Publications by authors named "Qing Duan"

143 Publications

Idebenone-Activating Autophagic Degradation of -Synuclein via Inhibition of AKT-mTOR Pathway in a SH-SY5Y-A53T Model of Parkinson's Disease: A Network Pharmacological Approach.

Evid Based Complement Alternat Med 2021 16;2021:8548380. Epub 2021 Sep 16.

School of Medicine, South China University of Technology, Guangzhou 510006, China.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, which currently lacks disease-modifying therapy to slow down its progression. Idebenone, a coenzyme Q10 (CQ10) analogue, is a well-known antioxidant and has been used to treat neurological disorders. However, the mechanism of Idebenone on PD has not been fully elucidated. This study aims to predict the potential targets of Idebenone and explore its therapeutic mechanism against PD.

Method: We obtained potential therapeutic targets through database prediction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Next, we constructed and analyzed a protein-protein interaction network (PPI) and a drug-target-pathway-disease network. A molecular docking test was conducted to identify the interactions between Idebenone and potential targets. Lastly, a PD cell line of SH-SY5Y overexpressing mutant -synuclein was used to validate the molecular mechanism.

Result: A total of 87 targets were identified based on network pharmacology. The enrichment analysis highlighted manipulation of MAP kinase activity and the PI3K-AKT signaling pathway as potential pharmacological targets for Idebenone against PD. Additionally, molecular docking showed that AKT and MAPK could bind tightly with Idebenone. In the cell model of PD, Idebenone activated autophagy and promoted -synuclein degradation by suppressing the AKT/mTOR pathway. Pretreating cells with chloroquine (CQ) to block autophagic flux could diminish the pharmacological effect of Idebenone to clear -synuclein.

Conclusion: This study demonstrated that Idebenone exerts its anti-PD effects by enhancing autophagy and clearance of -synuclein, thus providing a theoretical and experimental basis for Idebenone therapy against PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/8548380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463184PMC
September 2021

Comparing compressed sensing breath-hold 3D MR cholangiopancreatography with two parallel imaging MRCP strategies in main pancreatic duct and common bile duct.

Eur J Radiol 2021 Sep 24;142:109833. Epub 2021 Jun 24.

Diagnostic Imaging, Siemens Healthcare, Shanghai, China.

Purpose: To evaluate the image quality and image consistency between 3D Breath-hold (BH)-MRCP with parallel imaging (3D-BH-PI-MRCP) and 3D-BH compressed sensing (CS)-MRCP (3D-BH-CS-MRCP) in patients with suspected pancreaticobiliary diseases, compared with 3D navigator-triggered (NT)-MRCP.

Materials And Methods: The A total number of 109 patients who underwent 3D-NT-MRCP, 3D-BH-PI-MRCP and 3D-BH-CS-MRCP were prospectively enrolled in this study. The Friedman test was performed to compare quantitative values, image acquisition time, the presence of artifacts, overall image quality, and duct visualization among the three protocols. Additionally, we compared 3D-BH-PI-MRCP and 3D-BH-CS-MRCP with 3D-NT-MRCP in morphological consistency of main pancreatic duct and common bile duct (CBD) based on overall image quality score of = 4.

Results: Three MRCP methods were successfully performed in all the patients. The contrast ratio, SNR and CNR of the CBD were significantly higher for 3D-BH-CS-MRCP than those for 3D-NT-MRCP and 3D-BH-PI-MRCP images. Overall image quality did differ significantly across the three sequences. Visualization of the CBD, RHD, LHD, anterior branch, posterior branch and cystic duct was similar with the 3D-BH-CS-MRCP and 3D-BH-PI-MRCP sequences. In contrast, segment 2 or 3 branch and main pancreatic duct visualization were significantly better with 3D-BH-PI-MRCP than with 3D-BH-CS-MRCP and 3D-NT-MRCP (p < 0.001).

Conclusions: Both the two breath-hold approaches were considering the time-saving advantages without deterioration of image quality. Compared with 3D-BH-CS-MRCP, 3D-BH-PI-MRCP yielded significantly better visualization of the segment 2 and 3 branch of the intrahepatic duct and performed better consistency in main pancreatic duct and common bile duct morphology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2021.109833DOI Listing
September 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

Lasting antibody and T cell responses to SARS-CoV-2 in COVID-19 patients three months after infection.

Nat Commun 2021 02 9;12(1):897. Epub 2021 Feb 9.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15-30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3-4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4 or CD8 T cell responses 3-4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3-4 months after infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21155-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873066PMC
February 2021

MRI features of responsible contacts in vascular compressive trigeminal neuralgia and prediction modeling.

Acta Radiol 2021 Jan 7:284185120983971. Epub 2021 Jan 7.

Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, PR China.

Background: Multiple neurovascular contacts in patients with vascular compressive trigeminal neuralgia often challenge the diagnosis of responsible contacts.

Purpose: To analyze the magnetic resonance imaging (MRI) features of responsible contacts and establish a predictive model to accurately pinpoint the responsible contacts.

