bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting ALDHbright Human Carcinoma–Initiating Cells with ALDH1A1-Specific CD8+ T Cells
Authors: Visus Carmen , Wang Yangyang , Lozano-Leon Antonio , Ferris Robert L. , Silver Susan , Szczepanski Miroslaw J. , Brand Randall E. , Ferrone Cristina R. , Whiteside Theresa L. , Ferrone Soldano , DeLeo Albert B. , Wang Xinhui 
Published: August 2011

AbstractPurpose: Cancer-initiating cells (CIC) are considered to represent the subpopulation of tumor cells that is resistant to conventional cancer treatments, highly tumorigenic in immunodeficient mice, and responsible for tumor recurrence and metastasis. Based on an elevated aldehyde dehydrogenase (ALDH) activity attributable to ALDH1/3 isoforms, ALDHbright cells have been identified and isolated from tumors and shown to have characteristics of CIC. The ALDH1A1 isoform was previously identified as a tumor antigen recognized by CD8+ T cells. This study examines the ability of ALDH1A1-specific CD8+ T cells to eliminate ALDHbright cells and control tumor growth and metastases.Experimental Design: ALDHbright cells were isolated by flow cytometry using ALDEFLUOR from HLA-A2+ human head and neck, breast, and pancreas carcinoma cell lines and tested for their tumorigenicity in immunodeficient mice. ALDH1A1-specific CD8+ T cells were generated in vitro and tested for their ability to eliminate CICs in vitro and in vivo by adoptive transfer to immunodeficient mice bearing human tumor xenografts.Results: ALDHbright cells isolated by flow cytometry from HLA-A2+ breast, head and neck, and pancreas carcinoma cell lines at low numbers (500 cells) were tumorigenic in immunodeficient mice. ALDHbright cells present in these cell lines, xenografts, or surgically removed lesions were recognized by ALDH1A1-specific CD8+ T cells in vitro. Adoptive therapy with ALDH1A1-specific CD8+ T cells eliminated ALDHbright cells, inhibited tumor growth and metastases, or prolonged survival of xenograft-bearing immunodeficient mice.Conclusions: The results of this translational study strongly support the potential of ALDH1A1-based immunotherapy to selectively target CICs in human cancer. Clin Cancer Res; 17(19); 6174–84. ©2011 AACR.
Disease Flare after Tyrosine Kinase Inhibitor Discontinuation in Patients with EGFR-Mutant Lung Cancer and Acquired Resistance to Erlotinib or Gefitinib: Implications for Clinical Trial Design
Authors: Chaft Jamie E. , Oxnard Geoffrey R. , Sima Camelia S. , Kris Mark G. , Miller Vincent A. , Riely Gregory J. 
Published: August 2011

Abstract
Purpose: Treatment of patients with oncogene-addicted cancers with tyrosine kinase inhibitors (TKI) is biologically and clinically different than with cytotoxic chemotherapy. We have observed that some patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib (RECIST progression after initial benefit) have accelerated progression of disease after discontinuation of TKI. To examine this observation and define the course of patients following TKI discontinuation, we systematically evaluated patients enrolled on clinical trials of agents to treat acquired resistance to erlotinib or gefitinib.
Methods: We evaluated patients with EGFR-mutant lung cancer who participated in trials for patients with acquired resistance that mandated TKI discontinuation before administration of study therapy. Disease flare was defined as hospitalization or death attributable to disease progression during the washout period.
Results: Fourteen of 61 patients (23%; 95% CI: 14–35) experienced a disease flare. The median time to disease flare after TKI discontinuation was 8 days (range 3–21). Factors associated with disease flare included shorter time to progression on initial TKI (P = 0.002) and the presence of pleural (P = 0.03) or CNS disease (P = 0.01). There was no association between disease flare and the presence of T790M at the time of acquired resistance.
Conclusions: In patients with EGFR-mutant lung cancer and acquired resistance to epidermal growth factor receptor TKIs, discontinuation of erlotinib or gefitinib before initiation of study treatment is associated with a clinically significant risk of accelerated disease progression. Clinical trials in this patient population must minimize protocol-mandated washout periods. Clin Cancer Res; 17(19); 6298–303. ©2011 AACR.
MT1-MMP Cooperates with KrasG12D to Promote Pancreatic Fibrosis through Increased TGF-β Signaling
Authors: Krantz Seth B. , Shields Mario A. , Dangi-Garimella Surabhi , Cheon Eric C. , Barron Morgan R. , Hwang Rosa F. , Rao M. Sambasiva , Grippo Paul J. , Bentrem David J. , Munshi Hidayatullah G. 
Published: August 2011

