bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting the mTOR Pathway Synergistically Enhances Cytotoxicity in Ovarian Cancer Cells Induced by Etoposide through Upregulation of c-Jun
Authors: Itamochi Hiroaki , Oishi Tetsuro , Shimada Muneaki , Sato Shinya , Uegaki Kazunori , Naniwa Jun , Sato Seiya , Nonaka Michiko , Terakawa Naoki , Kigawa Junzo , Harada Tasuku 
Published: May 2011

Abstract
Purpose: The mTOR pathway is thought to be a central regulator of proliferation and survival of cells. Rapamycin and its analogs are undergoing clinical trials in patients with epithelial ovarian cancer. This study aimed to assess the potential to use rapamycin and anticancer agents in combination for first- and second-line chemotherapy to treat ovarian cancer.
Experimental Design: We used six ovarian serous adenocarcinoma cell lines (KF, KOC-2S, SHIN-3, SK-OV-3, TU-OS-3, and TU-OS-4) in this study. We treated the cells with rapamycin and anticancer agents, then assessed cell viability, apoptosis, and the expression of protein in apoptotic pathways and molecules downstream of the mTOR signaling pathways. We also investigated the effect of these drug combinations on survival in nude mouse xenograft models.
Results: Synergistic effects were observed in five cell lines from the combination of etoposide and rapamycin. However, we observed antagonistic effects when rapamycin was combined with gemcitabine, cisplatin, or paclitaxel on more than two cell lines. Rapamycin dramatically enhanced apoptosis induced by etoposide and the expression of cleaved caspase 9. This effect was associated with upregulation of phosphorylated c-Jun and downregulation of Bcl-xL. The synergistic interaction of rapamycin and etoposide was lower when the c-Jun pathway was suppressed by a c-Jun N-terminal kinase inhibitor (SP600125). Finally, treating nude mice with rapamycin and etoposide significantly prolonged survival in the model mice with ovarian cancer xenografts.
Conclusions: Chemotherapy with rapamycin and etoposide combined is worth exploring as a treatment modality for women with epithelial ovarian cancer. Clin Cancer Res; 17(14); 4742–50. ©2011 AACR.
Dual Targeting of Tumor Angiogenesis and Chemotherapy by Endostatin–Cytosine Deaminase–Uracil Phosphoribosyltransferase
Authors: Chen Chun-Te , Yamaguchi Hirohito , Lee Hong-Jen , Du Yi , Lee Heng-Huan , Xia Weiya , Yu Wen-Hsuan , Hsu Jennifer L. , Yen Chia-Jui , Sun Hui-Lung , Wang Yan , Yeh Edward T.H. , Hortobagyi Gabriel N. , Hung Mien-Chie 
Published: May 2011

Abstract
Several antiangiogenic drugs targeting VEGF/VEGF receptor (VEGFR) that were approved by the Food and Drug Administration for many cancer types, including colorectal and lung cancer, can effectively reduce tumor growth. However, targeting the VEGF signaling pathway will probably influence the normal function of endothelial cells in maintaining homeostasis and can cause unwanted adverse effects. Indeed, emerging experimental evidence suggests that VEGF-targeting therapy induced less tumor cell–specific cytotoxicity, allowing residual cells to become more resistant and eventually develop a more malignant phenotype. We report an antitumor therapeutic EndoCD fusion protein developed by linking endostatin (Endo) to cytosine deaminase and uracil phosphoribosyltransferase (CD). Specifically, Endo possesses tumor antiangiogenesis activity that targets tumor endothelial cells, followed by CD, which converts the nontoxic prodrug 5-fluorocytosine (5-FC) to the cytotoxic antitumor drug 5-fluorouracil (5-FU) in the local tumor area. Moreover, selective targeting of tumor sites allows an increasing local intratumoral concentration of 5-FU, thus providing high levels of cytotoxic activity. We showed that treatment with EndoCD plus 5-FC, compared with bevacizumab plus 5-FU treatment, significantly increased the 5-FU concentration around tumor sites and suppressed tumor growth and metastasis in human breast and colorectal orthotropic animal models. In addition, in contrast to treatment with bevacizumab/5-FU, EndoCD/5-FC did not induce cardiotoxicity leading to heart failure in mice after long-term treatment. Our results showed that, compared with currently used antiangiogenic drugs, EndoCD possesses potent anticancer activity with virtually no toxic effects and does not increase tumor invasion or metastasis. Together, these findings suggest that EndoCD/5-FC could become an alternative option for future antiangiogenesis therapy. Mol Cancer Ther; 10(8); 1327–36. ©2011 AACR.
A Model Investigation of Aerosol-Induced Changes in Boreal Winter Extratropical Circulation
Authors: Ming Y. , Ramaswamy V. , Chen Gang 
Published: May 2011