Material And Methods: Sixty-seven patients with unilateral trigeminal neuralgia were enrolled. A total of 153 definite contacts (45 responsible, 108 non-responsible) were analyzed for their MRI characteristics, including neurovascular compression (NVC) grading, distance from pons to contact (D), vascular origin of compressing vessels, diameter of vessel (D) and trigeminal nerve (D) at contact. The MRI characteristics of the responsible and non-responsible contacts were compared, and their diagnostic efficiencies were further evaluated using a receiver operating characteristic (ROC) curve. The significant MRI features were incorporated into the logistics regression analysis to build a predictive model for responsible contacts.

Results: Compared with non-responsible contacts, NVC grading and arterial compression ratio (84.44%) were significantly higher, D was significantly lower at responsible contacts ( < 0.001, 0.002, and 0.033, respectively). NVC grading had a highest diagnostic area under the ROC curve (AUC) of 0.742, with a sensitivity of 64.44% and specificity of 75.00%. The logistic regression model showed a higher diagnostic efficiency, with an AUC of 0.808, sensitivity of 88.89%, and specificity of 62.04%.

Conclusion: Contact degree and position are important MRI features in identifying the responsible contacts of the trigeminal neuralgia. The logistic predictive model based on D, NVC grading, and vascular origin can qualitatively improve the prediction of responsible contacts for radiologists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0284185120983971DOI Listing
January 2021

CT-based radiomics nomogram for preoperative prediction of No.10 lymph nodes metastasis in advanced proximal gastric cancer.

Eur J Surg Oncol 2021 06 24;47(6):1458-1465. Epub 2020 Nov 24.

Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China. Electronic address:

Introduction: Preoperative diagnosis of No.10 lymph nodes (LNs) metastases in advanced proximal gastric cancer (APGC) patients remains a challenge. The aim of this study was to develop a CT-based radiomics nomogram for identification of No.10 LNs status in APGCs.

Materials And Methods: A total of 515 patients with primary APGCs were retrospectively selected and divided into a training cohort (n = 340) and a validation cohort (n = 175). Total incidence of No.10 LNM was 12.4% (64/515). CT based radiomics nomogram combining with radiomic signature calculated from venous CT imaging features and CT-defined No.10 LNs status evaluated by radiologists was built and tested to predict the No.10 LNs status in APGCs.

Results: CT based radiomics nomogram yielded classification accuracy with areas under ROC curves, AUC = 0.896 and 0.814 in training and validation cohort, respectively, while radiomic signature and radiologist' diagnosis based on contrast-enhanced CT images yielded lower AUCs ranging in 0.742-0.866 and 0.619-0.685, respectively. In the specificity higher than 80%, the sensitivity of using radiomics nomogram, radiomic signature and radiologists' evaluation to detect No.10 LNs positive cases was 82.8% (53/64), 67.2% (43/64) and 39.1% (25/64), respectively.

Conclusions: The CT-based radiomics nomogram provides a promising and more effective method to yield high accuracy in identification of No.10 LNs metastases in APGC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejso.2020.11.132DOI Listing
June 2021

Contrast-Enhanced Ultrasound Characteristics of Renal Pelvis Urothelial Carcinoma and Its Relationship with Microvessel Density.

Ultrasound Med Biol 2021 02 4;47(2):236-243. Epub 2020 Nov 4.

Department of Urology, Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address:

We studied the characteristics of contrast-enhanced ultrasound (CEUS) in renal pelvic urothelial carcinomas and explored its performance in assessing microvessel density (MVD) of tumor tissues. We retrospectively analyzed the characteristics of 125 cases, which were confirmed pathologically to be renal pelvic urothelial carcinomas using CEUS. We performed CEUS and found that most tumors presented with an enhanced mode of "slow-in (mean = 16.7 ± 2.6 s, range: 12-25 s), hypo-enhancement and fast-out (mean = 69.3 ± 16.2 s, range: 42-113 s)." However, the wash-in pattern, homogeneity and wash-out pattern observed with CEUS was not correlated with pT stage and grade (p > 0.05). But advanced-pT-stage and high-grade tumors had a higher peak enhancement than early-pT-stage and low-grade tumors (p < 0.01). Peak enhancement obtained with CEUS can be used to evaluate the pT stage and grade of renal pelvic urothelial carcinomas more effectively. The MVD of those tissues was observed using immunohistochemical staining of cluster of differentiation 34 (CD34). MVD in the advanced-pT-stage and high-grade groups was significantly higher than that in the early-pT-stage and low-grade groups (p < 0.01). As tumor pT stage and grade improved, CEUS peak enhancement intensity and MVD of tumors also exhibited an upward trend. CEUS peak enhancement intensity has the potential to determine MVD of renal pelvic urothelial carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ultrasmedbio.2020.09.006DOI Listing
February 2021

The undiagnosed potential clinically significant incidental findings of neck CTA: A large retrospective single-center study.

Medicine (Baltimore) 2020 Oct;99(43):e22440

Department of Radiology, Fujian Medical University Union Hospital.

