bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Cholesterol‐Loaded Cyclodextrin in Donkey Semen Cryopreservation Improves Sperm Viability but Results in Low Fertility in Mares
Authors: Oliveira RR , Rates DM , Pugliesi G , Ker PG , Arruda RP , Moraes EA , Carvalho GR 
Published: August 2014

ContentsThe use of cholesterol‐loaded cyclodextrin (CLC) on semen cryopreservation has been related with better sperm viability in several species; however, the effect on fertility is not known in donkey semen. Ejaculates (n = 25) from five donkeys were diluted inS‐MEDIUMwith 0, 1, 2 or 3 mg ofCLC/120 × 106spermatozoa. Semen was frozen, and thawed samples were evaluated by computer‐assisted sperm analyser system (CASA), supravital test, hyposmotic swelling test and fluorescent dyes to assess the integrity of sperm membranes. Mares (n = 60) were inseminated with frozen‐thawed semen treated with the doses of 0 or 1 mgCLC. Percentages of sperm with progressive motility and with functional plasma membrane were greater (p < 0.05) in theCLC‐treated groups than in the control. Percentages of intact plasma membrane and intact plasma membrane and acrosome detected by fluorescent dyes were also greater (p < 0.05) inCLC‐treated groups. Although no difference (p > 0.05) in conception rates was detected between groups (control, 3/30, 10%;CLC‐treated, 1/30, 3.3%), fertility was low for artificial insemination programs in mares. Therefore, we firstly demonstrated that frozen semen treated withCLCinS‐MEDIAextender before freezing improves thein vitrosperm viability, but semen treated or not withCLCinS‐MEDIUMextender results in a very low conception rate in mares inseminated with thawed donkey semen.
Clinical COPD Questionnaire in patients with chronic respiratory disease
Authors: Canavan Jane L. , Dilaver Deniz , Clark Amy L. , Jones Sarah E. , Nolan Claire M. , Kon Samantha S. C. , Man William D.‐C. 
Published: August 2014

AbstractBackground and objectiveThe Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (CCQ) is an easy to complete, health‐related quality of life questionnaire which has been well‐validated in COPD. The responsiveness of the CCQ in chronic respiratory disease patients other than COPD has not been previously described. The study aims were to determine if the CCQ in chronic respiratory disease correlates with other health related quality of life questionnaires, to assess the responsiveness of the CCQ to pulmonary rehabilitation and to determine the minimum important difference.MethodsThe CCQ, COPD Assessment Test (CAT), the Chronic Respiratory Questionnaire (CRQ) and St George's Respiratory Questionnaire (SGRQ) were measured in 138 chronic respiratory disease patients completing pulmonary rehabilitation. Change in CCQ with pulmonary rehabilitation was correlated with change in the other questionnaires. The minimum important difference of the CCQ was calculated using distribution and anchor‐based approaches.ResultsThe CCQ, CAT, CRQ and SGRQ improved significantly with rehabilitation with effect sizes of −0.43, −0.26, 0.62, −0.37. Change in CCQ correlated significantly with CAT, CRQ and SGRQ (r = 0.53, −0.64, 0.30, all P < 0.0001). The minimum important difference was −0.42 at the population level and −0.4 at the individual level.ConclusionsThe CCQ is responsive to pulmonary rehabilitation in chronic respiratory disease patients, with an MID estimated at −0.4 at the individual level.
Vascular endothelial growth factor A polymorphism and risk of Kaposi's sarcoma herpesvirus viremia in kidney allograft recipients
Authors: Alkharsah K.R. , Alzahrani A.J. , Obeid O.E. , El‐Harith E.‐H.A. , Guella A. , Mohamed E.A. , Haykal A.H. , Stuhrmann M. , Al‐Ali A.K. 
Published: August 2014

AbstractBackgroundKaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease in immunocompromised patients including allograft recipients. Detection of KSHV DNA in blood, as well as host genetic polymorphisms has been found to be associated with an increased risk for KS. We investigated an association between single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA) gene region and KSHV viremia in kidney transplant recipients (KTR) in Saudi Arabia.MethodsIn total, 152 KTR who have survived kidney transplantation for at least 6 months were included in the study. KSHV viremia was determined by real‐time polymerase chain reaction (PCR). Genotyping of SNPs in the VEGFA region was performed by PCR and direct sequencing, as well as by restriction fragment length polymorphism.ResultsKSHV DNA was detected in 28.9% (n = 44) of the study population. The A‐allele at position C172A VEGFA gene promoter region was found to be associated with KSHV viremia (odd ratio [OR] = 4.8, P = 0.005). In addition, the G‐allele at position C+405G in the 5′‐untranslated region was associated with KSHV viremia in women, but not in men (OR = 3.98, P = 0.004).ConclusionsOur results suggest an association of VEGFA polymorphisms with KSHV viremia among KTR in this study population. A limitation of our study is that the results can only be predicated for patients 6 months after kidney transplantation and should be validated in another cohort with larger sample size.
Quantitative and qualitative morphologic, cytochemical, and ultrastructural characteristics of blood cells in captive Asian water monitors
Authors: Salakij Chaleow , Salakij Jarernsak , Prihirunkit Kreangsak , Narkkong Naul‐Anong , Sanyathitiseree Pornchai , Kranjanapitukkul Kwanjai 
Published: August 2014

