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Background: Acute gastroenteritis (AGE) is a common cause of pediatric morbidity and mortality worldwide. AGE can cause an imbalance in the intestinal microbiota. This study aimed to investigate the diversity of the gut microbiome in Korean children hospitalized for infectious AGE at a university hospital. Methods: A total of 23 stool samples from patients aged 5 months to 11 years with AGE were analyzed. Thirteen convalescent stool samples were collected 1 month after discharge. Multiplex polymerase chain reaction (PCR) for the five viruses and 16 bacteria-specific AGE pathogens (PowerChek Multiplex Real time PCR Kit, Seoul, Korea), and 16s rRNA sequencing (Illumina MiSeq Sequencing system, Illumina, USA) were performed. Results: According to the results of multiplex PCR for causative pathogens, the microbiome taxonomic profile (MTP) of the gut microbiome in three groups of AGE, norovirus AGE (n = 11), Campylobacter AGE (n = 7) and Salmonella AGE (n = 5) was compared. The phylum Actinobacteria was significantly more abundant in the norovirus AGE (P = 0.011), whereas the phylum Proteobacteria was significantly more abundant in Salmonella AGE (P = 0.012). Alpha diversity, which indicates species richness and diversity, showed no statistical differences. However, beta diversity, representing the similarity in MTP between norovirus, Campylobacter, and Salmonella AGE, was significantly different (P = 0.007). In convalescence, compared with their corresponding AGE samples, the phylum Firmicutes; and the lower taxa Christensenellaceae (P = 0.0152) and Lachnospiraceae (P = 0.0327) were significantly increased. Conclusions: In pediatric AGE, the type of infectious agent can affect the diversity and dominance of gut microbiota in pediatric patients. Furthermore, healthy gut bacteria increased during the period of 1 month after infection, allowing a return to a healthy state without causing long-term dysbiosis.

Abstract Background Although sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus, real-world evidence regarding their benefits to diabetic patients with acute myocardial infarction (AMI) is insufficient. This study evaluated cardiovascular outcomes by comparing SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4i) in combination with metformin in diabetic patients with AMI. Methods This study involved 779 diabetic participants with AMI from a Korean nationwide multicenter observational cohort, who were divided into two groups: (1) metformin plus SGLT2i group (SGLT2i group, n = 186) and (2) metformin plus DPP-4i (DPP-4i group, n = 593). The primary endpoint was one year of major adverse composite events (MACEs), a composite outcome of all-cause mortality, non-fatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis. To balance the baseline differences, inverse probability of treatment weighting (IPTW) was performed. Results After IPTW, the rate of MACEs in the SGLT2i group was not significantly lower than that in the DPP-4i group (hazard ratio [HR], 0.99; 95% confidence interval [Cl], 0.46 to 2.14, p = 0.983). In the unadjusted and adjusted analyses, all items for clinical outcomes were comparable between the two groups. In our exploratory analysis, the left ventricular ejection fraction showed a significant improvement in the SGLT2i group than in the DPP-4i group before achieving statistical balancing (6.10 ± 8.30 versus 2.95 ± 10.34, p = 0.007) and after IPTW adjustment (6.91 ± 8.91 versus 3.13 ± 10.41, p = 0.027). Conclusions Our findings demonstrated that SGLT2i did not influence the rate of MACEs compared with DPP-4i in combination with metformin in diabetic patients with AMI but did improve left ventricular ejection fraction. Trial registration Not applicable (retrospectively registered).

Background This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. Methods In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. Results The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. Conclusion Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Soil-transmitted helminth (STH) infections impact billions of individuals globally; however, there is a need to clarify the long-term impacts of these infections on pulmonary health owing to their transient migration and subsequent damage to the lungs. In mouse models of these infections using Nippostrongylus brasiliensis, lung pathology persists at later time points post single infection. These studies also indicate the persistent transcriptional expression of resistin-like molecule α (RELMα), an immunomodulatory protein induced in type 2 immunity and alternatively activated macrophages. Using constitutive and tamoxifen-inducible cell-specific RELMα knockout mouse strains, we identified that epithelial- and myeloid-derived RELMα protein remained elevated at 30 days post infection and altered the immune cell signature and gene expression in lung compartments. Histopathological assessment of alveolar damage revealed a role for RELMα in tissue repair, suggesting the importance of sustained RELMα expression for lung recovery from helminth infection. Acellular three-dimensional (3D) lung scaffolds were prepared from the lungs of wild-type (WT), RELMα KO-naive, or 30 days post N. brasiliensis-infected mice to assess their ability to support epithelial cell growth. N. brasiliensis infection significantly altered the scaffold and impaired epithelial cell growth and metabolic activity, especially in the RELMα KO scaffolds. These findings underscore a need to identify the long-term impacts of helminth infection on human pulmonary disease, particularly as alveolar destruction can develop into chronic obstructive pulmonary disease (COPD), which remains among the top global causes of death. Translation of these findings to human protein resistin, with sequence homology to RELMα therapeutic opportunities in lung repair.

