bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the Yield of Phase II Combination Therapy Trials in Medical Oncology
Authors: Maitland Michael L. , Hudoba Christine , Snider Kelly L. , Ratain Mark J. 
Published: September 2010

Abstract
Purpose: Phase II clinical studies screen for treatment regimens that improve patient care, but screening combination regimens is especially challenging. We hypothesized that recognized flaws of single-arm trials could be magnified in combination treatment studies, leading to many reported positive phase II trials but with a low fraction resulting in practice-changing phase III trials.
Experimental Design: We searched medline and identified 363 combination chemotherapy clinical trials published in 2001 and 2002. Studies were rated as positive, negative, or inconclusive based on a standardized review of abstract and text. The Web of Science Index (Thomson Reuters, NY, NY) was searched for all articles published between January 2003 and October 2007 that cited at least one of these 363 published trials.
Results: Of 363 published phase II combination chemotherapy trials, 262 (72%) were declared to be positive. Among 3,760 unique subsequent citing papers, 20 reported randomized phase III trials of the same combination in the same disease as the source paper, and 10 of these resulted in improved standards of care. Estimating from these data, the likelihood that a published, positive phase II combination chemotherapy trial will result in a subsequent trial showing an improvement in standard of care within five years was 0.038 (95% confidence interval, 0.016-0.064).
Conclusions: The contributory value of combination chemotherapy phase II trials done by 2001-2002 standards is low despite the participation of more than 16,000 subjects. Future phase II studies of combination regimens require better methods to screen for treatments most likely to improve standards of care. Clin Cancer Res; 16(21); 5296–302. ©2010 AACR.
Early Impairment of Transmural Principal Strains in the Left Ventricular Wall After Short-Term, High-Fat Feeding of Mice Predisposed to Cardiac Steatosis
Authors: Hankiewicz Janusz H. , Banke Natasha H. , Farjah Mariam , Lewandowski E. Douglas 
Published: September 2010

Background—
Myocardial lipid accumulation precedes some cardiomyopathies, but little is known of concurrent effects on ventricular mechanics. We tested the hypothesis that intramyocardial lipid accumulation during a short-term, high-fat diet (HFD) affects 2-dimensional strains in the heart. We examined the hearts of nontransgenic (NTG) mice and of transgenic mice predisposed to elevated triacylglyceride (TAG) storage linked to low-level overexpression of peroxisome proliferator activated receptor (PPAR-α).

Methods and Results—

Myocardial lipid and transmural principal strains E1 and E2 were determined in vivo with
1
H magnetic resonance spectroscopy/imaging before and after 2 weeks of an HFD in both PPAR-α and NTG littermate mice. Baseline lipid was elevated in PPAR-α compared with NTG mice. An HFD increased mobile lipid by 174% in NTG mice (
P
<0.05) and by 79% in PPAR-α mice (
P
<0.05). After an HFD, lipid and TAG were higher in PPAR-α versus NTG mice by 63% and 81%, respectively. However, TAG in PPAR-α mice after an HFD was similar to TAG in PPAR-α mice fed a regular diet, suggesting that the magnetic resonance spectroscopy signal from lipid is not exclusive to TAG. Only at the highest lipid contents, achieved in PPAR-α mice, were strains affected. Endocardial strain was most compromised, with a negative correlation to lipid (
P
<0.05).

Conclusions—
A short-term HFD elevated myocardial lipid measures as determined by magnetic resonance spectroscopy, which became dissociated from TAG content in hearts predisposed to cardiac steatosis. The increased lipid was associated with concurrent, transmural reductions in E1 and E2 strains across the left ventricular wall. Strains were attenuated at the highest levels of lipid accumulation, suggesting a threshold response. Thus, 2-dimensional strains are impaired early and without left ventricular diastolic dysfunction, owing to cardiac steatosis.
Long-Term Recording of Cardiac Arrhythmias With an Implantable Cardiac Monitor in Patients With Reduced Ejection Fraction After Acute Myocardial Infarction
Authors: Bloch Thomsen Poul Erik , Jons Christian , Raatikainen M.J. Pekka , Moerch Joergensen Rikke , Hartikainen Juha , Virtanen Vesa , Boland J. , Anttonen Olli , Gang Uffe Jakob , Hoest Nis , Boersma Lucas V.A. , Platou Eivin S. , Becker Daniel , Messier Marc D. , Huikuri Heikki V. ,   for the Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) Study Group
Published: September 2010

Background—
Knowledge about the incidence of cardiac arrhythmias after acute myocardial infarction has been limited by the lack of traditional ECG recording systems to document and confirm asymptomatic and symptomatic arrhythmias. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction (CARISMA) trial was designed to study the incidence and prognostic significance of arrhythmias documented by an implantable cardiac monitor among patients with acute myocardial infarction and reduced left ventricular ejection fraction.

Methods and Results—

A total of 1393 of 5869 patients (24%) screened in the acute phase (3 to 21 days) of an acute myocardial infarction had left ventricular ejection fraction ≤40%. After exclusions, 297 patients (21%) (mean±SD age, 64.0±11.0 years; left ventricular ejection fraction, 31±7%) received an implantable cardiac monitor within 11±5 days of the acute myocardial infarction and were followed up every 3 months for an average of 1.9±0.5 years. Predefined bradyarrhythmias and tachyarrhythmias were recorded in 137 patients (46%); 86% of these were asymptomatic. The implantable cardiac monitor documented a 28% incidence of new-onset atrial fibrillation with fast ventricular response (≥125 bpm), a 13% incidence of nonsustained ventricular tachycardia (≥16 beats), a 10% incidence of high-degree atrioventricular block (≤30 bpm lasting ≥8 seconds), a 7% incidence of sinus bradycardia (≤30 bpm lasting ≥8 seconds), a 5% incidence of sinus arrest (≥5 seconds), a 3% incidence of sustained ventricular tachycardia, and a 3% incidence of ventricular fibrillation. Cox regression analysis with time-dependent covariates revealed that high-degree atrioventricular block was the most powerful predictor of cardiac death (hazard ratio, 6.75; 95% confidence interval, 2.55 to 17.84;
P
<0.001).

Conclusions—
This is the first study to report on long-term cardiac arrhythmias recorded by an implantable loop recorder in patients with left ventricular ejection fraction ≤40% after myocardial infarction. Clinically significant bradyarrhythmias and tachyarrhythmias were documented in a substantial proportion of patients with depressed left ventricular ejection fraction after acute myocardial infarction. Intermittent high-degree atrioventricular block was associated with a very high risk of cardiac death.

Clinical Trial Registration—

URL:
http://www.ClinicalTrials.gov
, Unique identifier: NCT00145119.
Volume-Outcome Relationships and Abdominal Aortic Aneurysm Repair
Authors: Landon Bruce E. , O'Malley A. James , Giles Kristina , Cotterill Philip , Schermerhorn Marc L. 
Published: September 2010

Background—
There is a well-established literature relating procedure volume to outcomes, but incorporating such information into clinical decision making is problematic when there is >1 treatment option for a condition.

Methods and Results—
We used data from the Medicare program to investigate the relationship between institutional volume for open and endovascular abdominal aortic aneurysm (AAA) repair and outcomes, examine trends in volume, and explore the implications for physicians making referrals for AAA repair. Trends in institutional volume were measured for the time period 2001–2006, whereas outcomes were assessed with the use of a previously assembled propensity score–matched cohort covering the time period 2001–2004. Between 2001 and 2006, there were a total of 230 736 repairs of either an intact or ruptured AAA for traditional Medicare beneficiaries. During this time, the proportion of endovascular cases increased from ≈22 in 2001 to >50 of AAA repairs in 2006, but there was little shift in procedure volume to high-volume institutions. For endovascular repair, adjusted mortality by quintile showed a marked decrease between the first and second quintile, with continued smaller decreases over quintiles 3 to 5. For open repair, adjusted mortality showed a steady decrease across the quintiles of volume.

