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  • Ovid Technologies (Wolters Kluwer Health)  (134)
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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Journal of the American Heart Association Vol. 5, No. 9 ( 2016-09)
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 5, No. 9 ( 2016-09)
    Abstract: An early repolarization pattern ( ERP ) has been hypothesized to be arrhythmogenic in experimental studies, but the prognostic significance of the ERP in the general population is controversial. We performed a meta‐analysis to examine the link between ERP and the risk of sudden cardiac arrest ( SCA ), cardiac death, and death from any cause. Methods and Results We performed a literature search using MEDLINE (January 1, 1966 to July 31, 2015) and EMBASE (January 1, 1980 to July 31, 2015) with no restrictions. Studies that reported relative risk ( RR ) estimates with 95% confidence intervals ( CI s) for the associations of interest were included. Sixteen studies involving 334 524 subjects were identified. Compared with those without ERP , subjects with ERP experienced significantly increased risk for developing SCA ( RR 2.18; 95% CI 1.29–3.68), cardiac death ( RR 1.48; 95% CI 1.06–2.07), and death from any cause ( RR 1.21; 95% CI 1.02–1.42), respectively. The increased risk was present predominantly in Asians and whites but not in African Americans. ERP with J‐point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk. ERP was associated with an absolute risk increase of 139.6 (95% CI 130.3–149.3) additional SCA s per 100 000 person‐years and responsible for 7.3% (95% CI 1.9–15.2) of SCA in the general population. Conclusions ERP is associated with significant increased risk for SCA , cardiac death, and death from any cause. Future studies should focus on understanding the exact mechanisms for the arrhythmia risk and developing reliable tools for risk stratification.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2653953-6
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Heart Association Vol. 6, No. 5 ( 2017-05-05)
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 5 ( 2017-05-05)
    Abstract: Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of heart disease is uncertain. We performed a meta‐analysis to investigate the link between radiotherapy and long‐term cardiovascular morbidity and mortality in patients with breast cancer. Methods and Results We performed a literature search using MEDLINE (January 1966 to January 2015) and EMBASE (January 1980 to January 2015) with no restrictions. Studies that reported relative risk ( RR ) estimates with 95% CI s for the associations of interest were included. Pooled effect estimates were obtained by using random‐effects meta‐analysis. Thirty‐nine studies involving 1 191 371 participants were identified. Patients who received left‐sided radiotherapy, as compared with those receiving right‐sided radiotherapy, experienced increased risks of developing coronary heart disease ( RR 1.29, 95% CI 1.13‐1.48), cardiac death ( RR 1.22, 95% CI 1.08‐1.37) and death from any cause ( RR 1.05, 95% CI 1.01‐1.10). In a comparison of patients with radiotherapy and without radiotherapy, the RR s were 1.30 (95% CI 1.13‐1.49) for coronary heart disease and 1.38 (95% CI 1.18‐1.62) for cardiac mortality. Radiotherapy for breast cancer was associated with an absolute risk increase of 76.4 (95% CI 36.8‐130.5) cases of coronary heart disease and 125.5 (95% CI 98.8‐157.9) cases of cardiac death per 100 000 person‐years. The risk started to increase within the first decade for coronary heart disease and from the second decade for cardiac mortality. Conclusions Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent risk of coronary heart disease and cardiac mortality.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2653953-6
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  • 3
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 121, No. 15 ( 2008-08), p. 1433-1438
    Type of Medium: Online Resource
    ISSN: 0366-6999
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2008
    detail.hit.zdb_id: 2108782-9
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Clinical Journal of the American Society of Nephrology Vol. 16, No. 2 ( 2021-02), p. 213-224
    In: Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 16, No. 2 ( 2021-02), p. 213-224
    Abstract: IgA nephropathy is the most common form of primary GN worldwide. The evidence of geographic and ethnic differences, as well as familial aggregation of the disease, supports a strong genetic contribution to IgA nephropathy. Evidence for genetic factors in IgA nephropathy comes also from genome-wide association patient-control studies. However, few studies have systematically evaluated the contribution of coding variation in IgA nephropathy. Design, setting, participants, & measurements We performed a two-stage exome chip–based association study in 13,242 samples, including 3363 patients with IgA nephropathy and 9879 healthy controls of Han Chinese ancestry. Common variant functional annotation, gene-based low-frequency variants analysis, differential mRNA expression, and gene network integration were also explored. Results We identified three non-HLA gene regions ( FBXL21 , CCR6 , and STAT3 ) and one HLA gene region ( GABBR1 ) with suggestive significance ( P meta 〈 5×10 −5 ) in single-variant associations. These novel non-HLA variants were annotated as expression-associated single-nucleotide polymorphisms and were located in enhancer regions enriched in histone marks H3K4me1 in primary B cells. Gene-based low-frequency variants analysis suggests CFB as another potential susceptibility gene. Further combined expression and network integration suggested that the five novel susceptibility genes, TGFBI , CCR6 , STAT3 , GABBR1 , and CFB , were involved in IgA nephropathy. Conclusions Five novel gene regions with suggestive significance for IgA nephropathy were identified and shed new light for further mechanism investigation.
