bluuebunny/crossref_metadata_2025 huggingface dataset:
It’s All about Reward: Contrasting Joint Rewards and Individual Reward in Centralized Learning Decentralized Execution Algorithms
Authors: Atrazhev Peter , Musilek Petr
Published: March 2023

This paper addresses the issue of choosing an appropriate reward function in multi-agent reinforcement learning. The traditional approach of using joint rewards for team performance is questioned due to a lack of theoretical backing. The authors explore the impact of changing the reward function from joint to individual on learning centralized decentralized execution algorithms in a Level-Based Foraging environment. Empirical results reveal that individual rewards contain more variance, but may have less bias compared to joint rewards. The findings show that different algorithms are affected differently, with value factorization methods and PPO-based methods taking advantage of the increased variance to achieve better performance. This study sheds light on the importance of considering the choice of a reward function and its impact on multi-agent reinforcement learning systems.
Protective Role of Kelulut Honey against Toxicity Effects of Polystyrene Microplastics on Morphology, Hormones, and Sex Steroid Receptor Expression in the Uterus of Rats
Authors: Amran Nur Hanisah , Zaid Siti Sarah Mohamad , Meng Goh Yong , Salleh Annas , Mokhtar Mohd Helmy
Published: March 2023

Background: Microplastics (MPs) are an emerging global pollutant. Previous studies have revealed that chronic exposure to MPs can affect animal and human reproductive health, particularly by impairing the reproductive system’s normal functions, which may increase the risk of infertility in both males and females. Kelulut honey (KH), an excellent source of antioxidants, has been used to counteract the disruptive effects of Polystyrene microplastics (PS-MPs) in the rat uterus. Thus, this study aimed to investigate the potential protective effects of Kelulut honey against PS-MPs-induced uterine toxicity in pubertal rats. Methods: Prepubertal female Sprague Dawley rats were divided into four groups (n = 8): (i) normal control group (NC: treated with deionized water), MPs-exposed group (M: exposed to PS-MPs at 2.5 mg/kg), (iii) Kelulut honey group (DM: pretreated with 1200 mg/kg of KH 30 minutes before they were administered with PS-MPs at 2.5 mg/kg), and (iv) Kelulut honey control group (DC: only treated with KH at 2.5 mg/kg). The rats were treated orally once daily for six consecutive weeks. Results: Uterine abnormalities in PS-MPs-exposed rats were significantly improved after concurrent treatment with Kelulut honey. Morphology improvement was observed and luminal epithelial cells seemed thicker with more goblet cells, glandular cells had a more regular and circular shape, stromal cell increased in size, interstitial gaps between stromal cells expanded, and the myometrium layer was thicker. Kelulut honey treatment also effectively normalized the suppressive effect of PS-MPs on the expression and distribution of sex steroid receptors (ERα and ERβ), as well as the level of serum gonadotropin (LH and FSH) and sex steroid (estradiol and progesterone) hormones. Conclusion: Kelulut honey can protect the female reproductive system against the disruptive effects of PS-MPs. The phytochemical properties of Kelulut honey might be responsible for these beneficial benefits. However, future studies are warranted to identify the mechanisms involved.
Probing the Interactions of 31 Mycotoxins with Xanthine Oxidase: Alternariol, Alternariol-3-Sulfate, and α-Zearalenol Are Allosteric Inhibitors of the Enzyme
Authors: Balázs Orsolya , Dombi Ágnes , Zsidó Balázs Zoltán , Hetényi Csaba , Vida Róbert György , Poór Miklós
Published: March 2023

Mycotoxins are frequent toxic contaminants in foods and beverages, causing a significant health threat. Interactions of mycotoxins with biotransformation enzymes (e.g., cytochrome P450 enzymes, sulfotransferases, and uridine 5′-diphospho-glucuronosyltransferases) may be important due to their possible detoxification or toxic activation during enzymatic processes. Furthermore, mycotoxin-induced enzyme inhibition may affect the biotransformation of other molecules. A recent study described the strong inhibitory effects of alternariol and alternariol-9-methylether on the xanthine oxidase (XO) enzyme. Therefore, we aimed to test the impacts of 31 mycotoxins (including the masked/modified derivatives of alternariol and alternariol-9-methylether) on XO-catalyzed uric acid formation. Besides the in vitro enzyme incubation assays, mycotoxin depletion experiments and modeling studies were performed. Among the mycotoxins tested, alternariol, alternariol-3-sulfate, and α-zearalenol showed moderate inhibitory actions on the enzyme, representing more than tenfold weaker impacts compared with the positive control inhibitor allopurinol. In mycotoxin depletion assays, XO did not affect the concentrations of alternariol, alternariol-3-sulfate, and α-zearalenol in the incubates; thus, these compounds are inhibitors but not substrates of the enzyme. Experimental data and modeling studies suggest the reversible, allosteric inhibition of XO by these three mycotoxins. Our results help the better understanding of the toxicokinetic interactions of mycotoxins.
Diversity Begets Diversity When Diet Drives Snake Venom Evolution, but Evenness Rather Than Richness Is What Counts
Authors: Schaeffer Romane , Pascolutti Victoria J. , Jackson Timothy N. W. , Arbuckle Kevin
Published: March 2023

