Description: Author(s): C. G. Wang, Z. Li, J. Yang, L. Y. Xing, G. Y. Dai, X. C. Wang, C. Q. Jin, R. Zhou, and Guo-qing Zheng A magnetic order can be completely suppressed at zero temperature ( T ), by doping carriers or applying pressure, at a quantum critical point, around which physical properties change drastically. However, the situation is unclear for an electronic nematic order that breaks rotation symmetry. Here, we ... [Phys. Rev. Lett. 121, 167004] Published Fri Oct 19, 2018

Description: SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival, Published online: 17 April 2018; doi:10.1038/s41388-018-0223-2 SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival

Description: Objectives The primary healthcarecentre (PHCC) is the first place that medical students experience patient contact. Usually, medical students are frustrated by a lack of proper skills training for on-campus history taking (HT), physical examination (PE) and self-directed learning (SDL) to prepare for their PHCC and inhospital patient contact. For pre-clerks, this study aims to compare the effectiveness of PHCC training and PHCC training in combination with on-campus HT and PE training modules (PHCC+on-campus) on their clerkship preparedness. Design This comparative study utilised prospective, consecutive, end of pre-clerkship group objective structured clinical examination (GOSCE), beginning of clerkship OSCE and self-administered Preparation for Hospital Practice Questionnaire (PHPQ). Setting/participants 128 pre-clinical clerk volunteers (64 each year) receiving PHCC training (7 week PHCCtraining in addition to 7 week assignment based group learning, academic year 2014, controls) and PHCC training in combination with on-campus module training (academic year 2015, 7 week PHCCtraining in addition to 7 week on-campus sessions) were sequentially assessed before the module (week 1), at the end of the module (week 14) and at the beginning of clerkship (week 25). Results For overall HT and PE skills, both PHCC and PHCC+on-campus module trained pre-clerks performed better on OSCE than GOSCE. Additionally, the improvement was accompanied by higher self-reported PHPQ scores in ‘confidence/coping’ and ‘SDL’ domains. At the end of the pre-clerkship and the beginning of the clerkship stages, the degree of improvement in preparedness in ‘confidence/coping’ and ‘SDL’ domains was higher for those in the PHCC+on-campus group than for those in the PHCC group. Among the PHCC+on-campus module participants, a positive association was observed between high mean PHPQ-SDL scores and high OSCE scores. Conclusions Our study suggests that the PHCC+on-campus module, which is paired faculty led and pre-trained dyad student assisted, is effective in developing a preclinical clerk’s HT and PE skills and intensifying SDL/patient management abilities to prepare for hospital practice in clerkship.

Description: Objectives Inter-professional education (IPE) builds inter-professional collaboration (IPC) attitude/skills of health professionals. This interventional IPE programme evaluates whether benchmarking sharing can successfully cultivate seed instructors responsible for improving their team members’ IPC attitudes. Design Prospective, pre-post comparative cross-sectional pilot study. Setting/participants Thirty four physicians, 30 nurses and 24 pharmacists, who volunteered to be trained as seed instructors participated in 3.5-hour preparation and 3.5-hour simulation courses. Then, participants (n=88) drew lots to decide 44 presenters, half of each profession, who needed to prepare IPC benchmarking and formed Group 1. The remaining participants formed Group 2 (regular). Facilitators rated the Group 1 participants’ degree of appropriate transfer and sustainable practice of the learnt IPC skills in the workplace according to successful IPC examples in their benchmarking sharing. Results For the three professions, improvement in IPC attitude was identified by sequential increase in the post-course (second month, T 2 ) and end-of-study (third month, T 3 ) Interdisciplinary Education Perception Scale (IEPS) and Attitudes Towards Healthcare Teams Scale (ATHCTS) scores, compared with pre-course (first month, T 1 ) scores. By IEPS and ATHCTS-based assessment, the degree of sequential improvements in IPC attitude was found to be higher among nurses and pharmacists than in physicians. In benchmarking sharing, the facilitators’ agreement about the degree of participants’appropriate transfer and sustainable practice learnt ‘communication and teamwork’ skills in the workplace were significantly higher among pharmacists and nurses than among physicians. The post-intervention random sampling survey (sixth month, T post ) found that the IPC attitude of the three professions improved after on-site IPC skill promotion by new programme-trained seed instructors within teams. Conclusions Addition of benchmark sharing to a diamond-based IPE simulation programme enhances participants’ IPC attitudes, self-reflection, workplace transfer and practice of the learnt skills. Furthermore, IPC promotion within teams by newly trained seed instructors improved the IPC attitudes across all three professions.

Description: Purpose: Hepatocellular carcinoma (HCC) harbors highly metastatic properties, accounting for postoperative recurrence and metastasis. However, the mechanisms for metastasis and recurrence remain incompletely clear. This study aimed to investigate the role of hsa-miR-487a (miR-487a) in promoting the proliferation and metastasis of HCC and to elucidate the underlying molecular mechanisms. Experimental Design: 198 HCC samples were analyzed for association between miR-487a expression and patient clinicopathological features and prognosis. The roles of miR-487a in proliferation and metastasis were validated both in vivo and in vitro . The upstream regulator and downstream targets of miR-487a were determined using a dual luciferase reporter assay, chromatin immunoprecipitation and immunohistochemistry. Results: Our results demonstrate that upregulated miR-487a correlates with a poor prognosis for HCC patients. miR-487a enhances proliferation and metastasis of HCC cells by directly binding to sprouty-related EVH1 domain containing 2 (SPRED2) or phosphoinositide-3-Kinase regulatory subunit 1 (PIK3R1). Interestingly, miR-487a mainly promotes metastasis via SPRED2 induced mitogen activated protein kinase signaling and promotes proliferation via PIK3R1 mediated AKT signaling. Transcription of miR-487a was found to be activated by up-regulated heat shock factor 1, which we previously demonstrated to be an important metastasis-associated transcription factor in a previous study. Phosphorodiamidate morpholino oligomers effectively silenced miR-487a and inhibited HCC tumor progression in mouse models. Conclusions: Our findings show that miR-487a, mediated by heat shock factor 1, promotes proliferation and metastasis of HCC by PIK3R1 and SPRED2 binding, respectively. Our study provides a rationale for developing miR-487a as a potential prognostic marker or a potential therapeutic target against HCC. Clin Cancer Res; 23(10); 2593–604. ©2016 AACR .

