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This study aimed to investigate the association between proton pump inhibitor (PPI) use and risk of sensorineural hearing loss (SNHL) or tinnitus in patients with type 2 diabetes using hospital- and population-based data.For the case-control study using the Asan Biomedical Research Environment database, the characteristics between cases and sex-, age- and index-year-matched controls were compared by the chi-squared test. Conditional logistic regression was used to estimate the odds ratios (ORs). For the cohort study using the Korean National Health Insurance Service - National Sample Cohort, the hazard ratios (HRs) for SNHL or tinnitus associated with PPI use were analysed by the Cox proportional hazard regression model.The case-control study included 1379 cases and 5512 matched controls. After adjustment, PPI use was associated with an increased risk of SNHL or tinnitus (OR 1.61, 95% confidence interval [CI] 1.30-1.99). The ORs were higher for current or recent use of PPI and high average daily dose. In the cohort study including 17 233 pairs of PPI users and nonusers after propensity score matching, the risk of SNHL or tinnitus increased in PPI users compared with nonusers (HR 1.50, 95% CI 1.40-1.61). In the stratified analyses, risks remained significant and the magnitude of association was relatively high in those of younger age, patients without gastroesophageal reflux disease and patients not receiving histamine 2 receptor blockers.Our study suggests that PPI use is associated with an increased risk of SNHL or tinnitus. Given the widespread use of PPIs, the potential ototoxic effects of PPIs remain an important concern.

Serum concentrations of voriconazole are difficult to predict, especially in pediatric patients, because of its complex pharmacokinetic characteristics. This study aimed to identify the factors associated with the concentration of voriconazole in pediatric patients.This cohort study was based on retrospective data collection and involved the administration of voriconazole to pediatric patients younger than 18 years, between January 2010 and August 2017. Electronic medical records of the patients were reviewed to collect demographic characteristics, voriconazole treatment regimen, and factors that could potentially influence voriconazole trough concentrations. A voriconazole trough serum concentration of less than 1.0 mcg/mL or greater than 5.5 mcg/mL was defined as outside the therapeutic range and was set as the outcome of this study.Among the 114 patients enrolled, 61 patients were included in the analysis. Oral administration of a maintenance dose of voriconazole and C-reactive protein (CRP) level were significantly and independently associated with a low initial trough concentration of voriconazole (1.0 mcg/mL). Alanine aminotransferase levels were a significant factor associated with a high initial trough concentration of voriconazole (5.5 mcg/mL) after adjusting for sex, age, weight, and serum creatinine (odds ratio 5.42; 95% confidence interval 1.34-21.97).Considering the variability of voriconazole concentrations in pediatric patients, monitoring certain parameters and considering the route of administration could help determine the therapeutic range of voriconazole and subsequently avoid unwanted effects.

Although several studies have examined tyrosine kinase inhibitor (TKI)-induced hepatotoxicity, the majority of patients in those studies displayed low-grade (grade I–II) hepatotoxicity. The purpose of this study was to investigate factors affecting high-grade (grade III–IV) hepatotoxicity of TKIs. This multi-center, retrospective study used individual patient data from five studies that examined factors affecting hepatotoxicity by TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib). Odds ratio (OR) and adjusted OR (AOR) were estimated from univariate and multivariate analyses, respectively. Data from 1279 patients treated with TKIs were analyzed. The rate of patients who experienced high-grade hepatotoxicity after TKI administration was 5.5%. In multivariable analysis, H2 blockers and CYP3A4 inducers increased high-grade hepatotoxicity 2.2- (95% CI 1.255–3.944) and 3.3-fold (95% CI 1.260–8.698), respectively. Patients with liver metastasis revealed a 3.4-fold (95% CI 1.561–7.466) higher risk of high-grade hepatotoxicity. Among underlying malignancies, pancreatic cancer and other cancers including acute lymphoblastic leukemia increased the risk of high-grade hepatotoxicity by 2.6- and 24.3-fold, respectively, whereas breast cancer decreased the risk (AOR 0.3, 95% CI 0.106–0.852), compared to non-small cell lung cancer. In patients who administrated TKIs which form reactive metabolites, use of CYP3A4 inducers and liver metastasis increased incidence of high-grade hepatotoxicity by 3.0- and 2.3-fold, respectively. In patients with EGFR mutation, exon 19 deletion and use of proton pump inhibitors were risk factors for high-grade hepatotoxicity in addition to liver metastasis and use of H2 blockers. The use of H2 blockers, presence of liver metastasis, and CYP3A4 inducers were associated with high-grade hepatotoxicity of TKIs. In subgroup analyses, presence of exon 19 deletion, and/or proton pump inhibitors, was additional risk factors for high-grade hepatotoxicity in special patients and use of specific TKIs. Close liver function monitoring is recommended, especially in patients with liver metastasis or using H2 blockers or CYP3A4 inducers.

