bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of red blood cell preparation method on in vitro markers of red blood cell aging and inflammatory response
Authors: Radwanski Katherine , Garraud Olivier , Cognasse Fabrice , Hamzeh‐Cognasse Hind , Payrat Jean‐Marc , Min Kyungyoon 
Published: March 2013

BackgroundStudies are currently under way examining whether the age of stored red blood cells (RBCs) affects clinical outcome in transfusion recipients. The effects of storage duration on the RBC storage lesion are well documented, while fewer studies are available regarding the effect of RBC production method. In this study, we compared in vitro RBC quality variables and markers of inflammatory response in apheresis and whole blood (WB)‐derived RBCs, specifically those prepared after an overnight room temperature hold (RTH) of WB.Study Design and MethodsSAGM RBCs, prepared from WB after overnight RTH (n = 10), were compared to SAGM RBCs prepared using an apheresis device (Alyx, n = 10). As a control, SAGM RBCs were also prepared within 2 hours of WB collection (2‐hr WB, n = 10). All RBCs were stored at 4°C for 42 days with weekly assay of in vitro variables, cytokines and/or chemokines, and neutrophil activation after incubation with RBC supernatant.ResultsRTH WB RBCs exhibited decreased levels of 2,3‐diphosphoglycerate acid (2.3 μmol/g hemoglobin [Hb] ± 2.1 vs. 13.7 ± 1.3 μmol/g Hb) and morphology (160 ± 10 vs. 192 ± 5) on Day 1 and increased hemolysis (0.45 ± 0.21% vs. 0.31 ± 0.09%) and microparticles (6.1 ± 2.8/103 RBCs vs. 3.9 ± 1.1/103 RBCs) on Day 42 compared to apheresis RBCs. Gro‐α and ENA‐78 cytokine levels were significantly higher in RTH WB than Alyx RBCs during storage. CD11b expression was highest in neutrophils exposed to supernatant from RTH WB RBCs (p < 0.05).ConclusionRBC preparation method has a meaningful effect on the RBC storage lesion, which should be taken into account in addition to length of storage.
Inhibition of lysophosphatidic acid increase by prestorage whole blood leukoreduction in autologous CPDA‐1 whole blood
Authors: Nagura Yutaka , Tsuno Nelson H. , Ohkawa Ryunosuke , Nojiri Takahiro , Tokuhara Yasunori , Matsuhashi Mika , Yatomi Yutaka , Takahashi Koki 
Published: March 2013

BackgroundLysophosphatidylcholine (LPC) has been implicated in the onset of transfusion‐related acute lung injury (TRALI). In plasma, LPC is converted to lysophosphatidic acid (LPA) by autotaxin (ATX). The effect of leukoreduction in the accumulation of these bioactive lipids and ATX in human autologous blood has not been fully investigated.Study Design and MethodsThe accumulation of choline‐containing phospholipids (LPC, sphingomyelin [SM], and phosphatidylcholine [PC]), LPA, and ATX during the storage of autologous blood and the changes caused by leukoreduction were investigated. A total of 26 orthopedic patients were enrolled. Autologous blood was collected as whole blood and, after leukoreduction, preserved refrigerated until use. Prestorage leukoreduced (LR) and non‐LR autologous blood samples were analyzed. The time‐dependent changes and the effect of the filtration were compared.ResultsA time‐dependent and significant increase in the levels of LPA was observed in both non‐LR and LR samples. The concentration of LPA was significantly reduced in LR compared to non‐LR samples. The concentration of LPC was higher in LR compared to non‐LR samples. The levels of PC, SM, and ATX were not affected by either the storage period or the leukoreduction.ConclusionsLeukoreduction of autologous whole blood effectively reduced the accumulation of LPA. On the other hand, prestorage leukoreduction resulted in an increased concentration of LPC, without significantly affecting ATX. Further studies are necessary to confirm the role of LPA in the pathogenesis of adverse effects of blood transfusion, especially TRALI.
Some Surprising Facts About the Concentration of Trade Across Commodities and Trading Partners
Authors: Panagariya Arvind , Bagaria Nitika 
Published: March 2013

