bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term Use of Cholesterol-Lowering Drugs and Cancer Incidence in a Large United States Cohort
Authors: Jacobs Eric J. , Newton Christina C. , Thun Michael J. , Gapstur Susan M. 
Published: February 2011

Abstract
HMG-coA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use. However, little is known about the association between long-term statin use and incidence of most types of cancers. We examined the association between long-term use of cholesterol-lowering drugs, predominantly statins, and the incidence of ten common cancers, as well as overall cancer incidence, among 133,255 participants (60,059 men and 73,196 women) in the Cancer Prevention Study II Nutrition Cohort during the period from 1997 to 2007. Multivariate Cox proportional hazards regression was used to estimate relative risks (RR). Current use status and duration of use were updated during follow-up using information from biennial follow-up questionnaires. Current use of cholesterol-lowering drugs for five or more years was not associated with overall cancer incidence (RR = 0.97, 95% CI = 0.92–1.03), or incidence of prostate, breast, colorectal, lung, bladder, renal cell, or pancreatic cancer but was associated with lower risk of melanoma (RR = 0.79, 95% CI = 0.66–0.96), endometrial cancer (RR = 0.65, 95% CI = 0.45–0.94), and non-Hodgkin lymphoma (NHL; RR = 0.74, 95% CI = 0.62–0.89). These results suggest that long-term use of statins is unlikely to substantially increase or decrease overall cancer risk. However, associations between long-term statin use and risk of endometrial cancer, melanoma, and NHL deserve further investigation. Cancer Res; 71(5); 1763–71. ©2011 AACR.
p95HER2 and Breast Cancer
Authors: Arribas Joaquín , Baselga José , Pedersen Kim , Parra-Palau Josep Lluís 
Published: February 2011

Abstract
A subtype of HER2-positive tumors with distinct biological and clinical features expresses a series of carboxy-terminal fragments collectively known as p95HER2. One of these fragments, named 100- to 115-kDa p95HER2 or 611-CTF, is hyperactive because of its ability to form homodimers maintained by intermolecular disulfide bonds. Despite lacking the majority of the extracellular domain, this HER2 fragment drives breast cancer progression in vivo. The recent availability of specific anti-p95 antibodies has confirmed previous results indicating that the expression of p95HER2 is predictive of poor prognosis and correlates with resistance to the treatment with trastuzumab, a therapeutic antibody directed against the extracellular domain of HER2. Cancer Res; 71(5); 1515–9. ©2011 AACR.
Placental Growth Factor Upregulation Is a Host Response to Antiangiogenic Therapy
Authors: Bagley Rebecca G. , Ren Yi , Weber William , Yao Min , Kurtzberg Leslie , Pinckney Jason , Bangari Dinesh , Nguyen Cokey , Brondyk William , Kaplan Johanne , Teicher Beverly A. 
Published: February 2011

Abstract
Purpose: Placental growth factor (PlGF) is an angiogenic protein. Upregulation of PlGF has been observed in the clinic following antiangiogenic regimens targeting the VEGF pathway. PlGF has been proposed as a therapeutic target for oncology. sFLT01 is a novel fusion protein that neutralizes mouse and human PlGF (mPlGF, hPlGF) and mouse and human VEGF-A (mVEGF-A, hVEGF-A). It was tested in syngeneic and xenograft tumor models to evaluate the effects of simultaneously neutralizing PlGF and VEGF-A and to investigate changes observed in the clinic in preclinical models.
Experimental Design: Production of PlGF and VEGF-A by B16F10 and A673 cancer cells in vitro was assessed. Mice with subcutaneous B16F10 melanoma or A673 sarcoma tumors were treated with sFLT01. Tumor volumes and microvessel density (MVD) were measured to assess efficacy. Serum levels of hVEGF-A, hPlGF, and mPlGF at early and late time points were determined by ELISA.
Results: Exposure of cancer cell lines to sFLT01 caused a decrease in VEGF secretion. sFLT01 inhibited tumor growth, prolonged survival, and decreased MVD. Analysis of serum collected from treated mice showed that sFLT01 administration caused a marked increase in circulating mPlGF but not hPlGF or hVEGF. sFLT01 treatment also increased circulating mPlGF levels in non–tumor-bearing mice.
Conclusion: With the tumor cell lines and mouse models we used, antiangiogenic therapies that target both PlGF and VEGF may elicit a host response rather than, or in addition to, a malignant cell response that contribute to therapeutic resistance and tumor escape as suggested by others. Clin Cancer Res; 17(5); 976–88. ©2011 AACR.
Tropopause Characteristics and Variability from 11 yr of SHADOZ Observations in the Southern Tropics and Subtropics
Authors: Sivakumar V. , Bencherif H. , Bègue N. , Thompson A. M. 
Published: February 2011

