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형태학적 및 질감 표현 기반 통합 학습을 활용한 병리 이미지의 종양 이진 분류
No full textMaster1 서 론 1
2 재료 및 방법 5
2.1 병리 슬라이드 이미지 데이터셋 5
2.2 병리 슬라이드 이미지 전처리 과정 9
2.3 기준 모델 (Baseline Model: CLAM) 9
2.3.1 심층 특징 추출 (Deep Feature Extraction) 10
2.3.2 어텐션 기반 다중 인스턴스 학습 (Attention based Multiple Instance Learning) 10
2.4 형태학적 계층 (Morphological Layer) 12
2.4.1 형태학적 연산자 (Morphological Operators) 12
2.5 질감 기술자 (Texture Descriptor) 14
2.5.1 Gabor filter 14
2.5.2 Scale Invariant Feature Transform 16
2.5.3 Local Binary Pattern 17
2.5.4 Histogram of Oriented Gradients 18
2.5.5 Gray-Level Co-occurrence Matrix 19
2.6 제안 방법 (Proposed Method) 19
2.6.1 질감 및 형태학적 특징 추출 (Texture and Morphological Feature Extraction) 20
2.7 실험 설정 (Experimental Setting) 21
2.8 실험 환경 (Experimental Environment) 22
2.9 모델 성능 평가 (Evaluation) 22
3 실험 결과 24
3.1 실험 결과 24
3.2 Texture descriptor 비교 분석 25
3.3 Morphological operator 비교 분석 30
3.4 제안 모델 결과 비교 32
3.5 Instance-level Clustering 결과 분석 37
4 결론 및 고찰 39
참고문헌 42
영문요약 4
자궁내막암 치료후보로서 COX 저해제 유사체의 효능 평가 연구
No full textMaster제 1 장 서론 1
제 2 장 재료 및 방법 5
제 1 절 재료 5
제 1-1 항 Reagents 5
제 1-2 항 Maintenance of Cell Line 5
제 2 절 연구 방법 6
제 2-1 항 COX-2(Cyclooxygenase-2) Inhibitor Screening 6
제 2-2 항 Cell Viability Assay 7
제 2-3 항 Drug Preparation & Treatment 8
제 2-4 항 Scratch Wound Healing Assay 9
제 2-5 항 Transwell Invasion Assay 10
제 2-6 항 Western Blotting 11
제 2-7 항 Statistical Analysis 13
제 3 장 결과 14
제 1 항 Seven-G의 COX-2 효소 억제 효과 및 항염증 특성 14
제 2 항 HEC-1-A 세포주에서 Seven-G의 항증식 효과 15
제 3 항 Seven-G의 농도 의존적 HEC-1-A 세포주 Migration 억제 효과 16
제 4 항 Seven-G의 농도 의존적 HEC-1-A 세포주 Metastasis 억제 효과 17
제 5 항 HEC-1-A 세포주에서 Seven-G의 세포 자멸사(Apoptosis) 유도 효과 18
제 4 장 고 찰 31
참고 문헌 34
Abstract 3
Efficacy of combined CD38 and PD-1 inhibition with isatuximab and cemiplimab for relapsed/refractory NK/T-cell lymphoma
No full textThis study aimed to assess the efficacy and safety of combining cemiplimab, an anti-programmed cell death protein 1 (PD-1) antibody, with isatuximab, an anti-CD38 antibody, in relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL). The hypothesis was that CD38 blockade could enhance the antitumor activity of PD-1 inhibitors. Eligible patients received cemiplimab (250 mg on days 1 and 15) and isatuximab (10 mg/kg on days 2 and 16) IV every 4 weeks for 6 cycles. Responders then received cemiplimab (350 mg) and isatuximab (10 mg/kg) every 3 weeks for up to 24 months. The primary end point was the complete response (CR) rate based on the best response. Of 37 patients enrolled, the CR rate was 51% (19/37), exceeding the primary end point of 40%, and the objective response rate was 65% (24/37). After a median follow-up of 30.2 months (95% confidence interval [CI], 25.6-34.8 months), the median progression-free survival was 9.5 months (95% CI, 1.4-17.6 months), whereas the median overall survival had not yet been reached. Patients achieving CR received a median of 28 cycles (range, 4-33 cycles), and the median duration of response for responders (n = 24) was 29.4 months (95% CI, 15.4-43.4 months). Structural variations disrupting the 3'-untranslated region of PD-L1 and high programmed death ligand 1 (PD-L1) expression were observed in responders. Most adverse events were mild (grade 1-2), with grade >/=3 events (32%) and no treatment-related deaths. The combination of isatuximab and cemiplimab demonstrated sustained antitumor activity and a manageable safety profile in R/R ENKTL. This phase 2 trial is registered at www.clinicaltrials.gov as number NCT04763616
Impact of Qualified Trauma Center Implementation on Mortality From Severe Trauma in Korea: A Retrospective Cohort Study
