bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Outcome Pathway ‘Footprinting’: A Novel Approach to the Integration of 21st Century Toxicology Information into Chemical Mixtures Risk Assessment
Authors: Lambert Jason
Published: January 2023

For over a decade, New Approach Methodologies (NAMs) such as structure-activity/read-across, -omics technologies, and Adverse Outcome Pathway (AOP), have been considered within regulatory communities as alternative sources of chemical and biological information potentially relevant to human health risk assessment. Integration of NAMs into applications such as chemical mixtures risk assessment has been limited due to the lack of validation of qualitative and quantitative application to adverse health outcomes in vivo, and acceptance by risk assessors. However, leveraging existent hazard and dose–response information, including NAM-based data, for mixture component chemicals across one or more levels of biological organization using novel approaches such as AOP ‘footprinting’ proposed herein, may significantly advance mixtures risk assessment. AOP footprinting entails the systematic stepwise profiling and comparison of all known or suspected AOPs involved in a toxicological effect at the level of key event (KE). The goal is to identify key event(s) most proximal to an adverse outcome within each AOP suspected of contributing to a given health outcome at which similarity between mixture chemicals can be confidently determined. These key events are identified as the ‘footprint’ for a given AOP. This work presents the general concept, and a hypothetical example application, of AOP footprinting as a key methodology for the integration of NAM data into mixtures risk assessment.
Partitioning of Persistent Organic Pollutants between Adipose Tissue and Serum in Human Studies
Authors: Moriceau Meg-Anne , Cano-Sancho German , Kim MinJi , Coumoul Xavier , Emond Claude , Arrebola Juan-Pedro , Antignac Jean-Philippe , Audouze Karine , Rousselle Christophe
Published: January 2023

Blood is the most widely used matrix for biomonitoring of persistent organic pollutants (POPs). It is assumed that POPs are homogenously distributed within body lipids at steady state; however, the variability underlying the partitioning of POPs between fat compartments is poorly understood. Hence, the objective of this study was to review the state of the science about the relationships of POPs between adipose tissue and serum in humans. We conducted a narrative literature review of human observational studies reporting concentrations of POPs in paired samples of adipose tissue with other lipid-based compartments (e.g., serum lipids). The searches were conducted in SCOPUS and PUBMED. A meta-regression was performed to identify factors responsible for variability. All included studies reported high variability in the partition coefficients of POPs, mainly between adipose tissue and serum. The number of halogen atoms was the physicochemical variable most strongly and positively associated with the partition ratios, whereas body mass index was the main biological factor positively and significantly associated. To conclude, although this study provides a better understanding of partitioning of POPs to refine physiologically based pharmacokinetic and epidemiological models, further research is still needed to determine other key factors involved in the partitioning of POPs.
OnabotulinumtoxinA Treatment in Chronic Migraine: Investigation of Its Effects on Disability, Headache and Neck Pain Intensity
Authors: Onan Dilara , Bentivegna Enrico , Martelletti Paolo
Published: January 2023

Neck disability and pain are frequently encountered problems in patients with chronic migraine (CM). The long-term stimuli of neurons in the trigeminocervical junction may explain this situation. OnabotulinumtoxinA (ONA) treatment is one of the proven treatments for CM; however, there is no study data on the efficacy of ONA treatment on neck disability and pain in CM patients. Therefore, we aimed to investigate the effect of ONA treatment on disability, neck pain and headache intensity in CM patients. One hundred thirty-four patients who met the inclusion criteria were included in the study. ONA treatment was administered at a dose of 195 U to 39 sites in total as per Follow-the-Pain PREEMPT protocol. The disability was evaluated with the Neck Disability Index and the Migraine Disability Assessment; pain intensity was evaluated with the Visual Analogue Scale; the monthly number of headache days were recorded; quality of life was evaluated with the Headache Impact Test. All assessments were recorded at baseline and 3 months after treatment. After the treatment, neck–migraine disabilities decreased from severe to mild for neck and moderate for migraine (p < 0.001). Neck pain and headache intensities decreased by almost half (p < 0.001). The median number of monthly headache days decreased from 20 days to 6 days (p < 0.000). The quality-of-life level decreased significantly from severe to substantial level (p < 0.001). According to our results, ONA treatment was effective in reducing neck-related problems in CM patients. Long-term follow-up results may provide researchers with more comprehensive results in terms of the treatment of chronic migraine–neck-related problems.
Charged Amino Acids Contribute to ZorO Toxicity
Authors: Bogati Bikash , Shore Selene F. H. , Nipper Thomas D. , Stoiculescu Oana , Fozo Elizabeth M.
Published: January 2023

Chromosomally encoded toxin-antitoxin systems have been increasingly identified and characterized across bacterial species over the past two decades. Overproduction of the toxin gene results in cell growth stasis or death for the producing cell, but co-expression of its antitoxin can repress the toxic effects. For the subcategory of type I toxin-antitoxin systems, many of the described toxin genes encode a small, hydrophobic protein with several charged residues distributed across the sequence of the toxic protein. Though these charged residues are hypothesized to be critical for the toxic effects of the protein, they have not been studied broadly across different type I toxins. Herein, we mutated codons encoding charged residues in the type I toxin zorO, from the zor-orz toxin-antitoxin system, to determine their impacts on growth inhibition, membrane depolarization, ATP depletion, and the localization of this small protein. The non-toxic variants of ZorO accumulated both in the membrane and cytoplasm, indicating that membrane localization alone is not sufficient for its toxicity. While mutation of a charged residue could result in altered toxicity, this was dependent not only on the position of the amino acid within the protein but also on the residue to which it was converted, suggesting a complex role of charged residues in ZorO-mediated toxicity. A previous study indicated that additional copies of the zor-orz system improved growth in aminoglycosides: within, we note that this improved growth is independent of ZorO toxicity. By increasing the copy number of the zorO gene fused with a FLAG-tag, we were able to detect the protein expressed from its native promoter elements: an important step for future studies of toxin expression and function.
Generalized Unitarity Method for Unstable Particles
Authors: Menezes Gabriel
Published: January 2023

