The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.

Purpose: This study assessed the reproducibility and clinical value of the vascular index (VI), derived from superb microvascular imaging (SMI) using Doppler ultrasonography, for evaluating renal function in transplanted kidneys. Methods: This retrospective study included 63 renal transplant patients who underwent grayscale and Doppler ultrasonography with SMI from January 2022 to February 2023. The VI of the transplanted kidneys was measured using three methods (VI_box, VI_F1, VI_F2). The VI was compared across chronic kidney disease (CKD) groups categorized by estimated glomerular filtration rate (eGFR) and Kidney Disease: Improving Global Outcomes (KDIGO) CKD risk groups based on eGFR and albuminuria. The correlation between VI and renal function was evaluated. Univariate and multivariate linear regression analyses were used to identify predictors of eGFR. Results: Significant differences in VI were observed among CKD groups based on eGFR (VI_box, P=0.001; VI_F1, P<0.001; VI_F2, P<0.001) and KDIGO CKD groups based on eGFR and albuminuria (VI_box, P=0.039; VI_F1, P=0.001; VI_F2, P<0.001). VI_F1 and VI_F2 demonstrated moderate/high correlations with eGFR (r=0.627, P<0.001 and r=0.657, P<0.001, respectively) and serum creatinine (r=-0.626, P<0.001 and r=-0.649, P<0.001, respectively). VI_box moderately correlated with eGFR (r=0.445, P<0.001). Multivariate regression identified the urine albumincreatinine ratio (ACR) (adjusted odds ratio [aOR], 1.122; 95% confidence interval [CI], -0.007 to, 0.000; P=0.030) and VI_F2 (aOR, 1.114; 95% CI, 0.466 to 1.235; P<0.001) were independently associated with eGFR. Conclusion The VI measured by drawing a region of interest along the border of the transplanted kidney in SMI (VI_F2) is highly reproducible and correlates well with eGFR. Both VI_F2 and ACR independently predict eGFR.

Purpose: We investigated the results of endoscopic fenestration for deeply located intracranial cysts (DLICs), risk factors for reoperation, and symptom improvement. Materials and Methods: We included 51 patients with DLICs who underwent endoscopic fenestration between November 2006 and October 2022. The median age was 5±20 years (6 days–67 years), and 36 (70.6%) patients were aged <20 years. The male-tofemale ratio was 1.3:1. The ventriculoscope was used to fenestrate the cysts, which had diameters under 4.5 mm. The volume of DLICs was measured separately on serial magnetic resonance imaging, and the patients were followed up for 32±40 months. Results: The mean preoperative volume of DLICs was 63.5±87.4 cm, 3 , which decreased to 23.7±56.2 cm 3postoperatively, with a 45.4%±32.1% decrease rate in 32 months. All DLICs were approached appropriately, avoiding the eloquent areas. Overall, 39 (76.5%) patients showed symptom improvement after a single operation, which was preserved without recurrence, whereas 12 (23.5%) underwent a second operation [shunting (17.6%) or repeating the endoscopic fenestration (5.9%)] owing to symptom aggravation and recurrent cysts. Patients aged <12 months showed 7.4 times more re-operation rate (p>0.046) and 7.4 times less symptom improvement (p=0.038) compared to those with older age. Females showed 6.5 times more re-operation rate (p=0.037) and 7.1 times less symptom improvement (p=0.027) than males. No patients experienced complications such as cerebrospinal fluid leakage, postoperative hemorrhage, or infection. Conclusion Endoscopic surgery is feasible for the treatment of DLICs. Female sex and age <12 months are risk factors for re-operation and less symptom improvement.

