bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do Muscle Mass, Muscle Density, Strength, and Physical Function Similarly Influence Risk of Hospitalization in Older Adults?
Authors: Cawthon Peggy Mannen , Fox Kathleen M. , Gandra Shravanthi R. , Delmonico Matthew J. , Chiou Chiun‐Fang , Anthony Mary S. , Sewall Ase , Goodpaster Bret , Satterfield Suzanne , Cummings Steven R. , Harris Tamara B. ,   for the Health, Aging and Body Composition Study
Published: July 2009

OBJECTIVES: To examine the association between strength, function, lean mass, muscle density, and risk of hospitalization.DESIGN: Prospective cohort study.SETTING: Two U.S. clinical centers.PARTICIPANTS: Adults aged 70 to 80 (N=3,011) from the Health, Aging and Body Composition Study.MEASUREMENTS: Measurements were of grip strength, knee extension strength, lean mass, walking speed, and chair stand pace. Thigh computed tomography scans assessed muscle area and density (a proxy for muscle fat infiltration). Hospitalizations were confirmed by local review of medical records. Negative binomial regression models estimated incident rate ratios (IRRs) of hospitalization for race‐ and sex‐specific quartiles of each muscle and function parameter separately. Multivariate models adjusted for age, body mass index, health status, and coexisting medical conditions.RESULTS: During an average 4.7 years of follow‐up, 1,678 (55.7%) participants experienced one or more hospitalizations. Participants in the lowest quartile of muscle density were more likely to be subsequently hospitalized (multivariate IRR=1.47, 95% confidence interval (CI)=1.24–1.73) than those in the highest quartile. Similarly, participants with the weakest grip strength were at greater risk of hospitalization (multivariate IRR=1.52, 95% CI=1.30–1.78, Q1 vs. Q4). Comparable results were seen for knee strength, walking pace, and chair stands pace. Lean mass and muscle area were not associated with risk of hospitalization.CONCLUSION: Weak strength, poor function, and low muscle density, but not muscle size or lean mass, were associated with greater risk of hospitalization. Interventions to reduce the disease burden associated with sarcopenia should focus on increasing muscle strength and improving physical function rather than simply increasing lean mass.
Human epicardium: ultrastructural ancestry of mesothelium and mesenchymal cells
Authors: Gherghiceanu Mihaela , Popescu L.M. 
Published: July 2009

AbstractThe human sub‐epicardial area contains an unexplored cellular population under a layer of mesothelial cells. Transmission electron microscopy revealed the existence of interstitial Cajal‐like cells (ICLCs), isolated smooth muscle cells (iSMC) and mesenchymal cells besides other well‐known cells. The presence of iSMC in the sub‐epicardial space is quite unique and could explain why epicardial‐derived cells isolated from human epicardium generate smooth muscle cells in culture. Mesenchymal cells, guided by ICLCs, were found migrating from sub‐epicardial area in the mesothelial layer. These findings suggest that epithelial‐mesenchymal transition is not a common process involved in cardiac regeneration in vivo.
Pigmentary function and evolution of tyrp1 gene duplicates in fish
Authors: Braasch Ingo , Liedtke Daniel , Volff Jean‐Nicolas , Schartl Manfred 
Published: July 2009

SummaryThe function of the tyrosinase‐related protein 1 (Tyrp1) has not yet been investigated in vertebrates basal to tetrapods. Teleost fishes have two duplicates of the tyrp1 gene. Here, we show that the teleost tyrp1 duplicates have distributed the ancestral gene expression in the retinal pigment epithelium (RPE) and melanophores in a species‐specific manner. In medaka embryos, tyrp1a expression is found in the RPE and in melanophores while tyrp1b is only expressed in melanophores. In zebrafish embryos, expression of tyrp1 paralogs overlaps in the RPE and in melanophores. Knockdown of each zebrafish tyrp1 duplicate alone does not show pigmentary defects, but simultaneous knockdown of both tyrp1 genes results in the formation of brown instead of black eumelanin accompanied by severe melanosome defects. Our study suggests that the brown melanosome color in Tyrp1‐deficient vertebrates is an effect of altered eumelanin synthesis. Black eumelanin formation essentially relies on the presence of Tyrp1 and some of its function is most likely conserved from the common ancestor of bony vertebrates.
FRACTURE MECHANICS IN PERFORATED DOMAINS: A VARIATIONAL MODEL FOR BRITTLE POROUS MEDIA
Authors: FOCARDI MATTEO , GELLI M. S. , PONSIGLIONE M. 
Published: July 2009

