bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer
Authors: Kroeger David R. , Milne Katy , Nelson Brad H. 
Published: January 2016

Abstract
Purpose: CD8+ tumor-infiltrating lymphocytes (TIL) are key mediators of antitumor immunity and are strongly associated with survival in virtually all solid tumors. However, the prognostic effect of CD8+ TIL is markedly higher in the presence of CD20+ B cells, suggesting that cooperative interactions between these lymphocyte subsets lead to more potent antitumor immunity.
Experimental Design: We assessed the colocalization patterns, phenotypes, and gene expression profiles of tumor-associated T- and B-lineage cells in high-grade serous ovarian cancer (HGSC) by multicolor IHC, flow cytometry, and bioinformatic analysis of gene expression data from The Cancer Genome Atlas.
Results: T cells and B cells colocalized in four types of lymphoid aggregate, ranging from small, diffuse clusters to large, well-organized tertiary lymphoid structures (TLS) resembling activated lymph nodes. TLS were frequently surrounded by dense infiltrates of plasma cells (PC), which comprised up to 90% of tumor stroma. PCs expressed mature, oligoclonal IgG transcripts, indicative of antigen-specific responses. PCs were associated with the highest levels of CD8+, CD4+, and CD20+ TIL, as well as numerous cytotoxicity-related gene products. CD8+ TIL carried prognostic benefit only in the presence of PCs and these other TIL subsets. PCs were independent of mutation load, BRCA1/2 status, and differentiation antigens but positively associated with cancer–testis antigens.
Conclusions: PCs are associated with the most robust, prognostically favorable CD8+ TIL responses in HGSC. We propose that TLS facilitate coordinated antitumor responses involving the combined actions of cytolytic T cells and antibody-producing PCs. Clin Cancer Res; 22(12); 3005–15. ©2016 AACR.
Exemestane Use in Postmenopausal Women at High Risk for Invasive Breast Cancer: Evaluating Biomarkers of Efficacy and Safety
Authors: Gatti-Mays Margaret E. , Venzon David , Galbo Claudia E. , Singer Andrea , Reynolds James , Makariou Erini , Kallakury Bhaskar , Heckman-Stoddard Brandy M. , Korde Larissa , Isaacs Claudine , Warren Robert , Gallagher Ann , Eng-Wong Jennifer 
Published: January 2016

Abstract
This phase II trial evaluated clinical markers of efficacy and safety of exemestane in postmenopausal women at increased risk for breast cancer. Postmenopausal women (n = 42) at risk for invasive breast cancer received 25 mg exemestane daily for 2 years along with calcium and vitamin D. The primary outcome was change in mammographic density (MD) after one year. Secondary outcomes included change in serum steroid hormones as well as change in trefoil protein 1 (TFF1) and proliferating cell nuclear antigen (PCNA) in breast tissue. Safety and tolerability were also assessed. MD decreased at 1 year and was significant at 2 years [mean change = −4.1%; 95% confidence intervals (CI), −7.2 to −1.1; P = 0.009]. Serum estradiol and testosterone levels significantly decreased at 3 months and remained suppressed at 12 months. After 1 year of treatment, TFF1 intensity decreased (mean change −1.32; 95% CI, −1.87 to −0.76; P &lt; 0.001). Exemestane was safe and well tolerated. Exemestane decreased MD and expression of breast tissue TFF1. It was well tolerated with few clinically relevant side effects. MD and breast tissue TFF1 are potential biomarkers of breast cancer–preventive effects of exemestane in high-risk postmenopausal women. Cancer Prev Res; 9(3); 225–33. ©2016 AACR.
Carboxiterminal pro-endothelin-1 as an endothelial cell biomarker in thrombotic thrombocytopenic purpura
Authors: Sinkovits György , Farkas Péter , Csuka Dorottya , Rázsó Katalin , Réti Marienn , Radványi Gáspár , Demeter Judit , Prohászka Zoltán , Mikes Bálint 
Published: January 2016

