bluuebunny/crossref_metadata_2025 huggingface dataset:
Job Strain and Self-Reported Insomnia Symptoms among Nurses: What about the Influence of Emotional Demands and Social Support?
Authors: Portela Luciana Fernandes , Kröning Luna Caroline , Rotenberg Lúcia , Silva-Costa Aline , Toivanen Susanna , Araújo Tania , Griep Rosane Härter
Published: October 2015

Job strain, derived from high psychological demands and low job control, is associated with insomnia, but information on the role of emotional demands and social support in this relationship is scarce. The aims of this study were (i) to test the association between job strain and self-reported insomnia symptoms, (ii) to evaluate the combination of emotional demands and job control regarding insomnia symptoms, and (iii) to analyze the influence of social support in these relationships. This cross-sectional study refers to a sample of nurses (N= 3,013 andN= 3,035 for Job Strain and Emotional demand-control model, resp.) working at public hospitals in Rio de Janeiro, Brazil. Data were collected through a self-report questionnaire. The prevalence of insomnia symptoms was 34.3%. Job strain was associated with increased odds for insomnia symptoms (OR: 2.20); the same result was observed with the combination of emotional demands and low job control (OR: 1.99). In both models, the inclusion of low social support combined with high demands and low job control led to increased odds for insomnia symptoms, compared to groups with high social support from coworkers and supervisors. Besides job strain, the study of emotional demands and social support are promising with regards to insomnia symptoms, particularly among nurses.
A Systematic Design Method for Large-Scale Wireless Ad Hoc Network Protocol Based on Optimization Decomposition Theory
Authors: Xu Chaonong , Zhang Chi , Xu Yongjun , Wang Zhiguang
Published: October 2015

The idea of network protocol design based on optimization theory has been proposed and used practically in Internet for about 15 years. However, for large-scale wireless ad hoc network, although protocol could be viewed as a recursive solving of a global optimization problem, protocol design is still facing huge challenge because an effective distributed algorithm for solving global optimization problem is still lacking. We solve the problem by putting forward a systematic design method based on optimization decomposition. The systematic method includes primal decomposition method and dual decomposition method, with which a complex optimization problem can be decomposed into several smaller and independent optimization subproblems. By using subgradient method, each of these subproblems can be solved distributively. Further, the above two methods can be combined in different sequences or used recursively to solve more complex optimization problems. Two examples of wireless protocol design, the transmission control protocol and the joint congestion control and power control protocol, are given to demonstrate its validity.
A Method for Driving Route Predictions Based on Hidden Markov Model
Authors: Ye Ning , Wang Zhong-qin , Malekian Reza , Lin Qiaomin , Wang Ru-chuan
Published: October 2015

We present a driving route prediction method that is based on Hidden Markov Model (HMM). This method can accurately predict a vehicle’s entire route as early in a trip’s lifetime as possible without inputting origins and destinations beforehand. Firstly, we propose the route recommendation system architecture, where route predictions play important role in the system. Secondly, we define a road network model, normalize each of driving routes in the rectangular coordinate system, and build the HMM to make preparation for route predictions using a method of training set extension based onK-means++ and the add-one (Laplace) smoothing technique. Thirdly, we present the route prediction algorithm. Finally, the experimental results of the effectiveness of the route predictions that is based on HMM are shown.
Over-the-Counter Hearing Aids: A Lost Decade for Change
Authors: Chan Zoe Yee Ting , McPherson Bradley
Published: October 2015

Background. Hearing aids sold directly to consumers in retail stores or through the internet, without individual prescription by audiological professionals, are termed over-the-counter (OTC) devices. This study aimed to determine whether there was any change in the electroacoustic characteristics of OTC devices compared to research carried out a decade earlier. The previous results indicated that most OTC devices were low-frequency-emphasis devices and were unsuitable for elderly people with presbycusis, who were likely to be the major consumers of these products.Methods. Ten OTC devices were selected and their electroacoustic performance was measured. Appropriate clients for the OTC devices were derived, using four linear prescription formulae, and OTC suitability for elderly persons with presbycusis was investigated.Results. OTC electroacoustic characteristics were similar to those in the earlier study. Most OTC devices were not acoustically appropriate for potential consumers with presbycusis. Although several of the devices could match prescriptive targets for individuals with presbycusis, their poor electroacoustic performance—including ineffective volume control function, high equivalent input noise, and irregular frequency response—may override their potential benefit.Conclusion. The low-cost OTC devices were generally not suitable for the main consumers of these products, and there has been little improvement in the appropriateness of these devices over the past decade.
The Association between Primary Open-Angle Glaucoma and Blood Pressure: Two Aspects of Hypertension and Hypotension
Authors: Chung Hye Jin , Hwang Hyung Bin , Lee Na Young
Published: October 2015