No full textBACKGROUND: The Korean government and experts initiated a national trauma system development project in 2012. Its first major initiative was establishing and operating regional trauma centers across the country. We assessed whether the severity-adjusted mortality rates were lower in trauma centers compared with non-trauma centers and the specific benefits of trauma centers for patients with trauma. METHODS: This retrospective cohort study analyzed the data of patients with trauma registered in the National Emergency Department Information System from 2015 to 2019. Additionally, we used the Korean Trauma Data Bank and trauma center status data provided by the Ministry of Health and Welfare. We focused on patients with survival probabilities of < 0.5 according to the International Classification of Diseases Injury Severity Score, 9th Edition. The severity-adjusted mortality rates between the trauma centers and non-trauma centers were compared. RESULTS: The 7 qualified trauma centers had notably more younger patients with penetrating injuries than the non-trauma centers. Patients admitted to the trauma centers had more critical vital signs and a higher incidence of reduced consciousness than those admitted to the non-trauma centers. After adjusting for severity, the in-hospital mortality rates were significantly lower in the trauma centers than in the non-trauma centers (16.9% vs. 18.2%; relative risk, 0.933; 95% confidence interval, 0.874-0.997). Patients in shock conditions had significantly lower mortality rates when treated in trauma centers. The disparity in cumulative mortality rates between the trauma centers and non-trauma centers was most pronounced 2 days post-admission. CONCLUSION: This study confirmed that the national project for establishing regional trauma centers effectively reduced mortality rates among severely injured patients. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0009684
Large-Scale Profiling of Coding and Long Noncoding Transcriptomes in the Hippocampus of Mice Acutely Exposed to Vaporized CBD or THC
No full textCannabis vaping, particularly involving cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), rapidly delivers highly concentrated cannabinoids to the brain, potentially affecting the hippocampus. This study examined differential expression of long noncoding RNAs (lncRNAs) and mRNAs in the hippocampus after acute exposure to vaporized CBD or THC. Male ICR mice were exposed to vaporized CBD or THC (50 mg, n = 5/group), and hippocampal tissues were collected at 1, 3, and 14 days post-exposure. Total RNA sequencing was conducted on day 1 samples, and selected transcripts were validated using qRT-PCR across multiple time points. CBD led to significant up- or downregulation of L3mbtl1, Wnt7a, and Camk2b at day 1. However, Wnt7a showed gradual recovery at days 3 and 14. In the THC group, Grin2a, Gria3, and Golga2 were significantly upregulated, while Drd1, Drd2, Gnal, and Adcy5 were significantly downregulated at day 1. Time-course analysis showed that Drd2 expression returned to baseline by day 14, whereas Adcy5 remained persistently downregulated through days 3 and 14. In the CBD group, NONMMUT069014.2 was upregulated, while NONMMUT033147.2 and NONMMUT072606.2 were downregulated at day 1; notably, NONMMUT072606.2 showed a transient increase at day 3 before returning to baseline. In the THC group, NONMMUT085523.1 and NONMMUT123548.1 were upregulated, whereas NONMMUT019734.2, NONMMUT057101.2, and NONMMUT004928.2 were downregulated, with most showing gradual recovery by day 14. Correlation analysis revealed that THC-responsive lncRNAs-including NONMMUT004928.2, NONMMUT057101.2, and NONMMUT019734.2-were strongly associated with downregulated mRNAs such as Drd2 and Adcy5. These findings highlight cannabinoid-specific hippocampal transcriptomic responses and suggest potential regulatory roles for lncRNA-mRNA interactions in cannabinoid-induced neural changes
Is the next STEP on the BPROAD to intensive blood pressure lowering for all type 2 diabetic patients?: consensus statements from the Korean Society of Hypertension
No full textThe optimal blood pressure (BP) target in patients with type 2 diabetes mellitus (T2DM) continues to be debated. The 2022 guidelines from the Korean Society of Hypertension (KSH) recommend intensive BP lowering only for patients with diabetes who are at high cardiovascular (CV) risk. However, recent trials have demonstrated favorable outcomes associated with intensive BP lowering in T2DM. In response, the updated KSH consensus statements provide evidence-based recommendations supporting the implementation of intensive BP control strategies in hypertensive patients with diabetes, including those at low to moderate CV risk. The KSH consensus statements are as follows: 1) Hypertension is a common comorbidity of T2DM, with a prevalence of 59.6% among adults with diabetes aged 30 years and older in Korea. 