Damage-Free Plasma Source for Atomic-Scale Processing.

As atomic-scale etching and deposition processes become necessary for manufacturing logic and memory devices at the sub-5 nm node, the limitations of conventional plasma technology are becoming evident. For atomic-scale processes, precise critical dimension control at the sub-1 nm scale without plasma-induced damage and high selectivity between layers are required. In this paper, a plasma with very low electron temperature is applied for damage-free processing on the atomic scale. In plasmas with an ultralow electron temperature (ULET, Te < 0.5 eV), ion energies are very low, and the ion energy distribution is narrow. The absence of physical damage in ULET plasma is verified by exposing 2D structural material. In the ULET plasma, charging damage and radiation damage are also expected to be suppressed due to the extremely low Te. This ULET plasma source overcomes the limitations of conventional plasma sources and provides insights to achieve damage-free atomic-scale processes.

Long-term exposure to air pollution and precocious puberty in South Korea.

BACKGROUND AND AIM: The increasing prevalence of precocious puberty (PP) has emerged as a significant medical and social problem worldwide. However, research on the relationship between long-term air pollution exposure and PP has been relatively limited. We thus investigated the association between long-term air pollution exposure and the onset of PP in South Korea. METHODS: We investigated a retrospective cohort using the Korea National Health Insurance Database. Six-year-old children born from 2007 to 2009 were examined (2013-2015). We included boys ≤10 years and girls aged ≤9 years who visited hospitals for early pubertal development, were diagnosed with PP per the ICD-10 (E228, E301, and E309), and received gonadotropin-releasing hormone agonist treatment. We analyzed data for boys up until 10 years old (60-month follow-up) and for girls up to 9 years old (48-month follow-up). We assessed the association between long-term air pollution exposure and the onset of PP using a Cox proportional hazard model. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) per 1 µg/m3 increase in fine particulate matter (PM2.5) and particulate matter (PM10) and per 1 ppb increase in sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3). RESULTS: This study included 1,205,784 children aged six years old between 2013 and 2015. A positive association was found between the 48-month moving average PM2.5 (HR: 1.019; 95% CI: 1.012, 1.027), PM10 (HR: 1.009; 95% CI: 1.006, 1.013), SO2 (HR: 1.037; 95% CI: 1.018, 1.055), and O3 (HR: 1.006; 95% CI: 1.001, 1.010) exposure and PP in girls but not boys. CONCLUSIONS: This study provides valuable insights into the harmful effects of air pollution during childhood and adolescence, emphasizing that air pollution is a risk factor that should be managed and reduced.

Clinical characteristics and prognosis of postpartum breast cancer.

PURPOSE: Postpartum breast cancer (PPBC) is a not well-established subset of breast cancer, and only few studies address its poorer prognosis. However, previous studies show that PPBC is associated with worse outcome with higher rates of metastasis than in young women's breast cancer (YWBC). We aimed to analyze the clinical characteristics and prognosis of PPBC based on the diagnosis period of PPBC. METHODS: We retrospectively reviewed 208,780 patients with breast cancer from the Korean Breast Cancer Society registry (KBCSR) database between January 2000 and December 2014. We included premenopausal women aged 20-50 years who underwent breast cancer surgery. The patients were classified by 5-year intervals according to the diagnosis period of breast cancer, from the first birth to the breast cancer diagnosis. RESULTS: Compared with patients in the other groups, patients diagnosed within postpartum 5 years (PPBC < 5 years) group were younger, had a more advanced stage, had lower estrogen receptor (ER) and progesterone receptor (PR) expression, and had a higher human epidermal growth factor receptor 2 (HER2) positive rate. Further, PPBC < 5 years group had a worse survival rate than the nulliparous and other groups (5-year cumulative survival: PPBC < 5 years group, 89%; nulliparous group, 97.3%; 5 ≤ PPBC < 10 years group, 93%). In the multivariate analysis, the PPBC < 5 years group was associated with a worse survival rate (hazard ratio 1.55, 95% confidence interval [CI] 1.148-2.094, p 0.004) after adjustment for age at diagnosis, breast cancer stage, ER and HER2 status, Ki-67 level, and chemotherapy. CONCLUSION: Our findings indicated that patients diagnosed with breast cancer within the first 5 years after delivery had aggressive characteristics and a poor survival rate. It is important to elucidate the pathophysiology of PPBC and establish novel therapeutic strategies to improve the survival rate.