Glaucoma is the second leading cause of blindness worldwide. Although the mechanism of the development of primary open-angle glaucoma (POAG) is not fully understood, elevated intraocular pressure (IOP) is considered the most important risk factor. Several vascular factors have also been identified as risk factors and can lead to hypoperfusion of the optic nerve head and thus may play an important role in the pathogenesis and progression of POAG. The results of the present study suggest that both high and low blood pressure (BP) are associated with an increased risk of POAG based on a comprehensive literature review. Elevated BP is associated with elevated IOP, leading to increased risk of glaucoma, but excessive BP lowering in glaucoma patients may cause a drop in ocular perfusion pressure (OPP) and subsequent ischemic injury. The relationship between IOP, OPP, and BP suggests that the relationship between BP and glaucoma progression is U-shaped.
Antiproliferative and Antiestrogenic Activities of Bonediol an Alkyl Catechol fromBonellia macrocarpa
Authors: Moo-Puc Rosa , Caamal-Fuentes Edgar , Peraza-Sánchez Sergio R. , Slusarz Anna , Jackson Glenn , Drenkhahn Sara K. , Lubahn Dennis B.
Published: October 2015

The purpose of this study was to investigate antiproliferative activity of bonediol, an alkyl catechol isolated from the Mayan medicinal plantBonellia macrocarpa. Bonediol was assessed for growth inhibition of androgen-sensitive (LNCaP), androgen-insensitive (PC-3), and metastatic androgen-insensitive (PC-3M) human prostate tumor cells; toxicity on normal cell line (HEK 293) was also evaluated. Hedgehog pathway was evaluated and competitive 3H-estradiol ligand binding assay was performed. Additionally, antioxidant activity on Nrf2-ARE pathway was evaluated. Bonediol induced a growth inhibition on prostate cancer cell lines (IC50from 8.5 to 20.6 µM). Interestingly, bonediol binds to both estrogen receptors (ERα(2.5 µM) and ERβ(2.1 µM)) and displaces the native ligand E2 (17β-estradiol). No significant activity was found in the Hedgehog pathway. Additionally, activity of bonediol on Nrf2-ARE pathway suggested that bonediol could induce oxidative stress and activation of detoxification enzymes at 1 µM (3.8-fold). We propose that the compound bonediol may serve as a potential chemopreventive treatment with therapeutic potential against prostate cancer.
Qing Re Liang Xue Decoction Alleviates Hypercoagulability in Kawasaki Disease
Authors: Chen Jiao-yang , Yin Ji-ming , Du Zhong-dong , Hao Jing , Yan Hui-min
Published: October 2015

Objective. Kawasaki disease (KD) is a multisystemic autoimmune vasculitis. Intravenous immunoglobulin (IVIG) is the first-line treatment for KD. It is unclear whether traditional Chinese medicine (TCM) has an effect on KD. We aimed to observe the clinical efficacy of TCM on acute KD via serum interleukin-33 (IL-33) and tumor necrosis factor alpha (TNF-α) measurements.Methods. Thirty-one KD patients were treated with Qing Re Liang Xue decoction and Western medicine (integrative medicine treatment group), while 28 KD patients were treated with Western medicine only (Western medicine treatment group). Thirty patients were included in a febrile group and 28 healthy children were included in the control group. Clinical characteristics and laboratory findings were gathered and compared. Serum IL-33 and TNF-αlevels were measured by multiplex Luminex assay.Results. The platelet count in the integrative medicine treatment group was significantly lower than that in the Western medicine treatment group. The integrative medicine group had a shorter fever duration and lower IL-33 and TNF-αlevels than those in the Western medicine group, but there were no significant differences between the two KD groups after treatment.Conclusion. Qing Re Liang Xue decoction improved the hypercoagulable state of KD patients. Potential myocardial protective effects require further research.
Study on Engineering Design and Cost Performance of Borehole Heat Exchangers
Authors: Yu Lei , Cheng Jiemin
Published: October 2015

The ground source heat pump (GSHP) is an environmentally friendly and energy-efficient technology, and the investigations on the simulation models of borehole heat exchanger (BHE) have made progress. However, the researches on engineering design and economic performance based on the simulation models of BHE are a few. This paper firstly describes the interior and exterior heat transfer according to the existing achievements, and the corresponding characteristics of models are explained. Afterwards, the detailed design procedures of BHE size are provided and the cost performance is highlighted. Accordingly, an actual engineering project which employs GSHP system as the air conditioning system is researched; the necessary expenses on BHE, heat pump units, and indoor end equipment are all taken into account. The initial investment, operating cost, and other factors that exert influences on the cost performance are demonstrated. In addition, comparisons between different systems are conducted to show the advantages of GSHP. By means of thermal transfer analysis and the design of engineering project, the practicability, energy saving, and environmental protection of GSHP are brought into play, which means the promotion of this technology is the general trend of development of air condition system.
Kenaf Fibre Reinforced Polypropylene Composites: Effect of Cyclic Immersion on Tensile Properties
Authors: Haniffah W. H. , Sapuan S. M. , Abdan K. , Khalid M. , Hasan M. , Hoque M. Enamul
Published: October 2015

