334 results on '"KE Kim"'
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2. Dietary Effects of Natural Polyphenol Antioxidant on Laying Performance and Egg Quality of Laying Hens Fed Diets with Oxidized Oil
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HH Lee, DH Kim, KW Lee, KE Kim, DE Shin, and BK An
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Laying hens ,oxidized oil ,natural antioxidants ,vitamin E ,egg quality ,Animal culture ,SF1-1100 ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
ABSTRACT This study was conducted to investigate the effects of dietary oxidized oil and natural polyphenol antioxidants on laying performances and egg quality of laying hens. A total of two hundred, 61-week-old Lohmann Brown laying hens were divided into five groups, consisting in four replicates of 10 birds each. They were fed one of the five experimental diets (fresh oil only, oxidized oil without antioxidants, oxidized oil with vitamin E 200 ppm, oxidized oil with vitamin E 100 ppm + Cabanin CSDⓇ 100 ppm, oxidized oil with Cabanin CSDⓇ 500 ppm)respectively, for 6 weeks. There were no significant differences in laying performances and egg weight among the treatments. However, egg mass in group fed oxidized oil with vitamin E 100 ppm + Cabanin CSDⓇ 100 ppmwas significantly higher than group fed oxidized oil only (p
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- 2019
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3. Effects of β-mannanase on Egg Production Performance, Egg Quality, Intestinal Microbiota, Viscosity, and Ammonia Concentration in Laying Hens
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L Zheng, SH Cho, CW Kang, KW Lee, KE Kim, and BK An
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β-mannanase ,egg quality,laying hens ,metabolizable energy ,performance ,Animal culture ,SF1-1100 ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
ABSTRACT Two experiments were conducted to evaluate the effects of β-mannanase on egg production performance, egg quality, intestinal microbiota, viscosity, and ammonia concentration in laying hens. In Exp. 1, two hundred and seventy 30-wk-old Hy-Line Brown laying hens were assigned to 6 diets arranged in a 3 × 2 factorial of three levels of MEn and CP [(a corn-soybean meal based diet (HEHP), a diet containing 50 kcal of MEn/kg and 1.0% less energy and CP than the HEHP (MEMP), and a diet containing 80 kcal of MEn/kg and 1.5% less energy and CP than HEHP (LELP)], and β-mannanase supplementation (0 or 0.04%). In Exp. 2, A total of two hundred and sixteen62-wk-old Hy-Line Brown laying hens were assigned to 6 dietary treatments in a 3 × 2 factorial arrangement. In Exp. 1, β-mannanase supplementation increased egg production rate in hens fed LELP diet, but not in those fed HEHP or MEMP diet (interaction, p
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4. Impact of targeted drug administration and intermittent preventive treatment for forest goers using artesunate–pyronaridine to control malaria outbreaks in Cambodia
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Dysoley Lek, Nguon Sokomar, Top Samphornarann, Jeanne Rideout, Saad El-Din Hassan, Tol Bunkea, Saing Sam Ath, Rothpisey Seng, John Hustedt, Thomas J. Peto, Jayme Hughes, Ke Kimmen, Khoy Dy, and Bipin Adhikari
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Targeted drug administration ,Intermittent preventive treatment ,Outbreak response, forest goers ,Artesunate–pyronaridine ,Cambodia ,Arctic medicine. Tropical medicine ,RC955-962 - Abstract
Abstract Introduction The national malaria programme of Cambodia targets the rapid elimination of all human malaria by 2025. As clinical cases decline to near-elimination levels, a key strategy is the rapid identification of malaria outbreaks triggering effective action to interrupt local transmission. We report a comprehensive, multipronged management approach in response to a 2022 Plasmodium falciparum outbreak in Kravanh district, western Cambodia. Methods The provincial health department of Pursat in conjunction with the Center for Parasitology, Entomology and Malaria Control (CNM) identified villages where transmission was occurring using clinical records, and initiated various interventions, including the distribution of insecticide-treated bed nets, running awareness campaigns, and implementing fever screening with targeted drug administration. Health stations were set up at forest entry points, and later, targeted drug administrations with artesunate–pyronaridine (Pyramax) and intermittent preventive treatment for forest goers (IPTf) were implemented in specific village foci. Data related to adherence and adverse events from IPTf and TDA were collected. The coverage rates of interventions were calculated, and local malaria infections were monitored. Results A total of 942 individuals were screened through active fever surveillance in villages where IPTf and TDA were conducted. The study demonstrated high coverage and adherence rates in the targeted villages, with 92% (553/600) coverage in round one and 65% (387/600) in round two. Adherence rate was 99% (551/553) in round one and 98% (377/387) in round two. The study found that forest goers preferred taking Pyramax over repeated testing consistent with the coverage rates: 92% in round one compared to 65% in round two. All individuals reachable through health stations or mobile teams reported complete IPTf uptake. No severe adverse events were reported. Only six individuals reported mild adverse events, such as loss of energy, fever, abdominal pain, diarrhoea, and muscle aches. Two individuals attributed their symptoms to heavy alcohol intake following prophylaxis. Conclusions The targeted malaria outbreak response demonstrated high acceptability, safety, and feasibility of the selected interventions. Malaria transmission was rapidly controlled using the available community resources. This experience suggests the effectiveness of the programmatic response for future outbreaks.
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- 2024
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5. Abstract P4-14-15: Prospective study analyzing value of breast Density change predicting ENdocrine therapy response in postmenopausal women taking adjuvant ARomatase inhibitor [DEAR study] (interim analysis)
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Y Kim, Ke Kim, H-G Moon, JG Jung, Eunsik Lee, D-Y Noh, YW Ju, Wonshik Han, and H-B Lee
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Oncology ,Cancer Research ,medicine.medical_specialty ,Postmenopausal women ,Aromatase inhibitor ,medicine.drug_class ,business.industry ,medicine.medical_treatment ,Endocrine therapy ,Interim analysis ,Internal medicine ,medicine ,Breast density ,Prospective cohort study ,business ,Value (mathematics) ,Adjuvant - Abstract
Objective : To evaluate the value of breast density change of mammography and breast MRI as a predictive marker for a response to postoperative anti-hormone therapy by targeting ER-positive postmenopausal breast cancer patient Methods : Density change of mammography, breast MRI density being taken just before start of anti-hormone therapy, mammography being performed after 6 months, 1 year, 2 years thereafter and breast MRI being performed 1 year after start of therapy will be measured by volpara and 3D-MR method. Molecular profile including ER expression level that has a relation with response rate to anti-hormone therapy will be analyzed and outcome will be evaluated based on disease free survival and overall survival. Recurrence rate of each group was estimated based on the data of the patients in breast center of Seoul National University Hospital, 2006-2011, who underwent surgery of ER-positive breast cancer. Among 1065 persons, 7.5% (80/1065) showed recurrence rate and among these, recurrence rate of patients who took AI was 6.9% (12/175). Among these, based on MDR 5% cutoff, 1.6% vs 9.8% was represented. By designating recurrence rate as 1.5%, 9.5% and assuming dropout rate by refusal to clinical test as 10%, registration goal was set at total 411 persons based on each 137, 274 persons per each group. Results : (this is interim analysis) From 2012, total 156 patients are enrolled, among them, 32 patients were eliminated (affirmative consent, switched to Tamoxifen, recurrence and etc). From now total 124 patients are on-going to this study. Compare with Non AI group, breast density change of AI group is much decreased from base line study and it is statistically significant. (1 year follow up – base line, 2 year follow up– base line ; -12.2%, - 18.6% vs - 7.6%, -15.3% P-value 0.002, 0.009 respectively) Only one patient was relapsed within 5 year and there were no death. Psychological anxiety, medication compliance and side effects analysis were done. Psychological anxiety about disease and medication were improved as time goes by (p Discussion : 70% of breast cancer is ER-positive breast cancer. Endocrine therapy (ET) has been clarified as an effective target therapy in large scale, prospective randomized trial and up to the present, it has been settled down as a standard therapeutic method of ER-positive breast cancer. As a result of 20 years' follow-up after intake of AI (aromatase inhibitor) and 20 years' follow-up after intake of tamoxifen, recurrence was represented as 2-2.5% and at present, clear mechanism of such resistance and predictive biomarker have not been clarified. Due to this resistance, all the ER-positive breast cancer patients are forced to receive anti-hormone therapy for 5 years or 10 years. According to the taking AI, breast density is significantly decreased compare Non AI group. Of course need more follow up data and analysis, but we can confirm a meaning of endocrine responsiveness of breast density change being measured after anti-hormone therapy as predictive surrogate. Citation Format: Kim Y, Lee E, Lee H-B, Kim KE, Ju YW, Jung JG, Moon H-G, Noh D-Y, Han W. Prospective study analyzing value of breast Density change predicting ENdocrine therapy response in postmenopausal women taking adjuvant ARomatase inhibitor [DEAR study] (interim analysis) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-15.
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- 2019
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6. Abstract P2-14-15: Breast cancer-related lymphedema: Morbidity of sentinel node biopsy
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D-Y Noh, Wonshik Han, H-G Moon, YW Ju, Eunsik Lee, Ke Kim, H-B Lee, JG Jung, and Y Kim
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Cancer Research ,medicine.medical_specialty ,Univariate analysis ,business.industry ,Breast surgery ,medicine.medical_treatment ,Sentinel lymph node ,Axillary Lymph Node Dissection ,Cancer ,Sentinel node ,medicine.disease ,humanities ,body regions ,Lymphedema ,Breast cancer ,Oncology ,hemic and lymphatic diseases ,medicine ,Radiology ,business - Abstract
Purpose: Sentinel lymph node biopsy (SLNB) lowers morbidity of lymphedema then axillary lymph node dissection (ALND). However, there has been concern about incidence of lymphedema after SLNB especially when the number of harvested nodes during sentinel node biopsy procedure is more than a few. In this study, we assessed lymphedema incidence and its risk factors including the number excised lymph nodes in patients who underwent SLNB. Methods: Between January, 2011 and April, 2012, the records of 910 consecutive patients who underwent breast surgery with axillary staging (SLNB/ALND) for breast cancer at Seoul National University Hospital were reviewed. Lymphedema was assessed by circumferential upper extremity measurements. The lymphedema was defined as > 1cm for either the upper arm or the forearm. Patients with clinical records of the treatment for lymphedema in the rehabilitation clinic were regarded as having lymphedema. Univariate and multivariate analyses were performed to identify potential risk factors associated with lymphedema. Association of number of excised lymph nodes with lymphedema was analyzed by Spearman rank correlation coefficient. Results: At median follow-up of 69.8 months, 231 patients (25.4%) presented with lymphedema. In univariate analysis, body mass index (BMI) (P Conclusion: The risk of lymphedema is multifactorial in breast cancer surgery and adjuvant treatments. In SLNB alone patients, higher BMI was only significant factor correlated with lymphedema. Excised number of lymph nodes during sentinel biopsy procedure was not associated with lymphedema. Citation Format: Ju YW, Jung JG, Kim KE, Kim Y, Lee E, Lee H-B, Moon H-G, Han W, Noh D-Y. Breast cancer-related lymphedema: Morbidity of sentinel node biopsy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-15.