AbstractThe present paper documents unexplained concentration in trade. Bernard et al. (Producer Dynamics: New Evidence from Micro Data, 2009, University of Chicago Press) have documented concentration at the level of the firm and in exports. Taking a step forward, we document trade volume concentration at the level of nations and in both exports and imports. Firm level concentration has been relatively easy to explain in terms of models of heterogeneous‐firm models with entry costs in both the domestic and foreign markets. But as we shall see, the concentration at the level of the nation, especially in imports if not exports, turns out to be far more difficult to explain.
Renal pathophysiology: lessons learned from the canine remnant kidney model
Authors: Brown Scott A. 
Published: March 2013

AbstractObjectiveTo review the pathophysiology of chronic kidney disease (CKD) in dogs and the contributions of the canine remnant kidney model to our understanding of this disease.Data SourcesOriginal studies in the human and veterinary medical fields.Data SynthesisThree of the fundamental principles of modern nephrology—the intact nephron hypothesis, the trade‐off hypothesis, and the hyperfiltration theory were developed directly as a result of studies of the remnant kidney model. Most of the pivotal early studies were conducted in dogs. As a result, our understanding ofCKD, and of the renal and systemic adaptations toCKD, is largely based on studies of this model.ConclusionsStudies of the remnant kidney model have advanced our understanding of the pathophysiology ofCKD. Nearly every therapeutic intervention used inCKD, by veterinarians and physicians alike, has its basis in studies of the remnant kidney model or in knowledge that was derived from studies of this model. A great debt is owed to the canine participants in these studies and to a small number of key scientists who conducted this important and insightful research.
Building capacity and capability for patient safety education: a train-the-trainers programme for senior doctors
Authors: Ahmed Maria , Arora Sonal , Baker Paul , Hayden Jacky , Vincent Charles , Sevdalis Nick 
Published: March 2013

ObjectivesTo develop, implement and evaluate a training programme for senior doctors to become faculty leaders for patient safety training.MethodsSenior doctors were recruited from across 20 hospitals in the North Western Deanery, England, UK. The intervention comprised a half-day course in patient safety theory, root cause analysis and small-group facilitation, following which participants were invited to sign up as faculty for a region-wide patient safety training programme for trainees ‘Lessons Learnt’. Course evaluation comprised a prospective longitudinal study conducted in 2010–2012. Patient safety knowledge, attitudes and skills were evaluated pre and post course and retention further evaluated 8 months post course.Results216 senior doctors volunteered as faculty of whom 122 were appointed. Participants reported high levels of satisfaction with the course. Objective scores of patient safety knowledge significantly improved immediately post course (MedianPre course=70%, MedianPost course=80%, p<0.001) and were sustained at 8 months (Median8 month post course=90%). Similarly, measures of attitudes and self-reported safety skills also significantly improved post course and were sustained. Upon completion of the course, 88/122 (72%) participants facilitated 213 ‘Lessons Learnt’ sessions from January 2011 to July 2012 (mean 2, range 1–8 sessions per faculty member). Trainee satisfaction with faculty was high.ConclusionsThere is considerable appetite for senior doctors to engage with training in patient safety as teachers and learners. Training senior doctors in patient safety is feasible, acceptable and effective as a means of building capacity and capability for delivering training in this rapidly emerging field.
HIDDEN ATTRACTORS IN DYNAMICAL SYSTEMS. FROM HIDDEN OSCILLATIONS IN HILBERT–KOLMOGOROV, AIZERMAN, AND KALMAN PROBLEMS TO HIDDEN CHAOTIC ATTRACTOR IN CHUA CIRCUITS
Authors: LEONOV G. A. , KUZNETSOV N. V. 
Published: March 2013

