bluuebunny/crossref_metadata_2025 huggingface dataset:
Mouse Adapted SARS-CoV-2 (MA10) Viral Infection Induces Neuroinflammation in Standard Laboratory Mice
Authors: Amruta Narayanappa , Ismael Saifudeen , Leist Sarah R. , Gressett Timothy E. , Srivastava Akhilesh , Dinnon Kenneth H. , Engler-Chiurazzi Elizabeth B. , Maness Nicholas J. , Qin Xuebin , Kolls Jay K. , Baric Ralph S. , Bix Gregory
Published: January 2023

Increasing evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection impacts neurological function both acutely and chronically, even in the absence of pronounced respiratory distress. Developing clinically relevant laboratory mouse models of the neuropathogenesis of SARS-CoV-2 infection is an important step toward elucidating the underlying mechanisms of SARS-CoV-2-induced neurological dysfunction. Although various transgenic models and viral delivery methods have been used to study the infection potential of SARS-CoV-2 in mice, the use of commonly available laboratory mice would facilitate the study of SARS-CoV-2 neuropathology. Herein we show neuroinflammatory profiles of immunologically intact mice, C57BL/6J and BALB/c, as well as immunodeficient (Rag2−/−) mice, to a mouse-adapted strain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 (MA10)). Our findings indicate that brain IL-6 levels are significantly higher in BALB/c male mice infected with SARS-CoV-2 MA10. Additionally, blood-brain barrier integrity, as measured by the vascular tight junction protein claudin-5, was reduced by SARS-CoV-2 MA10 infection in all three strains. Brain glial fibrillary acidic protein (GFAP) mRNA was also elevated in male C57BL/6J infected mice compared with the mock group. Lastly, immune-vascular effects of SARS-CoV-2 (MA10), as measured by H&E scores, demonstrate an increase in perivascular lymphocyte cuffing (PLC) at 30 days post-infection among infected female BALB/c mice with a significant increase in PLC over time only in SARS-CoV-2 MA10) infected mice. Our study is the first to demonstrate that SARS-CoV-2 (MA10) infection induces neuroinflammation in laboratory mice and could be used as a novel model to study SARS-CoV-2-mediated cerebrovascular pathology.
Ebola Virus Activates IRE1α-Dependent XBP1u Splicing
Authors: Rohde Cornelius , Pfeiffer Sebastian , Baumgart Sara , Becker Stephan , Krähling Verena
Published: January 2023

Ebola (EBOV) and Marburg virus (MARV) are highly pathogenic filoviruses that influence cellular signaling according to their own needs. MARV has been shown to regulate the IRE1α-dependent unfolded protein response (UPR) to ensure optimal virus replication. It was not known whether EBOV affects this signaling cascade, which can be beneficial or detrimental for viruses. Activation of IRE1α leads to the expression of the transcription factor XBP1s, which binds to cis-acting UPR elements (UPRE), resulting in the expression of genes aimed at restoring homeostasis in the endoplasmic reticulum. We observed that EBOV infection, in contrast to MARV infection, led to UPR activation by IRE1α-dependent but not ATF6-dependent signaling. We showed an activation of IRE1α, XBP1s and UPRE target genes upon EBOV infection. ATF6, another UPRE transcription factor, was not activated. UPRE activation was mainly attributed to the EBOV nucleoprotein NP and the soluble glycoprotein sGP. Finally, activation of UPR by thapsigargin, a potent ER-stress inducer, in parallel to infection as well as knock-out of XBP1 had no effect on EBOV growth, while MARV proliferation was affected by thapsigargin-dependent UPR activation. Taken together EBOV and MARV differ in their strategy of balancing IRE1α-dependent signaling for their own needs.
Secular Trends of Clinical Characteristics and Survival of Hepatocellular Carcinoma in Taiwan from 2011 to 2019
Authors: Kee Kwong-Ming , Chen Chien-Hung , Hu Jui-Ting , Huang Yi-Hsiang , Wang Tsang-En , Chau Gar-Yang , Chen Kuo-Hsin , Chen Yao-Li , Lin Chih-Che , Hung Chien-Fu , Huang Shiu-Feng , Liu Tsang-Wu , Ku Hsiu-Ying , Huang Bing-Shen , Wang Yi-Pin , Tseng Hui-Ping , Chiang Chun-Ju , Lu Sheng-Nan
Published: January 2023

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Taiwan, and in the past 30–40 years, Taiwan has been committed to its prevention and treatment. We aimed to investigate the secular trends of characteristics and the survival of HCC in recent decades after making increased efforts. Between 2011 and 2019, a total of 73,817 cases were enrolled from the TCR database. The overall male-to-female ratio was 7/3. The overall, male and female mean ages increased from 63.8 to 66.1 years, 62.0 to 64.3 years and 68.3 to 70.4 years, respectively. After dividing by viral etiologies and gender, the mean age showed increasing trends in all subgroups. The proportions of HBV-HCC, HCV-HCC, HBV+HCV-HCC and Non-HBV+non-HCV-HCC were 48.3%, 25.2%, 5.3% and 21.3% in males, compared with 25.5%, 48.6%, 5.3% and 20.5% in females, respectively. The 5-year survival rates of BCLC stages 0, A, B, C and D were 70%, 58%, 34%, 11% and 4%, respectively. The proportion of BCLC stage 0 increased from 6.2% to 11.3%. Multivariate analysis showed that being female, older age, diagnostic year, BCLC stages, hospital level, body mass index, smoking, alcohol consumption, AFP, Child–Pugh classification and HBV/HCV status were independent predictors for survival. In recent decades, the overall survival of HCC in Taiwan has been improving and might be partly associated with increased BCLC 0 and Child–Pugh A patients, while with the consequent age of patients increasing over time. The proportion of viral-related HCC is decreasing, while nonviral-related HCC is increasing.
A Cross-Sectional Comparative Characterization of Hematological Changes in Patients with COVID-19 Infection, Non-COVID Influenza-like Illnesses and Healthy Controls
Authors: Kala Mansi , Ahmad Sohaib , Dhebane Meghali , Das Kunal , Raturi Manish , Tyagi Meghna , Kusum Anuradha
Published: January 2023