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- 2019
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7. Abstract P4-14-09: A nationwide data on the cardiovascular protective effect of tamoxifen and aromatase inhibitor in postmenopausal women with breast cancer
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Sung Hee Choi, H-B Lee, D-Y Noh, Eunsik Lee, H-J Yoon, Ke Kim, Yeong-Min Park, H-G Moon, Wonshik Han, JG Jung, Y Kim, and YW Ju
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Oncology ,Cancer Research ,medicine.medical_specialty ,Aromatase inhibitor ,business.industry ,medicine.drug_class ,Hazard ratio ,Cancer ,medicine.disease ,Breast cancer ,Diabetes mellitus ,Internal medicine ,medicine ,Hormonal therapy ,Family history ,business ,Tamoxifen ,medicine.drug - Abstract
A large proportion of breast cancer patients receive hormonal therapy as their adjuvant treatment options. For postmenopausal women, the initial choice for the hormonal therapy is aromatase inhibitor (AI), and tamoxifen (TM) is reserved for women experiencing severe side effects against AI or having low bone density. An important but unresolved clinical question regarding the use of AI in postmenopausal women is the safety of AI regarding the risk cardiovascular events. Studies have shown inconsistent results over the cardiovascular safety of AI and TM. In this study, we investigated the risk of developing cardiovascular and cerebrovascular events in women with breast cancer who receive hormonal therapy using AI, TM, or both. To this end, we used the National Health Insurance Sharing Service in Korea which is provided by National Health Insurance Service. The database provides anonymized insurance data for research purposes after the approval of the review committee. In the database, we identified 47,569 women with the age older than 55 who were diagnosed with breast cancer. Patients were classified as no hormonal treatment group (n=18,807), AI group (n=19,584), TM group (n=7,081), or Switch group (n=2,097). The Switch group was defined as the women with history of both AI and TM prescriptions. During the studied period, a total of 2,032 cardiovascular or cerebrovascular events (CVE) were recorded. Overall, the women prescribed with TM had significantly less hazard ratio for developing CVE when compared to the women who did not receive any hormonal treatment (HR 0.809 95% C.I. 0.706-0.928). However, this protective effect of tamoxifen was not observed in either AI or Switch group (HR 0.917 95% C.I. 0.833-1.010, and HR 0.856 95% C.I. 0.695-1.053, respectively). The protective effect of TM was also similar in women older than 60 (HR 0.808 95% C.I. 0.696-0.938). The cardiovascular and cerebrovascular protective effects of tamoxifen was also substantial in high risk women defined by their family history of cardiovascular diseases and the diagnosis of hypertension or diabetes. Our results suggest that the use of TM is associated with a substantial protective effect against developing cardiovascular or cerebrovascular events in women with breast cancer. However, the protective effect was not observed for women receiving AI. Our data suggest the potential tailored approach in hormonal treatment in breast cancer patients who are at high risk of cardiovascular of cerebrovascular events. Citation Format: Moon H-G, Choi SH, Park Y, Jung JG, Ju YW, Kim KE, Kim Y, Lee E, Lee H-B, Han W, Noh D-Y, Yoon H-J. A nationwide data on the cardiovascular protective effect of tamoxifen and aromatase inhibitor in postmenopausal women with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-09.
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- 2019
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8. Abstract P2-07-10: Not presented
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Sung Min Kwon, H-S Ryu, C-W Kim, MK Kim, D-Y Noh, JW Lee, Sang Kyu Yoon, S Kim, A Kim, H-B Lee, YW Ju, Wonshik Han, Ke Kim, S-K Lee, J.S. Kim, S-H Ahn, H-G Moon, Ia Park, HJ Lee, and J-G Jung
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Cancer Research ,Oncology - Abstract
This abstract was not presented at the conference. Citation Format: Lee H-B, Kim KE, Ju YW, Jung J-G, Ryu H-S, Lee SB, Lee JW, Lee HJ, Kim M-S, Kwon S, Kim J, Kim C, Moon H-G, Noh D-Y, Ahn S-H, Park I-A, Kim S, Yoon S, Kim A, Han W. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-10.
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- 2019
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9. Abstract P2-05-13: Detection of splice variants related to endocrine resistant hormone receptor-positive breast cancer
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MK Kim, D-Y Noh, YW Ju, H-B Lee, S Kim, J Rhu, E-S Lee, Ke Kim, Wonshik Han, H-G Moon, and Jung Ho Park
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Cancer Research ,Breast cancer ,Oncology ,business.industry ,Hormone receptor ,Cancer research ,Medicine ,Endocrine system ,splice ,business ,medicine.disease - Abstract
Introduction: Estrogen receptor is expressed in 75% of breast cancers and is related to a relatively indolent phenotype. Yet, up to 25% of these tumors develop resistance to endocrine therapy. Alternative splicing events are observed in almost every hallmarks of cancer, implying that dysregulation of splicing and cancer progression are closely related. The purpose of this study was to detect splice variants related to endocrine resistance in hormone receptor(HR)-positive breast cancer. Methods: RNA sequencing data of 455 HR-positive patients with documented endocrine treatment from The Cancer Genome Atlas (TCGA) database was used for analysis. Splice variants of 96 ESR1 pathway-related genes were detected using a data-mining algorithm recognizing spliceomic heterogeneity. A differential analysis of splice variants between 48 endocrine therapy-resistant and 407 endocrine therapy-responsive patients was performed to discover isoforms frequently detected in endocrine-resistant tumors. Isoforms related to endocrine resistance was further analyzed using whole transcriptome sequencing data from 59 HR-positive invasive breast cancer patients (24 endocrine therapy-resistant, 35 endocrine therapy-responsive who underwent operation at Seoul National University Hospital. Results: Of 96 ESR1 pathway-related genes, 17 genes showed statistically different splice variant isoforms frequencies (AKT1, ATF2, ATF4, CALM2, CALM3, CREB1, EGFR, ESR1, ESR2, GRM1, HRAS, HSP90AA1, OPRM1, PIK3R3, PRKACB, SHC1, and SHC4). A differential analysis of these isoforms using SNUH data confirmed a predominant isoform of HRAS (64.47% vs 57.14%, p-value 0.0037) and a minor isoform of SHC1 (25.53% vs 32.33%, p-value 0.0456) in endocrine therapy-resistant HR-positive patients. In the same analysis using HR-negative patients, the mean isoform percentage was similar between patients with distant recurrence and no recurrence. Potential Spliceomic Signatures Reproduced From Seoul National University Hospital Data Hormone Receptor Positive Hormone Receptor negative GeneMean Isoform % in Resistant SpecimensMean Isoform % in Responsive Specimensp-valueMean Isoform % in Resistant SpecimensMean Isoform % in Responsive Specimensp-valueHRAS64.4757.140.003757.9758.850.8413SHC125.5332.330.045628.3632.580.2551 Conclusions: Phenotype-specific splice variants can be detected using transcriptome sequencing data. Splice variants in HRAS and SHC1 are potential spliceomic signatures that may be used to predict endocrine therapy-resistant breast cancer. Further investigation is warranted to explore the biological role of these isoforms and identify the role of splice variants as a biomarker for endocrine resistance. Citation Format: Lee H-B, Kim M-S, Rhu J, Park JH, Kim KE, Ju YW, Lee E-S, Moon H-G, Noh D-Y, Kim S, Han W. Detection of splice variants related to endocrine resistant hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-05-13.
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- 2018
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10. Abstract P4-06-18: Clinical application of multigene panel testing and genetic counseling for hereditary/familial breast cancer risk assessment: Prospective single center study
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JH Park, Younjoo Kim, Ryul Kim, E-S Lee, J Rhu, H-B Lee, YW Ju, Wonshik Han, Ke Kim, D Noh, and H-G Moon
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Genetic counseling ,Cancer ,Gene mutation ,medicine.disease ,Lynch syndrome ,MSH6 ,Breast cancer ,Internal medicine ,Cancer screening ,medicine ,Family history ,business - Abstract
Background The identification of individuals at elevated risk for hereditary cancers has allowed the development of consensus recommendations for cancer screening and prevention. The introduction of multigene panels may identify more individuals with breast cancer gene mutations than does testing for BRCA1/2 alone. Therefore, the multigenerational panel increase the need for genetic counseling suggesting preventive approach or cancer-specific screening to patients and family members. The rapid clinical introduction of multigene panel testing, however, have several issues such as low- to moderate-risk gene mutations and clinical recommendations. We collect the mutation results and clinical recommendations after testing with multigene panel and giving genetic counseling. Methods We had developed multigene panel consisted of 64 genes related to hereditary cancer through previous study and prospectively enrolled 104 individuals who were appropriate candidates for hereditary breast cancer evaluation. The patients were tested with 64-gene panel(Celemics) and results were provided by us 4˜10 weeks later. We checked the family history of cancer and made a pedigree before testing. Result Among 104 participants, 26 patients harbored deleterious mutations, most commonly in high to moderate-risk breast/ovarian cancer genes (BRCA1/2, BRIP, RAD51 and RAD51D), Lynch syndrome gene(MSH6) and other genes(FH, SPINK1). We recommended the cancer-specific screening and/or preventive approach for mutation-positive patients and suggested additional genetic test for the family members. Among them, 6 (23%) patients received Risk reducing procedures (Prophylactic mastectomy or oophorectomy) and most of them(19 patients(73%)) received cancer specific screening. Conclusion We demonstrate the use of multigene panel testing for hereditary breast cancer and will suggest the process of the genetic counseling including indication and results analysis with multigene panel testing. Citation Format: Lee E-S, Han W, Kim Y, Rhu J, Park JH, Kim K-E, Ju YW, Kim R, Lee H-B, Moon H-G, Noh D-Y. Clinical application of multigene panel testing and genetic counseling for hereditary/familial breast cancer risk assessment: Prospective single center study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-18.
