bluuebunny/crossref_metadata_2025 huggingface dataset:
Updated National Diagnostic Reference Levels and Achievable Doses for CT Protocols: A National Survey of Korean Hospitals
Authors: Nam Sora , Park Hyemin , Kwon Soonmu , Cho Pyong-kon , Yoon Yongsu , Yoon Sang-wook , Kim Jungsu
Published: September 2022

Background: In 2021, the Korean government proposed a new CT diagnostic reference level. This study performed a nationwide survey and developed new DRLs and AD for 13 common CT examinations. We compared other countries’ DRLs for CT examinations. Methods: This study investigated the CTDIvol and DLP of the 12 types of CT protocols for adults and brain CT protocol for pediatrics. A total of 7829 CT examinations were performed using 225 scanners. We defined the DRLs values in the distribution of radiation exposure levels to determine the nationwide patient dose and distribution status of the dose. Results: This study showed that the new Korean national CT DRLs are slightly higher or similar to those of previous surveys and are similar or lower than those of other countries. In some protocols, although the DLP value increased, the CTDIvol decreased; therefore, it can be concluded that the patient’s dose in CT examinations was well managed. Conclusions: The new CT DRLs were slightly higher than or similar to that of the previous survey and were evaluated to be similar or lower than CT DRLs of other countries. These DRLs will be used for radiation optimization and effective dose calculation for an individual.
State Neuroticism at Home and in Fiji: The Positive Effects of Having a Holiday to Reset Mind and Brain
Authors: Hendriksen Pauline A. , Arnoldy Lizanne , Verster Joris C.
Published: September 2022

Neuroticism, i.e., the disposition to experiencing feelings of emotional distress, including anxiety, depression, and anger, is often considered a relatively stable and fundamental personality characteristic (trait neuroticism). However, the level of neuroticism can also vary within individuals (state neuroticism), depending on external factors such as life events and work stress. The aim of the current study was to examine to what extent having a holiday can reduce state neuroticism. A survey was conducted among n = 213 young adults who were on holiday in Fiji (mean ± SD age of 24.5 ± 4.3, 46.9% women). In addition to demographics, they completed the neuroticism scale of the Eysenck Personality Questionnaire—revised Short Scale (EPQ-RSS). Compared to at home, a significant reduction (p < 0.001) in neuroticism was reported when they were on holiday (mean ± SD of 4.5 ± 3.0 versus 2.1 ± 2.3, respectively). The effect was seen in both men and women. Women had significantly higher neuroticism ratings than men, both at home (mean ± SD of 5.4 ± 2.9 versus 3.6 ± 2.9, respectively, p < 0.001) and on holiday (mean ± SD of 2.5 ± 2.4 versus 1.6 ± 2.0, respectively, p < 0.001). No significant differences were seen between individuals with a job at home or students. The correlation between neuroticism at home and the difference rating in neuroticism (‘at home’—‘in Fiji’ assessment) was highly significant (r = 0.68, p < 0.001). In conclusion, having a holiday was associated with significantly reduced levels of neuroticism. Those with the highest levels of neuroticism at home benefited the most from having a holiday.
Correction: Fletcher et al. Effects of Phthalate Mixtures on Ovarian Folliculogenesis and Steroidogenesis. Toxics 2022, 10, 251
Authors: Fletcher Endia J. , Santacruz-Márquez Ramsés , Mourikes Vasiliki E. , Neff Alison M. , Laws Mary J. , Flaws Jodi A.
Published: September 2022

The authors wish to make the following corrections to this paper [...]
Longitudinal Metabolomics and Lipidomics Analyses Reveal Alterations Associated with Envenoming by Bothrops asper and Daboia russelii in an Experimental Murine Model
Authors: Wase Nishikant , Gutiérrez José María , Rucavado Alexandra , Fox Jay W.
Published: September 2022

Longitudinal metabolomics and lipidomics analyses were carried out on the blood plasma of mice injected intramuscularly with venoms of the viperid species Bothrops asper or Daboia russelii. Blood samples were collected 1, 3, 6, and 24 h after venom injection, and a control group of non-envenomed mice was included. Significant perturbations in metabolomics and lipidomics were observed at 1, 3, and 6 h, while values returned close to those of control mice by 24 h, hence reflecting a transient pattern of metabolic disturbance. Both venoms induced significant changes in amino acids, as well as in several purines and pyrimidines, and in some metabolites of the tricarboxylic acid cycle. KEGG analysis of metabolic pathways that showed those with the greatest change included aminoacyl tRNA synthesis and amino acid biosynthesis and metabolism pathways. With regard to lipid metabolism, there was an increase in triglycerides and some acyl carnitines and a concomitant drop in the levels of some phospholipids. In addition, envenomed mice had higher levels of cortisol, heme, and some oxidative stress markers. The overall pattern of metabolic changes in envenomed mice bears similarities with the patterns described in several traumatic injuries, thus underscoring a metabolic response/adaptation to the injurious action of the venoms.
Botulinum Toxin, a Drug with Potential Interest for Dentists—An Introduction
Authors: Bakke Merete
Published: September 2022

