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Journal of Neuro-Oncology - Brain tumor patients report an overwhelming sense of uncertainty when navigating the course of their terminal disease. Historically, organizational experts and/or...  相似文献   
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Ameloblastoma is an odontogenic neoplasm characterized by slow intraosseous growth with progressive jaw resorption. Recent reports have revealed that ameloblastoma harbours an oncogenic BRAFV600E mutation with mitogen-activated protein kinase (MAPK) pathway activation and described cases of ameloblastoma harbouring a BRAFV600E mutation in which patients were successfully treated with a BRAF inhibitor. Therefore, the MAPK pathway may be involved in the development of ameloblastoma; however, the precise mechanism by which it induces ameloblastoma is unclear. The expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C), induced by a combination of the EGF–MAPK pathway and Wnt/β-catenin signalling, has been shown to induce epithelial morphogenesis. It was also reported that the overexpression of ARL4C, due to alterations in the EGF/RAS–MAPK pathway and Wnt/β-catenin signalling, promotes tumourigenesis. However, the roles of ARL4C in ameloblastoma are unknown. We investigated the involvement of ARL4C in the development of ameloblastoma. In immunohistochemical analyses of tissue specimens obtained from 38 ameloblastoma patients, ARL4C was hardly detected in non-tumour regions but tumours frequently showed strong expression of ARL4C, along with the expression of both BRAFV600E and RAF1 (also known as C-RAF). Loss-of-function experiments using inhibitors or siRNAs revealed that ARL4C elevation depended on the RAF1–MEK/ERK pathway in ameloblastoma cells. It was also shown that the RAF1–ARL4C and BRAFV600E–MEK/ERK pathways promoted cell proliferation independently. ARL4C-depleted tumour cells (generated by knockdown or knockout) exhibited decreased proliferation and migration capabilities. Finally, when ameloblastoma cells were co-cultured with mouse bone marrow cells and primary osteoblasts, ameloblastoma cells induced osteoclast formation. ARL4C elevation in ameloblastoma further promoted its formation capabilities through the increased RANKL expression of mouse bone marrow cells and/or primary osteoblasts. These results suggest that the RAF1–MEK/ERK–ARL4C axis, which may function in cooperation with the BRAFV600E–MEK/ERK pathway, promotes ameloblastoma development. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.  相似文献   
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Clinical Oral Investigations - To investigate the effects of antiresorptive treatment on the survival of plateau-root form dental implants. Patients undergoing antiresorptive therapy via oral or...  相似文献   
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Military veterans have greater exposure to adverse childhood experiences (ACEs) than civilians and many also encounter warfare exposures, which can increase the likelihood of mental health problems. The purpose of this study was to test an interaction between childhood traumas and warfare exposures on the mental health of a sample of nearly 10,000 new post-9/11 veterans. Results revealed that male veterans exposed to one or two ACEs, but no warfare, were more likely to experience anxiety, depression, suicidal thinking, and angry outbursts than the reference group (i.e., no ACEs and no warfare exposure). Female veterans exposed to one or two ACEs, but no warfare, were only more likely to experience suicidal thinking. Male and female veterans exposed to three or more ACEs and no warfare were more likely to experience probable posttraumatic stress disorder (PTSD), anxiety, depression, suicidality, and angry outbursts. Among those veterans who experienced corollaries of combat only (e.g., seeing someone killed or seriously wounded), male, but not female veterans were more likely to have probable PTSD, anxiety, and depression. Veterans exposed to warfare (i.e., combat and the corollaries of combat), irrespective of ACEs exposure, were the most likely to report mental health symptoms. Implications for community-based mental health services are discussed.  相似文献   
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