bluuebunny/crossref_metadata_2025_split huggingface dataset:
Worldwide impact of economic cycles on suicide trends over 3 decades: differences according to level of development. A mixed effect model study
Authors: Blasco-Fontecilla Hilario , Perez-Rodriguez M Mercedes , Garcia-Nieto Rebeca , Fernandez-Navarro Pablo , Galfalvy Hanga , de Leon Jose , Baca-Garcia Enrique 
Published: May 2012

ObjectivesTo investigate the trends and correlations of gross domestic product (GDP) adjusted for purchasing power parity (PPP) per capita on suicide rates in 10 WHO regions during the past 30 years.DesignAnalyses of databases of PPP-adjusted GDP per capita and suicide rates. Countries were grouped according to the Global Burden of Disease regional classification system.Data sourcesWorld Bank's official website and WHO's mortality database.Statistical analysesAfter graphically displaying PPP-adjusted GDP per capita and suicide rates, mixed effect models were used for representing and analysing clustered data.ResultsThree different groups of countries, based on the correlation between the PPP-adjusted GDP per capita and suicide rates, are reported: (1) positive correlation: developing (lower middle and upper middle income) Latin-American and Caribbean countries, developing countries in the South East Asian Region including India, some countries in the Western Pacific Region (such as China and South Korea) and high-income Asian countries, including Japan; (2) negative correlation: high-income and developing European countries, Canada, Australia and New Zealand and (3) no correlation was found in an African country.ConclusionsPPP-adjusted GDP per capita may offer a simple measure for designing the type of preventive interventions aimed at lowering suicide rates that can be used across countries. Public health interventions might be more suitable for developing countries. In high-income countries, however, preventive measures based on the medical model might prove more useful.
Mitochondrial Bcl-2 Family Dynamics Define Therapy Response and Resistance in Neuroblastoma
Authors: Goldsmith Kelly C. , Gross Michelle , Peirce Susan , Luyindula Dema , Liu Xueyuan , Vu Annette , Sliozberg Michael , Guo Rong , Zhao Huaqing , Reynolds C. Patrick , Hogarty Michael D. 
Published: May 2012

Abstract
Neuroblastoma is a childhood tumor in which transient therapeutic responses are typically followed by recurrence with lethal chemoresistant disease. In this study, we characterized the apoptotic responses in diverse neuroblastomas using an unbiased mitochondrial functional assay. We defined the apoptotic set point of neuroblastomas using responses to distinct BH3 death domains providing a BH3 response profile and directly confirmed survival dependencies. We found that viable neuroblastoma cells and primary tumors are primed for death with tonic sequestration of Bim, a direct activator of apoptosis, by either Bcl-2 or Mcl-1, providing a survival dependency that predicts the activity of Bcl-2 antagonists. The Bcl-2/Bcl-xL/Bcl-w inhibitor ABT-737 showed single-agent activity against only Bim:Bcl-2 primed tumor xenografts. Durable complete regressions were achieved in combination with noncurative chemotherapy even for highest risk molecular subtypes with MYCN amplification and activating ALK mutations. Furthermore, the use of unique isogenic cell lines from patients at diagnosis and at the time of relapse showed that therapy resistance was not mediated by upregulation of Bcl-2 homologues or loss of Bim priming, but by repressed Bak/Bax activation. Together, our findings provide a classification system that identifies tumors with clinical responses to Bcl-2 antagonists, defines Mcl-1 as the principal mediator of Bcl-2 antagonist resistance at diagnosis, and isolates the therapy resistant phenotype to the mitochondria. Cancer Res; 72(10); 2565–77. ©2012 AACR.
Advances in the Genetics of High-Risk Childhood B-Progenitor Acute Lymphoblastic Leukemia and Juvenile Myelomonocytic Leukemia: Implications for Therapy
Authors: Loh Mignon L. , Mullighan Charles G. 
Published: May 2012

