Purpose: This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC). Materials and Methods: This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models. Results: Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course. Conclusion Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

The coronavirus disease-2019 (COVID-19) pandemic has significantly impacted adolescent health, highlighting the need for effective health promotion strategies. This qualitative study analyzed adolescent health concerns during the pandemic and explored management strategies through focus group interviews (FGIs).FGIs were conducted on November 23 and 25, 2023, with six secondary school nutrition teachers, six educational supervisors, and six adolescent students. Semi-structured questions were used to explore five key domains: health behaviors, factors contributing to health problems, social support, perceived health beliefs, and health education. The FGI recordings were transcribed, and Braun and Clarke’s (2006) thematic analysis method was applied to classify and categorize the data. To ensure the reliability and validity of the study, all processes were meticulously documented, and member checking and triangulation were conducted. The analysis revealed that adolescents faced reduced physical activity, irregular eating habits, school lunch disruptions, social isolation, worsening obesity, mental health challenges, and decreased engagement in health-promoting behaviors. Nutrition teachers and educational supervisors emphasized the importance of the food environment in schools and policy support, whereas adolescent students. highlighted motivation and accessibility as the key factors for adopting healthy behaviors. Based on these findings, strengthening social support, expanding health education, and establishing a national support system are essential for improving adolescent health. This study has implications for policy and education to address adolescent health challenges during a pandemic and serves as a foundation for future health promotion strategies.

The coronavirus disease-2019 (COVID-19) pandemic has significantly impacted adolescent health, highlighting the need for effective health promotion strategies. This qualitative study analyzed adolescent health concerns during the pandemic and explored management strategies through focus group interviews (FGIs).FGIs were conducted on November 23 and 25, 2023, with six secondary school nutrition teachers, six educational supervisors, and six adolescent students. Semi-structured questions were used to explore five key domains: health behaviors, factors contributing to health problems, social support, perceived health beliefs, and health education. The FGI recordings were transcribed, and Braun and Clarke’s (2006) thematic analysis method was applied to classify and categorize the data. To ensure the reliability and validity of the study, all processes were meticulously documented, and member checking and triangulation were conducted. The analysis revealed that adolescents faced reduced physical activity, irregular eating habits, school lunch disruptions, social isolation, worsening obesity, mental health challenges, and decreased engagement in health-promoting behaviors. Nutrition teachers and educational supervisors emphasized the importance of the food environment in schools and policy support, whereas adolescent students. highlighted motivation and accessibility as the key factors for adopting healthy behaviors. Based on these findings, strengthening social support, expanding health education, and establishing a national support system are essential for improving adolescent health. This study has implications for policy and education to address adolescent health challenges during a pandemic and serves as a foundation for future health promotion strategies.

The coronavirus disease-2019 (COVID-19) pandemic has significantly impacted adolescent health, highlighting the need for effective health promotion strategies. This qualitative study analyzed adolescent health concerns during the pandemic and explored management strategies through focus group interviews (FGIs).FGIs were conducted on November 23 and 25, 2023, with six secondary school nutrition teachers, six educational supervisors, and six adolescent students. Semi-structured questions were used to explore five key domains: health behaviors, factors contributing to health problems, social support, perceived health beliefs, and health education. The FGI recordings were transcribed, and Braun and Clarke’s (2006) thematic analysis method was applied to classify and categorize the data. To ensure the reliability and validity of the study, all processes were meticulously documented, and member checking and triangulation were conducted. The analysis revealed that adolescents faced reduced physical activity, irregular eating habits, school lunch disruptions, social isolation, worsening obesity, mental health challenges, and decreased engagement in health-promoting behaviors. Nutrition teachers and educational supervisors emphasized the importance of the food environment in schools and policy support, whereas adolescent students. highlighted motivation and accessibility as the key factors for adopting healthy behaviors. Based on these findings, strengthening social support, expanding health education, and establishing a national support system are essential for improving adolescent health. This study has implications for policy and education to address adolescent health challenges during a pandemic and serves as a foundation for future health promotion strategies.