This research studied the degradation of tensile properties of kenaf fibre reinforced polypropylene composites due to cyclic immersion into two different solutions, as well as comparison of the developed composites’ tensile properties under continuous and cyclic immersion. Composites with 40% and 60% fibre loadings were immersed in tap water and bleach for 4 cycles. Each cycle consisted of 3 days of immersion and 4 days of conditioning in room temperature (28°C and 55% humidity). The tensile strength and modulus of composites were affected by fibre composition, type of liquid of immersion, and number of cycles. The number of immersion cycles and conditioning caused degradation to tensile strength and modulus of kenaf fibre reinforced polypropylene composites. Continuous and cyclic immersion in bleach caused tensile strength of the composites to differ significantly whereas, for tensile modulus, the difference was insignificant in any immersion and fibre loadings. However, continuous immersion in the bleach reduced the tensile strength of composites more compared to cyclic immersion. These preliminary results suggest further evaluation of the suitability of kenaf fibre reinforced polypropylene composites for potential bathroom application where the composites will be exposed to water/liquid in cyclic manner due to discontinuous usage of bathroom.
Adaptive Ensemble with Human Memorizing Characteristics for Data Stream Mining
Authors: Jiang Yanhuang , Zhao Qiangli , Lu Yutong
Published: October 2015

Combining several classifiers on sequential chunks of training instances is a popular strategy for data stream mining with concept drifts. This paper introduces human recalling and forgetting mechanisms into a data stream mining system and proposes a Memorizing Based Data Stream Mining (MDSM) model. In this model, each component classifier is regarded as a piece of knowledge that a human obtains through learning some materials and has a memory retention value reflecting its usefulness in the history. The classifiers with high memory retention values are reserved in a “knowledge repository.” When a new data chunk comes, most useful classifiers will be selected (recalled) from the repository and compose the current target ensemble. Based on MDSM, we put forward a new algorithm, MAE (Memorizing Based Adaptive Ensemble), which uses Ebbinghaus forgetting curve as the forgetting mechanism and adopts ensemble pruning as the recalling mechanism. Compared with four popular data stream mining approaches on the datasets with different concept drifts, the experimental results show that MAE achieves high and stable predicting accuracy, especially for the applications with recurring or complex concept drifts. The results also prove the effectiveness of MDSM model.
Long-Term Monitoring of Physical Behavior Reveals Different Cardiac Responses to Physical Activity among Subjects with and without Chronic Neck Pain
Authors: Hallman David M. , Mathiassen Svend Erik , Lyskov Eugene
Published: October 2015

Background. We determined the extent to which heart rate variability (HRV) responses to daily physical activity differ between subjects with and without chronic neck pain.Method. Twenty-nine subjects (13 women) with chronic neck pain and 27 age- and gender-matched healthy controls participated. Physical activity (accelerometry), HRV (heart rate monitor), and spatial location (Global Positioning System (GPS)) were recorded for 74 hours. GPS data were combined with a diary to identify periods of work and of leisure at home and elsewhere. Time- and frequency-domain HRV indices were calculated and stratified by period and activity type (lying/sitting, standing, or walking). ANCOVAs with multiple adjustments were used to disclose possible group differences in HRV.Results. The pain group showed a reduced HRV response to physical activity compared with controls (p=.001), according to the sympathetic-baroreceptor HRV index (LF/HF, ratio between low- and high-frequency power), even after adjustment for leisure time physical activity, work stress, sleep quality, mental health, and aerobic capacity (p=.02). The parasympathetic response to physical activity did not differ between groups.Conclusions. Relying on long-term monitoring of physical behavior and heart rate variability, we found an aberrant sympathetic-baroreceptor response to daily physical activity among subjects with chronic neck pain.
Density Functional Investigation of Graphene Doped with Amine‐Based Organic Molecules
Authors: Hwang Yeun Hee , Chun Hyang Sook , Ok Kang Min , Lee Kyung-Koo , Kwak Kyungwon
Published: October 2015

To improve the electronic properties of graphene, many doping techniques have been studied. Herein, we investigate the electronic and molecular structure of doped graphene using density functional theory, and we report the effects of amine‐based benzene dopants adsorbed on graphene. Density functional theory (DFT) calculations were performed to determine the role of amine‐based aromatic compounds in graphene doping. These organic molecules bind to graphene through long‐range interactions such as π‐π interactions and C‐H⋯π hydrogen bonding. We compared the electronic structures of pristine graphene and doped graphene to understand the electronic structure of doped graphene at the molecular level. Also, work functions of doped graphene were obtained from electrostatic potential calculations. A decrease in the work function was observed when the amine‐based organic compounds were adsorbed onto graphene. Because these systems are based on physisorption, there was no obvious band structure change at point K at the Fermi level after doping. However, the amine‐based organic dopants did change the absolute Fermi energy levels. In this study, we showed that the Fermi levels of the doped graphene were affected by the HOMO energy level of the dopants and by the intermolecular charge transfer between the adsorbed molecules and graphene.
Models of Workplace Incivility: The Relationships to Instigated Incivility and Negative Outcomes
Authors: Holm Kristoffer , Torkelson Eva , Bäckström Martin
Published: October 2015

