Fifteen Years After the Gozan-Dong Glass Fiber Outbreak, Incheon in 1995

Objectives: In 1995, an outbreak survey in Gozan-dong concluded that an association between fiberglass exposure in drinking water and cancer outbreak cannot be established. This study follows the subjects from a study in 1995 using a data linkage method to examine whether an association existed. The authors will address the potential benefits and methodological issues following outbreak surveys using data linkage, particularly when informed consent is absent. Methods: This is a follow-up study of 697 (30 exposed) individuals out of the original 888 (31 exposed) participants (78.5%) from 1995 to 2007 assessing the cancer outcomes and deaths of these individuals. The National Cancer Registry (KNCR) and death certificate data were linked using the ID numbers of the participants. The standardized incidence ratio (SIR) and standardized mortality ratio (SMR) from cancers were calculated by the KNCR. Results: The SIR values for all cancer or gastrointestinal cancer (GI) occurrences were the lowest in the exposed group (SIR, 0.73; 95% CI, 0.10 to 5.21; 0.00 for GI), while the two control groups (control 1: external, control 2: internal) showed slight increases in their SIR values (SIR, 1.18 and 1.27 for all cancers; 1.62 and 1.46 for GI). All lacked statistical significance. All-cause mortality levels for the three groups showed the same pattern (SMR 0.37, 1.29, and 1.11). Conclusions: This study did not refute a finding of non-association with a 13-year follow-up. Considering that many outbreak surveys are associated with a small sample size and a cross-sectional design, follow-up studies that utilize data linkage should become standard procedure.OAIID:oai:osos.snu.ac.kr:snu2011-01/102/0000040632/15SEQ:15PERF_CD:SNU2011-01EVAL_ITEM_CD:102USER_ID:0000040632ADJUST_YN:YEMP_ID:A077602DEPT_CD:902CITE_RATE:0FILENAME:fifteen years after the gozan-dong glass fiber outbreak, incheon in 1995..pdfDEPT_NM:보건학과CONFIRM:

Liquid biopsy in lung cancer: Clinical applications of circulating biomarkers (CTCs and ctDNA)

Lung cancer is by far the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Recent advances in the understanding of the biology of tumors and in highly sensitive detection technologies for molecular analysis offer targeted therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. However, our understanding of an individual patient's lung cancer is often limited by tumor accessibility because of the high risk and invasive nature of current tissue biopsy procedures. Liquid biopsy, the analysis of circulating biomarkers from peripheral blood, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), offers a new source of cancer-derived materials that may reflect the status of the disease better and thereby contribute to more personalized treatment. In this review, we examined the clinical significance and uniqueness of CTCs and ctDNA from NSCLC patients, isolation and detection methods developed to analyze each type of circulating biomarker, and examples of clinical studies of potential applications for early diagnosis, prognosis, treatment monitoring, and prediction of resistance to therapy. We also discuss challenges that remain to be addressed before such tools are implemented for routine use in clinical settings

A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC

Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy

Soft X-ray absorption spectroscopy study of spin crossover Fe-compounds: Persistent high spin configurations under soft X-ray irradiation

Metal-organic complex exhibiting spin crossover (SCO) behavior has drawn attention for its functionality as a nanoscale spin switch. The spin states in the metal ions can be tuned by external stimuli such as temperature or light. This article demonstrates a soft X-ray?induced excited spin state trapping (SOXEISST) effect in Hofmann-like SCO coordination polymers of FeII (4-methylpyrimidine)2 [Au(CN)2 ]2 and FeII (pyridine)2 [Ni(CN)4 ]. A soft X-ray absorption spectroscopy (XAS) study on these polymers showed that the high spin configuration (HS; S = 2) was prevalent in Fe2+ ions during the measurement even at temperatures much lower than the critical temperatures (>170 K), manifesting HS trapping due to the X-ray irradiation. This is in strong contrast to the normal SCO behavior observed in FeII (1,10-phenanthroline)2 (NCS)2, implying that the structure of the ligand chains in the polymers with relatively loose Fe-N coordination might allow a structural adaptation to stabilize the metastable HS state under the soft X-ray irradiation. (C) 2018 by the authors. Licensee MDPI, Basel, Switzerlan

Circulating Tumor Cells Enumerated by a Centrifugal Microfluidic Device as a Predictive Marker for Monitoring Ovarian Cancer Treatment: A Pilot Study

We investigated the size-based isolation and enumeration of circulating tumor cells (CTCs) using a centrifugal microfluidic device equipped with a fluid-assisted separation technology (FAST) disc. We further assessed the correlations among CTCs, cancer antigen-125 (CA125) levels, and clinical course of the disease in a prospective analysis of 47 serial blood samples collected at multiple time-points from 13 ovarian cancer patients. CTCs were isolated from whole blood using the FAST disc and were classified as epithelial cell adhesion molecule (EpCAM)/cytokeratin+, CD45-, and 4 ',6-diamidino-2-phenylindole (DAPI)+. Mean CTC count at baseline was 20.2; 84.62% of patients had more than one CTC at baseline and had decreased CTCs counts after surgery and chemotherapy. The CTC counts in eight patients with complete responses were <3. CTC counts were correlated with CA125 levels in three patients without recurrence; they were elevated in three patients with recurrence and normal CA125 concentrations. CTC counts and CA125 levels showed high concordance with directional changes (increasing 71.4%; non-increasing 75.0%). CTC counts showed higher associations with clinical status, sensitivity (100.0% vs. 60.0%), positive predictive value (55.6% vs. 42.9%), and negative predictive value (100.0% vs. 87.5%) than CA125 levels. CTC counts were better associated with treatment response and recurrence than CA125 levels