Conclusions—
We found a steady increase in survival with increasing volume of open repair but relatively little improvement after reaching a relatively low threshold for endovascular repair. Because hospital experience with one repair method does not translate into improved outcomes for the alternative method, referring clinicians must consider both treatment options when making referral decisions.
Who Are the Long-QT Syndrome Patients Who Receive an Implantable Cardioverter-Defibrillator and What Happens to Them?
Authors: Schwartz Peter J. , Spazzolini Carla , Priori Silvia G. , Crotti Lia , Vicentini Alessandro , Landolina Maurizio , Gasparini Maurizio , Wilde Arthur A.M. , Knops Reinoud E. , Denjoy Isabelle , Toivonen Lauri , Mönnig Gerold , Al-Fayyadh Majid , Jordaens Luc , Borggrefe Martin , Holmgren Christina , Brugada Pedro , De Roy Luc , Hohnloser Stefan H. , Brink Paul A. 
Published: September 2010

Background—
A rapidly growing number of long-QT syndrome (LQTS) patients are being treated with an implantable cardioverter-defibrillator (ICD). ICDs may pose problems, especially in the young. We sought to determine the characteristics of the LQTS patients receiving an ICD, the indications, and the aftermath.

Methods and Results—
The study population included 233 patients. Beginning in 2002, data were collected prospectively. Female patients (77%) and LQT3 patients (22% of genotype positive) were overrepresented; mean QTc was 516±65 milliseconds; mean age at implantation was 30±17 years; and genotype was known in 59% of patients. Unexpectedly, 9% of patients were asymptomatic before implantation. Asymptomatic patients, almost absent among LQT1 and LQT2 patients, represented 45% of LQT3 patients. Patients with cardiac symptoms made up 91% of all study participants, but only 44% had cardiac arrest before ICD implantation. In addition, 41% of patients received an ICD without having first been on LQTS therapy. During follow-up, 4.6±3.2 years, at least 1 appropriate shock was received by 28% of patients, and adverse events occurred in 25%. Appropriate ICD therapies were predicted by age <20 years at implantation, a QTc >500 milliseconds, prior cardiac arrest, and cardiac events despite therapy; within 7 years, appropriate shocks occurred in no patients with none of these factors and in 70% of those with all factors.

Conclusions—
Reflecting previous concepts, ICDs were implanted in some LQTS patients whose high risk now appears questionable. Refined criteria for implantation, reassessment of pros and cons, ICD reprogramming, and consideration for other existing therapeutic options are necessary.
Homogeneity of Gridded Precipitation Datasets for the Colorado River Basin
Authors: Guentchev Galina , Barsugli Joseph J. , Eischeid Jon 
Published: September 2010

Abstract
Inhomogeneity in gridded meteorological data may arise from the inclusion of inhomogeneous station data or from aspects of the gridding procedure itself. However, the homogeneity of gridded datasets is rarely questioned, even though an analysis of trends or variability that uses inhomogeneous data could be misleading or even erroneous. Three gridded precipitation datasets that have been used in studies of the Upper Colorado River basin were tested for homogeneity in this study: that of Maurer et al., that of Beyene and Lettenmaier, and the Parameter–Elevation Regressions on Independent Slopes Model (PRISM) dataset of Daly et al. Four absolute homogeneity tests were applied to annual precipitation amounts on a grid cell and on a hydrologic subregion spatial scale for the periods 1950–99 and 1916–2006. The analysis detects breakpoints in 1977 and 1978 at many locations in all three datasets that may be due to an anomalously rapid shift in the Pacific decadal oscillation. One dataset showed breakpoints in the 1940s that might be due to the widespread change in the number of available observing stations used as input for that dataset. The results also indicated that the time series from the three datasets are sufficiently homogeneous for variability analysis during the 1950–99 period when aggregated on a subregional scale.
Variations of the East Asian Mei-Yu and Simulation and Prediction by the NCEP Climate Forecast System
Authors: Gao Hui , Yang Song , Kumar Arun , Hu Zeng-Zhen , Huang Bohua , Li Yueqing , Jha Bhaskar 
Published: September 2010

Abstract
The East Asian mei-yu (EAMY), which includes the mei-yu over eastern China, baiu over Japan, and changma over Korea, is an important component of the Asia summer monsoon system. The EAMY rain belt jumps northward to the Yangtze and Huaihe River valleys (in China), Japan, and Korea from mid-June to mid-July, with remarkable interannual variability. In this study, the variability and predictability of EAMY are investigated using the retrospective ensemble predictions of the NCEP Climate Forecast System (CFS). The CFS reasonably captures the centers, magnitude, northward jump, and other features of EAMY over most regions. It also reasonably simulates the interannual variations of EAMY and its main influencing factors such as the western Pacific subtropical high, the East Asian monsoon circulation, and El Niño–Southern Oscillation (ENSO). The CFS is skillful in predicting EAMY and related circulation patterns with a lead time of one month. An empirical orthogonal function analysis with maximized signal-to-noise ratio is applied to determine the most predictable patterns of EAMY. Furthermore, experiments in which the CFS is forced by observed sea surface temperature (SST) exhibit lower skill in EAMY simulation, suggesting the importance of ocean–atmosphere coupling in predicting EAMY.
The CFS, which exaggerates the precipitation over the southern–southeastern hills of the Tibetan Plateau, overestimates the relationship between EAMY and tropical–subtropical atmospheric circulation due to the overly strong ENSO signals in the model, whereas the experiments forced by observed SST produce a weaker relationship. On the contrary, the CFS underestimates the link of EAMY to higher-latitude processes. An increase in the horizontal resolution of the CFS is expected to reduce some of these errors.
Tularemia: Retrospective Review of 10 Years’ Experience in Arkansas
Authors: Snowden Jessica , Stovall Stephanie 
Published: September 2010

Purpose: The purpose of this study is to review all cases of tularemia, a tick-borne illness, among inpatients at Arkansas Children’s Hospital (ACH) from 1996-2006 to discuss clinical presentation, diagnosis and treatment. Records of the Infectious Disease Section were reviewed to identify cases of suspected or proven tularemia. Results: Seventeen patients presented with ulceroglandular tularemia and thirteen with glandular disease. Most patients had been ill for 10-14 days prior to admission and were evaluated at least once by another physician. Serology was positive in 77% of patients, including several positive on convalescent testing alone. Most patients responded well to treatment with gentamicin. Conclusions: This series emphasizes the importance of tularemia as an early consideration among children with fever and lymphadenopathy in Arkansas. Convalescent serology is an important tool, as many patients will remain seronegative early in illness. Gentamicin remains effective treatment and should be considered first-line therapy for suspected tularemia.
Genomic encyclopedia of sugar utilization pathways in the Shewanella genus
Authors: Rodionov Dmitry A , Yang Chen , Li Xiaoqing , Rodionova Irina A , Wang Yanbing , Obraztsova Anna Y , Zagnitko Olga P , Overbeek Ross , Romine Margaret F , Reed Samantha , Fredrickson James K , Nealson Kenneth H , Osterman Andrei L 
Published: September 2010

Abstract

Background
Carbohydrates are a primary source of carbon and energy for many bacteria. Accurate projection of known carbohydrate catabolic pathways across diverse bacteria with complete genomes constitutes a substantial challenge due to frequent variations in components of these pathways. To address a practically and fundamentally important challenge of reconstruction of carbohydrate utilization machinery in any microorganism directly from its genomic sequence, we combined a subsystems-based comparative genomic approach with experimental validation of selected bioinformatic predictions by a combination of biochemical, genetic and physiological experiments.

Results
We applied this integrated approach to systematically map carbohydrate utilization pathways in 19 genomes from the Shewanella genus. The obtained genomic encyclopedia of sugar utilization includes ~170 protein families (mostly metabolic enzymes, transporters and transcriptional regulators) spanning 17 distinct pathways with a mosaic distribution across Shewanella species providing insights into their ecophysiology and adaptive evolution. Phenotypic assays revealed a remarkable consistency between predicted and observed phenotype, an ability to utilize an individual sugar as a sole source of carbon and energy, over the entire matrix of tested strains and sugars.
Comparison of the reconstructed catabolic pathways with E. coli identified multiple differences that are manifested at various levels, from the presence or absence of certain sugar catabolic pathways, nonorthologous gene replacements and alternative biochemical routes to a different organization of transcription regulatory networks.

