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Jee Eun Lee Department of Business, Korea University, Seoul, 02841, Republic of KoreaCorrespondence: Jee Eun Lee, Department of Business, Korea University, 145, Anam-Ro, Seongbuk-Gu, Seoul, 02841, Korea, Email jelee89@korea.ac.krPurpose: Based on the attribution and appraisal theories of emotion, this study investigates whether a consumer’s frustration and anger after a service failure reduces in different ways after hearing explanations from different sources (other customer vs employee vs none) under different blame attribution circumstances (situational vs service provider), and its subsequent influence on complaining intention.Methods: In Study 1, valid data from 239 participants (46.9% female, Mage=35.6 years) were used to test the interaction effect of the explanation source and blame attribution on frustration and anger. In Study 2, using valid answers from 253 students at Korea University (57.9% female, Mage=20.9 years), Study 1 was replicated and, in addition, tested the moderated mediating impact on complaining intention. The overall theoretical model was tested with ANOVA and Hayes process model 8.Results: When blame attribution was situational, the employee’s explanation did not mitigate either frustration or anger, whereas the other customer’s explanation mitigated frustration but not anger. In contrast, when blame attribution was towards the service provider, the employee’s explanation mitigated both frustration and anger, whereas the other customer’s explanation mitigated only frustration. In addition, the mitigation of frustration and anger by other customers subsequently led to a decrease in complaining intention, which was stronger and only significant when blame attribution was situational. However, only anger acted as a mediator between the employee’s explanation and complaining intention, which did not vary according to blame attribution.Conclusion: The results of the study advance the current knowledge on informational support as a service recovery process by suggesting the crucial role of other consumers in mitigating the target customer’s frustration, especially under situational service failure, which successively leads to a decrease in complaining intention, whereas the employee’s explanation decreases complaining intention only through the mitigation of anger.Keywords: service recovery, other consumer’s explanation, employee’s explanation, frustration, anger

Jeong Eun Lee,1 Jinyoung Oh,1 Jun Nyung Lee,2 Hyun-Su Ri,3 Chang Sub Lee,3 Jinseok Yeo1 1Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Kyungpook National University Chilgok Hospital, Daegu, Korea; 2Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea; 3Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Kyungpook National University Hospital, Daegu, KoreaCorrespondence: Jinseok Yeo, Department of Anesthesiology and Pain Medicine Kyungpook National University School of medicine, Kyungpook National University Chilgok Hospital, Daegu, Korea, Tel +82-53-200-2644, Fax +82-53-200-2027, Email painfree@gmail.comBackground: Opioid use after surgery is a potential contributor to the opioid epidemic. An adequate pain control method after surgery while minimizing opioid exposure is needed. This study aimed to compare the effect of non-opioid multimodal analgesia (NOMA) protocol with opioid-based patient-controlled analgesia (PCA) for pain relief after robot-assisted radical prostatectomy (RARP).Methods: This prospective randomized, open, non-inferiority trial included 80 patients scheduled for RARP. The NOMA group received pregabalin, paracetamol, bilateral quadratus lumborum block, and pudendal nerve block. PCA group received PCA. Pain scores, postoperative nausea and vomiting, opioid requirements, and quality of recovery were recorded 48 hours after surgery.Results: We found no significant differences in pain scores. The mean difference in pain score during rest at 24 h was 0.5 (95% CI − 0.5 to 2.0). This result demonstrated the non-inferiority of NOMA protocol to PCA at our non-inferiority margin (− 1). In addition, 23 patients in the NOMA group did not receive any opioid agonist for 48 h after surgery. Recovery of bowel function was also faster in the NOMA group than in the PCA group (25.0 hours vs 33.4 hours, p = 0.01).Limitations: We did not evaluate whether our NOMA protocol could decrease the incidence of new continuous opioid use after surgery.Conclusion: NOMA protocol successfully controlled postoperative pain and was non-inferior to morphine-based PCA regarding patient-reported pain intensity. It also promoted recovery of bowel function and decreased postoperative nausea and vomiting.Keywords: multimodal analgesia, opioid sparing, postoperative pain, robot-assisted radical prostatectomy

