Topic Modeling of Social Networking Service Data on Occupational Accidents in Korea: Latent Dirichlet Allocation Analysis.

BACKGROUND: In most industrialized societies, regulations, inspections, insurance, and legal options are established to support workers who suffer injury, disease, or death in relation to their work; in practice, these resources are imperfect or even unavailable due to workplace or employer obstruction. Thus, limitations exist to identify unmet needs in occupational safety and health information. OBJECTIVE: The aim of this study was to explore hidden issues related to occupational accidents by examining social network services (SNS) data using topic modeling. METHODS: Based on the results of a Google search for the phrases occupational accident, industrial accident and occupational diseases, a total of 145 websites were selected. From among these websites, we collected 15,244 documents on queries related to occupational accidents between 2002 and 2018. To transform unstructured text into structure data, natural language processing of the Korean language was conducted. We performed the latent Dirichlet allocation (LDA) as a topic model using a Python library. A time-series linear regression analysis was also conducted to identify yearly trends for the given documents. RESULTS: The results of the LDA model showed 14 topics with 3 themes: workers' compensation benefits (Theme 1), illicit agreements with the employer (Theme 2), and fatal and non-fatal injuries and vulnerable workers (Theme 3). Theme 1 represented the largest cluster (52.2%) of the collected documents and included keywords related to workers' compensation (ie, company, occupational injury, insurance, accident, approval, and compensation) and keywords describing specific compensation benefits such as medical expense benefits, temporary incapacity benefits, and disability benefits. In the yearly trend, Theme 1 gradually decreased; however, other themes showed an overall increasing pattern. Certain queries (ie, musculoskeletal system, critical care, and foreign workers) showed no significant variation in the number of queries. CONCLUSIONS: We conducted LDA analysis of SNS data of occupational accident-related queries and discovered that the primary concerns of workers posting about occupational injuries and diseases were workers' compensation benefits, fatal and non-fatal injuries, vulnerable workers, and illicit agreements with employers. While traditional systems focus mainly on quantitative monitoring of occupational accidents, qualitative aspects formulated by topic modeling from unstructured SNS queries may be valuable to address inequalities and improve occupational health and safety.

Regulation of the epithelial Na+ channel by the RH domain of G protein-coupled receptor kinase, GRK2, and Galphaq/11.

The G protein-coupled receptor kinase (GRK2) belongs to a family of protein kinases that phosphorylates agonist-activated G protein-coupled receptors, leading to G protein-receptor uncoupling and termination of G protein signaling. GRK2 also contains a regulator of G protein signaling homology (RH) domain, which selectively interacts with α-subunits of the Gq/11 family that are released during G protein-coupled receptor activation. We have previously reported that kinase activity of GRK2 up-regulates activity of the epithelial sodium channel (ENaC) in a Na(+) absorptive epithelium by blocking Nedd4-2-dependent inhibition of ENaC. In the present study, we report that GRK2 also regulates ENaC by a mechanism that does not depend on its kinase activity. We show that a wild-type GRK2 (wtGRK2) and a kinase-dead GRK2 mutant ((K220R)GRK2), but not a GRK2 mutant that lacks the C-terminal RH domain (ΔRH-GRK2) or a GRK2 mutant that cannot interact with Gαq/11/14 ((D110A)GRK2), increase activity of ENaC. GRK2 up-regulates the basal activity of the channel as a consequence of its RH domain binding the α-subunits of Gq/11. We further found that expression of constitutively active Gαq/11 mutants significantly inhibits activity of ENaC. Conversely, co-expression of siRNA against Gαq/11 increases ENaC activity. The effect of Gαq on ENaC activity is not due to change in ENaC membrane expression and is independent of Nedd4-2. These findings reveal a novel mechanism by which GRK2 and Gq/11 α-subunits regulate the activity ENaC.

Mining Hidden Knowledge About Illegal Compensation for Occupational Injury: Topic Model Approach.

