1.Whole-Genome and Transcriptome Sequencing Identified NOTCH2 and HES1 as Potential Markers of Response to Imatinib in Desmoid Tumor (Aggressive Fibromatosis): A Phase II Trial Study
Joonha KWON ; Jun Hyeong LEE ; Young Han LEE ; Jeeyun LEE ; Jin-Hee AHN ; Se Hyun KIM ; Seung Hyun KIM ; Tae Il KIM ; Kum-Hee YUN ; Young Suk PARK ; Jeong Eun KIM ; Kyu Sang LEE ; Jung Kyoon CHOI ; Hyo Song KIM
Cancer Research and Treatment 2022;54(4):1240-1255
Purpose:
Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to treat desmoid tumor. However, the molecular mechanism of why imatinib works remains unclear. Here, we describe potential roles of NOTCH2 and HES1 in clinical response to imatinib at genome and transcriptome levels.
Materials and Methods:
We identified somatic mutations in coding and noncoding regions via whole-genome sequencing. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale whole-genome sequencing and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response.
Results:
Among 20 patients, four (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥ 1 year. With gene-wise functional analyses, we detected a significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on Pan-Cancer Analysis of Whole Genomes data analyses, NOTCH2 mutations affect expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate between responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders.
Conclusion
Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, and an important therapeutic consideration for desmoid tumor.
2.“Reading the Mind in the Eyes Test”: Translated and Korean Versions
Se Jun KOO ; Ye Jin KIM ; Jung Hwa HAN ; Eunchong SEO ; Hye Yoon PARK ; Minji BANG ; Jin Young PARK ; Eun LEE ; Suk Kyoon AN
Psychiatry Investigation 2021;18(4):295-303
Objective:
The Reading the Mind in the Eyes Test (RMET) was developed by using Caucasian eyes, which may not be appropriate to be used in Korean. The aims of the present study were 1) to develop a Korean version of the RMET (K-RMET) by using Korean eye stimuli and 2) to examine the psychometric properties of the Korean-translated version of the RMET and the K-RMET.
Methods:
Thirty-six photographs of Korean eyes were selected. A total of 196 (101 females) healthy subjects were asked to take the Korean-translated version of the RMET and K-RMET. To assess internal consistency reliability, Cronbach’s alpha coefficients were computed, and test–retest reliability was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman plots. Confirmatory factor analysis (CFA) and item analysis were also conducted.
Results:
Internal consistency, measured by Cronbach’s alpha, was 0.542 for the Korean-translated version of the RMET, and 0.540 for the K-RMET. Test–retest reliability (n=25), measured by the ICC, was 0.787 for the Korean-translated version of the RMET, and 0.758 for the K-RMET. In CFA, the assumed single and 3-factor model fit indices were not good in the both types of RMETs. There was difficulty in discrimination in nine items of the Korean-translated version of the RMET and 10 items of the K-RMET.
Conclusion
The psychometric properties of both the Korean-translated version of the RMET and the K-RMET are acceptable. Both tests are applicable to the clinical population, as well as the general population in Korea.
3.“Reading the Mind in the Eyes Test”: Translated and Korean Versions
Se Jun KOO ; Ye Jin KIM ; Jung Hwa HAN ; Eunchong SEO ; Hye Yoon PARK ; Minji BANG ; Jin Young PARK ; Eun LEE ; Suk Kyoon AN
Psychiatry Investigation 2021;18(4):295-303
Objective:
The Reading the Mind in the Eyes Test (RMET) was developed by using Caucasian eyes, which may not be appropriate to be used in Korean. The aims of the present study were 1) to develop a Korean version of the RMET (K-RMET) by using Korean eye stimuli and 2) to examine the psychometric properties of the Korean-translated version of the RMET and the K-RMET.
Methods:
Thirty-six photographs of Korean eyes were selected. A total of 196 (101 females) healthy subjects were asked to take the Korean-translated version of the RMET and K-RMET. To assess internal consistency reliability, Cronbach’s alpha coefficients were computed, and test–retest reliability was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman plots. Confirmatory factor analysis (CFA) and item analysis were also conducted.