The aim of the study was to investigate workplace incivility as a social process, examining its components and relationships to both instigated incivility and negative outcomes in the form of well-being, job satisfaction, turnover intentions, and sleeping problems. The different components of incivility that were examined were experienced and witnessed incivility from coworkers as well as supervisors. In addition, the organizational factors, social support, control, and job demands, were included in the models. A total of 2871 (2058 women and 813 men) employees who were connected to the Swedish Hotel and Restaurant Workers Union completed an online questionnaire. Overall, the results from structural equation modelling indicate that whereas instigated incivility to a large extent was explained by witnessing coworker incivility, negative outcomes were to a high degree explained by experienced supervisor incivility via mediation through perceived low social support, low control, and high job demands. Unexpectedly, the relationships between incivility (experienced coworker and supervisor incivility, as well as witnessed supervisor incivility) and instigated incivility were moderated by perceived high control and high social support. The results highlight the importance of including different components of workplace incivility and organizational factors in future studies of the area.
Impaired Circulating Angiogenic Cells Mobilization and Metalloproteinase-9 Activity after Dynamic Exercise in Early Metabolic Syndrome
Authors: Rocha Natalia G. , Sales Allan R. K. , Penedo Leticia A. , Pereira Felipe S. , Silva Mayra S. , Miranda Renan L. , Silva Jemima F. R. , Silva Bruno M. , Santos Aline A. , Nobrega Antonio C. L.
Published: October 2015

Increased levels of adhesion molecules or metalloproteinases (MMPs) may indicate endothelial dysfunction. Exercise mobilizes circulating angiogenic cells (CACs) from bone marrow in healthy subjects, improving vascular function. However, it is unclear whether this mechanism is preserved in the early stages of metabolic syndrome (early MetS). We aimed to evaluate the acute effects of exercise on adhesion molecules, angiogenic factors, MMPs, and CACs in early MetS. Fifteen subjects with early MetS and nine healthy controls underwent an exercise session and a nonexercise session, randomly. Adhesion molecules, angiogenic factors, CACs, and MMPs were evaluated before and after exercise or nonexercise sessions. At baseline, levels of sE-selectin, sICAM-1, and MMP-9 were higher in early MetS than in controls (P≤0.03). After exercise, sE-selectin, sICAM-1, and MMP-9 levels were still higher in early MetS (P<0.05). Subjects with early MetS presented less CACs (P=0.02) and higher MMP-9 activity (P≤0.04), while healthy controls presented higher MMP-2 activity after exercise. There was no difference between moments in nonexercise session (P>0.05). In conclusion, subjects with early MetS already presented impaired endothelial function at rest along with a decrease in CACs and an increase in MMP-9 activity in response to exercise.
Real-Time Analysis of Temperature Changes in Composite Increments and Pulp Chamber during Photopolymerization
Authors: Kim Ryan Jin-Young , Lee In-Bog , Yoo Jin-Young , Park Su-Jung , Kim Sin-Young , Yi Young-Ah , Hwang Ji-Yun , Seo Deog-Gyu
Published: October 2015

Objective. The aim of this study was to evaluate the temperature change at various sites within the composite and on the pulpal side of dentin during polymerization of two composite increments.Materials and Methods. Class I cavities prepared in third molars were restored in two composite increments (n= 5). Temperatures were measured for 110 s using eight thermocouples: bottom center of cavity (BC), top center of 1st increment (MC), top center of 2nd increment (TC), bottom corner of cavity (BE), top corner of 1st increment (ME), top corner of 2nd increment (TE), pulpal side of dentin (PD), and center of curing light guide tip (CL).Results. Maximum temperature values (°C) measured during polymerization of 1st increment were MC (59.8); BC (52.8); ME (51.3); CL (50.7); BE (48.4); and PD (39.8). Maximum temperature values during polymerization of 2nd increment were TC 58.5; TE (52.6); MC (51.7); CL (50.0); ME (48.0); BC (46.7); BE (44.5); and PD (38.8).Conclusion. Temperature at the floor of the cavity was significantly higher during polymerization of 1st increment compared to 2nd increment. Temperature rise was higher at the center than at the corner and at the top surface than at the bottom surface of each increment.
The Trend of CEACAM3 Blood Expression as Number Index of the CTCs in the Colorectal Cancer Perioperative Course
Authors: Taddei A. , Castiglione F. , Ringressi M. N. , Niccolai E. , Tofani L. , Boni L. , Bechi P. , Amedei A.
Published: October 2015

Pathological stage seems to be the major determinant of postoperative prognosis of solid tumors, but additional prognostic determinants need to be better investigated. The most important tumor marker for colorectal cancer (CRC) is the cell‐surface antigen, Carcinoembryonic Antigen (CEA), and its assessment is considered a valuable index of circulating tumor cells (CTCs). In this paper, CEACAM3 evaluation was applied given its great specificity in the CRC. Whole blood from the basilic vein of 38 CRC patients was collected before and at various time intervals after the curative resection. Also, from 20 of them, we have obtained two additional intraoperative samples. CEACAM3 expression was evaluated in all the samples by RT‐PCR. CEACAM3 duct values showed a decreasing trend from preoperative through early and later postoperative to 6th‐month samples (p < 0.001). The average values of CEACAM3 were related to the cancer size (T stage) (p = 0.034) and WHO stage (p = 0.035). A significant effect of the baseline value of CEACAM3 dCt on the temporal trend has been observed (p < 0.001). In this study, we have demonstrated the CEACAM3 specificity and a perioperative trend of CTCs which is coherent with the clinical/pathological considerations and with previous experimental findings in different cancer types.
Prognostic Role of MicroRNA-200c-141 Cluster in Various Human Solid Malignant Neoplasms
Authors: Li Xiao-yang , Li Hui , Bu Jie , Xiong Liang , Guo Hong-bin , Liu Li-hong , Xiao Tao
Published: October 2015

The miR-200 family has emerged recently as a noticeable marker for predicting cancer prognosis and tumor progression. We aimed to review the evidence of miR-200c-141 genomic cluster as prognostic biomarkers in cancers. The results suggested that high level of miR-200c had no significant impact on OS (HR = 1.14 [0.77–1.69],P=0.501) and DFS/PFS (HR = 0.72 [0.45–1.14],P=0.161). Stratified analyses revealed that high miR-200c expression was significantly related to poor OS in serum/plasma (HR = 2.12 [1.62–2.77],P=0.000) but not in tissues (HR = 0.89 [0.58–1.37],P=0.599). High miR-200c expression was significantly associated with favorable DFS/PFS in tissues (HR = 0.56 [0.43–0.73],P=0.000) but worse DFS/PFS in serum/plasma (HR = 1.90 [1.08–3.36],P=0.027). For miR-141, we found that high miR-141 expression predicted no significant impact on OS (HR = 1.18 [0.74–1.88],P=0.482) but poor DFS/PFS (HR = 1.11 [1.04–1.20],P=0.003). Similarly, subgroup analyses showed that high miR-141 expression predicted poor OS in serum/plasma (HR = 4.34 [2.30–8.21],P=0.000) but not in tissues (HR = 1.00 [0.92–1.09],P=0.093). High miR-141 expression was significantly associated with worse DFS/PFS in tissues (HR = 1.12 [1.04–1.20],P=0.002) but not in serum/plasma (HR = 0.90 [0.44–1.83],P=0.771). Our findings indicated that, compared to their tissue counterparts, the expression level of miR-200c and miR-141 in peripheral blood may be more effective for monitoring cancer prognosis. High miR-141 expression was better at predicting tumor progression than survival for malignant tumors.
Inhibition of PI3K Signalling Selectively Affects Medulloblastoma Cancer Stem Cells
Authors: Frasson Chiara , Rampazzo Elena , Accordi Benedetta , Beggio Giacomo , Pistollato Francesca , Basso Giuseppe , Persano Luca
Published: October 2015

Medulloblastoma is the most common malignant brain tumor of childhood. Although survival has slowly increased in the past years, the prognosis of these patients remains unfavourable. In this context, it has been recently shown that the intracellular signaling pathways activated during embryonic cerebellar development are deregulated in MDB. One of the most important is PI3K/AKT/mTOR, implicated in cell proliferation, survival, growth, and protein synthesis. Moreover, a fraction of MDB cells has been shown to posses stemlike features, to express typical neuronal precursor markers (Nestin and CD133), and to be maintained by the hypoxic cerebellar microenvironment. This subpopulation of MDB cells is considered to be responsible for treatment resistance and recurrence. In this study, we evaluated the effects of PI3K/AKT pathway inhibition on primary cultures of MDB and particularly on the cancer stem cell (CSC) population (CD133+). PI3K inhibition was able to counteract MDB cell growth and to promote differentiation of stemlike MDB cells. Moreover, PI3K/AKT pathway suppression induced dramatic cell death through activation of the mitochondrial proapoptotic cascade. Finally, analysis on the stem cells fraction revealed that the MDB CSC population is more sensitive to PI3K targeting compared to the whole cancerous population and its nonstem cell counterpart.
Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance
Authors: Li Bin , Xu Wen Wen , Guan Xin Yuan , Qin Yan Ru , Law Simon , Lee Nikki Pui Yue , Chan Kin Tak , Tam Pui Ying , Li Yuk Yin , Chan Kwok Wah , Yuen Hiu Fung , Tsao Sai Wah , He Qing Yu , Cheung Annie L.M.
Published: October 2015

Purpose: Chemoresistance is a major obstacle in cancer therapy. We found that fluorouracil (5-FU)-resistant esophageal squamous cell carcinoma cell lines, established through exposure to increasing concentrations of 5-FU, showed upregulation of Id1, IGF2, and E2F1. We hypothesized that these genes may play an important role in cancer chemoresistance.

Experimental Design: In vitro and in vivo functional assays were performed to study the effects of Id1–E2F1–IGF2 signaling in chemoresistance. Quantitative real-time PCR, Western blotting, immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays were used to investigate the molecular mechanisms by which Id1 regulates E2F1 and by which E2F1 regulates IGF2. Clinical specimens, tumor tissue microarray, and Gene Expression Omnibus datasets were used to analyze the correlations between gene expressions and the relationships between expression profiles and patient survival outcomes.

Results: Id1 conferred 5-FU chemoresistance through E2F1-dependent induction of thymidylate synthase expression in esophageal cancer cells and tumor xenografts. Mechanistically, Id1 protects E2F1 protein from degradation and increases its expression by binding competitively to Cdc20, whereas E2F1 mediates Id1-induced upregulation of IGF2 by binding directly to the IGF2 promoter and activating its transcription. The expression level of E2F1 was positively correlated with that of Id1 and IGF2 in human cancers. More importantly, concurrent high expression of Id1 and IGF2 was associated with unfavorable patient survival in multiple cancer types.

Conclusions: Our findings define an intricate E2F1-dependent mechanism by which Id1 increases thymidylate synthase and IGF2 expressions to promote cancer chemoresistance. The Id1–E2F1–IGF2 regulatory axis has important implications for cancer prognosis and treatment. Clin Cancer Res; 22(5); 1243–55. ©2015 AACR.
SAR405838: A Novel and Potent Inhibitor of the MDM2:p53 Axis for the Treatment of Dedifferentiated Liposarcoma
Authors: Bill Kate Lynn J. , Garnett Jeannine , Meaux Isabelle , Ma XiaoYen , Creighton Chad J. , Bolshakov Svetlana , Barriere Cedric , Debussche Laurent , Lazar Alexander J. , Prudner Bethany C. , Casadei Lucia , Braggio Danielle , Lopez Gonzalo , Zewdu Abbie , Bid Hemant , Lev Dina , Pollock Raphael E.
Published: October 2015

Purpose: Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy that can recur locally or disseminate even after multidisciplinary care. Genetically amplified and expressed MDM2, often referred to as a “hallmark” of DDLPS, mostly sustains a wild-type p53 genotype, substantiating the MDM2:p53 axis as a potential therapeutic target for DDLPS. Here, we report on the preclinical effects of SAR405838, a novel and highly selective MDM2 small-molecule inhibitor, in both in vitro and in vivo DDLPS models.

Experimental Design: The therapeutic effectiveness of SAR405838 was compared with the known MDM2 antagonists Nutlin-3a and MI-219. The effects of MDM2 inhibition were assessed in both in vitro and in vivo. In vitro and in vivo microarray analyses were performed to assess differentially expressed genes induced by SAR405838, as well as the pathways that these modulated genes enriched.

Results: SAR405838 effectively stabilized p53 and activated the p53 pathway, resulting in abrogated cellular proliferation, cell-cycle arrest, and apoptosis. Similar results were observed with Nutlin-3a and MI-219; however, significantly higher concentrations were required. In vitro effectiveness of SAR405838 activity was recapitulated in DDLPS xenograft models where significant decreases in tumorigenicity were observed. Microarray analyses revealed genes enriching the p53 signaling pathway as well as genomic stability and DNA damage following SAR405838 treatment.

Conclusions: SAR405838 is currently in early-phase clinical trials for a number of malignancies, including sarcoma, and our in vitro and in vivo results support its use as a potential therapeutic strategy for the treatment of DDLPS.
miR-138–Mediated Regulation of KINDLIN-2 Expression Modulates Sensitivity to Chemotherapeutics
Authors: Sossey-Alaoui Khalid , Plow Edward F.
Published: October 2015

Prostate cancer is the second leading cause of cancer-related death in men, second only to lung cancer, mainly due to disease reoccurrence as a result to lack of response to androgen deprivation therapies (ADT) after castration. Patients with metastatic castration–resistant prostate cancer (mCRPC) have very limited treatment options, with docetaxel as the first-line standard of care, for which resistance to this chemotherapeutic ultimately develops. Therefore, finding ways to sensitize tumors to chemotherapies and to limit chemoresistance provides a viable strategy to extend the survival of mCRPC patients. This study investigated the role of Kindlin-2 (FERMT2/K2), a member of the Kindlin family of FERM domain proteins and key regulators of the adhesive functions mediated by integrin, in the sensitization of mCRPC to chemotherapeutics. Loss of K2, which is overexpressed in prostate cancer cells derived from mCRPC tumors, compared with those cells derived from androgen-dependent tumors, significantly enhanced apoptosis and cell death of docetaxel-treated PC3 cells. Furthermore, it was determined that K2-mediated sensitization to docetaxel treatment is the result of inhibition of β1-integrin signaling. Finally, miR-138 specifically targeted K2 and inhibited its expression, thereby regulating a miR-138/K2/β1-integrin signaling axis in mCRPC that is critical for the modulation of sensitivity to chemotherapeutics. Thus, these data identify a novel signaling axis where K2 in combination with chemotherapeutics provides a new target for the treatment of mCRPC.

Implications: Targeted inhibition of Kindlin-2 in combination with chemotherapy represents an effective treatment option for mCRPC. Mol Cancer Res; 14(2); 228–38. ©2015 AACR.
Prognostic Importance of Changes in Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone
Authors: Shah Amil M. , Claggett Brian , Sweitzer Nancy K. , Shah Sanjiv J. , Deswal Anita , Anand Inder S. , Fleg Jerome L. , Pitt Bertram , Pfeffer Marc A. , Solomon Scott D.
Published: October 2015

Background—

Limited data exist regarding the impact of aldosterone antagonist therapy on cardiac structure and function in heart failure with preserved ejection fraction and on the prognostic relevance of changes in cardiac structure and function in heart failure with preserved ejection fraction.

Methods and Results—

Cardiac structure and function were assessed by quantitative echocardiography at baseline and at 12- to 18-month follow-up in 239 patients with heart failure with preserved ejection fraction (left ventricular [LV] ejection fraction [LVEF] ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. The impact of spironolactone therapy on measures of cardiac structure and function was assessed in the study population overall, and change in echocardiographic measures was associated with the subsequent occurrence of the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest. Spironolactone was not associated with alterations in cardiac structure and function compared with placebo. Decrease in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary outcome.

Conclusions—

Twelve to 18 months of spironolactone therapy was not associated with alterations in cardiac structure or function in patients with heart failure with preserved ejection fraction. Reduction in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary composite outcome.

Clinical Trial Registration—

URL:
http:///www.clinicaltrials.gov
. Unique identifier: NCT00094302.
Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life‐Threatening Arrhythmias
Authors: Spezzacatene Anita , Sinagra Gianfranco , Merlo Marco , Barbati Giulia , Graw Sharon L. , Brun Francesca , Slavov Dobromir , Di Lenarda Andrea , Salcedo Ernesto E. , Towbin Jeffrey A. , Saffitz Jeffrey E. , Marcus Frank I. , Zareba Wojciech , Taylor Matthew R. G. , Mestroni Luisa ,   the Familial Cardiomyopathy Registry
Published: October 2015

Background

Patients with dilated cardiomyopathy (
DCM
) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic
DCM
(
AR
‐
DCM
). We investigated the phenotype and natural history of patients with
AR
‐
DCM
.

Methods and Results

Two hundred eighty‐five patients with a recent diagnosis of
DCM
(median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months).
AR
‐
DCM
was defined by the presence of ≥1 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia (≥5 beats, ≥150 bpm), ≥1000 premature ventricular contractions/24 hours, and ≥50 ventricular couplets/24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (
SCD
), sustained ventricular tachycardia (
SVT
), or ventricular fibrillation (
VF
). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for
AR
‐
DCM
phenotype.
AR
‐
DCM
subjects had a higher incidence of
SCD
/
SVT
/
VF
compared with non–
AR
‐
DCM
patients (30.3% vs 17.6%,
P
=0.022), with no difference in the secondary end points. A family history of
SCD
/
SVT
/
VF
and the
AR
‐
DCM
phenotype were statistically significant and cumulative predictors of
SCD
/
SVT
/
VF
.

Conclusions

One‐third of
DCM
patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow‐up. A family history of ventricular arrhythmias in
DCM
predicts a poor prognosis and increased risk of
SCD
.
Association patterns and affiliative relationships outside a troop in wild male Japanese macaques, Macaca fuscata, during the non-mating season
Authors: Kawazoe Tatsuro
Published: October 2015

In many mammals, males disperse more than females. Although males in some male-dispersing species form all-male groups, little is known about the association patterns or social relationships among them. Studies on male–male social relationships have primarily focused on competition over fertile females, but affiliative relationships among males have attracted much interest recently. I suggested a novel method for the classification of males based on their behaviour by principal component analysis (PCA), and investigated association patterns, and affiliative relationships in male Japanese macaques, Macaca fuscata, during the non-mating season. I observed 12 wild male Japanese macaques for 809 h during the non-mating season. The number of other animals within visual range, the amount of time that males spent in the vicinity of other animals, and the frequency of grooming interactions were examined. I classified males into two distinctive clusters (Cluster 1 and 2) according to their association and interaction patterns. Cluster 1 males associated with females and participated in grooming with them. Cluster 2 males had less visual encounters with females and did not groom them. Cluster 2 males showed proximity to other Cluster 2 males in all possible dyads. Although Cluster 2 males showed less proximity to each other than Cluster 1 males did, they frequently exchanged grooming among themselves. Cluster 2 males groomed Cluster 1 males more frequently than they were groomed by them. These results suggested that Cluster 1 were troop males, and Cluster 2 were non-troop males. Cluster 2 males had less opportunity for social interaction than Cluster 1 (troop) males, and they may form all-male groups. Males in all-male groups engaged in more frequent grooming than troop males. In addition, they groomed troop males more frequently than they were groomed. These results suggest that males could be separated by their behaviour. Male–male affiliative relationships might be influenced by within-group potential competition and imbalanced grooming appears to cause troop males to tolerate non-troop males which might be immigrated in near future.
Aggression and hierarchical steepness inhibit social play in adult wolves
Authors: Cordoni Giada , Palagi Elisabetta
Published: October 2015

In canids, play dynamics seem to be more affected by dominance hierarchy rather than cooperative social bonds. To test this hypothesis we studied a colony of grey wolves (Canis lupus lupus). We quantified the dynamics of aggression and hierarchical changes in two periods (Sample 1 and Sample 2). Sample 2 was characterized by higher level of aggressiveness and by a more strict and steep linear hierarchy. The negative correlation between rank distance and play frequency characterizing both periods and the higher play asymmetry in Sample 2 suggest that rank rules dictate play rules thus highlighting the competitive side of wolf play behaviour. The overall affiliation rates showed no variation between the two samples. Yet, play performance was modified. In Sample 2, wolves reduced playful activity, limited the number of players per session and avoided playing during high competition contexts. Our findings support the hypothesis that wolf play is modulated by dominance relationships more than by cooperative social bonds.
General Responsivity Adherence in Juvenile Drug Treatment Court
Authors: Taylor Liana R.
Published: October 2015