Robot-assisted Nipple-sparing Mastectomy With Immediate Breast Reconstruction: An initial Experience of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG).

OBJECTIVE: The aim of this study was to present the results of early experience of robot-assisted nipple sparing mastectomy (RANSM). BACKGROUND: RANSM improves cosmetic outcomes over conventional nipple-sparing mastectomy. However, data on the feasibility and safety of the RANSM are limited. METHODS: Patients who underwent RANSM with immediate breast reconstruction as part of the Korea Robot-endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) from November 2016 to January 2020 were enrolled. clinicopathologic characteristics, perioperative complications, and operation time were collected. RESULTS: Overall, 73 women underwent 82 RANSM procedures conducted by 11 breast surgeons at 8 institutions. The median patient age was 45.5 years old (20-66 years), and 52 (63.4%) patients were premenopausal. Invasive breast cancer was noted in 55 cases (40 cases were stage i, 11 cases were stage ii, and 4 cases were stage iii, respectively) and ductal carcinoma in-situ was recorded in 20 cases. Of those, 3 patients with BRCA1/2 mutation carriers underwent contralateral risk-reducing RANSM. The median length of hospitalization was 12.0 days (5.0-24.0 days). The incision location was the mid-axillary line and the median incision length was 50.0 mm (30.0-60.0 mm). Median total operation time, median total mastectomy time, and median reconstruction time was 307.0 minutes (163.0-796.0 minutes), 189.5 minutes (97.5-325.0 minutes), and 119.5 minutes (45.0-689.0 minutes). Only 2 cases (2.5%) required reoperation. Nipple ischemia was found in 9 cases (10.9%) but only 1 case (1.2%) required nipple excision given that 8 cases (9.7%) resolved spontaneously. Skin ischemia was observed in 5 cases (6.1%) and only 2 (2.4%) cases needed skin excision whereas 3 cases (3.6%) resolved spontaneously. There was no conversion to open surgery orcases of mortality. The mean time for mastectomy among surgeons who performed more than 10 cases was 182.3 minutes (± 53.7, minutes) and 195.4 minutes (± 50.4, minutes). CONCLUSION: This was the first report of RANSM conducted in the KoREa-BSG. RANSM is technically feasible and acceptable with a short learning curve. Further prospective research to evaluate surgical and oncologic outcomes is needed.

Risk factors for level V metastasis in patients with N1b papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence has increased. Lateral lymph node metastasis (LLNM) implies a worse prognosis than central lymph node metastasis, with a higher recurrence rate and decreased disease-free survival. The 2015 American Thyroid Association guidelines recommend compartmental node dissection in patients with LLNM to reduce the risk of recurrence and mortality. The purpose of this study was to identify the risk factors for level V lymph node (LN) metastasis in patients with N1b papillary thyroid cancer (PTC). METHODS: A total of 110 consecutive patients who underwent total thyroidectomy with lateral neck dissection for PTC between April 2016 and April 2022 were retrospectively enrolled. Based on level V metastasis, 94 patients were divided into two groups, and their clinicopathological characteristics were compared. Univariable analysis were used to assess the factors associated with level V metastasis. Spearman correlation analysis were used to assess the correlation between tumors and LN. The receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value for the number of metastatic LNs at each level for level V metastasis. RESULTS: The number of metastatic LNs and lymph node ratio (LNR) in level II were significantly associated with level V metastasis (P = 0.011 and 0.001, respectively). The number of metastatic LNs in level II and those in the total number of levels correlated with the number of metastatic LNs in level V (rho = 0.331, 0.325, and P = 0.001, 0.001, respectively). The cutoff value for the number of metastatic LNs in level II was defined as 2.5 (area under the curve = 0.757, sensitivity = 50%, specificity = 82.5%, 95% confidence interval [CI] 0.626-0.889, P = 0.002). Simultaneous 3-level metastasis (level II, III, and IV) and 3-level with ≥ 2.5 metastatic LNs in level II were significantly associated with level V metastasis (P = 0.003 and 0.002). CONCLUSIONS: The number of metastatic LNs and LNR in level II, simultaneous 3-level metastasis (level II, III, and IV), and 3-level with ≥ 2.5 metastatic LNs in level II were significantly associated with level V metastasis. (P = 0.011, 0.001, 0.003, and 0.002, respectively). In the future, larger-scale multi-institutional studies were needed to find out predictors for level V metastasis.

