bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Variants in Region for Noncoding Interfering Transcript of Dihydrofolate Reductase Gene and Outcome in Childhood Acute Lymphoblastic Leukemia
Authors: Al-Shakfa Fidaa , Dulucq Stphanie , Brukner Ivan , Milacic Iva , Ansari Marc , Beaulieu Patrick , Moghrabi Albert , Laverdire Caroline , Sallan Stephen E. , Silverman Lewis B. , Neuberg Donna , Kutok Jeffery L. , Sinnett Daniel , Krajinovic Maja 
Published: October 2009

Abstract
Purpose: Dihydrofolate reductase (DHFR) is the major target of methotrexate, a key component in childhood acute lymphoblastic leukemia (ALL) treatment. We recently reported an association of DHFR promoter polymorphisms with ALL outcome. Lower event-free survival correlated with haplotype *1, defined by A317 and C1610 alleles. Haplotype *1 was also associated higher DHFR expression.
Experimental Design: Here, we analyzed adjacent 400-bp region participating in DHFR regulation as both a major promoter and a noncoding minor transcript.
Results: Six polymorphisms were identified, of which five were single nucleotide polymorphisms and one was length polymorphism composed of variable number of 9-bp elements and 9-bp insertion/deletion. Haplotype analysis including all promoter polymorphisms revealed diversification of haplotype *1 into five subtypes (*1a-*1e). DNA variations of major promoter/noncoding transcript region and haplotype *1 subtypes were subsequently analyzed for the association with ALL outcome. Lower event-free survival was associated with an A allele of G308A polymorphism (P = 0.02) and with *1b haplotype (P = 0.01). This association was particularly striking in high-risk patients (P = 0.001) and was subsequently confirmed in independent patient cohort (P = 0.02). Haplotype *1b was the only haplotype *1 subtype associated with higher mRNA levels.
Conclusions: The study provides a new insight into DHFR regulatory variations predisposing to an event in ALL patients. (Clin Cancer Res 2009;15(22):69318)
In vitro and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-p53 Injection for Oral Leukoplakia
Authors: Li Yi , Li Long-Jiang , Zhang Song-Tao , Wang Li-Juan , Zhang Zhuang , Gao Ning , Zhang Yuan-Yuan , Chen Qian-Ming 
Published: October 2009

Abstract
Purpose: Oral leukoplakia is a well-recognized precancerous lesion of squamous cell carcinoma. When accompanied with abnormal p53 expression, it suffered a higher risk of canceration. The present study was carried out to test whether the recombinant human adenovirus-p53 could introduce wild-type p53 gene to oral leukoplakia cells and induce cell cycle arrest and apoptosis.
Experimental Design: We select p53(−) oral dysplastic keratinocyte POE-9n, to observe the growth inhibition, cell cycle change, apoptosis-induced effects, and elaborate the corresponding molecular mechanism of recombinant adenovirus-p53 on POE-9n cells. Meanwhile, we evaluate the feasibility, safety, and biological activity of multipoints intraepithelial injections of recombinant adenovirus-p53 in 22 patients with dysplastic oral leukoplakia.
Results: Exogenous p53 could be successfully transduced into POE-9n cells by recombinant adenovirus-p53. The optimal infecting titer in this study was multiplicity of infection (MOI) = 100. Recombinant adenovirus-p53 could strongly inhibit cell proliferation, induce apoptosis, and arrest cell cycle in stage G1 in POE-9n cells by inducing p21CIP/WAF and downregulating bcl-2 expression. In the posttreatment patients, p53 protein and p21CIP/WAF protein expression were significantly enhanced, yet bcl-2 protein presented low expression. Sixteen patients showed clinical response to the treatment, and 14 patients showed obvious histopathologic improvement.
Conclusion: Intraepithelial injections of recombinant human adenovirus-p53 were safe, feasible, and biologically active for patients with dysplastic oral leukoplakia. (Clin Cancer Res 2009;15(21):6724–31)
Differential Cellular Responses to Prolonged LDR-IR in MLH1-Proficient and MLH1-Deficient Colorectal Cancer HCT116 Cells
Authors: Yan Tao , Seo Yuji , Kinsella Timothy J. 
Published: October 2009

