bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive network modeling of the high-resolution dynamic plant transcriptome in response to nitrate
Authors: Krouk Gabriel , Mirowski Piotr , LeCun Yann , Shasha Dennis E , Coruzzi Gloria M 
Published: January 2011

Abstract
Background
Nitrate, acting as both a nitrogen source and a signaling molecule, controls many aspects of plant development. However, gene networks involved in plant adaptation to fluctuating nitrate environments have not yet been identified.

Results
Here we use time-series transcriptome data to decipher gene relationships and consequently to build core regulatory networks involved in Arabidopsis root adaptation to nitrate provision. The experimental approach has been to monitor genome-wide responses to nitrate at 3, 6, 9, 12, 15 and 20 minutes using Affymetrix ATH1 gene chips. This high-resolution time course analysis demonstrated that the previously known primary nitrate response is actually preceded by a very fast gene expression modulation, involving genes and functions needed to prepare plants to use or reduce nitrate. A state-space model inferred from this microarray time-series data successfully predicts gene behavior in unlearnt conditions.

Conclusions
The experiments and methods allow us to propose a temporal working model for nitrate-driven gene networks. This network model is tested both in silico and experimentally. For example, the over-expression of a predicted gene hub encoding a transcription factor induced early in the cascade indeed leads to the modification of the kinetic nitrate response of sentinel genes such as NIR, NIA2, and NRT1.1, and several other transcription factors. The potential nitrate/hormone connections implicated by this time-series data are also evaluated.
Novel genes exhibit distinct patterns of function acquisition and network integration
Authors: Capra John A , Pollard Katherine S , Singh Mona 
Published: January 2011

Abstract
Background
Genes are created by a variety of evolutionary processes, some of which generate duplicate copies of an entire gene, while others rearrange pre-existing genetic elements or co-opt previously non-coding sequence to create genes with 'novel' sequences. These novel genes are thought to contribute to distinct phenotypes that distinguish organisms. The creation, evolution, and function of duplicated genes are well-studied; however, the genesis and early evolution of novel genes are not well-characterized. We developed a computational approach to investigate these issues by integrating genome-wide comparative phylogenetic analysis with functional and interaction data derived from small-scale and high-throughput experiments.

Results
We examine the function and evolution of new genes in the yeast Saccharomyces cerevisiae. We observed significant differences in the functional attributes and interactions of genes created at different times and by different mechanisms. Novel genes are initially less integrated into cellular networks than duplicate genes, but they appear to gain functions and interactions more quickly than duplicates. Recently created duplicated genes show evidence of adapting existing functions to environmental changes, while young novel genes do not exhibit enrichment for any particular functions. Finally, we found a significant preference for genes to interact with other genes of similar age and origin.

Conclusions
Our results suggest a strong relationship between how and when genes are created and the roles they play in the cell. Overall, genes tend to become more integrated into the functional networks of the cell with time, but the dynamics of this process differ significantly between duplicate and novel genes.
Management of Seminomatous Testicular Cancer: A Binational Prospective Population-Based Study From the Swedish Norwegian Testicular Cancer Study Group
Authors: Tandstad Torgrim , Smaaland Rune , Solberg Arne , Bremnes Roy M. , Langberg Carl W. , Laurell Anna , Stierner Ulrika K. , Ståhl Olof , Cavallin-Ståhl Eva K. , Klepp Olbjørn H. , Dahl Olav , Cohn-Cedermark Gabriella 
Published: January 2011

