Pilsen Tools (Czechia)

The genetic correlates of extreme impulsive violence are poorly understood, and there have been few studies that have characterized a large group of affected individuals both clinically and genetically. We performed whole exome sequencing (WES) in 290 males with the life‐course‐persistent, extremely impulsively violent form of antisocial personality disorder (APD) and analyzed the spectrum of rare protein‐truncating variants (rPTVs). Comparisons were made with 314 male controls and publicly available genotype data. Functional annotation tools were used for biological interpretation. Participants were significantly more likely to harbor rPTVs in genes that are intolerant to loss‐of‐function variants (odds ratio [OR] 2.06; p < 0.001), specifically expressed in brain (OR 2.80; p = 0.036) and enriched for those involved in neurotransmitter transport and synaptic processes. In 60 individuals (20%), we identified rPTVs that we classified as clinically relevant based on their clinical associations, biological function and gene expression patterns. Of these, 37 individuals harbored rPTVs in 23 genes that are associated with a monogenic neurological disorder, and 23 individuals harbored rPTVs in 20 genes reportedly intolerant to loss‐of‐function variants. The analysis presents evidence in support of a model where presence of either one or several private, functionally relevant mutations contribute significantly to individual risk of life‐course‐persistent APD and reveals multiple individuals who could be affected by clinically unrecognized neuropsychiatric Mendelian disease. Thus, Mendelian diseases and increased rPTV burden may represent important factors for the development of extremely impulsive violent life‐course‐persistent forms of APD irrespective of their clinical presentation.

Zdeněk Žabokrtský, Miloslav Konopik, Anna Nedoluzhko, Michal Novák, Maciej Ogrodniczuk, Martin Popel, Ondrej Prazak, Jakub Sido, Daniel Zeman. Proceedings of the CRAC 2023 Shared Task on Multilingual Coreference Resolution. 2023.

The paper presents a comparative analysis of different commercial and academic software. The comparison aims to examine how the integrated adaptive grid refinement methodologies can deal with challenging, electromagnetic-field related problems. For this comparison, two bench-mark problems were examined in the paper. The first example is a solution of an L-shape domain like test problem, which has a singularity at a certain point in the geometry. The second problem is an induction heated aluminum rod, which accurate solution needs to solve non-linear, coupled physical fields. The accurate solution of this problem requires applying adaptive mesh generation strategies or applying a very fine mesh in the electromagnetic domain, which can significantly increase the computational complexity. The results show that the fully-hp adaptive meshing strategies, which are integrated into Agros Suite, can significantly reduce the task's computational complexity compared to the automatic h-adaptivity, which is part of the examined, popular commercial solvers.

n-3 polyunsaturated fatty acids (PUFA) can exert beneficial effects on glucose homeostasis, especially in obese rodents. Gut incretin hormones regulate glucose and lipid homeostasis, but their involvement in the above effects is not entirely clear. This study aims to assess the effects of chronic n-3 PUFA administration on the insulin and incretin responses in C57BL/6N obese male mice subjected to oral glucose tolerance test (oGTT) after 8 weeks of feeding a corn-oil-based high-fat diet (cHF). The weight gain and adiposity were partially reduced in mice fed cHF in which some of the corn oil was replaced with n-3 PUFA concentrate containing ∼60% DHA and EPA in a 3 : 1 ratio. In addition, these mice had improved glucose tolerance, which was consistent with an increased insulin response to oral glucose and plasma glucagon-like peptide-1 (GLP-1) levels. While the stimulatory effects of n-3 PUFA on GLP-1 levels could not be attributed to changes in intestinal or plasma dipeptidyl peptidase-4 activity, their beneficial effects on glucose tolerance were abolished when mice were pretreated with the GLP-1 receptor antagonist exendin 9-39. Moreover, chronic n-3 PUFA intake prevented the detrimental effects of cHF feeding on glucose-stimulated insulin secretion in the pancreatic islets. Collectively, our data suggest that n-3 PUFA may modulate postprandial glucose metabolism in obese mice through a GLP-1-based mechanism. The significance of these findings in terms of the effective DHA and EPA ratio of the n-3 PUFA concentrate as well as the effect of n-3 PUFA in humans requires further research.