To assess the prevalence and missed reporting rate of potential clinically-significant incidental findings (IFs) in the neck CTA scans.All consecutive patients undergoing neck CTA imaging, from January 1, 2017 to December 31, 2018, were retrospectively evaluated by a radiologist for the presence of incidental findings in the upper chest, lower head and neck regions. These incidental findings were subsequently classified into 3 categories in terms of clinical significance: Type I, highly significant, Type II, moderately significant; and Type III, mildly or not significant. Type I and Type II IFs were determined as potential clinically significant ones and were retrospectively analyzed by another 2 radiologists in consensus. The undiagnosed findings were designated as those that were not reported by the initial radiologists. The differences in the rate of unreported potential clinically significant IFs were compared between the chest group and head or neck group.A total of 376 potential clinically significant IFs were detected in 1,698 (91.19%) patients, of which 175 IFs were classified as highly significant findings (Type I), and 201 (53.46%) as moderately significant findings (Type II). The most common potential clinically significant findings included thyroid nodules (n = 88, 23.40%), pulmonary nodules (n = 56, 14.89%), sinus disease (n = 39, 10.37%), intracranial or cervical artery aneurysms (n = 30, 7.98%), enlarged lymph nodes (n = 24, 6.38%), and pulmonary embolism (n = 19, 5.05%). In addition, 184 (48.94%) of them were not mentioned in the initial report. The highest incidence of missed potential clinical findings were pulmonary embolism and pathologic fractures and erosions (100% for both). The unreported rate of the chest group was significantly higher than that of the head or neck one, regardless of Type I, Type II or all potential clinically significant IFs (χ = 32.151, χ = 31.211, χ = 65.286, respectively; P < .001 for all).Important clinically significant incidental findings are commonly found in a proportion of patients undergoing neck CTA, in which nearly half of these patients have had potential clinically significant IFs not diagnosed in the initial report. Therefore, radiologists should beware of the importance of and the necessity to identify incidental findings in neck CTA scans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000022440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581090PMC
October 2020

Evaluation of the Therapeutic Effect of Magneto-Nanomicelles Based on Magneto-Thermal and Photo-Thermal Therapy.

J Nanosci Nanotechnol 2020 12;20(12):7406-7411

Department of Radiology, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou 350001, China.

In this study, we investigated the hyperthermia efficiency of magnetic hyperthermia therapy (MHT), photo-thermal therapy (PTT), and the combination of both techniques by employing SPIO-based magneto-nanomicelles as the heating agents. Magneto-nanomicelles in aqueous suspension were exposed to 808-nm laser irradiation (PTT mode), alternating magnetic field (MHT mode), and both modalities (DUAL mode). All the three methods can offer effective temperature increases (above 20 °C). DUAL-mode resulted in an approximately 2-fold increase in heating efficiency (36 °C) compared with PTT or MHT alone. For experiments, a total of 24 Lewis carcinoma-bearing mice were randomly divided into four groups: the control group (no therapy), PTT, MHT, and DUAL group. In the three therapy groups, magneto-nanomicelles were injected into the tumor and the corresponding treatment measures were performed every other day for a total of three times each. MRI scans were used to calculate tumor volume after each treatment. One-way analysis of variance (ANOVA) was employed to compare the curative effect of different treatment groups. Compared with the control group, PTT, MHT, and DUAL groups all showed a significant inhibitory effect on tumor volume ( < 0.05). In the DUAL group, the mean tumor volume was smaller than that of the PTT or the MHT group. Our work demonstrated that hyperthermia using SPIO-based magnetonanomicelles has a remarkable suppressive effect in anticancer therapy. Moreover, the combined model of hyperthermia can achieve synthetic effects with shorter healing time by using the same magneto-nanomicelles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jnn.2020.18521DOI Listing
December 2020

A direct comparison of 3 T contrast-enhanced whole-heart coronary cardiovascular magnetic resonance angiography to dual-source computed tomography angiography for detection of coronary artery stenosis: a single-center experience.

J Cardiovasc Magn Reson 2020 06 1;22(1):40. Epub 2020 Jun 1.

Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, China.

Background: In recent years, substantial advances have been made in noninvasive cardiac imaging, including cardiac computed tomography (CT) and cardiovascular magnetic resonance (CMR). The purpose of this study was to prospectively compare the diagnostic performance of contrast-enhanced whole heart coronary CMR angiography (CCMRA) to dual-source coronary CT angiography (CCTA) for the diagnosis of significant coronary stenoses (≥50%) in patients with known or suspected coronary artery disease (CAD) referred for conventional x-ray coronary angiography.

Methods: Our objective was to directly compare the diagnostic accuracy of contrast-enhanced whole-heart CCMRA (CE-CCMRA) to dual-source CCTA (DS-CCTA) for the detection of CAD. We prospectively studied 57 symptomatic patients with suspected or known CAD who were scheduled for conventional x-ray coronary angiography. Significant CAD was defined as an x-ray defined diameter reduction of ≥50% in a coronary artery with a reference diameter of ≥1.5 mm.

Results: CE-CCMRA and DS-CCTA were completed in 51 (89%) of 57 patients without complications. The acquisition times of CE-CCMRA and DS-CCTA, respectively, were 9.5 ± 3.1 min and 8.3 ± 1.4 s. On patient-based analysis, the sensitivity, specificity, positive and negative predictive value of CE-CCMRA and DS-CCTA were 93.5% versus 93.5%(P > 0.05), 85% versus 90%(P > 0.05), 90.6% versus 93.5%(P > 0.05), and 89.4% versus 90%(P > 0.05), respectively. The area under the curve (AUC) was 0.89 (95% CI: 0.79 to 0.99) for CE-CCMRA and 0.92 (95% CI: 0.83 to 1.00) for DS-CCTA.

