bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Erectile Function in CD73-Deficient Mice with Reduced Endogenous Penile Adenosine Production
Authors: Wen Jiaming , Dai Yingbo , Zhang Yujin , Zhang Weiru , Kellems Rodney E. , Xia Yang 
Published: May 2011

ABSTRACT

Introduction
Adenosine has been implicated in normal and abnormal penile erection. However, a direct role of endogenous adenosine in erectile physiology and pathology has not been established.

Aim
To determine the functional role of endogenous adenosine production in erectile function.

Methods
CD73-deficient mice (CD73–/–) and age-matched wild-type (WT) mice were used. Some WT mice were treated with alpha, beta-methylene adenosine diphosphate (ADP) (APCP), a CD73-specific inhibitor. High-performance liquid chromatography was used to measure adenosine levels in mouse penile tissues. In vivo assessment of intracorporal pressure (ICP) normalized to mean arterial pressure (MAP) in response to electrical stimulation (ES) of the cavernous nerve was used.

Main Outcome Measurement
The main outcome measures of this study were the in vivo assessment of initiation and maintenance of penile erection in WT mice and mice with deficiency in CD73 (ecto-5′-nucleotidase), a key cell-surface enzyme to produce extracellular adenosine.

Results
Endogenous adenosine levels were elevated in the erected state induced by ES of cavernous nerve compared to the flaccid state in WT mice but not in CD73–/– mice. At cellular levels, we identified that CD73 was highly expressed in the neuronal, endothelial cells, and vascular smooth muscle cells in mouse penis. Functionally, we found that the ratio of ES-induced ICP to MAP in CD73–/– mice was reduced from 0.48 ± 0.03 to 0.33 ± 0.05 and ES-induced slope was reduced from 0.30 ± 0.13 mm Hg/s to 0.15 ± 0.05 mm Hg/s (both P &lt; 0.05). The ratio of ES-induced ICP to MAP in APCP-treated WT mice was reduced from 0.49 ± 0.03 to 0.38 ± 0.06 and ES-induced slope was reduced from 0.29 ± 0.11 mm Hg/s to 0.19 ± 0.04 mm Hg/s (both P &lt; 0.05).

Conclusion
Overall, our findings demonstrate that CD73-dependent production of endogenous adenosine plays a direct role in initiation and maintenance of penile erection.
The Subjective Sexual Arousal Scale for Men (SSASM): Preliminary Development and Psychometric Validation of a Multidimensional Measure of Subjective Male Sexual Arousal
Authors: Althof Stanley E. , Perelman Michael A. , Rosen Raymond C. 
Published: May 2011

ABSTRACT

Introduction
Sexual arousal is a multifaceted process that involves both mental and physical components. No instrument has been developed and validated to assess subjective aspects of male sexual arousal.

Aim
To develop and psychometrically validate a self-administered scale for assessing subjective male sexual arousal.

Methods
Using recommendations of the Food and Drug Administration (FDA) guidance on patient-reported outcome instruments, important aspects of male sexual arousal were identified via qualitative research (focus groups and interviews) of U.S. men with erectile dysfunction (ED) and healthy controls. After a preliminary questionnaire was developed by a panel of experts, a quantitative study of men with ED and controls was conducted to psychometrically validate the Subjective Sexual Arousal Scale for Men (SSASM).

Main Outcome Measures
To develop a male sexual arousal scale and determine its factor structure, reliability, and construct validity.

Results
Five aspects of male sexual arousal were identified from the qualitative focus groups and cognitive interviews. Men's preferred language for describing sexual arousal and preferred response formats were incorporated into the questions. Factor analysis of data from the quantitative study of 304 men aged 21 to 70 years identified five domains with eigenvalues &gt;1: sexual performance (six items), mental satisfaction (five items), sexual assertiveness (three items), partner communication (three items), and partner relationship (three items). The five domains had a high degree of internal consistency (Cronbach's alpha values 0.88–0.94). Test–retest reliability over a 2- to 4-week period was high–moderately high (r values 0.75–0.88) for the five domain scores. Correlations between SSASM domain scores and standardized scale scores for social desirability, general health, life satisfaction, and sexual function demonstrated the construct validity of the scale.