Purpose A binational, population-based treatment protocol was established to prospectively treat and follow patients with seminomatous testicular cancer. The aim was to standardize care for all patients with seminoma to further improve the good results expected for this disease. Patients and Methods From 2000 to 2006, a total of 1,384 Norwegian and Swedish patients were included in the study. Treatment in clinical stage 1 (CS1) was surveillance, adjuvant radiotherapy, or adjuvant carboplatin. In metastatic disease, recommended treatment was radiotherapy in CS2A and cisplatin-based chemotherapy in CS2B or higher. Results At a median follow-up of 5.2 years, 5-year cause-specific survival was 99.6%. In CS1, 14.3% (65 of 512) of patients relapsed following surveillance, 3.9% (seven of 188) after carboplatin, and 0.8% (four of 481) after radiotherapy. We could not identify any factors predicting relapse in CS1 patients who were subjected to surveillance only. In CS2A, 10.9% (three of 29) patients relapsed after radiotherapy compared with no relapses in CS2A/B patients (zero of 73) treated with chemotherapy (P = .011). Conclusion An international, population-based treatment protocol for testicular seminoma is feasible with excellent results. Surveillance remains a good option for CS1 patients. No factors predicted relapse in CS1 patients on surveillance. Despite resulting in a lower rate of relapse than with adjuvant carboplatin, adjuvant radiotherapy has been abandoned in the Swedish and Norwegian Testicular Cancer Project (SWENOTECA) as a recommended treatment option because of concerns of induction of secondary cancers. The higher number of relapses in radiotherapy-treated CS2A patients when compared with chemotherapy-treated CS2A/B patients is of concern. Late toxicity of cisplatin-based chemotherapy versus radiotherapy must be considered in CS2A patients.
Understanding Surgical Decision Making in Early Hepatocellular Carcinoma
Authors: Nathan Hari , Bridges John F.P. , Schulick Richard D. , Cameron Andrew M. , Hirose Kenzo , Edil Barish H. , Wolfgang Christopher L. , Segev Dorry L. , Choti Michael A. , Pawlik Timothy M. 
Published: January 2011

Purpose The choice between liver transplantation (LT), liver resection (LR), and radiofrequency ablation (RFA) as initial therapy for early hepatocellular carcinoma (HCC) is controversial, yet little is known about how surgeons choose therapy for individual patients. We sought to quantify the impact of both clinical factors and surgeon specialty on surgical decision making in early HCC by using conjoint analysis. Methods Surgeons with an interest in liver surgery were invited to complete a Web-based survey including 10 case scenarios. Choice of therapy was then analyzed by using regression models that included both clinical factors and surgeon specialty (non-LT v LT). Results When assessing early HCC occurrences, non-LT surgeons (50% LR; 41% LT; 9% RFA) made significantly different recommendations compared with LT surgeons (63% LT; 31% LR; 6% RFA; P < .001). Clinical factors, including tumor number and size, type of resection required, and platelet count, had significant effects on the choice between LR, LT, and RFA. After adjusting for clinical factors, non-LT surgeons remained more likely than LT surgeons to choose LR compared with LT (relative risk ratio [RRR], 2.67). When the weight of each clinical factor was allowed to vary by surgeon specialty, the residual independent effect of surgeon specialty on the decision between LR and LT was negligible (RRR, 0.93). Conclusion The impact of surgeon specialty on choice of therapy for early HCC is stronger than that of some clinical factors. However, the influence of surgeon specialty does not merely reflect an across-the-board preference for one therapy over another. Rather, certain clinical factors are weighed differently by surgeons in different specialties.
Prognostic Importance of Histone MethyltransferaseMLL5Expression in Acute Myeloid Leukemia
Authors: Damm Frederik , Oberacker Tina , Thol Felicitas , Surdziel Ewa , Wagner Katharina , Chaturvedi Anuhar , Morgan Michael , Bomm Karoline , Göhring Gudrun , Lübbert Michael , Kanz Lothar , Fiedler Walter , Schlegelberger Brigitte , Heil Gerhard , Schlenk Richard F. , Döhner Konstanze , Döhner Hartmut , Krauter Jürgen , Ganser Arnold , Heuser Michael 
Published: January 2011

