bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adolescent and parental utilities for the health states associated with pelvic inflammatory disease
Authors: Trent Maria , Lehmann Harold P , Qian Qiang , Thompson Carol B , Ellen Jonathan M , Frick Kevin D 
Published: October 2011

PurposeThere is limited information about how the consumers of adolescent pelvic inflammatory disease (PID) care value health states associated with the disorder. The aim of this study is to determine and compare adolescent and parent PID-related health utilities.MethodsAdolescent girls (N=134) and parents (N=121) completed a web-based utility elicitation survey. Participants reviewed five scenarios describing the health states associated with PID (outpatient treatment (mild–moderate disease), inpatient treatment (severe disease), ectopic pregnancy, infertility and chronic abdominal pain). After each scenario, participants were asked to rate health-related quality of life (HRQL) using a Visual Analogue Scale (VAS) and to complete a time trade-off (TTO) assessment. Data were evaluated using multiple linear (VAS) and quantile (TTO) regression analyses.ResultsAdolescents had significantly lower mean valuations (p<0.01) than the parents on the VAS for HRQL in each health state (outpatient (62 vs 76), inpatient (57 vs 74), ectopic (55 vs 73), infertility (59 vs 68) and chronic abdominal pain (48 vs 61)). Using quantile regression analysis, adolescents were also willing to give up more time for health gains indicated by lower median TTO scores (p<0.01) for outpatient treatment (0.98 vs 1.0), inpatient treatment (0.96 vs 1.0) and ectopic pregnancy (0.98 vs 1.0).ConclusionsThe authors demonstrate that adolescents assign more disutility (lower valuations) than parents for HRQL and three of five of the TTO assessments for PID-related health states. Future economic evaluations using patient-specific preferences to determine resource allocation for PID management in adolescents should include adolescent health outcomes and utilities.
Glioblastoma-Derived Epidermal Growth Factor Receptor Carboxyl-Terminal Deletion Mutants Are Transforming and Are Sensitive to EGFR-Directed Therapies
Authors: Cho Jeonghee , Pastorino Sandra , Zeng Qing , Xu Xiaoyin , Johnson William , Vandenberg Scott , Verhaak Roel , Cherniack Andrew D. , Watanabe Hideo , Dutt Amit , Kwon Jihyun , Chao Ying S. , Onofrio Robert C. , Chiang Derek , Yuza Yuki , Kesari Santosh , Meyerson Matthew 
Published: October 2011

Abstract
Genomic alterations of the epidermal growth factor receptor (EGFR) gene play a crucial role in pathogenesis of glioblastoma multiforme (GBM). By systematic analysis of GBM genomic data, we have identified and characterized a novel exon 27 deletion mutation occurring within the EGFR carboxyl-terminus domain (CTD), in addition to identifying additional examples of previously reported deletion mutations in this region. We show that the GBM-derived EGFR CTD deletion mutants are able to induce cellular transformation in vitro and in vivo in the absence of ligand and receptor autophosphorylation. Treatment with the EGFR-targeted monoclonal antibody, cetuximab, or the small molecule EGFR inhibitor, erlotinib, effectively impaired tumorigenicity of oncogenic EGFR CTD deletion mutants. Cetuximab in particular prolonged the survival of intracranially xenografted mice with oncogenic EGFR CTD deletion mutants, compared with untreated control mice. Therefore, we propose that erlotinib and, especially, cetuximab treatment may be a promising therapeutic strategy in GBM patients harboring EGFR CTD deletion mutants. Cancer Res; 71(24); 7587–96. ©2011 AACR.
Isolation and Characterization of Atrioventricular Nodal Cells From Neonate Rabbit Heart
Authors: Ye Sheng Xiao , Qu Yang , Dan Pauline , Lin Eric , Korthout Linda , Bradford Aaron , Hove-Madsen Leif , Sanatani Shubhayan , Tibbits Glen F. 
Published: October 2011

Background—
The properties of the atrioventricular (AV) node in the neonate heart and its role in unique pediatric cardiac arrhythmias such as junctional ectopic tachycardia (JET) are poorly understood. This is due in large part to the dearth of information on the structure and physiology of the AV node in the immature myocardium.

