bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection of Third-Party Reverse Logistics Service Provider Based on Intuitionistic Fuzzy Multi-Criteria Decision Making
Authors: Song Jiekun , Jiang Lina , Liu Zhicheng , Leng Xueli , He Zeguo
Published: October 2022

The scientific selection of a third-party reverse logistics service provider (3PRLP) is helpful for enterprises to obtain the expected ecological and economic benefits. Different enterprises have different requirements for 3PRLP selection and, thus, should adopt personalized and simplified evaluation criteria. However, there is a lack of research on criteria screening. Therefore, this paper proposes a criteria screening method based on a rough set for the first time. The 3PRLP selection is a multi-criteria decision making (MCDM) problem in essence, and different criteria can be expressed in different forms. The existing research mostly uses one method for 3PRLP selection, lacking the comprehensive application of various methods. In this paper, various criteria values are transformed into intuitionistic fuzzy numbers (IFNs) for the comparison and combination of various intuitionistic fuzzy MCDM methods. In terms of criteria weighting, a subjective weighting method based on an analytical network process (ANP) is proposed due to the possible correlation between the criteria at the same level. Meanwhile, an objective weighting method based on intuitionistic fuzzy entropy is proposed. The subjective and objective weights are integrated to form the more scientific combination weights. Combining the modeling principles of different intuitionistic fuzzy MCDM methods, the representative methods under each principle are chosen to build a combination evaluation idea that integrates multiple single evaluation models, and the specific evaluation steps are given, including the single evaluation, Kendall compatibility test, combination evaluation, and Spearman consistency test. An illustrative example of 3PRLP selection is provided to verify the feasibility of the methods of criteria screening and weighting and the combination evaluation idea.
Endoscopy Lifetime Systems Architecture: Scoping Out the Past to Diagnose the Future Technology
Authors: Browning Craig M. , Cloutier Robert , Rich Thomas C. , Leavesley Silas J.
Published: October 2022

Systems engineering captures the desires and needs of the customer to conceptualize a system from the overall goal down to the small details prior to any physical development. While many systems projects tend to be large and complicated (i.e., cloud-based infrastructure, long-term space travel shuttles, missile defense systems), systems engineering can also be applied to smaller, complex systems. Here, the system of interest is the endoscope, a standard biomedical screening device used in laparoscopic surgery, screening of upper and lower gastrointestinal tracts, and inspection of the upper airway. Often, endoscopic inspection is used to identify pre-cancerous and cancerous tissues, and hence, a requirement for endoscopic systems is the ability to provide images with high contrast between areas of normal tissue and neoplasia (early-stage abnormal tissue growth). For this manuscript, the endoscope was reviewed for all the technological advancements thus far to theorize what the next version of the system could be in order to provide improved detection capabilities. Endoscopic technology was decomposed into categories, using systems architecture and systems thinking, to visualize the improvements throughout the system’s lifetime from the original to current state-of-the-art. Results from this review were used to identify trends in subsystems and components to estimate the theoretical performance maxima for different subsystems as well as areas for further development. The subsystem analysis indicated that future endoscope systems will focus on more complex imaging and higher computational requirements that will provide improved contrast in order to have higher accuracy in optical diagnoses of early, abnormal tissue growth.
The Influencing Factors of Users’ Attitudes and Continuance Intention for Olympic Viewing on Mobile Applications in China
Authors: Yu Zhiyuan , Huang Yuke
Published: October 2022

Along with the proliferation of the mobile information system, broadcasters depend on multiple channels to distribute the massive amount of Olympic content. Users’ viewing habits for the Olympics gradually tend to be diverse, and undergo changes from the outlets of television to mobile broadcasting on smartphones. Through the mobile application of rights holding broadcasters, the users not only watch high-quality live-streaming content via multiple platforms but also enjoy interviews with athletes after the competition. In this way, it is necessary to investigate the users’ potential attitudes and intentions toward mobile viewing regarding the emerging techniques. In this study, we conduct an online survey to reveal the influencing factors of users’ attitudes and continuance intention of Olympic viewing on a mobile app during the period of Tokyo 2020 Summer and Beijing 2022 Winter Olympics, where a total of 439 valid responses are collected. A conceptual model integrating the technology acceptance model and information system success model is established, which consists of information quality (IQ), system quality (SYQ), subjective norms (SN), innovativeness (INN), perceived ease of use (PEOU), perceived enjoyment (PE), attitude (ATT), and continuance intention (CI). For the measurement, partial least square structural equation modeling is adopted to test the proposed model. The results show that respondents hold positive attitudes and robust continuous intentions towards mobile viewing. We also find that the constructs of IQ, SYQ, SN, INN, PEOU, and PE have a direct impact on attitude and continuance intention, which explained 80.6% and 70.8% of the variance, respectively. Although PEOU, PE, and SN are unexpected to have no direct correlation with CI, all of them can indirectly impact CI via the mediation of ATT. Therein, the moderation effects of average time focusing on Olympic contents and app usage time per session exists between PEOU and CI and SN and CI, accordingly. Through empirical investigation, this study offers a glimpse into individuals’ perception and willingness to mobile Olympic viewing, which aims to provide a reference for relevant Olympic service providers.
Evaluation Based on the Distance from the Average Solution Approach: A Derivative Model for Evaluating and Selecting a Construction Manager
Authors: Phan Phuong Thanh , Nguyen Phong Thanh
Published: October 2022

