bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective Activity of Cytokine-Induced Killer Cells against Autologous Metastatic Melanoma Including Cells with Stemness Features
Authors: Gammaitoni Loretta , Giraudo Lidia , Leuci Valeria , Todorovic Maja , Mesiano Giulia , Picciotto Franco , Pisacane Alberto , Zaccagna Alessandro , Volpe Maria Giuseppa , Gallo Susanna , Caravelli Daniela , Giacone Elena , Venesio Tiziana , Balsamo Antonella , Pignochino Ymera , Grignani Giovanni , Carnevale-Schianca Fabrizio , Aglietta Massimo , Sangiolo Dario 
Published: June 2013

AbstractPurpose: We investigate the unknown tumor-killing activity of cytokine-induced killer (CIK) cells against autologous metastatic melanoma and the elusive subset of putative cancer stem cells (mCSC).Experimental Design: We developed a preclinical autologous model using same patient-generated CIK cells and tumor targets to consider the unique biology of each patient/tumor pairing. In primary tumor cell cultures, we visualized and immunophenotypically defined a putative mCSC subset using a novel gene transfer strategy that exploited their exclusive ability to activate the promoter of stemness gene Oct4.Results: The CIK cells from 10 patients with metastatic melanoma were successfully expanded (median, 23-fold; range, 11–117). Primary tumor cell cultures established and characterized from the same patients were used as autologous targets. Patient-derived CIK cells efficiently killed autologous metastatic melanoma [up to 71% specific killing (n = 26)]. CIK cells were active in vivo against autologous melanoma, resulting in delayed tumor growth, increased necrotic areas, and lymphocyte infiltration at tumor sites. The metastatic melanoma cultures presented an average of 11.5% ± 2.5% putative mCSCs, which was assessed by Oct4 promoter activity and stemness marker expression (Oct4, ABCG2, ALDH, MITF). Expression was confirmed on mCSC target molecules recognized by CIK cells (MIC A/B; ULBPs). CIK tumor killing activity against mCSCs was intense (up to 71%, n = 4) and comparable with results reported against differentiated metastatic melanoma cells (P = 0.8).Conclusions: For the first time, the intense killing activity of CIK cells against autologous metastatic melanoma, including mCSCs, has been shown. These findings move clinical investigation of a new immunotherapy for metastatic melanoma, including mCSCs, closer. Clin Cancer Res; 19(16); 4347–58. ©2013 AACR.
Contribution of Abcc4-Mediated Gastric Transport to the Absorption and Efficacy of Dasatinib
Authors: Furmanski Brian D. , Hu Shuiying , Fujita Ken-ichi , Li Lie , Gibson Alice A. , Janke Laura J. , Williams Richard T. , Schuetz John D. , Sparreboom Alex , Baker Sharyn D. 
Published: June 2013

Abstract
Purpose: Several oral multikinase inhibitors are known to interact in vitro with the human ATP-binding cassette transporter ABCC4 (MRP4), but the in vivo relevance of this interaction remains poorly understood. We hypothesized that host ABCC4 activity may influence the pharmacokinetic profile of dasatinib and subsequently affect its antitumor properties.
Experimental Design: Transport of dasatinib was studied in cells transfected with human ABCC4 or the ortholog mouse transporter, Abcc4. Pharmacokinetic studies were done in wild-type and Abcc4-null mice. The influence of Abcc4 deficiency on dasatinib efficacy was evaluated in a model of Ph+ acute lymphoblastic leukemia by injection of luciferase-positive, p185(BCR-ABL)-expressing Arf(−/−) pre-B cells.
Results: Dasatinib accumulation was significantly changed in cells overexpressing ABCC4 or Abcc4 compared with control cells (P &lt; 0.001). Deficiency of Abcc4 in vivo was associated with a 1.75-fold decrease in systemic exposure to oral dasatinib, but had no influence on the pharmacokinetics of intravenous dasatinib. Abcc4 was found to be highly expressed in the stomach, and dasatinib efflux from isolated mouse stomachs ex vivo was impaired by Abcc4 deficiency (P &lt; 0.01), without any detectable changes in gastric pH. Abcc4-null mice receiving dasatinib had an increase in leukemic burden, based on bioluminescence imaging, and decreased overall survival compared with wild-type mice (P = 0.048).
Conclusions: This study suggests that Abcc4 in the stomach facilitates the oral absorption of dasatinib, and it possibly plays a similar role for other orally administered substrates, such as acetylsalicylic acid. This phenomenon also provides a mechanistic explanation for the malabsorption of certain drugs following gastric resection. Clin Cancer Res; 19(16); 4359–70. ©2013 AACR.
Residual Prostate Cancer Cells after Docetaxel Therapy Increase the Tumorigenic Potential via Constitutive Signaling of CXCR4, ERK1/2 and c-Myc
Authors: Hatano Koji , Yamaguchi Souhei , Nimura Keisuke , Murakami Kouki , Nagahara Akira , Fujita Kazutoshi , Uemura Motohide , Nakai Yasutomo , Tsuchiya Mutsumi , Nakayama Masashi , Nonomura Norio , Kaneda Yasufumi 
Published: June 2013

