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  • Ovid Technologies (Wolters Kluwer Health)  (74)
  • 2020-2024  (74)
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  • Ovid Technologies (Wolters Kluwer Health)  (74)
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  • 2020-2024  (74)
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  • 1
    Online Resource
    Online Resource
    Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3–MAPK Signaling to Trigger Spontaneous Aortic Dissection
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Circulation Vol. 148, No. 7 ( 2023-08-15), p. 589-606
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 148, No. 7 ( 2023-08-15), p. 589-606
    Abstract: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive. METHODS: Smooth muscle cell–specific and endothelial cell–specific Best3 knockout mice (Best3 SMKO and Best3 ECKO , respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels. RESULTS: Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3 SMKO but not Best3 ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II–infused Best3 SMKO and ApoE −/− mice. CONCLUSIONS: These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3–MEKK2/3 signaling represents a novel therapeutic target for AD.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.122.063029
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1466401-X
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  • 2
    Online Resource
    Online Resource
    Dual Antiplatelet Therapies and Causes in Minor Stroke or Transient Ischemic Attack: A Prespecified Analysis in the CHANCE-2 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Abstract: It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II). METHODS: This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. Patients with centralized evaluation of TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification of large-artery atherosclerosis, small-vessel occlusion, and stroke of undetermined cause were included. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. Cox proportional hazards models were used to assess the interaction of TOAST classification with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin. RESULTS: A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63–1.18]; P =0.34); 32 (3.6%) and 61 (7.0%) patients with small-vessel occlusion (hazard ratio, 0.51 [95% CI, 0.33–0.79]; P =0.002); and 68 (4.8%) and 87 (5.9%) patients with stroke of undetermined cause (hazard ratio, 0.80 [95% CI, 0.58–1.10]; P =0.17), with P =0.08 for the treatment×cause subtype interaction effect. There were no significant differences in severe or moderate bleeding events in patients with different cause and different treatment. CONCLUSIONS: In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04078737.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.042233
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 3
    Online Resource
    Online Resource
    Validation and Disease Risk Assessment of Previously Reported Genome-Wide Genetic Variants Associated With Brugada Syndrome : SADS-TW BrS Registry
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation: Genomic and Precision Medicine Vol. 13, No. 4 ( 2020-08)
    Details
    In: Circulation: Genomic and Precision Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 13, No. 4 ( 2020-08)
    Abstract: Brugada syndrome (BrS) is an oligogenic arrhythmic disease with increased risk of sudden cardiac arrest. Several BrS or ECG traits-related single-nucleotide polymorphisms (SNPs) were identified through previous genome-wide association studies in white patients. We aimed to validate these SNPs in BrS patients in the Taiwanese population, assessing the cumulative effect of risk alleles and the BrS-polygenic risk score in predicting cardiac events. Methods: We genotyped 190 unrelated BrS patients using the TWB Array, and Taiwan Biobank was used as controls. SNPs not included in the array were imputed by IMPUTE2. Cox proportional hazards model was used to evaluate the associations between each particular SNP, the collective BrS-polygenic risk score, and clinical outcomes. Results: Of the 88 previously reported SNPs, 22 were validated in Taiwanese BrS patients ( P 〈 0.05). Of the 22 SNPs, 2 (rs10428132 and rs9388451) were linked with susceptibility to BrS, 10 were SNPs previously reaching genome-wide significance, and 10 were SNPs associated with ECG traits. For the 3 most commonly reported SNPs, disease risk increased consistently with the number of risk alleles (odds ratio, 3.54; P trend =1.38×10 −9 for 5 risk alleles versus 1). Similar patterns were observed in both SCN5A mutation+ (odds ratio, 3.66; P trend =0.049) and SCN5A mutation− (odds ratio, 3.75; P trend =8.54×10 −9 ) subgroups. Furthermore, BrS patients without SCN5A mutations had more risk alleles than BrS patients with SCN5A mutations regardless of the range of polygenic risk scores. Three SNPs (rs4687718, rs7784776, and rs2968863) showed significant associations with the composite outcome (sudden cardiac arrest plus syncope, hazard ratio, 2.13, 1.48, and 0.41; P =0.02, 0.006, and 0.008, respectively). Conclusions: Our findings suggested that some SNPs associated with BrS or ECG traits exist across multiple populations. The cumulative risk of the BrS-related SNPs is similar to that in white BrS patients, but it appears to correlate with the absence of SCN5A mutations.
