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  • Oxford University Press (OUP)  (48)
  • 1
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 5, No. suppl_1 ( 2018-11-26), p. S733-S733
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2757767-3
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2000
    In:  FEMS Microbiology Letters Vol. 182, No. 2 ( 2000-01), p. 313-317
    In: FEMS Microbiology Letters, Oxford University Press (OUP), Vol. 182, No. 2 ( 2000-01), p. 313-317
    Type of Medium: Online Resource
    ISSN: 0378-1097 , 1574-6968
    URL: Issue
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2000
    detail.hit.zdb_id: 1501716-3
    SSG: 12
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  • 3
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. 9 ( 2023-09-01), p. 3014-3024
    Abstract: To explore the course of lung function and RA disease activity and predictive factors for deteriorating lung function in patients with RA-interstitial lung disease (ILD). Methods The Korean Rheumatoid Arthritis–Interstitial Lung Disease cohort is a multicentre, prospective observational cohort. Patients with RA-ILD were enrolled and followed up annually for 3 years for RA disease activity and ILD status assessment. Group-based modelling was used to cluster a similar predicted percentage of forced vital capacity (FVC%) patterns into trajectories. Results This study included 140 patients who underwent at least two pulmonary function tests. Four distinctive trajectories for predicted FVC% were ‘improving’ [n = 11 (7.9%)], ‘stable’ [n = 68 (38.4%)] , ‘slowly declining’ [n = 54 (48.6%)] and ‘rapidly declining’ [n = 7 (5.0%)] . Most (77.7%) patients maintained or improved to low RA disease activity. The lung function trajectory was not comparable to the RA disease activity trajectory. Age ≥70 years [relative risk (RR) 10.8 (95% CI 1.30, 89.71)] and early RA diagnosed within the preceding 2 years [RR 10.1 (95% CI 1.22, 84.2)] were associated with increased risk for rapidly declining predicted FVC%. The risk for deterioration or mortality increased in patients with a simultaneous diagnosis of RA and ILD within 24 weeks [RR 9.18 (95% CI 2.05, 41.0)] and the extent of lung involvement [RR 3.28 (95% CI 1.12, 9.60)] . Conclusion Most patients with RA-ILD experienced stable or slowly declining lung function. In 5% of patients, predicted FVC% deteriorated rapidly, especially in older adults with early RA. The lung function trajectory was not comparable to the RA disease activity trajectory.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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  • 4
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. 7 ( 2023-07-05), p. 2377-2385
    Abstract: To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD). Methods The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. Results Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression. Conclusion None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1474143-X
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  • 5
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), ( 2023-05-26)
    Abstract: Metabolic syndrome (MetS) is prevalent in patients with end-stage kidney disease, and kidney transplantation is expected to modify the metabolic status. However, whether changes in metabolic status at the time of transplantation affect recipient outcomes remains unclear. Methods We analyzed 4187 recipients registered in a nationwide prospective cohort from 2014 to 2020. MetS was defined as the presence of three or more components of the metabolic syndrome. Patients were classified based on the pre- and post-transplant MetS status: MetS-free, MetS-developed, MetS-recovered and MetS-persistent. Study outcomes were occurrence of death-censored graft loss and a composite of cardiovascular events and death. Results Among recipients without pre-transplant MetS, 19.6% (419/2135) developed post-transplant MetS, and MetS disappeared in 38.7% (794/2052) of the recipients with pre-transplant MetS. Among the four groups, the MetS-developed group showed the worst graft survival rate, and the MetS-persistent group had a poorer composite event-free survival rate. Compared with the MetS-free