Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study

PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. Materials and Methods: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.ope

다중 후류 효과를 고려한 부유식 풍력발전기의 위치 최적화

학위논문 (석사)-- 서울대학교 대학원 : 공과대학 기계항공공학부, 2019. 2. 이수갑.본 논문은 부유식 풍력 발전 단지의 경제적으로 최적화된 배치를 구하기 위한 연구를 수행하였다. 기존의 단일 부유식 풍력발전기의 공력 해석과 풍력 발전 단지의 최적화 설계를 조합하여 부유식 풍력 발전 단지의 배치 최적화를 수행하였다. 부유식 풍력 발전기의 모든 동적 특징을 고려하기 위해, National Renewable Energy Laboratory(NREL)에서 개발한 FAST 코드를 사용하였다. 정확한 공력 해석을 수행하기 위해서 FAST에서 사용하던 기존의 공력 해석 모델(BEM, GDW) 대신 비정상 와류 격자 기법(UVLM)을 사용하여 FAST의 공력 해석 모델을 대체하였다. 또한, 비정상 유동의 정확한 공력 해석을 위해서 비선형 와류 보정 기법(NVCM)을 사용하여 비정상 와류 격자 기법의 문제를 해결하였다. FAST의 공력 해석 프로그램의 대체를 통해 기존보다 더 정확한 해석을 수행 한 것을 검증하기 위해서 0.2도에서 3.9도까지 피치가 변하는 2MW Tjaereborg 풍력발전기를 이용하였다. Tjaereborg 풍력발전기의 실험 데이터를 고려하여 기존의 공력해석 모델(BEM, GDW)와 비교하여 UVLM가 더 정확한 해석을 수행한다는 것을 확인하였다. 풍력 발전 단지의 최적화는 EU의 TOPFARM프로젝트에서 개발한 TOPFARM 플랫폼을 이용하여 여러 경제적 요소들을 고려한 최적 설계를 수행하였다. 비용함수이자 목적함수로는 연간에너지 생산량(Annual energy production), 기반 설치 비용(foundation cost), 그리고 전력 망 설치 비용(grid cost)을 사용하였다. 최적 설계에 사용한 알고리즘은 전역 최적화에 적합한 비우위 정렬 진화 알고리즘(NSGA2)을 사용하였다. 최적화 대상으로는 가상의 풍력 발전 단지를 이용했고, 위에 언급한 여러 목적 함수에 대한 최적 설계를 수행하였다.This paper investigates the economically optimized layout of floating wind farms. This paper optimized the layout of the floating wind farm by combining the aerodynamic analysis of the previous single - float wind turbine and the optimized design of the wind turbine. To consider all dynamic characteristics of floating wind turbine, FAST code developed by National Renewable Energy Laboratory (NREL) is used. In order to perform accurate aerodynamic analysis, FAST 's aerodynamic analysis model was replaced by the unsteady vortex lattice method (UVLM) instead of the existing aerodynamic model (BEM, GDW) used in FAST. We also solve the problem of the unsteady vortex lattice method using the Nonlinear Vortex Correction Method (NVCM) for fix problem of UVLM. This paper used a 2MW Tjaereborg wind turbine, which pitch varied from 0.2 ° to 3.9 °, in order to verify that the more accurate analysis is performed by replacing FAST's aerodynamic analysis program. Considering the experimental data of Tjaereborg wind turbine, it is confirmed that UVLM performs more accurate analysis than the existing aerodynamic analysis model (BEM, GDW). The optimization of the wind farm was carried out using the TOPFARM platform developed by the TOPFARM project of the EU, and the optimum design was taken considering various economic factors. Annual energy production, foundation cost, and grid cost are used as cost function and objective function. The algorithm used for the optimal design was a non-dominated sorting genetic algorithm (NSGA2) suitable for global optimization. We used a virtual wind farm as an optimization target and performed an optimal design for various objective functions mentioned above. 6초록 i 목 차 iii 그림 목차 v 표 목차 v 기호 및 약어 vi 제 1 장 서 론 1 1.1 연구 배경 1 1.2 연구 목적 및 내용 4 제 2 장 공력 해석 모델 6 2.1 블레이드 요소-운동량 이론 6 2.2 Generalized dynamic wake 모델 8 2.3 비정상 와류 격자 기법 10 2.4 비선형 와류 보정 기법 12 2.5 GCL 모델 13 제 3 장 부유식 풍력발전기 동적 특성 해석 14 3.1 FAST 14 3.2 FAST + 비정상 와류 격자 모델 16 3.3 모델 검증 17 제 4 장 풍력 발전 단지 최적 설계 20 4.1 최적화 플랫폼 20 4.2 최적화 알고리즘 23 4.3 비용 함수 24 4.4 풍력발전 단지 최적 설계 26 제 5 장 결론 31 참고 문헌 33 Abstract 35Maste

