bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGFR1 Expression Levels Predict BGJ398 Sensitivity of FGFR1-Dependent Head and Neck Squamous Cell Cancers
Authors: Göke Friederike , Franzen Alina , Hinz Trista K. , Marek Lindsay A. , Yoon Petros , Sharma Rakesh , Bode Maike , von Maessenhausen Anne , Lankat-Buttgereit Brigitte , Göke Antonia , Golletz Carsten , Kirsten Robert , Boehm Diana , Vogel Wenzel , Kleczko Emily K. , Eagles Justin R. , Hirsch Fred R. , Van Bremen Tobias , Bootz Friedrich , Schroeck Andreas , Kim Jihye , Tan Aik-Choon , Jimeno Antonio , Heasley Lynn E. , Perner Sven 
Published: May 2015

Abstract
Purpose: FGFR1 copy-number gain (CNG) occurs in head and neck squamous cell cancers (HNSCC) and is used for patient selection in FGFR-specific inhibitor clinical trials. This study explores FGFR1 mRNA and protein levels in HNSCC cell lines, primary tumors, and patient-derived xenografts (PDX) as predictors of sensitivity to the FGFR inhibitor, NVP-BGJ398.
Experimental Design: FGFR1 status, expression levels, and BGJ398 sensitive growth were measured in 12 HNSCC cell lines. Primary HNSCCs (n = 353) were assessed for FGFR1 CNG and mRNA levels, and HNSCC TCGA data were interrogated as an independent sample set. HNSCC PDXs (n = 39) were submitted to FGFR1 copy-number detection and mRNA assays to identify putative FGFR1-dependent tumors.
Results: Cell line sensitivity to BGJ398 is associated with FGFR1 mRNA and protein levels, not FGFR1 CNG. Thirty-one percent of primary HNSCC tumors expressed FGFR1 mRNA, 18% exhibited FGFR1 CNG, 35% of amplified tumors were also positive for FGFR1 mRNA. This relationship was confirmed with the TCGA dataset. Using high FGFR1 mRNA for selection, 2 HNSCC PDXs were identified, one of which also exhibited FGFR1 CNG. The nonamplified tumor with high mRNA levels exhibited in vivo sensitivity to BGJ398.
Conclusions: FGFR1 expression associates with BGJ398 sensitivity in HNSCC cell lines and predicts tyrosine kinase inhibitor sensitivity in PDXs. Our results support FGFR1 mRNA or protein expression, rather than FGFR1 CNG as a predictive biomarker for the response to FGFR inhibitors in a subset of patients suffering from HNSCC. Clin Cancer Res; 21(19); 4356–64. ©2015 AACR.
Sunitinib Treatment Exacerbates Intratumoral Heterogeneity in Metastatic Renal Cancer
Authors: Stewart Grant D. , O'Mahony Fiach C. , Laird Alexander , Eory Lel , Lubbock Alexander L.R. , Mackay Alan , Nanda Jyoti , O'Donnell Marie , Mullen Peter , McNeill S. Alan , Riddick Antony C.P. , Berney Daniel , Bex Axel , Aitchison Michael , Overton Ian M. , Harrison David J. , Powles Thomas 
Published: May 2015

AbstractPurpose: The aim of this study was to investigate the effect of VEGF-targeted therapy (sunitinib) on molecular intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mccRCC).Experimental Design: Multiple tumor samples (n = 187 samples) were taken from the primary renal tumors of patients with mccRCC who were sunitinib treated (n = 23, SuMR clinical trial) or untreated (n = 23, SCOTRRCC study). ITH of pathologic grade, DNA (aCGH), mRNA (Illumina Beadarray) and candidate proteins (reverse phase protein array) were evaluated using unsupervised and supervised analyses (driver mutations, hypoxia, and stromal-related genes). ITH was analyzed using intratumoral protein variance distributions and distribution of individual patient aCGH and gene-expression clustering.Results: Tumor grade heterogeneity was greater in treated compared with untreated tumors (P = 0.002). In unsupervised analysis, sunitinib therapy was not associated with increased ITH in DNA or mRNA. However, there was an increase in ITH for the driver mutation gene signature (DNA and mRNA) as well as increasing variability of protein expression with treatment (P &lt; 0.05). Despite this variability, significant chromosomal and transcript changes to key targets of sunitinib, such as VHL, PBRM1, and CAIX, occurred in the treated samples.Conclusions: These findings suggest that sunitinib treatment has significant effects on the expression and ITH of key tumor and treatment specific genes/proteins in mccRCC. The results, based on primary tumor analysis, do not support the hypothesis that resistant clones are selected and predominate following targeted therapy. Clin Cancer Res; 21(18); 4212–23. ©2015 AACR.
miR-181a Targets RGS16 to Promote Chondrosarcoma Growth, Angiogenesis, and Metastasis
Authors: Sun Xiaojuan , Charbonneau Cherie , Wei Lei , Chen Qian , Terek Richard M. 
Published: May 2015

