1.Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis
Youngtaek KIM ; Joon Yeon HWANG ; Kwangmin NA ; Dong Kwon KIM ; Seul LEE ; Seong-san KANG ; Sujeong BAEK ; Seung Min YANG ; Mi Hyun KIM ; Heekyung HAN ; Seong Su JEONG ; Chai Young LEE ; Yu Jin HAN ; Jie-Ohn SOHN ; Sang-Kyu YE ; Kyoung-Ho PYO
Yonsei Medical Journal 2024;65(12):683-694
Purpose:
We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data.
Materials and Methods:
The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type.
Results:
Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite.
Conclusion
Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.
2.Development of the Diagnostic Matrix of the Seoul Cognitive Status Test, Compared to Traditional Paper-andPencil Neuropsychological Tests
Seunghee NA ; Young Ju KIM ; Si Eun KIM ; Na-Yeon JUNG ; Seung Joo KIM ; Hee Jin KIM ; Joon Soo SHIN ; Duk L. NA ; Sang Won SEO ; Yeshin KIM ; Eek-Sung LEE
Dementia and Neurocognitive Disorders 2024;23(4):224-235
Background:
and Purpose: We aimed to develop the diagnostic matrix of the Seoul Cognitive Status Test (SCST) and compare its performance with traditional paper-and-pencil neuropsychological tests, including the Seoul Neuropsychological Screening Battery-II (SNSB-II) and the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-K).
Methods:
We recruited 197 participants from the head-to-head SCST-SNSB cohort, and 204 participants from the head-to-head SCST-CERAD cohort. They underwent either SNSB-II or CERAD-K, in addition to SCST. The diagnostic matrix was developed by combining cognitive function, determined by neuropsychological tests, and activities of daily living (ADL), determined by Instrumental-ADL scales.
Results:
The diagnostic agreement between the SCST and the SNSB-II was 83.9% (weighted kappa=0.87). The agreement between the SCST and the CERAD-K was 84.3% (weighted kappa=0.88). In the SCST-SNSB cohort, all differences in SCST scores between the cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia diagnosed with the SNSB-II were significant in all cognitive domains (all p<0.01), except for the executive domain between CU and MCI (p=0.145). In the SCST-CERAD cohort, all differences in SCST scores between the 3 groups diagnosed with the CERAD-K were significant in all cognitive domains (all p<0.01), except for the language and visuospatial domains between MCI and dementia (p=0.169 and p=0.778, respectively).
Conclusions
Our findings suggest that the tablet-based SCST may be another option to traditional paper-and-pencil neuropsychological tests, especially in situations where time and space are relatively limited, and neuropsychological testing specialists are not available.
3.Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis
Youngtaek KIM ; Joon Yeon HWANG ; Kwangmin NA ; Dong Kwon KIM ; Seul LEE ; Seong-san KANG ; Sujeong BAEK ; Seung Min YANG ; Mi Hyun KIM ; Heekyung HAN ; Seong Su JEONG ; Chai Young LEE ; Yu Jin HAN ; Jie-Ohn SOHN ; Sang-Kyu YE ; Kyoung-Ho PYO
Yonsei Medical Journal 2024;65(12):683-694
Purpose:
We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data.
Materials and Methods:
The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type.
Results:
Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite.
Conclusion
Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.
4.Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis
Youngtaek KIM ; Joon Yeon HWANG ; Kwangmin NA ; Dong Kwon KIM ; Seul LEE ; Seong-san KANG ; Sujeong BAEK ; Seung Min YANG ; Mi Hyun KIM ; Heekyung HAN ; Seong Su JEONG ; Chai Young LEE ; Yu Jin HAN ; Jie-Ohn SOHN ; Sang-Kyu YE ; Kyoung-Ho PYO
Yonsei Medical Journal 2024;65(12):683-694
Purpose:
We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data.
Materials and Methods:
The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR, ALK, BRAF, KRAS, TP53, and the wild-type.
Results:
Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS, TP53, and EGFR+TP53 mutations (MC1); and EGFR, BRAF, and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF, IL1B, and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR+TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR+TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite.
Conclusion
Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.
5.An explanatory study on periodontal disease programs by public health centers in Korea
Na-Yeon TAK ; Su-Jin KIM ; Jae-In RYU ; Belong CHO ; Nam-Yoon KIM ; Seung-Min YANG ; Kyoung-Man MIN ; In-Woo CHO ; Ji-Young HAN ; Seung-Yun SHIN
Journal of Korean Academy of Oral Health 2024;48(4):186-191
Objectives:
This study aimed to investigate the current status of periodontal disease programs implemented by public health centers in the Republic of Korea.
