bluuebunny/crossref_metadata_2025_split huggingface dataset:
MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection
Authors: Blanié Sophie , Gelfi Jacqueline , Bertagnoli Stéphane , Camus-Bouclainville Christelle 
Published: March 2010

Abstract
Myxoma virus (MYXV), a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor) and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has drawn considerable attention for its potential role in modulating the host ubiquitin-proteasome system during viral infection. To date, many members of this novel protein family have been shown to interact with SCF components, in vitro. Here, we focus on MNF gene, which has been shown to express a nuclear protein presenting nine ANK repeats, one of which has been identified as a nuclear localization signal. In transfection, MNF has been shown to colocalise with the transcription factor NF-κB in the nucleus of TNFα-stimulated cells. Functionally, MNF is a critical virulence factor since its deletion generates an almost apathogenic virus. In this study, to pursue the investigation of proteins interacting with MNF and of its mechanism of action, we engineered a recombinant MYXV expressing a GFP-linked MNF under the control of MNF native promoter. Infection of rabbits with MYXV-GFPMNF recombinant virus provided the evidence that the GFP fusion does not disturb the main function of MNF. Hence, cells were infected with MYXV-GFPMNF and immunoprecipitation of the GFPMNF fusion protein was performed to identify MNF's partners. For the first time, endogenous components of SCF (Cullin-1 and Skp1) were co-precipitated with an ANK myxoma virus protein, expressed in an infectious context, and without over-expression of any protein.
Kinin B1 Receptors Contributes to Acute Pain following Minor Surgery in Humans
Authors: Hamza May , Wang Xiao-Min , Adam Albert , Brahim Jaime S , Rowan Janet S , Carmona Gilberto N , Dionne Raymond A 
Published: March 2010

Background: Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Results: Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. Conclusions: These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B1 receptors may contribute to acute inflammatory pain through TRPV1 activation.
Phase I/II Study of Combination Therapy With Sorafenib, Idarubicin, and Cytarabine in Younger Patients With Acute Myeloid Leukemia
Authors: Ravandi Farhad , Cortes Jorge E. , Jones Daniel , Faderl Stefan , Garcia-Manero Guillermo , Konopleva Marina Y. , O'Brien Susan , Estrov Zeev , Borthakur Gautam , Thomas Deborah , Pierce Sherry R. , Brandt Mark , Byrd Anna , Bekele B. Nebiyou , Pratz Keith , Luthra Rajyalakshmi , Levis Mark , Andreeff Michael , Kantarjian Hagop M. 
Published: March 2010

Purpose To determine the efficacy and toxicity of the combination of sorafenib, cytarabine, and idarubicin in patients with acute myeloid leukemia (AML) younger than age 65 years. Patients and Methods In the phase I part of the study, 10 patients with relapsed AML were treated with escalating doses of sorafenib with chemotherapy to establish the feasibility of the combination. We then treated 51 patients (median age, 53 years; range, 18 to 65 years) who had previously untreated AML with cytarabine at 1.5 g/m2 by continuous intravenous (IV) infusion daily for 4 days (3 days if > 60 years of age), idarubicin at 12 mg/m2 IV daily for 3 days, and sorafenib at 400 mg orally twice daily for 7 days. Results Overall, 38 (75%) patients have achieved a complete remission (CR), including 14 (93%) of 15 patients with mutated FMS-like tyrosine kinase-3 (FLT3; the 15th patient had complete remission with incomplete platelet recovery [CRp]) and 24 (66%) of 36 patients with FLT3 wild-type (WT) disease (three additional FLT3-WT patients had CRp). FLT3-mutated patients were more likely to achieve a CR than FLT3-WT patients (P = .033). With a median follow-up of 54 weeks (range, 8 to 87 weeks), the probability of survival at 1 year is 74%. Among the FLT3-mutated patients, 10 have relapsed and five remain in CR with a median follow-up of 62 weeks (range, 10 to 76 weeks). Plasma inhibitory assay demonstrated an on-target effect on FLT3 kinase activity. Conclusion Sorafenib can be safely combined with chemotherapy, produces a high CR rate in FLT3-mutated patients, and inhibits FLT3 signaling.
Comparison of Error Rates in Single-Arm Versus Randomized Phase II Cancer Clinical Trials
Authors: Tang Hui , Foster Nathan R. , Grothey Axel , Ansell Stephen M. , Goldberg Richard M. , Sargent Daniel J. 
Published: March 2010