Conclusions: DS-CCTA was found to be superior to CE-CCMRA in the diagnosis of significant coronary stenoses (≥50%) in patients with suspected or known CAD scheduled for conventional x-ray coronary angiography, owing to shorter scanning times and higher spatial resolution. However, CE-CCMRA and DS-CCTA have similar diagnostic accuracies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12968-020-00630-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262765PMC
June 2020

Gene networks and expression quantitative trait loci associated with adjuvant chemotherapy response in high-grade serous ovarian cancer.

BMC Cancer 2020 May 13;20(1):413. Epub 2020 May 13.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

Background: A major impediment in the treatment of ovarian cancer is the relapse of chemotherapy-resistant tumors, which occurs in approximately 25% of patients. A better understanding of the biological mechanisms underlying chemotherapy resistance will improve treatment efficacy through genetic testing and novel therapies.

Methods: Using data from high-grade serous ovarian carcinoma (HGSOC) patients in the Cancer Genome Atlas (TCGA), we classified those who remained progression-free for 12 months following platinum-taxane combination chemotherapy as "chemo-sensitive" (N = 160) and those who had recurrence within 6 months as "chemo-resistant" (N = 110). Univariate and multivariate analysis of expression microarray data were used to identify differentially expressed genes and co-expression gene networks associated with chemotherapy response. Moreover, we integrated genomics data to determine expression quantitative trait loci (eQTL).

Results: Differential expression of the Valosin-containing protein (VCP) gene and five co-expression gene networks were significantly associated with chemotherapy response in HGSOC. VCP and the most significant co-expression network module contribute to protein processing in the endoplasmic reticulum, which has been implicated in chemotherapy response. Both univariate and multivariate analysis findings were successfully replicated in an independent ovarian cancer cohort. Furthermore, we identified 192 cis-eQTLs associated with the expression of network genes and 4 cis-eQTLs associated with BRCA2 expression.

Conclusion: This study implicates both known and novel genes as well as biological processes underlying response to platinum-taxane-based chemotherapy among HGSOC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-020-06922-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218510PMC
May 2020

Histogram analysis in predicting the grade and histological subtype of meningiomas based on diffusion kurtosis imaging.

Acta Radiol 2020 Sep 27;61(9):1228-1239. Epub 2020 Jan 27.

Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, PR China.

Background: Presurgical grading is particularly important for selecting the best therapeutic strategy for meningioma patients.

Purpose: To investigate the value of histogram analysis of diffusion kurtosis imaging (DKI) maps in the differentiation of grades and histological subtypes of meningiomas.

Material And Methods: A total of 172 patients with histopathologically proven meningiomas underwent preoperative magnetic resonance imaging (MRI) and were classified into low-grade and high-grade groups. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) histograms were generated based on solid components of the whole tumor. The following parameters of each histogram were obtained: 10th, 25th, 75th, and 90th percentiles, mean, median, maximum, minimum, and kurtosis, skewness, and variance. Comparisons of different grades and subtypes were made by Mann-Whitney U test, Kruskal-Wallis test, ROC curves analysis, and multiple logistic regression. Pearson correlation was used to evaluate correlations between histogram parameters and the Ki-67 labeling index.

Results: Significantly higher maximum, skewness, and variance of MD, mean, median, maximum, variance, 10th, 25th, 75th, and 90th percentiles of MK were found in high-grade than low-grade meningiomas (all  < 0.05). DKI histogram parameters differentiated 7/10 pairs of subtype pairs. The 90th percentile of MK yielded the highest AUC of 0.870 and was the only independent indicator for grading meningiomas. Various DKI histogram parameters were correlated with the Ki-67 labeling index ( < 0.05).

Conclusion: The histogram analysis of DKI is useful for differentiating meningioma grades and subtypes. The 90th percentile of MK may serve as an optimal parameter for predicting the grade of meningiomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0284185119898656DOI Listing
September 2020

Rapid 3D navigator-triggered MR cholangiopancreatography with SPACE sequence at 3T: only one-third acquisition time of conventional 3D SPACE navigator-triggered MRCP.

Abdom Radiol (NY) 2020 01;45(1):134-140

Diagnostic Imaging, Siemens Healthcare, Shanghai, China.

Purpose: The purpose of this study was to compare the proposed rapid NT-MRCP protocol and the conventional NT-MRCP protocol with respect to image quality as well as the acquisition time.

Materials And Methods: Between January 2019 and May 2019, a total number of 67 consecutive patients with suspected pancreaticobiliary diseases were included in this prospective study and underwent 3D rapid MRCP and 3D conventional MRCP sequences. Both acquisition protocols were set from the same navigator-triggered 3D SPACE sequence. The acquisition time was recorded. Two blinded radiologists performed qualitative analyses with respect to overall image quality, motion artifacts, and CBD visibility using a four-point scale. Quantitative evaluation included the contrast, signal-noise ratio (SNR), and contrast-noise ratio (CNR) between the common bile duct (CBD) and periductal tissues. A paired t test was used to assess differences in the qualitative and quantitative evaluations between the two acquisition methods.

