CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein ${\alpha}$ ($SIRP{\alpha}$) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout ($CD47^{-/-}$ hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, $CD47^{-/-}$ mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male $CD47^{-/-}$ mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female $CD47^{-/-}$ mice became evident at 26 weeks, but splenomegaly was identified in both genders of $CD47^{-/-}$ mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of $CD47^{-/-}$ mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our $CD47^{-/-}$ mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.
Journal of the Korea Academia-Industrial cooperation Society
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v.20
no.1
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pp.85-95
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2019
Recently, studies on the fourth industrial revolution have been actively conducted in the areas of government, business, and academia. Corporate business models that utilize the major agendas of the fourth industrial revolution such as robots, artificial intelligence, Internet of things (IoT), and block chains have been created, and various changes have occurred in not only business, education, and living environments but also in international relations. In this study, we looked at changes in social contribution activities from the perspective of a company facing impacts of the fourth industrial revolution. This study examines the definition and activities of corporate social contribution and how we can contribute to society through corporate activities. 'AT Educom', LG Uplus 'Social Contribution through IoT', KT's anti-infectious disease prevention platform and cases of Intel using IoT. In addition, we have presented what we need to do in the future to promote corporate social contribution activities that will make more meaningful impacts on how corporate social contribution activities will change according to technology development. The first, measuring the performance of corporate social contribution activities needs a standardized methodology and social contribution activities through platform business and ICT should be actively pursued. Lastly, social contribution activities between companies and sectors will increase.
Kim, Bong Kyun;Jeong, Joon;Han, Wonshik;Yoon, Tae-In;Seong, Min-Ki;Jung, Jin Hyang;Jung, Sung Hoo;Lee, Jina;Sun, Woo Young;Korean Breast Cancer Society
Journal of Breast Disease
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v.6
no.2
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pp.60-72
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2018
Purpose: According to American Society of Clinical Oncology/College of American Pathologists guidelines, breast cancer is human epidermal growth factor receptor 2 (HER2) positive if there is HER2 protein overexpression at a 3+ level on immunohistochemistry (IHC 3+) or gene amplification (more than six copies per nucleus) on fluorescence in situ hybridization (FISH+). However, there have been few reports on whether outcomes differ based on diagnosis by these two techniques. In this study, we compared outcomes based on the two methods in patients with HER2-positive breast cancer. Methods: This study was a retrospective analysis of HER2-positive breast cancer in 18,304 patients, including 14,652 IHC 3+ patients and 3,652 FISH+ patients from the Korean Breast Cancer Society Registry. We compared breast cancer-specific survival and overall survival based on IHC 3+ and FISH+ status with or without trastuzumab. Results: Breast cancer-specific survival was significantly different between the IHC 3+ and FISH+ groups, with 5-year cumulative survival rates of 95.0% for IHC 3+ and 98.5% for FISH+ patients who did not receive trastuzumab (p=0.001) in Kaplan-Meier methods. However, there were no significant differences in breast cancer-specific survival and overall survival between IHC 3+ and FISH+ groups regardless of trastuzumab treatment in Cox proportional hazards models. Conclusion: The survival outcomes were not affected by the different two diagnostic methods of HER2-positive breast cancer. Further research to evaluate differences in prognosis and other characteristics according to the diagnostic methods of HER2 positivity is needed in the future.
