bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of a Mestranol 2‐N‐Piperazino‐Substituted Derivative Showing Potent and Selective in vitro and in vivo Activities in MCF‐7 Breast Cancer Models
Authors: Perreault Martin , Maltais René , Roy Jenny , Dutour Raphaël , Poirier Donald 
Published: January 2017

AbstractAnticancer structure–activity relationship studies on aminosteroid (5α‐androstane) derivatives have emerged with a promising lead candidate: RM‐133 (2β‐[1‐(quinoline‐2‐carbonyl)pyrrolidine‐2‐carbonyl]‐N‐piperazine‐5α‐androstane‐3α,17β‐diol), which possesses high in vitro and in vivo activities against several cancer cells, and selectivity over normal cells. However, the relatively weak metabolic stability of RM‐133 has been a drawback to its progression toward clinical trials. We investigated the replacement of the androstane backbone by a more stable mestranol moiety. The resulting compound, called RM‐581 ({4‐[17α‐ethynyl‐17β‐hydroxy‐3‐methoxyestra‐1,3,5(10)‐trien‐2‐yl]piperazin‐1‐yl}[(2S)‐1‐(quinolin‐2‐ylcarbonyl)pyrrolidin‐2‐yl]methanone), was synthesized efficiently in only five steps from commercially available estrone. In comparison with RM‐133, RM‐581 was found to be twice as metabolically stable, retains potent cytotoxic activity in breast cancer MCF‐7 cell culture, and fully blocks tumor growth in a mouse xenograft model of breast cancer. Advantageously, the selectivity over normal cells has been increased with this estrane version of RM‐133. In fact, RM‐581 showed a better selectivity index (15.3 vs. 3.0) for breast cancer MCF‐7 cells over normal breast MCF‐10A cells, and was found to be nontoxic toward primary human kidney proximal tubule cells at doses reaching 50 μm.
Confirmation of ProMisE: A simple, genomics‐based clinical classifier for endometrial cancer
Authors: Talhouk Aline , McConechy Melissa K. , Leung Samuel , Yang Winnie , Lum Amy , Senz Janine , Boyd Niki , Pike Judith , Anglesio Michael , Kwon Janice S. , Karnezis Anthony N. , Huntsman David G. , Gilks C. Blake , McAlpine Jessica N. 
Published: January 2017

BACKGROUNDClassification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on The Cancer Genome Atlas genomic subgroups, and sought to confirm both feasibility and prognostic ability in a new, large cohort of ECs.METHODSImmunohistochemistry (IHC) for the presence or absence of mismatch repair (MMR) proteins (to identify MMR deficiency [MMR‐D]), sequencing for polymerase‐ɛ (POLE) exonuclease domain mutations (POLE EDMs), and IHC for tumor protein 53 (p53) (wild type vs null/missense mutations; p53 wt and p53 abn, respectively) were performed on 319 new EC samples. Subgroups were characterized and assessed relative to outcomes. The prognostic ability of ProMisE was compared with that of current risk‐stratification systems (European Society of Medical Oncology [ESMO]).RESULTSProMisE decision‐tree classification achieved categorization of all cases and identified 4 prognostic subgroups with distinct overall, disease‐specific, and progression‐free survival (P < .001). Tumors with POLE EDMs had the most favorable prognosis, and those with p53 abn the worst prognosis, and separation of the 2 middle survival curves (p53 wt and MMR‐D) was observed. There were no significant differences in survival between the ESMO low‐risk and intermediate‐risk groups. ProMisE improved the ability to discriminate outcomes compared with ESMO risk stratification. There was substantial overlap (89%) between the p53 abn and high‐risk ESMO subgroups; but, otherwise, there were no predictable associations between molecular and ESMO risk groups.CONCLUSIONSMolecular classification of ECs can be achieved using clinically applicable methods and provides independent prognostic information beyond established clinicopathologic risk factors available at diagnosis. Consistent, biologically relevant categorization enables stratification for clinical trials and/or targeted therapy, identification of women who are at increased risk of having Lynch syndrome, and may guide clinical management. Cancer 2017;123:802–13. © 2016 American Cancer Society.
Multidimensional parallel combinatory transform domain communication system
Authors: Chang Cheng , Huan Hao , Xu Jiarui , Tao Ran 
Published: January 2017