Abstract
Chondrosarcoma is the most common primary malignant bone tumor in adults, has no effective systemic treatment, and patients with this disease have poor survival. Altered expression of microRNA (miR) is involved in tumorigenesis; however, its role in chondrosarcoma is undetermined. miR-181a is overexpressed in high-grade chondrosarcoma, is upregulated by hypoxia, and increases VEGF expression. Here, the purpose was to determine the mechanism of miR-181a regulation of VEGF, determine whether miR-181a overexpression promotes tumor progression, and to evaluate an antagomir-based approach for chondrosarcoma treatment. Therapeutic inhibition of miR-181a decreased expression of VEGF and MMP1 in vitro, and angiogenesis, MMP1 activity, tumor growth, and lung metastasis, all by more than 50%, in a xenograft mouse model. A target of miR-181a is a regulator of G-protein signaling 16 (RGS16), a negative regulator of CXC chemokine receptor 4 (CXCR4) signaling. CXCR4 signaling is increased in chondrosarcoma, its expression is also increased by hypoxia, and is associated with angiogenesis and metastasis; however, receptor blockade is only partially effective. RGS16 expression is restored after miR-181a inhibition and partially accounts for the antiangiogenic and antimetastatic effects of miR-181a inhibition. These data establish miR-181a as an oncomiR that promotes chondrosarcoma progression through a new mechanism involving enhancement of CXCR4 signaling by inhibition of RGS16.
Implications: Targeting miR-181a can inhibit tumor angiogenesis, growth, and metastasis, thus suggesting the possibility of antagomir-based therapy in chondrosarcoma. Mol Cancer Res; 13(9); 1347–57. ©2015 AACR.
Relationship Between Alcohol Consumption and Cardiac Structure and Function in the Elderly
Authors: Gonçalves Alexandra , Jhund Pardeep S. , Claggett Brian , Shah Amil M. , Konety Suma , Butler Kenneth , Kitzman Dalane W. , Rosamond Wayne , Fuchs Flavio D. , Solomon Scott D. 
Published: May 2015

Background—
Excessive alcohol consumption is associated with cardiomyopathy, but the influence of moderate alcohol use on cardiac structure and function is largely unknown.

Methods and Results—

We studied 4466 participants from visit 5 of the Atherosclerosis Risk in Communities (ARIC) study (76±5 years and 60% women) who underwent transthoracic echocardiography, excluding former drinkers and those with significant valvular disease. Participants were classified into 4 categories based on self-reported alcohol intake: nondrinkers, drinkers of ≤7, ≥7 to 14, and ≥14 drinks per week. We related alcohol intake to measures of cardiac structure and function, stratified by sex, and fully adjusted for covariates. In both genders, increasing alcohol intake was associated with larger left ventricular diastolic and systolic diameters and larger left atrial diameter (
P
<0.05). In men, increasing alcohol intake was associated with greater left ventricular mass (8.2±3.8 g per consumption category;
P
=0.029) and higher E/E′ ratio (0.82±0.33 per consumption category;
P
=0.014). In women, increasing alcohol intake was associated with lower left ventricular ejection fraction (−1.9±0.6% per consumption category;
P
=0.002) and a tendency for worse left ventricular global longitudinal strain (0.45±0.25% per consumption category;
P
=0.07).

