The receptor activator of nuclear factor kappa B (RANK) is a member of the tumor necrosis factor (TNF) receptor superfamily. It plays a critical role in osteoclast differentiation, lymph node organogenesis, and mammary gland development. The stimulation of RANK causes the activation of transcription factors NF-κB and activator protein 1 (AP1), and the mitogen activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). In the signal transduction of RANK, the recruitment of the adaptor molecules, TNF receptor-associated factors (TRAFs), is an initial cytoplasmic event. Recently, the association of the MAPK kinase kinase, transforming growth factor-β-activated kinase 1 (TAK1), with TRAF6 was shown to mediate the IL-1 signaling to NF-κB and JNK. We investigated whether or not TAK1 plays a role in RANK signaling. A dominant-negative form of TAK1 was discovered to abolish the RANK-induced activation of AP1 and JNK. The AP1 activation by TRAF2, TRAF5, and TRAF6 was also greatly suppressed by the dominantnegative TAK1. The inhibitory effect of the TAK1 mutant on RANK-and TRAF-induced NF-κB activation was also observed, but less efficiently. Our findings indicate that TAK1 is involved in the MAPK cascade and NF-κB pathway that is activated by RANK.
Background: Previous studies analyzed risk factors for postoperative pancreatic fistula (POPF) and developed risk prediction tool using scoring system. However, no study has built a nomogram based on individual risk factors. This study aimed to evaluate individual risks of POPF and propose a nomogram for predicting POPF. Methods: From 2007 to 2016, medical records of 1771 patients undergoing pancreaticoduodenctomy were reviewed retrospectively. Variables with p < 0.05 in multivariate logistic regression analysis were included in the nomogram. Internal performance validation was executed using a repeated cross validation method. Results: Of 1771 patients, 222 (12.5%) experienced POPF. In multivariable analysis, sex (p = 0.004), body mass index (BMI) (p < 0.001), ASA score (p = 0.039), preoperative albumin (p = 0.035), pancreatic duct diameter (p = 0.002), and location of tumor (p < 0.001) were identified as independent predictors for POPF. Based on these six variables, a POPF nomogram was developed. The area under the curve (AUC) estimated from the receiver operating characteristic (ROC) graph was 0.709 in the train set and 0.652 in the test set. Conclusions: A POPF nomogram was developed. This nomogram may be useful for selecting patients who need more intensified therapy and establishing customized treatment strategy.
SE-BOLD fMRI improves spatial specificity to microvessels compared to GE-BOLD at both fields. BOLD sensitivity is similar at the both fields and can be improved at ultrahigh fields only for thermal-noise-dominant ultrahigh-resolution fMRI.
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