Glioblastoma multiforme (GBM) is one of the most lethal primary central nervous system cancers with a median overall survival of only 12–15 months. The best documented treatment is surgical tumor debulking followed by chemoradiation and adjuvant chemotherapy with temozolomide, but treatment resistance and therefore tumor recurrence, is the usual outcome. Although advances in molecular subtyping suggests GBM can be classified into four subtypes, one concern about using the original histology for subsequent treatment decisions is that it only provides a static snapshot of heterogeneous tumors that may undergo longitudinal changes over time, especially under selective pressure of ongoing therapy. Liquid biopsies obtained from bodily fluids like blood and cerebro-spinal fluid (CSF) are less invasive, and more easily repeated than surgery. However, their deployment for patients with brain cancer is only emerging, and possibly suppressed clinically due to the ongoing belief that the blood brain barrier prevents the egress of circulating tumor cells, exosomes, and circulating tumor nucleic acids into the bloodstream. Although brain cancer liquid biopsy analyses appear indeed challenging, advances have been made and here we evaluate the current literature on the use of liquid biopsies for detection of clinically relevant biomarkers in GBM to aid diagnosis and prognostication. Full article

Giardia intestinalis is an intestinal protozoan most commonly found in humans. It has been grouped into 8 assemblages (A-H). Markers such as the glutamate dehydrogenase gene, triose phosphate isomerase and beta-giardin (β-giardin) have been widely used for genotyping. In addition, different genetic targets have been proposed as a valuable alternative to assess diversity and genetics of this microorganism. Thus, our objective was to evaluate new markers for the study of the diversity and intra-taxa genetic structure of G. intestinalis in silico and in DNA obtained from stool samples. We analysed nine constitutive genes in 80 complete genome sequences and in a group of 24 stool samples from Colombia. Allelic diversity was evaluated by locus and for the concatenated sequence of nine loci that could discriminate up to 53 alleles. Phylogenetic reconstructions allowed us to identify AI, AII and B assemblages. We found evidence of intra- and inter-assemblage recombination events. Population structure analysis showed genetic differentiation among the assemblages analysed. Full article

Polychlorinated biphenyls (PCBs) and naphthalenes (PCNs) are ubiquitous environmental contaminants with varying degrees of toxicity. There are hundreds of possible congeners with similar chemical characteristics, which make these compounds difficult to isolate in environmental samples. Historically, PCBs and PCNs were identified by using an Aroclor or Halowax mixture instead of the individual compounds, which was impractical because of limited numbers of individual standards. A retention index database was developed with all 209 PCBs and 36 PCNs to help identify these chemicals in environmental and biological matrixes. This study uses linear and Lee retention indices to identify all 209 PCBs and 36 PCNs on nine gas chromatography columns. The most toxic congeners, the 12 dioxin-like PCBs, were compared across all columns to determine which stationary phases gave the best selectivity for those compounds. Column selectivity was also examined to determine columns for confirmatory analyses and GC×GC separations. The Rxi-17SilMS demonstrated the most drastic difference in PCB selectivity and, to a lesser extent, PCNs when compared with the other eight columns and could work as a confirmatory column or as a 2nd dimension column for GC×GC separations. Full article

