Background: We compared the immunoglobulin (IG) heavy chain (IGH) leader and FR1 primer sets to measure clone sizes and detect immunoglobulin heavy chain variable (IGHV) region somatic hypermutations (SHMs) in Korean patients with chronic lymphocytic leukemia (CLL). We also analyzed IGH and immunoglobulin kappa (IGK) to identify Korean-specific IGs in CLL. Methods: Next-generation sequencing (NGS)–based gene rearrangements and IGHV SHMs were assessed in 40 patients using IGH leader, IGH FR1, and IGK primers. Flow cytometry, karyotyping, interphase FISH, and NGS-based variant analyses were performed for 165 genes. Results: Clonal IGH and IGK rearrangements were detected in 100.0% and 97.5% of patients, respectively. Clonal size was generally smaller per NGS than per flow cytometry, particularly when using the IGH leader (median: 52.5%) versus the IGH FR1 primer set (73.2%). IGHV SHMs occurred in approximately 70% of patients; 10% showed primer set discrepancies. The incidence of IGHV SHMs was low in patients at high risk (i.e., with TP53 abnormalities; complex karyotypes; and ATM, NOTCH1, SF3B1, or BIRC3 variants). IGHV3 was the most common IGHV (58.3%), and IGHV4-34 was most frequently identified (14.6%). IGHV1 and IGHV1-69 usage differed significantly between Koreans and westerners. IGHJ4 was the most common IGHJ (56.3%). A single IGKV–IGKJ gene rearrangement was most frequently observed (18.9%), whereas intron-KDE was the most common rearrangement (30.6%). Conclusions NGS may underestimate CLL clonal size, particularly when using the IGH leader primer set. IGHV SHMs were inversely associated with negative prognostic factors.Our data suggest ethnic differences in CLL pathogenesis.

Objective: To evaluate ruminoreticular temperature and body activity after vaccination, stratified by pregnancy status. Methods: This prospective observational cohort study investigated ruminoreticular temperature and body activity in Hanwoo cows after experimental administration of FMD and LSD vaccines. Sixty-three Hanwoo cows (pregnant n = 23 [100–175 days], nonpregnant n = 40) were monitored using a rumen-insertable biosensor that records ruminoreticular temperature and activity every 10 min. Groups received FMD, LSD, simultaneous FMD/LSD, or saline (control). Outcomes were analyzed using analysis of covariance with age and parity as covariates. Results: In pregnant cows, simultaneous FMD/LSD vaccination increased ruminoreticular temperature at day 1 and returned to baseline by day 3; single-vaccine groups showed more prolonged elevations. In nonpregnant cows, simultaneous vaccination increased temperature at day 1, normalizing by day 3–4. Body activity did not differ among pregnant groups;in nonpregnant cows, the simultaneous group showed lower activity than single-vaccine groups on some days. Conclusions and Relevance: In pregnant Hanwoo cows, post-vaccination temperature increase may enhance the risk of abortion, stillbirth, and premature birth, but this cannot be concluded to be the effect of vaccination. Since vaccination is the sole prevention for infectious diseases, it is unavoidable. Therefore, further research on reproduction related side effects after simultaneous vaccination are needed, and the findings of this study may provide valuable data to support such investigations.

Purpose: The accurate localization of bifurcation points in the brain near the circle of Willis is essential for labeling cerebral arteries and detecting potential aneurysms. Studies on the development of segmentation-based landmark localization methods for cerebral angiography are lacking. This study aimed to develop and validate a method for localizing anatomical landmarks using a three-dimensional (3D) encoder-decoder deep convolutional neural network architecture. Materials and Methods: Time-of-flight magnetic resonance angiography (MRA) images of 224 subjects obtained from publicly available datasets were used. Ten anatomical landmark points were annotated, and four different landmark subset configurations were trained and validated. For each configuration, 3D U-Net-based models were developed using the MRA images and their corresponding annotated landmarks. The deep learning prediction results were evaluated in terms of landmark localization errors. Results: Among the four configurations, the configuration with five landmark subsets produced the smallest landmark localization errors in the test dataset. Post-processing of the U-Net-predicted segmentation masks further reduced the mean localization errors across all landmark points for the configuration with five subsets. Conclusion The proposed landmark localization method effectively identified major anatomical landmarks around the circle of Willis and showed the potential to automate segmental analyses of intracranial arterial tortuosity.

Although oxidative stress is the main pathophysiology of the development of diabetic neuropathy, oral administration of antioxidants has given disappointing results. Here, we hypothesized that local delivery of antioxidants would provide protective effects on Schwann cells due to the high concentration of local lesions. We prepared alpha-tocopherol (ATF)-loaded liposomes and tested their skin penetration after sonication. An in vitro study using IMS-32 cells was conducted to determine the level of reactive oxygen species (ROS) scavenging effects of ATF-liposomes. ATF reduced ROS in high-glucose-exposed IMS-32 cells in a dosedependent manner. ATF-liposomes also reduced the ROS level in vitro and ultrasound irradiation enhanced delivery to the dermis in porcine ear skin. This study showed that it is feasible to deliver ATF through the skin and can effectively reduce ROS. This model is worthy of development for clinical use.