Hydrothermal Preparation and Characterization of BaTiO3 from Hydroxide Precursors

High-purity ultrafine BaTiO3 powders are mainly applied in manufacturing electronic ceramics. Among them, the multi-layer ceramic capacitor(MLCC) and PTC thermistor have a close relation with our daily life and the latter has wide applications, such as starter for refrigerator, automatic magnetic eliminator for color TV, heater in the specified temperature range, dial telephone and energy saving lamp, etc. The BaTiO3 is superior to the product made by the conventional solid-state reaction method due to its advantages such as high purity, homogeneous chemical composition, fine particle size and high sinterability of granules. These advantages contribute to the physical and electrical properties of the sintered ceramics. According to the conventional hydrothermal process, the crystalline BaTiO3 powders can only be synthesized above pH 13 and the processes requires strong basic conditions using KOH or NaOH mineralizer. The hydrothermal process often needs relatively high temperature and takes long reaction time. The alkaline cations (K+ or Na+), which are known to be difficult to remove, deteriorate the sintering and electronic properties of the final ceramic products. For these reasons before, a modified hydrothermal process was studied with next objectives8H2O) was used as both the Ba precursor and the mineralizer in the alkali-free system. Present process offers advantageous synthesis conditions at considerably lower temperature (≥80℃) with shorter reaction time (even without reaction time at 100℃) comparing to the conventional hydrothermal processes. As the result, BaTiO3 powders were prepared by a modified hydrothermal synthesis from barium hydroxide and titanium-peroxo-hydroxide (TiO2O5(OH)2) precuresor. The advantageous features of the modified hydrothermal process are an alkali-free system, lower reaction temperature, and shorter reaction time comparing to the conventional hydrothermal process. The phase-pure BaTiO3 powders with a cubic perovskite structure were synthesized at temperature as low as 80℃. Synthesized powders were a ball shape having a particle diameter ranging from 0.5 to 1 ㎛. Well-developed crystalline (perovskite) BaTiO3 was obtained in the mild synthesis conditions (temperature <130℃, reaction time < 2 h, pH <13). The BaTiO3 ceramics sintered at a temperature as low as 1150℃ for 1 h had a density over 95 of theoretical.to develope a modified hydrothermal synthesis in alkali-free system via a novel synthesis route from the titanium-peroxo-hydroxide precursor and to prepare BaTiO3 without alkaline mineralizer, KOH or NaOH, which influence the performance of the prepared powders and resulting sintered ceramics. Barium hydroxide octahydrate(Ba(OH)2 &#82281. 서론 1 2. 이론적배경 4 2.1 Barium titanate (BaTiO3) 4 2.1.1 BaTiO3의 역사적 고찰 및 일반특성 4 2.1.2 BaTiO3의 결정구조 및 특성 4 2.1.3 BaTiO3의 세라믹스의 재료특성과 응용 및 전망 10 2.1.4 BaTiO3등의 강유전체 응용 및 발전과정 14 2.1.5 BaTiO3의 국내외 생산과 연구동향 16 2.2 BaTiO3 분말합성 기술 17 2.2.1 일반적인 고상합성법에 의한 BaTiO3 분말의 합성 17 2.2.2 습식화학적합성법에 의한 BaTiO3 분말의 합성 18 2.3 BaTiO3 수열합성 22 2.3.1 수열합성 메카니즘 22 2.3.2 수열합성에서의 pH의 영향과 원료물질 25 3. 실험방법 28 4. 실험결과 및 고찰 32 4.1 Ti-과산화수산화물의 침전 32 4.2 수열합성 36 4.2.1 반응온도에 따른 분말합성 경향 36 4.2.2 반응물의 Ba/Ti 비율에 따른 분말합성 특성 41 4.2.3 반응유지 시간이 수열합성에 미치는 영향 45 4.2.4 소결특성 및 전기적 물성 48 5. 결론 51 참고문헌 5

