Chapmanjohnson7583
Several scoring systems have been devised to objectively predict survival for patients with intrahepatic cholangiocellular carcinoma (ICC) and support treatment stratification, but they have failed external validation. The aim of the present study was to improve prognostication using an artificial intelligence-based approach. We retrospectively identified 417 patients with ICC who were referred to our tertiary care center between 1997 and 2018. Of these, 293 met the inclusion criteria. Selleckchem P7C3 Established risk factors served as input nodes for an artificial neural network (ANN). We compared the performance of the trained model to the most widely used conventional scoring system, the Fudan score. Predicting 1-year survival, the ANN reached an area under the ROC curve (AUC) of 0.89 for the training set and 0.80 for the validation set. The AUC of the Fudan score was significantly lower in the validation set (0.77, p less then 0.001). In the training set, the Fudan score yielded a lower AUC (0.74) without reaching significance (p = 0.24). Thus, ANNs incorporating a multitude of known risk factors can outperform conventional risk scores, which typically consist of a limited number of parameters. In the future, such artificial intelligence-based approaches have the potential to improve treatment stratification when models trained on large multicenter data are openly available.Prostate cancer chemoresistance is a major therapeutic problem, and the underlying mechanism is not well understood and effective therapies to overcome this problem are not available. Phosphodiesterase-4 (PDE4), a main intracellular enzyme for cAMP hydrolysis, has been previously shown to involve in the early chemo-sensitive prostate cancer cell proliferation and progression, but its role in the more-advanced chemo-resistant prostate cancer is completely unknown. Here we found that the expression of PDE4 subtype, PDE4D, is highly elevated in the chemo-resistant prostate cancer cells (DU145-TxR and PC3-TxR) in comparison to the chemo-sensitive prostate cancer cells (DU145 and PC3). Inhibition of PDE4D with a potent and selective PDED4 inhibitor, Eggmanone, effectively decreases the invasion and proliferation as well as induces cell death of the chemo-resistant prostate cancer cells (DU145-TxR and PC3-TxR). These results were confirmed by siRNA knockdown of PDE4D. We and colleagues previously reported that Eggmanone can effectively blocked sonic Hedgehog signaling via PDE4D inhibition, and here our study suggests that that Eggmanone downregulated proliferation of the chemo-resistant prostate cancer cells via sonic Hedgehog signaling. In addition, Eggmanone treatment dose-dependently increases docetaxel cytotoxicity to DU145-TxR and PC3-TxR. As cancer stem cells (CSCs) are known to be implicated in cancer chemoresistance, we further examined Eggmanone impacts on CSC-like properties in the chemo-resistant prostate cancer cells. Our study shows that Eggmanone effectively down-regulates the expression of CSCs' marker genes Nanog and ABC sub-family G member 2 (ABCG2) and attenuates sphere formation in DU145-TxR and PC3-TxR cells. In summary, our work shows that Eggmanone effectively overcomes the chemoresistance of prostate cancer cells presumably through sonic Hedgehog signaling and targeting CSCs, suggesting that Eggmanone may serve as a novel agent for chemo-resistant prostate cancer.High prevalence of depression and physical inactivity have been consistently reported among college students, especially in females. Guided by Lubans et al.'s conceptual framework, the primary purpose of this study was to examine the longitudinal relationships of PA motivation with leisure-time PA and depressive symptoms among college students over one academic year. Employing a longitudinal repeated measure design, 1004 college students in China were recruited in this study (28.3% males and 71.7% females; M age = 18.93 ± 0.64 years; 18-22 years old). Participants completed previously validated questionnaires assessing PA motivation (perceived competence beliefs and task values toward PA), leisure-time PA participation, and depressive symptoms in Fall 2016 (Time 1) and Fall 2017 (Time 2). Both male and female college students showed a significant increase of depressive symptoms from freshmen to sophomores (p less then 0.05). The regression models indicated that perceived competence beliefs and task values toward PA were significant predictors of depressive symptoms at Time 2 (p less then 0.05) after controlling for Time 1 measures in males and females, respectively. Physically active college students consistently demonstrated higher PA motivation, and they displayed fewer depressive symptoms compared to inactive peers over time (p less then 0.05). The findings suggest sex-specified motivational intervention strategies and PA promotion programs/opportunities are needed to reduce depression symptoms among college students over time.Objective Cardiovascular magnetic resonance imaging (CMR) late gadolinium enhancement technique (LGE) detects thrombus rather than anatomical presence based on tissue properties and is theoretically highly accurate. The present study's goal was to compare the diagnostic accuracy obtained with various CMR techniques and transthoracic echocardiography to diagnose left ventricular thrombus and evaluate the prevalence and perspectives of left ventricular (LV) thrombus among patients with impaired systolic left ventricular function. Methods In a single academic referral center, a retrospective database review of all CMR assessments of the established left ventricular thrombus was carried out in 206 consecutive patients with reduced systolic function for five years. To assess thrombus risk factors, clinical and imaging parameters were analyzed. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), echocardiography, and cine-CMR sequence accuracy have been identified. LV structured with transthoracic echocardiography. An additional parameter available from LGE-CMR and shown as an independent risk factor for left ventricular thrombus is the myocardial scar.