Spatiotemporal evolution and mechanisms of tourism efficiency and its decomposition: Evidence from 63 counties in Zhejiang, China.

Although efficiency analysis could reflect the state and quality of tourism's economic development, no research has been conducted investigating the spatiotemporal evolution and mechanisms of county-level tourism efficiency. We quantified tourism efficiency and its decomposition in 63 counties of Zhejiang, employing the bootstrap data envelopment analysis (DEA), hot spot analysis, and quantile regression to explore the spatiotemporal evolution and influencing factors of tourism efficiency, and examine its driving and constraining mechanisms. The results uncovered obvious upward trends in the tourism efficiency of Zhejiang's counties, with the mean value increasing from 0.285 to 0.688. Compared with scale efficiency, the influence of technological efficiency on the growth of comprehensive efficiency increased remarkably. Significant differences were evident in the spatial distributions of the identified hot and cold spots of comprehensive efficiency, which were respectively distributed in northern and southern Zhejiang. The distributions of decomposition efficiency were found to be spatially dependent. The driving mechanism of tourism efficiency involve two driving influences and two constraining influences, including economy and resource driving, market and traffic driving, industry and traffic constraining, and market and industry constraining. The findings of this study contribute to understanding of tourism efficiency growth in regional destinations and provide insights for strategic policymaking in various counties of Zhejiang.

Investigating Structural Relationships between Professional Identity, Learning Engagement, Academic Self-Efficacy, and University Support: Evidence from Tourism Students in China.

In order to foster students' development and enhance the training quality within tourism programs at universities, this study aims to investigate the relationships among tourism students' professional identity, academic self-efficacy, learning engagement, and university support. Professional identity refers to learners' recognition and understanding of their study programs and is viewed as a dynamic, progressive process consisting of professional cognition, professional emotion, and professional appraisal. Data were collected from 333 tourism students studying at Chinese universities. They were analyzed through SPSS and SmartPLS. The results revealed that there is no significant correlation between students' professional cognition and learning engagement. However, students' professional emotions and professional appraisals positively influence learning engagement. Moreover, all three dimensions of professional identity exhibit positive effects on students' academic self-efficacy. Additionally, students' academic self-efficacy demonstrates a positive impact on learning engagement, and university support is associated with increased learning engagement and academic self-efficacy. This study contributes to a comprehensive understanding of the learning experience of tourism students and aims to facilitate the advancement of tourism education through cultivating students' professional identity towards tourism and developing students' career commitment in the tourism industry. Theoretical and practical implications are discussed.

Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development.

Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC50 of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC50 = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.

Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumor.

Pamiparib, an investigational Poly (ADP-ribose) polymerase (PARP) inhibitor in clinical development, demonstrates excellent selectivity for both PARP1 and PARP2, and superb anti-proliferation activities in tumor cell lines with BRCA1/2 mutations or HR pathway deficiency (HRD). Pamiparib has good bioavailability and is 16-fold more potent than olaparib in an efficacy study using BRCA1 mutated MDA-MB-436 breast cancer xenograft model. Pamiparib also shows strong anti-tumor synergy with temozolomide (TMZ), a DNA alkylating agent used to treat brain tumors. Compared to other PARP inhibitors, pamiparib demonstrated improved penetration across the blood brain barrier (BBB) in mice. Oral administration of pamiparib at a dose as low as 3 mg/kg is sufficient to abrogate PARylation in brain tumor tissues. In SCLC-derived, TMZ-resistant H209 intracranial xenograft model, combination of pamiparib with TMZ overcomes its resistance and shows significant tumor inhibitory effects and prolonged life span. Our data suggests that combination of pamiparib with TMZ has unique potential for treatment of brain tumors. Currently, the combination therapy of pamiparib with TMZ is evaluated in clinical trial [NCT03150862].

IDO1 Inhibition Synergizes with Radiation and PD-1 Blockade to Durably Increase Survival Against Advanced Glioblastoma.

Purpose: Glioblastoma is the most aggressive primary brain tumor in adults with a median survival of 15-20 months. Numerous approaches and novel therapeutics for treating glioblastoma have been investigated in the setting of phase III clinical trials, including a recent analysis of the immune checkpoint inhibitor, nivolumab (anti-PD-1), which failed to improve recurrent glioblastoma patient survival. However, rather than abandoning immune checkpoint inhibitor treatment for glioblastoma, which has shown promise in other types of cancer, ongoing studies are currently evaluating this therapeutic class when combined with other agents.Experimental Design: Here, we investigated immunocompetent orthotopic mouse models of glioblastoma treated with the potent CNS-penetrating IDO1 enzyme inhibitor, BGB-5777, combined with anti-PD1 mAb, as well as radiotherapy, based on our recent observation that tumor-infiltrating T cells directly increase immunosuppressive IDO1 levels in human glioblastoma, the previously described reinvigoration of immune cell functions after PD-1 blockade, as well as the proinflammatory effects of radiation.Results: Our results demonstrate a durable survival benefit from this novel three-agent treatment, but not for any single- or dual-agent combination. Unexpectedly, treatment efficacy required IDO1 enzyme inhibition in non-glioblastoma cells, rather than tumor cells. Timing of effector T-cell infiltration, animal subject age, and usage of systemic chemotherapy, all directly impacted therapy-mediated survival benefit.Conclusions: These data highlight a novel and clinically relevant immunotherapeutic approach with associated mechanistic considerations that have formed the basis of a newly initiated phase I/II trial for glioblastoma patients. Clin Cancer Res; 24(11); 2559-73. ©2018 AACR.