Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Background: The accuracy of Logical Observation Identifiers Names and Codes (LOINC) mappings is reportedly low, and the LOINC codes used for research purposes in Korea have not been validated for accuracy or usability. Our study aimed to evaluate the discrepancies and similarities in interoperability using existing LOINC mappings in actual patient care settings. Methods: We collected data on local test codes and their corresponding LOINC mappings from seven university hospitals. Our analysis focused on laboratory tests that are frequently requested, excluding clinical microbiology and molecular tests. Codes from nationwide proficiency tests served as intermediary benchmarks for comparison. A research team, comprising clinical pathologists and terminology experts, utilized the LOINC manual to reach a consensus on determining the most suitable LOINC codes. Results: A total of 235 LOINC codes were designated as optimal codes for 162 frequent tests.Among these, 51 test items, including 34 urine tests, required multiple optimal LOINC codes, primarily due to unnoted properties such as whether the test was quantitative or qualitative, or differences in measurement units. We analyzed 962 LOINC codes linked to 162 tests across seven institutions, discovering that 792 (82.3%) of these codes were consistent. Inconsistencies were most common in the analyte component (38 inconsistencies, 33.3%), followed by the method (33 inconsistencies, 28.9%), and properties (13 inconsistencies, 11.4%). Conclusion This study reveals a significant inconsistency rate of over 15% in LOINC mappings utilized for research purposes in university hospitals, underlining the necessity for expert verification to enhance interoperability in real patient care.

Background: The accuracy of Logical Observation Identifiers Names and Codes (LOINC) mappings is reportedly low, and the LOINC codes used for research purposes in Korea have not been validated for accuracy or usability. Our study aimed to evaluate the discrepancies and similarities in interoperability using existing LOINC mappings in actual patient care settings. Methods: We collected data on local test codes and their corresponding LOINC mappings from seven university hospitals. Our analysis focused on laboratory tests that are frequently requested, excluding clinical microbiology and molecular tests. Codes from nationwide proficiency tests served as intermediary benchmarks for comparison. A research team, comprising clinical pathologists and terminology experts, utilized the LOINC manual to reach a consensus on determining the most suitable LOINC codes. Results: A total of 235 LOINC codes were designated as optimal codes for 162 frequent tests.Among these, 51 test items, including 34 urine tests, required multiple optimal LOINC codes, primarily due to unnoted properties such as whether the test was quantitative or qualitative, or differences in measurement units. We analyzed 962 LOINC codes linked to 162 tests across seven institutions, discovering that 792 (82.3%) of these codes were consistent. Inconsistencies were most common in the analyte component (38 inconsistencies, 33.3%), followed by the method (33 inconsistencies, 28.9%), and properties (13 inconsistencies, 11.4%). Conclusion This study reveals a significant inconsistency rate of over 15% in LOINC mappings utilized for research purposes in university hospitals, underlining the necessity for expert verification to enhance interoperability in real patient care.

Background: The accuracy of Logical Observation Identifiers Names and Codes (LOINC) mappings is reportedly low, and the LOINC codes used for research purposes in Korea have not been validated for accuracy or usability. Our study aimed to evaluate the discrepancies and similarities in interoperability using existing LOINC mappings in actual patient care settings. Methods: We collected data on local test codes and their corresponding LOINC mappings from seven university hospitals. Our analysis focused on laboratory tests that are frequently requested, excluding clinical microbiology and molecular tests. Codes from nationwide proficiency tests served as intermediary benchmarks for comparison. A research team, comprising clinical pathologists and terminology experts, utilized the LOINC manual to reach a consensus on determining the most suitable LOINC codes. Results: A total of 235 LOINC codes were designated as optimal codes for 162 frequent tests.Among these, 51 test items, including 34 urine tests, required multiple optimal LOINC codes, primarily due to unnoted properties such as whether the test was quantitative or qualitative, or differences in measurement units. We analyzed 962 LOINC codes linked to 162 tests across seven institutions, discovering that 792 (82.3%) of these codes were consistent. Inconsistencies were most common in the analyte component (38 inconsistencies, 33.3%), followed by the method (33 inconsistencies, 28.9%), and properties (13 inconsistencies, 11.4%). Conclusion This study reveals a significant inconsistency rate of over 15% in LOINC mappings utilized for research purposes in university hospitals, underlining the necessity for expert verification to enhance interoperability in real patient care.

