bluuebunny/crossref_metadata_2025_split huggingface dataset:
The chemokine receptor CXCR7 influences prognosis in human glioma in an IDH1-dependent manner
Authors: Birner Peter , Tchorbanov Andrey , Natchev Sevdalin , Tuettenberg Jochen , Guentchev Marin 
Published: June 2015

AimsThe chemokine receptor CXCR7 is found on glioma cells and glioma-associated vessels and dependent upon its localisation on tumour or endothelial cells the CXCR7 receptor can mediate glioma cell invasion and tumour angiogenesis. Its expression predicts survival in several types of cancers.MethodsWe immunohistochemically studied the expression of CXCR7 and its ligand SDF1α in a cohort of 354 human patients with glioma. In an in vivo glioma model, we studied the effect of selective CXCR7 inhibition on mean vascular density.ResultsHere we show that expression of either mutant isocitrate dehydrogenase (IDH) 1 or podoplanin (PDPN), two proteins present in basically non-overlapping glioma populations, predicts the prognostic significance of CXCR7. Specifically, expression of CXCR7 on endothelial cells in IDH1 mutant cases predicted poor outcome. Surprisingly, in PDPN expressing gliomas, one of the marker genes for the recently identified mesenchymal subgroup, expression of CXCR7 predicts diminished prognosis on tumour cells and better prognosis on endothelial cells.ConclusionsSince CXCR7 is expressed on migrating cells our data suggest that, although ubiquitously present, angiogenesis and invasion are outcome-relevant events in specific glioma subgroups, providing a potentially important tool for targeted therapy assignment.
Treatment choices in elderly patients with ST: elevation myocardial infarction—insights from the Vital Heart Response registry
Authors: Toleva Olga , Ibrahim Quazi , Brass Neil , Sookram Sunil , Welsh Robert 
Published: June 2015

BackgroundManagement of elderly patients with ST elevation myocardial infarction (STEMI) is challenging and they are under-represented in trials. Accordingly, we analysed reperfusion strategies and their effectiveness in patients with STEMI ≥75 years compared to <75 years within a comprehensive inclusive registry.MethodsConsecutive patients with STEMI admitted to hospital and tracked within a regional registry (2006–2011) were analysed comparing reperfusion strategy (primary percutaneous coronary intervention (PPCI), fibrinolysis and no reperfusion) between patients ≥75 vs <75 years old as well as across the reperfusion strategies in those ≥75 years.ResultsThere were 3588 patients with STEMI with 646 (18%) ≥75 years old. Elderly patients were more likely female (46.9% vs 18.4%) and had more prior: angina (28.2% vs 17.2%), myocardial infarction (MI; 22.8% vs 13.9%), hypertension (67.6% vs 44.2%), heart failure (2.3% vs 0.3%) and atrial fibrillation (2.2% vs 0.5%) (all p<0.001). The reperfusion strategy for patients ≥75 vs <75: PPCI 45.3% vs 41.2%, fibrinolysis 24.8% vs 45.7%, and no reperfusion 29.9% vs 13.1% (p<0.001). Time from symptoms to first medical contact (median, 93 vs 78 min p=0.008) and PPCI (median, 166 vs 136 min (p<0.001) were longer for ≥75 years. In those ≥75 years outcomes by reperfusion (PPCI, fibrinolysis and none) were: in-hospital death 13.3%, 9.4% and 19.7% (p=0.018), and composite of death, recurrent-MI, cardiogenic shock and congestive heart failure 28%, 20% and 33.2% (p=0.022).ConclusionsElderly patients have more comorbidities, worst in-hospital clinical outcomes and are less likely to receive reperfusion. Acknowledging physician selection of the reperfusion strategy; outcomes appear favourable in the elderly receiving fibrinolysis.
A preliminary investigation into the moral reasoning abilities of UK veterinarians
Authors: Batchelor C. E. M. , Creed A. , McKeegan D. E. F. 
Published: June 2015

