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  • The Endocrine Society  (10)
  • Medicine  (10)
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  • The Endocrine Society  (10)
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  • Medicine  (10)
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  • 1
    Online Resource
    Online Resource
    Altered Static and Dynamic Brain Functional Topological Organization in Patients with Dysthyroid Optic Neuropathy
    The Endocrine Society ; 2024
    In:  The Journal of Clinical Endocrinology & Metabolism ( 2024-01-31)
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, ( 2024-01-31)
    Abstract: Dysthyroid optic neuropathy (DON) is a serious vision-threatening complication of thyroid-associated ophthalmopathy (TAO). Exploration of the underlying mechanisms of DON is critical for its timely clinical diagnosis. Objective We hypothesized that TAO patients with DON may have altered brain functional networks. We aimed to explore the alterations of static and dynamic functional connectomes in patients with and without DON using resting-state functional MRI with graph theory method. Design A cross-sectional study. Setting Grade A tertiary hospital. Participants Sixty-six TAO patients (28 DON and 38 non-DON) and 30 healthy controls (HCs). Main Outcome Measures Topological properties of functional networks Results For static properties, DON patients exhibited lower global efficiency (Eg), local efficiency, normalized clustering coefficient, small-worldness (σ), and higher characteristic path length (Lp) than HCs. Both DON and non-DON patients exhibited varying degrees of abnormalities in nodal properties. Meanwhile, compared with non-DON, DON patients exhibited abnormalities in nodal properties in orbitofrontal cortex and visual network (VN). For dynamic properties, DON group exhibited higher variance in Eg and Lp than non-DON and HC groups. A strengthened subnetwork with VN as the core was identified in DON cohort. Significant correlations were found between network properties and clinical variables. For distinguishing DON, the combination of static and dynamic network properties exhibited optimal diagnostic performance. Conclusion Functional network alterations were observed in both DON and non-DON patients, providing novel insights into the underlying neural mechanisms of disease. Functional network properties may be potential biomarkers for reflecting the progression of TAO from non-DON to DON.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgae062
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2024
    detail.hit.zdb_id: 2026217-6
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  • 2
    Online Resource
    Online Resource
    Gene Expression and RNA Splicing Imputation Identifies Novel Candidate Genes Associated with Osteoporosis
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 12 ( 2020-12-01), p. e4742-e4757
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 12 ( 2020-12-01), p. e4742-e4757
    Abstract: Though genome-wide association studies (GWASs) have identified hundreds of genetic variants associated with osteoporosis related traits, such as bone mineral density (BMD) and fracture, it remains a challenge to interpret their biological functions and underlying biological mechanisms. Objective Integrate diverse expression quantitative trait loci and splicing quantitative trait loci data with several powerful GWAS datasets to identify novel candidate genes associated with osteoporosis. Design, Setting, and Participants Here, we conducted a transcriptome-wide association study (TWAS) for total body BMD (TB-BMD) (n = 66 628 for discovery and 7697 for validation) and fracture (53 184 fracture cases and 373 611 controls for discovery and 37 857 cases and 227 116 controls for validation), respectively. We also conducted multi-SNP-based summarized mendelian randomization analysis to further validate our findings. Results In total, we detected 88 genes significantly associated with TB-BMD or fracture through expression or ribonucleic acid splicing. Summarized mendelian randomization analysis revealed that 78 of the significant genes may have potential causal effects on TB-BMD or fracture in at least 1 specific tissue. Among them, 64 genes have been reported in previous GWASs or TWASs for osteoporosis, such as ING3, CPED1, and WNT16, as well as 14 novel genes, such as DBF4B, GRN, TMUB2, and UNC93B1. Conclusions Overall, our findings provide novel insights into the pathogenesis mechanisms of osteoporosis and highlight the power of a TWAS to identify and prioritize potential causal genes.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgaa572
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 3
    Online Resource
    Online Resource
    Cytotoxic T Lymphocyte-Associated Molecule-4 Polymorphism and Relapse of Graves’ Hyperthyroidism after Antithyroid Withdrawal
    The Endocrine Society ; 2004
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 1 ( 2004-01-01), p. 169-173
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 89, No. 1 ( 2004-01-01), p. 169-173
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2003-030854
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2004
    detail.hit.zdb_id: 2026217-6
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  • 4
    Online Resource
    Online Resource
    Bivariate Genome-Wide Association Study Implicates ATP6V1G1 as a Novel Pleiotropic Locus Underlying Osteoporosis and Age at Menarche
