-2 aerosol was detected in the samples collected that were adjacent to the patient when the mask was being worn. These data indicate that the IACM is useful for containing the exhaled aerosol of infected individuals and can be used to quantify the viral aerosol production rates during respiratory activities.
Histopathologic and Immunohistochemical Evaluation of Induced Lesions, Tissue Tropism and Host Responses following Experimental Infection of Egyptian Rousette Bats (Rousettus aegyptiacus) with the Zoonotic Paramyxovirus, Sosuga Virus
Authors: Kirejczyk Shannon G. M. , Amman Brian R. , Schuh Amy J. , Sealy Tara K. , Albariño César G. , Zhang Jian , Brown Corrie C. , Towner Jonathan S.
Published: June 2022

Ecological and experimental infection studies have identified Egyptian rousette bats (ERBs; Rousettus aegyptiacus: family Pteropodidae) as a reservoir host for the zoonotic rubula-like paramyxovirus Sosuga virus (SOSV). A serial sacrifice study of colony-bred ERBs inoculated with wild-type, recombinant SOSV identified small intestines and salivary gland as major sites of viral replication. In the current study, archived formalin-fixed paraffin-embedded (FFPE) tissues from the serial sacrifice study were analyzed in depth—histologically and immunohistochemically, for SOSV, mononuclear phagocytes and T cells. Histopathologic lesion scores increased over time and viral antigen persisted in a subset of tissues, indicating ongoing host responses and underscoring the possibility of chronic infection. Despite the presence of SOSV NP antigen and villus ulcerations in the small intestines, there were only mild increases in mononuclear phagocytes and T cells, a host response aligned with disease tolerance. In contrast, there was a statistically significant, robust and targeted mononuclear phagocyte cell responses in the salivary glands at 21 DPI, where viral antigen was sparse. These findings may have broader implications for chiropteran–paramyxovirus interactions, as bats are hypothesized to be the ancestral hosts of this diverse virus family and for ERB immunology in general, as this species is also the reservoir host for the marburgviruses Marburg virus (MARV) and Ravn virus (RAVV) (family Filoviridae).
Review of Medicinal Plants and Active Pharmaceutical Ingredients against Aquatic Pathogenic Viruses
Authors: Liao Wenyu , Huang Lin , Han Shuyu , Hu Dasheng , Xu Youhou , Liu Mingzhu , Yu Qing , Huang Shuaishuai , Wei Dongdong , Li Pengfei
Published: June 2022

Aquaculture offers a promising source of economic and healthy protein for human consumption, which can improve wellbeing. Viral diseases are the most serious type of diseases affecting aquatic animals and a major obstacle to the development of the aquaculture industry. In the background of antibiotic-free farming, the development and application of antibiotic alternatives has become one of the most important issues in aquaculture. In recent years, many medicinal plants and their active pharmaceutical ingredients have been found to be effective in the treatment and prevention of viral diseases in aquatic animals. Compared with chemical drugs and antibiotics, medicinal plants have fewer side-effects, produce little drug resistance, and exhibit low toxicity to the water environment. Most medicinal plants can effectively improve the growth performance of aquatic animals; thus, they are becoming increasingly valued and widely used in aquaculture. The present review summarizes the promising antiviral activities of medicinal plants and their active pharmaceutical ingredients against aquatic viruses. Furthermore, it also explains their possible mechanisms of action and possible implications in the prevention or treatment of viral diseases in aquaculture. This article could lay the foundation for the future development of harmless drugs for the prevention and control of viral disease outbreaks in aquaculture.
Perception and Coverage of Conventional Vaccination among University Students from Rouen (Normandy), France in 2021
Authors: Arias Andreina , Ladner Joel , Tavolacci Marie-Pierre
Published: June 2022

