Missing Value Imputation of Time-Series Air-Quality Data via Deep Neural Networks.

To prevent severe air pollution, it is important to analyze time-series air quality data, but this is often challenging as the time-series data is usually partially missing, especially when it is collected from multiple locations simultaneously. To solve this problem, various deep-learning-based missing value imputation models have been proposed. However, often they are barely interpretable, which makes it difficult to analyze the imputed data. Thus, we propose a novel deep learning-based imputation model that achieves high interpretability as well as shows great performance in missing value imputation for spatio-temporal data. We verify the effectiveness of our method through quantitative and qualitative results on a publicly available air-quality dataset.

Nationwide Representative Survey of Dietary Iodine Intake and Urinary Excretion in Postpartum Korean Women.

Iodine is an essential component of thyroid hormones, but excessive iodine intake can lead to thyroid dysfunction. Traditionally, Korean mothers consume brown seaweed soup (miyeokguk), a high source of iodine, after childbirth. There is controversy regarding the effects of excessive postpartum iodine intake on the health of mothers and infants. Thus far, there have been no nationwide large-scale surveys regarding the status of iodine intake among postpartum women in Korea. Therefore, we conducted a nationwide survey of postpartum dietary iodine intake among Korean women. In total, 1054 Korean women aged ≥19 years, at less than 8 weeks postpartum, participated in this survey. Dietary data were collected using self-reported 2-day dietary records, along with before-and-after meal photos. To evaluate the correlation between dietary iodine and urinary iodine excretion (UIE), spot urine, and 24 h urine samples were collected from 98 and 29 participants, respectively. The mean daily iodine intake among all participants was 2945.6 µg, and it gradually decreased over time after childbirth. Dietary iodine intake was significantly correlated with 24 h UIE (r = 0.396, p < 0.05) and spot urine UIE (r = 0.312, p < 0.05). Follow-up studies are required to examine the influence of excessive postpartum iodine intake on thyroid health in mothers and their infants.

Enhanced Single Image Super Resolution Method Using Lightweight Multi-Scale Channel Dense Network.

Super resolution (SR) enables to generate a high-resolution (HR) image from one or more low-resolution (LR) images. Since a variety of CNN models have been recently studied in the areas of computer vision, these approaches have been combined with SR in order to provide higher image restoration. In this paper, we propose a lightweight CNN-based SR method, named multi-scale channel dense network (MCDN). In order to design the proposed network, we extracted the training images from the DIVerse 2K (DIV2K) dataset and investigated the trade-off between the SR accuracy and the network complexity. The experimental results show that the proposed method can significantly reduce the network complexity, such as the number of network parameters and total memory capacity, while maintaining slightly better or similar perceptual quality compared to the previous methods.

A model for population exposure to PM2.5: Identification of determinants for high population exposure in Seoul.

Outdoor concentrations of particulate matter with an aerodynamic diameter of <2.5 µm (PM2.5) are often used as a surrogate for population exposure to PM2.5 in epidemiological studies. However, people spend most of their daily activities indoors; therefore, the relationship between indoor and outdoor PM2.5 concentrations should be considered in the estimation of population exposure to PM2.5. In this study, a population exposure model was developed to predict seasonal population exposure to PM2.5 in Seoul, Korea. The input data for the population exposure model comprised 3984 time-location patterns, outdoor PM2.5 concentrations, and the microenvironment-to-outdoor PM2.5 concentrations in seven microenvironments. A probabilistic approach was used to develop the Korea simulation exposure model. The determinants for the population exposure group were identified using a multinomial logistic regression analysis. Population exposure to PM2.5 varied significantly among the three seasons (p < 0.01). The mean ± standard deviation of population exposures to PM2.5 was 21.3 ± 4.0 µg/m3 in summer, 9.8 ± 2.7 µg/m3 in autumn, and 29.9 ± 10.6 µg/m3 in winter. Exposure to PM2.5 higher than 35 µg/m3 mainly occurred in winter. Gender, age, working hours, and health condition were identified as significant determinants in the exposure groups. An "unhealthy" health condition was the most significant determinant. The high PM2.5 exposure group was characterized as a higher proportion of males of a lower age with longer working hours. The population exposure model for PM2.5 could be used to implement effective interventions and evaluate the effectiveness of control policies to reduce exposure.

