Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Background: Malaria elimination strategies in the Republic of Korea (ROK) have decreased malaria incidence but face challenges due to delayed case detection and response. To improve this, machine learning models for predicting malaria, focusing on high-risk areas, have been developed. Methods: The study targeted the northern region of ROK, near the demilitarized zone, using a 1-km grid to identify areas for prediction. Grid cells without residential buildings were excluded, leaving 8,425 cells. The prediction was based on whether at least one malaria case was reported in each grid cell per month, using spatial data of patient locations. Four algorithms were used: gradient boosted (GBM), generalized linear (GLM), extreme gradient boosted (XGB), and ensemble models, incorporating environmental, sociodemographic, and meteorological data as predictors. The models were trained with data from May to October (2019–2021) and tested with data from May to October 2022. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Results: The AUROC of the prediction models performed excellently (GBM = 0.9243, GLM = 0.9060, XGB = 0.9180, and ensemble model = 0.9301). Previous malaria risk, population size, and meteorological factors influenced the model most in GBM and XGB. Conclusion Machine-learning models with properly preprocessed malaria case data can provide reliable predictions. Additional predictors, such as mosquito density, should be included in future studies to improve the performance of models.

Codonopsis lanceolata, which is predominantly found in Korea and East Asia, has attracted considerable scientific attention due to its long-standing use in traditional medicine. However, despite both its roots and stems being utilized as functional food and medicinal resources, there has been limited phytochemical investigation into its aerial parts. Therefore, the aim of this study is to isolate compounds present in the aerial parts of C. lanceolata. Through repeated chromatography, two alkaloids (1 and 2), seven flavones (3-9), and three isoflavones (10-12) and one type of phenylpropanoid (13) and polyacetylene (14) were isolated from a 70% ethanol extract of C. lanceolata. The structure of each compound was determined through the analysis of spectroscopic data ( 1 H and 13 C NMR), and by comparing them with previous research results. Among the isolates, the presence of methyl 2-formyl-5-(methoxymethyl)-1H-pyrrole-1-butanoate (1), chrysoeriol 5-O-β-D-glucopyranoside (3), apigenin-5-O-β-D-glucopyranoside (5), and 3′-O-methylorobol 7-O-β-D-glucopyranoside (12) were reported for the first time in plants belonging to the Campanula family in this study. In addition, the current study marked the isolation of luteolin 4′-O-β-D-glucopyranoside (4) from C. lanceolata for the first time.

Objective: The economic hardship brought by the coronavirus disease-2019 (COVID-2019) pandemic has caused mental health problems among people of different socioeconomic status (SES). As social support helps to buffer these problems, we investigated the association between job loss related to COVID-19 and depression, anxiety, and suicidal thoughts; the differences in the effects according to SES; and the mediating effects of social support. Methods: The effects of COVID-19-related job loss on depression, anxiety, and suicidal thoughts among 1,364 people were investigated through semi-structured and self-administered questionnaires: Patient Health Questionnaire–9, General Anxiety Disorder–7, and the Functional Social Support Questionnaire. Logistic regression and subgroup analyses were performed to assess the association between job loss and mental health status, and the moderating effects of income and educational levels. Moreover, the mediating effects of perceived social support on the association between job loss and depression, anxiety, and suicidal thoughts were analyzed. Results: COVID-19-related job loss increased the risk of depression and suicidal thoughts. Adults with lower income and education level were at higher risk of depression, anxiety, and suicidal thoughts; perceived social support level had significant mediating effects on the association between job loss and depression/anxiety; and income level had significant moderating effects on this mediating pathway. Conclusion COVID-19-related job loss were likely to be significantly associated with negative mental health outcomes, especially among individuals with low income and education levels. As social support had buffering effects on such outcomes, related government policies in cooperation with the governance of communities and stakeholders must be prepared.

Background: and PurposeThe prevalence of dementia is increasing in South Korea. Multidomain interventions may be useful for preventing dementia. Such programs need to be disseminated to elderly Koreans throughout the country. We have developed programs of the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), which consists of a facility-based multidomain intervention (FMI) program and a home-based multidomain intervention (HMI) program suitable for elderly Koreans. We aim to determine the feasibility of the SUPERBRAIN programs before a large-scale randomized controlled trial. Methods: We will recruit 150 participants among those without dementia aged 60–79 years with at least 1 modifiable dementia risk factor. They will be randomly assigned in a 1:1:1 ratio to the FMI, HMI, and the waiting-list control arm. The 6-month multidomain intervention consists of management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The primary outcomes are adherence and retention rates and changes in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to the study end. The main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire. There will be an exploratory evaluation of neurotrophic, neurodegeneration, and neuroinflammation factors, microbiome, telomere length, electroencephalography, and neuroimaging measures. Conclusions The results obtained will provide information on the applicability of these multidomain intervention programs to at-risk elderly people.

