Miracle-dz/UniFAR-FTUs huggingface dataset:
Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against Pseudomonas aeruginosa

The co-occurrence of increasing rates of resistance to current antibiotics and the paucity of novel antibiotics pose major challenges for the treatment of bacterial infections. In this scenario, treatments targeting bacterial virulence have gained considerable interest as they are expected to exert a weaker selection for resistance than conventional antibiotics. In a previous study, we demonstrated that a low-molecular-weight quaternized chitosan derivative, named QAL, displays antibiofilm activity against the major pathogen Pseudomonas aeruginosa at subinhibitory concentrations. The aim of this study was to investigate whether QAL was able to inhibit the production of relevant virulence factors of P. aeruginosa. When tested in vitro at subinhibiting concentrations (0.31–0.62 mg/mL), QAL markedly reduced the production of pyocyanin, pyoverdin, proteases, and LasA, as well as inhibited the swarming motility of three out of four P. aeruginosa strains tested. Furthermore, quantitative reverse transcription PCR (qRT-PCR) analyses demonstrated that expression of lasI and rhlI, two QS-related genes, was highly downregulated in a representative P. aeruginosa strain. Confocal scanning laser microscopy analysis suggested that FITC-labelled QAL accumulates intracellularly following incubation with P. aeruginosa. In contrast, the reduced production of virulence factors was not evidenced when QAL was used as the main polymeric component of polyelectrolyte-based nanoparticles. Additionally, combination of sub-MIC concentrations of QAL and tobramycin significantly reduced biofilm formation of P. aeruginosa, likely due to a synergistic activity towards planktonic bacteria. Overall, the results obtained demonstrated an antivirulence activity of QAL, possibly due to polymer intracellular localization and QS-inhibition, and its ability to inhibit P. aeruginosa growth synergizing with tobramycin.
The Role of Marrow Microenvironment in the Growth and Development of Malignant Plasma Cells in Multiple Myeloma

The development and effectiveness of novel therapies in multiple myeloma have been established in large clinical trials. However, multiple myeloma remains an incurable malignancy despite significant therapeutic advances. Accumulating data have elucidated our understanding of the genetic background of the malignant plasma cells along with the role of the bone marrow microenvironment. Currently, the interaction among myeloma cells and the components of the microenvironment are considered crucial in multiple myeloma pathogenesis. Adhesion molecules, cytokines and the extracellular matrix play a critical role in the interplay among genetically transformed clonal plasma cells and stromal cells, leading to the proliferation, progression and survival of myeloma cells. In this review, we provide an overview of the multifaceted role of the bone marrow microenvironment in the growth and development of malignant plasma cells in multiple myeloma.
Polyphenols Rich Diets and Risk of Type 2 Diabetes

Type 2 diabetes is an increasing health concern worldwide. Both genetic and environmental risk factors as improper dietary habits or physical inactivity are known to be crucial in the pathogenesis of type 2 diabetes. Polyphenols are a group of plant-derived compounds with anti-inflammatory and antioxidant properties that are associated with a low prevalence of metabolic conditions characterized by insulin resistance, including obesity, diabetes, and hypertension. Moreover, there is now full awareness that foods that are rich in phytochemicals and polyphenols could play an important role in preserving human cardiovascular health and substantial clinical evidence indicates that regular dietary consumption of such foods affects favorably carbohydrate metabolism. This review briefly summarizes the evidence relating dietary patterns rich in polyphenols with glucose metabolism and highlights the potential benefits of these compounds in the prevention of type 2 diabetes.
Editorial for Special Issue: Anthocyanin

What do jabuticaba (Myrciaria jaboticaba), Jamun berry (Syzygium cumini), Malay apple (Syzygium malaccense), crimson glory vine (Vitis coignetiae) and roselle (Hibiscus sabdariffa) have in common [. ].
Development and Limitations of Exposure Biomarkers to Dietary Contaminants Mycotoxins

