• BMB Reports
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• v.55 no.11
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• pp.547-552
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• 2022

Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.

• Journal of Biomedical Engineering Research
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• v.43 no.4
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• pp.185-192
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• 2022

Early detection of mild cognitive impairment can help prevent the progression of dementia. The purpose of this study was to design and validate a machine learning model that automatically differential diagnosed patients with mild cognitive impairment and identified cognitive decline characteristics compared to a control group with normal cognition using resting-state quantitative electroencephalogram (qEEG) with eyes closed. In the first step, a rectified signal was obtained through a preprocessing process that receives a quantitative EEG signal as an input and removes noise through a filter and independent component analysis (ICA). Frequency analysis and non-linear features were extracted from the rectified signal, and the 3067 extracted features were used as input of a linear support vector machine (SVM), a representative algorithm among machine learning algorithms, and classified into mild cognitive impairment patients and normal cognitive adults. As a result of classification analysis of 58 normal cognitive group and 80 patients in mild cognitive impairment, the accuracy of SVM was 86.2%. In patients with mild cognitive impairment, alpha band power was decreased in the frontal lobe, and high beta band power was increased in the frontal lobe compared to the normal cognitive group. Also, the gamma band power of the occipital-parietal lobe was decreased in mild cognitive impairment. These results represented that quantitative EEG can be used as a meaningful biomarker to discriminate cognitive decline.

• Proceedings of the Korean Society of Computer Information Conference
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• 2022.07a
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• pp.333-335
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• 2022

본 논문에서는 기존에 두 가지 모델이 필요했던 작업을 하나의 모델로 처리할 수 있는 자연어 처리 아키텍처를 제안한다. 단일 모델로 알츠하이머 환자의 언어패턴과 대화맥락을 분석하고 두 가지 결과인 환자분류와 챗봇의 대답을 도출한다. 일상생활에서 챗봇으로 환자의 언어특징을 파악한다면 의사는 조기진단을 위해 더 정밀한 진단과 치료를 계획할 수 있다. 제안된 모델은 전문가가 필요했던 질문지법을 대체하는 챗봇 개발에 활용된다. 모델이 수행하는 자연어 처리 작업은 두 가지이다. 첫 번째는 환자가 병을 가졌는지 여부를 확률로 표시하는 '자연어 분류'이고 두 번째는 환자의 대답에 대한 챗봇의 다음 '대답을 생성'하는 것이다. 전반부에서는 셀프어탠션 신경망을 통해 환자 발화 특징인 맥락벡터(context vector)를 추출한다. 이 맥락벡터와 챗봇(전문가, 진행자)의 질문을 함께 인코더에 입력해 질문자와 환자 사이 상호작용 특징을 담은 행렬을 얻는다. 벡터화된 행렬은 환자분류를 위한 확률값이 된다. 행렬을 챗봇(진행자)의 다음 대답과 함께 디코더에 입력해 다음 발화를 생성한다. 이 구조를 DementiaBank의 쿠키도둑묘사 말뭉치로 학습한 결과 인코더와 디코더의 손실함수 값이 유의미하게 줄어들며 수렴하는 양상을 확인할 수 있었다. 이는 알츠하이머병 환자의 발화 언어패턴을 포착하는 것이 향후 해당 병의 조기진단과 종단연구에 기여할 수 있음을 보여준다.

• Korean Journal of Psychosomatic Medicine
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• v.24 no.2
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• pp.184-190
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• 2016

Objectives : This study analyzed the differences of body mass index(BMI) in Korean patients with Alzheimer's diseases(AD), Mild Cognitive Impairment(MCI), and healthy controls to verify whether low BMI is associated with cognitive impairment. Furthermore, this study also sought to examine any association between BMI and Mini Mental State Examination-Korean version(MMSE-K), Clinical Dementia Rating(CDR), and Global Deterioration Scale(GDS). Methods : A total of 257 subjects were included in the study. History taking, mental status examination, physical examination and neurocognitive function test were carried out for the diagnosis of AD and MCI. The subjects' demographic data and presence of diseases were also surveyed. The overall cognitive function and severity of diseases were assessed using MMSE-K, GDS, and CDR. Results : The order of BMI was found to be healthy controls>MCI>AD, with statistically significant differences among the groups. The order of MMSE-K scores was similar, with healthy controls>MCI>AD in statistically significant differences. The healthy controls had the lowest CDR and GDS scores, and AD patients had the highest scores. There was a significant positive correlation between BMI and MMSE scores(r=0.238, p=0.000). BMI was negatively correlated with CDR(r=-0.174, p=0.008) as well as with GDS(r=-0.233, p= 0.000). Conclusions : Measuring BMI of patients with AD or MCI is expected to be meaningful in that BMI could be a clinical indicator of AD. We expect this to be beneficial for the diagnosis, prevention, and therapeutic approach of AD and also expect large-scale, long-term longitudinal studies to follow.

