The past three decades have borne witness to many advances in the understanding of the molecular biology and treatment of nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer ...endemic to southern China, southeast Asia and north Africa. In this Review, we provide a comprehensive, interdisciplinary overview of key research findings regarding NPC pathogenesis, treatment, screening and biomarker development. We describe how technological advances have led to the advent of proton therapy and other contemporary radiotherapy approaches, and emphasize the relentless efforts to identify the optimal sequencing of chemotherapy with radiotherapy through decades of clinical trials. Basic research into the pathogenic role of EBV and the genomic, epigenomic and immune landscape of NPC has laid the foundations of translational research. The latter, in turn, has led to the development of new biomarkers and therapeutic targets and of improved approaches for individualizing immunotherapy and targeted therapies for patients with NPC. We provide historical context to illustrate the effect of these advances on treatment outcomes at present. We describe current preclinical and clinical challenges and controversies in the hope of providing insights for future investigation.
This article studies a dynamic event-triggered security control problem for networked control systems subject to deception attacks and packet dropouts. First, a combined cyber-attack model is ...proposed, which utilises two sets of independent stochastic sequences to reflect randomly occurring cyber-attacks. Subsequently, a dynamic event-triggered protocol is constructed to relieve the restricted bandwidth pressure by reducing the data transmission of the communication channel from the plant to the controller. With the consideration of randomly occurring deception attacks, packet dropouts, and dynamic event-triggered protocols, an online model predictive control algorithm is established to ensure the stochastic stability of the closed-loop model with expected H2/H∞ performance. Finally, two examples are simulated to interpret the validity and effectiveness of the proposed design strategy.
A sliding mode controller is proposed for the attitude control of spacecraft reorientation with attitude constraints. By introducing a potential function, a novel sliding function is designed. With ...the structure of the proposed sliding function, uniqueness of the equilibrium and fixed-time convergence are rigorously proven. Another advantage of the proposed controller is that the feasibility of attitude constraints can be proven not only on the sliding surface but also outside it. Moreover, the singularity issue of the proposed controller is resolved. Effectiveness of the proposed method is demonstrated by carrying out two numerical simulation.
ABSTRACT
BACKGROUND
Insufficient sleep among students is a major school health problem. School‐based sleep education programs tailored to reach large number of students may be one of the solutions. A ...systematic review and meta‐analysis was conducted to summarize the programs' effectiveness and current status.
METHODS
Electronic databases were searched up until May 2015. Randomized controlled trials of school‐based sleep intervention among 10‐ to 19‐year‐old students with outcome on total sleep duration were included. Methodological quality of the studies was assessed using the Cochrane's risk of bias assessment.
RESULTS
Seven studies were included, involving 1876 students receiving sleep education programs and 2483 attending classes‐as‐usual. Four weekly 50‐minute sleep education classes were most commonly provided. Methodological quality was only moderate, with a high or an uncertain risk of bias in several domains. Compared to classes‐as‐usual, sleep education programs produced significantly longer weekday and weekend total sleep time and better mood among students at immediate post‐treatment, but the improvements were not maintained at follow‐up.
CONCLUSIONS
Limited by the small number of studies and methodological limitations, the preliminary data showed that school‐based sleep education programs produced short‐term benefits. Future studies should explore integrating sleep education with delayed school start time or other more effective approaches.
Abstract Objectives To compare the psychometric properties of the Chinese versions of Insomnia Severity Index (ISI), Athens Insomnia Scale (AIS) and Sleep Quality Index (SQI) for assessment and ...screening of insomnia in adolescents. Methods This is a school-based survey of 1516 adolescents aged 12–19 years. Sleep-wake habit questionnaire, ISI, AIS, SQI, Epworth Sleepiness Scale (ESS) and 12-item General Health Questionnaire (GHQ-12) were administered. Insomnia Interview Schedule was used to assess the severity of insomnia symptoms and DSM-IV-TR diagnosis of insomnia. Results The Cronbach’s alpha of ISI, AIS and SQI were 0.83, 0.81 and 0.65, respectively, and the 2-week test–retest reliability were 0.79, 0.80 and 0.72. All three scales had a 2-factor structure, and their scores were significantly correlated with sleep-wake variables, ESS and GHQ-12 scores, smoking and drinking habits, and academic performance. The areas under curve of ISI, AIS and SQI for detecting clinical insomnia were 0.85, 0.80 and 0.85, respectively. The optimal cut-offs for ISI, AIS and SQI were a total score of nine (sensitivity/specificity: 0.87/0.75), seven (sensitivity/specificity: 0.78/0.74) and five (sensitivity/specificity: 0.83/0.79), respectively. Conclusion The Chinese versions of ISI, AIS and SQI are reliable and valid instruments. The ISI and AIS appear to have better psychometric properties than the SQI.