Abstract
Pancreatic cancer is associated with a pronounced fibrotic reaction that was recently shown to limit delivery of chemotherapy. To identify potential therapeutic targets to overcome this fibrosis, we examined the interplay between fibrosis and the key proteinase membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14), which is required for growth and invasion in the collagen-rich microenvironment. In this article, we show that compared with control mice (Kras+/MT1-MMP−) that express an activating KrasG12D mutation necessary for pancreatic cancer development, littermate mice that express both MT1-MMP and KrasG12D (Kras+/MT1-MMP+) developed a greater number of large, dysplastic mucin-containing papillary lesions. These lesions were associated with a significant amount of surrounding fibrosis, increased α-smooth muscle actin (+) cells in the stroma, indicative of activated myofibroblasts, and increased Smad2 phosphorylation. To further understand how MT1-MMP promotes fibrosis, we established an in vitro model to examine the effect of expressing MT1-MMP in pancreatic ductal adenocarcinoma (PDAC) cells on stellate cell collagen deposition. Conditioned media from MT1-MMP–expressing PDAC cells grown in three-dimensional collagen enhanced Smad2 nuclear translocation, promoted Smad2 phosphorylation, and increased collagen production by stellate cells. Inhibiting the activity or expression of the TGF-β type I receptor in stellate cells attenuated MT1-MMP conditioned medium–induced collagen expression by stellate cells. In addition, a function-blocking anti–TGF-β antibody also inhibited MT1-MMP conditioned medium–induced collagen expression in stellate cells. Overall, we show that the bona fide collagenase MT1-MMP paradoxically contributes to fibrosis by increasing TGF-β signaling and that targeting MT1-MMP may thus help to mitigate fibrosis. Mol Cancer Res; 9(10); 1294–304. ©2011 AACR.
Resveratrol Inhibits Proliferation and Survival of Epstein Barr Virus–Infected Burkitt's Lymphoma Cells Depending on Viral Latency Program
Authors: De Leo Alessandra , Arena Giuseppe , Stecca Claudia , Raciti Marisa , Mattia Elena 
Published: August 2011

Abstract
Resveratrol (3,4′,5-trihydroxy-trans-stilbene), a polyphenolic natural product, shows chemopreventive properties against several cancers, heart diseases, inflammation, and viral infections. Epstein Barr virus (EBV), a γ-herpesvirus, contributes to the development of several human cancers including Burkitt's lymphoma (BL). In this study, we asked whether treatment with resveratrol would affect the viability of EBV-positive BL cells displaying different forms of latency. We report here that resveratrol, regardless of EBV status, induces caspase-dependent apoptosis by arresting cell-cycle progression in G1 phase. However, resveratrol strongly induced apoptosis in EBV(−) and latency I EBV(+) cells, whereas latency II and latency III EBV(+) BL cells showed a survival advantage that increased with the extent of the pattern of viral gene expression. Resveratrol-induced cell-cycle arrest and apoptosis occurred in association with induction of p38 MAPK phosphorylation and suppression of ERK1/2 signaling pathway. Moreover, NF-κB DNA-binding activity was inhibited in all BL lines except EBV(+) latency III cells.
LMP1 oncogene, which is expressed in latency III phenotype, is involved with the higher resistance to the antiproliferative effect of resveratrol because siRNA-mediated inhibition of LMP1 greatly increased the sensitivity of latency III BL cells as well as that of lymphoblastoid cell lines to the polyphenol. We propose that a combined resveratrol/siRNA strategy may be a novel approach for the treatment of EBV-associated B-cell malignancies in which the viral pattern of gene expression has been defined. Mol Cancer Res; 9(10); 1346–55. ©2011 AACR.
Effect of the Inositol Polyphosphate InsP6 on DNA-PK–Dependent Phosphorylation
Authors: Hanakahi Les 
Published: August 2011