Introduction: Studies have documented the role of the “neutrophil-to-lymphocyte ratio” (NLR) in influenza virus infection. In addition, morphometric parameters derived from automated analyzers on the volume, scatter and conductivity of monocytes, neutrophils and lymphocytes in many viral etiologies have helped with their early differentiation. With this background, we aimed to characterize the hematological changes of coronavirus-positive cases and also compare them with the healthy controls and patients affected by non-COVID Influenza-like illnesses so that early isolation could be considered. Material and Methods: This was a cross-sectional analytical study carried out in the years 2020–2022. All cases with COVID-19 and non-COVID-19 Influenza-like illnesses and healthy controls above 18 years were included. Cases were diagnosed according to the WHO guidelines. All samples were processed on a Unicel DxH 800 (Beckman Coulter, California, USA) automated hematology analyzer. The demographic, clinical and regular hematological parameters along with additional parameters such as volume, conductivity and scatter (VCS) of the three groups were compared. Results: The 169 COVID-19 cases were in the moderate to severe category. Compared with 140 healthy controls, the majority of the routine hematological values including the NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio) showed statistically significant differences. A cutoff of an absolute neutrophil count of 4350 cell/cumm was found to have a sensitivity of 76% and specificity of 70% in differentiating moderate and severe COVID-19 cases from healthy controls. COVID-19 and the non-COVID-19 Influenza-like illnesses were similar statistically in all parameters except the PLR, mean neutrophilic and monocytic volume, scatter parameters in neutrophils, axial light loss in monocytes and NLR. Interestingly, there was a trend of higher mean volumes and scatter in neutrophils and monocytes in COVID-19 cases as compared to non-COVID-19 Influenza-like illnesses. Conclusion: We demonstrated morphological changes in neutrophils, monocytes and lymphocytes in COVID-19 infection and also non-COVID-19 Influenza-like illnesses with the help of VCS parameters. A cutoff for the absolute neutrophils count was able to differentiate COVID-19 infection requiring hospitalization from healthy controls and eosinopenia was a characteristic finding in cases with COVID-19 infection.
Factors Associated with Dog Rabies Immunization in Changsha, China: Results of a Cross-Sectional Cluster Survey, 2015–2021
Authors: Ji Chunxiao , Feng Jia , Li Siying , Yang Hui , Wang Hui , Geng Xiangchang , Wang Hongliang , Liu Zengzai , Zhang Tao , He Yu , Liu Wei
Published: January 2023

The objective of this study was to examine longitudinal trends in the prevalence of dogs that are successfully immunized against rabies virus (as measured by sufficient serum antibodies) in Changsha, an urban center of China. The secondary objective was to investigate the factors affecting the seroprevalence of rabies virus antibodies in dogs. In this study, 4515 canine serum samples were collected from 57 pet hospitals (immunization points) during the period of 2015–2021 in five major urban areas of Kaifu, Furong, Tianxin, Yuhua, and Yuelu in Changsha, China. The enzyme-linked immunosorbent assay (ELISA) method was used to analyze the level and trend of rabies virus antibodies in serum and further evaluate the potential factors affecting the immunization effect from five factors: sex, age, time interval after most recent vaccination and sample collection, number of vaccinations, and vaccine manufacturer. The results showed that the seroconversion from the urban dog in Changsha steadily increased from 46.13% to 73.38% during 2015–2017. The seropositivity prevalence remained above the international standard (70%) from 2018 to 2020 and up to 90.99% in 2021. Further analysis showed that the seroconversion of rabies virus among dogs was significantly affected by the age, the number of vaccinations, time interval after the most recent vaccination and sample collection, and vaccine manufacturer, while sex had less influence. The overall rabies vaccination situation in urban areas of Changsha generally meets international standards, with only a few areas showing low levels of antibodies in dogs after vaccination and risk of infectiousness. Therefore, it is recommended that the first vaccination should be given when the dog is about three months old and regularly repeated every year after that. At the same time, antibody concentrations in dogs, especially in newborn puppies and older dogs, need to be tested promptly after vaccination at the required time to ensure that they are at a high level of immune protection, which can strengthen the supervision of rabies.
Fast and Sensitive Detection of Soil-Borne Cereal Mosaic Virus in Leaf Crude Extract of Durum Wheat
Authors: Marra Monica , D’Errico Chiara , Montemurro Cinzia , Ratti Claudio , Baldoni Elena , Matic Slavica , Accotto Gian Paolo
Published: January 2023