Type 2 cytokines like IL-4 are hallmarks of helminth infection and activate macrophages to limit immunopathology and mediate helminth clearance. In addition to cytokines, nutrients and metabolites critically influence macrophage polarization. Choline is an essential nutrient known to support normal macrophage responses to lipopolysaccharide; however, its function in macrophages polarized by type 2 cytokines is unknown. Using murine IL-4-polarized macrophages, targeted lipidomics revealed significantly elevated levels of phosphatidylcholine, with select changes to other choline-containing lipid species. These changes were supported by the coordinated up-regulation of choline transport compared to naïve macrophages. Pharmacological inhibition of choline metabolism significantly suppressed several mitochondrial transcripts and dramatically inhibited select IL-4-responsive transcripts, most notably, Retnla. We further confirmed that blocking choline metabolism diminished IL-4-induced RELMα (encoded by Retnla) protein content and secretion and caused a dramatic reprogramming toward glycolytic metabolism. To better understand the physiological implications of these observations, naïve or mice infected with the intestinal helminth Heligmosomoides polygyrus were treated with the choline kinase α inhibitor, RSM-932A, to limit choline metabolism in vivo. Pharmacological inhibition of choline metabolism lowered RELMα expression across cell-types and tissues and led to the disappearance of peritoneal macrophages and B-1 lymphocytes and an influx of infiltrating monocytes. The impaired macrophage activation was associated with some loss in optimal immunity to H. polygyrus, with increased egg burden. Together, these data demonstrate that choline metabolism is required for macrophage RELMα induction, metabolic programming, and peritoneal immune homeostasis, which could have important implications in the context of other models of infection or cancer immunity.

Abstract Background Cancer cells have developed molecular strategies to cope with evolutionary stressors in the dynamic tumor microenvironment. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) is a metabolic rheostat that regulates diverse cellular adaptive behaviors, including growth and survival. However, the mechanistic role of PGC1α in regulating cancer cell viability under metabolic and genotoxic stress remains elusive. Methods We investigated the PGC1α-mediated survival mechanisms in metabolic stress (i.e., glucose deprivation-induced metabolic stress condition)-resistant cancer cells. We established glucose deprivation-induced metabolic stress-resistant cells (selected cells) from parental tumor cells and silenced or overexpressed PGC1α in selected and parental tumor cells. Results Several in vitro and in vivo mouse experiments were conducted to elucidate the contribution of PGC1α to cell viability in metabolic stress conditions. Interestingly, in the mouse xenograft model of patient-derived drug-resistant cancer cells, each group treated with an anti-cancer drug alone showed no drastic effects, whereas a group that was co-administered an anti-cancer drug and a specific PMCA inhibitor (caloxin or candidate 13) showed marked tumor shrinkage. Conclusions Our results suggest that PGC1α is a key regulator of anti-apoptosis in metabolic and genotoxic stress-resistant cells, inducing PMCA expression and allowing survival in glucose-deprived conditions. We have discovered a novel therapeutic target candidate that could be employed for the treatment of patients with refractory cancers.