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- 2018
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11. Abstract P3-01-14: Nomogram predicting axillary lymph node metastases to skip intraoperative analysis of sentinel lymph nodes
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H-B Lee, Ke Kim, H-G Moon, D-Y Noh, Eunsik Lee, Jung Ho Park, YW Ju, Wonshik Han, Y Kim, and J Rhu
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Cancer Research ,medicine.medical_specialty ,medicine.anatomical_structure ,Oncology ,business.industry ,medicine ,Radiology ,Lymph ,Nomogram ,business ,Lymph node - Abstract
Background: According to the American College of Surgeons Oncology Group Z0011 trial, complete axillary lymph node dissection (ALND) did not affect survival of patients with clinical T1-T2 invasive breast cancer and one to two sentinel lymph nodes (SLNs) metastases treated with lumpectomy, adjuvant systemic therapy, and radiation therapy. A significant proportion of breast cancer patients may not require ALND, in whom intraoperative analysis of SLNs can be omitted reducing operation time and cost. The aim of this study was to develop a nomogram predicting three or more axillary lymph nodes (ALNs) metastases based on preoperative imaging and clinicopathological factors. Methods: The training set consisted of 1030 patients with clinical T1-T2 invasive breast cancer and clinically negative ALN who received surgery at Seoul National University Hospital (SNUH) between January 2010 and December 2013. Preoperative imaging techniques including ultrasonography (US), computed tomography (CT), positron emission tomography (PET), and clinicopathological features associated with three or more ALN metastases were evaluated by logistic regression analysis. A nomogram predicting three or more ALNs was developed with statistically significant factors. The validation set consisted of 781 independent patients who received surgery at SNUH between January 2014 and December 2015. Results: Of the 1030 patients, 89 (8.6%) had three or more ALN metastases. Multivariate analysis showed that three or more ALN metastases was independently associated with tumor size (cm) by US (p Conclusion: Patients with a strong possibility of three or more ALNs metastases can be identified using preoperative imaging methods including US, CT, and PET. The nomogram measuring this prospect may be valuable in skipping intraoperative analysis of SLNs with advantage of reduced operation time and cost. Citation Format: Park JH, Ju YW, Kim KE, Rhu J, Kim Y, Lee E, Lee H-B, Moon H-G, Noh D-Y, Han W. Nomogram predicting axillary lymph node metastases to skip intraoperative analysis of sentinel lymph nodes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-14.
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- 2018
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12. Relevance assumed: a case study of balanced scorecard development using system dynamics
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van Ke Kim Oorschot, Henk Akkermans, Operations Planning Acc. & Control, and Innovation Technology Entrepr. & Marketing
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Marketing ,021103 operations research ,Balanced scorecard ,Process management ,Operations research ,business.industry ,Strategy and Management ,Causal loop diagram ,0211 other engineering and technologies ,02 engineering and technology ,Management Science and Operations Research ,Management Information Systems ,System dynamics ,0202 electrical engineering, electronic engineering, information engineering ,Information system ,Economics ,020201 artificial intelligence & image processing ,Performance measurement ,Customer satisfaction ,Job satisfaction ,Project management ,business - Abstract
The balanced scorecard (BSC) has become a popular concept for performance measurement. It focuses attention of management on only a few performance measures and bridges different functional areas as it includes both financial and non-financial measures. However, doubts frequently arise regarding the quality of the BSCs developed as well as the quality of the process in which this development takes place. This article describes a case study in which system dynamics (SD) modelling and simulation was used to overcome both kinds of problems. In a two-stage modelling process (qualitative causal loop diagramming followed by quantitative simulation), a BSC was developed for management of one organizational unit of a leading Dutch insurer. This research illustrates how, through their involvement in this development process, management came to understand that seemingly contradictory goals such as customer satisfaction, employee satisfaction and employee productivity were, in fact, better seen as mutually reinforcing. Also, analysis of the SD model showed how, contrary to ex ante management intuition, performance would first have to drop further before significant improvements could be realized. Finally, the quantitative modelling process also helped to evaluate several improvement initiatives that were under consideration at the time, proving some of them to have unclear benefits, others to be very promising indeed.
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- 2005
13. Field studies into the dynamics of product development tasks
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CG Christel Rutte, Jwm Will Bertrand, van Ke Kim Oorschot, Operations Planning Acc. & Control, and Human Performance Management
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Process management ,business.industry ,Computer science ,Strategy and Management ,Time to market ,media_common.quotation_subject ,General Decision Sciences ,Outcome (game theory) ,Project planning ,Work (electrical) ,Management of Technology and Innovation ,New product development ,Quality (business) ,Product (category theory) ,Marketing ,Project management ,business ,media_common - Abstract
PurposeThis paper aims to describe three exploratory field studies investigating which characteristics add to later time to market and/or low product functionality of newly developed products. The studies are conducted at the level of developments tasks, or work packages. The first and second studies investigate to what extent the unpredictability of the project's outcome is the result of the unpredictability of the completion time of individual work packages, and of the instability of the total network of work packages.Design/methodology/approachStatistical analysis of the empirical data about the progress of three design projects carried out in the development department of a high‐tech capital equipment manufacturer was used. The third study examines the reasons that members of the product development teams in this firm give for the unpredictability of time and quality of the project's outcome.FindingsThe results result indicate the existence of three very different sources of unpredictability: the usual uncertainty about the duration of a design task, the discovery of unexpected new problems in a design task, and the reprioritization of a work package by project leaders due to new problems in other work packages.Originality/valueTogether the three studies provide a detailed account of the operational characteristics of time‐paced product development projects in a particular firm and suggest ways to effectively manage such a project.
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- 2005
14. Dimethylbenzanthracene carcinogenesis in Gadd45a-null mice is associated with decreased DNA repair and increased mutation frequency
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Mc, Hollander, Kovalsky O, Jm, Salvador, Ke, Kim, Ad, Patterson, Dc, Haines, and Albert Fornace
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Male ,Ovarian Neoplasms ,DNA Repair ,9,10-Dimethyl-1,2-benzanthracene ,Intracellular Signaling Peptides and Proteins ,Proteins ,Neoplasms, Experimental ,Vascular Neoplasms ,Mice ,Liver Neoplasms, Experimental ,Mutation ,Carcinogens ,Animals ,Female ,Gene Deletion - Abstract
Mice lacking the Gadd45a gene are susceptible to ionizing radiation-induced tumors. Increased levels of Gadd45a transcript and protein are seen after treatment of cells with ionizing radiation as well as many other agents and treatments that damage DNA. Because cells deficient in Gadd45a were shown to have a partial defect in the global genomic repair component of the nucleotide excision repair pathway of UV-induced photoproducts, dimethylbenzanthracene (DMBA) carcinogenesis was investigated because this agent produces bulky adducts in DNA that are also repaired by nucleotide excision repair. Wild-type mice and mice deficient for Gadd45a were injected with a single i.p. dose of DMBA at 10-14 days of age. The latency for spontaneous deaths was slightly decreased for Gadd45a-null mice compared with wild-type mice. At 17 months, all surviving animals were killed, and similar percentages of each genotype were found to have tumors. However, nearly twice as many Gadd45a-null than wild-type mice had multiple tumors, and three times as many had multiple malignant tumors. The predominant tumor types in wild-type mice were lymphoma and tumors of the intestines and liver. In Gadd45a-null mice, there was a dramatic increase in female ovarian tumors, male hepatocellular tumors, and in vascular tumors in both sexes. In wild-type mice, this dose of DMBA induced a5-fold increase in Gadd45a transcript in the spleen and ovary, whereas the increase in liver was20-fold. Nucleotide excision repair, which repairs both UV- and DMBA-induced DNA lesions, was substantially reduced in Gadd45a-null lymphoblasts. Mutation frequency after DMBA treatment was threefold higher in Gadd45a-null liver compared with wild-type liver. Therefore, lack of basal and DMBA-induced Gadd45a may result in enhanced tumorigenesis because of decreased DNA repair and increased mutation frequency. Genomic instability, decreased cell cycle checkpoints, and partial loss of normal growth control in cells from Gadd45a-null mice may also contribute to this process.
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- 2001
15. Effects of β-mannanase on Egg Production Performance, Egg Quality, Intestinal Microbiota, Viscosity, and Ammonia Concentration in Laying Hens
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SH Cho, Chang Won Kang, Kyung-Woo Lee, Ke Kim, Byoung-Ki An, and L Zheng
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Meal ,lcsh:Veterinary medicine ,Protein diet ,Lower energy ,Ammonia ,chemistry.chemical_compound ,Animal science ,chemistry ,β-mannanase ,metabolizable energy ,lcsh:Zoology ,lcsh:SF600-1100 ,Animal Science and Zoology ,lcsh:Animal culture ,lcsh:QL1-991 ,β mannanase ,egg quality,laying hens ,performance ,Production rate ,lcsh:SF1-1100 - Abstract
Two experiments were conducted to evaluate the effects of β-mannanase on egg production performance, egg quality, intestinal microbiota, viscosity, and ammonia concentration in laying hens. In Exp. 1, two hundred and seventy 30-wk-old Hy-Line Brown laying hens were assigned to 6 diets arranged in a 3 × 2 factorial of three levels of MEn and CP [(a corn-soybean meal based diet (HEHP), a diet containing 50 kcal of MEn/kg and 1.0% less energy and CP than the HEHP (MEMP), and a diet containing 80 kcal of MEn/kg and 1.5% less energy and CP than HEHP (LELP)], and β-mannanase supplementation (0 or 0.04%). In Exp. 2, A total of two hundred and sixteen62-wk-old Hy-Line Brown laying hens were assigned to 6 dietary treatments in a 3 × 2 factorial arrangement. In Exp. 1, β-mannanase supplementation increased egg production rate in hens fed LELP diet, but not in those fed HEHP or MEMP diet (interaction, p
16. Effect of postoperative complications on 5-year survival following laparoscopic surgery for resectable colorectal cancer: a retrospective study.
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Lee JE, Kim KE, Jeong WK, Baek SK, and Bae SU
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- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Disease-Free Survival, Adult, Kaplan-Meier Estimate, Aged, 80 and over, Neoplasm Staging, Proportional Hazards Models, Laparoscopy adverse effects, Laparoscopy mortality, Colorectal Neoplasms surgery, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Postoperative Complications etiology
- Abstract
Purpose: The purpose of this study was to investigate the effects of postoperative complications on long-term survival after laparoscopic surgery for resectable colorectal cancer., Methods: We retrospectively included 204 patients who underwent laparoscopic surgery for colorectal cancer from January 2016 to June 2020., Results: Overall, 68 (33.3%) patients had postoperative complications, twelve (17.6%) of which were classified as Clavien-Dindo class 3a or higher. The 5-year overall survival rate of the non-complication and complication groups were 93.0% and 81.7%, respectively (p = 0.048; Kaplan-Meier analysis and log-rank test), and those among patients with stage III disease were 87.0% and 61.3%, respectively (p = 0.045). The 5-year disease-free survival rates were 85.6% and 77.4%, respectively (p = 0.042). Multivariable Cox proportional-hazards analysis revealed that nodal stage (hazard ratio, 8.392; 95% confidence interval, 1.892-37.175; p = 0.005) was an independent prognostic factor for overall survival, and postoperative complications (hazard ratio, 2.996; 95% confidence interval, 1.076-8.340; p = 0.036) were independent prognostic factors for disease-free survival., Conclusion: Postoperative complications were associated with poor oncological outcomes, especially among patients with stage III colorectal cancer, and independent prognostic factors for disease-free survival., (© 2024. The Author(s).)
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- 2024
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17. Precision proteomics with TurboID: mapping the suborganelle landscape.