Results: All MRCP studies were completed successfully. The mean acquisition time of rapid NT-MRCP (96.64 ± 30.55 s) was significantly lower than that of the conventional NT-MRCP (271.42 ± 61.63 s; p < 0.001).The contrast ratio, SNR, and CNR of the CBD were significantly higher for conventional NT-MRCP than with rapid NT-MRCP images (0.95 ± 0.02 vs. 0.93 ± 0.03, p < 0.001; 10.36 ± 4.63 vs. 8.90 ± 4.71, p = 0.011; 14.01 ± 6.02 vs. 12.22 ± 6.36, p = 0.020, respectively). The rapid MRCP depicted the overall image quality, artifacts, CBD visibility, right and left hepatic duct, segment 2 branch, main pancreatic duct, and cystic duct significantly better compared with conventional MRCP (p < 0.05). There were no statistically significant differences between the two methods regarding visibility of anterior, posterior, and segment 3 branches (p > 0.05).

Conclusions: In conclusion, the proposed rapid MRCP protocol yielded significantly higher overall image quality and better visualization of the pancreaticobiliary tree with a significantly reduced imaging time without deterioration of image quality compared with the conventional MRCP at 3T.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00261-019-02342-3DOI Listing
January 2020

Human milk fatty acid composition is associated with dietary, genetic, sociodemographic, and environmental factors in the CHILD Cohort Study.

Am J Clin Nutr 2019 12;110(6):1370-1383

Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.

Background: Fatty acids are a vital component of human milk. They influence infant neurodevelopment and immune function, and they provide ∼50% of milk's energy content.

Objectives: The objectives of this study were to characterize the composition of human milk fatty acids in a large Canadian birth cohort and identify factors influencing their variability.

Methods: In a subset of the CHILD cohort (n = 1094), we analyzed milk fatty acids at 3-4 mo postpartum using GLC. Individual and total SFAs, MUFAs, and n-3 and n-6 PUFAs were analyzed using SD scores and principal component analysis (PCA). Maternal diet, sociodemographic, health, and environmental factors were self-reported. Single-nucleotide polymorphisms were assessed in the fatty acid desaturase 1 (FADS1-rs174556) and 2 (FADS2-rs174575) genes.

Results: Fatty acid profiles were variable, with individual fatty acid proportions varying from 2- to >30-fold between women. Using PCA, we identified 4 milk fatty acid patterns: "MUFA and low SFA," "high n-6 PUFA," "high n-3 PUFA," and "high medium-chain fatty acids." In multivariable-adjusted analyses, fish oil supplementation and fatty cold water fish intake were positively associated with DHA and the "high n-3 PUFA" pattern. Mothers carrying the minor allele of FADS1-rs174556 had lower proportions of arachidonic acid (ARA; 20:4n-6). Independent of selected dietary variables and genetic variants, Asian ethnicity was associated with higher linoleic acid (18:2n-6) and total n-3 PUFAs. Ethnic differences in ARA were explained by FADS1 genotype. Maternal obesity was independently associated with higher total SFAs, the "high medium-chain fatty acid" pattern, and lower total MUFAs. Lactation stage, season, study site, and maternal education were also independently associated with some milk fatty acids. No associations were observed for maternal age, parity, delivery mode, or infant sex.

Conclusions: This study provides unique insights about the "normal" variation in the composition of human milk fatty acids and the contributing dietary, genetic, sociodemographic, health, and environmental factors. Further research is required to assess implications for infant health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqz229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885479PMC
December 2019

Three-Dimensional Breath-Hold MRCP Using SPACE Pulse Sequence at 3 T: Comparison With Conventional Navigator-Triggered Technique.

AJR Am J Roentgenol 2019 12 6;213(6):1247-1252. Epub 2019 Aug 6.

MR Application, Siemens Healthineers Ltd., Guangzhou, People's Republic of China.

The purpose of this study was to evaluate the clinical feasibility of breath-hold (BH) MRCP with multichannel receiver coils in comparison with conventional navigator-triggered (NT) MRCP at 3 T. We prospectively studied 53 consecutive patients who underwent MRCP with BH sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) and NT SPACE. The acquisition time for each MRCP image was noted. The contrast ratio, the signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) between the common bile duct (CBD) and periductal tissues on 3D MRCP images were evaluated quantitatively. The overall image quality, motion artifacts, and CBD visibility were scored on a 4-point scale by two blinded radiologists. A paired test was used to analyze the differences in the qualitative and quantitative evaluations between the two MRCP acquisition methods. Both MRCP methods were successfully performed for all subjects without any complications. The mean acquisition time of BH MRCP was significantly shorter than that of NT MRCP (18 seconds vs 264.64 ± 89.66 [SD] seconds; < 0.001). The mean SNR, the contrast ratio, and the CNR of the CBD were significantly higher on NT MRCP images than on BH MRCP images (11.58 ± 6.24 vs 8.71 ± 4.21, 0.93 ± 0.04 vs 0.92 ± 0.03, and 15.42 ± 8.04 vs 12.00 ± 5.76, respectively; < 0.05). All visual scores were significantly higher with BH MRCP than with conventional NT MRCP ( < 0.001). Using 3D BH MRCP with a SPACE sequence at 3 T is feasible in clinical patients, yielding significantly better perceived image quality of the pancreaticobiliary tree in a single BH (mean acquisition time, 18 seconds) without losing image quality compared with the conventional NT MRCP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.19.21399DOI Listing
December 2019

Downregulating NF-κB signaling pathway with triterpenoids for attenuating inflammation: in vitro and in vivo studies.

Food Funct 2019 Aug 30;10(8):5080-5090. Epub 2019 Jul 30.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, Guangdong, China.

