bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiogenesis- and Hypoxia-Associated Proteins as Early Indicators of the Outcome in Patients with Metastatic Breast Cancer Given First-Line Bevacizumab-Based Therapy
Authors: Lam Siu W. , Nota Nienke M. , Jager Agnes , Bos Monique M.E.M. , van den Bosch Joan , van der Velden Ankie M.T. , Portielje Johanneke E.A. , Honkoop Aafke H. , van Tinteren Harm , Boven Epie 
Published: January 2016

Abstract
Purpose: We examined whether pretreatment levels of angiogenesis- or hypoxia-related proteins and their changes after one cycle of first-line bevacizumab-based therapy were associated with response, PFS, or OS in patients with metastatic breast cancer.
Experimental Design: We included 181 patients enrolled in the phase II ATX trial evaluating first-line paclitaxel and bevacizumab without or with capecitabine (NTR1348). Plasma samples were analyzed for VEGF-A, soluble VEGFR2 (sVEGFR2), angiopoietin 2 (ANG2), soluble TIE2 (sTIE2), IL6, IL8, and carbonic anhydrase 9 (CA9). Baseline serum CA15-3 was documented. HR was adjusted for confounding factors. Where appropriate, an optimal cut-off value defining a high and a low group was determined with Martingale residuals.
Results: At baseline, multiple proteins were significantly associated with PFS (ANG2, IL6, IL8, CA9, CA15-3) and OS (ANG2, sTIE2, IL6, IL8, CA9, CA15-3). After one cycle, VEGF-A, ANG2, sTIE2, and IL8 significantly decreased, while sVEGFR2 and CA9 significantly increased. The relative change in sVEGFR2 (P = 0.01) and IL8 (P = 0.001) was associated with response. Defining optimal cut-off, patients with a high CA9 rise (&gt;2.9%) had better PFS (HR 0.45) and OS (HR 0.54) than those with low/no rise.
Conclusions: Multiple angiogenesis- or hypoxia-related proteins were prognostic for PFS and OS. Molecular agents targeting these proteins might be beneficial in patients with high levels. Changes in IL8 or sVEGFR2 levels at second cycle appear predictive for response. Changes in CA9 levels during bevacizumab-based therapy for prediction of PFS and OS merit further study. Clin Cancer Res; 22(7); 1611–20. ©2016 AACR.
CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains
Authors: Shiina Satoshi , Ohno Masasuke , Ohka Fumiharu , Kuramitsu Shunichiro , Yamamichi Akane , Kato Akira , Motomura Kazuya , Tanahashi Kuniaki , Yamamoto Takashi , Watanabe Reiko , Ito Ichiro , Senga Takeshi , Hamaguchi Michinari , Wakabayashi Toshihiko , Kaneko Mika K. , Kato Yukinari , Chandramohan Vidyalakshmi , Bigner Darell D. , Natsume Atsushi 
Published: January 2016

AbstractGlioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Several solid tumors overexpress PDPN, including the mesenchymal type of GBM, which has been reported to present the worst prognosis among GBM subtypes. Chimeric antigen receptor (CAR)–transduced T cells can recognize predefined tumor surface antigens independent of MHC restriction, which is often downregulated in gliomas. We constructed a lentiviral vector expressing a third-generation CAR comprising a PDPN-specific antibody (NZ-1–based single-chain variable fragment) with CD28, 4-1BB, and CD3ζ intracellular domains. CAR-transduced peripheral blood monocytes were immunologically evaluated by calcein-mediated cytotoxic assay, ELISA, tumor size, and overall survival. The generated CAR T cells were specific and effective against PDPN-positive GBM cells in vitro. Systemic injection of the CAR T cells into an immunodeficient mouse model inhibited the growth of intracranial glioma xenografts in vivo. CAR T-cell therapy that targets PDPN would be a promising adoptive immunotherapy to treat mesenchymal GBM. Cancer Immunol Res; 4(3); 259–68. ©2016 AACR.
Mediadores do sagrado: os auxiliares indígenas dos missionários nas reduções jesuíticas da Amazônia ocidental (c. 1638-1767)
Authors: Carvalho Francismar Alex Lopes de 
Published: January 2016