In theories with unstable particles, unitarity is satisfied by the inclusion of only stable states in unitarity sums. Therefore, unitarity cuts are not to be taken through unstable particles. This presents a challenge to the generalized unitarity method, whose aim is to reconstruct amplitudes by analyzing sets of unitarity cuts. Nevertheless, under some general physical conditions, and perhaps some methodological modifications, we prove that the method is still reliable for one-loop amplitudes containing resonances. We discuss some simple examples which illustrate these features.
Mathematical Singularities in the Farthest Confines of the Universe—And a Brief Report on Its Evolutionary History
Authors: Elizalde Emilio
Published: January 2023

It is advisable to avoid and, even better, demystify such grandiose terms as “infinity” or “singularity” in the description of the cosmos. Its proliferation does not positively contribute to the understanding of key concepts that are essential for an updated account of its origin and evolutionary history. It will be here argued that, as a matter of fact, there are no infinities in physics, in the real world: all that appears, in any given formulation of nature by means of mathematical equations, actually arises from extrapolations, which are made beyond the bounds of validity of the equations themselves. Such a crucial point is rather well known, but too often forgotten, and is discussed in this paper with several examples; namely, the famous Big Bang singularity and others, which appeared before in classical mechanics and electrodynamics, and notably in the quantization of field theories. A brief description of the Universe’s history and evolution follows. Special emphasis is put on what is presently known, from detailed observations of the cosmos and, complementarily, from advanced experiments of very high-energy physics. To conclude, a future perspective on how this knowledge might soon improve is given.
Genomic Epidemiology of the SARS-CoV-2 Epidemic in Cyprus from November 2020 to October 2021: The Passage of Waves of Alpha and Delta Variants of Concern
Authors: Chrysostomou Andreas C. , Vrancken Bram , Haralambous Christos , Alexandrou Maria , Aristokleous Antonia , Christodoulou Christina , Gregoriou Ioanna , Ioannides Marios , Kalakouta Olga , Karagiannis Christos , Koumbaris George , Loizides Charalambos , Mendris Michail , Papastergiou Panagiotis , Patsalis Philippos C. , Pieridou Despo , Richter Jan , Schmitt Markus , Shammas Christos , Stylianou Dora C. , Themistokleous Giorgos ,   the COMESSAR Network, Lemey Philippe , Kostrikis Leondios G.
Published: January 2023

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 resulted in the coronavirus disease 2019 (COVID-19) pandemic, which has had devastating repercussions for public health. Over the course of this pandemic, the virus has continuously been evolving, resulting in new, more infectious variants that have frequently led to surges of new SARS-CoV-2 infections. In the present study, we performed detailed genetic, phylogenetic, phylodynamic and phylogeographic analyses to examine the SARS-CoV-2 epidemic in Cyprus using 2352 SARS-CoV-2 sequences from infected individuals in Cyprus during November 2020 to October 2021. During this period, a total of 61 different lineages and sublineages were identified, with most falling into three groups: B.1.258 & sublineages, Alpha (B.1.1.7 & Q. sublineages), and Delta (B.1.617.2 & AY. sublineages), each encompassing a set of S gene mutations that primarily confer increased transmissibility as well as immune evasion. Specifically, these lineages were coupled with surges of new infections in Cyprus, resulting in the following: the second wave of SARS-CoV-2 infections in Cyprus, comprising B.1.258 & sublineages, during late autumn 2020/beginning of winter 2021; the third wave, comprising Alpha (B.1.1.7 & Q. sublineages), during spring 2021; and the fourth wave, comprising Delta (B.1.617.2 & AY. sublineages) during summer 2021. Additionally, it was identified that these lineages were primarily imported from and exported to the UK, Greece, and Sweden; many other migration links were also identified, including Switzerland, Denmark, Russia, and Germany. Taken together, the results of this study indicate that the SARS-CoV-2 epidemic in Cyprus was characterized by successive introduction of new lineages from a plethora of countries, resulting in the generation of waves of infection. Overall, this study highlights the importance of investigating the spatiotemporal evolution of the SARS-CoV-2 epidemic in the context of Cyprus, as well as the impact of protective measures placed to mitigate transmission of the virus, providing necessary information to safeguard public health.
Four-Year Follow-Up of the Maternal Immunological, Virological and Clinical Settings of a 36-Year-Old Woman Experiencing Primary Cytomegalovirus Infection Leading to Intrauterine Infection
Authors: Forner Gabriella , Saldan Alda , Mengoli Carlo , Pizzi Sara , Fedrigo Marny , Gussetti Nadia , Visentin Silvia , Angelini Annalisa , Cosmi Erich , Barzon Luisa , Abate Davide Antonio
Published: January 2023

