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- Sekiguchi, M, et al.
(författare)
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Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets
- 2020
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Ingår i: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 4:1, s. 20-
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Tidskriftsartikel (refereegranskat)abstract
- Although hepatoblastoma is the most common pediatric liver cancer, its genetic heterogeneity and therapeutic targets are not well elucidated. Therefore, we conducted a multiomics analysis, including mutatome, DNA methylome, and transcriptome analyses, of 59 hepatoblastoma samples. Based on DNA methylation patterns, hepatoblastoma was classified into three clusters exhibiting remarkable correlation with clinical, histological, and genetic features. Cluster F was largely composed of cases with fetal histology and good outcomes, whereas clusters E1 and E2 corresponded primarily to embryonal/combined histology and poor outcomes. E1 and E2, albeit distinguishable by different patient age distributions, were genetically characterized by hypermethylation of the HNF4A/CEBPA-binding regions, fetal liver-like expression patterns, upregulation of the cell cycle pathway, and overexpression of NQO1 and ODC1. Inhibition of NQO1 and ODC1 in hepatoblastoma cells induced chemosensitization and growth suppression, respectively. Our results provide a comprehensive description of the molecular basis of hepatoblastoma and rational therapeutic strategies for high-risk cases.
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| 4. |
- Nannya, Y, et al.
(författare)
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Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms
- 2023
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 7:14, s. 3624-3636
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Tidskriftsartikel (refereegranskat)abstract
- Azacitidine is a mainstay of therapy for MDS-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their post-treatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pre- (n=449) and post- (n=289) treatment bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their post-treatment clone size on treatment outcomes. In Cox proportional hazard modeling, multi-hit TP53 mutation (HR, 2.03; 95% CI, 1.42-2.91; P<.001), EZH2 mutation (HR, 1.71; 95% CI, 1.14-2.54; P=.009), and DDX41 mutations (HR, 0.33; 95% CI, 0.17-0.62; P<.001), together with age, high-risk karyotypes, low platelet, and high blast counts, independently predicted OS. Post-treatment clone size accounting for all drivers significantly correlated with International Working Group (IWG)-response (P<.001, trend test), except for that of DDX41-mutated clones, which did not predict IWG-response. Combined, IWG-response and post-treatment clone size further improved the prediction of the original model and even that of a recently proposed molecular prediction model, IPSS-M (c-index, 0.653 vs 0.688; P<.001, likelihood ratio test). In conclusion, evaluation of post-treatment clone size, together with pre-treatment mutational profile as well as IWG-response have a role in better prognostication of azacitidine-treated myelodysplasia patients.
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- Goetz, C., et al.
(författare)
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Cometary plasma science : Open science questions for future space missions
- 2021
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Ingår i: Experimental astronomy. - : Springer Nature. - 0922-6435 .- 1572-9508.
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Tidskriftsartikel (refereegranskat)abstract
- Comets hold the key to the understanding of our Solar System, its formation and its evolution, and to the fundamental plasma processes at work both in it and beyond it. A comet nucleus emits gas as it is heated by the sunlight. The gas forms the coma, where it is ionised, becomes a plasma, and eventually interacts with the solar wind. Besides these neutral and ionised gases, the coma also contains dust grains, released from the comet nucleus. As a cometary atmosphere develops when the comet travels through the Solar System, large-scale structures, such as the plasma boundaries, develop and disappear, while at planets such large-scale structures are only accessible in their fully grown, quasi-steady state. In situ measurements at comets enable us to learn both how such large-scale structures are formed or reformed and how small-scale processes in the plasma affect the formation and properties of these large scale structures. Furthermore, a comet goes through a wide range of parameter regimes during its life cycle, where either collisional processes, involving neutrals and charged particles, or collisionless processes are at play, and might even compete in complicated transitional regimes. Thus a comet presents a unique opportunity to study this parameter space, from an asteroid-like to a Mars- and Venus-like interaction. The Rosetta mission and previous fast flybys of comets have together made many new discoveries, but the most important breakthroughs in the understanding of cometary plasmas are yet to come. The Comet Interceptor mission will provide a sample of multi-point measurements at a comet, setting the stage for a multi-spacecraft mission to accompany a comet on its journey through the Solar System. This White Paper, submitted in response to the European Space Agency’s Voyage 2050 call, reviews the present-day knowledge of cometary plasmas, discusses the many questions that remain unanswered, and outlines a multi-spacecraft European Space Agency mission to accompany a comet that will answer these questions by combining both multi-spacecraft observations and a rendezvous mission, and at the same time advance our understanding of fundamental plasma physics and its role in planetary systems.
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| 15. |
- Oyama, S., et al.
(författare)
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An Ephemeral Red Arc Appeared at 68 degrees MLat at a Pseudo Breakup During Geomagnetically Quiet Conditions
- 2020
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 125:10
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Tidskriftsartikel (refereegranskat)abstract
- Various subauroral optical features have been studied by analyzing data collected during periods of geomagnetic disturbances. Most events have been typically found at geomagnetic latitudes of 45-60 degrees. In this study, however, we present a red arc event found at geomagnetic 68 degrees north (L approximate to 7.1) in the Scandinavian sector during a period of geomagnetically quiet conditions within a short intermission between two high-speed solar wind events. The red arc appeared to coincide with a pseudo breakup at geomagnetic 71-72 degrees N and a rapid equatorward expansion of the polar cap. However, the red arc disappeared in approximately 7 min. Simultaneous measurements with the Swarm A/C satellites indicated the appearance of the red arc at the ionospheric trough minimum and a conspicuous enhancement of the electron temperature, suggesting the generation of the arc by heat flux. Since there are meaningful differences in the red arc features from already-known subauroral optical features such as the stable auroral red (SAR) arc, we considered that the red arc is a new phenomenon. We suggest that the ephemeral red arc may represent the moment of SAR arc birth associated with substorm particle injection, which is generally masked by bright dynamic aurorae.
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- Kamio, S., et al.
(författare)
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First experiments on plasma production using field-aligned ICRF fast wave antennas in the large helical device
- 2021
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Ingår i: Nuclear Fusion. - : Institute of Physics (IOP). - 0029-5515 .- 1741-4326. ; 61:11
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Tidskriftsartikel (refereegranskat)abstract
- The results of the first experimental series to produce a plasma using the ion cyclotron range of frequency (ICRF) in the large helical device (LHD) within the minority scenario developed at Uragan-2M (U-2M) are presented. The motivation of this study is to provide plasma creation in conditions when an electron cyclotron resonance heating start-up is not possible, and in this way widen the operational frame of helical machines. The major constraint of the experiments is the low RF power to reduce the possibility of arcing. No dangerous voltage increase at the radio-frequency (RF) system elements and no arcing has been detected. As a result, a low plasma density is obtained and the antenna-plasma coupling is not optimal. However, such plasmas are sufficient to be used as targets for further neutral beam injection (NBI) heating. This will open possibilities to explore new regimes of operation at LHD and Wendelstein 7-X (W7-X) stellarator. The successful RF plasma production in LHD in this experimental series stimulates the planning of further studies of ICRF plasma production aimed at increasing plasma density and temperature within the ICRF minority scenario as well as investigating the plasma prolongation by NBI heating.
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- Kasahara, K., et al.
(författare)
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Gut bacterial metabolism contributes to host global purine homeostasis
- 2023
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Ingår i: Cell Host & Microbe. - 1931-3128. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- The microbes and microbial pathways that influence host inflammatory disease progression remain largely undefined. Here, we show that variation in atherosclerosis burden is partially driven by gut microbiota and is associated with circulating levels of uric acid (UA) in mice and humans. We identify gut bacterial taxa spanning multiple phyla, including Bacillota, Fusobacteriota, and Pseudomonadota, that use multiple purines, including UA as carbon and energy sources anaerobically. We identify a gene cluster that encodes key steps of anaerobic purine degradation and that is widely distributed among gut-dwelling bacteria. Furthermore, we show that colonization of gnotobiotic mice with purine-degrading bacteria modulates levels of UA and other purines in the gut and systemically. Thus, gut microbes are important drivers of host global purine homeostasis and serum UA levels, and gut bacterial catabolism of purines may represent a mechanism by which gut bacteria influence health.
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