303 results on '"P. Uguen"'
Search Results
2. RIS-Enabled NLoS Near-Field Joint Position and Velocity Estimation under User Mobility
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Rahal, Moustafa, Denis, Benoit, Keskin, Musa Furkan, Uguen, Bernard, and Wymeersch, Henk
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Electrical Engineering and Systems Science - Signal Processing - Abstract
In the context of single-base station (BS) non-line-of-sight (NLoS) single-epoch localization with the aid of a reflective reconfigurable intelligent surface (RIS), this paper introduces a novel three-step algorithm that jointly estimates the position and velocity of a mobile user equipment (UE), while compensating for the Doppler effects observed in near-field (NF) at the RIS elements over the short transmission duration of a sequence of downlink (DL) pilot symbols. First, a low-complexity initialization procedure is proposed, relying in part on far-field (FF) approximation and a static user assumption. Then, an alternating optimization procedure is designed to iteratively refine the velocity and position estimates, as well as the channel gain. The refinement routines leverage small angle approximations and the linearization of the RIS response, accounting for both NF and mobility effects. We evaluate the performance of the proposed algorithm through extensive simulations under diverse operating conditions with regard to signal-to-noise ratio (SNR), UE mobility, uncontrolled multipath and RIS-UE distance. Our results reveal remarkable performance improvements over the state-of-the-art (SoTA) mobility-agnostic benchmark algorithm, while indicating convergence of the proposed algorithm to respective theoretical bounds on position and velocity estimation., Comment: 11 pages, 9 figures, journal
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- 2023
3. Review on radiomic analysis in 18F-fluorodeoxyglucose positron emission tomography for prediction of melanoma outcomes
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Amrane, Karim, Meur, Coline Le, Thuillier, Philippe, Berthou, Christian, Uguen, Arnaud, Deandreis, Désirée, Bourhis, David, Bourbonne, Vincent, and Abgral, Ronan
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- 2024
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4. Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy
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Fehlings, Darcy L., Zarrei, Mehdi, Engchuan, Worrawat, Sondheimer, Neal, Thiruvahindrapuram, Bhooma, MacDonald, Jeffrey R., Higginbotham, Edward J., Thapa, Ritesh, Behlim, Tarannum, Aimola, Sabrina, Switzer, Lauren, Ng, Pamela, Wei, John, Danthi, Prakroothi S., Pellecchia, Giovanna, Lamoureux, Sylvia, Ho, Karen, Pereira, Sergio L., de Rijke, Jill, Sung, Wilson W. L., Mowjoodi, Alireza, Howe, Jennifer L., Nalpathamkalam, Thomas, Manshaei, Roozbeh, Ghaffari, Siavash, Whitney, Joseph, Patel, Rohan V., Hamdan, Omar, Shaath, Rulan, Trost, Brett, Knights, Shannon, Samdup, Dawa, McCormick, Anna, Hunt, Carolyn, Kirton, Adam, Kawamura, Anne, Mesterman, Ronit, Gorter, Jan Willem, Dlamini, Nomazulu, Merico, Daniele, Hilali, Murto, Hirschfeld, Kyle, Grover, Kritika, Bautista, Nelson X., Han, Kara, Marshall, Christian R., Yuen, Ryan K. C., Subbarao, Padmaja, Azad, Meghan B., Turvey, Stuart E., Mandhane, Piush, Moraes, Theo J., Simons, Elinor, Maxwell, George, Shevell, Michael, Costain, Gregory, Michaud, Jacques L., Hamdan, Fadi F., Gauthier, Julie, Uguen, Kevin, Stavropoulos, Dimitri J., Wintle, Richard F., Oskoui, Maryam, and Scherer, Stephen W.