AbstractDespite an increasing prevalence of patients with docetaxel-refractory prostate cancer, little is known about the tumor biology of the docetaxel-resistant residual tumor cells compared with primary tumor cells. In this study, tumorigenic potential was increased in the docetaxel-resistant residual prostate cancer cell lines (DRD, 1G7 and PC3DR) compared with parental cells (DU145 or PC3). Enhanced tumorigenic potential was conferred by oncogenic c-Myc, which was stabilized by constitutively activated ERK1/2 in DRD, 1G7, and PC3DR cells. Constitutively activated ERK1/2 was maintained by CXCR4, which was upregulated in DRD, 1G7, and PC3DR cells. In docetaxel-treated DU145 cells, transiently activated ERK1/2 induced CXCR4 expression by stabilizing c-Myc. Furthermore, constitutive activation of CXCR4, ERK1/2, and c-Myc signaling was evident in clinical tissue samples from human patients with docetaxel-resistant prostate cancer. In DTX-resistant residual prostate cancer cells, the enhanced tumorigenic potential was reduced by ERK1/2 inhibition, or by AMD3100, a CXCR4 antagonist. Thus, docetaxel treatment constitutively activated the CXCR4, ERK1/2, and c-Myc signaling loop in docetaxel-resistant residual prostate cancer cells.Implications: Constitutive signaling pathways are viable therapeutic targets for residual prostate tumor cells following acquisition of docetaxel resistance. Mol Cancer Res; 11(9); 1088–100. ©2013 AACR.
A1C and Coronary Artery Calcification in Nondiabetic Men and Women
Authors: Chang Yoosoo , Yun Kyung Eun , Jung Hyun-Suk , Kim Chan-Won , Kwon Min-Jung , Sung Eunju , Ryu Seungho 
Published: June 2013

Objective—
This study aimed to examine the association between glycohemoglobin (A1C) and coronary artery calcification (CAC) in nondiabetic men and women without overt cardiovascular disease or diabetes mellitus after accounting for fasting glucose and traditional cardiovascular disease risk factors.

Approach and Results—
A cross-sectional study was performed in 25 564 Korean adults (41.4±7.0 years) with no diabetes mellitus (fasting glucose, ≥7.0 mmol/L or a history of diabetes mellitus) and no clinically evident cardiovascular disease, who underwent a health checkup, including a cardiac computed tomography estimation of CAC scores and measurements of cardiovascular risk factors. The presence of CAC was defined as a CAC score >0; CAC was observed in 12.0% of men and 4.9% of women. Age-adjusted odds ratios (95% confidence interval) for CAC comparing A1C of 5.5% to 5.6%, 5.7% to 5.9%, and 6.0% to 6.4% with A1C <5.5% were 1.12 (0.99–1.28), 1.44 (1.27–1.63), and 1.63 (1.39–1.90) in men and 1.76 (0.96–3.25), 1.86 (1.05–3.29), and 3.09 (1.68–5.70) in women, respectively. After adjusting for potential confounders, the odds ratios (95% confidence interval) comparing A1C of 5.5% to 5.6%, 5.7% to 5.9%, and 6.0% to 6.4% with A1C of <5.5% were 1.04 (0.91–1.19), 1.21 (1.07–1.38), and 1.25 (1.05–1.48) in men and 1.75 (0.94–3.29), 1.59 (0.88–2.87), and 2.48 (1.29–4.74) in women, respectively. These associations persisted in subjects without any metabolic abnormalities, including fasting glucose ≥100 mg/dL.