Soil-borne cereal mosaic virus (SBCMV) is a furovirus with rigid rod-shaped particles containing an ssRNA genome, transmitted by Polymyxa graminis Led., a plasmodiophorid that can persist in soil for up to 20 years. SBCMV was reported on common and durum wheat and it can cause yield losses of up to 70%. Detection protocols currently available are costly and time-consuming (real-time PCR) or have limited sensitivity (ELISA). To facilitate an efficient investigation of the real dispersal of SBCMV, it is necessary to develop a new detection tool with the following characteristics: no extraction steps, very fast results, and high sensitivity to allow pooling of a large number of samples. In the present work, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) protocol with such characteristics, and we have compared it with real-time PCR. Our results show that the sensitivity of LAMP and real-time PCR on cDNA and RT-LAMP on crude extracts are comparable, with the obvious advantage that RT-LAMP produces results in minutes rather than hours. This paves the way for extensive field surveys, leading to a better knowledge of the impact of this virus on wheat health and yield.
Durability of ChAdOx1 nCoV-19 (Covishield®) Vaccine Induced Antibody Response in Health Care Workers
Authors: Verma Alka , Goel Amit , Katiyar Harshita , Tiwari Prachi , Mayank Mayank , Sana Asari , Khetan Dheeraj , Bhadauria Dharmendra Singh , Raja Ajay , Khokher Neelam , Shalimar Shalimar , Singh Ratendra Kumar , Aggarwal Amita
Published: January 2023

(i) Background: ChAdOx1 nCoV-19 (Covishield®) vaccine is widely used in India. We studied the Covishield® induced antibody response and its durability among health care workers (HCWs) (ii) Method: HCWs received two doses (0.5 mL) four weeks apart. Blood specimens, collected before each dose, day (D)60, D150 and D270 after second dose, were tested for anti-spike antibody (ASAb) titre and neutralising antibody (%) (NAb) using Elecsys Anti-SARS-CoV-2 S (Roche) and SARS-CoV-2 NAb ELISA Kit (Invitrogen), respectively. Data are expressed as proportions and median (interquartile range) and compared using non-parametric (iii) Result: Among 135 HCWs (83 males; age 45 (37–53); 36 had pre-existing ASAb), 29 (21.5%) acquired COVID-19 after 60 (39–68) days of vaccination. ASAb titre before second dose and at D60, D150, D270 were 77.2 (19.4–329.4), 512 (114.5–9212), 149 (51.6–2283) and 2079 (433.9–8644) U/mL, respectively. Compared to those without pre-existing ASAb, titres were significantly higher before second dose (5929 vs. 41, p < 0.001), D60 (3395 vs. 234, p = 0.007) and D150 (1805 vs. 103, p < 0.001) in participants with pre-existing ASAb; NAb were also higher (80 vs. 18, p < 0.001) before second dose. Between those who acquired infection or not after vaccination, ASAb titres were comparable before second dose (77 vs. 78, p = 0.362) but significantly higher at D60 (14,019 vs. 317, p < 0.001) and D150 (2062 vs. 121, p = 0.002) in the former group, though NAb percentage were higher at D60 (87 vs. 27, p < 0.001) and D150 (79 vs. 25, p = 0.007) only (iv) Conclusions: Covishield® induces a higher antibody titre in those with pre-existing ASAb. The vaccine induced antibody starts falling 5 months after vaccination.
Development and Validation of the Outcome Expectancy Scale for COVID-19 Vaccination in the Adult General Population
Authors: Yu Yanqiu , Fong Vivian W. I. , Lau Mason M. C. , Lau Joseph T. F.
Published: January 2023

Promotion of COVID-19 vaccination requires understanding its determinants, an important one of which is outcome expectancy. However, reliable and valid measurement tools are absent. This study thus developed and validated an Outcome Expectancy Scale for COVID-19 Vaccination (OES-COVID-19). An inductive approach was used for scale development; content validity of the items was then assessed by an independent evaluation expert panel. Iteratively, 17 scale items were created and validated in a population-based telephone survey conducted among 500 adults of the general population in Hong Kong, China, from August to September 2021. Using half of the sample (n = 249), exploratory factor analyses identified four factors of the OES-COVID-19, including (a) positive contribution to society, (b) functional benefits, (c) protective effect, and (d) negative impacts. Confirmatory factor analysis of these factors conducted on the second subsample (n = 251) was satisfactory. The OES-COVID-19 showed good psychometric properties in terms of internal consistency, absence of floor/ceiling effects, and concurrent validity. The newly created and validated OES-COVID-19 is deemed suitable for application. It may advance future studies related to COVID-19 vaccination behavior and intention, and potentially allows for comparisons across studies. Further validation with modifications across countries, populations, and phase of the pandemic are warranted.
Revaccination in Age-Risk Groups with Sputnik V Is Immunologically Effective and Depends on the Initial Neutralizing SARS-CoV-2 IgG Antibodies Level
Authors: Godkov Mikhail A. , Ogarkova Darya A. , Gushchin Vladimir A. , Kleymenov Denis A. , Mazunina Elena P. , Bykonia Evgeniia N. , Pochtovyi Andrei A. , Shustov Valeriy V. , Shcheblyakov Dmitry V. , Komarov Andrey G. , Tsibin Alexander N. , Zlobin Vladimir I. , Logunov Denis Y. , Gintsburg Alexander L.
Published: January 2023