The UV-Index (UVI) is aimed at the prevention of skin cancer as well as other negative implications of ultraviolet radiation exposure. In order to support health related applications, assessments and planning that rely on long term data in high spatial resolution and as there exist only limited ground-based measurements, satellite products from reliable atmospheric monitoring services are used as sustainable data sources to create a climatology of the UVI at the local noon. In this study, the (all-sky) UVI as well as the hypothetically clear-sky UVI were analysed for the European region from 30° North to 65° North and from 25° West to 35° East in a spatial resolution of 0.05° for the time period 1983 to 2015. Maps of the monthly mean UVI provide an overview of the distribution of UVI for Europe as well as the spatial and temporal differences and regional variability at local solar noon. Additionally, eight selected locations provide insight into the effects of latitude and altitude on UVI in Europe. Monthly boxplots for each location provide information about regional differences in the variability of UVI, showing maximum variability in Northern and Central Europe in summer, where in Southern Europe this basically occurs in spring. The frequency of the World Health Organization exposure categories moderate, high and very high UVI is provided based on ten-day means for each month. The maximum difference between mean values per decade of 2006–2015 compared to 1983–1992 ranges from −1.2 to +1.2 for UVI and from −0.4 to +0.6 for UVI ${}_{clear-sky}$ . All locations, except the Northern European site, show an increase of UVI during spring and early summer months. A statistically significant increase in the annual mean all-sky UVI has been found for four sites, which ranges from +1.2% to +3.6% per decade. The latest eleven-year period of the UVI climatology (2005–2015) has been validated with UVI measured in five sites. The sites that are located north of the Alps show an underestimation of the UVI, likely due to the cloud modification. In the south, the UVI climatology provides values that are on average overestimated, possibly related to the use of climatological aerosol information. For the site within the Alps, a switch between underestimation and overestimation during the course of the year has been found. 7% to 9% of the UVI values of the climatology differ from the measured UVI by more than one unit. Full article

The ionic gelation technique allows us to obtain nanoparticles able to function as carriers for hydrophobic anticancer drugs, such as 5-fluoruracil (5-FU). In this study, reticulated chitosan– docosahexaenoic acid (Chi–DHAr) nanoparticles were synthesized by using a chemical reaction between amine groups of chitosan (Chi) and carboxylic acids of docosahexaenoic acid (DHA) and the presence of a link between Chi and DHA was confirmed by FT-IR, while the size and morphology of the obtained Chi-DHAr nanoparticles was evaluated with dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. Drug-loading content (DLC) and drug-loading efficiency (DLE) of 5-FU in Chi-DHAr nanoparticles were 33.74 ± 0.19% and 7.9 ± 0.26%, respectively, while in the non-functionalized nanoparticles (Chir + 5FU), DLC, and DLE were in the ranges of 23.73 ± 0.14%, 5.62%, and 0.23%, respectively. The in vitro release profile, performed in phosphate buffer saline (PBS, pH 7.4) at 37 °C, indicated that the synthetized Chi–DHAr nanoparticles provided a sustained release of 5-FU. Based on the obtained regression coefficient value (R²), the first order kinetic model provided the best fit for both Chir and Chi-DHAr nanoparticles. Finally, cytotoxicity studies of chitosan, 5-FU, Chir, Chir + 5-FU, Chi-DHAr, and Chi-DHAr + 5-FU nanoparticles were conducted. Overall, Chi-DHAr nanoparticles proved to be much more biocompatible than Chir nanoparticles while retaining the ability to release the drug with high efficiency, especially towards specific types of cancerous cells. Full article

Heliotropium taltalense is an endemic species of the northern coast of Chile and is used as folk medicine. The polyphenolic composition of the methanolic and aqueous extract of the endemic Chilean species was investigated using Ultrahigh-Performance Liquid Chromatography, Heated Electrospray Ionization and Mass Spectrometry (UHPLC-Orbitrap-HESI-MS). Fifty-three compounds were detected, mainly derivatives of benzoic acid, flavonoids, and some phenolic acids. Furthermore, five major compounds were isolated by column chromatography from the extract, including four flavonoids and one geranyl benzoic acid derivative, which showed vascular relaxation and were in part responsible for the activity of the extracts. Since aqueous extract of H. taltalense (83% ± 9%, 100 μg/mL) produced vascular relaxation through an endothelium-dependent mechanism in rat aorta, and the compounds rhamnocitrin (89% ± 7%; 10⁻⁴ M) and sakuranetin (80% ± 6%; 10⁻⁴ M) also caused vascular relaxation similar to the extracts of H. taltalense, these pure compounds are, to some extent, responsible for the vascular relaxation. Full article

