Miracle-dz/UniFAR-FTUs huggingface dataset:
Thirty Years’ Experience in RELAP5 Applications at GRNSPG & NINE

Abstract The application of RELAP5 at GRNSPG & NINE (Nuclear Research Group of San Piero a Grado&Nuclear and Industrial Engineering) started more than 30 years ago during which several versions of the code have been applied for the analysis of a very large variety of scenarios occurring in facilities and nuclear installations. The present paper has two goals: (1) to summarize the results and main outcomes achieved through the application of RELAP5 to international projects and benchmarks in which GRNSPG & NINE was involved and (2) to qualify the system’s thermal-hydraulic code calculations through the systematic application of a set of developed procedures. Among the analyses performed, this paper will provide insights into the code results and, whenever possible, into the comparison with the reference/experimental data of scenarios measured in (1) integral test facilities: PSB-VVER, ATLAS, PKL, LOBI, LOFT, SPES, PACTEL; (2) separate effect test facilities: BFBT, Neptun, PANDA; (3) research reactors: Experimental Breeder Reactor (EBR); and (4) nuclear power plants: Atucha-II [pressurized heavy water reactor (PHWR)-Konvoi], VVER-1000, Darlington (CANDU). In relation to the methodology developed for qualifying a system thermal-hydraulic code calculation, this paper provides a short description and spot results of the systematic application to the cases mentioned above in respect to some of the following steps: (1) demonstration of the geometrical fidelity; (2) demonstration of the steady-state achievement; (3) qualification at the on-transient level, which implies the characterization of (a) phenomenological windows and (b) relevant thermal-hydraulic aspects; and (4) quantitative analysis to evaluate the accuracy of the code calculation using the fast Fourier transform based method. Finally, the main outcomes of the analyses summarized in this paper are the characterization of the level of assessment of RELAP5 and the demonstration of existence of a robust procedure to qualify system thermal-hydraulic code calculations.
High Intrinsic Expression of P-glycoprotein and Breast Cancer Resistance Protein in Canine Mammary Carcinomas Regardless of Immunophenotype and Outcome

Simple Summary Multidrug resistance of neoplastic cells to chemotherapeutic drugs is a phenomenon mediated by several molecular mechanisms. Among these, P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) counteract the intracellular load of multiple drugs, preventing their efficacy. The basal (intrinsic) cellular expression can be further stimulated by drug exposure. P-gp and BCRP are a subject of intense investigation both in human and veterinary oncology since a better understanding of how their expression is distributed across different tumors allows planning alternative therapeutic strategies. In canine mammary carcinomas, a phenotypic classification similar to the one widely adopted for breast cancer is currently employed. For Basal- and Normal-like phenotypes, chemotherapy is still the main option. In this study, we observed that canine mammary carcinomas bear a high intrinsic expression of both P-gp and BCRP, regardless of their molecular phenotype, and their presence does not influence the outcome. Abstract P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are major actors in multidrug resistance (MDR) phenomenon in both human and canine mammary carcinomas (CMCs). The aim of this study was to investigate an association between the intrinsic expression of P-gp and BCRP compared to the immunophenotypes and outcome in CMCs. Fifty CMCs were evaluated at immunohistochemistry (IHC) for P-gp, BCRP, Estrogen receptor alpha (ER), Progesterone receptors (PR), Human Epidermal Growth Factor Receptor type 2 (HER2), basal cytokeratins 5/6 (CK5/6), Epidermal Growth Factor Receptor 1 (EGFR), and Ki67 proliferation index. P-gp and BCRP positive cases were, respectively, 52% and 74.5%, with a significantly higher expression of BCRP than P-gp. Five immunophenotypes were defined in 37 out of 50 CMCs: 9 (24.3%) Luminal A, 5 (13.5%) Luminal B, 9 (24.3%) HER2 overexpressing, 9 (24.3%) Triple-negative basal-like, and 5 (13.5%) Triple-negative non-basal-like. In all CMCs at least one marker was expressed. Follow-up data were available for 25 animals. The average cancer-specific survival was 739 ± 444 days. A number of CMCs bear a high expression of P-gp and BCRP but no significant association was found between their expression and the immunophenotypes, Ki67 index, the histological grade, and tumor-related death.
Primary Processing and Storage Affect the Dominant Microbiota of Fresh and Chill-Stored Sea Bass Products