Background: The accuracy of Logical Observation Identifiers Names and Codes (LOINC) mappings is reportedly low, and the LOINC codes used for research purposes in Korea have not been validated for accuracy or usability. Our study aimed to evaluate the discrepancies and similarities in interoperability using existing LOINC mappings in actual patient care settings. Methods: We collected data on local test codes and their corresponding LOINC mappings from seven university hospitals. Our analysis focused on laboratory tests that are frequently requested, excluding clinical microbiology and molecular tests. Codes from nationwide proficiency tests served as intermediary benchmarks for comparison. A research team, comprising clinical pathologists and terminology experts, utilized the LOINC manual to reach a consensus on determining the most suitable LOINC codes. Results: A total of 235 LOINC codes were designated as optimal codes for 162 frequent tests.Among these, 51 test items, including 34 urine tests, required multiple optimal LOINC codes, primarily due to unnoted properties such as whether the test was quantitative or qualitative, or differences in measurement units. We analyzed 962 LOINC codes linked to 162 tests across seven institutions, discovering that 792 (82.3%) of these codes were consistent. Inconsistencies were most common in the analyte component (38 inconsistencies, 33.3%), followed by the method (33 inconsistencies, 28.9%), and properties (13 inconsistencies, 11.4%). Conclusion This study reveals a significant inconsistency rate of over 15% in LOINC mappings utilized for research purposes in university hospitals, underlining the necessity for expert verification to enhance interoperability in real patient care.

Purpose: Due to the shortage of lung donors relative to the number of patients waiting for lung transplantation (LTx), more than one-third of patients on the waitlist have died without receiving LTx in Korea. Therefore, the importance of fair and effective allocation policies has been emphasized. This study investigated the characteristics of the current urgency-based allocation system in Korea by simulating the Eurotransplant lung allocation score (ET-LAS) using a nationwide multi-institutional registry for LTx in Korea. Materials and Methods: This study used data from the Korean Organ Transplantation Registry (KOTRY), along with additional retrospective data for ET-LAS calculation. A total of 194 patients were included in this study between January 2015 and December 2019. The Korean urgency definition classifies an LTx candidate as having statuses 0–3 according to urgency. The ET-LAS was analyzed according to the Korean urgency status. Results: In total, 92 patients received lung transplants at status 0, 85 at status 1, and 17 at status 2/3. The ET-LAS showed a bimodal distribution with distinct peaks corresponding to status 0 and non-status 0. There was no significant difference in the ET-LAS among non-status 0 patients. In logistic and decision tree analyses, oxygen supplementation methods, particularly oxygen masks and high-flow nasal cannulas, were significantly associated with a high ET-LAS (≥50) among non-status 0 patients. Conclusion Simulation of the ET-LAS with KOTRY data showed that the Korean urgency definition may not allocate lungs by urgency, especially for patients in non-status 0; therefore, it needs to be revised.

