bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease
Authors: Skirnisdottir Ingiridur , Mayrhofer Markus , Rydåker Maria , Åkerud Helena , Isaksson Anders 
Published: September 2012

Abstract

Background
Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome.

Methods
Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified.

Results
The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function.

Conclusions
The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.
GCH1-Polymorphism and Pain Sensitivity among Women with Provoked Vestibulodynia
Authors: Heddini Ulrika , Bohm-Starke Nina , Grönbladh Alfhild , Nyberg Fred , Nilsson Kent W , Johannesson Ulrika 
Published: September 2012

Background: Provoked vestibulodynia (PVD) is a pain disorder localized in the vestibular mucosa. It is the most common cause of dyspareunia among young women and it is associated with general pain hypersensitivity and other chronic pain conditions. Polymorphism in the guanosine triphosphate cyclohydrolase ( GCH1) gene has been found to influence general pain sensitivity and the risk of developing a longstanding pain condition. The aim of this study was to investigate GCH1-polymorphism in women with PVD and healthy controls, in correlation to pain sensitivity. Results: We found no correlation between the previously defined pain-protective GCH1-SNP combination and the diagnosis of PVD. Nor any correlation with pain sensitivity measured as pressure pain thresholds on the arm, leg and in the vestibule, coital pain scored on a visual analog scale and prevalence of other bodily pain conditions among women with PVD (n = 98) and healthy controls (n = 102). However, among patients with current treatment (n = 36), there was a significant interaction effect of GCH1-gene polymorphism and hormonal contraceptive (HC) therapy on coital pain (p = 0.04) as well as on pressure pain thresholds on the arm (p = 0.04). PVD patients carrying the specified SNP combination and using HCs had higher pain sensitivity compared to non-carriers. In non-HC-users, carriers had lower pain sensitivity. Conclusions: The results of this study gave no support to the hypothesis that polymorphism in the GCH1-gene contributes to the etiology of PVD. However, among patients currently receiving treatment an interaction effect of the defined SNP combination and use of hormonal contraceptives on pain sensitivity was found. This finding offers a possible explanation to the clinically known fact that some PVD patients improve after cessation of hormonal contraceptives, indicating that PVD patients carrying the defined SNP combination of GCH1 would benefit from this intervention.
Ultrabithorax confers spatial identity in a context-specific manner in the Drosophila postembryonic ventral nervous system
Authors: Marin Elizabeth C , Dry Katie E , Alaimo Danielle R , Rudd Kirstin T , Cillo Anthony R , Clenshaw Michael E , Negre Nicolas , White Kevin P , Truman James W 
Published: September 2012

Abstract

Background
In holometabolous insects such as Drosophila melanogaster, neuroblasts produce an initial population of diverse neurons during embryogenesis and a much larger set of adult-specific neurons during larval life. In the ventral CNS, many of these secondary neuronal lineages differ significantly from one body segment to another, suggesting a role for anteroposterior patterning genes.

Results
Here we systematically characterize the expression pattern and function of the Hox gene Ultrabithorax (Ubx) in all 25 postembryonic lineages. We find that Ubx is expressed in a segment-, lineage-, and hemilineage-specific manner in the thoracic and anterior abdominal segments. When Ubx is removed from neuroblasts via mitotic recombination, neurons in these segments exhibit the morphologies and survival patterns of their anterior thoracic counterparts. Conversely, when Ubx is ectopically expressed in anterior thoracic segments, neurons exhibit complementary posterior transformation phenotypes.

Conclusion
Our findings demonstrate that Ubx plays a critical role in conferring segment-appropriate morphology and survival on individual neurons in the adult-specific ventral CNS. Moreover, while always conferring spatial identity in some sense, Ubx has been co-opted during evolution for distinct and even opposite functions in different neuronal hemilineages.
The Evolving Threat of Influenza Viruses of Animal Origin and the Challenges in Developing Appropriate Diagnostics
Authors: Mak Polly WY , Jayawardena Shanthi , Poon Leo LM 
Published: September 2012

BACKGROUND
An H1N1 subtype of swine origin caused the first influenza pandemic in this century. This pandemic strain was a reassortant of avian, swine, and human influenza viruses. Many diagnostic laboratories were overwhelmed by the testing demands related to this pandemic. Nevertheless, there remains the threat of other animal influenza viruses, such as highly pathogenic H5N1. As a part of pandemic preparedness, it is essential to identify the diagnostic challenges that will accompany the next pandemic.