Conclusions
Preliminary validation data suggest that the 20-item SSASM scale may be useful as a multidimensional, reliable, self-administered instrument for assessing subjective sexual arousal in men of different ages.
Oral antimicrobial use in outpatient cystic fibrosis pulmonary exacerbation management: a single‐center experience
Authors: Briggs Elissa Charlotte , Nguyen Thuan , Wall Michael Abraham , MacDonald Kelvin David 
Published: May 2011

AbstractIntroduction:  Cystic fibrosis (CF) pulmonary disease is characterized by intermittent episodes of acute lung symptoms known as ‘pulmonary exacerbations’. While exacerbations are classically treated with parenteral antimicrobials, oral antibiotics are often used in ‘mild’ cases.Objectives:  We determined how often management progressed to intravenous (IV) therapy. We also examined multiple courses of oral antimicrobials within one exacerbation, and identified patient factors associated with unsuccessful treatment.Methods:  We performed a retrospective chart audit of oral antibiotic use in CF patients, from March 2009 through March 2010, for ‘mild’ CF exacerbations.Results:  Administration of a single vs multiple courses of oral antibiotics for treatment of ‘mild’ CF exacerbation avoided progression to IV therapy 79.8% and 50.0% of the time, respectively. Overall, oral antibiotics circumvented the need for IV therapy 73.8% of the time. Using multi‐variant analysis, we found multiple patient characteristics to be independent risk factors for oral antibiotic failure including a history of pseudomonas infection [odds ratio (OR) 2.13, confidence interval (CI) 1.29–3.54], CF‐related diabetes (OR 1.85, CI 1.00–3.41), allergic Bronchopulmonary aspergillosis (OR 3.81, CI 1.38–10.56), low socioeconomic status (OR 1.67, CI 1.04–2.67), and calculated baseline forced expiratory volume in 1 s (FEV1) <75% of predicted prior to an acute exacerbation (OR 1.93, CI 1.20–3.08). Decline in FEV1 > 10%, weight for age, body mass index, distance from the CF center and gender were not significant.Conclusion:  Our observations suggest that one course of oral antimicrobials is frequently effective in outpatient CF pulmonary exacerbations but exacerbations requiring more than one course of oral antibiotics are likely to require IV therapy.Please cite this paper as: Briggs EC, Nguyen T, Wall MC and MacDonald KD. Oral antimicrobial use in outpatient cystic fibrosis pulmonary exacerbation management: a single‐center experience. Clin Respir J 2012; 6: 56–64.
Kakusan4 and Aminosan: two programs for comparing nonpartitioned, proportional and separate models for combined molecular phylogenetic analyses of multilocus sequence data
Authors: TANABE AKIFUMI S. 
Published: May 2011

AbstractProportional and separate models able to apply different combination of substitution rate matrix (SRM) and among‐site rate variation model (ASRVM) to each locus are frequently used in phylogenetic studies of multilocus data. A proportional model assumes that branch lengths are proportional among partitions and a separate model assumes that each partition has an independent set of branch lengths. However, the selection from among nonpartitioned (i.e., a common combination of models is applied to all‐loci concatenated sequences), proportional and separate models is usually based on the researcher's preference rather than on any information criteria. This study describes two programs, ‘Kakusan4’ (for DNA sequences) and ‘Aminosan’ (for amino‐acid sequences), which allow the selection of evolutionary models based on several types of information criteria. The programs can handle both multilocus and single‐locus data, in addition to providing an easy‐to‐use wizard interface and a noninteractive command line interface. In the case of multilocus data, SRMs and ASRVMs are compared at each locus and at all‐loci concatenated sequences, after which nonpartitioned, proportional and separate models are compared based on information criteria. The programs also provide model configuration files for mrbayes, paup*, phyml, raxml and Treefinder to support further phylogenetic analysis using a selected model. When likelihoods are optimized by Treefinder, the best‐fit models were found to differ depending on the data set. Furthermore, differences in the information criteria among nonpartitioned, proportional and separate models were much larger than those among the nonpartitioned models. These findings suggest that selecting from nonpartitioned, proportional and separate models results in a better phylogenetic tree. Kakusan4 and Aminosan are available at http://www.fifthdimension.jp/. They are licensed under gnugpl Ver.2, and are able to run on Windows, MacOS X and Linux.
Field guide to next‐generation DNA sequencers
Authors: GLENN TRAVIS C. 
Published: May 2011