AbstractHematologic malignancies of childhood comprise the most common childhood cancers. These neoplasms derive from the pathologic clonal expansion of an abnormal cancer-initiating cell and span a diverse spectrum of phenotypes, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and myelodysplastic syndromes (MDS). Expansion of immature lymphoid or myeloid blasts with suppression of normal hematopoiesis is the hallmark of ALL and AML, whereas MPN is associated with proliferation of 1 or more lineages that retain the ability to differentiate, and MDS is characterized by abnormal hematopoiesis and cytopenias. The outcomes for children with the most common childhood cancer, B-progenitor ALL (B-ALL), in general, is quite favorable, in contrast to children affected by myeloid malignancies. The advent of highly sensitive genomic technologies reveals the remarkable genetic complexity of multiple subsets of high-risk B-progenitor ALL, in contrast to a somewhat simpler model of myeloid neoplasms, although a number of recently discovered alterations displayed by both types of malignancies may lead to common therapeutic approaches. This review outlines recent advances in our understanding of the genetic underpinnings of high-risk B-ALL and juvenile myelomonocytic leukemia, an overlap MPN/MDS found exclusively in children, and we also discuss novel therapeutic approaches that are currently being tested in clinical trials. Recent insights into the clonal heterogeneity of leukemic samples and the implications for diagnostic and therapeutic approaches are also discussed. Clin Cancer Res; 18(10); 2754–67. ©2012 AACR.
Genetically InFormed Therapies—A “GIFT” for Children with Cancer
Authors: Thiele Carol J. , Cohn Susan L. 
Published: May 2012

Abstract
The national investment that was made in oncology research with the passage of the National Cancer Act in 1971 is now coming to fruition. Nowhere is this more apparent than in the exciting prospects for genetically informed precision medicine as applied to the treatment of children with cancer. The wealth of information gleaned from intensive genetic analyses and NexGen sequencing studies has identified a number of viable targets in leukemias and solid tumors. Our rapidly evolving understanding of the enzymatic controls that regulate chromatin dynamics during normal differentiation of stem cells and their mutation or dysregulation in tumor cells is leading to a new library of therapeutically tractable tumor targets. The recent identification of germline variants associated with toxicity and/or response to therapy has further enhanced our ability to deliver individualized treatments for pediatric cancer patients. Our challenge today is to determine how best to use genomic data and integrate it into evolving clinical protocols to provide more efficacious therapies and a better quality of life for children with cancer. Clin Cancer Res; 18(10); 2735–9. ©2012 AACR.
SAR131675, a Potent and Selective VEGFR-3–TK Inhibitor with Antilymphangiogenic, Antitumoral, and Antimetastatic Activities
Authors: Alam Antoine , Blanc Isabelle , Gueguen-Dorbes Geneviève , Duclos Olivier , Bonnin Jacques , Barron Pauline , Laplace Marie-Claude , Morin Gaelle , Gaujarengues Florence , Dol Frédérique , Hérault Jean-Pascal , Schaeffer Paul , Savi Pierre , Bono Françoise 
Published: May 2012

Abstract
SAR131675 is a potent and selective VEGFR-3 inhibitor. It inhibited VEGFR-3 tyrosine kinase activity and VEGFR-3 autophosphorylation in HEK cells with IC50 values of 20 and 45 nmol/L, respectively. SAR131675 dose dependently inhibited the proliferation of primary human lymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC50 of about 20 nmol/L. SAR131675 was found to be highly selective for VEGFR-3 versus 107 receptors, enzymes, ion channels, and 65 kinases. However, it was moderately active on VEGFR-2 with a VEGFR-3/VEGFR-2 ratio of about 10. SAR131675 had no antiproliferative activity on a panel of 30 tumors and primary cells, further showing its high specificity and indicating that SAR131675 is not a cytotoxic or cytostatic agent. SAR131675 was very well tolerated in mice and showed a potent antitumoral effect in several orthotopic and syngenic models, including mammary 4T1 carcinoma and RIP1.Tag2 tumors. Interestingly, it significantly reduced lymph node invasion and lung metastasis, showing its antilymphangiogenic activity in vivo. Moreover, treatment of mice before resection of 4T1 primary tumors was sufficient to prevent metastasis. Tumor-associated macrophages (TAM) play an important role in tumor growth and metastasis. The expression of VEGFR-3 on TAMs has been recently described. F4/80 immunostaining clearly showed that SAR131675 significantly reduced TAM infiltration and aggregation in 4T1 tumors. Taken together, SAR131675 is the first highly specific VEGFR-3-TK inhibitor described to date, displaying significant antitumoral and antimetastatic activities in vivo through inhibition of lymphangiogenesis and TAM invasion. Mol Cancer Ther; 11(8); 1637–49. ©2012 AACR.
From Baghdad to London: Unraveling Urban Development in Europe, the Middle East, and North Africa, 800–1800
Authors: Bosker Maarten , Buringh Eltjo , van Zanden Jan Luiten 
Published: May 2012

