bluuebunny/crossref_metadata_2025_split huggingface dataset:
GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer
Authors: Nebiker Christian A. , Han Junyi , Eppenberger-Castori Serenella , Iezzi Giandomenica , Hirt Christian , Amicarella Francesca , Cremonesi Eleonora , Huber Xaver , Padovan Elisabetta , Angrisani Basilio , Droeser Raoul A. , Rosso Raffaele , Bolli Martin , Oertli Daniel , von Holzen Urs , Adamina Michel , Muraro Manuele G. , Mengus Chantal , Zajac Paul , Sconocchia Giuseppe , Zuber Markus , Tornillo Luigi , Terracciano Luigi , Spagnoli Giulio C. 
Published: April 2014

AbstractPurpose: Colorectal cancer infiltration by CD16+ myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene and protein expression of cytokines potentially associated with macrophage polarization.Experimental Design: GM-CSF or M-CSF–stimulated peripheral blood CD14+ cells from healthy donors were cocultured with colorectal cancer cells. Tumor cell proliferation was assessed by 3H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including &gt;1,200 colorectal cancer specimens was stained with GM-CSF- and M-CSF–specific antibodies. Clinicopathological features and overall survival were analyzed.Results: GM-CSF induced CD16 expression in 66% ± 8% of monocytes, as compared with 28% ± 1% in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF–stimulated macrophages significantly (P &lt; 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n = 45, P &lt; 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1β and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P &lt; 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P = 0.02), “pushing” growth pattern (P = 0.004) and significantly (P = 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16+ and CD8+ cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance.Conclusions: GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer. Clin Cancer Res; 20(12); 3094–106. ©2014 AACR.
Genetic Variations Associated with Postoperative Recurrence in Stage I Non–Small Cell Lung Cancer
Authors: Yoon Kyong-Ah , Jung Mee Kyung , Lee Donghoon , Bae Kieun , Joo Jung Nam , Lee Geon Kook , Lee Hyun-Sung , Lee Jin Soo 
Published: April 2014

AbstractPurpose: Postoperative recurrence in stage I non–small cell lung cancer (NSCLC) is the major cause of a poor prognosis. This study aims to identify genetic variants that are associated with the prognosis of early-stage NSCLCs.Experimental Design: A genome-wide association study (GWAS) was conducted in 250 patients in stage I NSCLCs and the results were replicated in additional 308 patients.Results: Results from an Affymetrix Genome-wide Human SNP array in 250 patients identified 94 SNPs with significant associations (P &lt; 2 × 10−4), which were selected for replication in 308 additional patients. Pooled analysis of the 558 patients determined that rs1454694 in chromosome 4q34 was the most significant marker of lung cancer prognosis in the stage I patients (adjusted HR = 2.81; P = 5.91 × 10−8). After the candidate loci were mapped, an additional four markers at chromosome 4q34.3 were significantly associated with recurrence-free survival (RFS; P &lt; 5 × 10−5). A haplotype of five SNPs in 4q34 also showed significant association with RFS (P = 4.29 × 10−6).Conclusions: A genetic polymorphism rs1454694 was identified as a novel genetic risk factor for RFS of stage I NSCLCs. This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLCs. Clin Cancer Res; 20(12); 3272–9. ©2014 AACR.
U.S. Food and Drug Administration Inspections of Clinical Investigators: Overview of Results from 1977 to 2009
Authors: Morgan-Linnell Sonia K. , Stewart David J. , Kurzrock Razelle 
Published: April 2014