Immunonutrition, which uses specific nutrients to modulate the immune response, has emerged as a vital adjunct to perioperative care. Surgery-induced stress triggers immune responses that can lead to complications, such as infections and delayed wound healing. Traditional nutritional support often overlooks the immunological needs of surgical patients. Immunonutrition addresses this oversight by providing key nutrients, such as arginine, omega-3 fatty acids, glutamine, nucleotides, and antioxidants (vitamins C and E) to enhance immune function and support tissue repair. This review examined the efficacy and safety of immunonutrition in surgical settings, guided by the recommendations of the American Society for Parenteral and Enteral Nutrition and the European Society for Clinical Nutrition and Metabolism. Both organizations recommend immunonutrition for high-risk or malnourished patients undergoing major surgery and support its use in reducing complications and improving recovery. The key nutrients in immunonutrition aim to improve immune cell function, reduce inflammation, and enhance wound healing. Clinical studies and meta-analyses have demonstrated that immunonutrition lowers the infection rate, shortens the length of hospital stay, and accelerates recovery. Challenges hindering the clinical application of immunonutrition include cost, logistics, and a lack of standardized and personalized protocols. Future studies should focus on biomarker-driven approaches, pharmacogenomics, and innovative nutrient formulations. Addressing these issues will help to integrate immunonutrition into clinical practice, ultimately improving surgical outcomes and patient recovery.

Background: Lung dysfunction and high apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio are both recognized risk factors for cardiovascular disease. However, few studies have examined the association between the apoB/ApoA-I ratio and lung function. Therefore, we investigated whether this ratio is associated with decreased lung function in a large healthy cohort. Methods: We performed a cohort study on 68,418 healthy Koreans (34,797 males, mean age:38.1 years) who underwent a health examination in 2019. ApoB/apoA-I ratio was categorized into quartiles. Spirometric values at the fifth percentile in our population were considered the lower limit of normal (LLN), which was used to define lung function impairment. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs), using the lowest quartile as the reference, were estimated to determine lung function impairment. Results: Mean apoB/apoA-I ratio was 0.67 ± 0.21. Subjects with the highest quartile of this ratio had the lowest predicted forced expiratory volume in one second (FEV1 %) and forced vital capacity (FVC%) after controlling for covariates (P < 0.001). However, FEV1 /FVC ratio was not significantly different among the four quartiles (P = 0.059). Compared with the lowest quartile (Q1, reference), the aORs (95% CI) for FEV1 % < LLN across increasing quartiles (from Q2 to Q4) were 1.216 (1.094–1.351), 1.293 (1.156–1.448), and 1.481 (1.311– 1.672) (P for trend < 0.001), respectively. Similarly, the aORs for FVC% < LLN compared with the reference were 1.212 (1.090–1.348), 1.283 (1.147–1.436), and 1.502 (1.331–1.695) with increasing quartiles (P for trend < 0.001). However, the aORs for FEV1 /FVC < LLN were not significantly different among groups (P for trend = 0.273). Conclusion High apoB/apoA-I ratio was associated with decreased lung function. However, longitudinal follow-up studies are required to validate our findings.

Purpose: Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines. Materials and Methods: We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing. Results: The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group. Conclusion We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy.

Background and Objectives: Spermatogonial stem cells (SSCs) are the most primitive cells in spermatogenesis and are the only adult stem cells capable of passing on the genome of a given species to the next generation. SSCs are the only adult stem cells known to exhibit high Oct4 expression and can be induced to self-reprogram into pluripotent cells depending on culture conditions. Epigenetic modulation is well known to be involved in the induction of pluripotency of somatic cells. However, epigenetic modulation in self-reprogramming of SSCs into pluripotent cells has not been studied. Methods: and Results: In this study, we examined the involvement of epigenetic modulation by assessing whether selfreprogramming of SSCs is enhanced by treatment with epigenetic modulators. We found that second-generation selective class I HDAC inhibitors increased SSC reprogramming efficiency, whereas non-selective HDAC inhibitors had no effect. Conclusions We showed that pluripotent stem cells derived from adult SSCs by treatment with small molecules with epigenetic modulator functions exhibit pluripotency in vitro and in vivo. Our results suggest that the mechanism of SSC reprogramming by epigenetic modulator can be used for important applications in epigenetic reprogramming research.

Background: Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology. Methods: We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured. Results: There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336). Conclusions Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.