bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant Activation of Fatty Acid Synthesis Suppresses Primary Cilium Formation and Distorts Tissue Development
Authors: Willemarck Nicolas , Rysman Evelien , Brusselmans Koen , Van Imschoot Griet , Vanderhoydonc Frank , Moerloose Katrien , Lerut Evelyne , Verhoeven Guido , van Roy Frans , Vleminckx Kris , Swinnen Johannes V. 
Published: October 2010

Abstract
Aberrant activation of fatty acid synthesis is a key feature of many advanced human cancers. Unlike in classical lipogenic tissues, this process has been implicated in membrane production required for rapid cell proliferation. Here, to gain further insight into the consequences of tumor-associated fatty acid synthesis, we have mimicked the lipogenic phenotype of cancer cells in Xenopus embryos by microinjection of RNA encoding the lipogenic transcription factor sterol regulatory element binding protein 1c (SREBP1c). Dramatic morphologic changes were observed that could be linked to alterations in Wnt and Hedgehog signaling, and ultimately to a distortion of the primary cilium. This is a sophisticated microtubular sensory organelle that is expressed on the surface of nearly every cell type and that is lost in many cancers. SREBP1c-induced loss of the primary cilium could be confirmed in mammalian Madin-Darby canine kidney (MDCK) cells and was mediated by changes in the supply of fatty acids. Conversely, inhibition of fatty acid synthesis in highly lipogenic human prostate cancer cells restored the formation of the primary cilium. Lipid-induced ciliary loss was associated with mislocalization of apical proteins, distortion of cell polarization, and aberrant epithelial tissue development as revealed in three-dimensional cultures of MDCK cells and in the developing mouse prostate. These data imply that tumor-associated lipogenesis, in addition to rendering cells more autonomous in terms of lipid supply, disturbs cilium formation and contributes to impaired environmental sensing, aberrant signaling, and distortion of polarized tissue architecture, which are all hallmarks of cancer. Cancer Res; 70(22); 9453–62. ©2010 AACR.
Expression, Cellular Distribution, and Prognostic Relevance of TRAIL Receptors in Hepatocellular Carcinoma
Authors: Kriegl Lydia , Jung Andreas , Engel Jutta , Jackstadt Rene , Gerbes Alexander L. , Gallmeier Eike , Reiche Jana A. , Hermeking Heiko , Rizzani Antonia , Bruns Christiane J. , Kolligs Frank T. , Kirchner Thomas , Göke Burkhard , De Toni Enrico N. 
Published: October 2010

Abstract
Purpose: After the advent of targeted therapies for hepatocellular carcinoma (HCC), much work is being done to provide a comprehensive description of the different signaling pathways contributing to cell survival and proliferation in this tumor. Apoptotic signaling mediated by tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) represents an important mechanism of tumor surveillance, but its importance in the development of HCC is not known. We thus investigated the cellular distribution and the prognostic importance of TRAIL receptors in HCC.
Experimental Design: Immunohistochemical staining for TRAIL receptors was evaluated in HCC tissues and in matched surrounding nontumor tissues of 157 HCC patients treated with liver transplantation or partial hepatectomy. Survival was analyzed in 93 patients who underwent partial hepatectomy.
Results: The fraction of HCC samples with positive membrane staining for TRAIL receptor 1 (TRAIL-R1) and 2 (TRAIL-R2) was 1.4- and 2.7-fold lower compared with that of hepatocytes from surrounding tissues (P = 0.01). Loss of either TRAIL-R1 or TRAIL-R2, as confirmed by a multivariate analysis, significantly worsened 5-year survival of HCC patients {survival, 27% versus 52% and 15% versus 43%; hazard ratio (HR), 2.3 [95% confidence interval (CI), 1.1-4.4] and 2.4 (95% CI, 1.1-5.2), respectively}. Loss of both TRAIL receptors further decreased survival of patients [HR, 5.72 (95% CI, 2.1-15.5) versus double-negative staining; P = 0.001], indicating an additive effect on survival of TRAIL-R1 and TRAIL-R2.
Conclusions: This pilot study suggests that loss of TRAIL receptors is a frequent feature of HCCs and an independent predictor of survival in patients undergoing partial hepatectomy. Future therapeutic protocols are likely to profit from the characterization of their expression and cellular distribution. Clin Cancer Res; 16(22); 5529–38. ©2010 AACR.
Glycogen Synthase Kinase-3β: A Prognostic Marker and a Potential Therapeutic Target in Human Bladder Cancer
Authors: Naito Sei , Bilim Vladimir , Yuuki Kaori , Ugolkov Andrey , Motoyama Teiichi , Nagaoka Akira , Kato Tomoyuki , Tomita Yoshihiko 
Published: October 2010