Snake venoms are primarily used to subjugate prey, and consequently, their evolution has been shown to be predominantly driven by diet-related selection pressure. Venoms tend to be more lethal to prey than non-prey species (except in cases of toxin resistance), prey-specific toxins have been identified, and preliminary work has demonstrated an association between the diversity of diet classes and that of toxicological activities of whole venom. However, venoms are complex mixtures of many toxins, and it remains unclear how toxin diversity is driven by diet. Prey-specific toxins do not encompass the molecular diversity of venoms, and whole venom effects could be driven by one, few, or all components, so the link between diet and venom diversity remains minimally understood. Here, we collated a database of venom composition and diet records and used a combination of phylogenetic comparative methods and two quantitative diversity indices to investigate whether and how diet diversity relates to the toxin diversity of snake venoms. We reveal that venom diversity is negatively related to diet diversity using Shannon’s index but positively related using Simpson’s index. Since Shannon’s index predominantly considers the number of prey/toxins, whereas Simpson’s index more strongly reflects evenness, we provide insights into how the diet–venom diversity link is driven. Specifically, species with low diet diversity tend to have venoms dominated by a few abundant (possibly specialised) toxin families, whereas species with diverse diets tend to ‘hedge their bets’ by having venoms with a more even composition of different toxin classes.
Community-Led Data Collection: Enhancing Local-Level Scabies Surveillance in Remote Aboriginal Communities in Australia
Authors: Glennie Miriam , Dowden Michelle , Scolyer Meg , O’Meara Irene , Angeles Geoffrey , Woerle Hannah , Campbell Patricia T. , Gardner Karen
Published: March 2023

Novel approaches to geohealth data analysis offer major benefits to neglected tropical disease control by identifying how social, economic and environmental elements of place interact to influence disease outcomes. However, a lack of timely and accurate geohealth data poses substantial risks to the accuracy of risk identification and challenges to the development of suitably targeted disease control programs. Scabies is one of many skin-related NTDs that is nominated as a priority for global disease control by the World Health Organization, but for which there remains a lack of baseline geospatial data on disease distribution. In this opinion paper, we consider lessons on impediments to geohealth data availability for other skin-related NTDs before outlining challenges specific to the collection of scabies-related geohealth data. We illustrate the importance of a community-centred approach in this context using a recent initiative to develop a community-led model of scabies surveillance in remote Aboriginal communities in Australia.
Dynamical Systems Analysis of f(Q) Gravity
Authors: Böhmer Christian , Jensko Erik , Lazkoz Ruth
Published: March 2023

Modified gravity theories can be used for the description of homogeneous and isotropic cosmological models through the corresponding field equations. These can be cast into systems of autonomous differential equations because of their sole dependence on a well-chosen time variable, be it the cosmological time, or an alternative. For that reason, a dynamical systems approach offers a reliable route to study those equations. Through a model-independent set of variables, we are able to study all f(Q) modified gravity models. The drawback of the procedure is a more complicated constraint equation. However, it allows the dynamical system to be formulated in fewer dimensions than using other approaches. We focus on a recent model of interest, the power-exponential model, and generalize the fluid content of the model.
Tracking the Genomic Evolution of SARS-CoV-2 for 29 Months in South Korea
Authors: Jeong Seri , Kim Jae-Seok , Lee Su Kyung , Cho Eun-Jung , Hyun Jungwon , Song Wonkeun , Kim Hyun Soo
Published: March 2023

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, with the persistent emergence of variants of concern (VOCs). Therefore, this study aimed to track the genomic evolution of SARS-CoV-2 strains by sequencing the spike protein for 29 months, which accounted for the majority of the COVID-19 pandemic period. A total of 109 swabs from patients with confirmed coronavirus disease 2019 (COVID-19) infection were randomly collected between March 2020 and July 2022. After genomic sequencing, we analyzed the naming systems and phylogenetic trees. Five surge peaks of COVID-19 cases have been reported in South Korea, resulting in 14,000,000 cumulative confirmed cases and 17,000 deaths. Among the sequenced samples, 34 wild-type strains and 75 VOCs, including 4 Alpha, 33 Delta, 2 Epsilon, and 36 Omicron VOCs, were identified. Omicron strains were comprised of 8 BA.1.1 (21 K), 27 BA.2 (21 L), and 1 BA.2.12.1 (22C). Phylogenetic analysis of the identified isolates and representative sequences of SARS-CoV-2 strains revealed clusters that presented the WHO VOCs. Specific or unique mutations for each VOC waxed and waned according to the variant waves. Our findings allowed recognition of the overall trends of SARS-CoV-2 isolates, which implicated replication advantage, immune evasion, and disease management.
Development and Evaluation of an Enzyme-Linked Immunosorbent Assay Targeting Rabies-Specific IgM and IgG in Human Sera
Authors: Zajac Michelle D. , Ortega Maria Teresa , Moore Susan M.
Published: March 2023