Clinical impact of radioactive iodine dose selection based on the number of metastatic lymph nodes in patients with papillary thyroid carcinoma: A multicenter retrospective cohort study.

OBJECTIVE: The aim of this study is to investigate whether the number of metastatic lymph nodes (LNs) could be used as a basis in the radioactive iodine (RAI) dose selection for patients with papillary thyroid carcinoma (PTC). PATIENTS: A total of 595 patients with PTC who received first RAI therapy after total or near-total thyroidectomy and had no evidence of disease in treatment response assessment were retrospectively enroled from five hospitals. The patients were classified into two subgroups based on the number of metastatic LNs (>5). The multivariate Cox-proportional hazard model was performed to identify the significant factors for recurrence prediction in each group as well as all enroled patients. RESULTS: Overall, 22 (3.7%) out of 595 patients had the recurrent disease during the follow-up period. The number of metastatic LNs (>5) was only a significant factor for recurrence prediction in all enroled patients (odds ratio: 7.834, p < .001). In the subgroup with ≤5 metastatic LNs, the presence of extrathyroidal extension was only associated with recurrence (odds ratio: 7.333, p = .024) in multivariate analysis. RAI dose was significantly associated with recurrence rate in which the patients with high-dose RAI (3.7 GBq or higher) had less incidence of recurrence than those with low-dose RAI (1.11 GBq) in the subgroup with more than five metastatic LNs (odds ratio: 6.533, p = .026). CONCLUSIONS: High-dose RAI (≥3.7 GBq) therapy significantly lowered the recurrence rate in patients with more than five metastatic LNs. Therefore, RAI dose should be determined based on the number of metastatic LNs as well as conventional risk factors.

Response to neoadjuvant chemotherapy based on pathologic complete response in very young patients with ER-positive breast cancer: a large, multicenter, observational study.

BACKGROUND: In estrogen receptor (ER)-positive breast cancer (BC), young age is associated with poor prognosis. While very young patients respond better to chemotherapy, chemotherapy is less effective in ER-positive tumors than in ER-negative tumors. The authors tried to evaluate chemotherapy response of very young patients with ER-positive BC by pathologic complete response (pCR) after neoadjuvant chemotherapy excluding the effect of endocrine treatment to the extent possible. METHODS: We collected individual patient data from 1992 to 2013 from the Korean Breast Cancer Society (KBCS). Total 1048 ER-positive and 797 ER-negative patients aged < 50 years who had been treated with neoadjuvant chemotherapy were included for analysis. We compared pCR rate between patients aged < 35 years with ER-positive tumors and the other groups. RESULTS: The proportion of patients aged < 35 years was 14.0% of patients with ER-positive BC in this cohort of under 50 years old, and 16.8% of patients with ER-negative BC in this cohort of under 50 years old. Although most characteristics of tumors according to age were comparable, tumors with high Ki-67 expression were more common in patients aged < 35 years than in patients aged 35-49 years in both ER-positive and -negative group (P = 0.001). Breast conservation rates were not significantly different according to age (44.2% vs. 46.8% in ER-positive group, 55.2% vs. 48.0% in ER-negative group). pCR rate was not different according to age in ER-positive group (P = 0.71) but significantly better in patients aged < 35 years in ER-negative group (P = 0.009). After adjusting for confounding variables, young patients maintained the higher probability of pCR than older patients in ER-negative tumors. However, pCR rate did not differ according to age in ER-positive tumors. In multivariate analysis, young age (< 35 years) was correlated with poor overall survival (P = 0.003, HR = 1.98) and there was only one event in a few patients achieved pCR in ER-positive group. CONCLUSIONS: Chemotherapy response based on pCR was not better in young patients (< 35 years) with ER-positive BC than in older premenopausal patients with non-metastatic ER-positive BC. Young age cannot be a predictive factor of response to neoadjuvant chemotherapy in ER-positive BC. Different biological characteristics such as high proliferative index should be considered. TRIAL REGISTRATION: Retrospectively registered.