Abstract
Purpose: Although recent studies have shown glycogen synthase kinase-3β (GSK-3β), a serine/threonine kinase, as a positive regulator of pancreatic, colon, and kidney cancer cell survival and proliferation, the role of GSK-3 in bladder cancer remains unknown. Our objectives were to determine the subcellular localization of GSK-3β and to evaluate the effect of GSK-3 inhibition in bladder cancer.
Experimental Design: We used immunohistochemical staining and nuclear/cytosolic fractionation to determine the expression pattern of GSK-3β in human urothelial carcinomas. To study the effect of GSK-3 inhibition on bladder cancer cell proliferation and survival, we used pharmacologic inhibitors of GSK-3, RNA interference, MTS assay, bromodeoxyuridine incorporation assay, quantitative reverse transcriptase-PCR, and Western blotting.
Results: We found aberrant nuclear accumulation of GSK-3β in 62% (43 of 69) and 91% (21 of 23) of noninvasive and invasive human urothelial carcinomas, respectively. GSK-3β nuclear staining was significantly associated with high-grade tumors (P &lt; 0.001), advanced stage of bladder cancer (P &lt; 0.05), metastasis (P &lt; 0.05), and worse cause-specific survival (P &lt; 0.05) in bladder cancer patients. Moreover, we found that pharmacologic inhibition or genetic depletion of GSK-3β resulted in decreased viability of bladder cancer cells.
Conclusions: Our results suggest nuclear accumulation of GSK-3β as a novel prognostic marker in bladder cancer, show that GSK-3 contributes to urothelial cancer cell proliferation and survival, and identify GSK-3 as a potential therapeutic target in human bladder cancer. Clin Cancer Res; 16(21); 5124–32. ©2010 AACR.
Mechanisms of Synergistic Antileukemic Interactions between Valproic Acid and Cytarabine in Pediatric Acute Myeloid Leukemia
Authors: Xie Chengzhi , Edwards Holly , Xu Xuelian , Zhou Hui , Buck Steven A. , Stout Mark L. , Yu Qun , Rubnitz Jeffrey E. , Matherly Larry H. , Taub Jeffrey W. , Ge Yubin 
Published: October 2010

AbstractPurpose: To determine the possibility of synergistic antileukemic activity and the underlying molecular mechanisms associated with cytarabine combined with valproic acid (VPA; a histone deacetylase inhibitor and a Food and Drug Administration–licensed drug for treating both children and adults with epilepsy) in pediatric acute myeloid leukemia (AML).Experimental Design: The type and extent of antileukemic interactions between cytarabine and VPA in clinically relevant pediatric AML cell lines and diagnostic blasts from children with AML were determined by MTT assays and standard isobologram analyses. The effects of cytarabine and VPA on apoptosis and cell cycle distributions were determined by flow cytometry analysis and caspase enzymatic assays. The effects of the two agents on DNA damage and Bcl-2 family proteins were determined by Western blotting.Results: We showed synergistic antileukemic activities between cytarabine and VPA in four pediatric AML cell lines and nine diagnostic AML blast samples. t(8;21) AML blasts were significantly more sensitive to VPA and showed far greater sensitivities to combined cytarabine and VPA than non-t(8;21) AML cases. Cytarabine and VPA cooperatively induced DNA double-strand breaks, reflected in induction of γH2AX and apoptosis, accompanied by activation of caspase-9 and caspase-3. Further, VPA induced Bim expression and short hairpin RNA knockdown of Bim resulted in significantly decreased apoptosis induced by cytarabine and by cytarabine plus VPA.Conclusions: Our results establish global synergistic antileukemic activity of combined VPA and cytarabine in pediatric AML and provide compelling evidence to support the use of VPA in the treatment of children with this deadly disease. Clin Cancer Res; 16(22); 5499–510. ©2010 AACR.
Cytochrome P450 1B1 Gene Polymorphisms as Predictors of Anticancer Drug Activity: Studies withIn vitroModels
Authors: Laroche-Clary Audrey , Morvan Valérie Le , Yamori Takao , Robert Jacques 
Published: October 2010

