bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticandidal activity and biocompatibility of a rechargeable antifungal denture material
Authors: Villar CC , Lin AL , Cao Z , Zhao X‐R , Wu L‐A , Chen S , Sun Y , Yeh C‐K 
Published: July 2012

ObjectivesCandida‐associated denture stomatitis is a recurrent and debilitating oral mucosal disease. Development of anticandidal denture materials represents a promising strategy to manage this condition. We have previously shown that miconazole incorporated in methacrylic acid (MAA) copolymerized diurethane dimethacrylate (UDMA) denture materials has long‐term anticandidal activity. In this study, we examined the ability of culture medium conditioned with drug‐free‐ or miconazole‐MAA‐UDMA discs to prevent Candida infection in an in vitro oral epithelial cell/Candida albicans coculture system.Materials and MethodsCandida albicans (C. albicans)‐induced OKF6/TERT‐2 cell damage was quantified by the release of lactate dehydrogenase from epithelial cells, cytokine production was quantified using protein cytokine arrays, and the expression of C. albicans genes was measured by RT‐qPCR.ResultsCandida albicans had limited growth with altered expression levels of secreted aspartyl proteinase‐2 and ‐5 in culture medium conditioned by miconazole‐MAA‐UDMA discs. Significantly, the ability of C. albicans to induce oral epithelial cell damage and trigger epithelial proinflammatory cytokine production was also inhibited by miconazole disc conditioned media.ConclusionMiconazole released from MAA‐UDMA denture materials effectively prevents the development of candidal infection in an in vitro oral epithelial system. Further characterization of this drug‐rechargeable denture material is warranted.
Aspirin administration by emergency medical dispatchers using a protocol-driven aspirin diagnostic and instruction tool
Authors: Barron Tracey , Clawson Jeff , Scott Greg , Patterson Brett , Shiner Ronald , Robinson Donald , Wrigley Fenella , Gummett James , Olola Christopher H O 
Published: July 2012

BackgroundThe American College of Cardiology and the American Heart Association recommend early aspirin administration to patients with symptoms of acute coronary syndrome (ACS)/acute myocardial infarction (AMI). The primary objective of this study was to determine if Emergency Medical Dispatchers (EMD) can provide chest pain/heart attack patients with standardised instructions effectively, using an aspirin diagnostic and instruction tool (ADxT) within the Medical Priority Dispatch System (MPDS) before arrival of an emergency response crew.MethodsThis retrospective study involved three dispatch centres in the UK and USA. We analysed 6 months of data involving chest pain/heart attack symptoms taken using the MPDS chest pain and heart problems/automated internal cardiac defibrillator protocols.ResultsThe EMDs successfully completed the ADxT on 69.8% of the 44 141 cases analysed. The patient's mean age was higher when the ADxT was completed, than when it was not (mean±SD: 53.9±19.9 and 49.9±20.2; p<0.001, respectively). The ADxT completion rate was higher for second-party than first-party calls (70.3% and 69.0%; p=0.024, respectively). A higher percentage of male than female patients took aspirin (91.3% and 88.9%; p=0.001, respectively). Patients who took aspirin were significantly younger than those who did not (mean±SD: 61.8±17.5 and 64.7±17.9, respectively). Unavailability of aspirin was the major reason (44.4%) why eligible patients did not take aspirin when advised.ConclusionsEMDs, using a standardised protocol, can enable early aspirin therapy to treat potential ACS/AMI prior to responders' arrival. Further research is required to assess reasons for not using the protocol, and the significance of the various associations discovered.
Designing and optimizing swarming in a distributed base station network
Authors: Leroux Philippe , Roy Sébastien 
Published: July 2012