<p>Este artigo analisa a participação indígena na difusão da doutrina cristã nas missões jesuíticas instaladas na Amazônia ocidental. Estudiosos têm destacado, nas últimas décadas, o papel de intermediários dos chefes nativos, que atuavam em instituições municipais aos moldes ibéricos, a saber, os <em>cabildos</em>, as confrarias e as milícias. Este texto aborda particularmente a figura dos auxiliares indígenas dos missionários. Ao iniciar uma redução, os jesuítas geralmente treinavam alguns caciques para exercerem a tarefa de catequistas; com o tempo, educavam os filhos dos chefes destacados e algumas crianças escolhidas entre os índios comuns e cativos para formar, através deles, um grupo seleto de “fiscais da doutrina”, sacristãos e músicos. Também estimulavam a constituição de confrarias, em que apenas os índios de comportamento exemplar e provada devoção religiosa podiam participar. Em todos os casos, esses índios atuavam como mediadores entre duas culturas. O presente estudo estabelece uma análise de situações e casos relevantes sucedidos nas missões de Maynas, Mojos e Chiquitos. O argumento central consiste em demonstrar que, ao depender de agentes indígenas para viabilizar a tradução da doutrina cristã aos neófitos, os jesuítas não podiam desterrar completamente certas práticas e representações que asseguravam a legitimidade dos seus mediadores. Assim, era comum que costumes nativos, como festas e danças, se introduzissem em celebrações cristãs. Do mesmo modo, a delegação aos mesmos índios da tarefa de catequizar conduzia a formas híbridas de apropriação da doutrina cristã.</p><div> </div>
Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo
Authors: Schossleitner Klaudia , Rauscher Sabine , Gröger Marion , Friedl Heinz Peter , Finsterwalder Richard , Habertheuer Andreas , Sibilia Maria , Brostjan Christine , Födinger Dagmar , Citi Sandra , Petzelbauer Peter 
Published: January 2016

Objective—
Cingulin is a cytoplasmic component of tight junctions. Although modulation of cingulin levels in cultured epithelial model systems has no significant effect on barrier function, evidence from cingulin knockout mice suggests that cingulin may be involved in the regulation of the behavior of epithelial or endothelial cells. Here, we investigate the role of cingulin in the barrier function of endothelial cells.

Approach and Results—
We show that cingulin is expressed in human endothelial cells of the skin, brain, and lung in vivo and in vitro. Endothelial cingulin colocalizes and coimmunoprecipitates with the tight junction proteins zonula occludens-1 and guanine nucleotide exchange factor-H1. Cingulin overexpression in human umbilical vein endothelial cell induces tight junction formation, increases transendothelial electric resistance, and strengthens barrier function for low and high molecular weight tracers. In contrast, cultured endothelial cells lacking cingulin are more permeable for low molecular weight tracers. In cingulin knockout mice, neurons of the area postrema and Purkinje cells show an increased uptake of small molecular weight tracers indicating decreased barrier function at these sites.

Conclusions—
We demonstrate that cingulin participates in the modulation of endothelial barrier function both in human cultured cells in vitro and in mouse brains in vivo. Understanding the role of cingulin in maintaining tight barriers in endothelia may allow developing new strategies for the treatment of vascular leak syndromes.
Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity
Authors: Koskinas Konstantinos C. , Siontis George C.M. , Piccolo Raffaele , Franzone Anna , Haynes Alan , Rat-Wirtzler Julie , Silber Sigmund , Serruys Patrick W. , Pilgrim Thomas , Räber Lorenz , Heg Dik , Jüni Peter , Windecker Stephan 
Published: January 2016

Background—
Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score.

Methods and Results—

In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ≤11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%;
P
<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (
P
<0.001 and
P
=0.028, respectively;
P
for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03–1.53;
P
=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18–2.01;
P
=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96–2.07;
P
=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64–1.22;
P
=0.45), without significant interaction with SYNTAX score ≤11 or >11 for any of the end points.

Conclusions—
In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104.
Gomphonema grande sp. nov., a new diatom (Bacillariophyta) from the Democratic Republic of the Congo, Tropical Africa
Authors: Karthick Balasubramanian , Kociolek Patrick John , Taylor Jonathan C , Cocquyt Christine 
Published: January 2016

Gomphonema grande sp. nov. is described from a single sample collected from the Congo River Basin, Tropical Africa. The morphological features of the new species are described and documented through light microscopy and scanning electron microscopy analyses. Gomphonema grande differs from most species of the genus by its relatively large size, robust valves, unique shape, and distinctive suite of valve features such as a labium-shaped internal stigma opening. Further discussion on the diverse nature of certain characters in the genus Gomphonema is presented.
Temporal and Spatial Variability of Precipitation from Observations and Models*
Authors: Trammell James H. , Jiang Xun , Li Liming , Kao Angela , Zhang Guang J. , Chang Edmund K. M. , Yung Yuk 
Published: January 2016