Abstract
This paper empirically investigates why, between 800 and 1800, the urban center of gravity moved from the Islamic world to Europe. Using a large new city-specific data set covering Europe, the Middle East, and North Africa, we unravel the role of geography and institutions in determining long-run city development in the two regions. We find that the main reasons for the Islamic world's stagnation and Europe's long-term success are specific to each region: any significant positive interaction between cities in the two regions hampered by their different main religious orientation. Together, the long-term consequences of a different choice of main transport mode (camel versus ship) and the development of forms of local participative government in Europe that made cities less dependent on the state explain why Europe's urban development eventually outpaced that in the Islamic world.
Efficacy of ICON® Maxx in the laboratory and against insecticide-resistant Anopheles gambiae in central Côte d'Ivoire
Authors: Winkler Mirko S , Tchicaya Emile , Koudou Benjamin G , Donzé Jennifer , Nsanzabana Christian , Müller Pie , Adja Akré M , Utzinger Jürg 
Published: May 2012

Abstract

Background
Long-lasting treatment kits, designed to transform untreated nets into long-lasting insecticidal nets (LLINs), may facilitate high coverage with LLINs where non-treated nets are in place. In this study, the efficacy of ICON® Maxx (Syngenta) was evaluated under laboratory conditions and in an experimental hut trial in central Côte d'Ivoire, where Anopheles gambiae s.s. are resistant to pyrethroid insecticides.

Methods
In the laboratory, polyester and polyethylene net samples were treated with ICON® Maxx, washed up to 20 times and their efficacy determined in World Health Organization (WHO) cone assays against a susceptible laboratory An. gambiae s.s. colony. Over a 12-month period, the polyester nets were evaluated in a hut trial to determine mosquito deterrence, induced exophily, blood-feeding inhibition and mortality.

Results
In the laboratory, ICON® Maxx-treated polyethylene nets showed higher efficacy against pyrethroid-susceptible mosquitoes than polyester nets. After 20 washings, insecticidal efficacy in bioassays was 59.4% knockdown (KD) and 22.3% mortality for polyethylene, and 55.3% KD and 17.9% mortality for polyester nets. In experimental huts, treated nets showed strong deterrence, induced exophily and an over three-fold reduction in blood-fed mosquitoes. More than half (61.8%) of the mosquitoes entering the huts with treated nets were found dead the next morning despite high levels of KD resistance. After washing the treated nets, KD and mortality rates were close to or exceeded predefined WHO thresholds in cone bioassays.

Conclusion
In contrast to previous laboratory investigation, ICON® Maxx-treated nets showed only moderate KD and mortality rates. However, under semi-field conditions, in an area where mosquitoes are resistant to pyrethroids, ICON® Maxx showed high deterrence, induced exophily and provided a significant reduction in blood-feeding rates; features that are likely to have a positive impact in reducing malaria transmission. The WHO cone test may not always be a good proxy for predicting product performance under field conditions.
Employment of a noninvasive magnetic method for evaluation of gastrointestinal transit in rats
Authors: Quini Caio C , Américo Madileine F , Corá Luciana A , Calabresi Marcos FF , Alvarez Matheus , Oliveira Ricardo B , Miranda JoseRicardo A 
Published: May 2012

Abstract
AC Biosusceptometry (ACB) was previously employed towards recording gastrointestinal motility. Our data show a reliable and successful evaluation of gastrointestinal transit of liquid and solid meals in rats, considering the methods scarcity and number of experiments needed to endorsement of drugs and medicinal plants. ACB permits real time and simultaneous experiments using the same animal, preserving the physiological conditions employing both meals with simplicity and accuracy.
Adoption of Gene Expression Profile Testing and Association With Use of Chemotherapy Among Women With Breast Cancer
Authors: Hassett Michael J. , Silver Samuel M. , Hughes Melissa E. , Blayney Douglas W. , Edge Stephen B. , Herman James G. , Hudis Clifford A. , Marcom P. Kelly , Pettinga Jane E. , Share David , Theriault Richard , Wong Yu-Ning , Vandergrift Jonathan L. , Niland Joyce C. , Weeks Jane C. 
Published: May 2012