CONTENT
We discuss the natural reservoir of influenza viruses and the possible role of livestock in the emergence of pandemic strains. The current commonly used molecular tests for influenza diagnosis or surveillance are also briefly reviewed. Some of these approaches are also used to detect animal viruses. Unfortunately, owing to a lack of systematic surveillance of animal influenza viruses, established tests may not be able to detect pandemic strains that have yet to emerge from the animal reservoir. Thus, multiple strategies need to be developed for better identification of influenza viruses. In addition, molecular assays for detection of mutations associated with antiviral resistance and for viral segment reassortments should also be encouraged.

SUMMARY
Influenza viruses are highly dynamic viruses. Regular and systematic influenza surveillance in both humans and animals is essential to provide a more comprehensive picture of the prevalent influenza viruses. To better prepare for the next pandemic, we should develop some simple and easy-to-use tests for characterizing newly emerging influenza viruses.
The monster and the zombie: English as a lingua franca and the Latin analogy
Authors: Wilton, Antje 
Published: September 2012

Abstract
This article discusses how current sociolinguistic research in ELF, a comparison of English and Latin as linguae francae (the Latin analogy) and language teaching can be drawn upon to bring the phenomenon of ELF to the attention of young language users and learners in order to help them understand what is happening in the linguistic world around them. The discussion involves considerations of the following issues: (1) the emotionally charged debates, both academically and publicly, of English as a lingua franca; (2) sociolinguistic research on English as a lingua franca; (3) the Latin analogy, making reference to the historical development of Latin as an indicator for the future development of English; (4) the integration of sociolinguistic issues such as the use of English as a lingua franca into the language curriculum; and (5) the development of cross-curricular language teaching units.
Impact of a Pediatric Clinic-Based Multidisciplinary Asthma Education and Management Program
Authors: Condren Michelle , Boger James A 
Published: September 2012

OBJECTIVE The objective of this study was to determine if a multidisciplinary asthma education and management program within a general pediatric clinic impacts clinical outcomes of children with asthma.
METHODS An asthma education and management clinic was started by a general pediatrician, a pharmacist, and a nurse. At a patient's initial clinic visit, data were collected summarizing hospitalizations, emergency department visits, and number of systemic corticosteroid courses for the previous year. The same data were collected at each subsequent visit. A retrospective review of this data was performed for patients who enrolled in the clinic between February 1999 and 2002 to compare outcomes between the year before enrollment in the clinic and the following year. Patients were included if they received follow-up for at least one year.
RESULTS Fifty-seven patients with a mean age of 8.5 years qualified for data analysis. Forty-eight percent of the study population was classified as having moderate persistent asthma, and 11% of patients were severe persistent. Compared to the year prior to clinic enrollment, the number of hospitalizations per patient decreased by 82% (P &lt; .001). Emergency department visits decreased by 81% (P &lt; .001). The number of systemic corticosteroid courses decreased by 72% (P &lt; 0.001).
CONCLUSIONS Patient enrollment in a general pediatric clinic-based multidisciplinary asthma education and management program decreases hospitalizations, emergency department visits, and systemic corticosteroid exposure.
An Open Label Comparison of Calfactant and Poractant Alfa Administration Traits and Impact on Neonatal Intensive Care Unit Resources
Authors: Gerdes Jeffrey S. , Seiberlich William , Sivieri Emidio M. , Marsh Wallace , Varner Dwight L. , Turck Charles J , York John M. 
Published: September 2012