AbstractIn this paper, tropopause characteristics observed from tropical to subtropical Southern Hemisphere stations using Southern Hemisphere Additional Ozonesonde (SHADOZ) data are presented for the 11-yr period of 1998–2008. Three different definitions of tropopause—cold-point tropopause (CPT), lapse-rate tropopause (LRT), and ozone tropopause (OT)—are determined, and their variability for nine different SHADOZ sites is studied for the purpose of evaluating their usefulness as indicators of possible tropopause trends. For each station, the OT is uniquely defined by the ozone gradient and is found to be more variable than either LRT or CPT. The OT roughly coincides with the upper boundary of the region of most active convective mixing over the western Pacific Ocean and with the lower boundary of the transition region from the troposphere to the lower stratosphere that is generally referred to as the tropical tropopause layer. The monthly and year-to-year variations in the tropopause are examined, and the annual cycle in OT, the dominant signal, is described. The distance of separation of the OT from the CPT or LRT is smaller for the tropics (stations at 0°–15°S) than for the subtropics (15°–25°S). The decadal trend in tropopause heights is measured using a statistical model that accounts for natural variations expressed in El Niño–Southern Oscillation, the quasi-biennial oscillation, and the Indian Ocean dipole. The decadal trend estimation shows no statistically significant trend for the CPT and LRT in the tropics, in contrast to other studies. A decrease in altitude for the OT is significant. In the subtropics, the CPT and LRT decline significantly, by −240 and −190 m (10 yr)−1, respectively, but the OT increases.
Modulations of the Phase Speed of Convectively Coupled Kelvin Waves by the ITCZ
Authors: Dias Juliana , Pauluis Olivier 
Published: February 2011

AbstractA number of studies suggest a two-way feedback between convectively coupled Kelvin waves (CCKWs) and the intertropical convergence zone (ITCZ). Viewed here as a proxy for deep convection, analysis of brightness temperature data reveals several aspects of these interdependencies. A wavenumber–frequency spectral analysis is applied to the satellite data in order to filter CCKWs. The ITCZ is characterized by a region of low brightness temperature and a proxy for both the ITCZ location and width are defined. The phase speed of CCKW data is determined using the Radon transform method. Linear regression techniques and probability density analysis are consistent with previous theoretical predictions and observational results. In particular, the fastest waves are found when the ITCZ is the farthest from the equator and the narrowest. Conversely, the slowest waves coincide with broad ITCZs that are located near the equator.
Genetic determinants of plasma von Willebrand factor antigen levels: a target gene SNP and haplotype analysis of ARIC cohort
Authors: Campos Marco , Sun Wei , Yu Fuli , Barbalic Maja , Tang Weihong , Chambless Lloyd E. , Wu Kenneth K. , Ballantyne Christie , Folsom Aaron R. , Boerwinkle Eric , Dong Jing-fei 
Published: February 2011