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- 2024
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5. Performance of RIS-Aided Nearfield Localization under Beams Approximation from Real Hardware Characterization
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Rahal, Moustafa, Denis, Benoit, Keykhosravi, Kamran, Keskin, Musa Furkan, Uguen, Bernard, Alexandropoulos, George C., and Wymeersch, Henk
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Electrical Engineering and Systems Science - Signal Processing - Abstract
The technology of reconfigurable intelligent surfaces (RIS) has been showing promising potential in a variety of applications relying on Beyond-5G networks. Reconfigurable intelligent surface (RIS) can indeed provide fine channel flexibility to improve communication quality of service (QoS) or restore localization capabilities in challenging operating conditions, while conventional approaches fail (e.g., due to insufficient infrastructure, severe radio obstructions). In this paper, we tackle a general low-complexity approach for optimizing the precoders that control such reflective surfaces under hardware constraints. More specifically, it allows the approximation of any desired beam pattern using a pre-characterized look-up table of feasible complex reflection coefficients for each RIS element. The proposed method is first evaluated in terms of beam fidelity for several examples of RIS hardware prototypes. Then, by means of a theoretical bounds analysis, we examine the impact of RIS beams approximation on the performance of near-field downlink positioning in non-line-of-sight conditions, while considering several RIS phase profiles (incl. directional, random and localization-optimal designs). Simulation results in a canonical scenario illustrate how the introduced RIS profile optimization scheme can reliably produce the desired RIS beams under realistic hardware limitations. They also highlight its sensitivity to both the underlying hardware characteristics and the required beam kinds in relation to the specificity of RIS-aided localization applications., Comment: 27 pages, 8 figures, journal
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- 2023
6. Review on radiomic analysis in 18F-fluorodeoxyglucose positron emission tomography for prediction of melanoma outcomes
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Karim Amrane, Coline Le Meur, Philippe Thuillier, Christian Berthou, Arnaud Uguen, Désirée Deandreis, David Bourhis, Vincent Bourbonne, and Ronan Abgral
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Melanoma ,Radiomic ,FDG-PET ,Immune checkpoint inhibition ,Immunotherapy ,BRAF ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Over the past decade, several strategies have revolutionized the clinical management of patients with cutaneous melanoma (CM), including immunotherapy and targeted tyrosine kinase inhibitor (TKI)-based therapies. Indeed, immune checkpoint inhibitors (ICIs), alone or in combination, represent the standard of care for patients with advanced disease without an actionable mutation. Notably BRAF combined with MEK inhibitors represent the therapeutic standard for disease disclosing BRAF mutation. At the same time, FDG PET/CT has become part of the routine staging and evaluation of patients with cutaneous melanoma. There is growing interest in using FDG PET/CT measurements to predict response to ICI therapy and/or target therapy. While semiquantitative values such as standardized uptake value (SUV) are limited for predicting outcome, new measures including tumor metabolic volume, total lesion glycolysis and radiomics seem promising as potential imaging biomarkers for nuclear medicine. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on radiomics approaches that could improve outcomes in CM.
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- 2024
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7. LARP1 haploinsufficiency is associated with an autosomal dominant neurodevelopmental disorder
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James Chettle, Raymond J. Louie, Olivia Larner, Robert Best, Kevin Chen, Josephine Morris, Zinaida Dedeic, Anna Childers, R. Curtis Rogers, Barbara R. DuPont, Cindy Skinner, Sébastien Küry, Kevin Uguen, Marc Planes, Danielle Monteil, Megan Li, Aviva Eliyahu, Lior Greenbaum, Nofar Mor, Thomas Besnard, Bertrand Isidor, Benjamin Cogné, Alyssa Blesson, Anne Comi, Ingrid M. Wentzensen, Blake Vuocolo, Seema R. Lalani, Roberta Sierra, Lori Berry, Kent Carter, Stephan J. Sanders, and Sarah P. Blagden
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LARP1 ,autism ,ASD ,NDD ,neurodevelopmental ,metabolism ,Genetics ,QH426-470 - Abstract
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and metabolic plasticity. Using lymphocytes collected and immortalized from an index proband who carries a truncating variant in one allele of LARP1, we demonstrated that lower cellular levels of LARP1 protein cause reduced rates of aerobic respiration and glycolysis. As expression of LARP1 increases during neurodevelopment, with higher levels in neurons and astrocytes, we propose that LARP1 haploinsufficiency contributes to ASD or related NDDs through attenuated metabolic activity in the developing fetal brain.
