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  • 1
    In: Laboratory Animal Research, Springer Science and Business Media LLC, Vol. 38, No. 1 ( 2022-12)
    Abstract: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.
    Type of Medium: Online Resource
    ISSN: 2233-7660
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2623220-0
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  • 2
    In: Diagnostic Pathology, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2020-12)
    Abstract: The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials. Methods We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines. Results PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. “Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8 +/low tumor-infiltrating lymphocytes (TILs),” and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3 +/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3 +/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(−) cell lines. Conclusions The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of “tumoral PD-L1/immune cell PD-L1/CD8 + TILs” may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(−)/CD8 +/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.
    Type of Medium: Online Resource
    ISSN: 1746-1596
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2210518-9
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  • 3
    In: Endocrinology and Metabolism, Korean Endocrine Society, Vol. 36, No. 6 ( 2021-12-31), p. 1189-1200
    Abstract: Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.Results: rs12803256, in the actin epsilon 1, pseudogene ( 〈 i 〉 ACTE1P 〈 /i 〉 ) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B ( 〈 i 〉 PDE3B 〈 /i 〉 ) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase ( 〈 i 〉 NADSYN1 〈 /i 〉 ) and 7-dehydrocholesterol reductase ( 〈 i 〉 DHCR7 〈 /i 〉 ), showed significantly different expression according to alleles.Conclusion: The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, 〈 i 〉 PDE3B 〈 /i 〉 , 〈 i 〉 NADSYN1 〈 /i 〉 , and 〈 i 〉 ACTE1P 〈 /i 〉 genes. The biological mechanism of a non-coding SNP (rs12803256) for 〈 i 〉 DHCR7 〈 /i 〉 / 〈 i 〉 NADSYN1 〈 /i 〉 on vitamin D concentrations is unclear, warranting further investigations.
    Type of Medium: Online Resource
    ISSN: 2093-596X , 2093-5978
    Language: English
    Publisher: Korean Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2802452-7
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  • 4
    In: World Allergy Organization Journal, Elsevier BV, Vol. 17, No. 2 ( 2024-02), p. 100871-
    Type of Medium: Online Resource
    ISSN: 1939-4551
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 2581968-9
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2019
    In:  Knee Surgery, Sports Traumatology, Arthroscopy Vol. 27, No. 7 ( 2019-7), p. 2082-2089
    In: Knee Surgery, Sports Traumatology, Arthroscopy, Springer Science and Business Media LLC, Vol. 27, No. 7 ( 2019-7), p. 2082-2089
    Type of Medium: Online Resource
    ISSN: 0942-2056 , 1433-7347
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 1473170-8
    SSG: 31
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Genetics Vol. 11 ( 2020-12-21)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 11 ( 2020-12-21)
    Abstract: Multiple studies have demonstrated the effects of type 2 diabetes (T2D) on various human diseases; however, most of these were observational epidemiological studies that suffered from many potential biases including reported confounding and reverse causations. In this article, we investigated whether cancer and vascular disease can be affected by T2D-related traits, including fasting plasma glucose (FPG), 2-h postprandial glucose (2h-PG), and glycated hemoglobin A1c (HbA1c) levels, by using Mendelian randomization (MR). The summary statistics for FPG, 2h-PG, and HbA1c level were obtained through meta-analyses of large-scale genome-wide association studies that included data from 133,010 nondiabetic individuals from collaborating Meta-analysis of Glucose and Insulin Related Traits Consortium studies. Thereafter, based on the statistical assumptions for MR analyses, the most reliable approaches including inverse-variance-weighted (IVW), MR-Egger, MR-Egger with a simulation extrapolation (SIMEX), weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were applied to identify traits affected by FPG, 2h-PG, and HbAlc. We found that coronary artery disease is affected by FPG, as per the IVW [log odds ratio (logOR): 0.21; P = 0.012], MR-Egger (SIMEX) (logOR: 0.22; P = 0.014), MR-PRESSO (logOR: 0.18; P = 0.045), and weighted median (logOR: 0.29; P & lt; 0.001) methods but not as per the MR-Egger (logOR: 0.13; P = 0.426) approach. Furthermore, low-density lipoprotein cholesterol levels are affected by HbA1c, as per the IVW [beta (B): 0.23; P = 0.015), MR-Egger (B: 0.45; P = 0.046), MR-Egger (SIMEX) (B: 0.27; P = 0.007), MR-PRESSO (B; 0.14; P = 0.010), and the weighted median (B: 0.15; P = 0.012] methods. Further studies of the associated biological mechanisms are required to validate and understand the disease-specific differences identified in the TD2-related causal effects of each trait.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606823-0