Dehnokhalaji, Morteza;Golbakhsh, Mohammad Reza;Siavashi, Babak;Talebian, Parham;Javidmehr, Sina;Bozorgmanesh, Mohammadreza
Asian Spine Journal
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v.12
no.6
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pp.1060-1068
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2018
Study Design: Retrospective study. Purpose: Lumbar intervertebral disc degeneration is an important cause of low back pain. Overview of Literature: Spinal fusion is often reported to have a good course for adolescent idiopathic scoliosis (AIS). However, many studies have reported that adjacent segment degeneration is accelerated after lumbar spinal fusion. Radiography is a simple method used to evaluate the orientation of the vertebral column. magnetic resonance imaging (MRI) is the method most often used to specifically evaluate intervertebral disc degeneration. The Pfirrmann classification is a well-known method used to evaluate degenerative lumbar disease. After spinal fusion, an increase in stress, excess mobility, increased intra-disc pressure, and posterior displacement of the axis of motion have been observed in the adjacent segments. Methods: we retrospectively secured and analyzed the data of 15 patients (four boys and 11 girls) with AIS who underwent a spinal fusion surgery. We studied the full-length view of the spine (anterior-posterior and lateral) from the X-ray and MRI obtained from all patients before surgery. Postoperatively, another full-length spine X-ray and lumbosacral MRI were obtained from all participants. Then, pelvic tilt, sacral slope, curve correction, and fused and free segments before and after surgery were calculated based on X-ray studies. MRI images were used to estimate the degree to which intervertebral discs were degenerated using Pfirrmann grading system. Pfirrmann grade before and after surgery were compared with Wilcoxon signed rank test. While analyzing the contribution of potential risk factors for the post-spinal fusion Pfirrmann grade of disc degeneration, we used generalized linear models with robust standard error estimates to account for intraclass correlation that may have been present between discs of the same patient. Results: The mean age of the participant was 14 years, and the mean curvature before and after surgery were 67.8 and 23.8, respectively (p<0.05). During the median follow-up of 5 years, the mean degree of the disc degeneration significantly increased in all patients after surgery (p<0.05) with a Pfirrmann grade of 1 and 2.8 in the L2-L3 before and after surgery, respectively. The corresponding figures at L3-L4, L4-L5, and L5-S1 levels were 1.28 and 2.43, 1.07 and 2.35, and 1 and 2.33, respectively. The lower was the number of free discs below the fusion level, the higher was the Pfirrmann grade of degeneration (p<0.001). Conversely, the higher was the number of the discs fused together, the higher was the Pfirrmann grade. Conclusions: we observed that the disc degeneration aggravated after spinal fusion for scoliosis. While the degree of degeneration as measured by Pfirrmann grade was directly correlated by the number of fused segments, it was negatively correlated with the number of discs that remained free below the lowermost level of the fusion.
Objectives : Osteoporosis is a systemic skeletal disease that decreases bone density and increases the risk of fractures. Bisphosphonates and SERMs are mainly used to treat osteoporosis, but, long-term use increases the risk of side effects such as jaw bone necrosis and breast cancer. Therefore, it is necessary to develop a therapeutic agent for a natural product with few side effects. Water extract of Lonicerae Japonicae Flos (wLF) was mainly found to have anti-cancer and anti-inflammatory effects. However, the effect of wLF on osteoporosis has not been elucidated. Therefore, this experiment investigated the effect of wLF on osteoclasts, osteoblasts and osteoporosis models. Methods : In order to study the effect of wLF on osteoporosis, the OVX-induced rat model was used for in vivo study. After 8 weeks, we measured body weight, uterine weight, liver weight, femur weight, bone density, trabecular area and tibia ash weight. To determine the effect of wLF on osteoclast differentiation, we measured the number of TRAP-positive cells and TRAP activity. To examine the effect of wLF on the expression of osteoblast-related genes, we measured the mRNA expression of alkaline phosphatase (ALP, Alpl) and osteocalcin (OCN, Bglap2). Results : In vivo experiment, wLF inhibited the reduction of femur weight, trabecular area, bone density and tibia ash weight. In vitro experiment, wLF had no significant effect on osteoclast differentiation. However, wLF increased the mRNA expression of Alpl and Bglap2 in MC3T3-E1 cell. Conclusions : This result suggested that wLF may be used for the treatment and prevention of postmenopausal osteoporosis.
Lee, Soobin;Kim, Seongdeok;Lee, Juhee;Ko, Youngsoo;Song, Min
Journal of the Korean Society for information Management
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v.38
no.2
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pp.153-172
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2021
This study is to create a deep learning based classification model to examine the characteristics of panic disorder and to classify the panic disorder tendency literature by the panic disorder corpus constructed for the present study. For this purpose, 5,884 documents of the panic disorder corpus collected from social media were directly annotated based on the mental disease diagnosis manual and were classified into panic disorder-prone and non-panic-disorder documents. Then, TF-IDF scores were calculated and word co-occurrence analysis was performed to analyze the lexical characteristics of the corpus. In addition, the co-occurrence between the symptom frequency measurement and the annotated symptom was calculated to analyze the characteristics of panic disorder symptoms and the relationship between symptoms. We also conducted the performance evaluation for a deep learning based classification model. Three pre-trained models, BERT multi-lingual, KoBERT, and KcBERT, were adopted for classification model, and KcBERT showed the best performance among them. This study demonstrated that it can help early diagnosis and treatment of people suffering from related symptoms by examining the characteristics of panic disorder and expand the field of mental illness research to social media.
