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  • Oxford University Press (OUP)  (8)
  • 2020-2024  (8)
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  • Oxford University Press (OUP)  (8)
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  • 2020-2024  (8)
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  • 1
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii394-iii394
    Abstract: In this study, we report the follow-up results of reduced-dose of craniospinal radiotherapy (CSRT) followed by tandem high-dose chemotherapy (HDCT) in patients with high-risk medulloblastoma (MB). METHODS Newly diagnosed high-risk MB patients (metastatic disease, postoperative residual tumor & gt; 1.5 cm2 or large cell/anaplastic histology) over 3 years of age were enrolled in this study. Two cycles of pre-RT chemotherapy, RT including reduced-dose CSRT (23.4 or 30.6 Gy), 4 cycles of post-RT chemotherapy and tandem HDCT were given. NanoString and DNA sequencing were done with archival tissues. RESULTS Forty patients were enrolled, and molecular subgrouping was possible in 21 patients (2 WNT, 3 SHH, 8 Group 3 and 8 group 4). All patients including two patients who experienced progression during the induction chemotherapy underwent HDCT. Relapse/progression occurred only in four patients (10-year cumulative incidence 10.4 ± 0.3%). However, six patients died from treatment-related mortality (TRM) (4 acute TRMs and 2 late TRMs) resulting in 18.5 ± 0.5% of 10-year cumulative incidence. Taken together, the 10-year event-free survival and overall survival were 71.1 ± 8.0% and 68.9 ± 8.5%, respectively. Late effects were evaluated in 25 patients and high-tone hearing loss, endocrine dysfunction, dyslipidemia, and growth retardation were common. CONCLUSIONS Strategy using tandem HDCT following reduced-dose CSRT showed promising results in terms of low relapse/progression rate, however, the high TRM rate indicates that modification of HDCT regimen and careful selection of patients who can have benefit from HDCT will be needed in the future study.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Previous studies at our institution evaluating rapid diagnostic testing (RDT) for blood culture identification (BCID) did not show significant differences in time to optimal antimicrobial therapy for Gram negative bloodstream infections (GNBSI). Recent studies of Accelerate Pheno® system (Accelerate-PS) for blood culture identification and susceptibility have shown significant reduction in time to optimal antimicrobial therapy. This study evaluated the impact of Accelerate-PS compared to BCID RDT on time to optimal antimicrobial therapy for GNBSI. Methods A single center, retrospective, cohort study included adult patients with GNBSI from February 2017 to January 2018 (pre-implementation) and February 2020 to January 2021 (post-implementation). The primary outcome was time to optimal antimicrobial therapy for GNBSI, defined as time from positive blood cultures to time patient received optimal antimicrobial therapy. Secondary outcomes include duration of therapy, rate of antimicrobial-related adverse effects, hospital length of stay, in-hospital mortality, and infection-related readmission. Results The final cohort included 190 patients in pre-implementation group and 179 patients in post-implementation group. Escherichia coli and Klebsiella species were the most common pathogens and urinary tract was the most common source of bacteremia in both groups. More patients in the pre-implementation group had congestive heart failure while more patients in the post-implementation group had peripheral vascular disease. Patients in the post-implementation group had higher Pitt bacteremia scores (1.05 vs. 1.37, P=0.017). Patients in the post-implementation group had significantly shorter time to optimal therapy (mean 60.62 hours vs. 20.17 hours, P & lt; 0.001) and shorter duration of therapy (mean 366.56 vs 310.24 hours, P & lt; 0.001) than in the pre-implementation group. There were no differences in mortality or readmission at 30-days. Conclusion The results of this study indicate that incorporation of Accelerate-PS into microbiology lab workflow significantly reduces time to optimal antimicrobial therapy for GNBSI. Rapid diagnostic testing is a vital component of a robust antimicrobial stewardship program. Disclosures John Schrank, MD, Gilead: Speaker's Bureau.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 3
    In: Toxicological Sciences, Oxford University Press (OUP), Vol. 193, No. 1 ( 2023-05-12), p. 31-47
    Abstract: Cannabis use by adolescents is widespread, but its effects on the ovaries remain largely unknown. Δ9-tetrahydrocannabinol (THC) exerts its pharmacological effects by activating, and in some conditions hijacking, cannabinoid receptors (CBRs). We hypothesized that adolescent exposure to THC affects ovarian function in adulthood. Peripubertal female C57BL/6N mice were given THC (5 mg/kg) or its vehicle, once daily by intraperitoneal injection. Some mice received THC from postnatal day (PND) 30–33 and their ovaries were harvested PND34; other mice received THC from PND30–43, and their ovaries were harvested PND70. Adolescent treatment with THC depleted ovarian primordial follicle numbers by 50% at PND70, 4 weeks after the last dose. The treatment produced primordial follicle activation, which persisted until