    Type of Medium: Online Resource
    ISSN: 1555-9041 , 1555-905X
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2216582-4
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  • 5
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Clinical Journal of the American Society of Nephrology Vol. 6, No. 9 ( 2011-09), p. 2175-2184
    In: Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 9 ( 2011-09), p. 2175-2184
    Type of Medium: Online Resource
    ISSN: 1555-9041
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 2216582-4
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Society of Nephrology Vol. 28, No. 5 ( 2017-5), p. 1651-1664
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 28, No. 5 ( 2017-5), p. 1651-1664
    Abstract: Epitopes of phospholipase A2 receptor (PLA2R), the target antigen in idiopathic membranous nephropathy (iMN), must be presented by the HLA–encoded MHC class II molecules to stimulate autoantibody production. A genome–wide association study identified risk alleles at HLA and PLA2R loci, with the top variant rs2187668 within HLA-DQA1 showing a risk effect greater than that of the top variant rs4664308 within PLA2R1. How the HLA risk alleles affect epitope presentation by MHC class II molecules in iMN is unknown. Here, we genotyped 261 patients with iMN and 599 healthy controls at the HLA-DRB1, HLA-DQA1, HLA-DQB1, and HLA-DPB1 loci with four-digit resolution and extracted the encoded amino acid sequences from the IMGT/HLA database. We predicted T cell epitopes of PLA2R and constructed MHC-DR molecule-PLA2R peptide-T cell receptor structures using Modeler. We identified DRB1*1501 (odds ratio, 4.65; 95% confidence interval [95% CI], 3.39 to 6.41; P 〈 0.001) and DRB1*0301 (odds ratio, 3.96; 95% CI, 2.61 to 6.05; P 〈 0.001) as independent risk alleles for iMN and associated with circulating anti–PLA2R antibodies. Strong gene-gene interaction was noted between rs4664308(AA) and HLA-DRB1*1501/DRB1*0301. Amino acid positions 13 ( P 〈 0.001) and 71 ( P 〈 0.001) in the MHC-DR β 1 chain independently associated with iMN. Structural models showed that arginine13 and alanine71, encoded by DRB1*1501, and lysine71, encoded by DRB1*0301, facilitate interactions with T cell epitopes of PLA2R. In conclusion, we identified two risk alleles of HLA class II genes and three amino acid residues on positions 13 and 71 of the MHC-DR β 1 chain that may confer susceptibility to iMN by presenting T cell epitopes on PLA2R.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2029124-3
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Clinical Journal of the American Society of Nephrology Vol. 11, No. 6 ( 2016-6), p. 947-955
    In: Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 6 ( 2016-6), p. 947-955
    Abstract: Proteinuria is an independent predictor for IgA nephropathy (IgAN) progression. Urine albumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, and 24-hour urine protein excretion (UPE) are widely used for proteinuria evaluation in clinical practice. Here, we evaluated the association of these measurements with clinical and histologic findings of IgAN and explored which was the best predictor of IgAN prognosis. Design, setting, participants, & measurements Patients with IgAN were followed up for ≥12 months, were diagnosed between 2003 and 2012, and had urine samples available (438 patients). Spot urine ACR, protein-to-creatinine ratio, and 24-hour UPE at the time of renal biopsy were measured on a Hitachi Automatic Biochemical Analyzer 7180 (Hitachi, Yokohama, Japan). Results In our patients, ACR, protein-to-creatinine ratio, and 24-hour UPE were highly correlated (correlation coefficients: 0.71–0.87). They showed good relationships with acknowledged markers reflecting IgAN severity, including eGFR, hypertension, and the biopsy parameter (Oxford severity of tubular atrophy/interstitial fibrosis parameter). However, only ACR presented with positive association with the Oxford segmental glomerulosclerosis/adhesion parameter and extracapillary proliferation lesions. The follow-up time was 37.0 (22.0–58.0) months, with the last follow-up on April 18, 2014. In total, 124 patients