Todays' networks are becoming increasingly complex. They must provide a growing variety of services to a wide range of devices. In order to do so, they must make efficient use of modern technologies including MIMO, macrodiversity, power control, channel allocation, beamforming, and so on.
In this context, the centralized management of radio resources on a large scale is rapidly becoming intractable. Distributed intelligence constitutes an increasingly attractive solution to provide network-wide self-configuration and adaptation capabilities. This article presents the design of a swarming system for autonomous power control which adapts naturally to the changing conditions of mobile networks where interference patterns are in constant flux. Empirical methods proposed by Parunak [1997] to develop MultiAgent Systems with Swarming (MASS) are applied to the current context while emphasizing the key concepts that lead to swarming (emergent behavior). A simulation-based study reveals how the system can be fine-tuned to obtain various solutions, balancing resources differently to achieve different trade-off points. Finally, it is shown that the distributed approach based on swarming is not only feasible but leads to higher global QoS levels than comparable centralized approaches.
Ursolic Acid Inhibits Growth and Metastasis of Human Colorectal Cancer in an Orthotopic Nude Mouse Model by Targeting Multiple Cell Signaling Pathways: Chemosensitization with Capecitabine
Authors: Prasad Sahdeo , Yadav Vivek R. , Sung Bokyung , Reuter Simone , Kannappan Ramaswamy , Deorukhkar Amit , Diagaradjane Parmeswaran , Wei Caimiao , Baladandayuthapani Veerabhadran , Krishnan Sunil , Guha Sushovan , Aggarwal Bharat B. 
Published: July 2012

AbstractPurpose: Development of chemoresistance, poor prognosis, and metastasis often renders the current treatments for colorectal cancer (CRC) ineffective. Whether ursolic acid, a component of numerous medicinal plants, either alone or in combination with capecitabine, can inhibit the growth and metastasis of human CRC was investigated.Experimental design: The effect of ursolic acid on proliferation of CRC cell lines was examined by mitochondrial dye uptake assay, apoptosis by esterase staining, NF-κB activation by DNA-binding assay, and protein expression by Western blot. The effect of ursolic acid on the growth and chemosensitization was also examined in orthotopically implanted CRC in nude mice.Results: We found that ursolic acid inhibited the proliferation of different colon cancer cell lines. This is correlated with inhibition of constitutive NF-κB activation and downregulation of cell survival (Bcl-xL, Bcl-2, cFLIP, and survivin), proliferative (cyclin D1), and metastatic (MMP-9, VEGF, and ICAM-1) proteins. When examined in an orthotopic nude mouse model, ursolic acid significantly inhibited tumor volume, ascites formation, and distant organ metastasis, and this effect was enhanced with capecitabine. Immunohistochemistry of tumor tissue indicated that ursolic acid downregulated biomarkers of proliferation (Ki-67) and microvessel density (CD31). This effect was accompanied by suppression of NF-κB, STAT3, and β-catenin. In addition, ursolic acid suppressed EGF receptor (EGFR) and induced p53 and p21 expression. We also observed bioavailability of ursolic acid in the serum and tissue of animals.Conclusion: Overall, our results show that ursolic acid can inhibit the growth and metastasis of CRC and further enhance the therapeutic effects of capecitabine through the suppression of multiple biomarkers linked to inflammation, proliferation, invasion, angiogenesis, and metastasis. Clin Cancer Res; 18(18); 4942–53. ©2012 AACR.
The European Medicines Agency Review of Eribulin for the Treatment of Patients with Locally Advanced or Metastatic Breast Cancer: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use
Authors: Pean Elias , Klaar Sigrid , Berglund Eva Gil , Salmonson Tomas , Borregaard Jeanett , Hofland Kenneth F. , Ersbøll Jens , Abadie Eric , Giuliani Rosa , Pignatti Francesco 
Published: July 2012

