67 results on '"Hanzlikova P"'
Search Results
2. PARG-deficient tumor cells have an increased dependence on EXO1/FEN1-mediated DNA repair
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Andronikou, Christina, Burdova, Kamila, Dibitetto, Diego, Lieftink, Cor, Malzer, Elke, Kuiken, Hendrik J, Gogola, Ewa, Ray Chaudhuri, Arnab, Beijersbergen, Roderick L, Hanzlikova, Hana, Jonkers, Jos, and Rottenberg, Sven
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- 2024
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3. Novel liquid biopsy CNV biomarkers in malignant melanoma
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E. Lukacova, Z. Hanzlikova, P. Podlesnyi, T. Sedlackova, T. Szemes, M. Grendar, M. Samec, T. Hurtova, B. Malicherova, K. Leskova, J. Budis, and T. Burjanivova
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Melanoma ,Liquid biopsy ,ctDNA ,Biomarker ,ddPCR ,lcWGS ,Medicine ,Science - Abstract
Abstract Malignant melanoma (MM) is known for its abundance of genetic alterations and a tendency for rapid metastasizing. Identification of novel plasma biomarkers may enhance non-invasive diagnostics and disease monitoring. Initially, we examined copy number variations (CNV) in CDK genes (CDKN2A, CDKN2B, CDK4) using MLPA (gDNA) and ddPCR (ctDNA) analysis. Subsequently, low-coverage whole genome sequencing (lcWGS) was used to identify the most common CNV in plasma samples, followed by ddPCR verification of chosen biomarkers. CNV alterations in CDK genes were identified in 33.3% of FFPE samples (Clark IV, V only). Detection of the same genes in MM plasma showed no significance, neither compared to healthy plasmas nor between pre- versus post-surgery plasma. Sequencing data showed the most common CNV occurring in 6q27, 4p16.1, 10p15.3, 10q22.3, 13q34, 18q23, 20q11.21-q13.12 and 22q13.33. CNV in four chosen genes (KIF25, E2F1, DIP2C and TFG) were verified by ddPCR using 2 models of interpretation. Model 1 was concordant with lcWGS results in 54% of samples, for model 2 it was 46%. Although CDK genes have not been proven to be suitable CNV liquid biopsy biomarkers, lcWGS defined the most frequently affected chromosomal regions by CNV. Among chosen genes, DIP2C demonstrated a potential for further analysis.
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- 2024
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4. Systematic Approach Revealed SERPING1 Splicing-Affecting Variants to be Highly Represented in the Czech National HAE Cohort
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Grombirikova, Hana, Bily, Viktor, Soucek, Premysl, Kramarek, Michal, Hakl, Roman, Ballonova, Lucie, Ravcukova, Barbora, Ricna, Dita, Kozena, Karolina, Kratochvilova, Lucie, Sobotkova, Marta, Zachova, Radana, Kuklinek, Pavel, Kralickova, Pavlina, Krcmova, Irena, Hanzlikova, Jana, Vachova, Martina, Krystufkova, Olga, Dankova, Eva, Jesenak, Milos, Novackova, Martina, Svoboda, Michal, Litzman, Jiri, and Freiberger, Tomas
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- 2023
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5. Longitudinal analysis of T2 relaxation time variations following radiotherapy for prostate cancer
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Pavla Hanzlikova, Dominik Vilimek, Radana Vilimkova Kahankova, Martina Ladrova, Valeria Skopelidou, Zuzana Ruzickova, Radek Martinek, and Jakub Cvek
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Prostate cancer ,Radiation therapy ,Quantitative MRI ,T2 relaxation times ,Treatment response ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Aim of this paper is to evaluate short and long-term changes in T2 relaxation times after radiotherapy in patients with low and intermediate risk localized prostate cancer. A total of 24 patients were selected for this retrospective study. Each participant underwent 1.5T magnetic resonance imaging on seven separate occasions: initially after the implantation of gold fiducials, the required step for Cyberknife therapy guidance, followed by MRI scans two weeks post-therapy and monthly thereafter. As part of each MRI scan, the prostate region was manually delineated, and the T2 relaxation times were calculated for quantitative analysis. The T2 relaxation times between individual follow-ups were analyzed using Repeated Measures Analysis of Variance that revealed a significant difference across all measurements (F (6, 120) = 0.611, p << 0.001). A Bonferroni post hoc test revealed significant differences in median T2 values between the baseline and subsequent measurements, particularly between pre-therapy (M0) and two weeks post-therapy (M1), as well as during the monthly interval checks (M2 - M6). Some cases showed a delayed decrease in relaxation times, indicating the prolonged effects of therapy. The changes in T2 values during the course of radiotherapy can help in monitoring radiotherapy response in unconfirmed patients, quantifying the scarring process, and recognizing the therapy failure.
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- 2024
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6. Is high accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) sufficient for its implementation in the urological practice?
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Katerina Rysankova, Pavla Hanzlikova, Vladimir Zidlik, Adela Vrtkova, Maryna Slisarenko, Jozef Skarda, Michal Grepl, and Jan Krhut
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bladder cancer ,diagnostics ,haematuria ,magnetic resonance imaging ,Medicine - Abstract
Aims. Currently, the only method used to differentiate between MIBC and NMIBC is transurethral resection of the bladder tumour (TURBT). Magnetic resonance and Vesical Imaging-Reporting and Data System (VI-RADS) would allow for discrimination between NMIBC and MIBC. We evaluate the sensitivity and specificity of VI-RADS in the diagnosis of muscle-invasive bladder cancer and discuss its value in everyday urological practice. Methods. 64 patients with bladder cancer (BC) were enrolled into this prospective study. Multiparametric magnetic resonance imaging (mpMRI) was performed before transurethral resection of the bladder tumour (TURBT) and evaluated using the VI-RADS score. Score were compared to histopathology results. We evaluated the sensitivity, specificity, positive and negative predictive value of this system using both cut-off VI-RADS ≥ 3 and ≥ 4. Results. Sensitivity of 92.3% (95%CI: 64.0; 99.8), specificity of 81.4% (95%CI: 69.1; 90.3), positive predictive value of 52.2% (95%CI: 30.6; 73.2) and negative predictive value of 98.0% (95%CI: 89.1; 99.9) was determined using cut off VI-RADS ≥ 3, while sensitivity of 76.9% (95%CI: 46.2; 95.0), specificity of 91.5% (95%CI: 81.3; 97.2), positive predictive value of 66.7% (95%CI: 38.4; 88.2), and negative predictive value of 94.7% (95%CI: 85.4; 98.9) was determined using cut-off VI-RADS ≥ 4. Based on our results, we consider the optimal cut-off point to be VI-RADS ≥ 3 with the overall prediction accuracy of 83.3% (95%CI: 72.7; 91.1). Conclusions. We acknowledge that mpMRI provides valuable information with regard to BC staging, however, despite its high overall accuracy, we do not consider the VI-RADS could replace TURBT in discrimination between non-muscle invasive and MIBC.
