bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EIA SYSTEM AND HAZARD MANAGEMENT OF SEDIMENT-RELATED DISASTER IN JAPAN — A CASE STUDY IN WIND FARM PROJECTS
Authors: AZECHI KEITA , NISHIKIZAWA SHIGEO 
Published: September 2014

Japan suffers many sediment-related disasters due to intense rainfall and other geographical and meteorological features. This paper aims to clarify the potential role and challenges of Environmental Impact Assessment (EIA) as a hazard management tool of sediment-related disaster, through surveys of the regulatory framework and analyses of case studies of wind farm projects. Based on the analysis, this paper mainly obtains the following conclusions: (1) One of the important roles of the EIA is to identify potential hazards of sediment-related disaster, because a large proportion of the projects involve potential hazards in terms of the siting, nevertheless, few of EIAs evaluate the hazards; (2) Long-term monitoring is a needed and essential role for EIA because, while re-vegetation would be carried out as a hazard mitigation on average for half the area with land change, in some cases re-vegetation has not been successful in 5 years since the implementation; (3) Improvements in the EIA system are required in order to be able to integrate the various features of hazardous information, including non-legally binding hazardous areas and local knowledge, into a common consideration for robust hazard management.
Body Mass Index, Physical Activity, and Serum Markers of Inflammation, Immunity, and Insulin Resistance
Authors: Kitahara Cari M. , Trabert Britton , Katki Hormuzd A. , Chaturvedi Anil K. , Kemp Troy J. , Pinto Ligia A. , Moore Steven C. , Purdue Mark P. , Wentzensen Nicolas , Hildesheim Allan , Shiels Meredith S. 
Published: September 2014

Abstract
Background: Epidemiologic studies examining circulating levels of inflammatory markers in relation to obesity and physical inactivity may aid in our understanding of the role of inflammation in obesity-related cancers. However, previous studies on this topic have focused on a limited set of markers.
Methods: We evaluated associations between body mass index (BMI) and vigorous physical activity level, based on self-report, and serum levels of 78 inflammation-related markers. Markers were measured using a bead-based multiplex method among 1,703 men and women, ages 55–74 years, and with no prior history of cancer at blood draw, and selected for case–control studies nested within the Prostate, Lung, Ovarian, and Colorectal Cancer Screening Trial. Analyses were adjusted for age, sex, smoking, case–control study, physical activity, and BMI.
Results: Twelve markers were positively associated with BMI after FDR correction. ORs and 95% confidence interval (CI) for highest versus lowest levels of CCL2/MCP-1, CXCL5/ENA-78, sTNFRII, CXCL10/IP-10, CXCL6/GCP2, CCL13/MCP-4, amylin, CRP, C-peptide, CCL19/MIP-3b, insulin, and leptin were: 1.50 (1.14–1.98), 1.52 (1.12–2.05), 1.61 (1.17–2.20), 1.69 (1.25–2.28), 1.74 (1.24–2.44), 1.75 (1.22–2.50), 1.91 (1.31–2.78), 2.41 (1.36–4.25), 2.78 (1.83–4.24), 3.30 (2.28–4.78), 4.05 (2.51–6.55), and 50.03 (19.87–125.99) per 5 kg/m2, respectively. Only CXCL12/SDF-1a was associated with physical activity (≥3 vs. &lt;1 h/wk; OR, 3.28; 95% CI, 1.55–6.94) after FDR correction.
Conclusions: BMI was associated with a wide range of circulating markers involved in the inflammatory response.
Impact: This cross-sectional analysis identified serum markers could be considered in future studies aimed at understanding the underlying mechanisms linking inflammation with obesity and obesity-related cancers. Cancer Epidemiol Biomarkers Prev; 23(12); 2840–9. ©2014 AACR.
Intratumor Heterogeneity in Hepatocellular Carcinoma
Authors: Friemel Juliane , Rechsteiner Markus , Frick Lukas , Böhm Friederike , Struckmann Kirsten , Egger Michèle , Moch Holger , Heikenwalder Mathias , Weber Achim 
Published: September 2014