Abstract
The European Commission issued on March 17, 2011, a marketing authorization valid throughout the European Union (EU) for eribulin (Halaven; Eisai Limited). The decision was based on the favorable opinion of the Committee for Medicinal Products for Human Use recommending a marketing authorization for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least 2 chemotherapeutic regimens for advanced disease. Eribulin mesylate is a structurally simplified synthetic analogue of halichondrin B, which is a natural product isolated from the marine sponge Halichondria okadai (ATC code L01XX41). Eribulin is a nontaxane, microtubule dynamics inhibitor belonging to the halichondrin class of antineoplastic agents. Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates leading to G2–M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. The recommended dose of eribulin is 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate) to be administered intravenously over 2 to 5 min on days 1 and 8 of a 3-week cycle. In the pivotal trial, eribulin was associated with increased overall survival in patients with locally advanced or metastatic breast cancer who received at least 2 prior chemotherapy lines for advanced disease (median overall survival was 13.2 months in the eribulin arm vs. 10.6 months in the control arm; HR = 0.805; 95% confidence interval, 0.677–0.958; P = 0.014). The most common side effects are asthenia or fatigue and neutropenia. The objective of this article is to summarize the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary report and product information, including product characteristics, are available on the European Medicines Agency website. Clin Cancer Res; 18(17); 4491–7. ©2012 AACR.
Personalized Nanomedicine
Authors: Lammers Twan , Rizzo Larissa Y. , Storm Gert , Kiessling Fabian 
Published: July 2012

Abstract
Personalized medicine aims to individualize chemotherapeutic interventions on the basis of ex vivo and in vivo information on patient- and disease-specific characteristics. By noninvasively visualizing how well image-guided nanomedicines—that is, submicrometer-sized drug delivery systems containing both drugs and imaging agents within a single formulation, and designed to more specifically deliver drug molecules to pathologic sites—accumulate at the target site, patients likely to respond to nanomedicine-based therapeutic interventions may be preselected. In addition, by longitudinally monitoring how well patients respond to nanomedicine-based therapeutic interventions, drug doses and treatment protocols can be individualized and optimized during follow-up. Furthermore, noninvasive imaging information on the accumulation of nanomedicine formulations in potentially endangered healthy tissues may be used to exclude patients from further treatment. Consequently, combining noninvasive imaging with tumor-targeted drug delivery seems to hold significant potential for personalizing nanomedicine-based chemotherapeutic interventions, to achieve delivery of the right drug to the right location in the right patient at the right time. Clin Cancer Res; 18(18); 4889–94. ©2012 AACR.
Determinants and Prognostic Significance of Exercise Pulmonary Hypertension in Asymptomatic Severe Aortic Stenosis
Authors: Lancellotti Patrizio , Magne Julien , Donal Erwan , O'Connor Kim , Dulgheru Raluca , Rosca Monica , Pierard Luc A. 
Published: July 2012

Background—
Recent studies emphasized the usefulness of exercise stress echocardiography in asymptomatic patients with aortic stenosis. Nevertheless, the additive value of exercise pulmonary hypertension (Ex-PHT) in such patients remains unexplored. We therefore aimed to identify the determinants and to test the impact on outcome of Ex-PHT in asymptomatic patients with severe aortic stenosis.

Method and Results—

Asymptomatic patients with severe aortic stenosis (n=105; aortic valve area <0.6 cm
2
/m
2
; age, 71±9 years; male, 59%) and preserved left ventricular systolic function (ejection fraction ≥55%) were prospectively submitted to exercise stress echocardiography. Resting PHT and Ex-PHT were defined as a systolic pulmonary arterial pressure >50 and >60 mm Hg, respectively. Ex-PHT was more frequent than resting PHT (55% versus 6%;
P
<0.0001). On multivariable logistic regression, the independent predictors of Ex-PHT were male sex (odds ratio, 4.3;
P
=0.002), resting systolic pulmonary arterial pressure (odds ratio, 1.16;
P
=0.002), exercise indexed left ventricular end-diastolic volume (odds ratio, 1.04;
P
=0.026), exercise e′-wave velocity (odds ratio, 1.35;
P
=0.047), and exercise-induced changes in indexed left atrial area (odds ratio, 1.36;
P
=0.006). Ex-PHT was associated with reduced cardiac event-free survival (at 3 years, 22±7% versus 55±9%;
P
=0.014). In a multivariable Cox proportional hazards model, Ex-PHT was identified as an independent predictor of cardiac events (hazard ratio, 1.8; 95% confidence interval, 1.0–3.3;
P
=0.047). When exercise-induced changes in mean aortic pressure gradient were added to the multivariable model, Ex-PHT remained independently associated with reduced cardiac event-free survival (hazard ratio, 2.0; 95% confidence interval, 1.1–3.6;
P
=0.025).