reached the composite end point (30% eGFR decline, ESRD, or death). In univariate survival analysis, ACR consistently had better performance than protein-to-creatinine ratio and 24-hour UPE as represented by higher area under the curve using time–dependent survival analysis. When adjusted for well known risk factors for IgAN progression, ACR was most significantly associated with the composite end point (hazard ratio, 1.56 per 1-SD change of standard normalized square root–transformed ACR; 95% confidence interval, 1.29 to 1.89; P 〈 0.001). Compared with protein-to-creatinine ratio and 24-hour UPE, addition of ACR to traditional risk factors resulted in more improvement in the predictive ability of IgAN progression ( c statistic: ACR=0.70; protein-to-creatinine ratio =0.68; 24-hour UPE =0.69; Akaike information criterion: ACR=1217.85; protein-to-creatinine ratio =1229.28; 24-hour UPE =1234.96; P 〈 0.001). Conclusions In IgAN, ACR, protein-to-creatinine ratio, and 24-hour UPE had comparable association with severe clinical and histologic findings. Compared with protein-to-creatinine ratio and 24-hour UPE, ACR showed slightly better performance in predicting IgAN progression.
    Type of Medium: Online Resource
    ISSN: 1555-9041 , 1555-905X
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2216582-4
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Journal of the American Society of Nephrology Vol. 32, No. 3 ( 2021-3), p. 545-552
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. 3 ( 2021-3), p. 545-552
    Abstract: Galactose-deficient IgA1 plays a key role in the pathogenesis of IgA nephropathy. Although variability in serum levels of galactose-deficient IgA1 has a strong genetic component, the genetic link between this molecule and IgA nephropathy has not yet been clearly determined. The authors performed a genome-wide association study of serum galactose-deficient IgA1 levels among 1127 patients with IgA nephropathy in a Chinese population, identifying two genome-wide significant loci, of which one is novel. They also observed potential associations between galactose-deficient IgA1 loci and susceptibility to IgA nephropathy. In addition, they found genetic interactions between the two loci associated with both serum levels of galactose-deficient IgA1 and susceptibility to developing IgA nephropathy. This study provides novel insights into the genetic link between galactose-deficient IgA1 and IgA nephropathy. Background Galactose-deficient IgA1 plays a key role in the pathogenesis of IgA nephropathy, the most common primary GN worldwide. Although serum levels of galactose-deficient IgA1 have a strong genetic component, the genetic link between this molecule and IgA nephropathy has not yet been clearly established. Methods To identify novel loci associated with galactose-deficient IgA1, we performed a quantitative genome-wide association study for serum galactose-deficient IgA1 levels, on the basis of two different genome-wide association study panels conducted in 1127 patients with IgA nephropathy. To test genetic associations with susceptibility to IgA nephropathy, we also enrolled 2352 patients with biopsy-diagnosed IgA nephropathy and 2632 healthy controls. Peripheral blood samples from 59 patients and 27 healthy controls were also collected for gene expression analysis. Results We discovered two loci, in C1GALT1 and GALNT12, that achieved genome-wide significance, explaining about 3.7% and 3.4% of variance in serum galactose-deficient IgA1 levels, respectively. We confirmed the previously reported association of C1GALT1 with serum galactose-deficient IgA1 levels, but with a different lead single-nucleotide polymorphism (rs10238682; β=0.26, P =1.20×10 −9 ); the locus we identified at GALNT12 (rs7856182; β=0.73, P =2.38×10 −9 ) was novel. Of more interest, we found that GALNT12 exhibits genetic interactions with C1GALT1 in both galactose-deficient IgA1 levels ( P =1.40×10 −2 ) and disease risk ( P =6.55×10 −3 ). GALNT12 mRNA expression in patients with IgA nephropathy was significantly lower compared with healthy controls. Conclusions Our data identify GALNT12 as a novel gene associated with galactose-deficient IgA1 and suggest novel genetic interactions. These findings support a key role of genetically conferred dysregulation of galactose-deficient IgA1 in the development of IgA nephropathy.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2029124-3