AbstractThe diversity of available 2nd and 3rd generation DNA sequencing platforms is increasing rapidly. Costs for these systems range from <$100 000 to more than $1 000 000, with instrument run times ranging from minutes to weeks. Extensive trade‐offs exist among these platforms. I summarize the major characteristics of each commercially available platform to enable direct comparisons. In terms of cost per megabase (Mb) of sequence, the Illumina and SOLiD platforms are clearly superior (≤$0.10/Mb vs. >$10/Mb for 454 and some Ion Torrent chips). In terms of cost per nonmultiplexed sample and instrument run time, the Pacific Biosciences and Ion Torrent platforms excel, with the 454 GS Junior and Illumina MiSeq also notable in this regard. All platforms allow multiplexing of samples, but details of library preparation, experimental design and data analysis can constrain the options. The wide range of characteristics among available platforms provides opportunities both to conduct groundbreaking studies and to waste money on scales that were previously infeasible. Thus, careful thought about the desired characteristics of these systems is warranted before purchasing or using any of them. Updated information from this guide will be maintained at: http://dna.uga.edu/ and http://tomato.biol.trinity.edu/blog/.
Analysing recombination in nucleotide sequences
Authors: MARTIN DARREN P. , LEMEY PHILIPPE , POSADA DAVID 
Published: May 2011

AbstractThroughout the living world, genetic recombination and nucleotide substitution are the primary processes that create the genetic variation upon which natural selection acts. Just as analyses of substitution patterns can reveal a great deal about evolution, so too can analyses of recombination. Evidence of genetic recombination within the genomes of apparently asexual species can equate with evidence of cryptic sexuality. In sexually reproducing species, nonrandom patterns of sequence exchange can provide direct evidence of population subdivisions that prevent certain individuals from mating. Although an interesting topic in its own right, an important reason for analysing recombination is to account for its potentially disruptive influences on various phylogenetic‐based molecular evolution analyses. Specifically, the evolutionary histories of recombinant sequences cannot be accurately described by standard bifurcating phylogenetic trees. Taking recombination into account can therefore be pivotal to the success of selection, molecular clock and various other analyses that require adequate modelling of shared ancestry and draw increased power from accurately inferred phylogenetic trees. Here, we review various computational approaches to studying recombination and provide guidelines both on how to gain insights into this important evolutionary process and on how it can be properly accounted for during molecular evolution studies.
Rapid development and screening of microsatellite loci for Artibeus lituratus and their utility for six related species within Phyllostomidae
Authors: McCULLOCH EVE S. , STEVENS RICHARD D. 
Published: May 2011

AbstractMicrosatellites are often the marker of choice for population genetic studies at intermediate spatial and temporal scales. Developing large numbers of markers has traditionally been technically difficult, and this has limited our ability to investigate evolutionary phenomena that emerge across short temporal scales. Moreover, few markers tend to successfully amplify across species boundaries. As rapid advancements in high‐throughput sequencing make microsatellite development cost‐ and time‐effective, new avenues for evolutionary, population genetic and chromosome linkage mapping research are emerging. We used a published PERL script and second‐generation sequencing to rapidly and affordably develop microsatellite loci for a widespread phyllostomid bat, Artibeus lituratus, for which no markers were previously available. We used Roche FLX (Titanium) Genome Sequencing to randomly sequence ∼101 Mb (255 065 unique reads) of genomic DNA for A. lituratus, within which we discovered 30 100 microsatellite loci. We designed primers for 19 395 loci that contained suitable flanking regions. We ordered primers for 96 loci, 90 of which produced a single PCR product in A. lituratus. We genotyped 52 loci, and 45 were polymorphic in A. lituratus. We tested cross‐species amplification for 96 loci in six additional phyllostomid species: A. planirostris, A. fimbriatus, A. phaeotis, Enchisthenes hartii, Sturnira lilium, and Carollia perspicillata. Cross‐species amplification was successful for at least one species for 87 loci (A. fimbriatus), and in all species, at least 66 loci were amplified. These markers will not only facilitate future work on these seven species, but also illustrate the utility of this high‐throughput method for development of primers across many species simultaneously.
Suppression of α5 gene expression is closely related to the tumorigenic properties of uveal melanoma cell lines
Authors: Landreville Solange , Vigneault François , Bergeron Marjorie‐Allison , Leclerc Steeve , Gaudreault Manon , Morcos Mohib , Mouriaux Frédéric , Salesse Christian , Guérin Sylvain L. 
Published: May 2011