Veterinary medicine is an ethically challenging profession, but the ethical reasoning abilities of practising veterinarians in the UK have never been formally assessed. This study investigated moral reasoning ability in 65 qualified veterinarians (38 practising and 27 academic) and 33 members of the public in the UK using the Defining Issues Test. Academic veterinarians had higher scores than members of the public but practising veterinarians did not. There was large variation in moral reasoning abilities among qualified veterinarians. Moral reasoning score in veterinarians did not improve with years of experience. These results show that despite having a professional degree moral reasoning skills of practising veterinarians may be insufficient to deal with the demands of their profession. This could have implications for animal welfare, client services and veterinarian wellbeing. The results highlight the need for more training in this area.
Validating variational principle for higher order theory of gravity
Authors: Ruz Soumendranath , Sarkar Kaushik , Sk Nayem , Sanyal Abhik Kumar 
Published: June 2015

Metric variation of higher order theory of gravity requires fixing of the Ricci scalar in addition to the metric tensor at the boundary. Fixing Ricci scalar at the boundary implies that the classical solutions are fixed once and forever to the de Sitter or anti-de Sitter (dS/AdS) solutions. Here, we justify such requirement from the standpoint of Noether symmetry.
Report on the First Workshop on Supporting Complex Search Tasks
Authors: Gäde Maria , Hall Mark M. , Huurdeman Hugo , Kamps Jaap , Koolen Marijn , Skove Mette , Toms Elaine , Walsh David 
Published: June 2015

There is broad consensus in the field of IR that search is complex in many use cases and applications, both on theWeb and in domain specific collections, and both in our professional and in our daily life. Yet our understanding of complex search tasks, in comparison to simple look up tasks, is fragmented at best. The workshop addressed many open research questions: What are the obvious use cases and applications of complex search? What are essential features of work tasks and search tasks to take into account? And how do these evolve over time? With a multitude of information, varying from introductory to specialized, and from authoritative to speculative or opinionated, when to show what sources of information? How does the information seeking process evolve and what are relevant differences between different stages? With complex task and search process management, blending searching, browsing, and recommendations, and supporting exploratory search to sensemaking and analytics, UI and UX design pose an overconstrained challenge. How do we know that our approach is any good? Supporting complex search tasks requires new collaborations across the whole field of IR, and the proposed workshop brought together a diverse group of researchers to work together on one of the greatest challenges of our field.
The workshop featured three main elements. First, a keynote on an emerging theory of task difficulty by Diane Kelly. Second, a lively boaster and poster session in which seven contributed papers were presented. Third, three breakout groups on: 1) user interfaces and user experience, 2) tasks and users, and 3) information needs on controversial topics. There was an general feeling that the discussion made progress, and built new connections between related strands of research in IR.
Reducing Latency via Redundant Requests
Authors: Gardner Kristen , Zbarsky Samuel , Doroudi Sherwin , Harchol-Balter Mor , Hyytia Esa 
Published: June 2015

Recent computer systems research has proposed using redundant requests to reduce latency. The idea is to run a request on multiple servers and wait for the first completion (discarding all remaining copies of the request). However there is no exact analysis of systems with redundancy.
This paper presents the first exact analysis of systems with redundancy. We allow for any number of classes of redundant requests, any number of classes of non-redundant requests, any degree of redundancy, and any number of heterogeneous servers. In all cases we derive the limiting distribution on the state of the system.
In small (two or three server) systems, we derive simple forms for the distribution of response time of both the redundant classes and non-redundant classes, and we quantify the "gain" to redundant classes and "pain" to non-redundant classes caused by redundancy. We find some surprising results. First, the response time of a fully redundant class follows a simple Exponential distribution and that of the non-redundant class follows a Generalized Hyperexponential. Second, fully redundant classes are "immune" to any pain caused by other classes becoming redundant.
We also compare redundancy with other approaches for reducing latency, such as optimal probabilistic splitting of a class among servers (Opt-Split) and Join-the-Shortest-Queue (JSQ) routing of a class. We find that, in many cases, redundancy outperforms JSQ and Opt-Split with respect to overall response time, making it an attractive solution.
Keratin-17 Promotes p27KIP1 Nuclear Export and Degradation and Offers Potential Prognostic Utility
Authors: Escobar-Hoyos Luisa F. , Shah Ruchi , Roa-Peña Lucia , Vanner Elizabeth A. , Najafian Nilofar , Banach Anna , Nielsen Erik , Al-Khalil Ramsey , Akalin Ali , Talmage David , Shroyer Kenneth R. 
Published: June 2015