AbstractCytochrome P450 1B1 (CYP1B1) is found in tumor tissue and is suspected to play a role in oncogenesis and drug resistance. CYP1B1 gene polymorphisms have been associated with the risk of developing lung and other cancers. They may be associated with tumor response to anticancer drugs. We have determined 4 frequent nonsynonymous gene polymorphisms of CYP1B1 in the human tumor cell lines panels of the National Cancer Institute (NCI) and the Japanese Foundation for Cancer Research (JFCR): rs10012 (R48G), rs1056827 (A119S), rs1056836 (L432V), and rs1800440 (N453S). Numerous anticancer drugs have been tested against these panels that offer the opportunity to detect associations between gene polymorphisms and drug sensitivity. CYP1B1 single nucleotide polymorphisms were in marked linkage disequilibrium. The L432V allelic variants were significantly associated with reduced sensitivity to DNA-interacting anticancer agents, alkylators, camptothecins, topoisomerase II inhibitors, and some antimetabolites. For instance, in the NCI panel, cell lines homozygous for the V432 allele were globally 2-fold resistant to alkylating agents (P = 5 × 10−10) and 4.5-fold to camptothecins (P = 6.6 × 10−9) than cell lines homozygous for the L432 allele. Similar features were exhibited by the JFCR panel. Cell lines homozygous for the V432 allele were globally less sensitive to DNA-interfering drugs than cell lines having at least 1 common allele. There was no significant association between mRNA expression of CYP1B1 and CYP1B1 genotype, and no significant association between CYP1B1 mRNA expression and drug cytotoxicity. These observations open the way to clinical studies exploring the role of CYP1B1 gene polymorphisms for predicting tumor sensitivity to chemotherapy. Mol Cancer Ther; 9(12); 3315–21. ©2010 AACR.
Outcomes After Acute Myocardial Infarction in South Asian, Chinese, and White Patients
Authors: Khan Nadia A. , Grubisic Maja , Hemmelgarn Brenda , Humphries Karen , King Kathryn M. , Quan Hude 
Published: October 2010

Background—
Cardiac mortality rates vary substantially between countries and ethnic groups. It is unclear, however, whether South Asian, Chinese, and white populations have a variable prognosis after acute myocardial infarction (AMI). To clarify this association, we compared mortality, use of revascularization procedures, and risk of recurrent AMI and hospitalization for heart failure between these ethnic groups in a universal-access healthcare system.

Methods and Results—
We used a population cohort study design using hospital administrative data linked to cardiac procedure registries from British Columbia and the Calgary Health Region Area in Alberta (1994 to 2003) to identify AMI cases. Patient ethnicity was categorized using validated surname algorithms. There were 2190 South Asian, 946 Chinese, and 38479 white patients with AMI identified. There was no significant difference in use of revascularization procedures between ethnic groups at 30 d and 1 year. Short-term (30-day) mortality was higher among Chinese relative to white patients (odds ratio, 1.23; 95% confidence interval, 1.02 to 1.48). There was no significant difference in 30-day mortality between South Asian and white patients. South Asian patients had a 35% lower relative risk of long-term mortality compared with white patients (hazard ratio, 0.65; 95% confidence interval, 0.57 to 0.72). There was no significant difference in long-term mortality between Chinese and white patients. Among AMI survivors, Chinese patients had a lower risk of recurrent AMI, whereas there was no difference between South Asian and white patients.

