bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospitalisation trends in India from serial cross-sectional nationwide surveys: 1995 to 2014
Authors: Pandey Anamika , Ploubidis George B , Clarke Lynda , Dandona Lalit 
Published: December 2017

ObjectivesWe report hospitalisation trends for different age groups across the states of India and for various disease groups, compare the hospitalisation trends among the older (aged 60 years or more) and the younger (aged under 60 years) population and quantify the factors that contribute to the change in hospitalisation rates of the older population over two decades.DesignSerial cross-sectional study.SettingNationally representative sample, India.Data sourcesThree consecutive National Sample Surveys (NSS) on healthcare utilisation in 1995–1996, 2004 and 2014.ParticipantsSix hundred and thirty-three thousand four hundred and five individuals in NSS 1995–1996, 385 055 in NSS 2004 and 335 499 in NSS 2014.MethodsDescriptive statistics, multivariable analyses and a regression decomposition technique were used to attain the study objectives.ResultThe annual hospitalisation rate per 1000 increased from 16.6 to 37.0 in India from 1995–1996 to 2014. The hospitalisation rate was about half in the less developed than the more developed states in 2014 (26.1 vs 48.6 per 1000). Poor people used more public than private hospitals; this differential was higher in the more developed (40.7% vs 22.9%) than the less developed (54.3% vs 40.1%) states in 2014. When compared with the younger population, the older population had a 3.6 times higher hospitalisation rate (109.9 vs 30.7) and a greater proportion of hospitalisation for non-communicable diseases (80.5% vs 56.7%) in 2014. Among the older population, hospitalisation rates were comparatively lower for females, poor and rural residents. Propensity change contributed to 86.5% of the increase in hospitalisation among the older population and compositional change contributed 9.3%.ConclusionThe older population in India has a much higher hospitalisation rate and has continuing greater socioeconomic differentials in hospitalisation rates. Specific policy focus on the requirements of the older population for hospital care in India is needed in light of the anticipated increase in their proportion in the population.
Handling the procurement of prostheses for total hip replacement: description of an original value based approach and application to a real-life dataset reported in the UK
Authors: Messori Andrea , Trippoli Sabrina , Marinai Claudio 
Published: December 2017

ObjectivesIn most European countries, innovative medical devices are not managed according to cost–utility methods, the reason being that national agencies do not generally evaluate these products. The objective of our study was to investigate the cost-utility profile of prostheses for hip replacement and to calculate a value-based score to be used in the process of procurement and tendering for these devices.MethodsThe first phase of our study was aimed at retrieving the studies reporting the values of QALYs, direct cost, and net monetary benefit (NMB) from patients undergoing total hip arthroplasty (THA) with different brands of hip prosthesis. The second phase was aimed at calculating, on the basis of the results of cost–utility analysis, a tender score for each device (defined according to standard tendering equations and adapted to a 0–100 scale). This allowed us to determine the ranking of each device in the simulated tender.ResultsWe identified a single study as the source of information for our analysis. Nine device brands (cemented, cementless, or hybrid) were evaluated. The cemented prosthesis Exeter V40/Elite Plus Ogee, the cementless device Taperloc/Exceed, and the hybrid device Exeter V40/Trident had the highest NMB (£152 877, £156 356, and £156 210, respectively) and the best value-based tender score.ConclusionsThe incorporation of value-based criteria in the procurement process can contribute to optimising the value for money for THA devices. According to the approach described herein, the acquisition of these devices does not necessarily converge on the product with the lowest cost; in fact, more costly devices should be preferred when their increased cost is offset by the monetary value of the increased clinical benefit.
Predictive value of prebronchodilator and postbronchodilator spirometry for COPD features and outcomes
Authors: Fortis Spyridon , Eberlein Michael , Georgopoulos Dimitris , Comellas Alejandro P 
Published: December 2017

