bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benchmark Tests for Numerical Weather Forecasts on Inexact Hardware
Authors: Düben Peter D. , Palmer T. N. 
Published: July 2014

Abstract
A reduction of computational cost would allow higher resolution in numerical weather predictions within the same budget for computation. This paper investigates two approaches that promise significant savings in computational cost: the use of reduced precision hardware, which reduces floating point precision beyond the standard double- and single-precision arithmetic, and the use of stochastic processors, which allow hardware faults in a trade-off between reduced precision and savings in power consumption and computing time. Reduced precision is emulated within simulations of a spectral dynamical core of a global atmosphere model and a detailed study of the sensitivity of different parts of the model to inexact hardware is performed. Afterward, benchmark simulations were performed for which as many parts of the model as possible were put onto inexact hardware. Results show that large parts of the model could be integrated with inexact hardware at error rates that are surprisingly high or with reduced precision to only a couple of bits in the significand of floating point numbers. However, the sensitivities to inexact hardware of different parts of the model need to be respected, for example, via scale separation. In the last part of the paper, simulations with a full operational weather forecast model in single precision are presented. It is shown that differences in accuracy between the single- and double-precision forecasts are smaller than differences between ensemble members of the ensemble forecast at the resolution of the standard ensemble forecasting system. The simulations prove that the trade-off between precision and performance is a worthwhile effort, already on existing hardware.
Reducing the Risk of Hypoglycemia Associated With Intravenous Insulin
Authors: Sandler Victoria , Misiasz Meaghan R. , Jones Jocelyn , Baldwin David 
Published: July 2014

Background: Computerized insulin infusion protocols have facilitated more effective blood glucose (BG) control in intensive care units (ICUs). This is particularly important in light of the risks associated with hypoglycemia. End stage renal disease (ESRD) increases the risk of insulin-induced hypoglycemia. Methods: We evaluated BG control in 210 patients in 2 medical ICUs and in 2 surgical ICUs who were treated with a computerized insulin infusion program (CIIP). Our CIIP was programmed for a BG target of 140-180 mg/dL for medical ICU patients or 120-160 mg/dL for surgical ICU patients. In addition, we focused on BG control in the 11% of our patients with ESRD. Results: Mean BG was 147 ± 20 mg/dL for surgical ICU patients and 171 ± 26 mg/dL for medical ICU patients. Of both surgical and medical ICU patients, 17% had 1 or more BG 60-79 mg/dL, while 3% of surgical ICU and 8% of medical ICU patients had 1 or more BG < 60 mg/dL. Mean BG in ESRD patients was 147 ± 16 mg/dL similar to 152 ± 23 mg/dL in patients without ESRD. Of ESRD patients, 41% had 1 or more BG < 79 mg/dL as compared with 17.8% of non-ESRD patients ( P < .01). Conclusions: A higher BG target for medical ICU patients as compared with surgical ICU patients yielded comparably low rates of moderate or severe hypoglycemia. However, hypoglycemia among ESRD patients was more common compared to non-ESRD patients, suggesting a need for a higher BG target specific to ESRD patients.
ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells
Authors: Guedan Sonia , Chen Xi , Madar Aviv , Carpenito Carmine , McGettigan Shannon E. , Frigault Matthew J. , Lee Jihyun , Posey Avery D. , Scholler John , Scholler Nathalie , Bonneau Richard , June Carl H. 
Published: July 2014

Key Points
ICOS-based CARs program bipolar TH17/TH1 cells with augmented effector function and in vivo persistence. The expression of selected CAR endodomains can program T cells for their subsequent differentiation fates and effector functions.
VEGFR-3 and CXCR4 as predictive markers for treatment with fluorouracil, leucovorin plus either oxaliplatin or cisplatin in patients with advanced esophagogastric cancer: a comparative study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: Thomaidis Thomas , Maderer Annett , Al-Batran Salah-Eddin , Kany Janis , Pauligk Claudia , Steinmetz Kristina , Schad Arno , Hofheinz Ralf , Schmalenberg Harald , Homann Nils , Galle Peter Robert , Moehler Markus 
Published: July 2014

Abstract

Background
Combination of fluoropyrimidines and a platinum derivative are currently standards for systemic chemotherapy in advanced adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Nevertheless, individual likelihood for response to these therapeutic regimes remains uncertain. Even more, no predictive markers are available to determine which patients may benefit more from oxaliplatin versus cisplatin or vice versa. The new invasion and stem cell markers VEGFR-3 and CXCR4 have been linked prognostically with more aggressive esophagogastric cancer types. Thus, we aimed to assess correlations of VEGFR-3 and CXCR4 expression levels with clinical outcome in a randomized phase III study of patients with oxaliplatin/leucovorin/5-FU (FLO) versus cisplatin/leucovorin/5-FU (FLP).