From a computational point of view, in nonlinear dynamical systems, attractors can be regarded as self-excited and hidden attractors. Self-excited attractors can be localized numerically by a standard computational procedure, in which after a transient process a trajectory, starting from a point of unstable manifold in a neighborhood of equilibrium, reaches a state of oscillation, therefore one can easily identify it. In contrast, for a hidden attractor, a basin of attraction does not intersect with small neighborhoods of equilibria. While classical attractors are self-excited, attractors can therefore be obtained numerically by the standard computational procedure. For localization of hidden attractors it is necessary to develop special procedures, since there are no similar transient processes leading to such attractors.At first, the problem of investigating hidden oscillations arose in the second part of Hilbert's 16th problem (1900). The first nontrivial results were obtained in Bautin's works, which were devoted to constructing nested limit cycles in quadratic systems, that showed the necessity of studying hidden oscillations for solving this problem. Later, the problem of analyzing hidden oscillations arose from engineering problems in automatic control. In the 50–60s of the last century, the investigations of widely known Markus–Yamabe's, Aizerman's, and Kalman's conjectures on absolute stability have led to the finding of hidden oscillations in automatic control systems with a unique stable stationary point. In 1961, Gubar revealed a gap in Kapranov's work on phase locked-loops (PLL) and showed the possibility of the existence of hidden oscillations in PLL. At the end of the last century, the difficulties in analyzing hidden oscillations arose in simulations of drilling systems and aircraft's control systems (anti-windup) which caused crashes.Further investigations on hidden oscillations were greatly encouraged by the present authors' discovery, in 2010 (for the first time), of chaotic hidden attractor in Chua's circuit.This survey is dedicated to efficient analytical–numerical methods for the study of hidden oscillations. Here, an attempt is made to reflect the current trends in the synthesis of analytical and numerical methods.
Serum 25-Hydroxyvitamin D and Cancer Risk in Older Adults: Results from a Large German Prospective Cohort Study
Authors: Ordóñez-Mena José M. , Schöttker Ben , Haug Ulrike , Müller Heiko , Köhrle Josef , Schomburg Lutz , Holleczek Bernd , Brenner Hermann 
Published: March 2013

AbstractBackground: Several observational studies assessed the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and the risk of cancer but results were inconclusive.Methods: We measured 25(OH)D concentrations in a population-based cohort study of 9,949 men and women ages 50 to 74 years in Saarland, Germany. Comprehensively adjusted Cox regression models were applied to estimate HRs and 95% confidence intervals (CI) for the association between season-standardized 25(OH)D concentrations and total and site-specific cancer incidence.Results: Overall, during a median of 8 years of follow-up, 873 subjects developed cancer; the most common being prostate (171), breast (137), lung (136), and colorectal (136) cancer. Low season-standardized 25(OH)D (&lt;30, 35, 40, or 36 nmol/L in winter, spring, summer, and autumn, respectively) was neither significantly associated with total cancer incidence (HR, 1.10; 95% CI, 0.93–1.30) nor with site-specific cancer incidence. However, a significantly increased overall cancer risk was observed for low 25(OH)D among men, nonobese subjects and subjects reporting low fish consumption and for high 25(OH)D in nonsmokers and nonobese subjects. Accordingly, restricted cubic splines to investigate dose–response relationships curves showed an inverse association of 25(OH)D levels and total cancer risk in men but not in women.Conclusions: 25(OH)D concentrations were significantly associated with overall cancer incidence in subgroups of this large cohort from Germany. No significant association was observed with site-specific cancers but this could be due to a limited statistical power for these endpoints.Impact: Further research should clarify whether and to what extent specific risk groups might profit from vitamin D supplementation. Cancer Epidemiol Biomarkers Prev; 22(5); 905–16. ©2013 AACR.
Comparison of Nicotine and Carcinogen Exposure with Water Pipe and Cigarette Smoking
Authors: Jacob Peyton , Abu Raddaha Ahmad H. , Dempsey Delia , Havel Christopher , Peng Margaret , Yu Lisa , Benowitz Neal L. 
Published: March 2013