Results:
Internal consistency, measured by Cronbach’s alpha, was 0.542 for the Korean-translated version of the RMET, and 0.540 for the K-RMET. Test–retest reliability (n=25), measured by the ICC, was 0.787 for the Korean-translated version of the RMET, and 0.758 for the K-RMET. In CFA, the assumed single and 3-factor model fit indices were not good in the both types of RMETs. There was difficulty in discrimination in nine items of the Korean-translated version of the RMET and 10 items of the K-RMET.
Conclusion
The psychometric properties of both the Korean-translated version of the RMET and the K-RMET are acceptable. Both tests are applicable to the clinical population, as well as the general population in Korea.
4.Impact of Cardiovascular Risk Factors and Cardiovascular Diseases on Outcomes in Patients Hospitalized with COVID-19 in Daegu Metropolitan City
Bo Eun PARK ; Jang Hoon LEE ; Hyuk Kyoon PARK ; Hong Nyun KIM ; Se Yong JANG ; Myung Hwan BAE ; Dong Heon YANG ; Hun Sik PARK ; Yongkeun CHO ; Bong Yul LEE ; Chang Wook NAM ; Jin Bae LEE ; Ung KIM ; Shung Chull CHAE ;
Journal of Korean Medical Science 2021;36(2):e15-
Background:
Data regarding the association between preexisting cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs) and the outcomes of patients requiring hospitalization for coronavirus disease 2019 (COVID-19) are limited. Therefore, the aim of this study was to investigate the impact of preexisting CVRFs or CVDs on the outcomes of patients with COVID-19 hospitalized in a Korean healthcare system.
Methods:
Patients with COVID-19 admitted to 10 hospitals in Daegu Metropolitan City, Korea, were examined. All sequentially hospitalized patients between February 15, 2020, and April 24, 2020, were enrolled in this study. All patients were confirmed to have COVID-19 based on the positive results on the polymerase chain reaction testing of nasopharyngeal samples. Clinical outcomes during hospitalization, such as requiring intensive care and invasive mechanical ventilation (MV) and death, were evaluated. Moreover, data on baseline comorbidities such as a history of diabetes, hypertension, dyslipidemia, current smoking, heart failure, coronary artery disease, cerebrovascular accidents, and other chronic cardiac diseases were obtained.
Results:
Of all the patients enrolled, 954 (42.0%) had preexisting CVRFs or CVDs. Among the CVRFs, the most common were hypertension (28.8%) and diabetes mellitus (17.0%). The prevalence rates of preexisting CVRFs or CVDs increased with age (P < 0.001). The number of patients requiring intensive care (P < 0.001) and invasive MV (P < 0.001) increased with age.The in-hospital death rate increased with age (P < 0.001). Patients requiring intensive care (5.3% vs. 1.6%; P < 0.001) and invasive MV (4.3% vs. 1.7%; P < 0.001) were significantly greater in patients with preexisting CVRFs or CVDs. In-hospital mortality (12.9% vs. 3.1%; P < 0.001) was significantly higher in patients with preexisting CVRFs or CVDs. Among the CVRFs, diabetes mellitus and hypertension were associated with increased requirement of intensive care and invasive MV and in-hospital death. Among the known CVDs, coronary artery disease and congestive heart failure were associated with invasive MV and in-hospital death. In multivariate analysis, preexisting CVRFs or CVDs (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.07–3.01; P = 0.027) were independent predictors of in-hospital death adjusting for confounding variables. Among individual preexisting CVRF or CVD components, diabetes mellitus (OR, 2.43; 95% CI, 1.51–3.90; P < 0.001) and congestive heart failure (OR, 2.43; 95% CI, 1.06–5.87; P = 0.049) were independent predictors of in-hospital death.
Conclusion
Based on the findings of this study, the patients with confirmed COVID-19 with preexisting CVRFs or CVDs had worse clinical outcomes. Caution is required in dealing with these patients at triage.after
5.etection of infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus in whiteleg shrimp (Penaeus vannamei) imported from Vietnam to South Korea
Seul Chan PARK ; Seong-Kyoon CHOI ; Se-Hyeon HAN ; Song PARK ; Hye Jin JEON ; Seung Chan LEE ; Kyeong Yeon KIM ; Young Seo LEE ; Ji Hyung KIM ; Jee Eun HAN
Journal of Veterinary Science 2020;21(2):e31-
n this study, whiteleg shrimp (Penaeus vannamei) imported from Vietnam were collected from South Korean markets, and examined for 2 viruses: infectious hypodermal and hematopoietic necrosis virus (IHHNV, recently classified as decapod penstyldensovirus-1), and white spot syndrome virus (WSSV). Among 58 samples, we detected IHHNV in 23 samples and WSSV in 2 samples, using polymerase chain reaction and sequencing analyses.This is the first report of IHHNV and WSSV detection in imported shrimp, suggesting that greater awareness and stricter quarantine policies regarding viruses infecting shrimp imported to South Korea are required.
