Purpose: Breast cancer is known to be influenced by genetic and environmental factors, and several susceptibility genes have been discovered. Still, the majority of genetic contributors remain unknown. We aimed to analyze the plasma proteome of breast cancer patients in comparison to healthy individuals to identify differences in protein expression profiles and discover novel biomarkers. Methods: This pilot study was conducted using bioresources from Seoul National University Bundang Hospital’s Human Bioresource Center. Serum samples from 10 breast cancer patients and 10 healthy controls were obtained. Liquid chromatography-mass spectrometry analysis was performed to identify differentially expressed proteins. Results: We identified 891 proteins; 805 were expressed in the breast cancer group and 882 in the control group. Gene set enrichment and differential expression analysis identified 30 upregulated and 100 downregulated proteins in breast cancer. Among these, 10 proteins were selected as potential biomarkers. Three proteins were upregulated in breast cancer patients, including cluster of differentiation 44, eukaryotic translation initiation factor 2-α kinase 3, and fibronectin 1. Seven proteins downregulated in breast cancer patients were also selected: glyceraldehyde-3-phosphate dehydrogenase, α-enolase, heat shock protein member 8, integrin‑linked kinase, tissue inhibitor of metalloproteinases-1, vasodilatorstimulated phosphoprotein, and 14-3-3 protein gamma. All proteins had been previously reported to be related to tumor development and progression. Conclusion The findings suggest that plasma proteome profiling can reveal potential diagnostic biomarkers for breast cancer and may contribute to early detection and personalized treatment strategies. A further validation study with a larger sample cohort of breast cancer patients is planned.

Neuropathic arthropathy (Charcot arthropathy) is a progressive joint disease often associated with conditions such as diabetes, leading to severe joint deformity and pain. However, its occurrence in patients with rheumatoid arthritis (RA) is rare and not well documented.This case report describes a 48-year-old woman with a long history of RA who developed a severe deformity of her right ankle, identified as neuropathic arthropathy extending to the subtalar joint (Brodsky classification type 3A). After excluding other potential causes, the condition was determined to be secondary to RA-associated peripheral neuropathy. Surgery, including allograft and autograft fixation, was performed to correct the deformity. Post-operative complications, such as wound infection, were treated with negative pressure wound therapy and skin grafting. At the 18-month follow-up, the patient was able to walk without pain, demonstrating successful joint fusion.

In schizophrenia, while antipsychotic medications are the primary treatment, auditory hallucinations may sometimes persist despite pharmacotherapy, and negative symptoms and cognitive impairments often show a limited response to these medications. Transcranial magnetic stimulation (TMS) has emerged as a promising adjunctive treatment, capable of modulating neuronal activity in targeted brain regions. Low-frequency repetitive TMS (rTMS) directed at the left temporoparietal cortex has demonstrated efficacy in reducing auditory hallucinations. In addressing negative symptoms, high-frequency rTMS applied to the dorsolateral prefrontal cortex has shown some effectiveness, though outcomes can vary. Innovative techniques, including theta burst stimulation and personalized approaches utilizing neuroimaging, are currently under investigation to further enhance the therapeutic potential of TMS. This review examines the application of TMS in the treatment of schizophrenia, emphasizing the necessity of ongoing research to refine and optimize its efficacy across diverse symptom domains.

Objective: Spatial normalization is an essential process for comparative analyses that heavily depends on the standard brain template used. Brain morphological differences are observed in different populations due to genetic and environmental factors, causing mismatches in regions when the data are normalized to different population templates. Recent studies have indicated differences between Caucasian and East Asian populations as well as within East Asian populations, suggesting the necessity of population-specific brain templates. Thus, this study aimed to construct a Korean young adult age-specific brain template utilizing an advanced method of template construction to update the currently available Korean template. Methods: The KOR152 template was constructed via affine and nonlinear iterative procedures based on prior studies. We compared the morphological features of different population templates (MNI152, Indian_157, and CN200). The distance and volumetric changes before and after registering the data to these templates were calculated for registration accuracy. Results: The KOR152 global brain features revealed a shorter overall length than the other population templates. The registration accuracy by distance and volumetric change was significantly lower than that of the other population templates, implying that the KOR152 was more accurate than other templates for the young adult Korean population. Conclusion This study provided evidence for the need for a population-specific template that may be more appropriate for structural and functional studies in Korean populations.