The large family of C-type lectin (CLEC) receptors comprises carbohydrate-binding proteins that require Ca²⁺ to bind a ligand. The prototypic receptor is the asialoglycoprotein receptor-1 (ASGR1, CLEC4H1) that is expressed primarily by hepatocytes. The early work on ASGR1, which is highly specific for N-acetylgalactosamine (GalNAc), established the foundation for understanding the overall function of CLEC receptors. Cells of the immune system generally express more than one CLEC receptor that serve diverse functions such as pathogen-recognition, initiation of cellular signaling, cellular adhesion, glycoprotein turnover, inflammation and immune responses. The receptor CLEC10A (C-type lectin domain family 10 member A, CD301; also called the macrophage galactose-type lectin, MGL) contains a carbohydrate-recognition domain (CRD) that is homologous to the CRD of ASGR1, and thus, is also specific for GalNAc. CLEC10A is most highly expressed on immature DCs, monocyte-derived DCs, and alternatively activated macrophages (subtype M2a) as well as oocytes and progenitor cells at several stages of embryonic development. This receptor is involved in initiation of T_H1, T_H2, and T_H17 immune responses and induction of tolerance in naïve T cells. Ligand-mediated endocytosis of CLEC receptors initiates a Ca²⁺ signal that interestingly has different outcomes depending on ligand properties, concentration, and frequency of administration. This review summarizes studies that have been carried out on these receptors. Full article

This study presents a machine learning-based method for predicting the power grid state subjected to heavy-rain hazards. Machine learning models can recognize key knowledge from a dataset without any preliminary knowledge about the dataset. Hence, machine learning methods have been utilized for solving power grid-related problems. Two sets of historical data were used herein: Local weather data and power grid outage data. First, we investigated the heavy-rain-related outage distribution and analyzed the correlated characteristics between weather and outages to characterize the heavy rain events. The analysis results show that multiple weather effects are significant in causing power outages, even under heavy-rain conditions. Furthermore, this study proposes a cost-sensitive prediction method using a support vector machine (SVM) model. The accuracy of the model was improved by applying a cost-sensitive learning algorithm to the SVM model, which was subsequently used to predict the state of the grid. The developed model was evaluated using G-mean values. The proposed method was verified via actual data of a heavy rain event that occurred in South Korea. Full article

Short-interval intracortical inhibition (SICI) represents an inhibitory phenomenon acting at the cortical level. However, SICI estimation is based on the amplitude of a motor-evoked potential (MEP), which depends on the discharge of spinal motoneurones and the generation of compound muscle action potential (M-wave). In this study, we underpin the importance of taking into account the proportion of spinal motoneurones that are activated or not when investigating the SICI of the right flexor carpi radialis (normalization with maximal M-wave (Mmax) and MEP_test, respectively), in 15 healthy subjects. We probed SICI changes according to various MEP_test amplitudes that were modulated actively (four levels of muscle contraction: rest, 10%, 20% and 30% of maximal voluntary contraction (MVC)) and passively (two intensities of test transcranial magnetic stimulation (TMS): 120 and 130% of motor thresholds). When normalized to MEP_test, SICI remained unchanged by stimulation intensity and only decreased at 30% of MVC when compared with rest. However, when normalized to Mmax, we provided the first evidence of a strong individual relationship between SICI and MEP_test, which was ultimately independent from experimental conditions (muscle states and TMS intensities). Under similar experimental conditions, it is thus possible to predict SICI individually from a specific level of corticospinal excitability in healthy subjects. Full article