Abstract
Keratins that are overexpressed selectively in human carcinomas may offer diagnostic and prognostic utility. In this study, we show that high expression of keratin-17 (K17) predicts poor outcome in patients with cervical cancer, at early or late stages of disease, surpassing in accuracy either tumor staging or loss of p27KIP1 as a negative prognostic marker in this setting. We investigated the mechanistic basis for the biologic impact of K17 through loss- and gain-of-function experiments in human cervix, breast, and pancreatic cancer cells. Specifically, we determined that K17 functions as an oncoprotein by regulating the subcellular localization and degradation of p27KIP1. We found that K17 was released from intermediate filaments and translocated into the nucleus via a nuclear localization signal (NLS), specific among keratins, where it bound p27KIP1 during G1 phase of the cell cycle. p27KIP1 lacks a nuclear export signal (NES) and requires an adaptor for CRM1 binding for nuclear export. In K17, we defined and validated a leucine-rich NES that mediated CRM1 binding for export. Cervical cancer cells expressing K17 mutations in its NLS or NES signals exhibited an increase in levels of nuclear p27KIP1, whereas cells expressing wild-type K17 exhibited a depletion in total endogenous p27KIP1. In clinical specimens of cervical cancer, we confirmed that the expressions of K17 and p27KIP1 were inversely correlated, both across tumors and within individual tumors. Overall, our findings establish that K17 functions specially among keratins as an oncoprotein by controlling the ability of p27KIP1 to influence cervical cancer pathogenesis. Cancer Res; 75(17); 3650–62. ©2015 AACR.
Estrogen Metabolites Are Not Associated with Colorectal Cancer Risk in Postmenopausal Women
Authors: Falk Roni T. , Dallal Cher M. , Lacey James V. , Bauer Douglas C. , Buist Diana S.M. , Cauley Jane A. , Hue Trisha F. , LaCroix Andrea Z. , Tice Jeffrey A. , Pfeiffer Ruth M. , Xu Xia , Veenstra Timothy D. , Brinton Louise A. 
Published: June 2015

Abstract
Background: A potential protective role for estrogen in colon carcinogenesis has been suggested based on exogenous hormone use, but it is unclear from previous studies whether endogenous estrogens are related to colorectal cancer risk. These few prior studies focused on parent estrogens; none evaluated effects of estrogen metabolism in postmenopausal women.
Methods: We followed 15,595 women (ages 55–80 years) enrolled in the Breast and Bone Follow-up to the Fracture Intervention Trial (B∼FIT) who donated blood between 1992 and 1993 for cancer through December 2004. A panel of 15 estrogen metabolites (EM), including estradiol and estrone, were measured in serum from 187 colorectal cancer cases and a subcohort of 501 women not using exogenous hormones at blood draw. We examined EM individually, grouped by pathway (hydroxylation at the C-2, C-4, or C-16 position) and by ratios of the groupings using Cox proportional hazards regression models.
Results: No significant associations were seen for estrone (HRQ4 vs. Q1 = 1.15; 95% CI, 0.69–1.93; Ptrend = 0.54), estradiol (HRQ4 vs. Q1 = 0.98; 95% CI, 0.58–1.64; Ptrend &gt; 0.99), or total EM (the sum of all EM; HRQ4 vs. Q1 = 1.35; 95% CI, 0.81–2.24; Ptrend = 0.33). Most metabolites in the 2-, 4-, or 16-pathway were unrelated to risk, although a borderline trend in risk was associated with high levels of 17-epiestriol.
Conclusion: Circulating estrogens and their metabolites were generally unrelated to colorectal cancer risk in postmenopausal women.
Impact: Additional studies are needed to understand how exogenous estrogen may prevent colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(9); 1419–22. ©2015 AACR.
siRNA Lipid Nanoparticle Potently Silences Clusterin and Delays Progression When Combined with Androgen Receptor Cotargeting in Enzalutamide-Resistant Prostate Cancer
Authors: Yamamoto Yoshiaki , Lin Paulo J.C. , Beraldi Eliana , Zhang Fan , Kawai Yoshihisa , Leong Jeffrey , Katsumi Hidemasa , Fazli Ladan , Fraser Robert , Cullis Pieter R. , Gleave Martin 
Published: June 2015

