bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type 1 Responses of Human Vγ9Vδ2 T Cells to Influenza A Viruses
Authors: Qin Gang , Liu Yinping , Zheng Jian , Ng Iris H. Y. , Xiang Zheng , Lam Kwok-Tai , Mao Huawei , Li Hong , Peiris J. S. Malik , Lau Yu-Lung , Tu Wenwei 
Published: July 2011

ABSTRACTγδ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells participated in anti-influenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs)in vitro. However, little is known about the noncytolytic responses and trafficking program of γδ T cells to influenza virus. In this study, we found that Vγ9Vδ2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-γ). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated γδ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-γ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in Vγ9Vδ2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of Vγ9Vδ2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human Vγ9Vδ2 T cells against influenza virus infection.
Decreased Infectivity of a Neutralization-Resistant Equine Infectious Anemia Virus Variant Can Be Overcome by Efficient Cell-to-Cell Spread
Authors: Wu Wuwei , Blythe Derek C. , Loyd Hyelee , Mealey Robert H. , Tallmadge Rebecca L. , Dorman Karin S. , Carpenter Susan 
Published: July 2011

ABSTRACT

Two variants of equine infectious anemia virus (EIAV) that differed in sensitivity to broadly neutralizing antibody were tested in direct competition assays. No differences were observed in the growth curves and relative fitness scores of EIAVs of principal neutralizing domain variants of groups 1 (EIAV
PND-1
) and 5 (EIAV
PND-5
), respectively; however, the neutralization-resistant EIAV
PND-5
variant was less infectious in single-round replication assays. Infectious center assays indicated similar rates of cell-to-cell spread, which was approximately 1,000-fold more efficient than cell-free infectivity. These data indicate that efficient cell-to-cell spread can overcome the decreased infectivity that may accompany immune escape and should be considered in studies assessing the relative levels of fitness among lentivirus variants, including HIV-1.
Phase I Study of Oral Gemcitabine Prodrug (LY2334737) Alone and in Combination with Erlotinib in Patients with Advanced Solid Tumors
Authors: Koolen Stijn L.W. , Witteveen Petronella O. , Jansen Robert S. , Langenberg Marlies H.G. , Kronemeijer Roelien H. , Nol Annemarie , Garcia-Ribas Ignacio , Callies Sophie , Benhadji Karim A. , Slapak Christopher A. , Beijnen Jos H. , Voest Emile E. , Schellens Jan H.M. 
Published: July 2011

Abstract
Purpose: LY2334737 is an orally available prodrug of gemcitabine. The objective of this study was to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of daily administration of LY2334737 with or without erlotinib.
Experimental Design: Patients with advanced or metastatic cancer were treated with escalating doses of LY2334737 monotherapy or in combination with continuous daily administration of 100 mg erlotinib. LY2334737 was given once daily for 14 days of a 21-day cycle. The study was extended with a bioequivalence trial to investigate a novel LY2334737 drug formulation.
Results: A total of 65 patients were treated in this study. The MTD was 40 mg LY2334737. Fatigue was the most frequent DLT for LY2334737 monotherapy (4 patients) followed by elevated transaminase levels (2 patients), both observed at the 40- to 50-mg dose levels. Among the 10 patients in the combination arm, 2 had DLTs at the 40-mg dose level. These were fatigue and elevated liver enzyme levels. The most common adverse events were fatigue (n = 38), nausea (n = 27), vomiting (n = 24), diarrhea (n = 23), anorexia (n = 20), pyrexia (n = 18), and elevated transaminase levels (n = 14). The pharmacokinetics showed dose proportional increase in LY2334737 and gemcitabine exposure. The metabolite 2′,2′-difluorodeoxyuridine accumulated with an accumulation index of 4.3 (coefficient of variation: 20%). In one patient, complete response in prostate-specific antigen was observed for 4 cycles, and stable disease was achieved in 22 patients overall. Pharmacokinetic analysis showed that the 2 investigated LY2334737 drug formulations were bioequivalent.
Conclusions: LY2334737 displays linear pharmacokinetics and the MTD is 40 mg with or without daily administration of 100 mg erlotinib. Signs of antitumor activity warrant further development. Clin Cancer Res; 17(18); 6071–82. ©2011 AACR.
Targeting the Notch Ligand Jagged1 in Both Tumor Cells and Stroma in Ovarian Cancer
Authors: Steg Adam D. , Katre Ashwini A. , Goodman Blake , Han Hee-Dong , Nick Alpa M. , Stone Rebecca L. , Coleman Robert L. , Alvarez Ronald D. , Lopez-Berestein Gabriel , Sood Anil K. , Landen Charles N. 
Published: July 2011