SummaryTransform domain communication system is an adaptive anti‐interference system that can dynamically generate interference‐orthogonal waveforms. As a spread spectrum system, its low spectrum efficiency limits potential practical applications. In TDCS, cyclic code shift keying is an orthogonal modulation, whose symbols can be regarded as scalars in different dimensions. However, the constellation is restricted by signal time‐bandwidth product. In this study, extending constellation is proven to be a valid approach to improve spectrum efficiency. The combinatory of multidimensional vectors is designed mathematically to increase the variety of the scalars with the minimum orthogonality damage. On the basis of the design, an efficient modulation scheme, namely, multidimensional parallel combinatory transform domain communication system, is proposed, whose fundamental modulation symbols can be represented by the combinatory of a series of cyclic code shift keying symbols with phase shift keying modulation. Compared with the existing methods, multidimensional parallel combinatory transform domain communication system can achieve a considerably higher spectrum efficiency. The bit error rate performance is also improved to various extents. Theoretical spectrum efficiency and bit error rate of the proposed method are derived for additive white Gaussian noise and typical multipath fading channels. System with different spectral conditions and channel estimation methods is also simulated and analyzed to confirm the practical usability.
Nonsmooth dynamics prediction of measured bridge response involving deck‐abutment pounding
Authors: Shi Zhongqi , Dimitrakopoulos Elias G. 
Published: January 2017

SummaryEarthquake‐induced deck‐abutment contact alters the boundary conditions at the deck level and might activate a different mechanical system than the one assumed during the design of the bridge. Occasionally this discrepancy between the assumed and the actual seismic behavior has detrimental consequences, for example, pier damage, deck unseating, or even collapse. Recently, an insightful shake‐table testing of a scaled deck‐abutment bridge model , showed unexpected in‐plane rotations even though the deck was straight. These contact‐induced rotations produced significant residual displacements and damage to the piers and the bents. The present paper utilizes that experimental data to examine the validity and the limitations of a proposed nonsmooth dynamic analysis framework. The results show that the proposed approach satisfactorily captures the planar rigid‐body dynamics of the deck which is characterized by deck‐abutment contact. The analysis brings forward the role of friction on the physical mechanism behind the rotation of the deck, and underlines the importance of considering the frictional contact forces during deck‐abutment interaction even for straight bridges, which typically are neglected. Finally, the paper investigates the sensitivity of the rotation with respect to macroscopic contact parameters (i.e., the coefficient of friction and the coefficient of restitution). Copyright © 2017 John Wiley & Sons, Ltd.
Aquatic toxicity of photo-degraded insensitive munition 101 (IMX-101) constituents
Authors: Kennedy Alan J. , Poda Aimee R. , Melby Nicolas L. , Moores Lee C. , Jordan Shinita M. , Gust Kurt A. , Bednar Anthony J. 
Published: January 2017

Abstract

Insensitive munitions are desirable alternatives to historically used formulations, such as 2,4,6-trinitrotoluene (TNT), because of their so-called insensitivity to unintended detonation. The insensitive munition IMX-101 is a mixture of 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ). Environmental releases of munitions may be from production wastewaters or training; these munitions may be exposed to ultraviolet (UV) light. Therefore, it is useful to understand the relative toxicity of IMX-101 and its constituents both before and after photodegradation. The intent of the present study was to generate relative hazard information by exposing the standard ecotoxicological model Ceriodaphnia dubia to each insensitive munition constituent individually and to IMX-101 before and after the exposure solution was irradiated in a UV photoreactor. Without photodegradation, DNAN was more toxic (median lethal concentration [LC50] = 43 mg/L) than the other 2 constituents and it contributed predominantly to the toxicity of IMX-101 (LC50 = 206 mg/L) based on toxic units. Toxicity was observed only at high levels of NQ (LC50 = 1174 mg/L) and pH-adjusted NTO (LC50 = 799 mg/L). The toxicity of IMX-101 is lower than literature-reported TNT toxicity. Photodegradation efficiency was greater at lower insensitive munition concentrations. The observed degradation was greatest for NQ (42–99%), which in turn corresponded to the greatest relative increase in toxicity (100–1000-fold). Modest percent of degradation (4–18%) and increases in phototoxicity (2–100-fold) were observed for NTO and DNAN. Photodegraded NQ products were the predominant source of toxicity of photodegraded IMX-101. Future work involves research to enable analytical and computational confirmation of the specific degradation compounds inducing the observed photoenhanced toxicity. Environ Toxicol Chem 2017;36:2050–2057. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Postoperative anatomic and quality‐of‐life outcomes after vaginal sacrocolporectopexy for vaginal vault prolapse
Authors: Klapdor Rüdiger , Grosse Jolanda , Hertel Bettina , Hillemanns Peter , Hertel Hermann 
Published: January 2017