The present study aims to provide the sequential immunological, clinical and virological events occurring in a CMV-infected pregnant woman experiencing intrauterine CMV transmission. In brief, a case of primary CMV infection occurred in a 36-year-old pregnant woman. The patient exhibited early-sustained viremia and viruria, detectable presence of CMV in saliva concomitant with a strong CMV-specific cell-mediated response (427 EliSpots). CMV was detected in the amniotic fluid at 15 weeks of pregnancy (>1 × 106 CMV copies/mL). The pregnancy was deliberately interrupted at 16 weeks of gestation. Fetal histological and pathological examinations revealed placentitis and fetal brain alterations as microcephaly and cortical dysplasia. Interestingly, this clinical report shows: (1) there was a rapid and sustained CMV-specific cell mediated immune response (Th1) in association with low IgG avidity (Th2) correlated with fetal CMV transmission. (2) The levels of CMV-specific cell-mediated immune response persisted at high levels up to 200 weeks after infection despite clinical and viral clearance. (3) The histological and pathological evidence suggests that a potent pro-inflammatory condition at the placental level may lead to cCMV.
Molecular Epidemiology of HIV-1 in Ghana: Subtype Distribution, Drug Resistance and Coreceptor Usage
Authors: Appah Anna , Beelen Charlotte J. , Kirkby Don , Dong Winnie , Shahid Aniqa , Foley Brian , Mensah Miriam , Ganu Vincent , Puplampu Peter , Amoah Linda E. , Nii-Trebi Nicholas I. , Brumme Chanson J. , Brumme Zabrina L.
Published: January 2023

The greatest HIV-1 genetic diversity is found in West/Central Africa due to the pandemic’s origins in this region, but this diversity remains understudied. We characterized HIV-1 subtype diversity (from both sub-genomic and full-genome viral sequences), drug resistance and coreceptor usage in 103 predominantly (90%) antiretroviral-naive individuals living with HIV-1 in Ghana. Full-genome HIV-1 subtyping confirmed the circulating recombinant form CRF02_AG as the dominant (53.9%) subtype in the region, with the complex recombinant 06_cpx (4%) present as well. Unique recombinants, most of which were mosaics containing CRF02_AG and/or 06_cpx, made up 37% of sequences, while “pure” subtypes were rare (<6%). Pretreatment resistance to at least one drug class was observed in 17% of the cohort, with NNRTI resistance being the most common (12%) and INSTI resistance being relatively rare (2%). CXCR4-using HIV-1 sequences were identified in 23% of participants. Overall, our findings advance our understanding of HIV-1 molecular epidemiology in Ghana. Extensive HIV-1 genetic diversity in the region appears to be fueling the ongoing creation of novel recombinants, the majority CRF02_AG-containing, in the region. The relatively high prevalence of pretreatment NNRTI resistance but low prevalence of INSTI resistance supports the use of INSTI-based first-line regimens in Ghana.
Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro
Authors: Asfor Amin S. , Reddy Vishwanatha R. A. P. , Nazki Salik , Urbaniec Joanna , Brodrick Andrew J. , Broadbent Andrew J.
Published: January 2023

Infectious bursal disease virus (IBDV) vaccines do not induce sterilizing immunity, and vaccinated birds can become infected with field strains. Vaccine-induced immune selection pressure drives the evolution of antigenic drift variants that accumulate amino acid changes in the hypervariable region (HVR) of the VP2 capsid, which may lead to vaccine failures. However, there is a lack of information regarding how quickly mutations arise, and the relative contribution different residues make to immune escape. To model IBDV antigenic drift in vitro, we serially passaged a classical field strain belonging to genogroup A1 (F52/70) ten times, in triplicate, in the immortalized chicken B cell line, DT40, in the presence of sub-neutralizing concentrations of sera from birds inoculated with IBDV vaccine strain 2512, to generate escape mutants. This assay simulated a situation where classical strains may infect birds that have suboptimal vaccine-induced antibody responses. We then sequenced the HVR of the VP2 capsid at passage (P) 5 and 10 and compared the sequences to the parental virus (P0), and to the virus passaged in the presence of negative control chicken serum that lacked IBDV antibodies. Two escape mutants at P10 had the same mutations, D279Y and G281R, and a third had mutations S251I and D279N. Furthermore, at P5, the D279Y mutation was detectable, but the G281R mutation was not, indicating the mutations arose with different kinetics.
Identification of Two Novel Linear B Cell Epitopes on the CD2v Protein of African Swine Fever Virus Using Monoclonal Antibodies
Authors: Jiang Wenting , Jiang Dawei , Li Lu , Wang Jiabin , Wang Panpan , Shi Xuejian , Zhao Qi , Liu Boyuan , Ji Pengchao , Zhang Gaiping
Published: January 2023

African swine fever virus (ASFV) is a highly infectious viral pathogen that endangers the global pig industry, and no effective vaccine is available thus far. The CD2v protein is a glycoprotein on the outer envelope of ASFV, which mediates the transmission of the virus in the blood and recognition of the virus serotype, playing an important role in ASFV vaccine development and disease prevention. Here, we generated two specific monoclonal antibodies (mAbs), 6C11 and 8F12 (subtype IgG1/kappa-type), against the ASFV CD2v extracellular domain (CD2v-ex, GenBank: MK128995.1, 1–588 bp) and characterized their specificity. Peptide scanning technology was used to identify the epitopes recognized by mAbs 6C11 and 8F12. As a result, two novel B cell epitopes, 38DINGVSWN45 and 134GTNTNIY140, were defined. Amino acid sequence alignment showed that the defined epitopes were conserved in all referenced ASFV strains from various regions of China including the highly pathogenic, epidemic strain, Georgia2007/1 (NC_044959.2), with the same noted substitutions compared to the four foreign ASFV wild-type strains. This study provides important reference values for the design and development of an ASFV vaccine and useful biological materials for the functional study of the CD2v protein by deletion analysis.
Patients Treated for HCV Infection and Listed for Liver Transplantation in a French Multicenter Study: What Happens at Five Years?
Authors: Meunier Lucy , Belkacemi Mohamed , Pageaux George Philippe , Radenne Sylvie , Vallet-Pichard Anaïs , Houssel-Debry Pauline , Duvoux Christophe , Botta-Fridlund Danielle , de Ledinghen Victor , Conti Filomena , Anty Rodolphe , Di Martino Vincent , Debette-Gratien Marilyne , Leroy Vincent , Gerster Theophile , Lebray Pascal , Alric Laurent , Abergel Armand , Dumortier Jérôme , Besch Camille , Montialoux Helene , Samuel Didier , Duclos-Vallée Jean-Charles , Coilly Audrey
Published: January 2023