Abstract
Purpose: Jagged1, a Notch ligand, is expressed on both tumor epithelial and endothelial cells and therefore may be amenable to dual targeting of the tumor stroma and malignant cell compartments of the tumor microenvironment.
Experimental Design: We describe in vitro effects of targeting of Jagged1 on ovarian cancer cells and in vivo effects of independent targeting of stromal and malignant cell Jagged1 using species-specific human or murine siRNA constructs incorporated into chitosan nanoparticles and delivered intravenously in an orthotopic mouse model.
Results: Jagged1 expression was prominent in SKOV3ip1 and IGROV-AF1, and significantly overexpressed in SKOV3TRip2, a taxane-resistant SKOV3 subclone. Jagged1 silencing with siRNA decreased cell viability and reversed taxane chemoresistance. In two different orthotopic ovarian cancer models, treatment with anti-human Jagged1 siRNA-CH reduced growth by 54.4% to 58.3% and with anti-murine Jagged1 siRNA-CH reduced growth by 41.7% to 48.8%. The combination of both species-specific constructs reduced tumor weight by 87.5% to 93.1% and sensitized SKOV3TRip2 tumors to docetaxel in vivo. Tumors showed reduced microvessel density with anti-murine Jagged1 constructs and decreased proliferation with anti-human Jagged1 siRNAs-CH. In addition, we show that Jagged1 downregulation does not sensitize cells to taxanes through a reduction in MDR1 expression, but at least in part by cross-talk with the GLI2 mediator of the Hedgehog pathway.
Conclusions: Jagged1 plays dual roles in cancer progression through an angiogenic function in tumor endothelial cells and through proliferation and chemoresistance in tumor cells. Dual inhibition represents an attractive therapeutic strategy for ovarian and potentially other malignancies. Clin Cancer Res; 17(17); 5674–85. ©2011 AACR.
Pharmacokinetic Dose-Scheduling Study of Hedgehog Pathway Inhibitor Vismodegib (GDC-0449) in Patients with Locally Advanced or Metastatic Solid Tumors
Authors: LoRusso Patricia M. , Jimeno Antonio , Dy Grace , Adjei Alex , Berlin Jordan , Leichman Lawrence , Low Jennifer A. , Colburn Dawn , Chang Ilsung , Cheeti Sravanthi , Jin Jin Y. , Graham Richard A. 
Published: July 2011

Abstract
Purpose: This study was designed to evaluate whether less frequent dosing [three times per week (TIW) or once weekly (QW)] of 150 mg vismodegib following a loading dose [150 mg once daily (QD) for 11 days] would result in similar safety, tolerability, and steady-state levels of total and unbound vismodegib as continuous QD dosing.
Experimental Design: Sixty-seven patients with advanced solid tumors were stratified by baseline plasma alpha 1-acid glycoprotein (AAG) levels and randomized to one of three vismodegib 150 mg regimens: QD (n = 23), TIW (n = 22), or QW (n = 22) for up to 42 days after an 11-day loading phase (150 mg QD). Total and unbound (dialyzed) plasma vismodegib concentrations were determined by LC-MS/MS.
Results: The most frequently reported adverse events were consistent with those in prior monotherapy trials, with similar incidence and severity regardless of dosing schedule. After the 150 mg QD loading phase, a concentration-dependent change in protein binding (3-fold increase in vismodegib fraction unbound) was observed at steady state compared with single dose. Mean total and unbound vismodegib steady-state concentrations were lower after TIW and QW than QD dosing, with an average intrasubject decrease of 50% and 80%, respectively, for unbound drug. Mechanism-based PK model simulations accurately and prospectively predicted the PK results.
Conclusions: Vismodegib 150 mg TIW or QW failed to achieve unbound plasma concentrations previously associated with efficacy in patients with advanced basal cell carcinoma and medulloblastoma, even after a QD loading dose period. The 150 mg QD regimen is appropriate for vismodegib based on its clinical activity, tolerability, and favorable unbound concentrations. Clin Cancer Res; 17(17); 5774–82. ©2011 AACR.
Nutlin-3 Downregulates the Expression of the Oncogene TCL1 in Primary B Chronic Lymphocytic Leukemic Cells
Authors: Voltan Rebecca , di Iasio Maria Grazia , Bosco Raffaella , Valeri Nicola , Pekarski Yuri , Tiribelli Mario , Secchiero Paola , Zauli Giorgio 
Published: July 2011