Methods
The patients data examined in this study (n = 72) were from the collective of the FLO vs. FLP phase III AIO trial. Tumour tissues were stained via immunohistochemistry for VEGFR-3 and CXCR4 expression and results were evaluated by two independent, blinded investigators.
Outcome parameter: Survival analysis was calculated for patients receiving FLO vs. FLP in relation to VEGFR-3 and CXCR4 expression.

Results
54% and 36% of the examined tumour tissues showed strong positive expression of VEGFR-3 and CXCR4 respectively. No superiority of each regime was detected in terms of overall survival (OS) in the whole population. Patients with strong expression of CXCR4 on their tumour tissues profited more in terms of OS under the treatment of FLP (mOS: 28 vs 15 months, p = 0.05 respectively). Patients with negative VEGFR-3 and CXCR4 expression had a trend to live longer when FLO regime was applied (mOS: 22 vs. 9 months, p = 0.099 and 20 vs. 10 months, p = 0.073 respectively). In an exploratory analysis of patients older than 60 years at diagnosis, we observed a significant benefit in overall survival for VEGFR-3 and CXCR4-positive patients when treated with FLP (p = 0.002, p = 0.021 respectively).

Conclusions
CXCR4 positive patients profited in terms of OS from FLP, whereas FLO proved to be more effective in CXCR4 and VEGFR-3 negative patients. Our results suggest, despite the limited size of the study, a predictive value of these biomarkers concerning chemotherapy with FLP or FLO in advanced esophagogastric cancer.
Yoga management of breast cancer-related lymphoedema: a randomised controlled pilot-trial
Authors: Loudon Annette , Barnett Tony , Piller Neil , Immink Maarten A , Williams Andrew D 
Published: July 2014

Abstract

Background
Secondary arm lymphoedema continues to affect at least 20% of women after treatment for breast cancer requiring lifelong professional treatment and self-management. The holistic practice of yoga may offer benefits as an adjunct self-management option. The aim of this small pilot trial was to gain preliminary data to determine the effect of yoga on women with stage one breast cancer-related lymphoedema (BCRL). This paper reports the results for the primary and secondary outcomes.

Methods
Participants were randomised, after baseline testing, to receive either an 8-week yoga intervention (n = 15), consisting of a weekly 90-minute teacher-led class and a 40-minute daily session delivered by DVD, or to a usual care wait-listed control group (n = 13). Primary outcome measures were: arm volume of lymphoedema measured by circumference and extra-cellular fluid measured by bioimpedance spectroscopy. Secondary outcome measures were: tissue induration measured by tonometry; levels of sensations, pain, fatigue, and their limiting effects all measured by a visual analogue scale (VAS) and quality of life based on the Lymphoedema Quality of Life Tool (LYMQOL). Measurements were conducted at baseline, week 8 (post-intervention) and week 12 (four weeks after cessation of the intervention).

Results
At week 8, the intervention group had a greater decrease in tissue induration of the affected upper arm compared to the control group (p = 0.050), as well as a greater reduction in the symptom sub-scale for QOL (p = 0.038). There was no difference in arm volume of lymphoedema or extra-cellular fluid between groups at week 8; however, at week 12, arm volume increased more for the intervention group than the control group (p = 0.032).

Conclusions
An 8-week yoga intervention reduced tissue induration of the affected upper arm and decreased the QOL sub-scale of symptoms. Arm volume of lymphoedema and extra-cellular fluid did not increase. These benefits did not last on cessation of the intervention when arm volume of lymphoedema increased. Further research trials with a longer duration, higher levels of lymphoedema and larger numbers are warranted before definitive conclusions can be made.
Biometric quality: a review of fingerprint, iris, and face
Authors: Bharadwaj Samarth , Vatsa Mayank , Singh Richa 
Published: July 2014