Unilateral Psoriasis in a Woman with Ipsilateral Post-Mastectomy Lymphedema

Psoriasis is a multi-factorial disease with various clinical manifestations. We present a case of unilateral psoriasis associated with ipsilateral lymphedema that developed after mastectomy for breast cancer. A 42-year-old Korean woman was referred to our clinic with a 1-month history of multiple erythematous scaly patches on the right arm, back, and breast and was diagnosed with psoriasis by a skin biopsy. Three years previously, she had been diagnosed with breast cancer (T1N2), underwent a right quadrantectomy and axillary lymph node dissection, and completed adjuvant chemotherapy followed by high-dose adjuvant radiotherapy. She had started rehabilitation therapy on the right arm for secondary lymphedema 30 months previously. Because of the long interval between radiation and psoriasis, we speculated that changes in the local milieu caused by the lymphedema might be a causative factor. We hereby report a rare case of unilateral psoriasis following post-mastectomy lymphedema

Comparative Studies of Different Imputation Methods for Recovering Streamflow Observation

Faulty field sensors cause unreliability in the observed data that needed to calibrate and assess hydrology models. However, it is illogical to ignore abnormal or missing values if there are limited data available. This study addressed this problem by applying data imputation to replace incorrect values and recover missing streamflow information in the dataset of the Samho gauging station at Taehwa River (TR), Korea from 2004 to 2006. Soil and Water Assessment Tool (SWAT) and two machine learning techniques, Artificial Neural Network (ANN) and Self Organizing Map (SOM), were employed to estimate streamflow using reasonable flow datasets of Samho station from 2004 to 2009. The machine learning models were generally better at capturing high flows, while SWAT was better at simulating low flows.open

Potential Cause of Decrease in Bloom Events of the Harmful DinoflagellateCochlodinium polykrikoidesin Southern Korean Coastal Waters in 2016

Blooms of the ichthyotoxic dinoflagellateCochlodinium polykrikoidesare responsible for massive fish mortality events in Korean coastal waters (KCW). They have been consistently present in southern KCW over the last two decades, but they were not observed in 2016, unlike in the previous years. Despite extensive studies, the cause of this absence of this dinoflagellate bloom remains largely unknown. Thus, we compared physico-chemical and biological data from along the Tongyeong coast between 2016 and the previous four years (2012-2015). The averages of water temperature and salinity in August, 2016 were significantly (p< 0.001) different from those in the previous years. The amount of Changjiang River discharge, which can affect the environmental conditions in the southern Korean coastal area via ocean currents, was larger than in the previous years, resulting in a reduction in the salinity level in August when blooms ofC. polykrikoidesusually occurred. Moreover, compared to previous years, in 2016, there was a weak expansion ofC. polykrikoidesblooms in the Goheung-Oenarodo area whereC. polykrikoidesblooms were annually initiated in KCW. Lastly, the strong winds from the typhoon Lionrock may also have contributed to the early termination of this dinoflagellate bloom. Together with these findings, the combination of these environmental conditions in 2016, unlike in previous years, may have inhibited the formation ofC. polykrikoidesblooms along the Tongyeong coast

Environmental Enrichment Upregulates Striatal Synaptic Vesicle-Associated Proteins and Improves Motor Function

Environmental enrichment (EE) is a therapeutic paradigm that consists of complex combinations of physical, cognitive, and social stimuli. The mechanisms underlying EE-mediated synaptic plasticity have yet to be fully elucidated. In this study, we investigated the effects of EE on synaptic vesicle-associated proteins and whether the expression of these proteins is related to behavioral outcomes. A total of 44 CD-1® (ICR) mice aged 6 weeks were randomly assigned to either standard cages or EE (N = 22 each). Rotarod and ladder walking tests were then performed to evaluate motor function. To identify the molecular mechanisms underlying the effects of EE, we assessed differentially expressed proteins (DEPs) in the striatum by proteomic analysis. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry were conducted to validate the expressions of these proteins. In the behavioral assessment, EE significantly enhanced performance on the rotarod and ladder walking tests. A total of 116 DEPs (54 upregulated and 62 downregulated proteins) were identified in mice exposed to EE. Gene ontology (GO) analysis demonstrated that the upregulated proteins in EE mice were primarily related to biological processes of synaptic vesicle transport and exocytosis. The GO terms for these biological processes commonly included Synaptic vesicle glycoprotein 2B (SV2B), Rabphilin-3A, and Piccolo. The qRT-PCR and western blot analyses revealed that EE increased the expression of SV2B, Rabphilin-3A and Piccolo in the striatum compared to the control group. Immunohistochemistry showed that the density of Piccolo in the vicinity of the subventricular zone was significantly increased in the EE mice compared with control mice. In conclusion, EE upregulates proteins associated with synaptic vesicle transport and exocytosis such as SV2B, Rabphilin-3A and Piccolo in the striatum. These upregulated proteins may be responsible for locomotor performance improvement, as shown in rotarod and ladder walking tests. Elucidation of these changes in synaptic protein expression provides new insights into the mechanism and potential role of EE

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19

IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19