Background: Direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection have been proven safe and effective in cirrhotic patients awaiting liver transplantation (LT). However, in the long term, data remain minimal regarding the clinical impact of viral eradication on patients listed for decompensated cirrhosis or hepatocellular carcinoma (HCC). We aimed to elucidate the clinical outcomes of patients regarding delisting and the evolution of HCC during the long-term follow-up. Methods: An observational, multicenter, retrospective analysis was carried out on prospectively collected data from HCV-positive patients treated with an interferon-free regimen while awaiting LT in 18 French hospitals. Results: A total of 179 patients were included in the study. The indication for LT was HCC in 104 (58.1%) patients and cirrhosis in 75 (41.9%) patients. The sustained virological response was 84.4% and the treatment was well tolerated. At five years, among 75 patients with cirrhosis treated for HCV, 19 (25.3%) were delisted following improvement after treatment. Predictive factors for delisting highlighted an absence of ascites, MELD score ≤ 15, and Child–Pugh score ≤ 7. No patients with refractory ascites were delisted. Among patients with HCC, 82 (78.9%) were transplanted. The drop-out rate was low (6.7%) and few recurrences of HCC after LT were observed. Conclusions: DAAs are safe and effective in patients awaiting LT for cirrhosis or HCC. A quarter of patients with cirrhosis can be delisted because of clinical improvement. Predictive factors for delisting, as a result of improvement, may assist prescribers, before initiating HCV infection therapy in the long-term perspective.
Mutation Profile of HPV16 L1 and L2 Genes in Different Geographic Areas
Authors: Tsakogiannis Dimitris , Nikolaidis Marios , Zagouri Flora , Zografos Eleni , Kottaridi Christine , Kyriakopoulou Zaharoula , Tzioga Lamprini , Markoulatos Panayotis , Amoutzias Grigoris D. , Bletsa Garyfalia
Published: January 2023

The causal relationship between HPV and cervical cancer in association with the high prevalence of high risk HPV genotypes led to the design of HPV vaccines based on the major capsid L1 protein. In recent years, capsid protein L2 has also become a focal point in the field of vaccine research. The present review focuses on the variability of HPV16 L1 and L2 genes, emphasizing the distribution of specific amino acid changes in the epitopes of capsid proteins. Moreover, a substantial bioinformatics analysis was conducted to describe the worldwide distribution of amino acid substitutions throughout HPV16 L1, L2 proteins. Five amino acid changes (T176N, N181T; EF loop), (T266A; FG loop), (T353P, T389S; HI loop) are frequently observed in the L1 hypervariable surface loops, while two amino acid substitutions (D43E, S122P) are adjacent to L2 specific epitopes. These changes have a high prevalence in certain geographic regions. The present review suggests that the extensive analysis of the amino acid substitutions in the HPV16 L1 immunodominant loops may provide insights concerning the ability of the virus in evading host immune response in certain populations. The genetic variability of the HPV16 L1 and L2 epitopes should be extensively analyzed in a given population.
A Cost-Effectiveness Analysis of Pre-Exposure Prophylaxis to Avert Rabies Deaths in School-Aged Children in India
Authors: Royal Abhishek , John Denny , Bharti Omesh , Tanwar Ritesh , Bhagat Deepak Kumar , Padmawati Retna Siwi , Chaudhary Vishal , Umapathi Reddicherla , Bhadola Pradeep , Utarini Adi
Published: January 2023

Children contribute to one-half of the total painful rabies mortalities in India. The state-of-the-art rabies mortality averting strategies need exploration for the effective implementation of pre-exposure prophylaxis (PrEP) in India. This study reports on the economic evaluation of various PrEP and post-exposure prophylaxis (PEP) strategies to avert rabies mortalities in school-aged children in India. A decision tree model has been developed for children in the age group of 5–15 years to evaluate various PrEP + PEP and PEP only regimens. The 2-site intradermal regimen administered on day zero and seven was chosen as the intervention [PrEP (I)]. ICER was calculated from the quasi-societal and quasi-health systems’ perspectives for the base case analysis, along with one-way sensitivity, and scenario analyses for each regimen. The incremental DALYs averted per million population with the implementation of PrEP (I) ranged between 451 and 85,069 in 2020. The ICER was reported in the range of USD 384–352/DALY averted (non-dominant) in comparison to PEP regimens from a quasi-societal perspective. PrEP (I) is reported to be ‘very cost effective’ in comparison with PEP regimens from the quasi-societal and quasi-health systems’ perspectives and reduce deaths by up to 89.9%. This study concludes that the PrEP (I) regimen is a cost-effective and life-saving strategy to avert painful mortalities due to rabies in school-aged children in India.
Impact of Improper Storage of ChAdOx1-S (AstraZeneca) Vaccine on Its Efficacy and Safety
Authors: Mikołajczyk Marek , Lewandowski Roman A. , Goncharuk Anatoliy G.
Published: January 2023

