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.

Background: This study aimed to investigate the epidemiological characteristics and outcomes of myocarditis/pericarditis after BNT162b2 vaccination in Korean adolescents. Methods: This was a retrospective cohort analysis of adolescents aged 12–19 years old diagnosed with myocarditis/pericarditis within 42 days of BNT162b2 mRNA vaccination. All reported cases were investigated by city or government epidemiologists and the diagnostic certainty and causality was determined by the Korea Disease Control and Prevention Agency’s Adverse Event Following Immunization Expert Advisory Committee according to the modified version of Brighton Collaboration Myocarditis/Pericarditis Working group’s case definitions. Results: A total 3,709,063 adolescents aged 12–19 received 8,135,240 doses of the BNT162b2 vaccine in South Korea, and 184 cases met the Brighton criteria for the case definition of myocarditis and pericarditis with diagnostic certainty of possible and above. The median age was 17 years old (interquartile range [IQR], 15–18) and boys accounted for 81.5% (n = 150/184) of the cases. The overall incidence was 2.25 (95% confidence interval [CI], 1.94–2.60) cases per 100,000 doses and severe cases was 0.25 (95% CI, 0.15–3.80) cases per 100,000 doses.The highest incidence rate was observed in boys after the second dose, with 5.01 (95% CI, 4.12–6.17) cases per 100,000 doses. A total 89.1% (164/184) were classified as mild, and no deaths were reported. Conclusion The highest incidence of myocarditis/pericarditis after BNT162b2 immunization was observed in male adolescents after the second dose, with majority of the cases presenting with a mild clinical course and favorable outcome.

Background: This study aimed to investigate the epidemiological characteristics and outcomes of myocarditis/pericarditis after BNT162b2 vaccination in Korean adolescents. Methods: This was a retrospective cohort analysis of adolescents aged 12–19 years old diagnosed with myocarditis/pericarditis within 42 days of BNT162b2 mRNA vaccination. All reported cases were investigated by city or government epidemiologists and the diagnostic certainty and causality was determined by the Korea Disease Control and Prevention Agency’s Adverse Event Following Immunization Expert Advisory Committee according to the modified version of Brighton Collaboration Myocarditis/Pericarditis Working group’s case definitions. Results: A total 3,709,063 adolescents aged 12–19 received 8,135,240 doses of the BNT162b2 vaccine in South Korea, and 184 cases met the Brighton criteria for the case definition of myocarditis and pericarditis with diagnostic certainty of possible and above. The median age was 17 years old (interquartile range [IQR], 15–18) and boys accounted for 81.5% (n = 150/184) of the cases. The overall incidence was 2.25 (95% confidence interval [CI], 1.94–2.60) cases per 100,000 doses and severe cases was 0.25 (95% CI, 0.15–3.80) cases per 100,000 doses.The highest incidence rate was observed in boys after the second dose, with 5.01 (95% CI, 4.12–6.17) cases per 100,000 doses. A total 89.1% (164/184) were classified as mild, and no deaths were reported. Conclusion The highest incidence of myocarditis/pericarditis after BNT162b2 immunization was observed in male adolescents after the second dose, with majority of the cases presenting with a mild clinical course and favorable outcome.

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.

Background: This study aimed to investigate the epidemiological characteristics and outcomes of myocarditis/pericarditis after BNT162b2 vaccination in Korean adolescents. Methods: This was a retrospective cohort analysis of adolescents aged 12–19 years old diagnosed with myocarditis/pericarditis within 42 days of BNT162b2 mRNA vaccination. All reported cases were investigated by city or government epidemiologists and the diagnostic certainty and causality was determined by the Korea Disease Control and Prevention Agency’s Adverse Event Following Immunization Expert Advisory Committee according to the modified version of Brighton Collaboration Myocarditis/Pericarditis Working group’s case definitions. Results: A total 3,709,063 adolescents aged 12–19 received 8,135,240 doses of the BNT162b2 vaccine in South Korea, and 184 cases met the Brighton criteria for the case definition of myocarditis and pericarditis with diagnostic certainty of possible and above. The median age was 17 years old (interquartile range [IQR], 15–18) and boys accounted for 81.5% (n = 150/184) of the cases. The overall incidence was 2.25 (95% confidence interval [CI], 1.94–2.60) cases per 100,000 doses and severe cases was 0.25 (95% CI, 0.15–3.80) cases per 100,000 doses.The highest incidence rate was observed in boys after the second dose, with 5.01 (95% CI, 4.12–6.17) cases per 100,000 doses. A total 89.1% (164/184) were classified as mild, and no deaths were reported. Conclusion The highest incidence of myocarditis/pericarditis after BNT162b2 immunization was observed in male adolescents after the second dose, with majority of the cases presenting with a mild clinical course and favorable outcome.

Background: This study aimed to investigate the epidemiological characteristics and outcomes of myocarditis/pericarditis after BNT162b2 vaccination in Korean adolescents. Methods: This was a retrospective cohort analysis of adolescents aged 12–19 years old diagnosed with myocarditis/pericarditis within 42 days of BNT162b2 mRNA vaccination. All reported cases were investigated by city or government epidemiologists and the diagnostic certainty and causality was determined by the Korea Disease Control and Prevention Agency’s Adverse Event Following Immunization Expert Advisory Committee according to the modified version of Brighton Collaboration Myocarditis/Pericarditis Working group’s case definitions. Results: A total 3,709,063 adolescents aged 12–19 received 8,135,240 doses of the BNT162b2 vaccine in South Korea, and 184 cases met the Brighton criteria for the case definition of myocarditis and pericarditis with diagnostic certainty of possible and above. The median age was 17 years old (interquartile range [IQR], 15–18) and boys accounted for 81.5% (n = 150/184) of the cases. The overall incidence was 2.25 (95% confidence interval [CI], 1.94–2.60) cases per 100,000 doses and severe cases was 0.25 (95% CI, 0.15–3.80) cases per 100,000 doses.The highest incidence rate was observed in boys after the second dose, with 5.01 (95% CI, 4.12–6.17) cases per 100,000 doses. A total 89.1% (164/184) were classified as mild, and no deaths were reported. Conclusion The highest incidence of myocarditis/pericarditis after BNT162b2 immunization was observed in male adolescents after the second dose, with majority of the cases presenting with a mild clinical course and favorable outcome.

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.

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.

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.

Background and Objectives: Early diastolic mitral annular tissue (e’) velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e’ velocity in patients with mitral regurgitation (MR). Methods: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively.According to the current guidelines, the cut-off value of e’ velocity was defined as 7 cm/s. Results: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e’ velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634–0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477–0.998;p=0.049). Abnormal e’ velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170–5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189–21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e’ velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308– 0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680–1.356; p<0.001). Conclusions In patients aged <65 years with primary MR, e’ velocity served as an independent predictor of all-cause and cardiovascular deaths.