Background: Statins have emerged as protective agents against sensorineural hearing loss (SNHL) associated with dyslipidemia, but the effects of statins on SNHL are not consistent. The purpose of this study was to investigate the association between statin use and the risk of SNHL using a hospital cohort. Methods: This nested case-control study included type 2 diabetic patients over the age of 18 years without a history of hearing loss. Of these, 1379 patients newly diagnosed with SNHL or tinnitus were classified as cases, and 5512 patients matched to the cases based on age, sex, and index year were classified as controls. Chi-squared tests were used to compare categorical variables between the two groups. Odds ratios (ORs) and adjusted odds ratios (AOR) were calculated from univariate and multivariable unconditional logistic regression analyses, respectively. Results: There was a significant difference in the prevalence of statin use between the cases and controls (53.7% vs. 61.2%, respectively, p &lt, 0.001). The use of statins in type 2 diabetic patients significantly reduced the risk of SNHL or tinnitus by 24.8% (95% CI 14.2–34.1%, p &lt, 0.001) after controlling for confounders. Similar results were found for the association between statin use and SNHL (AOR = 0.706, 95% CI 0.616–0.811, p &lt, 0.001). The protective effects of statins against SNHL were consistent regardless of age and sex. Conclusion: The use of statins for type 2 diabetic patients was significantly associated with a reduced risk of SNHL, regardless of age and sex. Further studies are needed, especially large cohort studies, to evaluate the long-term protective effects of statins.

Growth hormone secretagogue receptor (GHS-R) is widely known to regulate food intake and adiposity, but its role in glucose homeostasis is unclear. In this study, we investigated the expression of GHS-R in mouse pancreatic islets and its role in glycemic regulation. We used Ghsr-IRES-tauGFPmice, with Green Fluorescent Protein (GFP) as a surrogate for GHS-R, to demonstrate the GFP co-localization with insulin and glucagon expression in pancreatic islets, confirming GHS-R expression in β and α cells. We then generated β-cell-specific GHSR-deleted mice with MIP-Cre/ERT and validated that GHS-R suppression was restricted to the pancreatic islets. MIP-Cre/ERT, Ghsrf/f mice showed normal energy homeostasis with similar body weight, body composition, and indirect calorimetry profile. Interestingly, MIP-Cre/ERT, Ghsrf/f mice exhibited an impressive phenotype in glucose homeostasis. Compared to controls, MIP-Cre/ERT, Ghsrf/f mice showed lower fasting blood glucose and insulin, reduced first-phase insulin secretion during a glucose tolerance test (GTT) and glucose-stimulated insulin secretion (GSIS) test in vivo. The isolated pancreatic islets of MIP-Cre/ERT, Ghsrf/f mice also showed reduced insulin secretion during GSIS ex vivo. Further, MIP-Cre/ERT, Ghsrf/f mice exhibited improved insulin sensitivity during insulin tolerance tests (ITT). Overall, our results confirmed GHS-R expression in pancreatic β and α cells, GHS-R cell-autonomously regulated GSIS and modulated systemic insulin sensitivity. In conclusion, β cell GHS-R was an important regulator of glucose homeostasis, and GHS-R antagonists may have therapeutic potential for Type 2 Diabetes.