This paper deals with fracture mechanics in periodically perforated domains. Our aim is to provide a variational model for brittle porous media in the case of anti-planar elasticity. Given the perforated domain Ωε ⊂ ℝN (ε being an internal scale representing the size of the periodically distributed perforations), we will consider a total energy of the type [Formula: see text] Here u is in SBV(Ωε) (the space of special functions of bounded variation), Su is the set of discontinuities of u, which is identified with a macroscopic crack in the porous medium Ωε, and [Formula: see text] stands for the (N - 1)-Hausdorff measure of the crack Su. We study the asymptotic behavior of the functionals [Formula: see text] in terms of Γ-convergence as ε → 0. As a first (nontrivial) step we show that the domain of any limit functional is SBV(Ω) despite the degeneracies introduced by the perforations. Then we provide explicit formula for the bulk and surface energy densities of the Γ-limit, representing in our model the effective elastic and brittle properties of the porous medium, respectively.
Human Hepatocellular Carcinoma Tumor–derived Endothelial Cells Manifest Increased Angiogenesis Capability and Drug Resistance Compared with Normal Endothelial Cells
Authors: Xiong Yu-Quan , Sun Hui-Chuan , Zhang Wei , Zhu Xiao-Dong , Zhuang Peng-Yuan , Zhang Ju-Bo , Wang Lu , Wu Wei-zhong , Qin Lun-Xiu , Tang Zhao-You 
Published: July 2009

Abstract
Purpose: Increasing evidence indicates that tumor-derived endothelial cells (TEC) possess a distinct and unique phenotype compared with endothelial cells (NEC) from adjacent normal tissue and may be able to acquire resistance to drugs. The aim of this study was to investigate the angiogenesis activity and response to drug treatment of TECs and NECs derived from human hepatocellular carcinoma (HCC).
Experimental Design: TECs or NECs were isolated from HCC or adjacent normal liver tissue using anti-CD105 antibody coupled to magnetic beads. The phenotypic and functional properties of endothelial cells were characterized by testing the expression of CD105, CD31, CD144, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and von Willebrand factor, and the ability of DiI-Ac-LDL-uptake and tube formations. CD105+ TECs were compared with CD105+ NECs and human umbilical vein endothelial cells (HUVEC) by examining their ability to proliferate, motility, ability to adhere to tumor cells, response to tumor conditioned medium, and reactions to the chemotherapy drugs Adriamycin and 5-fluorouracil and the antiangiogenic drug sorafenib.
Results: Compared with CD105+ NECs and HUVECs, CD105+ TECs showed increased apoptosis resistance and motility and proangiogenic properties. Meanwhile, CD105+ TECs had a greater ability to adhere to tumor cells and survive in the tumor environment. Moreover, CD105+ TECs acquired more resistance to Adriamycin, 5-fluorouracil, and sorafenib than CD105+ NECs and HUVECs.
Conclusions: TECs possessed enhanced angiogenic activity and resistance to chemotherapeutic drugs and an angiogenesis inhibitor, and may provide a better tool for studying tumor angiogenesis and antiangiogenesis drugs in HCC.
Targeting Rat Brainstem Glioma Using Human Neural Stem Cells and Human Mesenchymal Stem Cells
Authors: Lee Do-Hun , Ahn Yong , Kim Seung U. , Wang Kyu-Chang , Cho Byung-Kyu , Phi Ji Hoon , Park In Ho , Black Peter M. , Carroll Rona S. , Lee Joonyub , Kim Seung-Ki 
Published: July 2009