Journal of the Korean Association of Geographic Information Studies
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v.24
no.1
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pp.92-111
/
2021
As fine dust negatively affects disease, industry and economy, the people are sensitive to fine dust. Therefore, if the occurrence of fine dust can be predicted, countermeasures can be prepared in advance, which can be helpful for life and economy. Fine dust is affected by the weather and the degree of concentration of fine dust emission sources. The industrial sector has the largest amount of fine dust emissions, and in industrial complexes, factories emit a lot of fine dust as fine dust emission sources. This study targets regions with old industrial complexes in local cities. The purpose of this study is to explore the factors that cause fine dust and develop a predictive model that can predict the occurrence of fine dust. weather data and fine dust data were used, and variables that influence the generation of fine dust were extracted through multiple regression analysis. Based on the results of multiple regression analysis, a model with high predictive power was extracted by learning with a machine learning regression learner model. The performance of the model was confirmed using test data. As a result, the models with high predictive power were linear regression model, Gaussian process regression model, and support vector machine. The proportion of training data and predictive power were not proportional. In addition, the average value of the difference between the predicted value and the measured value was not large, but when the measured value was high, the predictive power was decreased. The results of this study can be developed as a more systematic and precise fine dust prediction service by combining meteorological data and urban big data through local government data hubs. Lastly, it will be an opportunity to promote the development of smart industrial complexes.
Wabo, Therese Martin Cheteu;Wu, Xiaoyan;Sun, Changhao;Boah, Michael;Nkondjock, Victorine Raissa Ngo;Cheruiyot, Janet Kosgey;Adjei, Daniel Amporfro;Shah, Imranulllah
Nutrition Research and Practice
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v.16
no.1
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pp.74-93
/
2022
BACKGROUND/OBJECTIVES: There has been an increased interest in determining calcium magnesium, sodium, and potassium's distinct effects on hypertension over the past decade, yet they simultaneously regulate blood pressure. We aimed at examining the association of dietary calcium, magnesium, sodium, and potassium independently and jointly with hypertension using National Health and Nutrition Examination Survey data from 2007 to 2014. MATERIALS/METHODS: The associations were examined on a large cross-sectional study involving 16684 US adults aged>20 years, using multivariate analyses with logistical models. RESULTS: Sodium and calcium quartiles assessed alone were not associated with hypertension. Potassium was negatively associated with hypertension in the highest quartile, 0.64 (95% confidence interval [CI], 0.48-0.87). When jointly assessed using the high and low cut-off points, low sodium and corresponding high calcium, magnesium, and potassium intake somewhat reduced the odds of hypertension 0.39 (95% CI, 0.20-0.76). The sodium-to-potassium ratio was positively associated with hypertension in the highest quartile1.50 (95% CI, 1.11-2.02). When potassium was adjusted for sodium intake and sodium-to-potassium ratio assessed among women, increased odds of hypertension were reported in the highest quartile as 2.02 (95% CI, 1.18-3.34) and 1.69 (95% CI, 1.12-2.57), respectively. The association of combined minerals on hypertension using dietary goals established that men meeting the reference intakes for calcium and exceeding for magnesium had reduced odds of hypertension 0.51 (95% CI, 0.30-0.89). Women exceeding the recommendations for both calcium and magnesium had the lower reduced odds of 0.30 (95% CI, 0.10-0.69). CONCLUSIONS: Our results suggest that the studied minerals' association on hypertension is stronger when jointly assessed, mostly after gender stratification. As compared to men, women increased their risk of hypertension even with a low sodium intake. Women would also reasonably reduce their risk of developing hypertension by increasing calcium and magnesium intake. In comparison, men would somewhat be protected from developing hypertension with calcium intake meeting the dietary goals and magnesium exceeding the nutritional goals.