AbstractObjectiveTo assess anatomic outcome and quality of life (QOL) after vaginal sacrocolporectopexy among patients with pelvic organ prolapse.MethodsA noncomparative observational study was conducted at Hanover Medical School, Germany, among patients who underwent vaginal sacrocolporectopexy for uterine or vaginal vault prolapse between May 1, 2006, and October 31, 2012. A validated German version of the Prolapse QOL (P‐QOL) questionnaire was sent to eligible patients; respondents were invited for follow‐up examination.ResultsOverall, 128 patients were enrolled. Concomitant hysterectomy was performed among 82 (64.1%) patients, anterior colporrhaphy among 105 (82.0%), and posterior colporrhaphy among 58 (45.3%). After a mean interval of 26.5 months (range 1.0–81.3 months), seven patients exhibited recurrent vaginal vault prolapse of at least stage 2, giving a success rate of 92.3% (95% confidence interval 85.9%–96.5%). The P‐QOL scores were either low (<40) or very low (<20), indicating high QOL. Regarding symptoms related to pelvic organ prolapse, patients reported little or no impact on QOL after vaginal sacrocolporectopexy.ConclusionVaginal sacrocolporectopexy seemed safe and feasible, leading to anatomically correct fixation of the vaginal apex, high anatomic success rates, and good QOL. This procedure might be considered as an alternative to laparoscopic or abdominal sacrocolpopexy.
Rosmarinic Acid Mediates Mitochondrial Biogenesis in Insulin Resistant Skeletal Muscle Through Activation of AMPK
Authors: Jayanthy Govindaraj , Roshana Devi Vellai , Ilango Kaliappan , Subramanian Sorimuthu Pillai 
Published: January 2017

ABSTRACTRosmarinic acid (RA), a polyphenol, is known to improve hepatic insulin sensitivity in experimental type 2 diabetes. However, its effect on skeletal muscle insulin resistance is meagerly understood. The present study was aimed to investigate the up‐ and downstream mediators of the molecular targets of RA in attenuating insulin resistance in the skeletal muscle both in vivo and in vitro. We found that supplementation of RA increased the expression of key genes involved in the mitochondrial biogenesis like PGC‐1α, SIRT‐1, and TFAM via activation of AMPK in the skeletal muscle of insulin resistant rats as well as in L6 myotubes. Further, RA treatment increased the glucose uptake and decreased the phosphorylation of serine IRS‐1 while increasing the translocation of GLUT 4. Together, our findings evidenced that RA treatment significantly inhibit insulin resistance in skeletal muscle cells by enhancing mitochondrial biogenesis. J. Cell. Biochem. 118: 1839–1848, 2017. © 2017 Wiley Periodicals, Inc.
Impact of vessel wall lesions and vascular stenoses on cerebrovascular reactivity in patients with intracranial stenotic disease
Authors: Cogswell Petrice M. , Davis Taylor L. , Strother Megan K. , Faraco Carlos C. , Scott Allison O. , Jordan Lori C. , Fusco Matthew R. , Frederick Blaise deB , Hendrikse Jeroen , Donahue Manus J. 
Published: January 2017