Methods and Results—

Sinoatrial nodal cells (SANCs), AV nodal tissues, and myocytes (AVNCs) were obtained from neonatal (10-day-old) rabbits, and the histological, immunohistological, and electrophysiological properties were characterized in detail. Masson's trichrome histological staining clearly delineated AV nodal structures including the inferior nodal extension, compact node, and the bundle of His region. AV tissue sections and AVNCs were immunolabeled against neurofilament 160 (NF160), connexin 43 (Cx43), hyperpolarization-activated, cyclic nucleotide modulated channel (HCN4), sodium/calcium exchanger, ryanodine receptor, sarcoplasmic/endoplasmic reticulum Ca
2+
pump (SERCA), and phospholamban (PLB). In AVNCs with triple-positive NF160, SERCA, and PLB labeling, SERCA and PLB were found with high degrees of colocalization. The majority (59%) of NF160-positive AVNCs were found to coexpress HCN4. NF160 and HCN4 expression was found to be even higher in SANCs, where 88% of SANCs exhibited coexpression. Spontaneous action potentials recorded from isolated neonatal AVNCs were uniformly of the atrionodal type, showing none of the action potential heterogeneities found in the mature heart. Current recordings found the hyperpolarization-activated funny current (
I
f
) in 55% (11 of 21 cells) of AVNCs, consistent with the immunocytochemistry results.

Conclusions—
This represents the first detailed electrophysiological and immunohistological report of the neonatal AV node and lays the groundwork for a better understanding of heart rate regulation and unique arrhythmias in the neonate heart.
An Empowerment-Based Diabetes Self-management Education Program for Hispanic/Latinos
Authors: Peña-Purcell Ninfa C. , Boggess May M. , Jimenez Natalia 
Published: October 2011

Purpose The purpose of this pilot study was to evaluate the effects of a culturally sensitive, empowerment-based diabetes self-management education program for Spanish-speaking Hispanic/Latinos. Methods A prospective quasi-experimental repeated measures design tested the effectiveness of the ¡Si, Yo Puedo Controlar Mi Diabetes! diabetes self-management education program. In sum, 144 persons residing in 2 Texas counties at the Texas-Mexico border (Starr and Hidalgo) served as participants. Two groups were formed, an intervention and a control (wait list). Clinical (A1C), cognitive, attitudinal, behavioral, and cultural assessments were collected at baseline and 3 months. Results Demographic characteristics for the intervention and control groups were similar. Both groups were predominately female, low income, older than 40 years, and minimally acculturated. Baseline and posttest findings showed that the intervention group had a significant reduction in A1C values; median difference was 0.3 (n = 45), especially for those with higher baseline values. Participants in the intervention group also improved in their self-efficacy and self-care scores. Conclusions Findings from the study suggest that additional dissemination of a diabetes self-management education program for Spanish-speaking Hispanic/Latinos is warranted to improve clinical outcomes and associated diabetes self-efficacy and self-care behaviors.
DEHP and its active metabolites: leaching from different tubing types, impact on proinflammatory cytokines and adhesion molecule expression. Is there a subsumable context?
Authors: Greiner TO , Volkmann AS , Hildenbrand S , Wodarz R , Perle N , Ziemer G , Rieger M , Wendel HP , Walker T 
Published: October 2011

Introduction: Di(2-ethylhexyl)phthalate (DEHP) is suspected to be toxic for several reasons. During contact with a lipophilic medium, DEHP leaks from polyvinylchloride (PVC), but its influence on inflammatory reactions remains unknown. We examined specific DEHP leaching out of different tubing types, the possibly modulated liberation of proinflammatory cytokines and the induction of adhesion molecule expression in primary endothelial cells. Materials and Methods: Blood samples were circulated in traditional PVC, nodioctyl phthalate (DOP) PVC and heparin-coated PVC tubing within a Chandler loop model. The blood was tested for the concentration of DEHP and its active metabolites as well as the liberation of the proinflammatory cytokines TNFα and IL1ß. Furthermore, we exposed human endothelial cells to circulated blood and analysed them for the expression of the adhesion molecules ICAM-1, VCAM-1 and E-selectin. Results: In contrast to the other tubing, PVC tubing showed significantly elevated DEHP levels, but no alteration was observed concerning a potential up-regulation of the cytokines or activation of the endothelial adhesion molecule receptors. Conclusions: Our data conclude that there is no correlation between DEHP leaching and the inflammatory response after ECC support, but this study showed that even DEHP-free material is leaching DEHP and its toxic metabolites.
Does 6% hydroxyethyl starch 130/0.4 impact differently on blood glucose than 4% gelatin in patients receiving open heart surgery?
Authors: Lou S , Bian L , Long C , Wang Z , Ma J , Zhou B 
Published: October 2011