A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a CRISPR-concatemer

CRISPR/Cas9 technology has greatly improved the feasibility and speed of loss-of-function studies that are essential in understanding gene function. In higher eukaryotes, paralogous genes can mask a potential phenotype by compensating the loss of a gene, thus limiting the information that can be obtained from genetic studies relying on single gene knockouts. We have developed a novel, rapid cloning method for guide RNA (gRNA) concatemers in order to create multi-gene knockouts following a single round of transfection in mouse small intestinal organoids. Our strategy allows for the concatemerization of up to four individual gRNAs into a single vector by performing a single Golden Gate shuffling reaction with annealed gRNA oligos and a pre-designed retroviral vector. This allows either the simultaneous knockout of up to four different genes, or increased knockout efficiency following the targeting of one gene by multiple gRNAs. In this protocol, we show in detail how to efficiently clone multiple gRNAs into the retroviral CRISPR-concatemer vector and how to achieve highly efficient electroporation in intestinal organoids. As an example, we show that simultaneous knockout of two pairs of genes encoding negative regulators of the Wnt signaling pathway (Axin1/2 and Rnf43/Znrf3) renders intestinal organoids resistant to the withdrawal of key growth factors.ope

Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters

PURPOSE: In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. MATERIALS AND METHODS: A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped. RESULTS: In univariate survival analysis, tumor grade (p 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. CONCLUSION: From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.ope

Prospective Single Arm Study on the Effect of Ilaprazole in Patients with Heartburn but No Reflux Esophagitis

PURPOSE: Patients with gastroesophageal reflux disease without esophagitis show varying responses to proton pump inhibitors (PPIs). The aim of this study was to objectively evaluate the effect of a new PPI, ilaprazole, on patients with heartburn but without reflux esophagitis. MATERIALS AND METHODS: This prospective study was performed on 20 patients with heartburn but without reflux esophagitis. All patients underwent upper endoscopy and 24-hr combined multichannel intraluminal impedance and pH esophageal monitoring (MII-pH). They were then treated with ilaprazole (20 mg) once daily for 4 weeks. The GerdQ questionnaire, histologic findings, and inflammatory biomarkers were used for assessment before and after ilaprazole. RESULTS: Among the 20 patients, 13 (65%) showed GerdQ score ≥8. Based on MII-pH results, patients were classified as true nonerosive reflux disease (n=2), hypersensitive esophagus (n=10), and functional heartburn (n=8). After treatment, patients showed a statistically significant improvement in GerdQ score (p<0.001). Among histopathologic findings, basal cell hyperplasia, papillary elongation, and infiltration of intraepithelial T lymphocytes improved significantly (p=0.008, p=0.021, and p=0.008; respectively). Expression of TNF-α, IL-8, TRPV1, and MCP-1 decreased marginally after treatment (p=0.049, p=0.046, p=0.045, and p=0.042; respectively). CONCLUSION: Daily ilaprazole (20 mg) is efficacious in improving symptom scores, histopathologic findings, and inflammatory biomarkers in patients with heartburn but no reflux esophagitis.ope

CDX-1/CDX-2 Expression Is a Favorable Prognostic Factor in Epstein-Barr Virus-Negative, Mismatch Repair-Proficient Advanced Gastric Cancers

Background/aims: Caudal type homeobox (CDX)-1 and -2 are reportedly involved in the development and progression of gastric cancer (GC). Although there are several reports on the prognostic significance of CDX-2 expression in GC, it remains controversial. In this study, we sought to validate the prognostic value of CDX-1 and -2 expression according to the histologic and molecular subtypes of GC. Methods: In total, 1,158 cases of advanced GC were investigated using immunohistochemical staining and tissue microarrays for CDX-1 and -2 expression, and survival analysis was performed according to different histological and molecular subtypes. Results: Of the 915 GCs with CDX-1 expression, 163 (17.8%) were Epstein-Barr virus (EBV)-positive or mismatch repair deficient (MMR-d), and the remaining 752 (82.2%) were EBV-negative or MMR-proficient (MMR-p). Of the 1,008 GCs with CDX-2 expression, 177 (17.5%) were EBV-positive or MMR-d, and the remaining 831 (82.5%) were EBV-negative or MMR-p. In the EBV-positive and MMR-d groups, CDX expression had no relationship with patient outcomes. In the EBV-negative and MMR-p groups, 404 (53.7%) and 523 (62.9%) samples were positive for CDX-1 and CDX-2 expression, respectively. Survival analysis demonstrated that CDX-1 and CDX-2 expression in all patients was correlated with favorable outcomes in terms of overall survival (multivariate analysis; p=0.018 and p=0.028, respectively). In the subgroup analysis, CDX-1 expression and CDX-2 expression were associated with favorable outcomes in EBV-negative and MMR-p intestinal (p=0.015 and p=0.010), and mixed and diffuse-type (p=0.019 and p=0.042) GCs, respectively. Conclusions: The expression of CDX-1 and CDX-2 is a favorable prognostic factor in EBVnegative, MMR-p advanced GC.ope