Commentary on "Novel Interaction of the Dopamine D2 Receptor and the Ca2+ Binding Protein S100B: Role in D2 Receptor Function".

We previously proposed that the dopamine D2 receptor-interacting protein S100B binds to a putative S100B-binding motif at residues R233-L240 toward the N terminus of the third intracellular loop. We used in vitro pull-down assays with FLAG-tagged fragments of the rat dopamine D2 receptor third intracellular loop (D2-IC3) and in vitro-synthesized S100B to evaluate this hypothesis. Our results indicate that the putative S100B-binding motif is neither necessary nor sufficient for strong binding of S100B to D2-IC3. Instead, two residues at the junction of the fifth membrane-spanning domain and the cytoplasmic extension of that α-helical domain, K211-I212, are required for robust, calcium-sensitive binding of S100B. This is also the approximate location of previously identified determinants for the binding of arrestin and calmodulin. A D2 receptor mutation converting I212 to phenylalanine has been described in patients with a hyperkinetic movement disorder. SIGNIFICANCE STATEMENT: S100B is a small calcium-binding protein that modulates signaling by the dopamine D2 receptor. New data suggest that the previous hypothesis about the involvement of an S100B-binding motif is incorrect, and that an important determinant of S100B binding includes a residue that is mutated in patients with a hyperkinetic movement disorder.

AniScan Using Extracellular Cyclic AMP-Dependent Protein Kinase A as a Serum Biomarker Assay for the Diagnosis of Malignant Tumors in Dogs.

The early detection of tumors improves chances of decreased morbidity and prolonged survival. Serum biomarkers are convenient to use and have several advantages over other approaches, such as accuracy and straightforward protocols. Reliable biomarkers from easily accessible sources are warranted for the development of cost-effective assays for routine screening, particularly in veterinary medicine. Extracellular c-AMP-dependent protein kinase A (ECPKA) is a cytosolic leakage enzyme. The diagnostic accuracy of detecting autoantibodies against ECPKA was found to be higher than that of ECPKA activity from enzymatic assays, which use a complicated method. Here, we investigated the diagnostic significance of measuring serum ECPKA autoantibody levels using an in-house kit (AniScan cancer detection kit; Biattic, Anyang, Korea). We used sera from 550 dogs, including healthy dogs and those with malignant and benign tumors. Serum ECPKA and immunoglobulin G were determined using the AniScan cancer detection kit. ECPKA autoantibody levels were significantly higher (p < 0.01) in malignant tumors than in benign tumors, non-tumor diseases, and healthy controls. On the basis of sensitivity and specificity values, AniScan ECPKA is a rapid and easy-to-use assay that can be applied to screen malignant tumors from benign tumors or other diseases in dogs.

Consumer exposure and risk assessment to selected chemicals of mold stain remover use in Korea.

Mold stain remover (MSR) is used to clean mold and mildew spots from surfaces and contains a variety of chemical substances. In this study, we estimated the inhalation and dermal exposures associated with the use of trigger spray MSRs, and performed screening-level risk assessments for the use of this type of product in Korea. Inhalation and dermal exposures were estimated using exposure algorithms based on exposure factors obtained from a nationwide survey of 10,000 participants and chemical analyses of the four most popular trigger spray MSRs. The hazard quotients (HQs) for noncancer risk and excess cancer risk (ECR) were calculated for each chemical. The mean inhalation exposure estimates for formaldehyde, benzene, chloroform, and carbon tetrachloride were 6.9 × 10-7, 1.7 × 10-7, 5.4 × 10-6, and 2.7 × 10-5 mg/kg/day, respectively. Dermal exposures of the chemicals were 5.7-6.5 times higher than inhalation exposures. The HQs for total exposure were all below 1, which indicated little noncancer risk from the use of MSRs. The safe ECR value of 1 × 10-6, was exceed in one subject for inhalation exposure of benzene and four subjects for dermal exposure of formaldehyde, while 19.8% for dermal exposure of benzene were above this value. Therefore, use of trigger spray MSRs in Korea should require more detailed exposure and risk assessment, especially for benzene.