Analysis of the Molecular Signature of Breast Implant-Associated Anaplastic Large Cell Lymphoma in an Asian Patient.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)-a new category of anaplastic large cell lymphoma associated with textured breast implants-has a distinct variation in incidence and is especially rare in Asia. We report the first case of BIA-ALCL in Korea and present its histological and genetic characteristics. A 44-year-old female patient presented with a typical clinical course and symptoms, including breast augmentation with textured breast implants, late-onset peri-implant effusion, and CD30+ALK- histology, followed by bilateral implant removal and total capsulectomy. For histological analysis, we performed immunohistochemistry of the bilateral breast capsules. For transcriptome analysis, we identified highly upregulated gene sets employing RNA-sequencing and characterized the lymphoma immune cell components. In the lymphoma-associated capsule, CD30+ cells infiltrated not only the lymphoma lesion but also the peritumoral lesion. The morphologies of the myofibroblasts and vessels in the peritumoral lesion were similar to those in the tumoral lesion. We observed strong activation of the JAK/STAT3 pathway and expression of programmed death ligand-1 in the lymphoma. Unlike the molecular profiles of BIA-ALCL samples from Caucasian patients-all of which contained activated CD4+ T cells-the Asian patient's profile was characterized by more abundant CD8+ T cells. This study contributes to a better understanding of the pathogenesis and molecular mechanisms of BIA-ALCL in Asian patients that will ultimately facilitate the development of clinical therapies.

Proteomic Analysis of Hippocampus in a Mouse Model of Depression Reveals Neuroprotective Function of Ubiquitin C-terminal Hydrolase L1 (UCH-L1) via Stress-induced Cysteine Oxidative Modifications.

Chronic physical restraint stress increases oxidative stress in the brain, and dysregulation of oxidative stress can be one of the causes of major depressive disorder. To understand the underlying mechanisms, we undertook a systematic proteomic analysis of hippocampus in a chronic restraint stress mouse model of depression. Combining two-dimensional gel electrophoresis (2D-PAGE) for protein separation with nanoUPLC-ESI-q-TOF tandem mass spectrometry, we identified sixty-three protein spots that changed in the hippocampus of mice subjected to chronic restraint stress. We identified and classified the proteins that changed after chronic stress, into three groups respectively functioning in neural plasticity, metabolic processes and protein aggregation. Of these, 5 proteins including ubiquitin C-terminal hydrolase L1 (UCH-L1), dihydropyrimidinase-related protein 2 (DPYL2), haloacid dehalogenase-like hydrolase domain-containing protein 2 (HDHD2), actin-related protein 2/3 complex subunit 5 (ARPC5) and peroxiredoxin-2 (PRDX2), showed pI shifts attributable to post-translational modifications. Further analysis indicated that UCH-L1 underwent differential oxidations of 2 cysteine residues following chronic stress. We investigated whether the oxidized form of UCH-L1 plays a role in stressed hippocampus, by comparing the effects of UCH-L1 and its Cys mutants on hippocampal cell line HT-22 in response to oxidative stress. This study demonstrated that UCH-L1 wild-type and cysteine to aspartic acid mutants, but not its cysteine to serine mutants, afforded neuroprotective effects against oxidative stress; there were no discernible differences between wild-type UCH-L1 and its mutants in the absence of oxidative stress. These findings suggest that cysteine oxidative modifications of UCH-L1 in the hippocampus play key roles in neuroprotection against oxidative stress caused in major depressive disorder.