Background: In May 2021, there was an incident regarding giving patients AstraZeneca vaccines stored improperly. They were stored at room temperature (21 degrees centigrade) for 18 h, 12 h longer than the producer recommends. Aim of the study: The paper aims to contribute to the body of knowledge concerning the efficacy and safety of the ChAdOx1-S (AstraZeneca) vaccine concerning the requirements for cold supply chain specification. Patients and methods: Improperly stored vaccines were given to 44 patients, and 39 of them decided to take part in the study. The Control group consisted of 56 people vaccinated on the same days by the same medical teams, using properly stored medicines. Results: The concentration of anti-S1 SARS-CoV-2 Spike protein IgG antibodies did not differ significantly between the groups. Examined group median 70 kU/L (20;100). Control group median 66 kU/L (32.75;100), p = 0.751. We did not observe any COVID-19 infections in either the control or examined group for half a year after the incident. People from each group reported that local and systemic adverse events occurred directly after the first and second doses. In the control group, one case of spontaneously subsiding face edema and joint pain was observed. There were no severe or fatal adverse events. There were no significant differences between the groups, besides the fatigue, after the second dose. Conclusion: AstraZeneca vaccine ChAdOx1-S stored at 21 degrees centigrade for 18 h before vaccination has the same safety profile (p < 0.05) and the same efficacy (p < 0.05) as the vaccines stored in conditions recommended by the producer.
Vaccination with Formulation of Nanoparticles Loaded with Leishmania amazonensis Antigens Confers Protection against Experimental Visceral Leishmaniasis in Hamster
Authors: González Marco Antonio Cabrera , Gonçalves Ana Alice Maia , Ottino Jennifer , Leite Jaqueline Costa , Resende Lucilene Aparecida , Melo-Júnior Otoni Alves , Silveira Patrícia , Cardoso Mariana Santos , Fujiwara Ricardo Toshio , Bueno Lilian Lacerda , Santos Renato Lima , Carvalho Tatiane Furtado de , Garcia Giani Martins , Paes Paulo Ricardo de Oliveira , Galdino Alexsandro Sobreira , Chávez-Fumagalli Miguel Angel , Melo Marília Martins , Silveira-Lemos Denise , Martins-Filho Olindo Assis , Dutra Walderez Ornelas , Mosqueira Vanessa Carla Furtado , Giunchetti Rodolfo Cordeiro
Published: January 2023

Visceral leishmaniasis (VL) is a fatal disease caused by the protozoa Leishmania infantum for which dogs are the main reservoirs. A vaccine against canine visceral leishmaniasis (CVL) could be an important tool in the control of human and CVL by reducing the infection pressure of L. infantum. Despite the CVL vaccine available on the market, the Brazilian Ministry of Health did not implement the use of it in their control programs. In this sense, there is an urgent need to develop more efficient vaccines. In this study, the association between two polymeric nanoformulations, (poly (D, L-lactic) acid (PLA) polymer) loading Leishmania amazonensis antigens, was evaluated as a potential immunobiological agent against VL using golden hamsters as an experimental model. The results indicated that no significant adverse reactions were observed in animals vaccinated with LAPSmP. LAPSmP presented similar levels of total anti-Leishmania IgG as compared to LAPSmG. The LAPSmP and LAPSmG groups showed an intense reduction in liver and spleen parasitic load by qPCR. The LAPSmP and LAPSmG vaccines showed exceptional results, indicating that they may be promising candidates as a VL vaccine.
Results of a Clinical Trial Showing Changes to the Faecal Microbiome in Racing Thoroughbreds after Feeding a Nutritional Supplement
Authors: Adams Vicki J. , LeBlanc Neil , Penell Johanna
Published: January 2023

Next-generation sequencing (NGS) has been used to evaluate the effect of various interventions on the equine microbiome. The aim of this randomised blinded clinical trial was to determine if a prebiotic nutritional supplement would result in a change from baseline in the faecal microbiome composition of racing Thoroughbred horses in training being fed a high concentrate/grain-based diet to be more similar to that found in forage fed/pasture grazed horses. Thirty-two horses on one training yard were randomised to either receive the supplement or not. Faecal samples were collected at baseline, 6 and 12 weeks for NGS of the 16S ribosomal subunit gene. Twenty-two horses completed the trial, met the inclusion criteria and were included in the intention to treat analysis; 20 horses were included in the per protocol analysis. The mean and median percent decreases in Bacteroidetes, increases in Firmicutes and the Firmicutes:Bacteroidetes ratio were significantly greater than zero for the treated horses only. Supplemented horses (8/10) were more likely than control horses (2/10) to show an increase in Firmicutes of a ≥9% with ≥24% increase in Clostridia, ≥5% decrease in Bacteroidetes, ≥16% increase in the F:B ratio and ≥2% increase in Actinobacteria (RR = 4, 95% CI: 1.1–14.4, p = 0.01). This provides useful information for further investigations on long-term effects on the microbiome and on health and racing-related outcomes.
Association of Paraoxonase-1 and NT-proBNP with Clinical, Clinico-Pathologic and Echocardiographic Variables in Dogs with Mitral Valve Disease
Authors: Rammal Diana , Koutinas Christos K. , Athanasiou Labrini V. , Tangalidi Melpomeni , Rubio Camila P. , Cerón José J. , Tamvakis Androniki , Patsikas Michael N. , Polizopoulou Zoe S.
Published: January 2023

The objective of the present study was to measure the concentration of Paraoxonase-1 (PON-1) and N-terminal-prohormone-B-type natriuretic peptide (NT-proBNP), in the serum of dogs with degenerative Mitral Valve Disease (MVD), in order to identify their association with the clinical stage and specific clinico-pathologic and echocardiographic findings.Eighty dogs diagnosed with MVD and staged according to the ACVIM (American College of Veterinary Internal Medicine) consensus statement (B1, B2, C and D), based on their clinical, radiographic, and echocardiographic findings, were included in the study. NT-proBNP was measured only in stage B1 and B2 dogs. Clinical stage did not have a significant effect on PON-1 concentrations (p = 0.149), but NT-proBNP levels were lower in B1 dogs (p = 0.001). A significant correlation between PON-1 and total plasma proteins (p = 0.001), albumin (p = 0.003) and white blood cell count (p = 0.041) was detected, whereas there was no significant correlation (p = 0.847) between PON-1 and NT-proBNP concentrations. PON-1 showed a significant but weak negative correlation with normalized left ventricular internal diameter at diastole (LVIDdn) (p = 0.022) and systole (LVIDsn) (p = 0.012), as well as mitral valve E to A wave velocity ratio (MV E/A) (p = 0.015), but not with Left Atrial to Aortic root ratio (LA/Ao) (p = 0.892) or fractional shortening (FS%) (p = 0.944). PON-1 seems to be an insensitive marker of clinical stage and disease severity in MVD, but can be indicative of some clinico-pathological and echocardiographic changes. NT-proBNP changes are independent of oxidative stress.
Current Status of Drinking Water Quality in a Latin American Megalopolis
Authors: Bacha Leonardo , da Silva Bandeira Márcio , Lima Vinícius Santos , Ventura Rodrigo , de Rezende Carlos E. , Ottoni Adacto B. , Tschoeke Diogo , Cosenza Carlos , Thompson Cristiane , Thompson Fabiano
Published: January 2023

