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    Excess mortality related to high air temperature: Comparison of the periods including 1994 and 2018, the worst heat waves in the history of South Korea

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    Climate change has caused extreme weather events, including frequent summer heat waves. We examined how the effects of high air temperatures on mortality have changed between the two study periods (1991–1995 and 2015–2019), including 1994 and 2018, the worst heat wave years in the meteorological history of South Korea. Temperature data from the Korea Meteorological Administration and mortality data from Statistics Korea were used in this study. We used distributed lag nonlinear models to estimate the cumulative relative risks (CRRs) to determine the association between daily maximum temperature in summer (June to September) and mortality. CRRs were estimated for each province and pooled using a random-effects meta-analysis for all provinces. Maximum temperature and annual average days in heat wave were 37.7̊C and 11.8 in 1991–1995 and 38.3̊C and 18.8 in 2015–2019. The slope of the CRR for mortality increases with increasing temperature and has been steeper in the past than in recent years and steeper in those over 65 than in those under 65. Excess mortality has recently declined compared with that in the past. The impact of high summer temperatures on mortality changed between the two periods, suggesting improved population resilience

    Genomic Insights into the Role of cAMP in Carotenoid Biosynthesis: Enhancing β-Carotene Production in Escherichia coli via cyaA Deletion

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    The gamma-ray-induced random mutagenesis of an engineered β-carotene-producing Escherichia coli XL1-Blue resulted in the variant Ajou 45, which exhibits significantly enhanced β-carotene production. The whole-genome sequencing of Ajou 45 identified 55 mutations, notably including a reduction in the copy number of cyaA, encoding adenylate cyclase, a key enzyme regulating intracellular cyclic AMP (cAMP) levels. While the parental XL1-Blue strain harbors two copies of cyaA, Ajou 45 retains only one, potentially leading to reduced intracellular cAMP concentrations. This reduction may alleviate catabolite repression and redirect metabolic flux toward the β-carotene biosynthesis pathway. To validate this mechanistic insight, a targeted cyaA knockout was engineered in XL1-Blue, and its β-carotene production and growth phenotypes were compared with those of Ajou 45 and XL1-Blue. The findings demonstrated that a reduced cyaA copy number substantially enhances β-carotene biosynthesis by modulating cAMP-mediated regulatory networks. This study highlights the efficacy of integrating random mutagenesis with integrative genomic analysis for microbial strain engineering and presents a novel strategy for enhancing carotenoid production in E. coli

    Systemic Inflammation Decreases Initial Brain Injury but Attenuates Neurite Extension and Synapse Formation during the Repair of Injured Brains

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    In this study, we explored the impact of systemic inflammation on initial brain injury and repair processes, including neurite extension and synapse formation. For this purpose, we established a brain injury model by administering adenosine triphosphate (ATP), a component of damage-associated molecular patterns (DAMPs), through stereotaxic injection into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). Bulk RNA-sequencing (RNA-seq) analyses and immunostaining for microtubule-associated protein 2 (MAP2) and tyrosine hydroxylase (TH) showed that LPS-ip led to a reduction in initial brain injury, but inhibited neurite extension into the damaged brain. LPS-ip upregulated expression of defense response genes and anti-apoptotic genes, but decreased expression of genes associated with repair and regeneration. In addition, LPS-ip reduced levels of vGlut1 and PSD95 (markers for excitatory pre and post synapses, respectively), but had little effect on vGAT and gephyrin (markers for inhibitory pre and post synapses, respectively). Taken together, these findings suggest that systemic inflammation reduce initial damage but impede subsequent repair process

    Personality traits and academic attitudes of medical students in the COVID-19 pandemic: a person-centered approach, empirical research, Korea

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    Purpose: Since the coronavirus disease 2019 (COVID-19) pandemic, the educational environment has moved toward online-based education, which may significantly impact medical students’ educational experiences. However, the same events may be understood differently by different individuals depending on their personalities. Therefore, the changing educational environment during the COVID-19 pandemic may not have been perceived equally by all students. This study aimed to investigate medical students’ personality profiles and the difference between academic burnout and engagement according to their personality profiles. Methods: During the 2021–2022 academic year, when online-based education was implemented due to the pandemic, a survey was conducted among medical students in Korea (N=325). First, we used latent profile analysis to identify the sub-types of the Big Five personalities. Second, we used analysis of variance and post hoc comparisons to study the difference between academic burnout and engagement among these sub-types. Results: The Big Five personality traits of medical students in our sample were classified into three profiles. Profiles with relatively high neuroticism, while other personality traits were low, had both the highest academic burnout and academic engagement. Alternatively, the profiles showing relatively low neuroticism, while other personality traits were high, had the lowest academic burnout and the highest academic engagement. Conclusion: Personality is a stable trait that affects an individual’s behavior and response to the environment. Thus, individuals with specific personalities differ in their reactions to their environment. This may provide an advantage to some medical students’ careers

