bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovarian Cancer Risk Associated with Inherited Inflammation-Related Variants
Authors: White Kristin L. , Schildkraut Joellen M. , Palmieri Rachel T. , Iversen Edwin S. , Berchuck Andrew , Vierkant Robert A. , Rider David N. , Charbonneau Bridget , Cicek Mine S. , Sutphen Rebecca , Birrer Michael J. , Pharoah Paul P.D. , Song Honglin , Tyrer Jonathan , Gayther Simon A. , Ramus Susan J. , Wentzensen Nicolas , Yang Hannah P. , Garcia-Closas Montserrat , Phelan Catherine M. , Cunningham Julie M. , Fridley Brooke L. , Sellers Thomas A. , Goode Ellen L. 
Published: January 2012

Abstract
The importance of inflammation pathways to the development of many human cancers prompted us to examine the associations between single-nucleotide polymorphisms (SNP) in inflammation-related genes and risk of ovarian cancer. In a multisite case–control study, we genotyped SNPs in a large panel of inflammatory genes in 930 epithelial ovarian cancer cases and 1,037 controls using a custom array and analyzed by logistic regression. SNPs with P &lt; 0.10 were evaluated among 3,143 cases and 2,102 controls from the Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) post-GWAS collaboration. Combined analysis revealed association with SNPs rs17561 and rs4848300 in the interleukin gene IL1A which varied by histologic subtype (Pheterogeneity = 0.03). For example, IL1A rs17561, which correlates with numerous inflammatory phenotypes, was associated with decreased risk of clear cell, mucinous, and endometrioid subtype, but not with the most common serous subtype. Genotype at rs1864414 in the arachidonate 5-lipoxygenase ALOX5 was also associated with decreased risk. Thus, inherited variation in IL1A and ALOX5 seems to affect ovarian cancer risk which, for IL1A, is limited to rarer subtypes. Given the importance of inflammation in tumorigenesis and growing evidence of subtype-specific features in ovarian cancer, functional investigations will be important to help clarify the importance of inherited variation related to inflammation in ovarian carcinogenesis. Cancer Res; 72(5); 1064–9. ©2012 AACR.
Relationship between 18F-Fluorodeoxyglucose Accumulation and KRAS/BRAF Mutations in Colorectal Cancer
Authors: Kawada Kenji , Nakamoto Yuji , Kawada Mayumi , Hida Koya , Matsumoto Takuya , Murakami Teppei , Hasegawa Suguru , Togashi Kaori , Sakai Yoshiharu 
Published: January 2012

Abstract
Purpose: Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) has been widely used in the management of colorectal cancer (CRC). However, the relationship between FDG accumulation and KRAS/BRAF mutations has not yet been investigated. The purpose of this study was to investigate whether KRAS/BRAF mutations affect FDG accumulation in CRC.
Experimental Design: Retrospective analysis was conducted in 51 patients with CRC who underwent FDG-PET/computed tomographic (CT) scans for staging before primary tumor resection. The maximum standardized uptake value (SUVmax) for the primary tumor and the tumor-to-liver ratio (TLR) were calculated from FDG accumulation and compared between KRAS/BRAF mutated and wild-type groups. Expression levels of glucose transporter-1 (GLUT1) and hexokinase type-II (HXK-II) were assessed by immunohistochemical analysis.
Results: Both SUVmax and TLR were significantly higher in the KRAS/BRAF-mutated group compared with the wild-type group (P = 0.006 and 0.001, respectively). Multivariate analysis indicated that SUVmax and TLR remained significantly associated with KRAS/BRAF mutations (P = 0.016 and 0.01, respectively). KRAS/BRAF status could be predicted with an accuracy of 75% when a SUVmax cutoff value of 13 or 14 was used. GLUT1 expression in cancer cells was positively correlated with FDG accumulation and KRAS/BRAF status whereas HXK-II expression was not.
Conclusion: FDG accumulation was higher in CRC with KRAS/BRAF mutations. FDG-PET/CT scans may be useful for predicting the KRAS/BRAF status of patients with CRC and thus aid in determination of therapeutic strategies for patients with CRC. Clin Cancer Res; 18(6); 1696–703. ©2012 AACR.
The Use and Interpretation of Competing Risks Regression Models
Authors: Dignam James J. , Zhang Qiang , Kocherginsky Masha 
Published: January 2012