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Kim HB and Kim KE
- Abstract
Recent research underscores the pivotal role of cellular organelles, such as mitochondria, the endoplasmic reticulum, and lysosomes, in maintaining cellular homeostasis. Their dynamic interactions are critical for metabolic regulation and stress response. Analysis of organelle proteomes offers valuable insights into their functions in both physiology and disease. Traditional proteomic approaches to studying isolated organelles are now complemented by innovative methodologies focusing on inter-organelle interactions. This review examines the integration of advanced proximity labeling technologies, including TurboID and split-TurboID, which address the inherent limitations of traditional techniques and enable precision proteomics of suborganelle compartments and inter-organellar contact sites. These innovations have led to discoveries regarding organelle interconnections, revealing mechanisms underlying metabolic processes such as cholesterol metabolism, glucose metabolism, and lysosomal repair. In addition to highlighting the advancements in TurboID applications, this review delineates the evolving trends in organelle research, underscoring the transformative potential of these techniques to significantly enhance organelle-specific proteomic investigations.
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- 2024
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18. Metavirome Insights into the Diversity and Potential Pathogenic Infection of Chlamys farreri in the Coastal Seas of the Republic of Korea.
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Shin JW, Kim KE, Park JS, Kim MJ, Lee TK, Kim YJ, Kim HJ, Kim SM, and Jung SW
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Chlamys farreri is primarily cultivated in Japan, China, and South Korea. Although mass mortality of scallops has been occurring recently, likely caused by high temperatures or infectious diseases, the underlying cause remains unclear. Little is known regarding the viral diseases affecting them. Therefore, we explored DNA virus diversity in the mid-gut gland of C. farreri and compared it with that of seawater. C. farreri was cultivated at depths below 5 m from the sea surface in the coastal waters of South Korea and sampled from May to August 2018. Different DNA viral communities were observed in both C. farreri and seawater. In C. farreri , prevalent groups included Mimiviridae (7%), Poxviridae (6%), and Phycodnaviridae (5%). Conversely, the dominant groups in seawater were Autographiviridae (20%), Kyanoviridae (12%), and Zobellviridae (10%). We identified C. farreri -specific viral communities and potentially infectious viruses, such as Ostreid herpesvirus 1 and Abalone herpesvirus Victoria/AUS/2009. Furthermore, C. farreri acts as a reservoir for various viruses, which impact microbial community dynamics and disease transmission in marine ecosystems. Understanding these viral communities is crucial to protecting and restoring coastal ecosystems by highlighting their role in the transmission of potential avian- and bivalve-specific viruses.
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- 2024
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19. Impact of adding preoperative magnetic resonance imaging to ultrasonography on male breast cancer survival: a matched analysis with female breast cancer.
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Lee J, Kim KE, Kim MK, Kim H, Ko ES, Ko EY, Han BK, and Choi JS
- Abstract
Purpose: The study investigated whether incorporating magnetic resonance imaging (MRI) alongside ultrasonography (US) in the preoperative evaluation is associated with differing survival outcomes between male and female breast cancer patients in a matched analysis. Additionally, clinicopathological prognostic factors were analyzed., Methods: Between January 2005 and December 2020, 93 male and 28,191 female patients who underwent breast surgery were screened. Exact matching analysis was conducted for age, pathologic T and N stages, and molecular subtypes. The clinicopathological characteristics and preoperative imaging methods of the matched cohorts were reviewed. Disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan-Meier analysis, and Cox proportional hazards regression analysis was used to identify prognostic factors., Results: A total of 328 breast cancer patients (61 men and 267 women) were included in the matched analysis. Male patients had worse DFS (10-year DFS, 70.6% vs. 89.2%; P=0.001) and OS (10-year OS, 64.4% vs. 96.3%; P<0.001) than female patients. The pathologic index cancer size (hazard ratio [HR], 2.013; 95% confidence interval [CI], 1.063 to 3.810; P=0.032) was associated with worse DFS, whereas there were no significant factors associated with OS. Adding MRI to US for preoperative evaluation was not associated with DFS (HR, 1.117; 95% CI, 0.223 to 5.583; P=0.893) or OS (HR, 1.529; 95% CI, 0.300 to 7.781; P=0.609) in male patients., Conclusion: Adding breast MRI to US in the preoperative evaluation was not associated with survival outcomes in male breast cancer patients, and the pathologic index cancer size was associated with worse DFS.
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- 2024
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20. Traumatic peripheral nerve injuries in young Korean soldiers: a recent 10-year retrospective study.
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Jung C, Yun JH, Kim EJ, Park J, Yeom J, and Kim KE
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Purpose: Traumatic peripheral nerve injury (PNI), which occurs in up to 3% of trauma patients, is a devastating condition that often leads to permanent disability. However, knowledge of traumatic PNI is limited. We describe epidemiology and clinical characteristics of traumatic PNI in Korea and identify the predictors of traumatic complete PNI., Methods: A list of enlisted soldier patients who were discharged from military service due to PNI over a 10-year period (2012-2021) was obtained, and their medical records were reviewed. Patients were classified according to the causative events (traumatic vs. nontraumatic) and injury severity (complete vs. incomplete). Of traumatic PNIs, we compared the clinical variables between the incomplete and complete PNI groups and identified predictors of complete PNI., Results: Of the 119 young male patients who were discharged from military service due to PNI, 85 (71.4%) were injured by a traumatic event; among them, 22 (25.9%) were assessed as having a complete injury. The most common PNI mechanism (n=49, 57.6%), was adjacent fractures or dislocations. Several injury-related characteristics were significantly associated with complete PNI: laceration or gunshot wound, PNI involving the median nerve, PNI involving multiple individual nerves (multiple PNI), and concomitant muscular or vascular injuries. After adjusting for other possible predictors, multiple PNI was identified as a significant predictor of a complete PNI (odds ratio, 3.583; P=0.017)., Conclusions: In this study, we analyzed the characteristics of enlisted Korean soldiers discharged due to traumatic PNI and found that the most common injury mechanism was adjacent fracture or dislocation (57.6%). Patients with multiple PNI had a significantly increased risk of complete injury. The results of this study contribute to a better understanding of traumatic PNI, which directly leads to a decline in functioning in patients with trauma.
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- 2024
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21. Exploration of a Machine Learning Model Using Self-rating Questionnaires for Detecting Depression in Patients with Breast Cancer.
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Park H, Kim K, Moon E, Lim HJ, Suh H, Kim KE, and Kang T
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Objective: Given the long-term and severe distress experienced during breast cancer treatment, detecting depression among breast cancer patients is clinically crucial. This study aimed to explore a machine-learning model using self-report questionnaires to screen for depression in patients with breast cancer., Methods: A total of 327 patients who visited the breast cancer clinic were included in this study. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9), Beck Depression Inventory (BDI), and Hospital Anxiety and Depression Scale (HADS). The depression was evaluated according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition. The prediction model's performance based on supervised machine learning was conducted using MATLAB2022., Results: The BDI showed an area under the curve (AUC) of 0.785 when using the logistic regression (LR) classifier. The HADS and PHQ-9 showed an AUC of 0.784 and 0.756 when using the linear discriminant analysis, respectively. The combinations of BDI and HADS showed an AUC of 0.812 when using the LR. The combinations of PHQ-9, BDI, and HADS showed an AUC of 0.807 when using LR., Conclusion: The combination model with BDI and HADS in breast cancer patients might be better than the method using a single scale. In future studies, it is necessary to explore strategies that can improve the performance of the model by integrating the method using questionnaires and other methods.
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- 2024
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22. In vitro antifungal and physicochemical properties of polymerized acrylic resin containing strontium-modified phosphate-based glass.
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Jang EJ, Hong YJ, Jeong YH, Kim KE, Jo ES, Lee MJ, and Yang SY
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- Polymerization, Hardness, Flexural Strength, Humans, In Vitro Techniques, Candida albicans drug effects, Acrylic Resins chemistry, Strontium pharmacology, Strontium chemistry, Antifungal Agents pharmacology, Glass chemistry, Phosphates pharmacology, Surface Properties, Materials Testing
- Abstract
Acrylic resins are widely used as the main components in removable orthodontic appliances. However, poor oral hygiene and maintenance of orthodontic appliances provide a suitable environment for the growth of pathogenic microorganisms. In this study, strontium-modified phosphate-based glass (Sr-PBG) was added to orthodontic acrylic resin at 0% (control), 3.75%, 7.5%, and 15% by weight to evaluate the surface and physicochemical properties of the novel material and its in vitro antifungal effect against Candida albicans (C. albicans). Surface microhardness and contact angle did not vary between the control and 3.75% Sr-PBG groups (p > 0.05), and the flexural strength was lower in the experimental groups than in the control group (p < 0.05), but no difference was found with Sr-PBG content (p > 0.05). All experimental groups showed an antifungal effect at 24 and 48 h compared to that in the control group (p < 0.05). This study demonstrated that 3.75% Sr-PBG exhibits antifungal effects against C. albicans along with suitable physicochemical properties, which may help to minimize the risk of adverse effects associated with harmful microbial living on removable orthodontic appliances and promote the use of various materials., (© 2024. The Author(s).)
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- 2024
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23. Rectal metastasis arising from breast cancer: a case report.
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Kim KE, Lee HW, and Bae SU
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Breast cancer is the most common cancer among women worldwide. Breast cancer often metastasizes to the regional lymph nodes, bone, brain, liver, and lungs, whereas gastrointestinal tract metastases are rare. Herein, we present a rare case of rectal metastasis from breast cancer that occurred during palliative chemotherapy. A 69-year-old female with a history of invasive ductal carcinoma, negative for hormonal receptors and positive for human epidermal growth factor receptor 2 (HER2) receptor, underwent various treatments, including neoadjuvant chemotherapy, breast-conserving surgery, and adjuvant therapy. Eight months postoperatively, the patient experienced axillary lymph node recurrence, requiring palliative chemotherapy. Despite ongoing treatment, metastatic lesions were confirmed in the lungs and pleura. During palliative chemotherapy, the patient developed anal pain, and subsequent examination revealed an infiltrating rectal lesion. Despite histological confirmation of metastatic breast carcinoma and tubular adenoma, a multidisciplinary decision was made regarding palliative chemotherapy over surgical intervention. Eribulin was administered, but due to the patient's inability to tolerate the treatment, she passed away 3 months after rectal lesion diagnosis. Although breast cancer metastasis to the rectum is rare, clinicians should consider the possibility of rectal involvement and perform a digital rectal examination if anal symptoms are present.
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- 2024
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24. Characteristics of Hirayama Disease in Young South Korean Soldiers.