한국 웹툰은 한국 설화의 원형과 모티프를 디지털 시대의 패러다임과 수용자의 요구에 부합하도록 변용해 재현해왔다. 그 중에서도 특히 ‘이물교구(異物交媾)모티프’가 웹툰의 다양한 장르의 작품에서 나타나는 점이 특이할 만하다. ‘이물교구 모티프’란 인간과 비인간이 관계를 맺는 것을 지칭한다. 표면적으로는 인간과 비인간의 결합을 나타내며 이면적으로는 다양한 존재의 혼종적 관계를 내포한다. 본 연구에서는 네이버에 연재된 웹툰 중, 이물교구 모티프가 적극적으로 활용된 7편의 웹툰을 블라디미르 프로프(Propp, Vladimir)의 이론을 중심으로 그 변용 양상 및 의미를 분석했다. 세부적으로는 웹툰에서 재현된 이물의 이미지와 타자성을 롤랑 바르트(Barthes, Roland)의 이미지론을 적용해 분석했다. 한국의 이물교구 설화는 교구의 주체에 따라 신적 존재와 동물의 결합, 신적존재와 인간의 결합, 인간과 동물의 결합인 세 가지로 유형으로 분류된다. 이러한 이물교구 모티프는 현대의 웹툰에서 수사적, 논리적, 역사적 변형을 통해 수용됐다. 리처드 커니(Richard Kearney)에 따르면 타자성은 타자와 에이리언으로 구분된다. 타자는 차별성을 인정받되 환대할 가치가 있는 이질성을 의미한다. 반면 에이리언은 무의식의 두려움이 투영된 존재로, 불법적이며 환영받지 못하는 안타고니스트로 표상된다. 서구의 설화 및 콘텐츠에서의 이물은 인간과 비인간을 구분하는 이분법적 관념에 따라 에이리언의 외형으로 재현되는 경우가 대다수이다. 반면 한국 웹툰에서 이물은 배척해야 할 타자가 아닌 ‘또 다른 자아’로서 인정받으면서 인간과의 결합 가능성을 드러낸다. 이처럼 한국 웹툰의 이물교구 모티프는 한국 설화 특유의 일원론적 세계관을 계승하면서, 나아가 서구 중심의 주체와 타자에 대한 이항대립을 극복할 수 있는 대안적 가치관을 제시한다. 이는 나아가 포스트 휴먼시대의 인간과 비인간의 관계에 대한 담론에 대안적 가치를 제시할 수 있으리라 기대된다.

Many approaches can derive information about a single speaker's identity from the speech by learning to recognize consistent characteristics of acoustic parameters. However, it is challenging to determine identity information when there are multiple concurrent speakers in a given signal. In this paper, we propose a novel deep speaker representation strategy that can reliably extract multiple speaker identities from an overlapped speech. We design a network that can extract a high-level embedding that contains information about each speaker's identity from a given mixture. Unlike conventional approaches that need reference acoustic features for training, our proposed algorithm only requires the speaker identity labels of the overlapped speech segments. We demonstrate the effectiveness and usefulness of our algorithm in a speaker verification task and a speech separation system conditioned on the target speaker embeddings obtained through the proposed method., Comment: Accepted in Interspeech 2020

Ultraviolet B (UVB) irradiation causes adverse effects on the skin. Corn silk contains flavonoids and other bioactive compounds and antioxidants, which may prevent skin photoaging through antioxidant and anti-inflammatory effects. We aimed to investigate the potential photoprotective effects of dietary corn silk on UVB-induced skin damage in mice and the mechanisms behind these effects on human skin cells. Oral administration of corn silk water extract (CS) (2 or 4 g/kg/day) for 19 weeks decreased epidermal thickness, wrinkle formation, and positive staining for PCNA, Ki67, and 8-OHdG, and increased collagen staining in UVB-irradiated SKH-1 hairless mice compared with controls. The pro-inflammatory NF-&kappa, B target genes (IL-1&beta, iNOS, and COX-2) and MMP-9 expressions were lower in the CS groups, and TGF-&beta, /Smad signaling increased. Low skin lipid peroxidation and blood DNA oxidation levels and high blood glutathione were detected. Antioxidant transcription factor Nrf2-related catalase and SOD1 proteins and glutaredoxin mRNA levels increased. The results of CS extract treatment and UVB irradiation in HaCaT cells showed the same results in Nrf2 and NF-&kappa, B target genes. An LC-MS/MS analysis showed that the CS extract contained potential antioxidants, which might have contributed to its anti-photoaging effects in tissues and cells. CS extract may reduce UVB-induced skin damage through antioxidant and anti-inflammatory mechanisms.