Objectives: To investigate whether starch-based colloid may impact differently on blood glucose than a gelatin-based colloid in adult patients receiving open heart surgery. Methods: 70 adult patients scheduled for elective first-time cardiac surgery were enrolled and randomized into two groups. The circuits were primed with either 6% HES 130/0.4 or 4% gelatin. The peak glucose level, incidence of hyperglycemia, glucose variation and glucose level at different time points during operation were compared between the two groups. A p-value ≤ 0.05 was accepted as significant. Results: The peak glucose (150±30mg/dl vs 142±27, p=0.236) and glucose variation demonstrated by standard deviation (26±12mg/dl vs 23±11mg/dl, p=0.202) were comparable between the two groups. Repeated measurement ANOVA revealed that the main effect for artificial colloid was not significant (p=0.349). Conclusions: With the data available, we could not prove that starch-based colloid (HES130) had a different impact on intra-operative blood glucose than a gelatin-based colloid in adult patients receiving open heart surgery.
Wind generation’s contribution to supporting peak electricity demand – meteorological insights
Authors: Brayshaw D J , Dent C , Zachary S 
Published: October 2011

Wind generation’s contribution to meeting extreme peaks in electricity demand is a key concern for the integration of wind power. In Great Britain (GB), robustly assessing this contribution directly from power system data (i.e. metered wind-supply and electricity demand) is difficult as extreme peaks occur infrequently (by definition) and measurement records are both short and inhomogeneous. Atmospheric circulation-typing combined with meteorological reanalysis data is proposed as a means to address some of these difficulties, motivated by a case study of the extreme peak demand events in January 2010. A preliminary investigation of the physical and statistical properties of these circulation types suggests that they can be used to identify the conditions that are most likely to be associated with extreme peak demand events. Three broad cases are highlighted as requiring further investigation. The high-over-Britain anticyclone is found to be generally associated with very low winds but relatively moderate temperatures (and therefore moderate peak demands, somewhat in contrast to the classic low-wind cold snap that is sometimes apparent in the literature). In contrast, both longitudinally extended blocking over Scotland/Scandinavia and latitudinally extended troughs over western Europe appear to be more closely linked to the very cold GB temperatures (usually associated with extreme peak demands). In both of these latter situations, wind resource averaged across GB appears to be more moderate.
AP-1 elements and TCL1 protein regulate expression of the gene encoding protein tyrosine phosphatase PTPROt in leukemia
Authors: Motiwala Tasneem , Zanesi Nicola , Datta Jharna , Roy Satavisha , Kutay Huban , Checovich Allyn M. , Kaou Mohamed , Zhong Yiming , Johnson Amy J. , Lucas David M. , Heerema Nyla A. , Hagan John , Mo Xiaokui , Jarjoura David , Byrd John C. , Croce Carlo M. , Jacob Samson T. 
Published: October 2011

Abstract
We previously demonstrated that the gene encoding PTPROt, the truncated form of protein tyrosine phosphatase receptor type O expressed predominantly in hematopoietic cells, is a candidate tumor suppressor and is down-regulated in chronic lymphocytic leukemia (CLL). Here, we show that PTPROt expression is significantly reduced in CD19+ spleen B cells from Eμ-T cell leukemia 1 (TCL1) transgenic mice relative to the wild-type mice. Strikingly, as much as a 60% decrease in PTPROt expression occurs at 7 weeks independently of promoter methylation. To elucidate the potential mechanism for this early suppression of PTPROt in these mice, we explored the role of activating protein-1 (AP-1) in its expression. We first demonstrate that AP-1 activation by 12-O-tetradecanoylphorbol-13-acetate induces PTPROt expression with concurrent recruitment of c-fos and c-jun to its promoter. The PTPROt promoter is also responsive to over- and underexpression of AP-1, confirming the role of AP-1 in PTPROt expression. Next, we demonstrate that TCL1 can repress the PTPROt promoter by altering c-fos expression and c-jun activation state. Finally, using primary CLL cells we have shown an inverse relationship between TCL1 and PTPROt expression. These findings further substantiate the role of TCL1 in PTPROt suppression and its importance in the pathogenesis of CLL.
Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice
Authors: Lilla Jennifer N. , Chen Ching-Cheng , Mukai Kaori , BenBarak Maya J. , Franco Christopher B. , Kalesnikoff Janet , Yu Mang , Tsai Mindy , Piliponsky Adrian M. , Galli Stephen J. 
Published: October 2011