BACKGROUND: Although injured employees are legally covered by workers' compensation insurance in South Korea, some employers make agreements to prevent the injured employees from claiming their compensation. Thus, this leads to underreporting of occupational injury statistics. Illegal compensation (called gong-sang in Korean) is a critical method used to underreport or cover-up occupational injuries. However, gong-sang is not counted in the official occupational injury statistics; therefore, we cannot identify gong-sang-related issues. OBJECTIVE: This study aimed to analyze social media data using topic modeling to explore hidden knowledge about illegal compensation-gong-sang-for occupational injury in South Korea. METHODS: We collected 2210 documents from social media data by filtering the keyword, gong-sang. The study period was between January 1, 2006, and December 31, 2017. After completing natural language processing of the Korean language, a morphological analyzer, we performed topic modeling using latent Dirichlet allocation (LDA) in the Python library, Gensim. A 10-topic model was selected and run with 3000 Gibbs sampling iterations to fit the model. RESULTS: The LDA model was used to classify gong-sang-related documents into 4 categories from a total of 10 topics. Topic 1 was the greatest concern (60.5%). Workers who suffered from industrial accidents seemed to be worried about illegal compensation and legal insurance claims, wherein keywords on the choice between illegal compensation and legal insurance claims were included. In topic 2, keywords were associated with claims for industrial accident insurance benefits. Topics 3 and 4, as the second highest concern (19%), contained keywords implying the monetary compensation of gong-sang. Topics 5 to 10 included keywords on vulnerable jobs (ie, workers in the construction and defense industry, delivery riders, and foreign workers) and body parts (ie, injuries to the hands, face, teeth, lower limbs, and back) to gong-sang. CONCLUSIONS: We explored hidden knowledge to identify the salient issues surrounding gong-sang using the LDA model. These topics may provide valuable information to ensure the more efficient operation of South Korea's occupational health and safety administration and protect vulnerable workers from illegal gong-sang compensation practices.

Direct targeting of tumor cell F(1)F(0) ATP-synthase by radioiodine angiostatin in vitro and in vivo.

UNLABELLED: Recent discoveries have identified endothelial cell-surface F(1)F(0) adenosine triphosphate (ATP) synthase as the key target for angiostatin (AST) action. As this enzyme is also present on tumor cells, we investigated whether radiolabeled AST may directly target cancer cell-surface ATP synthase in vitro and in vivo. METHODS: Cell-binding characteristics of (125)I-AST was evaluated on human umbilical vein endothelial (HUVE) and SNU-C5 colon carcinoma cells. The molecular target for binding was investigated with anti-ATP synthase antibodies and RGDyV. Biodistribution and imaging experiments were performed in mice xenografted with carcinoma and sarcoma tumors. Tumor localization of ATP synthase and exogenous AST was compared via double immunostaining. RESULTS: Both HUVE and SNU-C5 cells showed specific (125)I-AST binding that was dose-dependently inhibited by excess AST, with IC(50) values of 3.5 and 0.2 microM, respectively. Both cell types stained positive for ATP synthase and demonstrated an approximately 50% reduction in AST binding by antibodies against the alpha- and beta-subunit of the enzyme. (123)I-AST injected in mice allowed for the clear tumor visualization with significant tumor accumulation and uptake ratios. Immunostaining revealed a localization of exogenous AST to closely correlate to that of tumor-cell ATP synthase. CONCLUSIONS: AST can directly target tumor-cell ATP synthase, and AST imaging may thus be useful for monitoring tumor ATP synthase expression.

Radiolabeled RGD uptake and alphav integrin expression is enhanced in ischemic murine hindlimbs.