Abstract
The U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research is responsible for evaluating drug safety and efficacy, including oversight of clinical trials and principal investigators. The FDA Clinical Investigator Inspection List (CIIL) contains online, detailed, relevant information of all FDA inspections. We reviewed FDA inspections of clinical investigators to ascertain their outcome and included all inspections on the list (July 1977 through December 31, 2009; n = 9,481 inspections). Eighty-eight percent of inspections were “data audit” (primary purpose = verification of data), and the rest (12%) were “for cause.” The number of inspections each year significantly increased over time (P &lt; 0.0001) and averaged 350 per year in the past decade. No deficiencies were found in only 11.2% of all “data audit” and 5% of all “for cause” inspections. Only 31% of inspections resulted in “no action indicated.” About two thirds of inspections resulted in some finding, requiring either voluntary investigator action (61.3% of inspections) or official FDA action (3.9%). The most frequently cited deficiencies were failure to follow investigational plan (34%), inadequate informed consent form (28%), and inadequate/inaccurate records (27%). In conclusion, over the past decade, the FDA has performed approximately 350 inspections per year, with the number increasing over time. The vast majority of FDA inspections yield deficiency findings and, as a result, only about one third of inspections have an outcome of “no action indicated.” Clin Cancer Res; 20(13); 3364–70. ©2014 AACR.
Geranylgeranylacetone Blocks Doxorubicin-Induced Cardiac Toxicity and Reduces Cancer Cell Growth and Invasion through RHO Pathway Inhibition
Authors: Sysa-Shah Polina , Xu Yi , Guo Xin , Pin Scott , Bedja Djahida , Bartock Rachel , Tsao Allison , Hsieh Angela , Wolin Michael S. , Moens An , Raman Venu , Orita Hajime , Gabrielson Kathleen L. 
Published: April 2014

Abstract
Doxorubicin is a widely used chemotherapy for solid tumors and hematologic malignancies, but its use is limited due to cardiotoxicity. Geranylgeranylacetone (GGA), an antiulcer agent used in Japan for 30 years, has no significant adverse effects, and unexpectedly reduces ovarian cancer progression in mice. Because GGA reduces oxidative stress in brain and heart, we hypothesized that GGA would prevent oxidative stress of doxorubicin cardiac toxicity and improve doxorubicin's chemotherapeutic effects. Nude mice implanted with MDA-MB-231 breast cancer cells were studied after chronic treatment with doxorubicin, doxorubicin/GGA, GGA, or saline. Transthoracic echocardiography was used to monitor systolic heart function and xenografts evaluated. Mice were euthanized and cardiac tissue evaluated for reactive oxygen species generation, TUNEL assay, and RHO/ROCK pathway analysis. Tumor metastases were evaluated in lung sections. In vitro studies using Boyden chambers were performed to evaluate GGA effects on RHO pathway activator lysophosphatidic acid (LPA)–induced motility and invasion. We found that GGA reduced doxorubicin cardiac toxicity, preserved cardiac function, prevented TUNEL-positive cardiac cell death, and reduced doxorubicin-induced oxidant production in a nitric oxide synthase–dependent and independent manner. GGA also reduced heart doxorubicin-induced ROCK1 cleavage. Remarkably, in xenograft-implanted mice, combined GGA/doxorubicin treatment decreased tumor growth more effectively than doxorubicin treatment alone. As evidence of antitumor effect, GGA inhibited LPA-induced motility and invasion by MDA-MB-231 cells. These anti-invasive effects of GGA were suppressed by geranylgeraniol suggesting GGA inhibits RHO pathway through blocking geranylation. Thus, GGA protects the heart from doxorubicin chemotherapy-induced injury and improves anticancer efficacy of doxorubicin in breast cancer. Mol Cancer Ther; 13(7); 1717–28. ©2014 AACR.
Improved Hemodynamic Parameters in Middle Cerebral Artery Infarction After Decompressive Craniectomy
Authors: Amorim Robson Luis , de Andrade Almir Ferreira , Gattás Gabriel S. , Paiva Wellingson Silva , Menezes Marcos , Teixeira Manoel Jacobsen , Bor-Seng-Shu Edson 
Published: April 2014

Background and Purpose—
Decompressive craniectomy (DC) reduces mortality and improves functional outcome in patients with malignant middle cerebral artery infarction. However, little is known regarding the impact of DC on cerebral hemodynamics. Therefore, our goal was to study the hemodynamic changes that may occur in patients with malignant middle cerebral artery infarction after DC and to assess their relationship with outcomes.

Methods—
Twenty-seven patients with malignant middle cerebral artery infarction who were treated with DC were studied. The perfusion CT hemodynamic parameters, mean transit time, cerebral blood flow, and cerebral blood volume were evaluated preoperatively and within the first 24 hours after DC.