Abstract
Background: Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world and is perceived by many as relatively safe. We investigated biomarkers of toxicant exposure with water pipe compared with cigarette smoking.
Methods: We conducted a crossover study to assess daily nicotine and carcinogen exposure with water pipe and cigarette smoking in 13 people who were experienced in using both products.
Results: When smoking an average of 3 water pipe sessions compared with smoking 11 cigarettes per day (cpd), water pipe use was associated with a significantly lower intake of nicotine, greater exposure to carbon monoxide (CO), and a different pattern of carcinogen exposure compared with cigarette smoking, with greater exposure to benzene, and high molecular weight polycyclic aromatic hydrocarbon (PAH), but less exposure to tobacco-specific nitrosamines, 1,3-butadiene, acrolein, acrylonitrile, propylene oxide, ethylene oxide, and low molecular weight PAHs.
Conclusions: A different pattern of carcinogen exposure might result in a different cancer risk profile between cigarette and water pipe smoking. Of particular concern is the risk of leukemia related to high levels of benzene exposure with water pipe use.
Impact: Smoking tobacco in water pipes has gained popularity in the United States and around the world. Many believe that water pipe smoking is not addictive and less harmful than cigarette smoking. We provide data on toxicant exposure that will help guide regulation and public education regarding water pipe health risk. Cancer Epidemiol Biomarkers Prev; 22(5); 765–72. ©2013 AACR.
Inflammatory Plasma Markers and Pancreatic Cancer Risk: A Prospective Study of Five U.S. Cohorts
Authors: Bao Ying , Giovannucci Edward L. , Kraft Peter , Qian Zhi Rong , Wu Chen , Ogino Shuji , Gaziano J. Michael , Stampfer Meir J. , Ma Jing , Buring Julie E. , Sesso Howard D. , Lee I-Min , Rifai Nader , Pollak Michael N. , Jiao Li , Lessin Lawrence , Cochrane Barbara B. , Manson JoAnn E. , Fuchs Charles S. , Wolpin Brian M. 
Published: March 2013

Abstract
Chronic inflammation may play a role in the development of pancreatic cancer. However, few prospective studies have examined the association between plasma inflammatory markers and pancreatic cancer risk. Therefore, we investigated the association of prediagnostic circulating C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-α receptor II (TNF-αR2) with subsequent pancreatic cancer risk in a prospective, nested case–control study of 470 cases and 1,094 controls from Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. The median follow-up time of cases was 7.2 years (range 1–26 years). No association was observed between plasma CRP, IL-6, and TNF-αR2 and the risk of pancreatic cancer. Comparing extreme quintiles, the multivariate ORs were 1.10 [95% confidence interval (CI), 0.74–1.63; Ptrend = 0.81] for CRP, 1.19 (95% CI, 0.81–1.76; Ptrend = 0.08) for IL-6, and 0.88 (95% CI, 0.58–1.33; Ptrend = 0.57) for TNF-αR2. In conclusion, prediagnostic levels of circulating CRP, IL-6, and TNF-αR2 were not associated with the risk of pancreatic cancer, suggesting that systemic inflammation as measured by circulating inflammatory factors is unlikely to play a major role in the development of pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 22(5); 855–61. ©2013 AACR.
Autophagy Inhibition Sensitizes Colon Cancer Cells to Antiangiogenic and Cytotoxic Therapy
Authors: Selvakumaran Muthu , Amaravadi Ravi K. , Vasilevskaya Irina A. , O'Dwyer Peter J. 
Published: March 2013

Abstract
Purpose: Autophagy is a critical survival pathway for cancer cells under conditions of nutrient or oxygen limitation, or cell stress. As a consequence of antiangiogenic therapy, solid tumors encounter hypoxia induction and imbalances in nutrient supply. We wished to determine the role of autophagy in protection of tumor cells from the effects of antiangiogenic therapy and chemotherapy. We examined the effect of inhibiting autophagy on hypoxic colon cancer cells in vitro and on bevacizumab- and oxaliplatin-treated mouse xenografts in vivo.
Experimental Design: The autophagic response to hypoxia and DNA-damaging agents was assessed by fluorescent microscopic imaging, autophagy-related gene expression, and by electron microscopic ultrastructural analysis. Pharmacologic and molecular approaches to autophagy inhibition were taken in a panel of colon cancer cell lines. Mouse xenograft models were treated with combinations of oxaliplatin, bevacizumab, and chloroquine to assess effects on tumor growth reduction and on pharmacodynamic markers of autophagy inhibition.
Results: Autophagy was induced in colon cancer models by exposure to both hypoxia and oxaliplatin. Inhibition of autophagy, either with chloroquine or by downregulation of beclin1 or of ATG5, enhanced sensitivity to oxaliplatin under normal and hypoxic conditions in a synergistic manner. Both bevacizumab and oxaliplatin treatments activate autophagy in HT29 murine xenografts. The addition of chloroquine to bevacizumab-based treatment provided greater tumor control in concert with evidence of autophagy inhibition.
Conclusions: These findings implicate autophagy as a mechanism of resistance to antiangiogenic therapies and support investigation of inhibitory approaches in the management of this disease. Clin Cancer Res; 19(11); 2995–3007. ©2013 AACR.
Abcc4 Together with Abcb1 and Abcg2 Form a Robust Cooperative Drug Efflux System That Restricts the Brain Entry of Camptothecin Analogues
Authors: Lin Fan , Marchetti Serena , Pluim Dick , Iusuf Dilek , Mazzanti Roberto , Schellens Jan H.M. , Beijnen Jos H. , van Tellingen Olaf 
Published: March 2013