PND70. THC administration also caused DNA damage in primary follicles and increased PUMA protein expression in oocytes of primordial and primary follicles. Both CB1R and CB2R were expressed in oocytes and theca cells of ovarian follicles. Enzymes involved in the formation (N-acylphosphatidylethanolamine phospholipase D) or deactivation (fatty acid amide hydrolase) of the endocannabinoid anandamide were expressed in granulosa cells of ovarian follicles and interstitial cells. Levels of mRNA for CBR1 were significantly increased in ovaries after adolescent THC exposure, and upregulation persisted for at least 4 weeks. Our results support that adolescent exposure to THC may cause aberrant activation of the ovarian endocannabinoid system in female mice, resulting in substantial loss of ovarian reserve in adulthood. Relevance of these findings to women who frequently used cannabis during adolescence warrants investigation.
    Type of Medium: Online Resource
    ISSN: 1096-6080 , 1096-0929
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1471974-5
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  • 4
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Idiopathic membranous nephropathy (iMN) is a leading cause of nephrotic syndrome and one of the major causes of end-stage renal disease (ESRD). Various factors can affect renal and patient outcome in patients with iMN. In this study, we analyzed the predictors of renal and patient survival in patients with iMN. Method We analyzed 1,776 patients diagnosed with iMN in Korean GlomeruloNEphritis STudy (KoGNET), a retrospective database of patients with renal biopsy from 1979 to 2018 from 18 centers in Korea. Student t-test for continuous variables and Chi-square test for categorical variables were performed for analyses. Cox proportional hazard regression was used to determine risk factors affecting renal and patient survival. Results The mean age of patients was 53.0 ± 14.7 years old and 1,075 (60.5%) were male. At the time of renal biopsy, 755 (46.0%) and 266 (16.2%) had hypertension and diabetes, respectively. Serum albumin level was 2.7 ± 0.8 g/dL and 871 (49.0%) had nephrotic range of proteinuria. When analyzed by dividing over 65 and under, the hemoglobin and serum albumin level were lower, more patients showed nephrotic ranged proteinuria, and higher prevalence of comorbidities such as hypertension, diabetes, coronary heart disease and cerebrovascular disease in the group over 65 than in the group under 65. Median duration of follow-up was 88.0 (38.0 – 115.1) months. Complete or partial remission rates were 48.5%, 63.8%, and 68.0% at 6 months, 12months after biopsy, and last follow-up, respectively. In Cox proportional hazard regression, high hemoglobin [HR 0.66 (0.47 – 0.93), p=0.017], high serum albumin level [HR 0.41 (0.18 – 0.94), p=0.034] , and high estimated GFR by CKD-EPI equation [HR 0.94 (0.91 – 0.96), p & lt;0.001] at biopsy were good predictors for renal outcome, whereas presence of cerebrovascular disease at biopsy [HR 6.45 (1.16 – 35.71), p=0.033] were poor prognostic factors for ESRD. Age 65 and older [HR 3.26 (1.53 – 6.95), p=0.002] and presence of hypertension at biopsy [HR 2.45 (1.09 – 5.54), p=0.031] were significant risk factors for patient survival in multivariate Cox proportional regression analysis. Conclusion High hemoglobin and serum albumin, and good renal function at biopsy were good predictors for renal survival. Older age and hypertension at biopsy were poor prognostic factors for patient survival in iMN patients. Prognostic information of outcomes in this study might be helpful to optimize management in iMN patients.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1465709-0
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  • 5
    In: Rheumatology, Oxford University Press (OUP), Vol. 59, No. 8 ( 2020-08-01), p. 2135-2145
    Abstract: Kidney-infiltrating immune cells can contribute to the pathogenesis of lupus nephritis (LN). We investigated the immunological characteristics of CD11c+ macrophages and their functions associated with the pathogenesis of LN. Methods CD11c+ macrophages were examined in the urine samples of patients with LN. Phenotypic markers and pro-inflammatory cytokine expression levels were analysed by flow cytometry. To determine the origin of urinary macrophages, peripheral monocytes were treated with sera from patients with systemic lupus erythematosus (SLE). The pathogenic role of CD11c+ macrophages in tubulointerstitial damage was investigated using SLE sera-treated monocytes and HK-2 cells. Results Urinary CD11c+ macrophages expressed pro-inflammatory cytokines, such as IL-6 and IL-1β, and resembled infiltrated monocytes rather than tissue-resident macrophages with respect to surface marker expression. CD11c+ macrophages had high expression levels of the chemokine receptor CXCR3, which were correlated with cognate chemokine IP-10 expression in urinary tubular epithelial cells. When treated with sera from SLE patients, peripheral monocytes acquired the morphological and functional characteristics of urinary CD11c+ macrophages, which was blocked by DNase treatment. Finally, SLE sera-treated monocytes induced fibronectin expression, apoptosis and cell detachment in HK-2 cells via production of IL-6. Conclusion CD11c+ macrophages may be involved in the pathogenesis of tubulointerstitial injury in LN.