Abstract
Inositol hexakisphosphate (InsP6) is a member of the inositol polyphosphate group that participates in numerous intracellular signaling pathways. Cheung and colleagues previously reported that InsP6 stimulated double-strand break repair by nonhomologous end joining (NHEJ) in cell-free extracts and that InsP6 binding by the Ku70/80 subunit of the DNA-dependent protein kinase (DNA-PK) was required for stimulation of NHEJ in vitro. This report describes InsP6-dependent phosphorylation of two NHEJ factors, XRCC4 and XLF, in partially purified human cell extracts. XRCC4 and XLF are known substrates for DNA-PK, which does not require InsP6 for protein kinase activity. Consistent with a role for DNA-PK in these reactions, InsP6-dependent phosphorylation of XRCC4 and XLF was DNA dependent and not observed in the presence of DNA-PK inhibitors. Depletion of the Ku70/80 DNA-, InsP6-binding subunit of DNA-PK resulted in loss of InsP6-dependent phosphorylation and showed a requirement for Ku70/80 in these reactions. Complementation of Ku70/80-depleted reactions with recombinant wild-type Ku70/80 restored InsP6-dependent phosphorylation of XRCC4 and XLF. In contrast, addition of a Ku70/80 mutant with reduced InsP6 binding failed to restore InsP6-dependent phosphorylation. While additional protein kinases may participate in InsP6-dependent phosphorylation of XRCC4 and XLF, data presented here describe a clear requirement for DNA-PK in these phosphorylation events. Furthermore, these data suggest that binding of the inositol polyphosphate InsP6 by Ku70/80 may modulate the substrate specificity of the phosphoinositide-3-kinase–related protein kinase DNA-PK. Mol Cancer Res; 9(10); 1366–76. ©2011 AACR.
Arrhythmia Type After Persistent Atrial Fibrillation Ablation Predicts Success of the Repeat Procedure
Authors: Ammar Sonia , Hessling Gabriele , Reents Tilko , Fichtner Stephanie , Wu Jinjin , Zhu Pinjun , Kathan Susanne , Estner Heidi Louise , Jilek Clemens , Kolb Christof , Haller Bernhard , Deisenhofer Isabel 
Published: August 2011

Background—
The aim of the study was to investigate whether the type of arrhythmia recurrence after ablation of persistent atrial fibrillation (AF) has an impact on the maintenance of sinus rhythm after the repeat ablation procedure.

Methods and Results—

Included were 78 consecutive patients (82% men; mean age, 61±10 years; mean left atrial diameter, 47±4 mm) with persistent AF who underwent ≥1 repeat ablation. The initial ablation procedure had consisted of pulmonary vein isolation with additional substrate modification (ablation of complex fractionated atrial electrograms [n=63] or linear lesions [n=15]). Patients presented for reablation either with persistent atrial tachycardia (AT) (group 1, n=36), persistent AF (group 2, n=37), or paroxysmal AF (group 3, n=5). The primary end point was freedom from any arrhythmia off antiarrhythmic drugs 6 and 9 months after the reablation procedure. Estimated proportions of patients reaching the primary end point were 59% for group 1, 28% for group 2, and 100% for group 3 at 6 months and 51%, 23%, and 100%, for groups 1, 2, and 3, respectively, at 9 months (
P
=0.002).

Conclusions—
In patients presenting for a repeat procedure after ablation of persistent AF, the occurrence of AT is associated with a significantly better outcome compared with recurrent persistent AF. These results suggest that AT might be considered as a step toward sinus rhythm.
Improving reverse cycle defrosting performance of air source heat pumps using thermal storage-based refrigerant sub-cooling energy
Authors: Jiankai Dong , Yiqiang Jiang , Shiming Deng , Yang Yao , Minglu Qu 
Published: August 2011