Immunity from rabies depends on rabies virus neutralizing antibodies (RVNA) induced after immunization; however, the influence of antibody isotype switching has not been extensively investigated. This has become particularly relevant with changes in World Health Organization (WHO) recommended rabies vaccine regimens that may influence RVNA isotype kinetics, potentially affecting the peak, and longevity, of RVNA immunoglobulin (IgG) levels. We developed rapid and reliable assays for quantifying the anti-rabies IgM/IgG class switch in human serum based on an indirect ELISA technique. The immune response was tracked in ten individuals naïve to the rabies vaccine by quantifying serum titers weekly, from day seven to day 42 post-immunization, using a serum neutralization assay and the ELISA IgM/IgG assays. The average RVNA IU/mL levels were at D0 ≤ 0.1, D7 0.24, D14 8.36, D21 12.84, D28 25.74 and D42 28.68. Levels of specific IgM antibodies to rabies glycoprotein (EU/mL) were higher, on average, at D7, 1.37, and from D14, 5.49, to D21, 6.59. In contrast, average IgG antibodies (EU/mL) predominated from D28, 10.03, to D42, 14.45. We conclude that levels of anti-rabies IgM/IgG at D28 characterize the isotype class switch. These assays, combined with serum neutralization assays, distinguished the RVNA levels in terms of the IgM/IgG responses and are expected to add to the diagnostic repertoire, provide additional information in establishing rabies vaccine regimens, both post- and pre-exposure prophylaxis, and contribute to research efforts.
SARS-CoV-2 Variants Detection Strategies in Wastewater Samples Collected in the Bangkok Metropolitan Region
Authors: Tangwangvivat Ratanaporn , Wacharapluesadee Supaporn , Pinyopornpanish Papassorn , Petcharat Sininat , Hearn Suthida Muangnoicharoen , Thippamom Nattakarn , Phiancharoen Chadaporn , Hirunpatrawong Piyapha , Duangkaewkart Phattra , Supataragul Ananporn , Chaiden Chadaporn , Wechsirisan Wiriyachayon , Wandee Nantaporn , Srimuang Krongkan , Paitoonpong Leilani , Buathong Rome , Klungthong Chonticha , Pawun Vichan , Hinjoy Soawapak , Putcharoen Opass , Iamsirithaworn Sopon
Published: March 2023

Wastewater surveillance is considered a promising approach for COVID-19 surveillance in communities. In this study, we collected wastewater samples between November 2020 and February 2022 from twenty-three sites in the Bangkok Metropolitan Region to detect the presence of SARS-CoV-2 and its variants for comparison to standard clinical sampling. A total of 215 wastewater samples were collected and tested for SARS-CoV-2 RNA by real-time PCR with three targeted genes (N, E, and ORF1ab); 102 samples were positive (42.5%). The SARS-CoV-2 variants were determined by a multiplex PCR MassARRAY assay to distinguish four SARS-CoV-2 variants, including Alpha, Beta, Delta, and Omicron. Multiple variants of Alpha–Delta and Delta–Omicron were detected in the wastewater samples in July 2021 and January 2022, respectively. These wastewater variant results mirrored the country data from clinical specimens deposited in GISAID. Our results demonstrated that wastewater surveillance using multiple signature mutation sites for SARS-CoV-2 variant detection is an appropriate strategy to monitor the presence of SARS-CoV-2 variants in the community at a low cost and with rapid turn-around time. However, it is essential to note that sequencing surveillance of wastewater samples should be considered complementary to whole genome sequencing of clinical samples to detect novel variants.
In-Depth Analysis of the Re-Emergence of Respiratory Syncytial Virus at a Tertiary Care Hospital in Germany in the Summer of 2021 after the Alleviation of Non-Pharmaceutical Interventions Due to the SARS-CoV-2 Pandemic
Authors: Hönemann Mario , Thiem Stephanie , Bergs Sandra , Berthold Tom , Propach Christian , Siekmeyer Manuela , Frille Armin , Wallborn Tillmann , Maier Melanie , Pietsch Corinna
Published: March 2023

Following the extensive non-pharmaceutical interventions (NPIs) and behavioral changes in the wake of the SARS-CoV-2 pandemic, an interseasonal rise in respiratory syncytial virus (RSV) cases was observed in Germany in 2021. The aim of this study was to characterize the local molecular epidemiology of RSV infections in comparison to the three pre-pandemic seasons. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of RSV infections. RSV detections peaked in calendar week 40 of 2021, 18 weeks earlier than the usual peak observed in the three pre-pandemic seasons. Sequence analysis revealed a close phylogenetic relatedness regardless of the season of origin. A significantly higher amount of pediatric cases (88.9% of all cases, p < 0.001) was observed for season 2021/2022. For the pediatric cases, significant differences were observed for an increased number of siblings in the household (p = 0.004), a lower rate of fever (p = 0.007), and a reduced amount of co-infections (p = 0.001). Although the mean age of the adult patients was significantly younger (47.1 vs. 64.7, p < 0.001), high rates of comorbidities, lower respiratory tract infections and intensive care unit admissions prevailed. The NPIs in the wake of the SARS-CoV-2 pandemic had a tremendous impact on the epidemiologic characteristics and seasonality of RSV and warrant further epidemiologic studies of this important pathogen.
Evaluation of the Hematological Patterns from Up to 985 Days of Long COVID: A Cross-Sectional Study
Authors: Galúcio Vanessa Costa Alves , Menezes Daniel Carvalho de , Lima Patrícia Danielle Lima de , Palácios Vera Regina da Cunha Menezes , Vasconcelos Pedro Fernando da Costa , Quaresma Juarez Antônio Simões , Falcão Luiz Fábio Magno
Published: March 2023

