Model based arterial and portal vein input functions were automatically determined during the joint direct parameterization. Observations made on simulated fully and highly undersampled liver DCE MRI data were confirmed on acquired clinical data. INTRODUCTION Oral squamous cell carcinoma (OSCC) is the seventh most common cancer globally, and has been identified as a growing health concern. This study aims to evaluate the current literature comparing elective neck dissection to observation in the treatment of early-stage tongue SCC, focusing on nodal recurrence, overall survival, disease specific survival statistics from randomised controlled trials comparing the two interventions. METHODS Systematic review and meta-analysis was conducted according to PRISMA guidelines. The odds ratio (OR) was used as a summary statistic. RESULTS From 8 studies, there was a total of 372 cases of recurrence, 98 (15.1%) in END group and 274 (41.5%) in the Observation group. There was a significantly lower rate of recurrence in the END group compared to observation (OR 0.25, 95% CI 0.16-0.39, I2 = 54%, P  less then  0.00001). END was associated with higher overall survival rates when compared with observation (OR 1.95, 95% CI 1.40-2.73, I2 = 14%, P  less then  0.0001). END was also associated with higher disease-specific survival compared with observation (OR 1.88, 95% CI 1.21-2.93), I2 = 47%, P = 0.005), with no significant heterogeneity noted. CONCLUSIONS END was associated with significantly lower recurrence rates and higher overall and disease-specific survival compared to a conservative observation approach in early-stage oral SCC with clinically N0 neck. OBJECTIVES R-Spondins (RSPOs) and leucine-rich repeat-containing G-protein coupled receptors (LGRs) play a critical role in embryonic and cancer development through potentiation of WNT/ß-catenin signaling, but their prognostic significance in head and neck squamous cell carcinoma (HNSCC) is still unclear. HNSCC is a group of neoplasms that include, amongst others, oropharyngeal squamous cell carcinoma (OPSCC), some of which are induced by human papillomavirus (HPV). We aimed to investigate the potential prognostic value of RSPO2 and LGR4/5/6 on overall survival (OS) and disease-free survival (DFS) in HNSCC patients. METHODS We examined RSPO and LGR expression by means of immunohistochemistry in 126 HNSCC patients. Furthermore, in order to validate our findings externally, we examined RSPO2 and LGR6 mRNA expression levels using independent secondary datasets. RESULTS The five-year OS of our cohort was 59.6%. RSPO2 and LGR4/5/6 expression were not associated with OS or DFS in multivariable analyses. Within the HPV+ cases (n = 26, 33%), however, we observed a difference in OS by RSPO2 expression (5-year OS RSPO+ 45.4% vs. RSPO2- 84.6%) and LGR6 expression (5-year OS LGR6+ 52.9% vs. LGR6-100%). Evidence for an interaction of HPV status with RSPO2 and LGR6 was found for OS. Relative to HPV+/LGR6- patients, HPV+/LGR6+ patients were 12 times more likely to die. These results were replicated in the second dataset. CONCLUSION Our results indicated that the expression status of LGR6 had an influence on the aggressiveness of HPV+ OPSCC, potentially making this receptor a useful marker for identifying patients with a high risk of death. Rust fungi are major pathogens that negatively affect crops and ecosystems. Recent rust disease epidemics driven by the emergence of strains with novel virulence profiles demand a better understanding of the evolutionary mechanisms of these organisms. Here, we review research advances in genome-scale analysis coupled with functional validation of effector candidate genes that have been instrumental to elucidate processes that contribute to changes in virulence phenotypes. We highlight how haplotype-phased genome references have paved the road to link these processes to the reproductive phases of rust fungi and have provided evidence for somatic exchange between strains as an important mechanism for generating diversity in asexual populations. With increasing data availability, we envision the future development of molecular virulence diagnostic tools. The purpose of this study was to explore whether individual differences in glucocorticoid concentrations were associated with symptom improvement following exposure therapy for patients with social anxiety disorder. To do this, 60 participants with social anxiety disorder completed a randomized-controlled trial of exposure therapy, where participants were randomized to receive scopolamine-augmentation or placebo during their 7 exposure sessions. Scopolamine is an antimuscarinic which blocks the effects of acetylcholine and reduces autonomic arousal. During sessions 1, 4, 7, and during the post-treatment extinction assessment, participants provided up to 16 saliva samples (4 in each session). Pre-treatment, post-treatment, and at 1-month follow-up, participants completed the Liebowitz Social Anxiety Scale to monitor change in fear and avoidance symptoms. Elevated endogenous in-session cortisol during exposure sessions was associated with less symptom improvement from pre- to post-treatment and at 1-month follow-up. The association between elevated endogenous in-session cortisol and attenuated symptom change was not moderated by scopolamine treatment condition. Individuals with social anxiety disorder who have elevated neuroendocrine signaling may under-benefit from exposure therapy. This is the first study, to our knowledge, to examine whether endogenous in-session cortisol concentrations predict symptom changes following exposure therapy for the treatment of social anxiety disorder. More investigation of non-invasive and reliable biological markers that explain variability in responses to effective treatments are needed.  https://www.selleckchem.com/products/otx015.html  Pathological angiogenesis is necessary for tumor development and metastasis. Tumor-derived extracellular vesicles (EVs) play an important role in mediating the crosstalk between cancer cells and vascular endothelial cells. To date, whether and how microRNAs (miRNAs) encapsulated in tumor-derived EVs affect angiogenesis in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we showed that miR-181b-5p, an angiogenesis-promoting miRNA of ESCC, can be transferred from ESCC cells to vascular endothelial cells via EVs. In addition, ESCC-derived EVs-miR-181b-5p dramatically induced angiogenesis by targeting PTEN and PHLPP2, and thereby facilitated tumor growth and metastasis. Moreover, miR-181b-5p was highly expressed in ESCC tissues and serum EVs. High miR-181b-5p expression level in ESCC patients was well predicted for poor overall survival. Our work suggests that intercellular crosstalk between tumor cells and vascular endothelial cells is mediated by tumor-derived EVs. miR-181b-5p-enriched EVs secreted from ESCC cells are involved in angiogenesis that control metastasis of ESCC, providing a potential diagnostic biomarker or drug target for ESCC patients.