SummaryThrombotic thrombocytopenic purpura (TTP) is characterised by the deficiency of the von Willebrand factor (VWF) cleaving protease (ADAMTS-13). Although several observations indicate an important role of endothelial activation in the pathogenesis of TTP, no reliable endothelial activation markers are available in the clinical management of TTP. Our aim was to investigate the presence of endothelial activation in TTP and to determine its connections with disease activity, therapy and complement activation. We enrolled 54 patients (median age 40.5; 44 females) and 57 healthy controls (median age 34; 30 females),VWF antigen, carboxiterminal-pro-endothelin-1 (CT-proET-1), complement Factor H and complement activation products (C3bBbP and SC5b-9) were measured. In both the acute and remission phase of TTP we found increased CT-proET-1 and VWF levels, while Factor H levels decreased compared with healthy controls. In remission, however, the elevated CT-proET-1 levels showed 22 % decrease when compared with the acute phase in paired samples (p=0.0031), whereas no changes for VWF and Factor H levels were observed. We also found positive correlations between CT-proET-1 levels and alternative pathway activation markers (C3bBbP; p=0.0360; r=0.4299). The data we present here demonstrate a role of endothelium activation in patients with acute TTP. The finding that CT-proET-1 levels decreased in remission compared with the acute phase further supports endothelial involvement. In addition, we show that endothelial activation also correlated with the activation of the alternative complement pathway. The data suggest that complement and endothelium activation jointly contribute to the development of TTP episodes in patients with predisposition to TTP.Supplementary Material to this article is available online at www.thrombosis-online.com.
Effect of Left Atrial Ablation Process and Strategy on Microemboli Formation During Irrigated Radiofrequency Catheter Ablation in an In Vivo Model
Authors: Takami Mitsuru , Lehmann H. Immo , Parker Kay D. , Welker Kirk M. , Johnson Susan B. , Packer Douglas L. 
Published: January 2016

Background—
Formation of microemboli during catheter ablation has been suggested as a cause for asymptomatic cerebral emboli. However, it is unknown which part of the process and ablation setting/strategy is most strongly related to this occurrence.

Methods and Results—

A total of 27 pigs were used. Catheter/sheath manipulations in left atrium were performed in 25 of 27 pigs outfitted with microemboli monitoring systems. Ablations using open-irrigated radiofrequency catheters were performed in 18 of 25 pigs. Two of 27 pigs did not undergo left atrial procedures and were injected with microembolic materials in the carotid artery to serve as positive controls. In total, 334 sheath/catheter manipulations (transseptal puncture, sheath flushing, catheter insertion, pulmonary vein venography, and sheath exchange) and 333 radiofrequency applications (power setting, 30/50 W; point-by-point/drag ablations) were analyzed. High microbubble volume in the extracorporeal circulation loop and a high number of microembolic signals in carotid artery were observed during sheath/catheter manipulations especially in saline/contrast injections at fast speed and ablations with steam pop. Fast sheath flushing produced significantly higher microbubble volume than slow sheath flushing (median, 12 200 versus 121 nL;
P
<0.0001). A total of 44 of 126 (35%) blood filters in the circulation loop showed microparticles (thrombus/coagulum and tissue). Most of them were seen after radiofrequency application especially in 50-W ablations, drag ablations, and steam pop. Brain magnetic resonance imaging showed positive-embolic lesions in control pigs.

Conclusions—
Formation of microbubbles was the greatest during fast saline/contrast injections and steam pops, whereas high-power radiofrequency applications, drag ablations, and steam pops produced most of the microparticles.
Cortical Sparing in Preterm Ischemic Arterial Stroke
Authors: van der Aa Niek E. , Benders Manon J.N.L. , Nikkels Peter G. , Groenendaal Floris , de Vries Linda S. 
Published: January 2016

Background and Purpose—
Residual injury after perinatal arterial ischemic stroke in the middle cerebral artery territory usually involves the loss of cortical gray matter and subcortical white matter. In this article, we describe a different pattern of residual injury after middle cerebral artery stroke in preterm-born infants, in which the cortex is spared.