OBJECTIVE: To investigate whether a computer-aided diagnosis (CAD) system based on a deep learning framework (deep learning-based CAD) improves the diagnostic performance of radiologists in differentiating between malignant and benign masses on breast ultrasound (US). MATERIALS AND METHODS: B-mode US images were prospectively obtained for 253 breast masses (173 benign, 80 malignant) in 226 consecutive patients. Breast mass US findings were retrospectively analyzed by deep learning-based CAD and four radiologists. In predicting malignancy, the CAD results were dichotomized (possibly benign vs. possibly malignant). The radiologists independently assessed Breast Imaging Reporting and Data System final assessments for two datasets (US images alone or with CAD). For each dataset, the radiologists' final assessments were classified as positive (category 4a or higher) and negative (category 3 or lower). The diagnostic performances of the radiologists for the two datasets (US alone vs. US with CAD) were compared. RESULTS: When the CAD results were added to the US images, the radiologists showed significant improvement in specificity (range of all radiologists for US alone vs. US with CAD: 72.8–92.5% vs. 82.1–93.1%; p < 0.001), accuracy (77.9–88.9% vs. 86.2–90.9%; p = 0.038), and positive predictive value (PPV) (60.2–83.3% vs. 70.4–85.2%; p = 0.001). However, there were no significant changes in sensitivity (81.3–88.8% vs. 86.3–95.0%; p = 0.120) and negative predictive value (91.4–93.5% vs. 92.9–97.3%; p = 0.259). CONCLUSION: Deep learning-based CAD could improve radiologists' diagnostic performance by increasing their specificity, accuracy, and PPV in differentiating between malignant and benign masses on breast US.
Breast ; Dataset ; Diagnosis ; Humans ; Information Systems ; Learning ; Prospective Studies ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography ; Ultrasonography, Mammary

BACKGROUND AND PURPOSE: Several studies have validated the clinical efficacy of computerized cognitive training applications. However, few studies have investigated the neural substrates of these training applications using simultaneous multimodal neuroimaging modalities. We aimed to determine the effectiveness of computerized cognitive training and corresponding neural substrates through a multimodal approach. METHODS: Ten patients with mild cognitive impairment (MCI), six patients with subjective memory impairment (SMI), and 10 normal controls received custom-developed computerized cognitive training in the memory clinic of a university hospital. All of the participants completed 24 sessions of computerized cognitive training, each lasting 40 minutes and performed twice weekly. They were assessed using neuropsychological tests (both computerized and conventional), electroencephalography, fluorodeoxyglucose positron-emission tomography (FDG-PET), volumetric magnetic resonance imaging (MRI), and diffusion-tensor imaging (DTI) at pre- and posttraining. RESULTS: The patients with MCI exhibited significant improvements in the trail-making test–black & white-B, and memory domain of the computerized cognitive assessment. Subjects with normal cognition exhibited significant improvements in scores in the language and attention-/psychomotor-speed domains. There were no significant changes in subjects with SMI. In the pre- and posttraining evaluations of the MCI group, FDG-PET showed focal activation in the left anterior insula and anterior cingulate after training. Volumetric MRI showed a focal increase in the cortical thickness in the rostral anterior cingulate. DTI revealed increased fractional anisotropy in several regions, including the anterior cingulate. CONCLUSIONS: The anterior cingulate and anterior insula, which are parts of the salience network, may be substrates for the improvements in cognitive function induced by computerized cognitive training.
Anisotropy ; Cognition ; Electroencephalography ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Memory ; Mild Cognitive Impairment ; Neuroimaging ; Neuropsychological Tests ; Positron-Emission Tomography ; Treatment Outcome

PURPOSE: This study aimed to identify stress levels due to end-of-life care, coping strategies, and psychological well-being among nurses in neonatal intensive care unit, and to investigate the effect of stress levels and coping strategies on their well-being. METHODS: A total of 128 nurses in the neonatal intensive care units of general hospitals in B city participated. The data were collected using a self-report questionnaire. The collected data were analyzed using descriptive statistics, the t-test, ANOVA, the Pearson correlation coefficient, and hierarchical regression with SPSS version 22.0. RESULTS: The coping strategy that nurses most often used was seeking social support. The factors affecting the well-being of the participants were wishful thinking, problem-focused coping and seeking social support, in order. Those 3 variables explained 21 % of the total variance in psychological well-being. Problem-focused coping and seeking social support were positively associated with psychological well-being, while wishful thinking showed a negative association. CONCLUSION: In order to improve the psychological well-being of nurses in neonatal intensive care units, it is necessary to provide nurses with a program to build a social support system and to improve their problem-based coping skills.
Adaptation, Psychological ; Hospitals, General ; Infant, Newborn ; Intensive Care Units, Neonatal* ; Intensive Care, Neonatal* ; Stress, Psychological ; Terminal Care ; Thinking

BACKGROUND: As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. METHODS: Thirty observers from thirty different institutions reviewed Ki-67-stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis. RESULTS: For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. CONCLUSIONS: Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.
Breast Neoplasms* ; Breast* ; Observer Variation* ; Online Systems

Since IgG4-related pancreatitis was first reported in 2001, IgG4-related disease has been identified in other organs such as salivary gland, gallbladder, thyroid, retroperitoneum and kidney; but lung invasion is rare. A 63-year-old man presented with hemoptysis at the pulmonary clinic and chest computed tomography revealed about 4.1 cm irregular shaped mass with spiculated margin at the left upper lobe. Despite no elevation of serum IgG4 level, he was finally diagnosed as IgG4-related lung disease by transthoracic needle biopsy. After treatment with oral glucocorticoids, hemoptysis disappeared and the size of lung mass was decreased.
Biopsy, Needle ; Gallbladder ; Glucocorticoids ; Hemoptysis ; Humans ; Immunoglobulin G* ; Immunoglobulins ; Kidney ; Lung Diseases* ; Lung* ; Middle Aged ; Pancreatitis ; Salivary Glands ; Thorax ; Thyroid Gland