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Author Vershkov, D.; Benvenisty, N. url  doi
openurl 
  Title Human pluripotent stem cells in modeling human disorders: the case of fragile X syndrome Type Journal Article
  Year 2017 Publication Regenerative Medicine Abbreviated Journal Regen Med  
  Volume (up) 12 Issue 1 Pages 53-68  
  Keywords disease modeling; drug discovery; embryonic stem cells; fragile X syndrome; human pluripotent stem cells; neural differentiation  
  Abstract Human pluripotent stem cells (PSCs) generated from affected blastocysts or from patient-derived somatic cells are an emerging platform for disease modeling and drug discovery. Fragile X syndrome (FXS), the leading cause of inherited intellectual disability, was one of the first disorders modeled in both embryonic stem cells and induced PCSs and can serve as an exemplary case for the utilization of human PSCs in the study of human diseases. Over the past decade, FXS-PSCs have been used to address the fundamental questions regarding the pathophysiology of FXS. In this review we summarize the methodologies for generation of FXS-PSCs, discuss their advantages and disadvantages compared with existing modeling systems and describe their utilization in the study of FXS pathogenesis and in the development of targeted treatment.  
  Address The Azrieli Center for Stem Cells & Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1746-0751 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27900874 Approved no  
  Call Number ref @ user @ Serial 95909  
Permanent link to this record
 

 
Author Khalifa, J.; Tensaouti, F.; Lusque, A.; Plas, B.; Lotterie, J.-A.; Benouaich-Amiel, A.; Uro-Coste, E.; Lubrano, V.; Cohen-Jonathan Moyal, E. url  doi
openurl 
  Title Subventricular zones: new key targets for glioblastoma treatment Type Journal Article
  Year 2017 Publication Radiation Oncology (London, England) Abbreviated Journal Radiat Oncol  
  Volume (up) 12 Issue 1 Pages 67  
  Keywords Glioblastoma; Prognostic factors; Radiotherapy; Stem-cell niche; Subventricular Zone  
  Abstract BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic factors of survival and patterns of recurrence among patients with glioblastoma. METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our Cancer Center between 2006 and 2010 were identified. All patients received surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral (iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively segmented and radiation dose-volume histograms were generated. Multivariate analysis using the Cox proportional hazards model was assessed to examine the relationship between prognostic factors and time to progression (TTP) or overall survival (OS). RESULTS: Median age was 59 years (range: 25-85). Median follow-up, OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5-26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs 41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation dose coverage was compatible with an hippocampal sparing. On multivariate analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047, respectively). CONCLUSION: Our results suggest that contact to SVZ, as well as insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest for optimizing glioblastoma treatment.  
  Address INSERM U1037, Centre de Recherche contre le Cancer de Toulouse, 1 avenue Irene Joliot-Curie, Toulouse Cedex, 31059, France  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1748-717X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28424082 Approved no  
  Call Number ref @ user @ Serial 96593  
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Author Brown, D.V.; Filiz, G.; Daniel, P.M.; Hollande, F.; Dworkin, S.; Amiridis, S.; Kountouri, N.; Ng, W.; Morokoff, A.P.; Mantamadiotis, T. url  doi
openurl 
  Title Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume (up) 12 Issue 2 Pages e0172791  
  Keywords AC133 Antigen/*metabolism; Animals; Antigens, CD44/*metabolism; Basic Helix-Loop-Helix Transcription Factors/metabolism; Biomarkers, Tumor/metabolism; Brain Neoplasms/*metabolism/pathology; Cell Proliferation; Female; Glioblastoma/*metabolism/pathology; Humans; Hypoxia; Mice; Mice, Inbred BALB C; Neoplasm Recurrence, Local; Neoplastic Stem Cells/*metabolism/pathology; Nerve Tissue Proteins/metabolism; Phenotype  
  Abstract Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC). CD133 expression has been used as a marker of GSCs, however recent evidence suggests the relationship between CD133 expression, GSCs and molecular subtype is more complex than initially proposed. The expression of CD133, Olig2 and CD44 was investigated using patient derived glioma stem-like cells (PDGCs) in vitro and in vivo. Different PDGCs exhibited a characteristic equilibrium of distinct CD133+ and CD44+ subpopulations and the influence of environmental factors on the intra-tumor equilibrium of CD133+ and CD44+ cells in PDGCs was also investigated, with hypoxia inducing a CD44+ to CD133+ shift and chemo-radiotherapy inducing a CD133+ to CD44+ shift. These data suggest that surveillance and modulation of intra-tumor heterogeneity using molecular markers at initial surgery and surgery for recurrent GBM may be important for more effective management of GBM.  
