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Author (up) Guerrero, P.A.; Tchaicha, J.H.; Chen, Z.; Morales, J.E.; McCarty, N.; Wang, Q.; Sulman, E.P.; Fuller, G.; Lang, F.F.; Rao, G.; McCarty, J.H.
Title Glioblastoma stem cells exploit the alphavbeta8 integrin-TGFbeta1 signaling axis to drive tumor initiation and progression Type Journal Article
Year 2017 Publication Oncogene Abbreviated Journal Oncogene
Volume Issue Pages
Keywords
Abstract Glioblastoma (GBM) is a primary brain cancer that contains populations of stem-like cancer cells (GSCs) that home to specialized perivascular niches. GSC interactions with their niche influence self-renewal, differentiation and drug resistance, although the pathways underlying these events remain largely unknown. Here, we report that the integrin alphavbeta8 and its latent transforming growth factor beta1 (TGFbeta1) protein ligand have central roles in promoting niche co-option and GBM initiation. alphavbeta8 integrin is highly expressed in GSCs and is essential for self-renewal and lineage commitment in vitro. Fractionation of beta8high cells from freshly resected human GBM samples also reveals a requirement for this integrin in tumorigenesis in vivo. Whole-transcriptome sequencing reveals that alphavbeta8 integrin regulates tumor development, in part, by driving TGFbeta1-induced DNA replication and mitotic checkpoint progression. Collectively, these data identify the alphavbeta8 integrin-TGFbeta1 signaling axis as crucial for exploitation of the perivascular niche and identify potential therapeutic targets for inhibiting tumor growth and progression in patients with GBM.Oncogene advance online publication, 7 August 2017; doi:10.1038/onc.2017.248.
Address Department of Neurosurgery, M. D. Anderson Cancer Center, Houston, TX, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0950-9232 ISBN Medium
Area Expedition Conference
Notes PMID:28783169 Approved no
Call Number ref @ user @ Serial 96572
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Author (up) Harling, G.; Lima Neto, A.S.; Sousa, G.S.; Machado, M.M.T.; Castro, M.C.
Title Determinants of tuberculosis transmission and treatment abandonment in Fortaleza, Brazil Type Journal Article
Year 2017 Publication BMC Public Health Abbreviated Journal BMC Public Health
Volume 17 Issue 1 Pages 508
Keywords Brazil; Epidemiology; Fortaleza; Social determinants; Spatial analysis; Treatment; Treatment failure; Tuberculosis
Abstract BACKGROUND: Tuberculosis (TB) remains a public health problem, despite recent achievements in reducing incidence and mortality rates. In Brazil, these achievements were above the worldwide average, but marked by large regional heterogeneities. In Fortaleza (5th largest city in Brazil), the tuberculosis cure rate has been declining and treatment abandonment has been increasing in the past decade, despite a reduction in incidence and an increase in directly observed therapy (DOT). These trends put efforts to eliminate tuberculosis at risk. We therefore sought to determine social and programmatic determinants of tuberculosis incidence and treatment abandonment in Fortaleza. METHODS: We analyzed sociodemographic and clinical data for all new tuberculosis cases notified in the Notifiable Diseases Information System (SINAN) from Fortaleza between 2007 and 2014. We calculated incidence rates for 117 neighborhoods in Fortaleza, assessed their spatial clustering, and used spatial regression models to quantify associations between neighborhood-level covariates and incidence rates. We used hierarchical logistic regression models to evaluate how individual- and neighborhood-level covariates predicted tuberculosis treatment abandonment. RESULTS: There were 12,338 new cases reported during the study period. Case rates across neighborhoods were significantly positively clustered in two low-income areas close to the city center. In an adjusted model, tuberculosis rates were significantly higher in neighborhoods with lower literacy, higher sewerage access and homicide rates, and a greater proportion of self-reported black residents. Treatment was abandoned in 1901 cases (15.4%), a rate that rose by 71% between 2007 and 2014. Abandonment was significantly associated with many individual sociodemographic and clinical factors. Notably, being recommended for DOT was protective for those who completed DOT, but associated with abandonment for those who did not. CONCLUSION: Low socioeconomic status areas have higher tuberculosis rates, and low socioeconomic individuals have higher risk of treatment abandonment, in Fortaleza. Treatment abandonment rates are growing despite the advent of universal DOT recommendations in Brazil. Proactive social policies, and active contact tracing to find missed cases, may help reduce the tuberculosis burden in this setting.