Mycotoxins are toxic secondary fungal metabolites that frequently contaminate cereal crops globally, presenting exposure hazards to humans and livestock in many settings. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates for epidemiological studies, making validated exposure biomarkers better tools for informing epidemiological investigations. While biomarkers of exposure have served important roles for understanding the public health impact of mycotoxins such as aflatoxins (AF), the science of biomarkers must continue advancing to allow for better understanding of mycotoxins’ roles in the etiology of disease and the effectiveness of mitigation strategies. This review will discuss mycotoxin biomarker development approaches over several decades for four toxins of significant public health concerns, AFs, fumonisins (FB), deoxynivalenol (DON), and ochratoxin A (OTA). This review will also highlight some knowledge gaps, key needs and potential pitfalls in mycotoxin biomarker interpretation.
Additive Ensemble Neural Network with Constrained Weighted Quantile Loss for Probabilistic Electric-Load Forecasting

This work proposes a quantile regression neural network based on a novel constrained weighted quantile loss (CWQLoss) and its application to probabilistic short and medium-term electric-load forecasting of special interest for smart grids operations. The method allows any point forecast neural network based on a multivariate multi-output regression model to be expanded to become a quantile regression model. CWQLoss extends the pinball loss to more than one quantile by creating a weighted average for all predictions in the forecast window and across all quantiles. The pinball loss for each quantile is evaluated separately. The proposed method imposes additional constraints on the quantile values and their associated weights. It is shown that these restrictions are important to have a stable and efficient model. Quantile weights are learned end-to-end by gradient descent along with the network weights. The proposed model achieves two objectives: (a) produce probabilistic (quantile and interval) forecasts with an associated probability for the predicted target values. (b) generate point forecasts by adopting the forecast for the median (0.5 quantiles). We provide specific metrics for point and probabilistic forecasts to evaluate the results considering both objectives. A comprehensive comparison is performed between a selection of classic and advanced forecasting models with the proposed quantile forecasting model. We consider different scenarios for the duration of the forecast window (1 h, 1-day, 1-week, and 1-month), with the proposed model achieving the best results in almost all scenarios. Additionally, we show that the proposed method obtains the best results when an additive ensemble neural network is used as the base model. The experimental results are drawn from real loads of a medium-sized city in Spain.
Dosimetric Analysis of the Short-Ranged Particle Emitter 161Tb for Radionuclide Therapy of Metastatic Prostate Cancer

Simple Summary A tremendous effort and rapid development of the prostate-specific membrane antigen (PSMA)-targeting radio ligands for radionuclide therapy has resulted in encouraging response rates for advanced prostate cancer. Different radionuclides have been utilized or suggested as suitable candidates. In this study, a dynamic model of metastatic progress was developed and utilized to estimate a radiopharmaceutical’s potential of obtaining metastatic control of advanced prostate cancer. The simulations performed demonstrated the advantage of utilizing radionuclides with short-range particle emission, i.e., alpha-emitters and low-energy electrons. The recently-proposed beta-emitting radionuclide terbium-161 demonstrates great potential of being a future candidate towards targeted radionuclide therapy of advanced prostate cancer. This is in line with recent encouraging preclinical results and development of upscaling the product quality. Recently, the first in-human application with a [161Tb]Tb-DOTATOC also demonstrated good SPECT image quality, which can enable dosimetry calculations for new 161Tb-based radiopharmaceuticals. Abstract The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands.
Antimicrobial Resistance, FlaA Sequencing, and Phylogenetic Analysis of Campylobacter Isolates from Broiler Chicken Flocks in Greece