Purpose To improve the understanding of the appropriate design of phase II oncology clinical trials, we compared error rates in single-arm, historically controlled and randomized, concurrently controlled designs. Patients and Methods We simulated error rates of both designs separately from individual patient data from a large colorectal cancer phase III trials and statistical models, which take into account random and systematic variation in historical control data. Results In single-arm trials, false-positive error rates (type I error) were 2 to 4 times those projected when modest drift or patient selection effects (eg, 5% absolute shift in control response rate) were included in statistical models. The power of single-arm designs simulated using actual data was highly sensitive to the fraction of patients from treatment centers with high versus low patient volumes, the presence of patient selection effects or temporal drift in response rates, and random small-sample variation in historical controls. Increasing sample size did not correct the over optimism of single-arm studies. Randomized two-arm design conformed to planned error rates. Conclusion Variability in historical control success rates, outcome drifts in patient populations over time, and/or patient selection effects can result in inaccurate false-positive and false-negative error rates in single-arm designs, but leave performance of the randomized two-arm design largely unaffected at the cost of 2 to 4 times the sample size compared with single-arm designs. Given a large enough patient pool, the randomized phase II designs provide a more accurate decision for screening agents before phase III testing.
Comparison of Cladribine Plus Cyclophosphamide With Fludarabine Plus Cyclophosphamide As First-Line Therapy for Chronic Lymphocytic Leukemia: A Phase III Randomized Study by the Polish Adult Leukemia Group (PALG-CLL3 Study)
Authors: Robak Tadeusz , Jamroziak Krzysztof , Gora-Tybor Joanna , Stella-Holowiecka Beata , Konopka Lech , Ceglarek Bernadetta , Warzocha Krzysztof , Seferynska Ilona , Piszcz Jarosław , Calbecka Malgorzata , Kostyra Aleksandra , Dwilewicz-Trojaczek Jadwiga , Dmoszyñska Anna , Zawilska Krystyna , Hellmann Andrzej , Zdunczyk Andrzej , Potoczek Stanislaw , Piotrowska Magdalena , Lewandowski Krzysztof , Blonski Jerzy Z. 
Published: March 2010

Purpose Little is known about comparison of the activity of different purine nucleoside analogs in chronic lymphocytic leukemia (CLL). We conducted a randomized phase III trial to compare efficacy and safety of cladribine and fludarabine, each combined with cyclophosphamide, in previously untreated progressive CLL. Patients and Methods Patients received cladribine at 0.12 mg/kg combined with cyclophosphamide at 250 mg/m2 for 3 days intravenously (CC regimen) or fludarabine at 25 mg/m2 combined with cyclophosphamide at 250 mg/m2 for 3 days intravenously (FC regimen), every 28 days for up to six cycles. The primary end point was complete response (CR) rate. Secondary end points included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. Results Of 423 randomly assigned patients (211 to CC and 212 to FC), 395 were evaluated in the final analysis. The CR and ORR reached 47% and 88% in the CC arm and 46% and 82% in the FC arm (P = .25 and P = .11, respectively). The median PFS was 2.34 years with CC and 2.27 years with FC (P = .51). OS and grade 3/4 treatment-related toxicity were also comparable. Moreover, we did not observe any significant differences in CC and FC efficacy across different patient prognostic subgroups that included patients with 17p13 (TP53 gene) deletion who had poor survival in both study arms. Conclusion Cladribine and fludarabine in combination with cyclophosphamide are equally effective and safe first-line regimens for progressive CLL. Both combinations have unsatisfactory activity in patients with 17p13 (TP53 gene) deletion.
Phase III Placebo-Controlled Trial of Denileukin Diftitox for Patients With Cutaneous T-Cell Lymphoma
Authors: Prince H. Miles , Duvic Madeleine , Martin Ann , Sterry Wolfram , Assaf Chalid , Sun Yijun , Straus David , Acosta Mark , Negro-Vilar Andres 
Published: March 2010