Chronic low-grade inflammation is a hallmark of obesity, which is directly linked to nonalcoholic Fatty Liver Disease (NAFLD) and systemic insulin resistance. Ghrelin receptor, a growth hormone secretagogue receptor (GHS-R), mediates the stimulatory effect of ghrelin on food intake and fat deposition. We previously reported that global ablation of GHS-R in mice decreases adipose inflammation, and GHS-R knockdown in macrophage cell line reduces the expression of pro-inflammatory cytokine genes. To determine the physiological role of GHS-R in macrophages, we generated myeloid-specific GHS-R knockout mice (LysM-Cre;Ghsrf/f). Under diet-induced obesity (DIO), LysM-Cre;Ghsrf/f mice showed reduced circulating inflammatory cytokine levels, attenuated insulin resistance, but no change in body weight. Moreover, DIO-induced NAFLD was ameliorated in LysM-Cre;Ghsrf/f mice, showing reduced inflammation and lipid accumulation in the liver. To understand the regulatory mechanism of macrophage GHS-R in NAFLD pathogenesis and systemic inflammation and insulin sensitivity, we conducted ex vivo studies using bone marrow-derived macrophages (BMDMs). GHS-R deficient BMDMs showed reduced macrophage pro-inflammatory polarization and decreased expression of pro-inflammatory cytokine genes; consistently, exhibiting elevated mitochondrial respiration and improved mitochondrial dynamics. Moreover, the primary hepatocytes treated with conditioned media from BMDMs of LysM-Cre;Ghsrf/f mice showed gene expression of reduced inflammatory cytokines and increased insulin signaling. Taken together, our findings reveal that GHS-R is an important immunometabolic regulator and governs macrophage polarization through regulating mitochondrial function and cellular metabolism of macrophages, moderating hepatic and systemic inflammation and insulin sensitivity. GHS-R antagonist may present a novel therapeutic strategy for the metabolic disorders such as NAFLD. Disclosure D. Kim: None. J. Lee: None. Q. Pan: None. J. Noh: None. H. Wang: None. H. Han: None. C. Wu: None. S. Guo: None. Y. Sun: None. Funding American Diabetes Association (1-15- BS-177 to Y.S.); National Institutes of Health

Long-term surveillance is necessary to identify patients at risk of developing secondary lymphedema after breast cancer surgery. We assessed how sodium selenite supplementation would affect breast cancer-related lymphedema (BCRL) symptoms and parameters in association with antioxidant effects. A randomized, double-blind, controlled trial was conducted on 26 participants with clinical stage II to III BCRL. The control group (CTRL, n = 12) and selenium group (SE, n = 14) underwent five sessions of 0.9% saline and 500 &mu, g sodium selenite (Selenase&reg, ) IV injections, respectively, within 2 weeks. All patients were educated on recommended behavior and self-administered manual lymphatic drainage. Clinical diagnosis on lymphedema by physicians, bioimpedance data, blood levels of oxidative markers, including glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde (MDA), glutathione peroxidase activity (GSH-Px), and serum oxygen radical absorbance capacity (ORAC) levels, were investigated at timelines defined as baseline, 2-week, and follow-up. Sodium selenite increased whole blood selenium concentration in the SE group. Compared to the baseline, at 2 weeks, 75.0% of participants in clinical stage showed improvement, while there was no change in the CTRL group. At follow-up, 83.3% and 10.0% of the SE and CTRL, respectively, showed stage changes from III to II (p = 0.002). Extracellular water (ECW) ratios were significantly reduced at 2 weeks and follow-up, only in the SE group. Blood GSH, GSSG, GSH/GSSG ratio, MDA, and ORAC levels did not change by selenium supplementation. Sodium selenite improved diagnostic stages of BCRL along with ECW ratios, although the beneficial effect might not be related to its antioxidant activity. Selenite&rsquo, s effect on lymphedema may be associated with non-antioxidant properties, such as anti-inflammation and immune function. Further mechanistic research using a larger population is needed.

Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed studies analyzing the effects of PPI use on CDI risk are lacking. The present study investigated the association of the dose, duration, and types of PPIs with CDI risk. A single-center, cohort study was conducted on patients admitted to a hospital. The exposed cohort comprised patients who were prescribed PPIs at least once during the study period, and a control cohort was prepared by randomly assigning an index date to patients who did not use PPIs ensuring the same distribution of index dates as in the exposed cohort and matching sex, age, hospitalization period, and date of admission. PPI use increased the risk of CDI by 1.8-fold [95% confidence interval (CI) 1.5–2.2]. CDI risk increased by 1.8-fold with esomeprazole (95% CI 1.4–2.2) and 2.0-fold with pantoprazole (95% CI 1.5–2.8). Patients who used a high dose had a higher risk than those who used a medium dose [adjusted hazard ratio (HR) 2.0 vs 1.3]. The risk of CDI increased 4.2-fold when the PPI exposure period was 6 days or shorter than 6 days. Our study showed that PPI use was associated with an increased risk of developing CDI and the risk of CDI was dose dependent. Therefore, PPIs should only be used at proper doses and only for the necessary indications to avoid CDI risk.

In this paper, we propose a deep learning-based psychological stress detection algorithm using speech signals. With increasing demands for communication between human and intelligent systems, automatic stress detection is becoming an interesting research topic. Stress can be reliably detected by measuring the level of specific hormones (e.g., cortisol), but this is not a convenient method for the detection of stress in human-machine interactions. The proposed algorithm first extracts mel-filterbank coefficients using pre-processed speech data and then predicts the status of stress output using a binary decision criterion (i.e., stressed or unstressed) using long short-term memory (LSTM) and feed-forward networks. To evaluate the performance of the proposed algorithm, speech, video, and bio-signal data were collected in a well-controlled environment. We utilized only speech signals in the decision process from subjects whose salivary cortisol level varies over 10%. Using the proposed algorithm, we achieved 66.4% accuracy in detecting the stress state from 25 subjects, thereby demonstrating the possibility of utilizing speech signals for automatic stress detection.

This paper aims to propose the educational concept and design model of a Smart Board Game appropriate for lower elementary grade students. The Smart Board Game refers to a hybrid, or ‘convergent’, game format based on the offline format of the conventional board game augmented through the use of smart devices. The substantive aspects of this game format utilize the procedural deduction and problem-solving skills applicable in storytelling methodologies and games, in order to generate and propose contents ideal for the educational environment. The development of the Smart Board Game is conducted through the following stages. First, the study analyzes a number of Smart Board Games currently popular in Korea and abroad, based on identification of the key components and processes of the board game format. The subsequent review of the science curriculum for lower elementary grades aims to determine the aspects conducive for application to Smart Board Games. Lastly, the theoretical framework outlined through the previous stages is used as the basis for the proposal of a detailed model of contents for the smart board game concept.

The purpose of this paper is primarily to examine the characteristics of female protagonists in video games and to study the process through which they attain the identities of heroes. Over the 17 years of perpetual and repeated incarnation in the Tomb Raider series, Lara Croft serves as both a leading model and a mythical signifier for female protagonists. Therefore, we seek to identify the gender consciousness that underlies female characterization in video games, with a particular focus on Lara Croft. As a popular narrative medium, video games feature female heroes to represent gender values of the time. The synchronic and diachronic analysis of Croft’s features as a character and identity as a female hero leads us to the conclusion that female protagonists merely serve as the subject of desire, recreated to satisfy sadomasochistic male fantasies. They fulfill men’s sadistic desires through their glamorous physique and masochist desires, as reflected by their behavior. Through a process of denial regarding femininity, common representations as the mother, and the re-codifying of patriarchal values solely in favor of the patriarch, female protagonists faced the confusion of dual identity, wherein they would equate themselves with male heroes, while simultaneously identifying themselves as damsels-in-distress. To summarize, video games exclusively allow the existence of heroes, while a true heroine has yet to emerge. Female characters are limited by their adherence to patriarchal conventions even in the virtual world, which is like a mirror world and an alternative world at the same time.