Description: Interconnections between autophagy and the coagulation cascade in hepatocellular carcinoma Cell Death and Disease 5, e1244 (May 2014). doi:10.1038/cddis.2014.212 Authors: K-D Chen, C-C Wang, M-C Tsai, C-H Wu, H-J Yang, L-Y Chen, T Nakano, S Goto, K-T Huang, T-H Hu, C-L Chen & C-C Lin

Description: Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the Megalocytivirus genus, Iridoviridae family, causing a severe systemic disease with high mortality in mandarin fish ( Siniperca chuatsi ) in China and Southeast Asia. At present, the pathogenesis of ISKNV infection is still not fully understood. Based on a genome-wide bioinformatics analysis of ISKNV-encoded proteins, we found that ISKNV open reading frame 119L (ORF119L) is predicted to encode a three-ankyrin-repeat (3ANK)-domain-containing protein, which shows high similarity to the dominant negative form of integrin-linked kinase (ILK); i.e., viral ORF119L lacks the ILK kinase domain. Thus, we speculated that viral ORF119L might affect the host ILK complex. Here, we demonstrated that viral ORF119L directly interacts with particularly interesting Cys-His-rich protein (PINCH) and affects the host ILK-PINCH interaction in vitro in fathead minnow (FHM) cells. In vivo ORF119L overexpression in zebrafish ( Danio rerio ) embryos resulted in myocardial dysfunctions with disintegration of the sarcomeric Z disk. Importantly, ORF119L overexpression in zebrafish highly resembles the phenotype of endogenous ILK inhibition, either by overexpressing a dominant negative form of ILK or by injecting an ILK antisense morpholino oligonucleotide. Intriguingly, ISKNV-infected mandarin fish develop disorganized sarcomeric Z disks in cardiomyocytes. Furthermore, phosphorylation of AKT, a downstream effector of ILK, was remarkably decreased in ORF119L-overexpressing zebrafish embryos. With these results, we show that ISKNV ORF119L acts as a domain-negative inhibitor of the host ILK, providing a novel mechanism for the megalocytivirus pathogenesis. IMPORTANCE Our work is the first to show the role of a dominant negative inhibitor of the host ILK from ISKNV (an iridovirus). Mechanistically, the viral ORF119L directly binds to the host PINCH, attenuates the host PINCH-ILK interaction, and thus impairs ILK signaling. Intriguingly, ORF119L-overexpressing zebrafish embryos and ISKNV-infected mandarin fish develop similar disordered sarcomeric Z disks in cardiomyocytes. These findings provide a novel mechanism for megalocytivirus pathogenesis.

Description: The aim of this single-center study was to investigate whether obtaining an additional PET/CT scan before adjuvant radiotherapy or concurrent chemoradiotherapy (CCRT) could meaningfully improve 2-y disease-free survival (DFS) and disease-specific survival (DSS) rates. Methods: Six hundred seventy-four patients with oral cavity squamous cell carcinoma who received adjuvant therapy after radical surgery were included. Of these, 152 patients were initially scheduled to receive an additional preradiotherapy/CCRT PET/CT scan within 1 wk of starting adjuvant therapy. However, 16 patients were excluded because of either medical problems or refusal. Therefore, 136 patients underwent a preradiotherapy/CCRT PET/CT scan (PET group), and 522 did not (NO-PET group). All of the participants were followed up for at least 2 y or censored at the last follow-up. The impact of preradiotherapy/CCRT PET/CT imaging was examined using Kaplan–Meier curves and Cox proportional hazards models. Results: Two-year DFS (80% vs. 70%, P = 0.033) and DSS (84% vs. 75%, P = 0.010) rates were significantly higher in the PET than in the NO-PET group. In the PET group, both DFS and DSS were higher in patients with negative findings than in those without (88% vs. 22% and 91% vs. 36%, respectively; both P 〈 0.001). A prognostic scoring system based on the presence of the 2 independent risk factors in the PET group (extracapsular spread and lymphatic invasion) predicted both DFS ( P = 0.001 and P 〈 0.001, respectively) and DSS ( P = 0.001 and P 〈 0.001, respectively). Nineteen patients (14%) had their treatment modified by preradiotherapy/CCRT PET/CT findings. Of these, 15 were treated with curative intent due to the presence of locoregional disease, and 4 received palliative care due to distant metastases. Seven of the 15 patients are currently alive without disease. Conclusion: An additional preradiotherapy/CCRT PET/CT scan improves both DFS and DSS in patients with advanced oral cavity squamous cell carcinoma.

Description: Magnetoelectric materials which simultaneously exhibit electric polarization and magnetism have attracted more and more attention due to their novel physical properties and promising applications for next-generation devices. Exploring new materials with outstanding magnetoelectric performance, especially the manipulation of magnetization by electric field, is of great importance. Here, we demonstrate the cross-coupling between magnetic and electric orders in polycrystalline Co4Nb2O9, in which not only magnetic-field-induced electric polarization but also electric field control of magnetism is observed. These results reveal rich physical phenomenon and potential applications in this compound. Scientific Reports 4 doi: 10.1038/srep03860