AbstractBiometric systems encounter variability in data that influence capture, treatment, and u-sage of a biometric sample. It is imperative to first analyze the data and incorporate this understanding within the recognition system, making assessment ofbiometric qualityan important aspect of biometrics. Though several interpretations and definitions of quality exist, sometimes of a conflicting nature, a holistic definition of quality is indistinct. This paper presents a survey of different concepts and interpretations of biometric quality so that a clear picture of the current state and future directions can be presented. Several factors that cause different types of degradations of biometric samples, including image features that attribute to the effects of these degradations, are discussed. Evaluation schemes are presented to test the performance of quality metrics for various applications. A survey of the features, strengths, and limitations of existing quality assessment techniques in fingerprint, iris, and face biometric are also presented. Finally, a representative set of quality metrics from these three modalities are evaluated on a multimodal database consisting of 2D images, to understand their behavior with respect to match scores obtained from the state-of-the-art recognition systems. The analysis of the characteristic function of quality and match scores shows that a careful selection of complimentary set of quality metrics can provide more benefit to various applications of biometric quality.
Clinical significance of epithelial‐mesenchymal transition
Authors: Steinestel Konrad , Eder Stefan , Schrader Andres Jan , Steinestel Julie 
Published: July 2014

AbstractThe concept of epithelial‐mesenchymal transition (EMT), a process where cells change their epithelial towards a mesenchymal phenotype, has gained overwhelming attention especially in the cancer research community. Thousands of scientific reports investigated changes in gene, mRNA and protein expression compatible with EMT and their possible correlation with tumor invasion, metastatic spread or patient prognosis; however, up to now, a proof of clinical significance of the concept is still missing. This review, with a main focus on the role of EMT in tumors, will summarize the basic molecular events underlying EMT including the signaling pathways capable of its induction as well as changes in EMT‐associated protein expression and will very briefly touch the role of microRNAs in EMT. We then outline protein markers that are used most frequently for the assessment of EMT in research and diagnostic evaluation of tumor specimens and depict the link between EMT, a cancer stem cell (CSC) phenotype and resistance to conventional antineoplastic therapies. Furthermore, we evaluate a possible correlation between EMT marker expression and patient prognosis as well as current therapeutic concepts targeting the EMT process to slow down or prevent metastatic spread of malignant tumors.
4 weeks of high-intensity interval training does not alter the exercise-induced growth hormone response in sedentary men
Authors: Sasaki Hiroto , Morishima Takuma , Hasegawa Yuta , Mori Ayaka , Ijichi Toshiaki , Kurihara Toshiyuki , Goto Kazushige 
Published: July 2014

SummaryThis study determined the effects of high-intensity interval training on the exercise-induced growth hormone (GH) responses, whole body and regional fat content. Twenty-four sedentary males were randomized to either a high-intensity interval training (HIT) group or a low-intensity continuous training (LT) group. The HIT group performed intermittent exercises at 85% ofV˙O2max, whereas the LT group performed continuous exercise for 22 min at 45% ofV˙O2max. Before and after 4 weeks of training, hormonal and metabolic responses to acute exercise were determined. Acute exercise significantly increased GH concentrations in both groups (p < 0.05). However, the responses did not change after training period in either group. Furthermore, the training did not significantly affect intramyocellular or intrahepatic lipid content in either group. The present study indicates that 4 weeks of high-intensity interval training does not alter the exercise-induced GH responses, whole body fat mass or intramyocellular and intrahepatic lipid content in sedentary males.
Association of MAPT haplotypes with Alzheimer’s disease risk and MAPT brain gene expression levels
Authors: Allen Mariet , Kachadoorian Michaela , Quicksall Zachary , Zou Fanggeng , Chai High Seng , Younkin Curtis , Crook Julia E , Pankratz V Shane , Carrasquillo Minerva M , Krishnan Siddharth , Nguyen Thuy , Ma Li , Malphrus Kimberly , Lincoln Sarah , Bisceglio Gina , Kolbert Christopher P , Jen Jin , Mukherjee Shubhabrata , Kauwe John K , Crane Paul K , Haines Jonathan L , Mayeux Richard , Pericak-Vance Margaret A , Farrer Lindsay A , Schellenberg Gerard D ,   Alzheimer’s Disease Genetics Consortium (ADGC), Parisi Joseph E , Petersen Ronald C , Graff-Radford Neill R , Dickson Dennis W , Younkin Steven G , Ertekin-Taner Nilüfer 
Published: July 2014

Abstract
Introduction
MAPT encodes for tau, the predominant component of neurofibrillary tangles that are neuropathological hallmarks of Alzheimer’s disease (AD). Genetic association of MAPT variants with late-onset AD (LOAD) risk has been inconsistent, although insufficient power and incomplete assessment of MAPT haplotypes may account for this.