The review is an introduction to medical, non-cosmetic treatments with botulinum neurotoxin (BoNT) in the orofacial region. It focuses on the current most common, best-documented and safest indications of interest for dentists in terms of dystonia and sialorrhea. These conditions are recommended to start with and suitable to gain better skill and experience with BoNT. The introduction also stresses the importance of correct diagnostics based on interdisciplinary cooperation, precise targeting of the injections, measurements of treatment effect, and control of the oral health with regard to side effects.
Optimization of Aflatoxin B1-Lysine Analysis for Public Health Exposure Studies
Authors: Renaud Justin B , Walsh Jacob P , Sumarah Mark W
Published: September 2022

Aflatoxin B1 is a potent human carcinogen produced by several species of Aspergillus mainly found on nuts and maize. Exposures in parts of Africa, Latin America and Asia can be at multiples, sometimes orders of magnitude above tolerable daily levels. Although human exposure to aflatoxin can be estimated by analysis of the diet, only determination of the serum albumin aflatoxin adduct provides a health-relevant exposure measure. The lack of a reference serum limits interlaboratory method validation and data comparisons. In this study, we synthetically produced AFB1-dialdehyde and covalently coupled it to serum albumin in human serum. This synthetic produced aflatoxin-serum reference material was used in conjunction with isotopically labelled internal standards to evaluate sample digestion methods. This showed using sufficient Pronase in the digestion step was critical to ensure complete proteolytic digestion, which occurs within 4 h. Increasing the digestion temperature from 37 °C to 50 °C also provided a benefit to the overall analysis. In addition, the use of dried blood spots and Volumetric Absorptive Microsampling (VAMS) were investigated showing samples stored with VAMS produced equivalent results to serum samples.
COVID-Related Chronic Allograft Dysfunction in Lung Transplant Recipients: Long-Term Follow-up Results from Infections Occurring in the Pre-vaccination Era
Authors: Hage René , Schuurmans Macé M.
Published: September 2022

Introduction: We report on characteristics and lung function outcomes among lung transplant recipients (LTRs) after COVID-19 with infections occurring in the first year of the coronavirus pandemic prior to introduction of the vaccines. Methods: This was a retrospective study of 18 LTRs who tested positive for SARS-CoV-2 between 1 February 2020 and 1 March 2021. The mean age was 49.9 (22–68) years; 12 patients (67%) were male. Two patients died due to severe COVID-19. Results: During the study period, there were 18 lung transplant recipients with a community-acquired SARS-CoV-2 infection. In this cohort, seven had mild, nine had moderate, and two had severe COVID-19. All patients with mild and moderate COVID-19 survived, but the two patients with severe COVID-19 died in the intensive care unit while intubated and on mechanical ventilation. Most patients with moderate COVID-19 showed a permanent lung function decrease that did not improve after 12 months. Conclusion: A majority of LTRs in the current cohort did not experience an alteration in the trajectory of FEV1 evolution after developing SARS-CoV-2 infection. However, in the patients with moderate COVID-19, most patients had a decline in the FEV1 that was present after 1 month after recovery and did not improve or even deteriorated further after 12 months. In LTRs, COVID-19 can have long-lasting effects on pulmonary function. Treatment strategies that influence this trajectory are needed.
Socio-Structural Factors and HIV Care Engagement among People Living with HIV during the COVID-19 Pandemic: A Qualitative Study in the United States
Authors: Bleasdale Jacob , Leone Lucia A. , Morse Gene D. , Liu Yu , Taylor Shelby , Przybyla Sarahmona M.
Published: September 2022

Achieving HIV prevention goals will require successful engagement in each stage of the HIV continuum. The present study sought to understand the ways in which socio-structural factors influence HIV care engagement among people living with HIV (PLH) within the context of the ongoing COVID-19 pandemic. Twenty-five PLH were recruited from January to October 2021. Semi-structured interviews discussed various socio-contextual factors that influenced engagement in HIV-related care as a result of the pandemic. A thematic content analysis reported semantic level themes describing factors influencing HIV care following an integrated inductive–deductive approach. Qualitative analysis revealed three themes that either supported or hindered engagement in care within the context of the COVID-19 pandemic: (1) social determinants of health, (2) social support, and (3) modes of healthcare delivery. The results underscore the need to assess socio-structural factors of health as means to promote successful engagement in the HIV care continuum and shed new insights to guide future practice in the era of COVID-19.
Epidemiological Situation of Monkeypox Transmission by Possible Sexual Contact: A Systematic Review
Authors: León-Figueroa Darwin A. , Barboza Joshuan J. , Garcia-Vasquez Edwin A. , Bonilla-Aldana D. Katterine , Diaz-Torres Milagros , Saldaña-Cumpa Hortencia M. , Diaz-Murillo Melissa T. , Cruz Olga Campos-Santa , Rodriguez-Morales Alfonso J.
Published: September 2022