SummaryCancer aggressiveness is related to the ability of cancer cells to escape the anchorage dependency toward the extracellular matrix, a process regulated by the integrin α5β1 and its ligand fibronectin. Here, we characterized the expression of the α5 gene in human uveal melanoma cell lines with distinct tumorigenic properties and investigated some of the mechanisms underlying the variations of their malignancy. Strong and weak expression of α5 was observed in cells with no (T108/T115) and high (T97/T98) tumorigenic properties, respectively. Expression and DNA binding of the transcription factors Sp1, activator protein 1 (AP‐1) (both acting as activators), and nuclear factor I (NFI) (a strong repressor) to the α5 promoter were demonstrated in all cell lines. A reduced expression of AP‐1 combined with a dramatic increase in NFI correlated with the suppression of α5 expression in T97 and T98 cells. Restoring α5 expression in T97 cells entirely abolished their tumorigenicity in immunodeficient mice. These uveal melanoma cell lines might therefore prove particularly useful as cellular models to investigate α5β1 function in the pathogenesis of invasive uveal melanoma.
The role of visual evoked potential and electroretinography in the preoperative assessment of osteo‐keratoprosthesis or osteo‐odonto‐keratoprosthesis surgery
Authors: de Araujo Aline L. , Charoenrook Victor , de la Paz Maria F. , Temprano Jose , Barraquer Rafael I. , Michael Ralph 
Published: May 2011

Abstract.Purpose:  To determine the value of electroretinography (ERG) and visual evoked potential (VEP) in predicting visual outcome in patients undergoing osteo‐keratoprosthesis (OKP) or osteo‐odonto‐keratoprosthesis (OOKP) surgery.Methods:  We performed a retrospective cohort study of 143 eyes in 101 patients who underwent OKP or OOKP surgery. The subjects underwent ERG, VEP testing or both up to 6 months prior to surgery. The ERG and VEP results were classified into four categories based on wave amplitude, latency and configuration. The main outcome was the maximum best‐corrected visual acuity (maxBCVA) reached at any time postoperatively.Results:  One hundred thirty‐four cases had undergone preoperative ERG, 82 VEP and 73 both examinations. The sensitivities of ERG and VEP to detect maxBCVA ≥ 0.05 were 68.5% and 87%, respectively, while the specificity was 63.2% for ERG and 47.4% for VEP. The maxBCVA was significantly better in patients with normal ERG (p = 0.033) and those with normal VEP (p = 0.048), once having defined appropriate normal and abnormal cut‐off levels. When comparing fellow eyes in patients who underwent surgery in both eyes, maxBCVA was better in the eyes that had better VEP results (p = 0.013).Conclusion:  Eyes demonstrating normal ERG or VEP achieved better visual outcome than those with abnormal results. In addition, VEP proved instrumental in determining the eye with the best prognosis when comparing both eyes of a given patient.
Transretinal uveal melanoma biopsy with 25‐gauge vitrectomy system
Authors: Abi‐Ayad Neil , Grange Jean‐Daniel , Salle Monique , Kodjikian Laurent 
Published: May 2011

Abstract.Purpose:  To evaluate the efficacy and the safety of uveal melanoma transretinal biopsy using 25‐gauge vitrectomy system.Methods:  At the patient’s request of a tissue diagnosis, nine posterior uveal melanomas treated by proton‐beam therapy were biopsied during the insertion of tantalium markers.Results:  The diagnosis was uveal melanoma, confirmed in all cases using cytological (7 of 9) and histological analysis (2 of 9). Immunocytochemistry was performed on all samples (9 of 9). In eight of nine patients, minor postoperative vitreous haemorrhages were seen, which resolved in 1 day. No other ocular complications were noticed.Conclusion:  Uveal melanoma biopsy using 25‐gauge vitrectomy system is a valuable procedure to confirm the diagnosis, with adequate sample and low ocular morbidity.
Structure activity relationship, acute toxicity and cytotoxicity of antimycobacterial neolignan analogues
Authors: de Souza Ana Olívia , Alderete Joel Bernabé , Minarini Paulo Roberto Regazi , da Silva Melo Patrícia , Ferreira Iasmin , Barata Lauro Euclides Soares , Silva Célio Lopes 
Published: May 2011

Abstract

Objectives
The study's aims were to evaluate the antimycobacterial activity of 13 synthetic neolignan analogues and to perform structure activity relationship analysis (SAR). The cytotoxicity of the compound 2-phenoxy-1-phenylethanone (LS-2, 1) in mammalian cells, such as the acute toxicity in mice, was also evaluated.