group, the MetS-developed group was associated with an increased risk of graft loss [adjusted hazard ratio (aHR) 2.35; 95% confidence interval (CI) 1.17–4.98] and the risk of graft loss increased with increasing numbers of dysfunctional MetS components. MetS-persistent was associated with increased risks of cardiovascular events and death (aHR 2.46; 95% CI 1.12–5.63), but changes in the number of dysfunctional MetS components was not. Conclusion Kidney transplantation significantly alters the metabolic status. Newly developed MetS after transplantation was associated with an increased risk of graft loss, whereas persistent MetS exposure before and after transplantation was associated with increased risks cardiovascular events and patient survival.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 6
    In: Rheumatology, Oxford University Press (OUP), Vol. 59, No. 8 ( 2020-08-01), p. 2124-2134
    Abstract: This study was designed to investigate the role of mucosal-associated invariant T (MAIT) cells in gouty arthritis (GA) and their effects on osteoclastogenesis. Methods Patients with GA (n = 61), subjects with hyperuricaemia (n = 11) and healthy controls (n = 30) were enrolled in this study. MAIT cells, cytokines, CD69, programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells in the presence of M-CSF and RANK ligand. Results Circulating MAIT cell levels were significantly reduced in GA patients. However, their capacities for IFN-γ, IL-17 and TNF-α production were preserved. Expression levels of CD69, PD-1 and LAG-3 in MAIT cells were found to be elevated in GA patients. In particular, CD69 expression in circulating MAIT cells was increased by stimulation with MSU crystals, suggesting that deposition of MSU crystals might contribute to MAIT cell activation. Interestingly, MAIT cells were found to be accumulated in synovial fluid and infiltrated into gouty tophus tissues within joints. Furthermore, activated MAIT cells secreted pro-resorptive cytokines (i.e. IL-6, IL-17 and TNF-α) and facilitated osteoclastogenesis. Conclusion This study demonstrates that circulating MAIT cells are activated and numerically deficient in GA patients. In addition, MAIT cells have the potential to migrate to inflamed tissues and induce osteoclastogenesis. These findings provide an important role of MAIT cells in the pathogenesis of inflammation and bone destruction in GA patients.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1474143-X
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  • 7
    In: European Heart Journal - Cardiovascular Pharmacotherapy, Oxford University Press (OUP), Vol. 7, No. 2 ( 2021-03-15), p. 112-124
    Abstract: Potent P2Y12 inhibitors for dual antiplatelet therapy (DAPT) is crucial for managing acute myocardial infarction; however, the selection of drugs is based on limited clinical information such as age and body weight. The current study sought to develop and validate a new risk scoring system that can be used to guide the selection of potent P2Y12 inhibitors by balancing ischaemic benefit and bleeding risk. Methods and results Derivation cohort of 10 687 patients who participated in the Korea Acute Myocardial Infarction Registry-National Institutes of Health study was used to construct a new scoring system. We combined the ischaemic and bleeding models to establish a simple clinical prediction score. Among the low score group (n = 1764), the observed bleeding risk (8.7% vs. 4.4%, P  & lt; 0.001) due to potent P2Y12 inhibitors exceeded ischaemic benefit (1.3% vs. 2.2%, P = 0.185) during 12 months. Conversely, the high score group (n = 1898) showed an overall benefit from taking potent P2Y12 inhibitors from the standpoint of observed ischaemic (17.1% vs. 8.6%, P  & lt; 0.001) and bleeding events (10.1% vs. 6.8%, P = 0.073). The performance of ischaemic [integrated area under the curve (iAUC) = 0.809] and bleeding model (iAUC = 0.655) was deemed to be acceptable. Conclusion The new scoring system is a useful clinical tool for guiding DAPT by balancing ischaemic benefit and bleeding risk, especially among Asian populations. Further validation studies with other cohorts will be required to verify that the new system meets the needs of real clinical practice.
