bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Quassinoid Derivative NBT-272 Targets Both the AKT and ERK Signaling Pathways in Embryonal Tumors
Authors: Castelletti Deborah , Fiaschetti Giulio , Di Dato Valeria , Ziegler Urs , Kumps Candy , De Preter Katleen , Zollo Massimo , Speleman Frank , Shalaby Tarek , De Martino Daniela , Berg Thorsten , Eggert Angelika , Arcaro Alexandre , Grotzer Michael A. 
Published: October 2010

Abstract
The quassinoid analogue NBT-272 has been reported to inhibit MYC, thus warranting a further effort 7to better understand its preclinical properties in models of embryonal tumors (ET), a family of childhood malignancies sharing relevant biological and genetic features such as deregulated expression of MYC oncogenes. In our study, NBT-272 displayed a strong antiproliferative activity in vitro that resulted from the combination of diverse biological effects, ranging from G1/S arrest of the cell cycle to apoptosis and autophagy. The compound prevented the full activation of both eukaryotic translation initiation factor 4E (eIF4E) and its binding protein 4EBP-1, regulating cap-dependent protein translation. Interestingly, all responses induced by NBT-272 in ET could be attributed to interference with 2 main proproliferative signaling pathways, that is, the AKT and the MEK/extracellular signal-regulated kinase pathways. These findings also suggested that the depleting effect of NBT-272 on MYC protein expression occurred via indirect mechanisms, rather than selective inhibition. Finally, the ability of NBT-272 to arrest tumor growth in a xenograft model of neuroblastoma plays a role in the strong antitumor activity of this compound, both in vitro and in vivo, with its potential to target cell-survival pathways that are relevant for the development and progression of ET. Mol Cancer Ther; 9(12); 3145–57. ©2010 AACR.
Targeting Aldehyde Dehydrogenase Cancer Stem Cells in Ovarian Cancer
Authors: Landen Charles N. , Goodman Blake , Katre Ashwini A. , Steg Adam D. , Nick Alpa M. , Stone Rebecca L. , Miller Lance D. , Mejia Pablo Vivas , Jennings Nicolas B. , Gershenson David M. , Bast Robert C. , Coleman Robert L. , Lopez-Berestein Gabriel , Sood Anil K. 
Published: October 2010

Abstract
Aldehyde dehydrogenase-1A1 (ALDH1A1) expression characterizes a subpopulation of cells with tumor-initiating or cancer stem cell properties in several malignancies. Our goal was to characterize the phenotype of ALDH1A1-positive ovarian cancer cells and examine the biological effects of ALDH1A1 gene silencing. In our analysis of multiple ovarian cancer cell lines, we found that ALDH1A1 expression and activity was significantly higher in taxane- and platinum-resistant cell lines. In patient samples, 72.9% of ovarian cancers had ALDH1A1 expression in which the percentage of ALDH1A1-positive cells correlated negatively with progression-free survival (6.05 vs. 13.81 months; P &lt; 0.035). Subpopulations of A2780cp20 cells with ALDH1A1 activity were isolated for orthotopic tumor–initiating studies, where tumorigenicity was approximately 50-fold higher with ALDH1A1-positive cells. Interestingly, tumors derived from ALDH1A1-positive cells gave rise to both ALDH1A1-positive and ALDH1A1-negative populations, but ALDH1A1-negative cells could not generate ALDH1A1-positive cells. In an in vivo orthotopic mouse model of ovarian cancer, ALDH1A1 silencing using nanoliposomal siRNA sensitized both taxane- and platinum-resistant cell lines to chemotherapy, significantly reducing tumor growth in mice compared with chemotherapy alone (a 74%–90% reduction; P &lt; 0.015). These data show that the ALDH1A1 subpopulation is associated with chemoresistance and outcome in ovarian cancer patients, and targeting ALDH1A1 sensitizes resistant cells to chemotherapy. ALDH1A1-positive cells have enhanced, but not absolute, tumorigenicity but do have differentiation capacity lacking in ALDH1A1-negative cells. This enzyme may be important for identification and targeting of chemoresistant cell populations in ovarian cancer. Mol Cancer Ther; 9(12); 3186–99. ©2010 AACR.
GD3 Synthase Expression Enhances Proliferation and Tumor Growth of MDA-MB-231 Breast Cancer Cells through c-Met Activation
Authors: Cazet Aurélie , Lefebvre Jonathan , Adriaenssens Eric , Julien Sylvain , Bobowski Marie , Grigoriadis Anita , Tutt Andrew , Tulasne David , Le Bourhis Xuefen , Delannoy Philippe 
Published: October 2010

Abstract
The disialoganglioside GD3 is overexpressed in ∼50% of invasive ductal breast carcinoma, and the GD3 synthase gene (ST8SIA1) displays higher expression among estrogen receptor–negative breast cancer tumors, associated with a decreased overall survival of breast cancer patients. However, no relationship between ganglioside expression and breast cancer development and aggressiveness has been reported. We have previously shown that overexpression of GD3 synthase induces the accumulation of b- and c-series gangliosides (GD3, GD2, and GT3) at the cell surface of MDA-MB-231 breast cancer cells together with the acquisition of a proliferative phenotype in the absence of serum. Here, we show that phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways are constitutively activated in GD3 synthase–expressing cells. Analysis of phosphorylation of tyrosine kinase receptors shows a specific c-Met constitutive activation in GD3 synthase–expressing cells, in the absence of its ligand, hepatocyte growth factor/scatter factor. In addition, inhibition of c-Met or downstream signaling pathways reverses the proliferative phenotype. We also show that GD3 synthase expression enhances tumor growth in severe combined immunodeficient mice. Finally, a higher expression of ST8SIA1 and MET in the basal subtype of human breast tumors are observed. Altogether, our results show that GD3 synthase expression is sufficient to enhance the tumorigenicity of MDA-MB-231 breast cancer cells through a ganglioside-dependent activation of the c-Met receptor. Mol Cancer Res; 8(11); 1526–35. ©2010 AACR.
After This Strange Starting: Method, Theory and the Philosophy of Religion(s)
Authors: Rennie Bryan 
Published: October 2010

AbstractThis paper argues for the ineluctably philosophical nature of “method and theory” in the academic study of religion. More to the point, it encourages a significant re-consideration of what passes for the “Philosophy of Religion,” a subfield whose concentration on mediaeval and contemporary Christian philosophical theology has impeded the development of an effective philosophical treatment of global human religious behavior. The paper seeks a History of Religions that is more informed by and about philosophy as a tradition and as a method and which therefore includes a disciplinary Philosophy of Religion(s) that is more relevant, practical, far-ranging, and productive.
Reflections on the Limits of Reflection: An Invitation to the Discursive Study of Religion
Authors: von Stuckrad Kocku 
Published: October 2010

AbstractIt has repeatedly been claimed that the study of religion should not essentialize “religion” as an object of study that exists “out there,” waiting for us to discover and understand “it.” Reflection on the contexts and hidden agendas of concepts of religion are part and parcel of scholarly activity. But can there be an end to such a circle of reflection? This paper argues that definitions of and approaches to religion are intrinsically linked to the episteme and the discourse of the time. After clarifying the terms “discourse,” “episteme,” and “field,” this dynamic is exemplified with the emergence of the academic field of “Western esotericism.” The paper concludes that rather than looking for a better definition of religion, the academic study of religion should focus on describing, analyzing, and demarcating the religious fields of discourse. These fields are both the object of study for scholars of religion and the scholars’ habitat.
The Trouble with Transcendence: Carl Schmitt’s “Exception” as a Challenge for Religious Studies
Authors: Yelle Robert 
Published: October 2010

AbstractThe Weimar- and Nazi-era legal theorist Carl Schmitt was one of the first to recognize that Max Weber’s theory of “disenchantment” encoded Protestant presuppositions. Despite his unsavory politics, I argue that Schmitt’s thesis—namely, that secular liberalism is a disguised and disenchanted “political theology” which depends on an exclusion of charismatic ruptures in the natural and moral orders—must be taken seriously. A genealogy of the prohibition of the miracle by the radical Reformation provides evidence for Schmitt’s contention that an ostensibly secular modernity, no less than its theological opponents, has had its own trouble with transcendence or the “exception.”
Negotiating Respectable Masculinity: Gender and Recognition in the Somali Diaspora
Authors: Kleist Nauja 
Published: October 2010

AbstractFollowing years of civil war, many Somalis are displaced in Western countries as refugees or family re-unified persons. This situation has caused multiple losses of social position and upheavals in gender relations. Although both men and women are subject to these changes, Somalis describe the situations of men as more difficult. Taking departure in multi-sited fieldwork in Copenhagen, Somaliland and London, this article explores how Somalis negotiate respectable masculinity in the Diaspora, arguing that men’s difficulties are articulated as a transfer of male authority to the welfare state, reflecting female empowerment and male misrecognition. However, the focus on men’s loss can also be understood as processes of positioning and of re-instituting a ‘traditional’ gender baseline in which the positions of respectable versus failed masculinity are established. Finally, the article argues that Somali men negotiate and enact respectable masculinity through associational and community involvement, creating alternative social spaces of recognition.
African Americans, African Immigrants and Homeland-Diaspora Development in Africa
Authors: Alex-Assensoh Yvette M. 
Published: October 2010

AbstractMainstream understandings of nation-state development focus primarily on economic factors, consequently rendering invisible other viable ways, through which important development occurs in African societies. In extending the current theoretical framework beyond its focus on economics to encompass political, human capital and technological development, this article provides evidence linking African Americans to African attempts at development, first in Ethiopia, which remained uncolonised until 1938 and then through Ghana, which became the first sub-Saharan African nation to gain its independence from British colonial rule. The resulting theoretical payoff includes a broadened concept of development, which much more accurately represents and predicts reality. Empirically, the findings offer much-needed insight about the relationship, correspondence and differences between African historical Diaspora in the United States and more recent migration movements from African countries.
Negotiating Professionalism, Economics and Moral Obligation: An Appeal for Ethnographic Approaches to African Medical Migration
Authors: Sullivan Noelle C. , Dilger Hansjörg , Garcia David 
Published: October 2010

AbstractThis article provides a preliminary framework of useful methodologies and topics for future ethnographic research on medical migration from Africa to North America. We argue that medical professionals’ migrations must be understood in terms of their multiple struggles for meaning as they negotiate their professional and personal preferences in light of their desires to help rebuild ailing medical systems in their countries of origin. Our ethnographic interviews suggest that networks and family have been of critical importance to medical mobility, as well as providing a potential means of continued involvement in philanthropic investments in their countries of origin. Ultimately, we argue that economic perspectives on medical migration are insufficient, and leave out the complexities of balancing professionalism, personal goals and moral obligation to the country of origin.
Procheirisis: Porphyry Sent. 16 and Plotinus on the similes of the waxen block and the aviary
Authors: Berg Robbert van den 
Published: October 2010

AbstractThis paper studies Sentence 16 of Porphyry’s Pathways to the Intelligible. It is argued that it should be understood against the background of Plotinus’ discussions of the similes of the waxen block and the aviary from Plato’s Theaetetus. The first part of the paper concentrates on Plotinus’ reception of these similes. In the second part of the paper Plotinus’ discussions of the two similes are used to shed light on Sentence 16, in particular on the term προχείρισις. Furthermore it is argued that Porphyry does not reject Plotinus’ claim that, pace Aristotle, intellection does not require imaging.
Spine Abnormalities Depicted by Magnetic Resonance Imaging in Adolescent Rowers
Authors: Maurer Marvin , Soder Ricardo Bernardi , Baldisserotto Matteo 
Published: October 2010

Background: Most lesions of the spine of athletes, which often are detected incidentally, do not cause important symptoms or make the athletes discontinue their physical activities. To better understand the significance of these lesions, new imaging studies have been conducted with asymptomatic athletes in several sports, aiming to detect potentially deleterious and disabling abnormalities. Purpose: To compare the magnetic resonance imaging (MRI) lumbar spine findings in a group of asymptomatic adolescent rowers and in a control group of adolescents matched according to age and sex who do not practice any regular physical activity. Study Design: Cohort study (prevalence); Level of evidence, 3. Methods: Our study evaluated 44 asymptomatic adolescent boys distributed in 2 groups of 22 rowers and 22 control subjects. All the examinations were performed using a 0.35-T open-field MRI unit and evaluated by 2 experienced radiologists blinded to the study groups. Each MRI scan was analyzed for the presence of disc degeneration/desiccation, herniated or bulging disc, pars interarticularis stress reaction, and spondylolysis. The Student t test and the Fisher exact test were used for statistical analyses. Results: Nine rowers (40.9%) had at least 1 abnormality detected by MRI in the lumbar spine, whereas only 2 participants (9.1%) in the control group had at least 1 MRI abnormality ( P = .03). Seven disc changes (31.8%) and 6 pars abnormalities (27.3%) were found in the group of elite rowers. In the control group, 3 disc changes (13.6%) and no pars abnormalities were found in the MR scans. The comparison between groups showed statistically significant differences in stress reaction of the pars articularis. Conclusion: Disc disease and pars interarticularis stress reaction are prevalent abnormalities of the lumbar spine of high-performance rowers.
Strategies for Repair of Radial Tears Close to the Meniscal Rim—Biomechanical Analysis with a Cyclic Loading Protocol
Authors: Herbort Mirco , Siam Sami , Lenschow Simon , Petersen Wolf , Zantop Thore 
Published: October 2010