Abstract Human cyclophilin A (hCypA) is important for the replication of multiple coronaviruses (CoVs), and cyclosporine A inhibitors can suppress CoVs. The emergence of rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants has sparked concerns that mutations affect the binding ability of the spike (S) protein to the angiotensin‐converting enzyme 2 (ACE2) cell receptor, affecting the severity of coronavirus disease (COVID‐19). Far‐western blotting and surface plasmon resonance (SPR) results revealed that hCypA interacts strongly with the viral SARS‐CoV‐2 receptor‐binding domain (RBD), with a binding affinity of 6.85 × 10−8 M. The molecular interaction between hCypA and the viral protein interface was shown using three‐dimensional structural analysis, which revealed the blocking of key residues on the RBD interface by hCypA. The RBD facilitates binding to the ACE2 receptor. The hCypA–S protein complex suppressed the binding of RBD to the ACE2 receptor, which a required event for CoV entry into the host cell. The reliability of this postulated blocking mechanism of the hCypA–SARS‐CoV2 RBD complex with ACE was confirmed by SPR and molecular interaction lateral flow (MILF) strip assay, which offers the immunochromatographic signal read‐outs. The emergence of new SARS‐CoV‐2 variants with key mutations in RBD had a negligible effect on the binding of the RBD variants to hCypA, indicating an effective mitigation strategy for SARS‐CoV‐2 variants. The MILF strip assay results also highlight the neutralizing effect of hCypA by effectively blocking RBD (wild type and its variants) from binding ACE2. Given the importance of hCypA in viral entry regulation, it has the potential to be used as a target for antiviral therapy.

IntroductionIntestinal roundworms cause chronic debilitating disease in animals, including humans. Traditional experimental models of these types of infection use a large single-dose infection. However, in natural settings, hosts are exposed to parasites on a regular basis and when mice are exposed to frequent, smaller doses of Heligmosomoides polygyrus, the parasites are cleared more quickly. Whether this more effective host response has any negative consequences for the host is not known.ResultsUsing a trickle model of infection, we found that worm clearance was associated with known resistance-related host responses: increased granuloma and tuft cell numbers, increased levels of granuloma IgG and decreased intestinal transit time, as well as higher serum IgE levels. However, we found that the improved worm clearance was also associated with an inflammatory phenotype in and around the granuloma, increased smooth muscle hypertrophy/hyperplasia, and elevated levels of Adamts gene expression.DiscussionTo our knowledge, we are the first to identify the involvement of this protein family of matrix metalloproteinases (MMPs) in host responses to helminth infections. Our results highlight the delicate balance between parasite clearance and host tissue damage, which both contribute to host pathology. When continually exposed to parasitic worms, improved clearance comes at a cost.

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Summary: Overwriting counterselectable markers is an efficient strategy for removing wild-type DNA or replacing it with payload DNA of interest. Currently, one bottleneck of efficient genome engineering in mammals is the shortage of counterselectable (negative selection) markers that work robustly without affecting organismal developmental potential. Here, we report a conditional Piga knockout strategy that enables efficient proaerolysin-based counterselection in mouse embryonic stem cells. The conditional Piga knockout cells show similar proaerolysin resistance as full (non-conditional) Piga deletion cells, which enables the use of a PIGA transgene as a counterselectable marker for genome engineering purposes. Native Piga function is readily restored in conditional Piga knockout cells to facilitate subsequent mouse development. We also demonstrate the generality of our strategy by engineering a conditional knockout of endogenous Hprt. Taken together, our work provides a new tool for advanced mouse genome writing and mouse model establishment.

HANSSEM is a furniture company that leads the market of residential space in Korea. The goal of this case study is to focus on how HANSSEM copes with IKEA, the world"s largest furniture retailer after entering the Korean market in December 2014. IKEA’s entry into Korea is possible to destroy the existing orders in the retail industry and reduce the profit of incumbent local players by realigning industry relationships. However, HANSSEM achieved rapid growth with the largest market share in the furniture market through its internal capabilities. The authors propose the main success factors in three ways: (1) residents-database including apartment floorplans in Korea, (2) high-quality human services provided by construction and A/S (After-sales Service), (3) channel diversification that provides comprehensive consultations (e.g., flagship stores, home shopping channels, stores in marts, and interior dealers). Especially, there have been various consumer needs in Korean market, such as creating their own stylish space economically. HANSSEM meets customer’s needs by reinforcing the space-package (complete-interior is provided to customer in a package rather than combining individual piece of furniture) and opening showrooms, which makes customers freely experience the products and receive detailed consultations on interior designs by alleviating customers’ difficulties in decorating their homes. Based on HANSSEM"s outstanding activities and new investments, we look forward to seeing that HANSSEM will achieve its ultimate goal of maintaining the position of number one furniture company by attaining customer satisfaction through higher quality in Korea.