BackgroundThe Asian water monitor (Varanus salvator) is the most common monitor lizard in Thailand. Reported data regarding hematology and morphology of blood cells for this species are scarce.ObjectivesThe objective of this study was to assess routine hematologic variables and characterize the morphology, cytochemical staining, and ultrastructural features of blood cells in the Asian water monitor.MethodsBlood samples from 55 monitors (22 males and 33 females) were obtained for aCBC. Cytochemical staining (Sudan black B [SBB], peroxidase [PO], α‐naphthyl acetate esterase [ANAE], and beta‐glucuronidase [BG]), and scanning and transmission electron microscopy were performed using standard methods.ResultsDetermined mean (range) hematologic results of all monitors includedPCV0.32 L/L (0.20–0.44 L/L),HGB106 g/L (62–157 g/L),WBC15.9 × 109/L (4.0–34.0 × 109/L), heterophil 6.3 × 109/L (1.5–17.1 × 109/L, azurophil 2.6 × 109/L (0.7–9.5 × 109/L), basophil 0.1 (0.1–0.5 × 109/L), lymphocyte 6.8 × 109/L (0.5–13.1 × 109/L), and monocyte 0.2 × 109/L (0.04–1 × 109/L) counts. Heterophils and basophils stained strongly positive withSBB,ANAE, andBG. Heterophils contained 2 types of granules, roundSBB‐positive andPO‐negative granules, and electron‐dense, large rod‐shaped granules. Gamonts ofHepatozoonsp. were found in <1%RBCof 43 monitors. There was no significant difference between hematologic variables inHepatozoon‐positive and ‐negative monitors.ConclusionHeterophils in Asian water monitors may also function as eosinophils based on cytochemical and ultrastructural features. The quantitative results may be used as base for further studies in healthy and diseased Asian water monitors.
Sampling strategies for subsampled segmented EPI PRF thermometry in MR guided high intensity focused ultrasound
Authors: Odéen Henrik , Todd Nick , Diakite Mahamadou , Minalga Emilee , Payne Allison , Parker Dennis L. 
Published: August 2014

Purpose:To investigate k‐space subsampling strategies to achieve fast, large field‐of‐view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications.Methods:Five different k‐space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k‐space center more frequently. Two of the schemes utilized centric sampling to acquire the k‐space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non‐EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm.Results:The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root‐mean‐square‐error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes with variable density sampling implemented in zero and two dimensions in a non‐EPI GRE pulse sequence both resulted in accurate temperature measurements (RMSE of 0.70 °C and 0.63 °C, respectively). With sequential sampling in the described EPI implementation, temperature monitoring over a 192 × 144 × 135 mm3 FOV with a temporal resolution of 3.6 s was achieved, while keeping the RMSE compared to fully sampled “truth” below 0.35 °C.Conclusions:When segmented EPI readouts are used in conjunction with k‐space subsampling for MR thermometry applications, sampling schemes with sequential sampling, with or without variable density sampling, obtain accurate phase and temperature measurements when using a TCR reconstruction algorithm. Improved temperature measurement accuracy can be achieved with variable density sampling. Centric sampling leads to phase bias, resulting in temperature underestimations.
Evaluation of the Nanosphere Verigene BC-GN Assay for Direct Identification of Gram-Negative Bacilli and Antibiotic Resistance Markers from Positive Blood Cultures and Potential Impact for More-Rapid Antibiotic Interventions
Authors: Hill Joseph T. , Tran Kim-Dung T. , Barton Karen L. , Labreche Matthew J. , Sharp Susan E. 
Published: August 2014

ABSTRACT
The Verigene BC-GN assay correctly identified all 51 Gram-negative bacilli (GNB) from positive blood cultures and all 14 carbapenemase enzymes tested. The assay gave organism identification (ID) results an average of 24 h faster compared to conventional identifications. Medical management could have been modified for 31.8% of patients an average 33 h sooner. In conclusion, the BC-GN assay is a very accurate, rapid assay which would allow for more-immediate medical management decisions in patients with bacteremia from GNB.
Methyltransferase-Defective Avian Metapneumovirus Vaccines Provide Complete Protection against Challenge with the Homologous Colorado Strain and the Heterologous Minnesota Strain
Authors: Sun Jing , Wei Yongwei , Rauf Abdul , Zhang Yu , Ma Yuanmei , Zhang Xiaodong , Shilo Konstantin , Yu Qingzhong , Saif Y. M. , Lu Xingmeng , Yu Lian , Li Jianrong 
Published: August 2014