Abstractvon Willebrand factor (VWF) is an essential component of hemostasis and has been implicated in thrombosis. Multimer size and the amount of circulating VWF are known to impact hemostatic function. We associated 78 VWF single nucleotide polymorphisms (SNPs) and haplotypes constructed from those SNPs with VWF antigen level in 7856 subjects of European descent. Among the nongenomic factors, age and body mass index contributed 4.8% and 1.6% of VWF variation, respectively. The SNP rs514659 (tags O blood type) contributed 15.4% of the variance. Among the VWF SNPs, we identified 18 SNPs that are associated with levels of VWF. The correlative SNPs are either intronic (89%) or silent exonic (11%). Although SNPs examined are distributed throughout the entire VWF gene without apparent cluster, all the positive SNPs are located in a 50-kb region. Exons in this region encode for VWF D2, D′, and D3 domains that are known to regulate VWF multimerization and storage. Mutations in the D3 domain are also associated with von Willebrand disease. Fifteen of these 18 correlative SNPs are in 2 distinct haplotype blocks. In summary, we identified a cluster of intronic VWF SNPs that associate with plasma levels of VWF, individually or additively, in a large cohort of healthy subjects.
Importance of Expert Central Review in the Diagnosis of Lymphoid Malignancies in a Regional Cancer Network
Authors: Proctor Ian E. , McNamara Christopher , Rodriguez-Justo Manuel , Isaacson Peter G. , Ramsay Alan 
Published: February 2011

Purpose The accurate diagnosis of hematologic malignancies remains a challenging area for histopathologists. In 2003, the North Central London Lymphoma network was established to provide a centralized expert review service for general histopathologists based in peripheral nonspecialist hospitals. By studying samples sent for review, we sought to assess the diagnostic and clinical impact of centralized expert review in lymphoma diagnosis. Methods A total of 1,949 patient samples were subject to expert review between 2003 and 2008. Diagnostic discordance rates were identified after expert review, and the impact on patient management was assessed by a hematologic oncology specialist. Results An overall discordance rate of 27.3% was identified. Among the 10 most commonly referred lymphoid malignancies, the discordance rate varied between 3.6% and 34.1%. A small but significant number of reactive (n = 17) and malignant (n = 5) discordant diagnoses were also identified. Expert central review resulted in a major change to patient management in 2.1% of patients and prevented delays in treatment in 9.3% of patients. During the 6-year study, the discordance rate improved significantly, decreasing from 32% to 13%. Although centralized review incurred additional costs, these were relatively small compared with the costs associated with treatment. Conclusion This retrospective study demonstrates the importance of expert central review in the accurate diagnosis and timely management of lymphoid malignancies. Furthermore, it shows that where full centralization of services is not viable, a network comprising nonspecialist hospitals linked to a center providing expert review is a practical alternative to full unification of services at a single location and can help prevent local deskilling.
Efficient Synthesis of a Bisglycosyl Kaempferol from Fagonia taeckholmiana
Authors: Liu Qingchao , Li Wenhong , Guo Tiantian , Li Dong , Fan Zhen , Yan Suihong 
Published: February 2011

Abstract
The first total synthesis of kaempferol-3-O-β-l-arabinopyranosyl-(1→4)-α-l-rhamnopyranoside-7-O-α-l-rhamnopyranoside (1), a 3,7-triglycosylflavone, which was isolated from the aerial parts of Fagonia taeckholmiana, was accomplished in 13 steps and 9.2% overall yield from commercially available kaempferol. We efficiently employed phase-transfer-catalyzed (PTC) glycosylation for the construction of phenol glycosides. Applying this approach will allow the preparation of derivatives for further study of structure–activity relationships (SAR).
α-Synuclein in Parkinson disease and other neurodegenerative disorders
Authors: Eller Michael , Williams David R. 
Published: February 2011

Abstract
With the aging population in the Western hemisphere, neurodegenerative parkinsonism and dementia will become two of the great public health challenges of this century. A major pillar in the effort to treat these conditions will be the shift from symptomatic treatment to disease modifying therapy. This step will absolutely require cheap and reliable biomarkers; patients will need to be diagnosed before irreversible change has occurred. α-Synuclein (αS) is a recent candidate biomarker for Lewy body neurodegeneration. It is a 140 amino acid protein that forms the pathological substrate in idiopathic Parkinson's disease (IPD), dementia with Lewy bodies (DLB), as well as multiple system atrophy (MSA), a group of disorders collectively known as the synucleopathies. Biomarker research has investigated αS in blood, skin and cerebrospinal fluid (CSF). Plasma assays have demonstrated inconsistent results but CSF assays show a higher degree of uniformity, mostly demonstrating lower levels of αS in patients with Lewy body disease compared to controls. These results are not yet accurate or reliable enough to use as screening tools or isolated diagnostic tests in established disease. It has become clear that factors other than neurodegeneration affect αS concentrations in these tissue samples, such as genetic and environmental influences. Future studies using standardized techniques and larger patient numbers are awaited to realise the full potential of αS as a more definitive diagnostic biomarker.
Tau and p-tau as CSF biomarkers in dementia: a meta-analysis
Authors: van Harten Argonde C. , Kester Maartje I. , Visser Pieter-Jelle , Blankenstein Marinus A. , Pijnenburg Yolande A.L. , van der Flier Wiesje M. , Scheltens Philip 
Published: February 2011

