bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sites of disease as predictors of outcome in metastatic renal cell carcinoma patients treated with first-line sunitinib or sorafenib
Authors: Grassi Paolo , Verzoni Elena , Porcu Luca , Iacovelli Roberto , de Braud Filippo , Procopio Giuseppe 
Published: February 2015

Background: This study investigated whether the effectiveness of first-line tyrosine-kinase inhibitors was associated with sites of disease in patients with metastatic renal cell carcinoma (mRCC). Methods: A retrospective cohort of consecutive mRCC patients receiving first-line sorafenib (SO) or sunitinib (SU) was analyzed. Results: In total, 203 patients received SO and 99 SU. In patients with liver metastasis, SU was associated with a 18% higher risk of time-to-treatment failure (TTF), and a 39% higher risk of death than SO: conversely, patients without liver metastases who received SU showed a 46% decreased risk of TTF and 62% decreased risk of death. Conclusions: mRCC patients with liver metastases treated with first-line SO showed a better outcome compared with SU, while mRCC patients without liver metastases treated with first-line SU showed a better outcome compared with SO.
Admission From Nursing Home Residence Increases Acute Mortality After Hip Fractures
Authors: van Dijk Pim A. D. , Bot Arjan G. J. , Neuhaus Valentin , Menendez Mariano E. , Vrahas Mark S. , Ring David 
Published: February 2015

Background: Little is known about the effect of preinjury residence on inpatient mortality following hip fracture. This study addressed whether (1) admission from a nursing home residence and (2) admission from another hospital were associated with higher inpatient mortality after a hip fracture. Methods: Using the National Hospital Discharge Survey database, we analyzed an estimated 2 124 388 hip fractures discharges, from 2001 to 2007. Multivariable logistic regression analysis was performed to identify whether admission from a nursing home and admission from another hospital were independent risk factors for inpatient mortality. Our primary null hypothesis is that there is no difference in inpatient mortality rates after hip fracture in patients admitted from a nursing home, compared to other forms of admission. The secondary null hypothesis is that there is no difference in inpatient mortality after hip fracture in patients whose source of admission was another hospital, compared to other sources of admission. Results: Almost 4% of the patients were admitted from a nursing home and 6% from another hospital. The mean age was 79 years and 71% were women. The majority of patients were treated with internal fixation. Admission from a nursing home residence (odds ratio [OR] of 2.1, confidence interval [CI] 1.9-2.3) and prior hospital stay (OR 3.4, CI 3.2-3.7) were associated with a higher risk of inpatient mortality after accounting for other comorbidities and type of treatment. Conclusions: Patients transferred to an acute care hospital from a long-term care facility or another acute care hospital are at particularly high risk of inpatient death. This subset of patients should be considered separately from patients admitted from other sources. Level of Evidence: Prognostic level II.
Functions of BET proteins in erythroid gene expression
Authors: Stonestrom Aaron J. , Hsu Sarah C. , Jahn Kristen S. , Huang Peng , Keller Cheryl A. , Giardine Belinda M. , Kadauke Stephan , Campbell Amy E. , Evans Perry , Hardison Ross C. , Blobel Gerd A. 
Published: February 2015

Key Points
BETs promote GATA1 chromatin occupancy and subsequently activate transcription; they are generally not required for repression. BRD2 and BRD4 are essential for full GATA1 activity whereas BRD3 function overlaps with BRD2.
Human metabolic response to systemic inflammation: assessment of the concordance between experimental endotoxemia and clinical cases of sepsis/SIRS
Authors: Kamisoglu Kubra , Haimovich Beatrice , Calvano Steve E , Coyle Susette M , Corbett Siobhan A , Langley Raymond J , Kingsmore Stephen F , Androulakis Ioannis P 
Published: February 2015

