This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management.

Thyroid cancer is the predominant endocrine-related malignancy. ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.

As the global population grows, we are witnessing rapid urbanization and the development of industry and agriculture. Novel, largely toxic substances are being used in agriculture to improve yields. All of this has led to the generation of large amounts of pollutants that need to be disposed of and treated. Irresponsible behavior and discharges into nature and river channels not clearly defined by law or sanctioned, certainly have an environmental impact. The Drina River Basin occupies parts of the territories of four countries. It is one of the most important drainage areas in the West Balkans. It calls for international cooperation in many areas, such as public water supply, irrigation, hydropower generation, and the like. However, in order to achieve such cooperation, all the countries that “steward” the resource need to commit to water quality conservation and protection. The DPSIR approach proposed by the Water Framework Directive of the European Union is followed to identify major pressures (pollution sources) in the Serbian part of the Drina River Basin. The pressures are grouped into several categories and described in detail.

Hypotensive influences of benzodiazepines and other GABAA receptor ligands, recognized in clinical practice, seem to stem from the existence of "vascular" GABAA receptors in peripheral blood vessels, besides any mechanisms in the central and peripheral nervous systems. We aimed to further elucidate the vasodilatatory effects of ligands acting through GABAA receptors. Using immunohistochemistry, the rat aortic smooth muscle layer was found to express GABAA γ2 and α1-5 subunit proteins. To confirm the role of "vascular" GABAA receptors, we investigated the vascular effects of standard benzodiazepines, midazolam, and flumazenil, as well as the novel compound MP-III-058. Using two-electrode voltage clamp electrophysiology and radioligand binding assays, MP-III-058 was found to have modest binding but substantial functional selectivity for α5β3γ2 over other αxβ3γ2 GABAA receptors. Tissue bath assays revealed comparable vasodilatory effects of MP-III-058 and midazolam, both of which at 100 µmol/L concentrations had efficacy similar to prazosin. Flumazenil exhibited weak vasoactivity per se, but significantly prevented the relaxant effects of midazolam and MP-III-058. These studies indicate the existence of functional GABAA receptors in the rat aorta, where ligands exert vasodilatory effects by positive modulation of the benzodiazepine binding site, suggesting the potential for further quest for leads with optimized pharmacokinetic properties as prospective adjuvant vasodilators.

Zero Trust security has recently gained attention in enterprise network security. One of its key ideas is making network-level access decisions based on trust scores. However, score-based access control in the enterprise domain still lacks essential elements in our understanding, and in this paper, we contribute with respect to three crucial aspects. First, we provide a comprehensive list of 29 trust attributes that can be used to calculate a trust score. By introducing a novel mathematical approach, we demonstrate how to quantify these attributes. Second, we describe a dynamic risk-based method to calculate the trust threshold the trust score must meet for permitted access. Third, we introduce a novel trust algorithm based on Subjective Logic that incorporates the first two contributions and offers fine-grained decision possibilities. We discuss how this algorithm shows a higher expressiveness compared to a lightweight additive trust algorithm. Performance-wise, a prototype of the Subjective Logic-based approach showed similar calculation times for making an access decision as the additive approach. In addition, the dynamic threshold calculation showed only 7% increased decision-making times compared to a static threshold.

Urban logistics implementation causes environmental pollution; therefore, it is necessary to consider the impact on the environment when carrying out such logistics. Electric vehicles are alternative vehicles that reduce the impact on the environment. For this reason, this study investigated which electric vehicle has the best indicators for urban logistics. An innovative approach when selecting such vehicles is the application of a fuzzy–rough method based on expert decision making, whereby the decision-making process is adapted to the decision makers. In this case, two methods of multi-criteria decision making (MCDM) were used: SWARA (stepwise weight assessment ratio analysis) and MARCOS (measurement alternatives and ranking according to compromise solution). By applying the fuzzy–rough approach, uncertainty is included when making a decision, and it is possible to use linguistic values. The results obtained by the fuzzy–rough SWARA method showed that the range and price of electric vehicles have the greatest influence on the selection of an electric delivery vehicle. The results of applying the fuzzy–rough MARCOS method indicated that the Kangoo E-Tech Electric vehicle has the best characteristics according to experts’ estimates. These results were confirmed by validation and the application of sensitivity analysis. In urban logistics, the selection of an electric delivery vehicle helps to reduce the impact on the environment. By applying the fuzzy–rough approach, the decision-making problem is adjusted to the preferences of the decision makers who play a major role in purchasing a vehicle.