Chronologically changing patterns in the survival of korean patients with breast cancer and related clinical factors: a nationwide registry-based study.

PURPOSE: Advances in breast cancer treatment have contributed to marked improvements in patient outcomes over the past three decades. This study aims to chronologically evaluate the survival of patients with breast cancer and investigate the observed changes over time. METHODS: Statistics from the Korean National Cancer Registry, based on all 60,571 patients with invasive breast cancer during the 21 year period, were analyzed. We divided the study interval into four periods (P1: 1988-1992, P2: 1993-1997, P3: 1998-2002, P4: 2003-2008). RESULTS: The patients treated during P4 showed significantly better 5-year overall survival (OS) than did those treated during P1 (5Y OS; P1 = 79.0 vs. P4 = 92.2, p < 0.001). In the multivariate analyses, younger age, mastectomy, high stage, high tumor grade, lymphovascular invasion, and hormone receptor negativity were poor prognostic factors. The multivariate analysis demonstrated that diagnosis periods significantly and independently associated with OS in the overall group of patients. In our analysis of age-period-interaction models, the hazard ratio (HR) for death for patients who were under 35 years of age, compared to those who were older, tended to decrease over time (HR of age < 35 vs. 35 ~ 50; P1 = 0.739, p = 0.007; P2 = 0.744, p < 0.001; P3 = 0.886, p = 0.041; P4 = 0.983, p = 0.813). The survival rate of patients who underwent breast conserving surgery (BCS) has recently gotten better than that of mastectomy (HR of mastectomy vs. BCS; P1 = 0.957, p = 0.790; P2 = 0.542, p < 0.001; P3 = 0.543, p < 0.001; P4 = 0.425, p < 0.001). CONCLUSIONS: The clinical factors related to the changes in breast cancer survival have improved and increased patient OS over the past 20 years in Korea. In addition, we provided new insights into the effects of age and surgery methods on prognosis in each period.

Interleukin-13 receptor alpha 2 expression in tumor cells is associated with reduced disease-free survival in patients with luminal subtype invasive breast cancer.

Interleukin-13 receptor alpha 2 is one of the subunits of transmembrane receptor for interleukin-13. The aim of this study was to investigate the prognostic value of interleukin-13 receptor alpha 2 expression in invasive breast cancer. Interleukin-13 receptor alpha 2 expressions were assessed by immunohistochemistry in tissue microarrays of 1283 invasive breast cancer samples, and associations between these expressions and clinicopathological variables and clinical outcomes were investigated. Interleukin-13 receptor alpha 2 expression was observed in 138 (10.8%) samples, and found to be associated with positive estrogen receptor (p < 0.001) and progesterone receptor (p < 0.001) and with the luminal subtype (p < 0.001). No significant association was found between interleukin-13 receptor alpha 2 expression and other clinicopathological variables including age, tumor size, lymph node metastasis, histologic types, histologic grade, HER2 status, Ki-67 labeling index, or tumor-infiltrating lymphocytes levels. Patients with interleukin-13 receptor alpha 2 expression tended to have poorer disease-free survival, but the difference was not statistically significant (p = 0.069). Subgroup analysis showed luminal breast cancer patients positive for interleukin-13 receptor alpha 2 expression had significantly poorer disease-free survival (p = 0.018) than luminal breast cancer patients negative for interleukin-13 receptor alpha 2 expression. However, no association between interleukin-13 receptor alpha 2 expression and clinical outcome was observed in HER2-positive and triple-negative subgroups (p = 0.574 and p = 0.936, respectively). Multivariate analysis showed interleukin-13 receptor alpha 2 expression was an independent poor prognostic factor for luminal breast cancer (p = 0.03). This study shows interleukin-13 receptor alpha 2 expression could be a useful prognostic marker for selecting patients with luminal breast cancer likely to follow a clinically aggressive course despite receiving systemic therapy.

