bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating 25-Hydroxyvitamin D3 and Survival after Diagnosis with Kidney Cancer
Authors: Muller David C. , Scelo Ghislaine , Zaridze David , Janout Vladimir , Holcatova Ivana , Navratilova Marie , Mates Dana , Midttun Øivind , Ueland Per Magne , Brennan Paul , Johansson Mattias 
Published: May 2015

Abstract
Prospective cohort studies have provided some evidence that circulating vitamin D is associated with risk of, and survival from, renal cell carcinoma (RCC), but it is unclear whether concentrations of vitamin D at the time of diagnosis of RCC are associated with prognosis. We conducted a case–cohort study of 630 RCC cases, including 203 deaths, from a multicenter case–control study in Eastern Europe. Vitamin D was assessed as 25-hydroxyvitamin D3 [25(OH)D3], and we used weighted Cox models to estimate hazard ratios (HR) and 95% confidence intervals (CI) by categories of season-adjusted 25(OH)D3. Higher concentrations of 25(OH)D3 were associated with lower risk of death after adjusting for stage, age, sex, and country (HR highest vs. lowest category 0.57; 95% CI, 0.34–0.97). The inverse associations of 25(OH)D3 with death were most notable among those who died from non-RCC causes and those diagnosed with early-stage disease. In summary, 25(OH)D3 concentration at diagnosis of RCC was inversely associated with all-cause mortality rates, but not specifically with RCC outcome. Cancer Epidemiol Biomarkers Prev; 24(8); 1277–81. ©2015 AACR.
Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA-Damaging Agents
Authors: Vasilevskaya Irina A. , Selvakumaran Muthu , Hierro Lucia Cabal , Goldstein Sara R. , Winkler Jeffrey D. , O'Dwyer Peter J. 
Published: May 2015

Abstract
Purpose: We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance of hypoxia-induced signaling through JNK, we set out to investigate how modulation of kinase activities influences cellular responses of hypoxic colon cancer cells to cytotoxic drugs.
Experimental Design: In a panel of cell lines, we investigated effects of pharmacologic and molecular inhibition of JNK on sensitivity to oxaliplatin, SN-38, and 5-FU. Combination studies for the drugs and JNK inhibitor CC-401 were carried out in vitro and in vivo.
Results: Hypoxia-induced JNK activation was associated with resistance to oxaliplatin. CC-401 in combination with chemotherapy demonstrates synergism in colon cancer cell lines, although synergy is not always hypoxia specific. A more detailed analysis focused on HT29 and SW620 (responsive), and HCT116 (nonresponsive) lines. In HT29 and SW620 cells, CC-401 treatment results in greater DNA damage in the sensitive cells. In vivo, potentiation of bevacizumab, oxaliplatin, and the combination by JNK inhibition was confirmed in HT29-derived mouse xenografts, in which tumor growth delay was greater in the presence of CC-401. Finally, stable introduction of a dominant negative JNK1, but not JNK2, construct into HT29 cells rendered them more sensitive to oxaliplatin under hypoxia, suggesting differing input of JNK isoforms in cellular responses to chemotherapy.
Conclusions: These findings demonstrate that signaling through JNK is a determinant of response to therapy in colon cancer models, and support the testing of JNK inhibition to sensitize colon tumors in the clinic. Clin Cancer Res; 21(18); 4143–52. ©2015 AACR.
Metaphysics, 9.8, 1050a30—b4: The Identity of Soul and Energeia
Authors: Shikiar David Alan 
Published: May 2015

I argue that 1050a30—b3 contains an argument in which a series of analogies treating the ‘in’ relation are deployed to constrain how the relation between life and the soul is to be construed, such that, given other reasonable premises, it follows that the soul is identical with the activity life. The interpretation of the ‘in’ relation turns crucially upon the distinction between a subject and a site for an activity, which opens the way for understanding the relation designated as not being that of inherence, which would imply some form of ontological distinction. After establishing the conclusion concerning identity, I explain how the soul may be understood as possessing a modally graded internal structure, each higher-order modality corresponding to a higher level of completion, thinking being the highest grade in human beings. I then show how the identity of soul and living activities affirmed at b2—3 implies the substantial priority of energeia to potentiality affirmed at b3—4.
Caminhos para a divulgação de ciência
Authors: Mangini Jussara 
Published: May 2015