Long COVID affects many individuals following acute coronavirus disease 2019 (COVID-19), and hematological changes can persist after the acute COVID-19 phase. This study aimed to evaluate these hematological laboratory markers, linking them to clinical findings and long-term outcomes in patients with long COVID. This cross-sectional study selected participants from a ‘long COVID’ clinical care program in the Amazon region. Clinical data and baseline demographics were obtained, and blood samples were collected to quantify erythrogram-, leukogram-, and plateletgram-related markers. Long COVID was reported for up to 985 days. Patients hospitalized in the acute phase had higher mean red/white blood cell, platelet, and plateletcrit levels and red blood cell distribution width. Furthermore, hematimetric parameters were higher in shorter periods of long COVID than in longer periods. Patients with more than six concomitant long COVID symptoms had a higher white blood cell count, a shorter prothrombin time (PT), and increased PT activity. Our results indicate there may be a compensatory mechanism for erythrogram-related markers within 985 days of long COVID. Increased levels of leukogram-related markers and coagulation activity were observed in the worst long COVID groups, indicating an exacerbated response after the acute disturbance, which is uncertain and requires further investigation.
Development of an Indirect Enzyme-Linked Immunosorbent Assay Based on the Yeast-Expressed CO-26K-Equivalent Epitope-Containing Antigen for Detection of Serum Antibodies against Porcine Epidemic Diarrhea Virus
Authors: Yang Xuqiong , Li Liping , Su Xiaona , Li Jiadong , Liao Jiaming , Yang Jinyi , Xiao Zhili , Wen Peng , Wang Hong
Published: March 2023

Porcine epidemic diarrhea (PED) is a severe contagious intestinal disease caused by the porcine epidemic diarrhea virus (PEDV), which leads to high mortality in piglets. In this study, by analyzing a total of 53 full-length spike genes and COE domain regions of PEDVs, the conserved COE fragment of the spike protein from the dominant strain SC1402 was chosen as the target protein and expressed successfully in Pichia pastoris (P. pastoris). Furthermore, an indirect enzyme-linked immunosorbent assay (iELISA) based on the recombinant COE protein was developed for the detection of anti-PEDV antibodies in pig sera. The results showed that under the optimized conditions, the cut-off value of COE-based indirect ELISA (COE-iELISA) was determined to be 0.12. Taking the serum neutralization test as standard, the relative sensitivity of the COE-iELISA was 94.4% and specificity 92.6%. Meanwhile, no cross-reactivity to other porcine pathogens was noted with this assay. The intra-assay and inter-assay coefficients of variation were less than 7%. Moreover, 164 vaccinated serum samples test showed that overall agreement between COE-iELISA and the actual diagnosis result was up to 99.4%. More importantly, the developed iELISA exhibited a 95.08% agreement rate with the commercial ELISA kit (Kappa value = 0.88), which suggested that the expressed COE protein was an effective antigen in serologic tests and the established COE-iELISA is reliable for monitoring PEDV infection in pigs or vaccine effectiveness.
Grape Seed Proanthocyanidins Inhibit Replication of the Dengue Virus by Targeting NF-kB and MAPK-Mediated Cyclooxygenase-2 Expression
Authors: Chen Wei-Chun , Hossen Monir , Liu Wangta , Yen Chia-Hung , Huang Chung-Hao , Hsu Yao-Chin , Lee Jin-Ching
Published: March 2023

Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV infection, it is necessary to develop new agents or supplements that can do this. In this study, grape seed proanthocyanidins extract (GSPE), which is widely consumed as a dietary supplement, dose-dependently suppressed the replication of four DENV serotypes. The inhibitory mechanism demonstrated that GSPE downregulated DENV-induced aberrant cyclooxygenase-2 (COX-2) expression, revealing that the inhibitory effect of the GSPE on DENV replication involved targeting DENV-induced COX-2 expression. Mechanistic studies on signaling regulation have demonstrated that GSPE significantly reduced COX-2 expression by inactivating NF-κB and ERK/P38 MAPK signaling activities. Administrating GSPE to DENV-infected suckling mice reduced virus replication, mortality, and monocyte infiltration of the brain. In addition, GSPE substantially reduced the expression of DENV-induced inflammatory cytokines associated with severe dengue disease, including tumor necrosis factor-α, nitric oxide synthase, interleukin (IL)-1, IL-6, and IL-8, suggesting that GSPE has potential as a dietary supplement to attenuate DENV infection and severe dengue.
Thrombophilia and Immune-Related Genetic Markers in Long COVID
Authors: da Silva Rosilene , de Sarges Kevin Matheus Lima , Cantanhede Marcos Henrique Damasceno , da Costa Flávia Póvoa , dos Santos Erika Ferreira , Rodrigues Fabíola Brasil Barbosa , de Nazaré do Socorro de Almeida Viana Maria , de Meira Leite Mauro , da Silva Andréa Luciana Soares , de Brito Mioni Thieli Magalhães , da Silva Torres Maria Karoliny , Queiroz Maria Alice Freitas , Vallinoto Izaura Maria Vieira Cayres , Henriques Daniele Freitas , dos Santos Carla Pinheiro , Viana Giselle Maria Rachid , Quaresma Juarez Antônio Simões , Falcão Luiz Fábio Magno , Vallinoto Antonio Carlos Rosário , dos Santos Eduardo José Melo
Published: March 2023

Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development.
Effective Treatment of Staphylococcus aureus Intramammary Infection in a Murine Model Using the Bacteriophage Cocktail StaphLyse™
Authors: Brouillette Eric , Millette Guillaume , Chamberland Suzanne , Roy Jean-Pierre , Ster Céline , Kiros Tadele , Hickey Stephanie , Hittle Lauren , Woolston Joelle , Malouin François
Published: March 2023

Staphylococcus aureus causes intramammary infections (IMIs), which are refractory to antibiotic treatment and frequently result in chronic mastitis. IMIs are the leading cause of conventional antibiotic use in dairy farms. Phage therapy represents an alternative to antibiotics to help better manage mastitis in cows, reducing the global spread of resistance. A mouse mastitis model of S. aureus IMI was used to study the efficacy of a new cocktail of five lytic S. aureus-specific phages (StaphLyse™), administered either via the intramammary (IMAM) route or intravenously (IV). The StaphLyse™ phage cocktail was stable in milk for up to one day at 37 °C and up to one week at 4 °C. The phage cocktail was bactericidal in vitro against S. aureus in a dose-dependent manner. A single IMAM injection of this cocktail given 8 h after infection reduced the bacterial load in the mammary glands of lactating mice infected with S. aureus, and as expected, a two-dose regimen was more effective. Prophylactic use (4 h pre-challenge) of the phage cocktail was also effective, reducing S. aureus levels by 4 log10 CFU per gram of mammary gland. These results suggest that phage therapy may be a viable alternative to traditional antibiotics for the control of S. aureus IMIs.
Emerging Viral Infections in Pregnancy: What’s New in 2022?
Authors: Pomar Léo , Baud David
Published: March 2023

Dear contributors and readers, [...]
Evaluation of African Swine Fever Virus E111R Gene on Viral Replication and Porcine Virulence
Authors: Zhou Xintao , Fan Jiaqi , Zhang Yanyan , Yang Jinjin , Zhu Rongnian , Yue Huixian , Qi Yu , Li Qixuan , Wang Yu , Chen Teng , Zhang Shoufeng , Hu Rongliang
Published: March 2023

African swine fever (ASF) is an acute infectious disease of domestic pigs and wild boars caused by the African swine fever virus (ASFV), with up to a 100% case fatality rate. The development of a vaccine for ASFV is hampered by the fact that the function of many genes in the ASFV genome still needs to be discovered. In this study, the previously unreported E111R gene was analyzed and identified as an early-expressed gene that is highly conserved across the different genotypes of ASFV. To further explore the function of the E111R gene, a recombinant strain, SY18ΔE111R, was constructed by deleting the E111R gene of the lethal ASFV SY18 strain. In vitro, the replication kinetics of SY18ΔE111R with deletion of the E111R gene were consistent with those of the parental strain. In vivo, high-dose SY18ΔE111R (105.0 TCID50), administered intramuscularly to pigs, caused the same clinical signs and viremia as the parental strain (102.0 TCID50), with all pigs dying on days 8–11. After being infected with a low dose of SY18ΔE111R (102.0 TCID50) intramuscularly, pigs showed a later onset of disease and 60% mortality, changing from acute to subacute infection. In summary, deletion of the E111R gene has a negligible effect on the lethality of ASFV and does not affect the viruses’ ability to replicate, suggesting that E111R could not be the priority target of ASFV live-attenuated vaccine candidates.
Cost-Effectiveness of Vaccination of Older Adults with an MF59®-Adjuvanted Quadrivalent Influenza Vaccine Compared to Standard-Dose and High-Dose Vaccines in Denmark, Norway, and Sweden
Authors: Jacob Jorge , Biering-Sørensen Tor , Holger Ehlers Lars , Edwards Christina H. , Mohn Kristin Greve-Isdahl , Nilsson Anna , Hjelmgren Jonas , Ma Wenkang , Sharma Yuvraj , Ciglia Emanuele , Mould-Quevedo Joaquin
Published: March 2023

Individuals aged 65 years and above are at increased risk of complications and death from influenza compared with any other age group. Enhanced vaccines, as the MF59®-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (HD-QIV), provide increased protection for older adults in comparison to the traditional standard-dose quadrivalent influenza vaccines (SD-QIV). This study aimed to assess the cost-effectiveness of aQIV compared to SD-QIV and HD-QIV in Denmark, Norway, and Sweden for adults aged ≥65 years. A static decision tree model was used to evaluate costs and outcomes of different vaccination strategies from healthcare payer and societal perspectives. This model projects that compared to SD-QIV, vaccination with aQIV could prevent a combined total of 18,772 symptomatic influenza infections, 925 hospitalizations, and 161 deaths in one influenza season across the three countries. From a healthcare payer perspective, the incremental costs per quality adjusted life year (QALY) gained with aQIV versus SD-QIV were EUR 10,170/QALY in Denmark, EUR 12,515/QALY in Norway, and EUR 9894/QALY in Sweden. The aQIV was cost saving compared with HD-QIV. This study found that introducing aQIV to the entire population aged ≥65 years may contribute to reducing the disease and economic burden associated with influenza in these countries.
Influenza, Pneumococcal and Herpes Zoster Vaccination Rates in Patients with Autoimmune Inflammatory Rheumatic Diseases
Authors: Krasselt Marco , Wagner Ulf , Seifert Olga
Published: March 2023