(1) Background: Treated water distributed in a Latin American megapolis has been the target of criticism in recent years. During the summers of 2020 and 2021, treated water had a taste and smell of mud in the metropolitan area of Rio de Janeiro city, affecting ~10 million people. (2) Methods: To evaluate the SRJ water quality, a comprehensive dataset was analyzed. In total, 194,821 samples were analyzed between 2018 and 2021, corresponding to three parameters (chlorine concentration, n = 67,723; turbidity, n = 55,186; and coliform abundance, n = 71,912). The 92 SRJ cities were analyzed using two approaches according to the relevant law: a quantitative and qualitative approach. (3) Results: In the qualitative analyses, four groups of cities were found (Group A: three parameters analyzed; 49 to 51 cities; Group B, two parameters analyzed, 9 to 14 cities; Group C, one parameter analyzed, 17 cities; Group D, no parameters analyzed, 12 to 16 cities). (4) Conclusions: In 2021, the top ten cities in Group A showed 100% performance in both the qualitative and quantitative rankings. However, several large cities, such as Duque de Caxias and São Gonçalo, did not have the minimum required number of samples or analyses, which poses serious risks for water quality control and public health.
Okul Yöneticilerinin Kişisel İnisiyatif Alma ve Liderlik Stillerinin Öğretmen Motivasyonuna Etkisi
Authors: KILIÇ Yılmaz , YILMAZ Ercan
Published: January 2023

Bu çalışmanın amacı okul yöneticilerinin kişisel inisiyatif alma ve sergiledikleri liderlik davranışlarının öğretmen motivasyonuna etkisini ortaya koymaktır. Bu amaç çerçevesinde 2017-2018 akademik yılında Konya ilinin merkez ilçeleri olan Karatay, Meram ve Selçuklu’da bulunan kamuya ait ilköğretim ve ortaöğretimde görev yapan öğretmenlerden ölçekler aracılığıyla veriler toplanmıştır. Çalışmanın evrenini 15190 öğretmen oluşturmaktadır. Orantılı küme örnekleme yöntemiyle 720 öğretmene ulaşılarak çalışmanın örneklemi oluşturulmuştur. Yapılan analizler sonucunda aşağıdaki bulgulara ulaşılmıştır. Öğretmenlerin motivasyon düzeyleri cinsiyet, yaş, aynı okulda çalışma süresi, eğitim düzeyi değişkenlerine göre içsel faktörlerde anlamlı düzeyde farklılaştığı gözlenmiştir. Okul türüne göre dışsal ve yönetsel boyutlarda ilkokul ile lise ve ortaokul ile lise arasında anlamlı düzeyde farklılaşmanın olduğu görülmüştür. Branş değişkenine göre yönetsel faktörler boyutunda öğretmenlerin görüşlerinde anlamlı düzeyde bir farklılaşmanın olduğu sonucuna ulaşılmıştır. Okul yöneticilerinin kişisel inisiyatif alma durumları kendiliğinden başlama, proaktiflik ve ısrarcılık boyutları ile öğretmen motivasyonunun boyutları içsel, dışsal ve yönetsel faktörler arasında anlamlı ve pozitif yönlü ilişki bulunmuştur. Demokratik stil ile içsel faktörler arasında anlamlı ve pozitif yönlü ilişki saptanmıştır. Otokratik ve tam serbestlik tanıyan stil ile içsel faktörler arasında anlamlı ve negatif yönlü ilişki bulunmuştur. Dışsal ve yönetsel faktörlerle demokratik ve otokratik liderlik stilleri arasında anlamlı ve pozitif yönlü ilişki bulunmuştur. Kişisel inisiyatif almanın kendiliğinden başlama boyutu dışsal faktörleri anlamlı düzeyde yordamaktadır. Proaktiflik boyutu ise içsel faktörleri anlamlı olarak yordamaktadır. Diğer taraftan proaktiflik ve ısrarcılık boyutları yönetsel faktörleri anlamlı düzeyde yordamaktadır. Demokratik stil öğretmen motivasyonunu olumlu yordarken, otokratik ve tam serbestlik tanıyan stillerin ise olumsuz yordadıkları gözlenmiştir.
Students’ Attitudes in Preparatory Schools toward Learning Language Skills through Storytelling
Authors: ŞAHİN Muhammet
Published: January 2023