Correction to: Differentiation of endogenous and exogenous γ-Hydroxybutyrate in rat and human urine by GC/C/IRMS.

The above article was published online with incorrect author names. The right spelling should be Dong-Hun Lee instead of Donghun Lee, Sanggil Choe instead of Sanggil Choi. The correct names are presented here. The original article has been corrected.

Differentiation of endogenous and exogenous γ-Hydroxybutyrate in rat and human urine by GC/C/IRMS.

Gamma (γ)-hydroxybutyric acid (GHB) has been reported to be an endogenous compound in the mammalian brain. It used to treat symptoms of alcohol, opioid, and drug withdrawal and cataplexy of narcolepsy. However, it is often used for criminal purposes because it is colorless, tasteless, and has short half-life. For this reason, there is a need for a method of distinguishing between endogenous and exogenous GHB administration. Therefore, urine from rat before administration of GHB and GHB urine after the single intraperitoneal injection of GHB as 30 mg/100 g were collected from Sprague-Dawley rats (7 weeks old, 10 males and females). Negative control urine, urine from individuals suspected of taking GHB, and urine from victims who were GHB-involved crime were collected. In urine samples, GHB was extracted with two-step SPE and collected fraction was derivatized and analyzed by GC/MS and GC/C/IRMS. In GC/MS and GC/C/IRMS analysis of rat urine, there was a statistically significant difference between urine from rat before administration of GHB and GHB rat urine (p < 0.05). In GC/MS analysis of human urine samples, there was no significant difference among human urine groups (negative control, suspects' urine, and victims' urine), but in GC/C/IRMS analysis of human urine samples, there was a statistically significant difference among human urine groups (p = 0.0001). Through these results, GC/C/IRMS can be more effective tool to identify endogenous and exogenous GHB in urine than GC/MS. This study can build a drug management system in forensic investigation agency and offer interpretation method to forensic science and court.

Web-based Korean maximum residue limit evaluation tools: an applied example of maximum residue limit evaluation for trichlorfon in fishery products.

To ensure public safety against veterinary drug residues in food products from animal sources, maximum residue limits (MRLs) should be established by scientific evidence and a transparent estimation process. The Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) developed an Excel workbook-based tool for MRLs evaluation in 2003. In this study, we developed a web-based tool for MRL evaluation, called Korean MRL evaluation tools (KMET). While KMET used algorithms of JECFA workbook, it added some databases (e.g., Korean food consumption database) and provided additional functions (e.g., selection of target marker residue). Web-based KMET enabled regulatory policy makers to update the database. All input data and output results related to MRL evaluation based on residue depletion and food consumption datasets were archived and provided overall processes from the initial depletion data entry to MRL establishment with user-friendly interface. Our results demonstrated the stepwise processes whereby MRL for trichlorfon in the muscle of Paralichthys olivaceus was established with functional descriptions of KMET. MRL for trichlorfon derived from KMET was proposed and notified by the Ministry of Food and Drug Safety in 2018.

Development of nutritional risk assessment platform in Korea.

Risk assessment has been used to prevent health problems associated with eating habits in response to increased interest in a balanced diet. For nutritional risk assessment (NRA), it is important to 1) consider personal nutrition status based on year-round dietary intake, 2) organize core datasets such as food composition, intake, and health based guidance value (HBGV) datasets with public confidence, and 3) assess and predict the effects by using the computerized NRA tool. Our research staff constructed an integrated database system by compiling and organizing core datasets produced sporadically by different organizations and with different formats and developed a nutritional exposure and risk assessment system called Nutri-Risk (NUTRItional RISK assessment platform), which contained the database. Nutri-Risk is not only capable of NRA, but also contains additional data service functions. Here, the compilations and organization of an integrated database are outlined. In addition, the overall architectures of Nutri-Risk and dietary modeling are described and predictive simulation functions to support the regulatory decisions related to nutritional fortification or reduction policy were demonstrated.