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- 2023
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7. Cerebrospinal fluid neurofilament light chains and CXCL13 as predictive factors for clinical course of multiple sclerosis
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Pavel Hradilek, Kamila Zondra Revendova, Jana Horakova, Radovan Bunganic, Ondrej Pelisek, David Zeman, Pavla Hanzlikova, and Pavlina Kusnierova
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multiple sclerosis ,biomarkers ,neurofilament light chain ,cxcl13 ,clinical course ,Medicine - Abstract
Aim. The aim of this study was to identify whether NfL and CXCL13 cerebrospinal fluid (CSF) concentrations at diagnostic lumbar puncture can predict the course of multiple sclerosis (MS) in terms of relapses, higher expanded disability status scale (EDSS) and magnetic resonance imaging (MRI) activity. Methods. We conducted a single-centre prospective observational cohort study at the MS center, University Hospital Ostrava, Czech Republic. CSF NfL (cNfL) and CXCL13 concentrations were examined (ELISA method) in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) at the time of diagnostic lumbar puncture. Results. A total of 44 patients with CIS or early RRMS were enrolled, 31 (70.5%) of whom were women. The median age at the time of CSF sampling was 31.21 years (IQR 25.43-39.32), and the follow-up period was 54.6 months (IQR 44.03-59.48). In the simple and multiple logistic regression models, CXCL13 levels did not predict relapses, MRI activity or EDSS > 2.5. Similarly, cNfL concentrations did not predict relapses or MRI activity in either model. In the multiple regression, higher cNfL levels were associated with reaching EDSS > 2.5 (odds ratio [OR] 1.002, 95% confidence interval [CI] 1.000 to 1.003). Conclusions. Our data did not confirm cNfL and/or CXCL13 CSF levels were predictive factors for disease activity such as relapses and MRI activity at the time of diagnostic lumbar puncture in patients with RRMS. While cNfL CSF levels predicted higher disability only after adjustment for other known risk factors, elevated CSF CXCL13 did not predict higher disability at all.
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- 2023
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8. BRAT1 links Integrator and defective RNA processing with neurodegeneration
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Zuzana Cihlarova, Jan Kubovciak, Margarita Sobol, Katerina Krejcikova, Jana Sachova, Michal Kolar, David Stanek, Cyril Barinka, Grace Yoon, Keith W. Caldecott, and Hana Hanzlikova
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Science - Abstract
Mutations in BRAT1 are associated with neurodevelopmental delay and neurodegeneration. Here, the authors show that BRAT1 is a component of Integrator and is important for processing of specific RNAs. They further demonstrate that BRAT1 mutant patient-derived cells exhibit reduced levels of the Integrator catalytic subunit and increased levels of misprocessed UsnRNAs and impaired RNA processing.
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- 2022
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9. PARP inhibition impedes the maturation of nascent DNA strands during DNA replication
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Vaitsiankova, Alina, Burdova, Kamila, Sobol, Margarita, Gautam, Amit, Benada, Oldrich, Hanzlikova, Hana, and Caldecott, Keith W.
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- 2022
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10. Immunogenicity and Safety of COVID-19 mRNA Vaccine in STAT1 GOF Patients
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Bloomfield, Marketa, Parackova, Zuzana, Hanzlikova, Jana, Lastovicka, Jan, and Sediva, Anna
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- 2022
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11. BRAT1 links Integrator and defective RNA processing with neurodegeneration
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Cihlarova, Zuzana, Kubovciak, Jan, Sobol, Margarita, Krejcikova, Katerina, Sachova, Jana, Kolar, Michal, Stanek, David, Barinka, Cyril, Yoon, Grace, Caldecott, Keith W., and Hanzlikova, Hana
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- 2022
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12. XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair
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Adamowicz, Marek, Hailstone, Richard, Demin, Annie A., Komulainen, Emilia, Hanzlikova, Hana, Brazina, Jan, Gautam, Amit, Wells, Sophie E., and Caldecott, Keith W.
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- 2021
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13. Neuronal enhancers are hotspots for DNA single-strand break repair
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Wu, Wei, Hill, Sarah E., Nathan, William J., Paiano, Jacob, Callen, Elsa, Wang, Dongpeng, Shinoda, Kenta, van Wietmarschen, Niek, Colón-Mercado, Jennifer M., Zong, Dali, De Pace, Raffaella, Shih, Han-Yu, Coon, Steve, Parsadanian, Maia, Pavani, Raphael, Hanzlikova, Hana, Park, Solji, Jung, Seol Kyoung, McHugh, Peter J., Canela, Andres, Chen, Chongyi, Casellas, Rafael, Caldecott, Keith W., Ward, Michael E., and Nussenzweig, André
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- 2021
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14. Simplified performance assessment methodology for addressing soil quality of nature-based solutions
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Bouzouidja, Ryad, Béchet, Béatrice, Hanzlikova, Jitka, Sněhota, Michal, Le Guern, Cécile, Capiaux, Hervé, Jean-Soro, Liliane, Claverie, Rémy, Joimel, Sophie, Schwartz, Christophe, Guénon, René, Szkordilisz, Flora, Körmöndi, Barnabas, Musy, Marjorie, Cannavo, Patrice, and Lebeau, Thierry
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- 2021
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15. Risk Factors for Severe COVID-19 and Hospital Admission in Patients With Inborn Errors of Immunity - Results From a Multicenter Nationwide Study
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Tomas Milota, Marta Sobotkova, Jitka Smetanova, Marketa Bloomfield, Jana Vydlakova, Zita Chovancova, Jiri Litzman, Roman Hakl, Jiri Novak, Ivana Malkusova, Jana Hanzlikova, Dalibor Jilek, Beata Hutyrova, Vitezslav Novak, Irena Krcmova, Anna Sediva, and Pavlina Kralickova
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inborn errors of immunity ,COVID-19 ,SARS-CoV-2 ,risk factors ,mortality ,hospital admission ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44–3.53) risk ratio for hospital admission and a higher mortality ratio (2.4% vs. 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.
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- 2022
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16. Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair
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Hana Hanzlikova, Evgeniia Prokhorova, Katerina Krejcikova, Zuzana Cihlarova, Ilona Kalasova, Jan Kubovciak, Jana Sachova, Richard Hailstone, Jan Brazina, Shereen Ghosh, Sebahattin Cirak, Joseph G. Gleeson, Ivan Ahel, and Keith W. Caldecott
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Science - Abstract
Defects in DNA single-strand break repair are associated with neurodegenerative disease. Here the authors reveal that mutations in ARH3 interfere with the catabolism of mono-(ADP-ribose) and lead to its accumulation on core histones following repair of endogenous or exogenous DNA single-strand breaks.
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- 2020
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17. A Comparison Between Novel FPGA-Based Pad Monitoring System Using Ballistocardiography and the Conventional Systems for Synchronization and Gating of CMRI at 3 Tesla: A Pilot Study
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Radek Martinek, Jindrich Brablik, Jakub Kolarik, Martina Ladrova, Jan Nedoma, Radana Kahankova, Rene Jaros, Lubomir Vojtisek, and Pavla Hanzlikova
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Cardiac triggering ,triggering using ballistocardiography (BCG) ,pad monitoring system ,imaging of the heart ,electrocardiography (ECG) ,photoplethysmography (PPG) ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
This pilot pre-clinical study demonstrates the applicability of a new type of pneumatic cardiac triggering (PCT) for cardiac imaging. The pilot research compares the novel FPGA-based pad monitoring system for cardiac triggering using ballistocardiography (BCG) with conventional systems based on electrocardiography (ECG) and photoplethysmography (PPG). The implemented system enables cardiac triggering without the need to fix the sensors to the patient's body. This unique approach has the potential to reduce the preparation time for examination and the examination itself and to increase patient's comfort. The pilot pre-clinical study was conducted on 10 subjects at the Siemens Prisma 3T MRI Scanner within the CEITEC Multimodal and Functional Imaging Laboratory - Central European Institute of Technology, Masaryk University, upon the approval of the Ethics Committee. In total, 748 peaks (heart beats) were detected, with 7.347 correctly identified as true positive peaks, 140 incorrectly detected as false positive peaks, and 106 missed peaks (false negative). For all subjects, the total accuracy reached 96.31% and F1 score reached 98.18%. The applicability of the proposed BCG system was also analyzed in terms of objective (BRISQUE, NIQE, PIQE) and subjective evaluation of the images by 10 experts. The study compares images from two basic cardiac sequences - TRUE FISP (Free Induction Decay Steady-State Precession) and PSIR (Phase Sensitive Inversion Recovery) sequences. The BCG system achieves comparable results with the most frequently used and most accurate clinical ECG system used as gold standard. The results prove that the BCG signal captured by our new sensor can be used as a substitute for ECG signal during MRI exam with reliability of 97%.