In the current market of integration and globalization, the competition between engineering and construction companies is increasing. Construction contractors can improve their competitiveness by evaluating and selecting qualified personnel for the construction engineering manager position for their company’s civil engineering projects. However, most personnel evaluation and selection models in the construction industry rely on qualitative techniques, which leads to unsuitable decisions. To overcome this problem, this paper presents evaluation criteria and proposes a new model for selecting construction managers based on the evaluation based on the distance from the average solution approach (EDASA). The research results showed that EDASA has many strengths, such as solving the problem faster when the number of evaluation criteria or the number of alternatives is increased.
Simulation Experiment of Environmental Impact of Deep-Sea Mining: Response of Phytoplankton Community to Polymetallic Nodules and Sediment Enrichment in Surface Water
Authors: Ou Rimei , Cai Lei , Qiu Jinli , Huang Hao , Ou Danyun , Li Weiwen , Lin Fanyu , He Xuebao , Wang Lei , Wu Risheng
Published: October 2022

In this paper, simulation experiments were conducted to study the response of phytoplankton biomass and community composition to the influence of polymetallic nodules and sediment at four stations in the western Pacific in 2021. Chlorophyll a, pico-phytoplankton cell abundance, and metal concentration were measured before and after 24 h of deck incubation. The results show that there were three different patterns of response, namely, restrained, stimulated, and unaffected patterns. The restrained pattern appeared in the filtered treatments at station Incub.01, and the stimulated pattern appeared in the unfiltered treatments at station Incub.02. The response of the phytoplankton was not detectable at stations Incub.03 and 04. Regardless, positive and negative responses were found in the dominant pico-phytoplankton group—Prochlorococcus—and with slight variation in Synechococcus. The concentration of manganese varied among the treatments compared to that of iron and other metals. The factors affecting the growth of the phytoplankton in this study were metal concentrations and turbidity. The phytoplankton biomass baseline may also have played an important role: the lower the biomass, the higher the growth rate. This study proved that deep-sea polymetallic nodule mining will have a specific impact on surface phytoplankton biomass, but turbidity and particle retention time could be important factors in mitigating the extent of the impact.
Effects of Brush-Type Ionizer Materials on Virus Inactivation
Authors: Heo Jaeseok , Lee Jooyeon , Park Duckshin
Published: October 2022

Many studies have found that bioaerosols are harmful to humans. In particular, infectious viruses, such as the virus that causes COVID-19, are increasing. Therefore, the research on methods for reducing bioaerosols is becoming progressively more important. The purpose of this study was to improve the existing electrostatic precipitator, which generates high concentrations of ozone, by reducing bioaerosols effectively without significant ozone production. A brush-type ionizer was studied as a replacement for the existing electrostatic precipitator. The study, which was conducted at the laboratory scale, determined the amounts of ions generated with different ionizer materials (carbon, copper, and stainless steel) and voltages (−1, −2, and −3 kV), as well as it compared the virus inactivation efficiency under the various conditions. As a result, about two million ions were produced when a voltage of −3 kV was applied to all of the materials, and 99.9 ± 0.2% and 98.8 ± 0.6% virus inactivation efficiencies were confirmed in the cases of carbon and copper, respectively. In addition, an assessment of the effect of flow velocity confirmed that the inactivation efficiency decreased as the flow velocity increased. However, the results for the flow velocities of 0.2 and 0.4 m/s had similar trends. Therefore, this system can be used with flow velocities up to 0.4 m/s.
Embryonic Nicotine Exposure Disrupts Adult Social Behavior and Craniofacial Development in Zebrafish
Authors: Borrego-Soto Gissela , Eberhart Johann K.
Published: October 2022

Cigarette smoking remains the leading cause of preventable death and morbidity worldwide. Smoking during pregnancy is associated with numerous adverse birth outcomes, including craniofacial and behavioral abnormalities. Although tobacco smoke contains more than 4000 toxic substances, nicotine is addictive and is likely the most teratogenic substance in cigarette smoke. However, much remains to be determined about the effects of embryonic nicotine exposure on behavior and craniofacial development. Therefore, this study evaluated adult social behavior in zebrafish, craniofacial defects, and nicotine metabolism in embryos after embryonic nicotine exposure. Zebrafish embryos were exposed to different doses of nicotine beginning at 6 h post fertilization. To evaluate craniofacial defects, the embryos were collected at 4 days post fertilization and stained with Alizarin Red and Alcian Blue. For behavioral testing, embryos were reared to adulthood. To evaluate nicotine metabolism, cotinine levels were analyzed at various time points. Our findings demonstrate that embryonic exposure to nicotine modifies social behavior in adulthood, causes craniofacial defects with reduced size of craniofacial cartilages, and that zebrafish metabolize nicotine to cotinine, as in humans. Together, our data suggest that zebrafish are useful as a model for studying nicotine-related diseases.
Variability of Microcystin-LR Standards Available from Seven Commercial Vendors
Authors: Hill Donna , Lang Johnsie , McCord James , Strynar Mark , Rosal Charlita , Schmid Judith , Le Thanh-Thao , Chernoff Neil
Published: October 2022