Monkeypox (MPX), a zoonotic infection caused by the monkeypox virus (MPXV), has re-emerged worldwide with numerous confirmed cases with person-to-person transmission through close contacts, including in sexual networks. Therefore, this study aimed to determine the epidemiological situation of monkeypox transmission by possible sexual contact. A systematic literature review was conducted using PubMed, Scopus, Web of Science, and Embase databases until 18 August 2022. The key search terms used were “monkeypox”, “sexual contact”, “sexual intercourse” and “sexual transmission”. A total of 1291 articles were retrieved using the search strategy. After eliminating duplicates (n = 738) and examining by title, abstract, and full text, 28 studies reporting case reports of monkeypox with a detailed description of clinical features, sexually transmitted diseases, method of diagnosis, location and course of skin lesions, and treatment were included. A total of 4222 confirmed cases of monkeypox have been reported, of which 3876 monkeypox cases are the result of transmission by sexual contact distributed in twelve countries: 4152 cases were male with a mean age of 36 years. All confirmed cases of monkeypox were diagnosed by reverse transcriptase-polymerase chain reaction (RT-PCR). The most frequent clinical manifestations were fever, lymphadenopathy, headache, malaise, and painful perianal and genital lesions. The most frequent locations of the lesions were perianal, genital, oral, trunk, upper and lower extremities. Patients were in good clinical condition, with treatment based on analgesics and antipyretics to relieve some symptoms of monkeypox. A high proportion of STIs and frequent anogenital symptoms were found, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact during sexual activity. The highest risk of monkeypox transmission occurs in men who have sex with men, and MPXV DNA could be recovered in seminal fluid. It is essential to establish health policies for the early detection and management of patients with monkeypox.
Thermal Radiation from Compact Objects in Curved Space-Time
Authors: Mitra Abhas , Singh Krishna Kumar
Published: September 2022

We highlight here the fact that the distantly observed luminosity of a spherically symmetric compact star radiating thermal radiation isotropically is higher by a factor of (1+zb)2 compared to the corresponding flat space-time case, where zb is the surface gravitational redshift of the compact star. In particular, we emphasize that if the thermal radiation is indeed emitted isotropically along the respective normal directions at each point, this factor of increment (1+zb)2 remains unchanged even if the compact object would lie within its photon sphere. Since a canonical neutron star has zb≈0.1, the actual X-ray luminosity from the neutron star surface could be ∼20% higher than what would be interpreted by ignoring the general relativistic effects described here. For a static compact object, supported by only isotropic pressure, compactness is limited by the Buchdahl limit zb<2.0. However, for compact objects supported by anisotropic pressure, zb could be even higher (zb<5.211). In addition, in principle, there could be ultra-compact objects having zb≫1. Accordingly, the general relativistic effects described here might be quite important for studies of thermal radiation from some ultra-compact objects.
On the General Entangled State and Quantum Decoherence
Authors: Rostami Abasalt , Firouzjaee Javad T.
Published: September 2022

We study the primary entanglement effect on the decoherence of reduced-density matrices of scalar fields, which interact with other fields or independent mode functions. We study the (leading) tree-level evolution of the scalar bispectrum due to a coupling between two scalar fields. We show that the primary entanglement has a significant role in the decoherence of the given quantum state. We find that the existence of such an entanglement could couple dynamical equations coming from a Schrödinger equation. We show that if one wants to see no effect of the entanglement parameter in the decohering of the quantum system, then the ground state eigenvalues of the interaction terms in the Hamiltonian cannot be independent of each other Generally, including the primary entanglement destroys the independence of the interaction terms in the ground state. We show that the imaginary part of the entanglement parameter plays an important role in the decoherence process without posing any specific restriction to the interaction terms. Our results could be generalized to every scalar quantum field theory with a well-defined quantization of its fluctuations in a given curved space-time.
Solar Orbiter SWA Observations of Electron Strahl Properties Inside 1 AU
Authors: Owen Christopher J. , Abraham Joel Baby , Nicolaou Georgios , Verscharen Daniel , Louarn Philippe , Horbury Timothy S.
Published: September 2022

The Solar Wind Analyser (SWA) suite on Solar Orbiter includes an Electron Analyser System (SWA-EAS) which is capable of high temporal and angular resolution measurements of solar wind electrons in the energy range ∼1 eV to ∼5 keV. In this article we report early nominal phase observations of the suprathermal electron population at energies ≥70 eV (representative of the ’strahl’ population), and use a simple fitting routine and classification system to determine the characteristics of the distributions and determine the variations in their properties as a function of heliocentric distance and solar wind properties. We find that under our classification system a significant population of radially outward moving strahl beams is identifiable in the tested samples. These are seen in across solar wind speed regimes, but, consistent with earlier observations, are slightly more prevalent in high speed wind. These beams occur at all distances examined (∼0.43 to ∼1.0 AU), but do not show significant evolution with distance, suggesting a balance between focusing and scattering processes across the distance range covered. However, the data suggests that the beams broaden on average with increasing magnetic field strength and narrow on average with increasing solar wind speed. We also identify a small population, occurring in sporadic clusters, which have deficits in phase space density in the sunward moving part of the electron distribution. These clusters occur across the distance range sampled and show some variations in average properties with radial distance, suggesting they too are influenced by competing scattering and (de-)focusing processes. The implications for the origin and evolution of these electron populations derived from these new observations are explored.
Single-Photon Double-Slit Interference in the 4+1 Formalism
Authors: Strubbe Filip
Published: September 2022