    Type of Medium: Online Resource
    ISSN: 2574-8300
    URL: Article
    DOI: 10.1161/CIRCGEN.119.002797
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2927603-2
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  • 4
    Online Resource
    Online Resource
    Innate‐like bystander‐activated CD38+HLA‐DR+CD8+T cells play a pathogenic role in patients with chronic hepatitis C
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Hepatology Vol. 76, No. 3 ( 2022-09), p. 803-818
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 76, No. 3 ( 2022-09), p. 803-818
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    URL: Article
    DOI: 10.1002/hep.32349
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1472120-X
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  • 5
    Online Resource
    Online Resource
    Reciprocal Regulation Between Forkhead Box M1/NF‐κB and Methionine Adenosyltransferase 1A Drives Liver Cancer
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Hepatology Vol. 72, No. 5 ( 2020-11), p. 1682-1700
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 72, No. 5 ( 2020-11), p. 1682-1700
    Abstract: Forkhead box M1 (FOXM1) and nuclear factor kappa B (NF‐ĸB) are oncogenic drivers in liver cancer that positively regulate each other. We showed that methionine adenosyltransferase 1A (MAT1A) is a tumor suppressor in the liver and inhibits NF‐ĸB activity. Here, we examined the interplay between FOXM1/NF‐κB and MAT1A in liver cancer. Approach and Results We examined gene and protein expression, effects on promoter activities and binding of proteins to promoter regions, as well as effects of FOXM1 inhibitors T0901317 (T0) and forkhead domain inhibitory‐6 (FDI‐6) in vitro and in xenograft and syngeneic models of liver cancer. We found, in both hepatocellular carcinoma and cholangiocarcinoma, that an induction in FOXM1 and NF‐κB expression is accompanied by a fall in MATα1 (protein encoded by MAT1A). The Cancer Genome Atlas data set confirmed the inverse correlation between FOXM1 and MAT1A. Interestingly, FOXM1 directly interacts with MATα1 and they negatively regulate each other. In contrast, FOXM1 positively regulates p50 and p65 expression through MATα1, given that the effect is lost in its absence. FOXM1, MATα1, and NF‐κB all bind to the FOX binding sites in the FOXM1 and MAT1A promoters. However, binding of FOXM1 and NF‐κB repressed MAT1A promoter activity, but activated the FOXM1 promoter. In contrast, binding of MATα1 repressed the FOXM1 promoter. MATα1 also binds and represses the NF‐κB element in the presence of p65 or p50. Inhibiting FOXM1 with either T0 or FDI‐6 inhibited liver cancer cell growth in vitro and in vivo . However, inhibiting FOXM1 had minimal effects in liver cancer cells that do not express MAT1A. Conclusions We have found a crosstalk between FOXM1/NF‐κB and MAT1A. Up‐regulation in FOXM1 lowers MAT1A, but raises NF‐κB, expression, and this is a feed‐forward loop that enhances tumorigenesis.
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    URL: Article
    DOI: 10.1002/hep.31196
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1472120-X
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  • 6
    Online Resource
    Online Resource
    Rectal nonsteroidal anti-inflammatory drugs and pancreatic stents in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients : A network meta-analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Medicine Vol. 99, No. 42 ( 2020-10-16), p. e22672-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 42 ( 2020-10-16), p. e22672-
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000022672
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2049818-4
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  • 7
    Online Resource
    Online Resource
    The synergistic effect of full-spectrum light therapy and transient immunosuppressants prolonged allotransplant survival
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Plastic & Reconstructive Surgery
    Details
    In: Plastic & Reconstructive Surgery, Ovid Technologies (Wolters Kluwer Health)
    Abstract: The lifelong administration of immunosuppressants remains its largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model. Methods: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term anti-lymphocyte serum and cyclosporine-A. Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis. Results: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared to the control (group 1). However, group 4 with FBLT combined with short-term ALS/CsA significantly prolonged median composite tissue allograft survival time (266 days) compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) (p 〈 0.01). Group 4 also showed a significant increase in Treg cells (p = 0.04) and TGF-β1 levels (p = 0.02), and a trend toward a decrease in IL-1β levels (p = 0.03) at 16 weeks after transplantation as compared to control Group 1. Conclusions: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and anti-inflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival.
