Background: Histone deacetylase (HDAC) inhibition offers potential anticancer effects across diverse cancers due to HDAC's significant role in cancer development and progression. Consequently, we demonstrated the therapeutic efficacy of the novel HDAC inhibitor, CG-745, in comparison with existing inhibitors such as suberoylanilide hydroxamic acid (SAHA) in non-small cell lung cancer (NSCLC) cells. Methods: CG-745's effect on apoptosis and reactive oxygen species (ROS)-dependent mitochondrial dysfunction was investigated using annexin V assay, MitoSoX, and Western blot in human A549 and H460 cells. Additionally, HDAC expression was analyzed through real-time polymerase chain reaction. We also evaluated the inhibitory effect of CG-745 on epithelial-mesenchymal transition (EMT) induced by transforming growth factor β1 (TGF-β1) via Western blot, scratch analysis, and matrigel invasion analysis. Results: Compared to SAHA, CG-745 inhibited cell viability and mRNA expression of HDACs such as HDAC1, HDAC2, HDAC3, and HDAC8. It also induced apoptosis, ROS, and mitochondrial dysfunction in a concentration-dependent manner. CG-745 reversed EMT triggered by TGF-β1 in A549 and H460 cells, and curtailed the migration and invasion enhanced by TGF-β1. CG-745 has demonstrably inhibited EMT and induced apoptosis in NSCLC cells. Conclusion CG-745 may represent a novel therapeutic strategy for NSCLC treatment.

Objective: This study aims to objectively evaluate turning gait parameters in Parkinson’s disease (PD) patients using 2D-RGB video-based analysis and explore their relationships with imbalance. Methods: We prospectively enrolled PD patients for clinical assessment, balance analysis and gait with 180º turning. Spatiotemporal gait parameters during turning were derived using video-based analysis and correlated with modified Hoehn and Yahr (mHY) stages and center of pressure (COP) oscillations. Results: A total of 64 PD patients were enrolled. The PD patients with higher mHY stages (≥2.5) had significantly longer turning times, greater numbers of steps, wider step bases and less variability in step length during turns. COP oscillations were positively correlated with the mean turning time on both the anterior-posterior and right-left axes. Conclusion Spatiotemporal gait parameter during turning, derived from video-based gait analysis, may represent apromising biomarker for monitoring postural instability in PD patients.

Allogeneic stem cell transplantation (allo-SCT) is a salvage treatment option for patients with relapsed or refractory lymphoid malignancies. However, the clinical variables impacting outcomes in these patients remain unclear. We analyzed 58 patients who underwent allo-SCT for lymphoid malignancies, including B-cell lymphoma (BCL, n = 20), Hodgkin’s disease (n = 3), multiple myeloma (n = 9), natural killer/T-cell lymphoma (NK/TCL, n = 4), and TCL (n = 22).The median progression-free survival (PFS) was 27.4 months, while the median overall survival (OS) was 30.6 months.In univariate analysis, human leukocyte antigen (HLA) matching and complete remission status post-transplantation were associated with improved PFS and OS. However, only post-transplant response remained significant for both sur‑ vival outcomes in the multivariate analysis. Moreover, HLA matching was associated with a significantly improved PFS in patients with BCL and NK/TCL, but with better OS only in those with BCL. Complete remission after transplantation was associated with better PFS and OS in patients with BCL, NK/TCL, and TCL. Our results indicate that post-transplant response is an important prognostic indicator in allo-SCT for lymphoid malignancies and may guide clinical decisions and additional treatment.

Objective: Recently, various mental health promotion programs using virtual reality (VR) technology have been tried in the psychiatric field. Considering the importance of mental health in pregnant women, VR-assisted mental health promotion programs for pregnant women are needed to be developed. This study aimed to prospectively investigate the efficacy of a VR-assisted mental health promotion program for pregnant women. Methods: Fifty-five pregnant women were participated in this study. Mental health states such as depression, anxiety, perceived stress, and quality of life were assessed by Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Perceived Stress Scale, and World Health Organization Quality of Life Scale Abbreviated Version (WHOQOL-BREF) before and after using VR program treatment. Based on the mental health types of pregnant women classified by cluster analysis, the effects of the VR program were analyzed by paired t test and Wilcoxon signed rank test. Results: The VR program significantly reduced PHQ-9 (p = 0.033) and GAD-7 (p = 0.046) scores, and significantly increased WHOQOL-BREF (p = 0.026) score of the participants. Additionally, when classifying the mental health types of pregnant women, the VR program was significantly effective to improve depression, anxiety, and quality of life in the most severe group based on the cluster analysis. Conclusion The results of this study suggest that VR program may be effective to improve the mental health of pregnant women. Particularly, VR programs for the high-risk group of depression might be the most effective. Therefore, VR-assisted mental health promotion programs could be useful for managing the mental health in pregnant women.