AbstractIntroductionTwo recent, independent, studies conducted novel metabolomics analyses relevant to human sepsis progression; one was a human model of endotoxin (lipopolysaccharide (LPS)) challenge (experimental endotoxemia) and the other was community acquired pneumonia and sepsis outcome diagnostic study (CAPSOD). The purpose of the present study was to assess the concordance of metabolic responses to LPS and community-acquired sepsis.MethodsWe tested the hypothesis that the patterns of metabolic response elicited by endotoxin would agree with those in clinical sepsis. Alterations in the plasma metabolome of the subjects challenged with LPS were compared with those of sepsis patients who had been stratified into two groups: sepsis patients with confirmed infection and non-infected patients who exhibited systemic inflammatory response syndrome (SIRS) criteria. Common metabolites between endotoxemia and both these groups were individually identified, together with their direction of change and functional classifications.ResultsResponse to endotoxemia at the metabolome level elicited characteristics that agree well with those observed in sepsis patients despite the high degree of variability in the response of these patients. Moreover, some distinct features of SIRS have been identified. Upon stratification of sepsis patients based on 28-day survival, the direction of change in 21 of 23 metabolites was the same in endotoxemia and sepsis survival groups.ConclusionsThe observed concordance in plasma metabolomes of LPS-treated subjects and sepsis survivors strengthens the relevance of endotoxemia to clinical research as a physiological model of community-acquired sepsis, and gives valuable insights into the metabolic changes that constitute a homeostatic response. Furthermore, recapitulation of metabolic differences between sepsis non-survivors and survivors in LPS-treated subjects can enable further research on the development and assessment of rational clinical therapies to prevent sepsis mortality. Compared with earlier studies which focused exclusively on comparing transcriptional dynamics, the distinct metabolomic responses to systemic inflammation with or without confirmed infection, suggest that the metabolome is much better at differentiating these pathophysiologies. Finally, the metabolic changes in the recovering patients shift towards the LPS-induced response pattern strengthening the notion that the metabolic, as well as transcriptional responses, characteristic to the endotoxemia model represent necessary and “healthy” responses to infectious stimuli.
DGEclust: differential expression analysis of clustered count data
Authors: Vavoulis Dimitrios V , Francescatto Margherita , Heutink Peter , Gough Julian 
Published: February 2015

AbstractWe present a statistical methodology, DGEclust, for differential expression analysis of digital expression data. Our method treats differential expression as a form of clustering, thus unifying these two concepts. Furthermore, it simultaneously addresses the problem of how many clusters are supported by the data and uncertainty in parameter estimation. DGEclust successfully identifies differentially expressed genes under a number of different scenarios, maintaining a low error rate and an excellent control of its false discovery rate with reasonable computational requirements. It is formulated to perform particularly well on low-replicated data and be applicable to multi-group data. DGEclust is available at http://dvav.github.io/dgeclust/.
The three-body problem of therapy with induced pluripotent stem cells
Authors: Tolar Jakub , McGrath John A 
Published: February 2015

AbstractRegenerative medicine has a three-body problem: alignment of the dynamics of the genome, stem cell and patient. Focusing on the rare inherited fragile skin disorder epidermolysis bullosa, three recent innovative studies have used induced pluripotent stem cells and gene correction, revertant mosaicism or genome editing to advance the prospects of better cell-based therapeutics to restore skin structure and function for epidermolysis bullosa and potentially other inherited diseases.
Regulatory T cell-deficient scurfy mice develop systemic autoimmune features resembling lupus-like disease
Authors: Hadaschik Eva N , Wei Xiaoying , Leiss Harald , Heckmann Britta , Niederreiter Birgit , Steiner Günter , Ulrich Walter , Enk Alexander H , Smolen Josef S , Stummvoll Georg H 
Published: February 2015

Abstract
Introduction
Scurfy mice are deficient in regulatory T cells (Tregs), develop a severe, generalized autoimmune disorder that can affect almost every organ and die at an early age. Some of these manifestations resemble those found in systemic lupus erythematosus (SLE). In addition, active SLE is associated with low Treg numbers and reduced Treg function, but direct evidence for a central role of Treg malfunction in the pathophysiology of lupus-like manifestations is still missing. In the present study, we characterize the multiorgan pathology, autoantibody profile and blood count abnormalities in scurfy mice and show their close resemblances to lupus-like disease.