When an air source heat pump (ASHP) unit is used for space heating at a low ambient temperature in winter, frost may be formed on its outdoor coil surface. Over time, frost accumulation on coil surface may become sufficient to restrict air passage through the coil and increase the heat transfer resistance between ambient air and coil surface, leading to performance degradation for the outdoor coil, or even the shutdown of the ASHP unit. Therefore, periodic defrosting is necessary. Currently, the most widely used standard defrosting method for an ASHP unit is reverse cycle defrosting. During a standard reverse cycle defrosting (SRCD) operation, the indoor coil in an ASHP unit actually acts as an evaporator. Because the indoor fan is usually turned off during defrosting, there is an insignificant amount of energy from indoor coil, leading to a number of associated operational problems such as a longer defrosting duration and the risk of having a lower air temperature inside a heated space during defrosting, etc. To solve the fundamental problem of insufficient heat available during defrosting while ensuring the efficient and safe system operation, a novel reverse cycle defrosting (NRCD) method which is thermal energy storage-based using sub-cooling energy of refrigerant for ASHPs has been developed. Comparative experiments using both the SRCD method and the NRCD method were carried out on an experimental ASHP unit with a nominal 2.5 kW heating capacity. Experimental results clearly suggested that when using the NRCD method, the discharge and suction pressures were increased by 0.56 and 0.12 MPa, respectively. Furthermore, the defrosting duration and heating-resumption duration were shortened by 30.8% and 25.0%, respectively, and the defrosting energy consumption was reduced by 13.9%, compared to those when using the SRCD method. Practical application: ASHPs have been widely used worldwide due to their significant energy-saving potentials. However, frost can be formed on the outdoor coil surface when an ASHP unit operates for space heating. Frost accumulation on coil surface reduces the coil’s efficiency, or causes even the shutdown of the ASHP unit. Reverse cycle defrosting is the most widely used standard defrosting method. This paper presents the reverse cycle defrosting performance for an ASHP unit with a PCM-HE acting as both a sub-cooler during heating operation and a heat source during defrosting operation, which could help to ensure the safe operation and achieve a higher defrosting efficiency of the ASHP unit.
Modified ‘closure’ constants of the Standard k–ε turbulence model for the prediction of wind-induced natural ventilation
Authors: Stavrakakis GM , Tomazinakis NM , Markatos NC 
Published: August 2011

In this study, wind-driven natural ventilation in buildings is investigated by means of computational fluid dynamics. The airflow in and around three pilot buildings, which correspond to the most common natural-ventilation designs, i.e. cross-, windward- and leeward- single-sided ventilation, is simulated by applying both the Standard and a modified k–ε turbulence model. The latter represents a Prandtl number-modified version of the Standard k–ε model, based on the flow-variable (velocity and turbulence variables) distributions and on the atmospheric boundary layer (ABL) assumptions. Numerical results of streamwise and vertical velocity components, as well as of pressure coefficients at the facades, obtained by both turbulence models are compared with available wind tunnel experimental data found in literature. It is concluded that both models applied are in acceptable agreement with measurements, especially for the mean streamwise velocity component, while the proposed modified model is more accurate as far as flow within the windward and the internal parts (i.e. within the building) of the domain is concerned. Practical application: This study focuses on the development of a modified k–ε turbulence model for the prediction of wind-driven natural ventilation. The analysis described represents a methodology to produce ‘closure’ parameters, such as Prandtl numbers, compatible with the incoming wind characteristics (ABL). It was found that for all ventilation cases studied, i.e. cross- and single-sided ventilation, the proposed modified model is more accurate compared with the Standard k–ε model, and it accounts for the dumping effect near the walls and for kinetic energy reduction in the impinging region adequately. It is satisfying that the modified k–ε model leads to acceptable engineering results within relatively practical computer resources.
Health benefits of a view of nature through the window: a quasi-experimental study of patients in a residential rehabilitation center
Authors: Raanaas Ruth Kjærsti , Patil Grete Grindal , Hartig Terry 
Published: August 2011

Objective: To examine the health benefits of a bedroom window view to natural surroundings for patients undergoing a residential rehabilitation programme. Design: Longitudinal quasi-experiment. Setting: A residential rehabilitation centre. Subjects: Two-hundred and seventy-eight coronary and pulmonary patients provided data at all measurement points during the programme. Intervention: Blind, quasi-random allocation to a private bedroom with a panoramic view to natural surroundings or with a view either partially or entirely blocked by buildings. Main measures: Self-reported physical and mental health (SF-12), subjective well-being, emotional states, use of the private bedroom and leisure activities. Results: For women, a blocked view appeared to negatively influence change in physical health (time × view × gender interaction, F(4,504) = 2.51, P = 0.04), whereas for men, a blocked view appeared to negatively influence change in mental health (time × view × gender interaction, F(4,504) = 5.67, P < 0.01). Pulmonary patients with a panoramic view showed greater improvement in mental health than coronary patients with such a view (time × view × diagnostic group interaction, F(4,504) = 2.76, P = 0.03). Those with a panoramic view to nature more often chose to stay in their bedroom when they wanted to be alone than those with a blocked view (odds ratio (OR) = 2.32, 95% confidence interval (CI) 1.08–5.01). Conclusion: An unobstructed bedroom view to natural surroundings appears to have better supported improvement in self-reported physical and mental health during a residential rehabilitation programme, although the degree of change varied with gender and diagnostic group.
Responsiveness of the cervical Northern American Spine Society questionnaire (NASS) and the Short Form 36 (SF-36) in chronic whiplash
Authors: Angst Felix , Verra Martin L , Lehmann Susanne , Gysi Françoise , Benz Thomas , Aeschlimann André 
Published: August 2011