Abstract
Purpose: The oncogene TCL1 plays a key role in the development of B chronic lymphocytic leukemia (B-CLL), but it is not known whether TCL1 could be modulated by therapeutic approaches.
Experimental Design: B-CLL patient samples (n = 35) and B leukemic cell lines (EHEB, JVM2, JVM3, MEC1, MEC2, and BJAB) with different p53 status were exposed to Nutlin-3, a small-molecule inhibitor of the p53–MDM2 interaction. Modulations of the steady-state mRNA levels of TCL1 were analyzed by quantitative real-time PCR and Western blotting in both primary B-CLL samples and leukemic cell lines. In addition, transfection experiments with either p53 siRNA or with a TCL1 expression plasmid were carried out in the EHEB B-CLL cell line.
Results: Upon ex vivo treatment with Nutlin-3, TCL1 was significantly (P &lt; 0.05) decreased in 23 of 28 B-CLL p53wild-type. The functionality of the p53 pathway in the same leukemic cell samples was underscored by the concomitant ability of Nutlin-3 to significantly (P &lt; 0.05) upregulate the p53 target gene MDM2 in the p53wild-type leukemic cells. The dependence of TCL1 downregulation by a functional p53 pathway was confirmed in a panel of B lymphoblastoid cell lines and by p53 knockdown experiments with p53 siRNA. The importance of TCL1 in promoting leukemic cell survival was underscored in transfection experiments, in which TCL1 overexpression significantly counteracted the Nutlin-3–mediated induction of apoptosis in EHEB.
Conclusions: Our data indicate that the Nutlin-3 downregulates TCL1 mRNA and protein, which likely represents an important molecular determinant in the proapoptotic activity of Nutlin-3. Clin Cancer Res; 17(17); 5649–55. ©2011 AACR.
Outcomes of Cardiac Perforation Complicating Catheter Ablation of Ventricular Arrhythmias
Authors: Tokuda Michifumi , Kojodjojo Pipin , Epstein Laurence M. , Koplan Bruce A. , Michaud Gregory F. , Tedrow Usha B. , Stevenson William G. , John Roy M. 
Published: July 2011

Background—
Cardiac perforation is a recognized complication of catheter ablation procedures, most commonly encountered during ablation of atrial fibrillation. The study aims to investigate the incidence, management, and hospital outcomes of cardiac perforation complicating catheter ablation for ventricular arrhythmias.

Methods and Results—

Consecutive patients undergoing catheter ablation for ventricular arrhythmias at a tertiary referral center were included in this retrospective analysis. Of 1152 consecutive catheter ablation procedures in 892 patients over 12 years, 11 procedures (1.0%) were complicated by ventricular perforation. Emergent pericardial drainage and surgical repair were required in 10 (91%) and 6 (55%) cases, respectively. No perforation was apparent in patients with prior cardiac surgery. More than half of the perforations (6 of 11) occurred in the context of steam pops during radiofrequency ablation and were more likely to require surgical repair (
P
=0.07). Intra-aortic balloon counterpulsation, left ventricular assist device, and biventricular assist device were used in 2 patients, 1 patient, and 1 patient, respectively. Of 6 cases in which the site of perforation could be determined at cardiac surgery, 5 were in the right ventricle (4 outflow tract, 1 free wall) and only 1 was located in the left ventricle. All patients survived to discharge.

Conclusions—
Ventricular perforation and tamponade occurs in 1% of ventricular ablation procedures and in this series, occurred only in patients without a history of prior cardiac surgery. More than half the patients required surgical repair. Perforation is often associated with steam pops and emergent surgical repair is often required when perforation occurs after a steam pop.
Parsing Noun Phrases in the Penn Treebank
Authors: Vadas David , Curran James R. 
Published: July 2011

Noun phrases (nps) are a crucial part of natural language, and can have a very complex structure. However, this np structure is largely ignored by the statistical parsing field, as the most widely used corpus is not annotated with it. This lack of gold-standard data has restricted previous efforts to parse nps, making it impossible to perform the supervised experiments that have achieved high performance in so many Natural Language Processing (nlp) tasks. We comprehensively solve this problem by manually annotating np structure for the entire Wall Street Journal section of the Penn Treebank. The inter-annotator agreement scores that we attain dispel the belief that the task is too difficult, and demonstrate that consistent np annotation is possible. Our gold-standard np data is now available for use in all parsers. We experiment with this new data, applying the Collins (2003) parsing model, and find that its recovery of np structure is significantly worse than its overall performance. The parser's F-score is up to 5.69% lower than a baseline that uses deterministic rules. Through much experimentation, we determine that this result is primarily caused by a lack of lexical information. To solve this problem we construct a wide-coverage, large-scale np Bracketing system. With our Penn Treebank data set, which is orders of magnitude larger than those used previously, we build a supervised model that achieves excellent results. Our model performs at 93.8% F-score on the simple task that most previous work has undertaken, and extends to bracket longer, more complex nps that are rarely dealt with in the literature. We attain 89.14% F-score on this much more difficult task. Finally, we implement a post-processing module that brackets nps identified by the Bikel (2004) parser. Our np Bracketing model includes a wide variety of features that provide the lexical information that was missing during the parser experiments, and as a result, we outperform the parser's F-score by 9.04%. These experiments demonstrate the utility of the corpus, and show that many nlp applications can now make use of np structure.
Preoperative BRAF Mutation Has Different Predictive Values for Lymph Node Metastasis according to Tumor Size
Authors: So Yoon Kyoung , Son Young‐Ik , Park Joo Yeon , Baek Chung‐Hwan , Jeong Han‐Sin , Chung Man Ki 
Published: July 2011

ObjectiveTo investigate whether BRAF mutation of papillary thyroid carcinoma (PTC) has different predictive values for regional lymph node (LN) metastasis according to tumor size.Study DesignProspective cohort study.SettingA tertiary hospital.Subjects and MethodsFrom January 2009 to August 2009, the authors prospectively enrolled 102 consecutive patients with unifocal PTC based on the findings of ultrasonography‐guided fine‐needle aspiration biopsy (FNAB). BRAF mutation was tested on preoperative FNAB specimens. Total thyroidectomy and bilateral central neck dissection (± lateral neck dissection) was performed for all patients. Among 102 patients, 71 who were confirmed to have unifocal PTC by the surgical pathology were finally selected. The 71 patients were classified into 3 groups according to their tumor size: group I, ≤0.5 cm; group II, >0.5 cm and ≤1 cm; and group III, >1 cm. LN metastasis was evaluated in the surgical specimen as a dependent variable. The authors investigated whether BRAF mutation is predictive of LN metastasis in each group.ResultsOverall, BRAF mutation was a significant predictor of LN metastasis (P =. 045). When patients were classified into 3 groups, frequency of LN metastasis increased with tumor size: 4.8%, 50.0%, and 66.7% (P <. 001). However, the frequency of BRAF mutation was not different among 3 groups: 61.9%, 56.3%, and 72.2% (P =. 536). BRAF mutation was predictive of LN metastasis only in group II (P =. 026).ConclusionBRAF mutation of PTC may have differential predictive values for LN metastasis, according to tumor size.
Female Gender as a Risk Factor for Transient Post‐Thyroidectomy Hypocalcemia
Authors: Sands Noah B. , Payne Richard J. , Côté Valerie , Hier Michael P. , Black Martin J. , Tamilia Michael 
Published: July 2011

ObjectivesTransient post‐thyroidectomy hypocalcemia is a common complication following thyroid surgery. Studies have identified risk factors and possible ways to help predict post‐thyroidectomy hypocalcemia with the intent of ultimately limiting its incidence. This study evaluates the role of patient gender as a potential risk factor.Study DesignA retrospective case series with chart review of 270 consecutive total thyroidectomy patients was conducted.SettingJewish General Hospital, a McGill University–affiliated hospital in Montreal, Canada.Subjects and Methods219 women and 51 men were included. Postoperative hypocalcemia was defined as any 1 of the following: total serum calcium 1.90 mmol/L or less, or signs and symptoms of hypocalcemia. The following were evaluated as potential confounding factors in the study: age, menopause, preoperative calcium, parathyroid hormone, magnesium and phosphate levels, presence of carcinoma in the surgical specimen, number of parathyroid glands preserved in situ, thyroid gland volume, and nodule size.ResultsFemale patients experienced transient postoperative hypocalcemia in 24.7% (54/219) of cases, which was significantly greater than the 11.8% (6/51) incidence detected in men (P <. 05). This represents a female/male relative risk ratio of 2.1 (confidence interval, 1.0‐4.6). There was no significant difference in rates of hypocalcemia between premenopausal and postmenopausal women (22.7% vs 26.6%).ConclusionThese findings suggest that being female is likely a risk factor for transient post‐thyroidectomy hypocalcemia. Although this association is statistically significant, its magnitude and clinical relevance are uncertain and may be trivial. Additional research is needed to ascertain the physiologic mechanisms underlying this gender difference.
The Efficacy of Ankaferd Blood Stopper in Heparin‐Induced Hemostatic Abnormality in a Rat Epistaxis Model
Authors: Iynen Ismail , Sogut Ozgur , Kose Rustu 
Published: July 2011