AbstractThe authors examine the key characteristics of the boreal winter extratropical circulation changes in response to anthropogenic aerosols, simulated with a coupled atmosphere–slab ocean general circulation model. The zonal-mean response features a pronounced equatorward shift of the Northern Hemisphere subtropical jet owing to the midlatitude aerosol cooling. The circulation changes also show strong zonal asymmetry. In particular, the cooling is more concentrated over the North Pacific than over the North Atlantic despite similar regional forcings. With the help of an idealized model, the authors demonstrate that the zonally asymmetrical response is linked tightly to the stationary Rossby waves excited by the anomalous diabatic heating over the tropical east Pacific. The altered wave pattern leads to a southeastward shift of the Aleutian low (and associated changes in winds and precipitation), while leaving the North Atlantic circulation relatively unchanged.Despite the rich circulation changes, the variations in the extratropical meridional latent heat transport are controlled strongly by the dependence of atmospheric moisture content on temperature. This suggests that one can project reliably the changes in extratropical zonal-mean precipitation solely from the global-mean temperature change, even without a good knowledge of the detailed circulation changes caused by aerosols. On the other hand, such knowledge is indispensable for understanding zonally asymmetrical (regional) precipitation changes.
The Relationship between the North Atlantic Jet and Tropical Convection over the Indian and Western Pacific Oceans
Authors: Yuan Jiacan , Feldstein Steven B. , Lee Sukyoung , Tan Benkui 
Published: May 2011

Abstract
Boreal winter jet variability over the North Atlantic is investigated using 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40) data, where the variability is defined by the first EOF of the zonal wind on seven vertical levels. The principal component time series of this EOF is referred to as the jet index. A pattern correlation analysis indicates that the jet index more accurately describes intraseasonal North Atlantic zonal wind variability than does the North Atlantic Oscillation (NAO). A series of composite calculations of the jet index based on events of intraseasonal convective precipitation over the tropical Indian and western Pacific Oceans reveals the following statistically significant relationships: 1) negative jet events lead enhanced Indian Ocean precipitation, 2) positive jet events lag enhanced Indian Ocean precipitation, 3) positive jet events lead enhanced western Pacific Ocean precipitation, and 4) negative jet events lag enhanced western Pacific Ocean precipitation. These intraseasonal relationships are found to be linked through the circumglobal teleconnection pattern (CTP). Implications of the sign of the CTP being opposite to that of the jet index suggest that relationships 1 and 3 may arise from cold air surges associated with the CTP over these oceans. On interdecadal time scales, a much greater increase in the frequency of precipitation events from 1958 to 1979 (P1) to 1980 to 2001 (P2) was found for the Indian Ocean relative to the western Pacific Ocean. This observation, combined with relationships 2 and 4, leads to the suggestion that this change in the frequency of intraseasonal Indian Ocean precipitation events may make an important contribution to the excitation of interdecadal variability of the North Atlantic jet.
Comparative cost-efficiency across the European G5 countries of various regimens of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia
Authors: Aapro Matti , Cornes Paul , Abraham Ivo 
Published: May 2011

