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Comparative Risk for Neuropsychiatric Events in Leukotriene Receptor Antagonist vs. Inhaled Corticosteroid in Children With Asthma: A Nationwide Observational Study With a Complementary Analysis Using Natural Language Processing
No full textPURPOSE: Leukotriene receptor antagonists (LTRAs) are widely prescribed as controller medications for pediatric asthma. However, there have been increasing concerns about potential neuropsychiatric adverse reactions associated with LTRAs. Findings from observational studies have been inconsistent, and direct comparisons of the risk of neuropsychiatric events (NPEs) between LTRAs and inhaled corticosteroids (ICS) remain limited in the pediatric population. METHODS: A retrospective cohort study was conducted utilizing a nationwide claims database (January 2018-April 2022) and a multicenter electronic health record (EHR) database (January 2006-March 2022) from South Korea. Patients aged 5-18 years diagnosed with asthma before initiating LTRA or ICS were included. The primary outcome was NPEs within 90 days of exposure, defined using two methods: diagnostic code-based analysis and natural language processing (NLP)-based analysis using clinical notes. After propensity score stratification, Cox proportional hazards models were used to estimate risks. RESULTS: The diagnostic code-based analysis on the claims database included 169 636 LTRA users and 28 845 ICS users. There was no statistically significant difference in the risk of NPEs between LTRA and ICS (calibrated hazard ratios [HRs], 1.14 [95% CI, 0.92-1.42]). In the NLP-based analysis using EHR database, 1641 LTRA users and 1607 ICS users were included. The results were consistent with those of the diagnostic code-based analysis (calibrated HR, 1.33 [95% CI, 0.66-2.68]). CONCLUSIONS: LTRA use was not found to be associated with a significantly increased risk of NPEs in children with asthma. These findings offer valuable insights to support clinical decision-making in pediatric asthma treatment
초파리 생체시계에서 Peptidyl-Prolyl cis/trans Isomerase-like 4 가 이중 조절자로서 PERIOD 를 조절하는 기전에 대한 연구
No full textDoctorI. INTRODUCTION 1
1. Circadian timing system 1
2. Circadian clock cell network 1
3. Molecular mechanism of circadain clock 2
4. Post-tranlational modification of clock proteins 3
5. Peptidyl-Prolyl cis/trans isomerase 5
6. Aims of the study 6
II. Materials and Methods 8
1. Fly stocks 8
2. Transgenic fly generation 9
3. Locomotor behavior analysis 9
4. Western blotting and immunoprecipitation 10
5. Immunohistochemistry and confocal imaging 11
6. Real-time quantitative reverse transcription-PCR (qRT-PCR) 12
7. RNA sequencing and data analysis 13
8. DEXseq 14
9. Feeding assay 15
10. PER degradation rate analysis: cycloheximide (CHX) treatment 15
11. Statistical analysis 16
III. RESULTS 17
1. PPIases knockdown Drosophila mostly shows a long period 17
2. dppil4 knockdown in clock cells lengthens the free-running period 21
3. dPPIL4 is requried for Drosophila development 29
4. dPPIL4 ubiquitously expressed in brain icluding clock cells and is localized in the nucleus 32
5. Reduced PER levels are responsible for the long period of dppil4 KD flies 40
6. dPPIL4 regulates both per RNA and PER protein 50
7. dPPIL4 supports per transcription via RNA polymerase II CTD pSer5 regulation 59
8. dPPIL4 regulates PER degradation by stabilizing CUL1 in SCFSlimb complex 70
IV. DISCUSSION 77
V. CONCLUSION 83
REFERENCES 84
국문요약 9
Sirtuin 2 억제제들이 B형 간염 바이러스 증식에 미치는 영향
No full textMasterⅠ. Introduction 1
Ⅱ. Materials and Methods 6
A. DNA constructs 6
B. Cell culture and transfection of DNA 6
C. Establishment of stable cell lines 8
D. Preparation of HBV and cell infection 8
E. Drug treatments 10
F. SDS-PAGE and immunoblotting 11
G. Immunoblotting of core particles 11
H. Northern, Southern, and in situ nucleic acid blotting 12
I. Luciferase reporter assay 13
J. ELISAs for HBsAg and HBeAg 14
K. MTS assay 15
L. HBV cccDNA extraction 15
M. RT-qPCR and qPCR 16
N. Statistical analysis 17
Ⅲ. Results 19
A. SIRT2 inhibitors do not exhibit cytotoxicity in HCC cell lines 19
B. Endogenous SIRT2 levels are elevated in HBV replicating cells, leading to reduction of acetylated α-tubulin levels 22
