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In the shipbuilding industry, welding automation using welding robots often relies on arc-sensing techniques due to spatial limitations. However, the reliability of the feedback current value, core sensing data, is reduced when welding target workpieces have significant curvature or gaps between curved workpieces due to the control of short-circuit transition, leading to seam tracking failure and subsequent damage to the workpieces. To address these problems, this study proposes a new algorithm, MBSC (median-based spatial clustering), based on the DBSCAN (density-based spatial clustering of applications with noise) clustering algorithm. By performing clustering based on the median value of data in each weaving area and considering the characteristics of the feedback current data, the proposed technique utilizes detected outliers to enhance seam tracking accuracy and responsiveness in unstructured and challenging welding environments. The effectiveness of the proposed technique was verified through actual welding experiments in a yard environment.

Abstract We explored accumulated genomic alterations in patients with heavily treated HER2 + metastatic breast cancer enrolled in the KCSG BR18-14/KM10B trial. Targeted sequencing was performed with circulating tumor DNAs (ctDNAs) collected before the treatment of 92 patients. ctDNAs collected at the time of disease progression from seven patients who had a durable response for > 12 months were also analyzed. Sixty-five genes were identified as pathogenic alterations in 99 samples. The most frequently altered genes were TP53 (n = 48), PIKCA (n = 21) and ERBB3 (n = 19). TP53 and PIK3CA mutations were significantly related with shorter progression free survival (PFS), and patients with a higher ctDNA fraction showed a worse PFS. The frequency of homologous recombination deficiency (HRD)-related gene mutations was higher than that in matched tumor tissues, and these mutations tended to be associated with shorter PFS. New pathogenic variants were found at the end of treatment in all seven patients, including BRCA2, VHL, RAD50, RB1, BRIP1, ATM, FANCA, and PIK3CA mutations. In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract and is characterized by recurrent chronic inflammation and mucosal damage of the gastrointestinal tract. Recent studies have demonstrated that bamboo shoot (BS) and Artemisia capillaris (AC) extracts enhance anti-inflammatory effects in various disease models. However, it is uncertain whether there is a synergistic protective effect of BS and AC in dextran sodium sulfate (DSS)-induced colitis. In the current study, we tested the combined effects of BS and AC extracts (BA) on colitis using in vivo and in vitro models. Compared with control mice, oral administration of DSS exacerbated colon length and increased the disease activity index (DAI) and histological damage. In DSS-induced colitis, treatment with BA significantly alleviated DSS-induced symptoms such as colon shortening, DAI, histological damage, and colonic pro-inflammatory marker expression compared to single extracts (BS or AC) treatment. Furthermore, we found BA treatment attenuated the ROS generation, F-actin formation, and RhoA activity compared with the single extract (BS or AC) treatment in DSS-treated cell lines. Collectively, these findings suggest that BA treatment has a positive synergistic protective effect on colonic inflammation compared with single extracts, it may be a highly effective complementary natural extract mixture for the prevention or treatment of IBD.

We investigated the efficacy and safety of a trastuzumab biosimilar, Herzuma®, in combination with treatment of physician's choice (TPC) in patients with HER2+ metastatic breast cancer (MBC) who had failed at least two HER2 directed chemotherapies.

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

Purpose: This study evaluated the influence of prognostic factors and whole brain radiotherapy (WBRT) on overall survival (OS) of breast cancer (BC) patients with brain metastases (BM). Methods and materials: Medical records of 730 BC patients diagnosed with BM from 2000 to 2014 at 17 institutions were retrospectively reviewed. OS was calculated from BM diagnosis. Median follow-up duration was 11.9 months (range, 0.1–126.2). Results: Median OS was 15.0 months (95% CI: 14.0–16.9). Patients with different BC-specific graded prognostic assessment (GPA) scores showed significant differences (p 4; p = 0.002), hormone receptor negativity (p = 0.005), HER2-negativity (p = 0.003), and shorter time interval (0.673) subgroups; the high-risk subgroup had poorer median OS (10.1 months, 95% CI: 7.9–11.9 vs. 21.9 months, 95% CI: 19.5–27.1, p