The aim of this study was to assess vaccination perception and the prevalence of the overall vaccination coverage (VC) and associated factors among university students. An online study was conducted among students of a university in Rouen (Normandy), France, in January 2021, with questions about the VC and perception of the vaccines. The convenience sample included 3089 students (response rate of 10.3%), with a mean age of 20.3 (SD = 1.9). The overall VC was 27.8% (39.2% for the healthcare students (HCS) and 21.3% for the non-HCS; p < 0.0001). Confidence (efficacy and security) was lower than the conviction of usefulness. The characteristics associated with VC were having the intention to be vaccinated against COVID-19, high perceptions of usefulness for their own health, having confidence in the vaccines’ efficacy and security, and a high estimated level of knowledge about vaccination. Education about the general interest and mechanism of action of vaccines could improve the perception of vaccines. Then, it is relevant to improve vaccination literacy and confidence in university students, who, as future adults and parents, will vaccinate themselves and their children; as well as healthcare students who are future healthcare workers and, therefore, will vaccinate and counsel their patients.
Bacterial Ghosts of Pseudomonas aeruginosa as a Promising Candidate Vaccine and Its Application in Diabetic Rats
Authors: Sheweita Salah A. , Amara Amro A. , Gamal Heba , Ghazy Amany A. , Hussein Ahmed , Bahey-El-Din Mohammed
Published: June 2022

Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to immunocompromised patients. As a novel vaccine network for many kinds of bacteria, bacterial ghosts (BGs) have recently been introduced. In the present research, using Sponge-Like Reduced Protocol, P. aeruginosa ghosts (PAGs) were prepared to maintain surface antigens and immunogenicity. This is the first study, to our knowledge, on the production of chemically induced well-structured bacterial ghosts for PA using concentrations of different chemicals. The research was carried out using diabetic rats who were orally immunized at two-week intervals with three doses of PAGs. Rats were subsequently challenged either by the oral route or by the model of ulcer infection with PA. In challenged rats, in addition to other immunological parameters, organ bioburden and wound healing were determined, respectively. Examination of the scanning and transmission electron microscope (EM) proved that PAGs with a proper three-dimensional structure were obtained. In contrast to control groups, oral PAGs promoted the generation of agglutinating antibodies, the development of IFN-γ, and the increase in phagocytic activity in vaccinated groups. Antibodies of the elicited PAGs were reactive to PA proteins and lipopolysaccharides. The defense against the PA challenge was observed in PAGs-immunized diabetic rats. The resulting PAGs in orally vaccinated diabetic rats were able to evoke unique humoral and cell-mediated immune responses and to defend them from the threat of skin wound infection. These results have positive implications for future studies on the PA vaccine.
Traumatic Events and Vaccination Decisions: A Systematic Review
Authors: Christou-Ergos Maria , Wiley Kerrie E. , Leask Julie , Shapiro Gilla K.
Published: June 2022

Despite the apparent relationship between past experiences and subsequent vaccination decisions, the role of traumatic events has been overlooked when understanding vaccination intention and behaviour. We conducted a systematic review to synthesize what is known about the relationship between traumatic events and subsequent vaccination decisions. MEDLINE, PsycINFO and CINHAL electronic databases were searched, and 1551 articles were screened for eligibility. Of the 52 articles included in full-text assessment, five met the eligibility criteria. Findings suggest that the experience of trauma is associated with individual vaccination decisions. Social and practical factors related to both trauma and vaccination may mediate this relationship. As this is a relatively new field of inquiry, future research may help to clarify the nuances of the relationship. This review finds that the experience of psychological trauma is associated with vaccination intention and behaviour and points to the potential importance of a trauma-informed approach to vaccination interventions during the current global effort to achieve high COVID-19 vaccine coverage.
Reasons for the Intention to Refuse COVID-19 Vaccination and Their Association with Preferred Sources of Information in a Nationwide, Population-Based Sample in Italy, before COVID-19 Vaccines Roll Out
Authors: Del Riccio Marco , Bechini Angela , Buscemi Primo , Bonanni Paolo ,   on behalf of the Working Group DHS, Boccalini Sara
Published: June 2022