Results—
There was a global trend toward improved cerebral hemodynamics after DC. Preoperative and postoperative absolute mean transit times were associated with mortality at 6 months, and the ratio of post- and preoperative cerebral blood flow was significantly higher in patients with favorable outcomes than those with unfavorable outcomes. Patients who underwent surgery 48 hours after stroke, those with midline brain shift >10 mm, and those who were >55 years showed no significant improvement in any perfusion CT parameters.

Conclusions—
DC improves cerebral hemodynamics in patients with malignant middle cerebral artery infarction, and the level of improvement is related to outcome. However, some patients did not seem to experience any additional hemodynamic benefit, suggesting that perfusion CT may play a role as a prognostic tool in patients undergoing DC after ischemic stroke.
Sex Differences in Trends of Incidence and Mortality of First-Ever Stroke in Rural Tianjin, China, From 1992 to 2012
Authors: Wang Jinghua , Ning Xianjia , Yang Li , Tu Jun , Gu Hongfei , Zhan Changqing , Zhang Wenjuan , Su Ta-Chen 
Published: April 2014

Background and Purpose—
Sex differences in secular trends of stroke incidence are rarely reported. We aimed to explore sex differences in incidence and mortality of stroke in rural China from 1992 to 2012.

Methods—
In 1992, 14 920 residents were recruited to participate in the Tianjin Brain Study, a population-based study on stroke surveillance. Stroke events and all deaths were annually registered.

Results—

We observed 908 incident strokes (366 in women) from 1992 to 2012. Women were significantly younger than men (64±12 versus 68±11 years) in 1992 to 1998 (
P
=0.024). The incidence of first-ever stroke per 100 000 person-years for men was 166 in 1992 to 1998, 227 in 1999 to 2005, and 376 in 2006 to 2012; for women, the rates were 86 (1992–1998), 148 (1999–2005), and 264 (2006–2012). From 1992 to 2012, the incidence grew annually by 5.8% in men and 8.0% in women. The male/female incidence ratio declined significantly: 1.9 in 1992 to 1998, 1.5 in 1999 to 2005, and 1.4 in 2006 to 2012. There were no significant sex differences in mortality. The prevalence of obesity and diabetes mellitus, the levels of total cholesterol and triglycerides, and the age of menopause and reproductive years in women concurrently increased in 2011.

Conclusions—
There was a significant increase in the incidence of first-ever stroke in women annually and a declining trend in the male/female rate ratio in rural China during the past 21 years. These results suggest that stroke will become one of the major diseases affecting women in future decades in China.
Atherogenic Dyslipidemia and Residual Cardiovascular Risk in Statin-Treated Patients
Authors: Sirimarco Gaia , Labreuche Julien , Bruckert Eric , Goldstein Larry B. , Fox Kim M. , Rothwell Peter M. , Amarenco Pierre , Bousser Marie-Germaine , Chamorro Angel , Ford Ian , Fox Kim , Fisher Marc , Hennerici Michael G. , Mattle Heinrich , Rothwell Peter M. , Callahan Fred , Goldstein Larry B. , Sillesen Henrik , Welch K. Michael A. , Zivin Justin A. 
Published: April 2014

Background and Purpose—
Treatment with statins reduces the rate of cardiovascular events in high-risk patients, but residual risk persists. At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol (≤40 mg/dL) and high triglycerides (triglycerides ≥150 mg/dL).

Methods—
We studied subjects with stroke or transient ischemic attack in the Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin With Terutroban in Patients With a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM; n=19 100) and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL; n=4731) trials who were treated with a statin and who had high-density lipoprotein cholesterol and triglycerides measurements 3 months after randomization (n=10 498 and 2900, respectively). The primary outcome measure for this exploratory analysis was the occurrence of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We also performed a time-varying analysis to account for all available high-density lipoprotein cholesterol and triglyceride measurements.