Vaccination against COVID-19 has occurred in Russia for more than two years. According to the Russian official clinical guidelines to maintain tense immunity in the conditions of the ongoing COVID-19 pandemic, it is necessary to use booster immunization six months after primary vaccination or a previous COVID-19 contraction. It is especially important to ensure the maintenance of protective immunity in the elderly, who are at risk of severe courses of COVID-19. Meanwhile, the immunological effectiveness of the booster doses has not been sufficiently substantiated. To investigate the immunogenicity of Sputnik V within the recommended revaccination regimen and evaluate the effectiveness of booster doses, we conducted this study on 3983 samples obtained from individuals previously vaccinated with Sputnik V in Moscow. We analyzed the level of antibodies in BAU/mL three times: (i) six months after primary immunization immediately before the booster (RV), (ii) 3 weeks after the introduction of the first component of the booster (RV1), and (iii) 3 weeks after the introduction of the second component of the booster (RV2). Six months after the primary vaccination with Sputnik V, 95.5% of patients maintained a positive level of IgG antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. The degree of increase in the specific virus-neutralizing antibodies level after revaccination increased with a decrease in their initial level just before the booster dose application. In the group of people with the level of antibodies up to 100 BAU/mL six months after the vaccination, a more than eightfold increase (p < 0.001, Wilcoxon criterion with Bonferroni adjustment) in the level of specific antibodies was observed (Me = 8.84 (IQR: 3.63–30.61)). A significant increase in the IgG level after receiving both the first and the second booster doses occurred at the initial titer level up to 300 BAU/ mL (p < 0.001) in those who did not contract COVID-19 in the past and up to 100 BAU/mL (p < 0.001) in those who were previously infected with SARS-CoV-2. A significant increase in the antibody level after the first dose of the booster was noted for people who had up to 500 BAU/mL (p < 0.05), regardless of the previous COVID-19 infection. Thus, revaccination is most effective in individuals with an antibody level below 500 BAU/mL, regardless of the vaccinee age and COVID-19 contraction. For the first time, it has been shown that a single booster dose of the Sputnik vaccine is sufficient to form a protective immunity in most vaccinees regardless of age and preexisting antibody level.
Immunotherapy for Urological Tumors on YouTubeTM: An Information-Quality Analysis
Authors: Di Bello Francesco , Di Mauro Ernesto , Collà Ruvolo Claudia , Creta Massimiliano , La Rocca Roberto , Celentano Giuseppe , Capece Marco , Napolitano Luigi , Fraia Agostino , Pezone Gabriele , Morra Simone , Imbimbo Ciro , Mirone Vincenzo , Longo Nicola , Califano Gianluigi
Published: January 2023

Background: YouTubeTM is an open-access source for mass information. Several previous studies of YouTubeTM videos showed a high rate of misinformation in the urological field. The aim of the current study was to evaluate the quality of information on immunotherapy (IMT) for urological tumors uploaded to YouTubeTM. Methods: YouTubeTM videos were searched using nine keyword combinations. The PEMAT, the DISCERN tool, and the Misinformation scale were used to assess the quality of information in YouTubeTM videos about IMT for urological tumors. Descriptive statistics and Kruskal–Wallis, Chi-square, proportion, and Pearson’s tests were performed. Results: According to the selection criteria, 156 YouTubeTM videos were suitable for the analysis and stratified according to topic (urothelial carcinoma vs. renal cell cancer vs. prostate cancer vs. general information on IMT). According to PEMAT A/V, the overall Understandability score was 40% (Inter-Quartile Range [IQR]: 20–61.5) and the overall Actionability score was 0% (IQR: 0–25). According to the DISCERN tool, the overall DISCERN score was 44 (IQR: 39–53.2), defined as “fair”. According to the Misinformation scale, we recorded the lowest median overall score for item 4 (“IMT in multimodality approach”) and item 5 (“Future perspective”). Conclusions: YouTubeTM cannot be recommended as a reliable source of information on IMT for urological malignancies. In addition, YouTubeTM videos contributed to the spread of misinformation by underestimating the role of IMT in a multimodality approach and missing the findings of published clinical trial results.
Conserved Candidate Antigens and Nanoparticles to Develop Vaccine against Giardia intestinalis
Authors: Sangkanu Suthinee , Paul Alok K. , Chuprom Julalak , Mitsuwan Watcharapong , Boonhok Rachasak , de Lourdes Pereira Maria , Oliveira Sonia Marlene Rodrigues , Wilairatana Polrat , Rahmatullah Mohammed , Wiart Christophe , Nawaz Muhammad , Sin Chea , Kayesth Sunil , Nissapatorn Veeranoot
Published: January 2023

Giardia intestinalis (Giardia lambia, Giardia duodenalis) infections in humans may be asymptomatic or symptomatic and associated with diarrhea (without blood), abdominal cramps, bloating, flatulence, and weight loss. The protozoan Giardia is the third most common cause of diarrhea and death in children under five, preceded only by rotavirus and by Cryptosporidium parvum and C. hominis infections. Antimicrobial drugs, particularly 5-nitroimidazole (5-NIs), are used to treat giardiasis in humans. Immunologically naive or immunocompromised host are more vulnerable to Giardia infection, whereas a degree of resistance to this protozoan is present in humans living in endemic areas. This suggests that vaccination may be a potential and appropriate means to control this parasitic disease outbreak and protect the human population. This review discusses Giardia antigens related to vaccine development. Additionally, based on the latest development of nanoparticle technology, a combination of methods for future research and development is proposed for the design of the next generation of powerful immunogens and an effective vaccine against Giardia.
Strategies for Prevention and Control of Vibriosis in Asian Fish Culture
Authors: Xu Kangping , Wang Yushu , Yang Wangxiaohan , Cai Hongyan , Zhang Youyu , Huang Lixing
Published: January 2023

It is estimated that vibriosis account for about half of the economic losses in Asian fish culture. Consequently, the prevention and control of vibriosis is one of the priority research topics in the field of Asian fish culture disease. Relevant measures have been proposed to control some Vibrios that pose a threat to Asian fish culture, but there are currently only a few effective vaccines available to combat these Vibrios. The purpose of our review is to sum up the main prevention methods and the latest control strategies of seven Vibrio species that cause great harm to Asian aquaculture, including Vibrio harveyi, Vibrio vulnificus, Vibrio parahaemolyticus, Vibrio mimicus, Vibrio anguillarum, Vibrio alginolyticus and Vibrio cholerae. Strategies such as antibiotics, probiotics, bacteriophages, antimicrobials from plants and other natural sources, as well as vaccines, are compared and discussed here. We expect this review will provide some new views and recommendations for the future better prevention and control of vibriosis in Asian fish culture.
Inspiring Anti-Tick Vaccine Research, Development and Deployment in Tropical Africa for the Control of Cattle Ticks: Review and Insights
Authors: Kasaija Paul D. , Contreras Marinela , Kirunda Halid , Nanteza Ann , Kabi Fredrick , Mugerwa Swidiq , de la Fuente José
Published: January 2023