Methods
The extra and intracellular antimycobacterial activity was evaluated on Mycobacterium tuberculosis H37Rv. Cytotoxicity studies were performed using V79 cells, J774 macrophages and rat hepatocytes. Additionally, the in-vivo acute toxicity was tested in mice. The SAR analysis was performed by Principal Component Analysis (PCA).

Key findings
Among the 13 analogues tested, LS-2 (1) was the most effective, showing promising antimycobacterial activity and very low cytotoxicity in V79 cells and in J774 macrophages, while no toxicity was observed in rat hepatocytes. The selectivity index (SI) of LS-2 (1) was 91 and the calculated LD50 was 1870 mg/kg, highlighting the very low toxicity in mice. SAR analysis showed that the highest electrophilicity and the lowest molar volume are physical-chemical characteristics important for the antimycobacterial activity of the LS-2 (1).

Conclusions
LS-2 (1) showed promising antimycobacterial activity and very weak cytotoxicity in cell culture, as well as an absence of toxicity in primary culture of hepatocytes. In the acute toxicity study there was an indication of absence of toxicity on murine models, in vivo.
Design of clinically useful macromolecular iron chelators
Authors: Zhou Tao , Winkelmann Günther , Dai Zhi-Yuan , Hider Robert C 
Published: May 2011

Abstract

Objectives
In recent years, macromolecular iron chelators have received increasing attention as human therapeutic agents. The objectives of this article are: one, to discuss the factors which should be considered when designing iron binding macromolecules as human therapeutic agents, and two, to report recent achievements in the design and synthesis of appropriate macromolecular chelators that have resulted in the production of a number of agents with therapeutic potential.

Key findings
Macromolecular drugs exhibit unique pharmaceutical properties that are fundamentally different from their traditional small-molecule counterparts. By virtue of their high-molecular-weight characteristics, many are confined to extracellular compartments, for instance, the serum and the gastrointestinal tract. In addition, they have potential for topical administration. Consequently, these macromolecular drugs are free from many of the toxic effects that are associated with their low-molecular-weight analogues.

Summary
The design and synthesis of macromolecular iron chelators provides a novel aspect to chelation therapy. 3-Hydroxypyridin-4-one hexadentate-based macromolecular chelators have considerable potential for the development of new treatments for iron overload and for topical treatment of infection.
Multivesicular liposome (MVL) sustained delivery of a novel synthetic cationic GnRH antagonist for prostate cancer treatment
Authors: Wang Tao , Gao Lijun , Quan Dongqin 
Published: May 2011

Abstract

Objectives
Multivesicular liposomes (MVLs) are often used as an appropriate carrier for delivering peptides due to high drug loading, relative stability and extended-release behaviour. However, when cationic amphipathic peptides are involved, some challenges may be encountered, including instability of multiple emulsions due to interaction between peptides and lipid membranes (electrostatic and hydrophobic interaction). LXT-101, a cationic amphipathic peptide, is a novel antagonist of gonadotropin-releasing hormone (GnRH) for prostate cancer treatment. The purpose of the current research was to explore simple methods of determining the interaction between peptide and lipid bilayer and to prepare MVLs of LXT-101 (DepoLXT-101) by the modified DepoFoam technique.

Methods
The anionic surfactants were added in the process of DepoLXT-101 preparation in order to minimize the effect of instability resulting from cationic peptides.

Key findings
DepoLXT-101 was obtained with good efficiency and reproduction. The integrity of encapsulated peptide was maintained as shown by RP-HPLC. DepoLXT-101 particles were characterized by morphology and particle size distribution and in-vitro release was also investigated. The release behaviour in vitro in medium of sodium chloride at 37°C showed that 70–90% of LXT-101 was released slowly from MVLparticles over 11 days. According to the fitting results of Ritgar-Pepps model, the in-vitro release of DepoLXT-101 was mainly governed by Fick's diffusion.

Conclusions
The data obtained from in-vivo study indicated that a sustained anticancer effect can be achieved over a 7-day period with subcutaneous administration of DepoLXT-101 in rats.