Address Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Building I, Room 1113, Boston, MA, 02115, USA. mcastro@hsph.harvard.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1471-2458 ISBN Medium
Area Expedition Conference
Notes PMID:28545423 Approved no
Call Number ref @ user @ Serial 97635
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Author (up) Heffernan, J.M.; McNamara, J.B.; Borwege, S.; Vernon, B.L.; Sanai, N.; Mehta, S.; Sirianni, R.W.
Title PNIPAAm-co-Jeffamine(R) (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells Type Journal Article
Year 2017 Publication Biomaterials Abbreviated Journal Biomaterials
Volume 143 Issue Pages 149-158
Keywords Brain tumor initiating cells; Cancer stem cells; Radioresistance; Temperature responsive polymer scaffolds; Tissue engineering
Abstract Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance. Therefore, identifying GSC-niche interactions that regulate stem phenotypes may present a unique target for disrupting the maintenance and persistence of this treatment resistant population. In this work, we engineered 3D scaffolds from temperature responsive poly(N-isopropylacrylamide-co-Jeffamine M-1000(R) acrylamide), or PNJ copolymers, as a platform for enriching stem-specific phenotypes in two molecularly distinct human patient-derived GSC cell lines. Notably, we observed that, compared to conventional neurosphere cultures, PNJ cultured GSCs maintained multipotency and exhibited enhanced self-renewal capacity. Concurrent increases in expression of proteins known to regulate self-renewal, invasion, and stem maintenance in GSCs (NESTIN, EGFR, CD44) suggest that PNJ scaffolds effectively enrich the GSC population. We further observed that PNJ cultured GSCs exhibited increased resistance to radiation treatment compared to GSCs cultured in standard neurosphere conditions. GSC radioresistance is supported in vivo by niche microenvironments, and this remains a significant barrier to effectively treating these highly tumorigenic cells. Taken in sum, these data indicate that the microenvironment created by synthetic PNJ scaffolds models niche enrichment of GSCs in patient-derived GBM cell lines, and presents tissue engineering opportunities for studying clinically important behaviors such as radioresistance in vitro.
Address Barrow Brain Tumor Research Center, Barrow Neurological Institute, 350 W Thomas Ave, Phoenix, AZ, 85013, USA; School of Biological and Health Systems Engineering, Arizona State University, PO Box 879709, Tempe, AZ, 85287, USA. Electronic address: rachael.sirianni@dignityhealth.org
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0142-9612 ISBN Medium
Area Expedition Conference
Notes PMID:28802102 Approved no
Call Number ref @ user @ Serial 96570
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Author (up) Herrera-Ballesteros, V.H.; Zuniga, J.; Moreno, I.; Gomez, B.; Roa-Rodriguez, R.
Title [Quitting smoking and willingness to pay for cessation in Panama] Type Journal Article
Year 2017 Publication Salud Publica de Mexico Abbreviated Journal Salud Publica Mex
Volume 59Suppl 1 Issue Suppl 1 Pages 54-62
Keywords
Abstract Objective:: To characterize the desire for cessation and willingness to pay for abandonment therapy. Materials and methods:: The data source is the Global Adult Tobacco Survey (GATS). Cessation and willingness to pay were characterized by sociodemographic (SD) and socioeconomic (SE) variables. Logistic regressions were performed to estimate associations. Results:: A greater desire for cessation was observed in variables: women, education, non-governmental and inactive employees, rural areas, occasional smokers and middle income, and greater willingness to pay, in: education, over 60 years old, non-governmental, self-employed, urban area, occasional smokers and low median income. Conclusions:: There is a high relation between the desire for abandonment, and willingness to pay with SD and SE variables. Cessation therapies can be applied in work centers, and require a change of focus in the intervention.