  Address Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28241049 Approved no  
  Call Number ref @ user @ Serial 96604  
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Author Chae, S.; Desai, S.; Crowell, M.; Sedgh, G.; Singh, S. url  doi
openurl 
  Title Characteristics of women obtaining induced abortions in selected low- and middle-income countries Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume (up) 12 Issue 3 Pages e0172976  
  Keywords Abortion, Legal/*economics/psychology/*statistics & numerical data; Adolescent; Adult; Africa; Asia; Caribbean Region; Developing Countries/*economics; Educational Status; Europe; Female; Humans; Latin America; Marital Status/statistics & numerical data; Parity/physiology; Poverty/psychology/*statistics & numerical data; Pregnancy; *Pregnancy, Unplanned  
  Abstract BACKGROUND: In 2010-2014, approximately 86% of abortions took place in low- and middle-income countries (LMICs). Although abortion incidence varies minimally across geographical regions, it varies widely by subregion and within countries by subgroups of women. Differential abortion levels stem from variation in the level of unintended pregnancies and in the likelihood that women with unintended pregnancies obtain abortions. OBJECTIVES: To examine the characteristics of women obtaining induced abortions in LMICs. METHODS: We use data from official statistics, population-based surveys, and abortion patient surveys to examine variation in the percentage distribution of abortions and abortion rates by age at abortion, marital status, parity, wealth, education, and residence. We analyze data from five countries in Africa, 13 in Asia, eight in Europe, and two in Latin America and the Caribbean (LAC). RESULTS: Women across all sociodemographic subgroups obtain abortions. In most countries, women aged 20-29 obtained the highest proportion of abortions, and while adolescents obtained a substantial fraction of abortions, they do not make up a disproportionate share. Region-specific patterns were observed in the distribution of abortions by parity. In many countries, a higher fraction of abortions occurred among women of high socioeconomic status, as measured by wealth status, educational attainment, and urban residence. Due to limited data on marital status, it is unknown whether married or unmarried women make up a larger share of abortions. CONCLUSIONS: These findings help to identify subgroups of women with disproportionate levels of abortion, and can inform policies and programs to reduce the incidence of unintended pregnancies; and in LMICs that have restrictive abortion laws, these findings can also inform policies to minimize the consequences of unsafe abortion and motivate liberalization of abortion laws. Program planners, policymakers, and advocates can use this information to improve access to safe abortion services, postabortion care, and contraceptive services.  
  Address Guttmacher Institute, New York, New York, United States of America  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28355285 Approved no  
  Call Number ref @ user @ Serial 97183  
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Author Ross, I.; Mejia, C.; Melendez, J.; Chan, P.A.; Nunn, A.C.; Powderly, W.; Goodenberger, K.; Liu, J.; Mayer, K.H.; Patel, R.R. url  doi
openurl 
  Title Awareness and attitudes of pre-exposure prophylaxis for HIV prevention among physicians in Guatemala: Implications for country-wide implementation Type Journal Article
  Year 2017 Publication PloS one Abbreviated Journal PLoS One  
  Volume (up) 12 Issue 3 Pages e0173057  
  Keywords Adult; Anti-HIV Agents/therapeutic use; *Attitude of Health Personnel; Cross-Sectional Studies; Female; Guatemala; HIV Infections/*prevention & control; *Health Knowledge, Attitudes, Practice; Humans; Logistic Models; Male; Middle Aged; Physicians/psychology; Practice Patterns, Physicians'/*statistics & numerical data; Pre-Exposure Prophylaxis/*statistics & numerical data; Surveys and Questionnaires  
  Abstract INTRODUCTION: HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts. METHODS: We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP. RESULTS: Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for willingness to prescribe PrEP. In multivariate logistic regression, being a non-ID specialist was a significant predictor. CONCLUSIONS: Guatemalan physicians at an urban public hospital were PrEP aware and willing to prescribe, but few have actually done so yet. Future education programs should address the concerns identified, including the low potential for the development of antiretroviral resistance. These findings can aid PrEP implementation efforts in Guatemala.  
  Address Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, United States of America  
  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 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28257475 Approved no  
  Call Number ref @ user @ Serial 97185  
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