Backgrounds This study administered the Health Literacy Questionnaire (HLQ) among Korean adults to examine its factor structure, reliability, and validity. Methods The HLQ items were translated and culturally adapted to the Korean context. The convenience sampling method was used, and data were collected. The difficulty level, confirmatory factor analysis (CFA) using diagonal weighted least squares (DWLS) estimator in R, discriminant validity, and composite reliability were performed. Results The easiest scale to obtain a high score was “Scale 4. Social support for health” and the hardest was “Scale 7. Navigating the healthcare system.” Nine one-factor models fitted well. The nine-factor structural equation model fitted the data well. All HLQ scales were homogenous, with composite reliability. Conclusions The Korean version of the HLQ has a strong construct and high composite reliability when applied to Korean adults.

Mitochondrial dynamics continually maintain cell survival and bioenergetics through mitochondrial quality control processes (fission, fusion, and mitophagy). Aberrant mitochondrial quality control has been implicated in the pathogenic mechanism of various human diseases, including cancer, cardiac dysfunction, and neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and prion disease. However, the mitochondrial dysfunction-mediated neuropathological mechanisms in prion disease are still uncertain. Here, we used both in vitro and in vivo scrapie-infected models to investigate the involvement of mitochondrial quality control in prion pathogenesis. We found that scrapie infection led to the induction of mitochondrial reactive oxygen species (mtROS) and the loss of mitochondrial membrane potential (ΔΨm), resulting in enhanced phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and its subsequent translocation to the mitochondria, which was followed by excessive mitophagy. We also confirmed decreased expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and reduced ATP production by scrapie infection. In addition, scrapie-infection-induced aberrant mitochondrial fission and mitophagy led to increased apoptotic signaling, as evidenced by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. These results suggest that scrapie infection induced mitochondrial dysfunction via impaired mitochondrial quality control processes followed by neuronal cell death, which may have an important role in the neuropathogenesis of prion diseases.

Natural rubber (NR) presents a number of advantages over other types of rubber but has poor resistance to chemicals and aging. The incorporation of ethylene propylene diene monomer (EPDM) into the NR matrix may be able to address this issue. Mineral fillers, such as carbon black (CB) and silica are routinely incorporated into various elastomers owing to their low cost, enhanced processability, good functionality, and high resistance to chemicals and aging. Other fillers have been examined as potential alternatives to CB and silica. In this study, phlogopite was surface-modified using 10 phr of compatibilizers, such as aminopropyltriethoxysilane (A1S), aminoethylaminopropyltrimethoxysilane (A2S), or 3-glycidoxypropyltrimethoxysilane (ES), and mixed with NR/EPDM blends. The effects of untreated and surface-treated phlogopite on the mechanical properties of the rubber blend were then compared with those of common fillers (CB and silica) for rubbers. The incorporation of surface-modified phlogopite into NR/EPDM considerably enhanced various properties. The functionalization of the phlogopite surface using silane-based matters (amino- and epoxide-functionalized) led to excellent compatibility between the rubber matrix and phlogopite, thereby improving diverse properties of the elastomeric composites, with effects analogous to those of CB. The tensile strength and elongation at break of the phlogopite-embedded NR/EPDM composite were lower than those of the CB-incorporated NR/EPDM composite by 30% and 10%, respectively. Among the prepared samples, the ES-functionalized phlogopite showed the best compatibility with the rubber matrix, exhibiting a tensile strength and modulus of composites that were 35% and 18% higher, respectively, compared with those of the untreated phlogopite-incorporated NR/EPDM composite. The ES-functionalized phlogopite/NR/EPDM showed similar strength and higher modulus (by 18%) to the CB/NR/EPDM rubber composite, despite slightly lower elongation at break and toughness. The results of rebound resilience and compression set tests indicated that the elasticity of the surface-modified phlogopite/NR/EPDM rubber composite was higher than that of the silica- and CB-reinforced composites. These improvements could be attributed to enhancements in the physical and chemical interactions among the rubber matrix, stearic acid, and functionalized (compatibilized) phlogopite. Therefore, the functionalized phlogopite can be utilized in a wide range of applications for rubber compounding.