Methods—
Magnetic resonance imaging scans of 40 infants (12 preterm and 28 full-term infants) with a large middle cerebral artery stroke were reviewed and correlated with outcome.

Results—
Complete sparing of the cortex with cavitation of the underlying white matter was observed in 3 preterm infants, and partial sparing was noted in another 4 late preterm–born infants. One full-term infant had partial cortical sparing, and all others showed no sparing. Overall, 86% developed a hemiplegia and 30% had a developmental quotient below 85, but this did not vary between the different types of cortical injury.

Conclusions—
The pattern of cortical injury after middle cerebral artery stroke changes with gestational age and may be related to maturational changes of the vascular system. Outcome did not vary between the different patterns of cortical injury.
ERP Evidence for Implicit Priming of Top–Down Control of Attention
Authors: Blais Chris , Hubbard Emily , Mangun George R. 
Published: January 2016

AbstractProportion congruency effects are the observation that the magnitude of the Stroop effect increases as the proportion of congruent trials in a block increases. Contemporary work shows that proportion effects can be specific to a particular context. For example, in a Simon task in which items appearing above fixation are mostly congruent and items appearing below fixation are mostly incongruent, the Simon effect is larger for the items appearing at the top. There is disagreement as to whether these context-specific effects result from simple associative learning or, instead, a type of conflict-mediated associative learning. Here, we address this question in an ERP study using a Simon task in which the proportion congruency effect was context-specific, manipulating the proportion of congruent trials based on location (upper vs. lower visual field). We found significant behavioral proportion congruency effects that varied with the specific contexts. In addition, we observed that the N2 response of the ERPs to the stimuli was larger in amplitude for the high congruent (high conflict) versus low congruent (low conflict) conditions/contexts. Because the N2 is known to be greater in amplitude also for trials where conflict is high and is believed to be an electrical signal related to conflict detection in the medial frontal cortex, this supports the idea that conflict-mediated associative learning is involved in the proportion congruency effect.
Beckett and Geulincx's Metaphysics: “Without knowing why exactly”
Authors: Frost Everett C. 
Published: January 2016

This essay – the first in a two-part examination of why Beckett himself regarded the philosophy of the Cartesian occasionalist Arnold Geulincx as one of the “points of departure” for understanding his work – discusses Beckett's interest in the aspects of Geulincx's metaphysical theory that serve as a foundation for an ethics:
1. (Self-examination; ).
2. Absolute separation of body and mind.
3. (Whatever you do not in any way know how to do, that you cannot do).
A sequel, appearing separately in this issue, extends the discussion to “Beckett and Geulincx's Ethics.”
Informed Consent: Ezenwa–Ohaeto between Past and Future Uses of Pidgin
Authors: Zabus Chantal 
Published: January 2016

The essay shows how Ezenwa–Ohaeto's poetry in pidgin, particularly in his collection (1988), emblematizes a linguistic interface between, on the one hand, the pseudo-pidgin of Onitsha Market pamphleteers of the 1950s and 1960s (including in its gendered guise as in Cyprian Ekwensi) and, on the other, its quasicreolized form in contemporary news and television and radio dramas as well as a potential first language.
While locating Nigerian Pidgin or EnPi in the wider context of the emergence of pidgins on the West African Coast, the essay also draws on examples from Joyce Cary, Frank Aig–Imoukhuede, Ogali A. Ogali, Ola Rotimi, Wole Soyinka, and Tunde Fatunde among others. It is not by default but out of choice and with their 'informed consent' that EnPi writers such as Ezenwa–Ohaeto contributed to the unfinished plot of the pidgin–creole continuum.
Variability of Ratings in the Otolaryngology Standardized Letter of Recommendation
Authors: Kominsky Alan H. , Bryson Paul C. , Benninger Michael S. , Tierney William S. 
Published: January 2016