• Tuberculosis and Respiratory Diseases
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• v.79 no.1
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• pp.37-41
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• 2016

Iron supplements such as ferrous sulfate tablets are usually used to treat iron-deficiency anemia in some elderly patients with primary neurologic disorders or decreased gag reflexes due to stroke, senile dementia, or parkinsonism. While the aspiration of ferrous sulfate is rarely reported, it is a potentially life-threatening condition that can lead to airway necrosis and bronchial stenosis. A detailed history and high suspicion of aspiration are required to avoid delays in diagnosis and treatment. The diagnosis can be confirmed by bronchoscopic examination and a tissue biopsy. Early removal of the aspirated tablet prevents acute complications, such as bronchial necrosis, hemoptysis, and lobar consolidation. Tablet removal is also necessary to prevent late bronchial stenosis. We presented the first case in Korea of a ferrous sulfate tablet aspiration that induced severe endobronchial inflammation.

• Journal of Hospice and Palliative Care
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• v.19 no.3
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• pp.201-210
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• 2016

Delirium is a common symptom in patients with terminal cancer. The prevalence increases in the dying phase. Delirium causes negative effects on quality of life for both patients and their families, and is associated with higher mortality. However, some studies reported that it tends to remain unrecognized in palliative care setting. That may be related with difficulties to distinguish the symptom from others with overlapping characteristics such as depression and dementia, and a lack of knowledge regarding assessment and diagnostic tools. We suggest that accurate recognition with validated tools and early diagnosis of the symptom should be highly prioritized in delirium management in palliative care setting. After diagnosing delirium, it is important to identify and address reversible precipitants such as medication, dehydration, and infection. Non-pharmacological interventions including comfortable environment for the patient and family education are also essential in the management strategy. If such interventions prove ineffective or insufficient to control hyperactive symptoms, pharmacologic interventions with antipsychotics and benzodiazepine can be considered. Until now, low levels of haloperidol remains the standard treatment despite a lack of evidence. Atypical antipsychotics such as olanzapine, quetiapine and risperidone reportedly have similar efficacy with a stronger sedating property and less adverse effect compared to haloperidol. Currently, delirium medications that can be used in palliative care setting require more clinical trials, and thus, clinical guidelines are not sufficiently available. We suggest that it is warranted to develop clinical guidelines based on well-designed clinical studies for palliative care patients.

• Journal of the Korean Society of Radiology
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• v.82 no.5
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• pp.1124-1139
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• 2021

The objective assessment of atrophy and the measurement of brain volume is important in the early diagnosis of dementia and neurodegenerative diseases. Recently, several MR-based volumetry software have been developed. For their clinical application, several issues arise, including the standardization of image acquisition and their validation of software. Additionally, it is important to highlight the diagnostic performance of the volumetry software based on expert opinions. We instituted a task force within the Korean Society of Neuroradiology to develop guidelines for the clinical use of MR-based brain volumetry software. In this review, we introduce the commercially available software and compare their diagnostic performances. We suggest the need for a standard protocol for image acquisition, the validation of the software, and evaluations of the limitations of the software related to clinical practice. We present recommendations for the clinical applications of commercially available software for volumetry based on the expert opinions of the Korean Society of Neuroradiology.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.282-292
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• 1994