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  • 7
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-04-28)
    Abstract: Peritoneal recurrence (PR) is a major relapse pattern of colorectal cancer (CRC). We investigated whether peritoneal immune cytokines can predict PR. Cytokine concentrations of peritoneal fluid from CRC patients were measured. Patients were grouped according to peritoneal cancer burden (PCB): no tumor cells (≤ pT3), microscopic tumor cells (pT4), or gross tumors (M1c). Cytokine concentrations were compared among the three groups and the associations of those in pT4 patients with and without postoperative PR were assessed. Of the ten cytokines assayed, IL6, IL10, and TGFB1 increased with progression of PCB. Among these, IL10 was a marker of PR in pT4 (N = 61) patients based on ROC curve ( p  = 0.004). The IL10 cut-off value (14 pg/mL) divided patients into groups with a low (7%, 2 of 29 patients) or high (45%, 16 of 32 patients) 5-year PR ( p   〈  0.001). Multivariable analysis identified high IL10 levels as the independent risk factor for PR. Separation of patients into training and test sets to evaluate the performance of IL10 cut-off model validated this cytokine as a risk factor for PR. Peritoneal IL10 is a prognostic marker of PR in pT4 CRC. Further research is necessary to identify immune response of intraperitoneal CRC growth.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 8
    Online Resource
    Online Resource
    SAGE Publications ; 2021
    In:  Orthopaedic Journal of Sports Medicine Vol. 9, No. 5 ( 2021-05-01), p. 232596712110022-
    In: Orthopaedic Journal of Sports Medicine, SAGE Publications, Vol. 9, No. 5 ( 2021-05-01), p. 232596712110022-
    Abstract: Studies have reported that opening wedge high tibial osteotomy (OWHTO) without bone grafting has outcomes that are similar to or even better than those of OWHTO with bone grafting, especially after use of a locking plate. However, a consensus on managing the gap after OWHTO has not been established. Purpose: To determine the degree of gap healing achieved without bone grafting, the factors associated with gap healing, and whether additional gap healing would be obtained after plate removal. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective study included 73 patients who underwent OWHTO without bone grafting between 2015 and 2018. Patients in the study were divided into 2 groups based on the correction angle: small correction group ( 〈 10°; SC group) and large correction group (≥10°; LC group). The locking plate used in OWHTO was removed at a mean of 13.5 months after surgery in 65 patients. Radiographic indexes were measured: gap filling height, gap vacancy ratio (GVR), and osteotomy filling index. The acceptable gap healing was defined as an osteotomy filling index ≥3. The factors related to gap healing around the osteotomy site were selected after multicollinearity analysis. Results: Although both groups achieved acceptable gap healing regardless of the correction angle, the SC group showed higher and earlier gap healing than did the LC group (gap healing rate 81.4% in the SC group vs 41.7% in the LC group at 3 months postoperatively). The GVR was 8.6% in the SC group and 15.3% in the LC group at 12 months after surgery ( P = .005). Both the amount of time that elapsed after surgery and the correction angle were associated with gap healing ( P 〈 .05). Additional gap healing was observed after plate removal, as the GVR decreased 2.7% more in the patients with plate removal than in patients who did not have plate removal ( P = .012). Conclusion: All patients achieved acceptable gap healing without bone graft. The degree of gap healing was higher in the SC group and increased over time. Gap healing was promoted after plate removal. Considering the results of this study, a bone graft is not necessary in routine OWHTO in terms of gap healing.