PurposeTo compare cerebrovascular reactivity (CVR) and CVR lagtimes in flow territories perfused by vessels with vs. without proximal arterial wall disease and/or stenosis, separately in patients with atherosclerotic and nonatherosclerotic (moyamoya) intracranial stenosis.Materials and MethodsAtherosclerotic and moyamoya patients with >50% intracranial stenosis and <70% cervical stenosis underwent angiography, vessel wall imaging (VWI), and CVR‐weighted imaging (n = 36; vessel segments evaluated = 396). Angiography and VWI were evaluated for stenosis locations and vessel wall lesions. Maximum CVR and CVR lagtime were contrasted between vascular territories with and without proximal intracranial vessel wall lesions and stenosis, and a Wilcoxon rank‐sum was test used to determine differences (criteria: corrected two‐sided P < 0.05).ResultsCVR lagtime was prolonged in territories with vs. without a proximal vessel wall lesion or stenosis for both patient groups: moyamoya (CVR lagtime = 45.5 sec ± 14.2 sec vs. 35.7 sec ± 9.7 sec, P < 0.001) and atherosclerosis (CVR lagtime = 38.2 sec ± 9.1 sec vs. 35.0 sec ± 7.2 sec, P = 0.001). For reactivity, a significant decrease in maximum CVR in the moyamoya group only (maximum CVR = 9.8 ± 2.2 vs. 12.0 ± 2.4, P < 0.001) was observed.ConclusionArterial vessel wall lesions detected on noninvasive, noncontrast intracranial VWI in patients with intracranial stenosis correlate on average with tissue‐level impairment on CVR‐weighted imaging.Level of Evidence: 4Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2017;46:1167–1176.
Spatiotemporal variability modes of surface air temperature in South America during the 1951–2010 period: ENSO and non‐ENSO components
Authors: Kayano Mary Toshie , Andreoli Rita Valéria , de Souza Rodrigo Augusto Ferreira , Garcia Sâmia Regina 
Published: January 2017

ABSTRACTThe dominant seasonal surface air temperature (SAT) anomalous modes over entire South America (SA) for the 1951–2010 period were investigated. The El Niño‐Southern Oscillation (ENSO) and non‐ENSO (residual – RES) characteristics of the SAT anomalous modes and the associated precipitation and temperature advection anomalies were discussed. The SAT (referred to as TOT) and RES modes were obtained from the empirical orthogonal function analyses, and the ENSO modes from the correlation analyses between the SAT anomalies and the Oceanic Niño index. The SAT TOT modes are in general, weakly linked to the ENSO, except for the first summer and the fourth spring TOT modes. For these two modes, the precipitation variations are more crucial than the temperature advection variations in defining the SAT anomaly patterns. On the other hand, the first winter and autumn TOT modes contain mostly the non‐ENSO components and feature an extensive warmed area in tropical and subtropical SA. For these modes, the subtropical warming is due to the temperature advection. The TOT modes with a weak relation to the ENSO and the corresponding RES modes show a dipolar pattern with a warm node in tropical SA and the cold one in extratropical SA, and is determined mostly by the precipitation. Nevertheless, the cold advection reinforces the cold node of the winter and summer modes. In some cases, the regional systems contribute to the SAT anomalies. The South American low‐level jet contributes to the positive SAT anomalies in central and eastern Brazil for the second winter and first spring RES modes and the South Atlantic Convergence Zone influences the first summer RES mode. The SAT modes describe mostly the interannual variations of the SAT patterns over SA, but some of them also contain decadal and multidecadal time scale variations.
Reducing uncertainty when using knee‐specific finite element models by assessing the effect of input parameters
Authors: Guo Hongqiang , Santner Thomas J. , Lerner Amy L. , Maher Suzanne A. 
Published: January 2017

ABSTRACTLittle is known about knee‐specific factors that influence contact mechanics. Finite Element (FE) models offer a powerful tool to study contact mechanics, but there often exists ambiguity in the exact values of the inputs (e.g., tissue properties), which can result in a range of output values. Our objective was to quantify the reduction in the range of output values (defined herein as “uncertainty”) from FE models of the human knee joint when known pre‐defined values are used for clinically measurable inputs. To achieve this goal, we applied a statistically augmented FE approach to three human cadaveric knees for which full geometric and kinematic data were available. Two sets of conditions were simulated: All model inputs, clinically measurable or not, were varied to represent a “normal” patient population (Condition 1); subsets of clinically measurable variable inputs were fixed at specific values (called “patient derived inputs,” or PDIs) while the other variables were varied over “normal” values (Condition 2). We found that by fixing body mass index and the anterior–posterior position of the meniscal‐bony insertion points, model output uncertainty was reduced by one‐ to three‐fifths. The magnitude of uncertainty reduction was strongly influenced by the individual knee. It was observed that knees with great anterior–posterior translation during gait had greater reductions in uncertainty when PDIs were used. This study represents the first step in developing FE models of the human knee joint based on inputs that can be derived from patients in a clinical setting. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2233–2242, 2017.
The Impact of Ecological Construction Programs on Grassland Conservation in Inner Mongolia, China
Authors: Liu Min , Dries Liesbeth , Heijman Wim , Huang Jikun , Zhu Xueqin , Hu Yuanning , Chen Haibin 
Published: January 2017