Adhesive evaluation of three types of resilient denture liners bonded to heat-polymerized, autopolymerized, or CAD-CAM acrylic resin denture bases.

STATEMENT OF PROBLEM: Levels of bond strength between different types of resilient denture liner materials bonded to different denture base acrylic resins, CAD-CAM acrylic resins in particular, have not been well reported. PURPOSE: The purpose of this in vitro study was to measure the tensile bond strength and durability of various combinations of 3 different resilient denture liners bonded to 3 different poly(methyl methacrylate) denture base materials. MATERIAL AND METHODS: The tensile bond strength of 3 resilient denture liners, namely Ufi Gel SC, Silagum-Comfort, and Vertex Soft, combined with heat-polymerized (Vertex Rapid Simplified), autopolymerized (Vertex Self-Curing), and computer-aided design and computer-aided manufacturing (CAD-CAM) (IvoBase CAD) denture base resins were tested by using a universal testing machine (total N=138). Half of the specimens were thermocycled between 5°C and 55°C for 1500 cycles before testing. After testing, modes of failure and interface surfaces were examined using light microscopy and scanning electron microscopy, respectively. Thermogravimetric analysis was carried out to analyze the differences in content between the 3 different denture base acrylic resins. RESULTS: The mean tensile bond strength values ranged from 0.36 ±0.1 MPa to 1.51 ±0.46 MPa. CAD-CAM denture base materials showed the lowest range of bond strength when coupled to resilient denture liners (0.36 to 0.42 MPa). No statistically significant differences (P=.74) were found in bond strength between the thermocycled (0.71 ±0.23 MPa) and non-thermocycled groups (0.74 ±0.21 MPa). Silicone-based resilient denture liners exhibited the highest tensile strength with each type of denture resin. All 3 types of failure modes (adhesive, cohesive, and mixed modes) were observed. CONCLUSIONS: Silicone-based resilient denture liners produced the highest tensile bond strength to all denture bases tested. Resilient denture liners bonded to CAD-CAM denture bases produced the weakest tensile bond strengths. Thermocycling did not produce statistically significant differences in tensile bond strength of the resilient denture liners to the denture base resins.

Exploring the Knowledge Structure of Nursing Care for Older Patients With Delirium: Keyword Network Analysis.

Prevention of delirium is considered a critical part of the agenda for patient safety and an indicator of healthcare quality for older patients. As the incidence rate of delirium for older patients has increased in recent years, there has been a significant expansion in knowledge relevant to nursing care. The purposes of this study were to analyze the knowledge structure and trends in nursing care for older adults with delirium based on a keyword network analysis, and to provide a foundation for future research. Data analysis showed that knowledge structure in this area consists of three themes of research: postoperative acute care for older patients with delirium, prevention of delirium for older patients in intensive care units, and safety management for the improvement of outcomes for patients with delirium. Through research trend analysis, we found that research on care for patients with delirium has achieved both quantitative and qualitative improvements over the last decades. Concerning future research, we propose the expansion of patient- and family-centered care, community care, specific nursing interventions, and the integration of new technology into care for patients with delirium. These results provide a reference framework for understanding and developing nursing care for older adults with delirium.

Usefulness of the Braden Scale in Intensive Care Units: A Study Based on Electronic Health Record Data.

Nurses working in intensive care units have expressed concern that some categories of the Braden scale such as activity and nutrition are not suitable for intensive care unit patients. Upon examining the validity of the Braden scale using the electronic health data, we found relatively low predictability of the tool. Risk factors from the sensory perception and activity categories were not associated with risk of pressure ulcers.

RAR-Related Orphan Receptor Gamma (ROR-γ) Mediates Epithelial-Mesenchymal Transition Of Hepatocytes During Hepatic Fibrosis.