Veronica dahurica Steven (family Scrophulariaceae) is an ornamental plant from Korea. The aim of the present study was to produce multiple-branched plants by using 6-benzylaminopurine (BA) spray application at several time intervals after pinching. All 10 cm long plants were sprayed with 0, 500, 1000, and 2000 mg·L-1 BA at 0, 7, and 14 days after pinching. Growth characteristics were examined 10 weeks after pinching and flowering time was recorded. The number of branches was highest in the group sprayed with 1000 mg·L-1 BA at 0 d after pinching. The greatest plant height was observed in the group treated with 1000 mg·L-1 BA 14 d after pinching and the minimum plant height was observed in the group sprayed with 500 mg·L-1 BA at 0 d after pinching. The groups sprayed with higher BA concentrations and with longer intervals between pinching and spraying showed greater delay in the time to first flower. The flower length was decreased in the pinched and BA-treated group compared with the control. Thus, BA application and pinching could promote multiple branch induction and control flowering time in V. dahurica Steven.

Thyroid carcinoma, a disease in which malignant cells form in the thyroid tissue, is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for nearly 80% of total thyroid carcinoma cases. However, the management of metastatic or recurrent therapy-refractory PTC is challenging and requires complex carcinoma therapy. In this study, we proposed a new clinical approach for the treatment of therapy-refractory PTC. We identified sarco/endoplasmic reticulum calcium ATPase (SERCA) as an essential factor for the survival of PTC cells refractory to the treatment with paclitaxel or sorafenib. We validated its use as a potential target for developing drugs against resistant PTC, by using patient-derived paclitaxel- or sorafenib-resistant PTC cells. We further discovered novel SERCA inhibitors, candidates 7 and 13, using the evolutionary chemical binding similarity method. These novel SERCA inhibitors determined a substantial reduction of tumors in a patient-derived xenograft tumor model developed using paclitaxel- or sorafenib-resistant PTC cells. These results could provide a basis for clinically meaningful progress in the treatment of refractory PTC by identifying a novel therapeutic strategy: using a combination therapy between sorafenib or paclitaxel and specific SERCA inhibitors for effectively and selectively targeting extremely malignant cells such as antineoplastic-resistant and carcinoma stem-like cells.

RELMα is a small, secreted protein expressed by type 2 cytokine-activated “M2” macrophages in helminth infection and allergy. At steady state and in response to type 2 cytokines, RELMα is highly expressed by peritoneal macrophages, however, its function in the serosal cavity is unclear. In this study, we generated RELMα TdTomato (Td) reporter/knockout (RαTd) mice and investigated RELMα function in IL-4 complex (IL-4c)-induced peritoneal inflammation. We first validated the RELMαTd/Td transgenic mice and showed that IL-4c injection led to the significant expansion of large peritoneal macrophages that expressed Td but not RELMα protein, while RELMα+/+ mice expressed RELMα and not Td. Functionally, RELMαTd/Td mice had increased IL-4 induced peritoneal macrophage responses and splenomegaly compared to RELMα+/+ mice. Gene expression analysis indicated that RELMαTd/Td peritoneal macrophages were more proliferative and activated than RELMα+/+ macrophages, with increased genes associated with T cell responses, growth factor and cytokine signaling, but decreased genes associated with differentiation and maintenance of myeloid cells. We tested the hypothesis that RαTd/Td macrophages drive aberrant T cell activation using peritoneal macrophage and T cell co-culture. There were no differences in CD4+ T cell effector responses when co-cultured with RELMα+/+ or RELMαTd/Td macrophages, however, RELMαTd/Td macrophages were impaired in their ability to sustain proliferation of FoxP3+ regulatory T cells (Treg). Supportive of the in vitro results, immunofluorescent staining of the spleens revealed significantly decreased FoxP3+ cells in the RELMαTd/Td spleens compared to RELMα+/+ spleens. Taken together, these studies identify a new RELMα regulatory pathway whereby RELMα-expressing macrophages directly sustain Treg proliferation to limit type 2 inflammatory responses.

This study examines the relationship between social media advertisement and customer interest in the context of luxury brands. Further, this study investigates the effective ways to utilize visual types (pictorial advertisement and video advertisement) and contents types (website link and hash-tag) in social media advertising by proposing a time-series model to estimate the long-term effect of social media advertising on social search. We find that the pictorial advertisements are more effective than video advertisements, which provides a different result from previous existing research. In addition, advertisements using hashtags are more effective than web links due to efficiency of the search feature. Finally, since the number of brand fans also have a positive effect on advertising interest, it is essential to utilize social media advertising for the enhancement of customers’ interests. Confirming that the effectiveness of social media advertising varies depending on how the visual contents and text are presented, this research can help marketing managers to assess predicted outcomes of using various methods of social media advertising.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.