AbstractA series of Ecological Construction Programs have been initiated to protect the condition of grasslands in China during recent decades. However, grassland degradation is still severe, and conditions have not been restored as intended. This paper aims to empirically examine the effectiveness of these programs for protecting the grassland condition in the extensive pastoral areas of China. We focus on one major program that has been implemented widely on the grasslands, the Subsidy and Incentive System for Grassland Conservation (SISGC). The normalized difference vegetation index, measured with remote sensing technology, is used to quantify the grassland condition between 2001 and 2014. With data from 54 counties in the pastoral areas of Inner Mongolia, we estimate the impact of SISGC on the grassland condition. A fixed effects model is employed to control for livestock production, climate, time trends, and time‐invariant heterogeneity between counties. The model results provide quantitative evidence that the condition of the grasslands has improved significantly because of SISGC; but that the effectiveness of SISGC was offset to some extent by other socio‐economic and climate factors, such as increased producer prices and high temperature. This may explain why the actual grassland degradation has not been prevented as effectively as was expected. In addition, the impact of SISGC was stronger in counties with worse initial grassland condition. Furthermore, the effects of producer prices and climate changes were also more pronounced in these counties. Copyright © 2017 John Wiley & Sons, Ltd.
The implications and impact of 3 approaches to health information exchange: community, enterprise, and vendor‐mediated health information exchange
Authors: Everson Jordan 
Published: January 2017

AbstractIntroductionElectronic health information exchange (HIE) is considered essential to establishing a learning health system, reducing medical errors, and improving efficiency, but establishment of widespread, high functioning HIE has been challenging. Healthcare organizations now have considerable flexibility in selecting among several HIE strategies, most prominently community HIE, enterprise HIE (led by a healthcare organization), and electronic health record vendor‐mediated HIE. Each of these strategies is characterized by different conveners, capabilities, and motivations and may have different abilities to facilitate improved patient care.MethodsI reviewed the available scholarly literature to draw conceptual distinctions between these types of HIE, to assess the current evidence on each type of HIE, and to indicate important areas of future research.ResultsWhile community HIE seems to offer the most open approach to HIE allowing for high levels of connectivity, both enterprise HIE and vendor‐mediated HIE face lower barriers to formation and sustainability. Most existing evidence is focused on community HIE and points towards low overall use, challenges to usability, and ambiguous impact. To better guide organizational leaders and policymakers in the expansion of beneficial HIE and anticipate future trends, future research should work to better capture the prevalence of other forms of HIE, and to adopt common methods to allow comparisons of rate of use, usability, and impact on patient care across studies and types of HIE.ConclusionsHealthcare organizations' choice of HIE strategy influences the set of partners the organization is connected to and may influence the benefit that efforts supported by HIE can offer to patients. Current research is not fully capturing the diversity of approaches to HIE and their potentially varying impact on providers and patients.
Modelling maximum daily yearly rainfall in northern Algeria using generalized extreme value distributions from 1936 to 2009
Authors: Boudrissa Naima , Cheraitia Hassen , Halimi Lotfi 
Published: January 2017

ABSTRACTThe generalized extreme value distribution is generally used to model annual maximum daily precipitation, and it then allows the calculation of the return values of this phenomenon. The distribution was fitted for selected stations in the north of Algeria; it was found that the generalized extreme value distribution of type I or the Gumbel distribution is more suitable for the Algiers and Miliana stations and the Fréchet distribution is more appropriate for the Oran station. The parameters were estimated using the maximum likelihood method, and the return levels were calculated at selected return periodsT; for instance, about 100 years must elapse to record a level of 181.9 mm of rainfallperday in Algiers, 173 mm in Miliana and 109.54 mm in Oran.