Methods:
An explanatory survey was conducted by the Ministry of Health and Welfare from October to November 2023. The survey focused on the periodontal programs and the implementation status across different stages. Distributed and collected via Google Forms, the survey targeted 196 oral health teams within public health centers in Korea. A total of 109 public health centers responded to the study questionnaire, yielding a participation rate of 55.6%. Data were analyzed using IBM SPSS Statistics for Windows, version 26.
Results:
A majority of periodontal disease programs were implemented exclusively by oral health teams, with a rate of 33.0%. The implementation rate of collaboration with home-visiting health teams was 17.4% and with other teams was 10.1%. The implementation rates of periodontal management across stages were as follows: 11.9% for periodontal examination, 18.3% for periodontal treatment, and 11.9% for sustainable periodontal care.
Conclusions
Periodontal disease programs are predominantly conducted by oral health teams with limited collaboration across other health teams. Additionally, periodontal management activities, such as examinations and treatments, remain insufficient. Integration between oral health teams and other health teams within public health centers or private dental clinics should be improved.
6.An explanatory study on periodontal disease programs by public health centers in Korea
Na-Yeon TAK ; Su-Jin KIM ; Jae-In RYU ; Belong CHO ; Nam-Yoon KIM ; Seung-Min YANG ; Kyoung-Man MIN ; In-Woo CHO ; Ji-Young HAN ; Seung-Yun SHIN
Journal of Korean Academy of Oral Health 2024;48(4):186-191
Objectives:
This study aimed to investigate the current status of periodontal disease programs implemented by public health centers in the Republic of Korea.
Methods:
An explanatory survey was conducted by the Ministry of Health and Welfare from October to November 2023. The survey focused on the periodontal programs and the implementation status across different stages. Distributed and collected via Google Forms, the survey targeted 196 oral health teams within public health centers in Korea. A total of 109 public health centers responded to the study questionnaire, yielding a participation rate of 55.6%. Data were analyzed using IBM SPSS Statistics for Windows, version 26.
Results:
A majority of periodontal disease programs were implemented exclusively by oral health teams, with a rate of 33.0%. The implementation rate of collaboration with home-visiting health teams was 17.4% and with other teams was 10.1%. The implementation rates of periodontal management across stages were as follows: 11.9% for periodontal examination, 18.3% for periodontal treatment, and 11.9% for sustainable periodontal care.
Conclusions
Periodontal disease programs are predominantly conducted by oral health teams with limited collaboration across other health teams. Additionally, periodontal management activities, such as examinations and treatments, remain insufficient. Integration between oral health teams and other health teams within public health centers or private dental clinics should be improved.
7.Advances in induced pluripotent stem cell-based in vitro disease modeling for rare neurodegenerative disease: A narrative review
Seung-yeon LEE ; Hyo Jin SON ; Sang Won SEO ; Duk L. NA ; Hee Jin KIM
Precision and Future Medicine 2024;8(3):65-73
Understanding the genetic basis and pathomechanisms underlying dementia arising from single-gene mutations is crucial to expand our knowledge in the field of dementia research. In this review, we comprehensively summarize the results of existing research using induced pluripotent stem cells (iPSCs) to investigate familial Alzheimer’s disease caused by mutations in the presenilin-1 (PSEN1), presenilin-2 (PSEN2), or amyloid precursor protein (APP) genes. We further review existing iPSC studies in leukodystrophies, including Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), caused by mutations in the notch receptor 3 (NOTCH3) gene; and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We systematically review the advantages and necessity of using iPSCs in research to elucidate the pathogenesis of neurodegenerative diseases, particularly to facilitate disease modeling. Furthermore, we introduce applied research based on iPSC technology. Through this review, we aimed to help elucidate the mechanisms by which causative genes induce dementia symptoms in neurodegenerative diseases, which would help contribute to the development of effective treatment strategies.
8.Development of the Diagnostic Matrix of the Seoul Cognitive Status Test, Compared to Traditional Paper-andPencil Neuropsychological Tests
Seunghee NA ; Young Ju KIM ; Si Eun KIM ; Na-Yeon JUNG ; Seung Joo KIM ; Hee Jin KIM ; Joon Soo SHIN ; Duk L. NA ; Sang Won SEO ; Yeshin KIM ; Eek-Sung LEE
Dementia and Neurocognitive Disorders 2024;23(4):224-235
Background:
and Purpose: We aimed to develop the diagnostic matrix of the Seoul Cognitive Status Test (SCST) and compare its performance with traditional paper-and-pencil neuropsychological tests, including the Seoul Neuropsychological Screening Battery-II (SNSB-II) and the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-K).