Results—
A total of 10% of subjects in PERFORM and 9% in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy. After a follow-up of 2.3 years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials, respectively. The risk of major cardiovascular events was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence interval, 1.14–1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval, 1.06–1.85). The association was attenuated after multivariable adjustment (hazard ratio, 1.23; 95% confidence interval, 1.03–1.48 in PERFORM and hazard ratio, 1.24; 95% confidence interval, 0.93–1.65 in SPARCL). Time-varying analysis confirmed these findings.

Conclusions—
The presence of atherogenic dyslipidemia was associated with higher residual cardiovascular risk in PERFORM and SPARCL subjects with stroke or transient ischemic attack receiving statin therapy. Specific therapeutic interventions should now be trialed to address this residual risk.
Localized Retinal Nerve Fiber Layer Defects and Stroke
Authors: Wang Dandan , Li Yang , Wang Chunxue , Xu Liang , You Qi Sheng , Wang Ya Xing , Zhao Liang , Wei Wen Bin , Zhao Xingquan , Jonas Jost B. 
Published: April 2014

Background and Purpose—
Because the blood circulation system of retina and brain are closely related to each other, we examined whether stroke is associated with localized retinal nerve fiber layer defects (RNFLDs).

Methods—
Patients with acute ischemic stroke as part of a hospital-based study group were compared with the participants of the population-based group Beijing Eye Study. The retina was imaged by spectral-domain optical coherence tomography for the detection of localized RNFLDs.

Results—

The study included 154 patients with acute ischemic stroke and 2890 subjects from the Beijing Eye Study for whom optical coherence tomographic images of the retinal nerve fiber layer and data on a previous cerebral stroke were available. In logistic regression analysis, acute stroke was significantly associated with localized RNFLDs (
P
<0.001; odds ratio, 6.23; 95% confidence interval, 4.17–9.30) after adjusting for age, male sex, arterial hypertension, diabetes mellitus, and higher concentration of the C-reactive protein. In a similar manner, previous stroke was associated with localized RNFLDs (
P
=0.04; odds ratio, 1.48; 95% confidence interval, 1.02–2.16) in multivariate analysis. In a reverse manner, presence of localized RNFLDs was associated with cerebral stroke (
P
<0.001; odds ratio, 3.54; 95% confidence interval, 2.68–4.67) after adjusting for age, sex, and prevalence of diabetes mellitus.

Conclusions—
Localized RNFLDs showed a strong association with previous or acute cerebrovascular stroke and vice versa after adjustment for other systemic and ocular factors. Localized RNFLDs that can be assessed by noninvasive optical coherence tomographic imaging may be added to the panoply of retinal morphological features of stroke.
Coarse-to-fine Categorization of Visual Scenes in Scene-selective Cortex
Authors: Musel Benoit , Kauffmann Louise , Ramanoël Stephen , Giavarini Coralie , Guyader Nathalie , Chauvin Alan , Peyrin Carole 
Published: April 2014

AbstractNeurophysiological, behavioral, and computational data indicate that visual analysis may start with the parallel extraction of different elementary attributes at different spatial frequencies and follows a predominantly coarse-to-fine (CtF) processing sequence (low spatial frequencies [LSF] are extracted first, followed by high spatial frequencies [HSF]). Evidence for CtF processing within scene-selective cortical regions is, however, still lacking. In the present fMRI study, we tested whether such processing occurs in three scene-selective cortical regions: the parahippocampal place area (PPA), the retrosplenial cortex, and the occipital place area. Fourteen participants were subjected to functional scans during which they performed a categorization task of indoor versus outdoor scenes using dynamic scene stimuli. Dynamic scenes were composed of six filtered images of the same scene, from LSF to HSF or from HSF to LSF, allowing us to mimic a CtF or the reverse fine-to-coarse (FtC) sequence. Results showed that only the PPA was more activated for CtF than FtC sequences. Equivalent activations were observed for both sequences in the retrosplenial cortex and occipital place area. This study suggests for the first time that CtF sequence processing constitutes the predominant strategy for scene categorization in the PPA.
Motion-defined Surface Segregation in Human Visual Cortex
Authors: Vigano Gabriel J. , Maloney Ryan T. , Clifford Colin W. G. 
Published: April 2014