Conclusion—
The ethnic groups studied have striking differences in outcomes after AMI, with South Asian patients having significantly lower long-term mortality after AMI.
Searching for the Link between Religion and Violence by Means of the Thomas-Theorem
Authors: Kippenberg Hans G. 
Published: October 2010

AbstractCurrent religious violence is a challenge to students of religions. Do we need categories like “cult,” “fundamentalism,” or “terrorism” in order to distinguish it from allegedly “genuine” and peaceful religion? Do monotheistic religions—with their exclusive claims to truth—necessarily generate intolerance? Sociologists have demonstrated conclusively that every action is based on a definition of the situation. Social actors do not put a norm or a model into practice independent of the immediate context of action. I argue that this holds true for religious actors as well. It is not the personal motive of actors, but the religious meanings they attribute to a conflict of their faith community, which is crucial for understanding religious violence.
Talal Asad’s ‘Religion’ Trouble and a Way Out
Authors: Strenski Ivan 
Published: October 2010

AbstractBy this point, almost everyone is familiar with Talal Asad’s assault on the “religion” category. Despite his influence, Asad’s criticisms tend to oscillate between two mutually exclusive positions. I shall argue that Asad’s incoherence is instructive for the field as a whole. The study of religion would be better off constructing useful and revisable definitions of “religion” rather than abandoning the category all together.
No Field Is an Island: Fostering Collaboration between the Academic Study of Religion and the Sciences
Authors: Taves Ann 
Published: October 2010

AbstractWe can foster collaboration between the academic study of religion and the sciences, particularly the biological and psychological sciences, if we (1) construct a common object of study that can be positioned within an evolutionary paradigm, (2) adopt a building block approach to the study of religion that distinguishes between religions and the more elementary phenomena that comprise them, and (3) operationalize abstract concepts as behavioral interactions in order to gain a better understanding of the process whereby people construct religions and other complex things out of more elementary phenomena that they view as special.<xref ref-type="fn" rid="FN1">1</xref>
Response Theory, Quasi-theory and Pseudo-theory in the Study of Religion
Authors: Benavides Gustavo 
Published: October 2010

AbstractThis paper offers a series of critical observations on the essays that emerged from the roundtable co-sponsored by the North American Association for the Study of Religion and the Critical Theory and Discourses in Religion Group of the American Academy of Religion. Rather than simply responding to each paper, the essay takes these essays to provide a small but suggestive window into the work of theoretically-minded scholars of religion.
Simmias’ Objection to Socrates in the Phaedo: Harmony, Symphony and Some Later Platonic/ Patristic Responses to the Mind/Soul-Body Question
Authors: Corrigan Kevin 
Published: October 2010

AbstractSimmias’ famous epiphenomenalist analogy of the soul-body relation to the harmony and strings of a lyre (together with Cebes’ subsequent objection) leads to Socrates’ initial refutation and subsequent prolonged defense of soul’s immortality in the Phaedo. It also yields in late antiquity significant treatments of the harmony relation by Plotinus (Ennead III 6 [26] 4, 30-52) and Porphyry (Sentences 18, 8-18) that present a larger context for viewing the nature of harmony in the soul and the psycho-somatic compound. But perhaps the most detailed treatment of the musical analogy, and certainly the most radical, is to be found in Gregory of Nyssa’s De Hominis Opificio. Gregory’s remarkable development of the musical instrument analogy provides a multi-layered analysis of interrelated causality on the mechanistic, physiological, psycho-somatic and intellectual/spiritual planes. Gregory not only sees mind/soul and body as radically equal and yet multilayered in their mutual development; he also refuses to restrict mind to the brain alone, for all physiological systems, in his view, are holistically and individually expressive of mind’s activity. Gregory’s theory is more innovative than Augustine’s view of the mind/soul-body relation and, in my view, the most important account between Plotinus and Aquinas.
Plotinus and Magic
Authors: Helleman Wendy Elgersma 
Published: October 2010

AbstractContemporary scholarship accents incipient theurgical practice for Plotinus; this lends a certain urgency to the question of his acceptance of magic. While use of magic recorded in Porphyry’s Vita Plotini has received considerable attention, far less has been done to analyze actual discussion in the Enneads. Examination of key passages brings to light the context for discussion of magic, particularly issues of sympathy, prayer, astrology and divination. Equally important is Plotinus’ understanding of the cosmos and role of the heavenly bodies. Plotinus’ affirmation of the highest part of the soul as undescended, together with the claim that our soul has a common origin with the World Soul in Soul-Hypostasis, is significant for the relative unimportance he attributes to the role and effect of magic.
Descriptive Epidemiology of the Multicenter ACL Revision Study (MARS) Cohort
Authors:   The MARS Group, Wright Rick W. , Huston Laura J. , Spindler Kurt P. , Dunn Warren R. , Haas Amanda K. , Allen Christina R. , Cooper Daniel E. , DeBerardino Thomas M. , Lantz Brett (Brick) A. , Mann Barton J. , Stuart Michael J. 
Published: October 2010