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Society of Nephrology Vol. 28, No. 11 ( 2017-11), p. 3175-3181
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 28, No. 11 ( 2017-11), p. 3175-3181
    Abstract: IgA nephropathy (IgAN) is characterized by infections followed by episodic gross hematuria. Deficiency of mannose-binding lectin (MBL) is associated with recurrent infection in many diseases, but controversy exists regarding the role of MBL in IgAN. Here, we measured MBL2 variants and MBL levels in 749 patients with IgAN and 489 healthy controls. Overall, 5.2% (39 of 749) of patients with IgAN had MBL deficiency (MBL levels 〈 100 ng/ml), among whom LYPB/LYPB and LXPA/LYPB were the predominant MBL2 haplotypes (82%; 32 of 39). We found a nonlinear association between MBL levels and renal outcome in IgAN. Patients with IgAN and MBL deficiency had a higher incidence of prodromic infections and gross hematuria than those with sufficient MBL levels (100–3540 ng/ml). Moreover, MBL deficiency independently associated with poor renal outcome in IgAN after multiple adjustments (hazard ratio, 5.18; 95% confidence interval, 2.50 to 10.72; P 〈 0.001). Patients with high MBL levels ( 〉 3540 ng/ml) had more severe proteinuria and a higher proportion of crescents, although the association with IgAN progression did not reach statistical significance after adjustments. In conclusion, MBL deficiency and MBL excess may both have deleterious effects on IgAN progression, which suggests that MBL contributes to IgAN pathogenesis through multiple mechanisms.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2029124-3
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  • 10
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Clinical Journal of the American Society of Nephrology Vol. 16, No. 12 ( 2021-12), p. 1840-1850
    In: Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 16, No. 12 ( 2021-12), p. 1840-1850
    Abstract: IgA nephropathy is the most common primary GN worldwide. Previous research demonstrated that collectin11, an initiator of the complement lectin pathway, was involved in both AKI and chronic tubulointerstitial fibrosis. Here, we investigated the potential role of collectin11 in the pathogenesis of IgA nephropathy. Design, setting, participants, & measurements The deposition of collectin11 and other complement proteins was detected in glomeruli of 60 participants with IgA nephropathy by immunofluorescence. In vitro , human mesangial cells were treated with IgA1-containing immune complexes derived from participants with IgA nephropathy. Then, the expression of collectin11 in mesangial cells was examined by quantitative RT-PCR and immunofluorescence. The codeposition of collectin11 with IgA1 or C3 on mesangial cells was detected by immunofluorescence and proximity ligation assays. Results In total, 37% of participants with IgA nephropathy (22 of 60) showed codeposition of collectin11 with IgA in the glomerular mesangium. Using an injury model of mesangial cells, we demonstrated that IgA1-immune complexes derived from participants with IgA nephropathy increased the secretion of collectin11 in mesangial cells with the subsequent deposition of collectin11 on the cell surface via the interaction with deposited IgA1-immune complexes. In vitro , we found that collectin11 bound to IgA1-immune complexes in a dose-dependent but calcium-independent manner. Furthermore, deposited collectin11 initiated the activation of complement and accelerated the deposition of C3 on mesangial cells. Conclusions In situ –produced collectin11 by mesangial cells might play an essential role in kidney injury in a subset of patients with IgA nephropathy through the induction of complement activation.
    Type of Medium: Online Resource
    ISSN: 1555-9041 , 1555-905X
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2216582-4
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