Sources of information on health and vaccines such as social media, online forums, televisions, and newspapers contributed to the spread of information related to COVID-19 and, in some cases, misinformation and vaccine hesitancy. Understanding what can influence the intention to refuse COVID-19 vaccination may help to plan future public health strategies aimed at increasing vaccination coverage. This study aimed to assess the reasons for the intention to refuse the COVID-19 vaccines and the possible association between these reasons and the preferred sources of information on vaccines. An anonymous online survey was shared among the general adult population living in Italy. Only participants aged 18 or older and living in Italy were considered eligible. The questionnaires that reported the intention to refuse COVID-19 vaccination were analyzed. A total of 677 participants (from 7563 valid questionnaires) reported the intention to refuse to vaccinate against COVID-19. Most of them used search engines (n = 390, 57.6%) to seek information about vaccines, while the fear of adverse reactions to the COVID-19 vaccine was the most mentioned reason for being unwilling to get vaccinated (n = 402, 59.4%). These data may be important to build new knowledge on the impact that different sources of information can have on the willingness to get vaccinated against COVID-19.
A Randomized Clinical Trial of a Fractional Low Dose of BNT162b2 Booster in Adults Following AZD1222
Authors: Nantanee Rapisa , Jantarabenjakul Watsamon , Jaru-Ampornpan Peera , Sodsai Pimpayao , Himananto Orawan , Athipunjapong Jitthiwa , Sophonphan Jiratchaya , Nanthapisal Sira , Hirankarn Nattiya , Puthanakit Thanyawee
Published: June 2022

In the era of globally predominant omicron strains, a COVID-19 booster vaccine is needed. Our study aimed to evaluate the immunogenicity of a half-dose BNT162b2 booster after AZD1222 in healthy adults. A randomized trial of volunteers aged 18–69 years who received two-dose AZD1222 was conducted. The participants were randomized to receive the BNT162b2 vaccine intramuscularly—half (15 µg) vs. standard dose (30 µg). The immunogenicity was evaluated by a surrogate virus neutralization test (sVNT) against omicron variants and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG). From November–December 2021, 100 adults with a median age of 59.3 years (IQR 33.4–65.5) were enrolled. A booster dose was given at median of 98 days (IQR 92–128) after AZD1222. At day 14, the geometric means (GMs) of anti-S-RBD IgG in half- vs. standard-dose group were 2329.8 vs. 2574.7 BAU/mL, with a geometric mean ratio (GMR) of 0.90 (0.77–1.06). The GMs of sVNT against the omicron variant in the half- and standard-dose groups were 74.4% inhibition (95% CI 68.8–80.5) and 67.3% inhibition (57.9–78.1), respectively, with GMR of 0.95 (0.69–1.30). At day 90, the sVNT indicated 22.3% inhibition (95% CI 14.9–33.4) and 20.4% inhibition (13.1–32.0), respectively, with GMR of 1.09 (0.60–1.98). The fractional low-dose BNT162b2 mRNA booster vaccine provided non-inferior immunogenicity responses. During a shortage of vaccine supply, a fractional low dose should be considered for a booster vaccination program.
A Five Year Randomized Controlled Trial to Assess the Efficacy and Antibody Responses to a Commercial and Autogenous Vaccine for the Prevention of Infectious Bovine Keratoconjunctivitis
Authors: Hille Matthew M. , Spangler Matthew L. , Clawson Michael L. , Heath Kelly D. , Vu Hiep L. X. , Rogers Rachel E. S. , Loy John Dustin
Published: June 2022

A randomized control trial was performed over a five-year period to assess the efficacy and antibody response induced by autogenous and commercial vaccine formulations against infectious bovine keratoconjunctivitis (IBK). Calves were randomly assigned each year to one of three arms: an autogenous vaccine treatment that included Moraxella bovis (M. bovis), Moraxella bovoculi, and Mycoplasma bovoculi antigens, a commercial M. bovis vaccine treatment, or a sham vaccine treatment that consisted only of adjuvant. A total of 1198 calves were enrolled in the study. Calves were administered the respective vaccines approximately 21 days apart, just prior to turnout on summer pastures. Treatment effects were analyzed for IBK incidence, retreatment incidence, 205-day adjusted weaning weights, and antibody response to the type IV pilus protein (pili) of M. bovis as measured by a novel indirect enzyme-linked immunosorbent screening assay (ELISA). Calves vaccinated with the autogenous formulation experienced a decreased cumulative incidence of IBK over the entire study compared to those vaccinated with the commercial and sham formulations (24.5% vs. 30.06% vs. 30.3%, respectively, p = 0.25), and had less IBK cases that required retreatment compared to the commercial and sham formulations (21.4% vs. 27.9% vs. 34.3%, respectively, p = 0.15), but these differences were not significant. The autogenous formulation induced a significantly stronger antibody response than the commercial (p = 0.022) and sham formulations (p = 0.001), but antibody levels were not significantly correlated with IBK protection (p = 0.37).
Ocular Adverse Events after Inactivated COVID-19 Vaccination
Authors: Li Zhihua , Hu Feng , Li Qian , Wang Shuang , Chen Chunli , Zhang Yongpeng , Mao Yu , Shi Xuehui , Zhou Haiying , Cao Xusheng , Peng Xiaoyan
Published: June 2022