Objective: Obsessive-compulsive disorder (OCD) is a psychiatric condition that causes significant distress and social costs and often follows a chronic course with frequent relapses. Approximately 20% of patients do not respond to medication or cognitive behavioral therapy; gamma knife surgery (GKS) has been proposed as a treatment option for these patients. However, research on GKS for OCD patients is rare. Methods: In this study, 10 patients with treatment-resistant OCD underwent GKS, and the treatment response and side effects were assessed. The improvement in patients’ obsessive-compulsive symptoms was evaluated using the Yale-Brown Obsessive Compulsive Scale (YBOCS) scores following GKS. Additionally, the characteristics distinguishing the groups with favorable responses to GKS from those with less favorable responses were examined. Results: GKS was well tolerated, and patients demonstrated a statistically significant reduction in YBOCS scores before and after GKS (p=0.016). Patients that responded to GKS exhibited distinct characteristics from those who did not respond. Patients who responded poorly tended to present an earlier age of onset, a longer duration of illness, more frequent hospitalizations, poorer social functioning, and a greater incidence of suicide attempts/thoughts. Conclusion This study not only demonstrated that GKS is a safe and effective treatment method for intractable OCD but also revealed characteristics distinguishing patients who respond well to GKS from those who do not. These results may aid in the selection of patients for future application of GKS.

Purpose: High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. Materials and Methods: We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. Results: Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. Conclusion We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.

BACKGROUND: Retinal degenerative disease (RDD), one of the most common causes of blindness, is predominantly caused by the gradual death of retinal pigment epithelial cells (RPEs) and photoreceptors due to various causes. Cell-based therapies, such as stem cell implantation, have been developed for the treatment of RDD, but potential risks, including teratogenicity and immune reactions, have hampered their clinical application. Stem cell-derived extracellular vesicles (EVs) have recently emerged as a cell-free alternative therapeutic strategy; however, additional invasiveness and low yield of the stem cell extraction process is problematic. METHODS: To overcome these limitations, we developed therapeutic EVs for the treatment of RDD which were extracted from tonsil-derived mesenchymal stem cells obtained from human tonsil tissue discarded as medical waste following tonsillectomy (T-MSC EVs). To verify the biocompatibility and cytoprotective effect of T-MSC EVs, we measured cell viability by co-culture with human RPE without or with toxic all-trans-retinal. To elucidate the cytoprotective mechanism of T-MSC EVs, we performed transcriptome sequencing using RNA extracted from RPEs. The in vivo protective effect of T-MSC EVs was evaluated using Pde6b gene knockout rats as an animal model of retinitis pigmentosa. RESULTS: T-MSC EVs showed high biocompatibility and the human pigment epithelial cells were significantly protected in the presence of T-MSC EVs from the toxic effect of all-trans-retinal. In addition, T-MSC EVs showed a dosedependent cell death-delaying effect in real-time quantification of cell death. Transcriptome sequencing analysis revealed that the efficient ability of T-MSC EVs to regulate intracellular oxidative stress may be one of the reasons explaining their excellent cytoprotective effect. Additionally, intravitreally injected T-MSC EVs had an inhibitory effect on the destruction of the outer nuclear layer in the Pde6b gene knockout rat. CONCLUSIONS Together, the results of this study indicate the preventive and therapeutic effects of T-MSC EVs during the initiation and development of retinal degeneration, which may be a beneficial alternative for the treatment of RDD.