Abstract
Purpose: Brainstem gliomas are usually inoperable and have a dismal prognosis. Based on the robust tropisms of neural stem cells (NSC) and mesenchymal stem cells (MSC) to brain tumors, we compared the tumor-tropic migratory capacities of these stem cells and evaluated the therapeutic potential of genetically engineered human NSCs encoding cytosine deaminase (CD) and IFNβ against brainstem gliomas.
Experimental Design: The directed migratory capacities of NSCs and MSCs to brainstem glioma (F98) were evaluated both in vitro and in vivo. The human NSCs (HB1.F3) and various human MSCs, such as bone marrow–derived MSCs (HM3.B10), adipose tissue–derived MSCs, and umbilical cord blood–derived MSCs, were tested. Human fibroblast cells (HFF-1) were used as the negative control. As a proof of concept, the bioactivity of HB1.F3-CD-IFNβ was analyzed with a cell viability assay, and animals with brainstem gliomas were injected with HB1.F3-CD-IFNβ cells followed by systemic 5-fluorocytosine treatment.
Results: In an in vitro modified Transwell migration assay and in vivo stem cell injection into established brainstem gliomas in rats, all the stem cells showed a significant migratory capacity compared with that of the control (P &lt; 0.01). Histologic analysis showed a 59% reduction in tumor volume in the HB1.F3-CD-IFNβ–treated group (P &lt; 0.05). Apoptotic cells were increased 2.33-fold in animals treated with HB1.F3-CD-IFNβ compared with the respective control groups (P &lt; 0.01).
Conclusion: The brainstem glioma-tropic migratory capacities of MSCs from various sources were similar to those of NSCs. Genetically engineered NSCs show therapeutic efficacy against brainstem gliomas.
The Green Tea Polyphenol EGCG Potentiates the Antiproliferative Activity of c-Met and Epidermal Growth Factor Receptor Inhibitors in Non–small Cell Lung Cancer Cells
Authors: Milligan Shawn A. , Burke Patrick , Coleman David T. , Bigelow Rebecca L. , Steffan Joshua J. , Carroll Jennifer L. , Williams Briana Jill , Cardelli James A. 
Published: July 2009

Abstract
Purpose: Activation of the c-Met and epidermal growth factor receptors (EGFR) promotes the growth and survival of non–small cell lung cancer (NSCLC). Specific receptor antagonists have shown efficacy in the clinic, but tumors often become resistant to these therapies. We investigated the ability of (-)-epigallocatechin-3-gallate (EGCG) to inhibit cell proliferation, and c-Met receptor and EGFR kinase activation in several NSCLC cell lines.
Experimental Design: NSCLC cell lines with variable sensitivity to the EGFR antagonist erlotinib were studied. Cell growth was evaluated using proliferation and colony formation assays. Kinase activation was assessed via Western blot analysis. Experiments were conducted with EGCG, the EGFR antagonist erlotinib, and the c-Met inhibitor SU11274. The antagonists were also tested in a xenograft model using SCID mice.
Results: EGCG inhibited cell proliferation in erlotinib-sensitive and -resistant cell lines, including those with c-Met overexpression, and acquired resistance to erlotinib. The combination of erlotinib and EGCG resulted in greater inhibition of cell proliferation and colony formation than either agent alone. EGCG also completely inhibited ligand-induced c-Met phosphorylation and partially inhibited EGFR phosphorylation. The triple combination of EGCG/erlotinib/SU11274 resulted in a greater inhibition of proliferation than EGCG with erlotinib. Finally, the combination of EGCG and erlotinib significantly slowed the growth rate of H460 xenografts.
Conclusion: EGCG is a potent inhibitor of cell proliferation, independent of EGFR inhibition, in several NSCLC cell lines, including those resistant to both EGFR kinase inhibitors and those overexpressing c-Met. Therefore, EGCG might be a useful agent to study as an adjunct to other anticancer agents.
Tumor Endothelial Cells Join the Resistance
Authors: Dudley Andrew C. , Klagsbrun Michael 
Published: July 2009

Abstract
The field of antiangiogenesis research has been met with some surprises, including the realization that tumor blood vessels are more complex and labile than expected. In this issue of Clinical Cancer Research, Xiong and colleagues show that tumor-specific endothelial cells are less sensitive to cytotoxic and antiangiogenic drugs compared to their normal counterparts.
Persuading Natural Killer Cells to Eliminate Bad B Cells
Authors: Cooper Laurence J.N. 
Published: July 2009