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Yun JH, Jung C, Kim EJ, Park J, Yeom J, Jung JS, and Kim KE
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Background and Purpose: The purpose of this study was to describe the clinical presentation and features in electrodiagnostic and imaging investigations of young South Korean males diagnosed with Hirayama disease (HD)., Methods: We reviewed the electronic medical records of South Korean enlisted soldiers who were diagnosed with HD and discharged from military service during 2011-2021. We investigated the clinical characteristics and results of electrodiagnostic and magnetic resonance imaging (MRI) investigations. We analyzed laterality and identified the involved muscles using needle electromyography (EMG). Loss of lordosis, localized cervical cord atrophy, loss of attachment between the posterior dura and subjacent lamina, asymmetric flattening of the cord, crescent-shaped mass in the posterior epidural space, and noncompressive intramedullary T2-weighted high signal intensity were investigated using neutral- or flexion-position MRI., Results: Forty-two male patients aged 20.2±0.8 years (mean±standard deviation) were identified. All patients complained of hand weakness, and 10 complained of hand tremor (23.8%). Four patients (9.5%) had symptoms in both upper limbs, and five (11.9%) had sensory disturbances. Needle EMG revealed that muscles in the C7-T1 myotome were commonly involved, and C5-C6 involvement of the deltoid (10.5%) and biceps brachii (12.5%) was also observed. In cervical MRI, localized cord atrophy (90.0%) was the most characteristic finding, and cord atrophy was most severe at the C5-C6 level (58.3%)., Conclusions: This is the first description of a large number of patients with HD in South Korea. The clinical presentation and features found in electrodiagnostic and imaging investigations will improve the understanding of HD in the young South Korean male population., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Neurological Association.)
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- 2024
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25. Inhibitory Effects of Fermented Sprouted Oat Extracts on Oxidative Stress and Melanin Overproduction.
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Cho H, Yang J, Kang JY, and Kim KE
- Abstract
Hyperpigmentation occurs due to irregular secretion of melanin pigment in the skin. This can affect quality of life depending on its severity, so prevention and management are essential. Oats ( Avena sativa L.), a grain consumed worldwide, are known to offer improved health benefits upon germination and fermentation. This study is aimed to investigate the protective effects of lactobacilli-fermented sprouted oat extracts on oxidative stress and melanin overproduction in vitro. The anti-melanogenic effect was investigated using melanin content and tyrosinase activity assays in B16F10 cells, as well as a mushroom tyrosinase-based enzyme inhibition assay. The results showed that L. casei -fermented oat extracts were the most effective for reducing melanin formation by reducing the mRNA expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein 2. Furthermore, L. casei fermentation was effective in improving the total phenolic, flavonoid, and avenanthramide A contents of sprouted oat extracts. The results also demonstrated the antioxidant effects of L. casei -fermented sprouted oat extracts in promoting DPPH radical-scavenging activity, superoxide dismutase-like activity, and reduction in reactive oxygen species levels. Overall, the findings indicate that fermented sprouted oat extracts are promising candidates for antioxidant and anti-hyperpigmentation treatments.
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- 2024
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26. Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.
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Lee EH, Lee JH, Kim DY, Lee YS, Jo Y, Dao T, Kim KE, Song DK, Seo JH, Seo YK, Seong JK, Moon C, Han E, Kim MK, Ryu S, Shin M, Roh GS, Jung HR, Osborne TF, Ryu D, Jeon TI, and Im SS
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- Animals, Humans, Male, Mice, Carbon Tetrachloride pharmacology, Disease Models, Animal, Gene Expression Regulation, Hepatic Stellate Cells metabolism, Hepatic Stellate Cells pathology, Hepatocytes metabolism, Hepatocytes pathology, Mice, Inbred C57BL, Iron metabolism, Lipocalin-2 metabolism, Lipocalin-2 genetics, Liver Cirrhosis metabolism, Liver Cirrhosis pathology, Liver Cirrhosis etiology, Liver Cirrhosis genetics, Liver Cirrhosis chemically induced, Mice, Knockout, Non-alcoholic Fatty Liver Disease metabolism, Non-alcoholic Fatty Liver Disease etiology, Non-alcoholic Fatty Liver Disease pathology, Non-alcoholic Fatty Liver Disease genetics, Sterol Regulatory Element Binding Protein 1 metabolism, Sterol Regulatory Element Binding Protein 1 genetics
- Abstract
Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl
4 ), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4 -induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH., (© 2024. The Author(s).)- Published
- 2024
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27. Liquid-liquid surfactant partitioning drives dewetting of oil from hydrophobic surfaces.
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Kim KE, Xue W, and Zarzar LD
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Hypothesis: Sessile droplets solubilizing in surfactant solution are frequently encountered in practice, but the factors governing their non-equilibrium dynamics are not well understood. Here, we investigate mechanisms by which solubilizing, sessile oil droplets in aqueous surfactant solution dewet from hydrophobic substrates and spread on hydrophilic substrates., Experiments: We quantify the dependence of droplet contact line dynamics on drop size and oil, surfactant, and substrate chemistries. We consider halogenated alkane oils as well as aromatic oils and focus on common nonionic nonylphenol ethoxylate surfactants. We correlate these results with measurements of the interfacial tensions., Findings: Counter-intuitively, under a range of conditions, we observe complete dewetting of oil from hydrophobic substrates but spreading on hydrophilic substrates. The timescales needed to reach a steady-state contact angle vary widely, with some droplets examined taking over a day. We find that surfactant surface adsorption governs the contact angle on shorter timescales, while partitioning of surfactant from water to oil, and oil solubilization into the water, act on longer timescales to facilitate the complete dewetting. Understanding of the role played by surfactant and oil transport presents opportunities for tailoring sessile droplet behaviors and controlling droplet dynamics under conditions that would previously not have been considered., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lauren Zarzar reports financial support was provided by Charles E Kaufman Foundation. Lauren Zarzar reports financial support was provided by Camille and Henry Dreyfus Foundation Inc. Lauren Zarzar reports financial support was provided by US Army Research Office]., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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28. Comparison between liquid skin adhesive and wound closure strip for skin closure after subcuticular suturing in single-port laparoscopic appendectomy: a single-center retrospective study in Korea.
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Kim KE, Jeon YR, Bae SU, Jeong WK, and Baek SK
- Abstract
Purpose: This study was performed to evaluate the safety and feasibility of skin adhesives and to compare postoperative and cosmetic outcomes after wound closure in single-port laparoscopic appendectomy (SPLA) between skin adhesives and steri-strips., Methods: This was a single-center retrospective study. We included 22 and 47 patients in whom skin adhesive and steri-strips were used respectively, for skin closure after subcuticular suturing in SPLA between August 2014 and 2020. The patient scar assessment questionnaire (PSAQ) was completed postoperatively to assess postoperative cosmetic outcomes., Results: On the postoperative day, patients in whom skin adhesive was used had significantly lower numeric rating scores than in whom steri-strips were used (2.8 ± 0.8 vs. 3.9 ± 0.8, p < 0.001). The frequency of analgesic administration within 24 hours and between 24 and 48 hours after surgery was significantly lower in the skin adhesive group compared to the wound closure strip group (1.4 ± 0.8 vs. 2.7 ± 1.2, p = 0.013 and 0.2 ± 0.4 vs. 0.7 ± 0.9, p = 0.002, respectively). In the PSAQ, "satisfaction with appearance" and "satisfaction with symptoms" subitem scores were significantly lower in patients in whom skin adhesive was used (11.3 ± 3.0 vs. 15.1 ± 4.5, p = 0.006 and 6.5 ± 1.8 vs. 9.5 ± 3.3, p = 0.003), whereas, "appearance" and "consciousness" subitems revealed no statistically significant differences between the groups., Conclusion: Liquid skin adhesive closures seem to be safe and feasible and cause less postoperative pain, resulting in greater patient satisfaction with postoperative scars than wound closure strip closure after subcuticular suturing in SPLA.
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- 2024
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29. Effect of preoperative pan-immune-inflammation value on clinical and oncologic outcomes after colorectal cancer surgery: a retrospective study.
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Seo YJ, Kim KE, Jeong WK, Baek SK, and Bae SU
- Abstract
Purpose: Surgical resection, the primary treatment for colorectal cancer (CRC), is often linked with postoperative complications that adversely affect the overall survival rates (OS). The pan-immune-inflammation value (PIV), a novel biomarker, is promising in evaluating cancer prognoses. We aimed to explore the impact of preoperative immune inflammation status on postoperative and long-term oncological outcomes in patients with CRC., Methods: A retrospective analysis of 203 patients with CRC who underwent surgery (January 2016-June 2020) was conducted. The preoperative PIV was calculated as [(neutrophil count + platelet count + monocyte count) / lymphocyte counts]. The PIV optimal cutoff value was determined based on the OS using the Contal and O'Quigley methods., Results: A PIV value ≥155.90 was defined as high. Patients were categorized into low-PIV (n = 85) and high-PIV (n = 118) groups. Perioperative clinical outcomes (total operation time, time to gas out, sips of water, soft diet, and hospital stay) were not significantly different between the groups. The high-PIV group exhibited more postoperative complications (P = 0.024), and larger tumor size compared with the low-PIV group. Multivariate analysis identified that American Society of Anesthesiologists grade III (P = 0.046) and high-PIV (P = 0.049) were significantly associated with postoperative complications. The low-PIV group demonstrated higher OS (P = 0.001) and disease-free survival rates (DFS) (P = 0.021) compared with the high-PIV group. Advanced N stage (P = 0.005) and high-PIV levels (P = 0.047) were the identified independent prognostic factors for OS, whereas advanced N stage (P = 0.045) was an independent prognostic factor for DFS., Conclusion: Elevated preoperative PIV was associated with an increased incidence of postoperative complications and served as an independent prognostic factor for OS., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)
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- 2024
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30. Utility of targeted mean total deviation trend analysis for detecting progressive visual field changes in early-to-moderate stage glaucoma.
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Song WK, Kim KE, Lee A, Yoon J, and Kook MS
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- Humans, Visual Fields, Retrospective Studies, Thiram, Visual Field Tests, Vision Disorders diagnosis, Intraocular Pressure, Disease Progression, Glaucoma, Open-Angle diagnosis, Glaucoma diagnosis
- Abstract
Objectives: To evaluate the clinical utility of trend-based analysis of the targeted mean total deviation (TMTD) by comparing its rates of visual field (VF) change and sensitivities of detecting VF progression with those of the mean total deviation (mTD) in the global and hemifield VF area in early to-moderate glaucoma patients., Methods: A single eye from 139 open-angle glaucoma patients with hemifield VF defects and a minimum two year follow-up were retrospectively evaluated. The TMTD was estimated by averaging the total deviation (TD) values after excluding VF points that had a threshold sensitivity of <0 dB in three baseline tests, and the mTD by averaging the entire VF TD values. The study patients were classified as VF progressors vs. non-progressors using both event- and trend-based analysis. The rates of change and ratios of progression detection were compared between TMTD and mTD., Results: This study included 49 VF progressors and 90 non-progressors. Slopes for the global and VF-affected hemifield TMTD were significantly faster than those for the mTD in each subgroup and in the entire cohort (P < 0.001). Trend-based TMTD analysis detected VF progression in greater proportion than either trend-based mTD or event-based analysis (38.1% vs. 30.2% vs. 27.3%, respectively: VF affected hemifields)., Conclusions: The rates of change in the TMTD are significantly faster than those for the mTD globally and in the VF-affected hemifields. Trend-based TMTD analysis shows greater sensitivity for detecting VF progression than trend-based mTD or event-based analysis in early-to-moderate glaucoma patients with hemifield VF loss., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)
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- 2024
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31. Ecological Interaction between Bacteriophages and Bacteria in Sub-Arctic Kongsfjorden Bay, Svalbard, Norway.