The cultivable microbiota isolated from three sea bass products (whole, gutted, and filleted fish from the same batch) during chilled storage and the effect of primary processing on microbial communities in gutted and filleted fish were studied. Microbiological and sensory changes were also monitored. A total of 200 colonies were collected from TSA plates at the beginning and the end of fish shelf-life, differentiated by High Resolution Sequencing (HRM) and identified by sequencing analysis of the V3–V4 region of the 16S rRNA gene. Pseudomonas spp. followed by potential pathogenic bacteria were initially found, while Pseudomonas gessardii followed by other Pseudomonas or Shewanella species dominated at the end of fish shelf-life. P. gessardii was the most dominant phylotype in the whole sea bass, P. gessardii and S. baltica in gutted fish, while P. gessardii and P. fluorescens were the most dominant bacteria in sea bass fillets. To conclude, primary processing and storage affect microbial communities of gutted and filleted fish compared to the whole fish. HRM analysis can easily differentiate bacteria isolated from fish products and reveal the contamination due to handling and/or processing, and so help stakeholders to immediately tackle problems related with microbial quality or safety of fish.
Effects of L-Glutamine Supplementation during the Gestation of Gilts and Sows on the Offspring Development in a Traditional Swine Breed

Simple Summary Nutritional strategies during pregnancy in swine production are considered essential to increase the number of piglets born alive and improve their survival and development. Amino acids, such as glutamine, are among the best compound to introduce in commercial farms after obtaining positive results in trials carried out in selected swine breeds. However, several critical productive factors have to be assessed before translating these strategies to the farm level to ensure the best balance between benefits and investments. The current study focused on the effects of prenatal L-glutamine supplementation on the offspring of Iberian gilts and sows under farm conditions. It is the first trial of amino acid supplementation during pregnancy carried out in traditional swine breeds. These non-selected swine breeds show productive or physiological differences that could affect the supplementation effect. Indeed, although there were changes at the molecular and tissue level, these effects did not turn into advantageous effects for the offspring of traditional breeds. The present study shows the importance of pre-testing nutritional strategies under the final conditions and breeds of implementation and the need to deepen at the molecular level to improve the biological interpretation of findings. Abstract The use of amino acids during pregnancy, such as glutamine (Gln), seems to be a promising strategy in selected swine breeds to improve the offspring prenatal development. The main goal of the current study was to assess the development of the offspring from parity 1–3 sows of a traditional breed, which were supplemented with 1% glutamine after Day 35 of gestation, under farm conditions. A total of 486 (288 treated) piglets from 78 (46 treated) Iberian sows were used. At birth and slaughterhouse, fatty acid composition, metabolism, and mTOR pathway gene expression were analyzed. At birth, treated newborns showed greater amounts of specific amino acids in plasma, such as glutamine, asparagine, or alanine, and Σn-3 fatty acids in cellular membranes than control newborns. The expression of genes belonging to mTOR Complex 1 was also higher in treated piglets with normal birth-weight. However, these findings did not improve productive traits at birth or following periods in litters from supplemented gilts (parity 1) or sows (parities 2–3). Thus, further research is needed to properly understand the effects of prenatal glutamine supplementation, particularly in traditional swine breeds.
Natural Extracts to Augment Energy Expenditure as a Complementary Approach to Tackle Obesity and Associated Metabolic Alterations