Human campylobacteriosis caused by thermophilic Campylobacter species is the most commonly reported foodborne zoonosis. Consumption of contaminated poultry meat is regarded as the main source of human infection. This study was undertaken to determine the antimicrobial susceptibility and the molecular epidemiology of 205 Campylobacter isolates derived from Greek flocks slaughtered in three different slaughterhouses over a 14-month period. A total of 98.5% of the isolates were resistant to at least one antimicrobial agent. In terms of multidrug resistance, 11.7% of isolates were resistant to three or more groups of antimicrobials. Extremely high resistance to fluoroquinolones (89%), very high resistance to tetracycline (69%), and low resistance to macrolides (7%) were detected. FlaA sequencing was performed for the subtyping of 64 C. jejuni and 58 C. coli isolates. No prevalence of a specific flaA type was observed, indicating the genetic diversity of the isolates, while some flaA types were found to share similar antimicrobial resistance patterns. Phylogenetic trees were constructed using the neighbor-joining method. Seven clusters of the C. jejuni phylogenetic tree and three clusters of the C. coli tree were considered significant with bootstrap values >75%. Some isolates clustered together were originated from the same or adjacent farms, indicating transmission via personnel or shared equipment. These results are important and help further the understanding of the molecular epidemiology and antimicrobial resistance of Campylobacter spp. derived from poultry in Greece.
ADAM17 Inhibition Increases the Impact of Cisplatin Treatment in Ovarian Cancer Spheroids

Simple Summary Ovarian cancer (OvCa) treatment is still a challenge, mainly due to acquired resistance mechanisms during the course of chemotherapy. Here, we show the enhanced cytotoxicity of the combined treatment with the ADAM17 inhibitor GW280264X and cisplatin in comparison with cisplatin monotherapy. This effect was visible in five of five ovarian cancer cell lines grown as a monolayer and two of three tested cell lines in three-dimensional tumor spheroids. Tumor spheroids derived from primary tumor and ascites cells were sensitized to cisplatin treatment by GW280264X. In summary, the combination of ADAM17 inhibition with conventional chemotherapy seems to be a promising strategy to overcome chemotherapy resistance in OvCa. Abstract Chemotherapy resistance is a major challenge in ovarian cancer (OvCa). Thus, novel treatment combinations are highly warranted. However, many promising drug candidates tested in two-dimensional (2D) cell culture have not proved successful in the clinic. For this reason, we analyzed our drug combination not only in monolayers but also in three-dimensional (3D) tumor spheroids. One potential therapeutic target for OvCa is A disintegrin and metalloprotease 17 (ADAM17). ADAM17 can be activated by chemotherapeutics, which leads to enhanced tumor growth due to concomitant substrate cleavage. Therefore, blocking ADAM17 during chemotherapy may overcome resistance. Here, we tested the effect of the ADAM17 inhibitor GW280264X in combination with cisplatin on ovarian cancer cells in 2D and 3D. In 2D, the effect on five cell lines was analyzed with two readouts. Three of these cell lines formed dense aggregates or spheroids (HEY, SKOV-3, and OVCAR-8) in 3D and the treatment effect was analyzed with a multicontent readout (cytotoxicity, viability, and caspase3/7 activation). We tested the combined therapy on tumor spheroids derived from primary patient cells. In 2D, we found a significant reduction in the half minimal (50%) inhibitory concentration (IC50) value of the combined treatment (GW280264X plus cisplatin) in comparison with cisplatin monotherapy in all five cell lines with both 2D readout assays (viability and caspase activation). In contrast, the combined treatment only showed an IC50 reduction in HEY and OVCAR-8 3D tumor spheroid models using caspase3/7 activity or CelltoxTM Green as the readout. Finally, we found an improved effect of GW280264X with cisplatin in tumor spheroids derived from patient samples. In summary, we demonstrate that ADAM17 inhibition is a promising treatment strategy in ovarian cancer.
Stakeholder Views on the Idea of Medicines Reuse in the UK