Conclusions—
A higher A1C level was found to have a modest and independent association with the subclinical coronary atherosclerosis, even in metabolically healthy individuals.
Peroxisome Proliferator-activated Receptor γ, Coactivator 1α Deletion Induces Angiotensin II–Associated Vascular Dysfunction by Increasing Mitochondrial Oxidative Stress and Vascular Inflammation
Authors: Kröller-Schön Swenja , Jansen Thomas , Schüler Andrea , Oelze Matthias , Wenzel Philip , Hausding Michael , Kerahrodi Jasmin Ghaemi , Beisele Maike , Lackner Karl J. , Daiber Andreas , Münzel Thomas , Schulz Eberhard 
Published: June 2013

Objective—
Peroxisome proliferator-activated receptor γ, coactivator 1α (PGC-1α) is an important mediator of mitochondrial biogenesis and function. Because dysfunctional mitochondria might be involved in the pathogenesis of vascular disease, the current study was designed to investigate the effects of in vivo PGC-1α deficiency during chronic angiotensin II (ATII) treatment.

Approach and Results—
Although ATII infusion at subpressor doses (0.1 mg/kg per day for 7 days) did not cause vascular dysfunction in wild-type mice, it led to impaired endothelial-dependent and endothelial-independent relaxation in PGC-1α knockout mice. In parallel, oxidative stress was increased in aortic rings from ATII-treated PGC-1α knockout mice, whereas no change in nitric oxide production was observed. By using the mitochondrial-specific superoxide dye MitoSox and complex I inhibitor rotenone, we identified the mitochondrial respiratory chain as the major PGC-1α–dependent reactive oxygen species source in vivo, accompanied by increased vascular inflammation and cell senescence. In vivo treatment with the mitochondria-targeted antioxidant Mito-TEMPO partially corrected endothelial dysfunction and prevented vascular inflammation in ATII-treated PGC-1α mice, suggesting a causative role of mitochondrial reactive oxygen species in this setting.

Conclusions—
PGC-1α deletion induces vascular dysfunction and inflammation during chronic ATII infusion by increasing mitochondrial reactive oxygen species production.
Acute Rheumatic Fever and Rheumatic Heart Disease
Authors: Lawrence Joanna G. , Carapetis Jonathan R. , Griffiths Kalinda , Edwards Keith , Condon John R. 
Published: June 2013

Background—
Although acute rheumatic fever (ARF) and its sequel, rheumatic heart disease (RHD), continue to cause a large burden of morbidity and mortality in disadvantaged populations, most studies investigating the effectiveness of control programs date from the 1950s. A control program, including a disease register, in the Northern Territory of Australia where the Indigenous population has high rates of ARF and RHD allowed us to examine current disease incidence and progression.

Methods and Results—
ARF and RHD incidence rates, ARF recurrence rates, progression rates from ARF to RHD to heart failure, and RHD survival and mortality rates were calculated for Northern Territory residents from 1997 to 2010. For Indigenous people, ARF incidence was highest in the 5- to 14-year age group (males, 162 per 100 000; females, 228 per 100 000). There was little evidence that the incidence of ARF or RHD had declined. The ARF recurrence rate declined by 9% per year after diagnosis. After a first ARF diagnosis, 61% developed RHD within 10 years. After RHD diagnosis, 27% developed heart failure within 5 years. For Indigenous RHD patients, the relative survival rate was 88.4% at 10 years after diagnosis and the standardized mortality ratio was 1.56 (95% confidence interval, 1.23–1.96).

Conclusions—
For Indigenous Australians in the Northern Territory, ARF and RHD incidence and associated mortality remain very high. The reduction in ARF recurrence indicates that the RHD control program has improved secondary prophylaxis; a decline in RHD incidence is expected to follow.
The Lukan Special Material and the Tradition History of the Pericope Adulterae
Authors: Hughes Kyle R. 
Published: June 2013

Abstract
For nearly a century, scholars have wrestled with the presence of Lukanisms in the Pericope Adulterae ( John 7:53-8:11) even as the manuscript evidence clearly indicates this account was not originally part of the Third Gospel. A comparison of the version of this pericope found in Papias and the Didascalia with the pericopae associated with the Lukan special material (or “L source”) reveals remarkable similarities in style, form, and content. In light of these discoveries, we conclude that Papias and the Didascalia preserve a primitive form of the Pericope Adulterae that was originally part of the L source behind Luke’s Gospel, shedding light on the tradition history of this pericope as well as the nature of L.
Paul’s Rhetoric of Knowledge
Authors: Edsall Benjamin A. 
Published: June 2013