OBJECTIVE To compare calfactant (CA) and poractant alfa (PA) administration traits, short-term clinical responses, and resource use in the neonatal respiratory distress syndrome (RDS) setting.
METHODS An open label series of 277 (213 PA and 64 CA) infants was evaluated for 445 administrations. Registered respiratory therapists collected patient, surfactant administration, and postadministration clinical data. Economic analysis involved labor costs of surfactant administration and usage, wastage, and product average wholesale price. Analysis utilized the Mann-Whitney rank sum test for differences in administration time and either the chi-square or Fisher's exact test for categorical variables.
RESULTS PA had a statistically lower bedside administration time than CA (3.8 minutes vs. 5.3 minutes; P = .006) and a higher percentage of doses administered in less than five minutes (58.9% vs. 4.3%; P &lt; .001). Doses administered per patient were similar (1.67 vs. 1.72). PA and CA were similar in time to recovery (81.4% vs. 74.3%), percent desaturation (24.8% vs. 26.7%), and bradycardia (3.8% vs. 8.5%). Reflux was significantly higher (13.2% vs. 3.5%; P &lt; .001) with CA. Economic analyses found total administration costs per dose were $2.21 for PA and $3.08 for CA. Mean wastage costs were $141.21 for PA and $337.34 for CA (P &lt; .001).
CONCLUSIONS PA appeared to utilize fewer neonatal intensive care unit resources than CA due to reduced administration time and less wastage of drug product. Future studies should more closely evaluate time, resource, wastage, and post-administrative clinical effects to fully assess the impact of surfactant products in this setting.
Intraventricular Vancomycin In Pediatric Patients With Cerebrospinal Fluid Shunt Infections
Authors: Al-Jeraisy Majed , Phelps Stephanie J. , Christensen Michael L. , Einhaus Stephanie 
Published: September 2012

OBJECTIVES To determine: 1) the range and magnitude of vancomycin trough cerebrospinal fluid (CSF) concentrations following intraventricular (IVT) vancomycin; 2) any correlation between patient demographic and CSF vancomycin concentrations; and 3) eradication and complications rates following IVT vancomycin.
METHODS Medical records of pediatric patients with shunt infection who received IVT vancomycin during a 12 month period were reviewed. Demographic, microbiological data, IVT/intravenous (IV) vancomycin dosing, concomitant antibiotics, CSF and serum vancomycin concentrations, and CSF drainage output were recorded.
RESULTS Seventeen patients ages 4 months to 17 years were hospitalized for shunt infection. Staphylococcus epidermidis (n=12) was the predominant organism. Sixteen patients received 10 mg, and one patient received 5 mg of IVT vancomycin for 3–23 days. All but one received concurrent IV vancomycin. The mean maximum trough CSF vancomycin concentration noted for 16 patients who recieved 10 mg of IVT vancomycin was 18.4±21.8 μg/mL (range: between 0.4 to 187.3 μg/mL). All four adolescents ≥25 kg had CSF vancomycin concentrations ≤5 μg/mL, three of four infants/children between 10.1 and 24.9 kg had trough CSF vancomycin concentrations between 10–20 μg/mL, and five of nine infants &lt;10 kg had CSF concentrations &gt;20 μg/mL. All organisms were successfully eradicated. One patient developed chronic eosinophilia presumed related to elevated CSF vancomycin concentrations (187 μg/mL).
CONCLUSIONS –The combination of IVT and IV vancomycin effectively eradicated CSF shunt infections. CSF vancomycin concentrations are highly variable and poorly correlated with age and CSF output. Following a 10 mg IVT vancomycin dose, CSF concentrations appear to be lower in older children and elevated in infants/young children. One infant experienced a complication related to an elevated CSF vancomycin concentration; hence, therapy must be individualized, using CSF trough vancomycin concentrations.
Managing Asthma: Past, Present, and Future
Authors: Weinberger Miles 
Published: September 2012