PurposeTo assess the prognostic importance of mixed lineage leukemia 5 (MLL5) expression in acute myeloid leukemia (AML).Patients and MethodsMLL5 transcript levels from 509 patients with AML who were treated in multicenter trials AML SHG 0199 and AML SHG 0295 and 48 healthy volunteers were analyzed by real-time reverse-transcription polymerase chain reaction in the context of other molecular markers (NPM1, FLT3, CEBPA, IDH1/IDH2, NRAS, KIT, MN1, BAALC, ERG, and WT1).ResultsPatients with high (n = 127) compared with low (n = 382) MLL5 expression had a higher complete response rate in multivariate analysis (odds ratio, 1.87; 95% CI, 1.08 to 3.24; P = .026). In multivariate analysis, high MLL5 expression was a favorable prognostic marker for overall survival (OS; hazard ratio [HR], 0.66; 95% CI, 0.49 to 0.89; P = .007) and relapse-free survival (RFS; HR, 0.72; 95% CI, 0.52 to 1.01; P = .057). Patient characteristics, cytogenetic aberrations, and gene mutations were similarly distributed between patients with high and low MLL5 expression except for a higher platelet count in those with high MLL5 expression. MLL5 expression independently predicted prognosis in cytogenetically normal AML patients (n = 268; OS: HR, 0.53; 95% CI, 0.33 to 086; P = .011; RFS: HR, 0.61; 95% CI, 0.38 to 0.99; P = .05) and in patients with core-binding factor leukemias (n = 81; OS: HR, 0.12; 95% CI, 0.02 to 0.91; P = .04; RFS: HR, 0.18; 95% CI, 0.04 to 0.77; P = .02). The prognostic importance of high MLL5 expression was independently validated in 167 patients treated in the AMLSG 07/04 trial (OS: HR, 0.5; 95% CI, 0.27 to 0.92; P = .023; RFS: HR, 0.49; 95% CI, 0.25 to 0.96; P = .033).ConclusionHigh MLL5 expression levels are associated with a favorable outcome and may improve risk and treatment stratification in AML.
Physical Activity and Survival After Prostate Cancer Diagnosis in the Health Professionals Follow-Up Study
Authors: Kenfield Stacey A. , Stampfer Meir J. , Giovannucci Edward , Chan June M. 
Published: January 2011

Purpose To determine whether higher physical activity after prostate cancer (PCa) diagnosis decreases risk of overall and PCa-specific death. Patients and Methods We evaluated physical activity in relation to overall and PCa mortality among 2,705 men in the Health Professionals Follow-Up Study diagnosed with nonmetastatic PCa observed from 1990 to 2008. Proportional hazards models were used to evaluate physical activity and time to overall and PCa-specific death. Results Among men who lived at least 4 years after their postdiagnosis physical activity assessment, we documented 548 deaths, 20% of which were a result of PCa. In multivariable analysis, men who were physically active had lower risk of all-cause mortality (Ptrend < .001) and PCa mortality (Ptrend = .04). Both nonvigorous activity and vigorous activity were associated with significantly lower overall mortality. Those who walked ≥ 90 minutes per week at a normal to very brisk pace had a 46% lower risk of all-cause mortality (hazard ratio [HR] 0.54; 95% CI, 0.41 to 0.71) compared with shorter durations at an easy walking pace. Men with ≥ 3 hours per week of vigorous activity had a 49% lower risk of all-cause mortality (HR, 0.51; 95% CI, 0.36 to 0.72). For PCa-specific mortality, brisk walking at longer durations was suggestively inverse but not statistically significant. Men with ≥ 3 hours per week of vigorous activity had a 61% lower risk of PCa death (HR, 0.39, 95% CI, 0.18 to 0.84; P = .03) compared with men with less than 1 hour per week of vigorous activity. Men exercising vigorously before and after diagnosis had the lowest risk. Conclusion In men with PCa, physical activity was associated with lower overall mortality and PCa mortality. A modest amount of vigorous activity such as biking, tennis, jogging, or swimming for ≥ 3 hours a week may substantially improve PCa-specific survival.
Phase II Study of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine in Muscle-Invasive Bladder Cancer
Authors: Choudhury Ananya , Swindell Ric , Logue John P. , Elliott P. Anthony , Livsey Jacqueline E. , Wise Marcus , Symonds Paul , Wylie James P. , Ramani Vijay , Sangar Vijay , Lyons Jeanette , Bottomley Ian , McCaul Damian , Clarke Noel W. , Kiltie Anne E. , Cowan Richard A. 
Published: January 2011

Purpose The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX). Patients and Methods Fifty patients with transitional cell carcinoma, stage T2-3, N0, M0 after transurethral resection and magnetic resonance imaging, were recruited. Gemcitabine was given intravenously at 100 mg/m2 on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. Chemotherapy was stopped for Radiation Therapy Oncology Group (RTOG) grade 3 bladder or bowel toxicity. The primary end points were tumor response, toxicity, and survival. Results All patients completed RT; 46 tolerated all four cycles of gemcitabine. Two patients stopped after two cycles, and two stopped after three cycles, because of bowel toxicity. Forty-seven patients had a post-treatment cystoscopy; 44 (88%) achieved a complete endoscopic response. At a median follow-up of 36 months (range, 15 to 62 months), 36 patients were alive, and 32 of these had a functional and intact bladder. Fourteen patients died; seven died as a result of metastatic MIBC, five died as a result of intercurrent disease, and two died as a result of treatment-associated deaths. Four patients underwent cystectomy; three because of recurrent disease and one because of toxicity. One patient required a bowel resection for late toxicity. By using Kaplan-Meier analyses, 3-year cancer-specific survival was 82%, and overall survival was 75%. Conclusion Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.
Congestive Heart Failure Risk in Patients With Breast Cancer Treated With Bevacizumab
Authors: Choueiri Toni K. , Mayer Erica L. , Je Youjin , Rosenberg Jonathan E. , Nguyen Paul L. , Azzi Georges R. , Bellmunt Joaquim , Burstein Harold J. , Schutz Fabio A.B. 
Published: January 2011