Webtoons are popularly consumed in Korea. Especially the `Dailytoons`, which are composed of short episodes, are the most popular form of webtoons. This study focuses on the specific narrative structure of the dailytoons, and also tries to figure out what makes webtoons so popular. This study tried to analyze the special features of figures, events, and backgrounds of webtoons. Particularly in webtoons, Korean metropolitan is employed as a background and the daily life of the lower middle class in this big city is importantly used in the story. Each cut of a webtoon consists of simple words and images, and it shows the life of modern people and the way they recognize the reality. The important thing is that the image and the narrative of one cut often appears contradictively. `Irony` occurs in the process of combination of the words and images. And the life of the lower middle class is depicted `fun-and-sadly` through irony. For example, the main characters of webtoons are portrayed as persecuted victims because of their lack of information or ignorance. At this point, they are described ridiculously by a play on words. In addition, webtoons often presents twist plots using the scroll bars and margins of `web` interface. Also it uses parody to show reality in satire. With irony, webtoons represent the daily life of the public, which is cynical as well as humorous. This study tried to suggest that webtoons should attribute its success to `irony` in its narrative.

The purpose of this study is to analyze the story-retelling structure of tablet PC-based applications that designed to help infants to create stories. Owing to the popularization and the usability of smart devices, infants have become from content consumers to creators who reconstruct stories in creative ways, based on the stories they heard. In those participatory process, infants experience enjoying stories independently and expanding the meaning of texts. Story-retelling is an adequate methodology that cultivates creativity, expressiveness, and literacy ability to infant. Consequently, this study investigates three types of story-retelling in , , and , and searches structure elements and methods of story-retelling in integrated approach. In conclusion, the story-retelling applications that provide `creative gap` have educational value, because they allow infants to demonstrate imagination by filling in the gap and to realize the rule of stories.

This study was conducted to analyze the contents of the e-book and detail the properties of e-book experience. was written by Anthony E. Zuiker who is famous for American TV series C.S.I. is a thriller and is published for the iPad. This e-book provides three levels of interaction within the book. Zuiker calls this e-book a "Digi-Novel". The readers can choose the level of interaction:novel, digi-novel or ultimate digi-novel. The basic background story is the same. So we can compare the difference of reading experience of three levels. Digi-Novel are differentiated from other e-books through their complex characters. Consequently a well-throughout detailed background story is very important for Digi-Novels. In addition, it enrich the reading experience through the interactive elements and multimedia functions of iPad. Readers can interact with clues, manipulate evidence and listen to audio sounds. This serves to immerse the readers much more deeply in the reading experience and makes readers feel like they are a part of story.

In console game, controller is important medium that connects the users and contents. And technical advance and rising demand for console game controller allows it to change the game contents. This study analyses differences between classic controller and Wii controller from a structuralist approach, especially metaphor and metonymy. Also this study analyses correlation between console game controller and game contents. Since diversification of console game controller is predicted, it's significant to study correlation between console game platform and contents.

Humans are social existences who connect with others and live together. Communication between human has evolved into diverse formats and contents beyond time and space. Social Network Service builds social relationship based on web and its users increase rapidly in a global environment due to the user-friendly web circumstances, easy access and wide-spread supply of the smart phones. One of the aspect that is taking the center of Social Network Service is a Social Game. Social Games are based on web that has simple rules to play in fictional time and space background. This research is to analyze the relationship between social game, Social Network and user behavior through the Social Games Farm Villand Cafe World.This paper, firstly, is going to observe the characteristics of people who participate in the two social games `Farm Ville` and `Cafe World`. It, then, attempts to analyze individual and social human desires depicted in the games. In the social games, personal perception is revealed through an image of "possession", while one`s social activity is displayed by an image of "consumption."

A quest in MMORPG functions as a unit of game narrative. It is an essential part to progress game narrative and to construct player`s own storyline. In addition, it makes player to expand her territory and helps with character growth by giving reward. A quest consists of four essential elements : the quest giver, the background story, the objective and the reward. A quest shows a blanch structure with two nodes which is same as Claude Bremond`s elementary sequence. The sequence of each functions cannot be changed, therefore, it can be explained through a syntagma model. On the other hand, spatial disposition of quests follows a paradigm model. In order to construct a MMORPG narrative, a player connects quests into a single narrative by carrying out them.