This study aimed to investigate the effects and potential mechanisms of Chikusetsusaponin V (CsV) on endothelial nitric oxide synthase (eNOS) and vascular endothelial cell functions. Different concentrations of CsV were added to animal models, bovine aorta endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) cultured in vitro. qPCR, Western blotting (WB), and B ultrasound were performed to explore the effects of CsV on mouse endothelial cell functions, vascular stiffness and cellular eNOS mRNA, protein expression and NO release. Bioinformatics analysis, network pharmacology, molecular docking and protein mass spectrometry analysis were conducted to jointly predict the upstream transcription factors of eNOS. Furthermore, pulldown and ChIP and dual luciferase assays were employed for subsequent verification. At the presence or absence of CsV stimulation, either overexpression or knockdown of purine rich element binding protein A (PURA) was conducted, and PCR assay was employed to detect PURA and eNOS mRNA expressions, Western blot was used to detect PURA and eNOS protein expressions, cell NO release and serum NO levels. Tube formation experiment was conducted to detect the tube forming capability of HUVECs cells. The animal vasodilation function test detected the vasodilation functions. Ultrasonic detection was performed to determine the mouse aortic arch pulse wave velocity to identify aortic stiffness. CsV stimulus on bovine aortic cells revealed that CsV could upregulate eNOS protein levels in vascular endothelial cells in a concentration and time dependent manner. The expression levels of eNOS mRNA and phosphorylation sites Ser1177, Ser633 and Thr495 increased significantly after CsV stimulation. Meanwhile, CsV could also enhance the tube forming capability of HUVECs cells. Following the mice were gavaged using CsV, the eNOS protein level of mouse aortic endothelial cells was upregulated in a concentration- and time-dependent manner, and serum NO release and vasodilation ability were simultaneously elevated whereas arterial stiffness was alleviated. The pulldown, ChIP and dual luciferase assays demonstrated that PURA could bind to the eNOS promoter and facilitate the transcription of eNOS. Under the conditions of presence or absence of CsV stimulation, overexpression or knockdown of PURA indicated that the effect of CsV on vascular endothelial function and eNOS was weakened following PURA gene silence, whereas overexpression of PURA gene could enhance the effect of CsV upregulating eNOS expression. CsV could promote NO release from endothelial cells by upregulating the expression of PURA/eNOS pathway, improve endothelial cell functions, enhance vasodilation capability, and alleviate vessel stiffness. The present study plays a role in offering a theoretical basis for the development and application of CsV in vascular function improvement, and it also provides a more comprehensive understanding of the pharmacodynamics of CsV.
Chang, Yoo Jin;Bae, Jihyeon;Zhao, Yang;Lee, Geonseong;Han, Jeongpil;Lee, Yoon Hoo;Koo, Ok Jae;Seo, Sunmin;Choi, Yang-Kyu;Yeom, Su Cheong
Journal of Veterinary Science
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v.21
no.2
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pp.26.1-26.14
/
2020
Pancreatic ductal adenocarcinoma is a lethal cancer type that is associated with multiple gene mutations in somatic cells. Genetically engineered mouse is hardly applicable for developing a pancreatic cancer model, and the xenograft model poses a limitation in the reflection of early stage pancreatic cancer. Thus, in vivo somatic cell gene engineering with clustered regularly interspaced short palindromic repeats is drawing increasing attention for generating an animal model of pancreatic cancer. In this study, we selected Kras, Trp53, Ink4a, Smad4, and Brca2 as target genes, and applied Campylobacter jejuni Cas9 (CjCas9) and Streptococcus pyogens Cas9 (SpCas9) for developing pancreatic cancer using adeno associated virus (AAV) transduction. After confirming multifocal and diffuse transduction of AAV2, we generated SpCas9 overexpression mice, which exhibited high double-strand DNA breakage (DSB) in target genes and pancreatic intraepithelial neoplasia (PanIN) lesions with two AAV transductions; however, wild-type (WT) mice with three AAV transductions did not develop PanIN. Furthermore, small-sized Cjcas9 was applied to WT mice with two AAV system, which, in addition, developed high extensive DSB and PanIN lesions. Histological changes and expression of cancer markers such as Ki67, cytokeratin, Mucin5a, alpha smooth muscle actin in duct and islet cells were observed. In addition, the study revealed several findings such as 1) multiple DSB potential of AAV-CjCas9, 2) peri-ductal lymphocyte infiltration, 3) multi-focal cancer marker expression, and 4) requirement of > 12 months for initiation of PanIN in AAV mediated targeting. In this study, we present a useful tool for in vivo cancer modeling that would be applicable for other disease models as well.
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