Objectives: This cost-efficiency analysis of the granulocyte colony-stimulating factors (G-CSF) filgrastim (originator Neupogen® and biosimilar Zarzio®) and pegfilgrastim (Neulasta®) examined against a time horizon of 1–14 days of treatment and across the European Union G5 countries (a) when, cost-wise, using Neulasta® 6 mg versus Neupogen® or Zarzio® 300 µg may be cost-saving in reducing the incidence of chemotherapy-induced febrile neutropenia; and (b) if cost-wise, treatment with Zarzio® 300 µg yields a savings advantage over Neupogen® 300 µg. Methods: Cost-efficiency analysis of the direct costs a buyer or payer would incur when purchasing or covering any of these agents for managing one patient during one cycle of chemotherapy under regimens of 1–14 days of standard filgrastim using the population-weighted average unit dose cost of each agent per their public pack cost across the European G5 countries. Results: The cost of Neupogen® treatment ranged from €128.16 (1 day) to €1794.30 (14 days), compared to €95.46 and €1336.46 for Zarzio®, thus yielding potential cost savings from €32.70 to €457.84 for the latter. Neulasta® turns cost-saving at day 12 of Neupogen® treatment. At no point over a 14-day treatment period did Neulasta® yield a savings advantage over Zarzio®. Conclusion: Prophylaxis or treatment of febrile neutropenia with Zarzio® is cost-efficient under all possible treatment scenarios relative to Neupogen® and to Neulasta®. In the absence of convincing evidence that pegfilgrastim is pharmacotherapeutically superior to standard filgrastim, there is no cost-efficiency rationale to treat with Neulasta® over Zarzio®, though there may be a small window of approximately 3 days where Neulasta® is cost-efficient over Neupogen®. Regardless, our analysis shows Zarzio® to be the most cost-efficient approach to reducing the incidence of febrile neutropenia in chemotherapy-treated patients.
An Investigation of Nurses' Knowledge, Attitudes, and Practices Regarding Disinfection Procedures in Italy
Authors: Sessa Alessandra , Di Giuseppe Gabriella , Albano Luciana , Angelillo Italo F ,   the Collaborative Working Group
Published: May 2011

Abstract

Background
This study assessed the level of knowledge, attitudes, and practice regarding disinfection procedures among nurses in Italian hospitals.

Methods
A face-to-face interview gathered the following information: demographic and practice characteristics; knowledge about the healthcare-associated infections (HAIs) and the disinfection practices; attitudes towards the utility of guidelines/protocols and perception of the risks of acquiring/transmitting HAIs; compliance with antisepsis/disinfection procedures; and sources of information.

Results
Only 29% acknowledged that urinary and respiratory tract infections were the two most common HAIs and this knowledge was significantly higher in those with a higher level of education. Attitudes towards the utility of guidelines/protocols for disinfection procedures showed a mean score of 9.1. The results of the linear regression model indicated a more positive attitude in female nurses, in those with a lower number of years of activity, and in those needing additional information about disinfection procedures. Nurses with higher educational level and with a higher perception of risk of transmitting an infectious disease while working were more likely to perform appropriate antisepsis of the surgical wound and handwashing before and after medication.

Conclusions
Plan of successful prevention activities about HAIs and provide pointers to help optimize disinfection procedures and infection prophylaxis and management are needed.
Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia
Authors: Koroschetz Jana , Rehm Stefanie E , Gockel Ulrich , Brosz Mathias , Freynhagen Rainer , Tölle Thomas R , Baron Ralf 
Published: May 2011

Abstract

Background
Patients with diabetic neuropathy (DPN) and fibromyalgia differ substantially in pathogenetic factors and the spatial distribution of the perceived pain. We questioned whether, despite these obvious differences, similar abnormal sensory complaints and pain qualities exist in both entities. We hypothesized that similar sensory symptoms might be associated with similar mechanisms of pain generation. The aims were (1) to compare epidemiological features and co-morbidities and (2) to identify similarities and differences of sensory symptoms in both entities.

Methods
The present multi-center study compares epidemiological data and sensory symptoms of a large cohort of 1434 fibromyalgia patients and 1623 patients with painful diabetic neuropathy. Data acquisition included standard demographic questions and self-report questionnaires (MOS sleep scale, PHQ-9, PainDETECT). To identify subgroups of patients with characteristic combinations of symptoms (sensory profiles) a cluster analysis was performed using all patients in both cohorts.

Results
Significant differences in co-morbidities (depression, sleep disturbance) were found between both disorders. Patients of both aetiologies chose very similar descriptors to characterize their sensory perceptions. Burning pain, prickling and touch-evoked allodynia were present in the same frequency. Five subgroups with distinct symptom profiles could be detected. Two of the subgroups were characteristic for fibromyalgia whereas one profile occurred predominantly in DPN patients. Two profiles were found frequently in patients of both entities (20-35%).

