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61.
Valérie D. V. Sankatsing Nicolien T. van Ravesteyn Eveline A. M. Heijnsdijk Mireille J. M. Broeders Harry J. de Koning 《International journal of cancer. Journal international du cancer》2020,147(11):3059-3067
In mammography screening programmes, women are screened according to a one-size-fits-all principle. Tailored screening, based on risk levels, may lead to a better balance of benefits and harms. With microsimulation modelling, we determined optimal mammography screening strategies for women at lower (relative risk [RR] 0.75) and higher (RR 1.8) than average risk of breast cancer, eligible for screening, using the incremental cost-effectiveness ratio (ICER) of current uniform screening in the Netherlands (biennial [B] 50-74) as a threshold ICER. Strategies varied by interval (annual [A], biennial, triennial [T]) and age range. The number of life-years gained (LYG), breast cancer deaths averted, overdiagnosed cases, false-positive mammograms, ICERs and harm-benefit ratios were calculated. Optimal risk-based screening scenarios, below the threshold ICER of €8883/LYG, were T50-71 (€7840/LYG) for low-risk and B40-74 (€6062/LYG) for high-risk women. T50-71 screening in low-risk women resulted in a 33% reduction in false-positive findings, a similar reduction in costs and improved harm-benefit ratios compared to the current screening schedule. B40-74 in high-risk women led to an increase in screening benefit, compared to current B50-74 screening, but a relatively higher increase in false-positive findings. In conclusion, optimal screening consisted of a longer interval and lower stopping age than current uniform screening for low-risk women, and a lower starting age for high-risk women. Extending the interval for women at lower risk from biennial to triennial screening reduced harms and costs while maintaining most of the screening benefit. 相似文献
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Mireille Centlivre Maxime Petit Andrew J. Hutton Mélody Dufossée David Boccara Maurice Mimoun Angèle Soria Béhazine Combadière 《Experimental dermatology》2017,26(10):963-966
Development of new immunotherapeutic strategies relies on the ability to activate the right cells at the right place and at the right moment and on the capacity of these cells to home to the right organ(s). Skin delivery has shown high potency for immunotherapeutic administration. However, an adequate in vivo model of human skin immunity is still a critical bottleneck. We demonstrated here that the skin of human immune system mice is colonized by human hematopoietic cells, mainly human T cells and that complementation with human antigen‐presenting cells at the vaccination site allowed the induction of an immune response. 相似文献
64.
Inga Ebermann Jennifer B. Phillips Max C. Liebau Robert K. Koenekoop Bernhard Schermer Irma Lopez Ellen Sch?fer Anne-Francoise Roux Claudia Dafinger Antje Bernd Eberhart Zrenner Mireille Claustres Bernardo Blanco Gudrun Nürnberg Peter Nürnberg Rebecca Ruland Monte Westerfield Thomas Benzing Hanno J. Bolz 《The Journal of clinical investigation》2010,120(6):1812-1823
Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease. 相似文献
65.
Laurent Sulpice Michel Rayar Bruno Turlin Eveline Boucher Pascale Bellaud Mireille Desille Bernard Meunier Bruno Clément Karim Boudjema Cédric Coulouarn 《The Journal of surgical research》2014
Background
Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC.Methods
Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes.Results
Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3–5.1; P = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2–4.2; P = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival (P = 0.035).Conclusions
Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment. 相似文献66.
Duchenne muscular dystrophy (DMD) is a common childhood lethal X-linked recessive disorder, resulting from deletions, duplications and point mutations in the dystrophin gene. Single-cell protocols for preimplantation genetic diagnosis (PGD) still remain challenging due to the enormous size of the gene and the high risk of intragenic recombination, limitations that often lead to sex determination and selection of female embryos. This study describes direct and rapid decaplex and dodecaplex polymerase chain reaction protocols enabling the analysis of five or seven exons and four microsatellite markers scattered along the dystrophin gene, chosen to be located in the two deletion hotspots, and the analysis of amelogenin sequences for gender determination. The dodecaplex protocol may be applied to most of the couples requesting PGD for DMD in whom the female partner is a carrier of a deletion. This generic approach will allow prompt response to the PGD referrals by reducing the pre-clinical PGD work-up. It was successfully applied in three DMD families, resulting in the birth of a girl as well as in a healthy ongoing pregnancy. 相似文献
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68.
PiggyMac,a domesticated piggyBac transposase involved in programmed genome rearrangements in the ciliate Paramecium tetraurelia
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Céline Baudry Sophie Malinsky Matthieu Restituito Aurélie Kapusta Sarah Rosa Eric Meyer Mireille Bétermier 《Genes & development》2009,23(21):2478-2483
Programmed genome rearrangements drive functional gene assembly in ciliates during the development of the somatic macronucleus. The elimination of germline sequences is directed by noncoding RNAs and is initiated by DNA double-strand breaks, but the enzymes responsible for DNA cleavage have not been identified. We show here that PiggyMac (Pgm), a domesticated piggyBac transposase, is required for these rearrangements in Paramecium tetraurelia. A GFP-Pgm fusion localizes in developing macronuclei, where rearrangements take place, and RNAi-mediated silencing of PGM abolishes DNA cleavage. This is the first in vivo evidence suggesting an essential endonucleolytic function of a domesticated piggyBac transposase. 相似文献
69.
Mouna Barat-Houari Karine Nguyen Rafa?lle Bernard C��line Fernandez Catherine Vovan Corinne Bareil Philippe Khau Van Kien Delphine Thorel Sylvie Tuffery-Giraud Francis Vasseur Shahram Attarian Jean Pouget Anne Girardet Nicolas L��vy Mireille Claustres 《European journal of human genetics : EJHG》2010,18(5):533-538
70.
Vanessa Rouzier Karine Severe Marc Antoine Jean Juste Mireille Peck Christian Perodin Patrice Severe Marie Marcelle Deschamps Rose Irene Verdier Sabine Prince Jeannot Francois Jean Ronald Cadet Florence D. Guillaume Peter F. Wright Jean W. Pape 《The American journal of tropical medicine and hygiene》2013,89(4):671-681
Successful and sustained efforts have been made to curtail the major cholera epidemic that occurred in Haiti in 2010 with the promotion of hygiene and sanitation measures, training of health personnel and establishment of treatment centers nationwide. Oral cholera vaccine (OCV) was introduced by the Haitian Ministry of Health as a pilot project in urban and rural areas. This paper reports the successful OCV pilot project led by GHESKIO Centers in the urban slums of Port-au-Prince where 52,357 persons received dose 1 and 90.8% received dose 2; estimated coverage of the at-risk community was 75%. This pilot study demonstrated the effort, community mobilization, and organizational capacity necessary to achieve these results in a challenging setting. The OCV intervention paved the way for the recent launching of a national cholera vaccination program integrated in a long-term ambitious and comprehensive plan to address Haiti''s critical need in water security and sanitation. 相似文献