Background: Vaccination rates are known to be low in patients with autoimmune inflammatory rheumatic diseases (AIIRD). We therefore aimed to determine current vaccination rates against influenza, Streptococcus pneumoniae and herpes zoster in a cohort of patients with AIIRD in Germany. Methods: Consecutive adult patients with an AIIRD were recruited from our outpatient clinic during their regular consultations. The individual vaccination status regarding influenza, Streptococcus pneumoniae and herpes zoster was obtained by reviewing the vaccination documents. Results: A total of 222 AIIRD patients (mean age 62.9 ± 13.9 years) were included. In total, 68.5% were vaccinated against influenza, 34.7% against Streptococcus pneumoniae and 13.1% against herpes zoster (HZ). The pneumococcal vaccination was outdated in 29.4% of the vaccinated patients. Vaccination rates were significantly higher in patients ≥60 years old (odds ratio (OR) 2.167, 95% confidence interval (CI) 1.213–3.870, p = 0.008 for influenza, OR 4.639, 95% CI 2.555–8.422, p < 0.0001 for pneumococcal and OR 6.059, 95% CI 1.772–20.712, p = 0.001 for HZ vaccination). Ages > 60 years, female sex, glucocorticoid use and influenza vaccination were all independently associated with a pneumococcal vaccination. Regarding influenza vaccination, only a positive pneumococcal vaccination history remained independently associated. In patients with HZ vaccination, glucocorticoid use and a preceding pneumococcal vaccination were independently associated with HZ protection. Conclusions: The frequencies of vaccinations against influenza, Streptococcus pneumoniae and HZ have increased during recent years. While this can be partly explained by continuous efforts in patient education during the outpatient visits, the COVID-19 pandemic might also have contributed. Nevertheless, the persistently high incidence and mortality of these preventable diseases in patients with AIIRDs mandates further efforts to increase vaccination coverage, particularly in SLE patients.
Shedding Light on Novel Pathogenic and Therapeutic Aspects Related to Immune-Mediated Skin Diseases
Authors: Chiricozzi Andrea , Girolomoni Giampiero
Published: March 2023

Great advances in the understanding of the pathogenic mechanisms characterizing various immune-mediated skin diseases have been achieved [...]
The Emergence of Hybrid Variants of SARS-CoV-2: Towards Hybrid Immunity
Authors: Chavda Vivek , Vuppu Suneetha , Mishra Toshika , Balar Pankti
Published: March 2023

In this review work, the authors emphasize the discussion on different emerging variants of SARS-CoV-2 and vaccine effectiveness against them [...]
COVID-19 Vaccine Hesitancy in a Population-Based Study of Minnesota Residents
Authors: Brandt Sallee , Demmer Ryan T. , Walsh Sara , Mulcahy John F. , Zepeda Evelyn , Yendell Stephanie , Hedberg Craig , Ulrich Angela K. , Beebe Timothy
Published: March 2023

COVID-19 continues to be a public health concern in the United States. Although safe and effective vaccines have been developed, a significant proportion of the US population has not received a COVID-19 vaccine. This cross-sectional study aimed to describe the demographics and behaviors of Minnesota adults who have not received the primary series of the COVID-19 vaccine, or the booster shot using data from the Minnesota COVID-19 Antibody Study (MCAS) collected through a population-based sample between September and December 2021. Data were collected using a web-based survey sent to individuals that responded to a similar survey in 2020 and their adult household members. The sample was 51% female and 86% White/Non-Hispanic. A total of 9% of vaccine-eligible participants had not received the primary series and 23% of those eligible to receive a booster had not received it. Older age, higher education, better self-reported health, $75,000 to $100,000 annual household income, mask-wearing, and social distancing were associated with lower odds of hesitancy. Gender, race, and previous COVID-19 infection were not associated with hesitancy. The most frequently reported reason for not receiving a COVID-19 vaccination was safety concerns. Mask-wearing and being age 65 or older were the only strong predictors of lower odds of vaccine hesitancy for both the primary series and booster analyses.
What Type of Person Should I Be? About the Appeal to Virtues in Public Health Interventions
Authors: Refolo Pietro , Sacchini Dario , Raimondi Costanza , Calabrò Giovanna Elisa , Spagnolo Antonio Gioacchino
Published: March 2023

In line with how ethics has developed for the last three centuries, public health ethics has been widely dominated by a deontological as well as a utilitarian approach. The latter is a version of consequentialism, which states that maximizing utility is the primary goal of the majority of individuals or group action, while, on the other hand, virtue ethics, or at least the appeal to virtues, has been largely marginalized. The aim of this article is twofold. Firstly, we aim to highlight the political and ethical nature of public health interventions, often interpreted and presented as mere scientific enterprises. Secondly, we try to highlight the need to integrate or at least recognize the value of appeal to virtues in public health measures. The analysis will reference the Italian COVID-19 vaccination program as a case study. Initially, we will explore the political and ethical nature of any public health measure, using the implementation of the COVID-19 vaccination program in Italy as an example. Subsequently, we will illustrate the deontological approach to ethics, the utilitarian one, and the virtues one, focusing on the dynamic of the agent’s perspective. Lastly, we will briefly analyze both the Italian COVID-19 vaccination program and the communication campaign that promoted it.
The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling
Authors: Palakkott Abdul Rasheed , Alneyadi Aysha , Muhammad Khalid , Eid Ali Hussein , Amiri Khaled M. A. , Akli Ayoub Mohammed , Iratni Rabah
Published: March 2023