2) In patients with T2DM, coexisting hypertension increases the risk of both macrovascular and microvascular complications; however, tight BP control reduces diabetes-related morbidity and mortality. 3) Recent guidelines advocate tailored BP targets based on individual CV risk profiles to balance treatment safety and effectiveness, and recommend a BP target of < 130/80 mmHg for patients with T2DM. 4) The BPROAD (Intensive Blood-Pressure Control in Patients with Type 2 Diabetes) trial provides the strongest evidence for intensive BP control in patients with T2DM, while the STEP (Trial of Intensive Blood-Pressure Control in Older Patients with Hypertension) and the ESPRIT (Effects of Intensive Blood Pressure Lowering Treatment in Reducing the Risk of Cardiovascular Events) trials support intensive BP lowering in high-risk diabetic patients and extend the findings to broader high-risk populations, respectively. 5) A nationwide Korean study suggests that, if patients with T2DM can safely tolerate it, lower BP levels in patients with T2DM may provide protection even without established CV disease. 6) As white coat hypertension becomes more frequent following treatment in diabetic patients, precise BP measurement is essential to avoid overtreatment, particularly in real-world clinical settings. 7) The proportion of patients with T2DM who are at low to moderate risk is small. Accordingly, the updated consensus statement from the KSH recommends a target BP of 130/80 mmHg for most patients with T2DM, provided that this target is well tolerated
Laparoscopic intracorporeal bypass for splenic flexure colonic obstruction secondary to pancreatic cancer seeding: A video vignette
No full textImpaired Glymphatic Function in Diffuse Axonal Injury: Evaluation Using the Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) Method
No full textPURPOSE: Glymphatic system impairment has been suggested in previous animal and human studies regarding traumatic brain injury (TBI). Diffuse axonal injury (DAI) is an important pathological feature of TBI and is frequently diagnosed in patients with moderate to severe TBI. This study evaluated the glymphatic system function in patients with DAI using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), a non-invasive technique. METHODS: A total of 162 patients with TBI, including 84 with DAI and 78 without DAI, underwent MRI with DTI within 6 months of the date of injury. The ALPS index was calculated to assess the glymphatic system activity and compared between patients with and without DAI. Analysis of covariance (ANCOVA) was used to compare the ALPS index between patients with DAI grades 1, 2, and 3. Correlation analysis was performed between the ALPS index, DAI grade, and Glasgow Coma Scale (GCS) score. RESULTS: Patients with DAI (1.29 +/- 0.17) had a significantly lower ALPS index than those without DAI (1.42 +/- 0.19, P < 0.001). The ALPS index differed significantly between patients with different DAI grades (ANCOVA, P < 0.001). The ALPS index and DAI grades were negatively correlated (r =-0.47, P < 0.001). The ALPS index and GCS scores showed a weak positive correlation (r = 0.174, P = 0.027). CONCLUSIONS: Patients with DAI have a lower ALPS index, indicating impaired glymphatic system activity, which is more severe in patients with a higher DAI grade. These findings broaden the understanding of the pathophysiology of DAI and help predict patients' prognoses and recovery trends
Deescalation From Ticagrelor to Clopidogrel for Myocardial Infarction With Chronic Kidney Disease: A Secondary Analysis of a Randomized Clinical Trial