Abstract Rapid International Scientific Experiment Satellite (RISESAT) is a small Japanese experimental Earth‐observing, science and technology demonstration satellite. One of the scientific instruments onboard is a miniature radiation monitor telescope RISEPix with two Timepix detectors, developed and built at the Institute of Experimental and Applied Physics, Czech Technical University in Prague. After its successful launch in January 2019, RISESAT joined two other still operational satellites with our Timepix‐based radiation monitors, SATRAM onboard the ESA satellite Proba‐V (launched in 2013) and the Czech VZLUSAT‐1 cubesat (launched 2017). In this work, we present general technical and scientific details about the RISESAT satellite mission and the RISEPix module, and a basic comparison of space weather monitoring from SATRAM and VZLUSAT‐1 radiation monitors.

e23040 Background: The detection of circulating tumor DNA (ctDNA), referred to as “liquid biopsy” is becoming a preferred option for some patients with lung adenocarcinomas. The key for a suitable technology is high sensitivity enabling to detect small fractions of mutated alleles, the method has to be solid against false-positives. The aim of this work was to compare our method based on capillary electrophoresis under denaturing conditions (DCE) to FDA and CE IVD approved commercial kit - cobas EGFR Mutation Test v2. Methods: A total of 44 plasma samples were acquired from patients with clinicaly confirmed stage IV lung adenocarcinoma. There were samples from patients prior to receiving therapy (with a known tissue EGFR genotype) as well as several ones showing progression on a previously administered antiEGFR-therapy (with no tissue info available at the time of plasma sampling). DNA was isolated from multiple 2 mL aliquots of each plasma. The first aliquot was run on cobas z480 real-time instrument using unmodified manufacturer's protocol. Another 2ml aliquot was run by DCE assay (accredited method under ISO 15189:2012), which is based on a PCR followed by a fragment analysis on an ABI capillary analyzer (Sanger sequencer). Results: The mutual concordance was 84.1% (37/44). cobas assay identified 11 EGFR-positive plasma samples (6 x Ex19del, 3 x L858R, 1x T790M combined with Ex19del and 1x T790M combined with L858R). DCE identified 8 EGFR-positive samples (6 x Ex19del, 1 x L858R, 1xT790M combined with L858R). DCE missed 5 of cobas-positive samples (2x Ex19del, 2x L858R and 1x T790M) while in turn identifying 2x Ex19del plasma samples that were concordant with tissue, but missed by cobas. Overall concordance with tissue was 73.3% (22/30) for cobas, 70.0% (21/30) for DCE assay and 80.0% (24/30) for both combined. Conclusions: DCE approach is reliable for low levels of mutations in plasma of lung cancer patients and comparable (and complementary) to cobas. Its advantage is simplicity, low cost and a universal, straighforward adaptability to virtually any mutation at any site allowing to detect oncogenic as well as tumor supressor mutations in ctDNA. Supported by grant 17-30748A.

The spin polarized complex first-order linear optical dispersion reveals the spin-polarized electronic structure of α-Eu2(MoO4)3.

To identify tissue biomarkers that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC). Our study included 39 patients with mCRCC treated with sunitinib. Patients were stratified into two groups based on their response to sunitinib treatment: non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies before the initiation treatment with those performed at between 3rd and 7th months of treatment, depending on the patient. Histological samples of tumor tissue and healthy renal parenchyma, acquired during surgery of the primary tumor, were examined with immunohistochemistry to detect tissue targets involved in the signaling pathways of tumor growth and neoangiogenesis. We selected mammalian target of rapamycine, p53, vascular endothelial growth factor, hypoxia-inducible factor 1 and 2 and carbonic anhydrase IX. We compared the average levels of biomarker expression in both, tumor tissue, as well as in healthy renal parenchyma. Results were evaluated using the Student's t-test. For responders, statistically significant differences in marker expression in tumor tissue versus healthy parenchyma were found for mTOR (4%/16.7%; p=0.01031), p53 (4%/12.7%; p=0.042019), VEGF (62.7%/45%; p=0.019836) and CAIX (45%/15.33%; p=0.001624). A further significant difference was found in the frequency of high expression (more than 60%) between tumor tissue and healthy parenchyma in VEGF (65%/35%; p=0.026487) and CAIX (42%/8%; p=0.003328). CAIX was expressed at high levels in the tumor tissue in both evaluated groups. A significantly higher expression of VEGF in CRCC in comparison to healthy parenchyma can predict a better response to sunitinib.

Given two graphs $G_1$ and $G_2$, the Ramsey number $R(G_1, G_2)$ is the smallest integer $N$ such that, for any graph $G$ of order $N$, either $G_1$ is a subgraph of $G$, or $G_2$ is a subgraph of the complement of $G$. Let $P_n$ denote a path of order $n$ and $\widehat{K}_m$ a kipas of order $m+1$, i.e., the graph obtained from a $P_m$ by adding one new vertex $v$ and edges from $v$ to all vertices of the $P_m$.We close the gap in existing knowledge on exact values of the Ramsey numbers $R(P_n,\widehat{K}_m)$ by determining the exact values for the remaining open cases.

Elementary unit cell of α-MoO3containing four MoO3units.