Microcystins (MCs) are a large group of heptapeptide cyanobacterial toxins commonly produced in harmful algal blooms (HABs) and associated with adverse health effects in wildlife, livestock, pets, and humans. MC chemical standards are extracted from cyanobacteria biomass rather than produced synthetically and are used in water assessment methods and toxicological studies. MC standards are generally supplied in less than 1 mg quantities, and verification of the mass can only be accomplished by analytical chemistry methods using a certified reference of the specific MC for comparison. Analytical quantification of MCs in environmental samples and toxicology studies using accurate doses of test chemicals administered to experimental animals rely on the availability and accuracy of chemical standards. To check the accuracy and purity of available standards, seven individual microcystin-LR (MCLR) standards were purchased from separate commercial vendors and analyzed to determine the actual mass supplied and identify the presence of potential contaminants. To determine the effect of varying toxin mass in toxicological studies, each MCLR standard was administered to CD-1 mice in doses based on mass purchased, by a single 40 µg/kg intraperitoneal injection. The measured mass purchased varied from the vendor label mass by more than 35% for two of the seven MCLR standards. Contaminants, including trifluoroacetic acid (TFA), were identified in four of the seven samples. Comparative in vivo hepatotoxicity between vendor samples closely reflected the actual amount of MCLR present in each standard and demonstrated the toxicological impact of varying cyanotoxin mass.
Programmed Aptamer Screening, Characterization, and Rapid Detection for α-Conotoxin MI
Authors: Guo Han , Deng Bowen , Zhao Luming , Gao Yun , Zhang Xiaojuan , Yang Chengfang , Zou Bin , Chen Han , Sun Mingjuan , Wang Lianghua , Jiao Binghua
Published: October 2022

Conotoxins (CTXs) are a variety of mixed polypeptide toxins, among which α-conotoxin MI (CTX-MI) is the most toxic. Serious toxic symptoms, a lack of counteracting drugs, and cumbersome detection processes have made CTX-MI a hidden danger for humans. One of the obstacles to resolving this problem is the absence of specific recognition elements. Aptamers have shown great advantages in the fields of molecule detection, drug development, etc. In this study, we screened and characterized aptamers for CTX-MI through a programmed process. MBMI-01c, the isolated aptamer, showed great affinity, with an affinity constant (KD) of 0.524 μM, and it formed an antiparallel G-quadruplet (GQ) structure for the specific recognition of CTX-MI. Additionally, an aptasensor based on the biolayer interferometry (BLI) platform was developed and displayed high precision, specificity, and repeatability with a limit of detection (LOD) of 0.26 μM. This aptasensor provides a potential tool for the rapid detection of CTX-MI in 10 min. The aptamer can be further developed for the enrichment, detoxification, and biological studies of CTX-MI. Additionally, the programmed process is applicable to screening and characterizing aptamers for other CTXs.
Exploring Mindful Self-Care as a Potential Mediator between Compassion Satisfaction and Compassion Fatigue among Student Services Professionals
Authors: Preston Portia Jackson , Sanchez Delia , Preston Kathleen Suzanne Johnson
Published: October 2022

Higher education professionals are subject to high levels of stress as they support student populations at risk of trauma. Compassion fatigue, which represents dimensions of secondary traumatic stress and burnout, is associated with a poorer health-related quality of life (HRQOL) among those providing student services. Prior studies on helping professionals have found that mindful self-care mediates the relationship between compassion satisfaction, the positive aspects of helping others in one’s role, and compassion fatigue, but this has not been sufficiently explored in this population. A total of 559 respondents (faculty, students, and staff) who provide non-instructional support across 23 student service areas at 22 comprehensive regional universities completed a cross-sectional survey assessing mindful self-care, professional quality of life and HRQOL. Path analyses were conducted using EQS 6.4 software to test one model controlled for age, progressing from compassion satisfaction to mindful self-care, to compassion fatigue, to HRQOL. Mindful self-care, particularly supportive structure, mediated the relationship between compassion satisfaction and compassion fatigue. Compassion satisfaction was positively associated with HRQOL through mindful self-care and compassion fatigue. Institutions seeking to address compassion fatigue and promote well-being should implement policies to facilitate self-care by ensuring manageable workloads and balancing internal and external demands.
Mycobacterium tuberculosis Drug Resistance in Ethiopia: An Updated Systematic Review and Meta-Analysis
Authors: Reta Melese Abate , Tamene Birhan Alemnew , Abate Biruk Beletew , Mensah Eric , Maningi Nontuthuko Excellent , Fourie P. Bernard
Published: October 2022