Asthma has been recognized in the medical literature for almost 2000 years. Modern pharmaco-therapy for asthma began with the commencement of the 20th century following the development of epinephrine and the demonstration of its effectiveness for acute symptoms of asthma. Progressive development of this class of bronchodilator medication has provided greater β2 specificity and longer duration of action. Corticosteroids were introduced about 50 years ago. As a systemic medication, they provided anti-inflammatory activity that continues to be essential for exacerbations of symptoms that are unresponsive to a bronchodilator. Corticosteroids were subsequently developed as inhaled agents for long-term maintenance therapy. The availability of corticosteroids with high topical effect has permitted the use of smaller doses with minimal systemic effect; therefore, the inhaled corticosteroids have become the most effective monotherapeutic agents for chronic asthma.
Both theophylline and long-acting β2 agonists (e.g., salmeterol) provide additive clinical effect to small doses of inhaled corticosteroids. This effect is greater than that achieved with larger doses of the inhaled steroid used alone. A new approach to managing allergic asthma is now available in the form of a monoclonal antibody directed against immunoglobulin E (IgE). This agent, omalizumab, binds to circulating IgE, thereby preventing IgE from binding to mast cells. This subsequently prevents the release of mediators for bronchospasm and inflammation. Under investigation are monoclonal antibodies to modify the effects of interleukins involved in the inflammatory process of asthma. Phosphodiesterase inhibitors that are more specific than theophylline and monoclonal antibodies that prevent the attachment of rhinovirus to respiratory mucosa are being studied. Since rhinoviruses are major causes of acute exacerbations of asthma, these and other measures to prevent or modify the common cold provide great potential for further improvement in the outcome of asthma.
Faites un roi, ou faites la guerre : les organisations de l’Action française pendant la Grande Guerre (1914-1918)
Authors: Audet-Vallée Kevin 
Published: September 2012

Peu approfondie dans l’historiographie de l’Action française, la période de la Grande Guerre n’en reste pas moins déterminante dans l’histoire de ce mouvement néoroyaliste et nationaliste français dont le parcours va de l’affaire Dreyfus au régime de Vichy. Tandis que ses maîtres à penser appelèrent leurs troupes à se rallier sans condition à « l’Union sacrée » du monde politique en faveur de la défense nationale, les militants du mouvement s’exilèrent en masse vers les tranchées. L’Action française, qui dans l’avant-guerre était structurée en un ensemble d’organisations présentes partout en France sous la forme de sections, se retrouva donc dépourvue entre 1914 et 1918 de sa force militante publique. Néanmoins, grâce aux efforts de quelques-uns de ses animateurs restés à « l’arrière front » et maintenant les activités du quotidien qu’il publiait, les idées du mouvement néoroyaliste avaient atteint à la fin de la guerre une notoriété inédite.
Purification and Concentration of Nucleic Acids
Authors: Dowhan Dennis H. 
Published: September 2012

AbstractThe purification and concentration of nucleic acids have become routine procedures in most biology and molecular biology laboratories. This unit covers the basic principles and procedures for the isolation, purification, and manipulation of solutions of DNA or RNA. The basic DNA protocol, using phenol extraction and ethanol precipitation, is appropriate for the purification of DNA from small volumes (<0.4 ml) at concentrations ≤1 mg/ml. Purification of DNA using commercially available silica membrane spin columns is presented as an alternate protocol. Isolation and purification of RNA from mammalian cells or tissues is also examined. Use of the protein denaturant guanidine thiocyanate and water‐saturated phenol, followed by concentration by isopropanol precipitation, for producing small samples of RNA, is illustrated in the basic RNA protocol. Curr. Protoc. Essential Lab. Tech. 6:5.2.1‐5.2.21. © 2012 by John Wiley & Sons, Inc.
Highly Conductive Nanocomposites with Three‐Dimensional, Compactly Interconnected Graphene Networks via a Self‐Assembly Process
Authors: Wu Chao , Huang Xingyi , Wang Genlin , Lv Libing , Chen Gan , Li Guangyv , Jiang Pingkai 
Published: September 2012