Obesity is the epidemic of the 21st century. In developing countries, the prevalence of obesity continues to rise, and obesity is occurring at younger ages. Obesity and associated metabolic stress disrupt the whole-body physiology. Adipocytes are critical components of the systemic metabolic control, functioning as an endocrine organ. The enlarged adipocytes during obesity recruit macrophages promoting chronic inflammation and insulin resistance. Together with the genetic susceptibility (single nucleotide polymorphisms, SNP) and metabolic alterations at the molecular level, it has been highlighted that key modifiable risk factors, such as those related to lifestyle, contribute to the development of obesity. In this scenario, urgent therapeutic options are needed, including not only pharmacotherapy but also nutrients, bioactive compounds, and natural extracts to reverse the metabolic alterations associated with obesity. Herein, we first summarize the main targetable processes to tackle obesity, including activation of thermogenesis in brown adipose tissue (BAT) and in white adipose tissue (WAT-browning), and the promotion of energy expenditure and/or fatty acid oxidation (FAO) in muscles. Then, we perform a screening of 20 natural extracts (EFSA approved) to determine their potential in the activation of FAO and/or thermogenesis, as well as the increase in respiratory capacity. By means of innovative technologies, such as the study of their effects on cell bioenergetics (Seahorse bioanalyzer), we end up with the selection of four extracts with potential application to ameliorate the deleterious effects of obesity and the chronic associated inflammation.
Association of Inflammatory Metabolic Activity of Psoas Muscle and Acute Myocardial Infarction: A Preliminary Observational Study with 18F-FDG PET/CT

Inflamed skeletal muscle promotes chronic inflammation in atherosclerotic plaques, thereby contributing to the increased risk of coronary artery disease (CAD). In this study, we evaluated the metabolic activity of psoas muscle, using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), and its association with carotid artery inflammation and acute myocardial infarction (AMI). In total, 90 participants (32 AMI, 33 chronic stable angina (CSA), and 25 control) were enrolled in this prospective study. Metabolic activity of skeletal muscle (SM) was measured by using maximum standardized uptake value (SUVmax) of psoas muscle, and corresponding psoas muscle area (SM area) was also measured. Carotid artery inflammation was evaluated by using the target-to background ratio (TBR) of carotid artery. SM SUVmax was highest in AMI, intermediate in CSA, and lowest in control group. SM SUVmax was significantly correlated with carotid artery TBR and systemic inflammatory surrogate markers. Furthermore, SM SUVmax was independently associated with carotid artery TBR and showed better predictability than SM area for the prediction of AMI. Metabolic activity of psoas muscle assessed by 18F-FDG PET/CT was associated with coronary plaque vulnerability and synchronized with the carotid artery inflammation in the participants with CAD. Furthermore, it may also be useful to predict AMI.
Electrochemotherapy in the Treatment of Head and Neck Cancer: Current Conditions and Future Directions

Simple Summary Electrochemotherapy (ECT) was first introduced in the late 1980s and was initially used mainly on cutaneous tumors. It has now evolved into a clinically verified treatment approach. Thanks to its high feasibility, it has been extended to treating mucosal and deep-seated tumors, including head and neck cancer (HNC) and in heavily pretreated settings. This review describes current knowledge and data on the use of ECT in various forms of HNCs across different clinical settings, with attention to future clinical and research perspectives. Abstract Despite recent advances in the development of chemotherapeutic drug, treatment for advanced cancer of the head and neck cancer (HNC) is still challenging. Options are limited by multiple factors, such as a prior history of irradiation to the tumor site as well as functional limitations. Against this background, electrochemotherapy (ECT) is a new modality which combines administration of an antineoplastic agent with locally applied electric pulses. These pulses allow the chemotherapeutic drug to penetrate the intracellular space of the tumor cells and thereby increase its cytotoxicity. ECT has shown encouraging efficacy and a tolerable safety profile in many clinical studies, including in heavily pre-treated HNC patients, and is considered a promising strategy. Efforts to improve its efficacy and broaden its application are now ongoing. Moreover, the combination of ECT with recently developed novel therapies, including immunotherapy, represented by immune checkpoint inhibitor (ICI)s, has attracted attention for its potent theoretical rationale. More extensive, well-organized clinical studies and timely updating of consensus guidelines will bring this hopeful treatment to HNC patients under challenging situations.
Precision measurement of the growth rate and mechanism of ibuprofen {001} and {011} as a function of crystallization environment