Conclusions—
In asymptomatic patients with severe aortic stenosis, the main determinants of Ex-PHT are male sex, resting systolic pulmonary arterial pressure, and exercise parameters of diastolic burden. Moreover, Ex-PHT is associated with a 2-fold increased risk of cardiac events. These results strongly support the use of exercise stress echocardiography in asymptomatic aortic stenosis.
Effect of Lanz Pressure Regulating Valve on Self-sealing Mechanism and Air Leakage Across the Tracheal Tube Cuffs in a Benchtop Model
Authors: Dave Mital H. , Spielmann Nelly , Mauch Jacqueline , Weiss Markus 
Published: July 2012

Background: The aim of the present study was to investigate the effect of the Lanz system on air sealing by self-inflation in high volume–low pressure (HVLP) tube cuffs. Methods: In vitro tracheal air sealing was studied in HVLP tracheal tube cuffs (internal diameter [ID] 8.0 mm) made from polyurethane ([PU] Seal Guard tracheal tube, Covidien, Athlone, Ireland) and from polyvinylchloride ([PVC] HiLo tracheal tube, Covidien) with and without Lanz pressure regulating valve. Tube cuffs were placed in a vertical 22 mm ID artificial trachea and inflated to 5, 10, 15, 20, 25, or 30 cm H2O cuff pressures. Pressure control ventilation with peak inspiratory pressures (PIPs) of 20 or 25 cm H2O was applied and air leakage was assessed spirometrically as the ratio of expiratory to inspiratory tidal volumes. Nonparametric Mann-Whitney test was applied to compare the air leakage with and without Lanz system for both cuff types at each cuff pressure and PIP ( P < .05). Results: The PVC tube cuffs with Lanz system resulted in significant air leakage at both 20 and 25 cm H2O PIP as compared to those without the Lanz system, especially at cuff pressures lower than the preset PIP ( P < .05). Although PU tube cuffs with Lanz system showed reduced air sealing when compared with cuffs without Lanz, the difference was not statistically significant. Conclusion: Cuff pressure compensation with the Lanz system during cyclic respiratory pressure changes interferes with the self-sealing mechanism in HVLP tube cuffs at cuff pressures lower than PIP level. This results in larger air leak across tube cuffs particularly in tube cuffs made from PVC.
Interpositional Arthroplasty of the First Metatarsophalangeal Joint Using a Regenerative Tissue Matrix for the Treatment of Advanced Hallux Rigidus
Authors: Hyer Christopher F. , Granata Jaymes D. , Berlet Gregory C. , Lee Thomas H. 
Published: July 2012