Advanced cancer has been shown to be associated with a higher percentage of epigenetic changes than with genetic mutations. Preclinical models have shown that the combination of paclitaxel, sorafenib, and radiation therapy (RT) plays a crucial role in renal cell carcinoma (RCC) and breast cancer. This study aimed to investigate the involvement of mitochondrial cytochrome c–dependent apoptosis in the mechanism of action of a combination of paclitaxel, sorafenib, and RT in RCC and breast cancer. RCC and breast cancer cell lines were exposed to paclitaxel and sorafenib alone or combined in the presence of radiation, and cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The synergistic anticancer effects of the combination therapy on cell cycle and intracellular signaling pathways were estimated using flow cytometry and immunoblot analysis. RCC and breast cancer cell line xenograft models were used to examine the antitumor activity in vivo. Our results suggest that paclitaxel, sorafenib, and RT synergistically decreased the viability of RCC and breast cancer cells and significantly induced their apoptosis, as shown by caspase-3 cleavage. Paclitaxel, sorafenib, and radiation cotreatment reduced antiapoptotic factor levels in these cells and, thereby, significantly reduced the tumor volume of RCC and breast cancer cell xenografts. The current study suggests that paclitaxel, sorafenib, and radiation cotreatment was more effective than cotreatment with paclitaxel or sorafenib and radiation. These findings may offer a new therapeutic approach to RCC and breast cancer.

Lactobacillus plantarum has been identified as a probiotic bacterium owing to its role in immune regulation and maintenance of intestinal permeability. Here, we investigated the anti-colitic effects and mechanism of L. plantarum CBT LP3 (LP3). This in vivo study was performed using dextran sodium sulfate (DSS) to induce colitis in mice. Mice were randomly divided into three groups: a control supplied with normal drinking water, a DSS-treated group followed by oral administration of vehicle, and a DSS-treated group gavaged with LP3 daily for 7 days following DSS administration. An analysis of macrophages and T cell subsets harvesting from peritonium cavity cells and splenocytes was performed using a flow cytometric assay. Gene expression and cytokine profiles were measured using quantitative reverse transcriptase polymerase chain reaction. The administration of LP3 significantly attenuated disease activity and histolopathology compared to control. LP3 had anti-inflammatory effects, with increased induction of regulatory T cells and type 2 helper T cells in splenocytes and restoration of goblet cells accompanied by suppression of proinflammatory cytokine expressions. These findings suggest that L. plantarum CBT LP3 can be used as a potent immunomodulator, which has significant implications for IBD treatment.

Thyroid cancer (TC) includes tumors of follicular cells; it ranges from well differentiated TC (WDTC) with generally favorable prognosis to clinically aggressive poorly differentiated TC (PDTC) and undifferentiated TC (UTC). Papillary thyroid cancer (PTC) is a WDTC and the most common type of thyroid cancer that comprises almost 70–80% of all TC. PTC can present as a solid, cystic, or uneven mass that originates from normal thyroid tissue. Prognosis of PTC is excellent, with an overall 10-year survival rate >90%. However, more than 30% of patients with PTC advance to recurrence or metastasis despite anti-cancer therapy; consequently, systemic therapy is limited, which necessitates expansion of improved clinical approaches. We strived to elucidate genetic distinctions due to patient-derived anti-cancer drug-sensitive or -resistant PTC, which can support in progress novel therapies. Patients with histologically proven PTC were evaluated. PTC cells were gained from drug-sensitive and -resistant patients and were compared using mRNA-Seq. We aimed to assess the in vitro and in vivo synergistic anti-cancer effects of a novel combination therapy in patient-derived refractory PTC. This combination therapy acts synergistically to promote tumor suppression compared with either agent alone. Therefore, genetically altered combination therapy might be a novel therapeutic approach for refractory PTC.

Dongwon Systems established in 1977 to exclusively supply Dongwon tuna cans, the parent company. Instead of its stable management and profits by relying on the parent company, the company was not complacent and started innovating and challenging new markets. Dongwon Systems decided to expand the business area and pioneer new markets so that it becomes the first domestic company to successfully expand into independent businesses other than parent company products. Such success of Dongwon Systems was driven by its differentiated B2B strategies. Unlike the characteristics of usual B2B companies, Dongwon Systems has been thinking both of its client companies and end-consumers. In this case-study, we will explore how Dongwon Systems became the No.1 packaging solution company in Korea through technology innovation in the aspects of unique B2B marketing strategy. The key success factor can be summarized in three ways; product and technology development with customer centric mind-set, systematically extending new markets through business diversification, and marking Southeast Asia as a bridgehead for its global strategy. It is expected that the current case study of Dongwon Systems will be able to provide implications for B2C companies as well as B2B companies that try to expand their business portfolio and global business areas through B2B marketing case analysis.