The crystallisation of ibuprofen under diffusion-limited conditions measured as a function of supersaturation, solvent (95% ethanol/water, ethyl acetate, acetonitrile and toluene) and reactor scale is examined. Measurement of solubility as a function of temperature reveals less than ideal behaviour, consistent with strong solute–solute interactions, particularly in the case of acetonitrile. The crystal growth rates of the {001} and {011} faces of spontaneously nucleated crystals are precisely measured in situ using optical microscopy revealing that their respective growth rates increase with increasing supersaturation to different extents, depending on the solvent type, with concomitant impact on the crystal habit. The measured growth rates, as a function of supersaturation, are generally higher at the 15 mL than the 0.5 mL scale size. Analysis of the growth rates versus supersaturation is consistent with a 2-D surface nucleation (Birth and Spread) model for both faces and at both scale sizes. The growth rates of the {001} and {011} faces exhibit much less growth rate dispersion when compared to literature data for a stirred batch crystallizer. The data are rationalised by examining the surface chemistry of the growing faces revealing, e.g. that polar protic solvents inhibit the growth rate of faces containing available binding sites for hydrogen bond formation, such as carboxylic acid groups.
Clinical Usefulness of Anthropometric Indices to Predict the Presence of Prediabetes. Data from the ILERVAS Cohort

Prediabetes is closely related to excess body weight and adipose distribution. For this reason, we aimed to assess and compare the diagnostic usefulness of ten anthropometric adiposity indices to predict prediabetes. Cross-sectional study with 8188 overweight subjects free of type 2 diabetes from the ILERVAS project (NCT03228459). Prediabetes was diagnosed by levels of glycated hemoglobin (HbA1c). Total body adiposity indices [BMI, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) and Deurenberg’s formula] and abdominal adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora’s equation, A body shape index, and body roundness index) were calculated. The area under the receiver-operating characteristic (ROC) curve, the best cutoff and the prevalence of prediabetes around this value were calculated for every anthropometric index. All anthropometric indices other than the A body adiposity were higher in men and women with prediabetes compared with controls (p < 0.001 for all). In addition, a slightly positive correlation was found between indices and HbA1c in both sexes (r ≤ 0.182 and p ≤ 0.026 for all). None of the measures achieved acceptable levels of discrimination in ROC analysis (area under the ROC ≤ 0.63 for all). Assessing BMI, the prevalence of prediabetes among men increased from 20.4% to 36.2% around the cutoff of 28.2 kg/m2, with similar data among women (from 29.3 to 44.8% with a cutoff of 28.6 kg/m2). No lonely obesity index appears to be the perfect biomarker to use in clinical practice to detect individuals with prediabetes.
Effect of Repeated Freeze–Thaw Cycles on Influenza Virus Antibodies

Background: Vaccine effectiveness relies on various serological tests, whose aim is the measurement of antibody titer in serum samples collected during clinical trials before and after vaccination. Among the serological assays required by the regulatory authorities to grant influenza vaccine release there are: Hemagglutination inhibition (HAI), microneutralization (MN), and Single Radial Hemolysis (SRH). Although antibodies are regarded to be relatively stable, limited evidences on the effect of multiple freeze–thaw cycles on the stability of antibodies in frozen serum samples are available so far. In view of this, the present paper aimed to evaluate the impact of multiple freeze–thaw cycles on influenza antibody stability, performing HAI, MN and SRH assays. Methods: Ten serum samples were divided into 14 aliquots each, stored at −20 °C and taken through a total of 14 freeze–thaw cycles to assess influenza antibody stability. Each assay measurement was carried out following internal procedures based on World Health Organization (WHO) guidelines. Results: No statistically significant effect of 14 freeze–thaw cycles on antibody stability, measured through three different assays, was observed. Conclusions: Collectively, these data demonstrated that specific influenza antibody present in serum samples are stable up to 14 freeze–thaw cycles.
Production of Membrane Vesicles in Listeria monocytogenes Cultured with or without Sub-Inhibitory Concentrations of Antibiotics and Their Innate Immune Responses In Vitro