<p>Com 23 anos de carreira, a jornalista Jussara Mangini compartilha aprendizados adquiridos em doze anos de divulgação de ciência em diferentes instituições públicas - Universidade Federal de São Paulo (Unifesp), onde coordenou a assessoria de imprensa de 1999 a 2003, Universidade Federal do ABC (UFABC), que foi seu objeto de estudo na especialização em Gestão da Comunicação na ECA/USP, concluída em 2007, e atualmente na Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), onde é assistente da gerência de comunicação. Ela também fala sobre a propagação de sites e blogs de ciência como alternativa ao encolhimento dos espaços editoriais sobre o tema na mídia tradicional. Essa tendência mundial tem se consolidado como uma oportunidade de atuação profissional e de ampliação de público. </p>
Dalinianas e outras metamorfoses imagéticas
Authors: Balogh Anna Maria 
Published: May 2015

<p>A partir das propostas do seminário de Pós-Graduação ministrado na Universidade Paulista (UNIP) <em>Imagens e Travessias: suportes, experimentações, transmutações e transmediações.</em> (2014), a autora reflete sobre alguns processos de metamorfose imagética. Algumas obras do pintor catalão Salvador Dali servem como inspiração para apontar desafiadores processos de transformação da imagem, num amplo leque que vai desde metamorfoses intra-textuais até passagens de suportes como foto para pintura, instalação e até mesmo a serialização em objetos de grife. Se estabelecem também paralelos entre tais procedimentos na arte e na comunicação, sempre com base na semiótica visual, o suporte metalingüístico do artigo. </p>
Notch1 Mutation Leads to Valvular Calcification Through Enhanced Myofibroblast Mechanotransduction
Authors: Chen Joseph , Ryzhova Larisa M. , Sewell-Loftin M.K. , Brown Christopher B. , Huppert Stacey S. , Baldwin H. Scott , Merryman W. David 
Published: May 2015

Objective—
Calcific aortic valve disease (CAVD) is a significant cardiovascular disorder, and controversy exists as to whether it is primarily a dystrophic or osteogenic process in vivo. In this study, we sought to clarify the mechanism of CAVD by assessing a genetic mutation, Notch1 heterozygosity, which leads to CAVD with 100% penetrance in humans.

Approach and Results—

Murine immortalized Notch1
+/−
aortic valve interstitial cells (AVICs) were isolated and expanded in vitro. Molecular signaling of wild-type and Notch1
+/−
AVICs were compared to identify changes in pathways that have been linked to CAVD—transforming growth factor-β1/bone morphogenetic protein, mitogen-activated protein kinase, and phosphoinositide 3-kinase/protein kinase B—and assessed for calcification potential. Additionally, AVIC mechanobiology was studied in a physiologically relevant, dynamic mechanical environment (10% cyclic strain) to investigate differences in responses between the cell types. We found that Notch1
+/−
AVICs resembled a myofibroblast-like phenotype expressing higher amounts of cadherin-11, a known mediator of dystrophic calcification, and decreased Runx2, a known osteogenic marker. We determined that cadherin-11 expression is regulated by Akt activity, and inhibition of Akt phosphorylation significantly reduced cadherin-11 expression. Moreover, in the presence of cyclic strain, Notch1
+/−
AVICs exhibited significantly upregulated phosphorylation of Akt at Ser473 and smooth muscle α-actin expression, indicative of a fully activated myofibroblast. Finally, these Notch1-mediated alterations led to enhanced dystrophic calcific nodule formation.

Conclusions—
This study presents novel insights in our understanding of Notch1-mediated CAVD by demonstrating that the mutation leads to AVICs that are fully activated myofibroblasts, resulting in dystrophic, but not osteogenic, calcification.
Temporal Trends in Percutaneous Coronary Intervention Appropriateness
Authors: Bradley Steven M. , Bohn Chad M. , Malenka David J. , Graham Michelle M. , Bryson Chris L. , McCabe James M. , Curtis Jeptha P. , Lambert-Kerzner Anne , Maynard Charles 
Published: May 2015

Background—
It is unknown whether the appropriate use of percutaneous coronary intervention (PCI) has improved over time and whether trends in PCI appropriateness have been accompanied by changes in the use of PCI.