    모야모야 병에서 RNF213 변이의 손상된 자가포식과정을 통한 내피세포의 기능이상 유발

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    DoctorⅠ. INTRODUCTION 1 A. Moyamoya disease (MMD) 1 1. Moyamoya disease (MMD) 1 2. Clinical characteristics of MMD 1 3. Epidemiology of MMD 2 4. Pathophysiology of MMD 4 5. Therapeutic strategy for MMD 5 B. Ring finger protein 213 as a susceptibility gene of MMD 6 1. Ring finger protein 213 (RNF213) 6 2. Structure of RNF213 8 3. Function of RNF213 9 C. Autophagy 11 1. Autophagy 11 2. Autophagy associated with pathological conditions of MMD 13 D. Cilostazol (CSZ) as MMD therapeutics with an autophagy modulator 14 1. Cilostazol (CSZ) for the MMD patients 14 2. Autophagy modulation by CSZ 15 E. Aims of this study 16 Ⅱ. MATERIALS AND METHODS 18 A. Ethics statement 18 B. Subjects 18 C. Flow mediated dilation (FMD) analysis 19 D. Isolation of peripheral mononuclear cells (PBMCs) from MMD patients 19 E. Human umbilical vein endothelial cells (HUVECs) culture 20 F. Oxygen-glucose deprivation (OGD) 20 G. Plasmid and DNA purification 21 H. Electroporation 21 I. Western blot 21 J. Tube formation assay 22 K. Transmission electron microscopy (TEM) 23 L. Treatment of autophagy modulators 23 M. Statistical analysis 24 Ⅲ. RESULTS 28 PART A. Clinical characteristics of MMD patients carrying the RNF213 p.R4810K variant 28 1. A notable case of MMD patient carrying the RNF213 p.R4810K variant who experienced transient malnutrition 28 2. Endothelial dysfunction in MMD patients carrying the RNF213 p.R4810K variant 32 3. Autophagic dysfunction in MMD patients carrying the RNF213 p.R4810K variant 34 PART B. Experimental characteristics of human endothelial cells with the RNF213 p.R4810K variant under OGD stimulation 38 1. Autophagic dysfunction in HUVECs transfected with the RNF213 p.R4810K variant 38 2. Endothelial dysfunction in HUVECs transfected with the RNF213 p.R4810K variant 42 PART C. The pharmacological treatment for MMD prevention 44 1. Autophagic restoration by rapamycin (RA) in HUVECs transfected with the RNF213 p.R4810K variant 44 2. Autophagic restoration by cilostazol (CSZ) in HUVECs transfected with the RNF213 p.R4810K variant 50 Ⅳ. DISCUSSION 54 1. RNF213 p.R4810K variant response to environmental factors 57 2. Endothelial dysfunction by the RNF213 p.R4810K variant 59 3. Endothelial dysfunction related with autophagy 61 4. Autophagy impairment by the RNF213 p.R4810K variant 62 5. Autophagy inducers as a treatment strategy for MMD 63 Ⅴ. CONCLUSION 66 REFERENCES 68 국문요약 8