Unifying quantum theory with general relativity is challenging because of several problems related to time and to collapse in quantum measurements. In the double-slit experiment, the questions are how the momentum of the photon is transferred to a specific location on the screen and how the double slit recoils accordingly. This work investigates if these problems can be solved by adding a second time τ, which acts as an external evolution parameter, to standard four-dimensional spacetime. Within the resulting 4+1 formalism, a model for the single-photon double-slit experiment is developed. On the one hand, each spacetime associated to a value of τ relies on classical worldlines that obey local momentum conservation. On the other hand, these worldlines are allowed to readjust as a function of τ such that the quantum phenomenon of double-slit interference can be reproduced. The model explains how determinate outcomes are produced and how momentum transfer occurs in a way that satisfies the principles of relativity and local momentum conservation. As a result, the measurement problem and the problem of time evaporate, and an explanation for our experience of the present emerges. Since the presented model succeeds in explaining a key quantum phenomenon with essentially classical worldlines, this is relevant for the field of quantum gravity.
A Two-Period Model of Coastal Urban Adaptation Supported by Climate Services
Authors: Kovalevsky Dmitry V. , Scheffran Jürgen
Published: September 2022

Coastal zones are experiencing rapid urbanization at unprecedented rates. At the same time, coastal cities are the most prone to climate-related vulnerability, including impacts of sea-level rise and climate-related coastal hazards under the present and projected future climate. Decision making about coastal urban climate adaptation can be informed by coastal climate services based on modeling tools. We develop a two-period coastal urban adaptation model in which two periods—the present and the future—are distinguished. In the model, a city agent anticipates sea-level rise and related coastal flood hazards with adverse impacts in the future period that, through damages, will reduce the urban income. However, the magnitude of future sea-level rise and induced damages are characterized by uncertainty. The urban planning agent has to make an investment decision under uncertainty: whether to invest in climate adaptation (in the form of construction of coastal protection) or not, and if so, how much. The decision making of the urban agent is derived from intertemporal maximization of expected time-discounted consumption. An exact solution in the closed form is derived for an analytically tractable particular case, for which it is shown that investment decisions depend discontinuously on the value of a single non-dimensional model indicator. When this indicator exceeds a certain threshold value, the urban agent discontinuously switches from the ‘business-as-usual’ (BaU) strategy when no adaptation investment is taken to a proactive adaptation. The role of coastal climate services in informing the decision making on adaptation strategies is discussed.
Forty Years without Family: Three Novel Bacteriophages with High Similarity to SPP1 Reveal Decades of Evolutionary Stasis since the Isolation of Their Famous Relative
Authors: Delesalle Véronique A. , Tomko Brianne E. , Vill Albert C. , Lichty Katherine B. , Krukonis Greg P.
Published: September 2022

SPP1, an extensively studied bacteriophage of the Gram-positive Bacillus subtilis, is a model system for the study of phage–host interactions. Despite progress in the isolation and characterization of Bacillus phages, no previously fully sequenced phages have shared more than passing genetic similarity to SPP1. Here, we describe three virulent phages very similar to SPP1; SPP1 has greater than 80% nucleotide sequence identity and shares more that 85% of its protein coding genes with these phages. This is remarkable, given more than 40 years between the isolation of SPP1 and these phages. All three phages have somewhat larger genomes and more genes than SPP1. We identified a new putative gene in SPP1 based on a conserved sequence found in all phages. Gene conservation connotes purifying selection and is observed in structural genes and genes involved in DNA metabolism, but also in genes of unknown function, suggesting an important role in phage survival independent of the environment. Patterns of divergence point to genes or gene domains likely involved in adaptation to diverse hosts or different environments. Ultimately, comparative genomics of related phages provides insight into the long-term selective pressures that affect phage–bacteria interactions and alter phage genome content.
Chimeric Virus-like Particles Co-Displaying Hemagglutinin Stem and the C-Terminal Fragment of DnaK Confer Heterologous Influenza Protection in Mice
Authors: Liu Cui-Cui , Liu De-Jian , Yue Xin-Yu , Zhong Xiu-Qin , Wu Xuan , Chang Hai-Yan , Wang Bao-Zhong , Wan Mu-Yang , Deng Lei
Published: September 2022