Background: Tuberculosis (TB) remains a significant global public health issue, despite advances in diagnostic technologies, substantial global efforts, and the availability of effective chemotherapies. Mycobacterium tuberculosis, a species of pathogenic bacteria resistant to currently available anti-TB drugs, is on the rise, threatening national and international TB-control efforts. This systematic review and meta-analysis aims to estimate the pooled prevalence of drug-resistant TB (DR-TB) in Ethiopia. Materialsand Methods: A systematic literature search was undertaken using PubMed/MEDLINE, HINARI, the Web of Science, ScienceDirect electronic databases, and Google Scholar (1 January 2011 to 30 November 2020). After cleaning and sorting the records, the data were analyzed using STATA 11. The study outcomes revealed the weighted pooled prevalence of any anti-tuberculosis drug resistance, any isoniazid (INH) and rifampicin (RIF) resistance, monoresistance to INH and RIF, and multidrug-resistant TB (MDR-TB) in newly diagnosed and previously treated patients with TB. Results: A total of 24 studies with 18,908 patients with TB were included in the final analysis. The weighted pooled prevalence of any anti-TB drug resistance was 14.25% (95% confidence interval (CI): 7.05–21.44%)), whereas the pooled prevalence of any INH and RIF resistance was found in 15.62% (95%CI: 6.77–24.47%) and 9.75% (95%CI: 4.69–14.82%) of patients with TB, respectively. The pooled prevalence for INH and RIF-monoresistance was 6.23% (95%CI: 4.44–8.02%) and 2.33% (95%CI: 1.00–3.66%), respectively. MDR-TB was detected in 2.64% (95%CI: 1.46–3.82%) of newly diagnosed cases and 11.54% (95%CI: 2.12–20.96%) of retreated patients with TB, while the overall pooled prevalence of MDR-TB was 10.78% (95%CI: 4.74–16.83%). Conclusions: In Ethiopia, anti-tuberculosis drug resistance is widespread. The estimated pooled prevalence of INH and RIF-monoresistance rates were significantly higher in this review than in previous reports. Moreover, MDR-TB in newly diagnosed cases remained strong. Thus, early detection of TB cases, drug-resistance testing, proper and timely treatment, and diligent follow-up of TB patients all contribute to the improvement of DR-TB management and prevention. Besides this, we urge that a robust, routine laboratory-based drug-resistance surveillance system be implemented in the country.
Special Issue “Emerging Diseases/Viruses: Prevention, Control, Surveillance, and One Health”
Authors: Simonin Yannick
Published: October 2022

Zoonotic diseases account for at least 60% of all infectious diseases and no less than two-thirds of new emerging ones, which underlines the importance of monitoring them as early as possible [...]
Quality, Equity and Partnerships in Mixed Methods and Qualitative Research during Seven Years of Implementing the Structured Operational Research and Training Initiative in 18 Countries
Authors: Zachariah Rony , Abrahamyan Arpine , Rust Stefanie , Thekkur Pruthu , Khogali Mohammed , Kumar Ajay M. V. , Davtyan Hayk , Satyanarayana Srinath , Shewade Hemant D. , Delamou Alexandre , Zolfo Maria , Hermans Veerle , Berger Selma Dar , Reid Anthony , Aseffa Abraham , Dongre Amol R. , Harries Anthony D. , Reeder John C.
Published: October 2022

Introduction: Qualitative studies are often inadequately reported, making it difficult to judge their appropriateness for decision making in public health. We assessed the publication characteristics and quality of reporting of qualitative and mixed-method studies from the Structured Operational Research and Training Initiative (SORT IT), a global partnership for operational research capacity building. Methods: A cross-sectional analysis of publications to assess the qualitative component using an adapted version of the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Results: In 67 publications involving 18 countries, 32 journals and 13 public health themes, 55 were mixed-methods studies and 12 were qualitative studies. First authorship from low-and-middle-income (LMIC) countries was present in 64 (96%), LMIC last authorship in 55 (82%), and female first authorship in 30 (45%). The mean LMIC institutions represented per publication was five (range 1–11). Sixty-three (94%) publications were open access. Reporting quality was graded as ‘good’ to ‘excellent’ in 60 (89%) publications, ‘fair’ in five (8%) and ‘poor’ in two (3%). Conclusion: Most SORT IT publications adhered to COREQ standards, while supporting gender equity in authorship and the promotion of LMIC research leadership. SORT IT plays an important role in ensuring quality of evidence for decision making to improve public health.
Testing the Wave-Particle Duality of Gravitational Wave Using the Spin-Orbital-Hall Effect of Structured Light
Authors: Wu Qianfan , Zhu Weishan , Feng Longlong
Published: October 2022

Probing the polarization of gravitational waves (GWs) would provide evidence of graviton, indicating the quantization of gravity. Motivated by the next generation of gravitational wave detectors, we make an attempt to study the possible helicity coupling of structured lights to GWs. With the analog between gravitational fields and the generic electromagnetic media, we present a 4-vector optical Dirac equation based on the Maxwell theory under the paraxial approximation. It is found that twisted lights propagating in a gravitational field can be viewed as a non-Hermitian system with PT symmetry. We further demonstrate that the coupling effect between angular momentums of the GWs and twisted lights may make photons undergo both dipole and quadrupole transitions between different orbital-angular-momentum (OAM) eigenstates and lead to some measurable optical features, including the central intensity brightening and macroscopic rotation of the intensity pattern for twisted lights. The former is spin-independent, while the latter is a spin-dependent phenomenon, both of which can be viewed alternatively as the spin-orbital-Hall effect of structured lights in the GWs and can serve as an indicator of the particle nature of GWs.
Broad-Spectrum Antivirals and Antiviral Combinations: An Editorial Update
Authors: Kainov Denis , Oksenych Valentyn
Published: October 2022

Our Special Issue received a great deal of attention, and several important papers have recently been added to it [...]
Pseudorabies Virus Associations in Wild Animals: Review of Potential Reservoirs for Cross-Host Transmission
Authors: Liu Aijing , Xue Tong , Zhao Xiang , Zou Jie , Pu Hongli , Hu Xiaoliang , Tian Zhige
Published: October 2022