    The Endocrine Society ; 2015
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 100, No. 11 ( 2015-11), p. E1457-E1466
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 100, No. 11 ( 2015-11), p. E1457-E1466
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2015-2095
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2015
    detail.hit.zdb_id: 2026217-6
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  • 5
    Online Resource
    Online Resource
    Efficacy and Safety of First- and Second-Line Drugs to Prevent Glucocorticoid-Induced Fractures
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 3 ( 2020-03-01), p. 600-613
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 3 ( 2020-03-01), p. 600-613
    Abstract: The evidence about benefits and harms of drugs for glucocorticoid (GC)-induced osteoporosis (GIOP) is limited, and the comparative efficacy and safety of first-line and second-line agents to prevent GC-induced (GI) fractures remains unclear. Objective To assess the comparative clinical efficacy, safety, and tolerability of first-line and second-line agents in preventing GI fractures. Data Sources We searched 3 different databases through March 5, 2019. Study Selection We included randomized controlled trials enrolling patients receiving long-term GCs and compared a first-line and second-line agent with one another and with placebo. Data Extraction Two reviewers independently extracted study and participant characteristics and outcome data. Data Synthesis We performed multivariate random-effects network meta-analyses including base, 3 subgroups, and 12 sensitivity analyses. We included 22 papers from 19 unique trials involving 4328 patients receiving GCs. Teriparatide (risk ratio [RR] 0.11, 95% confidence interval [CI] 0.03–0.47), denosumab (RR 0.21, 95% CI 0.09–0.49), and risedronate (RR 0.33, 95% CI 0.19–0.58) reduced the risk of GI vertebral fractures, and the former 2 were the most efficacious according to violin plots including the surface under the cumulative ranking curve values calculated by base and sensitivity analyses. Oral alendronate (RR 0.33, 95% CI 0.12–0.93) reduced this risk in patients receiving GCs with at least 7.5 mg/day, while intravenous ibandronate (RR 0.25, 95% CI 0.06–0.99) was efficacious for the primary prevention of GIOP. Six drugs were similar in terms of the 5 other outcomes. Conclusions In terms of clinical efficacy and safety, second-line teriparatide and denosumab pose a challenge to first-line oral bisphosphonates for prevention of GI fractures.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgz023
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 6
    Online Resource
    Online Resource
    Circulating Lysophosphatidylcholines in Early Pregnancy and Risk of Gestational Diabetes in Chinese Women
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 4 ( 2020-04-01), p. e982-e993
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 4 ( 2020-04-01), p. e982-e993
    Abstract: This study aimed to explore associations of lysophosphatidylcholines (LPCs) in early pregnancy with gestational diabetes mellitus (GDM), and whether LPCs mediated the associations of bile acids with GDM risk or had interactive effects with bile acids on GDM risk. Design We conducted a 1:1 nested case-control study (n = 486) from a large prospective pregnant women cohort in urban Tianjin, China. Blood samples were collected at their first antenatal care visit (median at 10th gestational week). LPCs were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional binary logistic regression and restricted cubic spline analysis were used to identify cutoff points of these metabolites for GDM risk. Results Of the 6 detectable LPCs, LPC14:0 less than 0.24 nmol/mL, LPC15:0 at 0.45 nmol/mL or greater, and LPC18:0 at 18.00 nmol/mL or greater were independently associated with GDM risk. Adjustment for LPC18:0 slightly attenuated odds ratios (ORs) of deoxycholic acid (DCA, ≤ 0.36 nmol/mL) and glycoursodeoxycholic acid (GUDCA, ≤ 0.07 nmol/mL) for GDM, and the correlations of DCA and GUDCA with LPC18:0 were weak. However, the presence of DCA at 0.36 nmol/mL or less greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 8.18 (2.51-26.7) up to 17.7 (6.64-47.1), with significant additive interaction. Similarly, the presence of GUDCA at 0.07 nmol/mL or less also greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 17.2 (1.77-168) up to 73.8 (12.7-429), with significant additive interaction. Conclusions LPCs in early pregnancy were associated with GDM risk. Low DCA or GUDCA greatly amplified the effect of high LPC18:0 on GDM, and its molecular mechanism is worth further investigations.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgaa058
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 7
    Online Resource
    Online Resource
    Tumor-Infiltrating Neutrophils Predict Poor Survival of Non-Functional Pancreatic Neuroendocrine Tumor
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 7 ( 2020-07-01), p. 2217-2228
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 7 ( 2020-07-01), p. 2217-2228