IntroductionWe compared the predictive value of prebronchodilator and postbronchodilator spirometry for chronic obstructive pulmonary disease (COPD) features and outcomes.MethodsWe analysed COPDGene data of 10 192 subjects with smoking history. We created regressions models with the following dependent variables: clinical, functional and radiographic features, and the following independent variables: prebronchodilator airflow obstruction (PREO) and postbronchodilator airflow obstruction (POSTO), prebronchodilator and postbronchodilator FEV1% predicted. We compared the model performance using the Akaike information criterion (AIC).ResultsThe COPD prevalence was higher using PREO. About 8.5% had PREO but no airflow obstruction in postbronchodilator spirometry (POSTN) (PREO-POSTN) and 3% of all subjects had no aiflow obstruction in prebronchodilator spirometry (PREN) but POSTO (PREN-POSTO). We found no difference in COPD features and outcomes between PREO-POSTN and PREN-POSTO subjects. Although, both prebronchodilator and postbronchodilator spirometries are both associated with chronic bronchitis, dyspnoea, exercise capacity and COPD radiographic findings, models that included postbronchodilator spirometric measures performed better than models with prebronchodilator measures to predict these COPD features. The predictive value of prebronchodilator and postbronchodilator spirometries for respiratory exacerbations, change in forced expiratory volume in 1 s, dyspnoea and exercise capacity during a 5-year period is relatively similar, but postbronchodilator spirometric measures are better predictors of mortality based on AIC.ConclusionsPostbronchodilator spirometry may be a more accurate predictor of COPD features and outcomes.
Arterial pathophysiology and comparison of two devices for pulse wave velocity assessment in elderly men: the British regional heart study
Authors: Ellins Elizabeth A , Smith Kirsten E , Lennon Lucy T , Papacosta Olia , Wannamethee S Goya , Whincup Peter H , Halcox Julian P 
Published: December 2017

ObjectiveVascular disease is highly prevalent in the elderly. This study aimed to evaluate arterial phenotype in elderly men and compare carotid–femoral pulse wave velocity (cfPWV) assessed by two techniques (Sphygmocor (S)and Vicorder (V)).Methods1722 men (72–92 years), participants in the British Regional Heart Study, underwent ultrasound assessment of carotid intima–media thickness (cIMT), carotid distensibility coefficient and presence of carotid plaque. cfPWV and ankle brachial pressure index (ABPI) were also assessed. 123 men returned for between visit reproducibility assessments.ResultsGood reproducibility was demonstrated in all measures (Gwet’s agreement=0.8 for plaque, intraclass correlation=0.65 for ABPI and coefficient of variation <13% for all other measures). Measurements were obtained in >90% of men for all measures except cfPWV(S) and ABPI. In 1122 men with both cfPWV(V) and cfPWV(S) data, cfPWV(S) was greater than cfPWV(V) (mean difference=0.23,95%CI 0.10 to 0.37 m/s). cfPWV(V) was higher at low cfPWV values and cfPWV(S) was higher at high cfPWV values. Correlation of V transit time (TT) against S carotid and femoral TT demonstrated that the slope of the regression line for femoral TT was steeper than for carotid TT, resulting in a proportionally greater subtraction of carotid TT from femoral TT at higher PWVs.ConclusionsReproducible, satisfactory quality non-invasive measurements of vascular phenotype were obtainable in a large proportion of elderly men. The discrepancy in results between the two PWV measures may partly be due to the differential impact of subtracting carotid TT when deriving cfPWV(S) across the clinical PWV range.
Dynamic correlation of Eastern and Western markets and forecasting: Scale-by-scale wavelet-based approach
Authors: Oral Emrah , Unal Gazanfer 
Published: December 2017

In this paper, dynamic four-dimensional (4D) correlation of eastern and western markets is analyzed. A wavelet-based scale-by-scale analysis method has been introduced to model and forecast stock market data for strongly correlated time intervals. The daily data of stock markets of SP500, FTSE and DAX (western markets) and NIKKEI, TAIEX and KOSPI (eastern markets) are obtained from 2009 to the end of 2016 and their co-movement dependencies on time–frequency space using 4D multiple wavelet coherence (MWC) are determined. Once the data is detached into levels of different frequencies using scale-by-scale continuous wavelet transform, all of the time series possessing the same frequency scale are selected, inversed and forecasted using multivariate model, vector autoregressive moving average (VARMA). It is concluded that the efficiency of forecasting is increased substantially using the same-frequency highly correlated time series obtained by scale-by-scale wavelet transform. Moreover, the increasing or decreasing trend of prospected price shift is foreseen fairly well.
The CARMA3–Bcl10–MALT1 Signalosome Drives NFκB Activation and Promotes Aggressiveness in Angiotensin II Receptor–Positive Breast Cancer
Authors: Ekambaram Prasanna , Lee Jia-Ying (Lloyd) , Hubel Nathaniel E. , Hu Dong , Yerneni Saigopalakrishna , Campbell Phil G. , Pollock Netanya , Klei Linda R. , Concel Vincent J. , Delekta Phillip C. , Chinnaiyan Arul M. , Tomlins Scott A. , Rhodes Daniel R. , Priedigkeit Nolan , Lee Adrian V. , Oesterreich Steffi , McAllister-Lucas Linda M. , Lucas Peter C. 
Published: December 2017