ABSTRACT

Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. Since its discovery in the 1970s, aMPV has been recognized as an economically important pathogen in the poultry industry worldwide. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at guanine N-7 (G-N-7) and ribose 2′-O positions. In this study, we generated a panel of recombinant aMPV (raMPV) Colorado strains carrying mutations in the
S
-adenosyl methionine (SAM) binding site in the CR VI of L protein. These recombinant viruses were specifically defective in ribose 2′-O, but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of specific-pathogen-free (SPF) young turkeys. Importantly, turkeys vaccinated with these MTase-defective raMPVs triggered a high level of neutralizing antibody and were completely protected from challenge with homologous aMPV Colorado strain and heterologous aMPV Minnesota strain. Collectively, our results indicate (i) that aMPV lacking 2′-O methylation is highly attenuated
in vitro
and
in vivo
and (ii) that inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for aMPV and perhaps other paramyxoviruses.

IMPORTANCE
Paramyxoviruses include many economically and agriculturally important viruses such as avian metapneumovirus (aMPV), and Newcastle disease virus (NDV), human pathogens such as human respiratory syncytial virus, human metapneumovirus, human parainfluenza virus type 3, and measles virus, and highly lethal emerging pathogens such as Nipah virus and Hendra virus. For many of them, there is no effective vaccine or antiviral drug. These viruses share common strategies for viral gene expression and replication. During transcription, paramyxoviruses produce capped, methylated, and polyadenylated mRNAs. Using aMPV as a model, we found that viral ribose 2′-
O
methyltransferase (MTase) is a novel approach to rationally attenuate the virus for vaccine purpose. Recombinant aMPV (raMPV) lacking 2′-
O
MTase were not only highly attenuated in turkeys but also provided complete protection against the challenge of homologous and heterologous aMPV strains. This novel approach can be applicable to other animal and human paramyxoviruses for rationally designing live attenuated vaccines.
Increased Replicative Fitness Can Lead to Decreased Drug Sensitivity of Hepatitis C Virus
Authors: Sheldon Julie , Beach Nathan M. , Moreno Elena , Gallego Isabel , Piñeiro David , Martínez-Salas Encarnación , Gregori Josep , Quer Josep , Esteban Juan Ignacio , Rice Charles M. , Domingo Esteban , Perales Celia 
Published: August 2014

ABSTRACT
Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV.

IMPORTANCE
Viral drug resistance is usually attributed to the presence of amino acid substitutions in the protein targeted by the drug. In the present study with HCV, we show that high viral replicative fitness can confer a general drug resistance phenotype to the virus. The results exclude the possibility that genomes with drug resistance mutations are responsible for the observed phenotype. The fact that replicative fitness can be a determinant of multidrug resistance may explain why the virus is less sensitive to drug treatments in prolonged chronic HCV infections that favor increases in replicative fitness.
Targeting EphA3 Inhibits Cancer Growth by Disrupting the Tumor Stromal Microenvironment
Authors: Vail Mary E. , Murone Carmel , Tan April , Hii Linda , Abebe Degu , Janes Peter W. , Lee Fook-Thean , Baer Mark , Palath Varghese , Bebbington Christopher , Yarranton Geoffrey , Llerena Carmen , Garic Slavisa , Abramson David , Cartwright Glenn , Scott Andrew M. , Lackmann Martin 
Published: August 2014

Abstract
Eph receptor tyrosine kinases are critical for cell–cell communication during normal and oncogenic tissue patterning and tumor growth. Somatic mutation profiles of several cancer genomes suggest EphA3 as a tumor suppressor, but its oncogenic expression pattern and role in tumorigenesis remain largely undefined. Here, we report unexpected EphA3 overexpression within the microenvironment of a range of human cancers and mouse tumor xenografts where its activation inhibits tumor growth. EphA3 is found on mouse bone marrow–derived cells with mesenchymal and myeloid phenotypes, and activation of EphA3+/CD90+/Sca1+ mesenchymal/stromal cells with an EphA3 agonist leads to cell contraction, cell–cell segregation, and apoptosis. Treatment of mice with an agonistic α-EphA3 antibody inhibits tumor growth by severely disrupting the integrity and function of newly formed tumor stroma and microvasculature. Our data define EphA3 as a novel target for selective ablation of the tumor microenvironment and demonstrate the potential of EphA3 agonists for anticancer therapy. Cancer Res; 74(16); 4470–81. ©2014 AACR.
Abstract BS1-2: Reactive Stroma as Therapeutic Targets in Breast Cancer Bone Metastasis
Authors: Kang Y 
Published: August 2014