Although dye removal from wastewater streams has been investigated via several approaches using adsorbents, resins, or membranes, it is still hard to avoid the fact that dyes are persistently left in the adsorption materials or washing solutions used to regenerate the used adsorbents. In particular, given that cleaning agents are composed of acid/base, organic solvents, or electrolytes, dye adsorption and adsorbent regeneration processes leave behind more hard-to-manage wastewater containing dyes. In this study, we demonstrated that cold plasma (CP) treatment, which is one of the advanced oxidation processes (AOPs), can be used for zero discharge of dyes and regeneration of a washing solution in a membrane-based dye removal process. Specifically, CP treatment was found to successfully remove dyes released from a washing process to regenerate a used membrane, thereby effectively recycling a cleaning solution. As a result, the regenerated washing solution was more favorable for the adsorbed dyes’ elution, leading to the successful regeneration of a used membrane without a significant loss of dye removal efficiency. This fact was evidenced by a comparative study on the effect of CP treatment on the reusability of membranes and washing solutions and the kinetic analysis of the AOP of the desorbed dyes. We hope that this study contributes to opening a new door for environmentally friendly and sustainable dye removal.

Occult breast cancer (OBC) is an asymptomatic condition. We report a case of OBC in a 72-year-old male patient who presented with severe dyspnea and upper extremity swelling. Computed tomography scan showed multiple lymph node enlargements in the supraclavicular and infraclavicular areas, and ultrasound scan showed multiple axillary lymph node enlargements. Based on the radiological findings, clinicians suspected lymphoma or disseminated metastasis from unknown primary malignancies. However, the axillary biopsy specimen revealed invasive breast cancer with hormonal receptor positivity.

Abstract Background Oxaliplatin is a platinum derivative that has shown efficacy in advanced hepatocellular carcinoma. S-1 is an oral fluoropyrimidine that has substituted for 5-fluorouracil in many cancers. This was a multicenter, open-label, single-arm phase II trial that evaluated the efficacy of S-1 and oxaliplatin (SOX) in advanced hepatocellular carcinoma. All patients included in the present study were systemic treatment-naïve. Prior treatment with sorafenib was allowed, but other treatments were not. Methods Patients received S-1 (40 mg/m2 twice daily from day 1–14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. The primary end point was time to progression (TTP). Secondary end points included progression-free survival, overall survival (OS), response rate, and safety profile. Results Thirty six patients with advanced hepatocellular carcinoma were included in this study. The median TTP was 3.0 months (95% confidence interval (CI), 0.75–5.25), and the median OS was 10.3 months (95% CI, 6.4–14.3). Bone metastasis was associated with poorer TTP and OS. The efficacy of SOX was unaffected by prior sorafenib or locoregional therapy. The objective response rate was 13.9%. No grade 4 toxicity or death from adverse events occurred. The most common grade 3 toxicities were neutropenia (13.9%), thrombocytopenia (13.9%), and diarrhea (8.3%). Conclusions Although this trial did not meet its primary end point, the SOX regimen showed comparable efficacy and safety to the 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimen. As the SOX regimen is easier for patients, SOX may be a reasonable substitute for FOLFOX in hepatocellular carcinoma. Trial registration Clinicaltrials.gov NCT01429961. Registered 7 September 2011.