Conclusions
The reconstructed sugar catabolome in Shewanella spp includes 62 novel isofunctional families of enzymes, transporters, and regulators. In addition to improving our knowledge of genomics and functional organization of carbohydrate utilization in Shewanella, this study led to a substantial expansion of our current version of the Genomic Encyclopedia of Carbohydrate Utilization. A systematic and iterative application of this approach to multiple taxonomic groups of bacteria will further enhance it, creating a knowledge base adequate for the efficient analysis of any newly sequenced genome as well as of the emerging metagenomic data.
Identification of two Amino Acids in the C-terminal Domain of Mouse CRY2 Essential for PER2 Interaction
Authors: Ozber Natali , Baris Ibrahim , Tatlici Gulnaz , Gur Ibrahim , Kilinc Seda , Unal Evrim B , Kavakli Ibrahim H 
Published: September 2010

Abstract

Background
Cryptochromes (CRYs) are a class of flavoprotein blue-light signaling receptors found in plants and animals, and they control plant development and the entrainment of circadian rhythms. They also act as integral parts of the central circadian oscillator in humans and other animals. In mammals, the CLOCK-BMAL1 heterodimer activates transcription of the Per and Cry genes as well as clock-regulated genes. The PER2 proteins interact with CRY and CKIε, and the resulting ternary complexes translocate into the nucleus, where they negatively regulate the transcription of Per and Cry core clock genes and other clock-regulated output genes. Recent studies have indicated that the extended C-termini of the mammalian CRYs, as compared to photolyase proteins, interact with PER proteins.

Results
We identified a region on mCRY2 (between residues 493 and 512) responsible for direct physical interaction with mPER2 by mammalian two-hybrid and co-immunoprecipitation assays. Moreover, using oligonucleotide-based degenerate PCR, we discovered that mutation of Arg-501 and Lys-503 of mCRY2 within this C-terminal region totally abolishes interaction with PER2.

Conclusions
Our results identify mCRY2 amino acid residues that interact with the mPER2 binding region and suggest the potential for rational drug design to inhibit CRYs for specific therapeutic approaches.
Synergistic disruptions in seuss cyp85A2 double mutants reveal a role for brassinolide synthesis during gynoecium and ovule development
Authors: Nole-Wilson Staci , Rueschhoff Elizabeth E , Bhatti Huda , Franks Robert G 
Published: September 2010

Abstract

Background
The Arabidopsis SEUSS (SEU) gene encodes a transcriptional adaptor protein that is required for a diverse set of developmental events, including floral organ identity specification, as well as gynoecium, ovule and embryo development. In order to better understand the molecular mechanisms of SEUSS action we undertook a genetic modifier screen to identify seuss-modifier (sum) mutations.

Results
Screening of M2 lines representing approximately 5,000 M1 individuals identified mutations that enhance the seuss mutant phenotypic disruptions in ovules and gynoecia; here we describe the phenotype of the sum63 mutant and enhanced disruptions of ovule and gynoecial development in the seu sum63 double mutant. Mapping and genetic complementation tests indicate that sum63 is allelic to CYP85A2 (AT3G30180) a cytochrome p450 enzyme that catalyzes the final steps in the synthesis of the phytohormone brassinolide.

Conclusions
Our identification of mutations in CYP85A2 as enhancers of the seuss mutant phenotype suggests a previously unrecognized role for brassinolide synthesis in gynoecial and ovule outer integument development. The work also suggests that seuss mutants may be more sensitive to the loss or reduction of brassinolide synthesis than are wild type plants.
A case report of mesenteric mucinous cystoadenoma with review of the literature
Authors: Del Gobbo Alessandro , Bimbatti Manuela , Ferrero Stefano 
Published: September 2010

Abstract

Background
Few cases of primary retroperitoneal mucinous cystoadenoma, a rare benign tumor, have been reported in the literature so far. The pathogenesis of this tumour is not completely understood yet.
Our case is particularly significant since the localization in the mesentery has been described only once before in the literature. Unless biologically benign, this tumour can cause relevant clinical symptoms related to the size and site (compression or obstruction of organs).

Case presentation
We describe the case of a 52-years old woman who had presented with abdominal pain and underwent surgery in order to remove a palpable lump in the mesentery with histological diagnosis of primary mucinous cystoadenoma. The patient was followed-up for two years with no evidence of recurrence.

Conclusions
Mucinous cystoadenoma is more frequent in women, particularly when there is history of one or more pregnancies. A complete preoperative study with abdominal and pelvic tomographic images and an accurate physical examination are essentials for the management of the patient. Surgical resection is the only way to treat mucinous cystoadenomas, and to have the histological confirmation that the removed mass is a benign tumor.