Methods and Results—

We applied appropriate use criteria to determine the appropriateness of all 51 872 PCI performed in Washington State from 2010 through 2013. We evaluated the number of PCIs performed from 2006 through 2013 to provide a comparator period that preceded statewide appropriateness assessment beginning in 2010. Between 2010 and 2013, the overall number of PCI decreased by 6.8% (13 267 PCIs in 2010 to 12 193 in 2013) with a 43% decline in the number of PCIs for elective indications (3818 PCIs in 2010 to 2193 PCIs in 2013). The decline in the use of elective PCI was significantly larger after the onset of statewide PCI appropriateness assessment in 2010 (
P
=0.03). The proportion of elective PCIs classified as appropriate increased from 26% in 2010 to 38% in 2013, whereas the proportion of inappropriate PCIs decreased from 16% to 13% (
P
<0.001 for trends). Significant improvements in the proportion of inappropriate PCI were limited to the tertile of hospitals with the largest decline in PCIs classified as inappropriate (25% in 2010 to 12% in 2013;
P
=0.03).

Conclusions—
In Washington State, the use of PCI for elective indications has decreased over time with concurrent improvements in PCI appropriateness. However, improvements in PCI appropriateness were limited to a minority of hospitals. Understanding processes at these high-performing hospitals may inform efforts to improve PCI appropriateness.
Inter- and Intra-Rater Reliability of the Visual Vertical in Subacute Stroke
Authors: Piscicelli Celine , Barra Julien , Davoine Patrice , Chrispin Anne , Nadeau Sylvie , Pérennou Dominic 
Published: May 2015

Background and Purpose—
Visual vertical (VV) has been used increasingly as a routine clinical assessment to identify alteration of verticality perception as a possible cause of postural disorders after stroke. This study aims to determine whether the reliability of VV is sufficient to support a wide clinical use in neurorehabilitation for monitoring of patients with stroke.

Methods—
Twenty patients with subacute stroke in neurorehabilitation unit were tested after a first and unique hemispheric stroke. To evaluate the inter-rater reliability, VV was assessed the same day by 2 examiners whose degrees of expertise differed. The second examiner repeated the test the next day to investigate intrarater reliability. VV orientation (mean, primary criterion) and uncertainty (SD, secondary criterion) were calculated for 10 trials. Their reliability was quantified by the intraclass correlation coefficient, Bland–Altman plots, and the minimal detectable change. The concordance between 2 examiners was quantified by Cohen’s κ coefficients (κ).

Results—

About VV orientation, inter- and intrarater reliability were excellent (intraclass correlation coefficient, 0.979 and 0.982). The Bland–Altman plots and the minimal detectable change revealed a difference inferior to 2° between 2 tests. The concordance between 2 assessments for the diagnosis of abnormal VV orientation was absolute for the same examiner (κ=1;
P
<0.05) and excellent between 2 examiners (κ=0.92;
P
<0.05). As for VV uncertainty the intrarater reliability was satisfactory (intraclass correlation coefficient, 0.836) but the inter-rater reliability was poor (intraclass correlation coefficient, 0.211).

Conclusions—
The orientation of the VV is a highly reliable criterion, which may be used both in research and in routine clinical practice.
Evaluation of Subgrid-Scale Hydrometeor Transport Schemes Using a High-Resolution Cloud-Resolving Model
Authors: Wong May , Ovchinnikov Mikhail , Wang Minghuai 
Published: May 2015