Abstract
The angiotensin II receptor AGTR1, which mediates vasoconstrictive and inflammatory signaling in vascular disease, is overexpressed aberrantly in some breast cancers. In this study, we established the significance of an AGTR1-responsive NFκB signaling pathway in this breast cancer subset. We documented that AGTR1 overexpression occurred in the luminal A and B subtypes of breast cancer, was mutually exclusive of HER2 expression, and correlated with aggressive features that include increased lymph node metastasis, reduced responsiveness to neoadjuvant therapy, and reduced overall survival. Mechanistically, AGTR1 overexpression directed both ligand-independent and ligand-dependent activation of NFκB, mediated by a signaling pathway that requires the triad of CARMA3, Bcl10, and MALT1 (CBM signalosome). Activation of this pathway drove cancer cell–intrinsic responses that include proliferation, migration, and invasion. In addition, CBM-dependent activation of NFκB elicited cancer cell–extrinsic effects, impacting endothelial cells of the tumor microenvironment to promote tumor angiogenesis. CBM/NFκB signaling in AGTR1+ breast cancer therefore conspires to promote aggressive behavior through pleiotropic effects. Overall, our results point to the prognostic and therapeutic value of identifying AGTR1 overexpression in a subset of HER2-negative breast cancers, and they provide a mechanistic rationale to explore the repurposing of drugs that target angiotensin II–dependent NFκB signaling pathways to improve the treatment of this breast cancer subset.
Significance: These findings offer a mechanistic rationale to explore the repurposing of drugs that target angiotensin action to improve the treatment of AGTR1-expressing breast cancers. Cancer Res; 78(5); 1225–40. ©2017 AACR.
LSD1 Stimulates Cancer-Associated Fibroblasts to Drive Notch3-Dependent Self-Renewal of Liver Cancer Stem–like Cells
Authors: Liu Chungang , Liu Limei , Chen Xuejiao , Cheng Jiamin , Zhang Heng , Zhang Chengcheng , Shan Juanjuan , Shen Junjie , Qian Cheng 
Published: December 2017

Abstract
Cancer stem-like cells (CSC) in hepatocellular carcinoma (HCC) are thought to mediate therapeutic resistance and poor survival outcomes, but their intrinsic and extrinsic control is not well understood. In this study, we found that the chromatin modification factor LSD1 is highly expressed in HCC CSC where it decreases during differentiation. LSD1 was responsible for maintaining CSC self-renewal and tumorigenicity in HCC, and its overexpression was sufficient to drive self-renewal of non-CSC. Levels of acetylated LSD1 were low in CSC with high LSD1 activity, and these CSC were capable of self-renewal. Notch signaling activated LSD1 through induction of the sirtuin SIRT1, leading to deacetylation and activation of LSD1 and CSC self-renewal. Notably, we found that LSD1 expression was increased in cancer-associated fibroblasts (CAF) as an upstream driver of Notch3-mediated CSC self-renewal. In clinical specimens of HCC, the presence of CAF, LSD1, and Notch3 strongly associated with poor patient survival. Overall, our results reveal that CAF-induced expression of Notch3 is responsible for LSD1 activation in CSC, driving their self-renewal in HCC.
Significance: These seminal findings illuminate a complex pathway in the tissue microenvironment of liver cancer, which is responsible for orchestrating the self-renewal of stem-like cancer cells, with potential implications to improve therapy and limit relapses. Cancer Res; 78(4); 938–49. ©2017 AACR.
Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression
Authors: De Smedt Eva , Maes Ken , Verhulst Stefaan , Lui Hui , Kassambara Alboukadel , Maes Anke , Robert Nicolas , Heirman Carlo , Cakana Andrew , Hose Dirk , Breckpot Karine , van Grunsven Leo A. , De Veirman Kim , Menu Eline , Vanderkerken Karin , Moreaux Jérôme , De Bruyne Elke 
Published: December 2017

