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With regard to the medical use of the CAP device, it can be stated that there is an exposure to UVC radiation, which, depending on the duration of treatment, can also be above the maximum value legally specified in Europe. Shielding components on the CAP device can reduce UVC exposure to the operator as well as adverse side effects to the patient.Little is known about the mutational impact of ionizing radiation (IR) exposure on a genome-wide level in mammalian tissues. Recent advancements in sequencing technology have provided powerful tools to perform exome-wide analyses of genetic variation. This also opened up new avenues for studying and characterizing global genomic IR-induced effects. However, genotypes generated by next generation sequencing (NGS) studies can contain errors, which may significantly impact the power to detect signals in common and rare variant analyses. These genotyping errors are not explicitly detected by the standard Genotype Analysis ToolKit (GATK) and Variant Quality Score Recalibration (VQSR) tool and thus remain a potential source of false-positive variants in whole exome sequencing (WES) datasets. PI3K inhibitor In this context, the transition-transversion ratio (Ti/Tv) is commonly used as an additional quality check. In case of IR experiments, this is problematic when Ti/Tv itself might be influenced by IR treatment. It was the aim of this study to determine a suitable threshold for variant filters for NGS datasets from irradiated cells in order to achieve high data quality using Ti/Tv, while at the same time being able to investigate radiation-specific effects on the Ti/Tv ratio for different radiation doses. By testing a variety of filter settings and comparing the obtained results with publicly available datasets, we observe that a coverage filter setting of depth (DP) 3 and genotype quality (GQ) 20 is sufficient for high quality single nucleotide variants (SNVs) calling in an analysis combining GATK and VSQR and that Ti/Tv values are a consistent and useful indicator for data quality assessment for all tested NGS platforms. Furthermore, we report a reduction in Ti/Tv in IR-induced mutations in primary human gingiva fibroblasts (HGFs), which points to an elevated proportion of transversions among IR-induced SNVs and thus might imply that mismatch repair (MMR) plays a role in the cellular damage response to IR-induced DNA lesions.Ionizing radiation exposure produces direct or indirect biological effects on genomic DNA. The latter are ionizing radiation mediated by induction of free radicals and oxygen species (ROS). The study was conducted to evaluate the dose-effect/time-effect of antioxidant treatments in reducing the induction of double-strand breaks in human blood lymphocytes. Human peripheral blood samples of 2 mL each from healthy donors were irradiated with 10 mGy after pre-incubation with different antioxidants (β-carotene, vitamin E, vitamin C, N-acetyl L-cysteine). In order to assess their efficiency as prophylactic therapy for irradiation, various concentrations and combinations of antioxidants, as well as different incubation times, have been evaluated. link2 To assess double-strand breaks induced by ionizing radiation, the phosphorylated histone γ-H2AX has been used. A significant reduction (p less then 0.001) in double-strand breaks studied with a γ-H2AX assay was observed with N-acetyl L-cysteine with a 1-h incubation time, followed by vitamin C, vitamin E, and β-carotene. The use of antioxidants, especially N-acetyl L-cysteine before irradiation, significantly decreased the occurrence of double-strand breaks, demonstrating the potential radiological protection for exposure to ionizing radiation.The strategy toward personalized medicine in radiation oncology, nuclear medicine, and diagnostic and interventional radiology demands a specific set of assays for individualized estimation of radiation load for safety concerns and prognosis of normal tissue reactions caused by ionizing radiation. Apparently, it seems reasonable to use validated radiation dosimetric biomarkers for these purposes. However, a number of gaps in knowledge and methodological limitations still have to be resolved until dosimetric biomarkers will start to play a valuable role in clinical practice beyond radiation protection and radiation medicine. An extensive international multicenter research is necessary to improve the methodology of clinical applications of biodosimetry. That became a rationale for launching the IAEA Coordinated Research Project E35010 MEDBIODOSE "Applications of Biological Dosimetry Methods in Radiation Oncology, Nuclear Medicine, and Diagnostic and Interventional Radiology." At the 2 Coordination Meeting on MErelevant international standards, guidelines on good laboratory practice, and the IAEA EPR-Biodosimetry manual.The objective of this study was to establish radiation dose-response calibration curves using automated dicentric scoring to support rapid and accurate cytogenetic triage dose-assessment. Blood was drawn from healthy human volunteers and exposed to Co gamma rays at several dose rates (i.e., 1.0, 0.6, and 0.1 Gy min). After radiation, the blood was placed for 2 h in a 37 °C incubator for repair. Blood was then cultured in complete media to which a mitogen (i.e., phytoghemagglutinin, concentration 4%) was added for 48 h. Colcemid was added to the culture at a final concentration of 0.2 μg mL after 24 h for the purpose of arresting first-division metaphase mitotics. Cells were harvested at the end of 48 h. Samples were processed using an automated metaphase harvester and automated microscope metaphase finder equipped with a suite of software including a specialized automated dicentric scoring application. The data obtained were used to create dose-response tables of dicentric yields. The