Conclusions—
In an elderly community-based population, increasing alcohol intake is associated with subtle alterations in cardiac structure and function, with women appearing more susceptible than men to the cardiotoxic effects of alcohol.
Seasonal Changes in Tropical SST and the Surface Energy Budget under Global Warming Projected by CMIP5 Models
Authors: Huang Ping 
Published: May 2015

Abstract
The seasonal changes in tropical SST under global warming are investigated based on the representative concentration pathway 8.5 (RCP8.5) and historical runs in 31 models from phase 5 of CMIP (CMIP5). The tropical SST changes show three pronounced seasonal patterns: the peak locking to the equator throughout the year and the weaker equatorial changes and stronger hemispheric asymmetric changes (HACs) in boreal autumn. The magnitude of the seasonal patterns is comparable to the tropical-mean warming and the annual-mean patterns, implying great impacts on global climate changes. The peak locking to the equator is a result of the equatorial locking of the minimum damping of climatological latent heat flux and the ocean heat transport changes. Excluding the role of ocean heat transport suggested in previous studies, the weaker equatorial warming in boreal autumn is contributed by stronger evaporation damping as a result of stronger climatological evaporation and increased surface wind speed. The seasonal variations of the HAC are driven by the variations of the damping effect of climatological evaporation. In boreal summer, the damping effect of climatological evaporation, which is greater in the Southern Hemisphere, promotes the development of the HAC. Consequently, the HAC peaks in boreal autumn when the damping effect of climatological evaporation transforms to a reverse meridional pattern, which is greater in the Northern Hemisphere. The wind–evaporation–SST feedback, as the key process of the annual-mean HAC, amplifies the seasonal variations of the HAC in tropical SST.
Nonstationary Internal Tides Observed Using Dual-Satellite Altimetry
Authors: Zaron E. D. 
Published: May 2015

AbstractDual-satellite crossover data from the Jason-2 and Cryosat-2 altimeter missions are used in a novel approach to quantify stationary and nonstationary tides from time-lagged mean square sea surface height (SSH) differences, computed for lags from 1 to 1440 h (60 days). The approach is made feasible by removing independent estimates of the stationary tide and mesoscale SSH variance, which greatly reduces the sampling error of the SSH statistics. For the semidiurnal tidal band, the stationary tidal variance is approximately 0.73 cm2, and the nonstationary variance is about 0.33 cm2, or 30% of the total. The temporal correlation of the nonstationary tide is examined by complex demodulation and found to be oscillatory with first 0 crossing at 400 h (17 days). Because a significant fraction of the time-variable mesoscale signal is resolved at time scales of roughly 150 h by the present constellation of satellite altimeters, the results suggest that it may be feasible to predict the nonstationary tide from modulations of the resolved mesoscale, thus enhancing the efficacy of tidal corrections for planned wide-swath altimeters such as the Surface Water and Ocean Topography (SWOT) mission.
Changes in cortical N-methyl-d-aspartate receptors and post-synaptic density protein 95 in schizophrenia, mood disorders and suicide
Authors: Dean Brian , Gibbons Andrew S , Boer Simone , Uezato Akihito , Meador-Woodruff James , Scarr Elizabeth , McCullumsmith Robert E 
Published: May 2015

Objectives: In humans, depending on dose, blocking the N-methyl-d-aspartate receptor (NMDAR) with ketamine can cause psychomimetic or antidepressant effects. The overall outcome for drugs such as ketamine depends on dose and the number of its available binding sites in the central nervous system, and to understand something of the latter variable we measure NMDAR in the frontal pole, dorsolateral prefrontal, anterior cingulate and parietal cortices from people with schizophrenia, bipolar disorder, major depressive disorders and age/sex matched controls. Method: We measured levels of NMDARs (using [3H]MK-801 binding) and NMDAR sub-unit mRNAs (GRINs: using in situ hybridisation) as well as post-synaptic density protein 95 (anterior cingulate cortex only; not major depressive disorders: an NMDAR post-synaptic associated protein) in bipolar disorder, schizophrenia and controls. Results: Compared to controls, levels of NMDAR were lower in the outer laminae of the dorsolateral prefrontal cortex (–17%, p = 0.01) in people with schizophrenia. In bipolar disorder, levels of NMDAR binding (laminae IV–VI; –19%, p < 0.01) and GRIN2C mRNA (laminae I–VI; –27%, p < 0.05) were lower in the anterior cingulate cortex and NMDAR binding was lower in the outer lamina IV of the dorsolateral prefrontal cortex (–19%, p < 0.01). In major depressive disorders, levels of GRIN2D mRNA were higher in frontal pole (+22%, p < 0.05). In suicide completers, levels of GRIN2B mRNA were higher in parietal cortex (+20%, p < 0.01) but lower (–35%, p = 0.02) in dorsolateral prefrontal cortex while post-synaptic density protein 95 was higher (+26%, p < 0.05) in anterior cingulate cortex. Conclusion: These data suggest that differences in cortical NMDAR expression and post-synaptic density protein 95 are present in psychiatric disorders and suicide completion and may contribute to different responses to ketamine.
Resistive index for kidney evaluation in normal and diseased cats
Authors: Tipisca Vlad , Murino Carla , Cortese Laura , Mennonna Giuseppina , Auletta Luigi , Vulpe Vasile , Meomartino Leonardo 
Published: May 2015