Unresolved inflammation can lead to tissue fibrosis and impaired organ function. Macrophage–myofibroblast transition (MMT) is one newly identified mechanism by which ongoing chronic inflammation ...causes progressive fibrosis in different forms of kidney disease. However, the mechanisms underlying MMT are still largely unknown. Here, we discovered a brain-specific homeobox/POU domain protein Pou4f1 (Brn3a) as a specific regulator of MMT. Interestingly, we found that Pou4f1 is highly expressed by macrophages undergoing MMT in sites of fibrosis in human and experimental kidney disease, identified by coexpression of the myofibroblast marker, α-SMA. Unexpectedly, Pou4f1 expression peaked in the early stage in renal fibrogenesis in vivo and during MMT of bone marrow-derived macrophages (BMDMs) in vitro. Mechanistically, chromatin immunoprecipitation (ChIP) assay identified that Pou4f1 is a Smad3 target and the key downstream regulator of MMT, while microarray analysis defined a Pou4f1-dependent fibrogenic gene network for promoting TGF-β1/Smad3-driven MMT in BMDMs at the transcriptional level. More importantly, using two mouse models of progressive renal interstitial fibrosis featuring the MMT process, we demonstrated that adoptive transfer of TGF-β1-stimulated BMDMs restored both MMT and renal fibrosis in macrophage-depleted mice, which was prevented by silencing Pou4f1 in transferred BMDMs. These findings establish a role for Pou4f1 in MMT and renal fibrosis and suggest that Pou4f1 may be a therapeutic target for chronic kidney disease with progressive renal fibrosis.
Summary Self-help cognitive-behavioral therapy (CBT) is an increasingly popular treatment option for insomnia. The objective of this meta-analysis was to compile an up-to-date evaluation on the ...efficacy, adherence, acceptability and dropout rate of self-help CBT for insomnia. We systematically searched six key electronic databases up until May 2013. Two researchers independently selected relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. Twenty randomized controlled trials were included; 10 of which were published after the last review up until January 2007. Meta-analysis of self-help CBT vs. waiting-list, routine care or no treatment was performed. Results showed that self-help CBT improved sleep, sleep-related cognitions and anxiety and depressive symptoms. Effect sizes for sleep-diary-derived sleep efficiency, sleep onset latency, and wake after sleep onset at immediate posttreatment were 0.80, 0.66, and 0.55, respectively. The average dropout rate of self-help CBT at immediate posttreatment was 14.5%, which was not significantly different from the 16.7% in therapist-administered CBT. Subgroup analyses supported the added benefit of telephone consultation. In conclusion, self-help CBT is efficacious and acceptable as an entry level of a stepped care model for insomnia. In places where face-to-face treatments are unavailable or too costly, self-help CBT can be considered as a compromise.
Autophagic impairment is implicated in nonalcoholic fatty liver disease (NAFLD), but the molecular mechanism is unclear. We found that autophagic flux was significantly inhibited in 3 murine models ...of NAFLD. Interestingly, the number of acidic organelles and the level of mature cathepsin D were reduced, suggesting defective lysosome acidification. Asparagine synthetase (ASNS) was induced by endoplasmic reticulum stress, leading to the generation of asparagine, which inhibited lysosome acidification. Both steatotic‐ and asparagine‐ treated hepatocytes showed reduced lysosomal acidity and retention of lysosomal calcium. Knockdown of ASNS in steatotic hepatocytes restored autophagic flux. As a potential biomarker, increased serum p62/sequestosome 1 (SQSTM1) level was an independent risk factor for patients with steatosis and lobular inflammation. Impaired autophagy in NAFLD is elicited by defective lysosome acidification, which is caused by ASNS‐induced asparagine synthesis under endoplasmic reticulum stress and subsequent retention of lysosomal calcium. p62/SQSTM1 could be used as a noninvasive biomarker in the diagnosis of NAFLD patients.—Wang, X., Zhang, X., Chu, E. S. H., Chen, X., Kang, W., Wu, F., To, K.‐F., Wong, V. W. S., Chan, H. L. Y., Chan, M. T. V., Sung, J. J. Y., Wu, W. K. K., Yu, J. Defective lysosomal clearance of autophagosomes and its clinical implications in nonalcoholic steatohepatitis. FASEB J. 32, 37‐51 (2018). www.fasebj.org
Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells ...contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (
-smooth muscle actin
-SMA) markers. CD68
/
-SMA
cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and
-SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of
-SMA
myofibroblasts in renal allografts originated from recipient bone marrow-derived macrophages. Knockout of
protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in
-knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow-derived M2-type macrophages to myofibroblasts in the renal allograft is regulated
a Smad3-dependent mechanism.
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