Abstract
Purpose: Morphologic intratumor heterogeneity is well known to exist in hepatocellular carcinoma (HCC), but very few systematic analyses of this phenomenon have been performed. The aim of this study was to comprehensively characterize morphologic intratumor heterogeneity in HCC. Also, taken into account were well-known immunohistochemical markers and molecular changes in liver cells that are considered in proposed classifications of liver cell neoplasms or discussed as molecular therapeutic targets.
Experimental Design: In HCC of 23 patients without medical pretreatment, a total of 120 tumor areas were defined. Analyzed were cell and tissue morphology, expression of the liver cell markers cytokeratin (CK)7, CD44, α-fetoprotein (AFP), epithelial cell adhesion molecule (EpCAM), and glutamine synthetase (GS) along with mutations of TP53 and CTNNB1, assayed by both Sanger and next-generation sequencing.
Results: Overall, intratumor heterogeneity was detectable in the majority of HCC cases (20 of 23, 87%). Heterogeneity solely on the level of morphology was found in 6 of 23 cases (26%), morphologic heterogeneity combined with immunohistochemical heterogeneity in 9 of 23 cases (39%), and heterogeneity with respect to morphologic, immunohistochemical, and mutational status of TP53 and CTNNB1 in 5 of 23 cases (22%).
Conclusions: Our findings demonstrate that intratumor heterogeneity represents a challenge for the establishment of a robust HCC classification and may contribute to treatment failure and drug resistance in many cases of HCC. Clin Cancer Res; 21(8); 1951–61. ©2014 AACR.
See related commentary by Nault and Villanueva, p. 1786
STAT3 Mediates Regorafenib-Induced Apoptosis in Hepatocellular Carcinoma
Authors: Tai Wei-Tien , Chu Pei-Yi , Shiau Chung-Wai , Chen Yao-Li , Li Yong-Shi , Hung Man-Hsin , Chen Li-Ju , Chen Pei-Lung , Su Jung-Chen , Lin Ping-Yi , Yu Hui-Chuan , Chen Kuen-Feng 
Published: September 2014

Abstract
Purpose: Here, we aim to investigate the molecular mechanism of regorafenib and verify the potential druggable target for the treatment of hepatocellular carcinoma (HCC).
Experimental Design: HCC cell lines (PLC5, HepG2, Hep3B, SK-Hep1, and HA59T) were used to investigate the in vitro effect of regorafenib. Phosphatase activity was analyzed in HCC cells and purified SHP-1 proteins. PLC5-bearing mice were used to test the therapeutic efficiency of 20 and 40 mg/kg/d treatment with regorafenib (n \ge 8 mice). The clinical relevance of STAT3 signaling was investigated with 142 tumor samples from different patients with HCC. Descriptive statistical analysis was used to compare the baseline characteristics of patients and the expression of p-STAT3.
Results: Regorafenib inhibited STAT3-related signaling in a dose-dependent manner and was a more potent inhibitor of STAT3 than sorafenib. Regorafenib increased SHP-1 phosphatase activity in purified SHP-1 protein directly. N-SH2 domain deletion and D61A mutants mimicking open-form SHP-1 partially abolished regorafenib-induced STAT3 inhibition and apoptosis. Importantly, a higher level of expression of STAT3 was found in patients with advanced clinical stages (P = 0.009) and poorly differentiated tumors (P = 0.035).
Conclusions: Regorafenib induced significant tumor inhibition by relieving the autoinhibited N-SH2 domain of SHP-1 directly and inhibiting p-STAT3 signals. STAT3 may be suitable as a prognostic marker of HCC development, and may be a druggable target for HCC-targeted therapy using regorafenib. Clin Cancer Res; 20(22); 5768–76. ©2014 AACR.
Pazopanib, a Novel Multitargeted Kinase Inhibitor, Shows PotentIn VitroAntitumor Activity in Gastric Cancer Cell Lines withFGFR2Amplification
Authors: Kim Seung Tae , Jang Hye-Lim , Lee Su Jin , Lee Jeeyun , Choi Yoon-La , Kim Kyoung-Mee , Cho Jeonghee , Park Se Hoon , Park Young Suk , Lim Ho Yeong , Yashiro Masakazu , Kang Won Ki , Park Joon Oh 
Published: September 2014

