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    Standardizing Medical Imaging Data Using Radiology Common Data Model and Analysis of Retinal Thickness in Patients with Chronic Diseases with Standardized Optical Coherence Tomography Databases

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    DoctorI. Introduction 1 A. Background 1 1. Observational Medical Outcome Partnership Common Data Model 1 2. Efforts to Standardize Unstructured Data Using the OMOP-CDM Framework 3 3. Challenges in Utilizing Multi-Institutional Medical Imaging Data 4 4. The Potential Impact of R-CDM 6 5. Optical Coherence Tomography (OCT) 6 B. Objectives 9 II. Materials and Methods 10 A. Data sources 10 B. Designing a standard structure and terminology system for R-CDM 11 C. Constructing an R-CDM standardized OCT database 18 D. Study Design Using OMOP-CDM: Establishing Chronic Disease and Control Cohorts for OCT Imaging Analysis 21 E. Integration of R-CDM and OMOP-CDM: Extracting Specific OCT Data from Defined Cohorts 26 F. Analyzing Retinal Thickness Measurements from OCT Data Using Mixed-Effects Regression Models 28 III. Results 31 A. Composition of R-CDM Standardized OCT Databases 31 B. Study population 32 C. Clinical Outcomes 40 D. Sensitivity analyses 49 IV. Discussion 50 A. Main findings 50 1. The Global Impact and Application of R-CDM in Medical Imaging Research 51 2. Other Efforts to Standardize Medical Imaging Data 53 3. Retinal Thickness Alterations in Chronic Disease: A Comparative Review of Diabetic and Hypertensive Cohorts 56 4. Application of Large-Scale PSM and Multi-Institutional Analysis for Retinal Thickness Studies 57 B. Limitations 59 V. Conclusion 60 References 62 Appendix 68 국문요약 10

    진행성 자궁내막암에서 최소 침습 수술과 개복 수술의 비교

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    MasterI. Introduction 1 II. Materials and methods 2 III. Results 3 IV. Discussion 5 References 1

    Association of Intensive Endoscopic Burden with Esophageal Cancer Detection: A Nationwide Cohort Study

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    MasterI. INTRODUCTION 1 II. METHODS 3 A. Study population and design 3 B. The KNCSP and screening endoscopy protocol 3 C. Data collection and definitions 4 D. Statistical analysis 5 III. RESULTS 6 A. Study population and baseline characteristics 6 B. Monthly changes in the number of participants and monthly detection rates for EC 6 C. Factors related to endoscopic screening sensitivity for EC detection 7 D. Association between detection rates and calendar month 7 IV. DISCUSSION 9 V. CONCLUSION 14 REFERENCES 21 국문요약 2

    Tartaric Acid Exacerbates DSS-Induced Colitis by Promoting Eosinophilic Inflammation via IL-13 and IL-5Rα Upregulation

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    Eosinophils are granulocytes involved in the effector phase of type 2 T cell immune responses, which are elevated in inflammatory conditions like ulcerative colitis (UC) and other allergic diseases. UC is a chronic inflammatory colon disease, marked by excessive eosinophil infiltration and elevated Th2 cytokines, which contribute to mucosal inflammation and tissue damage. Dietary factors, including certain organic acids, can influence UC progression by modulating gut immune responses. This research is the first to explore the dose-dependent effects of tartaric acid (TA), a naturally occurring organic acid widely used in the food industry, on eosinophil activation and Th2 cytokine response in both normal mice and a dextran sulfate sodium (DSS)-induced colitis model. Normal mice were treated with TA at varying doses (5 µg, 25 µg, and 50 µg/mouse/day), while colitis mice received 50 µg TA. Eosinophil activation markers (CD11b+, SiglecF+, and CCR3+), Th2 cytokines (IL-4, IL-13, and IL-31), and IL-17 were assessed in peripheral blood leukocytes, lymph nodes, and splenocytes using flow cytometry. Additionally, mRNA expression levels of eosinophil-associated chemokines and cytokines in the splenocytes were quantified with real-time qPCR. Our results demonstrate a dose-dependent effect of TA, with the highest dose (50 µg) significantly increasing eosinophil activation markers, Th2 cytokines, IL-17, and mRNA expression of SiglecF, CCL11, and toll-like receptor 4 in normal mice. In colitis mice, treatment with 50 µg TA showed marked increases in IL-13 levels compared to those of untreated colitis mice, reflecting increased eosinophil recruitment to inflamed tissues. Moreover, mRNA expression of IL-5Rα was elevated in normal mice and colitis mice administered with TA. These results suggest that TA enhances eosinophil proliferation, the upregulation of their regulatory molecules, and Th2 immune profiles, potentially worsening the severity of colitis