The coronavirus disease-19 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the molecular and cellular levels, the SARS-CoV-2 uses its envelope glycoprotein, the spike S protein, to infect the target cells in the lungs via binding with their transmembrane receptor, the angiotensin-converting enzyme 2 (ACE2). Here, we wanted to investigate if other molecular targets and pathways may be used by SARS-CoV-2. We investigated the possibility of the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation were examined upon cell treatment with the recombinant full spike 1 S protein or RBD. We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical Extracellular signal-regulated kinase1/2 (ERK1/2) and AKT kinases and an increase in survivin expression controlling the survival pathway. Our study suggests the putative implication of EGFR and its related signaling pathways in SARS-CoV-2 infectivity and COVID-19 pathology. This may open new perspectives in the treatment of COVID-19 patients by targeting EGFR.
Gastrointestinal Parasites of Domestic Mammalian Hosts in Southeastern Iran
Authors: Hatam-Nahavandi Kareem , Carmena David , Rezaeian Mostafa , Mirjalali Hamed , Rahimi Hanieh Mohammad , Badri Milad , Vafae Eslahi Aida , Shahrivar Farzaneh Faraji , Rodrigues Oliveira Sonia M. , Pereira Maria de Lourdes , Ahmadpour Ehsan
Published: March 2023

Gastrointestinal parasites (GIP) are a major cause of disease and production loss in livestock. Some have zoonotic potential, so production animals can be a source of human infections. We describe the prevalence of GIP in domestic mammals in Southeastern Iran. Fresh fecal samples (n = 200) collected from cattle (n = 88), sheep (n = 50), goats (n = 23), camels (n = 30), donkeys (n = 5), horse (n = 1), and dogs (n = 3) were subjected to conventional coprological examination for the detection of protozoan (oo)cysts and helminth ova. Overall, 83% (166/200) of the samples were positive for one or more GIP. Helminths were found in dogs, donkeys, sheep (42%), camels (37%), goats (30%), and cattle (19%), but not in the horse. Protozoa were found in cattle (82%), goats (78%), sheep (60%), and camels (13%), but not in donkeys, dogs, or the horse. Lambs were 3.5 times more likely to be infected by protozoa than sheep (OR = 3.5, 95% CI: 1.05–11.66), whereas sheep were at higher odds of being infected by helminths than lambs (OR = 4.09, 95% CI: 1.06–16.59). This is the first study assessing the prevalence of GIP in domestic mammals in Southeastern Iran.
Batik Effluent Treatment and Decolorization—A Review
Authors: Zakaria Nuriah , Rohani Rosiah , Wan Mohtar Wan Hanna Melini , Purwadi Ronny , Sumampouw Giovanni Arneldi , Indarto Antonius
Published: March 2023

Batik is a piece of woven cloth decorated with beautiful patterns and designs and has become a signature product of the Malay Archipelago, including Malaysia and Indonesia. Batik industry consumes a large volume of water and produces a large amount of wastewater during the boiling process and dyeing process, both for hand-drawn (batik lukis) and block-printed (batik cap) batik. The release of colored effluents that contain a large number of dyes and chemicals can harm the environment and become a human health concern, particularly in south east Asian countries. Therefore, treatments of batik effluent are very crucial and have caught a lot of attention from researchers. The color removal is a major challenge, especially from this industry, as up until now there is no single and cost-effective treatment that can effectively decolorize as well as treat the dye effluent. Since batik is part of the textile industry, most treatment methods have been adapted from textile effluent treatment. Here, we review a variety of textile wastewater treatment techniques to make a good consideration of selecting the most appropriate method to be applied in batik wastewater. First, we briefly review the batik process, including the potential dyes that are mostly used in batik processing. Secondly, we describe all possible techniques and their performance to reduce dye concentration and decolorization. Finally, we review all advantages and disadvantages of these techniques for domestic and industrial applications.
Predicting Discharge Coefficient of Triangular Side Orifice Using LSSVM Optimized by Gravity Search Algorithm
Authors: Khosravinia Payam , Nikpour Mohammad Reza , Kisi Ozgur , Adnan Rana Muhammad
Published: March 2023

Side orifices are commonly installed in the side of a main channel to spill or divert some of the flow from the source channel to lateral channels. The aim of the present study is the accurate estimation of the discharge coefficient for flow through triangular (Δ-shaped) side orifices by applying three data-driven models including support vector machine (SVM), least squares support vector machine (LSSVM) and least squares support vector machine improved by gravity search algorithm (LSSVM-GSA). The discharge coefficient was estimated by utilizing five dimensionless variables resulted from experimental data (570 runs). Five different scenarios were applied based on the input variables. The models were evaluated through several statistical indices and graphical charts. The results showed that all of the models could successfully estimate the discharge coefficient of Δ-shaped side orifices with adequate accuracy. However, the LSSVM-GSA produced the best performance for the input combination of all variables with the highest coefficients of determination (R2) and Nash–Sutcliffe efficiency (NSE), equal to 0.965 and 0.993, and the least root mean square error (RMSE) and mean absolute error (MAE), equal to 0.0099 and 0.0077, respectively. The LSSVM-GSA improved the RMSE of the SVM and LSSVM by 26% and 20% in estimating the discharge coefficient. Furthermore, the ratio of orifice crest height to orifice height (W/H) was identified as having the highest influence on the discharge coefficient of triangular side orifices among the various input variables.
Direct Power Control of a Bipolar Output Active Rectifier for More Electric Aircraft Based on an Optimized Sector Division
Authors: Zhao Yajun , Huang Wenxin , Bu Feifei
Published: March 2023