Korea Ginseng Corporation is a global ginseng company, owning one of the most leading brands in Korea, CheongKwanJang. Although Korea Ginseng Corporation was an undoubted market leader in the red ginseng market, it faced a new challenge in 2012 due to the changes in market environment. In order to keep its market leadership in a saturated and competitive market, the company decided to extend its product lines alongside the launches of new brands. In this article, the authors demonstrate the development process of the company’s brand portfolio strategy to reveal how the company turned CheongKwanJang into a mega-brand. Also, this paper explores the impact of CheongKwanJang’s reputation on new brands, thereby illustrating how the company successfully managed to introduce new products outside of the red ginseng category, ranging from organic food to a pet food market.

The ability of induced pluripotent stem cells (iPSCs) to differentiate into all adult cell types makes them attractive for research and regenerative medicine; however, it remains unknown when and how this capacity is established. We characterized the acquisition of developmental pluripotency in a suitable reprogramming system to show that iPSCs prior to passaging become capable of generating all tissues upon injection into preimplantation embryos. The developmental potential of nascent iPSCs is comparable to or even surpasses that of established pluripotent cells. Further functional assays and genome-wide molecular analyses suggest that cells acquiring developmental pluripotency exhibit a unique combination of properties that distinguish them from canonical naive and primed pluripotency states. These include reduced clonal self-renewal potential and the elevated expression of differentiation-associated transcriptional regulators. Our observations close a gap in the understanding of induced pluripotency and provide an improved roadmap of cellular reprogramming with ramifications for the use of iPSCs.

A new reduced-dose tetanus–diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Methods: Healthy adolescents 11–12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. Results: A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. Conclusion: The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus.

This research explores two key facets of behavior (reward point accrual and redemption) that consist of a loyalty program. It focuses on assessing the impact of accrual effort level on three types of redemption behavior: speed, unit size, and hedonic preference at the individual level by using large scale transaction data from a multi-vendor loyalty program providing flexible environment for point accrual and redemption. Findings from this research demonstrate that customers tend 1) to speed up point redemption, 2) to enlarge the size of redeemed points, and 3) to prefer utilitarian rewards as the level of effort at the accrual stage of reward point increases.

Familial adenomatous polyposis (FAP) is a precancerous clinical entity, which is characterized by the development of numerous adenomatous polyps throughout the colon and rectum. The majority of FAP are associated with mutations of the adenomatous polyposis coli (APC) gene. Until now, more than 1,000 different APC mutations have been reported and some mutations express attenuated phenotypes which are milder forms with 10∼100 colorectal polyps. We identified a novel mutation of APC gene which expressed an attenuated FAP but caused large gastroduodenal tubular adenomas requiring repeated endoscopic resections. A 16-year-old girl was referred to Incheon St. Mary’s Hospital for evaluation of gastric polyposis. Initial esophagogastroduodenoscopy (EGD) showed numerous gastric polyps in the fundus and upper body and a few polyps in the duodenum. Pathologic examination confirmed gastric polyps as fundic gland polyps and duodenal polyps as tubular adenomas. Only a few colonic polyps of 2 to 5 mm in size were found on colonoscopy. Genetic analysis using polymerase chain reaction and direct sequencing revealed a novel stop codon mutation at codon 1522 in exon 16 of APC gene. At 12-month, 18-month, and 35-month follow-up EGD, large duodenal polyp and gastric polyps were removed endoscopically.