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- 2020
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18. A Novel FBG-Based Triggering System for Cardiac MR Imaging at 3 Tesla: A Pilot Pre-Clinical Study
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Jan Nedoma, Radek Martinek, Marcel Fajkus, Jindrich Brablik, Radana Kahankova, Michael Fridrich, Michal Kostelansky, Pavla Hanzlikova, Lubomir Vojtisek, and Khosrow Behbehani
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Fiber Bragg grating (FBG) ,optic system ,cardiac triggering ,electrocardiography (ECG) ,pulse oximetry (POX) ,magnetic resonance imaging (MRI) ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
This first-ever study demonstrates the applicability of a fiber Bragg grating (FBG) system for MR cardiac triggering of cardiovascular magnetic resonance at 3 Tesla. The unique patented system senses body movements caused by cardiac activity using a non-invasive ballistocardiography (BCG) sensor. The pilot research compares a novel FBG-based system with clinically used triggering systems based on electrocardiography (ECG) and pulse oximetry (POX). The pilot pre-clinical study was conducted on 8 subjects at a Siemens Prisma 3T MR Scanner. The study compares images from two basic cardiac sequences, TRUE FISP (Free Induction Decay Steady-State Precession) and PSIR (Phase Sensitive Inversion Recovery), using objective methods and subjective evaluation by clinical experts. The study presents original results that confirm the applicability of optical sensors in the field of cardiac triggering having a number of advantages in comparison to conventional solutions, such as no eddy current interference, ease of placement of the sensor on the patient's body, and senor reusability. The proposed FBG-based system achieves comparable results with the most frequently used and most accurate ECG-based and POX-based clinical systems. In terms of subjective evaluation by experts, the FBG system outperformed the POX-based system used in clinical practice.
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- 2020
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19. Comparative analysis of wavelet transform filtering systems for noise reduction in ultrasound images.
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Dominik Vilimek, Jan Kubicek, Milos Golian, Rene Jaros, Radana Kahankova, Pavla Hanzlikova, Daniel Barvik, Alice Krestanova, Marek Penhaker, Martin Cerny, Ondrej Prokop, and Marek Buzga
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Medicine ,Science - Abstract
Wavelet transform (WT) is a commonly used method for noise suppression and feature extraction from biomedical images. The selection of WT system settings significantly affects the efficiency of denoising procedure. This comparative study analyzed the efficacy of the proposed WT system on real 292 ultrasound images from several areas of interest. The study investigates the performance of the system for different scaling functions of two basic wavelet bases, Daubechies and Symlets, and their efficiency on images artificially corrupted by three kinds of noise. To evaluate our extensive analysis, we used objective metrics, namely structural similarity index (SSIM), correlation coefficient, mean squared error (MSE), peak signal-to-noise ratio (PSNR) and universal image quality index (Q-index). Moreover, this study includes clinical insights on selected filtration outcomes provided by clinical experts. The results show that the efficiency of the filtration strongly depends on the specific wavelet system setting, type of ultrasound data, and the noise present. The findings presented may provide a useful guideline for researchers, software developers, and clinical professionals to obtain high quality images.
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- 2022
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20. A Low-Cost System for Seismocardiography-Based Cardiac Triggering: A Practical Solution for Cardiovascular Magnetic Resonance Imaging at 3 Tesla
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Radek Martinek, Jindrich Brablik, Jakub Kolarik, Martina Ladrova, Jan Nedoma, Rene Jaros, Lukas Soustek, Radana Kahankova, Marcel Fajkus, Lubomir Vojtisek, Pavla Hanzlikova, and Petr Krupa
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Seismocardiography-based cardiac triggering ,seismocardiography (SCG) ,siemens prisma 3T ,monitor patient vital signs during MRI ,cardiac magnetic resonance imaging (CMRI) ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
This study describes a pilot clinical validation of a new low-cost system for the continuous monitoring of the human body's cardiorespiratory activities within the magnetic resonance examination area. This study primarily focuses on monitoring cardiac activity and the related cardiac triggering. The patented system tested by the authors is based on seismocardiography (SCG). The study was conducted on 18 subjects on a Siemens Prisma 3T MR scanner. Standard anatomical and diffusion sequences were used to test cardiac activity monitoring. A wide range of commonly used diagnostic sequences were used to test imaging of the heart by means of cardiac triggering. System functionality was verified against a commercially available electrocardiography (ECG) system. Monitoring of cardiac activity (detection of the R-R interval in ECG and the AO-AO interval in SCG) was objectively evaluated by determining the overall probability of correct detection (ACC), sensitivity (SE), positive predictive value (PPV), and harmonic mean between SE and PPV, i.e. F1. Imaging quality control using Cardiac Triggering was performed by subjective evaluation of images by the physicians. The study conducted clearly confirmed the functionality of the system in terms of continuous cardiac activity monitoring. In all 18 subjects, a mean PPV > 99 % was achieved; F1 > 99 %; SE > 99 %; ACC > 98 %; 1.96σ
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- 2019
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21. MR Fully Compatible and Safe FBG Breathing Sensor: A Practical Solution for Respiratory Triggering
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Marcel Fajkus, Jan Nedoma, Radek Martinek, Jindrich Brablik, Jan Vanus, Martin Novak, Stanislav Zabka, Vladimir Vasinek, Pavla Hanzlikova, and Lubomir Vojtisek
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Magnetic resonance imaging (MRI) ,respiratory rate (RR) ,fiber-optic sensor ,fiber Bragg grating (FBG) ,respiratory triggering ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
This publication describes an original simple low-cost MR fully-compatible and safe fiber-optic breathing sensor (FOBS), which can be used for respiratory triggering and for monitoring the development of respiratory rate within the MR environment and can, thus, serve as prevention from the hyperventilation syndrome. The sensor is created by encapsulation of the Bragg grating into conventional nasal oxygen cannulas. The sensor is immune to minor patient movements, thus limiting movement artifacts to a minimum. Thanks to this fact it can be used for the retrospective/prospective respiratory gating. The sensor is immune to electromagnetic interference (EMI) and can thus be used in any magnetic field (1.5T, 3T, and 7T). The sensor prototype has been tested in both laboratory and real magnetic resonance (3T) environments relative to conventional pneumatic respiration references (PRR). The data measured were statistically evaluated using the objective Bland-Altman method (BAM) and the functionality of the proposed solution was confirmed. Respiratory Triggering functionality was confirmed by the radiologic doctors on the basis of analyzing images using the most used respiratory triggered T2 TSE 3D sequences and by objective method using the Blind/Referenceless Image Spatial Quality Evaluator (BRISQUE).
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- 2019
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22. Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair
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Hanzlikova, Hana, Prokhorova, Evgeniia, Krejcikova, Katerina, Cihlarova, Zuzana, Kalasova, Ilona, Kubovciak, Jan, Sachova, Jana, Hailstone, Richard, Brazina, Jan, Ghosh, Shereen, Cirak, Sebahattin, Gleeson, Joseph G., Ahel, Ivan, and Caldecott, Keith W.