Abstract
Clinical trials are underway infusing T cells genetically modified to be specific for B-cell malignancies using a chimeric antigen receptor (CAR) to redirect specificity for CD19. However, issues remain about whether the CAR can provide a fully competent application signal and whether other lymphocytes with lytic capacity can target CD19+ tumors.
A novel agonistic antibody to human death receptor 4 induces apoptotic cell death in various tumor cells without cytotoxicity in hepatocytes
Authors: Sung Eun-Sil , Park Kyung-Jin , Lee Seung-Hyun , Jang Yoon-Seon , Park Sang-Koo , Park Yoo-Hoi , Kwag Won-Jae , Kwon Myung-Hee , Kim Yong-Sung 
Published: July 2009

AbstractThe proapoptotic tumor necrosis factor–related apoptosis inducing ligand (TRAIL) receptors death receptor (DR) 4 and DR5 are attractive targets to develop the receptor-specific agonistic monoclonal antibodies (mAb) as anticancer agents because of their tumor-selective cell death–inducing activity. Here, we report a novel agonistic mAb, AY4, raised against human DR4 in mice. ELISA analysis revealed that AY4 specifically bound to DR4 without competition with TRAIL for the binding. Despite distinct binding regions of AY4 on DR4 from those of TRAIL, AY4 as a single agent induced caspase-dependent apoptotic cell death of several tumor types through the extrinsic and/or intrinsic pathways without substantial cytotoxicity to normal human hepatocytes. Further, the AY4-sensitive cells followed the same cell death characteristics classified as type I and type II cells by the response to TRAIL, suggesting that the cell death profiles in responses to DR4 and/or DR5 stimulation are determined by the downstream signaling of the receptor rather than the kind of receptor. Noticeably, AY4 efficiently induced cell death of Jurkat cells, which have been reported to be resistant to other anti-DR4 agonistic mAbs, most likely due to the unique epitope property of AY4. In vivo administration of AY4 significantly inhibited tumor growth of human non–small cell lung carcinoma preestablished in athymic nude mice. Conclusively, our results provide further insight into the DR4-mediated cell death signaling and potential use of AY4 mAb as an anticancer therapeutic agent, particularly for DR4-responsive tumor types. [Mol Cancer Ther 2009;8(8):2276–85]
Fuzzy set-based uncertainty analysis of HVAC&R systems: a simulation study
Authors: Min Ning  , Zaheeruddin M. 
Published: July 2009

The accuracy of model predictions plays an important role in model-based applications. However, mathematical models exhibit more or less uncertainties. In this study, a full-scale dynamic model of a two-zone variable air volume heating, ventilation, air-conditioning and refrigeration (VAV-HVAC&R) system is considered. A fuzzy set-based uncertainty analysis method is employed to study the effects of uncertain parameters on HVAC&R system modelling and describe the associated inaccuracies in HVAC&R system model predictions. In this study, uncertain parameters, i.e. zone cooling loads, heat transfer coefficient, chilled water and condenser water mass flow rate and water temperature at condenser inlet are considered and treated as fuzzy parameters. The extended transformation approach is used to evaluate the uncertainties in the model outputs including time history of the zone temperature, discharge air temperature, temperature of chilled water and condenser water. The upper and lower bounds of these outputs are determined for each a-cut level, and the probability distributions of the outputs are presented. Practical applications: Compared to monitoring of real systems, model-based simulation provides an easier, faster and cheaper substitute to gather operating information and evaluate operating performance of HVAC&R systems. However, simulation results obtained from traditional methods by which model equations are solved with predetermined values cannot accurately represent the possible responses of the system. Thus investigating the probability distributions of the simulation results under parameter uncertainties is very important to ensure the accuracy of the model predictions. The fuzzy set-based uncertainty analysis method presented here helps in identifying the upper and lower bounds of model outputs by quantifying the range within which the responses fall under parameter uncertainties. Also, the contributions of individual uncertain parameters to the uncertainties of model outputs help in identifying the impact parameters.
EXCEED: Exforge®-intensive control of hypertension to evaluate efficacy in diastolic dysfunction: study rationale, design, and participant characteristics
Authors: Hassanein Amira , Desai Akshay , Verma Anil , Oparil Suzanne , Izzo Joseph , Rocha Richardo , Hilkert Robert , Seifu Youdit , Pitt Bertrand , Solomon Scott 
Published: July 2009