Methods
Scurfy mice have dysfunctional Tregs due to a genetic defect in the transcription factor Forkhead box protein 3 (Foxp3). We analyzed skin, joints, lung and kidneys of scurfy mice and wild-type (WT) controls by conventional histology and immunofluorescence (IF) performed hematological workups and tested for autoantibodies by IF, immunoblotting and enzyme-linked immunosorbent assay. We also analyzed the intestines, liver, spleen and heart, but did not analyze all organs known to be affected in scurfy mice (such as the testicle, the accessory reproductive structures, the pancreas or the eyes). We transferred CD4+ T cells of scurfy or WT mice into T cell-deficient B6/nude mice.

Results
We confirm previous reports that scurfy mice spontaneously develop severe pneumonitis and hematological abnormalities similar to those in SLE. We show that scurfy mice (but not controls) exhibited additional features of SLE: severe interface dermatitis, arthritis, mesangioproliferative glomerulonephritis and high titers of anti-nuclear antibodies, anti-double-stranded DNA antibodies, anti-histone antibodies and anti-Smith antibodies. Transfer of scurfy CD4+ T cells (but not of WT cells) induced autoantibodies and inflammation of lung, skin and kidneys in T cell-deficient B6/nude mice.

Conclusion
Our observations support the hypothesis that lupus-like autoimmune features develop in the absence of functional Tregs.
Prevalence, incidence and characteristics of the metabolic syndrome (MetS) in a cohort of Mexican Mestizo early rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs: the complex relationship between MetS and disease activity
Authors: Parra-Salcedo Federico , Contreras-Yáñez Irazú , Elías-López Daniel , Aguilar-Salinas Carlos A , Pascual-Ramos Virginia 
Published: February 2015

Abstract
Introduction
A higher prevalence of metabolic syndrome (MetS) has been described in rheumatoid arthritis (RA), along with an association with disease activity. Objectives were to describe prevalence of MetS at RA diagnosis in a cohort of Mexican Mestizo early RA patients, and to define a causal association between MetS and disease activity.

Methods
The study population was a prospective cohort. At baseline and at fixed 6-months-intervals, patients had medical evaluations, fasting serum glucose, triglycerides, high-density lipoprotein cholesterol and acute reactant-phase determinations. MetS was defined according to international criteria and body mass index (BMI) ≥30 kg/m2 was used as a surrogate of the waist circumference. The study was approved by the internal review board. Appropriated statistics and Cox regression analysis were used. All statistical tests were two-sided and evaluated at the 0.05 significance level.

Results
Up to March 2014, data from 160 patients were analyzed. At baseline, they were more frequently middle-aged females and had moderate to high disease activity. Prevalence of MetS varied from 11.3% to 17.5% in patients and was lower to that from matched controls (versus 26.3% to 30%, P ≤0.01).
Up to last follow-up, 39 patients (34.5%) developed incidental MetS. In the Cox regression analysis, cumulative disease activity score (DAS) 28 (odds ratio (OR): 1.81, 95% confidence interval (CI): 1.346 to 2.433, P = 0.000) and baseline BMI (OR: 1.13, 96% CI: 1.035 to 1.236, P = 0.007) were the only predictors for incidental MetS.
RA patients with incidental MetS accumulated more disease activity and had less frequent remission than their counterparts. Logistic regression analysis showed that incidental MetS (OR: 0.2, 95% CI: 0.01 to 0.99, P = 0.052) and baseline DAS28 (OR: 0.4, 95% CI: 0.2 to 0.9, P = 0.02) were the only predictors for achieving or maintaining sustained (≥6 months) remission.

Conclusions
MetS prevalence in a cohort of early RA patients was lower than that from matched controls. Cumulative disease activity and higher BMI were risk factors for incidental Mets; higher baseline disease activity and incidental MetS prevented sustained remission. In addition to disease activity, MetS needs to be controlled to impact disease outcomes.
Identification and characterization of epithelial cells derived from human ovarian follicular fluid
Authors: Lai Dongmei , Xu Minhua , Zhang Qiuwan , Chen Yifei , Li Ting , Wang Qian , Gao Yimeng , Wei Chunsheng 
Published: February 2015

Abstract
Introduction
Follicular fluid is important for follicular development and oocyte maturation. Evidence suggests that follicular fluid is not only rich in proteins but cells. Besides oocytes, the follicular fluid contains granulosa, thecal, and ovarian surface epithelial cells, and both granulosa and thecal cells are well-characterized. However, epithelial cells in follicular fluid are poorly studied. This study aims to isolate and characterize in vitro epithelial cells that originate from human ovarian follicular fluid retrieved in the assisted fertilization program.