Abstract
Purpose: Lipid nanoparticle (LNP) formulations facilitate tumor uptake and intracellular processing through an enhanced permeation and retention effect (EPR), and currently multiple products are undergoing clinical evaluation. Clusterin (CLU) is a cytoprotective chaperone induced by androgen receptor (AR) pathway inhibition to facilitate adaptive survival pathway signaling and treatment resistance. In our study, we investigated the efficacy of siRNA tumor delivery using LNP systems in an enzalutamide-resistant (ENZ-R) castration-resistant prostate cancer (CRPC) model.
Experimental Design: Gene silencing of a luciferase reporter gene in the PC-3M-luc stable cell line was first assessed in subcutaneous and metastatic PC-3 xenograft tumors. Upon validation, the effect of LNP siRNA targeting CLU in combination with AR antisense oligonucleotides (ASO) was assessed in ENZ-R CRPC LNCaP in vitro and in vivo models.
Results: LNP LUC-siRNA silenced luciferase expression in PC-3M-luc subcutaneous xenograft and metastatic models. LNP CLU-siRNA potently suppressed CLU and AR ASO-induced CLU and AKT and ERK phosphorylation in ENZ-R LNCaP cells in vitro, more potently inhibiting ENZ-R cell growth rates and increased apoptosis when compared with AR-ASO monotherapy. In subcutaneous ENZ-R LNCaP xenografts, combinatory treatment of LNP CLU-siRNA plus AR-ASO significantly suppressed tumor growth and serum PSA levels compared with LNP LUC-siRNA (control) and AR-ASO.
Conclusions: LNP siRNA can silence target genes in vivo and enable inhibition of traditionally non-druggable genes like CLU and other promising cotargeting approaches in ENZ-R CRPC therapeutics. Clin Cancer Res; 21(21); 4845–55. ©2015 AACR.
Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Patients With Mild Stroke in the Third International Stroke Trial-3
Authors: Khatri Pooja , Tayama Darren , Cohen Geoff , Lindley Richard I. , Wardlaw Joanna M. , Yeatts Sharon D. , Broderick Joseph P. , Sandercock Peter 
Published: June 2015

Background and Purpose—
Randomized trial evidence on the risk/benefit ratio of thrombolysis for mild stroke is limited. We sought to determine the efficacy of intravenous recombinant tissue-type plasminogen activator (IV r-tPA) in a subset of patients with mild deficit in the third International Stroke Trial (IST-3).

Methods—
IST-3 compared IV r-tPA with control within 6 hours of onset in patients for whom IV r-tPA was considered promising but unproven. Analysis was restricted to subjects randomized within 3 hours of onset with a baseline National Institutes of Health Stroke Scale ≤5, pretreatment blood pressure <185/110, and no other r-tPA exclusion criteria. We compared r-tPA and control arms for primary (Oxfordshire Handicap Score [OHS] 0–2) and secondary (ordinal OHS and OHS 0–1) outcomes at 6 months.

Results—
Among 3035 IST-3 subjects, 612 (20.2%) had an National Institutes of Health Stroke Scale ≤5; of these 106 (17.6%) met the restricted criteria. Allocation to r-tPA was associated with an increase in OHS 0 to 2 (84% r-tPA versus 65% control; adjusted odds ratio, 3.31; 95% confidence interval, 1.24–8.79) and a favorable shift in OHS distribution (adjusted odds ratio, 2.38; 95% confidence interval, 1.17–4.85). There was no significant effect of r-tPA on OHS 0 to 1 (60% versus 51%; adjusted odds ratio, 1.92; 95% confidence interval, 0.83–4.43).

Conclusions—
This post hoc analysis in a highly selected sample of IST-3 supports the rationale of A Study of the Efficacy and Safety of Activase (Alteplase) in Patients With Mild Stroke (PRISMS) trial—a randomized, phase IIIb study to evaluate IV r-tPA in mild ischemic stroke.
Drivers of the Recent Tropical Expansion in the Southern Hemisphere: Changing SSTs or Ozone Depletion?
Authors: Waugh Darryn W. , Garfinkel Chaim I. , Polvani Lorenzo M. 
Published: June 2015

