Objective: To investigate the prevalence of pathological findings and clinical outcomes of riskreducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). Methods: This retrospective study enrolled asymptomatic carriers with germline HR gene PV/ LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea.Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. Results: Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/ LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9–71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. Conclusion Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Society of Osteoporosis, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining Stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3-4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management.This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.

Background: The aim of this study is to investigate the specific pathway involved in human leukocyte antigen (HLA) sensitization using single-cell RNA-sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse. Methods: For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg(HLA-A2.1)1Enge/J mouse (allogeneic mouse, ALLO). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA-sequencing analysis on splenocytes isolated from ALLO and SYN and compared the gene expression between them. Results: We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN, respectively. Five major cell types (B cells, T cells, natural killer cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B cells was higher in ALLO than it was in SYN. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the highly expressed genes in the B cells from ALLO were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T cells of ALLO were involved in the interleukin (IL)-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO compared to those in the SYN. Conclusion Our results indicate that not only the B cell lineage but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Society of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Osteoporosis Society, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3 to 4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management. This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.

Objectives: Disability weights require regular updates, as they are influenced by both diseases and societal perceptions. Consequently, it is necessary to develop an up-to-date list of the causes of diseases and establish a survey panel for estimating disability weights. Accordingly, this study was conducted to calculate, assess, modify, and validate disability weights suitable for Korea, accounting for its cultural and social characteristics. Methods: The 380 causes of disease used in the survey were derived from the 2019 Global Burden of Disease Collaborative Network and from 2019 and 2020 Korean studies on disability weights for causes of disease. Disability weights were reanalyzed by integrating the findings of an earlier survey on disability weights in Korea with those of the additional survey conducted in this study. The responses were transformed into paired comparisons and analyzed using probit regression analysis. Coefficients for the causes of disease were converted into predicted probabilities, and disability weights in 2 models (model 1 and 2) were rescaled using a normal distribution and the natural logarithm, respectively. Results: The mean values for the 380 causes of disease in models 1 and 2 were 0.488 and 0.369, respectively. Both models exhibited the same order of disability weights. The disability weights for the 300 causes of disease present in both the current and 2019 studies demonstrated a Pearson correlation coefficient of 0.994 (p=0.001 for both models). This study presents a detailed add-on approach for calculating disability weights. Conclusions This method can be employed in other countries to obtain timely disability weight estimations.

Background: Colorectal cancer is one of the most common cancers worldwide. Colorectal cancer that has recurred and metastasized to other organs also has a very poor prognosis. According to recent studies, the long interspersed element-1 (LINE-1) retrotransposon open reading frame (ORF) is located in the intron of the c-Met proto-oncogene, which is involved in cancer progression and metastasis, and regulates its expression. However, no study has compared the expression patterns of LINE-1 ORF1 and c-Met, which are closely related to cancer progression and metastasis, and their correlation in primary and recurrent cancers. Methods: In the present study, we compared the expression patterns of LINE-1 ORF1 and c-Met in both primary and recurrent colorectal cancer tissues from 10 patients. Expression patterns and correlations between LINE-1 ORF1 and c-Met proto-oncogene proteins were analyzed by immunofluorescence staining using both LINE-1 ORF1 and c-Met antibodies. Results: The expression patterns of LINE-1 ORF1 and c-Met showed significant individual differences, and the expression of both proteins was correlated in all colorectal cancer patients. However, the expression levels of LINE-1 ORF1 and c-Met were not significantly different between primary and recurrent colorectal cancers. Conclusions The protein expression levels of LINE-1 ORF1 and c-Met were correlated, but did not change significantly in cases of recurrent colorectal cancer in the same patient.

Background: The scuticociliate Miamiensis avidus is a major pathogenic agent that causes significant economic losses in the flounder aquaculture industry. Many different types of drugs are being tested to control this disease, including mebendazole, which is a broad-spectrum antiprotozoal agent. The purpose of this study was to determine whether mebendazole worked in vitro against M. avidus and to explore its mechanism of action. Methods: Transcriptome and gene ontology analyses were conducted to investigate the specifically expressed gene profile. We confirmed the cytotoxic effect of mebendazole against M. avidus when it was applied intermittently for a total of three times. We also identified differentially expressed genes using transcriptome analysis. Results: Most of the upregulated genes were membrane transport-related genes, including Na+/K+-ATPase. Most of the downregulated genes were categorized into three groups: tubulin-related, metabolism-related, and transport-related genes. The expression levels of glucose uptake-related genes decreased due to the inhibition of tubulin polymerization, but this was not statistically significant. Conclusions Our results demonstrate that intermittent treatment with mebendazole has a significant cytotoxic effect on M. avidus. Furthermore, mebendazole induces downregulation of the tubulin-alpha chain and metabolism-related genes. It is presumed that this leads to a glucose shortage and the death of M. avidus. Transcriptome analysis will provide useful clues for further studies on mebendazole applications for scutica control.

Background: Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable. Objectives: To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro. Methods: Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive ( IDO, PTGS2, and PTGES ), inflammatory (IL6 and IL10 ), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR. Results: cA-MSCs were expressed cell surface markers such as CD90+/44+/29+/45- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes. Conclusions The administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.

Background: Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable. Objectives: To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro. Methods: Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive ( IDO, PTGS2, and PTGES ), inflammatory (IL6 and IL10 ), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR. Results: cA-MSCs were expressed cell surface markers such as CD90+/44+/29+/45- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes. Conclusions The administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.

Background/Aims: Although re-evaluation of radiographic follow-up after 2 to 3 months of therapy is recommended for patients administered anti-tuberculosis medication owing to suspected pulmonary tuberculosis, reported findings are limited. Therefore, this study aimed to investigate changes in 1- and 2-month chest X-ray (CXR) findings after the treatment initiation and compared them according to the final diagnosis of tuberculosis or non-tuberculosis. Methods: Patients who started anti-tuberculosis medication for suspected pulmonary tuberculosis were selected at a tertiary referral hospital in South Korea between January 2012 and December 2015. Changes in the 1- and 2-month CXR findings were classified as improved, unchanged, and aggravated. Results: Among the 120 patients enrolled in the 1-month CXR group, 76 (63.3%) had the final diagnosis of tuberculosis. Comparison between the 1-month CXR changes and diagnosis showed that the final diagnosis was tuberculosis in 81.8% (45/55), 50.0% (26/52), and 38.5% (5/13) of patients whose 1-month CXR was improved, unchanged, and aggravated, respectively. In the 2-month CXR group, 167 patients were enrolled, and 139 (83.2%) of them were diagnosed with tuberculosis. Tuberculosis was the final diagnosis in 92.6% (100/108), 70.0% (35/50), and 44.4% (4/9) patients with improved, unchanged, and aggravated 2-month CXR findings, respectively. In patients with the final diagnosis of non-tuberculosis, nontuberculousmycobacteria and malignancy were the most common causes of improved and aggravated 1- and 2-month CXR findings, respectively. Conclusions Two-month CXR findings were of limited value for deciding on whether to continue anti-tuberculosis treatment. One-month CXR findings could help determine the need for further work-up.