Methods
Follicular fluid samples were collected from 20 women in the assisted reproduction program. Epithelial cells were characterized by flow cytometry assay, immunofluorescence staining, real-time PCR, and time lapse photography.

Results
Epithelial cell cultures were established from 18 samples. A small population of epithelial cells expresses germ-line stem cell markers, such as octamer-binding transcription factor 4 (OCT4), NANOG, and DEAD box polypeptide 4 (DDX4). In the epithelial cell culture system, oocyte-like cells formed spontaneously in vitro and expressed the following transcription markers: deleted in azoospermia-like (DAZL), developmental pluripotency associated protein 3 stella-related protein (STELLA), zona pellucida gene family C (ZPC), Syntaptonemal complex protein (SCP), and growth and differentiation factor 9 (GDF9). Some of the oocyte-like cells developed a zona pellucida-like structure. Both the symmetric and asymmetric division split of epithelial cells and early developing oocytes were observed using time lapse photography. Cell colonies were formed during epithelial culturing, which maintained and proliferated in an undifferentiated way on the feeder layer and expressed some pluripotency markers. These colonies differentiated in vitro into various somatic cell types in all three germ layers, but did not form teratoma when injected into immunodeficient mice. Furthermore, these epithelial cells could be differentiated directly to functional hepatocyte-like cells, which do not exist in ovarian tissues.

Conclusions
The epithelial cells derived from follicular fluid are a potential stem cell source with a pluripotent/multipotent character for safe application in oogenesis and regenerative medicine.
Analysis of group paging with pre-backoff
Authors: Harwahyu Ruki , Wang Xian , Sari Riri Fitri , Cheng Ray-Guang 
Published: February 2015

Abstract
Group paging can simultaneously activate hundreds of user equipments (UEs) using a single paging message. Upon receiving the group paging message, all UEs should immediately transmit their paging response messages through the random access channels (RACHs). Simultaneous channel access from a huge group of UEs may result in severe collisions of the RACHs during a very short period of time. In this paper, we propose a pre-backoff method to reduce the collision probability of random access requests. We develop an analytical model to investigate the performance and optimize the setting of the pre-backoff method. The accuracy of the analytical model is verified through computer simulation. Results show that the proposed pre-backoff method can effectively enhance the performance of group paging.
Non-addictive opium alkaloids selectively induce apoptosis in cancer cells compared to normal cells
Authors: Afzali Monireh , Ghaeli Padideh , Khanavi Mahnaz , Parsa Maliheh , Montazeri Hamed , Ghahremani Mohammad Hossein , Ostad Seyed Nasser 
Published: February 2015

Abstract

Background
Cytotoxic effects of some of the members of papaveraceae family have been reported in Iranian folk medicine. Recent reports has indicated that alkaloids fraction of opium may be responsible for its cytotoxic effect; however, the mechanism of this effect is not fully understood. This study has been designed to investigate the selective cytotoxic, genotoxic and also apoptosis induction effects of noscapine, papaverine and narceine, three non-addictable opium alkaloids, on HT29, T47D and HT1080 cancer cell lines. Mouse NIH3T3 cell line was chosen to present non-cancerous cells and Doxorubicin was selected as the positive control.

Methods
Cells were treated by different concentrations of Noscapine, Papaverine, Narceine and doxorubicin; viability was assessed by MTT assay. The genotoxicity and apoptosis induction were tested with comet assay and Annexin-V affinity when the concentration of each these drugs is less than its IC50. In addition, the DNA damage and caspase activity of the T47D cells were examined and the results were compared.