The aim of the study is to find out preparatory school students’ attitudes toward learning language skills via storytelling. The sampling of the study consisted of 48 students with A2 language proficiency level at a state university. Turkish students between the ages of 18 and 22 were selected as the sample. The sampling included 25 females and 23 males whose mother tongues were Turkish. A Likert scale questionnaire was administered to investigate the students’ attitudes toward storytelling. Due to validity and reliability concerns, the questionnaire was adapted from an attitude test which was designed and used by Kim and Mcgarry (2014). The results revealed that students might have positive attitudes toward storytelling activities. The participants showed more interest in listening to stories than they did in any other storytelling activities. Overall, they felt competent in receptive skills and enjoyed doing listening activities rather than speaking activities. Finally, the participants were found to believe that using storytelling activities in the classroom is not only beneficial for young learners, but also for adults.
Humanism in Suryakanthan's Short Stories
Authors: A Immanuvel
Published: January 2023

foreigners. When this literary form entered Tamil Nadu, the creators retained only the form by taking it into their creations. They followed the old tradition without making any changes to the subject matter or the method of telling the story. The basic reason for this is that literature is based on the old literary ideals of taste, which are uncritical and instructive. This is what they defined in the theory of "art for art's sake". In the literature that arose on the basis of this theory, only certain communities were made the subject of the poem. The men who emerged from it appeared to be elevated by society, economy, and character. It was only after the arrival of Puthumaipithan and others that the short story literature underwent many changes in form and content. The basic reason for this is that they broke the legacy of the old creators, who thought those creators were those who flew in the sky, and they looked closely at the current society with the mindset that creators are also people who live as human beings. That is why the laborer, rickshaw puller, porter, sweeper, and other characters appeared in their works. Because of their forward-thinking and realistic outlook, they remained strong in the creative world, and their works were also successful. Suryakanthan was the one who entered the field of literature with progressive thinking and a realistic outlook. He stands in this new literary field and creates short stories and novels. Through his work for the last twenty-five years, Suryakanthan has made a unique mark for himself in the field of Tamil literature. He is equal to him in his work, which most vividly reflects the lives of working people and rural people. Suryakanthan has expressed humanity in his works in accordance with the idea that a creator should stand as a representative of the common man and as a humanist with unconditional love for mankind and reflect on life with the help of a writing pen.
Cultural Traditions in Poet Meera's Free Verses
Authors: V Ramesh
Published: January 2023

Meera's poems are classical, verse, satire, poems, poets' forum, and short poems. He also made his mark in the world of journalism through "Annam Vidu Thoothu, Kavi, Om Shakthi, and Moota Magazine." He is the recipient of many distinguished awards. He is a professor, fighter, poet, essayist, journalist, publisher, printer, and founder of the press, who created various dimensions. In the Tamil literary tradition, free verse, a literary form, has been of great value and influence in the last century and the present century. There were many innovations and revolutions in the subject matter and the method of singing, and a number of new poems were created. Not only that, but free verses are also being created today about the cultural virtues, thoughts, human emotions, and humanities that should be possessed by man. In this way, this article explores the cultural norms of contemporary society found in the poems of Meera, who is the pioneer of new poetry.
The Domestic Culture Shown by Valluvar
Authors: V Amutha
Published: January 2023

Thirukkural, the sweet, living entity of the Tamil man, is divided into three divisions, namely, virtue, wealth, and pleasure, and consists of 133 chapters and 1330 couplets in nine parts. Thirukkural is translated into more than 110 languages. Manakkudavar was the first to write the foreword to this book, which has been translated into the second most widely translated language in the world. Nevertheless, Parimelazhagar's foreword is hailed as the best text. Malaiyatthuvasamakanar Gnanaprakasam published this book in Thanjavur in 1812. Thirukkural has been praised by Leo Tolstoy, Bernard Shaw, G.U. Pope, Veerama Munivar, and many others. Bharathi said that Tamil Nadu has become famous by giving Valluvan to the world, and Bharathidasan praised that this world received fame due to having Valluvan. This article is intended to examine the cultural records found in the chapter on Married Life in Domestic Virtue in such an excellent Thirukkural.
A Study of the Humanistic Cultures Among Kings, Peoples, and Saints Found in the Purananuru
Authors: R Jeyapriya
Published: January 2023

The Sangam period signifies the noblest way of life, showing love to all living beings in the world and relieving the suffering of all living beings. Sangam society considered the welfare of not only the individual but also the society as a whole. The ancient Tamils were the ones who lived by the ethics of adhering to the chief of all the virtues, which is the partaking of food that has been shared with others. Selfish rivalries and jealousies are responsible for the major problems today. Literature, which gives pleasure not only to the human senses but also to knowledge, is a mirror that highlights the problems of human life. Literature in all languages has evolved and changed from time to time according to the situation. In that order, the Sangam literature that appeared during the Sangam period speaks of the disciplines to be followed in the life of man. What distinguishes man from other beings is the quality of humanity. The Purananuru points out such a culture. The purpose of this study is to illustrate the humanistic culture between the kings, the people, and the saints of the Sangam age through Purananuru.
Implementasi Pelatihan Metode Baca Gali Alkitab (BGA) Berbasis Genre Kitab bagi Anak Asrama GBI Rock Sikakap
Authors: Hutahaean Hasahatan , Mangentang Matheus , Wibowo Moses , Pakpahan Rugun
Published: January 2023