    Type of Medium: Online Resource
    ISSN: 2325-9671 , 2325-9671
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2706251-X
    SSG: 31
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  • 9
    In: BMC Medicine, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-01-11)
    Abstract: The pathogenesis of diabetic kidney disease (DKD) is complex, involving metabolic and hemodynamic factors. Although DKD has been established as a heritable disorder and several genetic studies have been conducted, the identification of unique genetic variants for DKD is limited by its multiplex classification based on the phenotypes of diabetes mellitus (DM) and chronic kidney disease (CKD). Thus, we aimed to identify the genetic variants related to DKD that differentiate it from type 2 DM and CKD. Methods We conducted a large-scale genome-wide association study mega-analysis, combining Korean multi-cohorts using multinomial logistic regression. A total of 33,879 patients were classified into four groups—normal, DM without CKD, CKD without DM, and DKD—and were further analyzed to identify novel single-nucleotide polymorphisms (SNPs) associated with DKD. Additionally, fine-mapping analysis was conducted to investigate whether the variants of interest contribute to a trait. Conditional analyses adjusting for the effect of type 1 DM (T1D)-associated HLA variants were also performed to remove confounding factors of genetic association with T1D. Moreover, analysis of expression quantitative trait loci (eQTL) was performed using the Genotype-Tissue Expression project. Differentially expressed genes (DEGs) were analyzed using the Gene Expression Omnibus database ( GSE30529 ). The significant eQTL DEGs were used to explore the predicted interaction networks using search tools for the retrieval of interacting genes and proteins. Results We identified three novel SNPs [rs3128852 ( P = 8.21×10 −25 ), rs117744700 ( P = 8.28×10 −10 ), and rs28366355 ( P = 2.04×10 −8 )] associated with DKD. Moreover, the fine-mapping study validated the causal relationship between rs3128852 and DKD. rs3128852 is an eQTL for TRIM27 in whole blood tissues and HLA-A in adipose-subcutaneous tissues. rs28366355 is an eQTL for HLA-group genes present in most tissues. Conclusions We successfully identified SNPs (rs3128852, rs117744700, and rs28366355) associated with DKD and verified the causal association between rs3128852 and DKD. According to the in silico analysis, TRIM27 and HLA-A can define DKD pathophysiology and are associated with immune response and autophagy. However, further research is necessary to understand the mechanism of immunity and autophagy in the pathophysiology of DKD and to prevent and treat DKD.
    Type of Medium: Online Resource
    ISSN: 1741-7015
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2131669-7
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  • 10
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-03-03)
    Abstract: Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass. As the genetic biomarkers for sarcopenia are not yet well characterised, this study aimed to investigate the genetic variations related to sarcopenia in a relatively aged cohort, using genome-wide association study (GWAS) meta-analyses of lean body mass (LBM) in 6961 subjects. Two Korean cohorts were analysed, and subgroup GWAS was conducted for appendicular skeletal muscle mass (ASM) and skeletal muscle index. The effects of significant single nucleotide polymorphisms (SNPs) on gene expression were also investigated using multiple expression quantitative trait loci datasets, differentially expressed gene analysis, and gene ontology analyses. Novel genetic biomarkers were identified for LBM (rs1187118; rs3768582) and ASM (rs6772958). Their related genes, including RPS10 , NUDT3 , NCF2 , SMG7, and ARPC5 , were differently expressed in skeletal muscle tissue, while GPD1L was not. Furthermore, the ‘ mRNA destabilisation ’ biological process was enriched for sarcopenia. Our study identified RPS10 , NUDT3, and GPD1L as significant genetic biomarkers for sarcopenia. These genetic loci were related to lipid and energy metabolism, suggesting that genes involved in metabolic dysregulation may lead to the pathogenesis of age-related sarcopenia.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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