Influenza virus hemagglutinin (HA) stem is currently regarded as an extremely promising immunogen for designing universal influenza vaccines. The appropriate antigen-presenting vaccine vector would be conducive to increasing the immunogenicity of the HA stem antigen. In this study, we generated chimeric virus-like particles (cVLPs) co-displaying the truncated C-terminal of DnaK from Escherichia coli and H1 stem or full-length H1 antigen using the baculovirus expression system. Transmission electronic micrography revealed the expression and presentation of H1 stem antigens on the surface of VLPs. Vaccinations of mice with the H1 stem cVLPs induced H1-specific immune responses and provided heterologous immune protection in vivo, which was more effective than vaccinations with VLPs displaying H1 stem alone in protecting mice against weight loss as well as increasing survival rates after lethal influenza viral challenge. The results indicate that the incorporation of the truncated C-terminal of DnaK as an adjuvant protein into the cVLPs significantly enhances the H1-specific immunity and immune protection. We have explicitly identified the VLP platform as an effective way of expressing HA stem antigen and revealed that chimeric VLP is an vaccine vector for developing HA stem-based universal influenza vaccines.
DNA Prime and Recombinant Protein Boost Vaccination Confers Chickens with Enhanced Protection against Chicken Infectious Anemia Virus
Authors: Liu Ling , Yin Mingrong , Li Yang , Su Hong , Fang Lichun , Sun Xiaolong , Chang Shuang , Zhao Peng , Wang Yixin
Published: September 2022

Chicken infectious anemia (CIA) is an immunosuppressive disease caused by chicken infectious anemia virus (CIAV) that poses a great threat to the poultry industry worldwide. At present, vaccination is an important way to prevent and control CIA. Apart from a CIAV-attenuated vaccine used in clinical practice, the research and development of a genetically engineered vaccine has good prospects. However, it is difficult to induce a strong protective effect with a single subunit vaccine or DNA vaccine. Therefore, the goal of this study is to develop and evaluate a DNA prime/protein boost vaccine strategy for defense against CIAV infection and spread. In this study, the recombinant proteins of CIAV VP1 and VP2 were prepared using an Escherichia coli (E. coli) expression system, and the eukaryotic expression plasmid pBud-VP1-VP2 was constructed. Subsequently, the effects of the DNA prime/protein boost strategy on antibody production and cellular immunity response were measured. The results showed that combined vaccination could induce a higher antibody titer than those of a DNA vaccine or subunit vaccine alone. In addition, spleen lymphocyte index (SI) and IL-2, IL-4, and IFN-γ levels were also significant in chickens the received the combined vaccination. To further investigate the protective effect of DNA prime/protein boost vaccination, a CIAV challenge experiment was carried out. The results showed that infection with CIAV reduced the hematocrit value (Hct) and thymus index, while vaccination recovered this reduction, and the combined immunization group was the least affected by CIAV infection. Furthermore, the CIAV viral load in the combined immunization group was the lowest, indicating that the combined immunization could provide a better protective efficacy. In conclusion, the DNA prime and recombinant protein boost vaccination can be used as an important anti-CIAV strategy, which can induce both enhanced cellular and humoral immunity responses in chickens and provide a new avenue for CIAV prevention and control.
Unmet Needs for the Treatment of Chronic Hepatitis E Virus Infection in Immunocompromised Patients
Authors: Kamar Nassim , Del Bello Arnaud , Abravanel Florence , Pan Qiuwei , Izopet Jacques
Published: September 2022

Hepatitis E virus (HEV) is the most prevalent hepatitis virus worldwide. Genotypes 3 (HEV3) and 4 (HEV4) as well as rat HEV can lead to chronic hepatitis E and cirrhosis in immunosuppressed patients. Within the last decade, several options for treating chronic hepatitis have been developed and have achieved a sustained virological response. However, there are still unmet needs such as optimizing immunosuppression to allow HEV clearance with or without ribavirin, as well as alternative therapies to ribavirin that are discussed in this paper.
Prevalence and Spectrum of HIV-1 Resistance Mutations in the Siberian Federal District
Authors: Shtrek Sergey , Levakhina Lidiya , Blokh Aleksey , Pasechnik Oksana , Pen’evskaya Nataliya
Published: September 2022

The Siberian Federal District is among the most affected regions with a high prevalence of HIV-infection and is characterized by high HIV-infection incidence rate and high mortality among the HIV-infected population. HIV drug resistance poses a major threat to public health and is associated with increased mortality, HIV incidence, and cost of epidemic control programs. A total of 1281 samples from HIV-infected patients were sequenced and analyzed with the DEONA and HIVdb Program to assess the prevalence of drug resistance mutations in patients in the Siberian Federal District in 2016–2018. The federal surveillance data obtained from 0.5% of HIV-infected patients during the long-term follow-up care in 2021 were also used. The incidence rate of HIV infection in the Siberian Federal District has declined since 2016: from 135.8 per 100 thousand population to 81.1 per 100 thousand population in 2021. Mutations associated with resistance to NRTI and NNRTI were found in 10.3% of the samples in 2016–2018 and in 28.4% of the samples in 2020. The rising prevalence of drug resistance in HIV-infected patients indicates that it is increasingly important to continuously monitor and improve the approaches to the use of effective treatment regimens.
CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients
Authors: Rizzi Manuela , Tonello Stelvio , Morani Francesca , Rizzi Eleonora , Casciaro Giuseppe Francesco , Matino Erica , Costanzo Martina , Zecca Erika , Croce Alessandro , Pedrinelli Anita , Vassia Veronica , Landi Raffaella , Mallela Venkata Ramana , D’Onghia Davide , Minisini Rosalba , Bellan Mattia , Castello Luigi Mario , Gavelli Francesco , Avanzi Gian Carlo , Patrucco Filippo , Pirisi Mario , Colangelo Donato , Sainaghi Pier Paolo
Published: September 2022