Although the number of juvenile drug treatment courts (JDTC) in operation has increased since the first JDTCs were implemented in the 1990s, research continues to lag regarding the effectiveness of the treatment interventions that are provided. The purpose of the present study was to explore how the risk-need-responsivity models’ general responsivity principle could be used to inform the effectiveness of the interventions provided to 1,176 participants in nine JDTCs in the United States. Responsivity adherence was measured using the number of general responsivity-adherent techniques included in each intervention. The results indicated that an increase in general responsivity adherence was associated with an increase in substance-use severity score, which suggests that the effect of the JDTC model on treatment outcomes could vary by the type of interventions provided to participants. In addition, the findings suggest the need to further specify adherence to the general responsivity principle, particularly among substance-involved juvenile offenders.
Revealing centrality in the spatial structure of cities from human activity patterns
Authors: Zhong Chen , Schläpfer Markus , Müller Arisona Stefan , Batty Michael , Ratti Carlo , Schmitt Gerhard
Published: October 2015

Identifying changes in the spatial structure of cities is a prerequisite for the development and validation of adequate planning strategies. Nevertheless, current methods of measurement are becoming ever more challenged by the highly diverse and intertwined ways of how people actually make use of urban space. Here, we propose a new quantitative measure for the centrality of locations, taking into account not only the numbers of people attracted to different locations, but also the diversity of the activities they are engaged in. This ‘centrality index’ allows for the identification of functional urban centres and for a systematic tracking of their relative importance over time, thus contributing to our understanding of polycentricity. We demonstrate the proposed index using travel survey data in Singapore for different years between 1997 and 2012. It is shown that, on the one hand, the city-state has been developing rapidly towards a polycentric urban form that compares rather closely with the official urban development plan. On the other hand, however, the downtown core has strongly gained in its importance, and this can be partly attributed to the recent extension of the public transit system.
Women Military Veterans, Disability, and Employment
Authors: Prokos Anastasia , Cabage LeAnn N.
Published: October 2015

This study contributes to the growing body of literature about women veterans of the U.S. military by investigating how veteran status and disability are related to women’s ability to work. The study uses nationally representative data to analyze labor market outcomes of women who served in the U.S. military since 1973, with a focus on findings about women who have served since 2001. Results indicate women who served after 2001 are more likely to have a disability when compared to men veterans and women nonveterans. Those women veterans who do not have a disability are more likely to be employed than their nonveteran counterparts, net of controls for demographic factors. Disability, including service-related disability, is strongly related to unemployment and being out of the labor force. The discussion considers the implications of women’s military service for their ability to work.
Informal Care and Labor Market Outcomes
Authors: Chen Lu , Zhao Na , Fan Hongli , Coyte Peter C.
Published: October 2015

Data were used from the 1991–2009 China Health and Nutrition Survey to examine the influence of informal care on labor market outcomes for married women of working aged, with emphasis on caregiving intensity. After accounting for potential endogeneity between caregiving and labor force participation (LFP) through simultaneous equations modeling, caregivers who provided more than 15 or 20 hr of caregiving per week were 4.5–7.7% less likely to be LFPs. Intensive caregivers who remained working had significantly lower (4.97–7.20) weekly hours of work. The significant positive effect of informal care on LFP only existed in the rural sample, and these women also had much lower hours of work than their urban counterparts. Opportunities exist for policy interventions that target intensive caregivers in order to allow them to balance both work and caregiving.
Retention of African American Women in a Lifestyle Physical Activity Program
Authors: Buchholz Susan W. , Wilbur JoEllen , Schoeny Michael E. , Fogg Louis , Ingram Diana M. , Miller Arlene , Braun Lynne
Published: October 2015

The purpose of the article is to examine how well individual characteristics, neighborhood characteristics, and intervention participation predict study retention and staff level of effort needed for retention, using a cohort of African American women enrolled in a physical activity program. Secondary data analysis was conducted from a randomized clinical trial. Participants were aged 40 to 65 years without major signs/symptoms of cardiovascular disease. Assessments were conducted at community sites in/bordering African American communities. Study retention was 90%. Of those retained, 24% required moderate/high level of staff effort for retention. Retention was predicted by being older, having lower perceived neighborhood walkability, living in neighborhoods with greater disadvantage and crime, and having greater program participation. More staff effort was predicted by participants being younger, having more economic hardships, poorer health, or lower intervention participation. We may be able to identify people at baseline likely to require more staff effort to retain.
Shattering the silence: The power of Purposeful Storytelling in challenging social security policy discourses of ‘blame and shame’ in Northern Ireland
Authors: Kent Gabi
Published: October 2015

This article reports on a pioneering engagement project between team members from the Poverty and Social Exclusion in the UK (PSE UK) study, the Community Foundation for Northern Ireland and marginalised communities, located in areas of high deprivation in Northern Ireland. Community conversations and a tailor-made methodology of ‘Purposeful Digital Storytelling’ to capture and share data, engendered empowerment, engaging individuals and communities as producers of knowledge and agents of change. Findings from this Participatory Action Research collaboration offer fresh insights into the potential of collective knowledge sharing to challenge the corrosive impact of poverty-induced shame.
Do I Really Know You? Do You Really Know Me? Empathy Amid Diversity in Differing Learning Contexts
Authors: Kasl Elizabeth , Yorks Lyle
Published: October 2015

We explore the need for empathy in diverse groups, conceptualize the epistemology of empathy in relationship to whole-person dialogue, and examine strategies for creating empathic space that take into consideration the paradox of diversity. Two examples from our practice illustrate the role of empathic connection in personal learning and organizational change.