UNLABELLED: Radiolabeled RGD peptides that target alpha(v)beta3 integrin are promising tracers for imaging tumor angiogenesis. Integrins and angiogenesis also play important roles in healing of ischemic lesions. Thus, we investigated the biodistribution of radiolabeled RGD and expression of alpha(v) integrin in a mouse model of hindlimb ischemia. METHODS: 125I-3-Iodo-D-Tyr4-cyclo(-Arg-Gly-Asp-D-Tyr-Val-) (125I-c(RGD(I)yV)) was synthesized and tested for endothelial binding. Hindlimb ischemia was induced in ICR mice through femoral artery ablation, and perfusion was measured with laser Doppler blood flowmetry. 125I-c(RGD(I)yV) biodistribution was evaluated in control animals (n = 7) and ischemic models on day 3, 8, or 14 (n = 6 each). Control experiments were performed using a radiolabeled peptide with a scrambled amino acid sequence (125I-GfVGV). Microsections of hindlimb tissue were immunostained for alpha(v) integrin expression and stained with alkaline phosphatase to localize vascular endothelial cells. RESULTS: 125I-c(RGD(I)yV) retained specific binding to human umbilical vein endothelial cells. Perfusion in ischemic hindlimbs immediately fell to 10% +/- 4% of contralateral levels and gradually recovered to 22% +/- 11% and 64% +/- 9% on days 8 and 14, respectively. 125I-c(RGD(I)yV) uptake in ischemic muscles significantly increased from a control level of 0.16 +/- 0.05 %ID/g (percentage injected dose per gram of tissue) to 0.85 +/- 0.76 %ID/g at day 3, 0.43 +/- 0.23 %ID/g at day 8, and 0.43 +/- 0.28 %ID/g at day 14 (all P < 0.05). Ischemic muscle-to-lung count ratios had a virtually identical trend: 0.42 +/- 0.25 for controls, 2.34 +/- 1.70 at day 3 (P < 0.02), 1.46 +/- 0.52 at day 8 (P < 0.001), and 1.39 +/- 0.94 at day 14 (P < 0.02). In contrast, uptake of the control peptide in ischemic hindlimbs was not different from that of controls. Immunohistochemistry revealed substantially increased alpha(v) integrin staining in ischemic hindlimb tissue. CONCLUSION: Radioiodine RGD uptake is significantly enhanced in ischemic hindlimbs of a mouse model, and is accompanied by an increase in alpha(v) integrin expression. Further investigation is thus warranted to illuminate the potential role of radiolabeled RGD for noninvasive monitoring of peripheral ischemic lesions.

Distribution and pharmacokinetic analysis of angiostatin radioiodine labeled with high stability.

OBJECTIVE: Radiotracers of anticancer agents provide important information on its in vivo handling. Angiostatin (AST) is a promising anticancer drug with potent antiangiogenic effects, but reported AST radiotracers suffer from poor in vivo stability. In this study, we synthesized an AST probe radioiodinated via the Bolton-Hunter reagent (125I-BH-AST) and investigated its stability and biokinetics in mice. METHODS: 125I-BH-AST and conventional direct radioiodinated 125I-AST were evaluated for human endothelial cell binding characteristics. In vivo stability of the radiotracers was compared by biodistribution studies in normal ICR mice. Angiostatin pharmacokinetics was analyzed by serial blood sampling after intravenous injection of 125I-BH-AST with varying AST concentrations in mice. RESULTS: Both 125I-AST and 125I-BH-AST retained selective endothelial binding as demonstrated by dose-dependent inhibition by nonradiolabeled AST. 125I-BH-AST was substantially more stable in mice than 125I-AST, with 28- and 7-fold lower 24-h thyroid and blood activities, respectively (15.5+/-1.5 vs. 430.9+/-32.2 and 0.1+/-0.0 vs. 0.8+/-0.0 %ID/g; both P<.005). Using (125)I-BH-AST, we found that 24-h AST accumulation was highest in the kidneys, followed by the liver and lungs. Kinetic analysis of 125I-BH-AST revealed AST to have linear pharmacokinetics with a T(1/2) of 5.8+/-2.6 h, volume of distribution (V(d)) of 6.8+/-1.3 ml and clearance of 0.8+/-0.1 ml/h. CONCLUSION: Radioiodine-labeled AST prepared by the BH method provides a radioprobe with superior stability and improved in vivo biokinetics that is useful for distribution and pharmacokinetic studies.

H-Ras mediates the inhibitory effect of epidermal growth factor on the epithelial Na+ channel.