ObjectiveTo assess the in vivo hemostatic effect of Ankaferd Blood Stopper (ABS).Study DesignAn experimental study of an animal anterior epistaxis model.SettingA tertiary care university hospital.Subjects and MethodsWistar rats were randomized into 4 groups of 7 each: group 1, control, no pretreatment, irrigated with saline; group 2, no pretreatment, irrigated with ABS; group 3, control, heparin pretreatment, irrigated with saline; and group 4, heparin pretreatment, irrigated with ABS. In all groups, a standardized rat epistaxis model was obtained by cutting the anterior nasal septal mucosa. To control bleeding, compressive dressings were placed after instilling 1 mL of either ABS or saline to the bleeding area. The hemostasis time and amount of nasal bleeding were measured in all groups to compare the treatments without and with ABS.ResultsWithout heparin pretreatment, ABS shortened the hemostasis time by 1.57 minutes (P =. 003) and reduced the amount of the bleeding by 0.35 g (P =. 006). With heparin pretreatment, ABS shortened the hemostasis time by 2.86 minutes and reduced the amount of the bleeding by 0.49 g (both P =. 002).ConclusionABS irrigation was more effective than saline irrigation for treating anterior epistaxis hemostasis in animals using a compressive dressing with or without heparin pretreatment.
MSI2 protein expression predicts unfavorable outcome in acute myeloid leukemia
Authors: Byers Richard J. , Currie Treeve , Tholouli Eleni , Rodig Scott J. , Kutok Jeffery L. 
Published: July 2011

AbstractMSI2 is highly expressed in human myeloid leukemia (AML) cell lines, and high expression of MSI2 mRNA is associated with decreased survival in AML, suggesting its use as a new prognostic marker. To test this, we measured MSI2 protein level by immunohistochemistry in 120 AML patients. Most cases (70%) showed some nuclear or cytoplasmic positivity, but the percentage of positive cells was low in most cases. Despite this, MSI2 protein expression was negatively associated with outcome, particularly for patients with good cytogenetic subgroup. For practical diagnostic purposes, the strongest significance of association was seen in cases with > 1% of cells showing strong MSI2 staining, these having a very poor outcome (P < .0001). Multivariate analysis with cytogenetic category, age, white cell count, and French-American-British subtype demonstrated that nuclear MSI2 levels were independently predictive of outcome (P = .0497). These results confirm the association of MSI2 expression with outcome in AML at the protein level and demonstrate the utility of MSI2 protein as a clinical prognostic biomarker. In addition, although positive at some level in most cases, its prognostic power derived from few positive cells, supporting its role in control of normal hematopoietic stem cell function and highlighting its role in disease progression.
The new TNM classification of lung cancer in practice
Authors: Rami-Porta R. , Giroux D.J. , Goldstraw P. 
Published: July 2011

Educational aimsTo describe the changes in the 7th edition of the TNM classification of lung cancerTo discuss the clinical implications of the incorporation of the new TNM classification in everyday practiceTo emphasise the key points for a proper pathologic classificationSummaryThe 7th edition of the TNM (tumour, node, metastases) classification of lung cancer incorporates the proposals of the International Association for the Study of Lung Cancer, whose database included more than 100,000 patients from Asia, Australia, Europe, and North America. The changes affect the T and the M components of the classification, and the stage grouping. The N component remained unaltered, although the present descriptors were validated both in the clinical and pathologic settings. This new TNM classification applies to non-small cell lung cancer, small cell lung cancer and, for the first time, to broncho-pulmonary carcinoids. The innovations allow for a better separation of tumours with significantly different prognosis, and imply a more careful determination of tumour size.