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Kim KE, Joo HM, Kim YJ, Kang D, Lee TK, Jung SW, and Ha SY
- Abstract
Marine virus diversity and their relationships with their hosts in the marine environment remain unclear. This study investigated the co-occurrence of marine DNA bacteriophages (phages) and bacteria in the sub-Arctic area of Kongsfjorden Bay in Svalbard (Norway) in April and June 2018 using metagenomics tools. Of the marine viruses identified, 48-81% were bacteriophages of the families Myoviridae , Siphoviridae , and Podoviridae . Puniceispirillum phage HMO-2011 was dominant (7.61%) in April, and Puniceispirillum phage HMO-2011 (3.32%) and Pelagibacter phage HTVC008M (3.28%) were dominant in June. Gammaproteobacteria (58%), including Eionea flava (14.3%) and Pseudomonas sabulinigri (12.2%), were dominant in April, whereas Alphaproteobacteria (87%), including Sulfitobacter profundi (51.5%) and Loktanella acticola (32.4%), were dominant in June. The alpha diversity of the bacteriophages and bacterial communities exhibited opposite patterns. The diversity of the bacterial community was higher in April and lower in June. Changes in water temperature and light can influence the relationship between bacteria and bacteriophages.
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- 2024
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32. Smoking behavior among Asian Americans during the initial phase of the COVID-19 pandemic: The influence of pandemic stressors and depression.
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Lozano P, Peters A, Southworth A, Mo Y, Lam H, Randal FT, and Kim KE
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Introduction: Heightened levels of distress among Asian Americans during the initial phases of the pandemic may be associated with current smoking behavior. In this study, we examine differences in current smoking among Asian Americans from two different ethnic backgrounds before and during the COVID-19 pandemic., Methods: We analyzed cross-sectional survey data (n=202) from Chinese and South Asian adults in Chicago, collected between February and May 2020. We conducted logistic regression models to estimate the relationship between exposure to the COVID-19 pandemic and current smoking. We tested whether the association varied by Asian American ethnic group, unemployment, racial discrimination, and depression symptoms., Results: We found that current smoking increased from 28% to 48% among Asian Americans (i.e. Chinese and South Asians) during the pandemic. We found a statistically significant interaction between the COVID-19 period indicator variable and current smoking by Asian American ethnic groups (p=0.014), such that current smoking was lower for Chinese compared to South Asians before COVID-19, but was comparable for both groups during the pandemic. We also found a statistically significant interaction between the period indicator variable and current smoking by racial discrimination (p=0.047) and depression symptoms (p=0.02). Results from these interactions suggest that Asian Americans who experienced racial discrimination and depression during the pandemic may be more likely to be current smokers compared to their pre-pandemic counterparts., Conclusions: The findings of the study highlight the need for culturally tailored smoking cessation interventions for Asian American communities that address pandemic-related stressors such as discrimination that may trigger cigarette use., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. K.E. Kim reports that in the past 36 months she received grants or contracts from the National Cancer Institute, NIH and CDC, and that she had a fiduciary role in Asian Health Coalition., (© 2024 Lozano P. et al.)
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- 2024
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33. Intermittent Fasting Reduces Neuroinflammation and Cognitive Impairment in High-Fat Diet-Fed Mice by Downregulating Lipocalin-2 and Galectin-3.
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Lee J, An HS, Shin HJ, Jang HM, Im CO, Jeong Y, Eum K, Yoon S, Lee SJ, Jeong EA, Kim KE, and Roh GS
- Subjects
- Animals, Mice, Neuroinflammatory Diseases, Diet, High-Fat adverse effects, Lipocalin-2, Intermittent Fasting, Galectin 3, Cognitive Dysfunction etiology, Cognitive Dysfunction prevention & control
- Abstract
Intermittent fasting (IF), an alternating pattern of dietary restriction, reduces obesity-induced insulin resistance and inflammation. However, the crosstalk between adipose tissue and the hippocampus in diabetic encephalopathy is not fully understood. Here, we investigated the protective effects of IF against neuroinflammation and cognitive impairment in high-fat diet(HFD)-fed mice. Histological analysis revealed that IF reduced crown-like structures and adipocyte apoptosis in the adipose tissue of HFD mice. In addition to circulating lipocalin-2 (LCN2) and galectin-3 (GAL3) levels, IF reduced HFD-induced increases in LCN2- and GAL3-positive macrophages in adipose tissue. IF also improved HFD-induced memory deficits by inhibiting blood-brain barrier breakdown and neuroinflammation. Furthermore, immunofluorescence showed that IF reduced HFD-induced astrocytic LCN2 and microglial GAL3 protein expression in the hippocampus of HFD mice. These findings indicate that HFD-induced adipocyte apoptosis and macrophage infiltration may play a critical role in glial activation and that IF reduces neuroinflammation and cognitive impairment by protecting against blood-brain barrier leakage.
- Published
- 2024
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- View/download PDF
34. Comparison of the Circumpapillary Structure-Function and Vasculature-Function Relationships at Different Glaucoma Stages Using Longitudinal Data.
- Author
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Song WK, Lee A, Yoon J, Kim KE, and Kook MS
- Subjects
- Humans, Retina, Linear Models, Research Design, Tomography, Optical Coherence, Glaucoma diagnosis
- Abstract
Purpose: This study investigated the global and regional correlations between longitudinal structure-function (S-F) and vasculature-function (V-F) data using circumpapillary retinal nerve fiber layer thickness (cpRNFLT) measurements from optical coherence tomography (OCT), circumpapillary vessel density (cpVD) from OCT angiography (OCTA), and the corresponding visual field mean sensitivities at different glaucoma stages., Methods: A total of 107 eyes from 107 glaucoma patients with progressive visual field (VF) changes followed up for an average of 3.33 ± 1.39 years were enrolled, including early-to-moderate (51 eyes) and advanced (56 eyes) stages. The rates of longitudinal change in the VF mean deviation (MD), cpRNFLT, and cpVD were evaluated using linear mixed-effects models and compared between different glaucoma stages. Longitudinal global and regional S-F and V-F relationships were assessed by repeated measures correlation analysis by glaucoma stage., Results: No significant differences were found in the rates of VF MD and cpVD changes (P > 0.05) between the two glaucoma stage groups. CpRNFLT decreased more rapidly in the early-to-moderate stage group (P < 0.001) in which significant longitudinal global and regional correlations were found in both S-F and V-F relationships (all P < 0.05), except for the nasal sector. Significant global and regional correlations were only found in V-F relationship in advanced stage cases (all P < 0.05)., Conclusions: Significant longitudinal V-F relationships exist globally and regionally regardless of glaucoma stage but no longitudinal S-F relationship is present in advanced glaucoma. Longitudinal follow-up of cpVD parameters may be useful for monitoring glaucomatous VF progression at all disease stages.
- Published
- 2024
- Full Text
- View/download PDF
35. A longitudinal molecular and cellular lung atlas of lethal SARS-CoV-2 infection in K18-hACE2 transgenic mice.
- Author
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Choi S, Lee J, Kim S, Lee YW, Kim GC, Hong SM, An SH, Noh H, Kim KE, On D, Lee SG, Jang HJ, Kim SH, Kim J, Seo JS, Kim JJ, Park IH, Oh J, Kim DJ, Yoon JH, Seok SH, Lee YJ, Kim SY, Kim YB, Hwang JY, Lee HJ, Kim HB, Park JW, Yun JW, Shin JS, Seo JY, Nam KT, Choi KS, Kwon HK, Lee HY, Kim JK, and Seong JK
- Subjects
- Animals, Cricetinae, Mice, Humans, SARS-CoV-2, Leukocytes, Mononuclear, Ferrets, Bronchi, Transforming Growth Factor beta, Mice, Transgenic, Disease Models, Animal, Lung, COVID-19, gamma-Globulins, Melphalan
- Abstract
Background: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus's impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research., Methods: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue., Findings: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1
+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor-ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFβ signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes., Interpretation: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFβ signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19., Funding: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020M3A9I2109027, 2021R1A2C2004501)., Competing Interests: Declaration of interests The authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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36. Systematic Multiomic Analysis of PKHD1L1 Gene Expression and Its Role as a Predicting Biomarker for Immune Cell Infiltration in Skin Cutaneous Melanoma and Lung Adenocarcinoma.
- Author
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Kang JY, Yang J, Lee H, Park S, Gil M, and Kim KE
- Subjects
- Humans, Biomarkers, Gene Expression, Multiomics, Tumor Microenvironment genetics, Adenocarcinoma of Lung genetics, Lung Neoplasms genetics, Melanoma genetics, Skin Neoplasms genetics
- Abstract
The identification of genetic factors that regulate the cancer immune microenvironment is important for understanding the mechanism of tumor progression and establishing an effective treatment strategy. Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is a large transmembrane protein that is highly expressed in immune cells; however, its association with tumor progression remains unclear. Here, we systematically analyzed the clinical relevance of PKHD1L1 in the tumor microenvironment in multiple cancer types using various bioinformatic tools. We found that the PKHD1L1 mRNA expression levels were significantly lower in skin cutaneous melanoma (SKCM) and lung adenocarcinoma (LUAD) than in normal tissues. The decreased expression of PKHD1L1 was significantly associated with unfavorable overall survival (OS) in SKCM and LUAD. Additionally, PKHD1L1 expression was positively correlated with the levels of infiltrating B cells, cluster of differentiation (CD)-8
+ T cells, and natural killer (NK) cells, suggesting that the infiltration of immune cells could be associated with a good prognosis due to increased PKHD1L1 expression. Gene ontology (GO) analysis also revealed the relationship between PKHD1L1 -co-altered genes and the activation of lymphocytes, including B and T cells. Collectively, this study shows that PKHD1L1 expression is positively correlated with a good prognosis via the induction of immune infiltration, suggesting that PKHD1L1 has potential prognostic value in SKCM and LUAD.- Published
- 2023
- Full Text
- View/download PDF
37. Topographic comparison of the retinal microvascular changes between patients with compressive and glaucomatous optic neuropathies.