Abstract
Purpose: MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining genomic stability by participating in the repair of endogenous and exogenous mispairs in the daughter strands during S phase. Exogenous mispairs can result following treatment with several classes of chemotherapeutic drugs, as well as with ionizing radiation. In this study, we investigated the role of the MLH1 protein in determining the cellular and molecular responses to prolonged lowdose rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer brachytherapy.
Experimental Design: An isogenic pair of MMR+ (MLH1+) and MMR (MLH1) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR (1.3-17 cGy/h 24-96 h). The clonogenic survival and gene mutation rates were examined. Cell cycle distribution was analyzed with flow cytometry. Changes in selected DNA damage repair proteins, DNA damage response proteins, and cell death marker proteins were examined with Western blotting.
Results: MLH1+ HCT116 cells showed greater radiosensitivity with enhanced expression of apoptotic and autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell cycle alterations (increased late-S population and a G2/M arrest) following LDR-IR compared with MLH1 HCT116 cells. Importantly, a progressive increase in MLH1 protein levels was found in MLH1+ cells during prolonged LDR-IR, which was temporally correlated with a progressive decrease in Rad51 protein (involved in homologous recombination) levels.
Conclusions: MLH1 status significantly affects cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to prolonged LDR-IR through inhibition of homologous recombination (through inhibition of Rad51). (Clin Cancer Res 2009;15(22):691220)
Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in mouse models and human cell lines
Authors: Wajapeyee Narendra , Kapoor Varun , Mahalingam Meera , Green Michael R. 
Published: October 2009

Abstract
We recently identified the secreted protein IGFBP7 as a factor required for an activated BRAF oncogene to induce senescence or apoptosis in primary human cells. In human melanomas containing an activating BRAF mutation (BRAF-positive melanomas), IGFBP7 is epigenetically silenced, which seems to be a critical step in melanoma genesis. Restoration of IGFBP7 function by the addition of recombinant IGFBP7 (rIGFBP7) induces apoptosis in BRAF-positive human melanoma cell lines, and systemically administered rIGFBP7 markedly suppresses the growth of BRAF-positive primary tumors in xenografted mice. Here we further evaluate the role of IGFBP7 in the treatment of BRAF-positive melanoma and other malignancies. We find that in human metastatic melanoma samples IGFBP7 is epigenetically silenced and at an even higher frequency than that found in primary melanomas. Using a murine experimental metastasis assay, we show that systemic administration of rIGFBP7 markedly suppresses the growth of metastatic disease and prolongs survival. An analysis of the NCI60 panel of human cancer cell lines reveals that in addition to melanoma, IGFBP7 induces apoptosis in several other cancer types, in particular colorectal cancer cell lines. In general, IGFBP7 induces apoptosis in human cancer cell lines that have an activating mutation in BRAF or RAS, and that are sensitive to chemical inhibition of BRAF-MEK-ERK signaling. Significantly, systemically administered rIGFBP7 blocks the growth of colorectal tumors containing an activating RAS or BRAF mutation in mouse xenografts. The results presented here, in conjunction with those from previous studies, justify the further development of IGFBP7 as an anticancer agent. [Mol Cancer Ther 2009;8(11):3009–14]
Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Stimulation of Glioma Cell Survival Is Dependent on Akt2 Function
Authors: Fortin Shannon P. , Ennis Matthew J. , Savitch Benjamin A. , Carpentieri David , McDonough Wendy S. , Winkles Jeffrey A. , Loftus Joseph C. , Kingsley Christopher , Hostetter Galen , Tran Nhan L. 
Published: October 2009