Ticks are worldwide ectoparasites to humans and animals, and are associated with numerous health and economic effects. Threatening over 80% of the global cattle population, tick and tick-borne diseases (TTBDs) particularly constrain livestock production in the East, Central and Southern Africa. This, therefore, makes their control critical to the sustainability of the animal industry in the region. Since ticks are developing resistance against acaricides, anti-tick vaccines (ATVs) have been proposed as an environmentally friendly control alternative. Whereas they have been used in Latin America and Australia to reduce tick populations, pathogenic infections and number of acaricide treatments, commercially registered ATVs have not been adopted in tropical Africa for tick control. This is majorly due to their limited protection against economically important tick species of Africa and lack of research. Recent advances in various omics technologies and reverse vaccinology have enabled the identification of many candidate anti-tick antigens (ATAs), and are likely to usher in the next generation of vaccines, for which Africa should prepare to embrace. Herein, we highlight some scientific principles and approaches that have been used to identify ATAs, outline characteristics of a desirable ATA for vaccine design and propose the need for African governments to investment in ATV research to develop vaccines relevant to local tick species (personalized vaccines). We have also discussed the prospect of incorporating anti-tick vaccines into the integrated TTBDs control strategies in the sub-Saharan Africa, citing the case of Uganda.
Amphotericin B Nano-Assemblies Circumvent Intrinsic Toxicity and Ensure Superior Protection in Experimental Visceral Leishmaniasis with Feeble Toxic Manifestation
Authors: Jamal Fauzia , Altaf Ishrat , Ahmed Ghufran , Asad Sheikh , Ahmad Hira , Zia Qamar , Azhar Asim , Farheen Saba , Shafi Taj , Karim Shabana , Zubair Swaleha , Owais Mohammad
Published: January 2023

In spite of its high effectiveness in the treatment of both leishmaniasis as well as a range of fungal infections, the free form of the polyene antibiotic amphotericin B (AmB) does not entertain the status of the most preferred drug of choice in clinical settings. The high intrinsic toxicity of the principal drug could be considered the main impedance in the frequent medicinal use of this otherwise very effective antimicrobial agent. Taking into consideration this fact, the pharma industry has introduced many novel dosage forms of AmB to alleviate its toxicity issues. However, the limited production, high cost, requirement for a strict cold chain, and need for parenteral administration are some of the limitations that explicitly compel professionals to look for the development of an alternate dosage form of this important drug. Considering the fact that the nano-size dimensions of drug formulation play an important role in increasing the efficacy of the core drug, we employed a green method for the development of nano-assemblies of AmB (AmB-NA). The as-synthesized AmB-NA manifests desirable pharmacokinetics in the treated animals. The possible mechanistic insight suggested that as-synthesized AmB-NA induces necrosis-mediated cell death and severe mitochondrial dysfunction in L. donovani promastigotes by triggering depolarization of mitochondrial membrane potential. In vivo studies demonstrate a noticeable decline in parasite burden in the spleen, liver, and bone marrow of the experimental BALB/c mice host. In addition to successfully suppressing the Leishmania donovani, the as-formed AmB-NA formulation also modulates the host immune system with predominant Th1 polarization, a key immune defender that facilitates the killing of the intracellular parasite.
SARS-CoV-2 mRNA Dual Immunization Induces Innate Transcriptional Signatures, Establishes T-Cell Memory and Coordinates the Recall Response
Authors: Papadatou Ioanna , Geropeppa Maria , Verrou Kleio-Maria , Tzanoudaki Marianna , Lagousi Theano , Liatsis Emmanouil , Spoulou Vana
Published: January 2023

Background: mRNA vaccines have played a crucial role in controlling the SARS-CoV-2 global pandemic. However, the immunological mechanisms involved in the induction, magnitude and longevity of mRNA-vaccine-induced protective immunity are still unclear. Methods: In our study, we used whole-RNA sequencing along with detailed immunophenotyping of antigen-specific T cells and humoral RBD-specific response to dual immunization with the Pfizer–BioNTech mRNA vaccine (BNT162b2) and correlated them with response to an additional dose, administered 10 months later, in order to comprehensively profile the immune response of healthy volunteers to BNT162b2. Results: Primary dual immunization induced upregulation of the Type I interferon pathway and generated spike protein (S)-specific IFN-γ+ and TNF-α+ CD4 T cells, S-specific memory CD4 T cells, and RBD-specific antibodies against SARS-CoV-2. S-specific CD4 T cells induced by the primary series correlated with the RBD-specific antibody titers to a third dose. Conclusions: This study demonstrates the induction of both innate and adaptive immunity in response to the BNT162b2 mRNA vaccine in a coordinated manner and identifies the central role of primarily induced CD4+ T cells as a predictive biomarker of the magnitude of anamnestic immune response.
Talking about the Vaccine after the Pandemic: A Cross-Sectional Study among Youth in Turkey and Ethical Issues
Authors: Özdinç Ahmet , Değer Mehmet Sait , Atak Muhammed , Demir İbrahim
Published: January 2023