The present study investigates the role of small G-proteins of the Ras family in the epidermal growth factor (EGF)-activated cellular signalling pathway that downregulates activity of the epithelial Na+ channel (ENaC). We found that H-Ras is a key component of this EGF-activated cellular signalling mechanism in M1 mouse collecting duct cells. Expression of a constitutively active H-Ras mutant inhibited the amiloride-sensitive current. The H-Ras-mediated signalling pathway that inhibits activity of ENaC involves c-Raf, and that the inhibitory effect of H-Ras on ENaC is abolished by the MEK1/2 inhibitor, PD98059. The inhibitory effect of H-Ras is not mediated by Nedd4-2, a ubiquitin protein ligase that regulates the abundance of ENaC at the cell surface membrane, or by a negative effect of H-Ras on proteolytic activation of the channel. The inhibitory effects of EGF and H-Ras on ENaC, however, were not observed in cells in which expression of caveolin-1 (Cav-1) had been knocked down by siRNA. These findings suggest that the inhibitory effect of EGF on ENaC-dependent Na+ absorption is mediated via the H-Ras/c-Raf, MEK/ERK signalling pathway, and that Cav-1 is an essential component of this EGF-activated signalling mechanism. Taken together with reports that mice expressing a constitutive mutant of H-Ras develop renal cysts, our findings suggest that H-Ras may play a key role in the regulation of renal ion transport and renal development.

The activity of the epithelial sodium channels is regulated by caveolin-1 via a Nedd4-2-dependent mechanism.

It has recently been shown that the epithelial Na(+) channel (ENaC) is compartmentalized in caveolin-rich lipid rafts and that pharmacological depletion of membrane cholesterol, which disrupts lipid raft formation, decreases the activity of ENaC. Here we show, for the first time, that a signature protein of caveolae, caveolin-1 (Cav-1), down-regulates the activity and membrane surface expression of ENaC. Physical interaction between ENaC and Cav-1 was also confirmed in a coimmunoprecipitation assay. We found that the effect of Cav-1 on ENaC requires the activity of Nedd4-2, a ubiquitin protein ligase of the Nedd4 family, which is known to induce ubiquitination and internalization of ENaC. The effect of Cav-1 on ENaC requires the proline-rich motifs at the C termini of the beta- and gamma-subunits of ENaC, the binding motifs that mediate interaction with Nedd4-2. Taken together, our data suggest that Cav-1 inhibits the activity of ENaC by decreasing expression of ENaC at the cell membrane via a mechanism that involves the promotion of Nedd4-2-dependent internalization of the channel.

Specific endothelial binding and tumor uptake of radiolabeled angiostatin.

Angiostatin (AS) is a potent antiangiogenic agent which inhibits tumor growth through specific action on proliferating endothelial cells. Imaging of radiolabeled AS would enhance our knowledge on the pharmacokinetics of AS and might provide useful information relating to tumor neovasculature. We therefore investigated the potential of radiolabeled AS as a novel tumor imaging agent. Human angiostatin was radioiodine labeled using the lactoperoxidase method. Competition binding studies showed a dose-dependent inhibition of (125)I-AS binding to endothelial cells by excess unlabeled AS, and a displacement curve demonstrated that specific binding was dose dependent and saturable, with a K(d) value of 169 n M. Gel analysis showed that (125)I-AS remained stable in serum for up to 24 h without significant degradation. Intravenously injected (125)I-AS in rats was cleared from the blood in an exponential fashion. Biodistribution data from human colon cancer-bearing Balb/C nude mice showed high uptake in the kidneys, stomach, liver, and lungs. Tumor uptake was 3.2+/-0.7, 2.6+/-0.2, and 1.7+/-0.2%ID/g at 2, 4, and 9 h after injection, respectively. Tumor to muscle count ratio increased from 3.1+/-0.5 at 2 h to 4.4+/-0.5 at 9 h. Serial scintigraphy from 1 to 5 h after (123)I-AS injection demonstrated high uptake in the kidneys and bladder, consistent with renal excretion. There was clear demarcation of tumor by 1 h, with gradual increase in contrast over time (4-h tumor to contralateral thigh ratio =4.7+/-1.1). Thus, radioiodine-labeled angiostatin binds specifically to endothelial cells and has potential as a novel tumor imaging agent.