C. AK7, a selective SIRT2 inhibitor, inhibits HBV replication in HBV WT-transfected cells 27
D. AK7 restricts HBV transcriptional activity and RNA production 33
E. AK7 reduces HBV cccDNA production in HBV- replicating stable HepAD38 cells 37
F. AK7 efficiently suppresses HBV replication in HBV- infection systems 39
G. Other SIRT2 inhibitors, SirReal2, thiomyristoyl, and tenovin-3, exhibit distinct anti-HBV effects compared to AK7 46
Ⅳ. Discussion 54
Ⅴ. References 58
국문 초록 6
흰쥐 뇌내출혈 모델에서 하이드로젤을 이용한 신경재생
No full textMasterI Introduction 1
1.Definition and epidemiology of intracerebral hemorrhage 1
1.1 Clinical manifestation and diagnosis 1
2. Pathophysiology 3
2.1 Primary Brain Injury 3
2.2 Secondary Brain Injury 3
2.3 Ferroptosis 4
2.4 Cellular and Extracellular Responses to Brain Injury 5
2.5 MMPs and BBB Disruption 7
2.6 Chronic Phase of Intracerebral Hemorrhage 7
3.Treatment and management of ICH 8
3.1 Emerging Preclinical novel Therapies for ICH 9
3.2 Hydrogel 9
4. Aim of this study 11
II Materials and Methods 12
1. Animals and surgical procedure 12
2.Hydrogel preparation and injection 14
3.Tissue processing and immunohistochemistry 14
4.Cresyl violet and Hematoxylin & Eosine staining 15
5.Image acquisition and analysis 16
6.Magnetic Resonance Imaging (MRI) 17
7.Behavioral study 17
7.1 Pellet retrieval test 17
7.2 Ladder rung test 19
7.3 Cylinder test 19
III Results 20
1.Temporal Evolution of the ICH Lesion 20
1.1 Histological Assessment (H&E) of Lesion and Cavity 20
1.2 Lesion 3D Volume Quantification 22
1.3 Ventricular Enlargement Following ICH 24
2. MRI-Based Lesion Evolution and Timepoint Selection 24
3. Baseline Glial and ECM Dynamics Post-ICH 27
3.1 GFAP and Fibronectin Expression Patterns Over Time 27
3.2.GFAP and Iba-1 Expression Patterns Over Time 29
4.Effect of Hydrogel Injection on Lesion Morphology 31
4.1 MRI Assessment of Lesion Evolution Post-Hydrogel Injection 31
4.2 Histological Evaluation of Lesion Repair 33
5.Hydrogel-Mediated Modulation of ECM and Glial Response 35
5.1 Fibronectin and GFAP Through the Time 35
5.2 IBA-1 and GFAP Through the Time 35
6. Behavioral Assessment Reveals Limited Functional Recovery 38
6.1 Ladder Rung Test 40
6.2 Single Pellet Retrieval Test 40
6.3 Cylinder Test 40
IV Discussion 42
V References 45
국문요약 4
Outcomes Comparison of Endovascular and Open Surgical Approaches for Subclavian Arterial Injury: A Nationwide Analysis
No full textBackground: The management of patients with subclavian artery injury is rapidly evolving from an open to an endovascular approach. We aim to present an analysis of management and a comparison of outcomes according to the type of approach used to treat these challenging injuries. Methods: Adult patients with subclavian arterial injuries were abstracted from the National Inpatient Sample database from 2012–2014 and 2016–2021. Patients were divided according to the type of management, which was endovascular management (EM; stent placement) or open surgery (OS), and clinical outcomes were compared. A multivariable logistic regression model was used to determine risk factors associated with in-hospital mortality. Results: A total of 1200 cases were analyzed. The EM and OS groups had similar baseline characteristics, including age, sex, All Patient Refined Diagnosis-Related Groups severity of illness and risk of mortality scores, and Charlson Comorbidity Scores. The presence of shock on admission was similar between groups (EM: 23.1% vs. OS: 34.2%; P = 0.115). Median injury severity score was higher in the EM group but with a lower mortality rate (5.5% vs. 14.8%, P = 0.045) than OS. Additionally, EM was associated with a lower fasciotomy rate (P = 0.018). Hemorrhagic shock on presentation (odds ratio: 3.72) was associated with a marked increase in the odds of in-hospital mortality, while EM was associated with a 67% decrease (odds ratio: 0.33). Conclusions: EM is associated with significantly better outcomes, including lower odds of in-hospital mortality and a decreased need for fasciotomy. Currently, EM is a feasible option in the management of subclavian arterial injuries
Diagnosis of invasive pancreatic cancer in endoscopic ultrasound images leveraging translation models