No full textIMPORTANCE: Chronic kidney disease (CKD) is a significant risk factor for both ischemic and bleeding complications following percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Optimizing dual antiplatelet therapy (DAPT) is essential for improving clinical outcomes. OBJECTIVE: To evaluate whether an 11-month, unguided deescalation strategy from ticagrelor to clopidogrel was associated with reduced bleeding without an increase in ischemic events in stabilized patients with CKD after AMI. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc secondary analysis of the multicenter, open-label, Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction (TALOS-AMI) randomized clinical trial conducted at 32 major cardiac centers in South Korea. Patients with biomarker-positive AMI who tolerated 1 month of ticagrelor-based DAPT after PCI were included in the trial. Patient enrollment occurred from February 2014 to December 2018, with follow-up at 30 days and 3, 6, and 12 months after PCI. The present analysis focused on the subgroup of patients with CKD (estimated glomerular filtration rate [eGFR]<60 mL/min/1.73 m2). Data analyses were performed from July 2023 to October 2024. INTERVENTIONS: In the TALOS-AMI trial, patients were randomized 1:1 to continue ticagrelor (active control group) or switch to clopidogrel (deescalation group) for 11 months after PCI. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of death from cardiovascular disease, myocardial infarction, stroke, and bleeding (Bleeding Academic Research Consortium [BARC] types 2, 3, or 5). RESULTS: Of 2646 patients included in the trial, 305 had CKD (11.5%; mean [SD] age, 67.2 [11.4] years; 223 males [73.1%]; mean [SD] eGFR, 49.7 [9.5] mL/min/1.73 m2) and 2341 did not have CKD (1975 male [84.4%]; mean [SD] age, 59.0 [11.0] years). Patients with CKD had an increased risk of ischemic events compared with patients without CKD (hazard ratio [HR], 2.47; 95% CI, 1.38-4.42; P = .002), but there was no difference in bleeding risk (HR, 1.36; 95% CI, 0.80-2.31; P = .26). Among patients with CKD, deescalation (n = 160) vs active control (n = 145) was associated with reduced risks of the primary end point (10 patients [6.2%] vs 19 [13.1%]; HR, 0.45 [95% CI, 0.21-0.98]; P = .04) and BARC 2, 3, or 5 bleeding (4 patients [2.5%] vs 12 [8.3%]; HR, 0.29 [95% CI, 0.09-0.89]; P = .03). No increased risk of ischemic events was observed following deescalation (7 patients [4.4%] vs 8 [5.5%]; HR, 0.78 [95% CI, 0.28-2.16]; P = .64). CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, deescalation from ticagrelor to clopidogrel at 1 month after PCI for AMI was associated with significant reduction in bleeding without increased risk of ischemic events among study-eligible patients with CKD. Further adequately powered studies are needed to validate these findings
Uric Acid Trajectories and CKD Progression in the African American Study of Kidney Disease and Hypertension
No full textINTRODUCTION: Serum uric acid levels increase with progressive kidney disease, and chronic elevations may contribute to chronic kidney disease (CKD) progression. We analyzed data from the African American Study of Kidney Disease and Hypertension (AASK) to examine the hypothesis that individuals with declining serum urate levels during follow-up would experience slower loss of kidney function. METHODS: The AASK recruited 1094 African-American individuals with reduced estimated glomerular filtration rate (eGFR) and followed up with them for up to 12 years. The eGFR and defined end-stage kidney disease (ESKD) composite score were used to establish CKD stages. We employed a Cox proportional hazards model to investigate the association between uric acid trajectories and the composite ESKD outcome. RESULTS: Compared with the normo-increasing uric acid group (i.e., those who had the lowest overall serum uric acid levels), the high-stable (hazard ratio [HR] = 2.28, P = 0.012), the high-increasing (HR = 1.95, P = 0.042), and extremely high-stable (HR = 3.21, P < 0.001) uric acid groups had higher risk of the composite ESKD outcome. The extremely high-stable group also had a greater ESKD risk than the high-decreasing group (HR = 1.98, P = 0.046). Adjustment for APOL1 risk allele, antihypertensive drug type, and mean arterial pressure treatment target did not alter the relationship between uric acid trajectories and the composite ESKD outcome. CONCLUSION: Uric acid trajectories are associated with ESKD incidence in African Americans with CKD. Tracking temporal changes in uric acid improves the assessment of ESKD risk in CKD progression