Methods
We examined the association of MAPT haplotypes with LOAD risk in more than 20,000 subjects (n-cases = 9,814, n-controls = 11,550) from Mayo Clinic (n-cases = 2,052, n-controls = 3,406) and the Alzheimer’s Disease Genetics Consortium (ADGC, n-cases = 7,762, n-controls = 8,144). We also assessed associations with brain MAPT gene expression levels measured in the cerebellum (n = 197) and temporal cortex (n = 202) of LOAD subjects. Six single nucleotide polymorphisms (SNPs) which tag MAPT haplotypes with frequencies greater than 1% were evaluated.

Results
H2-haplotype tagging rs8070723-G allele associated with reduced risk of LOAD (odds ratio, OR = 0.90, 95% confidence interval, CI = 0.85-0.95, p = 5.2E-05) with consistent results in the Mayo (OR = 0.81, p = 7.0E-04) and ADGC (OR = 0.89, p = 1.26E-04) cohorts. rs3785883-A allele was also nominally significantly associated with LOAD risk (OR = 1.06, 95% CI = 1.01-1.13, p = 0.034). Haplotype analysis revealed significant global association with LOAD risk in the combined cohort (p = 0.033), with significant association of the H2 haplotype with reduced risk of LOAD as expected (p = 1.53E-04) and suggestive association with additional haplotypes. MAPT SNPs and haplotypes also associated with brain MAPT levels in the cerebellum and temporal cortex of AD subjects with the strongest associations observed for the H2 haplotype and reduced brain MAPT levels (β = -0.16 to -0.20, p = 1.0E-03 to 3.0E-03).

Conclusions
These results confirm the previously reported MAPT H2 associations with LOAD risk in two large series, that this haplotype has the strongest effect on brain MAPT expression amongst those tested and identify additional haplotypes with suggestive associations, which require replication in independent series. These biologically congruent results provide compelling evidence to screen the MAPT region for regulatory variants which confer LOAD risk by influencing its brain gene expression.
Chronic Toll-like receptor 4 stimulation in skin induces inflammation, macrophage activation, transforming growth factor beta signature gene expression, and fibrosis
Authors: Stifano Giuseppina , Affandi Alsya J , Mathes Allison L , Rice Lisa M , Nakerakanti Sashidhar , Nazari Banafsheh , Lee Jungeun , Christmann Romy B , Lafyatis Robert 
Published: July 2014

Abstract
Introduction
The crucial role of innate immunity in the pathogenesis of systemic sclerosis (SSc) is well established, and in the past few years the hypothesis that Toll-like receptor 4 (TLR4) activation induced by endogenous ligands is involved in fibrogenesis has been supported by several studies on skin, liver, and kidney fibrosis. These findings suggest that TLR4 activation can enhance transforming growth factor beta (TGF-β) signaling, providing a potential mechanism for TLR4/Myeloid differentiation factor 88 (MyD88)-dependent fibrosis.

Methods
The expression of TLR4, CD14 and MD2 genes was analyzed by real-time polymerase chain reaction from skin biopsies of 24 patients with diffuse cutaneous SSc. In order to investigate the effects of the chronic skin exposure to endotoxin (Lipopolysaccharide (LPS)) in vivo we examined the expression of inflammation, TGF-β signaling and cellular markers genes by nanostring. We also identified cellular subsets by immunohistochemistry and flow cytometry.

Results
We found that TLR4 and its co-receptors, MD2 and CD14, are over-expressed in lesional skin from patients with diffuse cutaneous SSc, and correlate significantly with progressive or regressive skin disease as assessed by the Delta Modified Rodnan Skin Score. In vivo, a model of chronic dermal LPS exposure showed overexpression of proinflammatory chemokines, recruitment and activation of macrophages, and upregulation of TGF-β signature genes.

Conclusions
We delineated the role of MyD88 as necessary for the induction not only for the early phase of inflammation, but also for pro-fibrotic gene expression via activation of macrophages. Chronic LPS exposure might be a model of early stage of SSc when inflammation and macrophage activation are important pathological features of the disease, supporting a role for innate immune activation in SSc skin fibrosis.
Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer
Authors: Jovanović Bojana , Beeler J Scott , Pickup Michael W , Chytil Anna , Gorska Agnieszka E , Ashby William J , Lehmann Brian D , Zijlstra Andries , Pietenpol Jennifer A , Moses Harold L 
Published: July 2014

Abstract
Introduction
There is a major need to better understand the molecular basis of triple negative breast cancer (TNBC) in order to develop effective therapeutic strategies. Using gene expression data from 587 TNBC patients we previously identified six subtypes of the disease, among which a mesenchymal-stem like (MSL) subtype. The MSL subtype has significantly higher expression of the transforming growth factor beta (TGF-β) pathway-associated genes relative to other subtypes, including the TGF-β receptor type III (TβRIII). We hypothesize that TβRIII is tumor promoter in mesenchymal-stem like TNBC cells.