Abstract
Surface segregation provides an efficient way to parse the visual scene for perceptual analysis. Here, we investigated the segregation of a bivectorial motion display into transparent surfaces through a psychophysical task and fMRI. We found that perceptual transparency correlated with neural activity in the early areas of the visual cortex, suggesting these areas may be involved in the segregation of motion-defined surfaces. Two oppositely rotating, uniquely colored random dot kinematograms (RDKs) were presented either sequentially or in a spatially interleaved manner, displayed at varying alternation frequencies. Participants reported the color and rotation direction pairing of the RDKs in the psychophysical task. The spatially interleaved display generated the percept of motion transparency across the range of frequencies tested, yielding ceiling task performance. At high alternation frequencies, performance on the sequential display also approached ceiling, indicative of perceived transparency. However, transparency broke down in lower alternation frequency sequential displays, producing performance close to chance. A corresponding pattern mirroring the psychophysical data was also evident in univariate and multivariate analyses of the fMRI BOLD activity in visual cortical areas V1, V2, V3, V3AB, hV4, and V5/MT+. Using gray RDKs, we found significant presentation by frequency interactions in most areas; differences in BOLD signal between presentation types were significant only at the lower alternation frequency. Multivariate pattern classification was similarly unable to discriminate between presentation types at the higher frequency. This study provides evidence that early visual cortex may code for motion-defined surface segregation, which in turn may enable perceptual transparency.
Spatial distribution and habitat use of reed warblers Acrocephalus scirpaceus during the autumn migration
Authors: Andueza Miren , Arizaga Juan , Barba Emilio , Tamayo-Uria Ibon 
Published: April 2014

Spatial behaviour and habitat selection at stopover sites have a strong influence on the foraging and fuelling performance of migrating birds and hence are important aspects of stopover ecology. The aim of this study was to analyse the spatial behaviour and habitat use of reed warblers Acrocephalus scirpaceus during the autumn migration. We used radio tracking data from reed warblers surveyed at a stopover site in northern Iberia and assigned to three different groups: (1) local adult birds which were still at their breeding site, (2) migrating first-year birds (originating from beyond Iberian peninsula) and (3) migrating adult birds. Overall, migrating first-year birds tended to have larger home ranges than both local and migrating adults and to move more widely in the study area. They also showed lower fat deposition rates than adults. The proportion of habitats in home ranges (reed-beds and tidal flats being the most abundant habitats) was similar amongst groups. The spatial distribution and habitat use of organisms have been theorised to follow an ideal-free or ideal-despotic distribution. However, according to our results, other complex underlying mechanisms may play an important role in shaping the spatial behaviour of birds at stopover sites.
Evaluation of Multiple Satellite-Based Precipitation Products over Complex Topography
Authors: Derin Yagmur , Yilmaz Koray K. 
Published: April 2014

Abstract
This study evaluates the performance of four satellite-based precipitation (SBP) products over the western Black Sea region of Turkey, a region characterized by complex topography that exerts strong controls on the precipitation regime. The four SBP products include the Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis version 7 experimental near-real-time product (TMPA-7RT) and post-real-time research-quality product (TMPA-7A), the Climate Prediction Center morphing technique (CMORPH), and the Multisensor Precipitation Estimate (MPE) of the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT). Evaluation is performed at various spatial (point and grid) and temporal (daily, monthly, seasonal, and annual) scales over the period 2007–11. For the grid-scale evaluation, a rain gauge–based gridded precipitation dataset was constructed using a knowledge-based system in which “physiographic descriptors” are incorporated in the precipitation estimation through an optimization framework. The results indicated that evaluated SBP products generally had difficulty in representing the precipitation gradient normal to the orography. TMPA-7RT, TMPA-7A, and MPE products underestimated precipitation along the windward region and overestimated the precipitation on the leeward region, more significantly during the cold season. The CMORPH product underestimated the precipitation on both windward and leeward regions regardless of the season. Further investigation of the datasets used in the development of these SBP products revealed that, although both infrared (IR) and microwave (MW) datasets contain potential problems, the inability of MW sensors to detect precipitation especially in the cold season was the main challenge over this region with complex topography.