No full textBackground: In guiding treatment decisions for pancreatic cancer, assessing vascular invasion is critical, particularly for determining resectability. Deep learning techniques have demonstrated potential for diagnosing vascular invasion through the analysis of pancreatic endoscopic ultrasound (EUS) images. However, challenges arise when dealing with multicenter data sources and imbalanced datasets, which may affect the performance of deep learning models. Method: EUS images were collected from 170 patients with pancreatic cancer diagnosed at three endoscopy centers using various ultrasound systems. To diagnose vascular invasion while mitigating data variations, feature and image translation models were utilized to effectively align the source and target domains. An image translation model was utilized in the proposed approach (multicenter transfer learning (MCTL)) by employing CycleGAN and customized weighted loss classification models. The performance was compared with those of a feature translation model (multicenter domain adaptation (MCDA)) and widely accepted baseline classification models. Result: The translation models compensated for the distinctive data-specific features and improved the models for classifying vascular invasion. Although the feature translation model proved effective, its applicability was limited across different datasets. The proposed MCTL approach showed superior classification performance with accuracy improvements of 26.79%, 67.26%, and 50.91% over the baseline model and 17.86%, 48.81%, and 42.50% over the MCDA model for the three imbalanced datasets. Significance: This study leveraged a deep learning approach for enhancing the diagnosis of vascular invasion in pancreatic cancer using EUS images from multiple centers and addressed the issue of data imbalance
Psychometric validation of the Korean version of the debriefing experience scale
No full textBackground: Simulation-based nursing education is an essential pedagogical approach. The debriefing process is a key component of this type of education. The Debriefing Experience Scale (DES) is widely used to measure students' postsimulation debriefing experience, but its applicability in Korea has not been validated. Methods: This study translated the DES into Korean and validated it with 205 students from five nursing schools in South Korea. Reliability was assessed using Cronbach's alpha, and content validity was evaluated by a panel of experts. Convergent validity was assessed by correlating DES scores with the Satisfaction with Simulation Experience (SSE) scale, and construct validity was examined through confirmatory factor analysis. Results: The Korean version of the DES demonstrated high internal consistency and satisfactory content validity. The DES correlated strongly with the SSE scale, confirming convergent validity. Confirmatory factor analysis supported the construct validity of the scale, showing a well-defined factor structure and acceptable model fit indices. Conclusion: The Korean version of the DES is a reliable and valid tool for evaluating students’ debriefing experiences in simulation-based education. Its strong psychometric properties make it a valuable tool for educators and researchers to evaluate and enhance the effectiveness of simulation programs in diverse cultural contexts
Clinical Implications of the Obstructive Pattern on Chest Radiography in Children Aged 3–59 Months With Severe Lower Respiratory Tract Infections
No full textObjectives: To investigate the clinical implications of the obstructive pattern on plain chest radiography, defined as peribronchial cuffing or hyperinflation, in young children with severe lower respiratory tract infections (LRTIs). Methods: We reviewed all children aged 3‒59 months with LRTIs who underwent radiography and polymerase chain reaction in a Korean emergency department from 2016 through 2020. The radiographs were read as consolidation, peribronchial cuffing, or hyperinflation, with each interrater reliability computed. As per the obstructive pattern, we compared their clinical features, therapeutic interventions, outcomes, and microbiology. Results: Among 599 children with LRTIs, 465 were enrolled, of whom 98 (21.1%) had consolidation (κ = 0.60; 95% confidence interval, 0.50‒0.70), and 367 (78.9%) had peribronchial cuffing (0.55; 0.46‒0.65) or hyperinflation (0.59; 0.52‒0.67). The obstructive