Purpose: To report the clinical characteristics of ocular adverse events that have occurred, in China, after vaccination with inactivated COVID-19 vaccines. Methods: A retrospective cross-sectional observational study was conducted of ocular disorders that occurred within 15 days from any dose of an inactivated COVID-19 vaccine. Information on gender, age, the interval between the vaccination and ocular symptoms, laterality, duration of the ocular symptoms, primary visual acuity, and clinical diagnosis were retrospectively collected. Results: Twenty-four patients were involved in the study, including 15 females and 9 males, with a mean age of 41 ± 16 years (range of 8–71 years). The patients all denied a prior history of COVID-19 infection. Ocular adverse events occurred after the first dose of vaccine in 18 patients and, after the second or third doses, in six patients. The interval between vaccination with the inactivated COVID-19 vaccine and ocular symptoms was 6 ± 5 days; six patients were bilaterally involved and 18 patients were unilaterally involved. Regarding the diagnosis, 10 patients were diagnosed with white dot syndrome (WDS), 9 patients were diagnosed with uveitis, and 5 patients were diagnosed with retinal vascular disorders. The ages of patients with WDS were younger than those with uveitis or retinal vascular disorders (32 ± 10 vs. 48 ± 18, p < 0.05). For patients diagnosed with WDS, the best-corrected visual acuity (BCVA) was 0.74 ± 0.73 LogMAR. For patients diagnosed with retinal vascular disorders or uveitis, the BCVA was 1.44 ± 1.26 LogMAR. There was no significant difference (p > 0.05). Conclusions: A relationship cannot be established between inactivated COVID-19 vaccines and ocular disorders; therefore, further investigation of the clinical spectrum of ocular adverse events after vaccination with an inactivated COVID-19 vaccine is necessary.
Comparison of mRNA Vaccinations with BNT162b2 or mRNA-1273 in Anti-CD20-Treated Multiple Sclerosis Patients
Authors: Hammer Helly , Hoepner Robert , Friedli Christoph , Leib Stephen L. , Suter-Riniker Franziska , Diem Lara , Kamber Nicole , Chan Andrew , Salmen Anke , Kamm Christian P.
Published: June 2022

Objective: Anti-CD20-treated patients are at risk of a reduced humoral immune response during the SARS-CoV-2 pandemic. Our aim was to compare the antibody response after two vaccinations with the mRNA vaccines BNT162b2 or mRNA-1273 in patients with multiple sclerosis. Methods: Data from the University Hospital of Bern and Cantonal Hospital of Lucerne were retrospectively collected from medical records and then analyzed. Anti-spike IgG serum titers were collected from both centers and were considered to be protective from a value of ≥100 AU/mL. Continuous variables were given as the mean and 95% confidence interval (95% CI); categorical variables were given as frequencies. A Mann–Whitney test and Fisher’s exact test as well as a multivariable linear regression analysis with anti-spike IgG (AU/mL) as the dependent variable were run using SPSS Statistic 25 (IBM Corp., Amonk, NY, USA). Results: A total of 74 patients were included; 41/74 (63.51%) were female patients and the mean age was 46.6 years (95% CI 43.4–49.9). Of these patients, 36/74 were vaccinated with BNT162b2 and 38/74 with mRNA-1273, following the national vaccination recommendation. In both vaccine groups, protective anti-spike IgG titers (≥100 AU/mL) were infrequently achieved (5/74: mRNA-1273 3/38; BNT162b2 2/36). Conclusions: In addition to a low rate of protective anti-spike IgG titers in both vaccine groups, we identified a drop in anti-spike IgG serum titers over time. This observation bears therapeutic consequences, as initial positive titers should be checked in case of an infection with the SARS-CoV-2 virus to identify patients who would benefit from an intravenous anti-spike IgG treatment against acute COVID-19.