An Analysis of Effects of Boredom on Revisit Intention – A Case in Japanese Popular Tourism Destinations

This study focuses on the effects of visitors’ boredom of a destination on their intention to revisit it, using two Japanese popular tourism destinations as the cases. Relationships between three factors, which are satisfaction, boredom and revisit intention, were examined. In addition to the subjective index of visitors’ boredom based on ratings on a scale, the rate of remaining facilities (RoRF), which was the objective index of visitors’ boredom, is also employed. A questionnaire survey was conducted to obtain data related to the five factors. We conclude that subjective index of visitors’ boredom may not be effective for understanding of their revisit intention, while their revisit intention can arguably be relevant to the RoRF

MRI in the Diagnosis of Endometriosis and Related Diseases

Endometriosis, a common chronic inflammatory disease in female of reproductive age, is closely related to patient symptoms and fertility. Because of its high contrast resolution and objectivity, MRI can contribute to the early and accurate diagnosis of ovarian endometriotic cysts and deeply infiltrating endometriosis without the need for any invasive procedure or radiation exposure. The ovaries, which are the most frequent site of endometriosis, can be afflicted by multiple related conditions and diseases. For the diagnosis of deeply infiltrating endometriosis and secondary adhesions among pelvic organs, fibrosis around the ectopic endometrial gland is usually found as a T2 hypointense lesion. This review summarizes the MRI findings obtained for ovarian endometriotic cysts and their physiologically and pathologically related conditions. This article also includes the key imaging findings of deeply infiltrating endometriosis

CADLIVE Optimizer: Web-based Parameter Estimation for Dynamic Models

Computer simulation has been an important technique to capture the dynamics of biochemical networks. In most networks, however, few kinetic parameters have been measured in vivo because of experimental complexity. We develop a kinetic parameter estimation system, named the CADLIVE Optimizer, which comprises genetic algorithms-based solvers with a graphical user interface. This optimizer is integrated into the CADLIVE Dynamic Simulator to attain efficient simulation for dynamic models

CADLIVE optimizer: web-based parameter estimation for dynamic models

Computer simulation has been an important technique to capture the dynamics of biochemical networks. In most networks, however, few kinetic parameters have been measured in vivo because of experimental complexity. We develop a kinetic parameter estimation system, named the CADLIVE Optimizer, which comprises genetic algorithms-based solvers with a graphical user interface. This optimizer is integrated into the CADLIVE Dynamic Simulator to attain efficient simulation for dynamic models

Inhibitory Effect of Polypodium Leucotomos Extract on Cytochrome P450 3A-mediated Midazolam Metabolism

Polypodium leucotomos（PL）is a fern native to Latin America, and its extract is used as an oral sunscreen; however, its safety during use has not been adequately investigated. Therefore, the aim of this study was to evaluate food-drug interactions associated with PL extract mediated by cytochrome P450 3A（CYP3A）inhibition and induction. Inhibition of CYP3A-mediated midazolam（MDZ）1’-hydroxylation activity by PL extract and its major phenolic components was evaluated in vitro using pooled human liver microsomes. In addition, MDZ pharmacokinetics were investigated in rats after a single dose, as well as after 1 week treatment with PL extract（30mg/kg）in order to evaluate the inhibitory and inducible effects of PL on CYP3A in vivo, respectively. Serum MDZ concentrations were analyzed and pharmacokinetic parameters were compared between PL- and water（control）-treated groups. In vitro, PL extract decreased MDZ 1’-hydroxylation activity in a concentration-dependent manner. However, the major phenolic compounds in PL extracts, namely caffeic, chlorogenic, p-coumaric, ferulic, and vanillic acids, did not exhibit any marked inhibitory effects on MDZ 1’-hydroxylation activity. In vivo, administration of a single dose of PL extract to rats significantly increased the area under the serum concentration-time curve from time 0 to infinity（AUC0–∞）and the maximum serum concentration（Cmax）of MDZ（by 57％ and 88％, respectively; P＜0.05）. In contrast, there were no significant changes in MDZ pharmacokinetic parameters after 1 week of treatment with PL extract. These results suggest that PL extract can cause a food-drug interaction by inhibiting CYP3A

Magnetic transition due to the inter-singlet spin-exchange interaction and elastic softening by the interplay of electric quadrupoles in the distorted kagome lattice antiferromagnet Tb3Ru4Al12