Abstract
Observational evidence indicates that the southern edge of the Hadley cell (HC) has shifted southward during austral summer in recent decades. However, there is no consensus on the cause of this shift, with several studies reaching opposite conclusions as to the relative role of changes in sea surface temperatures (SSTs) and stratospheric ozone depletion in causing this shift. Here, the authors perform a meta-analysis of the extant literature on this subject and quantitatively compare the results of all published studies that have used single-forcing model integrations to isolate the role of different factors on the HC expansion during austral summer. It is shown that the weight of the evidence clearly points to stratospheric ozone depletion as the dominant driver of the tropical summertime expansion over the period in which an ozone hole was formed (1979 to late 1990s), although SST trends have contributed to trends since then. Studies that have claimed SSTs as the major driver of tropical expansion since 1979 have used prescribed ozone fields that underrepresent the observed Antarctic ozone depletion.
Kinematic GNSS Estimation of Zenith Wet Delay over a Range of Altitudes
Authors: Webb Samuel R. , Penna Nigel T. , Clarke Peter J. , Webster Stuart , Martin Ian , Bennitt Gemma V. 
Published: June 2015

AbstractAtmospheric water vapor estimates from static ground-based Global Navigation Satellite System (GNSS) receivers are now operationally assimilated into numerical weather prediction models, either as total precipitable water vapor (PWV) or zenith total delay. To extend this concept, the estimation of water vapor using kinematic GNSS has been investigated for over a decade. Previous kinematic GNSS PWV studies suggest a 2–3-mm PWV measurement agreement with radiosondes, almost commensurate with static GNSS PWV measurement accuracy, but the only comprehensive experiments undertaken have been shipborne. As a first step toward extending sea level–based studies to airborne experiments that obtain atmospheric profiles, the authors considered the kinematic GNSS estimation of atmospheric water vapor along a repeatable trajectory spanning substantial topographic relief, namely, the Snowdon Mountain Railway, United Kingdom. The atmospheric water vapor was indirectly quantified through the GNSS estimation of zenith wet delay (ZWD). Static GNSS [GPS+ Globalnaya Navigatsionnaya Sputnikovaya Sistema (GLONASS)] reference receivers were installed at the 950-m-altitude profile’s extremities, providing ZWD reference values that were interpolated to the train’s altitude, together with profiles from 100-m-resolution runs of the Met Office Unified Model. Similar GNSS ZWD accuracies to those from shipborne studies are demonstrated, namely, 12.1 mm (RMS) using double-difference relative kinematic GPS and 16.2 mm using kinematic GPS precise point positioning (PPP), but which is improved to 11.6 mm when using kinematic GPS+GLONASS PPP, commensurate with the relative kinematic GPS. The PPP solution represents a more typical airborne estimation scenario, that is, without relying on nearby GNSS reference stations.
Evaluation of Timed Up and Go Test as a tool to measure postoperative function and prediction of one year walking ability for patients with hip fracture
Authors: Nygard Heid , Matre Kjell , Fevang Jonas Meling 
Published: June 2015

Objective: To evaluate if the Timed Up and Go Test is a useful tool to measure postoperative function and to predict one-year results of rehabilitation in patients operated owing to hip fracture. Design: Prospective cohort study. Setting: The department of orthopaedic surgery at five hospitals in Norway. Patients were assessed five days postoperatively and after one year. Subjects: A total of 684 patients over 60 years with trochanteric or subtrochanteric hip fractures were included. A total of 171 (25%) patients died within a year and 373 (73% of patients still alive) attended follow-up one year after surgery. Main measures: Timed Up and Go Test and walking ability. Results: A total of 258 (38%) patients passed the postoperative Timed Up and Go Test. A total of 217 (56%) patients with a prefracture independent outdoor walking ability, passed the test. The average Timed Up and Go Test score was 71 seconds. A total of 171 (25%) patients could not rise from a chair without assistance; 8% of the patients with cognitive impairment, and 8% of those admitted from nursing homes, were able to pass the postoperative Timed Up and Go Test. The sensitivity and specificity of the Timed Up and Go Test in predicting walking ability one year after the operation were low. At one year follow-up, 38% of the patients not able to perform the postoperative Timed Up and Go Test, passed the test. A total of 81 (21%) patients did not use any walking-aid, 17 of them did not pass the postoperative Timed Up and Go Test. Conclusion: The Timed Up and Go Test performed the fifth postoperative day was not a suitable tool to assess functional mobility for the majority of the patients with hip fractures in our study. Neither was the postoperative Timed Up and Go Test a suitable tool to predict the walking ability one year after the operation.