Abstract
Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and significant technical advances in surgical and radiation treatment, the impact on clinical outcome for patients with malignant gliomas is disappointing. We have previously shown that tumor necrosis factor–like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, can stimulate glioma cell survival via binding to the Fn14 receptor, activation of the NF-κB pathway, and upregulation of BCL-XL gene expression. Here, we show that TWEAK treatment of glioma cells leads to phosphorylation of Akt and BAD. TWEAK stimulation results in the phosphorylation of both Akt1 and Akt2. However, small interfering RNA (siRNA)–mediated depletion of either Akt1 or Akt2 showed that BAD serine 136 phosphorylation is dependent specifically on Akt2 function. Depletion of Akt2 expression by siRNA also abrogates TWEAK-stimulated glioma cell survival, whereas no effect on glioma cell survival was observed after siRNA-mediated depletion of Akt1 expression. Surprisingly, although siRNA-mediated depletion of BAD in glioma cells abrogates cytotoxic- and chemotherapy-induced apoptosis, TWEAK still displays a strong protective effect, suggesting that BAD serine 136 phosphorylation plays a minor role in TWEAK-Akt2–induced glioma cell survival. We also report here that AKT2 gene expression levels increased with glioma grade and inversely correlate with patient survival. Additionally, immunohistochemical analysis showed that Akt2 expression positively correlates with Fn14 expression in glioblastoma multiforme specimens. We hypothesize that the TWEAK-Fn14 signaling axis functions, in part, to enhance glioblastoma cell survival by activation of the Akt2 serine/threonine protein kinase. (Mol Cancer Res 2009;7(11):1871–81)
A Novel Look into Estrogen Receptor–Negative Breast Cancer Prevention with the Natural, Multifunctional Signal Transduction Inhibitor Deguelin
Authors: Rodenberg Jennifer M. , Brown Powel H. 
Published: October 2009

Abstract
This perspective on Murillo et al. (beginning on page 942 in this issue of the journal) examines the potential of the naturally derived agent deguelin to prevent mammary tumorigenesis. These investigators showed that deguelin inhibits wnt/β-catenin signaling in breast cancer cell lines, in addition to inhibiting other previously reported signaling pathways. Our growing understanding of deguelin mechanisms could lead to important advances in the prevention of estrogen receptor–negative breast and other cancers.
Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting
Authors: Morath Tanja , Braun Siegmund , Stegherr Julia , Mehilli Julinda , Vogt Wolfgang , Schömig Albert , Kastrati Adnan , Beckerath Nicolas von , Sibbing Dirk 
Published: October 2009

SummaryClopidogrel low-responsiveness assessed with multiple electrode platelet aggregometry (MEA) has been shown to be a strong and independent predictor of early stent thrombosis (ST) after coronary stenting. The relation of clopidogrel response status, as assessed with MEA, with incidence and timing of ST during an extended follow-up period has never been reported. Here, we report the six-month follow-up results of a prospective trial assessing clopidogrel responsiveness with MEA in patients undergoing percutaneous coronary intervention (PCI). A total of 1,608 consecutive patients with planned drug-eluting stent placement were enrolled in this study. Before PCI patients uniformly received 600 mg clopidogrel and blood was taken directly before PCI to measure ADP-induced platelet aggregation with MEA. The upper quin-tile (20%) of patients according to MEA measurements (n=323) was defined as clopidogrel low responders. Compared with normal responders (n=1,285), the cumulative incidence of definite ST within six months was significantly higher in low responders [2.5% vs. 0.4%; OR 6.5; 95% CI, 2.4–17.0; P<0.001]. The combined incidence of definite or probable ST was higher as well in low vs. normal responders [4.1% vs. 0.7%; OR 5.8; 95% CI, 2.8–12.3; P<0.0001]. A significant inverse correlation of MEA values and the timing of definite or probable ST (in days) was observed (Spearman coefficient = –0.45; P=0.04) with events occurring earlier in the low-responder group. MEA measurements are highly predictive for the occurrence of ST during the first six months following coronary stenting. In the majority of clopidogrel low responders suffering ST, the ischaemic event occurs early in the course after the procedure.
Thromboprophylaxis with low-molecular-weight heparin after cesarean delivery
Authors: Perrier Arnaud , Nendaz Mathieu , Righini Marc , Boehlen Francoise , Boulvain Michel , Moerloose Philippe De , Blondon Marc 
Published: October 2009