The distorted kagome lattice antiferromagnet Tb3Ru4Al12 with a hexagonal structure has the Néel temperature TN = 22 K. To clarify the 4 f -electronic state and an influence of electric quadrupoles in Tb3Ru4Al12, ultrasonic measurements on a single-crystalline sample at zero magnetic field and under fields were carried. A characteristic elastic softening of the transverse modulus C66 originating from a quadrupole interaction was found. The crystal electric field parameters were determined to reproduce C66, magnetic susceptibilities, and magnetization curves. The obtained level scheme is that the ground and first excited states are singlets, despite the existence of both the magnetic transition and the quadrupole interaction, indicating that Tb3Ru4Al12 is a curious compound. The positive sign of the quadrupole-quadrupole coupling constant for C66 indicates a ferroquadrupolar-type interaction of the electric quadrupole Oxy or O2 2. The anisotropic magnetic field dependencies of TN in the field along [100] and [001] were also clarified.This work was supported by JSPS KAKENHI Grants No.17H06136, No. 18KK0078, and No. 19K03719. This work was also supported by CResCent (Chirality Research Center) in Hiroshima University (the MEXT program for promoting the enhancement of research universities, Japan) and by JSPS Core-to-Core Program, A. Advanced Research Networks. The work was supported by Projects No. 19-00925S and No. 19-07931Y of the Czech Science Foundation and by MGML within the Program of Czech Research Infrastructures (Project No. LM2018096)

Prognostic significance of cribriform adenocarcinoma of the lung: validation analysis of 1,057 Japanese patients with resected lung adenocarcinoma and a review of the literature

Background: Cribriform-predominant adenocarcinoma of the lung (Cribri-ADC) is a recently described tumor growth pattern. However, its prognostic impact has not been clearly determined. We analyzed the data of a series of 1, 057 Japanese patients with resected lung adenocarcinoma to identify the clinical significance of Cribri-ADC. Methods: Cribriform pattern (Cribri-p) is defined as invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests comprising tumors cells that produced glandular lumina. We investigated the correlations of Cribri-p and Cribri-ADC with clinicopathological factors as well as disease-free survival (DFS) and overall survival (OS). Results: Cribri-p was present in 217 patients (20.5%) and Cribri-ADC was determined in 25 patients (2.4%). Cribri-p was associated with larger tumor size, pleural invasion, vascular invasion, lymphatic invasion, and spreading through air spaces (STAS) (all, P<0.0001). Cribri-ADC was associated with younger age (P=0.019), vascular invasion (P=0.0025), STAS (P<0.0001), and ALK rearrangement (P=0.012). The DFS curve of patients with Cribri-ADC was identical to that of patients with solid adenocarcinoma; however, the OS curve was located between that of patients with papillary and acinar adenocarcinoma. Of the 10 patients who had tumor recurrences, eight had EGFR mutations or ALK rearrangement, six of whom achieved relatively long survival (median, 64.6, range, 37.4–113 months) following treatment with tyrosine kinase inhibitors (TKIs). In multivariate analysis, Cribri-ADC was not an independent prognostic factor of either recurrence or death. Conclusions: Cribri-ADC is associated with a higher risk of recurrence; however, most patients can be successfully treated with TKIs

Diagnostic Value of DCE-MRI for Differentiating Malignant Adnexal Masses Compared with Contrast-enhanced-T1WI

Purpose: To compare the diagnostic performance of dynamic contrast-enhanced-MR (DCE-MR) and delayed contrast-enhanced (CE)-MRI added to unenhanced MRI, including diffusion weighted image (DWI) for differentiating malignant adnexal tumors, conducting a retrospective blinded image interpretation study. Methods: Data of 80 patients suspected of having adnexal tumors by ultrasonography between April 2008 and August 2018 were used for the study. All patients had undergone preoperative MRI and surgical resection at our institution. Four radiologists (two specialized in gynecological radiology and two non-specialized) were enrolled for blinded review of the MR images. A 3-point scale was used: 0 = benign, 1 = indeterminate, and 2 = malignant. Three imaging sets were reviewed: Set A, unenhanced MRI including DWI; Set B, Set A and delayed CE-T1WI; and Set C, Set A and DCE-MRI. Imaging criteria for benign and malignant tumors were given in earlier reports. The diagnostic performance of the three imaging sets of the four readers was calculated. Their areas under the curve (AUCs) were compared using the DeLong method. Results: Accuracies of Set B were 81%–88%. Those of Set C were 81%–85%. The AUCs of Set B were 0.83 and 0.89. Those of Set C were 0.81–0.86. For two readers, Set A showed lower accuracy and AUC than Set B/Set C (less than 0.80), although those were equivalent in other readers. No significant difference in AUCs was found among the three sequence sets. Intrareader agreement was moderate to almost perfect in Sets A and B, and substantial to almost perfect in Set C. Conclusion: DCE-MR showed no superiority for differentiating malignant adnexal tumors from benign tumors compared to delayed CE-T1WI with conventional MR and DWI

Re-biopsy status among non-small cell lung cancer patients in Japan: A retrospective study