Abstract
Principal component analysis (PCA) is utilized to explore the temporal and spatial variability of precipitation from GPCP and a CAM5 simulation from 1979 to 2010. In the tropical region, the interannual variability of tropical precipitation is characterized by two dominant modes (El Niño and El Niño Modoki). The first and second modes of tropical GPCP precipitation capture 31.9% and 15.6% of the total variance, respectively. The first mode has positive precipitation anomalies over the western Pacific and negative precipitation anomalies over the central and eastern Pacific. The second mode has positive precipitation anomalies over the central Pacific and negative precipitation anomalies over the western and eastern Pacific. Similar variations are seen in the first two modes of tropical precipitation from a CAM5 simulation, although the magnitudes are slightly weaker than in the observations. Over the Northern Hemisphere (NH) high latitudes, the first mode, capturing 8.3% of the total variance of NH GPCP precipitation, is related to the northern annular mode (NAM). During the positive phase of NAM, there are negative precipitation anomalies over the Arctic and positive precipitation anomalies over the midlatitudes. Over the Southern Hemisphere (SH) high latitudes, the first mode, capturing 13.2% of the total variance of SH GPCP precipitation, is related to the southern annular mode (SAM). During the positive phase of the SAM, there are negative precipitation anomalies over the Antarctic and positive precipitation anomalies over the midlatitudes. The CAM5 precipitation simulation demonstrates similar results to those of the observations. However, they do not capture both the high precipitation anomalies over the northern Pacific Ocean or the position of the positive precipitation anomalies in the SH.
The Influence of Periodic Forcing on the Time Dependence of Western Boundary Currents: Phase Locking, Chaos, and Mechanisms of Low-Frequency Variability
Authors: Kiss Andrew E. , Frankcombe Leela M. 
Published: January 2016

AbstractIn this study an idealized gyre is put into a temporally periodic state by a steady wind stress curl forcing, and its nonlinear response to variable forcing is investigated by a detailed parameter survey varying the time-mean component of the wind and the amplitude and frequency of a periodic component. Periodic wind variations exceeding ~0.5% profoundly affect the western boundary current (WBC) time dependence, yielding regime diagrams with intricately interleaved regions of phase locking, quasiperiodicity, and chaos. In phase-locked states, the WBC period is locked to a rational multiple of the forcing period and can be shifted far outside its natural range. Quasiperiodic states can exhibit long intervals of near-synchrony interrupted periodically by brief slips out of phase with the forcing. Hysteresis and a period-doubling route to chaos are also found. The nonlinear WBC response can include variability at long time scales that are absent from both the forcing and the steadily driven current; this is a new mechanism for the generation of low-frequency WBC variability. These behaviors and their parameter dependence resemble the Devil’s staircase found in the “circle map” model of a periodically forced nonlinear oscillator, but with differences attributable to higher-dimensional dynamics. These nonlinear effects occur with forcing amplitudes in the observed range of the annual wind stress curl cycle and therefore should be considered when inferring the cause of observed WBC time scales. These results suggest that studies omitting either forcing variation or nonlinearity provide an unrealistically narrow view of the possible origins of time dependence in WBCs.
The relationship between gross motor function ability and time use in mothers of children with cerebral palsy
Authors: Ahmadi Kahjoogh Mina , Rassafiani Mehdi , Tahmasebi Ali , Ahmadi Kahjoogh Hossein , Sahaf Robab 
Published: January 2016

Introduction According to the World Health Organization, the balanced usage of time contributes to the health and welfare of individuals. Caring for a child with cerebral palsy imposes an extra pressure on parents, especially mothers as the main caregiver. Therefore, this study aims to investigate the relationship between gross motor function ability of children with cerebral palsy and time use of their mothers. Method Sixty mothers of children with cerebral palsy, sampled conveniently, participated in this cross-sectional study. Children aged between 6 and 11 years with a mean age of 9.04 years old (SD = 2.8). The Farsi version of Mothers’ Time Use Questionnaire and the Gross Motor Function Classification System (GMFCS) were utilized to collect data. The Spearman correlation coefficient was calculated. Results The results demonstrated that the allocated time for childcare ( rs = 0.44) and leisure ( rs = −0.37) activities in mothers have significant correlations with gross motor function abilities of their children ( P < 0.05). Conclusion Mothers who have children with higher scores according to the GMFCS, had to invest more time to meet needs of childcare activities. Consequently, they were not able to follow their interests and they felt an imbalanced use of time in their life.
Personal and professional values held by baccalaureate nursing students
Authors: Kaya Hülya , Işik Burçin , Şenyuva Emine , Kaya Nurten 
Published: January 2016