A Standardized Pathology Report for Gastric Cancer: 2nd Edition

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies. © 2023. Korean Gastric Cancer Association.ope

Differences in TGF-β1 signaling and clinicopathologic characteristics of histologic subtypes of gastric cancer

BACKGROUND: Aberrant TGF-β1 signaling is suggested to be involved in gastric carcinogenesis. However, the role of TGF-β1 in intestinal-type [i-GC] and diffuse-type [d-GC] gastric cancer remains largely unknown. In this study, we evaluated the expression of TGF-β1 signaling molecules and compared the clinicopathological features of i-GC and d-GC. METHODS: Patients (n=365, consecutive) who underwent curative gastrectomy for gastric adenocarcinoma in 2005 were enrolled. We performed immunohistochemical staining of TGF-β1, TGF-β1 receptor-2 (TβR2), Smad4, p-ERK1/2, TGF-activated kinase (TAK)1, and p-Akt in 68 paraffin-embedded tumor blocks (33 i-GC and 35 d-GC), scored the expression according to the extent of staining, and evaluated differences between the histologic subtypes. RESULTS: Patients with d-GC differed from those with i-GC as follows: younger and more likely to be female; more aggressive stage; higher recurrence rate. The expression of TGF-β1 and TβR2 was higher in i-GC (P = 0.05 and P <0.001, respectively). The expression of Smad4, a representative molecule of the Smad-dependent pathway, was decreased in both subtypes. TAK1 and p-Akt, two major molecules involved in the Smad-independent pathway, were over-expressed (69 ~87% of cases stained), without a statistically significant difference between i-GC and d-GC. Of note, the expression of p-ERK1/2, a Smad-independent pathway, was significantly increased in i-GC (P = 0.008). CONCLUSIONS: The clinicopathological characteristics vary in different histologic gastric cancer subtypes. Although TGF-β1 signaling in gastric cancer cells appears hyper-activated in i-GC compared to d-GC, the Smad-dependent pathway seems down-regulated while the Smad-independent pathway seems up-regulated in both histologic subtypes.ope

Pre- and post-ESD discrepancies in clinicopathologic criteria in early gastric cancer: the NECA-Korea ESD for Early Gastric Cancer Prospective Study (N-Keep)

BACKGROUND: Discrepancies in the clinicopathologic parameters pre- and post-endoscopic submucosal dissection (ESD) sometimes necessitate additional surgical resection. The aim of this study was to assess such discrepancies in clinicopathologic parameters before and after ESD in the context of reducing the risk of failure of curative ESD. METHODS: Data on 712 early gastric cancer patients were prospectively collected from 12 university hospitals nationwide. The inclusion criteria were differentiated carcinoma <3 cm in size, no ulceration, submucosal invasion <500 μm, and no metastasis. Clinicopathologic factors were compared retrospectively. RESULTS: The discrepancy rate was 20.1 % (148/737) and the most common cause of discrepancy was tumor size (64 cases, 8.7 %). Ulceration, undifferentiated histology, and SM2 invasion were found in 34 (4.6 %), 18 (2.4 %), and 51 cases (6.9 %), respectively. Lymphovascular invasion (LVI) was observed in 34 cases (4.6 %). Cases with lesions exceeding 3 cm in size showed more frequent submucosal invasion, an elevated gross morphology, and upper and middle locations (p < 0.05). In the cases with ulceration, depth of invasion (DOI) was deeper than in the cases without ulceration (p = 0.005). Differentiation was correlated with DOI and LVI (p = 0.021 and 0.007). DOI was correlated with tumor size, ulceration, differentiation, LVI, gross type, and location. There were statistically significant differences between mucosal cancer cases and submucosal cancer cases in tumor size, differentiation, ulceration, LVI, and location. CONCLUSIONS: The overall discrepancy rate was 20.1 %. To reduce this rate, it is necessary to evaluate the DOI very cautiously, because it is correlated with other parameters. In particular, careful checking for SM-invasive cancer is required due to the high incidence of LVI irrespective of the depth of submucosal invasion.ope