Background: Both diastolic dysfunction and increased vascular stiffness represent important measures of target-organ damage in hypertension. Whether intensive blood pressure (BP) control can further improve these measures remains unknown. Methods: EXCEED is a prospective, randomized open-label blinded endpoint trial (PROBE) design, aiming to test the hypothesis that more aggressive BP lowering would result in greater improvement in diastolic function among patients with stage II hypertension, evidence of diastolic dysfunction and preserved systolic function (EF ≥ 50%). Patients were randomized to one of two treatment strategies, targeting systolic blood pressure (SBP) <140 mmHg or <130 mmHg using a combination of amlodipine/valsartan with additional antihypertensive medications as needed to achieve the prescribed targets. Diastolic function was assessed using Doppler tissue imaging of early diastolic velocity of lateral mitral annulus (E'), while vascular stiffness was assessed using radial augmentation index (RAI) derived from radial artery tonometry. The study primary endpoint will be the change in lateral E' velocity between baseline and 24 weeks. Results: Two hundred and twenty eight patients (50% female) with mean age of (59.6±9.7) years and mean BP of (162±14/92±13 mmHg) were randomized equally to either treatment strategies. Left ventricular hypertrophy was present among <4% of the enrolled patients. Inspite diastolic function was impaired, baseline lateral E' velocity (7.6±1.2 cm/s) was not related to baseline SBP while baseline RAI was weakly related ( r = 0.2, p <0.01) to SBP even after adjustment to age, gender and heart rate. Conclusion: EXCEED will determine whether intensive BP lowering will further improve diastolic dysfunction and vascular stiffness among patients with uncontrolled hypertension.
A fundamental role of mAbp1 in neutrophils: impact on β2 integrin–mediated phagocytosis and adhesion in vivo
Authors: Schymeinsky Jürgen , Gerstl Ronald , Mannigel Ingrid , Niedung Katy , Frommhold David , Panthel Klaus , Heesemann Jürgen , Sixt Michael , Quast Thomas , Kolanus Waldemar , Mocsai Attila , Wienands Jürgen , Sperandio Markus , Walzog Barbara 
Published: July 2009

AbstractThe mammalian actin-binding protein 1 (mAbp1, Hip-55, SH3P7) is phosphorylated by the nonreceptor tyrosine kinase Syk that has a fundamental effect for several β2 integrin (CD11/CD18)–mediated neutrophil functions. Live cell imaging showed a dynamic enrichment of enhanced green fluorescence protein–tagged mAbp1 at the phagocytic cup of neutrophil-like differentiated HL-60 cells during β2 integrin–mediated phagocytosis of serum-opsonized Escherichia coli. The genetic absence of Syk or its pharmacologic inhibition using piceatannol abrogated the proper localization of mAbp1 at the phagocytic cup. The genetic absence or down-regulation of mAbp1 using the RNA interference technique significantly compromised β2 integrin–mediated phagocytosis of serum-opsonized E coli or Salmonella typhimurium in vitro as well as clearance of S typhimurium infection in vivo. Moreover, the genetic absence of mAbp1 almost completely abrogated firm neutrophil adhesion under physiologic shear stress conditions in vitro as well as leukocyte adhesion and extravasation in inflamed cremaster muscle venules of mice treated with tumor-necrosis factor α. Functional analysis showed that the down-regulation of mAbp1 diminished the number of β2 integrin clusters in the high-affinity conformation under flow conditions. These unanticipated results define mAbp1 as a novel molecular player in integrin biology that is critical for phagocytosis and firm neutrophil adhesion under flow conditions.
The role of complete response in multiple myeloma
Authors: Harousseau Jean-Luc , Attal Michel , Avet-Loiseau Herve 
Published: July 2009

AbstractIn multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures.