bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sauropod dinosaur research: a historical review
Authors: Taylor Michael P. 
Published: October 2010

Abstract

In the 169 years since Owen named a tooth as
Cardiodon
, the study of sauropod dinosaurs has gone through several distinct periods. In the early years, a sequence of descriptions of isolated skeletal elements gave rise to a gradually emerging understanding of the animals that would later be known as sauropods. The second phase began in 1871 with Phillips's description of
Cetiosaurus oxoniensis
, the first reasonably complete sauropod, and continued with the Marsh-Cope Bone Wars and the description of the nearly complete sauropods
Camarasaurus
and ‘
Brontosaurus
’ (=
Apatosaurus
). As these and other genera became better known, a third phase began, exploring not just the remains but the lives of these giants, with arguments about posture and habitat to the fore, and with the public becoming increasingly aware of sauropods owing to skeletal mounts. A ‘dark age’ followed during and after World War II, with sauropods considered uninteresting evolutionary dead ends and largely ignored. This was brought to an end by the ‘dinosaur renaissance’ that began in the late 1960s, since when work has recommenced with new vigour, and the public has been introduced to a more vigorous and terrestrial image of sauropods through film and television. Both diversity and disparity of sauropods continue to increase through new descriptive work, and the group is now seen as more fascinating and worthy of study than ever before.
‘Old bones, dry subject’: the dinosaurs and pterosaur collected by Alfred Nicholson Leeds of Peterborough, England
Authors: Noè Leslie F. , Liston Jeff J. , Chapman Sandra D. 
Published: October 2010

Abstract
Alfred Nicholson Leeds, F.G.S., amassed one of the largest collections of fossil vertebrates from a single geological horizon anywhere in the world. The Leeds Collection is world famous for its large marine reptiles, but also includes the remains of a fine range of dinosaurs and a fragmentary pterosaur. The Leeds Collection ornithodirans were almost exclusively recovered from the Peterborough Member of the Oxford Clay Formation, with a single specimen of a sauropod derived from the underlying Kellaways Formation. The Leeds Collection includes the remains of at least 12 individual dinosaurs representing at least eight taxa (with other remains currently generically indeterminate) and a single fragmentary rhamphorhynchid pterosaur. Perhaps most intriguingly of all, in 1898 Alfred Leeds discovered a probable reptile egg, later attributed to a dinosaur. Each dinosaur and the pterosaur from the Leeds Collection is discussed, and, where known, details of the provenance, a brief history of research and pertinent archive material are included to provide the most comprehensive and up-to-date survey of the Leeds Collection ornithodirans to date.
Identification of Predictive Markers of Response to the MEK1/2 Inhibitor Selumetinib (AZD6244) in K-ras–Mutated Colorectal Cancer
Authors: Tentler John J. , Nallapareddy Sujatha , Tan Aik Choon , Spreafico Anna , Pitts Todd M. , Morelli M. Pia , Selby Heather M. , Kachaeva Maria I. , Flanigan Sara A. , Kulikowski Gillian N. , Leong Stephen , Arcaroli John J. , Messersmith Wells A. , Eckhardt S. Gail 
Published: October 2010

Abstract
Mutant K-ras activity leads to the activation of the RAS/RAF/MEK/ERK pathway in approximately 44% of colorectal cancer (CRC) tumors. Accordingly, several inhibitors of the MEK pathway are under clinical evaluation in several malignancies including CRC. The aim of this study was to develop and characterize predictive biomarkers of response to the MEK1/2 inhibitor AZD6244 in CRC in order to maximize the clinical utility of this agent. Twenty-seven human CRC cell lines were exposed to AZD6244 and classified according to the IC50 value as sensitive (≤0.1 μmol/L) or resistant (&gt;1 μmol/L). All cell lines were subjected to immunoblotting for effector proteins, K-ras/BRAF mutation status, and baseline gene array analysis. Further testing was done in cell line xenografts and K-ras mutant CRC human explants models to develop a predictive genomic classifier for AZD6244. The most sensitive and resistant cell lines were subjected to differential gene array and pathway analyses. Members of the Wnt signaling pathway were highly overexpressed in cell lines resistant to AZD6244 and seem to be functionally involved in mediating resistance by shRNA knockdown studies. Baseline gene array data from CRC cell lines and xenografts were used to develop a k-top scoring pair (k-TSP) classifier, which predicted with 71% accuracy which of a test set of patient-derived K-ras mutant CRC explants would respond to AZD6244, providing the basis for a patient-selective clinical trial. These results also indicate that resistance to AZD6244 may be mediated, in part, by the upregulation of the Wnt pathway, suggesting potential rational combination partners for AZD6244 in CRC. Mol Cancer Ther; 9(12); 3351–62. ©2010 AACR.
Development and Validation of Risk Adjustment Models for Long-Term Mortality and Myocardial Infarction Following Percutaneous Coronary Interventions
Authors: Singh Mandeep , Holmes David R. , Lennon Ryan J. , Rihal Charanjit S. 
Published: October 2010

Background—
Existing models for outcome after percutaneous coronary interventions (PCIs) lack assessment of long-term prognosis. Our goal was to derive 1- and 5-year mortality and mortality/myocardial infarction (MI) risk models for PCI outcomes from simple, easily obtainable clinical and laboratory variables.

Methods and Results—
Using the Mayo Clinic registry, we analyzed long-term mortality and mortality/MI following PCIs on 9165 unique patients from January 1, 2001, through December 31, 2007. Cox proportional hazards regression was used to model the calculated risk score and major procedural complications. A total of 1243 patients died, and 696 had MI. Separate risk models derived from clinical, procedural, and laboratory characteristics were made for mortality and mortality/MI. Older age, comorbid conditions, low ejection fraction, acute MI, history of smoking, heart failure, hyperlipidemia, 3-vessel disease, procedural failure, ventricular arrhythmia during PCI, and low medication score were predictors of long-term mortality and mortality/MI. Simple integer scores stratified patients into low, moderate, high, and very high risk for subsequent events. Models had adequate goodness of fit, and areas under the receiver operating characteristic curve were 0.786 and 0.728 for mortality and mortality/MI, respectively, indicating good overall discrimination. Bootstrap analysis indicated that the model was not overfit to the available data set.

Conclusions—
Easily obtainable variables can be combined into a convenient risk scoring system at the time of patient dismissal following PCI to accurately predict long-term mortality and mortality/MI. This model may be useful for providing patients with individualized, evidence-based estimates of long-term risk.
Prognostic Value of Isolated Troponin I Elevation After Percutaneous Coronary Intervention
Authors: Cavallini Claudio , Verdecchia Paolo , Savonitto Stefano , Arraiz Gustavo , Violini Roberto , Olivari Zoran , Rubartelli Paolo , De Servi Stefano , Plebani Mario , Steffenino Giuseppe , Sbarzaglia Paolo , Ardissino Diego ,   on behalf of the Italian “Atherosclerosis, Thrombosis and Vascular Biology” and “Society for Invasive Cardiology–GISE” Investigators
Published: October 2010

Background—
Mild elevations of cardiac troponin are frequent after percutaneous coronary intervention (PCI). Their prognostic value is uncertain in the absence of changes in creatine kinase-MB (CK-MB).

Methods and Results—

We evaluated the relation between isolated elevations of cardiac troponin I (cTnI) and all-cause mortality. We studied 3494 consecutive patients who underwent PCI in 16 Italian tertiary cardiology centers. CK-MB and cTnI were analyzed in a central laboratory. Duration of follow-up was 2 years. The present analysis was restricted to 2362 patients with normal CK-MB and cTnI values at baseline and no CK-MB elevation after PCI. A rise in cTnI after PCI >0.15 ng/mL, the upper reference limit, was found in 932 patients (39.4%). A rise >0.45 ng/mL (>3×upper reference limit) was found in 467 patients (19.7%). Compared with patients with normal cTnI, those with cTnI elevation >0.15 ng/mL showed a slightly increased mortality (3.8% versus 2.6%; hazard ratio, 1.53; 95% confidence interval, 0.97 to 2.42;
P
=0.069). A cTnI elevation >0.45 ng/mL was associated with a higher risk of mortality (4.5% versus 2.7%; hazard ratio, 1.68; 95% confidence interval, 1.01 to 2.80;
P
=0.044), which, however, did not remain significant after adjustment for concomitant risk factors (hazard ratio, 1.45; 95% confidence interval, 0.86 to 2.46;
P
=0.162). Postprocedural cTnI elevation was associated with coronary and clinical features consistent with a worse risk profile.

Conclusions—
In the absence of a rise in CK-MB, elevated cTnI levels after PCI are associated with a modest increased risk of death. However, this is not independent of the concomitant adverse baseline clinical characteristics of these patients.
Utilization of Secondary Prevention Therapies in Patients With Nonobstructive Coronary Artery Disease Identified During Cardiac Catheterization
Authors: Maddox Thomas M. , Ho P. Michael , Roe Matthew , Dai David , Tsai Thomas T. , Rumsfeld John S. 
Published: October 2010

Background—
Secondary prevention therapies are indicated for patients with coronary artery disease (CAD). However, patients with nonobstructive CAD may be less likely to receive these therapies compared with patients with obstructive CAD. Therefore, we compared rates of secondary prevention medication prescription between patients with nonobstructive and obstructive CAD.

Methods and Results—
We conducted a retrospective cohort study of 1 489 745 CAD patients undergoing cardiac catheterization in 786 US centers between 2004 and 2007. We measured rates of aspirin, statin, β-blocker, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) prescription at hospital discharge among eligible patients; 237 167 (15.9%) patients had nonobstructive CAD and 1 252 578 (84.1%) had obstructive CAD. Compared with obstructive CAD patients, nonobstructive CAD patients had significantly lower rates of rates of aspirin (72.7% versus 90.9%), statin (60.0% versus 80.3%), β-blocker (57.9% versus 79.4%), and ACEI/ARB (45.9% versus 58.6%; all probability values <0.0001) prescription at hospital discharge. After multivariable adjustment, nonobstructive CAD patients remained significantly less likely to receive prescriptions for aspirin (odds ratio, 0.37; 95% confidence interval, 0.35 to 0.39), statins (odds ratio, 0.45; 95% confidence interval, 0.43 to 0.48), β-blockers (odds ratio, 0.46; 95% CI, 0.44 to 0.47), or ACEI/ARBs (odds ratio, 0.83; 95% confidence interval, 0.8 to 0.86) compared with obstructive CAD patients. Secondary analyses of selected subgroups supported the primary findings.

Conclusions—
Patients with nonobstructive CAD were significantly less likely to receive secondary prevention medication prescription at hospital discharge, as compared with patients with obstructive CAD. These findings highlight an opportunity to improve the quality of care for CAD patients with nonobstructive disease.
The Impact of Hospital Cardiac Specialization on Outcomes After Coronary Artery Bypass Graft Surgery
Authors: Girotra Saket , Lu Xin , Popescu Ioana , Vaughan-Sarrazin Mary , Horwitz Phillip A. , Cram Peter 
Published: October 2010

Background—
Hospital volume has been widely embraced as a proxy measure for hospital quality; little attention has been focused on an alternative quality measure–hospital specialization. Even though specialization occurs on a continuum, previous studies have only focused on a small number of highly specialized hospitals (single-specialty hospitals). Studies on the broad relationship between hospital specialization and outcomes after coronary artery bypass grafting (CABG) are limited.

Methods and Results—

We conducted a retrospective cohort study of 705 084 Medicare patients (1130 hospitals) who underwent CABG during 2001 to 2005. We stratified hospitals into quintiles, based on their degree of cardiac specialization (proportion of a hospital's Medicare discharges classified as Major Diagnostic Category 5–cardiovascular diseases). We compared patient and hospital characteristics and outcomes across quintiles of cardiac specialization. Patient characteristics were generally similar across quintiles, but mean annual CABG volume increased progressively from quintile 1 (least specialized) to quintile 5 (most specialized). Unadjusted 30-day mortality was similar at hospitals in quintiles 1 to 4 (4.8%), except quintile 5, where mortality was lower (4.3%). A strong inverse association was seen between hospital cardiac specialization and 30-day mortality after adjustment for patient characteristics (
P
trend
=0.001). However, this was no longer significant after additional adjustment for CABG volume (
P
trend
=0.65). Results were similar for other mortality outcomes and length of stay.

Conclusions—
After accounting for patient characteristics and CABG volume, greater cardiac specialization was not associated with clinically significant improvement in patient outcomes. This study calls into question the benefit of cardiac specialization for the vast majority of CABG-performing US hospitals.
Patients' Perspectives of a Multifaceted Intervention With a Focus on Technology
Authors: Lambert-Kerzner Anne , Havranek Edward P. , Plomondon Mary E. , Albright Karen , Moore Ashley , Gryniewicz Kelsey , Magid David , Ho P. Michael 
Published: October 2010

Background—
Few studies have investigated the effectiveness of multifaceted interventions from the study participants' perspective. We conducted qualitative interviews to understand patients' experiences with a multifaceted blood pressure (BP) control intervention involving interactive voice response technology, home BP monitoring, and pharmacist-led BP management. In the randomized study, the intervention resulted in clinically significant decreases in BP.

Methods and Results—
We used insights generated from in-depth interviews from all study participants randomly assigned to the multifaceted intervention or usual care (n=146) to create a model explaining the observed improvements in health behavior and clinical outcomes. The data were analyzed using qualitative content analysis methods and consultative and reflexive team analysis. Six explanatory factors emerged from the patients' interviews: (1) improved relationships with medical personnel; (2) increased knowledge of hypertension; (3) increased participation in their health care and personal empowerment; (4) greater understanding of the impact of health behavior on BP; (5) high satisfaction with technology used in the intervention; and, for some patients, (6) increased health care utilization. Eighty-six percent of the intervention patients and 62% of the usual care patients stated that study participation had a positive effect on them. Of those expressing a positive effect, 68% (intervention) and 55% (usual care) reached their systolic BP goal.

Conclusions—
Establishing bidirectional conversations between patients and providers is a key element of successful hypertension management. Home BP monitoring coupled with interactive voice response technology reporting facilitates such conversations.
Talin1 is required for integrin-dependent B lymphocyte homing to lymph nodes and the bone marrow but not for follicular B-cell maturation in the spleen
Authors: Manevich-Mendelson Eugenia , Grabovsky Valentin , Feigelson Sara W. , Cinamon Guy , Gore Yael , Goverse Gera , Monkley Susan J. , Margalit Raanan , Melamed Doron , Mebius Reina E. , Critchley David R. , Shachar Idit , Alon Ronen 
Published: October 2010

AbstractTalin1 is a key integrin coactivator. We investigated the roles of this cytoskeletal adaptor and its target integrins in B-cell lymphogenesis, differentiation, migration, and function. Using CD19 Cre-mediated depletion of talin1 selectively in B cells, we found that talin1 was not required for B-cell generation in the bone marrow or for the entry of immature B cells to the white pulp of the spleen. Loss of talin1 also did not affect B-cell maturation into follicular B cells but compromised differentiation of marginal zone B cells. Nevertheless, serum IgM and IgG levels remained normal. Ex vivo analysis of talin1-deficient spleen B cells indicated a necessary role for talin1 in LFA-1 and VLA-4 activation stimulated by canonical agonists, but not in B-cell chemotaxis. Consequently, talin1 null B splenocytes could not enter lymph nodes nor return to the bone marrow. Talin1 deficiency in B cells was also impaired in the humoral response to a T cell-dependent antigen. Collectively, these results indicate that talin1 is not required for follicular B-cell maturation in the spleen or homeostatic humoral immunity but is critical for integrin-dependent B lymphocyte emigration to lymph nodes and optimal immunity against T-dependent antigens.
Evaluation of endogenous references for gene expression profiling in different tissues of the oriental fruit fly Bactrocera dorsalis (Diptera: Tephritidae)
Authors: Shen Guang-Mao , Jiang Hong-Bo , Wang Xiao-Na , Wang Jin-Jun 
Published: October 2010

Abstract
Background
Quantitative real-time reverse transcriptase PCR (RT-qPCR) has been widely used for quantification of mRNA as a way to determine key genes involved in different biological processes. For accurate gene quantification analysis, normalization of RT-qPCR data is absolutely essential. To date, normalization is most frequently achieved by the use of internal controls, often referred to as reference genes. However, several studies have shown that the reference genes used for the quantification of mRNA expression can be affected by the experimental set-up or cell type resulting in variation of the expression level of these key genes. Therefore, the evaluation of reference genes is critical for gene expression profiling, which is often neglected in gene expression studies of insects. For this purpose, ten candidate reference genes were investigated in three different tissues (midgut, Malpighian tubules, and fat body) of the oriental fruit fly, Bactrocera dorsalis (Hendel).

Results
Two different programs, geNorm and Normfinder, were used to analyze the data. According to geNorm, α-TUB + ACT5 are the most appropriate reference genes for gene expression profiling across the three different tissues in the female flies, while ACT3 + α-TUB are considered as the best for males. Furthermore, we evaluated the stability of the candidate reference genes to determine the sexual differences in the same tissue. In the midgut and Malpighian tubules, ACT2 + α-TUB are the best choice for both males and females. However, α-TUB + ACT1 are the best pair for fat body. Meanwhile, the results calculated by Normfinder are quite the same as the results with geNorm; α-TUB is always one of the most stable genes in each sample validated by the two programs.

Conclusions
In this study, we validated the suitable reference genes for gene expression profiling in different tissues of B. dorsalis. Moreover, appropriate reference genes were selected out for gene expression profiling of the same tissues taking the sexual differences into consideration. This work not only formed a solid basis for future gene expression study in B. dorsalis, but also will serve as a resource to screen reference genes for gene expression studies in any other insects.
Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma
Authors: Taniguchi Kazuya , Yamada Terumasa , Sasaki Yo , Kato Kikuya 
Published: October 2010

Abstract

Background
Multiple carcinogenesis is one of the major characteristics of human hepatocellular carcinoma (HCC). The history of multiple tumors, that is, whether they derive from a common precancerous or cancerous ancestor or individually from hepatocytes, is a major clinical issue. Multiple HCC is clinically classified as either intratumor metastasis (IM) or multicentric carcinogenesis (MC). Molecular markers that differentiate IM and MC are of interest to clinical practitioners because the clinical diagnoses of IM and MC often lead to different therapies.

Methods
We analyzed 30 multiple tumors from 15 patients for somatic mutations of cancer-related genes, chromosomal aberrations, and promoter methylation of tumor suppressor genes using techniques such as high-resolution melting, array-comparative genomic hybridization (CGH), and quantitative methylation-specific PCR.

Results
Somatic mutations were found in TP53 and CTNNB1 but not in CDKN2A or KRAS. Tumors from the same patient did not share the same mutations. Array-CGH analysis revealed variations in the number of chromosomal aberrations, and the detection of common aberrations in tumors from the same patient was found to depend on the total number of chromosomal aberrations. A promoter methylation analysis of genes revealed dense methylation in HCC but not in the adjacent non-tumor tissue. The correlation coefficients (r) of methylation patterns between tumors from the same patient were more similar than those between tumors from different patients. In total, 47% of tumor samples from the same patients had an r ≥ 0.8, whereas, in contrast, only 18% of tumor samples from different patients had an r ≥ 0.8 (p = 0.01). All IM cases were highly similar; that is, r ≥ 0.8 (p = 0.025).

Conclusions
The overall scarcity of common somatic mutations and chromosomal aberrations suggests that biological IM is likely to be rare. Tumors from the same patient had a methylation pattern that was more similar than those from different patients. As all clinical IM cases exhibited high similarity, the methylation pattern may be applicable to support the clinical diagnosis of IM and MC.