Abstract
The force of the question “do you not know?” is often taken for granted in contemporary scholarship on 1 Corinthians. However, the rhetorical force of the question is closely linked with its referential value, neither of which is straightforward in every case. This article begins by surveying the use of the “do you not know?” question in 1 Corinthians, noting indications that the Corinthians may not in fact know what Paul is asking. Following that is a survey of the use of “do you not know?” in Greek sources ranging from the 5th century bce to the 4th century ce. It is demonstrated that the relationship between the question “do you not know?” and the audience’s actual knowledge is not invariable; the speaker may use the question to draw on actual knowledge or to introduce elements into the discussion that the interlocutor genuinely did not know. After this survey, some conclusions are drawn with relation to Paul’s use of “do you not know?” in 1 Corinthians.
Nighttime Turbulent Events in a Steep Valley: A Nested Large-Eddy Simulation Study
Authors: Zhou Bowen , Chow Fotini Katopodes 
Published: June 2013

Abstract
This numerical study investigates the nighttime flow dynamics in Owens Valley, California. Nested high-resolution large-eddy simulation (LES) is used to resolve stable boundary layer flows within the valley. On 17 April during the 2006 Terrain-Induced Rotor Experiment, the valley atmosphere experiences weak synoptic forcings and is largely dominated by buoyancy-driven downslope and down-valley flows. Tower instruments on the valley floor record a continuous decrease in temperature after sunset, except for a brief warming episode. This transient warming event is modeled with good magnitude and temporal precision with LES. Analysis of the LES flow field confirms the event to be the result of a slope to valley flow transition, as previously suggested by researchers based on field observations. On the same night, a northerly cold airflow from the Great Basin is channeled through a pass on the eastern valley sidewall. The current plunges into the stable valley atmosphere, overshooting the altitude of its neutral buoyancy, and generating a large-scale oscillatory motion. The resulting cross-valley flow creates strong vertical shear with the down-valley flow in the lower layers of the atmosphere. A portion of the cross-valley flow is captured by a scanning lidar. The nested LES is in good agreement with the lidar-recorded radial velocity. Furthermore, the LES is able to resolve Kelvin–Helmholtz waves, and ejection and sweep events at the two-layer interface, which lead to top-down vertical mixing.
Empiricism or rationalism: how should we measure proteinuria?
Authors: Methven Shona , MacGregor Mark S 
Published: June 2013

Proteinuria is the cardinal sign of renal disease, therefore accurate identification of clinically significant proteinuria is essential to the diagnosis and management of kidney disease. Spot samples are now widely used, namely protein: creatinine ratio (uPCR) and albumin: creatinine ratio (uACR). In this article we review the evidence comparing uPCR and uACR including clinical, laboratory and financial arguments. uPCR has a superior performance to uACR to predict 24-hour total proteinuria, the measurement on which the evidence for interventions in chronic kidney disease is based. Furthermore a retrospective study comparing uPCR and uACR as predictors of renal outcome found comparable performance to predict all-cause mortality, commencement of renal replacement therapy and doubling of serum creatinine. Only uPCR takes account of non-albumin proteinuria which has been shown to have prognostic significance. uACR was been thought to be superior at low levels (where there is less ‘noise’ from physiological urinary proteins), but uPCR has recently been shown to perform well at levels equivalent to <0.5 g/day (and even within the reference range) as a predictor of outcomes. uACR is measured using an immunoassay that may be technically superior, but is not without shortcomings (such as antigen excess) and is 2–10 times more expensive than uPCR. The theories explaining the superiority of albumin are appealing. However, the available comparative data do not seem to support the theory. We cannot explain the disparity, but in science, if the data do not fit the existing theory, then maybe it's time for a new theory.
Low-Back Pain Ratings for Lifetime, 1-Month Period, and Point Prevalences in a Large Occupational Population
Authors: Thiese Matthew S. , Hegmann Kurt T. , Wood Eric M. , Garg Arun , Moore J. Steven , Kapellusch Jay M. , Foster James , Greene Tom , Stoddard Greg , Biggs Jeremy ,   BackWorks Study Team
Published: June 2013