Background: Bone substitutes such as hydroxyapatite (HA) ceramic and recombinant bone morphogenetic protein-2 (BMP-2) are essential in treating bone defects. However, the challenges of controlled and localized BMP-2 delivery necessitate the development of advanced bone graft substitutes. This study introduces and evaluates an innovative, ready-to-use bone substitute employing 3-dimensional-printed poly-L-lactic acid (PLLA) scaffolds combined with BMP-2 to enhance bone regeneration efficiency. Methods: We conducted a comparative study using C57BL/6 mice to evaluate the efficacy of rhBMP-2-coated PLLA scaffolds against traditional HA-based bone graft materials. The PLLA scaffolds were coated with varying concentrations of BMP-2 using an alginate-catechol method. Bone regeneration was assessed through micro-computed tomography (CT) imaging and histological analysis 4 weeks after implantation. The statistical significance of bone mass and formation differences across groups was determined using Student t-test and analysis of variance. Results: Micro-CT analysis revealed substantial bone formation in the group with PLLA scaffolds containing 0.1% BMP-2, exhibiting a bone volume ratio of 11.1% ± 2.8%, significantly higher than all other groups (p = 0.008). Histological analysis corroborated these findings, showing dense collagen deposition and active osteoblast presence in this group, indicating enhanced bone regeneration. Conclusions The novel PLLA scaffold with alginate-catechol-coated BMP-2 significantly enhances bone regeneration compared to traditional bone graft materials. This innovative approach holds promising potential for clinical applications in orthopedics, particularly for treating bone defects.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: This study aimed to examine changes in nurse staffing grades and nursing fee revenues in intensive care units (ICUs) following the third amendment of the resource-based relative value scale, which was implemented in January 2024. Methods: Changes in staffing grades from the fourth quarter of 2023 to the first quarter of 2024 were analyzed among 588 general ICUs, 94 neonatal ICUs, and 13 pediatric ICUs. Annual nursing fee revenues per nurse were estimated based on the new nursing fee structure for each grade. Results: In general ICUs, the highest grade (grade S) and the second-highest grade (grade A) accounted for 7.3% and 41.5%, respectively, in tertiary hospitals, whereas 3.8% were grade S and 11.5% were grade A in general hospitals. In neonatal ICUs, the proportion of higher grades (S, A, and 1) was greater in general hospitals (54.3%) than in tertiary hospitals (38.6%). In pediatric ICUs, 30.8% were grade S and 61.5% were grade A. When applying the same grading criteria (i.e., beds per nurse) across both quarters, staffing levels remained unchanged in most ICUs. Nursing fees and their revenues did not increase proportionally to staffing requirements (i.e., the number of nurses required per patient). Conclusion Revisions to staffing grade and nursing fee systems are necessary to induce medical institutions to improve their ICU staffing levels.

Background: Group B Streptococcus (GBS) is one of the leading causes of neonatal earlyonset sepsis, resulting in high mortality and significant comorbidity. Intrapartum penicillin prophylaxis is recommended for pregnant women with GBS colonization to prevent vertical transmission. For pregnant women at high risk of anaphylaxis to penicillin, clindamycin is recommended only if the susceptibility of GBS isolates has been identified. We retrospectively examined the GBS detection rate and clindamycin resistance among Korean women of reproductive age over the last 20 years. Methods: Microbiologic studies using vaginal, vaginal–rectal or vaginal–perianal swabs from female patients 15–49 years of age during 2003–2022 were reviewed. Annual GBS detection rates and clindamycin resistance rates were calculated. The study period was divided into two periods (period 1, 2003–2015; period 2, 2016–2022) based on the introduction of universal culture-based GBS screening in our center in 2016. GBS detection rates and clindamycin resistance rates were compared between the periods using χ2 tests. Results: A total of 14,571 women were tested 16,879 times and GBS was isolated in 1,054 tests (6.2%), with 423 clindamycin-resistant isolates (40.1%). The GBS detection rate increased from 3.4% (301/8,869) in period 1 to 9.4% (2,753/8,010) in period 2 (P < 0.001). Even during period 1, the GBS detection rate was higher in 2009–2015 compared to 2003–2008 (P < 0.001). Clindamycin resistance rates have remained at similar levels since 2009, which were 39.5% (199/301) in period 1 and 40.2% (303/753) in period 2 (P = 0.833). Conclusion This study demonstrated that GBS detection rates in Korean women of reproductive age significantly increased almost three times during the twenty years of the study period, with a persistently high clindamycin resistance rate of up to 40%.

Background: The ionic mechanism underlying Brugada syndrome (BrS) arises from an imbalance in transient outward current flow between the epicardium and endocardium.Previous studies report that artemisinin, originally derived from a Chinese herb for antimalarial use, inhibits the Ito current in canines. In a prior study, we showed the antiarrhythmic effects of artemisinin in BrS wedge preparation models. However, quinidine remains a well-established antiarrhythmic agent for treating BrS. Therefore, this study aims to investigate the efficacy of combining artemisinin with low-dose quinidine in suppressing ventricular tachyarrhythmia (VTA) in experimental canine BrS models. Methods: Transmural pseudo-electrocardiogram and epicardial/endocardial action potential (AP) were recorded from coronary-perfused canine right ventricular wedge preparation. To mimic the BrS model, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and Ito agonist NS5806 (6–10 μM) were administered until VTA was induced. Subsequently, lowdose quinidine (1–2 μM) combined with artemisinin (100 μM) was perfused to mitigate VTA.Key parameters, including AP duration, J wave area, notch index, and T wave dispersion, were measured. Results: After administering the provocation agents, all sample models exhibited prominent J waves and VTA. Artemisinin alone (100–150 μM) suppressed VTA and restored the AP dome in all three preparations. Its infusion resulted in reductions in the J wave area and epicardial notch index. Consequently, low-dose quinidine (1–2 μM) did not fully restore the AP dome in all six sample models. However, when combined with additional artemisinin (100 μM), lowdose quinidine effectively suppressed VTA in all six models and restored the AP dome while also decreasing the J wave area and epicardial notch index. Conclusion Low-dose quinidine alone fails to fully alleviate VTA in the BrS wedge model.However, its combination with artemisinin effectively suppresses VTA. Artemisinin may reduce the therapeutic dose of quinidine, potentially minimizing its associated adverse effects.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.