Objective: To determine and compare the sensitivity to change of the condition-specific cervical Northern American Spine Society (NASS) and the generic Short Form 36 (SF-36). Design: Prospective cohort study. Subjects: One hundred and seventy five patients after whiplash injury. Interventions: Four-week inpatient interdisciplinary pain management programme. Main measures, analysis: Responsiveness of the NASS and the SF-36 was quantified by effect size and standardized response mean and compared within the same construct by the modified Jacknife test. Ability to detect improvement was compared using sensitivities determined from receiver operating characteristics curves. Results: In pain, the NASS was comparable responsive to the SF-36 at the one-month follow-up ( n = 175): effect sizes: 0.62 (NASS) versus 0.61 (SF-36), P = 0.914. The NASS was less responsive than the SF-36 in function: 0.23 versus 0.63, P < 0.001 and in pain+function: 0.35 versus 0.58 ( P = 0.001). These relationships remained consistent using standardized response means, at the six-month follow-up ( n = 103), and in the comparison of the sensitivities. Sensitivities at one month, pain: 70% (NASS) versus 62% (SF-36), P = 0.234; function: 65% versus 80%, P = 0.002; pain+function: 68% versus 78%, P = 0.035. The six-month data were similar. Conclusions: The generic SF-36 was more responsive in function and equally responsive in pain when compared to the condition-specific NASS. The SF-36 can be recommended as a responsive instrument for measurement of pain and function in chronic whiplash syndrome.
Prevalence of Septic Arthritis After Anterior Cruciate Ligament Reconstruction Among Professional Athletes
Authors: Sonnery-Cottet Bertrand , Archbold Pooler , Zayni Rachad , Bortolletto Juliano , Thaunat Mathieu , Prost Thierry , Padua Vitor B.C. , Chambat Pierre 
Published: August 2011

Background: Septic arthritis of the knee after anterior cruciate ligament (ACL) reconstruction is a rare complication. Its prevalence and characteristics have never been reported among professional athletes. Purpose: To report the prevalence and the characteristics of septic arthritis after ACL reconstruction in professional athletes and a general population of patients. Study Design: Case control study; Level of evidence, 3. Methods: A retrospective analysis of a consecutive series of 1957 patients who underwent an ACL reconstruction between 2003 and 2008 was performed; 88 patients were professional athletes. The patient demographics, the prevalence of infection, the involved organism, and the method of treatment were reviewed. Three potential risk factors for infection—level of sporting participation, indoor/outdoor sports, and the presence or not of a combined lateral tenodesis—were assessed using univariate and multivariate logistic regression analysis. Results: The prevalence of septic arthritis was 0.37% in the nonprofessional group and 5.7% in the professional athlete population. Being a professional athlete (odds ratio [OR], 16.0; 95% confidence interval [CI], 3.9-59.8; P = .0001) or having a combined lateral tenodesis (OR, 4.8; 95% CI, 1.04-18.04; P = .02) was found to be significantly correlated with septic arthritis after ACL reconstruction. A significant correlation exists between being a professional athlete and having a combined lateral tenodesis (χ2 = 16.7; P = 4 × 10−5), suggesting a potential confounding role is played by one of these variables. All the cases of infection in the professional athletes occurred in those who participated in outdoor sports, although this was not found to be statistically significant ( P = .17). Conclusion: Participation in professional sports and having a combined lateral tenodesis are risk factors for the development of infection after ACL reconstruction. We hypothesize that professional athletes may be part of a specific group of patients at higher risk of infection after ACL reconstruction.