Gliadin is a fraction of gluten, known to trigger celiac disease in susceptible people. To date, the life-long gluten-free diet is used for the prevention of this disease. Hence, methods for gluten control in foods are of significant importance. Being one of the most-used methods used for this purpose, ELISA should use high-affinity antibodies to gliadin peptides involved into celiac process. This study investigates the characteristics of a novel anti-gliadin antibody X6. We found the QXQPFPXP site to be a recognized epitope that provides specific binding of the antibody to cereal prolamins involved in celiac disease manifestation. A specificity study using immunoblotting shows the recognition of wheat, barley and rye proteins—as well as α-gliadin homologs from non-edible cereals (Dasypyrum villosum). Reactivity to avenin was less pronounced, as this protein does not contain the PFP motif most critical for antibody recognition. The proteins of Zea mays and Setaria italica were not recognized by X6. X6-based ELISA highly correlated with R5 and G12, which are Codex Alimentarius standards in the quantitative assessment of gluten content (Pearson’s R = 0.86 and 0.87, respectively). Qualitative assessment revealed no significant differences between R5 and G12 and X6. Full article

The increment of non-communicable chronic diseases is a constant concern worldwide, with type-2 diabetes mellitus being one of the most common illnesses. A mechanism to avoid diabetes-related hyperglycemia is to reduce food digestion/absorption by using anti-enzymatic (functional) ingredients. This research explored the potential of six common Chilean seaweeds to obtain anti-hyperglycemic polyphenol extracts, based on their capacity to inhibit key enzymes related with starch digestion. Ethanol/water hot pressurized liquid extraction (HPLE), which is an environmentally friendly method, was studied and compared to conventional extraction with acetone. Total polyphenols (TP), antioxidant activity, cytotoxicity and inhibition capacity on α-glucosidase and α-amylase were analyzed. Results showed that the Durvillaea antarctica (cochayuyo) acetone extract had the highest TP content (6.7 ± 0.7 mg gallic acid equivalents (GAE)/g dry seaweed), while its HPLE ethanol/water extract showed the highest antioxidant activity (680.1 ± 11.6 μmol E Trolox/g dry seaweed). No extract affected cell viability significantly. Only cochayuyo produced extracts having relevant anti-enzymatic capacity on both studied enzymes, showing a much stronger inhibition to α-glucosidase (even almost 100% at 1000 µg/mL) than to α-amylase. In conclusion, from the Chilean seaweeds considered in this study, cochayuyo is the most suitable for developing functional ingredients to moderate postprandial glycemic response (starchy foods), since it showed a clear enzymatic inhibition capacity and selectivity. Full article

Human resources management, which includes a wide range of activities, may vary between businesses. One of the reasons for these differences may be the fact that they are non-family or family businesses. The purpose of this study is to identify differences in the area of human resources management between non-family and family businesses operating in the Czech business environment. The authors formulated three research questions and two hypotheses. The article’s main findings are: non-family and family businesses do not substantially differ in human resources management. The article is formulating more general conclusions in the researched area, which can serve as a starting point for further directions of possible research on this issue. Full article

The tailings that remain after the collection and screening of Mn nodules are directly discharged into the ocean and are anticipated to influence the ocean environment and marine organisms. The primary factors determining the influence (diffusion) range are the ocean currents and the settling velocity of the tailings; the latter is directly correlated with the time that the tailings remain in the water column. Flocculation is affected by the actual tailing discharge conditions. The settling velocity of the tailings is expected to increase as a result of flocculation; therefore, data on the size distribution of flocs are needed to compute the settling velocity of the tailings. In this study, a method for estimating the floc size distribution of the tailings is proposed, and the general flocculation process is analyzed using the apparent settling velocity, which is readily estimated by simple settling experiments conducted with standard tailings at different concentrations. The apparent falling time-curve followed a power function, and the flocculated grain size was 3–4 times larger than that before flocculation. In addition, flocculation and falling were significantly inhibited by the time required for flocculation. The method suggested in this study was validated by using a numerical particle-tracking model based on the autoencoder concept, which estimates the apparent settling velocity using the flocculated grain size distribution. The computed time-velocity curve agreed well with the apparent time curve obtained in the experiment, with an error of approximately 5–10% except in the initial time range (0–30 s), despite the qualitative nature of the assumptions. Full article