Abstract
Metastasis represents the most devastating stage of cancer progression. Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients. Discovering bone metastasis genes that are clinically relevant and functionally important are critical for the development of novel therapeutics for high-risk breast cancer patients. We apply a multidisciplinary approach to analyze the molecular basis of breast cancer bone metastasis, combining functional genomics tools with animal models and clinical analysis of cancer metastasis. Candidate bone metastasis genes were identified from gene expression profiling of highly bone metastatic cells derived after in vivo selection in animal models. Functional characterization of these genes revealed their novel role in mediating tumor-stromal interactions essential for the formation of osteolytic bone metastasis. We discovered a novel metalloprotease-initiated, EGFR-dependent paracrine signaling cascade among tumor cells, osteoblasts and osteoclasts that promotes the maturation of bone-degrading osteoclasts and formation of osteolytic lesions. Using in vivo imaging technology, we showed that TGFbis released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGFb target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. More recently, we identified osteoclast-derived miRNAs as biomarkers and therapeutic targets of osteolytic bone metastasis. Importantly, pharmaceutical inhibitors against EGFR, TGFb and Notch signaling pathways and miRNAs blocking osteoclast differentiation significantly reduce the development of bone metastasis, suggesting novel avenues for clinical management of skeletal complications of breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr BS1-2.
Abstract ES3-2: Clinical Trial Designs for New Therapies: What Agents Should We Study?
Authors: DeMichele A 
Published: August 2014

Abstract
Biologically-targeted, novel agents hold great promise in breast cancer, but require adjustments to traditional study design, conduct and patient selection to be tested safely, effectively and economically. Key questions to be address in this talk include: Is the drug safe? Is it hitting the target? Can we identify the “right” patients to test? In what setting do we test it? Toxicities of these agents move well-beyond traditional myelosuppression and fatigue, encompassing almost every organ system and requiring changes in monitoring and management to assure safety. Dosing and assessment strategies must be aimed at optimally modulating target and assessing whether hitting the target has the desired effect on the natural history of the disease. The concurrent development of predictive biomarkers is necessary to select appropriate study subjects, which may be limited to a relatively small subset of patients with the disease. Finally, selecting the best therapeutic setting (treatment naïve, refractory, acquired resistance) can greatly impact the performance of the agent and requires knowledge of cancer biological evolution through the metastatic process.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES3-2.
Abstract ES4-1: Navigating the Obstacles and Risks of Survivorship: Breast Cancer Sexuality: Issues and Answers
Authors: Krychman M 
Published: August 2014

Abstract
The sexual consequences of breast cancer and its treatments are well known. Sexual difficulties include alteration in hormonal levels, changes in sexual organs and anatomy, vaginal and vulvar dryness, changes in libido, increased latency to orgasm and decreased intensity of orgasmic response. Changes in body image, sexual self-esteem and relationship dynamic tension may present as survivorship challenges for the breast cancer patient and her partner. Severe vulvo vaginal and clitoral atrophy as a result of chemotherapy and/or adjuvant hormone therapy, and loss of libido secondary to dyspareunia are widespread. Cytostatic medications that are prescribed for long-term use (aromatase inhibitors) can impact bone health, sexual functioning/satisfaction and overall quality of life. Many women on aromatase inhibitors have severe complaints of vulvar and vaginal atrophy.
Sexual dysfunction is common for breast cancer population and limited acceptable treatments are available. Minimally absorbed local vaginal estrogen use in this population remains controversial and a hotly debated controversial topic. More data should be forthcoming. There are multiple new innovative treatments in the research pipeline for female sexual dysfunction. DHEA intravaginal suppositories, Flibanserin and Bremelanotide (PT 141) remain promising although they have not been adequately studied in the breast cancer population. Ospemifene a novel estrogen agonist/ antagonist has demonstrated a strong estrogenic effect on the vaginal epithelium during a three month trial period and did not stimulate the endometrium; however, the medication did mildly aggravate hot flashes (this did not lead to drug discontinuation). Although not studied in breast cancer patients, pivotal Phase 3 data confirmed effectiveness of ospemifene as effective treatment for vulvovaginal atrophy. In a recent article in Menopause, Ospemifene and 4-hydroxyospemifene effectively prevented and treat breast cancer in Mtag. TG Transgenic Mouse.
Testosterone use remains off label and is not FDA approved, yet it is widely used in the non cancer population. New emerging safety data will be presented. Vaginal moisturizers, lubricants and dilators in association with genito pelvic floor therapy and intravaginal valium suppositories can be considered front line treatment for atrophy, dyspareunia and hypertonic vaginismus. New innovative data on non hormonal management of hot flashes is and important initial step in the overall management of the breast cancer patient who is suffering from sexual dysfunction.
A multi model treatment paradigm will be presented which will include pharmacologic, nonpharmacologic, and psychosocial interventions.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES4-1.