Conclusions
DPN and fibromyalgia patients experience very similar sensory phenomena. The combination of sensory symptoms - the sensory profile - is in most cases distinct and almost unique for each one of the two entities indicating aetiology-specific mechanisms of symptom generation. Beside the unique aetiology-specific sensory profiles an overlap of sensory profiles can be found in 20-35% of patients of both aetiologies.
The natural history of West Nile virus infection presenting with West Nile virus meningoencephalitis in a man with a prolonged illness: a case report
Authors: Mainali Shraddha , Afshani Mansoor , Wood James B , Levin Michael C 
Published: May 2011

Abstract

Introduction
Estimates indicate that West Nile virus infects approximately one and a half million people in the United States of America. Up to 1% may develop West Nile virus neuroinvasive disease, in which infected patients develop any combination of meningitis, encephalitis, or acute paralysis.

Case presentation
A 56-year-old African-American man presented to our hospital with headache, restlessness, fever, myalgias, decreased appetite, and progressive confusion. A cerebrospinal fluid examination showed mild leukocytosis and an elevated protein level. Testing for routine infections was negative. Brain T2-weighted magnetic resonance imaging scans showed marked enlargement of caudate nuclei and increased intensity within the basal ganglia and thalami. A West Nile virus titer was positive, and serial brain magnetic resonance imaging scans showed resolving abnormalities that paralleled his neurological examination.

Conclusion
This report is unusual as it portrays the natural history and long-term consequences of West Nile virus meningoencephalitis diagnosed on the basis of serial brain images.
Endotoxin-induced uveitis is primarily dependent on radiation-resistant cells and on MyD88 but not TRIF
Authors: Kezic J , Taylor S , Gupta S , Planck S R , Rosenzweig H L , Rosenbaum J T 
Published: May 2011

ABSTRACTTLR4 activation by LPS (endotoxin) is mediated by the MyD88 and TRIF intracellular signaling pathways. We determined the relative activation of these pathways in murine ocular tissue after LPS exposure. Additionally, we explored whether BM-derived or non-BM-derived cells were the major contributors to EIU. Mice deficient in TRIF or MyD88 and their congenic (WT) controls received 250 ng ultrapure LPS ivt at 0 h. Ocular inflammation was assessed by histological analysis at 4, 6, and 24 h, and additionally, in MyD88−/− mice, intravital microscopy was performed at 4 h and 6 h to assess adherent, rolling, and infiltrating cells in the iris vasculature and tissue. Cytokines associated with the MyD88 and TRIF intracellular signaling pathways were analyzed in ocular tissue at 4 h. BM chimeric mice (WT→WT, TLR4−/−→WT, WT→TLR4−/−) received 250 ng LPS by ivt injection, and ocular tissues were examined by histology at 6 h. Lack of MyD88 resulted in a markedly diminished cellular response and reduced production of MyD88-related cytokines 4 h post-LPS treatment. In contrast, lack of TRIF led to reduced production of TRIF-related cytokines and no change in the cellular response to LPS. Therefore, the MyD88 pathway appears to be the dominant TLR4 pathway in EIU. Only WT → TLR4−/− chimeric mice were resistant to EIU, and this suggests, surprisingly, that non-BM-derived (radiation-resistant) cells in the eye play a greater role than BM-derived cells.
Kinematics of the quadrate bone during feeding in mallard ducks
Authors: Dawson Megan M. , Metzger Keith A. , Baier David B. , Brainerd Elizabeth L. 
Published: May 2011