Although oxidative stress is the main pathophysiology of the development of diabetic neuropathy, oral administration of antioxidants has given disappointing results. Here, we hypothesized that local delivery of antioxidants would provide protective effects on Schwann cells due to the high concentration of local lesions. We prepared alpha-tocopherol (ATF)-loaded liposomes and tested their skin penetration after sonication. An in vitro study using IMS-32 cells was conducted to determine the level of reactive oxygen species (ROS) scavenging effects of ATF-liposomes. ATF reduced ROS in high-glucose-exposed IMS-32 cells in a dosedependent manner. ATF-liposomes also reduced the ROS level in vitro and ultrasound irradiation enhanced delivery to the dermis in porcine ear skin. This study showed that it is feasible to deliver ATF through the skin and can effectively reduce ROS. This model is worthy of development for clinical use.

Although oxidative stress is the main pathophysiology of the development of diabetic neuropathy, oral administration of antioxidants has given disappointing results. Here, we hypothesized that local delivery of antioxidants would provide protective effects on Schwann cells due to the high concentration of local lesions. We prepared alpha-tocopherol (ATF)-loaded liposomes and tested their skin penetration after sonication. An in vitro study using IMS-32 cells was conducted to determine the level of reactive oxygen species (ROS) scavenging effects of ATF-liposomes. ATF reduced ROS in high-glucose-exposed IMS-32 cells in a dosedependent manner. ATF-liposomes also reduced the ROS level in vitro and ultrasound irradiation enhanced delivery to the dermis in porcine ear skin. This study showed that it is feasible to deliver ATF through the skin and can effectively reduce ROS. This model is worthy of development for clinical use.

Although oxidative stress is the main pathophysiology of the development of diabetic neuropathy, oral administration of antioxidants has given disappointing results. Here, we hypothesized that local delivery of antioxidants would provide protective effects on Schwann cells due to the high concentration of local lesions. We prepared alpha-tocopherol (ATF)-loaded liposomes and tested their skin penetration after sonication. An in vitro study using IMS-32 cells was conducted to determine the level of reactive oxygen species (ROS) scavenging effects of ATF-liposomes. ATF reduced ROS in high-glucose-exposed IMS-32 cells in a dosedependent manner. ATF-liposomes also reduced the ROS level in vitro and ultrasound irradiation enhanced delivery to the dermis in porcine ear skin. This study showed that it is feasible to deliver ATF through the skin and can effectively reduce ROS. This model is worthy of development for clinical use.

Purpose: Minimal residual disease (MRD)-guided therapy is the global standard treatment for pediatric acute lymphoblastic leukemia (ALL). We assessed the impact of MRD-driven intensification along with protocol-defined risk groups in pediatric ALL treatment. Methods: This retrospective analysis included 209 patients with ALL (treated between January 2013 to June 2023).MRD was assessed using six- to eight-color flow cytometry at the end of each phase before the maintenance phase.Post-induction treatment was determined based on early response, National Cancer Institute risk, and cytogenet‑ ics. High-risk (HR) patients followed the Korean HR or CCG-1882 protocols and standard-risk (SR) patients followed the modified COG-AALL0331 protocol. Treatment was intensified if flow-MRD ≥ 0.1% was identified. Results: Overall, 103 and 106 patients were classified as having SR and HR, respectively. The 5-year overall survival (OS) and event-free survival (EFS) were 92.5% and 84.3%, respectively. Thirty SR and 18 HR patients received intensi‑ fied chemotherapy. Treatment intensification significantly improved EFS in patients with high MRD (94.2% vs. 75.5%, p = 0.04), particularly in post-induction patients with high MRD (90.0% vs. 19.0%, p = 0.035). The difference in survival between rapid early responder (RER) and slow early responder (SER) groups was eliminated after MRD-based intensifi‑ cation. The implementation rates of treatment intensification varied over time (9.1% before 2015, 28.6% during 2016– 2019, and 13.9% during 2020–2023), reflecting improved risk stratification and therapy selection. Conclusion MRD-guided therapy intensification markedly improved survival outcomes in patients with pediatric ALL when combined with risk-based protocols, highlighting the importance of MRD monitoring for optimizing riskadapted treatment strategies.

Frailty poses a complex challenge to the health and well-being of aging populations, particularly in South Korea, where its prevalence is substantial and increasing. This review explores the landscape of frailty assessment and management in Korea, emphasizing the transition from a disease-centric approach to one focused on maintaining functional abilities and promoting healthy aging. This review covers various frailty screening tools, comprehensive geriatric assessment methods, and targeted interventions across domains such as polypharmacy, physical activity, nutrition, oral health, vitamin D supplementation, cognitive function, falls, and social frailty. The integration of these strategies aims to address the multifaceted nature of frailty and improve health outcomes for older adults. Furthermore, the importance of regular monitoring and reassessment is highlighted to guide personalized interventions and optimize outcomes, particularly for older adults with chronic illnesses. Through a multifaceted approach encompassing medical, social, and functional dimensions, this review advocates for effective frailty management to enhance the health and well-being of elderly in Korea and globally.