Acanthopanax trifoliatus (L.) Merr., an edible medicinal plant from Southeast Asia, exerts a wide range of bioactivities, such as anti-inflammatory activity. However, the anti-inflammatory mechanisms of its action and active constituents remain unclear. Herein, the effects of two triterpenoids, namely impressic acid (IA) and acankoreanogenin A (AA), from A. trifoliatus in both in vitro and in vivo chronic inflammation models were investigated. The results indicated that AA and IA reduced lipopolysaccharide (LPS)-induced production of nitroxide significantly in murine macrophage RAW246.7 cells. In addition, AA and IA down-regulated the activation of NF-κB and decreased the release of inflammatory mediators (iNOS, COX-2, TNF-α, and IL-6) and tumorigenesis-associated factors (MMP-9 and VEGF) in RAW246.7 cells. Furthermore, in a tetradecanoylphorbolacetate (TPA)-treated mouse model, AA and IA could effectively attenuate mouse ear edema and pathological damage and reduced levels of cytokines including iNOS, COX-2, TNF-α, and IL-1β. Taken together, AA and IA, being of natural origin, are promising anti-inflammatory agents and may contribute to the overall anti-inflammatory effect of A. trifoliatus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9fo00561gDOI Listing
August 2019

Integrated Analysis of Human Milk Microbiota With Oligosaccharides and Fatty Acids in the CHILD Cohort.

Front Nutr 2019 16;6:58. Epub 2019 May 16.

Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.

Human milk contains many bioactive components that are typically studied in isolation, including bacteria. We performed an integrated analysis of human milk oligosaccharides and fatty acids to explore their associations with milk microbiota. We studied a sub-sample of 393 mothers in the CHILD birth cohort. Milk was collected at 3-4 months postpartum. Microbiota was analyzed by 16S rRNA gene V4 sequencing. Oligosaccharides and fatty acids were analyzed by rapid high-throughput high performance and gas liquid chromatography, respectively. Dimension reduction was performed with principal component analysis for oligosaccharides and fatty acids. Center log-ratio transformation was applied to all three components. Associations between components were assessed using Spearman rank correlation, network visualization, multivariable linear regression, redundancy analysis, and structural equation modeling. -values were adjusted for multiple comparisons. Key covariates were considered, including fucosyltransferase-2 (FUT2) secretor status of mother and infant, method of feeding (direct breastfeeding or pumped breast milk), and maternal fish oil supplement use. Overall, correlations were strongest between milk components of the same type. For example, FUT2-dependent HMOs were positively correlated with each other, and was negatively correlated with other core taxa. Some associations were also observed between components of different types. Using redundancy analysis and structural equation modeling, the overall milk fatty acid profile was significantly associated with milk microbiota composition. In addition, some individual fatty acids [22:6n3 (docosahexaenoic acid), 22:5n3, 20:5n3, 17:0, 18:0] and oligosaccharides (fucosyl-lacto-N-hexaose, lacto-N-hexaose, lacto-N-fucopentaose I) were associated with microbiota α diversity, while others (C18:0, 3'-sialyllactose, disialyl-lacto-N-tetraose) were associated with overall microbiota composition. Only a few significant associations between individual HMOs and microbiota were observed; notably, among mothers using breast pumps prevalence was associated with lower abundances of disialyl-lacto-N-hexaose. Additionally, among non-secretor mothers, was positively correlated with sialylated HMOs. Using multiple approaches to integrate and analyse milk microbiota, oligosaccharides, and fatty acids, we observed several associations between different milk components and microbiota, some of which were modified by secretor status and/or breastfeeding practices. Additional research is needed to further validate and mechanistically characterize these associations and determine their relevance to infant gut and respiratory microbiota development and health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2019.00058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532658PMC
May 2019

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Hum Mol Genet 2019 08;28(15):2615-2633

Icelandic Heart Association, Kopavogur, Iceland.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddz070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644157PMC
August 2019

Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.

Nat Genet 2019 04 29;51(4):636-648. Epub 2019 Mar 29.

Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0378-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467258PMC
April 2019

Single-Cell Heterogeneity Analysis and CRISPR Screen Identify Key β-Cell-Specific Disease Genes.

Cell Rep 2019 03;26(11):3132-3144.e7

Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address:

Identification of human disease signature genes typically requires samples from many donors to achieve statistical significance. Here, we show that single-cell heterogeneity analysis may overcome this hurdle by significantly improving the test sensitivity. We analyzed the transcriptome of 39,905 single islets cells from 9 donors and observed distinct β cell heterogeneity trajectories associated with obesity or type 2 diabetes (T2D). We therefore developed RePACT, a sensitive single-cell analysis algorithm to identify both common and specific signature genes for obesity and T2D. We mapped both β-cell-specific genes and disease signature genes to the insulin regulatory network identified from a genome-wide CRISPR screen. Our integrative analysis discovered the previously unrecognized roles of the cohesin loading complex and the NuA4/Tip60 histone acetyltransferase complex in regulating insulin transcription and release. Our study demonstrated the power of combining single-cell heterogeneity analysis and functional genomics to dissect the etiology of complex diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2019.02.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6573026PMC
March 2019

Characteristics of pro- and anti-inflammatory cytokines alteration in PTSD patients exposed to a deadly earthquake.

