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.Changes in the Work Patterns of Hospitalists in South Korea Following Medical School Expansion
Jisoo JEONG ; Yooju NAM ; Ju-Yeon OH ; Jongchan LEE ; Jung Hun OHN ; Jung-Hwan LEE ;
Korean Journal of Medicine 2024;99(6):315-321
		                        		
		                        			 Background:
		                        			s/Aims: The recent increase in medical school admissions has potentially altered the working conditions of hospitalists in South Korea. This study investigated how these changes have affected the work patterns and responsibilities of hospitalists, particularly in light of the ongoing exodus of medical trainees that began on February 22, 2024. 
		                        		
		                        			Methods:
		                        			We surveyed members of the Korean Society of Hospital Medicine and the Korean Society of Surgery Hospital Medicine Study Group working as hospitalists from April 2 to 30, 2024. The survey was conducted via email and excluded personally identifiable information. Respondents’ characteristics, work types, hours, patient loads, support staff availability, and changes in job scope post-policy were analyzed. 
		                        		
		                        			Results:
		                        			Sixty-three hospitalists responded, with an equitable gender distribution and a median age of 39 years. A significant shift in work patterns was noted, with full-day shifts increasing from 22.2% to 39.7%, and a corresponding decrease in weekday daytime shifts. Work hours also significantly increased from a median of 40 to 45 hours per week. Changes in patient distribution were observed, with fewer hospitalists managing mid-range patient numbers and more handling smaller or larger loads. Despite the increased demands in the latter case, more than 50% of hospitalists reported a lack of support staff and a significant portion did not receive overtime compensation. 
		                        		
		                        			Conclusions
		                        			The increase in medical school admissions and subsequent shifts in hospitalist workloads and hours indicate a strained healthcare system. Hospitalists are taking on more intensive and extended roles. The absence of adequate support staff and adjustments in compensation suggest that further systemic changes are necessary to sustain the efforts of hospitalists, thereby ensuring patient safety and care quality. 
		                        		
		                        		
		                        		
		                        	
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.Changes in the Work Patterns of Hospitalists in South Korea Following Medical School Expansion
Jisoo JEONG ; Yooju NAM ; Ju-Yeon OH ; Jongchan LEE ; Jung Hun OHN ; Jung-Hwan LEE ;
Korean Journal of Medicine 2024;99(6):315-321
		                        		
		                        			 Background:
		                        			s/Aims: The recent increase in medical school admissions has potentially altered the working conditions of hospitalists in South Korea. This study investigated how these changes have affected the work patterns and responsibilities of hospitalists, particularly in light of the ongoing exodus of medical trainees that began on February 22, 2024. 
		                        		
		                        			Methods:
		                        			We surveyed members of the Korean Society of Hospital Medicine and the Korean Society of Surgery Hospital Medicine Study Group working as hospitalists from April 2 to 30, 2024. The survey was conducted via email and excluded personally identifiable information. Respondents’ characteristics, work types, hours, patient loads, support staff availability, and changes in job scope post-policy were analyzed. 
		                        		
		                        			Results:
		                        			Sixty-three hospitalists responded, with an equitable gender distribution and a median age of 39 years. A significant shift in work patterns was noted, with full-day shifts increasing from 22.2% to 39.7%, and a corresponding decrease in weekday daytime shifts. Work hours also significantly increased from a median of 40 to 45 hours per week. Changes in patient distribution were observed, with fewer hospitalists managing mid-range patient numbers and more handling smaller or larger loads. Despite the increased demands in the latter case, more than 50% of hospitalists reported a lack of support staff and a significant portion did not receive overtime compensation. 
		                        		
		                        			Conclusions
		                        			The increase in medical school admissions and subsequent shifts in hospitalist workloads and hours indicate a strained healthcare system. Hospitalists are taking on more intensive and extended roles. The absence of adequate support staff and adjustments in compensation suggest that further systemic changes are necessary to sustain the efforts of hospitalists, thereby ensuring patient safety and care quality. 
		                        		
		                        		
		                        		
		                        	
6.Changes in the Work Patterns of Hospitalists in South Korea Following Medical School Expansion
Jisoo JEONG ; Yooju NAM ; Ju-Yeon OH ; Jongchan LEE ; Jung Hun OHN ; Jung-Hwan LEE ;
Korean Journal of Medicine 2024;99(6):315-321
		                        		
		                        			 Background:
		                        			s/Aims: The recent increase in medical school admissions has potentially altered the working conditions of hospitalists in South Korea. This study investigated how these changes have affected the work patterns and responsibilities of hospitalists, particularly in light of the ongoing exodus of medical trainees that began on February 22, 2024. 
		                        		
		                        			Methods:
		                        			We surveyed members of the Korean Society of Hospital Medicine and the Korean Society of Surgery Hospital Medicine Study Group working as hospitalists from April 2 to 30, 2024. The survey was conducted via email and excluded personally identifiable information. Respondents’ characteristics, work types, hours, patient loads, support staff availability, and changes in job scope post-policy were analyzed. 
		                        		