Background Lateral meniscectomy contributes to early-onset osteoarthritis. Biomechanical properties of sutures repairs for complete radial meniscal tears remain unknown. Hypothesis Double horizontal suture techniques for repair of radial meniscal tears with a shorter distance from the meniscal rim provide significantly higher structural properties than do comparable single-suture techniques with a wider distance from the meniscal rim. Study Design Controlled laboratory study. Methods In 55 fresh-frozen porcine menisci, standardized complete radial meniscal tears were repaired with different distances from the meniscal rim and tear edges and with different numbers of sutures. In group A, the suture was 4 mm from the tear and 8 mm from the meniscal rim; group B, 2 mm from tear; group C, 2 mm from tear, 12 mm from rim; group D, double-loop technique, 2 mm from tear, 5 mm and 10 mm from rim; group E, longitudinal tear sutured with 1 loop, 8 mm from rim, and 4 mm between stitches. The specimens were cyclically loaded 1000 times between 5 and 20 N and loaded to failure. Results All repaired constructs survived the cyclic loading protocol. Compared with the single-loop techniques, the double-loop technique (group D) showed a significantly higher maximum load and yield load and significantly lower displacement after 1000 cycles. Compared with group B, group C had a higher displacement after 1000 cycles (P < .05), and its stiffness showed a descriptive negative trend (P = .09). Displacement after cycling testing in group C was higher than in groups B and D (P < .05). Conclusion Repair of radial meniscal tears with a second suture and shorter distance from the meniscal rim has a positive influence on primary stability. Different distances from tear edges apparently have no influence on structural properties. Clinical Relevance Horizontal sutures for repair of radial meniscal tears provide high stability and can be enhanced with a second horizontal suture and shorter distance from the meniscal rim.
Potential for drug–drug interactions in treating cancer-related nausea and distress
Authors: Saylor Matthew S , Smetana Ronald F 
Published: October 2010

Purpose. To determine the extent and severity of drug–drug interactions between anti-emetics and antipsychotics or antidepressants. Summary. Oncology patients are often required to deal with chemotherapy-induced nausea and vomiting at the same time as psychosocial distress. A review of primary literature, as well as several drug interaction databases, was performed with anti-emetics used in The NCCN® 1.2010 Anti-emesis Guidelines ( n = 11) and all currently US-marketed antidepressants or antipsychotics ( n = 40).1 The results from these databases were compiled into a single easy-to-use chart that portrays the severity of the interaction and brief recommendation.2,3,4 In total, 197 drug–drug interactions out of a total of 440 possible combinations (44.8%) were discovered during the analysis. Conclusions. Although most anti-emetics had several serious interactions with antidepressants or antipsychotics, palonosetron, and granisetron were found to have no significant interactions. The results can be used to avoid or limit drug interactions in the prescribing of new medications for the oncology patient.1,2,3,4
Twelve Years of National Football League Concussion Data
Authors: Casson Ira R. , Viano David C. , Powell John W. , Pellman Elliot J. 
Published: October 2010