- Author
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Lim H, Lee BJ, Kook MS, Sung KR, Kim KE, and Moon Y
- Subjects
- Humans, Retinal Ganglion Cells, Retina, Retinal Vessels diagnostic imaging, Tomography, Optical Coherence methods, Optic Disk diagnostic imaging, Optic Disk blood supply, Optic Nerve Diseases diagnostic imaging, Glaucoma diagnostic imaging
- Abstract
We investigated the difference in optical coherence tomography angiography characteristics between the patients with compressive optic neuropathy (CON, n = 26) and glaucomatous optic neuropathy (GON, n = 26), who were matched for the severity of visual field defect. The peripapillary retinal nerve fiber layer (pRNFL) thickness in the nasal and temporal sectors was thinner in the CON group, whereas the inferior pRNFL thickness was thinner in the GON group. Accordingly, the CON group had lower peripapillary vessel density (pVD) in the nasal and temporal sectors, and the GON group in the inferior sector. In the macular area, the CON group had a thinner macular ganglion cell-inner plexiform layer in the superior and nasal sectors, whereas the GON group in the inferior sector. However, the CON group did not have a lower macular VD than the GON group in any sector, whereas the GON group exhibited lower superficial capillary plexus VD in the superior, inferior, and temporal sectors. Comparison of the structure-vasculature correlation revealed a significant difference in the nasal and temporal peripapillary areas and superior and nasal macular sectors; a decrease in VD was greater in the GON group than in the CON group when the comparable structural change occurred., (© 2023. The Author(s).)
- Published
- 2023
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38. One year of treating patients with open fractures of the lower extremity in a new military trauma center in Korea: a case series.
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Ko JW, Moon G, Kwon JG, Kim KE, Jeon H, and Lee K
- Abstract
Purpose: The Armed Forces Trauma Center of Korea was established in April 2022. This study was conducted to report our 1-year experience of treating soldiers with open fractures of the lower extremity., Methods: In this case series, we reviewed the medical records of 51 Korean soldiers with open fractures of the lower extremity between April 2022 and March 2023 at a trauma center. We analyzed patients with Gustilo-Anderson type II and III fractures and reported the duration of transportation, injury mechanisms, injured sites, and associated injuries. We also presented laboratory findings, surgery types, intensive care unit stays, hospital stays, rehabilitation results, and reasons for psychiatric consultation. Additionally, we described patients' mode of transport., Results: This study enrolled nine male patients who were between 21 and 26 years old. Six patients had type II and three had type III fractures. Transport from the accident scene to the emergency room ranged from 75 to 455 minutes, and from the emergency room to the operating room ranged from 35 to 200 minutes. Injury mechanisms included gunshot wounds, landmine explosions, grenade explosions, and entrapment by ship mooring ropes. One case had serious associated injuries (inhalation burn, open facial bone fractures, and hemopneumothorax). No cases with serious blood loss or coagulopathies were found, but most cases had a significant elevation of creatinine kinase. Two patients underwent vascular reconstruction, whereas four patients received flap surgery. After rehabilitation, six patients could walk, one patient could move their joints actively, and two patients performed active assistive movement. Eight patients were referred to the psychiatry department due to suicidal attempts and posttraumatic stress disorder., Conclusions: This study provides insights into how to improve treatment for patients with military trauma, as well as medical services such as the transport system, by revising treatment protocols and systematizing treatment., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (© 2023 The Korean Society of Traumatology.)
- Published
- 2023
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39. scAAV2-Mediated Expression of Thioredoxin 2 and C3 Transferase Prevents Retinal Ganglion Cell Death and Lowers Intraocular Pressure in a Mouse Model of Glaucoma.
- Author
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Kim HJ, Cha S, Choi JS, Lee JY, Kim KE, Kim JK, Kim J, Moon SY, Lee SHS, Park K, and Won SY
- Subjects
- Humans, Mice, Animals, Retinal Ganglion Cells metabolism, Fibronectins metabolism, Thioredoxins metabolism, HeLa Cells, Transferases metabolism, Disease Models, Animal, Intraocular Pressure, Glaucoma genetics, Glaucoma therapy, Glaucoma metabolism
- Abstract
Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3). We evaluated the therapeutic effects of this vector in vitro and in vivo using dexamethasone (DEX)-induced glaucoma models. We found that scAAV2-Trx2-C3-treated HeLa cells had significantly reduced GTP-bound active RhoA and increased phosphor-cofilin Ser3 protein expression levels. scAAV2-Trx2-C3 was also shown to inhibit oxidative stress, fibronectin expression, and alpha-SMA expression in DEX-treated HeLa cells. NeuN immunostaining and TUNEL assay in mouse retinal tissues was performed to evaluate its neuroprotective effect upon RGCs, whereas changes in mouse IOP were monitored via rebound tonometer. The present study showed that scAAV2-Trx2-C3 can protect RGCs from degeneration and reduce IOP in a DEX-induced mouse model of glaucoma, while immunohistochemistry revealed that the expression of fibronectin and alpha-SMA was decreased after the transduction of scAAV2-Trx2-C3 in murine eye tissues. Our results suggest that AAV2-Trx2-C3 modulates the outflow resistance of the trabecular meshwork, protects retinal and other ocular tissues from oxidative damage, and may lead to the development of a gene therapeutic for glaucoma.
- Published
- 2023
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40. TonEBP Haploinsufficiency Attenuates Microglial Activation and Memory Deficits in Middle-Aged and Amyloid β Oligomer-Treated Mice.
- Author
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Lee JY, Jeong EA, Lee J, Shin HJ, Lee SJ, An HS, Kim KE, Kim WH, Bae YC, Kang H, and Roh GS
- Subjects
- Animals, Mice, Haploinsufficiency, Memory Disorders metabolism, Microglia metabolism, Amyloid beta-Peptides metabolism, NFATC Transcription Factors metabolism
- Abstract
Age-related microglial activation is associated with cognitive impairment. Tonicity-responsive enhancer-binding protein (TonEBP) is a critical mediator of microglial activation in response to neuroinflammation. However, the precise role of TonEBP in the middle-aged brain is not yet known. We used TonEBP haploinsufficient mice to investigate the role of TonEBP in middle-aged or amyloid β oligomer (AβO)-injected brains and examined the effect of TonEBP knockdown on AβO-treated BV2 microglial cells. Consistent with an increase in microglial activation with aging, hippocampal TonEBP expression levels were increased in middle-aged (12-month-old) and old (24-month-old) mice compared with young (6-month-old) mice. Middle-aged TonEBP haploinsufficient mice showed reduced microglial activation and fewer memory deficits than wild-type mice. Electron microscopy revealed that synaptic pruning by microglial processes was reduced by TonEBP haploinsufficiency. TonEBP haploinsufficiency also reduced dendritic spine loss and improved memory deficits in AβO-treated mice. Furthermore, TonEBP knockdown attenuated migration and phagocytosis in AβO-treated BV2 cells. These findings suggest that TonEBP plays important roles in age-related microglial activation and memory deficits.
- Published
- 2023
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- View/download PDF
41. Prevalence of Neuromuscular Diseases in Young South Korean Males; A Korean Military Manpower Administration and Medical Command Data-Based Study.
- Author
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Kim KE, Kim EJ, Kim K, Park J, Jung C, Yun JH, and Son K
- Abstract
Background and Purpose: All young males in South Korea must undergo a physical examination for their participation in military service. We aimed to determine the prevalence rate (PR) of various neuromuscular diseases in young South Korean males using the data of exempted patients and soldiers., Methods: The number of males exempted based on specific items of physical examination corresponding to neuromuscular disease during 2011-2020 were obtained from the records of the Military Manpower Administration. The list of enlisted soldier patients who were discharged from military service due to neuromuscular diseases during 2011-2020 was obtained from the Armed Forces Medical Command, and their medical records were reviewed., Results: The PR of neuromuscular diseases was calculated among 948 identified males: 713 exempted males and 235 soldiers. The PRs of overall hereditary neuropathies, Hirayama disease (HD), myasthenia gravis (MG), and inherited muscle diseases in South Korean males in their early 20s were 8.34 (95% confidence interval [CI], 7.39-9.30), 5.54 (95% CI, 4.76-6.32), 2.97 (95% CI, 2.40-3.55), and 10.38 (95% CI, 9.31-11.46) per 100,000 persons, respectively. Among the enlisted soldiers, hereditary neuropathy with liability to pressure palsy was the most common neuromuscular disease, with a prevalence among the enlisted soldiers of 3.11 (95% CI, 2.42-3.80) per 100,000 persons. Myotonic dystrophy was the most prevalent myopathy, followed by facioscapulohumeral muscular dystrophy., Conclusions: The 10-year PRs of hereditary polyneuropathies, HD, MG, and inherited muscle diseases in young South Korean males have been reported. These data could be valuable to understanding each neuromuscular disease in the young male population of South Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)
- Published
- 2023
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- View/download PDF
42. Intermittent Fasting Attenuates Metabolic-Dysfunction-Associated Steatohepatitis by Enhancing the Hepatic Autophagy-Lysosome Pathway.
- Author
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Kim KE, Shin HJ, Ju Y, Jung Y, An HS, Lee SJ, Jeong EA, Lee J, Hwang GS, and Roh GS
- Subjects
- Mice, Animals, Intermittent Fasting, Liver metabolism, Inflammation metabolism, Diet, High-Fat adverse effects, Autophagy, Lysosomes metabolism, Lipids, Mice, Inbred C57BL, Fatty Liver metabolism, Non-alcoholic Fatty Liver Disease etiology, Non-alcoholic Fatty Liver Disease prevention & control, Non-alcoholic Fatty Liver Disease metabolism
- Abstract
An intermittent fasting (IF) regimen has been shown to protect against metabolic dysfunction-associated steatohepatitis (MASH). However, the precise mechanism remains unclear. Here, we explored how IF reduced hepatic lipid accumulation, inflammation, and fibrosis in mice with MASH. The mice were fed a high-fat diet (HFD) for 30 weeks and either continued on the HFD or were subjected to IF for the final 22 weeks. IF reduced body weight, insulin resistance, and hepatic lipid accumulation in HFD-fed mice. Lipidome analysis revealed that IF modified HFD-induced hepatic lipid composition. In particular, HFD-induced impaired autophagic flux was reversed by IF. The decreased hepatic lysosome-associated membrane protein 1 level in HFD-fed mice was upregulated in HFD+IF-fed mice. However, increased hepatic lysosomal acid lipase protein levels in HFD-fed mice were reduced by IF. IF attenuated HFD-induced hepatic inflammation and galectin-3-positive Kupffer cells. In addition to the increases in hepatic hydroxyproline and lumican levels, lipocalin-2-mediated signaling was reversed in HFD-fed mice by IF. Taken together, our findings indicate that the enhancement of the autophagy-lysosomal pathway may be a critical mechanism of MASH reduction by IF.
- Published
- 2023
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43. Foveal avascular zone vessel density is associated with visual field progression in early-stage glaucoma eyes with central visual field damage.