Purpose Gene expression profile (GEP) testing is a relatively new technology that offers the potential of personalized medicine to patients, yet little is known about its adoption into routine practice. One of the first commercially available GEP tests, a 21-gene profile, was developed to estimate the benefit of adjuvant chemotherapy for hormone receptor–positive breast cancer (HR-positive BC). Patients and Methods By using a prospective registry data set outlining the routine care provided to women diagnosed from 2006 to 2008 with HR-positive BC at 17 comprehensive and community-based cancer centers, we assessed GEP test adoption and the association between testing and chemotherapy use. Results Of 7,375 women, 20.4% had GEP testing and 50.2% received chemotherapy. Over time, testing increased (14.7% in 2006 to 27.5% in 2008; P < .01) and use of chemotherapy decreased (53.9% in 2006 to 47.0% in 2008; P < .01). Characteristics independently associated with lower odds of testing included African American versus white race (odds ratio [OR], 0.70; 95% CI, 0.54 to 0.92) and high school or less versus more than high school education (OR, 0.63; 95% CI, 0.52 to 0.76). Overall, testing was associated with lower odds of chemotherapy use (OR, 0.70; 95% CI, 0.62 to 0.80). Stratified analyses demonstrated that for small, node-negative cancers, testing was associated with higher odds of chemotherapy use (OR, 11.13; 95% CI, 5.39 to 22.99), whereas for node-positive and large node-negative cancers, testing was associated with lower odds of chemotherapy use (OR, 0.11; 95% CI, 0.07 to 0.17). Conclusion There has been a progressive increase in use of this GEP test and an associated shift in the characteristics of and overall reduction in the proportion of women with HR-positive BC receiving adjuvant chemotherapy.
Influence of Sex on the Survival of Patients With Esophageal Cancer
Authors: Bohanes Pierre , Yang Dongyun , Chhibar Ruchika S. , Labonte Melissa J. , Winder Thomas , Ning Yan , Gerger Armin , Benhaim Léonor , Paez David , Wakatsuki Takeru , Loupakis Fotios , El-Khoueiry Rita , Zhang Wu , Lenz Heinz-Josef 
Published: May 2012

Purpose The prognostic value of sex for esophageal cancer survival is currently unclear, and growing data suggest that hormonal influences may account for incidence disparities between men and women. Therefore, moving from the hypothesis that hormones could affect the prognosis of patients with esophageal cancer, we investigated the primary hypothesis that sex is associated with survival and the secondary hypotheses that the relationship between sex and survival depends, at least in part, on age, histology, and race/ethnicity. Patients and Methods By using the SEER databases from 1973 to 2007, we identified 13,603 patients (34%) with metastatic esophageal cancer (MEC) and 26,848 patients (66%) with locoregional esophageal cancer (LEC). Cox proportional hazards model for competing risks were used for analyses. Results In the multivariate analysis, women had longer esophageal cancer-specific survival (ECSS) than men in both MEC (hazard ratio [HR], 0.949; 95% CI, 0.905 to 0.995; P = .029) and LEC (HR, 0.920; 95% CI, 0.886 to 0.955; P < .001) cohorts. When age and histology were accounted for, there was no difference for ECSS between men and women with adenocarcinoma. In contrast, women younger than age 55 years (HR, 0.896; 95% CI, 0.792 to 1.014; P = .081) and those age 55 years or older (HR, 0.905; 95% CI, 0.862 to 0.950; P < .001) with squamous cell LEC had longer ECSS than men. In the squamous cell MEC cohort, only women younger than age 55 years had longer ECSS (HR, 0.823; 95% CI, 0.708 to 0.957; P = .011) than men. Conclusion Sex is an independent prognostic factor for patients with LEC or MEC. As secondary hypotheses, in comparison with men, women age 55 years or older with squamous cell LEC and women younger than age 55 years with squamous cell MEC have a significantly better outcome. These last two findings need further validation.
Intracutaneous and Intravesical Immunotherapy With Keyhole Limpet Hemocyanin Compared With Intravesical Mitomycin in Patients With Non–Muscle-Invasive Bladder Cancer: Results From a Prospective Randomized Phase III Trial
Authors: Lammers Rianne J.M. , Witjes Wim P.J. , Janzing-Pastors Maria H.D. , Caris Christien T.M. , Witjes J. Alfred 
Published: May 2012