Pseudorabies virus (PRV) has received widespread attention for its potential health effects on humans, wildlife, domestic animals, and livestock. In this review, we focus on PRV dynamics in wildlife, given the importance of wild-origin PRV transmission to domestic and farm animals. Wild boars, pigs, and raccoons can serve as reservoirs of PRV, with viral transmission to domestic livestock occurring via several routes, such as wild herd exposure, contaminated meat consumption, and insect vector transmission. Many endangered feline and canine species can be infected with PRV, with acute disease and death within 48 h. The first confirmed human case of PRV infection in mainland China was reported in 2017. Thus, PRV exhibits potentially dangerous cross-host transmission, which is likely associated with inappropriate vaccination, poor awareness, and insufficient biosecurity. Currently, no vaccine provides full protection against PRV in all animals. Here, we summarize the epidemiology and pathogenesis of PRV infection in wild, domestic, and farmed animals, which may facilitate the design of novel therapeutics and strategies for controlling PRV infection and improving wildlife protection in China.
Rhabdomyolysis after COVID-19 Infection: A Case Report and Review of the Literature
Authors: Bawor Monica , Sairam Shwetha , Rozewicz Rachel , Viegas Stuart , Comninos Alexander N. , Abbara Ali
Published: October 2022

Rhabdomyolysis is a condition in which muscle breaks down potentially leading to renal dysfunction, and often occurs secondary to a precipitating factor. Viral or bacterial infections are common precipitants for initiating rhabdomyolysis. Recently, healthcare systems across the world have been challenged by a pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing ‘coronavirus disease 2019’ (COVID-19) disease. SARS-CoV-2 infection is recognized to cause respiratory and cardiovascular compromise, thromboembolic events, and acute kidney injury (AKI); however, it is not known whether it can precipitate rhabdomyolysis, with only a limited number of cases of SARS-CoV-2 infection preceding rhabdomyolysis reported to date. Here, we report the case of a 64-year-old woman who developed rhabdomyolysis shortly after SARS-CoV-2 infection and COVID-19. She initially presented with muscular pain, a creatine kinase level of 119,301 IU/L, and a mild rise in her creatinine level to 92 µmol/L, but successfully recovered with intravenous fluid support. We also review the literature to summarise previously reported cases of rhabdomyolysis precipitated by SARS-CoV-2, highlighting the need to consider this diagnosis in patients presenting with SARS-CoV-2 and myalgia.
Prevalence and Risk Factors for HTLV-1/2 Infection inRiverside and Rural Populations of the State of Pará
Authors: de Lima Aline Cecy Rocha , Lopes Felipe Teixeira , de Oliveira Freitas Vanessa , Assad Michele Nascimento , de Sousa Renata Santos , Gonçalves Janete Silvana Souza , Gomes Jayanne Lílian Carvalho , dos Santos Bernardo Cintra , Lima Carlos Neandro Cordeiro , Abreu Isabella Nogueira , dos Santos Brito Wandrey Roberto , Pereira Keise Adrielle Santos , da Silva Torres Maria Karoliny , Lima Sandra Souza , Aben-Athar Cíntia Yolette Urbano , Guerreiro João Farias , Cayres Vallinoto Izaura M. V. , Vallinoto Antonio Carlos Rosário , Feitosa Rosimar Neris Martins
Published: October 2022

Human T-lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) infection has been described in several Amazonian populations; however, there is still a lack of data on the prevalence of the virus in riparian populations living in rural areas of the state of Pará. The present study aimed to evaluate the prevalence of HTLV-1/2 infection in four riverine communities and one rural area in the state of Pará and to describe the possible risk factors for infection. A total of 907 individuals responded to an epidemiological survey and gave blood samples collected for anti-HTLV-1/2 antibodies by immunoenzymatic assay (EIA). The serum-reactive samples were subjected to confirmation by an in-line assay (Inno-Lia) and by proviral DNA screening using real-time PCR (qPCR). The total prevalence was 0.8% (7/907) for HTLV-1/2 (CI: 0.2−1.3%), with 0.66% HTLV-1 and 0.11% HTLV-2. The prevalence by sex was 0.7% in women (4/565) and 0.9% in men (3/342). Among seropositive patients, 83.3% (5/7) reported being sexually active, and 57.1% (4/7) reported not having the habit of using condoms during their sexual relations. Intrafamily infection was also observed. The results reinforce the need for public policies to prevent and block the spread of HTLV, especially in riparian communities that are subject to difficulties in accessing the Unified Health System (Sistema Único de Saúde/SUS) because infected individuals need clinical monitoring for surveillance and early diagnosis of symptoms associated with HTLV-1.
Efficacy of Different Testing Scenarios in Reducing Transfusion-Transmitted Hepatitis B Virus (TT-HBV) Infection Risk
Authors: Lelie Nico , Busch Michael , Kleinman Steven
Published: October 2022