Abstract
RAS mutations occur frequently in multiple myeloma (MM), but apart from driving progression, they can also stimulate antitumor effects by activating tumor-suppressive RASSF proteins. Although this family of death effector molecules are often silenced in cancers, functional data about RASSF proteins in MM are lacking. Here, we report that RASSF4 is downregulated during MM progression and correlates with a poor prognosis. Promoter methylation analysis in human cell lines revealed an inverse correlation between RASSF4 mRNA levels and methylation status. Epigenetic modulating agents restored RASSF4 expression. Enforced expression of RASSF4 induced G2-phase cell-cycle arrest and apoptosis in human cell lines, reduced primary MM cell viability, and blocked MM growth in vivo. Mechanistic investigations showed that RASSF4 linked RAS to several pro-death pathways, including those regulated by the kinases MST1, JNK, and p38. By activating MST1 and the JNK/c-Jun pathway, RASSF4 sensitized MM cells to bortezomib. Genetic or pharmacological elevation of RASSF4 levels increased the anti-MM effects of the clinical relevant MEK1/2 inhibitor trametinib. Kinome analysis revealed that this effect was mediated by concomitant activation of the JNK/c-Jun pathway along with inactivation of the MEK/ERK and PI3K/mTOR/Akt pathways. Overall, our findings establish RASSF4 as a tumor-suppressive hub in MM and provide a mechanistic rationale for combining trametinib with HDAC inhibitors or bortezomib to treat patients with tumors exhibiting low RASSF4 expression.
Significance: These findings provide a mechanistic rationale for combining trametinib with HDAC inhibitors or bortezomib in patients with multiple myeloma whose tumors exhibit low RASSF4 expression. Cancer Res; 78(5); 1155–68. ©2017 AACR.
ER Stress Signaling Promotes the Survival of Cancer “Persister Cells” Tolerant to EGFR Tyrosine Kinase Inhibitors
Authors: Terai Hideki , Kitajima Shunsuke , Potter Danielle S. , Matsui Yusuke , Quiceno Laura Gutierrez , Chen Ting , Kim Tae-jung , Rusan Maria , Thai Tran C. , Piccioni Federica , Donovan Katherine A. , Kwiatkowski Nicholas , Hinohara Kunihiko , Wei Guo , Gray Nathanael S. , Fischer Eric S. , Wong Kwok-Kin , Shimamura Teppei , Letai Anthony , Hammerman Peter S. , Barbie David A. 
Published: December 2017

Abstract
An increasingly recognized component of resistance to tyrosine kinase inhibitors (TKI) involves persistence of a drug-tolerant subpopulation of cancer cells that survive despite effective eradication of the majority of the cell population. Multiple groups have demonstrated that these drug-tolerant persister cells undergo transcriptional adaptation via an epigenetic state change that promotes cell survival. Because this mode of TKI drug tolerance appears to involve transcriptional addiction to specific genes and pathways, we hypothesized that systematic functional screening of EGFR TKI/transcriptional inhibitor combination therapy would yield important mechanistic insights and alternative drug escape pathways. We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib + THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. As expected, suppression of multiple genes associated with transcriptional complexes (EP300, CREBBP, and MED1) enhanced erlotinib/THZ1 synergy. Unexpectedly, we uncovered nearly every component of the recently described ufmylation pathway in the synergy suppressor group. Loss of ufmylation did not affect canonical downstream EGFR signaling. Instead, absence of this pathway triggered a protective unfolded protein response associated with STING upregulation, promoting protumorigenic inflammatory signaling but also unique dependence on Bcl-xL. These data reveal that dysregulation of ufmylation and ER stress comprise a previously unrecognized TKI drug tolerance pathway that engages survival signaling, with potentially important therapeutic implications.
Significance: These findings reveal a novel function of the recently described ufmylation pathway, an ER stress survival signaling in drug-tolerant persister cells, which has important biological and therapeutic implications. Cancer Res; 78(4); 1044–57. ©2017 AACR.
FIH Is an Oxygen Sensor in Ovarian Cancer for G9a/GLP-Driven Epigenetic Regulation of Metastasis-Related Genes
Authors: Kang Jengmin , Shin Seung-Hyun , Yoon Haejin , Huh June , Shin Hyun-Woo , Chun Yang-Sook , Park Jong-Wan 
Published: December 2017