    Type of Medium: Online Resource
    ISSN: 2055-6837 , 2055-6845
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2808613-2
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  • 8
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii33-vii33
    Abstract: Human glioblastoma (GBM), originating from the subventricular zone (SVZ), occurs due to molecular disruptions in chromosomes. Most GBM tissues exhibit definitive chromosomal patterns: copy-number-variations (CNV) in chromosome 7 (gain) and 10 (loss), known as the earliest molecular events. Herein, we hypothesised that the origin-cells in SVZ of GBM patients can provide clues regarding these chromosomal alterations. We compared bulk RNA sequencing (RNAseq) data of GBM tumor tissue (n=126), tumour free GBM SVZ (n=40), and tumor-free control SVZ of non-glial tumor (n=9). Paired single-cell-level RNAseq samples of tumor free GBM SVZ (n=7) and GBM tumor tissue (n=10), were done to see cell specific CNVs. Using human SVZ and GBM samples as a background, we generated origin-cell and origin-cell-derived tumour cell using CRISPR/Cas9. In this work, we identified two GBM-origin-cell types with stem-cell signatures during single-cell level analyses of 60 SVZ tissue samples obtained from tumor-free regions of GBM patients. Furthermore, single-cell level analysis revealed that two origin-cell types in SVZ harbor ongoing patterns of CNV alterations. Among the origin-cells found in the SVZ of GBM patients, NO-like cells showed neural progenitor plus oligodendrocyte progenitor (NO) signature, while AN-like cells showed astrocyte plus neural stem cell (AN) signature. For the interconnectedness, we subjected single-cell-level RNA-seq data to ligand-receptor connection analysis. In the stem cell mode, NO-like cells was connected to AN-like cells in SVZ samples and while in the tumor samples, cycling cell was connected to AN-like cells. NO-like cells was common in TERT promoter wildtype GBM and AN-like cells was more common in TERT promoter mutant GBM. CRISPR/Cas9 models revealed accumulation copy-number alterations from non-tumorigenic origin-cells to tumor cells. These two origin-cells (NO-like cells and AN-like cells) derived from the SVZ of the adult human brain will facilitate the understanding of GBM genesis and development of potential novel therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
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  • 9
    In: European Heart Journal, Oxford University Press (OUP), Vol. 44, No. 19 ( 2023-05-14), p. 1718-1728
    Abstract: Atherothrombotic events are influenced by systemic hypercoagulability and fibrinolytic activity. The present study evaluated thrombogenicity indices and their prognostic implications according to disease acuity. Methods and results From the consecutive patients undergoing percutaneous coronary intervention (PCI), those with thrombogenicity indices (n = 2705) were grouped according to disease acuity [acute myocardial infarction (AMI) vs. non-AMI]. Thrombogenicity indices were measured by thromboelastography (TEG). Blood samples for TEG were obtained immediately after insertion of the PCI sheath, and TEG tracing was performed within 4 h post-sampling. Major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were evaluated for up to 4 years. Compared with non-AMI patients, AMI patients had higher platelet-fibrin clot strength [maximal amplitude (MA): 66.5 ± 7.8 vs. 65.3 ± 7.2 mm, P & lt; 0.001] and lower fibrinolytic activity [clot lysis at 30 min (LY30): 0.9 ± 1.8% vs. 1.1 ± 1.9%, P & lt; 0.001]. Index AMI presentation was associated with MA [per one-mm increase: odds ratio (OR): 1.024; 95% confidence interval (CI): 1.013–1.036; P & lt; 0.001] and LY30 (per one% increase: OR: 0.934; 95% CI: 0.893–0.978; P = 0.004). The presence of high platelet-fibrin clot strength (MA ≥68 mm) and low fibrinolytic activity (LY30 & lt; 0.2%) was synergistically associated with MACE occurrence. In the multivariable analysis, the combined phenotype of ‘MA ≥ 68 mm’ and ‘LY30 & lt; 0.2%’ was a major predictor of post-PCI MACE in the AMI group [adjusted hazard ratio (HR): 1.744; 95% CI: 1.135–2.679; P = 0.011], but not in the non-AMI group (adjusted HR: 1.031; 95% CI: 0.499–2.129; P = 0.935). Conclusion AMI occurrence is significantly associated with hypercoagulability and impaired fibrinolysis. Their combined phenotype increases the risk of post-PCI atherothrombotic event only in AMI patients. These observations may support individualized therapy that targets thrombogenicity for better outcomes in patients with AMI. Clinical Trial Registration Gyeongsang National University Hospital (G-NUH) Registry, NCT04650529.
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2001908-7
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  • 10
    In: Brain, Oxford University Press (OUP), ( 2024-06-25)
    Abstract: Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioral seizures. The mosaic burdens ranged from approximately 1,000 to 40,000 neurons expressing the mTOR mutant in the somatosensory (SSC) or medial prefrontal (PFC) cortex. Surprisingly, approximately 8,000 to 9,000 neurons expressing the MTOR mutant, which are extrapolated to constitute 0.08-0.09% of total cells or roughly 0.04% of variant allele frequency (VAF) in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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