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07–7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19–7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation.
Multifaceted Aspects of HIV-1 Nucleocapsid Inhibition by TAR-Targeting Peptidyl-Anthraquinones Bearing Terminal Aromatic Moieties
Authors: Sosic Alice , Frecentese Francesco , Olivato Giulia , Rollo Daniele , Carraro Caterina , Gamba Elia , Santagada Vincenzo , Gatto Barbara
Published: September 2022

2,6-dipeptidyl-anthraquinones are polycyclic planar systems substituted at opposite ring positions by short aminoacyl side chains. Derivatives with positively charged terminal amino acids showed in vitro inhibition of HIV-1 nucleocapsid (NC) protein correlating with threading intercalation through nucleic acid substrates. We found that the variation of the terminal amino acid into an aromatic moiety has profound effects on the NC inhibition of TAR–RNA melting, granting enhanced interaction with the protein. While all compounds showed appreciable NC and TAR binding, they exhibited different strengths driven by the length of the peptidyl side chains and by the stereochemistry of the terminal tyrosine. Unexpectedly, the best inhibitors of NC-induced TAR melting, characterized by the D- configuration of tyrosine, were able to form ternary complexes without competing with TAR–NC recognition sites, as shown by native mass spectrometry experiments. Furthermore, the hydrophobicity of the terminal residue enhances membrane permeation, with positive implications for further studies on these NC–TAR-targeted compounds.
Characterization of the Subclinical Infection of Porcine Deltacoronavirus in Grower Pigs under Experimental Conditions
Authors: Yen Lu , Mora-Díaz Juan Carlos , Rauh Rolf , Nelson William , Castillo Gino , Ye Fangshu , Zhang Jianqiang , Baum David , Zimmerman Jeffrey , Nelli Rahul , Giménez-Lirola Luis
Published: September 2022

This study characterized the susceptibility and dynamic of porcine deltacoronavirus infection in grower pigs under experimental conditions using a combination of syndromic and laboratory assessments. Seven-week-old conventional pigs (n = 24) were randomly distributed into PDCoV- (n = 12) and mock-inoculated (n = 12) groups. Serum was collected at −7, 0, 3, 7, 10, 14, 17, 21, 28, 35, and 42 days post-inoculation (DPI) to evaluate viremia (RT-qPCR) and antibody response (S1-based ELISA). Viral shedding and potential infectivity were determined using pen-based oral fluids and feces collected every other day between DPI 0 and 42. Pigs showed no clinical signs or viremia throughout the study. Active virus shedding was detected in feces (6-22 DPI) and oral fluids (2-30 DPI), peaking at DPI 10. IgG was first detected at DPI 10, being statistically significant after DPI 14 and increasing thereafter, coinciding with the progressive resolution of the infection. Likewise, a significant increase in proinflammatory IL-12 was detected between DPI 10 and 21 in PDCoV-inoculated pigs, which could enhance innate resistance to PDCoV infection. This study demonstrated that active surveillance based on systematic sampling and laboratory testing combining molecular and serological tools is critical for the accurate detection of subclinical circulation of PDCoV in pigs after weaning.
Immunogenicity after a Third COVID-19 mRNA Booster in Solid Cancer Patients Who Previously Received the Primary Heterologous CoronaVac/ChAdOx1 Vaccine
Authors: Luangdilok Sutima , Wanchaijiraboon Passakorn , Pakvisal Nussara , Susiriwatananont Thiti , Zungsontiporn Nicha , Sriuranpong Virote , Sainamthip Panot , Suntronwong Nungruthai , Vichaiwattana Preeyaporn , Wanlapakorn Nasamon , Poovorawan Yong , Teeyapun Nattaya , Tanasanvimon Suebpong
Published: September 2022

No data regarding the efficacy of a third mRNA vaccine for solid cancer patients previously primed with the heterologous CoronoVac/ChAdOx1 vaccination implemented in Thailand during the shortage of vaccine supply are available. Forty-four cancer patients who previously received the heterologous CoronaVac-ChAdOx1 regimen were boosted with a third mRNA COVID vaccine, either BNT162b2 or mRNA-1273. Anti-RBD IgG was measured immediately before, two weeks after, and four weeks after the third dose. The antibody response was compared to 87 age- and gender-matched cancer patients who were primed with the homologous ChAdOx1/ChAdOx1 regimens. Post-third dose anti-RBD IgG levels significantly increased compared to pre-third dose levels. There was no statistical difference in post-third dose antibody titers or neutralization levels between these two primary series regimens. Treatment with chemotherapy was associated with a lower antibody response compared to endocrine therapy/biologics. Similar antibody levels were observed after a third booster with either BNT162b2 or mRNA-1273 following heterologous CoronaVac/ChAdOx1 vaccination. There was no statistical difference in the immune response following the third-dose vaccination between cancer patients and healthy individuals who received the same heterologous CoronaVac/ChAdOx1 vaccination. In conclusion, a similar degree of enhanced immunogenicity was observed after a third mRNA COVID-19 vaccination in solid cancer patients who previously received the heterologous CoronaVac/ChAdOx1 regimens.
Dynamics of B-Cell Responses after SARS-CoV-2 Vaccination in Spain
Authors: José-Cascón Miriam San , de la Varga-Martínez Raquel , Campos-Caro Antonio , Rodríguez Carmen
Published: September 2022