Background: Concussion in the National Football League (NFL) remains an important issue. An initial description of the injury epidemiology involved 6 years from 1996 to 2001. Hypothesis: The increased attention to concussions may have resulted in team physicians being more conservative in treating players in recent years. Study Design: Two consecutive 6-year periods (1996-2001 and 2002-2007) were compared to determine changes in the circumstances associated with the injury, the patterns of signs and symptoms, and the players’ time loss from participation in the NFL. Methods: During 2002-2007, concussions were recorded by NFL team physicians and athletic trainers using the same standardized reporting form used from 1996 to 2001. Player position, type of play, concussion signs and symptoms, loss of consciousness, and medical action taken were recorded. Results: There were 0.38 documented concussions per NFL game in 2002-2007—7.6% lower than the 0.42 in the earlier period (1996-2001). The injury rate was lower in quarterbacks and wide receivers but significantly higher in tight ends during the second 6 years. The most frequent symptoms were headaches and dizziness; the most common signs were problems with information processing and immediate recall. During 2002-2007, a significantly lower fraction of concussed players returned to the same game, and more were removed from play. Most concussed players (83.5%) returned to play in < 7 days; the percentage decreased to 57.4% with loss of consciousness. The number of players returning in < 7 days was 8% lower during 2002-2007 and 25% lower for those with loss of consciousness. Conclusion: The most recent 6 years of NFL concussion data show a remarkable similarity to the earlier period. However, there was a significant decrease in the percentage of players returning to the same game, and players were held out of play longer. Clinical Relevance: There was a more conservative management of concussion in NFL players from 2002 to 2007 even though the clinical signs and symptoms remained similar to the earlier 6-year period.
Stimulation and inhibition of FVIII-specific memory B-cell responses by CpG-B (ODN 1826), a ligand for Toll-like receptor 9
Authors: Allacher Peter , Baumgartner Christina K. , Pordes Aniko G. , Ahmad Rafi U. , Schwarz Hans Peter , Reipert Birgit M. 
Published: October 2010

Abstract
Factor VIII (FVIII)–specific memory B cells are essential components for regulating anamnestic antibody responses against FVIII in hemophilia A with FVIII inhibitors. We asked how stimulation and inhibition of FVIII-specific memory B cells by low and high concentrations of FVIII, respectively, are affected by concurrent activation of the innate immune system. Using CD138− spleen cells from hemophilic mice treated with FVIII to study restimulation and differentiation of memory B cells in vitro, we tested modulating activities of agonists for Toll-like receptors (TLRs) 2, 3, 4, 5, 7, and 9. Ligands for TLR7 and 9 were most effective. They not only amplified FVIII-specific memory responses in the presence of stimulating concentrations of FVIII, but also countered inhibition in the presence of inhibitory concentrations of FVIII. Notably, CpG oligodeoxynucleotide (CpG-ODN), a ligand for TLR9, expressed biphasic effects. It amplified memory responses at low concentrations and inhibited memory responses at high concentrations, both in vitro and in vivo. Both stimulatory and inhibitory activities of CpG-ODN resulted from specific interactions with TLR9. Despite their strong immunomodulatory effects in the presence of FVIII, ligands for TLR induced negligible restimulation in the absence of FVIII in vitro and no restimulation in the absence of FVIII in vivo.
Constitutive BR3 receptor signaling in diffuse, large B-cell lymphomas stabilizes nuclear factor-κB–inducing kinase while activating both canonical and alternative nuclear factor-κB pathways
Authors: Pham Lan V. , Fu Lingchen , Tamayo Archito T. , Bueso-Ramos Carlos , Drakos Elias , Vega Francisco , Medeiros L. Jeffrey , Ford Richard J. 
Published: October 2010

Abstract
Aberrant nuclear factor κB (NF-κB) signaling has been found to be of particular importance in diffuse, large B-cell lymphoma (DLBCL) cell survival and proliferation. Although the canonical NF-κB signaling pathway has been studied in some detail, activation of the alternative NF-κB pathway in DLBCL is not well characterized. Important insights into the regulation of the alternative NF-κB pathway in B lymphocytes has recently revealed the regulatory importance of the survival kinase NIK (NF-κB–inducing kinase) in genetically engineered murine models. Our studies demonstrate that both the canonical and alternative NF-κB pathways are constitutively activated in DLBCL. We also demonstrate that NIK kinase aberrantly accumulates in DLBCL cells due to constitutive activation of B-cell activation factor (BAFF)–R (BR3) through interaction with autochthonous B-lymphocyte stimulator (BLyS) ligand in DLBCL cells. Activation of BR3 in DLBCL induces recruitment and degradation of tumor necrosis factor receptor-associated factor 3, which results in NIK kinase accumulation, IκBα phosphorylation, and NF-κB p100 processing, thereby resulting in continuous activation of both NF-κB pathways in DLBCL cells, leading to autonomous lymphoma cell growth and survival. These results further elucidate mechanisms involved in abnormal NF-κB activation in DLBCL, and should contribute to better future therapeutic approaches for patients with DLBCL.