6.Reading the Mind in the Eyes Test: Relationship with Neurocognition and Facial Emotion Recognition in Non-Clinical Youths
Eunchong SEO ; Se Jun KOO ; Ye Jin KIM ; Jee Eun MIN ; Hye Yoon PARK ; Minji BANG ; Eun LEE ; Suk Kyoon AN
Psychiatry Investigation 2020;17(8):835-839
Objective:
The Reading the Mind in the Eyes Test (RMET) is a common measure of the Theory of Mind. Previous studies found a correlation between RMET performance and neurocognition, especially reasoning by analogy; however, the nature of this relationship remains unclear. Additionally, neurocognition was shown to play a significant role in facial emotion recognition. This study is planned to examine the nature of relationship between neurocognition and RMET performance, as well as the mediating role of facial emotion recognition.
Methods:
One hundred fifty non-clinical youths performed the RMET. Reasoning by analogy was tested by Raven’s Standard Progressive Matrices (SPM) and facial emotion recognition was assessed by the Korean Facial Expressions of Emotion (KOFEE) test. The percentile bootstrap method was used to calculate the parameters of the mediating effects of facial emotion recognition on the relationship between SPM and RMET scores.
Results:
SPM scores and KOFEE scores were both statistically significant predictors of RMET scores. KOFEE scores were found to partially mediate the impact of SPM scores on RMET scores.
Conclusion
These findings suggested that facial emotion recognition partially mediated the relationship between reasoning by analogy and social cognition. This study highlights the need for further research for individuals with serious mental illnesses.
7.Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database
Yunghun YOU ; Jin Young JANG ; Song Cheol KIM ; Yoo Seok YOON ; Joon Seong PARK ; Chol Kyoon CHO ; Sang Jae PARK ; Jae Do YANG ; Woo Jung LEE ; Tae Ho HONG ; Keun Soo AHN ; Chi Young JEONG ; Hyeon Kook LEE ; Seung Eun LEE ; Young Hoon ROH ; Hee Joon KIM ; Hongbeom KIM ; In Woong HAN
Cancer Research and Treatment 2019;51(4):1639-1652
PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.
Classification
;
Discrimination (Psychology)
;
Disease-Free Survival
;
Humans
;
Joints
;
Neoplasm Staging
;
Neuroectodermal Tumors, Primitive
;
Neuroendocrine Tumors
;
Pancreas
;
Survival Rate
8.Quantitative Evaluation of Post-stroke Spasticity Using Neurophysiological and Radiological Tools: A Pilot Study.
Mi Jin HONG ; Jong Bum PARK ; Yung Jin LEE ; Hyeong Tae KIM ; Won Chul LEE ; Cheol Mog HWANG ; Hyun Kyoon LIM ; Dong Hyun LEE
Annals of Rehabilitation Medicine 2018;42(3):384-395
OBJECTIVE: To determine the possibility of a new measurement tool using electromyography and ultrasonography for quantitative spasticity assessment in post-stroke patients. METHODS: Eight hemiplegic stroke patients with ankle plantarflexor spasticity confirmed by a Modified Ashworth Scale (MAS) were enrolled. Spasticity was evaluated using the MAS and Modified Tardieu Scale (MTS). Each subject underwent surface electromyography (sEMG) using the Brain Motor Control Assessment (BMCA) protocol and was compared with a healthy control group. Using ultrasonography, muscle architecture and elasticity index were measured from the medial gastrocnemius muscle (GCM) on the affected and unaffected sides. RESULTS: MAS and MTS revealed significant correlation with sEMG activity. The fascicle length and pennation angle were significantly decreased in the medial GCM on the hemiplegic side compared with the unaffected side. The elasticity index of the spastic medial GCM was significantly increased compared with the unaffected side. The MTS X and R2–R1 values were significantly correlated with the elasticity index in the hemiplegic GCM. The relationship between clinical evaluation tools and both BMCA and sonoelastography was linear, but not statistically significant in the multiple regression analysis. CONCLUSION: The BMCA protocol and ultrasonographic evaluation provide objective assessment of post-stroke spasticity. Further studies are necessary to conduct accurate assessment and treatment of spasticity.