Ji-Hyun Kang,1,* Ji-Eun Lee,1,* So-Jeong Jeong,1 Chun-Woong Park,1 Dong-Wook Kim,2 Kwon-Yeon Weon3 1College of Pharmacy, Chungbuk National University, Cheongju, Korea; 2College of Pharmacy, Wonkwang University, Iksan, Korea; 3College of Pharmacy, Daegu Catholic University, Gyeongsan, Korea*These authors contributed equally to this workCorrespondence: Dong-Wook Kim, College of Pharmacy, Wonkwang University, Iksan, 54538, Korea, Tel +82-63-229-7130, Fax +82-63-850-7309, Email pharmengin@gmail.com Kwon-Yeon Weon, College of Pharmacy, Daegu Catholic University, Gyeongsan, 38430, Korea, Tel +82-53-850-3616, Fax +82-53-850-3602, Email weonky@cu.ac.krPurpose: This study aimed to ensure the convenience of administration and reproducibility of efficacy, regardless of the meal, by improving the solubility of rivaroxaban (RIV).Methods: RIV is a non-vitamin K antagonist oral anticoagulants that exhibits a coagulation effect by directly inhibiting coagulation factor Xa. However, RIV has a very low solubility; therefore, it must be administered with a meal at high doses. We used a drug- hydroxypropyl-beta-cyclodextrin (CD)-water-soluble polymer triple complex (R-C-P complex) to solubilize RIV. Using Minitab, we evaluated the effect of each factor on RIV solubility and developed an optimal R-C-P complex formulation. The amount of CD, amount of polymer, and polymer type were set as the independent variables X1, X2, and X3, respectively. RIV solubility (Y1) and dissolution rate for 45 min in pH 4.5 medium (Y2) and pH 1.2 medium (Y3) were set as response variables.Results: The most efficient RIV solubilization effect was obtained from the composition using CD and HPMC 2208, and physicochemical properties and dissolution parameters were analyzed. RIV in the R-C-P complex was present in an amorphous form and showed high solubility. Unlike commercial products, it showed a 100% dissolution rate. The R-C-P complex formulation secured high RIV solubility and 100% release regardless of pH.Conclusion: The results imply that high-dose RIV can be administered regardless of the meal, reducing the risk of changing the drug effect due to the patient’s administration mistake.Keywords: rivaroxaban, drug-cyclodextrin-polymer triple complex, solubilization, design of experiment

The development of new treatment agents in recent decades has significantly improved the survival of patients with multiple myeloma (MM). Nonetheless, MM remains an incurable disease; therefore, novel combination therapies are required. Natural killer (NK) cells are one of the safest immunotherapeutic options. In this study, we found that the anti-myeloma activity of expanded NK cells (eNKs) was improved by daratumumab, lenalidomide, and dexamethasone (DRd) in an MM xenograft mouse model. NK cells expanded from peripheral blood mononuclear cells collected from MM patients were highly cytotoxic against DRd pretreated tumor cells in vitro. To mimic the clinical protocol, a human MM xenograft model was developed using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγnull (NSG) mice. MM bearing mice were randomly divided into six groups: no treatment, eNK, Rd, Rd + eNKs, DRd, and DRd + eNKs. DRd significantly enhanced the cytotoxicity of eNKs by upregulating NK cell activation ligands and effector function. DRd in combination with eNKs significantly reduced the serum M-protein level and prolonged mouse survival. In addition, DRd significantly increased the persistence of eNK and homing to MM sites. These results show that the anti-myeloma activity of ex vivo-expanded and activated NK cells is augmented by the immunomodulatory effect of DRd in MM-bearing mice, suggesting the therapeutic potential of this combination for MM patients.

This paper describes the design and investigation of a high-school-affiliated esports program based on an enrichment learning model. In it, the authors detail the connections between esports and learning, self-reported impacts of the program and demographic differences among them, students' attitudes toward program features, and equity in results across demographic groups. Several methods over four years were used to document and evaluate the program including observational fieldwork, an online retrospective posttest survey, and a modified instrument given in an alternative one-sample pretest-posttest design. Authors find compelling evidence that an enrichment approach to youth esports yields positive outcomes in communication, social-emotional skills, and school affiliation. There are also indications that this approach temporarily staved off an overall downward trend in key variables including STEM interest, self-regulation, attendance, and GPA, during the COVID-19 global pandemic.