Background: Values are ideals and beliefs that individuals and groups uphold and lie at the core of the diverse world of human behaviour and are expressed in every human decision and action, both consciously and unconsciously. They represent basic beliefs of what is right, good or desirable and motivate both personal and professional behaviour. In the context of nursing profession, values are essential in order to maintain high standards of the nursing care. Objectives: This study was planned to examine changes in nursing students’ personal and professional values between entering and graduating from an undergraduate nursing programme. Ethical considerations: Measures to protect participants included obtaining Deaconship of Nursing Faculty approval, obtaining signed informed consent and maintaining confidentiality. Methods: This study was designed as longitudinal quality. The research population included 143 students registered at a first grade of a nursing faculty for the 2009–2010 academic year. Data were collected with a Questionnaire Form, the Value Preferences Scale, the Professional Values Precedence Scale and the Nursing Professional Values Scale. Findings: According to the results, social values have statistical differences in 4-year nursing education. Nursing students in second class have higher score in terms of social values than those in third class. Also, majority of students ranked human dignity as first and justice as second and third from first to fourth classes, and they have very high scores on Nursing Professional Values Scale and its subscales and stated that all items of Nursing Professional Values Scale are very important. Conclusion: As a result, nursing education has vital role in acquiring and maintaining professional values.
Wingspan stenting can effectively prevent long-term strokes for patients with severe symptomatic atherosclerotic basilar stenosis
Authors: Bai Wei-Xing , Gao Bu-Lang , Li Tian-Xiao , Wang Zi-Liang , Cai Dong-Yang , Zhu Liang-Fu , Xue Jiang-Yu , Li Zhao-Shuo 
Published: January 2016

Objective To investigate the safety and long-term effect of using the Wingspan stent for severe symptomatic atherosclerotic basilar artery stenosis (≥70%). Materials and methods Between July 2007 and April 2013, we had 91 consecutive patients (age range 41–82 years old) with symptomatic severe basilar stenosis (70–99%) who underwent Wingspan stenting at our center. All patients had stenosis-related temporary ischemic attack or strokes. We analyzed the demographic data, pre- and post-procedural cerebral angiography, technical success rate, peri-procedural complications, and clinical and imaging follow-ups. Results The Wingspan stenting procedure was successful in all patients: The stenosis was reduced from 82.2% ± 5.8% pre-stenting to 15.9% ± 5.7% post-stenting. The 30-day peri-operative rate for stroke or death was 14.3%, which included ischemic stroke in 12 cases (12/91 = 13.2%) and subarachnoid hemorrhage in one case (1/91 = 1.1%), with a fatal or disabling stroke rate of 2.2%. Among the 77 patients with clinical follow-up assessment within 7–60 months (mean 31.3 ± 15.1 months) after stenting, four patients (5.2%) had posterior ischemia, including one patient with disabling ischemic stroke (1.3%) and three patients (3.9%) with temporary ischemic attack. The 2-year cumulative stroke rate was 16% (95% CI: 8.2–23.8%). Among 46 patients with imaging assessments at 3–45 months (mean, 9.5 ± 8.3) post-stenting, six (13.0%) patients had restenosis, including two (2/46 = 4.3%) with symptomatic restenosis. Conclusions The benefit of stenting for patients with severe basilar artery stenosis (> 70%) may lie in lowering the long-term fatal and disabling stroke rate; and as long as the peri-operative stroke rate can be kept at a relatively lower level, patients with severe basilar stenosis can benefit from basilar artery stenting.
Policy versus Performance
Authors: Upadhyay Himanshu , Sheikh Nazma 
Published: January 2016

India’s constitutional audit institution (CAG of India) has undertaken performance reviews of the land acquisition and rehabilitation process in rapidly industrialising Odisha in last few years. In this article, we combine audit findings on both fronts and pose questions on how audited entity, legislators and communities responded to these audit findings. Three performance reviews of land acquisition process in Odisha including a comprehensive audit of land acquired for Odisha Industrial Infrastructure Development Corporation (IDCO) spanning the years between 2001 and 2012 provides insights into lapses committed often by administrators such as land acquisition officers (LAOs), DCs etc. during land acquisition process. Similarly, performance review on rehabilitation of people affected by industrial projects provides insights into lapses in implementing Odisha Resettlement and Rehabilitation (R&R) Policy, 2006. This article argues why activists and researchers need to engage with audit findings and ask crucial questions on the follow up processes on these audit findings.
Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure
Authors: Richardson Paul G. , Riches Marcie L. , Kernan Nancy A. , Brochstein Joel A. , Mineishi Shin , Termuhlen Amanda M. , Arai Sally , Grupp Stephan A. , Guinan Eva C. , Martin Paul L. , Steinbach Gideon , Krishnan Amrita , Nemecek Eneida R. , Giralt Sergio , Rodriguez Tulio , Duerst Reggie , Doyle John , Antin Joseph H. , Smith Angela , Lehmann Leslie , Champlin Richard , Gillio Alfred , Bajwa Rajinder , D’Agostino Ralph B. , Massaro Joseph , Warren Diane , Miloslavsky Maja , Hume Robin L. , Iacobelli Massimo , Nejadnik Bijan , Hannah Alison L. , Soiffer Robert J. 
Published: January 2016

Key Points
Defibrotide improves day +100 survival and CR in patients with VOD and MOF compared with a historical control. The historical control selection methodology offers a novel approach for investigation of a life-threatening orphan disease.