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- 2020
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23. Multifunctional adaptor protein Daxx interacts with chromatin-remodelling ATPase Brg1
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Jan Svadlenka, Jan Brazina, Hana Hanzlikova, Lukas Cermak, and Ladislav Andera
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Adapter ,Transcriptional repression ,Chromatin remodelling ,Interaction ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
Multifunctional adapter and chaperone protein Daxx participates in the regulation of a number of mainly transcription-related processes. Most notably in a complex with chromatin-remodelling ATPase ATRX, Daxx serves as a histone H3.3 chaperone at telomeric regions and certain genes. In this report we document that Daxx interacts with another chromatin-remodelling, ATPase Brg1. We confirm the Daxx-Brg1 association both in vitro and in cells and show that Daxx interacts with Brg1 in high-molecular-weight complexes. Ectopic co-expression of Daxx with Brg1 and PML could shift disperse nuclear localisation of Brg1 into PML bodies. Mapping the Daxx-Brg1 interaction revealed that Daxx preferentially binds the region between Brg1 N-terminal QLQ and HSA domains, but also weakly interacts with its C-terminal part. Brg1 interacted with both the central and N-terminal parts of Daxx. SiRNA-mediated down-regulation of Daxx in SW13 adrenal carcinoma cells markedly enhanced expression of Brg1-activated genes CD44 or SCEL, suggesting that Daxx either directly through Brg1 and/or indirectly via other factors is a negative regulator of their transcription. Our findings point to Brg1 as another chromatin-remodelling protein that might similarly, as ATRX, target Daxx to specific chromatin regions where it can carry out its chromatin- and transcription-regulating functions.
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- 2016
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24. Is high accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) sufficient for its implementation in the urological practice?
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Rysankova, Katerina, Hanzlikova, Pavla, Zidlik, Vladimir, Vrtkova, Adela, Slisarenko, Maryna, Skarda, Jozef, Grepl, Michal, and Krhut, Jan
- Abstract
Aims. Currently, the only method used to differentiate between MIBC and NMIBC is transurethral resection of the bladder tumour (TURBT). Magnetic resonance and Vesical Imaging-Reporting and Data System (VI-RADS) would allow for discrimination between NMIBC and MIBC. We evaluate the sensitivity and specificity of VI-RADS in the diagnosis of muscle-invasive bladder cancer and discuss its value in everyday urological practice. Methods. 64 patients with bladder cancer (BC) were enrolled into this prospective study. Multiparametric magnetic resonance imaging (mpMRI) was performed before transurethral resection of the bladder tumour (TURBT) and evaluated using the VI-RADS score. Score were compared to histopathology results. We evaluated the sensitivity, specificity, positive and negative predictive value of this system using both cut-off VI-RADS = 3 and = 4. Results. Sensitivity of 92.3% (95%CI: 64.0; 99.8), specificity of 81.4% (95%CI: 69.1; 90.3), positive predictive value of 52.2% (95%CI: 30.6; 73.2) and negative predictive value of 98.0% (95%CI: 89.1; 99.9) was determined using cut off VIRADS = 3, while sensitivity of 76.9% (95%CI: 46.2; 95.0), specificity of 91.5% (95%CI: 81.3; 97.2), positive predictive value of 66.7% (95%CI: 38.4; 88.2), and negative predictive value of 94.7% (95%CI: 85.4; 98.9) was determined using cut-off VI-RADS = 4. Based on our results, we consider the optimal cut-off point to be VI-RADS = 3 with the overall prediction accuracy of 83.3% (95%CI: 72.7; 91.1). Conclusions. We acknowledge that mpMRI provides valuable information with regard to BC staging, however, despite its high overall accuracy, we do not consider the VI-RADS could replace TURBT in discrimination between non-muscle invasive and MIBC. [ABSTRACT FROM AUTHOR]
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- 2023
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25. Cerebrospinal fluid neurofilament light chains and CXCL13 as predictive factors for clinical course of multiple sclerosis.
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Hradilek, Pavel, Revendova, Kamila Zondra, Horakova, Jana, Bunganic, Radovan, Pelisek, Ondrej, Zeman, David, Hanzlikova, Pavla, and Kusnierova, Pavlina
- Abstract
Aim. The aim of this study was to identify whether NfL and CXCL13 cerebrospinal fluid (CSF) concentrations at diagnostic lumbar puncture can predict the course of multiple sclerosis (MS) in terms of relapses, higher expanded disability status scale (EDSS) and magnetic resonance imaging (MRI) activity. Methods. We conducted a single-centre prospective observational cohort study at the MS center, University Hospital Ostrava, Czech Republic. CSF NfL (cNfL) and CXCL13 concentrations were examined (ELISA method) in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) at the time of diagnostic lumbar puncture. Results. A total of 44 patients with CIS or early RRMS were enrolled, 31 (70.5%) of whom were women. The median age at the time of CSF sampling was 31.21 years (IQR 25.43-39.32), and the follow-up period was 54.6 months (IQR 44.03-59.48). In the simple and multiple logistic regression models, CXCL13 levels did not predict relapses, MRI activity or EDSS > 2.5. Similarly, cNfL concentrations did not predict relapses or MRI activity in either model. In the multiple regression, higher cNfL levels were associated with reaching EDSS > 2.5 (odds ratio [OR] 1.002, 95% confidence interval [CI] 1.000 to 1.003). Conclusions. Our data did not confirm cNfL and/or CXCL13 CSF levels were predictive factors for disease activity such as relapses and MRI activity at the time of diagnostic lumbar puncture in patients with RRMS. While cNfL CSF levels predicted higher disability only after adjustment for other known risk factors, elevated CSF CXCL13 did not predict higher disability at all. [ABSTRACT FROM AUTHOR]
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- 2023
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26. Fatigue Behaviour of Nodular Cast Iron at Various Loading Cycle Asymmetry
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Stanislav Vechet, Jan Kohout, Klara Hanzlikova, and Vojtech Hruby
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no keywords ,Transportation and communications ,HE1-9990 ,Science ,Transportation engineering ,TA1001-1280 - Abstract
Fatigue behaviour of nodular cast irons is described in specialized literature quite well but the majority of fatigue tests in high cycle region has been made at symmetrical bending or at symmetrical tension-compression loading. The role of loading cycle asymmetry is very important because the fatigue limit of nodular cast irons is substantially influenced by mean static stress. Unfortunately, the number of papers describing the influence of mean static stress is quite low. The aim of the presented paper consists in presenting the results of long-term research of nodular cast irons at high cycle region at different loading cycle asymmetry. Several heats with various heat treatments leading to various structures of matrix were used for fatigue tests performed mainly at symmetrical tension-compression loading and at repeating tensile loading. From S-N curves the fatigue limits for 107 cycles were determined and then used for the calculation and construction of the Haigh and the Smith diagrams. Nodular cast irons seem to be more sensitive to mean static stress than structural steels. It was found that, in contrast to many papers, the dependence of upper stress on mean stress is not linear but parabolic with the exponent lower than 1 whose value is linear function of UTS.
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- 2006
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27. The Relation between Microstructure Composition and Fatigue Properties of ADI
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Klara Hanzlikova, Stanislav Vechet, and Jan Kohout
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no keywords ,Transportation and communications ,HE1-9990 ,Science ,Transportation engineering ,TA1001-1280 - Abstract
The presented work deals with a high-strength variant of nodular cast iron, so-called ADI (austempered ductile iron). This material ranks among prospective structural materials and is more and more applied in all important branches of machine industry. Recently it has even been applied to castings for cyclically loaded components, i.e. gears and traversing wheels, crankshafts of motor-cars, vans and trucks, swivel pins, rail brakes, pressure pipes in oil industry etc. The microstructure composition of an ADI matrix consists especially of bainitic ferrite and stabilized austenite. However, in dependence on transformation dwell some amount of martensite can appear as well.In this work the relation between mechanical properties and microstructure composition of the matrix mixture was studied in detail for the case of ADI transformed at 380 °C, with emphasis on fatigue properties.
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- 2006
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28. Comparison of SIMOA and VEUS technologies for serum neurofilament light chain measurement in multiple sclerosis.