Purpose Bevacizumab is a treatment option in patients with metastatic breast cancer. Congestive heart failure (CHF) has been reported, although the overall incidence and relative risk (RR) of this complication remains unclear. We performed an up-to-date, comprehensive meta-analysis to determine the risk of serious CHF in patients with breast cancer receiving bevacizumab. Methods The databases of Medline were searched for articles from 1966 to March 2010. Abstracts presented at the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium meetings were also searched for relevant clinical trials. Eligible studies include randomized trials with bevacizumab in patients with breast cancer. Adequate reporting of safety profile data was required for inclusion. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% CIs by using random-effects models. Results A total of 3,784 patients were included. Overall incidence results for high-grade CHF in bevacizumab- and placebo-treated patients were 1.6% (95% CI, 1.0% to 2.6%) and 0.4% (95% CI, 0.2% to 1.0%), respectively. The RR of CHF in bevacizumab-treated patients was 4.74 (95% CI, 1.66 to 11.18; P = .001) compared with placebo-treated ones. In subgroup analyses, there were no significant differences in CHF incidence or risk between patients treated with low-dose (2.5 mg/kg) versus high-dose (5 mg/kg) bevacizumab or among patients treated with different chemotherapy regimens. No evidence of publication bias was observed. Conclusion This is the first comprehensive report to show that bevacizumab is associated with an increased risk of significant heart failure in patients with breast cancer.
A Ruthenium-Catalyzed Hydrosilane-Induced Polymerization of 3-Alkyl-3-hydroxymethyloxetane Derivatives: Facile Access to Functionalized Polyoxetanes by Virtue of Organosilyl Groups
Authors: Harada Nari-aki , Yasuhara Jushiro , Motoyama Yukihiro , Fujimura Osamu , Tsuji Tetsuro , Takahashi Takeshi , Takahashi Yoshiaki , Nagashima Hideo 
Published: December 2010

Abstract
Ring-opening polymerization of 3-alkyl-3-alkoxymethyl- or 3-alkyl-3-siloxymethyloxetanes is catalyzed by a triruthenium cluster, [Ru3{μ3-(η2,η3,η5-C12H8)}(CO)7], in the presence of trialkylsilanes, providing a novel accessible method for functionalized polyoxetanes of Mn = 103–105. Oxetanes having alkoxy-, fluoroalkoxy-, triethyleneglycoloxy-, and trialkylsiloxy functions undergo polymerization and copolymerization. Consumption rates of two monomers in the copolymerization of 3-benzyloxymethyl- and 3-trimethylsiloxymethyl-3-alkyloxetanes are almost the same, indicating formation of random copolymers. The organosilyl group in the polymer and copolymers with siloxymethyl side chains is converted to CH2OH or CH2OCOR groups by hydrolysis or silyl/acyl exchange. These protocols give the way to access polymers or copolymers bearing OH and OCOR side chains. A ruthenium-catalyzed reaction of 3-ethyl-3-hydroxymethyloxetane with trialkylsilanes results in dehydrogenative silylation to give 3-ethyl-3-siloxymethyloxetane, which is followed by ring-opening polymerization. Combination of tandem dehydrogenative silylation/ring-opening polymerization/the silyl/acyl exchange realizes one-pot synthesis of polymers with CH2OCOR side chains from 3-ethyl-3-hydroxymethyloxetane. DSC analyses of the formed polymers provided Tg and Tm data, which are a good example showing that the polymer properties are controlled by appropriate selection of functional groups at the side chain.
Physician Perceptions About Generic Drugs
Authors: Shrank William H , Liberman Joshua N , Fischer Michael A , Girdish Charmaine , Brennan Troyen A , Choudhry Niteesh K 
Published: January 2011