Abstract
Potential ways of parameterizing vertical turbulent fluxes of hydrometeors are examined using a high-resolution simulation of continental deep convection. The cloud-resolving model uses a double-moment microphysics scheme that contains prognostic variables for four hydrometeor types: rain, graupel, cloud ice, and snow. The benchmark simulation with a horizontal grid spacing of 250 m is analyzed to evaluate three different ways of parameterizing the turbulent vertical fluxes of hydrometeors: an eddy-diffusion approximation, a quadrant-based decomposition, and a scaling method that accounts for within-quadrant (subplume) correlations. Results show that the downgradient nature of the eddy-diffusion approximation enforces transport of mass away from concentrated regions, whereas the benchmark simulation indicates that the vertical transport often moves mass from below the level of maximum concentration to aloft. Unlike the eddy-diffusion approach, the quadrimodal decomposition is able to capture the signs of the flux gradient but underestimates the magnitudes. The scaling approach, which accounts empirically for within-quadrant correlations, improves the representation of the vertical fluxes for all hydrometeors except snow. A sensitivity study is performed to illustrate how vertical transport effects on the vertical distribution of hydrometeors are compounded by accompanying changes in microphysical process rates. Results from the sensitivity tests show that suppressing rain or graupel transport drastically alters vertical profiles of cloud ice and snow through changes in the distribution of cloud water, which in turn governs the production of cloud ice and snow aloft. Last, a viable subgrid-scale hydrometeor transport scheme in an assumed probability density function parameterization is discussed.
Assimilating Surface Mesonet Observations with the EnKF to Improve Ensemble Forecasts of Convection Initiation on 29 May 2012
Authors: Sobash Ryan A. , Stensrud David J. 
Published: May 2015

Abstract
Surface data assimilation (DA) has the potential to improve forecasts of convection initiation (CI) and short-term forecasts of convective evolution. Since the processes driving CI occur on scales inadequately observed by conventional observation networks, mesoscale surface networks could be especially beneficial given their higher temporal and spatial resolution. This work aims to assess the impact of high-frequency assimilation of mesonet surface DA on ensemble forecasts of CI initialized with ensemble Kalman filter (EnKF) analyses of the 29 May 2012 convective event over the southern Great Plains.
Mesonet and conventional surface observations were assimilated every 5 min for 3 h from 1800 to 2100 UTC and 3-h ensemble forecasts were produced. Forecasts of CI timing and location were improved by assimilating the surface datasets in comparison to experiments where mesonet data were withheld. This primarily occurred due to a more accurate representation of the boundary layer moisture profile across the domain, especially in the vicinity of a dryline and stationary boundary. Ensemble forecasts produced by assimilating surface observations at hourly intervals, instead of every 5 min, showed only minor improvements in CI.
The 5-min assimilation of mesonet data improved forecasts of the placement and timing of CI for this particular event due to the ability of mesonet data to capture rapidly evolving mesoscale features and to constrain model biases, particularly surface moisture errors, during the cycling period.
Endogenous pro-thrombotic biomarkers from the arm and leg may not have the same value
Authors: Lattimer Christopher R , Kalodiki Evi , Geroulakos George , Hoppensteadt Debra , Fareed Jawed 
Published: May 2015

Objective Assessments of endogenous pro-thrombotic biomarkers are performed invariably on arm blood. However, the commonest site for thrombosis is in the leg. A leg blood sample may reflect local pro-thrombotic processes more accurately than systemic arm blood. The aim was to determine whether pro-thrombotic biomarkers from standard venous arm samples differed significantly from leg samples. Method Concurrent blood samples were taken from an ankle/lower calf varicose vein and an ante-cubital vein in 24 patients awaiting laser treatment as well as age approximated and sex matched healthy controls without venous disease. The following assays were performed: thrombin–antithrombin (ng/ml), antithrombin (%) activity, microparticles (nM), fibrinogen (mg/dl), prothrombin fragment 1.2 (F1.2) (pM) and P-selectin (ng/ml). Results Expressed as median (inter-quartile range). Significant arm/leg differences were observed in thrombin–antithrombin, antithrombin, prothrombin fragment 1.2 and P-selectin. The legs of patients had significantly reduced antithrombin activity and P-selectin concentrations compared to their arms (leg: 101 (90–108) versus arm: 112 (99–126), P = 0.001 and leg: 42 (26–52) versus 45 (27–52), P = 0.044, respectively). Control leg samples had significantly increased thrombin–antithrombin and P-selectin compared to control arm samples (leg: 2.1 (0.9–3.2) versus arm: 0.8 (0.5–1.7), P = 0.015 and leg: 36 (24–50) versus arm: 30 (23–41), P = 0.007, respectively). However, the control legs had significantly reduced F1.2 (leg: 265 (230–333) versus arm: 299 (236–361), P = 0.028). No significant arm/leg differences were detected in the microparticle or fibrinogen levels. Conclusions These findings indicate that venous arm blood is significantly different from venous leg blood in four out of six biomarkers studied. Recognition of local venous leg sampling as a site for investigation may unravel why the leg has a greater predisposition to thrombosis and lead the way towards an arm/leg differential test.
Clinical, serologic, and immunogenetic characterization (HLA-DRB1) of late-onset lupus erythematosus in a Colombian population
Authors: Peñaranda-Parada E , Quintana G , Yunis J J , Mantilla R , Rojas W , Panqueva U , Caminos J E , Garces M F , Sanchez E , Rondón-Herrera F , de Jesús Iglesias-Gamarra A 
Published: May 2015