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Pelisek, Ondrej, Kusnierova, Pavlina, Hradilek, Pavel, Horakova, Jana, Svub, Krystof, Siprova, Katerina, Sobek, Ondrej, Ganesh, Aravind, Hanzlikova, Pavla, Volny, Ondrej, and Revendova, Kamila Zondra
- Abstract
The gold standard for serum neurofilament light chain (sNfL) determination is the single molecule array (SIMOA), the use of which is limited by availability and cost. The VEUS method is a fully automated, user-friendly diagnostic system requiring no sample preparation, with high reported sensitivity, multiplexing capability, and rapid diagnostics. The aim of this study was to compare the SIMOA and VEUS methods for determining sNfL levels in patients with multiple sclerosis (MS). A single-centre cross-sectional study was conducted at the MS Centre of University Hospital Ostrava. Patients were enrolled in the study from January 18 to January 31, 2024. Inclusion criteria were: 1) diagnosis of MS according to the revised 2017 McDonald criteria, 2) age ≥18 years, and 3) signed informed consent. The NF-light V2 diagnostic kit (SIMOA, Quanterix) and the Singleplex Neurology assay kit (VEUDx, EZDiatech) were used to determine sNfL concentrations. The two methods were compared by use of Spearman correlation, Passing–Bablok regression, and Bland–Altman analysis. A total of 49 patients were included in the study, of whom 39 (79.6 %) were female. The median sNfL concentration was 7.73 (IQR 5.80–9.93) ng/L determined by SIMOA and 1.31 (IQR 1.18–1.65) ng/L by VEUS. We did not find a correlation between SIMOA and VEUS (r s = 0.025, p = 0.866). Passing–Bablok regression demonstrated a systematic and proportional difference between the two methods. A significant disagreement between them was also confirmed by the Bland–Altman plots. On average, sNfL values measured by SIMOA were 3.56 ng/L (95 % CI 0.78 to 6.34) higher than those measured by VEUS. Our investigation uncovered noteworthy disparities between the SIMOA and VEUS techniques in determining sNfL levels. Specifically, the VEUS technique systematically produces lower estimates of sNFL levels. This substantial variance emphasizes the importance of carefully evaluating assay methods when quantifying sNfL. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Fatigue Properties of ADI in Dependence on Isothermal Transformation DWELL
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Stanislav Vechet, Jan Kohout, and Klara Hanzlikova
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no keywords ,Transportation and communications ,HE1-9990 ,Science ,Transportation engineering ,TA1001-1280 - Abstract
As a result of excellent both mechanical and technological properties, austempered ductile iron (ADI) is ranked with very perspective structural materials. Recently it has been applied even to castings for dynamically loaded components and a considerable part of ADI production is applied also in military industry. The structure of ADI matrix, mostly created by the mixture of bainite and stabilized austenite, strongly depends on transformation conditions, i.e. temperature and the length of isothermal transformation dwell. An ADI transformed at 380 °C during a temporal range from 2 minutes to 9 hours was studied in details, with emphasis on structural composition and fatigue properties. The highest level of fatigue properties was obtained for the transformation dwell of 60 minutes when the maximum portion of austenite was found in ADI structure.
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- 2004
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30. Mycobacterium tuberculosis in animal and human populations in six Central European countries during 1990-1999
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I. Pavlik, W. Yayo Ayele, I. Parmova, I. Melicharek, M. Hanzlikova, M. Svejnochova, B. Körmendy, G. Nagy, Z. Cvetnic, V. Katalinic-Jankovic, M. Ocepek, M. Zolnir-Dovc, M. Lipiec, and M. Havelkova
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mycobacterium bovis ,human tuberculosis ,risk assessment ,Veterinary medicine ,SF600-1100 - Abstract
Results of Mycobacterium tuberculosis detection in animals from six Central European countries (Croatia, the Czech Republic, Hungary, Poland, Slovakia and Slovenia) spreading over 610 402 km2 with a population of 11.8 million heads of cattle were analysed. In the monitoring period, 1990 to 1999, M. tuberculosis from animals was isolated only in two countries (Poland and Slovak Republic) from 16 animals with tuberculous lesions. These comprise nine heads of cattle (Bos taurus), four domestic pigs (Sus scrofa f. domestica) and three wild animals, an African elephant (Loxodonta africana), agouti (Dasyprocta aguti) and terrestrial tapir (Tapirus terrestris), originated form a zoological garden Gdansk in Poland. Steady decrease in the incidence of tuberculosis in humans was recorded during the monitoring period in all countries. The human population of the study countries was 68.03 million. In the period monitored, infection caused by M. tuberculosis was identified in a total of 241 040 patients with a decreasing incidence of tuberculosis found in all countries. The lowest relative bacteriologically confirmed disease was found in theCzechRepublic,SlovakRepublic andSlovenia. Given the low number of infected domestic and wild animals, the epidemiological and epizootiological situation may be considered auspicious.
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- 2003
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31. Incidence of bovine tuberculosis in wild and domestic animals other than cattle in six Central European countries during 1990-1999
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I. Pavlik, M. Machackova, W. Yayo Ayele, J. Lamka, I. Parmova, I. Melicharek, M. Hanzlikova, B. Körmendy, G. Nagy, Z. Cvetnic, M. Ocepek, and M. Lipiec
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mycobacterium bovis ,veterinary epidemiology ,zoological gardens ,game parks ,farmed deer ,wild animals ,Veterinary medicine ,SF600-1100 - Abstract
The study was undertaken in Croatia, Czech Republic, Hungary, Poland, Slovakia and Slovenia laying between Baltic and Adriatic seas on 610 402 km2. Mycobacterium bovis infection was diagnosed in 70 animals belonging to 17 species other than cattle. The set of wild animals comprised 12 European bison (Bison bonasus), one red deer (Cervus elaphus), five wild boars (Sus scrofa), and one European wild goat (Capra aegagrus) bred in a game park. Further positive animals included two farmed red deer (Cervus elaphus) and one bactrian camel (Camelus ferus) owned by a circus. The infection was also demonstrated in 18 domestic animals belonging to 3 species living on farms where bovine tuberculosis was diagnosed in cattle. This set included 12 domestic pigs (Sus scrofa f. domestica), two domestic sheep (Ovis ammon f. aries), and four dogs (Canis lupus f. familiaris). The set of animals bred in zoological gardens consisted of 30 animals belonging to 9 species as follows: three bison (Bison bison), four tapirs (Tapirus terrestris), one cassowary (Casuarius casuarius - isolate identified by the biological assay in guinea pigs only), eight sitatungas (Tragelaphus spekei), three elands (Taurotragus oryx), one gnu (Connochaetes taurinus), eight reticulated giraffes (Giraffa cameloparadlis reticulata), one puma (Puma concolor), and one Vietnamese pot-bellied pig (Sus bucculentus). Although, considering the population sizes, absolute numbers of the infected individuals are rather low, wild animals or such animals bred in captivity should be regarded as possible reservoirs of the causative agent of bovine tuberculosis. Tests for bovine tuberculosis are therefore necessary before transportation of all wild animals. Any lesion arousing suspicion of tuberculosis found on necropsy of wild animals must be laboratory examined for the presence of mycobacteria.