Purpose Despite current treatment after transurethral resection of a bladder tumor, recurrences and progression remain a problem. Keyhole limpet hemocyanin (KLH) was beneficial in earlier studies. In this study, safety and efficacy of KLH were compared with that of mitomycin (MM). Patients and Methods Patients with intermediate- and high-risk non–muscle-invasive bladder cancer (NMIBC) without carcinoma in situ were enrolled in a randomized phase III trial. In all, 283 patients were randomly assigned for 16 adjuvant intravesical instillations with KLH after preimmunization, and 270 patients were randomly assigned for 11 adjuvant intravesical instillations with MM. Primary outcome measurement was recurrence-free survival (RFS). Secondary outcome measurements were progression-free survival, adverse events (AEs), and the effect of delayed-type hypersensitivity (DTH) response on clinical outcome. Results There were significantly more pT1 tumors in the MM group (P = .01). In a log-rank test, univariate and multivariate Cox regression analysis, KLH was less effective than MM regarding RFS (all P < .001). Progression was uncommon (n = 20). In univariate Cox regression analyses, KLH tended to prevent progression more effectively than MM, but in multivariate Cox regression analyses, this could not be shown. AEs were common but mild. Fever, flu-like symptoms, and fatigue occurred significantly more after KLH treatment. Allergic reactions and other skin disorders occurred significantly more after MM treatment. Significantly more DTH-positive patients developed a recurrence than DTH-negative patients. Conclusion KLH had a different safety profile and was inferior to MM in preventing NMIBC recurrences. KLH tended to be more effective than MM in preventing progression. More research is needed to clarify the immunologic effects of KLH and the effects of KLH on progression.
Gene Expression Profiling Identifies ESRP1 as a Potential Regulator of Epithelial Mesenchymal Transition in Somatotroph Adenomas from a Large Cohort of Patients with Acromegaly
Authors: Lekva Tove , Berg Jens Petter , Fougner Stine Lyngvi , Olstad Ole Kristoffer , Ueland Thor , Bollerslev Jens 
Published: May 2012

Abstract

Context:
The epithelial marker E-cadherin plays a crucial role in epithelial-mesenchymal transition (EMT). Decreased protein content in somatotroph adenomas has been associated with increased tumor size, invasion, and poor response to somatostatin analog (SA) treatment, but the potential mechanisms of EMT progression in these adenomas are lacking.

Objective:
We hypothesized that characterization of EMT-related transcripts in somatotroph adenomas could identify novel therapeutic targets in individuals with poor response to SA treatment and provide more knowledge of the mechanism of EMT progression.

Patients:
Fifty-three patients with acromegaly participated in the study.

Research Design and Methods:
We performed microarray analysis of 16 adenomas, eight with high expression and eight with low expression of E-cadherin, in order to identify EMT-related transcripts. Candidate transcripts were further explored in vivo in 53 adenomas and in vitro in a rat pituitary GH-producing cell (GH3) after exploring three models for reducing E-cadherin and inducing a mesenchymal phenotype.

Results:
In vivo E-cadherin mRNA expression in tumor tissue is associated negatively with tumor size and invasiveness and positively with GH and IGF-I levels in serum and response to SA treatment. Microarray and subsequent PCR analysis identify several EMT-related genes associated with E-cadherin expression. In vitro, few of these EMT-related genes were regulated by silencing E-cadherin or by TGF-β1 treatment in GH3 cells. In contrast, silencing Esrp1 in GH3 cells regulated many of the EMT-related transcripts.

Conclusion:
These results indicate that ESRP1 could be a master regulator of the EMT process in pituitary adenomas causing acromegaly.
Die Idee eines intergenerationellen Libertarismus
Authors: Rinderle Peter 
Published: May 2012

AbstractThe contents and foundations of intergenerational justice have only recently become the focus of controversial debates in political philosophy. My main purpose in this essay is to outline the idea of an intergenerational libertarianism and contrast it with a skeptical rejection of the moral rights of future persons by contractarians on the one hand and egalitarian conceptions of intergenerational justice by utilitarians on the other. As far as its contents are concerned, the idea contains three main principles: future persons have a moral right to satisfy their basic needs, they have a moral right to develop and exercise their capacity of political and personal autonomy, and they have a moral right to be compensated for harmful actions by their predecessors. And as far as its foundations are concerned, these principles can be justified by a contractualist procedure: considerations of sufficiency, of liberty and of reciprocity cannot reasonably be rejected by either members of future generations or by members of the present one.