AbstractIt has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/6 mice in which Cre recombinase is expressed under the control of a segment of the carboxypeptidase A3 (Cpa3) promoter. C57BL/6-Cpa3-Cre; Mcl-1fl/fl mice are severely deficient in mast cells (92%-100% reduced in various tissues analyzed) and also have a marked deficiency in basophils (58%-78% reduced in the compartments analyzed), whereas the numbers of other hematopoietic cell populations exhibit little or no changes. Moreover, Cpa3-Cre; Mcl-1fl/fl mice exhibited marked reductions in the tissue swelling and leukocyte infiltration that are associated with both mast cell- and IgE-dependent passive cutaneous anaphylaxis (except at sites engrafted with in vitro–derived mast cells) and a basophil- and IgE-dependent model of chronic allergic inflammation, and do not develop IgE-dependent passive systemic anaphylaxis. Our findings support the conclusion that Mcl-1 is required for normal mast cell and basophil development/survival in vivo in mice, and also suggest that Cpa3-Cre; Mcl-1fl/fl mice may be useful in analyzing the roles of mast cells and basophils in health and disease.
Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia
Authors: Karp Judith E. , Vener Tatiana I. , Raponi Mitch , Ritchie Ellen K. , Smith B. Douglas , Gore Steven D. , Morris Lawrence E. , Feldman Eric J. , Greer Jacqueline M. , Malek Sami , Carraway Hetty E. , Ironside Valerie , Galkin Steven , Levis Mark J. , McDevitt Michael A. , Roboz Gail R. , Gocke Christopher D. , Derecho Carlo , Palma John , Wang Yixin , Kaufmann Scott H. , Wright John J. , Garret-Mayer Elizabeth 
Published: October 2011

Abstract
Tipifarnib (T) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia (AML). Based on preclinical synergy, a phase 1 trial of T plus etoposide (E) yielded 25% complete remission (CR). We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults (age range, 70-90 years; median, 76 years) who were not candidates for conventional chemotherapy. Arm A (T 600 mg twice a day × 14 days, E 100 mg days 1-3 and 8-10) and arm B (T 400 mg twice a day × 14 days, E 200 mg days 1-3 and 8-10) yielded similar CR, but arm B had greater toxicity. Total CR was 25%, day 30 death rate 7%. A 2-gene signature of high RASGRP1 and low aprataxin (APTX) expression previously predicted for T response. Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78% CR rate and negative predictive value 87%. This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies. The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively. This study is registered at www.clinicaltrials.gov as #NCT00602771.
The neonatal Fc receptor (FcRn) is not required for IVIg or anti-CD44 monoclonal antibody–mediated amelioration of murine immune thrombocytopenia
Authors: Crow Andrew R. , Suppa Sara J. , Chen Xi , Mott Patrick J. , Lazarus Alan H. 
Published: October 2011

Abstract
To definitively determine whether the neonatal Fc receptor (FcRn) is required for the acute amelioration of immune thrombocytopenia (ITP) by IVIg, we used FcRn-deficient mice in a murine ITP model. Mice injected with antiplatelet antibody in the presence or absence of IVIg displayed no difference in platelet-associated IgG between FcRn deficient versus C57BL/6 mice. FcRn-deficient mice treated with high-dose (2 g/kg) IVIg or a low–dose (2 mg/kg) of an IVIg-mimetic CD44 antibody were, however, protected from thrombocytopenia to an equivalent extent as wild-type mice. To verify and substantiate the results found with FcRn-deficient mice, we used β2-microglobulin–deficient mice (which do not express functional FcRn) and found that IVIg or CD44 antibody also protected them from thrombocytopenia. These data suggest that for both high-dose IVIg as well as low-dose CD44 antibody treatment in an acute ITP model, FcRn expression is neither necessary nor required.
Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection
Authors: Kok Wai Ling , Denney Laura , Benam Kambez , Cole Suzanne , Clelland Colin , McMichael Andrew J , Ho Ling-Pei 
Published: October 2011