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- 2002
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32. Incidence of bovine tuberculosis in cattle in seven Central European countries during the years 1990-1999
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I. Pavlik, W. Yayo Ayele, I. Parmova, I. Melicharek, M. Hanzlikova, B. Körmendy, G. Nagy, Z. Cvetnic, M. Ocepek, N. Fejzic, and M. Lipiec
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mycobacterium bovis ,veterinary epidemiology ,Veterinary medicine ,SF600-1100 - Abstract
The post-eradication incidence of bovine tuberculosis in seven Central European Countries (Bosnia and Herzegovina, Croatia, Czech Republic, Hungary, Poland, Slovakia and Slovenia) was studied between 1990 and 1999. The majority of cattle to the age of 24 months were screened by tuberculin skin test on annual basis. Tuberculous lesions observed during meat inspection at abattoirs were further laboratory examined by direct microscopy, cultivation and histology for the presence of mycobacteria. Data describing the incidence of the disease in animals for the whole period were obtained from all countries except Bosnia and Herzegovina, where data were obtained after the year 1995. Between the years 1990 and 1999, bovine tuberculosis was diagnosed in a total of 1 084 cattle herds. Nine hundred and seventy five (89.9%) outbreaks of the disease were reported in small herds (10 cows) and 109 (10.1%) outbreaks in large cattle herds (>10 cows). The last outbreak of bovine tuberculosis in cattle was diagnosed in Slovakia, Slovenia, the Czech Republic, Croatia and Bosnia and Herzegovina in 1993, 1993, 1995, 1999 and 1999, respectively. Bovine tuberculosis was diagnosed under proper quarantine in Slovenia in 37 fattening bulls imported from two European countries before animals were introduced to the targeting farms.
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- 2002
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33. Stereotactic radiotherapy for spinal hemangioblastoma -- disease control and volume analysis in long-term follow up.
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Cvek, Jakub, Knybel, Lukas, Reguli, Stefan, Lipina, Radim, Hanzlikova, Pavla, Šilhán, Petr, Resova, Kamila, Blazek, Tomas, Palicka, Martin, and Feltl, David
- Abstract
Background: This retrospective analysis evaluated the long-term outcome of spinal stereotactic body radiotherapy (SBRT) treatment for hemangioblastomas. Materials and methods: Between 2010 and 2018, 5 patients with 18 Von-Hippel Lindau-related pial-based spinal hemangioblastomas were treated with fractionated SBRT. After precisely registering images of all relevant datasets, we delineated the gross tumor volume, spinal cord (including intramedullary cysts and/or syrinxes), and past radiotherapy regions. A sequential optimization algorithm was used for dose determinations, and patients received 25-26 Gy in five fractions or 24 Gy in three fractions. On-line image guidance, based on spinal bone structures, and two orthogonal radiographs were provided. The actuarial nidus control, surgery-free survival, cyst/syrinx changes, and progression-free survival were calculated with the Kaplan-Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Results: The median follow-up was 5 years after SBRT. Patients displayed one nidus progression, one need of neurosurgery, and two cyst/syrinx progressions directly connected to symptom worsening. No SBRT-related complications or acute adverse radiation-related events occurred. However, one asymptomatic radiological sign of myelopathy occurred two years after SBRT. All tumors regressed; the one-year equivalent tumor volume reduction was 0.2 mL and the median volume significantly decreased by 28% (p = 0.012). Tumor volume reductions were not correlated with the mean (p = 0.19) or maximum (p = 0.16) dose. Conclusions: SBRT for pial-based spinal hemangioblastomas was an effective, safe, viable alternative to neurosurgery in asymptomatic patients. Escalating doses above the conventional dose-volume limits of spinal cord tolerance showed no additional benefit. [ABSTRACT FROM AUTHOR]
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- 2022
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34. Time-Resolved Fluorescence Spectroscopy Reveals Fine Structure and Dynamics of poly(L-Lysine) and Polyethylenimine Based DNA Polyplexes
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Lisitsyna, Ekaterina S., Ketola, Tiia-Maaria Caroline, Morin-Picardat, Emmanuelle, Liang, Huamin, Hanzlikova, Martina, Urtti, Arto, Yliperttula, Marjo, and Vuorimaa-Laukkanen, Elina
- Abstract
Structural dynamics of the polyethyleneimine – DNA and poly(L-lysine) – DNA complexes (polyplexes) was studied by steady-state and time-resolved fluorescence spectroscopy using fluorescence resonance energy transfer (FRET) technique. During the formation of the DNA polyplexes the negative phosphate groups (P) of DNA are bound by the positive amine groups (N) of the polymer. At N/P ratio 2 nearly all the DNA’s P–groups are bound by the polymer N groups: these complexes form the core of the polyplexes. The excess polymer, added to this system to increase the N/P ratio to the values giving efficient gene delivery, forms a positively charged shell around the core polyplex. We investigated whether the exchange between the core and shell regions of PEI and PLL polyplexes takes place. Our results demonstrated a clear difference between the two studied polymers. Shell PEI can replace PEIs previously attached to DNA in the polyplex core while PLL can not. Such a dynamic structure of PEI polyplexes compared to a more static one found for PLL polyplexes partially explains the observed difference in the DNA transfection efficiency of these polyplexes. Moreover, the time-resolved fluorescence spectroscopy revealed additional details on the structure of PLL polyplexes: in between the core and shell there is an intermediate layer where both core and shell PLLs or their parts overlap.
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- 2024
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35. Intermembrane inclusions induced by anoxia in heart and skeletal muscle mitochondria
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Schiaffino, Stefano, Severin, Elzo, and Hanzlikova, Vera
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- 1979
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36. Two-Step Mechanism of Cellular Uptake of Cationic Gold Nanoparticles Modified by (16-Mercaptohexadecyl)trimethylammonium Bromide.
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Zarska, Monika, Novotny, Filip, Havel, Filip, Sramek, Michal, Babelova, Andrea, Benada, Oldrich, Novotny, Michal, Saran, Hilal, Kuca, Kamil, Musilek, Kamil, Hvezdova, Zuzana, Dzijak, Rastislav, Vancurova, Marketa, Krejcikova, Katerina, Gabajova, Blanka, Hanzlikova, Hana, Kyjacova, Lenka, Bartek, Jiri, Proska, Jan, and Hodny, Zdenek
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- 2016
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37. XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia
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Hoch, Nicolas C., Hanzlikova, Hana, Rulten, Stuart L., Tétreault, Martine, Komulainen, Emilia, Ju, Limei, Hornyak, Peter, Zeng, Zhihong, Gittens, William, Rey, Stephanie A., Staras, Kevin, Mancini, Grazia M. S., McKinnon, Peter J., Wang, Zhao-Qi, Wagner, Justin D., Yoon, Grace, and Caldecott, Keith W.
- Abstract
XRCC1 is a molecular scaffold protein that assembles multi-protein complexes involved in DNA single-strand break repair. Here we show that biallelic mutations in the human XRCC1 gene are associated with ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia. Cells from a patient with mutations in XRCC1 exhibited not only reduced rates of single-strand break repair but also elevated levels of protein ADP-ribosylation. This latter phenotype is recapitulated in a related syndrome caused by mutations in the XRCC1 partner protein PNKP and implicates hyperactivation of poly(ADP-ribose) polymerase/s as a cause of cerebellar ataxia. Indeed, remarkably, genetic deletion of Parp1 rescued normal cerebellar ADP-ribose levels and reduced the loss of cerebellar neurons and ataxia in Xrcc1-defective mice, identifying a molecular mechanism by which endogenous single-strand breaks trigger neuropathology. Collectively, these data establish the importance of XRCC1 protein complexes for normal neurological function and identify PARP1 as a therapeutic target in DNA strand break repair-defective disease.
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- 2017
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38. Prognostic value of intrathecal IgM synthesis determined by various laboratory methods in patients with early multiple sclerosis - a prospective observational study.