The efficacy of different screening scenarios in reducing hepatitis B virus (HBV) transmission risk as compared to the risk without screening was modeled in 9,337,110 donations from four geographical regions that had been subjected to hepatitis B surface antigen (HBsAg) and individual donation nucleic acid amplification testing (ID-NAT). We used the Weusten models for estimating infectivity risk for Red Blood Cell (RBC) transfusions in eight HBV infection stages and then evaluated multiple screening strategies based on minipool (MP) and ID-NAT options of different sensitivity for their efficacy in reducing this risk. The efficacy in reducing HBV transmission risk by screening scenarios across the regions varied between 81% (HBsAg only) and 99.2% (ID-NAT and anti-HBc). Highly sensitive ID-NAT alone achieved a slightly higher risk reduction (97.6–99.0%) than minipool of 6 donations (MP6)-NAT in combination with HBsAg and anti-HBc (96.3–98.7%). In ID-NAT screened lapsed and repeat donors, the additional risk removed by HBsAg testing was minimal (<0.1%). The modeling outcomes in this and two previous reports using this multi-regional database suggest that one could consider an ID-NAT alone testing scenario as an alternative to MP-NAT and serology-based testing algorithms and restrict serologic testing to first-time donors only.
TDP-43 Toxicity in Yeast Is Associated with a Reduction in Autophagy, and Deletions of TIP41 and PBP1 Counteract These Effects
Authors: Park Sei-Kyoung , Park Sangeun , Liebman Susan W.
Published: October 2022

When human TDP-43 is overexpressed in yeast it is toxic and forms cytoplasmic aggregates. The mechanism of this toxicity is unknown. Genetic screens for TDP-43 toxicity modifiers in the yeast system previously identified proteins, including PBP1, that enhance TDP-43 toxicity. The determination in yeast that deletion of PBP1 reduces TDP-43 toxicity while overexpression enhances toxicity, led to the discovery that its human homolog, ATXN2, is associated with ALS risk. Thus, the yeast system has relevance to human disease. We now show that deletion of a new yeast gene, tip41Δ, likewise suppresses TDP-43 toxicity. We also found that TDP-43 overexpression and toxicity is associated with reduced autophagy. This is consistent with findings in other systems that increasing autophagy reduces TDP-43 toxicity and is in contrast to a report of enhanced autophagy when TDP-43 was overexpressed in yeast. Interestingly, we found that deletions of PBP1 and TIP41, which reduced TDP-43 toxicity, eliminated TDP-43′s inhibition of autophagy. This suggests that toxicity of TDP-43 expressed in yeast is in part due to its inhibition of autophagy and that deletions of PBP1 and TIP41 may reduce TDP-43 toxicity by preventing TDP-43 from inhibiting autophagy.
A Novel Self-Cleaving Viroid-Like RNA Identified in RNA Preparations from a Citrus Tree Is Not Directly Associated with the Plant
Authors: Navarro Beatriz , Li Shuai , Gisel Andreas , Chiumenti Michela , Minutolo Maria , Alioto Daniela , Di Serio Francesco
Published: October 2022

Viroid and viroid-like satellite RNAs are infectious, circular, non-protein coding RNAs reported in plants only so far. Some viroids (family Avsunviroidae) and viroid-like satellite RNAs share self-cleaving activity mediated by hammerhead ribozymes (HHRzs) endowed in both RNA polarity strands. Using a homology-independent method based on the search for conserved structural motifs of HHRzs in reads and contigs from high-throughput sequenced RNAseq libraries, we identified a novel small (550 nt) viroid-like RNA in a library from a Citrus reticulata tree. Such a viroid-like RNA contains a HHRz in both polarity strands. Northern blot hybridization assays showed that circular forms of both polarity strands of this RNA (tentatively named citrus transiently-associated hammerhead viroid-like RNA1 (CtaHVd-LR1)) exist, supporting its replication through a symmetric pathway of the rolling circle mechanism. CtaHVd-LR1 adopts a rod-like conformation and has the typical features of quasispecies. Its HHRzs were shown to be active during transcription and in the absence of any protein. CtaHVd-LR1 was not graft-transmissible, and after its first identification, it was not found again in the original citrus source when repeatedly searched in the following years, suggesting that it was actually not directly associated with the plant. Therefore, the possibility that this novel self-cleaving viroid-like RNA is actually associated with another organism (e.g., a fungus), in turn, transiently associated with citrus plants, is proposed.
Comparative Pharmacokinetics of a Dual Inhibitor of HIV-1, NBD-14189, in Rats and Dogs with a Proof-of-Concept Evaluation of Antiviral Potency in SCID-hu Mouse Model
Authors: Stoddart Cheryl A. , Curreli Francesca , Horrigan Stephen , Altieri Andrea , Kurkin Alexander V. , Debnath Asim K.
Published: October 2022

We earlier reported substantial progress in designing gp120 antagonists. Notably, we discovered that NBD-14189 is not only the most active gp120 antagonist but also shows antiviral activity against HIV-1 Reverse Transcriptase (RT). We also confirmed its binding to HIV-1 RT by X-ray crystallography. The dual inhibition is highly significant because, intriguingly, this compound bridges the dNTP and NNRTI-binding sites and inhibits the polymerase activity of isolated RT in the enzymatic assay. This novel finding is expected to lead to new avenues in designing a novel class of HIV-1 dual inhibitors. Therefore, we needed to advance this inhibitor to preclinical assessment. To this end, we report the pharmacokinetics (PK) study of NBD-14189 in rats and dogs. Subsequently, we assessed the toxicity and therapeutic efficacy in vivo in the SCID-hu Thy/Liv mouse model. The PK data indicated a favorable half-life (t1/2) and excellent oral bioavailability (%F = 61%). NBD-14189 did not show any measurable toxicity in the mice, and treatment reduced HIV replication at 300 mg/kg per day in the absence of clear evidence of protection from HIV-mediated human thymocyte depletion. The data indicated the potential of this inhibitor as an anti-HIV-1 agent and needs to be assessed in a non-human primate (NHP) model.
Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders
Authors: Onisiforou Anna , Spyrou George M.
Published: October 2022

Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 and the development of ten neurological disorders and three neuropsychiatric disorders by exploring two pathological mechanisms: (i) dysregulation of host biological processes via virus–host protein–protein interactions (PPIs), and (ii) autoreactivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes with host “self” proteins via molecular mimicry. We also identify potential genetic risk factors which in combination with SARS-CoV-2 infection might lead to disease development. Our analysis indicated that neurodegenerative diseases (NDs) have a higher number of disease-associated biological processes that can be modulated by SARS-CoV-2 via virus–host PPIs than neuropsychiatric disorders. The sequence similarity analysis indicated the presence of several matching 5-mer and/or 6-mer linear motifs between SARS-CoV-2 epitopes with autoreactive epitopes found in Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Myasthenia Gravis (MG) and Multiple Sclerosis (MS). The results include autoreactive epitopes that recognize amyloid-beta precursor protein (APP), microtubule-associated protein tau (MAPT), acetylcholine receptors, glial fibrillary acidic protein (GFAP), neurofilament light polypeptide (NfL) and major myelin proteins. Altogether, our results suggest that there might be an increased risk for the development of NDs after COVID-19 both via autoreactivity and virus–host PPIs.
Cost-Effectiveness of COVID-19 Sequential Vaccination Strategies in Inactivated Vaccinated Individuals in China
Authors: Fu Yaqun , Zhao Jingyu , Wei Xia , Han Peien , Yang Li , Ren Tao , Zhan Siyan , Li Liming
Published: October 2022

To effectively prevent and control the COVID-19 pandemic, countries have adopted a booster vaccination strategy. This study aimed to estimate the cost-effectiveness of sequential booster COVID-19 vaccination compared to two-dose inactivated vaccination in China from a societal perspective. A Markov model was developed to estimate the cost-effectiveness of sequential vaccination, including two doses of an inactivated vaccine followed by a booster shot of an inactivated vaccine, adenovirus vectored vaccine, protein subunit vaccine, or mRNA vaccine. The incremental effects of a booster shot with an inactivated vaccine, protein subunit vaccine, adenovirus vectored vaccine, and mRNA vaccine were 0.0075, 0.0110, 0.0208, and 0.0249 QALYs and saved costs of US$163.96, US$261.73, US$583.21, and US$724.49, respectively. Under the Omicron virus pandemic, the sequential vaccination among adults and the elderly (aged 60–69, 70–79, over 80) was consistently cost-saving, and a booster shot of the mRNA vaccine was more cost-saving. The results indicate that the sequential vaccination strategy is cost-effective in addressing the COVID-19 pandemic, and improving vaccination coverage among the elderly is of great importance in avoiding severe cases and deaths.
A Scoping Review of Three Dimensions for Long-Term COVID-19 Vaccination Models: Hybrid Immunity, Individual Drivers of Vaccinal Choice, and Human Errors
Authors: Beerman Jack T. , Beaumont Gwendal G. , Giabbanelli Philippe J.
Published: October 2022

The virus that causes COVID-19 changes over time, occasionally leading to Variants of Interest (VOIs) and Variants of Concern (VOCs) that can behave differently with respect to detection kits, treatments, or vaccines. For instance, two vaccination doses were 61% effective against the BA.1 predominant variant, but only 24% effective when BA.2 became predominant. While doses still confer protection against severe disease outcomes, the BA.5 variant demonstrates the possibility that individuals who have received a few doses built for previous variants can still be infected with newer variants. As previous vaccines become less effective, new ones will be released to target specific variants and the whole process of vaccinating the population will restart. While previous models have detailed logistical aspects and disease progression, there are three additional key elements to model COVID-19 vaccination coverage in the long term. First, the willingness of the population to participate in regular vaccination campaigns is essential for long-term effective COVID-19 vaccination coverage. Previous research has shown that several categories of variables drive vaccination status: sociodemographic, health-related, psychological, and information-related constructs. However, the inclusion of these categories in future models raises questions about the identification of specific factors (e.g., which sociodemographic aspects?) and their operationalization (e.g., how to initialize agents with a plausible combination of factors?). While previous models separately accounted for natural- and vaccine-induced immunity, the reality is that a significant fraction of individuals will be both vaccinated and infected over the coming years. Modeling the decay in immunity with respect to new VOCs will thus need to account for hybrid immunity. Finally, models rarely assume that individuals make mistakes, even though this over-reliance on perfectly rational individuals can miss essential dynamics. Using the U.S. as a guiding example, our scoping review summarizes these aspects (vaccinal choice, immunity, and errors) through ten recommendations to support the modeling community in developing long-term COVID-19 vaccination models.
Barriers and Facilitators of Romanian HPV (Human Papillomavirus) Vaccination
Authors: Manolescu Loredana Sabina Cornelia , Zugravu Corina , Zaharia Corneliu Nicolae , Dumitrescu Anca Irina , Prasacu Irina , Radu Mihaela Corina , Letiția Goraneanu Draghici , Nita Irina , Cristache Corina Marilena , Gales Laurentia Nicoleta
Published: October 2022