ObjectiveTo determine the variability of ratings given to students on the otolaryngology standardized letter of recommendation (SLOR).Study DesignRetrospective review.SettingAcademic otolaryngology training program.Subjects and Methods496 SLORs to the Cleveland Clinic Otolaryngology Training Program were reviewed. The SLORs were extracted from the applications and analyzed. The distributions of ratings across the 10 categories were statistically analyzed including distribution and standard deviation. Rankings were grouped into deciles for this analysis.ResultsRatings across the 10 domains revealed clustering of results across the top 2 deciles. The distribution of the bell‐shaped curve was shifted significantly to the left, representing the upper deciles. No evidence of gender or geographic bias was found. Longer length of time of association between the applicant and the letter writer correlated to a higher ranking.ConclusionThe explosion of applications being sent out by candidates for otolaryngology residency programs has prompted the implementation of the SLOR. The lack of variation in the ratings across the 10 domains does not allow for differentiation among student applicants. Reliance on the narrative letter of recommendation attached to the SLOR still remains the most significant way to differentiate among applicants. Refinements will need to be made in either the structure or use of the SLOR for it to be a more useful tool.
Pathophysiology and treatment of pulmonary hypertension in sickle cell disease
Authors: Gordeuk Victor R. , Castro Oswaldo L. , Machado Roberto F. 
Published: January 2016

AbstractPulmonary hypertension affects ∼10% of adult patients with sickle cell disease (SCD), particularly those with the homozygous genotype. An increase in pulmonary artery systolic pressure, estimated noninvasively by echocardiography, helps identify SCD patients at risk for pulmonary hypertension, but definitive diagnosis requires right-heart catheterization. About half of SCD-related pulmonary hypertension patients have precapillary pulmonary hypertension with potential etiologies of (1) a nitric oxide deficiency state and vasculopathy consequent to intravascular hemolysis, (2) chronic pulmonary thromboembolism, or (3) upregulated hypoxic responses secondary to anemia, low O2 saturation, and microvascular obstruction. The remainder have postcapillary pulmonary hypertension secondary to left ventricular dysfunction. Although the pulmonary artery pressure in SCD patients with pulmonary hypertension is only moderately elevated, they have a markedly higher risk of death than patients without pulmonary hypertension. Guidelines for diagnosis and management of SCD-related pulmonary hypertension were published recently by the American Thoracic Society. Management of adults with sickle-related pulmonary hypertension is based on anticoagulation for those with thromboembolism; oxygen therapy for those with low oxygen saturation; treatment of left ventricular failure in those with postcapillary pulmonary hypertension; and hydroxyurea or transfusions to raise the hemoglobin concentration, reduce hemolysis, and prevent vaso-occlusive events that cause additional increases in pulmonary pressure. Randomized trials have not identified drugs to lower pulmonary pressure in SCD patients with precapillary pulmonary hypertension. Patients with hemodynamics of pulmonary arterial hypertension should be referred to specialized centers and considered for treatments known to be effective in other forms of pulmonary arterial hypertension. There have been reports that some of these treatments improve SCD-related pulmonary hypertension.
Variable selection for binary classification using error rate p-values applied to metabolomics data
Authors: van Reenen Mari , Reinecke Carolus J. , Westerhuis Johan A. , Venter J. Hendrik 
Published: January 2016

Abstract
Background
Metabolomics datasets are often high-dimensional though only a limited number of variables are expected to be informative given a specific research question. The important task of selecting informative variables can therefore become complex. In this paper we look at discriminating between two groups. Two tasks need to be performed: (i) finding variables which differ between the two groups; and (ii) determining how the selected variables can be used to classify new subjects. We introduce an approach using minimum classification error rates as test statistics to find discriminatory and therefore informative variables. The thresholds resulting in the minimum error rates can be used to classify new subjects. This approach transforms error rates into p-values and is referred to as ERp.

Results
We show that non-parametric hypothesis testing, based on minimum classification error rates as test statistics, can find statistically significantly shifted variables. The discriminatory ability of variables becomes more apparent when error rates are evaluated based on their corresponding p-values, as relatively high error rates can still be statistically significant. ERp can handle unequal and small group sizes, as well as account for the cost of misclassification. ERp retains (if known) or reveals (if unknown) the shift direction, aiding in biological interpretation. The threshold resulting in the minimum error rate can immediately be used to classify new subjects.
We use NMR generated metabolomics data to illustrate how ERp is able to discriminate subjects diagnosed with Mycobacterium tuberculosis infected meningitis from a control group. The list of discriminatory variables produced by ERp contains all biologically relevant variables with appropriate shift directions discussed in the original paper from which this data is taken.