SUMMARYAvian cranial kinesis, in which mobility of the quadrate, pterygoid and palatine bones contribute to upper bill elevation, is believed to occur in all extant birds. The most widely accepted model for upper bill elevation is that the quadrate rotates rostrally and medially towards the pterygoid, transferring force to the mobile pterygoid–palatine complex, which pushes on the upper bill. Until now, however, it has not been possible to test this hypothesis in vivo because quadrate motions are rapid, three-dimensionally complex and not visible externally. Here we use a new in vivo X-ray motion analysis technique, X-ray reconstruction of moving morphology (XROMM), to create precise (±0.06 mm) 3-D animations of the quadrate, braincase, upper bill and mandible of three mallard ducks, Anas platyrhynchos. We defined a joint coordinate system (JCS) for the quadrato-squamosal joint with the axes aligned to the anatomical planes of the skull. In this coordinate system, the quadrate's 3-D rotations produce an elliptical path of pterygoid process motion, with medial and rostrodorsal then lateral and rostrodorsal motion as the upper bill elevates. As the upper bill depresses, the pterygoid process continues along the ellipsoidal path, with lateral and caudoventral then medial and caudoventral motion. We also found that the mandibular rami bow outwards (streptognathy) during mandibular depression, which may cause the lateral component of quadrate rotation that we observed. Relative to the JCS aligned with the anatomical planes of the skull, a second JCS aligned with quadrato-squamosal joint anatomy did not produce a simpler description of quadrate kinematics.
The influence of trout cardiac troponin I and PKA phosphorylation on the Ca2+ affinity of the cardiac troponin complex
Authors: Kirkpatrick Kelly P. , Robertson Andrew S. , Klaiman Jordan M. , Gillis Todd E. 
Published: May 2011

SUMMARY
The trout heart is 10-fold more sensitive to Ca2+ than the mammalian heart. This difference is due, in part, to cardiac troponin C (cTnC) from trout having a greater Ca2+ affinity than human cTnC. To determine what other proteins are involved, we cloned cardiac troponin I (cTnI) from the trout heart and determined how it alters the Ca2+ affinity of a cTn complex containing all mammalian components (mammalian cTn). Ca2+ activation of the complex was characterized using a human cTnC mutant that contains anilinonapthalenesulfote iodoacetamide attached to Cys53. When the cTn complex containing labeled human cTnC was titrated with Ca2+, its fluorescence changed, reaching an asymptote upon saturation. Our results reveal that trout cTnI lacks the N-terminal extension found in cTnI from all other vertebrate groups. This protein domain contains two targets (Ser23 and Ser24) for protein kinase A (PKA) and protein kinase C. When these are phosphorylated, the rate of cardiomyocyte relaxation increases. When rat cTnI in the mammalian cTn complex was replaced with trout cTnI, the Ca2+ affinity was increased ∼1.8-fold. This suggests that trout cTnI contributes to the high Ca2+ sensitivity of the trout heart. Treatment of the two cTn complexes with PKA decreased the Ca2+ affinity of both complexes. However, the change for the complex containing rat cTnI was 2.2-fold that of the complex containing trout cTnI. This suggests that the phosphorylation of trout cTnI does not play as significant a role in regulating cTn function in trout.
Loading effects on jump performance in green anole lizards,Anolis carolinensis
Authors: Kuo Chi-Yun , Gillis Gary B. , Irschick Duncan J. 
Published: May 2011

SUMMARYLocomotor performance is a crucial determinant of organismal fitness but is often impaired in certain circumstances, such as increased mass (loading) resulting from feeding or gravidity. Although the effects of loading have been studied extensively for striding locomotion, its effects on jumping are poorly understood. Jumping is a mode of locomotion that is widely used across animal taxa. It demands large amounts of power over a short time interval and, consequently, may be affected by loading to a greater extent than other modes of locomotion. We placed artificial loads equal to 30% body mass on individuals of the species Anolis carolinensis to simulate the mass gain following the consumption of a large meal. We investigated the effects of loading on jump performance (maximum jump distance and accuracy), kinematics and power output. Loading caused a significant 18% decline in maximum jump distance and a significant 10% decline in takeoff speed. In other words, the presence of the load caused the lizards to take shorter and slower jumps, whereas takeoff angle and takeoff duration were not affected. By contrast, jump accuracy was unaffected by loading, although accuracy declined when lizards jumped to farther perches. Finally, mass-specific power output did not increase significantly when lizards jumped with loads, suggesting that the ability to produce mechanical power may be a key limiting factor for maximum jump performance. Our results suggest that mass gain after a large meal can pose a significant locomotor challenge and also imply a tradeoff between fulfilling energy requirement and moving efficiently in the environment.