Objectives The objectives were to determine the resistive index (RI) in normal cats and in cats with various renal diseases, and to evaluate the effect of age on RI. Methods The subjects were cats that had ultrasonography (US) of the urinary tract and RI measurement at our centre between January 2003 and April 2014. Based on clinical evaluation, biochemical and haematological tests, urinalysis and US, the cats were classified as healthy or diseased. RI measurements were made from the interlobar or arcuate arteries. Data were analysed for differences between the right and the left kidney, the two sexes, different age groups in healthy cats, and between healthy and diseased cats. Results A total of 116 cats (68 males, 48 females) were included: 24 healthy and 92 diseased. In the healthy cats, RI (mean ± SD) differed significantly ( P = 0.02) between the right kidney (0.54 ± 0.07) and the left kidney (0.59 ± 0.08). For the left kidney, RI was significantly higher in cats with chronic kidney disease (0.73 ± 0.12) and acute kidney injury (0.72 ± 0.08) ( P = 0.0008). For the right kidney, RI was significantly higher in cats with chronic kidney disease (0.72 ± 0.11), acute kidney injury (0.74 ± 0.08), polycystic kidney disease (0.77 ± 0.11) and renal tumour (0.74 ± 0.001) ( P <0.0001). There was no significant effect on RI value in either kidney in terms of age or sex. Conclusions and relevance RI could be considered a valuable diagnostic tool in cats, useful in the differential diagnosis of diffuse renal diseases. While it does not change with the age of the cat, ultrasonographers should be aware that RI may differ between the two kidneys.
Montage
Authors: Kennedy Fiona , Bathurst Ralph , Carroll Brigid 
Published: May 2015

The Problem Adaptive leadership calls for leaders to open up conflicts and differences and to help others engage with them. However, this sets up some tension with organizational priorities such as order and productivityWorking with difference and conflict is built on assumptions other than those that privilege efficiencies and smooth functioning. Taken-for-granted habits and assumptions about what is “good” and productive are at issue. Engaging with differences and conflict is not just a matter of learning new skills, it involves engaging with questions of mind-set and assumptions. The prospect of making space for differences may be threatening or seem to be out of bounds, particularly in traditional organizations. The Solution In this article, we argue that new practices privileging conflict and difference call for methods that disrupt habitual ways of working and that support people as they learn to respond to familiar situations in new ways. We offer montage, a technique adopted from the movie industry that sets disparate images side-by-side, as promising in this regard, providing temporary “new rules” that enable people to experience new ways of working. The Stakeholders This article will be of interest to human resource (HR) professionals who select and sponsor leadership development interventions It will be particularly relevant for those in the area of learning and development who support new learning beyond workshops, in the context of day-to-day organizational life. It will also be of interest to researchers who seek to understand felt experiences in organizations and managers who are interested in reshaping their practice.
Exploring Critical Perspectives of Toxic and Bad Leadership Through Film
Authors: Edwards Gareth , Schedlitzki Doris , Ward Jenna , Wood Martin 
Published: May 2015

The Problem This article considers concepts of toxic and bad leadership from a critical, post-structuralist perspective and illustrates how this can be conveyed to management students through the use of film analysis. In response to the paucity of critical approaches within toxic and bad leadership studies, we suggest that film is a useful way of developing in-depth discussion in student and management groups to uncover underlying subtleties and complexity in leadership theory and practice. The Solution We connect to film clips from Batman: The Dark Knight, and explain how this film is used with students and managers to illustrate the ambiguous nature of “good” and “bad” leadership and explore the fluid, shifting, and relational nature of these two concepts. We conclude that students and managers can recognize this more readily through viewing, discussing, and analyzing film clips such as the ones discussed herein. The Stakeholders University lecturers and students, executive educators and managers, general human resource development (HRD) professionals
Aggressive change of a carotid-cavernous fistula in a patient with Ehlers–Danlos syndrome type IV
Authors: Kojima Atsuhiro , Saga Isako , Tomio Ryosuke , Kosho Tomoki , Hatamochi Atsushi 
Published: May 2015