J Affect Disord 2019 04 28;248:52-58. Epub 2019 Jan 28.

CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, 100049, China.

Background: Many studies have shown that the disturbance of pro-inflammatory and/or anti-inflammatory cytokines is involved in the modulation of traumatic stress and related psychiatric disorders, typically posttraumatic stress disorder (PTSD). However, the specific immune alterations associated with PTSD symptoms are still unclear. The present study compared levels of pro- and anti-inflammatory cytokines between PTSD and non-PTSD controls, and investigated the relationships of immune changes with PTSD symptomatology.

Methods: In this study, 51 earthquake-exposed PTSD patients and 136 earthquake-exposed healthy controls were recruited. We assessed trauma exposure, PTSD and depression severity, and quantified a panel of pro- inflammatory cytokines, including interleukin (IL)-1β, IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), interferon ϒ (IFN), and anti-inflammatory cytokines, including IL-4, IL-10 and IL-13 with enzyme-linked immunosorbent assays. Additionally, total pro-inflammatory cytokines score and total anti-inflammatory cytokines score were calculated to reflect the status of two balance system.

Results: Behavioral data showed that the PTSD group had greater severity of depression, as well as total symptoms and every symptom cluster in the seven-factor model of PTSD compared to the non-PTSD control group. Immune data showed that PTSD subjects had higher levels of IL-1β and TNFα, as well as total pro-inflammatory cytokine scores compared to controls, suggesting an increase of inflammatory activity in PTSD. In all subjects, the IL-1β levels were correlated with PCL scores, after controlling for covariates, including age, education, marital status and gender, trauma exposure severity and depression.

Limitations: The current study did not include a non-traumatized healthy control group, and PTSD was assessed using a self-reported measure.

Conclusions: Thus, by including a control group comprised entirely of earthquake-exposed individuals as means to discriminate specific alterations of cytokine levels in PTSD, these findings suggest that the increased inflammatory cytokines, especially IL-1β, may play a role in the pathophysiology of PTSD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2019.01.029DOI Listing
April 2019

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

Am J Epidemiol 2019 06;188(6):1033-1054

Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwz005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545280PMC
June 2019

Identification of deleterious and regulatory genomic variations in known asthma loci.

Respir Res 2018 Dec 12;19(1):248. Epub 2018 Dec 12.

Department of Biomedical and Molecular Sciences, Queen's University, Botterell Hall, Room 530 - 18 Stuart St, Kingston, ON, K7L3N6, Canada.

Background: Candidate gene and genome-wide association studies have identified hundreds of asthma risk loci. The majority of associated variants, however, are not known to have any biological function and are believed to represent markers rather than true causative mutations. We hypothesized that many of these associated markers are in linkage disequilibrium (LD) with the elusive causative variants.

Methods: We compiled a comprehensive list of 449 asthma-associated variants previously reported in candidate gene and genome-wide association studies. Next, we identified all sequence variants located within the 305 unique genes using whole-genome sequencing data from the 1000 Genomes Project. Then, we calculated the LD between known asthma variants and the sequence variants within each gene. LD variants identified were then annotated to determine those that are potentially deleterious and/or functional (i.e. coding or regulatory effects on the encoded transcript or protein).

Results: We identified 10,130 variants in LD (r > 0.6) with known asthma variants. Annotations of these LD variants revealed that several have potentially deleterious effects including frameshift, alternate splice site, stop-lost, and missense. Moreover, 24 of the LD variants have been reported to regulate gene expression as expression quantitative trait loci (eQTLs).

Conclusions: This study is proof of concept that many of the genetic loci previously associated with complex diseases such as asthma are not causative but represent markers of disease, which are in LD with the elusive causative variants. We hereby report a number of potentially deleterious and regulatory variants that are in LD with the reported asthma loci. These reported LD variants could account for the original association signals with asthma and represent the true causative mutations at these loci.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-018-0953-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292105PMC
December 2018

Differentiation between vestibular schwannomas and meningiomas with atypical appearance using diffusion kurtosis imaging and three-dimensional arterial spin labeling imaging.

Eur J Radiol 2018 Dec 12;109:13-18. Epub 2018 Oct 12.

Department of Radiology, Fujian Medical University Union Hospital, Fujian Medical University, Fuzhou, Fujian, China; School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, Fujian, China. Electronic address:

Purpose: An accurate differentiation between vestibular schwannomas (VS) and meningiomas is critical in determining treatment strategies and clinical prognoses. However, misdiagnoses may occur when typical imaging appearances are absent. The purpose of this study was to assess the performances of diffusion kurtosis imaging (DKI) and three-dimensional arterial spin labeling imaging (3D-ASL) in the differentiation of VS and meningiomas with atypical appearance.

Materials And Methods: Thirty-eight patients with pathologically proven VS and meningiomas were consecutively enrolled. All patients had no typical appearance and underwent DKI and 3D-ASL scan. Then, the DKI and 3D-ASL parameters were measured. Statistical analyses were performed using independent-sample t-tests, Mann-Whitney U tests and receiver operating characteristic (ROC) curve analyses.

Results: Mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), fractional anisotropy (FA) and cerebral blood flow (CBF) were significantly lower in VS than those in meningiomas, mean diffusivity (MD) were significantly higher in VS than that in meningiomas (all P < 0.05). ROC curve analyses showed that the diagnostic performance of kurtosis values outperformed those of other MR parameters. A cut-off RK value of 0.766 yielded a sensitivity of 91.67%, a specificity of 100.0%, and an accuracy of 94.74%, with an AUC of 0.988.