    The Characteristics of Senescent Tumor Cells in Colorectal Cancer

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    DoctorⅠ. INTRODUCTION 1 1. Cellular Senescence and Cancer 1 2. Detection of Senescent Tumor Cells in Vitro and in Vivo 2 3. Cancer Promoting Features of Senescent Cells in cancer tissues 3 4. Cellular Senescence and Spatial Evolution of Cancer 5 Ⅱ. MATERIALS & METHODS 7 1. IHC analysis of CRC tissues 7 2. IHC Imaging Analysis 8 3. Visium Spatial Transcriptomics Analysis 8 4. Single-cell RNA-sequencing (scRNA-seq) 9 5. Microdissection-assisted RNA-sequencing (mdaRNA-seq) 10 6. Cell Culture and Induction of Cellular Senescence in Vitro 10 7. SA-β-Gal Staining 11 8. SW620 Bulk RNA-sequencing 11 9. Immunoblotting 12 10. Transfection of Vectors and siRNAs 12 11. TCGA Data Set Analysis 13 12. Real-time Polymerase Chain Reaction (RT-PCR) 13 13. Cell Invasion Assay 14 14. Methylation-specific PCR (MSP) 14 15. Estimation of ROS Levels in vivo 14 16. Lentivirus preparation 15 17. Statistical analysis 15 Ⅲ. RESULT 16 Part I: Finding Novel Markers for Senescent Tumor Cells 16 1. Detecting Senescent Tumor Cells using Conventional Senescence Markers 16 2. scRNA-seq of CRC Dataset GSE166555 19 3. scRNA-seq Analysis of CDKN2A-positive Cells Using GSEA 21 4. In vivo validation of p15INK4B as a marker for senescent tumor cells in CRC 23 5. In vitro validation of p15INK4B as a marker for senescent tumor cells in CRC 25 6. Cytokeratin 7 as a marker for senescent tumor cells in CRC 28 Part II: Cancer-promoting features of senescent tumor cells 30 1. Location of senescent tumor cells is in the CRC tissue 30 2. Spatial transcriptomics analysis of CRC tissues using FFPE samples 39 3. Senescent Tumor Cells at the Invasive Front Exhibit Distinctive Phenotype 42 4. Senescent Cells Evolve from Non-senescent Tumor Cells 52 5. Senescence-related Epigenetic Reprogramming in Cancer Evolution 58 6. Senescent Tumor Cells Express Unique Genes to Invade 71 7. LAMC2-EGFR-MMP7 Signaling Axis in Type II Senescent Tumor Cells 81 8. Type II Senescent Tumor Cells are Related to Lymph Node Metastasis 90 Ⅳ. DISCUSSION 98 1. Detection of Senescent Tumor Cells and Limitations 98 2. Cellular Senescence and Cancer Evolution 101 Ⅴ. REFERENCES 10

    The Impact of Head Elevation on Preventing Emergence Cough during Endotracheal Extubation in Male Patients

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    DoctorⅠ. Introduction 1 Ⅱ. Material and Method 3 A. Ethics Statement 3 B. Patient Allocation 3 C. Anesthesia 3 D. Definition and Measurements 4 E. Statistical Analysis 5 Ⅲ. Results 6 A. Cough Profiles 6 B. Emergence and Recovery Profiles 6 C. Hemodynamics 6 IV. Discussion 7 Ⅴ. Conclusions 11 Ⅵ. List of Figures 12 A. Patient enrollment 12 B. The heart rate and mean arterial pressure during perioperative period 13 Ⅶ. List of Tables 14 A. Characteristics and intraoperative data of male patients 14 B. Incidence and severity of cough 15 C. Anesthetic emergence and recovery outcomes 16 Ⅷ. References 1