The authors report a rare case of a carotid-cavernous fistula (CCF) secondary to Ehlers–Danlos syndrome (EDS) type IV which showed an aggressive angiographical change. A 59-year-old woman presented with headache, right pulsatile tinnitus, and diplopia on the right side. The diagnostic angiography demonstrated a right CCF. Accordingly transarterial embolization of the fistula was attempted 5 days later. The initial right internal carotid angiography showed an aneurysm on the petrous portion of the internal carotid artery (ICA) which was not recognized in the diagnostic angiography. Spontaneous reduction of the shunt flow and long dissection of the ICA were also revealed. The aneurysm was successfully occluded with coils, and only minor shunt flow was shown on the final angiogram. EDS type IV was diagnosed with a skin biopsy for a collagen abnormality. After the operation, the stenosis of the right ICA gradually progressed, although there was no recurrence of the CCF. Interventional treatment for patients with EDS can cause devastating vascular complication. We should be aware of the possibility of EDS type IV when a spontaneous CCF shows unusual angiographical change because early diagnosis of EDS type IV is crucial for determination of the optimum treatment option.
Higher specialist urology trainees’ opinions on preparation for the consultant role
Authors: Cleaveland Paul , Parnham Arie , Tang Vincent , Ali Zubeir , Brown Stephen 
Published: May 2015

Introduction: Trainees are objectively assessed during their surgical training rotations in order to be awarded the certificate of completion of training, thereby allowing independent consultant practice. Our study looks at senior trainees’ opinions on UK urology training in preparation to becoming a consultant. Patients and methods: A questionnaire was sent to UK senior urology trainees ST 6 or above and new consultants. Parameters including demographics, qualifications, sub-specialist interests and questions related to the candidates’ perceived readiness to carry out a range of activities as a consultant were recorded. Results: Twenty-eight candidates completed the questionnaire. All trainees thought the FRCS exam covered topics useful for consultant practice. The majority of respondents felt comfortable dealing with emergencies, general urological procedures and managing research/audit (85%, 96% and 90%, respectively). However, a number of respondents felt unprepared for educational and leadership/management roles (30% and 40%). A further 55% felt unprepared to achieve a good work/life balance. Overall, 93% felt training prepared them for the consultant role. Conclusion: The survey has highlighted that most trainees feel confident in dealing with clinical and academic aspects of urology. However, there seem to be concerns with achieving a good work/life balance and in particular limited confidence in delivering educational, management and leadership roles. With an increasing emphasis within the NHS for consultants to adopt managerial roles and increasing pressures on their personal time, this survey highlights the need for specific training to address these issues.
Prevalence and Pattern of Chronic Kidney Disease in Antiretroviral-Naïve Patients with HIV/AIDS
Authors: Adedeji Tewogbade Adeoye , Adedeji Nife O. , Adebisi Simeon A. , Idowu Ademola A. , Fawale Michael B. , Jimoh Kayode A. 
Published: May 2015

Background: Chronic renal failure and HIV/AIDS are both prevalent in Nigeria. We performed a cross-sectional analysis of renal function in newly diagnosed, treatment-naive HIV-infected patients before initiating highly active antiretroviral therapy. Methods: Treatment-inexperienced individuals were recruited. Patients with diabetes mellitus and hypertension were excluded. Plasma creatinine level was used to measure the estimated glomerular filtration rate ([eGFR] by Modification of Diet in Renal Disease equation). Predictors of creatinine and eGFR were determined by univariate and multivariate analyses. Results: We evaluated 183 patients. In all, 44 (24%) patients had a GFR <60 mL/min/1.73 m2, implying moderate chronic kidney disease (CKD). Considering the eGFR, 22 (12%) patients had stage 1, 117 (63.9%) stage 2, 13 (7.1%) stage 3, 27 (14.8%) stage 4, and 4 (2.2%) stage 5 CKD. Creatinine inversely correlated with CD4 ( r = −.228, P = .025). CD4 predicts creatinine (odds ratio 1.6, 95% confidence interval 1.0-1.8, P = .003). Conclusion: In ART-naive patients, CKD is common, and low eGFR was associated with lower CD4 counts.