People’s views about medicines reuse are being examined in a handful of qualitative studies and this commentary adds to that work by drawing on our own discussions with groups of stakeholders in the UK in the past two years. The reuse of medicines within the community pharmacy setting is not permitted in the UK but our multidisciplinary team anticipates that this position will change in the coming years as medication shortages and worries about environmental waste and financial losses from the destruction of unused medicines are brought to the fore. Indeed, for many stakeholders, the issue of waste is a strong feature of conversations about medicines reuse. In addition to this, stakeholders identify the numerous barriers to medicines reuse in the UK. This includes the current uncertainty about the quality of unused medicines returned to pharmacies, which could otherwise be reused. However, stakeholders have also been very willing to propose solutions to a range of existing barriers. Our commentary draws on stakeholder meetings to elaborate the range of views about medicines reuse within a UK context. The challenge is to move forward from these views to advance the technologies that will facilitate medicines reuse practically as well as legally.
Determinants of worry using the SARS‐CoV‐19 worry (CoV‐Wo) scale among United States residents

Abstract We sought to develop a brief Severe Acute Respiratory Syndrome Coronavirus 2‐related worry (CoV‐Wo) scale to understand COVID‐19‐related worry among adults in the United States. We also aimed to model key determinants of worry in the early stage of the COVID‐19 pandemic in the United States. A total of 806 participants completed an online survey in late March 2020. Exploratory and confirmatory factor analyses assessed scale structure. Factor analysis stratified by depression was used to assess measurement invariance. Linear regression models examined COVID‐19‐related worry determinants. The CoV‐Wo scale exhibited good reliability (α = 0.80) and a two‐factor structure: health (α = 0.83) and resources (α = 0.71). The full scale and both subscales were higher among participants who stopped working due to COVID‐19 and those with depression. Perception of quality medical care if infected with COVID‐19 was associated with reduced worry. The CoV‐Wo scale is a low burden assessment of COVID‐19‐related worry, that captures common worries in domains affected by COVID‐19 and can be used to develop psychosocial resources.
Impact of Exercise Intensity on Calprotectin Levels in Healthy Volunteers and Patients with Inflammatory Rheumatic Diseases

Exercise influences inflammatory response and immune system performance. The regular practice of a moderate activity positively regulates immunity and the inflammatory process, while intensive training depresses it and enhances inflammatory marker secretion. Calprotectin is involved in the inflammatory process, promoting neutrophil recruitment, cell degranulation, and inflammatory mediators. Furthermore, calprotectin has been associated with various inflammatory diseases, including inflammatory rheumatic diseases. The present review explores the effect of exercise on calprotectin levels in both healthy and inflammatory rheumatic conditions. Data show that the intensity duration and the type of exercise modulate calprotectin levels and participant inflammatory status. The exact role of calprotectin in the exercise response is yet unknown. Calprotectin could constitute an interesting biomarker for monitoring both the effect of exercise on the inflammatory process in healthy volunteers and the efficiency of exercise treatment programs in a patient with inflammatory rheumatic disease.
The Acute Effect of Hyperoxia on Onset of Blood Lactate Accumulation (OBLA) and Performance in Female Runners during the Maximal Treadmill Test

The objective of this study was to analyze the acute effect of hyperoxia during the maximal treadmill test (MTT) of runners. Participants included 10 female street runners who performed the MTT under two different conditions: hyperoxia (HYPX), inhaling oxygen (60% O2) every 3 min; and normoxia (NORM), without additional oxygen inhalation. Both groups performed the MTT with increases in the slope of the run every 3 min until voluntary exhaustion. The variables of lactate concentration, the onset of blood lactate accumulation (OBLA), peripheral oxygen saturation (SpO2), heart rate (HR), and Borg scale were evaluated. It was verified after the comparison (HYPX vs. NORM) that stage 3 (p = 0.012, Cohen’s d = 1.76) and stage 4 (p < 0.001; Cohen’s d = 5.69) showed a reduction in lactate under the HYPX condition. OBLA under the HYPX condition was identified at a later stage than NORM. There were no differences in Borg scale, SpO2, and HR between the different conditions. It was concluded that the HYPX condition contributed to a reduction in lactate concentration and delayed OBLA in runners.
Potential Application of Resistant Starch Sorghum in Gluten-Free Pasta: Nutritional, Structural and Sensory Evaluations