Abstract

Background: To evaluate the value of total tau (tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) in the differential diagnosis of dementia, more specifically: dementia with Lewy Bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD), and Creutzfeldt-Jacob disease (CJD).

Methods: A systematic literature search was performed to identify studies on tau and p-tau in DLB, FTLD, VaD and CJD. Tau concentrations were compared to healthy controls and to subjects with Alzheimer's disease (AD) using random effect meta-analysis. Outcome measures were Cohen's delta, sensitivity and specificity.

Results: Compared to controls, tau concentrations are moderately elevated in DLB, FTLD and VaD, while p-tau concentrations are only slightly elevated in DLB and not elevated in FTLD and VaD. Compared to AD, lower tau concentrations differentiated DLB with a sensitivity of 73% and a specificity of 90%, FTLD with sensitivity and specificity of 74%, and VaD with a sensitivity of 73% and a specificity of 86%. Relative to AD, lower p-tau values differentiated FTLD with a sensitivity of 79% and specificity of 83%, and VaD with a sensitivity of 88% and a specificity of 78%. CJD is characterized by extremely elevated tau concentrations with a sensitivity of 91% and a specificity of 98% vs. AD.

Conclusions: CSF tau concentrations in DLB, FTLD and VaD are intermediate between controls and AD patients. Overlap with both controls and AD patients results in insufficient diagnostic accuracy, and the development of more specific biomarkers for these disorders is needed. CJD is characterized by extremely increased tau values, resulting in a sensitivity and specificity that exceeds 90%.
On the core width and Peierls stress of bubble rafts dislocations within the framework of modified Peierls-Nabarro model
Authors: Wu Xiaozhi , Liu Lili , Wang Rui , Ji Na 
Published: February 2011

Abstract
Using Foreman’s method, the core structure and Peierls stress of dislocations in bubble rafts have been investigated within the framework of the modified Peierls-Nabarro (P-N) model in which the discrete lattice effect is taken into account. The core width obtained from the modified P-N model is much wider than that from the P-N model owing to the discrete lattice effect. It is found that the core width of dislocation increases with a decrease of the bubble radius. The elastic strain energy associated with the discrete effect is considered while calculating the Peierls stress. The new expression of the Peierls stress obtained in this paper is not explicitly dependent on the particular form of the restoring force law, which is only related to the core structure parameter and can be used expediently to predict the Peierls stress of dislocations. The Peierls stress decreases rapidly with the decrease of the bubble radius.
Improved and isotropic resolution in tomographic diffractive microscopy combining sample and illumination rotation
Authors: Vertu Stanislas , Flügge Jens , Delaunay Jean-Jacques , Haeberlé Olivier 
Published: February 2011

Abstract
Tomographic Diffractive Microscopy is a technique, which permits to image transparent living specimens in three dimensions without staining. It is commonly implemented in two configurations, by either rotating the sample illumination keeping the specimen fixed, or by rotating the sample using a fixed illumination. Under the first-order Born approximation, the volume of the frequency domain that can be mapped with the rotating illumination method has the shape of a “doughnut”, which exhibits a so-called “missing cone” of non-captured frequencies, responsible for the strong resolution anisotropy characteristic of transmission microscopes. When rotating the sample, the resolution is almost isotropic, but the set of captured frequencies still exhibits a missing part, the shape of which resembles that of an apple core. Furthermore, its maximal extension is reduced compared to tomography with rotating illumination. We propose various configurations for tomographic diffractive microscopy, which combine both approaches, and aim at obtaining a high and isotropic resolution. We illustrate with simulations the expected imaging performances of these configurations.
Quantitative evaluation of movement and strength of the upper limb after transection of the C-7 nerve: is it possible in an animal model?
Authors: Wang Huan , Spinner Robert J. , Windebank Anthony J. 
Published: February 2011