Introduction Late-onset systemic lupus erythematosus (SLE) represents a specific subgroup that is defined as onset after 50 years of age. Late-onset lupus may have a different clinical course and serological findings, which may delay diagnosis and timely treatment. Objectives The objective of this paper is to determine the clinical, serologic, and immunogenetic differences among Colombian patients with late-onset SLE versus conventional SLE patients. Methodology This was a cross-sectional study in a Colombian population. Patients and their medical records were analyzed from the services of Rheumatology in Bogotá and met the criteria for SLE, according to the American College of Rheumatology (ACR) revised criteria for the classification of SLE. In a reference group of late-onset SLE patients (98 participants, with an onset after 50 years of age) and a group of conventional SLE patients (72 participants, with an onset of age of 49 years or less), multiple clinical variables (age, clinical criteria for lupus, alopecia, weight loss, fever, Raynaud’s phenomenon) and multiple serological variables (blood count, blood chemistry profile, autoantibodies) were analyzed. Additionally, the HLA class II (DRB1) of all the patients was genotyped, including an additional group of patients without the autoimmune disease. Statistical analysis was performed using the STATA 10.0 package. Results In the group of late-onset lupus, there was a higher frequency of pleurisy ( p = 0.002), pericarditis ( p = 0.026), dry symptoms ( p = 0.029), lymphopenia ( p = 0.007), and higher titers of rheumatoid factor ( p = 0.001) compared with the group of conventional SLE. Late-onset SLE patients had a lower seizure frequency ( p = 0.019), weight loss ( p = 0.009), alopecia ( p < 0.001), and Raynaud’s phenomenon ( p = 0.013) compared to the conventional SLE group. In late-onset SLE, HLA DR17 (DR3) was found more frequently compared with individuals without autoimmune disease (OR 3.81, 95% CI 1.47 to 10.59) ( p = 0.0016). Conclusion In the Colombian SLE population analyzed, there may be a probable association of several clinical and serologic variants, which would allow the differentiation of variables in the presentation of the disease among patients with late-onset SLE vs. conventional SLE.
Generalized anxiety disorder: psychopharmacotherapy update on a common and commonly overlooked condition
Authors: Starcevic Vladan 
Published: May 2015

Objective: This article provides a brief review of the practical implications of the current diagnostic conceptualisation of generalised anxiety disorder (GAD) and an update on its pharmacotherapy. Conclusions: The diagnostic criteria for GAD need to be refined, to better reflect its clinical features and to make GAD more clinically useful. Various pharmacological agents are effective for GAD and to some extent, allow a tailored treatment approach. In addition to effectiveness, the choice of medication is influenced by the speed of therapeutic action, tolerability and habit-forming properties.
Nail-Patella Syndrome
Authors: Al-Dawsari Najla , Al-Mokhadam Ahmed , Al-Abdulwahed Hind , Al-Sannaa Nouriya 
Published: May 2015

Background: Nail-patella syndrome (NPS) is an autosomal dominant disorder with a variable interfamilial and intrafamilial clinical expressivity and penetrance. It is caused by loss-of-function heterozygous mutation in the LIM-homeodomain transcription factor (LMX1B) located on chromosome 9q. The pleiotropic LMB1X gene, a member of the homeogene family, is involved in the development of glomerular basement membrane, dorsoventral limb structures, along with the nails and the anterior segment of the eye. Objective: Here, we report a Saudi Arab consanguineous family with 2 affected sisters presented with the typical nail changes of NPS. Methods: DNA samples were collected from the sisters and their parents after consent. Results: Both sisters were found to be homozygous for a previously described disease-causing mutation (c.268C>T) at the (LMX1B) gene. Both of the phenotypically normal parents were confirmed to be heterozygous for the same mutation. Conclusion: This finding supports the autosomal recessive mode of inheritance in this family.