- Author
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Revendova, Kamila, Zeman, David, Kusnierova, Pavlina, Bunganic, Radovan, Hanzlikova, Pavla, Karasova, Katerina, Volny, Ondrej, and Bar, Michal
- Abstract
Intrathecal IgM synthesis has been identified as an adverse prognostic factor in patients with multiple sclerosis (MS); however, some studies have not confirmed this association. The objective of this study was to evaluate the clinical utility of intrathecal IgM synthesis for prediction of disease activity and disability in patients after the first demyelinating event of MS. We conducted a single-centre prospective observational cohort study at the Department of Neurology, University Hospital Ostrava, Czech Republic. Intrathecal IgM synthesis was demonstrated by the presence of cerebrospinal fluid-restricted oligoclonal IgM bands and calculated using the Reiber, Auer, and Öhman formula and IgM index. A total of 61 patients with a clinically isolated syndrome or early relapsing-remitting MS were enrolled into the analysis of which 37 (61 %) were women. The median age at the disease onset was 32 years (interquartile range [IQR] 25 – 42), and the median disease duration was 2.8 years (IQR 2.4 – 3.5). Thirty-eight (62 %) patients experienced a second relapse of MS with a median of 312 days (IQR 192 – 424), and 29 (47.5 %) developed magnetic resonance imaging (MRI) activity during the follow-up. Intrathecal IgM synthesis did not affect the risk of a second relapse or evidence of MRI activity in univariate and multivariate Cox regression analysis. There was no significant difference in disability using the Expanded Disability Status Scale and progression index in patients with or without intrathecal IgM synthesis. This prospective cohort study did not demonstrate that intrathecal IgM synthesis is a risk factor for a second relapse or MRI activity. It was not associated with higher disability in patients after the first demyelinating event. [ABSTRACT FROM AUTHOR]
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- 2022
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39. Multifunctional adaptor protein Daxx interacts with chromatin-remodelling ATPase Brg1
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Svadlenka, Jan, Brazina, Jan, Hanzlikova, Hana, Cermak, Lukas, and Andera, Ladislav
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Multifunctional adapter and chaperone protein Daxx participates in the regulation of a number of mainly transcription-related processes. Most notably in a complex with chromatin-remodelling ATPase ATRX, Daxx serves as a histone H3.3 chaperone at telomeric regions and certain genes. In this report we document that Daxx interacts with another chromatin-remodelling, ATPase Brg1. We confirm the Daxx-Brg1 association both in vitro and in cells and show that Daxx interacts with Brg1 in high-molecular-weight complexes. Ectopic co-expression of Daxx with Brg1 and PML could shift disperse nuclear localisation of Brg1 into PML bodies. Mapping the Daxx-Brg1 interaction revealed that Daxx preferentially binds the region between Brg1 N-terminal QLQ and HSA domains, but also weakly interacts with its C-terminal part. Brg1 interacted with both the central and N-terminal parts of Daxx. SiRNA-mediated down-regulation of Daxx in SW13 adrenal carcinoma cells markedly enhanced expression of Brg1-activated genes CD44 or SCEL, suggesting that Daxx either directly through Brg1 and/or indirectly via other factors is a negative regulator of their transcription. Our findings point to Brg1 as another chromatin-remodelling protein that might similarly, as ATRX, target Daxx to specific chromatin regions where it can carry out its chromatin- and transcription-regulating functions.
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- 2016
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40. DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase
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Brazina, Jan, Svadlenka, Jan, Macurek, Libor, Andera, Ladislav, Hodny, Zdenek, Bartek, Jiri, and Hanzlikova, Hana
- Abstract
Death domain-associated protein 6 (DAXX) is a histone chaperone, putative regulator of apoptosis and transcription, and candidate modulator of p53-mediated gene expression following DNA damage. DAXX becomes phosphorylated upon DNA damage, however regulation of this modification, and its relationship to p53 remain unclear. Here we show that in human cells exposed to ionizing radiation or genotoxic drugs etoposide and neocarzinostatin, DAXX became rapidly phosphorylated in an ATM kinase-dependent manner. Our deletion and site-directed mutagenesis experiments identified Serine 564 (S564) as the dominant ATM-targeted site of DAXX, and immunofluorescence experiments revealed localization of S564-phosphorylated DAXX to PML nuclear bodies. Furthermore, using a panel of human cell types, we identified the p53-regulated Wip1 protein phosphatase as a key negative regulator of DAXX phosphorylation at S564, both in vitroand in cells. Consistent with the emerging oncogenic role of Wip1, its DAXX-dephosphorylating impact was most apparent in cancer cell lines harboring gain-of-function mutant and/or overexpressed Wip1. Unexpectedly, while Wip1 depletion increased DAXX phosphorylation both before and after DNA damage and increased p53 stability and transcriptional activity, knock-down of DAXX impacted neither p53 stabilization nor p53-mediated expression of Gadd45a, Noxa, Mdm2, p21, Puma, Sesn2, Tigar or Wip1. Consistently, analyses of cells with genetic, TALEN-mediated DAXXdeletion corroborated the notion that neither phosphorylated nor non-phosphorylated DAXX is required for p53-mediated gene expression upon DNA damage. Overall, we identify ATM kinase and Wip1 phosphatase as opposing regulators of DAXX-S564 phosphorylation, and propose that the role of DAXX phosphorylation and DAXX itself are independent of p53-mediated gene expression.
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- 2015
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41. Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage
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Moudry, Pavel, Lukas, Claudia, Macurek, Libor, Hanzlikova, Hana, Hodny, Zdenek, Lukas, Jiri, and Bartek, Jiri
- Abstract
The cellular DNA damage response (DDR) machinery that maintains genomic integrity and prevents severe pathologies, including cancer, is orchestrated by signaling through protein modifications. Protein ubiquitylation regulates repair of DNA double-strand breaks (DSBs), toxic lesions caused by various metabolic as well as environmental insults such as ionizing radiation (IR). Whereas several components of the DSB-evoked ubiquitylation cascade have been identified, including RNF168 and BRCA1 ubiquitin ligases, whose genetic defects predispose to a syndrome mimicking ataxia-telangiectasia and cancer, respectively, the identity of the apical E1 enzyme involved in DDR has not been established. Here, we identify ubiquitin-activating enzyme UBA1 as the E1 enzyme required for responses to IR and replication stress in human cells. We show that siRNA-mediated knockdown of UBA1, but not of another UBA family member UBA6, impaired formation of both ubiquitin conjugates at the sites of DNA damage and IR-induced foci (IRIF) by the downstream components of the DSB response pathway, 53BP1 and BRCA1. Furthermore, chemical inhibition of UBA1 prevented IRIF formation and severely impaired DSB repair and formation of 53BP1 bodies in G1, a marker of response to replication stress. In contrast, the upstream steps of DSB response, such as phosphorylation of histone H2AX and recruitment of MDC1, remained unaffected by UBA1 depletion. Overall, our data establish UBA1 as the apical enzyme critical for ubiquitylation-dependent signaling of both DSBs and replication stress in human cells, with implications for maintenance of genomic integrity, disease pathogenesis and cancer treatment.
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- 2012
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42. Regulation of the PML tumor suppressor in drug-induced senescence of human normal and cancer cells by JAK/STAT-mediated signaling
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Hubackova, Sona, Novakova, Zora, Krejcikova, Katerina, Kosar, Martin, Dobrovolna, Jana, Duskova, Pavlina, Hanzlikova, Hana, Vancurova, Marketa, Barath, Peter, Bartek, Jiri, and Hodny, Zdenek
- Abstract
The Promyelocytic leukemia protein (PML) tumor suppressor is upregulated in several forms of cellular senescence, however the mechanism of its induction is elusive. Here we show that genotoxic drugs that induce senescence, such as 5-bromo-2'deoxyuridine (BrdU), thymidine (TMD), distamycin A (DMA), aphidicolin (APH), etoposide (ET) and camptothecin (CPT) all evoke expansion of PML nuclear compartment and its association with persistent DNA lesions in several human cancer cell lines and normal diploid fibroblasts. This phenomenon was accompanied by elevation of PML transcripts after treatment with BrdU, TMD, DMA and CPT. Chemical inhibition of all JAK kinases and RNAi-mediated knock-down of JAK1 suppressed PML expression, implicating JAK/STAT-mediated signaling in regulation of the PML gene. As PML protein stability remained unchanged after drug treatment, decreased protein turnover was unlikely to explain the senescence-associated increased abundance of PML. Furthermore, binding activity of Interferon Stimulated Response Element (ISRE) within the PML gene promoter, and suppression of reporter gene activity after deletion of ISRE from the PML promoter region suggested that drug-induced PML transcription is controlled via transcription factors interacting with this element. Collectively, our data show that upregulation of the PML tumor suppressor in cellular senescence triggered by diverse drugs including clinically used anti-cancer chemotherapeutics relies on stimulation of PML transcription by JAK/STAT-mediated signaling, possibly evoked by the autocrine/paracrine activities of senescence-associated cytokines.