Results
This study noted the cytotoxicity and genotoxicity of noscapine and papaverine, specifically on cancerous cell lines. Furthermore, papaverine induces apoptosis in all studied cancer cell lines and noscapine showed this effect in T47D and HT29 cells but not in NIH-3 T3 cells as noncancerous cell line. narceine also showed genototoxicity in the studied cell lines at its IC50 concentration.

Conclusions
This experiment suggests that noscapine and papaverine may be of use in cancer treatment due to their specific cytotoxicity and genotoxicity. However, further in vivo studies are needed to confirm its usefulness in cancer treatment.
Failure time regression with continuous informative auxiliary covariates
Authors: Ghosh Lipika , Jiang Jiancheng , Sun Yanqing , Zhou Haibo 
Published: February 2015

AbstractIn this paper we use Cox’s regression model to fit failure time data with continuous informative auxiliary variables in the presence of a validation subsample. We first estimate the induced relative risk function by kernel smoothing based on the validation subsample, and then improve the estimation by utilizing the information on the incomplete observations from non-validation subsample and the auxiliary observations from the primary sample. Asymptotic normality of the proposed estimator is derived. The proposed method allows one to robustly model the failure time data with an informative multivariate auxiliary covariate. Comparison of the proposed approach with several existing methods is made via simulations. Two real datasets are analyzed to illustrate the proposed method.Mathematics Subject Classification (MSC):62G07, 62G20
Television Advertising and Online Shopping
Authors: Liaukonyte Jura , Teixeira Thales , Wilbur Kenneth C. 
Published: February 2015

Media multitasking competes with television advertising for consumers’ attention, but may also facilitate immediate and measurable response to some advertisements. This paper explores whether and how television advertising influences online shopping. We construct a massive data set spanning $3.4 billion in spending by 20 brands, measures of brands’ website traffic and transactions, and ad content measures for 1,224 commercials. We use a quasi-experimental design to estimate whether and how TV advertising influences changes in online shopping within two-minute pre/post windows of time. We use nonadvertising competitors’ online shopping in a difference-in-differences approach to measure the same effects in two-hour windows around the time of the ad. The findings indicate that television advertising does influence online shopping and that advertising content plays a key role. Action-focus content increases direct website traffic and sales. Information-focus and emotion-focus ad content actually reduce website traffic while simultaneously increasing purchases, with a positive net effect on sales for most brands. These results imply that brands seeking to attract multitaskers’ attention and dollars must select their advertising copy carefully. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mksc.2014.0899 .
Does Corporate Social Responsibility Lead to Superior Financial Performance? A Regression Discontinuity Approach
Authors: Flammer Caroline 
Published: February 2015

This study examines the effect of shareholder proposals related to corporate social responsibility (CSR) on financial performance. Specifically, I focus on CSR proposals that pass or fail by a small margin of votes. The passage of such “close call” proposals is akin to a random assignment of CSR to companies and hence provides a quasi-experiment to study the effect of CSR on performance. I find that the adoption of close call CSR proposals leads to positive announcement returns and superior accounting performance, implying that these proposals are value enhancing. When I examine the channels through which companies benefit from CSR, I find that labor productivity and sales growth increase after the vote. Finally, I document that close call CSR proposals differ from non-close proposals along several dimensions. Accordingly, although my results imply that adopting close call CSR proposals is beneficial to companies, they do not necessarily imply that CSR proposals are beneficial in general.Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2014.2038 .This paper was accepted by Wei Jiang, finance.
Allard-type boundary regularity for C
1,α boundaries
Authors: Bourni Theodora 
Published: February 2015

Abstract
In this paper, we show boundary monotonicity formulae for rectifiable varifolds having a C
1,α “boundary”. In particular, we show that the area ratios of balls centered at this “boundary” satisfy a nice monotonicity formula, similar to that for interior balls proved by Allard in [Ann. of Math. (2) 95 (1972), 417–491]. This extends the boundary monotonicity formulae of Allard [Ann. of Math. (2) 101 (1975), 418–446], which require that the boundary is C
1,1. As a corollary, the regularity results of [Ann. of Math. (2) 101 (1975), 418–446] extend to this case and provide a regularity result for rectifiable varifolds with a C
1,α “boundary”.