The epithelial-mesenchymal transition (EMT) is involved in many different types of cellular behavior, including liver fibrosis. In this report, we studied a novel function of RAR-related orphan receptor gamma (ROR-γ) in hepatocyte EMT during liver fibrosis. To induce EMT in vitro, primary hepatocytes and FL83B cells were treated with TGF-ß1. Expression of ROR-γ was analyzed by Western blot in the fibrotic mouse livers and human livers with cirrhosis. To verify the role of ROR-γ in hepatocyte EMT, we silenced ROR-γ in FL83B cells using a lentiviral short hairpin RNA (shRNA) vector. The therapeutic effect of ROR-γ silencing was investigated in a mouse model of TAA-induced fibrosis by hydrodynamic injection of plasmids. ROR-γ expression was elevated in hepatocyte cells treated with TGF-ß1, and ROR-γ protein levels were elevated in the fibrotic mouse livers and human livers with cirrhosis. Knockdown of ROR-γ resulted in the attenuation of TGF-ß1-induced EMT in hepatocytes. Strikingly, ROR-γ bound to ROR-specific DNA response elements (ROREs) in the promoter region of TGF-ß type I receptor (Tgfbr1) and Smad2, resulting in the downregulation of Tgfbr1 and Smad2 after silencing of ROR-γ. Therapeutic delivery of shRNA against ROR-γ attenuated hepatocyte EMT and ameliorated liver fibrosis in a mouse model of TAA-induced liver fibrosis. Overall, our results suggest that ROR-γ regulates TGF-ß-induced EMT in hepatocytes during liver fibrosis. We suggest that ROR-γ may become a potential therapeutic target in treating liver fibrosis. J. Cell. Biochem. 118: 2026-2036, 2017. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals Inc.

Different prognosis of young breast cancer patients in their 20s and 30s depending on subtype: a nationwide study from the Korean Breast Cancer Society.

PURPOSE: Numerous studies have demonstrated that breast cancer in young women (BCY) has unfavorable prognostic features and more unfavorable subtypes. However, few studies have evaluated the effect of subtype disparities on breast cancer prognosis by age, especially for BCY. We analyzed breast cancer mortality stratified by tumor subtype according to age among patients younger than 50 years. METHODS: Data from the Korean Breast Cancer Society Registry for patients diagnosed with invasive breast cancer when aged less than 50 years between 2003 and 2010 were reviewed retrospectively. RESULTS: We identified 30,793 patients with breast cancer who were eligible for analysis. Of these, 793 (2.6%) were aged 20-29 and 8926 (28.8%) were aged 30-39. Median follow-up duration was 84 months. Mean age was 42.4 years. Patients in their 20s were more likely to have cancer of advanced stage and higher nuclear grade, present with lymphovascular invasion, and have unfavorable subtypes. Patients in the 20s group showed worse prognosis. In multivariate analysis for overall survival (OS), the hazard ratio (HR) for patients in the 20s group was higher than that for the 30s and 40s groups, and patients with triple-negative breast cancer (TNBC) showed higher HR than patients with HER-2 or luminal subtype (all p < 0.0001). When stratified by subtype, luminal subtype showed significantly worse prognosis in the 20s group than the 30s and 40s groups, whereas HER-2 and TNBC subtypes showed no significant difference. CONCLUSION: Patients in their 20s with breast cancer had unfavorable characteristics and worse prognosis than patients in their 30s and 40s. When stratified by tumor subtype, patients in their 20s with luminal subtype of breast cancer showed worse prognosis than older patients, whereas HER-2 and TNBC subtypes showed no significant differences.

Prognostic significance of CD9 expression differs between tumour cells and stromal immune cells, and depends on the molecular subtype of the invasive breast carcinoma.