Examining the factors that affect the vaccination rate among young people in an ethical frame can support vaccination promotion. Therefore, this study will elaborate, through an ethical lens, on young people’s hesitation about and decisions regarding getting vaccinated. The cross-sectional study was conducted with 2428 people aged 15–30 in Turkey in June 2022. The questionnaire included the following subtitles: psycho-social situation, health services and health policies, COVID-19 vaccine, and predictions about life and health after the pandemic. The average age was 22.9 years. In the study sample, 80% were vaccinated, while 20% were not. Vaccinated participants acted more cautiously to protect their health. Receiving accurate and sufficient information on proposed vaccines affects vaccination status. The primary reason for getting vaccinated was “to protect their health, families, and relatives”, and the primary reason for not getting vaccinated was “not trusting the vaccine content or the country where the vaccine was produced”. Specifically, those vaccinated felt more relaxed physically, psychologically, and socially. In addition, the expectations for the future of those vaccinated were significantly higher. Accurate and adequate information is essential for reducing vaccine hesitancy. In addition, promoting prosocial behaviors in young people and highlighting related values will support vaccination.
Improved Immunogenicity of the Inactivated F Genotype Mumps Vaccine against Diverse Circulating Mumps Viruses in Mice
Authors: Won Hyeran , Kim Ah-Ra , Chung Gyung Tae , Kim Su Hwan , Yoo Jung-Sik , Lee June-Woo
Published: January 2023

Mumps is an acute infectious disease caused by the mumps virus (MuV). Despite high global vaccination coverage, mumps outbreaks continue to occur, even in vaccinated populations. Therefore, we aimed to identify candidate vaccines that can induce an immunogenic response against diverse MuV genotypes with greater efficacy than the currently available options. Vaccine candidates were sourced using formalin-inactivated viral strains. The inactivated vaccines were administered to BALB/c mice (through a primer and booster dose administered after a three-week interval). We tested the neutralizing antibodies of the candidate vaccines against various MuV genotypes to determine their overall efficacy. The formalin-inactivated F genotype vaccine was found to have higher cross-neutralizing titers against genotypes F, H, and G as well as significant Th1 cytokines responses, IFN-γ, TNF-α, and IL-2 than the Jeryl Lynn (JL) vaccine. Our findings suggest that the inactivated F genotype mumps vaccine has higher immunogenicity than the JL vaccine against diverse circulating MuVs.
From Co-Administration to Co-Formulation: The Race for New Vaccines against COVID-19 and Other Respiratory Viruses
Authors: Focosi Daniele
Published: January 2023

Combined (concomitant or synchronous) vaccination is crucial to increasing the compliance rate during mass campaigns by reducing the time to deployment (i [...]
Synbiotic-IgY Therapy Modulates the Mucosal Microbiome and Inflammatory Indices in Dogs with Chronic Inflammatory Enteropathy: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Sahoo Dipak Kumar , Allenspach Karin , Mochel Jonathan P. , Parker Valerie , Rudinsky Adam Joseph , Winston Jenessa A. , Bourgois-Mochel Agnes , Ackermann Mark , Heilmann Romy M. , Köller Gabor , Yuan Lingnan , Stewart Tracey , Morgan Shannon , Scheunemann Kaitlyn R , Iennarella-Servantez Chelsea A. , Gabriel Vojtech , Zdyrski Christopher , Pilla Rachel , Suchodolski Jan S , Jergens Albert E.
Published: January 2023

Chronic inflammatory enteropathy (CE) is a common cause of persistent gastrointestinal signs and intestinal inflammation in dogs. Since evidence links dysbiosis to mucosal inflammation, probiotics, prebiotics, or their combination (synbiotics) may reduce intestinal inflammation and ameliorate dysbiosis in affected dogs. This study’s aim was to investigate the effects of the synbiotic-IgY supplement on clinical signs, inflammatory indices, and mucosal microbiota in dogs with CE. Dogs with CE were enrolled in a randomized prospective trial. Twenty-four client-owned dogs were fed a hydrolyzed diet and administered supplement or placebo (diet) for 6 weeks. Dogs were evaluated at diagnosis and 2- and 6-week post-treatment. Outcome measures included clinical activity, endoscopic and histologic scores, inflammatory markers (fecal calprotectin, C-reactive protein), and composition of the mucosal microbiota via FISH. Eleven supplement- and nine placebo-treated dogs completed the trial. After 6 weeks of therapy, clinical activity and endoscopic scores decreased in both groups. Compared to placebo-treated dogs, dogs administered supplement showed decreased calprotectin at 2-week post-treatment, decreased CRP at 2- and 6-week post-treatment increased mucosal Clostridia and Bacteroides and decreased Enterobacteriaceae in colonic biopsies at trial completion. Results suggest a beneficial effect of diet and supplements on host responses and mucosal microbiota in dogs with CE.
Lectin Histochemistry of the Normal Feline Kidney
Authors: Noguchi Ayana , Kurahara Natsume , Yamato Osamu , Ichii Osamu , Yabuki Akira
Published: January 2023