Objective: This manuscript systematically quantifies multiple measures of low-back pain (LBP) prevalence by pain rating in a large, multisite cohort of workers. Background: Published LBP prevalence rates vary. Studies rely on one measure of LBP and none report prevalence stratified by pain rating. Method: Cross-sectional analyses of baseline data from a multicenter prospective cohort study were performed to evaluate differences in lifetime prevalence, 1-month period prevalence, and point prevalence of LBP. Workers were from 28 different employment settings in 4 diverse U.S. states. All workers completed computerized questionnaires and structured interviews. LBP prevalence measures were stratified by pain ratings. Results: A total of 828 subjects had complete health data at baseline. Lifetime prevalence, 1-month period prevalence, and point prevalence for any LBP (≥1/10) were 63.4%, 44.0%, and 20.8% respectively. Prevalence of LBP decreased with increasing pain ratings. As an example, using a threshold of LBP ≥ 3/10 pain, prevalence measures were 61.0%, 37.6%, and 16.7% respectively. A threshold of LBP ≥ 5/10 had prevalence measures of 51.2%, 22.9%, and 9.9% respectively. Age, systolic and diastolic blood pressure, high cholesterol, high blood pressure, and tobacco use were statistically significantly related to lifetime prevalence of LBP. Conclusion: Lifetime LBP prevalence, 1-month period prevalence, and point prevalence stratified by pain ratings demonstrate a wide variation of prevalence measures of LBP and self-reported pain ratings. Higher pain rating thresholds yield lower prevalence measures and may impact assessments of risk factors. Differences in pain ratings may allow for focused surveillance within an occupational cohort.
Mapping accountability changes in labour market administrations: from concentrated to shared accountability?
Authors: Jantz Bastian , Jann Werner 
Published: June 2013

The article explores how recent changes in the governance of employment services in three European countries (Denmark, Germany and Norway) have influenced accountability relationships. The overall assumption in the growing literature about accountability is that the number of actors involved in accountability arrangements is rising, that accountability relationships are becoming more numerous and complex, and that these changes may lead to contradictory accountability relationships, and finally to ‘multi accountability disorder’. The article tries to explore these assumptions by analysing the different actors involved and the information requested in the new governance arrangements in all three countries. It concludes that the considerable changes in organizational arrangements and more managerial information demanded and provided have led to more shared forms of accountability. Nevertheless, a clear development towards less political or administrative accountability could not be observed. Points for practitioners Public organizations in many areas are confronted with and are using ever more and more sophisticated accountability measures to monitor and improve their performance. But many citizens still perceive them as being not accountable enough. These accountability problems are normally treated by recommending and establishing new and more accountability structures with more actors and information requirements and the assumption that these systems will lead to better output and outcome. At the same time there is a widespread fear that these new shared and fragmented accountability structures weaken established political accountability and legitimacy. The article explores these developments by comparing changes in accountability in labour market administration in three countries and finds that there is more shared accountability but at the same time no weakening of political and administrative accountability.
Negative Emotions and Risk for Type 2 Diabetes Among Korean Immigrants
Authors: Choi Sarah E. , Rush Elizabeth B. , Henry Shayna L. 
Published: June 2013

Purpose The purpose of this study is to examine the relationship between negative emotions and bio-behavioral risk factors among Korean immigrants at risk for type 2 diabetes (T2DM). Methods Data were collected from 148 Korean immigrant adults who are “at risk” for T2DM as defined by having family history of T2DM in first-degree relatives, body mass index greater than 23, or history of gestational diabetes in women. Participants completed questionnaires and underwent biological measures. Negative emotions included feeling nervous, hopeless, restless, anxious, and stressed as well as depressive symptoms. Results High percentages of participants had T2DM risk factors including overweight, greater than normal waist to hip ratio, and blood glucose readings that are indicative of T2DM. Feeling stressed was the most commonly reported negative emotion (66%), followed by feeling anxious (51%), restless (38%), nervous (30%), and hopeless (13%). Experience of negative emotions was significantly related to behavioral risk factors; higher levels of experiencing negative emotions were related to increased soda intake and a decreased likelihood of doing at least 10 minutes of moderate exercise. Stress and anxiety were each negatively related to moderate exercise, and depressive symptoms were negatively related to both moderate and vigorous exercise. No significant relationship was found between negative emotions and biological risk factors. Conclusions Findings suggest that negative emotions, individually and taken together, may be related to T2DM risk behaviors in high-risk Korean immigrants. Behavioral interventions to prevent T2DM in this population should consider assessing and addressing negative emotions.