- Author
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Yoon J, Kim KE, Lee A, Song WK, and Kook MS
- Subjects
- Humans, Visual Fields, Intraocular Pressure, Retinal Ganglion Cells, Scotoma, Tomography, Optical Coherence methods, Visual Field Tests, Retrospective Studies, Glaucoma, Open-Angle, Glaucoma
- Abstract
We investigated the relationship between foveal avascular zone (FAZ)-related parameters, assessed by optical coherence tomography angiography (OCT-A), and visual field (VF) progression in early-stage open-angle glaucoma (OAG) eyes with central visual field (CVF) defects. Early-stage glaucoma eyes [VF mean deviation (MD) ≥ - 6 dB] with CVF defects were included. The rates of longitudinal change in FAZ-related parameters and structural parameters were evaluated and compared between VF progressors and non-progressors, using linear mixed effects models. Cox proportional hazards model and linear regression models were used to identify factors associated with VF progression, the VF MD reduction rate and the change rate of mean total deviation in central 12 VF points (MTD
10 ). A total of 131 eyes were included and VF progression was detected in 32 eyes (24.4%) during 3.45 years of follow-up. The rates of reduction in vessel density in the 300 µm width annular region surrounding the FAZ (FD300) and macular ganglion cell-inner plexiform layer thickness (mGCIPLT) were significantly faster in progressors than in non-progressors. The faster VF MD or MTD10 reduction rates were associated with faster rates of FD300 loss and mGCIPLT reduction. The FD300 reduction rate is significantly associated with VF progression in early-stage OAG eyes with CVF defects. FD300 may be an adjunctive biomarker of VF progression in glaucomatous eyes with CVF defects., (© 2023. Springer Nature Limited.)- Published
- 2023
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44. Periorbital Skin Rejuvenation of Asian Skin Using Microneedle Fractional Radiofrequency.
- Author
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Kim KE, Park JH, Seul TW, Kim IH, and Ryu HJ
- Abstract
Background: The periorbital area plays an important role cosmetically. Periorbital wrinkles are attributed to long-term, repeated use of orbicularis oris muscles and UV-induced dermal collagen degeneration. Fractional microneedle radiofrequency (RF) treats scars and laxity by creating vertical channels of injury in the dermis, triggering a scarless healing cascade and neocollagenesis., Objective: To evaluate the effect and safety of a novel fractional microneedle RF device on periorbital wrinkles based on several objective indicators., Methods: Eleven healthy Korean patients aged 30 to 75 years with periorbital wrinkles were included in this study. Wrinkle grades were evaluated using the Fitzpatrick wrinkle assessment scale (WAS). The melanin and erythema index, transepidermal water loss (TEWL), and three parameters for elasticity were recorded. Skin biopsies were obtained in patients who consented., Results: All patients exhibited wrinkle improvement in the lateral periorbital area, and two patients also showed efficacy in the lower eyelid area. There was a statistically significant decrease in WAS and a significant improvement in the melanin index of V4 and V5. TEWL also showed a considerable decline on V4 and V5, suggesting that the water content of the skin increased with repeated laser sessions. A peak increase in viscoelasticity and a decrease in retraction time following the first laser application were observed. In the histopathologic examination, the dermis had a denser collagen and elastin content., Conclusion: Microneedle fractional RF resulted in statistically significant long-term clinical improvement of periorbital wrinkles and enhanced pigmentation and skin hydration., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)
- Published
- 2023
- Full Text
- View/download PDF
45. Coexistence of open-angle glaucoma and sarcoidosis-associated optic neuropathy.
- Author
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Jung EH, Kim W, Yoon RG, and Kim KE
- Subjects
- Humans, Male, Middle Aged, Rare Diseases, Glaucoma, Open-Angle complications, Glaucoma, Open-Angle diagnosis, Optic Nerve Diseases complications, Optic Nerve Diseases diagnosis, Optic Disk, Glaucoma, Sarcoidosis complications, Sarcoidosis diagnosis
- Abstract
Background: In cases with advanced glaucomatous disc changes, further changes associated with other optic neuropathies cannot be easily identified. We present a case of preexisting open-angle glaucoma and concurrent involvement of sarcoidosis-associated optic neuropathy., Case Presentation: A 53-year-old man presented with gradual visual loss in his left eye, which began 1 year ago and accelerated 3 months ago. The best-corrected visual acuity in the right eye was 20/20 and counting fingers in the left. Intraocular pressures (IOP) were 12 mmHg in the right eye and 34 mmHg in the left. We diagnosed him with advanced open-angle glaucoma in the left eye based on the advanced glaucomatous cupping of the left optic disc. The IOP in the left eye dropped to 10 mmHg and was well controlled with antiglaucomatous medication; however, his left optic disc developed pallor 3 months after the treatment. The patient was revealed to be diagnosed with sarcoidosis a month ago and had been treated with systemic corticosteroids thereafter by a pulmonologist. Orbital magnetic resonance imaging revealed sarcoidosis-associated optic neuropathy in the left eye. Subsequently, optic neuropathy occurred in his right eye., Conclusions: In eyes with advanced glaucomatous disc change, detecting the coexistence of other optic neuropathies can be difficult. This report highlights the importance of careful ophthalmic examinations and investigation for etiologies of other optic neuropathies if non-glaucomatous changes are suspected even in eyes with advanced glaucoma., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
46. Marine Bacterioplankton Community Dynamics and Potentially Pathogenic Bacteria in Seawater around Jeju Island, South Korea, via Metabarcoding.
- Author
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Kim HJ, Kim KE, Kim YJ, Kang H, Shin JW, Kim S, Lee SH, Jung SW, and Lee TK
- Subjects
- Ecosystem, RNA, Ribosomal, 16S genetics, Seawater, Water, Republic of Korea, Aquatic Organisms, Alteromonadaceae, Pseudoalteromonas genetics, Rhodobacteraceae, Sphingomonadaceae
- Abstract
Understanding marine bacterioplankton composition and distribution is necessary for improving predictions of ecosystem responses to environmental change. Here, we used 16S rRNA metabarcoding to investigate marine bacterioplankton diversity and identify potential pathogenic bacteria in seawater samples collected in March, May, September, and December 2013 from two sites near Jeju Island, South Korea. We identified 1343 operational taxonomic units (OTUs) and observed that community diversity varied between months. Alpha- and Gamma-proteobacteria were the most abundant classes, and in all months, the predominant genera were Candidatus Pelagibacter , Leisingera , and Citromicrobium . The highest number of OTUs was observed in September, and Vibrio (7.80%), Pseudoalteromonas (6.53%), and Citromicrobium (6.16%) showed higher relative abundances or were detected only in this month. Water temperature and salinity significantly affected bacterial distribution, and these conditions, characteristic of September, were adverse for Aestuariibacter but favored Citromicrobium . Potentially pathogenic bacteria, among which Vibrio (28 OTUs) and Pseudoalteromonas (six OTUs) were the most abundant in September, were detected in 49 OTUs, and their abundances were significantly correlated with water temperature, increasing rapidly in September, the warmest month. These findings suggest that monthly temperature and salinity variations affect marine bacterioplankton diversity and potential pathogen abundance.
- Published
- 2023
- Full Text
- View/download PDF
47. YWHAZ and TBP are potential reference gene candidates for qPCR analysis of response to radiation therapy in colorectal cancer.
- Author
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Kim S, Park JY, Lee HW, Bae SU, Kim KE, Byun SJ, and Seo I
- Subjects
- Humans, 14-3-3 Proteins genetics, Caco-2 Cells, Genes, Essential genetics, Real-Time Polymerase Chain Reaction methods, Reference Standards, Gene Expression Profiling methods, Colorectal Neoplasms genetics, Colorectal Neoplasms radiotherapy
- Abstract
The expression profiles of conventional reference genes (RGs), including ACTB and GAPDH, used in quantitative real-time PCR (qPCR), vary depending on tissue types and environmental conditions. We searched for suitable RGs for qPCR to determine the response to radiotherapy in colorectal cancer (CRC) cell lines, organoids, and patient-derived tissues. Ten CRC cell lines (Caco-2, COLO 205, DLD-1, HCT116, HCT-15, HT-29, RKO, SW1116, SW480, and SW620) and organoids were selected and irradiated with 2, 10 or 21 grays (Gy) based on the previous related studies conducted over the last decade. The expression stability of 14 housekeeping genes (HKGs; ACTB, B2M, G6PD, GAPDH, GUSB, HMBS, HPRT1, IPO8, PGK1, PPIA, TBP, TFRC, UBC, and YWHAZ) after irradiation was evaluated using RefFinder using raw quantification cycle (Cq) values obtained from samples before and after irradiation. The expression stability of HKGs were also evaluated for paired fresh frozen tissues or formalin-fixed, paraffin-embedded samples obtained from CRC patients before and after chemoradiotherapy. The expression of YWHAZ and TBP encoding 14-3-3-zeta protein and TATA-binding protein were more stable than the other 12 HKGs in CRC cell lines, organoids, and patient-derived tissues after irradiation. The findings suggest that YWHAZ and TBP are potential RG candidates for normalizing qPCR results in CRC radiotherapy experiments., (© 2023. Springer Nature Limited.)
- Published
- 2023
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- View/download PDF
48. Author Correction: Effect of tamoxifen with or without gonadotropin-releasing hormone analog on DXA values in women with breast cancer.
- Author
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Kim EH, Jeon YK, Pak K, Kang T, Kim KE, Kim SJ, Kim IJ, and Kim K
- Published
- 2023
- Full Text
- View/download PDF
49. A tunnel coaxial 3D hyperspectral scanning system for underground mine investigation.
- Author
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Baik H, Son YS, and Kim KE
- Abstract
A hyperspectral scanning system was developed for three-dimensional (3D) surface mapping in underground spaces, such as mine shafts and tunnels. A hyperspectral line-scanning camera was mounted on the rotating driver unit coaxial with the tunnel to image both the mine wall and the ceiling. Uniform light was illuminated on the target surface to be imaged using a halogen lamp rotating together with the hyperspectral imaging sensor. Inertial Measuring Unit (IMU) was also attached to the sensor unit together with the hyperspectral camera so that sensor's geometric information could be acquired simultaneously during imaging. All sensor and controller units were mounted on a cart-type platform for easy movement in the tunnel, and a battery mounted on the platform supplied power for system operation and the halogen light source. The developed scanning system was tested in an actual mine, and 3D hyperspectral images of the internal surface of the mine shaft were successfully obtained., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
50. Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice.
- Author
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Park A, Kim KE, Park I, Lee SH, Park KY, Jung M, Li X, Sleiman MB, Lee SJ, Kim DS, Kim J, Lim DS, Woo EJ, Lee EW, Han BS, Oh KJ, Lee SC, Auwerx J, Mun JY, Rhee HW, Kim WK, Bae KH, and Suh JM
- Subjects
- Animals, Male, Mice, Adipocytes, Brown metabolism, Mice, Knockout, Mitochondria metabolism, Uncoupling Protein 1 genetics, Uncoupling Protein 1 metabolism, Adipose Tissue, Brown metabolism, Mitochondrial Proteins genetics, Mitochondrial Proteins metabolism, Thermogenesis genetics
- Abstract
Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
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