AbstractPazopanib is an orally bioavailable, ATP-competitive, multitargeted tyrosine kinase inhibitor mainly targeting VEGFR2 and PDGFR tyrosine kinases, but the biologic sequences of pazopanib activities beyond antiangiogenesis are poorly defined. We used a panel of 38 gastric cancer cell lines to test the efficacy of pazopanib. In a growth inhibition assay, genomic changes indicated that pazopanib had differential effects on cell growth. Treatment of the KATO-III, OCUM-2M, SNU-16, and HSC-39 gastric cancer cell lines harboring FGFR2 amplification with pazopanib resulted in marked decreases of cell survival with IC50 in ranges of 0.1 to 2.0 μmol/L, whereas the same treatment of those cell lines without FGFR2 amplification had no growth-inhibitory effects. In the ectopic FGFR2-expressing model, treatment with the indicated concentrations of pazopanib significantly inhibited cell growth and colony formation by FGFR2-expressing NIH 3T3 cells with wild-type (WT) FGFR2 and mutant FGFR2 (S252W). Pazopanib also selectively suppressed constitutive FGFR2 signaling and phosphorylation of downstream effectors. In cell-cycle analysis, FGFR2-amplified cells underwent cell-cycle arrest at the G1–S phase after pazopanib treatment, whereas there were no significant effects on cell-cycle progression in cells without FGFR2 amplification treated with pazopanib. In addition, pazopanib increased a substantial fraction of sub-G1 only in FGFR2-amplified cells. These findings show that the activation of FGFR2 signaling by amplification may be a critical mediator of cell proliferation in a small subset of gastric cancer patients and that pazopanib may provide genotype-correlated clinical benefits beyond the setting of highly vascular tumors. Mol Cancer Ther; 13(11); 2527–36. ©2014 AACR.
Eflornithine (DFMO) Prevents Progression of Pancreatic Cancer by Modulating Ornithine Decarboxylase Signaling
Authors: Mohammed Altaf , Janakiram Naveena B. , Madka Venkateshwar , Ritchie Rebekah L. , Brewer Misty , Biddick Laura , Patlolla Jagan Mohan R. , Sadeghi Michael , Lightfoot Stan , Steele Vernon E. , Rao Chinthalapally V. 
Published: September 2014

AbstractOrnithine decarboxylase (ODC) is the key rate-limiting enzyme in the polyamine synthesis pathway and it is overexpressed in a variety of cancers. We found that polyamine synthesis and modulation of ODC signaling occurs at early stages of pancreatic precursor lesions and increases as the tumor progresses in Kras-activated p48Cre/+-LSL-KrasG12D/+ mice. Interest in use of the ODC inhibitor eflornithine (DFMO) as a cancer chemopreventive agent has increased in recent years since ODC was shown to be transactivated by the c-myc oncogene and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. We tested the effects of DFMO on pancreatic intraepithelial neoplasias (PanIN) and their progression to pancreatic ductal adenocarcinoma (PDAC) in genetically engineered Kras mice. The KrasG12D/+ mice fed DFMO at 0.1% and 0.2% in the diet showed a significant inhibition (P &lt; 0.0001) of PDAC incidence compared with mice fed control diet. Pancreatic tumor weights were decreased by 31% to 43% (P &lt; 0.03–0.001) with both doses of DFMO. DFMO at 0.1% and 0.2% caused a significant suppression (27% and 31%; P &lt; 0.02–0.004) of PanIN 3 lesions (carcinoma in situ). DFMO-treated pancreas exhibited modulated ODC pathway components along with decreased proliferation and increased expression of p21/p27 as compared with pancreatic tissues derived from mice fed control diet. In summary, our preclinical data indicate that DFMO has potential for chemoprevention of pancreatic cancer and should be evaluated in other PDAC models and in combination with other drugs in anticipation of future clinical trials. Cancer Prev Res; 7(12); 1198–209. ©2014 AACR.
Mendelian Randomization Provides No Evidence for a Causal Role of Serum Urate in Increasing Serum Triglyceride Levels
Authors: Rasheed Humaira , Hughes Kim , Flynn Tanya J. , Merriman Tony R. 
Published: September 2014