    Proteome-wide microarray-based screening of PAR-binding proteins

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    Poly (ADP-ribose) (PAR) plays a crucial role in intracellular signaling and scaffolding through covalent modification or non-covalent binding to target proteins. The non-covalent PAR binding proteome (PARylome) has not been extensively characterized. Here we performed a PAR-binding screen using a human protein microarray that covers most of the human proteome to characterize the non-covalent binding PARylome. A total of 356 PAR-binding proteins were identified. The PAR-binding PARylome suggests that PAR binding regulates a variety of biological processes beyond DNA damage signaling and DNA repair. Proteins that may be reprogrammed by PAR binding include signaling molecules, transcription factors, nucleic acid binding proteins, calcium binding proteins, ligases, oxidoreductases, enzymes, transferases, hydrolases, and receptors. The global database of PAR-binding proteins that we established will be a valuable tool for further in-depth analysis of the role of PARylation in a wide range of biological contexts

    Sirtuin 2 inhibitor AGK2 exerts antiviral effects by inducing epigenetic suppression of hepatitis B virus covalently closed circular DNA through recruitment of repressive histone lysine methyltransferases and reduction of cccDNA

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    Chronic hepatitis B virus (HBV) infection continues to be a global health concern because current treatments such as interferon-alpha and nucleos(t)ide analogs cannot fully eliminate the virus due to persistence of covalently closed circular DNA (cccDNA) and integrated HBV DNA. Earlier research suggests that AGK2, a selective SIRT2 inhibitor, suppresses HBV replication by modifying key signaling pathways. This study aimed to further explore the anti-HBV effects of AKG2, particularly its effects on the epigenetic landscape of cccDNA. HBV-transfected and -infected cells were used to assess the impact of AGK2 on viral replication. Changes in SIRT2 expression and alpha-tubulin acetylation (SDS-PAGE-immunoblotting), core particle formation (native agarose gel electrophoresis and immunoblotting), HBV RNA (northern blotting) and DNA (Southern blotting) synthesis, and cccDNA levels (Southern blotting) were measured. Chromatin immunoprecipitation assays were performed to examine deposition of transcriptionally repressive epigenetic markers on cccDNA. AGK2 reduced expression of SIRT2, increased acetylated alpha-tubulin levels, and reduced synthesis of HBV RNA and DNA. Importantly, AGK2 also reduced cccDNA levels and increased deposition of repressive histone markers H4K20me1, H3K27me3, and H3K9me3 on cccDNA, mediated by histone lysine methyltransferases such as PR-Set7, EZH2, SETDB1, and SUV39H1. Additionally, there was a reduction in recruitment of RNA polymerase II and acetylated H3 to cccDNA, indicating that AGK2 enhances transcriptional repression. AGK2 suppresses HBV replication through direct antiviral actions, and by epigenetic modulation of cccDNA, indicating that using AGK2 to target SIRT2 and associated epigenetic regulators shows promise as a functional cure for chronic hepatitis B

    Clinical Course and Prognosis of Long-Term Survivors of Hepatocellular Carcinoma

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    BACKGROUND AND AIMS: This study investigated the long-term prognosis and clinical course of patients who survived for more than 5 years after hepatocellular carcinoma (HCC) diagnosis. METHODS: This retrospective cohort study used data from the Korean National Health Insurance Service database. A total of 35,348 subjects newly diagnosed with HCC between January 2008 and December 2010 were followed up until December 2018. RESULTS: A total of 11,514 (32.6%) survived for 5 years after diagnosis of HCC among 35,348 patients diagnosed with HCC. Long-term survivors (>/= 5 years) had a higher proportion of females, younger age, more frequent aetiology of hepatitis B virus, less frequent liver cirrhosis, diabetes mellitus and hypertension, and received curative treatment more frequently than nonsurvivors (< 5 years). The additional 1-, 3- and 5-year cumulative survival probabilities were 90.7%, 77.6% and 68.4% respectively. Patients who underwent curative treatment as the first treatment for HCC showed a higher additional 5-year cumulative survival probabilities than those treated with noncurative therapy (74.5% vs. 64.2%). Among the long-term survivors, 44.4% underwent HCC retreatment 5 years after HCC diagnosis. The additional 5-year cumulative survival probability was 54.9% in the HCC retreatment group. The overall 5- and 10-year cumulative probabilities of second primary malignancies in long-term survivors were 15.36% and 27.54% respectively. The most frequent second primary malignancy was prostate cancer, followed by colorectal and pancreatic cancers. CONCLUSION: Our study highlights that a significant proportion of patients with HCC achieve long-term survival beyond 5 years, with favourable outcomes associated with curative treatments

    Changes in cognitive function and functional brain networks in chemotherapy-exposed patients with breast cancer: A longitudinal study