The cellular prion protein (PrPC) is a cell surface glycoprotein expressed in many cell types that plays an important role in normal cellular processes. However, an increase in PrPC expression has been associated with a variety of human cancers, where it may be involved in resistance to the proliferation and metastasis of cancer cells. PrP-deficient (Prnp0/0) and PrP-overexpressing (Tga20) mice were studied to evaluate the role of PrPC in the invasion and metastasis of cancer. Tga20 mice, with increased PrPC, died more quickly from lung cancer than did the Prnp0/0 mice, and this effect was associated with increased transforming growth factor-beta (TGF-β) and programmed death ligand-1 (PD-L1), which are important for the development and function of regulatory T (Treg) cells. The number of FoxP3+CD25+ Treg cells was increased in Tga20 mice compared to Prnp0/0 mice, but there was no significant difference in either natural killer or cytotoxic T cell numbers. In addition, mice infected with the ME7 scrapie strain had decreased numbers of Treg cells and decreased expression of TGF-β and PD-L1. These results suggest that PrPC plays an important role in invasion and metastasis of cancer cells by inducing Treg cells through upregulation of TGF-β and PD-L1 expression.

Scrapie infection, which converts cellular prion protein (PrPC) into the pathological and infectious isoform (PrPSc), leads to neuronal cell death, glial cell activation and PrPSc accumulation. Previous studies reported that PrPC regulates RhoA/Rho-associated kinase (ROCK) signaling and that connexin 43 (Cx43) expression is upregulated in in vitro and in vivo prion-infected models. However, whether there is a link between RhoA/ROCK and Cx43 in prion disease pathogenesis is uncertain. Here, we investigated the role of RhoA/ROCK signaling and Cx43 in prion diseases using in vitro and in vivo models. Scrapie infection induced RhoA activation, accompanied by increased phosphorylation of LIM kinase 1/2 (LIMK1/2) at Thr508/Thr505 and cofilin at Ser3 and reduced phosphorylation of RhoA at Ser188 in hippocampal neuronal cells and brains of mice. Scrapie infection-induced RhoA activation also resulted in PrPSc accumulation followed by a reduction in the interaction between RhoA and p190RhoGAP (a GTPase-activating protein). Interestingly, scrapie infection significantly enhanced the interaction between RhoA and Cx43. Moreover, RhoA and Cx43 colocalization was more visible in both the membrane and cytoplasm of scrapie-infected hippocampal neuronal cells than in controls. Finally, RhoA and ROCK inhibition reduced PrPSc accumulation and the RhoA/Cx43 interaction, leading to decreased Cx43 hemichannel activity in scrapie-infected hippocampal neuronal cells. These findings suggest that RhoA/ROCK regulates Cx43 activity, which may have an important role in the pathogenesis of prion disease.

Hepatic stellate cells (HSCs) play pivotal roles in hepatic fibrosis as they synthesize glial fibrillary acidic protein (GFAP), which is increased in activated HSCs. GFAP-expressing HSCs and myofibroblasts accumulate in and around hepatic fibrosis lesions. Peptidylarginine deiminase 2 (PAD2) is responsible for the citrullination of GFAP (cit-GFAP). However, the involvement of PAD2 and cit-GFAP in hepatic fibrosis remains unclear. To determine the expression of PAD2 and cit-GFAP in hepatic fibrosis, C57BL/6 mice underwent bile duct ligation (BDL) or a sham operation. In BDL livers, the expression of PAD2 and its enzyme activity were significantly increased compared with controls. In addition, PAD2-postitive cells were rarely observed in only the portal vein and the small bile duct in sham-operated livers, whereas an increased number of PAD2-positive cells were detected in the bile duct and Glisson's sheath in BDL livers. Interestingly, PAD2 was colocalized with α-SMA-positive cells and CK19-positive cells in BDL livers, indicating upregulated PAD2 in activated HSCs and portal fibroblasts of the livers of BDL mice. We also found that citrullinated proteins were highly accumulated in the livers of BDL mice compared with controls. Moreover, the expression level of GFAP and the amount of cit-GFAP were higher in BDL livers than in control livers. In correlation with PAD2 localization, cit-GFAP was observed in α-SMA-positive and CK19-positive cells in the livers of BDL mice. These results suggest that the increased expression and activation of PAD2 along with increased citrullinated proteins, specifically cit-GFAP, may play important roles in the pathogenesis of hepatic fibrosis.