Abstract
Purpose: Competing risks observations, in which patients are subject to a number of potential failure events, are a feature of most clinical cancer studies. With competing risks, several modeling approaches are available to evaluate the relationship of covariates to cause-specific failures. We discuss the use and interpretation of commonly used competing risks regression models.
Experimental Design: For competing risks analysis, the influence of covariate can be evaluated in relation to cause-specific hazard or on the cumulative incidence of the failure types. We present simulation studies to illustrate how covariate effects differ between these approaches. We then show the implications of model choice in an example from a Radiation Therapy Oncology Group (RTOG) clinical trial for prostate cancer.
Results: The simulation studies illustrate that, depending on the relationship of a covariate to both the failure type of principal interest and the competing failure type, different models can result in substantially different effects. For example, a covariate that has no direct influence on the hazard of a primary event can still be significantly associated with the cumulative probability of that event, if the covariate influences the hazard of a competing event. This is a logical consequence of a fundamental difference between the model formulations. The example from RTOG similarly shows differences in the influence of age and tumor grade depending on the endpoint and the model type used.
Conclusions: Competing risks regression modeling requires that one considers the specific question of interest and subsequent choice of the best model to address it. Clin Cancer Res; 18(8); 2301–8. ©2012 AACR.
Design and Validation of a Specific Scavenger Receptor Class AI Binding Peptide for Targeting the Inflammatory Atherosclerotic Plaque
Authors: Segers Filip M.E. , Yu Haixiang , Molenaar Tom J.M. , Prince Perry , Tanaka Toshiki , van Berkel Theo J.C. , Biessen Erik A.L. 
Published: January 2012

Objective—
Scavenger receptor A (SR-A) is abundantly expressed by macrophage and plays a critical role in foam cell formation and atherogenesis. In search of selective SR-AI antagonists, we have used affinity selection of a phage displayed peptide library on the synthetic extracellular domain of SR-AI.

Methods and Results—

Phage selection led to an almost 1,000-fold enrichment of SR-AI binding phage, which bound avidly to human THP-1 cells. A 15-mer corresponding to the peptide insert of the major SR-AI binding phage (PP1) displaced phage binding to SR-AI. Peptides, docked to a streptavidin scaffold, were effectively internalized by macrophages in an SR-AI-dependent manner. The enriched phage pool and streptavidin bound PP1 exhibited marked uptake by hepatic macrophages in mice. Importantly, PP1 significantly increased streptavidin as well as particulate accumulation in advanced aortic plaques, and in particular intraplaque macrophage, of apolipoprotein E
−/−
mice.

Conclusion—
We have identified a novel peptide antagonist selective for SR-AI; this antagonist could be a valuable tool in SR-AI targeted imaging of atherosclerotic lesions.
TGF-β1 Downregulates AT1 Receptor Expression via PKC-δ-Mediated Sp1 Dissociation From KLF4 and Smad-Mediated PPAR-γ Association With KLF4
Authors: Zhang Xin-hua , Zheng Bin , Gu Chun , Fu Jian-ran , Wen Jin-kun 
Published: January 2012

Objective—
Cardiovascular effects of angiotensin II are primarily mediated via the angiotensin II type 1 receptor (AT1R). Krüppel-like factor 4 (KLF4), a transcription factor that binds to the transforming growth factor (TGF)-β control element (TCE), regulates a variety of receptor expression in vascular smooth muscle cells. In the present study, we investigated the mechanisms of TGF-β-mediated KLF4 regulation of AT1R expression.