The correlation between concentrations of zolpidem and benzodiazepines in segmental hair samples and use patterns.

The aim of this study was to investigate the correlation between histories of zolpidem and benzodiazepines use and their concentrations in hair as determined by segmental hair analysis, that is, by analyzing hair samples taken 0-1, 1-2, 2-3, 3-4, 4-5, and 5-6cm etc. and 0-3cm from the scalp, and whole hair. Of the 23 hair samples examined, 18 were collected from patients in a rehabilitation program and five were from patients that had taken zolpidem only once by prescription. All 23 patients provided written informed consent after reviewing the research plan, described their zolpidem and benzodiazepines use histories accurately, and provided hair samples, which were weighed, washed, cut into lengths of <1mm, and extracted in 100% methanol for 16h (diazepam-d5 was used as an internal standard). Extracts were evaporated under reduced pressure and reconstituted with aqueous methanol (1:1 v/v). These extracts (10µL) were analyzed by Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS). The method used was validated by determining LOD, LOQ, calibration curves, intra- and inter-accuracies, precisions, matrix effects, process efficiencies, extraction efficiencies, and processed sample stabilities. Five hundred and ninety-five 1cm hair segments showed 61.59% positive probability and 86.71% negative probability of quality correlation between zolpidem and benzodiazepines use and concentrations in hair. Good qualitative correlations were observed between drug use and detection in hair. False positivity and false negativity were very low. Of the hair samples taken from patients in a rehabilitation program, subject nos. 4, 5, and 12 had correlation coefficients of 0.68, 0.54 and 0.71, respectively, for relationships between zolpidem use and concentration of zolpidem in hair. For the 5 patients taking only a single dose of zolpidem (10mg), the average zolpidem concentrations in hair were 20, 15 and 40pg/mg after 5, 30 and 60 days, respectively. This study shows a relationship between history of zolpidem and benzodiazepines use and their concentrations in 1cm hair segment.

Korean Ministry of Environment's web-based visual consumer product exposure and risk assessment system (COPER).

With support from the Korean Ministry of the Environment (ME), our interdisciplinary research staff developed the COnsumer Product Exposure and Risk assessment system (COPER). This system includes various databases and features that enable the calculation of exposure and determination of risk caused by consumer products use. COPER is divided into three tiers: the integrated database layer (IDL), the domain specific service layer (DSSL), and the exposure and risk assessment layer (ERAL). IDL is organized by the form of the raw data (mostly non-aggregated data) and includes four sub-databases: a toxicity profile, an inventory of Korean consumer products, the weight fractions of chemical substances in the consumer products determined by chemical analysis and national representative exposure factors. DSSL provides web-based information services corresponding to each database within IDL. Finally, ERAL enables risk assessors to perform various exposure and risk assessments, including exposure scenario design via either inhalation or dermal contact by using or organizing each database in an intuitive manner. This paper outlines the overall architecture of the system and highlights some of the unique features of COPER based on visual and dynamic rendering engine for exposure assessment model on web.

ΔN-ASPP2, a novel isoform of the ASPP2 tumor suppressor, promotes cellular survival.

ASPP2 is a tumor suppressor that works, at least in part, through enhancing p53-dependent apoptosis. We now describe a new ASPP2 isoform, ΔN-ASPP2, generated from an internal transcription start site that encodes an N-terminally truncated protein missing a predicted 254 amino acids. ΔN-ASPP2 suppresses p53 target gene transactivation, promoter occupancy, and endogenous p53 target gene expression in response to DNA damage. Moreover, ΔN-ASPP2 promotes progression through the cell cycle, as well as resistance to genotoxic stress-induced growth inhibition and apoptosis. Additionally, we found that ΔN-ASPP2 expression is increased in human breast tumors as compared to adjacent normal breast tissue; in contrast, ASPP2 is suppressed in the majority of these breast tumors. Together, our results provide insight into how this new ASPP2 isoform may play a role in regulating the ASPP2-p53 axis.

Chemically induced hepatotoxicity in human stem cell-induced hepatocytes compared with primary hepatocytes and HepG2.