Abstract
The prolyl hydroxylase domain-containing proteins (PHD1-3) and the asparaginyl hydroxlyase factor inhibiting HIF (FIH) are oxygen sensors for hypoxia-inducible factor-driven transcription of hypoxia-induced genes, but whether these sensors affect oxygen-dependent epigenetic regulation more broadly is not known. Here, we show that FIH exerts an additional role as an oxygen sensor in epigenetic control by the histone lysine methyltransferases G9a and GLP. FIH hydroxylated and inhibited G9a and GLP under normoxia. When the FIH reaction was limited under hypoxia, G9a and GLP were activated and repressed metastasis suppressor genes, thereby triggering cancer cell migration and peritoneal dissemination of ovarian cancer xenografts. In clinical specimens of ovarian cancer, expression of FIH and G9a were reciprocally associated with patient outcomes. We also identified mutations of FIH target motifs in G9a and GLP, which exhibited excessive H3K9 methylation and facilitated cell invasion. This study provides insight into a new function of FIH as an upstream regulator of oxygen-dependent chromatin remodeling. It also implies that the FIH-G9a/GLP pathway could be a potential target for inhibiting hypoxia-induced cancer metastasis.
Significance: These findings deepen understanding of oxygen-dependent gene regulation and cancer metastasis in response to hypoxia. Cancer Res; 78(5); 1184–99. ©2017 AACR.
Vitamin D Status and Resting Metabolic Rate May Modify through Expression of Vitamin D Receptor and Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene in Overweight and Obese Adults
Authors: Sajjadi Seyedeh Forough , Mirzaei Khadijeh , Khorrami-Nezhad Leila , Maghbooli Zhila , Keshavarz Seyed Ali 
Published: December 2017

<b><i>Background:</i></b> Resting metabolic rate (RMR) used to prognosticate and measure the amount of energy required. Vitamin D is known as a new predictor of RMR. The aim of this study is to investigate the relationship between vitamin D effects on RMR in connection with the vitamin D receptor (<i>VDR</i>) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (<i>PGC-1α</i>) gene expression. <b><i>Methods:</i></b> We enrolled 298 overweight and obese adults in this cross-sectional study. Body mass index (BMI), fat mass, fat-free mass, insulin level, visceral fat, and vitamin D status were assessed. RMR was measured by means of indirect calorimetry. The real-time polymerase chain reaction using specific primer pairs for <i>VDR</i> and <i>PGC-1α</i> was performed. <b><i>Results:</i></b> There were significant differences in terms of fat free mass, fat percentage, insulin levels, RMR/kg body weight, and RMR/BMI, <i>VDR</i>, and <i>PGC-1α</i> among participants were categorized based on the vitamin D status. But after using general linear model for adjusting, all significant results missed their effectiveness except RMR/kg body weight and <i>VDR</i>. Linear regression analysis used to show the mediatory role of <i>VDR</i> and <i>PGC-1α</i> on the RMR/kg body weight and vitamin D status relationship. Our results showed that <i>VDR</i> had a mediatory effect on the relationship between RMR/kg body weight and vitamin D status (β = 0.38, 95% CI –0.48 to 1.60; β = –1.24, 95% CI –5.36 to 1.70). However, <i>PGC-1α</i> did not affect the relationship between RMR/kg body weight and vitamin D status (β = 0.50, 95% CI = –0.02 to 3.42; β = 0.59, 95% CI 0.14–3.90). <b><i>Conclusion:</i></b> Our study showed the mediatory effect of <i>VDR</i> gene expression in the association of 25(OH)<sub>2</sub>D plasma levels and resting metabolic rate among obese individuals.