null hypothesis that the data is Poisson-distributed could not be rejected at the significance level of α = 0.05 using results from a Shiny R Studio application (goodness-of-fit Poisson). Calibration curves based on linear-quadratic fits for Co gamma rays at the three different dose rates were generated using these data. The calibration curves were used to detect blind test cases. In conclusion, using the automated harvester and automated microscope metaphase finder with associated automated dicentric scoring software demonstrates high-throughput with suitable accuracy for triage radiation dose assessment.Low-dose radiation effects were studied in Ukrainian personnel of the Chernobyl exclusion zone. The aim of this study was to determine the influence of borderline exposure to annual professional limits and age on expression of molecular markers. Study groups included 300 radiation workers performing construction work on the New Safe Confinement (Arch) upon the Chernobyl "Shelter" [external dose, 26.1 ± 18.1 mSv; age, 43.1 ± 10.3 y overall and 48.7 ± 5.9 y for 69 control persons]. Methods included gene expression using RT-PCR, flow cytometry of lymphocyte antigens, gamma-H2AX, Cyclin D1 expression, and relative telomere length using flow-FISH. link3 A statistically significant upregulation of VEGFA BAX, DDB2, NFKB1 was shown at doses below 35 mSv. In workers aged under 40 y with doses higher than 35 mSv, an upregulation of 16 genes was revealed-VEGFA, TERF2, TERF1, BIRC5, BAX, TP53, DDB2, CDKN1B, CDKN2A, NFKB2, MAPK14, TGFBR1, MKNK2, CDKN1A, NFKB1, TP53I3; and four genes were downregulated-MADD, FASL, CSF2, and TERT. In workers older than 40 y, 8 genes were upregulated and 12 were downregulated. All groups showed an increased and dose-dependent gamma-H2AX expression. Downregulation of CCND1 genes in older groups was accompanied by lower numbers of Cyclin D1 protein expression and lower CD3 and CD4 cell counts. Upregulation of CSF2 in those over 40 y old positively correlated with B-cell and NK-cell counts. A non-linear type of gene expression response was demonstrated in doses over 35 mSv for those over 40 y, the increased expression of gamma-H2AX is associated with upregulation of cell survival positive regulators-BIRC5, BRCA1, DDB2, CCND1, TERT genes, and longer telomeres; the younger age group was characterized by TERF1 and TERF2 upregulation and telomere shortening.Background The Sleep Tiredness Observed Pressure-Body mass index Age Neck circumference Gender (STOP-Bang) questionnaire is a validated preoperative screening tool for identifying patients with obstructive sleep apnea (OSA). Although it has a high sensitivity at scores ≥3, its specificity is moderate, particularly for scores of 3-4. This study aimed to externally validate the STOP-Bang questionnaire and the alternative scoring models that have been proposed to improve its predictive performance. Methods This prospective cohort study included 115 surgical patients with preoperative STOP-Bang scores of 3-8. Type 3 sleep recordings identified moderate-to-severe OSA, reflected by an apnea-hypopnea index (AHI) of >15. Patients were categorized into 2 subgroups patients with an intermediate (STOP-Bang 3-4) or a high risk of OSA (STOP-Bang 5-8). For patients with scores of 3-4, we tested approaches identified in previous studies stepwise stratification of the STOP-Bang questionnaire and additional preoperative measurement of serum bicarbonate concentrations. Results The incidence of moderate-to-severe OSA was significantly higher in patients with STOP-Bang scores of 5-8 than in patients with scores of 3-4 45 of 58 patients (78%) versus 30 of 57 patients (53%), respectively (P less then .01). For patients with STOP-Bang scores of 3-4, we found no differences regarding their OSA diagnosis between patients included in the alternative scoring models and those not included. Conclusions The STOP-Bang questionnaire detected moderate-to-severe OSA patients when scores reached 5-8. However, its performance was altered in patients with STOP-Bang scores of 3-4, and alternative scoring models with specific combinations of factors failed to improve the screening of these patients.Background Induction of anesthesia is a phase characterized by rapid changes in both drug concentration and drug effect. Conventional mammillary compartmental models are limited in their ability to accurately describe the early drug distribution kinetics. Recirculatory models have been used to account for intravascular mixing after drug administration. However, these models themselves may be prone to misspecification. Artificial neural networks offer an advantage in that they are flexible and not limited to a specific structure and, therefore, may be superior in modeling complex nonlinear systems. They have been used successfully in the past to model steady-state or near steady-state kinetics, but never have they been used to model induction-phase kinetics using a high-resolution pharmacokinetic dataset. This study is the first to use an artificial neural network to model early- and late-phase kinetics of a drug. Methods Twenty morbidly obese and 10 lean subjects were each administered propofol for induction to the 4-compartment model (mean prediction error 0.108; mean square error 31.61), which suffered from overprediction bias during the first 5 minutes followed by under-prediction bias after 5 minutes. Conclusions A recirculatory model and gated recurrent unit artificial neural network that incorporated ensemble learning both had similar performance and were both superior to a compartmental model in describing our high-resolution pharmacokinetic data of propofol. The potential of neural networks in pharmacokinetic modeling is encouraging but may be limited by the amount of training data available for these models.

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