		                        			Results:
		                        			Sixty-three hospitalists responded, with an equitable gender distribution and a median age of 39 years. A significant shift in work patterns was noted, with full-day shifts increasing from 22.2% to 39.7%, and a corresponding decrease in weekday daytime shifts. Work hours also significantly increased from a median of 40 to 45 hours per week. Changes in patient distribution were observed, with fewer hospitalists managing mid-range patient numbers and more handling smaller or larger loads. Despite the increased demands in the latter case, more than 50% of hospitalists reported a lack of support staff and a significant portion did not receive overtime compensation. 
		                        		
		                        			Conclusions
		                        			The increase in medical school admissions and subsequent shifts in hospitalist workloads and hours indicate a strained healthcare system. Hospitalists are taking on more intensive and extended roles. The absence of adequate support staff and adjustments in compensation suggest that further systemic changes are necessary to sustain the efforts of hospitalists, thereby ensuring patient safety and care quality. 
		                        		
		                        		
		                        		
		                        	
7.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. 
		                        		
		                        		
		                        		
		                        	
8.Changes in the Work Patterns of Hospitalists in South Korea Following Medical School Expansion
Jisoo JEONG ; Yooju NAM ; Ju-Yeon OH ; Jongchan LEE ; Jung Hun OHN ; Jung-Hwan LEE ;
Korean Journal of Medicine 2024;99(6):315-321
		                        		
		                        			 Background:
		                        			s/Aims: The recent increase in medical school admissions has potentially altered the working conditions of hospitalists in South Korea. This study investigated how these changes have affected the work patterns and responsibilities of hospitalists, particularly in light of the ongoing exodus of medical trainees that began on February 22, 2024. 
		                        		
		                        			Methods:
		                        			We surveyed members of the Korean Society of Hospital Medicine and the Korean Society of Surgery Hospital Medicine Study Group working as hospitalists from April 2 to 30, 2024. The survey was conducted via email and excluded personally identifiable information. Respondents’ characteristics, work types, hours, patient loads, support staff availability, and changes in job scope post-policy were analyzed. 
		                        		
		                        			Results:
		                        			Sixty-three hospitalists responded, with an equitable gender distribution and a median age of 39 years. A significant shift in work patterns was noted, with full-day shifts increasing from 22.2% to 39.7%, and a corresponding decrease in weekday daytime shifts. Work hours also significantly increased from a median of 40 to 45 hours per week. Changes in patient distribution were observed, with fewer hospitalists managing mid-range patient numbers and more handling smaller or larger loads. Despite the increased demands in the latter case, more than 50% of hospitalists reported a lack of support staff and a significant portion did not receive overtime compensation. 
		                        		
		                        			Conclusions
		                        			The increase in medical school admissions and subsequent shifts in hospitalist workloads and hours indicate a strained healthcare system. Hospitalists are taking on more intensive and extended roles. The absence of adequate support staff and adjustments in compensation suggest that further systemic changes are necessary to sustain the efforts of hospitalists, thereby ensuring patient safety and care quality. 
		                        		
		                        		
		                        		
		                        	
9.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. 
		                        		
		                        		
		                        		
		                        	
10.Exploring the Expression and Function of T Cell Surface Markers Identified through Cellular Indexing of Transcriptomes and Epitopes by Sequencing
Joon Yeon HWANG ; Youngtaek KIM ; 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(9):544-555
		                        		
		                        			 Purpose:
		                        			By utilizing both protein and mRNA expression patterns, we can identify more detailed and diverse immune cells, providing insights into understanding the complex immune landscape in cancer ecosystems. 
		                        		
		                        			Materials and Methods:
		                        			This study was performed by obtaining publicly available Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) data of peripheral blood mononuclear cells (PBMCs) from the Gene Expression Omnibus database. A total of 94674 total cells were analyzed, of which 32412 were T cells. There were 228 protein features and 16262 mRNA features in the data.The Seurat package was used for quality control and preprocessing, principal component analysis was performed, and Uniform Manifold Approximation and Projection was used to visualize the clusters. Protein and mRNA levels in the CITE-seq were analyzed. 
		                        		
		                        			Results:
		                        			We observed that a subset of T cells in the clusters generated at the protein level divided better. By identifying mRNA markers that were highly correlated with the CD4 and CD8 proteins and cross-validating CD26 and CD99 markers using flow cytometry, we found that CD4 + and CD8+ T cells were better discriminated in PBMCs. Weighted Nearest Neighbor clustering results identified a previously unobserved T cell subset. 
		                        		
		                        			Conclusion
		                        			In this study, we used CITE-seq data to confirm that protein expression patterns could be used to identify cells more precisely. These findings will improve our understanding of the heterogeneity of immune cells in the future and provide valuable insights into the complexity of the immune response in health and disease. 
		                        		
		                        		
		                        		
		                        	
            
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