Background: Many countries had initial success with HPV vaccination campaigns worldwide. The HPV vaccine coverage during the COVID-19 pandemic dropped consistently. The aim of our research is to assess the barriers and facilitators of the current Romanian HPV vaccination campaign. Methods: An analytical cross-sectional observational survey was conducted in the Romanian general population; a self-administered questionnaire was used. Results: 1122 responders were interviewed; 666 (59.36%) were parents, and 67 (5.97%) HPV vaccinated themselves. A multinominal logistic regression carried out in the parents’ category showed that women with university studies and informed from medical sources have greater chances to HPV vaccinate. Reticence regarding vaccination comes from the high cost of the vaccine and a lack of information. Only 118 (10.51%) vaccinated against HPV. From the logistic regression analysis, gender (ORa 0.461 = 95% CI: (0.196; 1.083)), geographic area of residence (ORa = 0.517; 95% CI: (0.331; 0.807)), and the inclusion of the HPV vaccine in the National Vaccination Program (ORa = 2.4; 95% CI: (1.361; 4.235)) were the factors found most associated with HPV vaccination. Conclusions: In the general population, the inclusion of HPV vaccination in the National Vaccination Program would be the most important facilitator of HPV vaccination in Romania. In parents that did not vaccinate their children, one important barrier to HPV vaccination was the high cost of the HPV vaccine and the lack of proper information. The acceptability of HPV vaccination in Romania is low; therefore, public health educational programs are needed.
Development of a Well-Characterized Cynomolgus Macaque Model of Sudan Virus Disease for Support of Product Development
Authors: Alfson Kendra J. , Goez-Gazi Yenny , Gazi Michal , Chou Ying-Liang , Niemuth Nancy A. , Mattix Marc E. , Staples Hilary , Klaffke Benjamin , Rodriguez Gloria F. , Escareno Priscilla , Bartley Carmen , Ticer Anysha , Clemmons Elizabeth A. , Dutton III John W. , Griffiths Anthony , Meister Gabe T. , Sanford Daniel C. , Cirimotich Chris M. , Carrion Ricardo
Published: October 2022

The primary objective of this study was to characterize the disease course in cynomolgus macaques exposed to Sudan virus (SUDV), to determine if infection in this species is an appropriate model for the evaluation of filovirus countermeasures under the FDA Animal Rule. Sudan virus causes Sudan virus disease (SVD), with an average case fatality rate of approximately 50%, and while research is ongoing, presently there are no approved SUDV vaccines or therapies. Well characterized animal models are crucial for further developing and evaluating countermeasures for SUDV. Twenty (20) cynomolgus macaques were exposed intramuscularly to either SUDV or sterile phosphate-buffered saline; 10 SUDV-exposed animals were euthanized on schedule to characterize pathology at defined durations post-exposure and 8 SUDV-exposed animals were not part of the scheduled euthanasia cohort. Survival was assessed, along with clinical observations, body weights, body temperatures, hematology, clinical chemistry, coagulation, viral load (serum and tissues), macroscopic observations, and histopathology. There were statistically significant differences between SUDV-exposed animals and mock-exposed animals for 26 parameters, including telemetry body temperature, clinical chemistry parameters, hematology parameters, activated partial thromboplastin time, serum viremia, and biomarkers that characterize the disease course of SUDV in cynomolgus macaques.
Development of the Sm14/GLA-SE Schistosomiasis Vaccine Candidate: An Open, Non-Placebo-Controlled, Standardized-Dose Immunization Phase Ib Clinical Trial Targeting Healthy Young Women
Authors: Santini-Oliveira Marília , Machado Pinto Patrícia , Santos Tatiane dos , Vilar Mônica Magno , Grinsztejn Beatriz , Veloso Valdilea , Paes-de-Almeida Elan C. , Amaral Maria A. Z. , Ramos Celso R. , Marroquin-Quelopana Miryam , Coler Rhea , Reed Steven , Ciol Marcia A. , Savino Wilson , Parra Juçara de Carvalho , Almeida Marília Sirianni dos Santos , Tendler Miriam
Published: October 2022

We report the successful closure of Phase I clinical trials, comprising Phases Ia and Ib, of the vaccine candidate against human schistosomiasis: the Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) + glucopyranosyl lipid A in squalene emulsion (GLA-SE). Shown here are the results of Phase Ib, an open, non-placebo-controlled, standardized-dose immunization trial involving 10 healthy 18–49-year-old women. Fifty micrograms of the Sm14 protein plus 10 µg GLA-SE per dose was given intramuscularly thrice at 30-day intervals. Participants were assessed clinically, biochemically, and immunologically for up to 120 days. In preambular experiments involving vaccinated pregnant female rabbits, we did not find any toxicological features in either the offspring or mothers, and the vaccine induced adaptive immunity in the animals. In women, no adverse events were observed, and vaccination induced high titers of anti-Sm14 serum IgG antibody production. Vaccination also elicited robust cytokine responses, with increased TNFα, IFNγ, and IL-2 profiles in all vaccinees on days 90 and 120. The completion of Phase I clinical trials, which were performed to the highest standards set by Good Clinical Research Practice (GCP) standards, and preclinical data in pregnant rabbits enabled the vaccine candidate to proceed to Phase II clinical trials in endemic areas.