Methods:
We recruited 197 participants from the head-to-head SCST-SNSB cohort, and 204 participants from the head-to-head SCST-CERAD cohort. They underwent either SNSB-II or CERAD-K, in addition to SCST. The diagnostic matrix was developed by combining cognitive function, determined by neuropsychological tests, and activities of daily living (ADL), determined by Instrumental-ADL scales.
Results:
The diagnostic agreement between the SCST and the SNSB-II was 83.9% (weighted kappa=0.87). The agreement between the SCST and the CERAD-K was 84.3% (weighted kappa=0.88). In the SCST-SNSB cohort, all differences in SCST scores between the cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia diagnosed with the SNSB-II were significant in all cognitive domains (all p<0.01), except for the executive domain between CU and MCI (p=0.145). In the SCST-CERAD cohort, all differences in SCST scores between the 3 groups diagnosed with the CERAD-K were significant in all cognitive domains (all p<0.01), except for the language and visuospatial domains between MCI and dementia (p=0.169 and p=0.778, respectively).
Conclusions
Our findings suggest that the tablet-based SCST may be another option to traditional paper-and-pencil neuropsychological tests, especially in situations where time and space are relatively limited, and neuropsychological testing specialists are not available.
9.Development of the Diagnostic Matrix of the Seoul Cognitive Status Test, Compared to Traditional Paper-andPencil Neuropsychological Tests
Seunghee NA ; Young Ju KIM ; Si Eun KIM ; Na-Yeon JUNG ; Seung Joo KIM ; Hee Jin KIM ; Joon Soo SHIN ; Duk L. NA ; Sang Won SEO ; Yeshin KIM ; Eek-Sung LEE
Dementia and Neurocognitive Disorders 2024;23(4):224-235
Background:
and Purpose: We aimed to develop the diagnostic matrix of the Seoul Cognitive Status Test (SCST) and compare its performance with traditional paper-and-pencil neuropsychological tests, including the Seoul Neuropsychological Screening Battery-II (SNSB-II) and the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-K).
Methods:
We recruited 197 participants from the head-to-head SCST-SNSB cohort, and 204 participants from the head-to-head SCST-CERAD cohort. They underwent either SNSB-II or CERAD-K, in addition to SCST. The diagnostic matrix was developed by combining cognitive function, determined by neuropsychological tests, and activities of daily living (ADL), determined by Instrumental-ADL scales.
Results:
The diagnostic agreement between the SCST and the SNSB-II was 83.9% (weighted kappa=0.87). The agreement between the SCST and the CERAD-K was 84.3% (weighted kappa=0.88). In the SCST-SNSB cohort, all differences in SCST scores between the cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia diagnosed with the SNSB-II were significant in all cognitive domains (all p<0.01), except for the executive domain between CU and MCI (p=0.145). In the SCST-CERAD cohort, all differences in SCST scores between the 3 groups diagnosed with the CERAD-K were significant in all cognitive domains (all p<0.01), except for the language and visuospatial domains between MCI and dementia (p=0.169 and p=0.778, respectively).
Conclusions
Our findings suggest that the tablet-based SCST may be another option to traditional paper-and-pencil neuropsychological tests, especially in situations where time and space are relatively limited, and neuropsychological testing specialists are not available.
10.An explanatory study on periodontal disease programs by public health centers in Korea
Na-Yeon TAK ; Su-Jin KIM ; Jae-In RYU ; Belong CHO ; Nam-Yoon KIM ; Seung-Min YANG ; Kyoung-Man MIN ; In-Woo CHO ; Ji-Young HAN ; Seung-Yun SHIN
Journal of Korean Academy of Oral Health 2024;48(4):186-191
Objectives:
This study aimed to investigate the current status of periodontal disease programs implemented by public health centers in the Republic of Korea.
Methods:
An explanatory survey was conducted by the Ministry of Health and Welfare from October to November 2023. The survey focused on the periodontal programs and the implementation status across different stages. Distributed and collected via Google Forms, the survey targeted 196 oral health teams within public health centers in Korea. A total of 109 public health centers responded to the study questionnaire, yielding a participation rate of 55.6%. Data were analyzed using IBM SPSS Statistics for Windows, version 26.
Results:
A majority of periodontal disease programs were implemented exclusively by oral health teams, with a rate of 33.0%. The implementation rate of collaboration with home-visiting health teams was 17.4% and with other teams was 10.1%. The implementation rates of periodontal management across stages were as follows: 11.9% for periodontal examination, 18.3% for periodontal treatment, and 11.9% for sustainable periodontal care.
Conclusions
Periodontal disease programs are predominantly conducted by oral health teams with limited collaboration across other health teams. Additionally, periodontal management activities, such as examinations and treatments, remain insufficient. Integration between oral health teams and other health teams within public health centers or private dental clinics should be improved.

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