Stem cell-induced hepatocytes (SC-iHeps) have been suggested as a valuable model for evaluating drug toxicology. Here, human-induced pluripotent stem cells (QIA7) and embryonic stem cells (WA01) were differentiated into hepatocytes, and the hepatotoxic effects of acetaminophen (AAP) and aflatoxin B1 (AFB1) were compared with primary hepatocytes (p-Heps) and HepG2. In a cytotoxicity assay, the IC50 of SC-iHeps was similar to that in p-Heps and HepG2 in the AAP groups but different from that in p-Heps of the AFB1 groups. In a multi-parameter assay, phenotypic changes in mitochondrial membrane potential, calcium influx and oxidative stress were similar between QIA7-iHeps and p-Heps following AAP and AFB1 treatment but relatively low in WA01-iHeps and HepG2. Most hepatic functional markers (hepatocyte-specific genes, albumin/urea secretion, and the CYP450 enzyme activity) were decreased in a dose-dependent manner following AAP and AFB1 treatment in SC-iHeps and p-Heps but not in HepG2. Regarding CYP450 inhibition, the cell viability of SC-iHeps and p-Heps was increased by ketoconazole, a CYP3A4 inhibitor. Collectively, SC-iHeps and p-Heps showed similar cytotoxicity and hepatocyte functional effects for AAP and AFB1 compared with HepG2. Therefore, SC-iHeps have phenotypic characteristics and sensitivity to cytotoxic chemicals that are more similar to p-Heps than to HepG2 cells.

Relationship between methamphetamine use history and segmental hair analysis findings of MA users.

The aim of this study was to investigate the relationship between methamphetamine (MA) use history and segmental hair analysis (1 and 3cm sections) and whole hair analysis results in Korean MA users in rehabilitation programs. Hair samples were collected from 26 Korean MA users. Eleven of the 26 subjects used cannabis with MA and two used cocaine, opiates, and MDMA with MA. Self-reported single dose of MA from the 26 subjects ranged from 0.03 to 0.5g/one time. Concentrations of MA and its metabolite amphetamine (AP) in hair were determined by gas chromatography mass spectrometry (GC/MS) after derivatization. The method used was well validated. Qualitative analysis from all 1cm sections (n=154) revealed a good correlation between positive or negative results for MA in hair and self-reported MA use (69.48%, n=107). In detail, MA results were positive in 66 hair specimens of MA users who reported administering MA, and MA results were negative in 41 hair specimens of MA users who denied MA administration in the corresponding month. Test results were false-negative in 10.39% (n=16) of hair specimens and false-positive in 20.13% (n=31) of hair specimens. In false positive cases, it is considered that after MA cessation it continued to be accumulated in hair still, while in false negative cases, self-reported histories showed a small amount of MA use or MA use 5-7 months previously. In terms of quantitative analysis, the concentrations of MA in 1 and 3cm long hair segments and in whole hair samples ranged from 1.03 to 184.98 (mean 22.01), 2.26 to 89.33 (mean 18.71), and 0.91 to 124.49 (mean 15.24)ng/mg, respectively. Ten subjects showed a good correlation between MA use and MA concentration in hair. Correlation coefficient (r) of 7 among 10 subjects ranged from 0.71 to 0.98 (mean 0.85). Four subjects showed a low correlation between MA use and MA concentration in hair. Correlation coefficient (r) of 4 subjects ranged from 0.36 to 0.55. Eleven subjects showed a poor correlation between MA use and MA concentration in hair. Correlation between MA use and MA concentration in hair of remaining one subject could not be determined or calculated. In this study, the correlation between accurate MA use histories obtained by psychiatrists and well-trained counselors and MA concentrations in hair was shown. This report provides objective scientific findings that should considerably aid the interpretation of forensic results and of the results of trials related to MA use.

Giant ureteral polyps causing proximal ureter obstruction: emphasis on the surgical method and ureteroscopy.