SummaryAlthough venous thromboembolism (VTE) is the leading cause of maternal mortality in developed countries, the usefulness of preventive low-molecular-weight heparin (LMWH) after cesarean delivery remains a matter of controversy. It was the objective of this study to evaluate the usefulness of thromboprophylaxis with LMWH after cesarean delivery. A decision model was constructed to evaluate the risks and benefits associated with a seven-day LMWH prophylaxis, compared with none. All probabilities were obtained from literature according to the highest level of evidence. We performed our analysis on two different sets of outcomes (utilities and disutilities), to calculate the quality-adjusted life expectancy at three months. Finally, we calculated the outcomes for four hypothetical cases with different risk. Prophylaxis with LMWH yielded the highest quality-adjusted life expectancy, with a net gain of 1.5–2.8 quality-adjusted days. Sensitivity analyses showed the incidence of VTE after cesarean delivery and the haemorrhagic risk related to LMWH to be critical, at threshold values of 0.15–0.22% and 0.23–0.35%, respectively. In the hypothetical cases, LMWH was safe but only marginally more effective in women with no risk factors. In case of an emergency procedure, a body-mass index >25kg/m2, tobacco smoking, or any combination of these, reductions in VTE greatly outnumbered the increase in major haemorrhages, with a modest benefit on mortality. Our decision analysis suggests that the benefits of LMWH after cesarean delivery exceed the risks. This benefit is, however, very low in women with no risk factors.
Effect of compression stockings on venous blood velocity and blood flow
Authors: Matta Fadi , Yaekoub Abdo , Ahsan Syed , Badshah Aaref , Younas Fahad , Denier James , Stein Paul 
Published: October 2009

SummaryThe effects of graduated compression stockings (GCS) on venous blood velocity have not been established. In healthy subjects, most investigations showed no effect on blood velocity, but mixed results have been reported. In this investigation we to test the hypothesis that popliteal blood velocity is increased by properly fitted GCS. Time average peak velocity in the popliteal vein, as well as time average mean velocity, vein diameter and mean volumetric flow were measured by pulsed wave Doppler ultrasound in 25 healthy male volunteers without compression stockings and repeated with fitted thigh-length compression stockings. Measurements were obtained while supine and while sitting at rest and during ankle exercise. Thigh-length GCS did not increase popliteal vein blood velocity, diameter, or volumetric blood flow while supine or sitting, with or without ankle exercise.
A potential role for islet-1 in post-natal angiogenesis and vasculogenesis
Authors: Barzelay Aya , Ben-Shoshan Jeremy , Entin-Meer Michal , Maysel-Auslender Sofia , Afek Arnon , Barshack Iris , Keren Gad , George Jacob 
Published: October 2009

SummaryThe LIM-homeobox transcription factor islet-1 (Isl1) marks a cell population which gives rise to myocardial, pacemaker, endothelial and smooth muscle cells, which are derived from the secondary heart field during heart embryogenesis. Isl1+ precursors have the potential of self-renewal and differentiation into endothelial, cardiomyocyte and smooth muscle lineages. The primary objective of this study was to determine whether retroviral gene delivery of Isl1 to endothelial cells and mesenchymal stem cells (MSCs) could promote angiogenic and vasculogenic properties. To this end, endothelial cells and rat MSCs were retrovirally transduced to express Isl1. Isl1 expression in endothelial cells resulted in enhanced proliferation and adhesion to fibronectin. In addition, increased IL-1b and VEGF secretion was evident in Isl1 transduced endothelial cells, concomitant with increased migratory and tube formation properties of the endothelial cells. Isl1 expression in MSCs promoted their vasculogenic properties and resulted in enhanced in vitro tube formation. Finally, Isl1 expressing endothelial cells induced enhanced in vivo vascularisation in C57BL/6J mice. These data suggest, for the first time, that Isl1 promotes postnatal angiogenesis and vasculogenesis by improving the angiogenic properties of endothelial cells and MSCs.
Prasugrel compared with high-dose clopidogrel in acute coronary syndrome
Authors: Sideris Georgios , Cohen Remy , Meuleman Catherine , Sollier Claire Bal dit , Barthélémy Olivier , Henry Patrick , Lim Pascal , Beygui Farzin , Collet Jean-Philippe , Marshall Debra , Luo Junxiang , Petitjean Helene , Drouet Ludovic , Montalescot Gilles 
Published: October 2009