Dendritic cells (DCs) are the most potent antigen-presenting cells, and have thus been used in clinical cancer vaccines. However, the effects of DC vaccines are still limited, leading researchers to explore novel ways to make them effective. In this study, we investigated whether human monocyte-derived DCs generated via the addition of interleukin 15 (IL-15) had a higher capacity to induce antigen-specific T cells compared to conventional DCs. We isolated CD14+ monocytes from peripheral blood from multiple myeloma (MM) patients, and induced immature DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 in the presence or absence of IL-15 for 4-6 days. Then we generated mature DCs (mDCs) with lipopolysaccharide for another 2 days [IL-15 mDCs (6 days), IL-15 mDCs (8 days), and conventional mDCs (8 days)]. IL-15 mDCs (6 days) showed higher expression of MHC I and II, CD40, CD86, and CCR7, and the secretion of IFN-γ was significantly higher compared to conventional mDCs. IL-15 mDCs (6 days) showed superior polarization of naïve T cells toward Th1 cells and a higher proportion of activated T cells, cytokine-induced killer (CIK) cells, and natural killer (NK) cells for inducing strong cytotoxicity against myeloma cells, and lower proportion of regulatory T cells compared to conventional mDCs. These data imply that novel multipotent mDCs generated by the addition of IL-15, which can be cultivated in 6 days, resulted in outstanding activation of T cells, CIK cells and NK cells, and may facilitate cellular immunotherapy for cancer patients.

BACKGROUND: Natural killer (NK) cell-based immunotherapy is a promising treatment approach for multiple myeloma (MM), but obtaining a sufficient number of activated NK cells remains challenging. Here, we report an improved method to generate ex vivo expanded NK (eNK) cells from MM patients based on genetic engineering of K562 cells to express OX40 ligand and membrane-bound (mb) IL-18 and IL-21. METHODS: K562-OX40L-mbIL-18/-21 cells were generated by transducing K562-OX40L cells with a lentiviral vector encoding mbIL-18 and mbIL-21, and these were used as feeder cells to expand NK cells from peripheral blood mononuclear cells of healthy donors (HDs) and MM patients in the presence of IL-2/IL-15. Purity, expansion rate, receptor expression, and functions of eNK cells were determined over four weeks of culture. RESULTS: NK cell expansion was enhanced by short exposure of soluble IL-18 and IL-21 with K562-OX40L cells. Co-culture of NK cells with K562-OX40L-mbIL-18/-21 cells resulted in remarkable expansion of NK cells from HDs (9,860-fold) and MM patients (4,929-fold) over the 28-day culture period. Moreover, eNK cells showed increased expression of major activation markers and enhanced cytotoxicity towards target K562, U266, and RPMI8226 cells. CONCLUSIONS: Our data suggest that genetically engineered K562 cells expressing OX40L, mbIL-18, and mbIL-21 improve the expansion of NK cells, increase activation signals, and enhance their cytolytic activity towards MM cells.

Various combination treatments have been considered to attain the effective therapy threshold by combining independent antitumor mechanisms against the heterogeneous characteristics of tumor cells in malignant brain tumors. In this study, the natural killer (NK) cells associated with bevacizumab (Bev) plus irinotecan (Iri) against glioblastoma multiforme (GBM) were investigated. For the experimental design, NK cells were expanded and activated by K562 cells expressing the OX40 ligand and membrane-bound IL-18 and IL-21. The effects of Bev and Iri on the proliferation and NK ligand expression of GBM cells were evaluated through MTT assay and flow cytometry. The cytotoxic effects of NK cells against Bev plus Iri-treated GBM cells were also predicted via the LDH assay in vitro. The therapeutic effect of different injected NK cell routes and numbers combined with the different doses of Bev and Iri was confirmed according to tumor size and survival in the subcutaneous (s.c) and intracranial (i.c) U87 xenograft NOD/SCID IL-12Rγnull mouse model. The presence of injected-NK cells in tumors was detected using flow cytometry and immunohistochemistry ex vivo. As a result, Iri was found to affect the proliferation and NK ligand expression of GBM cells, while Bev did not cause differences in these cellular processes. However, the administration of Bev modulated Iri efficacy in the i.c U87 mouse model. NK cells significantly enhanced the cytotoxic effects against Bev plus Iri-treated GBM cells in vitro. Although the intravenous (IV) injection of NK cells in combination with Bev plus Iri significantly reduced the tumor volume in the s.c U87 mouse model, only the direct intratumorally (IT) injection of NK cells in combination with Bev plus Iri elicited delayed tumor growth in the i.c U87 mouse model. Tumor-infiltrating NK cells were detected after IV injection of NK cells in both s.c and i.c U87 mouse models. In conclusion, the potential therapeutic effect of NK cells combined with Bev plus Iri against GBM cells was limited in this study. Accordingly, further research is required to improve the accessibility and strength of NK cell function in this combination treatment.