    근골격계 조직공학을 위한 자가조립 활용 중간엽 줄기세포 집합체의 개발 및 변형

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    DoctorBACKGROUND 1 1.1. Mesenchymal stromal cells (MSCs) 2 1.1.1. Synovium-derived mesenchymal stem cells (SMSCs) 2 1.1.2. SMSCs for musculoskeletal tissue engineering 3 1.2. Self-assembly 4 1.2.1. Self-assembly techniques as recapitulation of early stage chondrogenesis 4 1.2.2. Musculoskeletal tissue engineering by using self-assembly techniques 5 1.3. Decellularized extracellular matrix (dECM) 6 1.3.1. dECM powder as one of formulation for tissue engineering approach 6 1.3.2. Decellularized cartilage and meniscus ECM powder 7 1.4. Thesis overview 8 CHAPTER I: Fabrication of scaffold-free fibrocartilage microtissues for bone-tendon interface healing 10 2.1. Introduction 11 2.2. Materials and methods 13 2.2.1. Isolation of synovial stem cells and cultivation of the cells 13 2.2.2. Fabrication of cell-based fibrocartilage microtissues without scaffold 13 2.2.3. Histological analysis of cell-based fibrocartilage constructs 15 2.2.4. Biochemical characterization of cell-based fibrocartilage constructs 15 2.2.5. Utilization of collagenase for tendon to fibrocartilage constructs integration 16 2.2.6. Evaluation of tendon to fibrocartilage constructs interface 16 2.2.7. Integration of tendon with a bone/cell-based fibrocartilage construct in vitro 17 2.2.8. Integration failure stress analysis 17 2.2.9. In vivo bone-to-tendon healing efficacy 18 2.2.10. Statistical analysis 19 2.3. Results 20 2.3.1. In vitro fabrication of cell-based fibrocartilage microtissues 20 2.3.2. Improvement of tendon integration with SMSCs after collagenase employment 22 2.3.3. In vitro integration evaluation of cell-based fibrocartilage microtissues 24 2.3.4. Effectiveness of cell-based fibrocartilage microtissues in bone-to-tendon repair in vivo 26 2.4. Discussion 28 CHAPTER II: Extracellular matrix-guided self-assembled meniscal microtissue engineering for replication of transitional meniscal tissue in a partial meniscectomy animal model 31 3.1. Introduction 32 3.2. Materials and methods 34 3.2.1. Isolation and culture of cells 34 3.2.2. Characterization of multipotency 34 3.2.3. Flow cytometry 35 3.2.4. The process for producing porcine acellular meniscal extracellular matrix (DMECM) 35 3.2.5. Engineering of self-assembled meniscal microtissues 36 3.2.6. Repression of self-assembly 37 3.2.7. Characterization of self-assembled microtissue with DMECM in vitro 37 3.2.8. Surgery for micropig meniscus defect model 39 3.2.9. Cell tracking for micropig meniscus defect model 40 3.2.10. Histological evaluation for micropig meniscus defect model 41 3.2.11. Biomechanical analysis for micropig meniscus defect model 42 3.2.12. Statistical analysis 43 3.3. Results 44 3.3.1. Optimization of cells concentration for engineering self-assembled microtissue 44 3.3.2. Optimization of DMECM concentration for engineering self-assembled microtissue 46 3.3.3. Developing meniscal microtissues using SMSCs and DMECM by self-assembly 48 3.3.4. Impacts on the self-assembly process at early differentiation and morphology 50 3.3.5. Effects of region-specific DMECM on maturity of meniscal microtissues by evaluating histological analysis 52 3.3.6. Effects of region-specific DMECM on maturity of meniscal microtissues by evaluating biochemical analysis 54 3.3.7. Effects of region-specific DMECM on maturity of meniscal microtissues by evaluating biomechanical analysis 56 3.3.8. Self-assembled microtissue as a meniscal filler and its handling for surgery 58 3.3.9. The effectiveness of a meniscal microtissues in a partially meniscectomized porcine model 60 3.3.10. Evaluation of mechanics related to tibiofemoral joint at the porcine model 63 3.3.11. Mechanical properties of regenerated meniscus 65 3.3.12. Evaluation of articular cartilage following a six-month implantation 67 3.4. Discussion 69 CHAPTER III: Preparation of printable cartilage tissue utilizing self-assembly of synovial stromal cells and decellularized cartilage extracellular matrix 74 4.1. Introduction 75 4.2. Materials and methods 77 4.2.1. Preparation of of decellularized cartilage extracellular matrix (DCECM) 77 4.2.2. Preparation of porcine synovium-derived stem cells 77 4.2.3. Fabrication of DCECM-guided self-assembled microtissue (DSA) 78 4.2.4. Physical characterization of DSA 80 4.2.5. Biological characterization of DSA 80 4.2.6. Biochemical characterization of DSA 81 4.2.7. Rheological characterization of DSA 82 4.2.8. Printing of DSA 82 4.2.9. Evaluation of printed constructs 83 4.2.10. Surgery for implantation of printed construct 84 4.2.11. Histologic analysis and cell tracking for implantation of printed construct 84 4.2.12. Biomechanical analysis for implantation of printed construct 85 4.2.13. Statistical analysis 85 4.3. Results 86 4.3.1. Optimization of DCECM concentration and DCECM size for fabrication of DSA 86 4.3.2. Characterization of DSA bioink 88 4.3.3. Rheological properties of DSA for 3D bioprinting 94 4.3.4. Printing condition adjustments 96 4.3.5. 3D bioprinting of DSA bioink 98 4.3.6. Evaluation of printed constructs 100 4.3.7. Implantation of printed construct using DSA bioink for porcine full-thickness cartilage defect model 102 4.3.8. pSMSCs tracking after 6-month implantation 105 4.4. Discussion 107 CONCLUSIONS 110 REFERENCES 112 국문요약 12