Background Revision anterior cruciate ligament (ACL) reconstruction has worse outcomes than primary reconstructions. Predictors for these worse outcomes are not known. The Multicenter ACL Revision Study (MARS) Group was developed to perform a multisurgeon, multicenter prospective longitudinal study to obtain sufficient subjects to allow multivariable analysis to determine predictors of clinical outcome. Purpose To describe the formation of MARS and provide descriptive analysis of patient demographics and clinical features for the initial 460 enrolled patients to date in this prospective cohort. Study Design Cross-sectional study; Level of evidence, 2. Methods After training and institutional review board approval, surgeons began enrolling patients undergoing revision ACL reconstruction, recording patient demographics, previous ACL reconstruction methods, intra-articular injuries, and current revision techniques. Enrolled subjects completed a questionnaire consisting of validated patient-based outcome measures. Results As of April 1, 2009, 87 surgeons have enrolled a total of 460 patients (57% men; median age, 26 years). For 89%, the reconstruction was the first revision. Mode of failure as deemed by the revising surgeon was traumatic (32%), technical (24%), biologic (7%), combination (37%), infection (<1%), and no response (<1%). Previous graft present at the time of injury was 70% autograft, 27% allograft, 2% combination, and 1% unknown. Sixty-two percent were more than 2 years removed from their last reconstruction. Graft choice for revision ACL reconstruction was 45% autograft, 54% allograft, and more than 1% both allograft and autograft. Meniscus and/or chondral damage was found in 90% of patients. Conclusion The MARS Group has been able to quickly accumulate the largest revision ACL reconstruction cohort reported to date. Traumatic reinjury is deemed by surgeons to be the most common single mode of failure, but a combination of factors represents the most common mode of failure. Allograft graft choice is more common in the revision setting than autograft. Concomitant knee injury is extremely common in this population.
Making Sense of China’s Economic Transformation
Authors: Lo Dic , Zhang Yu 
Published: October 2010

China’s sustained rapid economic growth in the post-1978 reform era, which is also the era of capitalist globalization, is of worldwide importance. This growth experience has been based mainly on China’s internal dynamics. In the first half of the era, economic growth was driven by improvement in both allocative efficiency and productive efficiency. From the early 1990s until the present time, however, economic growth has been increasingly based on dynamic increasing returns associated with a growth path that is characterized by capital deepening. In both periods, the growth paths and their associated institutional frameworks appear to contradict principles of the free market economy: the mainstream doctrines of globalization. In the form of an analytical overview, this paper seeks to explain and interpret the dynamics and developmental implications of China’s economic transformation. The analytics draws on a range of relevant economic theories including Marxian theory of capital accumulation, post-Keynesian theory of demand determination, and Schumpeterian theory of innovation. It is posited that these alternative theoretical perspectives offer better insights than mainstream neoclassical economics in explaining and interpreting China’s economic transformation. JEL classificationO14, O53, P36,
How effective are the linkages between self-management programmes and primary care providers, especially for disadvantaged patients?
Authors: Williams Anna M. , Dennis Sarah , Harris Mark F. 
Published: October 2010

Objectives: To describe the extent and effectiveness of strategies that have been used to improve linkages between primary healthcare (PHC) and chronic disease self-management programmes, especially for disadvantaged patients. Methods: A systematic review of the published peer-reviewed literature. Studies conducted in an Organisation for Economic Co-operation and Development country evaluating a group self-management programme of at least 4-week duration with some linkage between PHC and the programme were included. Linkage strategies were qualitatively derived. Studies were descriptively analysed in terms of the type of self-management programme, strategy for linking with PHC, culturally and linguistically diverse and socio-economic status and impact on health service usage. Results: Sixteen studies were identified that used linkage strategies for a variety of functions—supporting communication, ongoing clinical care, programme development, recruitment or implementation. Of the four studies that evaluated impact on health service use, only one reported a positive change. Discussion: Few programmes of self-management support included specific strategies to increase linkages with PHC as part of their intervention. There is insufficient evidence to determine which strategies or linkages are more effective and in what context.