The high mortality rate due to COVID-19 has necessitated the mass vaccination against SARS-CoV-2 to induce protective humoral and cellular immunity. (1) Objective: To study the dynamics of SARS-CoV-2-specific B cells after two doses of the Pfizer-BioNTech SARS-CoV-2 vaccine. (2) Methods: Immunophenotyping and cellular cultures were used to determine the kinetics of B-cell subpopulations and vaccine responses in volunteers before and seven days, three months and seven months after the second dose in Spain (n = 19). (3) Results: Seven days after immunisation, memory B cells and plasmablasts expressing receptors for factors implicated in the maturation of plasma cells were augmented in blood. Three months after vaccination, SARS-CoV-2 spike-specific plasmablasts disappeared from circulation while spike-specific memory-B cells circulated, with heterogeneous dynamics among individuals. (4) Conclusion: After vaccination, specific plasmablasts equipped with receptors for maturation factors were quickly generated and disappeared rapidly from the blood, while specific memory B cells circulated for at least seven months.
Double Auxotrophy to Improve the Safety of a Live Anti-Pseudomonas aeruginosa Vaccine
Authors: Fuentes-Valverde Víctor , García Patricia , Moscoso Miriam , Bou Germán
Published: September 2022

Pseudomonas aeruginosa is an opportunistic nosocomial pathogen that causes serious infections in the respiratory tract of immunocompromised or critically ill patients, and it is also a significant source of bacteremia. Treatment of these infections can be complicated due to the emergence of multidrug-resistant P. aeruginosa strains worldwide. Hence, the development of prophylactic vaccines is a priority for at-risk patients. We have previously developed a vaccine candidate with a single auxotrophy for D-glutamate, PAO1 ΔmurI, which protects against sepsis and acute pneumonia caused by P. aeruginosa. Given the paramount importance of safety in the development of live attenuated vaccines, we have improved the safety of the vaccine candidate by reducing the probability of a reversion to virulence by the inclusion of an additional auxotrophy for D-alanine. Single and double auxotrophs behaved in a similar manner in relation to the attenuation level, immunogenicity and protective efficacy, but the double auxotroph has the advantage of being more stable and safer as a candidate vaccine against respiratory infections caused by P. aeruginosa.
Physiological Indicators of Acute and Chronic Stress in Securely and Insecurely Attached Dogs Undergoing a Strange Situation Procedure (SSP): Preliminary Results
Authors: Riggio Giacomo , Borrelli Carmen , Campera Marco , Gazzano Angelo , Mariti Chiara
Published: September 2022

The quality of the attachment bond towards the caregiver may affect the dog’s physiological responses to stressful stimuli. This study aimed to measure chronic and acute physiological parameters of stress in ten securely and ten insecurely attached dogs. The twenty experimental subjects were selected from a sample of dogs that participated with their owners in the Strange Situation Procedure. Saliva samples were collected before (T0) and after (T1) the test. Blood pressure, heart rate, respiratory rate, and rectal temperature were measured after the test, only. At this time, a hair sample was also collected. RM ANOVA was used to analyse cortisol concentrations between secure and insecure dogs at T0 and T1. Mann–Whitney U test or T test were used for other physiological parameters. Insecure dogs had significant higher salivary cortisol concentrations than secure dogs at T1 (p = 0.024), but only a non-significant trend towards higher cortisol concentrations at T0 (p = 0.099). Post-test heart rate also tended to be higher in insecure compared to secure dogs (p = 0.077). No significant differences in hair cortisol concentration were found. The quality of attachment may affect the dog’s physiological response to acute stress, at least when related to separation from the caregiver. The effect of attachment on chronic stress requires further investigation.
Vet-OncoNet: Malignancy Analysis of Neoplasms in Dogs and Cats
Authors: Pinello Katia , Amorim Irina , Pires Isabel , Canadas-Sousa Ana , Catarino José , Faísca Pedro , Branco Sandra , Peleteiro Maria C. , Silva Daniela , Severo Milton , Niza-Ribeiro João
Published: September 2022