This paper presents a novel direct power control (DPC) strategy based on an optimized sector division for a three-phase coupled inductor-based bipolar output active rectifier (TCIBAR) applied in more electric aircraft (MEA). First, based on the instantaneous power theory, the power model of the TCIBAR is built in the synchronous rotating coordinate system. Second, to implement the hysteresis power control of TCIBAR without causing the runaway of the zero-sequence current in the three-phase coupled inductor (TCI), a set of new voltage vectors that have the same zero-sequence voltage (ZSV) component are synthesized and adopted in the proposed DPC strategy. Third, by quantitatively analyzing the effect of the new synthesized voltage vectors on the power variation of TCIBAR, an optimized sector division method is proposed to improve the accuracy of power control and reduce the phase current harmonics in TCIBAR. Finally, to maintain the voltage balance of the bipolar dc ports in TCIBAR, voltage balance control is studied in the proposed DPC strategy. The proposed DPC strategy is researched on an experimental platform of TCIBAR, and the results show that the proposed DPC strategy is feasible and has good static and dynamic performance.
Topical fluoride treatment effectiveness: a systematic review
Authors: Brusnitsyna E. V. , Ginkel D. A. , Prihodkin A. S. , Zakirov T. V. , Ioshchenko E. S. , Shishmareva A. S.
Published: March 2023

Relevance. The systematic review aimed to evaluate the effectiveness of topical fluoride in children based on the analysis of modern randomized clinical trial (RCT) data.

Materials and methods. This review was carried out using the PRISMA checklist (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The proposed criteria determined the quality of the studies for inclusion in the review and then during the result summary. A preliminary search was conducted among articles published between 2013 and 2023 where fluoride varnishes were one of the preventive products. The search included MeSH terms, the keywords "fluorides", "fluorine varnish", "caries prevention", "remineralisation", and "children". A preliminary search found 346 studies. After excluding duplicates and irrelevant studies, two independent reviewers analysed nine RCTs based on the PRISMA criteria.

Results. Children aged eight months to five years old participated in five out of nine RCTs on the fluoride varnish application included in the review, and four studies included adolescents aged 14–20 y.o. The duration of the studies ranged from 2 months to 3.5 years. Six studies described the use of fluoride varnish in children, and three studies reported on the application of calcium phosphate gels with fluoride versus fluoride varnish. Various ways determined enamel condition, namely, visual method, digitally processed photography, analysis of radiographs, QLF (quantitative light fluorescence method), and laser fluorescence analysis method (Diagnodent). The dmft, ICDAS indices, caries increment, the WSL (white spot lesion) index, and the assessment of changes in the tooth damage area evaluated the prevalence and intensity of caries. In the control groups, most studies used 1000 to 1500 ppm fluoride toothpastes according to the usual scheme. None of the studies statistically proved the additional preventive effectiveness of the fluoride varnishes.

Conclusions. The analysis of RCTs did not reveal the advantages of fluoride varnishes for caries prevention in children and adolescents compared to standard oral hygiene procedures using fluoride toothpastes.
Los principios procesales dentro del nuevo paradigma constitucional: breves comentarios al Código Orgánico General de Procesos del Ecuador
Authors: Linzán-Saltos María Fernanda , Navarro-Cejas Mercedes , Párraga-Lino Andrea Beatriz
Published: March 2023

El presente trabajo tiene como objetivo general analizar jurídicamente los principios de carácter procesal previstos en el ordenamiento constitucional y la relevancia que estos han adquirido dentro del nuevo escenario jurídico que vive el Ecuador desde el 2008 con la nueva Constitución y posteriormente, en el 2016, con el Código Orgánico General de Procesos. En la investigación se tratan las nociones que surgieron a raíz del nuevo paradigma constitucional, como elemento central del quehacer público, particularmente, en la esfera judicial, al centrarse el argumento en los aspectos procesales preponderantes a la hora de la sustanciación de juicios. Para lo anterior, se aborda el tema desde una visión técnico - jurídica, bajo la aplicación metodológica del enfoque cualitativo, en el cual, se realiza un análisis documental y la confrontación de posiciones, al tenerse como instrumento de información, investigaciones previas. Lo que, permitió en primera instancia, realizar la distinción entre reglas y principios, en relación a la seguridad jurídica. Así como, identificar los principales cambios que surgieron a raíz de la implementación de la oralidad. El estudio concluye que, los principios procesales al estar constitucionalizados, han adquirido mayor relevancia al punto de ser los parámetros rectores y como resultado el imperativo de su observancia, sin que aquello pueda ser entendido como la sobre posición de estos respecto de las reglas procesales de orden legal, sino por el contrario, como instrumento que armoniza las últimas, con el propósito de tutelar los derechos fundamentales, tales como el del debido proceso.