AbstractPolymer‐based materials with high electrical conductivity are of considerable interest because of their wide range of applications. The construction of a 3D, compactly interconnected graphene network can offer a huge increase in the electrical conductivity of polymer composites. However, it is still a great challenge to achieve desirable 3D architectures in the polymer matrix. Here, highly conductive polymer nanocomposites with 3D compactly interconnected graphene networks are obtained using a self‐assembly process. Polystyrene (PS) and ethylene vinyl acetate (EVA) are used as polymer matrixes. The obtained PS composite film with 4.8 vol% graphene shows a high electrical conductivity of 1083.3 S/m, which is superior to that of the graphene composite prepared by a solvent mixing method. The electrical conductivity of the composites is closely related to the compact contact between graphene sheets in the 3D structures and the high reduction level of graphene sheets. The obtained EVA composite films with the 3D graphene structure not only show high electrical conductivity but also exhibit high flexibility. Importantly, the method to fabricate 3D graphene structures in polymer matrix is facile, green, low‐cost, and scalable, providing a universal route for the rational design and engineering of highly conductive polymer composites.
Chaperone discovery
Authors: Quan Shu , Bardwell James C. A. 
Published: September 2012

AbstractMolecular chaperones assist de novo protein folding and facilitate the refolding of stress‐denatured proteins. The molecular chaperone concept was coined nearly 35 years ago, and since then, tremendous strides have been made in understanding how these factors support protein folding. Here, we focus on how various chaperone proteins were first identified to play roles in protein folding. Examples are used to illustrate traditional routes of chaperone discovery and point out their advantages and limitations. Recent advances, including the development of folding biosensors and promising methods for the stabilization of proteins in vivo, provide new routes for chaperone discovery.
Design of Cyclic Peptides Featuring Proline Predominantly in the cis Conformation under Physiological Conditions
Authors: Malešević Miroslav , Schumann Michael , Jahreis Günther , Fischer Gunter , Lücke Christian 
Published: September 2012

AbstractTurns are secondary‐structure elements that are omnipresent in natively folded polypeptide chains. A large variety of four‐residue β‐turns exist, which differ mainly in the backbone dihedral angle values of the two central residues i+1 and i+2. The βVI‐type turns are of particular biological interest because the i+2 residue is always a proline in the cis conformation and might thus serve as target of peptidyl prolyl cis/trans isomerases (PPIases). We have designed cyclic hexapeptides containing two proline residues that predominantly adopt the cis conformation in aqueous solution. NMR data and MD calculations indicated that the cyclic peptide sequences c‐(‐DXaa‐Ser‐Pro‐DXaa‐Lys‐Pro‐) result in highly symmetric backbone structures when both prolines are in the cis conformation and the D‐amino acids are either alanine or phenylalanine residues. Replacement of the serine residue either by phosphoserine or by tyrosine compromises this symmetry, but further increases the cis conformation content of both prolines. As a result, we obtained a cyclic hexapeptide that exists almost exclusively as the cis‐Pro/cis‐Pro conformer but shows no cis/trans interconversion even in the presence of the PPIase Pin1, apparently due to an energetically quite favorable but highly restricted conformational space.
Asymmetric Total Synthesis of (−)‐Stenine and 9a‐epi‐Stenine
Authors: Fujioka Hiromichi , Nakahara Kenji , Kotoku Naoyuki , Ohba Yusuke , Nagatomi Yasushi , Wang Tsung‐Lung , Sawama Yoshinari , Murai Kenichi , Hirano Kie , Oki Tomohiro , Wakamatsu Shintaro , Kita Yasuyuki 
Published: September 2012

AbstractA route for the asymmetric synthesis of (−)‐stenine, a member of the Stemona alkaloid family used as folk medicine in Asian countries, is described. The key features of the sequence employed include stereoselective transformations on a cyclohexane ring controlled by a chiral auxiliary unit and an intramolecular Mitsunobu reaction to construct the perhydroindole ring system. By using an intermediate in the route to (−)‐stenine, an asymmetric synthesis of 9a‐epi‐stenine was also executed. The C(9a) stereocenter in 9a‐epi‐stenine was installed by using a Staudinger/aza‐Wittig reaction of a keto–azide precursor followed by reduction of the resulting imine. The results of this effort demonstrate the applicability of the chiral auxiliary based strategy to the preparation of naturally occurring alkaloids that contain highly functionalized cyclohexane cores.