Background With constrained health-care resources, there is a need to understand barriers to cost-effective medication use. Objective To study physician perceptions about generic medications. Methods Physicians used 5-point Likert scales to report perceptions about cost-related medication nonadherence, the efficacy and quality of generic medications, preferences for generic use, and the implications of dispensing medication samples. Descriptive statistics were used to assess physician perceptions and logistic regression models were used to evaluate predictors of physician perceptions. Results: Among the invited sample. 839 (30.4%) responded and 506 (18.3%) were eligible and included in the final study population. Over 23% of physicians surveyed expressed negative perceptions about efficacy of generic drugs, almost 50% reported negative perceptions about quality of generic medications, and more than one quarter do not prefer to use generics as first-line medications for themselves or for their family. Physicians over the age of 55 years were 3.3 times more likely to report negative perceptions about generic quality, 5.8 times more likely to report that they would not use generics themselves, and 7.5 times more likely to state that they would not recommend generics for family members (p < 0.05 for all). Physicians reported that pharmaceutical company representatives are the most common (75%) source of information about market entry of a generic medication. Almost half of the respondents expressed concern that free samples may adversely affect subsequent affordability, yet two thirds of respondents provide free samples. Conclusions: A meaningful proportion of physicians expressed negative perceptions about generic medications, representing a potential barrier to generic use. Payors and policymakers trying to encourage generic use may consider educational campaigns targeting older physicians.
Elevated International Normalized Ratio from Vitamin K Supplement Discontinuation
Authors: Miesner Andrew R , Sullivan Timothy S 
Published: January 2011

Objective To report a case of a critically elevated international normalized ratio (INR) following discontinuation of a vitamin K supplement in a patient receiving warfarin. Case Summary: A 64-year-old man with atrial fibrillation received warfarin for primary stroke prevention. He was initialed on tow-dose vitamin K supplementation therapy secondary to a high level of INR variability. The patient was stabilized on this therapy for approximately 9 months with a mean INR of 2.02 and a warfarin dose ranging from 6.5 to 7.5 mg/week. At a visit with his primary care physician, the patient's INR was subtherapeutic at 1.5. He had not been taking his vitamin K supplement for nearly a week, but had not missed any doses of warfarin. The vitamin K supplement was discontinued and his warfarin dose was increased by 14.3%. Nearly 2 weeks later the patient presented with a critically elevated INR of 8.5, but no acute bleeding. No other factors affecting the INR could be determined. After a dose of 2.5 mg of vitamin K was administered and warfarin was withheld for 2 days, the patient's INR returned to 2.9. Low-dose vitamin K supplementation and warfarin at a lower dose of 7 mg/week were restarted. His INR remained relatively stable, with no ensuing critical INR changes or other sequelae. Discussion: Vitamin K supplement removal was believed to be a major contributor to the critically elevated INR. White the warfarin dose had been increased according to the clinic protocol (14.3% for an INR of 1.5), the timing of the INR elevation following supplement removal follows pharmacodynamic expectations of clotting factor synthesis. This case is labeled a category D error. Conclusions: Discontinuation of vitamin K supplementation therapy might result in elevation of INR.
Spielräume kultureller Kontakte im Roman des 16. Jahrhunderts: Der Finckenritter (Straßburg 1560)
Authors: Röcke Werner 
Published: January 2011

Zusammenfassung
Das Eigene und das Fremde  die vertraute Welt des christlichen Europa einerseits, die fremden Kulturen Indiens und Ostasiens andererseits  werden im Mittelalter strikt getrennt gedacht. Darstellungsmuster dieser Fremde sind monströse Lebewesen und andere Wunder, die im Osten bis zum Rand der Welt imaginiert werden. Das Erstaunliche des Finckenritter, eines parodistischen Reiseromans des 16. Jhdts. (um 1560), liegt darin, dass er den Dualismus von fremder und eigener Welt aufhebt und die Topoi der Fremde in die Vertrautheit der eigenen Welt verpflanzt. Damit schafft er die Möglichkeit einer Hybridisierung von Eigenem und Fremdem, welche einerseits neue Perspektiven von Kulturkontakten, andererseits ganz neue moments of wonder (Greenblatt) eröffnet: eine prinzipielle Verkehrung von Sinn und Ordnung der Welt, der Wahrnehmung und der sozialen Kommunikation, die jede mögliche Orientierung des Lesers aufhebt.