The benefit of additional reperfusion attempts in patients with partial angiographic reperfusion (TICI2b) is unknown. The PROCEED model predicts subsequent favorable occurrence of complete reperfusion (i.e. delayed reperfusion [DR]) at 24 hours after initial incomplete angiographic reperfusion at the conclusion of thrombectomy. This study aims to externally validate the PROCEED model using pooled data from multiple international trials that systematically performed follow‐up perfusion imaging. Individual patient data for external validation were obtained from the EXTEND‐IA, EXTEND‐IA TNK part 1 and 2 trials (clinicaltrials.gov, unique‐identifier: NCT01492725, NCT02388061 and NCT03340493). The model’s primary outcome of interest was the occurrence of DR, defined as the absence of any focal perfusion deficit on follow‐up CT or MRI perfusion imaging maps, despite initial incomplete angiographic reperfusion on the final thrombectomy angiography series. The updated model’s performance was evaluated with discrimination, calibration and clinical decision curves. We analyzed 267 patients for the external validation, with median age of 74 (IQR 64 – 80), 44.2% were female and 62% had DR. The externally validated model had good discrimination (C‐statistic 0.81, 95% CI 0.72 – 0.86) and was well calibrated (intercept 0.22, 95% CI 0.18‐0.33 and slope 0.96, 95% CI 0.81‐1.23). With threshold probability of R=12% (i.e. 88% chance of having DR), pursuing additional reperfusion attempts to pursue complete angiographic reperfusion in a patient with high‐likelihood of DR were seven times worse (Cost:Benefit Ratio 1:7, Figure 1) than no further endovascular maneuver. In terms of standardized net reduction, the PROCEED model could reduce one in five unnecessary interventions without missing an intervention for any patient who would eventually have DR. Across a wide range of threshold probabilities, the model outperformed the scenario of the typical decision‐making process in the angiography suite, based on the current treatment guidelines. The externally validated model had good predictive accuracy and discrimination. Depending on the acceptable risk threshold, the model may compliment clinical judgment of the treating physicians and inform on natural progression of untreated incomplete reperfusion.
Exclusive semileptonic b hadron decays (b → uℓν) serve as a sandbox for probing strong and electroweak interactions and for extracting the CKM element Vub. Instead, this work investigates their underexplored potential to reveal new short-distance physics. Utilizing SMEFT as a conduit to chart territory beyond the SM, we demonstrate that substantive new physics contributions in b → uℓν are necessarily linked to correlated effects in rare neutral-current b decays, neutral B meson mixing or high-mass Drell-Yan tails. We find that measurements of the latter processes strongly restrict the allowed deviations in the former. A complete set of tree-level mediators, originating from a perturbative ultraviolet model and matching at dimension 6, is thoroughly explored to support this assertion. As a showcase application, we examine the feasibility of a new physics interpretation of the recent tension in exclusive |Vub| extraction from B → Vℓν where V = (ρ, ω).
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.
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.
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.
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.
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