SummaryCompared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 μM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.
From Reproduction to Performance: Media-Specific Music for Compact Disc
Authors: Straebel Volker 
Published: October 2009

ABSTRACT
When the compact disc was introduced in 1982, it was considered the first recording medium to vanish behind the audio information carried by it. Artists nevertheless discovered media-specific features unique to the CD. This paper focuses not so much on sound production (skipping CDs, glitches, etc.) as on musical form and listener participation in music for CD, which seems to have anticipated certain aspects of iPod culture.
Infrasonic Music
Authors: Hope Cat 
Published: October 2009

ABSTRACT
Low-frequency sound on the cusp of the audible offers the possibility of redefining the way we think about listening to music. As the perception of pitch is lost in very low-frequency sound emissions, an opportunity arises for a different kind of music and a different way of listening. Low frequencies can be engaged to activate responses other than the aural or be used as a kind of “silent activator,” enabling or affecting other sounds. This article explores the possibilities for what may be called an “infrasonic music.”
The Stochastic Synthesis of Iannis Xenakis
Authors: Luque Sergio 
Published: October 2009

ABSTRACT
In the late 1960s, composer, architect and theoretician Iannis Xenakis (1922–2001) began his research on stochastic synthesis: an approach to microsound synthesis that uses probability distributions to manipulate individual digital samples. He continued with this research for most of the 1970s and from the late 1980s until the end of his career. This article traces the aesthetic origins of this non-standard synthesis technique and gives a historical presentation of its development, including a discussion of the works in which Xenakis used it and a full description of the dynamic stochastic synthesis algorithms. In addition, a new extension of these techniques is put forward: the stochastic concatenation of dynamic stochastic synthesis.
Non-Standard Sound Synthesis with L-Systems
Authors: Manousakis Stelios 
Published: October 2009

ABSTRACT
This paper presents a new non-standard technique for waveform synthesis in the time domain using L-systems, a formalism related to grammars, fractals and automata. This technique, developed as part of a larger-scale compositional system, is based on waveform segmentation and offers various methods for generating wavetables. The paper first introduces L-systems and some specifics of their interpretation and discusses extensions such as incorporating genetic algorithms and designing hierarchical L-systems and L-system networks. The second half describes the implementation model in detail, proposes some sound synthesis strategies and presents paths for further work.
Hallucinations and Related Perceptual Disturbance in a Non-Clinical Spanish Population
Authors: Cangas Adolfo J. , Langer Álvaro I. , Moriana Juan A. 
Published: October 2009

Background: Several studies have suggested the continuity of psychotic symptoms between the general population and clinical samples, and have shown that, in fact, the predisposition to hallucinations is a multi-dimensional construct. However, there is no agreement concerning the number of factors comprising it or the significance of psychotic-like experiences. An examination of the beliefs associated with these experiences could increase knowledge of the continuity of hallucinations. Aims: The purpose of this work was to analyze the structure of the Revized Hallucination Scale (RHS), applied to a sample of Spanish university students to find out the meaning for the participants and their associated beliefs on each item. Methods: The RHS was administered to a total of 265 participants. Along with the frequency of each experience, participants were asked to provide an example of each situation described and to what they attributed it. Results: The results emphasized the presence of four factors that are variously made up of six types of beliefs: personal difficulties; psychological explanations; dreamlike experiences; vivid thoughts; perceptive distortions; and personal desires. Conclusions: The relevance of these results with regard to the differences that might exist in hallucinations in clinical and normal populations is discussed.