Methods and Results—
Coimmunoprecipitation, chromatin immunoprecipitation, and luciferase assays were performed, with the results suggesting that Sp1 forms a complex with KLF4 bound to the TCE of the AT1R promoter and cooperatively activates AT1R transcription in vascular smooth muscle cells under basal conditions. On activation of TGF-β1 signaling, Sp1 is dissociated from the KLF4-Sp1 complex through PKC-δ-mediated KLF4 phosphorylation at Thr401, downregulating AT1R expression. Simultaneously, TGF-β1 facilitates KLF4-PPAR–γ complex formation and its binding to the TCE of the AT1R promoter through Smad-mediated KLF4 phosphorylation at Ser470, subsequently leading to inhibition of AT1R transcription.

Conclusion—
KLF4 functions as a protein platform that is able to bind to the TCE of the AT1R promoter. On activation of TGF-β signaling, KLF4 mediates Sp1 dissociation from, and PPAR-γ association with, the AT1R promoter, leading to downregulation of AT1R expression in VSMCs.
Association of Plasma Phospholipid Long-Chain Omega-3 Fatty Acids With Incident Atrial Fibrillation in Older Adults
Authors: Wu Jason H.Y. , Lemaitre Rozenn N. , King Irena B. , Song Xiaoling , Sacks Frank M. , Rimm Eric B. , Heckbert Susan R. , Siscovick David S. , Mozaffarian Dariush 
Published: January 2012

Background—
Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure.

Methods and Results—

Among 3326 US men and women ≥65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992–2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95% confidence interval, 0.57–0.89;
P
for trend=0.004) and of DHA levels was 0.77 (95% confidence interval, 0.62–0.96;
P
for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results.

Conclusions—
In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.
Pyruvate Protects the Brain Against Ischemia–Reperfusion Injury by Activating the Erythropoietin Signaling Pathway
Authors: Ryou Myoung-Gwi , Liu Ran , Ren Ming , Sun Jie , Mallet Robert T. , Yang Shao-Hua 
Published: January 2012

Background and Purpose—
Pyruvate is known to be cytoprotective through antioxidant and anti-inflammatory mechanisms. We tested the hypothesis that pyruvate protects the brain against ischemia–reperfusion injury by inducing endogenous erythropoietin (EPO) expression.

Methods—
Pyruvate's protective effect was evaluated in C6 glioma cells and HT22 neuronal cells subjected to transient oxygen glucose deprivation. Cell viability (calcein AM assay) and expression of hypoxia-inducible factor-1α, EPO, Akt and Erk (immunoblot), and EPO receptor (reverse transcription–polymerase chain reaction) were analyzed. Transient focal cerebral ischemia in rats was induced by 2 hours middle cerebral artery occlusion followed by 24 hours reperfusion. Pyruvate or saline was infused from 60 minutes occlusion until 30 minutes reperfusion. Lesion volume and DNA fragmentation were assessed by 2,3,5-triphenyltetrazolium staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, respectively. Immunoblots were conducted to determine cerebral EPO contents.

Results—
Pyruvate increased cell viability, hypoxia-inducible factor-1α, EPO, and Akt phosphorylation. Small interfering RNA suppression of hypoxia-inducible factor-1α and EPO abolished pyruvate-induced cytoprotection. In the rat stroke model, pyruvate reduced lesion volume by 84% and DNA fragmentation by 77% versus controls; increased EPO content paralleled these cerebroprotective actions of pyruvate.

Conclusions—
Pyruvate activation of the hypoxia-inducible factor-1α–EPO signaling cascade in neurons and glia could protect the brain from ischemia–reperfusion injury.
Lumbar Drainage of Cerebrospinal Fluid After Aneurysmal Subarachnoid Hemorrhage
Authors: Al-Tamimi Yahia Z. , Bhargava Deepti , Feltbower Richard G. , Hall Gregory , Goddard Anthony J.P. , Quinn Audrey C. , Ross Stuart A. 
Published: January 2012

Background and Purpose—
A single-center prospective randomized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome.

Methods—
Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grades 2, 3, 4, and 3+4 were randomized to either the study group of standard therapy plus insertion of a lumbar drain or the control group of standard therapy alone. The primary outcome measure was the prevalence of delayed ischemic neurological deficit.

