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- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 4. |
- Hernandez, Natalie V.M., et al.
(författare)
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Depression severity is associated with increased inflammation in veterans with peripheral artery disease
- 2018
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Ingår i: Vascular Medicine (United Kingdom). - 1358-863X. ; 23:5, s. 445-453
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Tidskriftsartikel (refereegranskat)abstract
- The present study examines the association between depressive symptoms and inflammatory markers in peripheral artery disease (PAD) to better understand the mechanistic relationship between depression and PAD. A cross-sectional sample of 117 patients with PAD (97% male, 76% Caucasian) was recruited from the San Francisco Veterans Affairs Medical Center. Patients were categorized into three subgroups based upon current depressive symptom severity, as defined by Patient Health Questionnaire-8 scores: no symptoms (score of 0–4, n = 62), mild symptoms (score of 5–9, n = 33), and moderate/severe symptoms (score ≥ 10, n = 22). Serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-alpha (TNF-α) were assayed and log-transformed for multivariable analysis. To decrease the possibility of Type 1 errors, inflammatory markers were standardized and summed to create a total inflammatory score. In a multivariable analysis controlling for demographics, PAD severity, and atherosclerotic risk factors, mild and moderate/severe depressive symptoms were predictive of a higher total inflammatory score when compared to the group with no symptoms (mild symptoms p = 0.04, moderate/severe symptoms p = 0.007). Exploratory multivariable analyses of individual inflammatory markers found IL-6 levels were significantly higher in the moderate/severe symptoms group (p = 0.006) than in the no symptoms group. Moreover, hs-CRP and ICAM-1 trended upwards with increasing depression severity. TNF-α was not associated with depression severity. We conclude that depressive symptom severity was independently associated with greater inflammation in PAD. Future research should examine the strength and directionality of this association through larger prospective cohort studies, as well as investigate the pathophysiological mechanisms responsible.
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| 7. |
- 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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| 8. |
- Ochi, Y, et al.
(författare)
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Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2833-
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Tidskriftsartikel (refereegranskat)abstract
- Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.
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