Objective: In the triple-network model, the salience network (SN) plays a crucial role in switching between the default-mode network (DMN) and the central executive network (CEN). Aberrant patterns of triple-network connectivity have been reported in schizophrenia patients, while findings have been less consistent for patients in the early stages of psychotic disorders. Thus, the present study examined the connectivity among the SN, DMN, and CEN in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis. Methods: Thirty-nine patients with FEP, 78 patients with CHR for psychosis, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We compared the SN, DMN, and CEN connectivity patterns of the three groups. The role of the SN in networks with significant connectivity differences was examined by mediation analysis. Results: FEP patients showed lower SN-DMN and SN-CEN (cluster-level F=5.83, false discovery rate [FDR] corrected-p=0.001) connectivity than HCs. There was lower SN-DMN connectivity (cluster-level F=3.06, FDR corrected-p=0.053) at a trend level in CHR subjects compared to HCs. Between HCs and FEP patients, mediation analysis showed that SN-DMN connectivity was a mediator between group and SN-CEN connectivity. Additionally, SN-CEN connectivity functioned as a mediator between group and SN-DMN connectivity. Conclusion Aberrant connectivity between the SN and DMN/CEN suggests disrupted network switching in FEP patients, although CHR subjects showed trend-level SN-DMN dysconnectivity. Our findings suggest that dysfunctional triple-network dynamics centered on the SN can appear in patients in the early stages of psychotic disorders.

Purpose: The correlation between the existence of the preoperative condition of ≥10 prism diopters (PD) in patients with basic type of intermittent exotropia (IXT) and postoperative outcomes was analyzed.
Methods: The medical records of patients that underwent surgery for IXT were analyzed retrospectively. The analysis was conducted by dividing the patients into a group with change of <10 PD (group 1) and ≥10 PD (group 2) before the time of the surgery. Patients who received at least 6 months of follow-up after surgery were included. The age, sex, angle of deviation and stereoacuity of the patients were studied. Surgical success was defined as exodeviation of <10 PD or esodeviation of <4 PD at the final visit after the surgery. The correlation between clinical factors and surgical success rate was analyzed by using correlative analysis.
Results: A total of 129 patients participated in the study. There were 108 (83.7%) and 21 (16.3%) patients in groups 1 and 2, respectively. There were 89 (82.4%) and 17 (80.1%) patients with surgical successes in groups 1 and 2, respectively (p = 0.18). Moreover, 13 (12.0%) patients in group 1 and three (14.3%) patients in group 2 required reoperation, showing no significant difference (p = 0.12). There was no statistically significant correlation between surgical success and preoperative change of angle of deviation <10 PD (odds ratio, 1.78; p = 0.17).
Conclusions Among the patients with basic type of IXT subjected to the analysis, 16.3% had a change of ≥10 PD before surgery, and there was no significant correlation between surgical success and preoperative change of angle of deviation.

Purpose: The correlation between the existence of the preoperative condition of ≥10 prism diopters (PD) in patients with basic type of intermittent exotropia (IXT) and postoperative outcomes was analyzed.
Methods: The medical records of patients that underwent surgery for IXT were analyzed retrospectively. The analysis was conducted by dividing the patients into a group with change of <10 PD (group 1) and ≥10 PD (group 2) before the time of the surgery. Patients who received at least 6 months of follow-up after surgery were included. The age, sex, angle of deviation and stereoacuity of the patients were studied. Surgical success was defined as exodeviation of <10 PD or esodeviation of <4 PD at the final visit after the surgery. The correlation between clinical factors and surgical success rate was analyzed by using correlative analysis.
Results: A total of 129 patients participated in the study. There were 108 (83.7%) and 21 (16.3%) patients in groups 1 and 2, respectively. There were 89 (82.4%) and 17 (80.1%) patients with surgical successes in groups 1 and 2, respectively (p = 0.18). Moreover, 13 (12.0%) patients in group 1 and three (14.3%) patients in group 2 required reoperation, showing no significant difference (p = 0.12). There was no statistically significant correlation between surgical success and preoperative change of angle of deviation <10 PD (odds ratio, 1.78; p = 0.17).
Conclusions Among the patients with basic type of IXT subjected to the analysis, 16.3% had a change of ≥10 PD before surgery, and there was no significant correlation between surgical success and preoperative change of angle of deviation.