Background—
Triglycerides and their lipoprotein transport molecules are risk factors for heart disease. Observational studies have associated elevated levels of serum urate (SU) with triglycerides and risk of heart disease. However, owing to unmeasured confounding, observational studies do not provide insight into the causal relationship between SU and triglyceride. The aim of this study was to test for a causal role of SU in increasing triglyceride using Mendelian randomization that accounts for unmeasured confounding.

Methods and Results—

Subjects were of European ancestry from the atherosclerosis risk in communities (n=5237) and Framingham heart (n=2971) studies. Mendelian randomization by the 2-stage least squares regression method was done with SU as the exposure, a uric acid transporter genetic risk score as instrumental variable, and triglyceride as the outcome. In ordinary linear regression, SU was significantly associated with triglyceride levels (
β
=2.69 mmol/L change in triglyceride per mmol/L increase in SU). However, Mendelian randomization–based estimation showed no evidence for a direct causal association of SU with triglyceride concentration—there was a nonsignificant 1.01 mmol/L decrease in triglyceride per mmol/L increase in SU attributable to the genetic risk score (
P
=0.21). The reverse analysis using a triglyceride genetic risk score provided evidence of a causal role for triglyceride in raising urate in men (
P
Corrected
=0.018).

Conclusions—
These data provide no evidence for a causal role for SU in raising triglyceride levels, consistent with a previous Mendelian randomization report of no association between SU and ischemic heart disease.
Chronic Kidney Disease and Bleeding Complications After Intravenous Thrombolytic Therapy for Acute Ischemic Stroke
Authors: Ovbiagele Bruce , Smith Eric E. , Schwamm Lee H. , Grau-Sepulveda Maria V. , Saver Jeffrey L. , Bhatt Deepak L. , Hernandez Adrian F. , Peterson Eric D. , Fonarow Gregg C. 
Published: September 2014

Background—
The safety of intravenous thrombolysis in ischemic stroke (IS) patients with chronic kidney disease (CKD) is uncertain. We assessed whether CKD is associated with bleeding complications after intravenous tissue-type plasminogen activator administration to patients with IS.

Methods and Results—
Data were analyzed from 44 410 patients with IS treated with intravenous tissue-type plasminogen activator in the Get With The Guidelines-Stroke Program. Glomerular filtration rate based on admission serum creatinine was categorized as dichotomous (presence of CKD as <60) or as distinct categories: normal (≥90), mild (≥60–<90), moderate (≥30–< 60), severe (≥15–<30), and kidney failure (<15 or dialysis). Primary outcomes evaluated were symptomatic intracranial hemorrhage and serious systemic hemorrhage; secondary outcomes were in-hospital mortality, independent functional status. There were 15 191 of 44 410 (34%) intravenous tissue-type plasminogen activator-treated IS patients with CKD. Presence of CKD (versus no CKD) was not associated with risk-adjusted symptomatic intracranial hemorrhage (adjusted odds ratio, 1.0; 95% confidence interval: 0.91–1.10) or serious systemic hemorrhage (adjusted odds ratio, 0.97; 95% confidence interval: 0.80–1.18) and did not significantly vary by kidney dysfunction stage for either of these primary end points in multivariable analyses. Compared with patients with normal kidney function, those with CKD were more likely to die in the hospital (adjusted odds ratio, 1.22; 95% confidence interval: 1.14–1.32) and have an unfavorable discharge functional status (adjusted odds ratio, 1.13; 95% CI: 1.07–1.19).

Conclusions—
Presence of CKD among patients with IS treated with intravenous tissue-type plasminogen activator is associated with higher unadjusted odds of symptomatic intracranial hemorrhage or serious systemic hemorrhage, but this is explained by non-CKD related factors.
National Trends in Recurrent AMI Hospitalizations 1 Year After Acute Myocardial Infarction in Medicare Beneficiaries: 1999–2010
Authors: Chaudhry Sarwat I. , Khan Rabeea F. , Chen Jersey , Dharmarajan Kumar , Dodson John A. , Masoudi Frederick A. , Wang Yun , Krumholz Harlan M. 
Published: September 2014

Background

There are few data characterizing temporal changes in hospitalization for recurrent acute myocardial infarction (
AMI
) after
AMI
.