Brain perfusion SPECT shows typical regional perfusion abnormalities in Alzheimer's disease(AD) and is useful for its diagnosis. However, there is also arguement that these patterns show significant overlap with other causes, and the accuracy for SPECT in differentiating AD has shown conflicting results. We postulate that the variation in re-ported results are partly due to a difference in patient or control selection with special reference to the mixture of ischemic cerebral disease in the studied population. To deter-mine the effect of ischemic lesions and the nature of control subjects on SPECT studies for AD, we performed $^{99m}Tc$-HMPAO single photon emission computed tomography (SPECT) in 11 probable AD patients with a low (<4) Hachinski ischemic score and 12 non-demented age matched controls. Magnetic resonance imaging(MRI) disclosed ischemic cerebral lesions in 27% (3/11) of the PAD group and 25% (3/12) of the control group. Regional perfusion indices were quantitated from the SPECT images as follows and the distribution of perfusion indices from both groups were compared. This was repeated with controls after excluding those with significant ischemic lesions by MRI : regional perfusion index = average regional count/average cerebellar count All PAD patients showed perfusion abnormality in SPECT. However, 53% (10/12) of controls also showed perfusion at-normalities, and no pattern could reliably differentiate the two groups. After excluding controls with significant cerebral ischemia, the difference in temporal and parietal perfusion index was increased. A decreased tempore-parietal and any parietal or temporal per-fusion index had a sensitivity of 18% and 36% in detecting AD, respectively. When using a separate group of normal age mathced controls, the indices showed an even more difference in the temporal and parietal lobes and the sensitivity of a decreased tempore-parietal and any parietal or temporal perfusion index had a sensitivity of 36% and 55% in detecting AD, respectively. Thus, the type of control with special reference to the pres-once of ischemic cerebral lesions contribute significantly to the accuracy of perfusion SPECT in diagnosing AD. This nay have particular importance in the diagnosis of AD in populations where the prevalance of cerebrovascular disease is high.

• Journal of Preventive Medicine and Public Health
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• v.32 no.3
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• pp.400-414
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• 1999

Objectives: This is a descriptive study which was carried out to identify characteristics of the chronic mentally ill and their families in a rural area and the influencing factors on family burden. Methods : Data was collected for seven months beginning April 1, 1998 by questionnaire from chronic mentally ill patients and their families in two towns and seven townships of the rural areas of Kyonggi Province. In additional to the mental diagnosis of the mentally ill patients, family burden was measured by interviewing the other family members using the questionnaire developed by Pai & Kapur (1981). Of those interviewed, 103 patients were selected for final analysis. Results : Of 103 mentally ill patients, 36.1% of the subjects were not under treatment. In particular, of 29 patients with schizophrenia, 48.3% of the subjects had stopped taking medication and 6.9% of the subjects had never been treated. According to the results of a specialized examination by a psychologist, 81% of patients were in need of Hospitalization. Most primary caregivers were parents. Of the 101 primary caregivers in the study, 39.6% were over 65 years old. In case of death of the primary caregiver, 50.5% of these 101 mentally ill patients would not have anyone to care for them. Of the various kinds of family burden, primary caregivers most often reported psychological stress. Overall, the families of dementia and schizophrenia patients complained of the most family burden. Through univariative analysis, the variables of sex, education and current treatment type of the patients, the relationship with the patient and marital status of the primary caregiver and the number of people living together in the household showed significant correlation with the family burden of schizophrenia patients. Univariative analysis also showed that there were a number of variables which were correlated to the family burden in mentally retarded patients. Concerning the need for mental health services, the most common requests were for entitlement to disability benefits and housing programs. Conclusions: Community mental health services in rural areas must be developed, planned and executed in consideration of the local situation. In particular, the development of various family support programs is needed in order to mitigate emotional, mental and economic burdens and carry out a positive role to care for and rehabilitate patients.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.14 no.5
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• pp.2393-2399
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• 2013

In this paper, we proposed a method to screening of Alzheimer's disease (AD) from Raman spectra of platelet with synthesis of basis spectra using singular value decomposition (SVD). Raman spectra of platelet from AD transgenic mice are preprocessed with denoising, removal background and normalization method. The column vectors of each data matrix consist of Raman spectrum of AD and normal (NR). The matrix is factorized using SVD algorithm and then the basis spectra of AD and NR are determined by 12 column vectors of each matrix. The classification process is completed by select the class that minimized the root-mean-square error between the validation spectrum and the linear synthesized spectrum of the basis spectra. According to the experiments involving 278 Raman spectra, the proposed method gave about 97.6% classification rate, which is better performance about 6.1% than multi-layer perceptron (MLP) with extracted features using principle components analysis (PCA). The results show that the basis spectra using SVD is well suited for the diagnosis of AD by Raman spectra from platelet.