Address Ministerio de Salud. Panama
Corporate Author Thesis
Publisher Place of Publication Editor
Language Spanish Summary Language Original Title Quienes quieren dejar fumar y su disposicion a pagar por cesacion en Panama
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0036-3634 ISBN Medium
Area Expedition Conference
Notes PMID:28658453 Approved no
Call Number ref @ user @ Serial 98019
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Author (up) Herrero, M.; Thornton, P.K.; Power, B.; Bogard, J.R.; Remans, R.; Fritz, S.; Gerber, J.S.; Nelson, G.; See, L.; Waha, K.; Watson, R.A.; West, P.C.; Samberg, L.H.; van de Steeg, J.; Stephenson, E.; van Wijk, M.; Havlik, P.
Title Farming and the geography of nutrient production for human use: a transdisciplinary analysis Type Journal Article
Year 2017 Publication The Lancet. Planetary Health Abbreviated Journal Lancet Planet Health
Volume 1 Issue 1 Pages e33-e42
Keywords
Abstract BACKGROUND: Information about the global structure of agriculture and nutrient production and its diversity is essential to improve present understanding of national food production patterns, agricultural livelihoods, and food chains, and their linkages to land use and their associated ecosystems services. Here we provide a plausible breakdown of global agricultural and nutrient production by farm size, and also study the associations between farm size, agricultural diversity, and nutrient production. This analysis is crucial to design interventions that might be appropriately targeted to promote healthy diets and ecosystems in the face of population growth, urbanisation, and climate change. METHODS: We used existing spatially-explicit global datasets to estimate the production levels of 41 major crops, seven livestock, and 14 aquaculture and fish products. From overall production estimates, we estimated the production of vitamin A, vitamin B12, folate, iron, zinc, calcium, calories, and protein. We also estimated the relative contribution of farms of different sizes to the production of different agricultural commodities and associated nutrients, as well as how the diversity of food production based on the number of different products grown per geographic pixel and distribution of products within this pixel (Shannon diversity index [H]) changes with different farm sizes. FINDINGS: Globally, small and medium farms (</=50 ha) produce 51-77% of nearly all commodities and nutrients examined here. However, important regional differences exist. Large farms (>50 ha) dominate production in North America, South America, and Australia and New Zealand. In these regions, large farms contribute between 75% and 100% of all cereal, livestock, and fruit production, and the pattern is similar for other commodity groups. By contrast, small farms (</=20 ha) produce more than 75% of most food commodities in sub-Saharan Africa, southeast Asia, south Asia, and China. In Europe, west Asia and north Africa, and central America, medium-size farms (20-50 ha) also contribute substantially to the production of most food commodities. Very small farms (</=2 ha) are important and have local significance in sub-Saharan Africa, southeast Asia, and south Asia, where they contribute to about 30% of most food commodities. The majority of vegetables (81%), roots and tubers (72%), pulses (67%), fruits (66%), fish and livestock products (60%), and cereals (56%) are produced in diverse landscapes (H>1.5). Similarly, the majority of global micronutrients (53-81%) and protein (57%) are also produced in more diverse agricultural landscapes (H>1.5). By contrast, the majority of sugar (73%) and oil crops (57%) are produced in less diverse ones (H</=1.5), which also account for the majority of global calorie production (56%). The diversity of agricultural and nutrient production diminishes as farm size increases. However, areas of the world with higher agricultural diversity produce more nutrients, irrespective of farm size. INTERPRETATION: Our results show that farm size and diversity of agricultural production vary substantially across regions and are key structural determinants of food and nutrient production that need to be considered in plans to meet social, economic, and environmental targets. At the global level, both small and large farms have key roles in food and nutrition security. Efforts to maintain production diversity as farm sizes increase seem to be necessary to maintain the production of diverse nutrients and viable, multifunctional, sustainable landscapes. FUNDING: Commonwealth Scientific and Industrial Research Organisation, Bill & Melinda Gates Foundation, CGIAR Research Programs on Climate Change, Agriculture and Food Security and on Agriculture for Nutrition and Health funded by the CGIAR Fund Council, Daniel and Nina Carasso Foundation, European Union, International Fund for Agricultural Development, Australian Research Council, National Science Foundation, Gordon and Betty Moore Foundation, and Joint Programming Initiative on Agriculture, Food Security and Climate Change-Belmont Forum.
Address International Institute for Applied Systems Analysis, Laxenburg, Austria
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2542-5196 ISBN Medium
Area Expedition Conference
Notes PMID:28670647 Approved no
Call Number ref @ user @ Serial 97264
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