pattern was significantly associated with more frequent wheezing (obstructive, 28.6% vs. consolidation, 10.2%) and the use of inhaled albuterol or systemic steroids (39.0% vs. 23.5%), and lower median values or frequencies of age (22.0 vs. 35.0 months), crackle or diminished breath sound (42.0% vs. 61.2%), C-reactive protein (1.4 vs. 2.9 mg/dL), antibiotic therapy (72.2% vs. 93.9%), length of hospital stay (4.0 vs 5.0 days), fever lasting 3 days or longer (7.9% vs. 29.6%), and complications (0.5% vs. 9.2%). Microbiologically, viruses, such as respiratory syncytial virus, were more frequently detected in children with the obstructive pattern or at a younger age. Conclusions: This study confirms an association of the obstructive pattern on radiography with viral infection and inflammatory airway obstruction-relieving therapy in young children with severe LRTIs
Urinary trace elements and thyroid nodule formation in a longitudinal cohort of older women: Findings from KoGES
No full textThyroid nodules are common in older populations, but the role of trace elements in their development and growth remains unclear. Previous studies have reported inconsistent findings regarding the association between trace elements and thyroid nodules. This study investigated the associations between urinary concentrations of various trace elements and the prevalence and incidence of thyroid nodules in older women, a population at higher risk for thyroid disorders. Cross-sectional and longitudinal analyses were conducted using data from 653 women aged 60 years and older in the Ansung cohort of the Korean Genome and Epidemiology Study (KoGES). Urinary concentrations of 18 elements were analyzed using inductively coupled plasma mass spectrometry (ICP-MS), and mercury was analyzed using a Direct Mercury Analyzer (DMA). Logistic regression was used to assess associations between trace element exposure and thyroid nodule prevalence, stratified by nodule size (3.0-4.9 mm, 5.0-9.9 mm, and >/=10.0 mm). Higher urinary concentrations of Mn (OR 2.04; 95 % CI, 1.27-3.28), Cu (OR 1.71; 95 % CI, 1.08-2.72), and Co (OR 1.48; 95 % CI, 0.94-2.31) were significantly associated with larger thyroid nodules (>/=10.0 mm). Zinc (OR 1.33; 95 % CI, 0.84-2.11) showed a weaker but positive association with larger nodules, while uranium exposure was notably linked to the development of new nodules during follow-up (OR 7.70; 95 % CI, 1.56-38.10 for nodules >/=5.0 mm). The findings suggest that trace elements, particularly Mn, Cu, Co, Zn, and U, may contribute to the formation and growth of thyroid nodules in older women. Future research should investigate the underlying mechanisms and expand to other populations to better understand these associations
Genome-wide identification and functional validation of the WW domain containing oxidoreductase gene associated with sleep duration
No full textIndividual differences in sleep duration have been reported, and genetic components of sleep duration have been identified showing various heritability. To identify genetic variants that contribute to sleep duration, we conducted a human genome-wide identification on sleep duration and performed confirmatory experiments using a Drosophila model. Genome-wide association study in human was analyzed to determine the association of the genetic variants with self-aware sleep duration from two community-based cohort, Ansan (cohort 1, n = 4635) and Ansung (cohort 2, n = 4205), recruited from the Korean Genome and Epidemiology Study. Individual single nucleotide variants (rs16948804 and rs4887991) in the WW domain containing oxidoreductase (WWOX) gene were associated with self-aware sleep duration in human (p-values, 1.11 x 10(- 7) and 2.05 x 10(- 7), retrospectively). To examine the functional relevance of the WWOX gene identified in the genome-wide association study, we analyzed the sleep duration of Drosophila loss-of-function mutants. The deletion of Wwox in flies reduced sleep duration and quality with average bout length during daytime and increased night-time sleep duration (all of p-values < 0.01). Our findings suggested that WWOX expression is associated with sleep duration in both humans and Drosophila and genetic factors play a role in inter-individual variability in sleep characteristics