Purpose This phase III, placebo-controlled, randomized trial was designed to investigate efficacy and safety of two doses of denileukin diftitox (DD; DAB389–interleukin-2 [IL-2]), a recombinant fusion protein targeting IL-2 receptor–expressing malignant T lymphocytes, in patients with stage IA to III, CD25 assay–positive cutaneous T-cell lymphoma (CTCL), including the mycosis fungoides and Sézary syndrome forms of the disease, who had received up to three prior therapies. The primary end point was overall response rate (ORR). Patients and Methods Patients (N = 144) with biopsy-confirmed, CD25 assay–positive CTCL were randomly assigned to DD 9 μg/kg/d (n = 45), DD 18 μg/kg/d (n = 55), or placebo infusions (n = 44), administered for 5 consecutive days every 3 weeks for up to eight cycles. Patients were monitored for drug efficacy, clinical benefit, and safety of DD. Results ORR was 44% for all participants treated with DD (n = 100; 10% complete response [CR] and 34% partial response [PR]) compared with 15.9% for placebo-treated patients (2% CR and 13.6% PR). ORR was higher in the 18 μg/kg/d group versus the 9 μg/kg/d group (49.1% v 37.8%, respectively), and both doses were significantly superior to placebo. Progression-free survival (PFS) was significantly longer (median, > 2 years) for both DD doses compared with placebo (median, 124 days; P < .001). Rates of moderately severe and severe adverse events (AEs) were slightly higher in the DD groups, whereas moderate and mild AEs were similar to placebo. No statistical differences were observed for drug-related serious AEs. Conclusion DD had a significant and durable effect on ORR and PFS with an acceptable safety profile in patients with early- and late-stage CTCL.
Sedulus, fidus, dignus honore, vigil:1varietas et construction de la figure du médecin dans la préface médicale à la Renaissance
Authors: Kozluk Magdalena 
Published: March 2010

Resume:
Notre étude porte sur le discours préfaciel des ouvrages médicaux à la Renaissance. Les médecins, dans leur préfaces, prennent conscience de leur statut d'écrivains et se prennent au jeu de la «varietas» et de ses diverses facettes: choix des matières et éloquence du discours. L'exornatio verbomm sert à l'illustration du discours et à garantir sa «perspicuitas» conformément aux exigences de la tradition rhétorique. Mais dans la préface médicale, elle contribue aussi à la construction de la «persona» de l'auteur-médecin, principalement, dans sa dimension morale. C'est ainsi que s'établit une sorte de symbiose entre l'èthos de l'auteur et l'éthique du médecin.
Single photon emission computed tomography (SPECT)/computed tomography using Iodine-123 in patients with differentiated thyroid cancer: additional value over whole body planar imaging and SPECT
Authors: Barwick Tara , Murray Iain , Megadmi Hakim , Drake William M , Plowman P Nick , Akker Scott A , Chew Shern L , Grossman Ashley B , Avril Norbert 
Published: March 2010