Mental health problems related to chronic stress in workers appear to be sex-specific. Psychosocial factors related to work–life balance partly explain these sex differences. In addition, physiological markers of stress can provide critical information on the mechanisms explaining how chronic stress gets “under the skull” to increase vulnerability to mental health disorders in working men and women. Stress hormones access the brain and modulate attentional and memory process in favor of threatening information. In the present study, we tested whether male and female workers present a memory bias towards work-stress related information, and whether this bias is associated with concentrations of stress hormones in reactivity to a laboratory stressor (reactive levels) and samples taken in participants’ workday (diurnal levels). In total, 201 participants (144 women) aged between 18 and 72 years underwent immediate and delayed recall tasks with a 24-word list, split as a function of valence (work-stress, positive, neutral). Participants were exposed to a psychosocial stressor in between recalls. Reactivity to stress was measured with saliva samples before and after the stressor. Diurnal cortisol was also measured with five saliva samples a day, during 2 workdays. Our exploratory results showed that men presented greater cortisol reactivity to stress than women, while women recalled more positive and neutral words than men. No sex difference was detected on the recall of work-stress words, before or after exposure to stress. These results do not support the hypothesis of a sex-specific cognitive bias as an explanatory factor for sex differences in stress-related mental health disorders in healthy male and female workers. However, it is possible that such a work-stress bias is present in individuals who have developed a mental-health disorder related to workplace stress or who have had one in the recent past. Consequently, future studies could use our stress memory bias task to assess this and other hypotheses in diverse working populations. Full article

The impact of work zones on traffic is a common problem encountered in traffic management. The reconstruction of roads is inevitable, and it is necessary and urgent to reduce the impact of the work zone on the operation of traffic. There are many existing research results on the influence of highway work zones, including management strategies, traffic flow control strategies, and various corresponding model theories. There are also many research results on the impacts of urban road and subway construction on traffic operation, including construction efficiency, economic impact, and travel matrix. However, there are few studies concerning the choice of work zone location, and most previous studies have assumed that the work zone choice was scientific and reasonable. Therefore, it is reasonable to choose the location of the work zone and to assess whether there is room for improvement in the road form of the work zone, but this remains a research gap. Therefore, we studied a seven-lane main road T-intersection in Xi’an, China, and investigated a work zone located at this intersection that caused a road offset, leading to the non-aligned flow of main traffic. We designed two road improvement schemes and multiple transition schemes, used VISSIM software to evaluate the traffic operation of the two schemes, and used the entropy method to choose the suitability of the two schemes under different conditions. According to the results, in the best case, the driving time, delay, and number of stops are reduced by 44%, 66%, and 92%. Full article

To define the role of spleen stiffness (SS) and liver stiffness (LS) in myelofibrosis and other Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), we studied, by ultrasonography (US) and elastography (ES), 70 consecutive patients with myelofibrosis (MF) (no.43), essential thrombocythemia (ET) (no.10), and polycythemia vera (PV) (no.17). Overall, the median SS was not different between patients with MF and PV (p = 0.9); however, both MF and PV groups had significantly higher SS than the ET group (p = 0.011 and p = 0.035, respectively) and healthy controls (p < 0.0001 and p = 0.002, respectively). In patients with MF, SS values above 40 kPa were significantly associated with worse progression-free survival (PFS) (p = 0.012; HR = 3.2). SS also correlated with the extension of bone marrow fibrosis (BMF) (p < 0.0001). SS was higher in advanced fibrotic stages MF-2, MF-3 (W.H.O. criteria) than in pre-fibrotic/early fibrotic stages (MF-0, MF-1) (p < 0.0001) and PFS was significantly different in the two cohorts, with values of 63% and 85%, respectively (p = 0.038; HR = 2.61). LS significantly differed between the patient cohort with MF and healthy controls (p = 0.001), but not between the patient cohorts with ET and PV and healthy controls (p = 0.999 and p = 0.101, respectively). We can conclude that organ stiffness adds valuable information to the clinical work-up of MPNs and could be employed to define patients at a higher risk of progression. Full article