Conclusion: DKI and 3D-ASL are useful for differentiating VS and meningiomas with atypical appearance, with kurtosis values of DKI have the best diagnostic efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2018.10.009DOI Listing
December 2018

3.0T Contrast-enhanced whole-heart coronary magnetic resonance angiography for simultaneous coronary artery angiography and myocardial viability in chronic myocardial infarction: A single-center preliminary study.

Medicine (Baltimore) 2018 Nov;97(45):e13138

Department of Cardiology, Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.

To evaluate the accuracy of contrast-enhanced whole-heart magnetic resonance coronary angiography at 3.0T for assessing significant stenosis (≥50% lumen diameter reduction) in patients with myocardial infarction, by using conventional coronary artery angiography as the reference standard, and also test the performance of that for the detection and assessment of chronic myocardial infarction (MI), compared with standard delayed-enhancement coronary magnetic resonance (DE-CMR) for the determination of infarct size.We studied 42 consecutive patients (37 men, 5 women, mean age 58.5 ± 10.7 years) with MI scheduled for conventional coronary angiography. Contrast-enhanced whole-heart coronary magnetic resonance angiography (CMRA) was employed after sublingual nitroglycerin (NTG) with the abdominal banding rolled tightly along the side of ribs. Finally, a 3D phase-sensitive inversion-recovery gradient-echo (3D-PSIR-GRE) sequence was performed during free breathing. The assessment of MI sizes on WH-CMRA reconstructed images and 3D-PSIR-GRE images were compared using a paired student t test.The acquisition of CMRA was completed in 40 (95.2%) of 42 patients, with an imaging time averaged at 9.5 ± 3.1 minutes. The average navigator efficiency was 47%. The sensitivity, specificity, and positive and negative predictive values of whole-heart CMRA for the detection of significant lesions on a segment-by-segment analysis were 91.7% (95% confidence interval [CI] 83.8-96.1), 84.0% (95% CI 80.0-87.4), 57.9% (95% CI 50.0-65.8), 97.7% (95% CI 95.3-98.9), respectively, and on a patient-based analysis 93.5% (95% CI 77.2-98.9), 88.9% (95% CI 50.7-99.4), 96.7% (95% CI 80.9-99.8), and 80.0% (95% CI 44.2-96.5), respectively. Infarcts were generally higher on the CE-CMRA technique compared with the standard technique (18.0 ± 7.2 cm vs 16.1 ± 6.4 cm; P < .0001).Contrast-enhanced whole-heart CMRA with 3.0-T not only may permit reliable detection of significant obstructive coronary artery disease in patients with myocardial infarction, but also could identify and quantify the volume of myocardial infarction. This technique could be considered the preferred approach in patients who could not overcome longer scanning times or unable to hold their breath instead of delayed-enhancement magnetic resonance imaging for detection of infarcted myocardium. However, compared with standard imaging, the volume of myocardial infarction is slightly overestimated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000013138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250500PMC
November 2018

Analysis of genetic and nongenetic factors influencing triglycerides-lowering drug effects based on paired observations.

BMC Proc 2018 17;12(Suppl 9):46. Epub 2018 Sep 17.

1Department of Statistics, University of Nebraska, 340 Hardin Hall North Wing, Lincoln, NE 68588 USA.

Obesity is a risk factor for heart disease, stroke, diabetes, high blood pressure, and other chronic diseases. Some drugs, including fenofibrate, are used to treat obesity or excessive weight by lowering the level of specific triglycerides. However, different groups have different drug sensitivities and, consequently, there are differences in drug effects. In this study, we assessed both genetic and nongenetic factors that influence drug responses and stratified patients into groups based on differential drug effect and sensitivity. Our methodology of investigating genetic factors and nongenetic factors is applicable to studying differential effects of other drugs, such as statins, and provides an approach to the development of personalized medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12919-018-0153-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157156PMC
September 2018

Whole genome sequencing identifies high-impact variants in well-known pharmacogenomic genes.

Pharmacogenomics J 2019 04 14;19(2):127-135. Epub 2018 Sep 14.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

More than 1100 genetic loci have been correlated with drug response outcomes but disproportionately few have been translated into clinical practice. One explanation for the low rate of clinical implementation is that the majority of associated variants may be in linkage disequilibrium (LD) with the causal variants, which are often elusive. This study aims to identify and characterize likely causal variants within well-established pharmacogenomic genes using next-generation sequencing data from the 1000 Genomes Project. We identified 69,319 genetic variations within 160 pharmacogenomic genes, of which 8207 variants are in strong LD (r>0.8) with known pharmacogenomic variants. Of the latter, eight are coding or structural variants predicted to have high impact, with 19 additional missense variants that are predicted to have moderate impact. In conclusion, we identified putatively functional variants within known pharmacogenomics loci that could account for the association signals and represent the missing causative variants underlying drug response phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41397-018-0048-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417988PMC
April 2019

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Nat Commun 2018 07 30;9(1):2976. Epub 2018 Jul 30.

University of California Los Angeles, Los Angeles, CA, 90095, USA.

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-05369-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065313PMC
July 2018
-->