    Type of Medium: Online Resource
    ISSN: 0032-1052
    URL: Article
    DOI: 10.1097/PRS.0000000000011135
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2037030-1
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  • 8
    Online Resource
    Online Resource
    Acute Miliary Tuberculosis and Pelvic Tuberculosis after In vitro Fertilization
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Reproductive and Developmental Medicine Vol. 4, No. 2 ( 2020-04), p. 123-127
    Details
    In: Reproductive and Developmental Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 4, No. 2 ( 2020-04), p. 123-127
    Type of Medium: Online Resource
    ISSN: 2589-8728
    URL: Article
    DOI: 10.4103/2096-2924.288020
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 3046168-6
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  • 9
    Online Resource
    Online Resource
    Socioeconomic Status and Outcomes in Heart Failure With Reduced Ejection Fraction From Asia
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation: Cardiovascular Quality and Outcomes Vol. 14, No. 4 ( 2021-04)
    Details
    In: Circulation: Cardiovascular Quality and Outcomes, Ovid Technologies (Wolters Kluwer Health), Vol. 14, No. 4 ( 2021-04)
    Abstract: Little is known regarding the impact of socioeconomic factors on the use of evidence-based therapies and outcomes in patients with heart failure with reduced ejection fraction across Asia. Methods: We investigated the association of both patient-level (household income, education levels) and country-level (regional income level by World Bank classification, income disparity by Gini index) socioeconomic indicators on use of guideline-directed therapy and clinical outcomes (composite of 1-year mortality or HF hospitalization, quality of life) in the prospective multinational ASIAN-HF study (Asian Sudden Cardiac Death in Heart Failure). Results: Among 4540 patients (mean age: 60±13 years, 23% women) with heart failure with reduced ejection fraction, 39% lived in low-income regions; 34% in regions with high-income disparity (Gini ≥42.8%); 64.4% had low monthly household income ( 〈 US$1000); and 29.5% had no/only primary education. The largest disparity in treatment across regional income levels pertained to β-blocker and device therapies, with patients from low-income regions being less likely to receive these treatments compared with those from high-income regions and even greater disparity among patients with lower education status and lower household income within each regional income strata. Higher country- and patient-level socioeconomic indicators related to higher quality of life scores and lower risk of the primary composite outcome. Notably, we found a significant interaction between regional income level and both household income and education status ( P interaction 〈 0.001 for both), where the association of low household income and low education status with poor outcomes was more pronounced in high-income compared with lower income regions. Conclusions: These findings highlight the importance of socioeconomic determinants among patients with heart failure in Asia and suggest that attention should be paid to address disparities in access to care among the poor and less educated, including those from wealthy regions. Registration: URL: https://clinicaltrials.gov ; Unique Identifier: NCT01633398.
    Type of Medium: Online Resource
    ISSN: 1941-7713 , 1941-7705
    URL: Article
    DOI: 10.1161/CIRCOUTCOMES.120.006962
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2453882-6
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  • 10
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    Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph– high-risk B-cell acute lymphoblastic leukemia
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Chinese Medical Journal Vol. 135, No. 8 ( 2021-11-30), p. 930-939
    Details
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 135, No. 8 ( 2021-11-30), p. 930-939
    Abstract: Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph–) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph– high-risk B-ALL. Methods: This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+. Results: A total of 335 patients with Ph– high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%–34.7%) and 42.6% (35.5%–49.6%) in the HID and MSD groups (P  = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P  = 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%–25.4%) and 25.9% (19.9%–32.3%; P  = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%–74.4%) and 61.6% (54.2%–68.1%; P  = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%–70.7%) and 58.2% (50.8%–64.9%; P  = 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%–59.5%) and 37.8% (30.9%–44.6%; P  = 0.041), respectively, in the HID and MSD groups. Conclusion: HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph– high-risk B-ALL patients. Trial registration: ClinicalTrials.gov: NCT01883180, NCT02673008.
    Type of Medium: Online Resource
    ISSN: 0366-6999 , 2542-5641
    URL: Article
    DOI: 10.1097/CM9.0000000000001852
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2108782-9
    SSG: 6,25
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