Methods
Representative MSL cell lines SUM159, MDA-MB-231 and MDA-MB-157 were used to study the roles of TβRIII in the MSL subtype. We stably expressed short hairpin RNAs specific to TβRIII (TβRIII-KD). These cells were then used for xenograft tumor studies in vivo; and migration, invasion, proliferation and three dimensional culture studies in vitro. Furthermore, we utilized human gene expression datasets to examine TβRIII expression patterns across all TNBC subtypes.

Results
TβRIII was the most differentially expressed TGF-β signaling gene in the MSL subtype. Silencing TβRIII expression in MSL cell lines significantly decreased cell motility and invasion. In addition, when TβRIII-KD cells were grown in a three dimensional (3D) culture system or nude mice, there was a loss of invasive protrusions and a significant decrease in xenograft tumor growth, respectively. In pursuit of the mechanistic underpinnings for the observed TβRIII-dependent phenotypes, we discovered that integrin-α2 was expressed at higher level in MSL cells after TβRIII-KD. Stable knockdown of integrin-α2 in TβRIII-KD MSL cells rescued the ability of the MSL cells to migrate and invade at the same level as MSL control cells.

Conclusions
We have found that TβRIII is required for migration and invasion in vitro and xenograft growth in vivo. We also show that TβRIII-KD elevates expression of integrin-α2, which is required for the reduced migration and invasion, as determined by siRNA knockdown studies of both TβRIII and integrin-α2. Overall, our results indicate a potential mechanism in which TβRIII modulates integrin-α2 expression to effect MSL cell migration, invasion, and tumorigenicity.
Plasma and urine neutrophil gelatinase-associated lipocalin in the diagnosis of new onset acute kidney injury in critically ill patients
Authors: Matsa Ramprasad , Ashley Emma , Sharma Vivek , Walden Andrew P , Keating Liza 
Published: July 2014

Abstract
Introduction
Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a useful early diagnostic biomarker of acute kidney injury (AKI) where the timing of the insult is certain. However, NGAL is not well validated in adult critical care practice because of indeterminate timing of injury. Therefore, we sought to establish the predictive ability of both urine and plasma NGAL to detect AKI in ICU patients.

Method
This prospective observational study was performed in a busy large district general hospital mixed surgical-medical ICU in Reading, UK. Consecutive adult admissions to the ICU, with absence of chronic kidney disease, renal transplant or AKI as defined by RIFLE criteria were included. Blood and urine specimens were collected at admission and every 24 hours until 72 hours and tested for NGAL. The purpose of the study was to assess whether urinary NGAL (uNGAL) or plasma NGAL (pNGAL) can predict the occurrence of AKI at an earlier point of time than the conventional markers, that is creatinine and urine output as is used in RIFLE criteria.

Results
Over a 12-month period, 194 patients were enrolled. In total, 59 (30.4%) patients developed AKI. The admission pNGAL and uNGAL were significantly higher in the patients who developed AKI compared to the non-AKI patients (436 ng/mL (240, 797) versus 168 ng/mL (121.3, 274.3) P <0.001 and 342 ng/mL (61.5, 1,280) versus 34.5 ng/mL (11.5, 107.75) P <0.001 respectively). Hospital mortality was higher in the AKI group (17% versus 4%). Plasma NGAL performed fairly on admission (AUROC 0.77) and thereafter performance improved at 24 and 48 hours (AUROC 0.88 and 0.87) following ICU admission. Urine NGAL had a fair predictive value on admission (AUROC 0.79) and at 24 hours (AUROC 0.78) and was good at 48 hours (AUROC 0.82).

Conclusions
In critically ill patients without pre-existing kidney disease, both pNGAL and uNGAL measured at admission can predict AKI (defined by RIFLE criteria) occurrence up to 72 hours post-ICU admission and their performance (AUROC) was fair. The accuracy of NGAL appeared to improve slightly as patients progressed through their ICU stay. Serial measurements of NGAL (both pNGAL and uNGAL) may be of added value in an ICU setting to predict the occurrence of AKI.