Background and Objectives: Metformin, a commonly used antidiabetic drug, has been reported to exhibit promising anticancer effects across various tumor types. This study investigated the effectiveness of combining metformin with radiotherapy (RT) to treat head and neck squamous cell carcinoma (HNSCC).Materials and Method In vitro experiments were conducted in which FaDu and SCC-25 cells were treated with metformin, followed by irradiation. Cell proliferation was evaluated by MTT assay, and apoptosis was assessed by staining with annexin V-fluorescein isothiocyanate/ propidium iodide, followed by flow cytometry. Western blotting was performed to evaluate changes in apoptotic markers. In vivo experiments were performed using a murine AT-84 allograft model, where tumor volume was measured and serum samples were collected to assess the level of vascular endothelial growth factor (VEGF). Results: The combination of metformin and RT significantly reduced cell proliferation in a dose- and time-dependent manner, and led to a significant increase in the apoptotic rate, accompanied by the upregulation of cleaved caspase-8 and FoxO3, and the downregulation of Bcl-2. The combination treatment also exhibited antiangiogenic effects, as shown by the reduced hypoxia-inducible factor-1 alpha level and inhibited tube formation in the endothelial cells. The combined therapy in the mouse model led to marked decrease in tumor volume and the serum VEGF level in comparison to both the control group and the RT alone. Conclusion The concurrent use of metformin and RT successfully suppressed cell proliferation, triggered apoptosis, and increased the antiangiogenic effects in HNSCC. These results support the use of metformin as an adjunct to RT for the treatment of HNSCC.

Background and Objectives: Metformin, a commonly used antidiabetic drug, has been reported to exhibit promising anticancer effects across various tumor types. This study investigated the effectiveness of combining metformin with radiotherapy (RT) to treat head and neck squamous cell carcinoma (HNSCC).Materials and Method In vitro experiments were conducted in which FaDu and SCC-25 cells were treated with metformin, followed by irradiation. Cell proliferation was evaluated by MTT assay, and apoptosis was assessed by staining with annexin V-fluorescein isothiocyanate/ propidium iodide, followed by flow cytometry. Western blotting was performed to evaluate changes in apoptotic markers. In vivo experiments were performed using a murine AT-84 allograft model, where tumor volume was measured and serum samples were collected to assess the level of vascular endothelial growth factor (VEGF). Results: The combination of metformin and RT significantly reduced cell proliferation in a dose- and time-dependent manner, and led to a significant increase in the apoptotic rate, accompanied by the upregulation of cleaved caspase-8 and FoxO3, and the downregulation of Bcl-2. The combination treatment also exhibited antiangiogenic effects, as shown by the reduced hypoxia-inducible factor-1 alpha level and inhibited tube formation in the endothelial cells. The combined therapy in the mouse model led to marked decrease in tumor volume and the serum VEGF level in comparison to both the control group and the RT alone. Conclusion The concurrent use of metformin and RT successfully suppressed cell proliferation, triggered apoptosis, and increased the antiangiogenic effects in HNSCC. These results support the use of metformin as an adjunct to RT for the treatment of HNSCC.

Background and Objectives: Metformin, a commonly used antidiabetic drug, has been reported to exhibit promising anticancer effects across various tumor types. This study investigated the effectiveness of combining metformin with radiotherapy (RT) to treat head and neck squamous cell carcinoma (HNSCC).Materials and Method In vitro experiments were conducted in which FaDu and SCC-25 cells were treated with metformin, followed by irradiation. Cell proliferation was evaluated by MTT assay, and apoptosis was assessed by staining with annexin V-fluorescein isothiocyanate/ propidium iodide, followed by flow cytometry. Western blotting was performed to evaluate changes in apoptotic markers. In vivo experiments were performed using a murine AT-84 allograft model, where tumor volume was measured and serum samples were collected to assess the level of vascular endothelial growth factor (VEGF). Results: The combination of metformin and RT significantly reduced cell proliferation in a dose- and time-dependent manner, and led to a significant increase in the apoptotic rate, accompanied by the upregulation of cleaved caspase-8 and FoxO3, and the downregulation of Bcl-2. The combination treatment also exhibited antiangiogenic effects, as shown by the reduced hypoxia-inducible factor-1 alpha level and inhibited tube formation in the endothelial cells. The combined therapy in the mouse model led to marked decrease in tumor volume and the serum VEGF level in comparison to both the control group and the RT alone. Conclusion The concurrent use of metformin and RT successfully suppressed cell proliferation, triggered apoptosis, and increased the antiangiogenic effects in HNSCC. These results support the use of metformin as an adjunct to RT for the treatment of HNSCC.

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.