BackgroundThe objective of the current study was to determine whether there was an association between urinary albumin excretion and cardiovascular disease (CVD) risk by estimating the Framingham Risk Score (FRS) in postmenopausal women without diabetes.MethodsThis study was based on data from the Korea National Health and Nutrition Examination Survey, which was conducted by the Korean Ministry of Health and Welfare in 2011 to 2013. Data on 2,316 postmenopausal women from a total of 24,594 participants was included in the analysis.ResultsThe mean FRS was significantly different in each of the urinary albumin to creatinine ratio (UACR) subgroups, and it increased with UACR. The FRS was 12.69±0.12 in the optimal group, 14.30±0.19 in the intermediate normal group, 14.62±0.26 in the high normal group, and 15.86±0.36 in the microalbuminuria group. After fully adjusting for potential confounding factors, high normal levels and microalbuminuria were significantly associated with the highest tertile of FRS ([odds ratio (OR), 1.642; 95% confidence interval (CI), 1.124 to 2.400] and [OR, 3.385; 95% CI, 2.088 to 5.488], respectively) compared with the optimal subgroup. High normal levels and microalbuminuria were also significantly associated with a ≥10% 10-year risk of CVD ([OR, 1.853; 95% CI, 1.122 to 3.060] and [OR, 2.831; 95% CI, 1.327 to 6.037], respectively) after adjusting for potential confounding covariates.ConclusionUrinary albumin excretion reflects CVD risk in postmenopausal women without diabetes, and high normal levels and microalbuminuria were independently associated with a higher risk of CVD.

Although corporate social responsibility (CSR) activities are common in the pharmaceutical industry, there is little empirical evidence on consumer responses to CSR practices. We investigated public awareness, preferences, and expectations regarding social contribution of the pharmaceutical industry's CSR activities, and identified the factors associated with such activities. We conducted an online survey with 1,298 respondents comprising two groups: healthy individuals (546) and patients (752). Most respondents (78%) expressed interest in CSR activities undertaken by pharmaceutical companies. However, they reported a lack of awareness and experience thereof; only 26.9% were aware of and 7.9% had experience with such activities. Among our six CSR activity categories, both survey groups showed the highest preference for the "promoting public health" (healthy group: 6.34/10; patient group: 6.37/10) and "emergency disaster relief support" (6.31 and 6.35) categories. Among sub-categories, activities related to "development of innovative drugs in untreated areas" (6.63 and 6.82) and "support for research on new drug development" (6.59 and 6.84) received the highest scores. The mean expectation score of social contribution of all CSR activities was slightly higher than the mean preference score (6.37 and 6.06, respectively). The patient group exhibited a larger difference between the highest and lowest expectation scores than the healthy group (1.11 and 0.64, respectively). The results of the regression analysis revealed that being a patient, being male, and having positive attitudes toward CSR and its expected effects significantly and positively affected public preferences regarding CSR activities. We can conclude that CSR activities with high public preference might be an effective strategy to improve public awareness of the pharmaceutical industry's CSR activities. Furthermore, the highest preference for CSR activities relates to new drug development, indicating that our society believes the pharmaceutical industry's key CSR activity should be to pursue its intrinsic mission: to fulfill unmet medical needs by developing new drugs.

Anaplastic thyroid cancer (ATC) is an undifferentiated and advanced form of thyroid cancer, accompanied with a high ratio of epigenetic adjustment, which occurs more than genetic mutations. In this study, we aimed to evaluate the synergistic anticancer effect (in vitro and in vivo) of the new combination of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) and sorafenib with radiation therapy in pre-clinical models of ATC. The ATC cell lines, YUMC-A1 and YUMC-A2, were isolated from the current patients who were treated with HNHA and sorafenib, either as monotherapy or combination therapy. Synergistic anticancer effect of the combination therapy on the intracellular signaling pathways and cell cycle was assessed via flow cytometry and immunoblot analysis. To examine tumor shrinkage activity in vivo, an ATC cell line-derived mouse xenograft model was used. Results showed that the combination therapy of HNHA and sorafenib with radiation promoted tumor suppression via caspase cleavage and cell cycle arrest in patient-derived ATC. In addition, the combination therapy of HNHA and sorafenib with radiation was more effective against ATC than therapy with HNHA or sorafenib with radiation. Thus, the combination of HNHA and sorafenib with radiation may be used as a novel curative approach for the treatment of ATC.