Lectins have a strict binding specificity to carbohydrate moieties of cellular components, and can thus indicate changes in the glycosylation of cells in diseases. However, lectin-binding patterns in nephron segments of feline kidneys have not been fully surveyed. The present study reported lectin-binding patterns in normal feline kidneys by histochemical investigations of eight commercially available lectin detection kits. Kidneys from four normal cats (intact males, 23–27 months old) were fixed in 4% paraformaldehyde, and embedded in paraffin; lectin histochemistry was performed for WGA, s-WGA, RCA-I, ConA, PNA, SBA, DBA, and UEA-I lectins. WGA, RCA, and ConA binding was observed from Bowman’s capsule to the collecting ducts, while only WGA was detected in the glomerular capillary. s-WGA was observed from the proximal tubules to the collecting ducts, showing discriminative heterogeneous binding. PNA and SBA were detected in the distal nephrons, such as the thin limbs of the loops of Henle, distal tubules, and collecting ducts. UEA-I binding was observed in the thick ascending limbs of the loops of Henle, especially in the macula densa regions. DBA lectin showed no positive labeling in nephrons. The observed binding patterns may prove beneficial for the analysis of changes in glycosylation in feline kidney diseases.
Variation in Diffusion Tensor Imaging Parameters in the Cervical and Thoracic Spinal Cord (C1-C5 and C6-T2) Segments of Normal Beagle Dogs
Authors: Arai Kiyotaka , Itoi Takamasa , Akashi Natsuki , Miyabe Masahiro , Sugimoto Keisuke , Matsuda Akira , Maeta Noritaka , Kanda Teppei , Kutara Kenji
Published: January 2023

This study aimed to determine the characteristics and reference values of each vertebra in the cervicothoracic region by performing diffusion tensor imaging (DTI) scans and analyzing DTI parameters in normal Beagle dogs. In five adult Beagles under anesthetic maintenance, DTI was performed using a 1.5-T magnetic resonance imaging (MRI) scanner. Axial DTI was performed using three overlapping slabs to cover the cervical and thoracic spinal cords. After post-processing, DTI parameters were calculated along the entire spinal cord. Among DTI parameters, fractional anisotropy, relative anisotropy, and axonal diffusivity significantly decreased in the caudal direction. However, the apparent diffusion coefficient, radial diffusivity, and mean diffusivity values were not significantly correlated with vertebral levels. We provide evidence for the existence of segment-dependent DTI parameters in the canine cervical spinal cord. Therefore, comparisons of DTI parameters between lesions at different vertebral levels should be avoided unless normative data are available. Furthermore, the DTI data obtained in this study may contribute to the development of a clinical reference for spinal cord evaluation in dogs using DTI parameters.
Determination of Non-Digestible Parts in Dairy Cattle Feces Using U-NET and F-CRN Architectures
Authors: Özden Cevher , Bulut Mutlu , Çanga Boğa Demet , Boğa Mustafa
Published: January 2023

Deep learning algorithms can now be used to identify, locate, and count items in an image thanks to advancements in image processing technology. The successful application of image processing technology in different fields has attracted much attention in the field of agriculture in recent years. This research was done to ascertain the number of indigestible cereal grains in animal feces using an image processing method. In this study, a regression-based way of object counting was used to predict the number of cereal grains in the feces. For this purpose, we have developed two different neural network architectures based upon Fully Convolutional Regression Networks (FCRN) and U-Net. The images used in the study were obtained from three different dairy cows enterprises operating in Nigde Province. The dataset consists of the 277 distinct dropping images of dairy cows in the farm. According to findings of the study, both models yielded quite acceptable prediction accuracy with U-Net providing slightly better prediction with a MAE value of 16.69 in the best case, compared to 23.65 MAE value of FCRN with the same batch.
PFAS in the Drinking Water Source: Analysis of the Contamination Levels, Origin and Emission Rates
Authors: Mussabek Dauren , Söderman Anna , Imura Tomomi , Persson Kenneth M. , Nakagawa Kei , Ahrens Lutz , Berndtsson Ronny
Published: January 2023

Groundwater contamination caused by the use of the aqueous film-forming foam (AFFF) containing per- and polyfluoroalkyl substances (PFAS) was investigated in southern Sweden. ΣPFAS concentrations in groundwater ranged between 20 and 20,000 ng L−1; PFAS composition was primarily represented by PFOS and PFHxS. The PFAS chain length was suggested to have an impact on the contaminant distribution and transport in the groundwater. PFAS profiling showed that the use of PFSAs- and PFCAs/FTSAs-based PFAS-AFFF can be a contributor to PFAS contamination of the drinking water source (groundwater). PFAS emission was connected to PFAS-AFFF use during the fire-training and fire-fighting equipment tests at the studied location. PFAS emission per individual fire training was (semi-quantitatively) estimated as [1.4 < 11.5 ± 5.7 < 43.7 kg] (n = 20,000). The annual emission estimates varied as [11 < 401 ± 233 < 1125 kg yr−1] (n = 1005) considering possible [2 < 35 ± 20 < 96] individual fire-training sessions per year.
Rainfall-Runoff Time Lags from Saltwater Interface Interactions in Atlantic Coastal Plain Basins
Authors: Evans Brady , Klammler Harald , Annable Michael D. , Jawitz James W.
Published: January 2023

The dynamic behavior of the freshwater-saltwater interface (FSI) in coastal aquifers can introduce unexpected lags between recharge and stream discharge, especially when recharge is forced by long-term cyclical precipitation patterns. This work seeks to assess these FSI impacts at the watershed scale. Recharge-discharge time lags were evaluated in 68 watersheds overlying the Floridan Aquifer System in the coastal region of the southeastern United States (Florida, Georgia, and South Carolina). Utilizing the strength of the Atlantic multidecadal oscillation (AMO) signal in this region, 10–20 year averaged recharge and discharge time series were used for the selected watersheds. Lags of 10–25 years between recharge and discharge were found in 16% of the basins considered, possibly induced by a dynamic FSI which responded slowly to the AMO-scale recharge signal. Freshwater storage coefficients (S) were estimated from time series of change-in-storage and groundwater level, with 11 basins showing S>1.5 indicating water storage well above that expected for unconfined aquifers. These 11 basins with both multidecadal recharge-discharge time lags and high S values showed a positive linear relationship between time lag and FSI depth with slope 0.016 yr/m (R-squared = 0.30). These large time lags may be directly impacting the management of these basins as they obscure water and solute mass balances in the southeastern US.
Spatial–Temporal Dynamic Evolution and Influencing Factors of Green Efficiency of Agricultural Water Use in the Yellow River Basin, China
Authors: Lu Weinan , Guo Xinyi , Liu Wenxin , Du Ruirui , Chi Shuyao , Zhou Boyang
Published: January 2023