Results—

Two hundred ten patients with aneurysmal subarachnoid hemorrhage (166 female, 44 male; median age, 54 years; interquartile range, 45–62 years) were recruited into the control (n=105) and study (n=105) groups of the trial. World Federation of Neurological Surgeons grade was: 1 (n=139), 2 (n=60), and 3 (n=11); Fisher grade was: 2 (n=87), 3 (n=85), and 4 (n=38). The prevalence of delayed ischemic neurological deficit was 35.2% and 21.0% in the control and study groups, respectively (
P
=0.021). The prevalence of a modified Rankin Scale score of 4, 5, or 6 at Day 10 and 6 months, respectively, was 62.5% and 18.6% in the control group and 44.8% and 19.8% in the study group (
P
=0.009 and 0.83, respectively).

Conclusions—
Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage has been shown to reduce the prevalence of delayed ischemic neurological deficit and improve early clinical outcome but failed to improve outcome at 6 months after aneurysmal subarachnoid hemorrhage.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT00842049.
Flow Diverters at and Beyond the Level of the Circle of Willis for the Treatment of Intracranial Aneurysms
Authors: Pistocchi Silvia , Blanc Raphaël , Bartolini Bruno , Piotin Michel 
Published: January 2012

Background and Purpose—
Flow Diverters (FD) are a new emerging therapy for intracranial aneurysms. Initial reports focused on the treatment of proximally located aneurysms. We report our experience with FDs in the treatment of aneurysms at and beyond the circle of Willis.

Methods—
We treated 30 aneurysms at and beyond the circle of Willis with FDs (silk and pipeline). Aneurysms were treated with FDs alone in 73.3% (22/30) and with FDs and coils in 23.3% (7/30). One procedure was converted in parent vessel occlusion.

Results—

Thirty aneurysms (21/30, 70.0% saccular; 7/30, 23.3% fusiform; 2/30, 6.7% blister-like; sizes 1.2–19.6, mean 6.8 mm) were treated in 26 patients (17 women, 9 men; mean age, 49 years) during 27 procedures. Access site complication was noted in 3.7% (1/27). Reversible neurological complications were noted in 7.4% (2/27), permanent neurological complication in 3.7% (1/27). There was no mortality. No aneurysms bled or rebled after treatment. Aneurysms treated with FDs alone were significantly smaller than those treated with FDs and coils (5.7 and 10.0 mm, respectively;
P
=0.0174). Immediate angiographic occlusion was achieved in 18.2% (4/22) with FDs alone, in 0.0% (0/7) with FDs and coils. Twenty-four aneurysms (80.0%) had been followed (mean, 13 months). Fifteen of 19 aneurysms (78.9%) treated with FDs against 4 of 4 of aneurysms (100%) treated with FDs and coils were occluded. There was no angiographic recurrence of initially totally occluded aneurysms.

Conclusions—
Aneurysms at and beyond the circle of Willis are amenable to selective treatment with FDs.
Free Fatty Acids and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage
Authors: Badjatia Neeraj , Seres David , Carpenter Amanda , Schmidt J. Michael , Lee Kiwon , Mayer Stephan A. , Claassen Jan , Connolly E. Sander , Elkind Mitchell S. 
Published: January 2012

Background and Purpose—
The purpose of this study was to understand factors related to increases in serum free fatty acid (FFA) levels and association with delayed cerebral ischemia (DCI) after subarachnoid hemorrhage.

Methods—
We performed serial measurement of systemic oxygen consumption by indirect calorimetry and FFA levels by liquid chromatography/mass spectrometry in the first 14 days after ictus in 50 consecutive patients with subarachnoid hemorrhage. Multivariable generalized estimating equation models identified associations with FFA levels in the first 14 days after SAH and Cox proportional hazards model used to identified associations with time to DCI.

Results—

There were 187 measurements in 50 patients with subarachnoid hemorrhage (mean age, 56±14 years old; 66% women) with a median Hunt–Hess score of 3. Adjusting for Hunt–Hess grade and daily caloric intake, n-6 and n-3 FFA levels were both associated with oxygen consumption and the modified Fisher score. Fourteen (28%) patients developed DCI on median postbleed Day 7. The modified Fisher score (
P
=0.01), mean n-6:n-3 FFA ratio (
P
=0.02), and mean oxygen consumption level (
P
=0.04) were higher in patients who developed DCI. In a Cox proportional hazards model, the mean n-6:n-3 FFA ratio (
P
<0.001), younger age (
P
=0.05), and modified Fisher scale (
P
=0.004) were associated with time to DCI.