Listeriosis is a food-borne illness caused by Listeria monocytogenes. Ampicillin (AMP) alone or in combination with gentamicin (GEN) is the first-line treatment option. Membrane vesicle (MV) production in L. monocytogenes under antibiotic stress conditions and pathologic roles of these MVs in hosts have not been reported yet. Thus, the aim of this study was to investigate the production of MVs in L. monocytogenes cultured with sub-minimum inhibitory concentrations (MICs) of AMP, GEN, or trimethoprim/sulfamethoxazole (SXT) and determine pathologic effects of these MVs in colon epithelial Caco-2 cells. L. monocytogenes cultured in tryptic soy broth with 1/2 MIC of AMP, GEN, or SXT produced 6.0, 2.9, or 1.5 times more MV particles, respectively, than bacteria cultured without antibiotics. MVs from L. monocytogenes cultured with AMP (MVAMP), GEN (MVGEN), or SXT (MVSXT) were more cytotoxic to Caco-2 cell than MVs obtained from cultivation without antibiotics (MVTSB). MVAMP induced more expression of tumor necrosis factor (TNF)-α gene than MVTSB, MVGEN and MVSXT, whereas MVTSB induced more expression of interleukin (IL)-1β and IL-8 genes than other MVs. Expression of pro-inflammatory cytokine genes by L. monocytogenes MVs was significantly inhibited by proteinase K treatment of MVs. In conclusion, antibiotic stress can trigger the biogenesis of MVs in L. monocytogenes and MVs produced by L. monocytogenes exposed to sub-MIC of AMP can induce strong pro-inflammatory responses by expressing TNF-α gene in host cells, which may contribute to the pathology of listeriosis.
Metabolome-Wide, Phylogenetically Controlled Comparison Indicates Higher Phenolic Diversity in Tropical Tree Species

Tropical plants are expected to have a higher variety of defensive traits, such as a more diverse array of secondary metabolic compounds in response to greater pressures of antagonistic interactions, than their temperate counterparts. We test this hypothesis using advanced metabolomics linked to a novel stoichiometric compound classification to analyze the complete foliar metabolomes of four tropical and four temperate tree species, which were selected so that each subset contained the same amount of phylogenetic diversity and evenness. We then built Bayesian phylogenetic multilevel models to test for tropical–temperate differences in metabolite diversity for the entire metabolome and for four major families of secondary compounds. We found strong evidence supporting that the leaves of tropical tree species have a higher phenolic diversity. The functionally closer group of polyphenolics also showed moderate evidence of higher diversity in tropical species, but there were no differences either for the entire metabolome or for the other major families of compounds analyzed. This supports the interpretation that this tropical–temperate contrast must be related to the functional role of phenolics and polyphenolics.
MYLK and PTGS1 Genetic Variations Associated with Osteoporosis and Benign Breast Tumors in Korean Women

Osteoporosis, characterized by reduced bone mass and increased bone fragility, is a disease prevalent in women. Likewise, breast cancer is a multifactorial disease and considered the major cause of mortality in premenopausal and postmenopausal women worldwide. Our data demonstrated the association of the MYLK gene and PTGS1 gene variants with osteoporosis and benign breast tumor risk and the impact of ovariectomy on osteoporosis in Korean women. We performed a genome-wide association study (GWAS) of women with osteoporosis and benign breast tumors. There were 60 single nucleotide polymorphisms (SNPs) and 12 SNPs in the MYLK and PTGS1 genes, associated with benign breast tumors and osteoporosis. Our study showed that women with homozygous MYLK rs12163585 major alleles had an increased risk of osteoporosis following ovariectomy compared to those with minor alleles. Women carrying the minor PTGS1 rs1213265 allele and not treated via ovariectomy carried a higher risk of osteoporosis than those who underwent ovariectomy with a homozygous genotype at the major alleles. Our results suggest that both the MYLK and PTGS1 genes are genetic factors associated with the phenotypes, and these associations appear to be modulated by ovariectomy.