Background. Painful osteoarthritis of the first metatarsophalangeal (MTP) joint, known as hallux rigidus, can be difficult to treat in young and active patients that who fail conservative treatment. The purpose of this study is to report the 5-year follow-up of a joint preservation technique for the treatment of advanced hallux rigidus. Methods. Preservation of the first MTP joint is performed using a human acellular dermal regenerative matrix as an interpositional arthroplasty graft. A retrospective chart review was performed and compared with follow-up modified American Orthopedic Foot and Ankle scores (AOFAS) obtained by telephone. Of the first 9 consecutive patients in the original study cohort, 6 patients were available for follow-up. The outcome measures include AOFAS modified for pain and function, reoperation rates, and overall satisfaction with the procedure. Results. The average follow-up was 5.43 years. No patient had a subsequent fusion or additional procedure performed on their first MTP joint. Average preoperative modified AOFAS were 38 (range, 34 to 43). Average postoperative AOFAS were 65.8 (range, 58 to 68). All patients were satisfied with their results. Conclusion. Interpositional arthroplasty of the first MTP joint using a regenerative tissue matrix has led to reliable pain relief and preserved function at an average follow-up of 5.4 years in 6 patients. The authors recommend this technique to active patients with advanced hallux rigidus who want to delay a fusion of their first MTP joint. Levels of Evidence: Therapeutic, Level IV
Cosmetic Results of Wedge Resection of Nail Matrix (Winograd Technique) in the Treatment of Ingrown Toenail
Authors: Kose Ozkan , Guler Ferhat , Gurcan Serkan , Arik Hasan Onur , Baz Ali Bulent , Akalin Serdar 
Published: July 2012

Objective: The purpose of this retrospective study is to evaluate the cosmetic results of wedge resection of the nail matrix (Winograd technique) in the treatment of ingrown toenail. Materials and methods: This study retrospectively reviewed medical charts of 68 patients with 75 ingrown toenails who underwent surgical correction with the Winograd technique between January, 2008, and December, 2009, at the Orthopaedics and Traumatology Department, Antalya Education and Research Hospital. For the final follow-up, patients were contacted by telephone and completed a telephone questionnaire. Recurrence, cosmetic results, and satisfaction of the patients were the major outcome measures. Results: There was recurrence in 9 patients (13.2%). The mean recurrence time was 6.7 months (range = 2-12 months). All recurrences involved the lateral border of the toenail. Cosmetic ratings were statistically lower in female patients (P = .005). The reasons for poor and acceptable cosmetic results were proximal-incision scar and narrowing of the nail plate. Conclusion: Wedge resection of nail matrix has a considerably high recurrence rate. Furthermore, narrowing of the nail plate is a disadvantage of this procedure. All patients should be informed about the possibility of recurrence and disfigurement in their toenails (narrow nail plate). Particularly, female patients who care about the cosmesis may be dissatisfied with this surgical technique. Levels of Evidence: Therapeutic, Level IV
Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea(L.) and their relevance for perfume manufacture
Authors: Caniard Anne , Zerbe Philipp , Legrand Sylvain , Cohade Allison , Valot Nadine , Magnard Jean-Louis , Bohlmann Jörg , Legendre Laurent 
Published: July 2012

Abstract

Background
Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea) and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species.

Results
Based on previous general knowledge of diterpene biosynthesis in angiosperms, and based on mining of our recently published transcriptome database obtained by deep 454-sequencing of cDNA from clary sage calices, we cloned and functionally characterized two new diterpene synthase (diTPS) enzymes for the complete biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS) produced labda-13-en-8-ol diphosphate as major product from geranylgeranyl diphosphate (GGPP) with some minor quantities of its non-hydroxylated analogue, (9 S, 10 S)-copalyl diphosphate. A class I diTPS (SsSS) then transformed these intermediates into sclareol and manool, respectively. The production of sclareol was reconstructed in vitro by combining the two recombinant diTPS enzymes with the GGPP starting substrate and in vivo by co-expression of the two proteins in yeast (Saccharomyces cerevisiae). Tobacco-based transient expression assays of green fluorescent protein-fusion constructs revealed that both enzymes possess an N-terminal signal sequence that actively targets SsLPPS and SsSS to the chloroplast, a major site of GGPP and diterpene production in plants.

Conclusions

SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid specialized metabolite sclareol in a two-step process. They represent two of the first characterized hydroxylating diTPSs in angiosperms and generate the dihydroxylated labdane sclareol without requirement for additional enzymatic oxidation by activities such as cytochrome P450 monoxygenases. Yeast-based production of sclareol by co-expresssion of SsLPPS and SsSS was efficient enough to warrant the development and use of such technology for the biotechnological production of scareol and other oxygenated diterpenes.