Ankle
;
Brain
;
Elasticity
;
Elasticity Imaging Techniques
;
Electromyography
;
Evaluation Studies as Topic*
;
Humans
;
Muscle Spasticity*
;
Muscle, Skeletal
;
Muscles
;
Pilot Projects*
;
Stroke
;
Ultrasonography
9.Predicting Working Memory Capacity in Older Subjects Using Quantitative Electroencephalography.
Jae Hyuk SHIN ; Kyungun JHUNG ; Jae Seok HEO ; Suk Kyoon AN ; Jin Young PARK
Psychiatry Investigation 2018;15(8):790-795
OBJECTIVE: We utilized a spectral and network analysis technique with an integrated support vector classification algorithm for the automated detection of cognitive capacity using resting state electroencephalogram (EEG) signals. METHODS: An eyes-closed resting EEG was recorded in 158 older subjects, and spectral EEG parameters in seven frequency bands, as well as functional brain network parameters were, calculated. In the feature extraction stage, the statistical power of the spectral and network parameters was calculated for the low-, moderate-, and high-performance groups. Afterward, the highly-powered features were selected as input into a support vector machine classifier with two discrete outputs: low- or high-performance groups. The classifier was then trained using a training set and the performance of the classification process was evaluated using a test set. RESULTS: The performance of the Support Vector Machine was evaluated using a 5-fold cross-validation and area under the curve values of 70.15% and 74.06% were achieved for the letter numbering task and the spatial span task. CONCLUSION: In this study, reliable results for classification accuracy and specificity were achieved. These findings provide an example of a novel method for parameter analysis, feature extraction, training, and testing the cognitive function of elderly subjects based on a quantitative EEG signal.
Aged
;
Brain
;
Classification
;
Cognition
;
Electroencephalography*
;
Humans
;
Memory, Short-Term*
;
Methods
;
Sensitivity and Specificity
;
Support Vector Machine
10.Clinical Characteristics of False-Positive Lymph Node on Chest CT or PET-CT Confirmed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Lung Cancer.
Jongmin LEE ; Young Kyoon KIM ; Ye Young SEO ; Eun Kyoung CHOI ; Dong Soo LEE ; Yeon Sil KIM ; Sook Hee HONG ; Jin Hyoung KANG ; Kyo Young LEE ; Jae Kil PARK ; Sook Whan SUNG ; Hyun Bin KIM ; Mi Sun PARK ; Hyeon Woo YIM ; Seung Joon KIM
Tuberculosis and Respiratory Diseases 2018;81(4):339-346
BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard procedure to evaluate suspicious lymph node involvement of lung cancer because computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT (PET-CT) have limitations in their sensitivity and specificity. There are a number of benign causes of false positive lymph node such as anthracosis or anthracofibrosis, pneumoconiosis, old or active tuberculosis, interstitial lung disease, and other infectious conditions including pneumonia. The purpose of this study was to evaluate possible causes of false positive lymph node detected in chest CT or PET-CT. METHODS: Two hundred forty-seven patients who were initially diagnosed with lung cancer between May 2009 and December 2012, and underwent EBUS-TBNA to confirm suspicious lymph node involvement by chest CT or PET-CT were analyzed for the study. RESULTS: Of 247 cases, EBUS-TBNA confirmed malignancy in at least one lymph node in 189. The remaining 58 patients whose EBUS-TBNA results were negative were analyzed. Age ≥65, squamous cell carcinoma as the histologic type, and pneumoconiosis were related with false-positive lymph node involvement on imaging studies such as chest CT and PET-CT. CONCLUSION: These findings suggest that lung cancer staging should be done more carefully when a patient has clinically benign lymph node characteristics including older age, squamous cell carcinoma, and benign lung conditions.
Anthracosis
;
Carcinoma, Squamous Cell
;
Electrons
;
Humans
;
Lung Diseases, Interstitial
;
Lung Neoplasms*
;
Lung*
;
Lymph Nodes*
;
Needles*
;
Pneumoconiosis
;
Pneumonia
;
Sensitivity and Specificity
;
Thorax*
;
Tomography, X-Ray Computed*
;
Tuberculosis

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