| 1. |
- Leng, HF, et al.
(author)
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Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 7868-
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Journal article (peer-reviewed)abstract
- Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as evidenced by TRAF3 lysosomal and cytoplasmic accumulation. Eliglustat blocked autophagy by altering glycosphingolipid composition whilst restoration of missing glycosphingolipids rescued autophagy markers and TRAF3 degradation thus restoring osteoclastogenesis in bone marrow cells from myeloma patients. This work delineates both the mechanism by which glucosylceramide synthase inhibition prevents autophagic degradation of TRAF3 to reduce osteoclastogenesis as well as highlighting the clinical translational potential of eliglustat for the treatment of myeloma bone disease.
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| 3. |
- Lou, HF, et al.
(author)
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Predictive significance of tissue eosinophilia for nasal polyp recurrence in the Chinese population
- 2015
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In: American journal of rhinology & allergy. - : SAGE Publications. - 1945-8932 .- 1945-8924. ; 29:5, s. 350-356
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Journal article (peer-reviewed)abstract
- Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenging clinical entity with its propensity for recurrence. Tissue eosinophilia is a hallmark of CRSwNP, and its role in polyp recurrence is a subject of much investigation.ObjectiveThe aim of this study was to evaluate the association between clinical parameters, especially tissue eosinophilia and polyp recurrence, and to identify the optimal cutoff value of tissue eosinophilia as a predictor for polyp recurrence in Chinese subjects.MethodsOverall, 387 patients with CRSwNP were enrolled in this retrospective analysis and postoperative follow-up for polyp recurrence was over a period that lasted >24 months (mean [standard deviation], 34.03 ± 4.95 months). The baseline demographic and clinical features and the preoperative computed tomography were compared, and mucosal specimens obtained at endoscopic sinus surgery were assessed for inflammatory cells by using histocytologic staining. Predictive factors associated with polyp recurrence were analyzed by logistic regression analysis, and optimal cutoff points of the predictors were determined by receiver operating characteristic curves and the Youden index.ResultsA total of 55.3% patients (214β87) experienced recurrence. Tissue eosinophilia markedly outweighed other parameters and correlated with polyp recurrence. Receiver operating characteristic curves indicated that a cutoff value of 27% tissue eosinophils predicted recurrence with 96.7% sensitivity and 92.5% specificity (area under the curve = 0.969; p < 0.001); and an absolute count of 55 eosinophils per high power field predicted recurrence with 87.4% sensitivity and 97.1% specificity (area under the curve = 0.969; p < 0.001).ConclusionA tissue eosinophil proportion of >27% of total cells or a tissue eosinophil absolute count of >55 eosinophils per high power field may act as a reliable prognostic indicator for nasal polyp recurrence within 2 years after surgery.
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| 4. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 8. |
- Zhang, Y, et al.
(author)
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Chronic rhinosinusitis in Asia
- 2017
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In: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 140:5, s. 1230-1239
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Journal article (peer-reviewed)
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