ABSTRACT
Little is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6ChiLy6G– inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (Jα18−/− mice) have increased levels of inflammatory monocytes, which correlated with increased lung injury and mortality (but not viral load). Activation of iNKT cells correlated with reduction of MCP-1 levels and improved outcome. iNKT cells were able to selectively lyse infected, MCP-1-producing monocytes in vitro, in a CD1d-dependent process. Our study provides a detailed profile and kinetics of innate immune cells in the lungs during severe IAV infection, highlighting inflammatory monocytes as the major infiltrate and identifying a role for iNKT cells in control of these cells and lung immune-pathology.
Serine phosphorylation of FcγRI cytoplasmic domain directs lipid raft localization and interaction with protein 4.1G
Authors: Gibson Andrew W , Li Xinrui , Wu Jianming , Baskin Julie G , Raman Chander , Edberg Jeffrey C , Kimberly Robert P 
Published: October 2011

ABSTRACT
The high-affinity IgG receptor (CD64, FcγRI) has several special capacities, including the receptor-stimulated cleavage of the cell surface B cell-activating factor of the TNF superfamily (TNFSF13B). With the use of the yeast two-hybrid system, we and others have shown that FcγRI interacts with protein 4.1G (EPB41L2). Our mutational analyses identified two required 4.1G-interacting regions in the FcγRI CY and one FcγRI-interacting site in the C-terminus of protein 4.1G. Herein, we explore mechanism(s) that may regulate the interaction between protein 4.1G and FcγRI CY and influence FcγRI membrane mobility and function. We show that FcγRI CY interacts with protein 4.1G in vitro and that FcγRI coimmunoprecipitates protein 4.1G in freshly isolated human PBMC. With the use of immunostaining, we show that FcγRI colocalizes with protein 4.1G in unstimulated U937 cells, in which the FcγRI CY is constitutively serine-phosphorylated, but significant uncoupling occurs following FcγRI cross-linking, suggesting phosphoserine-regulated interaction. In vitro, protein 4.1G interacted preferentially with CK2-phosphorylated FcγRI CY, and compared with WT FcγRI, a nonphosphorylatable FcγRI mutant receptor was excluded from lipid rafts, suggesting a key role for protein 4.1G in targeting phosphorylated FcγRI to rafts. These data are consistent with a phosphoserine-dependent tethering role for protein 4.1G in maintaining FcγRI in lipid rafts and provide insight into the unique phosphoserine-based regulation of receptor signaling by FcγRI CY.
Efficient Two-Dimensional Packing Algorithms for Mobile WiMAX
Authors: Lodi Andrea , Martello Silvano , Monaci Michele , Cicconetti Claudio , Lenzini Luciano , Mingozzi Enzo , Eklund Carl , Moilanen Jani 
Published: October 2011

We present the result of research, developed within Nokia Siemens Networks, to solve the downlink sub-frame allocation problem in Mobile WiMAX (IEEE 802.16) technology in its full complexity, while simultaneously fulfilling real-life constraints on processing power and delay. We describe the IEEE 802.16 standard, and introduce two system models. A theoretical analysis of the two-dimensional packing problems originated by such models shows that they are both 𝒩𝒫-hard in the strong sense. From a practical point of view, the processing budget for scheduling in the base station was estimated to be 1 ms on a state-of-the-art PC. Thus, we introduce two highly efficient heuristics that were developed to handle the system practically. A thorough computational analysis of their optimization characteristics and a system-level evaluation in realistic scenarios proved that the algorithms offer significant capacity gain in Mobile WiMAX systems that translate to increased operator revenues. This paper was accepted by Dimitris Bertsimas, optimization.