Methods and Results

Using a national sample of 2 305 441 Medicare beneficiaries hospitalized for
AMI
from 1999 to 2010, we evaluated changes in the incidence of 1‐year recurrent
AMI
hospitalization and mortality using Cox proportional hazards models. The observed recurrent
AMI
hospitalization rate declined from 12.1% (95%
CI
11.9 to 12.2) in 1999 to 8.9% (95%
CI
8.8 to 9.1) in 2010, a relative decline of 26.4%. The observed recurrent
AMI
hospitalization rate declined by a relative 27.7% in whites, from 11.9% (95%
CI
11.8 to 12.1) to 8.6% (95%
CI
8.5 to 8.8) versus a relative decline in blacks of 13.6% from 13.2% (95%
CI
12.6 to 13.8) to 11.4% (95%
CI
10.9 to 12.0). The risk‐adjusted rate of annual decline in recurrent
AMI
hospitalizations was 4.1% (
HR
0.959; 95%
CI
0.958 to 0.961), and whites experienced a higher rate of decline (
HR
0.957, 95%
CI
0.956 to 0.959) than blacks (
HR
0.974, 95%
CI
0.970 to 0.979).The overall, observed 1‐year mortality rate after hospitalization for recurrent
AMI
declined from 32.4% in 1999 to 29.7% in 2010, a relative decline of 8.3% (
P
<0.05). In adjusted analyses, 1‐year mortality after recurrent
AMI
hospitalization declined 1.8% per year (
HR
, 0.982; 95%
CI
0.980 to 0.985).

Conclusions

In a national sample of Medicare beneficiaries hospitalized for
AMI
from 1999 to 2010, hospitalization for recurrent
AMI
decreased, as did subsequent mortality, albeit to a lesser extent. The risk of recurrent
AMI
hospitalization declined less in black patients than in whites, increasing observed racial disparities by the end of the study period.
A Novel Protein Glycan Biomarker and Future Cardiovascular Disease Events
Authors: Akinkuolie Akintunde O. , Buring Julie E. , Ridker Paul M , Mora Samia 
Published: September 2014

Background

Glycosylated proteins partake in multiple cellular processes including inflammation. We hypothesized that GlycA, a novel biomarker of protein glycan
N
‐acetyl groups, is related to incident cardiovascular disease (
CVD
), and we compared it with high‐sensitivity C‐reactive protein (hs
CRP
).

Methods and Results

In 27 491 initially healthy women, baseline GlycA was quantified by nuclear magnetic resonance spectroscopy and hs
CRP
by an immunoturbidimetric assay. During median follow‐up of 17.2 years, 1648 incident
CVD
events occurred (myocardial infarction, ischemic stroke, coronary revascularization, and
CVD
death). GlycA and hs
CRP
were moderately correlated (Spearman
r
=0.61,
P
<0.0001). In Cox regression models that included age, ethnicity, smoking, blood pressure, medications, menopausal status, body mass index, and diabetes, hazard ratios for
CVD
across quartiles 1 to 4 of GlycA were 1.00, 1.10 (95%
CI
, 0.92 to 1.30), 1.34 (95%
CI
, 1.13 to 1.58), and 1.64 (95%
CI
, 1.39 to 1.93), similar to hs
CRP, for which hazard ratios were
1.00, 1.18 (95%
CI
, 0.99 to 1.41), 1.35 (95%
CI
, 1.14 to 1.61), and 1.75 (95%
CI
, 1.47 to 2.09) (both
P
trend
<0.0001). Associations were attenuated after additionally adjusting for lipids: the hazard ratio of quartile 4 versus 1 for GlycA was 1.23 (95%
CI
, 1.04 to 1.46;
P
trend
=0.002) and for hs
CRP
was 1.44 (95%
CI
, 1.20 to 1.72;
P
trend
<0.0001). Further adjustment for the other biomarker resulted in a hazard ratio of quartile 4 versus 1 for GlycA of 1.03 (95%
CI
, 0.85 to 1.24;
P
trend
=0.41) and for hs
CRP
of 1.29 (95%
CI
, 1.06 to 1.56;
P
trend
=0.001).