Gluten-free (GF) pasta samples containing rice flour replaced with 0, 5, 10, 15 g/100 g (w/w) of a resistant starch ingredient from annealed sorghum starch (annRS) were formulated. The highest total dietary fiber and RS contents (p < 0.05) were measured in uncooked pasta with 15 g/100 g of annRS addition (15-annRS). After cooking, the 15-annRS pasta was characterized by an RS content of 5.8 g/100 g dry matter, confirming the thermal resistance of annRS. The use of annRS positively influenced the optimal cooking time, the cooking loss, the firmness, and the stickiness of the cooked samples, with not remarkably change in color after cooking. The starch hydrolysis index values decreased as the level of annRS increased. Despite a significant decrease in the overall sensory with increasing levels of annRS, all samples were characterized by a value > 5, which is considered the limit of acceptability. The use of annRS in GF pasta up to 15 g/100 g can contribute to creating GF products with high total dietary fiber content, slowly digestible starch properties, and without drastically compromising the sensory attributes.
Dissection of Genetic Basis Underpinning Kernel Weight-Related Traits in Common Wheat

Genetic dissection kernel weight-related traits is of great significance for improving wheat yield potential. As one of the three major yield components of wheat, thousand kernel weight (TKW) was mainly affected by grain length (GL) and grain width (GW). To uncover the key loci for these traits, we carried out a quantitative trait loci (QTL) analysis of an F6 recombinant inbred lines (RILs) population derived from a cross of Henong 5290 (small grain) and 06Dn23 (big grain) with a 50 K single nucleotide polymorphism (SNP) array. A total of 17 stable and big effect QTL, including 5 for TKW, 8 for GL and 4 for GW, were detected on the chromosomes 1B, 2A, 2B, 2D, 4B, 5A, 6A and 6D, respectively. Among these, there were two co-located loci for three traits that were mapped on the chromosome 4BS and 6AL. The QTL on 6AL was the most stable locus and explained 15.4–24.8%, 4.1–8.8% and 15.7–24.4% of TKW, GW and GL variance, respectively. In addition, two more major QTL of GL were located on chromosome arm 2BL and 2DL, accounting for 9.7–17.8% and 13.6–19.8% of phenotypic variance, respectively. In this study, we found one novel co-located QTL associated with GL and TKW in 2DL, QGl.haaf-2DL.2/QTkw.haaf-2DL.2, which could explain 13.6–19.8% and 9.8–10.7% phenotypic variance, respectively. Genetic regions and linked markers of these stable QTL will help to further refine mapping of the corresponding loci and marker-assisted selection (MAS) breeding for wheat grain yield potential improvement.
Immunoglobulin-Storing Histiocytosis: A Case Based Systemic Review

Crystal-storing histiocytosis (CSH) is a rare event in disorders associated with monoclonal gammopathy and is mostly associated with the accumulation of immunoglobulins (Igs) in the cytoplasm of histiocytes. In this article, we present a case of a 75-year-old female with IgG kappa monoclonal gammopathy of undetermined significance (MGUS) and signs of a non-crystallized version of immunoglobulin-storing histiocytosis (IgSH) in a vertebra corpus. Furthermore, we performed a literature review based on all cases of storing histiocytosis identified by literature search between 1987 and 2020 and identified 140 cases in total. The median age at diagnosis was 60 years (range 18–91), with an equal sex distribution (51% men). The majority of the patients had an underlying neoplastic B-cell disorder, most often multiple myeloma (MM), MGUS, or lymphoplasmacytic lymphoma (LPL). The main affected organ systems or tissue sites were bone (n = 52), followed by head and neck (n = 31), kidney (n = 23), lung (n = 20), and gastrointestinal (GI)-tract (n = 18). IgG was the main immunoglobulin class involved, and most cases were associated with kappa light chain expression. We conclude that IgSH is a rare disease entity but should be considered with unusual findings in several organ systems associated with monoclonal gammopathy, especially with kappa light chain expression.