Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

Background: The significance of risk modification in patients with acute coronary syndrome (ACS) is well recognized; however, the optimal timing for adminstering PCSK9 inhibitors remains unclear. Additionally, the lipid-lowering efficacy of evolocumab and alirocumab has not been fully established. This study evaluated the lipid-lowering effects of these two PCSK9 inhibitors. Methods: Patients diagnosed with ACS, including unstable angina, ST-segment elevation myocardial infarction, and non-ST-segment elevation myocardial infarction, who were treated with a PCSK9 inhibitor (evolocumab or alirocumab) during hospitalization for ACS between 2021 and 2023 were retrospectively analyzed. Baseline low-density lipoprotein cholesterol (LDL-C) levels were assessed, and changes in LDL-C levels during the acute and subacute phases after PCSK9 inhibitor administration were compared between the evolocumab and alirocumab groups. Results: Among 80 patients diagnosed with ACS, 36 received evolocumab, while 44 were treated with alirocumab. The mean baseline LDL-C level was 123 mg/dL in the evolocumab group and 128 mg/dL in the alirocumab group (p=0.456). In the subacute phase, the mean follow-up LDL-C levels were 47.05 mg/dL in the evolocumab group and 49.5 mg/dL in the alirocumab group (p=0.585). The mean percentage reduction in LDL-C levels during the subacute phase was 60.41% in the evolocumab group and 58.51% in the alirocumab group (p=0.431). These differences were not statistically significant. Conclusions No significant differences were observed between evolocumab and alirocumab. LDL-C levels exhibited a similar trend, characterized by a rapid decline in the acute phase, followed by a slight rebound in the subacute phase.

Background: The significance of risk modification in patients with acute coronary syndrome (ACS) is well recognized; however, the optimal timing for adminstering PCSK9 inhibitors remains unclear. Additionally, the lipid-lowering efficacy of evolocumab and alirocumab has not been fully established. This study evaluated the lipid-lowering effects of these two PCSK9 inhibitors. Methods: Patients diagnosed with ACS, including unstable angina, ST-segment elevation myocardial infarction, and non-ST-segment elevation myocardial infarction, who were treated with a PCSK9 inhibitor (evolocumab or alirocumab) during hospitalization for ACS between 2021 and 2023 were retrospectively analyzed. Baseline low-density lipoprotein cholesterol (LDL-C) levels were assessed, and changes in LDL-C levels during the acute and subacute phases after PCSK9 inhibitor administration were compared between the evolocumab and alirocumab groups. Results: Among 80 patients diagnosed with ACS, 36 received evolocumab, while 44 were treated with alirocumab. The mean baseline LDL-C level was 123 mg/dL in the evolocumab group and 128 mg/dL in the alirocumab group (p=0.456). In the subacute phase, the mean follow-up LDL-C levels were 47.05 mg/dL in the evolocumab group and 49.5 mg/dL in the alirocumab group (p=0.585). The mean percentage reduction in LDL-C levels during the subacute phase was 60.41% in the evolocumab group and 58.51% in the alirocumab group (p=0.431). These differences were not statistically significant. Conclusions No significant differences were observed between evolocumab and alirocumab. LDL-C levels exhibited a similar trend, characterized by a rapid decline in the acute phase, followed by a slight rebound in the subacute phase.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

Background: The significance of risk modification in patients with acute coronary syndrome (ACS) is well recognized; however, the optimal timing for adminstering PCSK9 inhibitors remains unclear. Additionally, the lipid-lowering efficacy of evolocumab and alirocumab has not been fully established. This study evaluated the lipid-lowering effects of these two PCSK9 inhibitors. Methods: Patients diagnosed with ACS, including unstable angina, ST-segment elevation myocardial infarction, and non-ST-segment elevation myocardial infarction, who were treated with a PCSK9 inhibitor (evolocumab or alirocumab) during hospitalization for ACS between 2021 and 2023 were retrospectively analyzed. Baseline low-density lipoprotein cholesterol (LDL-C) levels were assessed, and changes in LDL-C levels during the acute and subacute phases after PCSK9 inhibitor administration were compared between the evolocumab and alirocumab groups. Results: Among 80 patients diagnosed with ACS, 36 received evolocumab, while 44 were treated with alirocumab. The mean baseline LDL-C level was 123 mg/dL in the evolocumab group and 128 mg/dL in the alirocumab group (p=0.456). In the subacute phase, the mean follow-up LDL-C levels were 47.05 mg/dL in the evolocumab group and 49.5 mg/dL in the alirocumab group (p=0.585). The mean percentage reduction in LDL-C levels during the subacute phase was 60.41% in the evolocumab group and 58.51% in the alirocumab group (p=0.431). These differences were not statistically significant. Conclusions No significant differences were observed between evolocumab and alirocumab. LDL-C levels exhibited a similar trend, characterized by a rapid decline in the acute phase, followed by a slight rebound in the subacute phase.

Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

Rosai-Dorfman disease (RDD) is an uncommon proliferative histiocytic disorder of unknown etiology typically presenting as massive lymphadenopathy, and in some cases, with extranodal involvement. However, serous membranes are rarely involved in extranodal RDDs, and reports regarding pericardial involvement are scarce. Herein, we report a case of extranodal RDD manifesting as diffuse pericardial thickening and effusion in a 79-year-old man with monoclonal gammopathy. The patient complained of dyspnea, hence chest CT and PET scans were performed. They showed irregular thickening of the pericardium with a marked increase in metabolic activity. Pericardial biopsy showed the characteristic S100-positive and CD68-positive histiocytes exhibiting emperipolesis. The disease progressively evolved to bilateral pleural thickening with effusion of the pericardium, and finally led to death even with corticosteroid treatment. Although exceedingly rare, this case demonstrates the importance of RDD in the differential diagnosis of effusion in serous cavities based on imaging findings.