BackgroundStudies have shown that long‐term exposure to air pollution such as fine particulate matter (≤2.5 μm in aerodynamic diameter [PM2.5]) increases the risk of all‐cause and cardiovascular mortality. To date, however, there are limited data on the impact of air pollution on specific cardiovascular diseases. This study aimed to evaluate cardiovascular effects of long‐term exposure to air pollution among residents of Seoul, Korea. Methods and ResultsHealthy participants with no previous history of cardiovascular disease were evaluated between 2007 and 2013. Exposure to air pollutants was estimated by linking the location of outdoor monitors to the ZIP code of each participant's residence. Crude and adjusted analyses were performed using Cox regression models to evaluate the risk for composite cardiovascular events including cardiovascular mortality, acute myocardial infarction, congestive heart failure, and stroke. A total of 136 094 participants were followed for a median of 7.0 years (900 845 person‐years). The risk of major cardiovascular events increased with higher mean concentrations of PM2.5 in a linear relationship, with a hazard ratio of 1.36 (95% confidence interval, 1.29–1.43) per 1 μg/m3 PM2.5. Other pollutants including PM2.5–10 of CO, SO2, and NO2, but not O3, were significantly associated with increased risk of cardiovascular events. The burden from air pollution was comparable to that from hypertension and diabetes mellitus. ConclusionsThis large‐scale population‐based study demonstrated that long‐term exposure to air pollution including PM2.5 increases the risk of major cardiovascular disease and mortality. Air pollution should be considered an important modifiable environmental cardiovascular risk factor.

Algal bloom significantly alters the physicochemical properties of water due to drastic pH change, dissolved oxygen depletion/super-saturation, and toxicity, which lead to ecosystem destruction. To prevent this, this study evaluated the reduction performance of algal biomass by applying a non-thermal or cold plasma process. We used chlorophyll-a (chl-a), suspended solids (SS), and turbidity as indicators of the biomass. Results demonstrated that their removal efficiencies were in the ranges 88−98%, 70%−90%, and 53%−91%, respectively. Field emission scanning electron microscopy indicated how the cell wall of microalgae was destroyed by cold plasma. Also, the removal kinetics of cold plasma confirmed the enhanced removal rate constants. The estimated required times for 99% removal were 0.4−1.2 d (chl-a), 1.3−3.4 d (SS), and 1.6−6.2 d (turbidity), respectively. Overall, cold plasma could be a useful option to effectively treat pollution associated with algal bloom in surface water.

Calsenilin modulates A-type potassium channels, regulates presenilin-mediated γ-secretase activity, and represses prodynorphin and c-fos genes expression. RhoA is involved in various cellular functions including proliferation, differentiation, migration, transcription, and regulation of the actin cytoskeleton. Although recent studies demonstrate that calsenilin can directly interact with RhoA and that RhoA inactivation is essential for neuritogenesis, it is uncertain whether there is a link between calsenilin and RhoA-regulated neuritogenesis. Here, we investigated the role of calsenilin in RhoA-regulated neuritogenesis using in vitro and in vivo systems. We found that calsenilin induced RhoA inactivation, which accompanied RhoA phosphorylation and the reduced phosphorylation levels of LIM kinase (LIMK) and cofilin. Interestingly, PC12 cells overexpressing either full-length (FL) or the caspase 3-derived C-terminal fragment (CTF) of calsenilin significantly inactivated RhoA through its interaction with RhoA and p190 Rho GTPase-activating protein (p190RhoGAP). In addition, cells expressing FL and the CTF of calsenilin had increased neurite outgrowth compared to cells expressing the N-terminal fragment (NTF) of calsenilin or vector alone. Moreover, Tat-C3 and Y27632 treatment significantly increased the percentage of neurite-bearing cells, neurite length, and the number of neurites in cells. Finally, calsenilin deficiency in the brains of calsenilin-knockout mice significantly interfered with RhoA inactivation. These findings suggest that calsenilin contributes to neuritogenesis through RhoA inactivation.