    태국 간호대학생의 감성지능과 자기효능감이 임상실습스트레스에 미치는 영향

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    MasterⅠ. 서론 . 1 A. 연구필요성 1 B. 연구의 목적 3 C. 용어의 정의 4 Ⅱ. 문헌고찰 6 A. 간호대학생의 임상실습스트레스 . 6 B. 간호대학생의 임상실습스트레스 관련요인 . 8 Ⅲ. 연구방법 . 12 A. 연구설계 12 B. 연구대상 12 C. 연구도구 12 D. 자료수집방법 . 14 E. 자료분석방법 . 14 F. 윤리적 고려 15 Ⅳ. 연구결과 . 16 A. 대상자의 일반적 특성 16 B. 대상자의 감성지능, 자기효능감 및 임상실습스트레스 정도 18 C. 대상자의 일반적 특성에 따른 임상실습스트레스 차이 . 20 D. 대상자의 감성지능, 자기효능감 및 임상실습스트레스의 상관관계 . 22 E. 대상자의 임상실습스트레스에 영향을 미치는 요인 . 23 Ⅴ. 논의 25 Ⅵ. 결론 및 제언 . 30 A. 결론 30 B. 제언 31 참고문헌 . 32 부 록 . 42 ABSTRACT . 5

    예술활동을 통한 지역사회 건강 증진 효과분석 및 정책적 제언

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    DoctorI. 서론 1 1. 연구의 필요성 1 2. 연구 목적 5 II. 관련 이론 및 선행 연구 6 1. 예술과 건강 현황 6 2. 대한민국 예술과 건강의 역사 7 3. 예술치유 프로그램 12 3.1. 서울문화재단 예술 치유 프로그램 13 3.2. 민간부문에서의 예술과 건강 13 4. 예술과 건강 프로그램의 효과에 대한 연구 14 5. 예술과 건강, 미술치료, 미술교육 간의 관계 17 6. 예술과 건강의 발전 프로세스 및 정책적 제언 19 III. 예술과 건강의 생리학적 기전 23 1. 예술치유와 신경과학 23 1.1 자율신경계 25 1.2. 자율신경계가 사고와 인체에 미치는 영향 26 1.3. 다 미주신경 이론 (Polyvagal theory) 28 1.4. 뇌 가소성 31 2. 예술활동의 생리학적 기전 32 IV. 연구방법 및 모형 34 1. 연구 방법 34 1.1. 분석 대상 및 기준 34 1.2. 연구 선정 과정 35 1.3. 효과크기 산출 35 2. 메타분석 결과· 36 2.1 데이터 추출 36 2.2. 연구 특성 39 2.3. 예술활동이 웰빙, 불안과 우울감에 미치는 영향 41 2.3.1. 웰빙, 불안, 우울감에 대한 예술 중재의 효과 크기 41 2.3.2. 건강과 웰빙에 미치는 예술 중재의 효과 변인에 대한 요인 45 2.4. 논의 48 2.5. 메타분석 결론 51 V. 암환자를위한디지털예술활동의효과연구프로토콜 52 1. 연구배경 및 필요성 52 1.1. 예술활동이 건강에 미치는 영향에 관한 임상연구 현황 52 1.2. 암 53 1.3. 방사선 치료 55 1.4. 디지털 미술치료 55 2. 방법 57 2.1 연구 방법 57 2.1.1. 연구대상 선정 기준 및 제외기준 57 2.1.2. 연구대상자 산출 근거 및 집단 배정 57 2.1.3. 디지털 미술치료 절차, 프로그램, 방문, 검사 60 2.1.4. 수집 항목 65 가. 디스트레스 온도계(Distress Thermometer) 65 나. 수행능력 상태(ECOG PS Eastern Cooperative Oncology Group) 66 다. 불안 척도(State-Trait Anxiety Inventory: STAI-X-1, STAI-X-2 ) 66 라. 통증-시각적 아날로그 척도(Visual Analogue Scale-Pain, VAS-Pain) 66 마. 피로도 (linear Analogue Self Assessment, LASA) 67 바. RT 불안(The Amsterdam Preoperative Anxiety and Information Scale, APAIS) 67 사. 미술치료 평가(Satisfaction and Acceptability) 67 아. 심박변이도(Heart Rate Variability, HRV) 67 자. 기타 비침습적 바이오마커 측정 69 2.1.5. 기존의 표준 치료 및 진료와의 차이점 69 2.1.6. 통계 분석 방법 70 VI. 결론 및 한계점 70 1. 종합 결론 70 2. 한계점 및 향후 연구 72 § 참고문헌 74 § 부록. 척도 86 § Abstract 9

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