Conclusions
ERp performs variable selection and classification, is non-parametric and aids biological interpretation while handling unequal group sizes and misclassification costs. All this is achieved by a single approach which is easy to perform and interpret. ERp has the potential to address many other characteristics of metabolomics data. Future research aims to extend ERp to account for a large proportion of observations below the detection limit, as well as expand on interactions between variables.
Multivariate fixed point theorems for contractions and nonexpansive mappings with applications
Authors: Su Yongfu , Petruşel Adrian , Yao Jen-Chih 
Published: January 2016

AbstractThe first purpose of this paper is to prove an existence and uniqueness result for the multivariate fixed point of a contraction type mapping in complete metric spaces. The proof is based on the new idea of introducing a convenient metric space and an appropriate mapping. This method leads to the changing of the non-self-mapping setting to the self-mapping one. Then the main result of the paper will be applied to an initial-value problem related to a class of differential equations of first order. The second aim of this paper is to prove strong and weak convergence theorems for the multivariate fixed point of a N-variables nonexpansive mapping. The results of this paper improve several important works published recently in the literature.
Existence of fixed points for Θ-type contraction and Θ-type Suzuki contraction in complete metric spaces
Authors: Liu Xin-dong , Chang Shih-sen , Xiao Yun , Zhao Liang Cai 
Published: January 2016

AbstractThe purpose of this paper is to introduce the notions of Θ-type contractions and Θ-type Suzuki contractions and to establish some new fixed point theorems for these two kinds of mappings in the setting of complete metric spaces. The results presented in the paper are an extension of the Banach contraction principle, the Suzuki contraction theorem, and the Jleli and Samet fixed point theorem. As an application, we utilize our results to study the existence problem of solutions of nonlinear Hammerstein integral equations.
ReCAP: Serum Tumor Marker Use in Patients With Advanced Solid Tumors
Authors: Accordino Melissa K. , Wright Jason D. , Vasan Sowmya , Neugut Alfred I. , Tergas Ana , Hu Jim C. , Hershman Dawn L. , Accordino Melissa K. , Wright Jason D. , Vasan Sowmya , Neugut Alfred I. , Tergas Ana , Hu Jim C. , Hershman Dawn L. 
Published: January 2016

QUESTION ASKED: The objective of this study is to evaluate the frequency of tumor marker use in patients with advanced solid tumors. SUMMARY ANSWER: Over a 1-year period, the mean number of any individual test per patient was seven tests, and the maximum number was 35 tests; the mean number of total tests per patient was 12 tests, and the maximum number was 70 tests. In a 1-year time frame, 16.3% of patients had more than 12 individual tests, and 34.3% had more than one individual test in a 1-month span. METHODS: For each patient with a diagnosis of advanced solid tumor who had outpatient visits between July 1, 2013, and June 30, 2014, at Columbia University Medical Center, we recorded the dates of the following tumor marker tests: α-fetoprotein, CA-125, CA 15-3, CA 19-9, CA 27-29, and carcinoembryonic antigen (CEA). BIAS, CONFOUNDING FACTOR(S), DRAWBACKS: This was a 1-year evaluation of tumor marker use at a single institution. As a result, our findings may be skewed by the practice patterns of a few individual providers. Our cancer center is an urban academic tertiary care center; as a result, our experience may not be applicable to the general population. REAL-LIFE IMPLICATIONS: We found a high rate of serum tumor marker testing overuse in patients with advanced solid tumors. There is currently a lack of evidence supporting the effectiveness of frequent tumor marker testing, and additional studies are needed to inform practice. Interventions to reduce overuse could help reduce the financial burden of cancer care. Future research should define the minimal frequency of testing. In the meantime, efforts should be made to limit use of tumor marker testing in patients with advanced solid tumors. [Figure: see text]