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    Despite the accumulating evidence on cognitive impairment in patients with cancer after chemotherapy, it remains unclear whether changes in cognitive function after chemotherapy are related to changes in brain function, because most of the previous studies were cross-sectional. Additionally, little is known regarding changes in functional brain network topological measurements (which quantify different features of brain network organization) after chemotherapy. Therefore, by applying graph theoretical analysis to resting-state functional magnetic resonance imaging data in a longitudinal study design, we investigated whether patients with breast cancer (n = 17) had changes in cognitive function and in topological properties of the functional brain network before and after chemotherapy (particularly within 6 months to 1 year after chemotherapy) and whether these changes were correlated. Patients exhibited a higher cognitive function (visual and spatial memory) and some network topological properties at a certain sparsity threshold after treatment, showing better memory function, network segregation, and small-worldness. We also observed a correlation between changes in the observed cognitive functions and network topological properties. These novel findings improve our understanding of the long-term effects of chemotherapy on cognitive function and functional brain network in patients with breast cancer, revealing part of the trajectories of changes after chemotherapy. Furthermore, these findings provide insights into cognitive and neural recovery and the associated neural mechanisms of network topological properties

    Comparison of spinal instability and postoperative complications between laminoplasty and laminectomy surgery for spinal cord tumors

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    This study aimed to compare kyphotic changes and postoperative complications between laminectomy and laminoplasty for spinal cord tumors. We retrospectively included 110 patients who underwent spinal cord tumor resection at the Ajou University Medical Center, Korea, between January 1994 and March 2022 to compare the complications and postoperative kyphotic changes between laminectomy and laminoplasty. A total of 59 and 51 patients underwent laminectomy and laminoplasty, respectively. The groups had similar demographic characteristics. Tumor locations were classified as cervical, thoracic, and lumbar lesions and were compared. We measured preoperative and postoperative radiological parameters and identified postoperative complications. In the laminoplasty group, we studied 7, 19, and 25 cases at the cervical, thoracic, and lumbar levels, respectively. In the laminectomy group, we studied 13, 31, and 15 cases at the cervical, thoracic, and lumbar levels, respectively. At the cervical level, lordosis from C2 to C7 was 8.66 +/- 5.06 degrees before and 15.86 +/- 12.54 degrees after surgery and was 10.5 +/- 6.82 degrees before and 9.16 +/- 6.5 degrees after surgery in the laminoplasty and laminectomy groups, respectively. At the thoracic level, kyphosis from T5 to T12 was 27.89 +/- 9.93 degrees before and 23.18 +/- 9.10 degrees after surgery and was 29.94 +/- 9.56 degrees before and 28.41 +/- 12.58 degrees after surgery in the laminoplasty and laminectomy groups, respectively. At the lumbar level, lordosis from L1 to S1 was 40.86 +/- 14.12 degrees before and 42.62 +/- 10.39 degrees after surgery and was 43.65 +/- 8.47 degrees before and 37.44 +/- 13.32 degrees after surgery in the laminoplasty and laminectomy groups, respectively. Postoperative complications, such as cerebrospinal fluid leakage, infection, and hematoma, were more frequent in the laminectomy group than in the laminoplasty group. Laminoplasty rather than laminectomy for spinal cord tumor surgery can reduce postoperative complications and prevent kyphosis

    Impact of single-port laparoscopic approach on scar assessment by patients and observers: a multicenter retrospective study

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    PURPOSE: This study aimed to compare the wound cosmesis of a single-incision approach on scar assessment after laparoscopic surgery for colon cancer. METHODS: This study included 32 patients undergoing single-port laparoscopic surgery (SPLS) and 61 patients undergoing multiport laparoscopic surgery (MPLS) for colon cancer at 3 tertiary referral hospitals between September 2011 and December 2019. We modified and applied the Korean version of the Patient and Observer Scar Assessment Scale (POSAS) to assess cosmetic outcomes. To assess the interobserver reliability using intraclass correlation coefficient values for the Observer Scar Assessment Scale (OSAS), the surgeons evaluated 5 images of postoperative scars. RESULTS: No significant differences were observed in the time before the return of normal bowel function, time to sips of water and soft diet initiation, length of in-hospital stay, and postoperative complication rate. The SPLS group had a shorter total incision length than the MPLS group. The POSAS favored the SPLS approach, revealing significant differences in the Patient Scar Assessment Scale (PSAS), OSAS, and overall scores. The SPLS approach was an independent factor influencing the POSAS, PSAS, and OSAS scores. Eleven colorectal surgeons had a significantly substantial intraclass coefficient. CONCLUSION: The cosmetic outcomes of SPLS as assessed by the patients and surgeons were superior to those of MPLS in colon cancer. Reducing the number of ports is an independent factor affecting scar assessment by patients and observers

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