This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Purpose: Although human epidermal growth factor receptor 2 (HER2) positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy. Materials and Methods: The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed. Results: The analysis included 799 female patients. The median age was 51 years (range, 23 to 79 years), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n=238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% confidence interval [CI], 114.0 to 127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1 to 93.3), 97.5% (95% CI, 96.4 to 98.7), and 98.8% (95% CI, 98.0 to 99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease. Conclusion A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.

Spinal melanocytoma (SMC) is a rare, slow-growing tumor arising from melanocytes in the spinal cord. We report a patient with a cervical intra- and extradural spinal tumor causing progressive weakness and numbness. On magnetic resonance imaging (MRI), the lesion showed intense homogeneous enhancement, similar to that seen in common neurogenic spinal tumors. After complete resection, pathological examination confirmed melanocytoma. A review of previously reported cases identified 26 reports of this tumor in the cervical spine, most of which were treated with complete surgical resection. Gross total resection is the preferred treatment, although radiation therapy may be considered when residual tumor remains. We report a 25-year-old male patient who presented with progressive weakness and numbness in both the upper and lower extremities for 3 months. MRI showed homogeneous enhancement. The mass compressed the spinal cord at C6–7 and extended through the neural foramen. Based on the MRI findings, spinal schwannoma was suspected preoperatively. Surgical resection was performed with laminectomy, durotomy, and right facetectomy. A dark-colored mass with well-demarcated margins was exposed and removed. Postoperative MRI confirmed complete removal of the mass. The patient recovered well, and his preoperative myelopathic symptoms gradually improved. SMC is a rare benign tumor that may be mistaken for schwannoma. The treatment of choice is gross total resection.

Background/Aims: Cardiovascular disease is the leading cause of death worldwide. This study aimed to investigate the recent nationwide trends in major dietary risk factors for dyslipidemia and atherosclerosis. Methods: We estimated age-standardized mean intakes of fresh fruits, fresh vegetables, whole grains, dietary fiber, and sugar-sweetened beverages (SSBs); and mean percentage of energy intake from protein, total fat, saturated fat, and polyunsaturated fat using nationally representative samples from the Korean National Health Examination and Nutrition Survey 2013–2022. To assess overall diet quality, we calculated mean Korean Healthy Eating Index (KHEI) (range 0–100, higher scores indicating greater diet quality). Results: In 2013–2022, there were overall decreasing trends in age-standardized mean KHEI score and intakes of fresh fruits and vegetables, whole grains, and dietary fiber; and overall increasing trends in mean intakes of SSBs, protein, and dietary fat among both male and female. The KHEI score increased in older adults aged ≥ 60 years, whereas it decreased among younger adults. Throughout the study period, younger adults tended to have lower intakes of fresh fruits, fresh vegetables, and whole grains; higher intakes of SSBs, protein, and dietary fat; and lower KHEI score. The mean KHEI score was lower in male (vs. female) and lower (vs. higher) income groups. Conclusions Our data suggest that, from 2013 to 2022, there was a trend toward an unhealthy diet in Korean adults. Our findings also suggest dietary inequalities among age, sex, and income groups, suggesting the need for more intense interventions targeting the vulnerable populations.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

This study aimed to derive insights into professional self-concept, teamwork, and job satisfaction among emergency department (ED) nurses and to prepare basic data for improving job satisfaction among ED nurses. Methods: The study was conducted between October 2023 and April 2024 at two certified tertiary hospitals and one general hospital in Gyeonggi-do, Korea, among 124 ED nurses. Data were analyzed using SPSS version 26.0, and the analysis included descriptive statistics, the t-test, Pearson correlation, and multiple regression. Results: The factors affecting job satisfaction in ED nurses were professional self-concept (β = .66, p < .001), teamwork (β = .17, p = .003), and ED work satisfaction (β = .17, p = .003), and the overall explanatory power of the model was 67.7%. Conclusion: This study makes a significant contribution by demonstrating that professional self-concept and teamwork can increase job satisfaction in ED nurses. Therefore, as a strategy to increase job satisfaction through improving ED nurses’ professional self-concept and teamwork, effort should be made to apply team simulation programs that provide education and self-improvement opportunities for frequent diseases and situations encountered in the ED, and to communicate effectively about patient treatment strategies.

This study aimed to derive insights into professional self-concept, teamwork, and job satisfaction among emergency department (ED) nurses and to prepare basic data for improving job satisfaction among ED nurses. Methods: The study was conducted between October 2023 and April 2024 at two certified tertiary hospitals and one general hospital in Gyeonggi-do, Korea, among 124 ED nurses. Data were analyzed using SPSS version 26.0, and the analysis included descriptive statistics, the t-test, Pearson correlation, and multiple regression. Results: The factors affecting job satisfaction in ED nurses were professional self-concept (β = .66, p < .001), teamwork (β = .17, p = .003), and ED work satisfaction (β = .17, p = .003), and the overall explanatory power of the model was 67.7%. Conclusion: This study makes a significant contribution by demonstrating that professional self-concept and teamwork can increase job satisfaction in ED nurses. Therefore, as a strategy to increase job satisfaction through improving ED nurses’ professional self-concept and teamwork, effort should be made to apply team simulation programs that provide education and self-improvement opportunities for frequent diseases and situations encountered in the ED, and to communicate effectively about patient treatment strategies.