AbstractObjectiveDisease progression because of acquired resistance is common in advanced or metastatic epidermal growth factor receptor (EGFR)-mutation positive non-small cell lung cancer (NSCLC), despite initial response to EGFR-tyrosine kinase inhibitors (TKIs). In Japan, transbronchial tissue biopsy is the most common sampling method used for re-biopsy to identify patients eligible for treatment. We aimed to investigate the success rate of re-biopsy and re-biopsy status of patients with advanced or metastatic NSCLC completing first-line EGFR-TKI therapy.Patients and methodsThis was a retrospective, multi-center, Japanese study. The target patients in the study were EGFR mutation-positive NSCLC patients. The primary endpoint was the success rate (number of cases in which tumor cells were detected/total number of re-biopsies performed×100). Secondary endpoints included differences between the status of the first biopsy and that of the re-biopsy in the same patient population, and the details of cases in which re-biopsy could not be carried out. Re-biopsy-associated complications were also assessed.ResultsOverall, 395 patients were evaluated (median age 63 years), with adenocarcinoma being the most common tumor type. Re-biopsy was successful in 314 patients (79.5%). Compared with the sampling method at first biopsy, at re-biopsy, the surgical resection rate increased from 1.8% to 7.8%, and percutaneous tissue biopsy increased from 7.6% to 29.1%, suggesting the difficulty of performing re-biopsy. Approximately half of the patients had T790M mutations, which involved a Del19 mutation in 55.6% of patients and an L858R mutation in 43.0%. Twenty-three patients (5.8%) had re-biopsy- associated complications, most commonly pneumothorax.ConclusionsSuccess rate for re-biopsy in this study was approximately 80%. Our study sheds light on the re-biopsy status after disease progression in patients with advanced or metastatic NSCLC. This information is important to improve the selection of patients who may benefit from third-generation TKIs

Selection of immunobiotic ligilactobacillus salivarius strains from the intestinal tract of wakame-fed pigs: Functional and genomic studies

In this article, Ligilactobacillus salivarius FFIG strains, isolated from the intestinal tract of wakame-fed pigs, are characterized according to their potential probiotic properties. Strains were evaluated by studying their interaction with porcine intestinal epithelial (PIE) cells in terms of their ability to regulate toll-like receptor (TLR)-3- or TLR4-mediated innate immune responses, as well as by assessing their adhesion capabilities to porcine epithelial cells and mucins. These functional studies were complemented with comparative genomic evaluations using the complete genome sequences of porcine L. salivarius strains selected from subgroups that demonstrated different ‘immune’ and ‘adhesion’ phenotypes. We found that their immunomodulatory and adhesion capabilities are a strain-dependent characteristic. Our analysis indicated that the differential immunomodulatory and adhesive activities of FFIG strains would be dependent on the combination of several surface structures acting simultaneously, which include peptidoglycan, exopolysaccharides, lipoteichoic acid, and adhesins. Of note, our results indicate that there is no correlation between the immunomodulatory capacity of the strains with their adhesion ability to mucins and epithelial cells. Therefore, in the selection of strains destined to colonize the intestinal mucosa and modulate the immunity of the host, both properties must be adequately evaluated. Interestingly, we showed that L. salivarius FFIG58 functionally modulated the innate immune responses triggered by TLR3 and TLR4 activation in PIE cells and efficiently adhered to these cells. Moreover, the FFIG58 strain was capable of reducing rotavirus replication in PIE cells. Therefore, L. salivarius FFIG58 is a good candidate for further in vivo studying the protective effect of lactobacilli against intestinal infections in the porcine host. We also reported and analyzed, for the first time, the complete genome of several L. salivarius strains that were isolated from the intestine of pigs after the selective pressure of feeding the animals with wakame. Further genomic analysis could be of value to reveal the metabolic characteristics and potential of the FFIG strains in general and of the FFIG58 strain, in particular, relating to wakame by-products assimilation.Fil: Zhou, Binghui. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Ciencias de la Computación; Argentina. Tohoku University; JapónFil: Indo, Yuhki. Tohoku University; JapónFil: Arce, Lorena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Tohoku University; JapónFil: Masumizu, Yuki. Tohoku University; JapónFil: Tomokiyo, Mikado. Tohoku University; JapónFil: Islam, Md Aminul. Bangladesh Agricultural University; Bangladesh. Tohoku University; JapónFil: Garcia Castillo, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Ikeda Ohtsubo, Wakako. Tohoku University; JapónFil: Nochi, Tomonori. Tohoku University; JapónFil: Morita, Hidetoshi. Okayama University; JapónFil: Takahashi, Hideki. Tohoku University; JapónFil: Kurata, Shoichiro. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Kitazawa, Haruki. Tohoku University; Japó