Analysis of canine and feline tumor malignancy data can help clinicians identify high-risk patients and make more accurate decisions. Based on a sample of 16,272 cancer records, including 3266 cats and 13,006 dogs, collected from January 2019 to December 2021 in the Vet-OncoNet Network database, this study aimed to compare the tumor malignancy profile between cats and dogs, considering animal-related factors (sex, age, and breed), topography, and geographic location using a mixed-effects logistic regression model. Cats had a higher proportion of malignant tumors (78.7%) than dogs (46.2%), and the malignancy profile was very different regarding tumors’ topographies. The mean age of malignant tumors occurred eight months later than benign ones (9.1, SD = 3.4; 9.8, SD = 3.2), in general. Species (OR = 3.96, 95%CI 3.57: 4.39) and topography (MOR = 4.10) were the two most important determinants of malignancy risk. Female dogs had a higher risk than male dogs (OR = 1.19, 95%CI 1.08: 1.31), which does not appear to be the case in cats (OR = 0.98, 95%CI 0.77: 1.23). Breed contributed significantly to differences in malignancy risk in dogs (MOR = 1.56), particularly in pit bulls and boxers. District of residence was not so relevant in predicting malignancy risk (MOR = 1.14). In both species, the risk of malignancy increased by approximately 20% every three years. It could be hypothesized that species differences in genetic structure may contribute to tumor malignancy.
The Effectiveness of Commercial Vaccination against Lawsonia intracellularis in Mitigating the Reduction in ADWG, the Increased Mortality and Fecal Shedding of the Vaccinated Pigs: A Systematic Review and Meta-Analysis
Authors: Won Gayeon , Chi Na-Kyoung , Park Yebin
Published: September 2022

In this study, a systematic review and meta-analysis was conducted to assess the efficacy of commercial vaccines against PPE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Of the 373 articles reviewed, 16 fulfilled the pre-specified inclusion criteria. Three independent reviewers extracted the data, and vaccine effectiveness was assessed using the outcomes of interest. The majority of studies had a low or unclear risk of bias as assessed using the ARRIVE guidelines. The results of the meta-analysis indicated that the vaccination resulted in statistically significant reductions in bacterial fecal shedding (odds ratio, OR = 0.122, 95% confidence interval, CI 0.054–0.278) and mortality rate (risk ratio, RR = 0.199; 95% CI, 0.066–0.605). Furthermore, ADWG was significantly increased in the vaccinated pigs compared to the unvaccinated controls (standardized mean difference (SMD) = 0.606, 95% CI 0.243–0.969). In the subgroup analysis, the production phase and study type significantly influenced the effect size (p < 0.1). The Egger’s regression test showed no evidence of publication bias (p > 0.1). The effectiveness of commercially available vaccines against PPE-related weight loss, fecal shedding, and mortality suggests that the vaccines may help control PPE on affected swine farms.
Intensity-Duration-Frequency Curve for Extreme Rainfall Event Characterization, in the High Tropical Andes
Authors: Escobar-González Diego , Singaña-Chasi Mélany S. , González-Vergara Juan , Erazo Bolívar , Zambrano Miguel , Acosta Darwin , Villacís Marcos , Guallpa Mario , Lahuatte Braulio , Peluffo-Ordóñez Diego H.
Published: September 2022

In fields such as hydrology, meteorology, and civil engineering, the study of extreme precipitation events is useful to prevent rainfall related disasters. A widely-used practice to address such a problem is by using statistical inferences about precipitation intensity, duration and frequency (IDF). Despite of its great usefulness, the selection of the adequate data and methodology to characterize precipitation’s IDF in the urban area of high-altitude Andean cities remains an open issue for practitioners and decision makers. In this sense, the present paper develops an approach to schematically build the IDF curves for a sub-basin of the study case Andean city, Quito–Ecuador. The here-used data holds information from 12 meteorological stations. Then, the IDF curves are obtained by using both a parametrization followed by a Gamma distribution and a 3-parameter cumulative distribution function, also called mnp. Finally, the curve-fitting process is estimated numerically by adjusting the Sherman equation. Results (average R2=0.9) demonstrated that the framework is well-suited for the high-altitude regime. As a noticeable outcome, a novel spatial interpolation-based analysis is introduced, which enabled the identification of extreme rainfall events according to its duration.
Dual-Functional Nanostructures for Purification of Water in Severe Conditions from Heavy Metals and E. coli Bacteria
Authors: AMulla Abdulaziz Abdulrahman , Saber Osama , Ezzeldin Mohamed Farouk , Berekaa Mahmoud Mohamed , El-Azab Waleed I. M.
Published: September 2022

Because of industrial water, many groundwater sources and other water bodies have a strongly acidic medium. Increased bacterial resistance against multiple antibiotics is one of the main challenges for the scientific society, especially those commonly found in wastewater. Special requirements and materials are needed to work with these severe conditions and treat this kind of water. In this trend, nanolayered structures were prepared and modified in different ways to obtain an optimum material for removing different kinds of heavy metals from water in severe conditions, alongside purifying water from a Gram-negative bacteria (E. coli), which is an indication for fecal pollution. An ultrasonic technique effectively achieved this dual target by producing nanolayered structures looking like nanotapes with dimensions of 25 nm. The maximum removal percentages of the heavy metals studied (i.e., iron (Fe), copper (Cu), chromium (Cr), nickel (Ni), and manganese (Mn)) were 85%, 79%, 68%, 63%, and 61%, respectively for one prepared structure. In addition, this nanostructure showed higher antimicrobial activity against the most common coliform bacterium, E. coli (inhibition zone up to 18.5 mm). This study introduces dual-functional material for removing different kinds of heavy metals from water in severe conditions and for treating wastewater for Gram-negative bacteria (E. coli).