    Abstract: This study retrospectively characterized the immune infiltrating profile in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs). Methods Tumor tissues from the 109-patient Fudan cohort and a 73-patient external validation set were evaluated by immunohistochemistry for 9 immune cell types: tumor-infiltrating neutrophils (TINs), tumor-associated macrophages (TAMs), CD11c+ dendritic cells, anti-NCR1+ natural killer (NK) cells, CD4+ and CD8+ T cells, CD45RO+ memory T cells, FOXP3+ regulatory T cells (Tregs), and CD20+ B cells. Results TINs were primarily distributed in the intratumoral area, dendritic cells and NK cells were scattered evenly in intratumoral and stromal areas, and Tregs were rarely detected. The remaining 5 cell types were primarily present in peritumoral stroma. Total TINs (P & lt; .001) and TAMs (P = .002) increased as NF-PanNET grade rose. Kaplan-Meier analyses showed that high intratumoral TINs, total TAMs, and stromal CD4+ T-cell infiltration correlated with shorter recurrence-free survival (RFS, P = .010, P = .027, and P = .035, respectively) and overall survival (OS, P = .017, P = .029, and P = .045, respectively). Additionally, high intratumoral CD8+ T cell infiltration correlated with prolonged RFS (P = .039). Multivariate Cox regression demonstrated that intratumoral TINs, World Health Organization (WHO) classification, and eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC8th TNM) were independent factors for RFS (P = .043, P = .023, and P = .029, respectively), whereas intratumoral TINs and WHO classification were independent factors for OS (P = .010 and P = .007, respectively). Furthermore, the combination of TINs, WHO classification, and AJCC8th TNM remarkably improved prognostic accuracy for RFS. These results have been verified in the external validation set. Conclusion Intratumoral TINs are an independent and unfavorable predictor of postoperative NF-PanNETs. A combination of TINs, WHO classification, and AJCC8th TNM could improve prognostic accuracy for RFS.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgaa196
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 8
    Online Resource
    Online Resource
    Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women
    The Endocrine Society ; 2021
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 106, No. 8 ( 2021-07-13), p. e3159-e3177
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 8 ( 2021-07-13), p. e3159-e3177
    Abstract: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. Objective We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. Design and Methods We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. Results Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM). Conclusions This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgab146
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2026217-6
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  • 9
    Online Resource
    Online Resource
    Transcriptome Analyses Identify a Metabolic Gene Signature Indicative of Dedifferentiation of Papillary Thyroid Cancer
    The Endocrine Society ; 2019
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 104, No. 9 ( 2019-09-01), p. 3713-3725
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 9 ( 2019-09-01), p. 3713-3725
    Abstract: Metabolic reprogramming is a common feature of tumorigenesis. It remains unknown concerning the expression pattern of metabolism-associated genes in dedifferentiated thyroid cancer (DDTC). Objective This study aimed to identify a useful signature to indicate dedifferentiation of papillary thyroid cancer (PTC). Design and Setting We used one discovery and two validation cohorts to screen out aberrant metabolic genes in DDTC, and further used The Cancer Genome Atlas (TCGA) cohort to search for independent risk factors for the low-differentiated phenotype of PTC as a signature of dedifferentiation. The prediction of the signature for DDTC was validated in the TCGA cohort and the combined Gene Expression Omnibus cohort. We also analyzed the correlations of the signature risk score with clinicopathological features of PTC. Gene set enrichment analyses were performed in the TCGA cohort. Results Significant enrichment of metabolic pathways correlated with differentiation status of PTC. A signature of metabolic genes including LPCAT2, ACOT7, HSD17B8, PDE8B, and ST3GAL1 was discovered and validated across three cohorts. The signature was not only predictive of DDTC but also significantly associated with BRAFV600E mutation (P 〈 0.001), T3/T4 stage (P 〈 0.001), extrathyroidal extension (P 〈 0.001), lymph node metastasis (P 〈 0.001), and tumor/lymph node/metastasis III/IV stage (P 〈 0.001) in PTC. Downregulations of LPCAT2 expression (P = 0.009) and ST3GAL1 expression (P = 0.005) increased risks of decreased disease-free survival for patients. Furthermore, the signature was implicated in a number of oncogenic biological pathways. Conclusions Our findings suggest that metabolic deregulations mediate dedifferentiation of PTC, and that the metabolic gene signature can be used as a biomarker for DDTC.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2018-02686
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2026217-6
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  • 10
    Online Resource
    Online Resource
    Identification of Novel Potentially Pleiotropic Variants Associated With Osteoporosis and Obesity Using the cFDR Method
    The Endocrine Society ; 2018
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 103, No. 1 ( 2018-01-01), p. 125-138
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 103, No. 1 ( 2018-01-01), p. 125-138
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2017-01531
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2018
    detail.hit.zdb_id: 2026217-6
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