Abstract
Purpose: Multidrug resistance–associated protein 4 (ABCC4) shares many features with P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), including broad substrate affinity and expression at the blood–brain barrier (BBB). However, the pharmacologic relevance of ABCC4 at the BBB is difficult to evaluate, as most drugs are also substrates of ABCB1 and/or ABCG2.
Experimental Design: We have created a mouse strain in which all these alleles are inactivated to assess their impact on brain delivery of camptothecin analogues, an important class of antineoplastic agents and substrates of these transporters. Wild-type (WT), Abcg2−/−, Abcb1a/b−/−, Abcc4−/−, Abcb1a/b;Abcg2−/−, Abcg2;Abcc4−/−, and Abcb1a/b;Abcg2;Abcc4−/− mice received i.v. topotecan, irinotecan, SN-38, or gimatecan alone or with concomitant oral elacridar. Drug levels were analyzed by high-performance liquid chromatography (HPLC).
Results: We found that additional deficiency of Abcc4 in Abcb1a/b;Abcg2−/− mice significantly increased the brain concentration of all camptothecin analogues by 1.2-fold (gimatecan) to 5.8-fold (SN-38). The presence of Abcb1a/b or Abcc4 alone was sufficient to reduce the brain concentration of SN-38 to the level in WT mice. Strikingly, the brain distribution of gimatecan in brain of WT mice was more than 220- and 40-fold higher than that of SN-38 and topotecan, respectively.
Conclusion: Abcc4 limits the brain penetration of camptothecin analogues and teams up with Abcb1a/b and Abcg2 to form a robust cooperative drug efflux system. This concerted action limits the usefulness of selective ABC transport inhibitors to enhance drug entry for treatment of intracranial diseases. Our results also suggest that gimatecan might be a better candidate than irinotecan for clinical evaluation against intracranial tumors. Clin Cancer Res; 19(8); 2084–95. ©2013 AACR.
Prediagnostic Leptin, Adiponectin, C-Reactive Protein, and the Risk of Postmenopausal Breast Cancer
Authors: Ollberding Nicholas J. , Kim Yeonju , Shvetsov Yurii B. , Wilkens Lynne R. , Franke Adrian A. , Cooney Robert V. , Maskarinec Gertraud , Hernandez Brenda Y. , Henderson Brian E. , Le Marchand Loïc , Kolonel Laurence N. , Goodman Marc T. 
Published: March 2013

Abstract
Obesity has been associated with an increased risk of postmenopausal breast cancer. Adipokines and systemic inflammation have been hypothesized to underlie this association. In a case–control study nested within the Multiethnic Cohort, conditional logistic regression was used to calculate the ORs and 95% confidence intervals (CI) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin, adiponectin, the leptin:adiponectin ratio, and C-reactive protein (CRP). The 706 cases and 706 controls were matched on ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, hours fasting before blood draw, and hormone replacement therapy use at blood draw. Higher circulating levels of leptin [ORQ4 vs. Q1, 1.94 (1.37–2.75); Ptrend ≤ 0.001), the leptin:adiponectin ratio [OR, 1.91 (1.36–2.68); Ptrend = 0.005], and CRP [OR, 1.41 (1.01–1.96); Ptrend = 0.014] were associated with an increased risk of postmenopausal breast cancer. The positive associations for these markers remained after adjustment for body mass index (BMI). No associations were detected for adiponectin. These data suggest that adipokines and systemic inflammation may be associated with the risk of postmenopausal breast cancer independently of BMI. Further prospective studies examining the role of adipokines and inflammatory processes in the etiology of postmenopausal breast cancer are warranted. Cancer Prev Res; 6(3); 188–95. ©2013 AACR.