The progression of agricultural production, ever-increasing industrialization, population boom, and more water-concentrated lifestyles has placed a severe burden on Yellow River Basin’s existing water resources, particularly in the current century. In the context of resource and environmental constraints, improving the green efficiency of agricultural water use (AWGE) is an important measure for alleviating the shortage of water resources as well as meeting the intrinsic requirement to promote the green transformation and upgrading of agriculture. This study used the Super Slack-Based Measure (Super-SBM) to measure the AWGE of 87 regions in the Yellow River Basin from 2000 to 2019. Based on spatial and temporal perspectives, it applied Exploratory Spatial Data Analysis (ESDA) to explore the dynamic evolution and regional differences in AWGE. Then, this study used a spatial econometric model to analyze the main factors that influence AWGE in the Yellow River Basin. The results show that, firstly, the AWGE of the Yellow River Basin shows a steady upward trend from 2000 to 2019, but the differences among regions were obvious. Secondly, the AWGE showed an obvious spatial autocorrelation in the Yellow River Basin and showed significant high–high and low–low agglomeration characteristics. Thirdly, rural per capita disposable income and effective irrigation have a positive influence on AWGE, while rural labor transfer, the input intensity of agricultural machinery and water structure have a negative influence. The spatial econometric model regression results show that the influence factors of AWGE in the Yellow River Basin showed significant spatial spillover effects and spatial heterogeneity in their effect. Finally, when improving AWGE in the Yellow River Basin, plans should be formulated according to local conditions. The results of this study can provide new ideas on the study of AWGE in the Yellow River Basin and provide references for the formulation of regional agricultural water resource utilization policies as well.
Assessment and Influencing Factors of Water Supply Capacity and Water Resource Utilization Efficiency in Southwest China
Authors: Bao Rui , Wu Jiahui , Li Tao , Deng Hongbing
Published: January 2023

China has been facing serious water scarcity, and improving the supply and utilization of water resources from the perspective of resource endowment, economic development and water infrastructure is of great significance toward sustainable water development. In this work, two index systems for evaluating the water supply capacity (WSC) and the water infrastructure construction level (WICL) were constructed; the water resource utilization efficiency (WRUE) was measured by applying a super slack-based measure model; the ordinary least squares and geographically weighted regression models were used to explore the heterogeneity of spatial relationships. The results showed that both WSC (0.15~0.67) and WRUE (0.25~1.18) had spatial heterogeneity. WSC was positively correlated with water resource accessibility and GDP per capita (R2 = 0.406, p < 0.01), which represented water resource endowment and economic development, respectively. WRUE was positively correlated with GDP per capita but was negatively correlated with accessibility (R2 = 0.654, p < 0.01). The relationship of WICL with accessibility and GDP per capita varied over the study’s area. We found that the WSC in the southeast, WRUE in the north and WICL in the south were mainly associated with water resource endowments. The WSC in the north, WRUE in the southwest and WICL in the north were mainly associated with the economic development level. Noteworthily, strengthening the construction of water conservancy is one of the effective ways to improve water supply. Suggestions on improving WSC and WRUE were provided based on different accessibility and economic conditions, to promote the sustainable development of water resources.
Wastewater Management Using Coagulation and Surface Adsorption through Different Polyferrics in the Presence of TiO2-g-PMAA Particles
Authors: Alawamleh Heba , Mousavi Seyedsahand , Ashoori Danial , Salman Hayder , Zahmatkesh Sasan , Sillanpää Mika
Published: January 2023

For the surface adsorption process, a wide range of studies have been carried out to describe the adsorption process. However, no extensive study has been carried out to investigate the pre-treatment method effect on the separation process. The purpose of the present study is to improve the performance of the membrane process in the treatment of oily wastewater. For this purpose, the effects of pre-treatment, membrane modification, and operational parameters were investigated on the microfiltration membrane system. Two methods of coagulation and surface adsorption were used as pre-treatment, and then a modified polysulfone (PSf) membrane containing TiO2 nanoparticles was applied in the microfiltration process. In order to reduce the membrane fouling and increase the permeate flux, the surface of the nanoparticle was modified. In order to check the performance of coagulation, pretreatments of polyferric sulfate (PFS) and polyferric chloride (PFC) were applied. The results showed that the Chemical Oxygen Demand (COD) reduction of 98% can be obtained using 1 g/L of PFS coagulant at pH = 6, while only 81% of COD was removed using 1 g/L PFC. It was also found that the best pH for the performance of this type of coagulant was measured as pH = 10 and the removal efficiency for 1 and 2 g/L of PFC coagulant was obtained as 96.1% and 91.7%, respectively. The results show that in the case of using a coagulant of less than 1 g/L, using PFS is more efficient than PFC; meanwhile, in more than 1 g/L of coagulant, this effect is reversed and the use of PFS will be less efficient than PFC. The performance of the PSf-TiO2 membrane fabricated by the Nonsolvent-induced phase separation (NIPS) method was investigated using modified nanoparticles with an initial size of 10 nm at different operating conditions. The results show that the permeate flux and the rejection can be increased to 563 L/h m2 and 99%, respectively, using the modified PSf membrane. The results of this paper showed that the performance of the adsorption process can be improved by using the coagulation process as a pre-treatment method.