Abstract: Reading activities, and digging into the Bible are believed to be able to form a strong, fresh, and swift spirituality amid the congregation. Both categorical children, adolescents, adults, and the elderly because the Bible is the Word of God that can transform people in the work of the Holy Spirit. This study aims to find the right method to give to the younger generation is facing an era that is constantly advancing, and changing but in that, but it has a good and bad impact at the same time. Of course, it is bad if faith is not solid. The activity was carried out by the workshop method by providing Bible Reading (BGA) training to GBI Rock dormitory children in South Pagai, Mentawai Islands. The result seems to arouse the curiosity of the younger generation in reading and meditating on God's Word. Together with this passion, faith with good quality, bibles, and is believed to be swift to walk the future.
Abstrak: Kegiatan membaca, menggali Alkitab diyakini mampu membentuk kerohanian yang kuat, segar dan sigap di tengah-tengah jemaat. Baik kategorial anak, remaja, dewasa hingga warga lansia sebab Alkitab adalah Firman Allah yang sanggup mengubah manusia dalam karya Roh Kudus. Penelitian ini bertujuan menemukan metode yang tepat untuk diberikan kepada generasi muda dalam menghadapi zaman yang terus-menerus maju, berubah namun memberi dampak baik dan buruk sekaligus. Tentu berdampak buruk jika iman tidak kokoh. Kegiatan dilakukan dengan metode workshop dengan memberikan pelatihan Baca Gali Alkitab (BGA) kepada anak asrama GBI Rock di Pagai Selatan, Kepulauan Mentawai. Hasilnya tampak menggugah keingintahuan generasi muda dalam membaca dan merenungkan Firman Tuhan. Bersama dengan gairah tersebut tumbuh juga iman dengan kualitas yang baik, biblis dan diyakini sigap untuk menapaki masa depan.
Nilai-Nilai Kristiani dalam Ritual Dipelima Sundun pada Upacara Adat Rambu Solo’
Authors: Randalele Christian Elyesar , Budi Bartolomius , Nabu' Dorce Desi
Published: January 2023

Abstrak: Penelitian ini bertujuan untuk menganalisis nilai-nilai Kristiani yang terdapat dalam ritual Dipelima Sundun pada upacara adat rambu solo’ di Lembang Ma’kodo Kecamatan Simbuang. Rambu Solo’ adalah prosesi upacara kematian yang digelar pada saat seseorang meninggal dan merupakan bagian terpenting dalam kehidupan masyarakat Toraja. Ritual Dipelima sundun adalah upacara pemakaman bagi orang yang meninggal atau masyarakat dangan status sosial yang tinggi (bangsawan) yang disebut Ma’dika. Penelitian ini menggunakan penelitian kualitatif. Penelitian kualitatif digunakan sebagai upaya peneliti untuk menggali informasi dan menganalisis makna dan nilai dari objek yang sedang diteliti. Teknik pengumpulan data dilakukan melalui studi pustaka dan wawancara. Telaah literatur dilakukan dengan mengumpulkan referesi berupa buku, jurnal dan monograf yang relevan dengan topik. Wawancara dilakukan untuk menggali informasi di lapangan, Hasil penelitian ditemukan beberapa nilai dalam ritual dipelima sundun yang berkesesuaian dengan nilai-nilai Kristiani antara lain: empati dan kepedulian sosial, kasih sayang dan penghormatan, gotong-royong serta nilai sukacita. Nilai empati dan kepedulian sosial ditunjukkan oleh kerabat atau masyarakat kepada keluarga yang berduka. Nilai kasih sayang dan penghormatan dinyatakan oleh keluarga kepada yang mati melalui tahapan-tahapan dalam ritus. Nilai gotong-royong merupakan nilai kebersamaan yang ditunjukan oleh masyarakat dengan saling membantu mendukung keluarga yang berduka. Nilai sukacita terungkap lewat perilaku dari keluarga ketika menjamu kerabat atau masyarakat yang datang mengungkapkan dukacita, dan juga ketika keluarga tidak lagi larut dalam kesedihan yang disimbolkan dengan ukkandean bo’bo’.
WAHYU DALAM ALUK MAPPURONDO
Authors: Saputra Jefri Andri
Published: January 2023

Abstract: “Wahyu dalam Aluk Mappurondo” is the author's critique which is motivated by concern about the stereotypes that develop among Christians against Aluk Mappurondo. The stereotype in question is the label "to malillim", which literally means "people who are in the dark". This label is used to distinguish Christians from Aluk Mappurondo adherents. In this paper, the author identifies the label attached to Aluk Mappurondo as a Christian error in understanding God's work in other religions. To prove this error, the author examines the story of the development of the Bible in Buntu Malangka' and also the story of Cornelius (Acts 10:1-48). Both of these texts tell about the work or revelation of God that occurs in religions outside of Christianity. The approach used is cross-textual reading. At the end of this paper, the author finds that the story of the arrival of the Gospel in Buntu Malangka and the story of Cornelius indicates that religions other than Christianity also receive revelations from God, and are able to guide them towards God's plan. This conclusion confirms that the stereotype that regards Aluk Mappurondo as To Malilim is a wrong assumption.
Abstrak: “Wahyu dalam Aluk Mappurondo” adalah kritik penulis yang dilatarbelakangi oleh keprihatinan terhadap stereotip yang berkembang dikalangan penganut agama Kristen terhadap Aluk Mappurondo. Stereotip yang dimaksud adalah label “to malillim”, yang secara harafiah diartikan sebagai “orang yang berada di dalam kegelapan”. Label ini digunakan untuk membedakan  orang Kristen dengan penganut Aluk Mappurondo. Dalam tulisan ini, penulis mengidentifikasi label yang disematkan pada Aluk Mappurondo sebagai sebuah kekeliruan kekristenan memahami karya Allah dalam agama lain. Untuk membuktikan kekeliruan tersebut, penulis mengkaji kisah perkembangan Injil di Buntu Malangka’ dan juga kisah Kornelius (Kis. 10:1-48). Kedua teks ini mengisahkan tentang pekerjaan atau wahyu Allah yang terjadi dalam agama di luar kekristenan. Pendekatan yang digunakan adalah cross-textual reading. Di akhir tulisan ini, penulis menemukan bahwa baik kisah masuknya Injil di Buntu Malangka’ maupun kisah Kornelius, mengindikasikan bahwa agama di luar Kristen juga menerima wahyu dari Allah, dan mampu menuntun mereka sampai kepada rencana Allah. Kesimpulan ini menegaskan bahwa stereotip yang menganggap Aluk Mappurondo sebagai To Malillim adalah asumsi yang keliru.