K-Pop is hugely promoted offline/online in East Asia, while efforts to promote it elsewhere are kept to a minimum. Whilst addressing the role of digital marketing in the promotion of K-Pop in the Brazilian music industry this study aims to demonstrate that K-pop will provide its audience with a unique and engaging experience if it thinks globally and acts locally in its marketing and communication strategies. A survey of K-Pop’s world fan base was carried out online with 1,074 fans to determine the validity of the hypothesis. The results have demonstrated the need to adapt global and intercultural strategies to local markets with increasing brand awareness through utilizing digital marketing. For example, to increase K-Pop’s popularity and market share in Brazil, it is not required to sing in Brazilian Portuguese, contrary to what might be perceived but fully singing in English would help breaking into the market dominated by domestic music as songs would have a higher probability to be included in the international soundtrack of a Brazilian telenovela and promote the K-Pop artist not only across Brazil but also give the artist exposure in all the markets the Brazilian telenovela is exported to, opening an entry door to those markets. K-Pop audience segmentation and psychographic profiling is crucial to the understanding of each market’s consumer’s preferences, likes, dislikes and their buying habits as it was proven through Brazil’s digital media, social media, digital music market and K-Pop market analysis within the global context of the study. It should be also considered that brand extensions are not standard everywhere and that there are cultures where different product categories are not directly associated with its main corporate owner which requires extensive local market knowledge to succeed. The primary and secondary data research that we conducted for this study intended to demonstrate that K-Pop can be successful in Brazil and in Latin America and increase their local and regional market share if digital marketing and communication strategies are tailored to each individual market.

BackgroundThe objective of this study was to evaluate the validity of fine needle aspiration biopsy (FNAB) according to ultrasonography (US) characteristics in thyroid nodules 4 cm and larger.MethodsWe retrospectively reviewed the cases of 263 patients who underwent thyroid surgery for thyroid nodules larger than 4 cm between January 2001 and December 2010.ResultsThe sensitivity of US-FNAB was significantly higher in nodules with calcifications (micro- or macro-) than those without (97.9% vs. 87.% P

Atherothrombotic complications are important causes of morbidity and mortality in diabetic patients. Diabetes has been considered to be a prothrombotic status. Several factors contribute to the prothrombotic condition, such as increasing coagulation, impaired fibrinolysis, endothelial dysfunction, and platelet hyperreactivity. Among the factors that contribute to the prothrombotic status in diabetes, altered platelet function plays a crucial role. Although understanding platelet function abnormalities in diabetes still remains as a challenge, more attention should be focused on platelet function for effective management and the prediction of atherothrombotic events in diabetic patients. This review will provide an overview on the current status of knowledge of platelet function abnormalities and clinical marker of platelet hyperreactivity in patients with diabetes.

BackgroundSeveral studies have suggested that elevated levels of hemoglobin A1c (HbA1c) are associated with cardiovascular disease (CVD) in nondiabetic individuals. However, it is unclear whether HbA1c levels can serve as a simple screening marker for increased CVD risk in nondiabetic individuals. Our objective was to evaluate the relationship between HbA1c levels and CVD risk using the Framingham risk score (FRS) in older, apparently healthy nondiabetic Korean adults.MethodsWe retrospectively studied 2,879 Korean adults between the ages of 40 and 79 who underwent voluntary health check-ups at the Health Promotion Center of our hospital from July 2009 to June 2011. Subjects were subdivided based on their HbA1c levels into four groups: tertiles within the HbA1c normal tolerance range and a group for subjects with an increased risk for diabetes (IRD).ResultsThe mean FRS for the upper tertile (9.6±3.8) group was significantly higher than that of the middle tertile (8.4±4.0) and lower tertile (7.6±3.8) groups. In addition, FRS was highest in the IRD group (10.5±3.7). Multiple linear regression analysis demonstrated that HbA1c levels exhibited a significant positive correlation with FRS when adjusted for confounding variables in all subjects (β±standard error [SE], 0.018±0.002; R2, 0.131), women (β±SE, 0.023±0.003; R2, 0.170), and men (β±SE, 0.016±0.004; R2, 0.109).ConclusionHbA1c levels were positively correlated with FRS in older, apparently healthy nondiabetic Korean adults. We propose that HbA1c levels may reflect CVD risk in nondiabetic individuals.

We determined the carrier diffusion lengths in TiO2 nanoporous layers of dye-sensitized solar cells by using scanning photocurrent microscopy using an ultraviolet laser. Here, we excited the carrier directly in the nanoporous layers where the diffusion lengths were found to 140 μm as compared to that of visible illumination measured at 90 μm. The diffusion length decreased with increasing laser modulation frequency, in which we determined the electron lifetimes and the diffusion coefficients for both visible and UV illuminations. The diffusion lengths have been studied in terms of the sintering temperatures for both cells with and without binding molecules. We found a strong correlation between the diffusion length and the overall light-to-current conversion efficiency, proving that improving the diffusion length and hence the interparticle connections, is key to improving cell efficiency.