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- 2010
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43. Conformation of the Dipeptide Cyclo(<SCP>L</SCP>-Pro-<SCP>L</SCP>-Pro) Monitored by the Nuclear Magnetic Resonance and Raman Optical Activity Spectra. Experimental and ab Initio Computational Study
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Bour, P., Sychrovsky, V., Malon, P., Hanzlikova, J., Baumruk, V., Pospisek, J., and Budesinsky, M.
- Abstract
Nuclear magnetic resonance (NMR) and Raman optical activity (ROA) spectra of the cyclic dipeptide were measured and analyzed with respect to their ability to sense molecular structure and conformation. Data obtained by both techniques were simulated using ab initio quantum mechanical computations. Calculated chemical shifts, hydrogen−hydrogen spin−spin coupling constants and ROA intensities agreed well with the experimental values. The spin−spin NMR coupling constants were found to be most suitable for estimating of the conformational ratio. The ROA intensities provided additional information about the absolute configuration. The relation of the NMR chemical shifts to molecular structure was obscured by the solvent effect. The experimental results and calculated relative conformer energies suggest that equilibrium of three conformations takes place in the solution at the room temperature with a prevalence (~80%) of the conformation present in the crystalline state.
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- 2002
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44. Patterns of Treatment and Retreatment of Acute Attacks of Hereditary Angioedema (HAE) with Standard of Care (SOC) On-Demand Medication: Results from the APeX-2 Study.
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Aygoren-Pursun, Emel, Johnston, Douglas, Lumry, William, Li, Huamin, Banerji, Aleena, Zuraw, Bruce, Christiansen, Sandra, Kinaciyan, Tamar, Hanzlikova, Jana, Gower, Richard, Gagnon, Remi, Cicardi, Marco, Cornpropst, Melanie, Dobo, Sylvia, Hutchinson, Kathryn, Iocca, Heather, Nagy, Eniko, Murray, Sharon, Sheridan, William, and Bernstein, Jonathan
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- 2020
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45. Metalation of positively charged water soluble mesoporphyrins studied via time-resolved SERRS spectroscopy
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Prochazka, M., Hanzlikova, J., Stepanek, J., and Baumruk, V.
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- 1997
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46. P165 Hereditary angioedema laryngeal attacks treated with recombinant C1-INH: report from the Czech National Registry.
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Hakl, R., Kuklinek, P., Krcmova, I., Kralickova, P., Hanzlikova, J., Vachova, M., Sobotkova, M., Strenkova, J., and Litzman, J.
- Published
- 2017
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47. Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks
- Author
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Craig, Timothy, Zuraw, Bruce, Longhurst, Hilary, Cicardi, Marco, Bork, Konrad, Grattan, Clive, Katelaris, Constance, Sussman, Gordon, Keith, Paul K., Yang, William, Hébert, Jacques, Hanzlikova, Jana, Staubach-Renz, Petra, Martinez-Saguer, Inmaculada, Magerl, Markus, Aygören-Pürsün, Emel, Farkas, Henriette, Reshef, Avner, Kivity, Shmuel, Neri, Sergio, Crisan, Ioana, Caballero, Teresa, Baeza, Maria L., Hernandez, Maria Dolores, Li, Henry, Lumry, William, Bernstein, Jonathan A., Hussain, Iftikar, Anderson, John, Schwartz, Lawrence B., Jacobs, Joshua, Manning, Michael, Levy, Donald, Riedl, Marc, Christiansen, Sandra, Feuersenger, Henrike, Pragst, Ingo, Mycroft, Sarah, Pawaskar, Dipti, and Jacobs, Iris
- Abstract
For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT).
- Published
- 2019
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48. The Follow of Changes in Inflammatory Markers in Induced Sputum of Patients with Bronchial Asthma and Allergic Rhinitis in Relation to Exposure to Pollen Allergens.
- Author
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Hrasko, V., Malkusova, I., Hanzlikova, J., and Panzner, P.
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- 2006
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49. Impact of CVVH on monocyte activation in the critically ill
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Rokyta, R, Holub, M, Matejovic, M, Hanzlikova, J, Novak, I, Hora, P, Balihar, K, and Sramek, V
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- 1999
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50. Hypocretin-1/orexin-A, sleep and excessive daytime sleepiness in patients with nonconvulsive status epilepticus: A cross-sectional cohort study.
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Slonkova J, Togtokhjargal A, Revendova KZ, Bartos V, Hanzlikova P, and Volny O
- Subjects
- Humans, Female, Male, Aged, Cross-Sectional Studies, Sleep physiology, Cohort Studies, Middle Aged, Magnetic Resonance Imaging, Orexins cerebrospinal fluid, Status Epilepticus cerebrospinal fluid, Disorders of Excessive Somnolence cerebrospinal fluid, Polysomnography
- Abstract
Background and Objectives: Nonconvulsive status epilepticus (NCSE) manifests as a change in mental status without a coma (NCSE proper) or comatose NCSE. Hypocretin-1/orexin-A (H/O) is involved in alertness and sleep maintenance. Sleep impairment and excessive daytime sleepiness (EDS) have a negative impact on cognitive functions and activities of daily living (ADL)., Methods: Patients meeting the NCSE criteria underwent cerebrospinal fluid and brain magnetic resonance imaging examinations, polysomnographies (PSG), multiple latency sleep tests (MSLT), and completed Epworth Sleepiness Scale (ESS). Montreal Cognitive Assessment was used to evaluate cognitive functions, and the Barthel Index was used to assess ADL in the acute phase (V1) and three months follow-up (V2)., Results: From May 2020 to May 2023, we enrolled 15 patients, eight (53.3 %) women, with a median age of 69 (14) years. The median H/O CSF concentration was 250 (63.6) pg/ml; however, only three CSF samples (20 %) decreased below the borderline concentration of 200 pg/ml. Fourteen out of 15 patients (93.3 %) completed the PSG study. The median of wakefulness after sleep onset was 167 (173.5) min, sleep efficiency (SE) was 62.9 (63) %, sleep latency (SL) was 6 (32) min, REM sleep was 2.85 (7.2) %, and REM first episode latency was 210.5 (196.5) minutes. The medians of the stages N1 NREM were 4.65 (15) %, N2 NREM 68.4 (29.9) %, and N3 NREM 21.8 (35.5) %. MSLT mean latency was 7.7 (12.6) minutes. A significant negative correlation exists between H/O CSF concentrations and the stage N1 NREM (r
s = -0.612, p = 0.02), and the proportion of cumulative sleep time with oxygen saturation below 90 % in total sleep time (TST) t90 (rs = -0.57, p = 0.03). MSLT had significant negative correlation with TST (rs = -0.5369, p = 0.0478), with SE (rs = -0.5897, p = 0.0265), with apnea-hypopnea index (rs = -0.7631, p = 0.0002) and with deoxygenation index (rs = -0.8009, p = 0.0006). A positive correlation exists between MSLT and SL (rs = 0.6284, p = 0.0161) and between ESS and t90 (rs = 0.9014, p = 0.0004). The correlation between H/O CSF concentrations and EDS, cognitive performance, and ADL was not proved., Conclusions: Patients after NCSE exhibited sleep impairment and excessive daytime sleepiness. Hypocretin-1/orexin-A concentrations decreased only in 20 % of these cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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