Conclusions—
Injury severity and oxygen consumption hypermetabolism are associated with higher n-FFA levels and an increased n-6:n-3 FFA ratio is associated with DCI. This may indicate a role for interventions that modulate both oxygen consumption and FFA levels to reduce the occurrence of DCI.
Country Comparisons of Human Stroke Research Since 2001
Authors: Asplund Kjell , Eriksson Marie , Persson Olle 
Published: January 2012

Background and Purpose—
This is the first bibliometric comparison between countries of the development of stroke research over time.

Methods—
Clinical and epidemiological articles on stroke published 2001 to mid-2011 were identified in Science Citation Index Expanded. Article fractions, citation fractions, h-index, and international collaboration were calculated using the BibExcel software and adjusted for population size and gross domestic product.

Results—

The United States dominated with 28.7% of the sum of article fractions and 36.2% of the sum of citation fractions. The United States, Japan, the United Kingdom, and Germany together accounted for 52.1% of articles and 61.0% of citations. When adjusted for population size or gross domestic product, several small European countries, together with Israel and Taiwan, ranked the highest. Per population, there was a negative association (
r
=0.60) between burden of stroke (disability-adjusted life-years lost) and number of articles per population. In China, South Korea, and Singapore, the annual growth of stroke articles was more than twice the worldwide average. Whereas multinational collaboration was common within Europe and North America, it was relatively uncommon between Asian countries.

Conclusions—
The Big 4 in scientific literature on stroke, as to both number of articles and citations, are the United States, Japan, the United Kingdom, and Germany. Many small European countries have, in relation to their size, a high scientific production. Several countries with rapidly expanding economies have very fast growth of scientific production on stroke. Our results emphasize the need for stroke research in countries with a high population burden of stroke and they highlight the role of multinational collaboration.
Frontal Infarcts and Anxiety in Stroke
Authors: Tang Wai Kwong , Chen Yangkun , Lu Jinyan , Liang Huajun , Chu Winnie Chiu Wing , Tong Mok Vincent Chung , Ungvari Gabor Sandor , Wong Ka Sing 
Published: January 2012

Background and Purpose—
This study examined the association between poststroke anxiety symptoms (PSA) and frontal lobe infarcts.

Methods—
A cohort of 693 patients was recruited. PSA was defined as an anxiety subscale of the Hospital Anxiety and Depression Scale score of 8 or above. The presence and location of infarcts were evaluated with MRI.

Results—

Compared with the non-PSA group, PSA patients were more likely to have right frontal acute infarcts. Right frontal infarcts remained independent predictors of PSA in the multivariate analysis, with an odds ratio of 4.44 (
P
=0.002).

Conclusions—
The results suggest that right frontal acute infarcts may play a role in the development of PSA.
Searching for Information in 133 Years of California Snowfall Observations
Authors: Christy John R. 
Published: January 2012

Abstract
Monthly snowfall totals from over 500 stations in California, some of which date back to 1878, are examined. Most data were accessed through the NOAA archive, but several thousand station months of data were separately keyed in from image files of original documents. Over 26 000 of these entries were new relative to the NOAA archive, generally providing data prior to 1920. The stations were then subdivided into 18 regions for the construction of representative time series of each area. There were problems with the basic data—the most difficult with which to deal was the increasing presence of “zero” totals that should have been recorded as “missing.” This and other issues reduce the confidence that the regional time series are representative of true variations and trends, especially for regions with few systematically reporting stations. Interpreting linear trends on time series with infrequent large anomalies of one sign (i.e., heavy snowfall years) and unresolved data issues should be done with caution. For those regions characterized by consistent monitoring and with the most robust statistical reproducibility, no statistically significant trends in their periods of record (up to 133 years) nor in the most recent 50 years are found. This result encompasses the main snowfall region of the western slope of the Sierra Nevada Mountains.