Institution
Charles University in Prague
Education•Prague, Czechia•
About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.
Topics: Population, Large Hadron Collider, Czech, Magnetization, Transplantation
Papers published on a yearly basis
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TL;DR: It is hypothesized that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR), and the absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR Syndrome.
Abstract: Thrombocytopenia-absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Other frequent associations are congenital heart disease and a high incidence of cow's milk intolerance. Evidence for autosomal recessive inheritance comes from families with several affected individuals born to unaffected parents, but several other observations argue for a more complex pattern of inheritance. In this study, we describe a common interstitial microdeletion of 200 kb on chromosome 1q21.1 in all 30 investigated patients with TAR syndrome, detected by microarray-based comparative genomic hybridization. Analysis of the parents revealed that this deletion occurred de novo in 25% of affected individuals. Intriguingly, inheritance of the deletion along the maternal line as well as the paternal line was observed. The absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR syndrome. We hypothesize that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR).
300 citations
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University College London1, University of Melbourne2, University of Cambridge3, Charles University in Prague4, Université du Québec à Montréal5, University of Bari6, Amiri Hospital7, University of Queensland8, Cliniques Universitaires Saint-Luc9, Ondokuz Mayıs University10, John Hunter Hospital11, Flinders University12, Isfahan University of Medical Sciences13, University of Parma14, Royal Melbourne Hospital15, University Hospital of Wales16, University of Bristol17, University College Dublin18, Cardiff University19, Monash University20
TL;DR: The probability of conversion was lower when glatiramer acetate or interferon beta was started within 5 years of disease onset vs later, and initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion.
Abstract: Importance:
Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.
Objective:
To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.
Design, Setting, and Participants:
Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years’ follow-up.
Exposures:
The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).
Main Outcome and Measure:
Conversion to objectively defined secondary progressive MS.
Results:
Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressive MS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P < .001; 5-year absolute risk, 12% [49 of 407] vs 27% [58 of 213]; median follow-up, 7.6 years [IQR, 5.8-9.6]), as did fingolimod (HR, 0.37; 95% CI, 0.22-0.62; P < .001; 5-year absolute risk, 7% [6 of 85] vs 32% [56 of 174]; median follow-up, 4.5 years [IQR, 4.3-5.1]); natalizumab (HR, 0.61; 95% CI, 0.43-0.86; P = .005; 5-year absolute risk, 19% [16 of 82] vs 38% [62 of 164]; median follow-up, 4.9 years [IQR, 4.4-5.8]); and alemtuzumab (HR, 0.52; 95% CI, 0.32-0.85; P = .009; 5-year absolute risk, 10% [4 of 44] vs 25% [23 of 92]; median follow-up, 7.4 years [IQR, 6.0-8.6]). Initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion than initial treatment with glatiramer acetate or interferon beta (HR, 0.66; 95% CI, 0.44-0.99; P = .046); 5-year absolute risk, 7% [16 of 235] vs 12% [46 of 380]; median follow-up, 5.8 years [IQR, 4.7-8.0]). The probability of conversion was lower when glatiramer acetate or interferon beta was started within 5 years of disease onset vs later (HR, 0.77; 95% CI, 0.61-0.98; P = .03; 5-year absolute risk, 3% [4 of 120] vs 6% [2 of 38]; median follow-up, 13.4 years [IQR, 11-18.1]). When glatiramer acetate or interferon beta were escalated to fingolimod, alemtuzumab, or natalizumab within 5 years vs later, the HR was 0.76 (95% CI, 0.66-0.88; P < .001; 5-year absolute risk, 8% [25 of 307] vs 14% [46 of 331], median follow-up, 5.3 years [IQR], 4.6-6.1).
Conclusions and Relevance:
Among patients with relapsing-remitting MS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressive MS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies’ risks, may help inform decisions about DMT selection.
299 citations
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TL;DR: This work outlines the signaling pathways involved in mesenchymal and amoeboid types of tumor cell motility and summarizes the molecular mechanisms that are involved in transitions between them and focuses on the Rho family of small GTPases that regulate the cytoskeleton-dependent processes taking place during the cell migration.