We describe here the case of a 13-year-old boy who had right flank pain for 3 months. An intravenous pyelogram showed filling defects in the right upper part of the ureter as well as hydronephrosis. Because the diseased part of the ureter was about 5 cm in length and we wished to avoid short ureter after surgery, we performed a minimal segmental resection of the ureter including the entire stalk. Perioperative ureteroscopic examination showed another polyp 3 cm below the primary polyp, which was also removed. End-to-end ureteral anastomosis was performed without mobilization of the kidney. Frozen and formal microscopic examination showed that these polyps were fibroepithelial.

Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response thresholds.

The expression of ASPP2 (53BP2L), a proapoptotic member of a family of p53-binding proteins, is frequently suppressed in many human cancers. Accumulating evidence suggests that ASPP2 inhibits tumor growth; however, the mechanisms by which ASPP2 suppresses tumor formation remain to be clarified. To study this, we targeted the ASPP2 allele in a mouse by replacing exons 10-17 with a neoR gene. ASPP2(-/-) mice were not viable because of an early embryonic lethal event. Although ASPP2(+/-) mice appeared developmentally normal, they displayed an increased incidence of a variety of spontaneous tumors as they aged. Moreover, gamma-irradiated 6-week-old ASPP2(+/-) mice developed an increased incidence of high-grade T cell lymphomas of thymic origin compared with ASPP2(+/+) mice. Primary thymocytes derived from ASPP2(+/-) mice exhibited an attenuated apoptotic response to gamma-irradiation compared with ASPP2(+/+) thymocytes. Additionally, ASPP2(+/-) primary mouse embryonic fibroblasts demonstrated a defective G(0)/G(1) cell cycle checkpoint after gamma-irradiation. Our results demonstrate that ASPP2 is a haploinsufficient tumor suppressor and, importantly, open new avenues for investigation into the mechanisms by which disruption of ASPP2 pathways could play a role in tumorigenesis and response to therapy.

MDMX promotes proteasomal turnover of p21 at G1 and early S phases independently of, but in cooperation with, MDM2.

We have shown previously that MDM2 promotes the degradation of the cyclin-dependent kinase inhibitor p21 through a ubiquitin-independent proteolytic pathway. Here we report that the MDM2 analog, MDMX, also displays a similar activity. MDMX directly bound to p21 and mediated its proteasomal degradation. Although the MDMX effect was independent of MDM2, they synergistically promoted p21 degradation when coexpressed in cells. This degradation appears to be mediated by the 26S proteasome, as MDMX and p21 bound to S2, one of the subunits of the 19S component of the 26S proteasome, in vivo. Conversely, knockdown of MDMX induced the level of endogenous p21 proteins that no longer cofractionated with 26S proteasome, resulting in G(1) arrest. The level of p21 was low at early S phase but markedly induced by knocking down either MDMX or MDM2 in human cells. Ablation of p21 rescued the G(1) arrest caused by double depletion of MDM2 and MDMX in p53-null cells. These results demonstrate that MDMX and MDM2 independently and cooperatively regulate the proteasome-mediated degradation of p21 at the G(1) and early S phases.

SCF TrCP1 activates and ubiquitylates TAp63gamma.

p63 is a member of the p53 tumor suppressor family that is critical for epithelial differentiation and also has an important role in cancer progression. Currently, the molecular mechanisms governing regulation of p63 function remain largely unclear. This study identifies a unique E3 ubiquitin ligase for p63, SCF(betaTrCP1). SCF(betaTrCP1) is able to bind p63gamma isoforms, with a higher affinity for the TAp63gamma isoform. Strikingly, co-expression of TAp63gamma and betaTrCP1 leads to the stabilization of TAp63gamma. This stabilization of TAp63gamma leads to up-regulation of p21 at the mRNA and protein level by increased binding of TAp63gamma at the p21 promoter. The up-regulation of p21 causes a subsequent increase in G(1) phase cell cycle arrest. Last, SCF(betaTrCP1) is able to ubiquitylate TAp63gamma, and this ubiquitylation, as well as the increased activity of TAp63gamma, is ablated with the expression of a ubiquitin-deficient mutant of betaTrCP1 (DeltaFbetaTrCP1). Therefore, our study reveals that SCF(betaTrCP1) is an E3 ligase that activates p63 through ubiquitylation.