Object
Contralateral C-7 nerve transfer has been used clinically for more than 20 years. The increased interest in studies of transfer effectiveness at different target muscles, posttransfer cocontraction, and brain plasticity has prompted the need for an animal model. In addition to the conventional electrophysiological, histomorphometric, and biomechanical evaluation modalities, quantitative functional and behavioral evaluation will be crucial in applying this kind of model. The aim of this study was to establish a C-7 transection animal model and quantify the changes in upper-limb joint movement and muscle power.

Methods
A C-7 nerve transection model was created in Sprague-Dawley rats, the brachial plexus of which resembles the human brachial plexus. The impact of C-7 transection on donor limb function—namely, strength, movement, and coordination—was evaluated in 6 rats. Muscle strength (power reported in g) was measured as a grasping task. The active range of motion (ROM; angle reported in °) of the elbow, wrist, and metacarpophalangeal joints was quantified by computerized video motion analysis. Antiresistance coordinated movement (speed reported in seconds) was assessed by the vertical rope-climbing test. These tests were carried out before surgery and at 2, 4, 6, 8, 10, 14, 21, and 28 days after C-7 transection. Repeated-measures 1-way analysis of variance was applied for statistical analysis. When the overall probability value was < 0.05, the Dunnett multiple-comparison posttest was used to compare postoperative values with preoperative baseline values.

Results
Immediately after C-7 transection, the mean ± SD grip strength declined from 378.50 ± 20.55 g to 297.77 ± 15.04 g. Active elbow extension was impaired, as shown by a significant decrease of the elbow extension angle. The speed of vertical rope climbing was also reduced. Elbow flexion, wrist flexion and extension, and metacarpophalangeal joint flexion and extension were not impaired. Fast recovery of motor function was observed thereafter. Grip strength, range of active elbow extension, and speed of rope climbing returned to baseline values at postoperative Days 4, 8, and 8, respectively.

Conclusions
The ROM and muscle strength of the upper limb in rats can be measured quantitatively in studies that simulate clinical situations. Application of these functional evaluation modalities in a C-7 nerve transection rat model confirmed that transection of C-7 causes only temporary functional dysfunction to the donor limb. The results obtained in this animal model mimic those seen in humans who undergo contralateral C-7 nerve harvesting.
Biomechanical rigidity of cadaveric cervical spine with posterior versus combined posterior and anterior instrumentation
Authors: Dahdaleh Nader S. , Nakamura Satoshi , Torner James C. , Lim Tae-Hong , Hitchon Patrick W. 
Published: February 2011

Object
In patients with cervical stenosis with myelopathy, posterior instrumentation following cervical laminectomy has been shown to reduce the incidence of postoperative instability and kyphosis. However, the indications for posterior plus anterior instrumentation are not always obvious, and using both posterior and anterior instrumentation routinely is unnecessary and excessive. This study examines the rigidity of the intact isolated cadaveric cervical spine, after C4–6 laminectomy, with posterior lateral mass instrumentation, and following posterior plus anterior instrumentation.

Methods
Ten fresh-frozen human cadaveric cervical spines from C-1 to T-2 were potted in the neutral position, and retroreflective markers were placed on C-3 and C-7. Specimens were mounted on a biomechanical testing frame, and angular rotations of C-3 relative to C-7 were measured. Pure moments of 0, 0.3, 0.6, 0.9, and 1.2 Nm were applied at C-2 in all 3 planes. Each specimen was load tested as follows: 1) in the intact state; 2) after C4–6 laminectomy; 3) with C3–7 lateral mass instrumentation; and 4) with C3–7 posterior plus anterior instrumentation.

Results
Laminectomy was not associated with a significant increase in motion compared with the intact state with any load or in any direction. Instrumentation was associated with reduction in motion in all directions, and there was no significant difference in posterior versus combined posterior and anterior instrumentation.

Conclusions
Rigidity imparted to the cervical spine by a 5-level posterior lateral mass fixation is not augmented by anterior instrumentation.