ObjectiveThe aim of the study was to assess the diagnostic performance of co-registered single photon emission computed tomography (SPECT)/computed tomography (CT) compared to Iodine-123 whole body gamma camera (WBGC) imaging and to SPECT alone in patients with differentiated thyroid cancer.MethodsWBGC and SPECT/CT (n=85) imaging of the neck and thorax was performed in 79 consecutive patients. Three experienced observers reviewed: i) WBGC images followed by ii) SPECT alone, and iii) co-registered SPECT/CT. Foci of increased radioiodine uptake were classified on a five-point scale. Biopsy, other imaging modalities, and clinical follow-up served as the reference standard.ResultsTwenty-two patients had local recurrence or metastatic thyroid cancer (11 were radioiodine negative), 9 had remnant thyroid tissue, and 54 had no evidence of disease. When classifying equivocal, probably, and definitely malignant findings as positive for malignancy, the sensitivity, specificity, positive predictive value, and negative predictive value were as follows: 41, 68, 31, and 77% for WBGC imaging; 45, 89, 59, and 82% for WBGC plus SPECT imaging; and 50, 100, 100, and 85% for WBGC plus SPECT/CT imaging respectively. The specificity was improved by the addition of SPECT (P=0.0002) and SPECT/CT (P<0.0001) than to WBGC imaging. SPECT/CT was also more specific than WBGC plus SPECT imaging (P=0.016). In a study-based analysis, SPECT/CT provided additional diagnostic information in 42% (36/85) of cases. SPECT/CT provided further characterization in 70% (63/90) of foci and improved the diagnostic confidence of all three observers.ConclusionThe addition of SPECT/CT significantly improved the diagnostic information over Iodine-123 WBGC imaging and WBGC plus SPECT imaging alone.
Randomized Trial of Drainage, Irrigation and Fibrinolytic Therapy for Premature Infants with Posthemorrhagic Ventricular Dilatation: Developmental Outcome at 2 years
Authors: Whitelaw Andrew , Jary Sally , Kmita Grazyna , Wroblewska Jolanta , Musialik-Swietlinska Ewa , Mandera Marek , Hunt Linda , Carter Michael , Pople Ian 
Published: March 2010

Background:
Preterm infants who develop posthemorrhagic ventricular dilatation (PHVD) have a high risk of cognitive and motor disability. No clinical intervention has been proven to reduce neurodevelopmental disability in such infants. We investigated whether drainage, irrigation, and fibrinolytic therapy (DRIFT), which aims to lower pressure, distortion, free iron, and cytokines, reduces death or severe disability in PHVD.

Methods:
We randomly assigned 77 preterm infants with PHVD to either DRIFT or standard treatment (ie tapping off cerebrospinal fluid to control excessive expansion). Severe disability was assessed at 2 years' corrected age and included severe sensorimotor disability and cognitive disability (&lt;55 on the Bayley Mental Development Index).

Results:
Of 39 infants assigned to DRIFT, 21 (54%) died or were severely disabled versus 27 of 38 (71%) in the standard group (adjusted odds ratio 0.25 [95% confidence interval: 0.08–0.82]). Among the survivors, 11 of 35 (31%) in the DRIFT group had severe cognitive disability versus 19 of 32 (59%) in the standard group (adjusted odds ratio: 0.17 [95% confidence interval: 0.05–0.57]). Median Mental Development Index was 68 with DRIFT and &lt;50 with standard care. Severe sensorimotor disability was not significantly reduced.

Conclusions:
Despite an increase in secondary intraventricular bleeding, DRIFT reduced severe cognitive disability in survivors and overall death or severe disability.
Mobilizing Science to Break Yield Barriers
Authors: Phillips Ronald L. 
Published: March 2010

