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Change, speed, uncertainty, disruption, surprise — all are constants in today’s business environment. As a result, leaders who devise strategy can no longer simply plan for what they believe will happen in the long term. Instead, to prepare themselves for the threats and opportunities that can emerge at any moment from any direction, they need to adopt much broader view. In this article the authors explain why taking the broad view of strategy is so important, and they recommend that leaders who want to take the broad view need to think differently in three important ways — by focusing on systems not sectors, scenarios not forecasts, and playbooks not plans.

There is stark global inequity in health research in terms of where studies happen, who leads the research and the ultimate beneficiaries of the results generated. Despite significant efforts made, limited research ideas are conceptualised and implemented in low-resource settings to tackle diseases of poverty, and this is especially true in sub-Saharan Africa. There is strong evidence to show that the barriers to locally led research do not vary largely between disease, study type and location and can be largely solved by addressing these common gaps. The European & Developing Countries Clinical Trials Partnership (EDCTP) was established in 2003 as a European response to the global health crisis caused by the three main poverty-related diseases HIV, tuberculosis and malaria. EDCTP has established a model of long-term sustainable capacity development integrated into clinical trials which addresses this lack of locally led research in sub-Saharan Africa, supporting the development of individual and institutional capacity and research outputs that change the management, prevention and treatment of poverty-related and neglected infectious diseases across Africa. In recognition of emergent data on what the barriers and enablers are to long-term, sustainable capabilities to run studies, EDCTP formed a new collaboration with The Global Health Network (TGHN) in September 2017, with the aim to make a set of cross-cutting tools and resources to support the planning, writing and delivery of high-quality clinical trials available to research staff wherever they are in the world, especially those in low- and middle-income countries (LMICs) via TGHN platform. These new resources developed on the ‘EDCTP Knowledge Hub’ are those identified in the mixed method study described in this commentary as being key to addressing the gaps that the research community report as the most limiting elements in their ability to design and implement studies. The Knowledge Hub aims to make these tools freely available to any potential health research team in need of support and guidance in designing and running their own studies, particularly in low-resource settings. The purpose is to provide open access to the specific guidance, information and tools these teams cannot otherwise access freely. Ultimately, this will enable them to design and lead their own high-quality studies addressing local priorities with global alignment, generating new data that can change health outcomes in their communities.

Yucong Li,1– 3 Dong Wang,1 Jingshu Liu,1 Yunzhe Li,1 Duke Chen,1 Lei Zhou,4 Tingyuan Lang,1– 3 Qi Zhou1– 3 1Department of Gynecologic Oncology, Chongqing University Cancer Hospital, Chongqing 400030, People’s Republic of China; 2Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, People’s Republic of China; 3Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing 400044, People’s Republic of China; 4Singapore Eye Research Institute, Singapore, 169856, SingaporeCorrespondence: Qi Zhou; Tingyuan LangDepartment of Gynecologic Oncology, Chongqing University Cancer Hospital, Chongqing 400030, People’s Republic of ChinaTel +86 18908384529; +86 18717859346Fax +86 23 65311341Email cqzl_zq@163.com; michaellang2009@163.comPurpose: This study aims to reveal the mechanism underlying baicalin-suppressing ovarian cancer stemness.Methods: OVCAR-3 and the primary ovarian cancer cells were used for cell model. The ovarian cancer stem cells were isolated by suspension culture. Cell viability and clonogenicity were examined by CCK-8 assay and colony formation assay. The self-renewal of the cells was evaluated by the determination of sphere-forming capacity and the frequency of in vitro sphere-forming and in vivo tumor-initiating cells. The mRNA and protein levels were relatively quantified by qRT-PCR and Western blot. The transcription regulation of target genes was tested by luciferase reporter assay and a modified nuclear rn-on qRT-PCR assay.Results: Treatment with a non-toxic dose of baicalin significantly inhibited the spherogenicity of ovarian cancer cells. Moreover, a non-toxic dose of baicalin treatment suppressed the frequency of sphere-forming and tumor-initiating ovarian cancer cells. Furthermore, the expression of ovarian cancer stem cell markers (CD133 and ALDH1A1) was inhibited by a non-toxic dose of baicalin treatment. Baicalin inhibits YAP activity and suppresses RASSF6, a positive regulator of YAP, at the transcriptional level. Overexpression of both YAP and RASSF6 abolished the inhibitory effect of baicalin on the proliferation and stemness of ovarian cancer cells.Conclusion: The results in this study demonstrated that baicalin suppresses the stemness of ovarian cancer cells by attenuating YAP activity via inhibiting RASSF6 at the transcriptional level. This finding revealed baicalin as a novel YAP inhibitor that could serve as an anti-cancer drug for eradicating ovarian cancer stem cells.Keywords: baicalin, ovarian cancer, stemness, YAP, RASSF6

Hui Zhang,1–4,* Ting-yuan Lang,5,* Dong-ling Zou,5 Lei Zhou,6–8 Meng Lou,5 Jing-shu Liu,9 Yun-zhe Li,9 Dong-yan Ding,9 Yu-cong Li,5,9 Na Zhang,5 Xiao-dong Zheng,2 Xiao-hua Zeng,2 Qi Zhou,1,3–5 Li Li1 1Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China; 2Breast Cancer Center, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, Chongqing, People’s Republic of China; 4Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, Chongqing, 400030, People’s Republic of China; 5Department of Gynecologic Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, Chongqing, People’s Republic of China; 6Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; 7Singapore Eye Research Institute, Singapore 169856, Singapore; 8Ophthalmology and Visual Sciences Academic Clinical Research Program, Duke-NUS Medical School, Singapore 169867, Singapore; 9Bioengineering College of Chongqing University, Chongqing University, Chongqing 400030, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li LiDepartment of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of ChinaEmail lili5310430@163.comQi ZhouDepartment of Gynecologic Oncology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, Chongqing, People’s Republic of ChinaEmail cqzl_zq@163.comIntroduction: The breast cancer stem cells contribute to the initiation, progression, recurrence, metastasis as well as resistance of breast cancer. However, the mechanisms underlying the maintenance of breast cancer stemness have not been fully understood.Materials and methods: TCGA and GEO data were used for measuring miR-520b expression in breast cancer tissues. Kaplan-meier analysis was used for determining the relationship between miR-520b expression level and the prognosis of patients. Genetic manipulation was performed by lentivirus system and miR-520b inhibitor was used for knockdown of miR-520b. qRT-PCR and Western blot were employed to determine the mRNA and protein levels, respectively. The stemness and EMT (Epithelial to mesenchymal transition) were assessed by sphere-formation and transwell assay as well as the expression of the related markers. The target genes of miR-520b were identified using the online database starBase V3.0.Results: miR-520b is upregulated in cancer tissues of breast cancer patients and predicts poor prognosis. Upregulation of miR-520b was found in breast cancer stem cells. Ectopic expression of miR-520b promotes the stemness of the breast cancer cells, conversely, depletion of miR-520b attenuates the stemness of these cells. miR-520b positively regulates Hippo/YAP signaling pathway and overexpression of LAST2 abolished the effect of miR-520b on the stemness of breast cancer cells.Conclusion: miR-520b promotes the stemness of breast cancer patients by activating Hippo/YAP signaling via targeting LATS2.Keywords: miR-520b, breast cancer, stemness, Hippo/YAP, LATS2