Abstract: Tumor cells exhibit at least two distinct modes of migration when invading the 3D environment. A single tumor cell’s invasive strategy follows either mesenchymal or amoeboid patterns. Certain cell types can use both modes of invasiveness and undergo transitions between them. This work outlines the signaling pathways involved in mesenchymal and amoeboid types of tumor cell motility and summarizes the molecular mechanisms that are involved in transitions between them. The focus is on the signaling of the Rho family of small GTPases that regulate the cytoskeleton-dependent processes taking place during the cell migration. The multiple interactions among the Rho family of proteins, their regulators and effectors are thought to be the key determinants of the particular type of invasiveness. Mesenchymal and amoeboid invasive strategies display different adhesive and proteolytical interactions with the surrounding matrix and the alterations influencing these interactions can also lead to the transitions.
298 citations
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TL;DR: A review and state of the art of these methods can be found in this article, which discusses their derivation, proposes some alternative choices of parameters in the methods and categorizes them.
298 citations
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Max Planck Society1, Heidelberg University2, Durham University3, Polish Academy of Sciences4, North-West University5, Dublin Institute for Advanced Studies6, Nagoya University7, Humboldt University of Berlin8, University of Erlangen-Nuremberg9, University of Hamburg10, University of Tübingen11, Jagiellonian University12, Stanford University13, Charles University in Prague14, Ruhr University Bochum15, Joseph Fourier University16, University of Namibia17
TL;DR: The W28 field was observed at Very High Energy (VHE) gamma-ray energies (E>0.1 TeV) with the H.E.S. Cherenkov telescopes to indicate a hadronic origin for HESSJ1801-233 and HessJ1800-240, and several cloud components in projection may contribute to the VHE emission.
Abstract: We observed the W28 field (for ~40 h) at Very High Energy (VHE) gamma-ray energies (E>0.1 TeV) with the H.E.S.S. Cherenkov telescopes. A reanalysis of EGRET E>100 MeV data was also undertaken. Results from the NANTEN 4m telescope Galactic plane survey and other CO observations have been used to study molecular clouds. We have discovered VHE gamma-ray emission (HESSJ1801-233) coincident with the northeastern boundary of W28, and a complex of sources (HESSJ1800-240A, B and C) ~0.5 deg south of W28, in the Galactic disc. The VHE differential photon spectra are well fit by pure power laws with indices Gamma~2.3 to 2.7. The NANTEN ^{12}CO(J=1-0) data reveal molecular clouds positionally associating with the VHE emission, spanning a ~15 km s^{-1} range in local standard of rest velocity. The VHE/molecular cloud association could indicate a hadronic origin for HESSJ1801-233 and HESSJ1800-240, and several cloud components in projection may contribute to the VHE emission. The clouds have components covering a broad velocity range encompassing the distance estimates for W28 (~2 kpc), and extending up to ~4 kpc. Assuming a hadronic origin, and distances of 2 and 4 kpc for cloud components, the required cosmic ray density enhancement factors (with respect to the solar value) are in the range ~10 to ~30. If situated at 2 kpc distance, such cosmic ray densities may be supplied by a SNR like W28. Additionally and/or alternatively, particle acceleration may come from several catalogued SNRs and SNR candidates, the energetic ultra compact HII region W28A2, and the HII regions M8 and M20 along with their associated open clusters. Further sub-mm observations would be recommended to probe in detail the dynamics of the molecular clouds at velocites >10 km s^{-1}, and their possible connection to W28.
297 citations
Authors
Showing all 32719 results
Name | H-index | Papers | Citations |
---|---|---|---|
Ronald C. Petersen | 178 | 1091 | 153067 |
P. Chang | 170 | 2154 | 151783 |
Vaclav Vrba | 141 | 1298 | 95671 |
Milos Lokajicek | 139 | 1511 | 98888 |
Christopher D. Manning | 138 | 499 | 147595 |
Yves Sirois | 137 | 1334 | 95714 |
Rupert Leitner | 136 | 1201 | 90597 |
Gerald M. Reaven | 133 | 799 | 80351 |
Roberto Sacchi | 132 | 1186 | 89012 |
S. Errede | 132 | 1481 | 98663 |
Mark Neubauer | 131 | 1252 | 89004 |
Peter Kodys | 131 | 1262 | 85267 |
Panos A Razis | 130 | 1287 | 90704 |
Vit Vorobel | 130 | 919 | 79444 |
Jehad Mousa | 130 | 1226 | 86564 |