AIMS: CD9, a tetraspanin transmembrane protein, modulates cell motility, migration, and proliferation. The aim of this study was to investigate the prognostic significance of CD9 expression in patients with invasive breast carcinoma (IBC). METHODS AND RESULTS: CD9 expression was evaluated in tissue microarrays of 1349 IBC samples via immunohistochemistry. CD9 expression in tumour cells (T-CD9 expression) and CD9 expression in stromal immune cells (S-CD9 expression) were analysed separately. T-CD9 expression was observed in 732 (54.3%) cases, and was associated with lymph node metastasis, histological type, lymphovascular invasion, high histological grade, HER2 positivity, a high Ki67 labelling index, and distant metastasis. S-CD9 expression was observed in 833 (61.7%) cases, and was associated with large tumour size, histological type, high histological grade, negative hormone receptors, HER2 positivity, a high Ki67 labelling index, and tumour-infiltrating lymphocytes. Patients with T-CD9 expression had shorter disease-free survival (DFS) than those without T-CD9 expression in the univariate and multivariate analyses. However, S-CD9 expression correlated significantly with a favourable DFS in the univariate and multivariate analyses. In the subgroup analysis, T-CD9 expression and S-CD9 expression were independent markers for DFS in luminal A and luminal B (HER2-negative) subgroups, respectively. CONCLUSIONS: T-CD9 expression could be a biomarker for poor prognosis in luminal A IBC, whereas S-CD9 expression could be a marker of good prognosis in luminal B (HER2-negative) IBC. Therefore, tumour compartment-specific analyses considering molecular subtypes are necessary to study the prognostic significance of CD9 expression in IBC.

Germ Cell Tumor Targeting Chemotherapy in Gastric Adenocarcinoma with an Endodermal Sinus Tumor Component: A Case Report.

The most common sites for extragonadal germ cell tumors are the midline mediastinum, retroperitoneum and, much less frequently, the stomach. The stomach-originated primary germ cell tumor carries a poor prognosis, especially when metastasis occurs to the liver, with a mean survival time of 1 month. We describe the case of a 77-year-old male who presented with usual symptoms of gastric malignancy. Gastrectomy was performed. Histopathology of surgically resected tissue revealed a mixture of adenocarcinoma and endodermal sinus tumor components with α-fetoprotein production. After liver metastasis was identified, oxaliplatin and capecitabine were administered as palliative chemotherapy. The response was poor. For the second-line therapy, bleomycin, etoposide, and cisplatin (BEP) therapy was initiated. The overall response to these drugs was a partial response and the residual liver lesion was considered to be resectable. The patient died of pneumonia 11 months following the BEP session, representing an overall survival time of 22 months. Gastric adenocarcinoma with a germ cell tumor component is uncommon and an effective combination of chemotherapeutic agents is not yet clear. In this case, the patient received germ cell tumor-targeting chemotherapy and showed a durable response. Hence, germ cell-targeting cytotoxic agents have potential as the 'front-line regimen'.

Nursing home nurses conceptualize how to care for residents with cardiac vulnerability.

BACKGROUND: With ageing, older people face cardiovascular problems as the major cause of disability and death. Although immediate medical attention is a major factor in determining outcomes of cardiac problems, lack of personnel (i.e. registered nurse, certified nursing assistant and home care aide) in nursing homes without residing doctor limits the awareness of such problems, thus making it difficult to initiate timely and appropriate intervention. AIM: The aim of this study was to conceptualize critical care for nursing home residents with cardiac vulnerability and develop practical knowledge in nursing practice. METHODS: Conventional content analysis was performed on date from interviews with 30 nurses from 10 nursing homes in South Korea between July and November 2010. RESULTS: The analysis revealed three major cardiac problems resulting from residents' cardiac vulnerability: angina, myocardial infarction (MI) and cardiogenic shock. Through content analysis, we extracted 6 themes and 21 subthemes for nurses' conceptualization of critical care for nursing home residents with cardiac vulnerability. In nursing homes without a residing doctor, nurses assessed the physical, functional and cognitive conditions along with the responses and symptoms of residents when emergency situations related to the cardiac problems occurred. Moreover, with a lack of infrastructures of a hospital, nurses provided critical care to the elderly by using personal practice strategies based on their personal experience in facilities along with practical knowledge of nurses while following the management principles of emergencies. CONCLUSIONS AND RELEVANCE TO CLINICAL PRACTICE: We found that nurses conceptualized critical nursing care for cardiac problems at nursing homes, which are different from those of general hospitals. The results of this study will provide basis for the development of care guidelines and educational materials that can be used by novice nurses or nursing students.