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.

Purpose: Early identification of patients at risk for acute respiratory failure (ARF) could help clinicians devise preventive strategies. Analyzing biosignals with artificial intelligence (AI) can uncover hidden information and variability within time series. We aimed to develop and validate AI models to predict ARF within 72 h after emergency department admission, primarily using highresolution biosignals collected within 4 h of arrival. Materials and Methods: Our AI model, built on convolutional recurrent neural networks, combines biosignal feature extraction and sequence modeling. The model was developed and internally validated with data from 5284 admissions [1085 (20.5%) positive for ARF], and externally validated using data from 144 admissions [7 (4.9%) positive for ARF] from another institution. We defined ARF as the application of advanced respiratory support devices. Results: Our AI model performed well in predicting ARF, achieving area under the receiver operating characteristic curve (AUROC) of 0.840 and 0.743 in internal and external validations, respectively. It outperformed the Modified Early Warning Score (MEWS) and XGBoost models built only with clinical variables. High predictive ability for mortality was observed, with AUROC up to 0.809. A 10% increase in AI prediction scores was associated with 1.44-fold and 1.42-fold increases in ARF risk and mortality risk, respectively, even after adjusting for MEWS and demographic variables. Conclusion Our AI model demonstrates high predictive accuracy and significant associations with clinical outcomes. Our AI model has the potential to promptly aid in triage decisions. Our study shows that using AI to analyze biosignals advances disease detection and prediction.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Purpose: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma.Radiation therapy (RT) has served as the primary treatment option for PMBCL; however, its role has been questioned with the advent of intensified immunochemotherapy. This study aimed to investigate the role of consolidative RT in the primary treatment of PMBCL. Methods: This single-center retrospective study analyzed the survival outcomes of 65 patients newly diagnosed with PMBCL. The patients were divided into three treatment groups: (1) EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), (2) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and (3) R-CHOP with consolidative RT. Results: The objective response and complete remission rates were 86.2% and 63.1%, respectively, with 3-year pro‑ gression-free survival (PFS) and overall survival (OS) rates of 72% and 81%, respectively. All patients in the R-CHOP + RT group achieved an objective response with better PFS) than those who did not receive consolidative RT (p = 0.028), although there was no significant difference in OS (p = 0.102). Consolidative RT benefited patients with an initially bulky disease or insufficient end-of-treatment response. The predictive value of  18 F-fluorodeoxyglucose positronemission tomography-computed tomography (PET-CT) in assessing the treatment response in PMBCL was revali‑ dated, showing that patients who achieved negative end-of-treatment PET-CT had significantly better survival outcomes than others. Conclusions R-CHOP is a useful alternative regimen when intensified chemotherapy is not feasible. Consolidative RT should be considered in cases with an initially bulky disease and insufficient end-of-treatment response.

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: In Korea, the Act on Hospice and Palliative Care and Decisions on Life-Sustaining Treatment (LST) was implemented on February 4, 2018. We aimed to investigate relevant factors and clinical changes associated with LST decisions after law enforcement. Materials and Methods: This single-center retrospective study included patients who completed LST documents using legal forms at Asan Medical Center from February 5, 2018, to June 30, 2020. Results: 5,896 patients completed LST documents, of which 2,704 (45.8%) signed the documents in person, while family members of 3,192 (54%) wrote the documents on behalf of the patients. Comparing first year and following year of implementation of the act, the self-documentation rate increased (43.9% to 47.2%, p=0.014). Moreover, the number of LST decisions made during or after intensive care unit admission decreased (37.8% vs. 35.2%, p=0.045), and the completion rate of LST documents during chemotherapy increased (6.6% vs. 8.9%, p=0.001). In multivariate analysis, age < 65 (odds ratio [OR], 1.724; 95% confidence interval [CI], 1.538 to 1.933; p < 0.001), unmarried status (OR, 1.309; 95% CI, 1.097 to 1.561; p=0.003), palliative care consultation (OR, 1.538; 95% CI, 1.340 to 1.765; p < 0.001), malignancy (OR, 1.864; 95% CI, 1.628 to 2.133; p < 0.001), and changes in timing on the first year versus following year (OR, 1.124; 95% CI, 1.003 to 1.260; p=0.045) were related to a higher self-documentation rate. Conclusion Age < 65 years, unmarried status, malignancy, and referral to a palliative care team were associated with patients making LST decisions themselves. Furthermore, the subject and timing of LST decisions have changed with the LST act.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function. Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test. Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight. Conclusion These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.