ABSTRACTYield barriers must be broken. The diminished stock of staple foods, higher grain prices, and increases in production failing to keep up with demand, coupled with 80 million people being added to the world population every year, suggests that we are on a collision course with famine unless greater investments are made in research and development, as well as education. Genetic improvement of staples has accounted for more than half of the past increases in yields. Fortunately, a revolution in genetic knowledge is co‐evolving with the increased demand for food, feed, fiber, and fuel. Utilizing genetic diversity has been a mainstay of past production improvements High throughput DNA sequencing, the related bioinformatics, and a cascade of genetic technologies can now be employed to detect previously hidden genetic variability, to understand gene functions, to make greater use of accessions in germplasm banks, and to make breeding schemes more efficacious. The involvement of outstanding scientists who can bring interdisciplinary ideas to the question of how to break yield barriers must be part of the strategy. Educational programs at all levels, even high school, should emphasize the opportunities in international agriculture to build a cadre of dedicated scientists for the future.
Relearning Old Lessons for the Future of Food—By Bread Alone No Longer: Diversifying Diets with Fruit and Vegetables
Authors: Keatinge John D. H. , Waliyar Farid , Jamnadas Ramni H. , Moustafa Ahmed , Andrade Maria , Drechsel Pay , Hughes Jacqueline d'A. , Kadirvel Palchamy , Luther Kartini 
Published: March 2010

ABSTRACTDiversifying diets and agricultural enterprises with fruit and vegetables is a potent weapon in the current global battle against malnutrition and poverty. Agricultural science can contribute substantially to enhance the development prospects and health of not only disadvantaged and vulnerable individuals at one end of the spectrum but also the growth and equity of national economies at the other. Moreover, with relatively simple applied research, new crop species and technologies can rapidly enter the development pathway to benefit even the poorest people or nations. More upstream research can help to guard fruit and vegetable production against the vagaries of potential climatic uncertainty, which is projected to become more prominent over future decades. However, historical and continuing widespread underinvestment in fruit and vegetable research and development from the national to the global level may severely compromise the world's ability to use such high‐value species for crop diversification and as a major engine of development growth to ensure global food and nutritional security.
Biorefineries– A Path to Sustainability?
Authors: Hatti‐Kaul Rajni 
Published: March 2010

ABSTRACTBiorefining of crops for production of power, transport fuels, and a diverse array of chemicals has potential for providing significant added economic value to biomass. A shift in the industrial resource base from fossil resources to biomass also requires a shift in the technology base for producing, handling, and processing of raw materials. Biotechnology will play an important role in providing tools for different stages ranging from biomass production, treatment, and valorization to various products. First generation refineries have raised some critical issues related to land use and insufficient environmental benefits due to energy‐intensive cultivation of crops. The abundant residual lignocellulosic biomass will constitute an important feedstock for the future biorefineries so as to have a minimal impact on the food availability. Necessary investments in technological development will be needed to realize the benefits of the new bioeconomy in the long term.
More than Eco‐efficiency is Required to Improve Food Security
Authors: Park S. E. , Howden S. M. , Crimp S. J. , Gaydon D. S. , Attwood S. J. , Kokic P. N. 
Published: March 2010

ABSTRACTAgricultural eco‐efficiency is promoted as a means of increasing agricultural production and improving the security of food systems in response to climate change. The rationale is that economic and environmental resources will be used more efficiently, enabling increased amounts of food to be produced from the same amount or fewer inputs. We used (i) a quantitative literature analysis to examine current usage of the eco‐efficiency concept to assess strategies aimed at improving food security under climate change, and (ii) a wheat (Triticum aestivum L.) simulation experiment to consider possible tradeoffs between economic benefits of agricultural intensification, environmental performance, and social impacts. Two issues were highlighted from this. First, the relationship between economic and environmental outcomes is regularly assumed, leading to potentially erroneous conclusions and unintended outcomes. Second, the lack of any consideration for the social dimensions of food security ignores variability in incomes generated from agricultural production, and the potential for reduced quantities of food to be produced as a rational response to maximizing gross margins. We suggest the eco‐efficiency concept explicitly include social as well as economic and environmental criteria if it is to avoid poor rates of uptake of eco‐efficiency technologies, the promotion of practices that reduce the effectiveness of hunger‐reduction efforts, and unintended environmental degradation.