    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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  • 6
    In: FEMS Microbiology Ecology, Oxford University Press (OUP), Vol. 99, No. 2 ( 2023-01-24)
    Abstract: Fructooligosaccharides (FOS), Ad-fructooligosaccharides (Ad-FOS), resistant maltodextrin (RMD), and maltooligosaccharides (MOS) are commercially available prebiotic oligosaccharides. In this study, the effects of prebiotics on the human gut microbial ecosystem were evaluated using an in vitro gut model. FOS and Ad-FOS showed tolerance to digestion, whereas RMD and MOS showed moderate digestion by digestive enzymes. In in vitro fecal fermentation, Bifidobacterium spp. increased in the following order: FOS, Ad-FOS, MOS, and RMD, whereas Bacteroides spp. increased in RMD medium. Bacteroides xylanisolvens exhibited cross-feeding by enabling the growth of other beneficial bacteria during co-culture in RMD medium. In metabolome analysis, total short-chain fatty acids (SCFAs) were highly produced in the following order: RMD, FOS, MOS, and Ad-FOS; acetate in the order of FOS, MOS/RMD, and Ad-FOS; butyrate in the order of RMD, MOS, FOS, and Ad-FOS; and propionate only in RMD. In addition, the conversion of betaine to trimethylamine was rarely affected in the following order: MOS, RMD, FOS, and Ad-FOS. Lastly, the four oligosaccharides inhibited the adhesion of pathogenic Escherichia coli to human epithelial cells to a similar extent. The comparative analysis results obtained in this study will provide comprehensive information of these substances to manufacturers and customers.
    Type of Medium: Online Resource
    ISSN: 1574-6941
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1501712-6
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  • 7
    In: Human Molecular Genetics, Oxford University Press (OUP), Vol. 31, No. 15 ( 2022-08-17), p. 2655-2667
    Abstract: Human leukocyte antigen (HLA) gene variants in the major histocompatibility complex (MHC) region are associated with numerous complex human diseases and quantitative traits. Previous phenome-wide association studies (PheWAS) for this region demonstrated that HLA association patterns to the phenome have both population-specific and population-shared components. We performed MHC PheWAS in the Korean population by analyzing associations between phenotypes and genetic variants in the MHC region using the Korea Biobank Array project data samples from the Korean Genome and Epidemiology Study cohorts. Using this single-population dataset, we curated and analyzed 82 phenotypes for 125 673 Korean individuals after imputing HLA using CookHLA, a recently developed imputation framework. More than one-third of these phenotypes showed significant associations, confirming 56 known associations and discovering 13 novel association signals that were not reported previously. In addition, we analyzed heritability explained by the variants in the MHC region and genetic correlations among phenotypes based on the MHC variants.
    Type of Medium: Online Resource
    ISSN: 0964-6906 , 1460-2083
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474816-2
    SSG: 12
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  • 8
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 225, No. 5 ( 2022-03-02), p. 777-784
    Abstract: There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections. Method We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses. Results A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96] ; P  & lt; .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1. Conclusions Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1473843-0
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