Conclusions

In this prospective study of initially healthy women, baseline GlycA was associated with incident
CVD
, consistent with a possible role for protein glycans in inflammation and
CVD
.

Clinical Trial Registration

URL
: http//clinicaltrials.gov/. Unique identifier
NCT
00000479.
An Assessment of SAPHIR Calibration Using Quality Tropical Soundings
Authors: Clain G. , Brogniez H. , Payne V. H. , John V. O. , Luo M. 
Published: September 2014

AbstractThe Sondeur Atmosphérique du Profil d’Humidité Intertropicale par Radiométrie (SAPHIR) instrument on board the Megha-Tropiques (MT) platform is a cross-track, multichannel microwave humidity sounder with six channels near the 183.31-GHz water vapor absorption line, a maximum scan angle of 42.96° (resulting in a maximum incidence angle of 50.7°), a 1700-km-wide swath, and a footprint resolution of 10 km at nadir. SAPHIR L1A2 brightness temperature (BT) observations have been compared to BTs simulated by the radiative transfer model (RTM) Radiative Transfer for the Television and Infrared Observation Satellite (TIROS) Operational Vertical Sounder (RTTOV-10), using in situ measurements from radiosondes as input. Selected radiosonde humidity observations from the Cooperative Indian Ocean Experiment on Intraseasonal Variability in the Year (CINDY)–Dynamics of the Madden–Julian Oscillation (DYNAMO) campaign (September 2011–March 2012) were spatiotemporally collocated with MT overpasses. Although several sonde systems were used during the campaign, all of the sites selected for this study used the Vaisala RS92-SGPD system and were chosen in order to avoid discrepancies in data quality and biases.To interpret the results of the comparison between the sensor data and the RTM simulations, uncertainties associated with the data processing must be propagated throughout the evaluation. The magnitude of the bias was found to be dependent on the observing channel, increasing from 0.18 K for the 183.31 ± 0.2-GHz channel to 2.3 K for the 183.31 ± 11-GHz channel. Uncertainties and errors that could impact the BT biases were investigated. These can be linked to the RTM input and design, the radiosonde observations, the chosen methodology of comparison, and the SAPHIR instrument itself.
The Effect of the Equivalent-Weights Particle Filter on Dynamical Balance in a Primitive Equation Model
Authors: Ades Melanie , Jan van Leeuwen Peter 
Published: September 2014

Abstract
The disadvantage of the majority of data assimilation schemes is the assumption that the conditional probability density function of the state of the system given the observations [posterior probability density function (PDF)] is distributed either locally or globally as a Gaussian. The advantage, however, is that through various different mechanisms they ensure initial conditions that are predominantly in linear balance and therefore spurious gravity wave generation is suppressed.
The equivalent-weights particle filter is a data assimilation scheme that allows for a representation of a potentially multimodal posterior PDF. It does this via proposal densities that lead to extra terms being added to the model equations and means the advantage of the traditional data assimilation schemes, in generating predominantly balanced initial conditions, is no longer guaranteed.
This paper looks in detail at the impact the equivalent-weights particle filter has on dynamical balance and gravity wave generation in a primitive equation model. The primary conclusions are that (i) provided the model error covariance matrix imposes geostrophic balance, then each additional term required by the equivalent-weights particle filter is also geostrophically balanced; (ii) the relaxation term required to ensure the particles are in the locality of the observations has little effect on gravity waves and actually induces a reduction in gravity wave energy if sufficiently large; and (iii) the equivalent-weights term, which leads to the particles having equivalent significance in the posterior PDF, produces a change in gravity wave energy comparable to the stochastic model error. Thus, the scheme does not produce significant spurious gravity wave energy and so has potential for application in real high-dimensional geophysical applications.