Purpose: Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC. Materials and Methods: This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association. Results: We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy. Conclusion Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Purpose: This study aimed to identify predictive factors affecting adolescents’ subjective happiness using data from the 2023 Korea Youth Risk Behavior Survey. A random forest model was applied to determine the strongest predictive factors, and its predictive performance was compared with traditional regression models. Methods: Responses from a total of 44,320 students from grades 7 to 12 were analyzed. Data pre-processing involved handling missing values and selecting variables to construct an optimal dataset. The random forest model was employed for prediction, and SHAP (Shapley Additive Explanations) analysis was used to assess variable importance. Results: The random forest model demonstrated a stable predictive performance, with an R2 of .37. Mental and physical health factors were found to significantly affect subjective happiness. Adolescents’ subjective happiness was most strongly influenced by perceived stress, perceived health, experiences of loneliness, generalized anxiety disorder, suicidal ideation, economic status, fatigue recovery from sleep, and academic performance. Conclusion This study highlights the utility of machine learning in identifying factors influencing adolescents’ subjective happiness, addressing limitations of traditional regression approaches. These findings underscore the need for multidimensional interventions to improve mental and physical health, reduce stress and loneliness, and provide integrated support from schools and communities to enhance adolescents’ subjective happiness.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Background: Long-term use of bisphosphonate is a risk factor for atypical femoral fractures (AFFs). Femoral bowing is known to be associated with AFFs. However, whether femoral bowing quickens the occurrence of AFF is unknown. The purpose of this study was to determine whether AFF occurs earlier in patients with severe femoral bowing than in those without severe bowing. Methods: One hundred and sixty-four patients (186 AFFs) from January 2006 to December 2022 were included in this study.According to severity of femoral bowing, patients were divided into 2 groups: severe bowing group (26 femurs) and minimal to moderate bowing group (160 femurs). Age, sex, and completeness and location of AFF were compared between the 2 groups. We compared the time of AFF occurrence after bisphosphonate therapy using cumulative percentage between the 2 groups. Results: Age and sex were similar between the 2 groups, while body mass index (BMI) was lower (22.5 ± 3.0 kg/m 2 vs. 24.5 ± 3.5 kg/m 2 , p = 0.003) in the severe bowing group. The duration of bisphosphonate use was shorter in the severe bowing group than in the minimal to moderate bowing group (3.3 ± 3.8 years vs. 5.0 ± 4.0 years, p = 0.048). In the severe bowing group, 85% of AFFs were diaphyseal in contrast to the 46% in the minimal to moderate bowing group (p < 0.001). Cumulative percentage plot of AFFs in the severe bowing group was left-shifted compared to the minimal to moderate bowing group. Conclusions At the time of AFF diagnosis, the severe bowing group exhibited shorter duration of bisphosphonate use, lower BMI, and a higher incidence of diaphyseal location. Shortening the duration of bisphosphonate therapy may be advisable in patients with severe femoral bowing.

Background/Aims: We investigated the clinical practice patterns of Korean endoscopists for the endoscopic resection of colorectal polyps. Methods: From September to November 2021, an online survey was conducted regarding the preferred resection methods for colorectal polyps, and responses were compared with the international guidelines. Results: Among 246 respondents, those with <4 years, 4–9 years, and ≥10 years of experiencein colonoscopy practices accounted for 25.6%, 34.1%, and 40.2% of endoscopists, respectively. The most preferred resection methods for non-pedunculated lesions were cold forceps polypectomy for ≤3 mm lesions (81.7%), cold snare polypectomy for 4–5 mm (61.0%) and 6–9 mm (43.5%) lesions, hot endoscopic mucosal resection (EMR) for 10–19 mm lesions (72.0%), precut EMR for 20–25 mm lesions (22.0%), and endoscopic submucosal dissection (ESD) for ≥26 mm lesions (29.3%). Hot EMR was favored for pedunculated lesions with a head size <20 mm and stalk size <10 mm (75.6%) and for those with a head size ≥20 mm or stalk size ≥10 mm (58.5%). For suspected superficial and deep submucosal lesions measuring 10–19 mm and ≥20 mm, ESD (26.0% and 38.6%) and surgery (36.6% and 46.3%) were preferred, respectively. The adherence rate to the guidelines ranged from 11.2% to 96.9%, depending on the size, shape, and histology of the lesions. Conclusions Adherence to the guidelines for endoscopic resection techniques varied depend-ing on the characteristics of colorectal polyps. Thus, an individualized approach is required to increase adherence to the guidelines.