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- 2024
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8. The dual loss and gain of function of the FPN1 iron exporter results in the ferroportin disease phenotype
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Kevin Uguen, Marlène Le Tertre, Dimitri Tchernitchko, Ahmad Elbahnsi, Sandrine Maestri, Isabelle Gourlaouen, Claude Férec, Chandran Ka, Isabelle Callebaut, and Gérald Le Gac
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Ferroportin disease ,SLC40A1-related hemochromatosis ,MFS transporters ,Hepcidin ,Pathogenicity of missense variants ,Genetics ,QH426-470 - Abstract
Summary: Heterozygous mutations in SLC40A1, encoding a multi-pass membrane protein of the major facilitator superfamily known as ferroportin 1 (FPN1), are responsible for two distinct hereditary iron-overload diseases: ferroportin disease, which is associated with reduced FPN1 activity (i.e., decrease in cellular iron export), and SLC40A1-related hemochromatosis, which is associated with abnormally high FPN1 activity (i.e., resistance to hepcidin). Here, we report three SLC40A1 missense variants with opposite functional consequences. In cultured cells, the p.Arg40Gln and p.Ser47Phe substitutions partially reduced the ability of FPN1 to export iron and also partially reduced its sensitivity to hepcidin. The p.Ala350Val substitution had more profound effects, resulting in low FPN1 iron egress and weak FPN1/hepcidin interaction. Structural analyses helped to differentiate the first two substitutions, which are predicted to cause local instabilities, and the third, which is thought to prevent critical rigid-body movements that are essential to the iron transport cycle. The phenotypic traits observed in a total of 12 affected individuals are highly suggestive of ferroportin disease. Our findings dismantle the classical dualism of FPN1 loss versus gain of function, highlight some specific and unexpected functions of FPN1 transmembrane helices in the molecular mechanism of iron export and its regulation by hepcidin, and extend the spectrum of rare genetic variants that may cause ferroportin disease.
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- 2024
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9. Protocol to study the direct binding of proteins to RNA:DNA hybrids or RNA-DNA chimeras in living cells using cross-linking immunoprecipitation
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Clara Bonnet, Ana Luisa Dian, Mélissa Leriche, Patricia Uguen, and Stéphan Vagner
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Cell Biology ,Cell-based Assays ,Molecular Biology ,Science (General) ,Q1-390 - Abstract
Summary: RNA-binding proteins (RBPs) are involved in many biological processes. The direct interaction between protein and RNA can be studied using cross-linking immunoprecipitation (CLIP) techniques in living cells. Here, we present a protocol to characterize the direct binding of proteins to RNA:DNA hybrids or RNA-DNA chimeras in living cells using CLIP. We describe steps for RNA-protein UV-C cross-linking in living cells, isolating RNA-protein complexes, RNA labeling, and extracting nucleic acid. We then detail procedures for nuclease treatment and nucleic acid migration. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
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- 2024
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10. Influence of cirrhosis on outcomes of patients with advanced intrahepatic cholangiocarcinoma receiving chemotherapy
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d’Abrigeon, Constance, McNamara, Mairéad G., Le Sourd, Samuel, Lamarca, Angela, Lièvre, Astrid, Bourien, Héloïse, Peinoit, Alexandre, Uguen, Thomas, Hubner, Richard A., Valle, Juan W., and Edeline, Julien
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- 2023
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11. Constrained RIS Phase Profile Optimization and Time Sharing for Near-field Localization
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Rahal, Moustafa, Denis, Benoît, Keykhosravi, Kamran, Keskin, Furkan, Uguen, Bernard, and Wymeersch, Henk
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Electrical Engineering and Systems Science - Signal Processing - Abstract
The rising concept of reconfigurable intelligent surface (RIS) has promising potential for Beyond 5G localization applications. We herein investigate different phase profile designs at a reflective RIS, which enable non-line-of-sight positioning in nearfield from downlink single antenna transmissions. We first derive the closed-form expressions of the corresponding Fisher information matrix (FIM) and position error bound (PEB). Accordingly, we then propose a new localization-optimal phase profile design, assuming prior knowledge of the user equipment location. Numerical simulations in a canonical scenario show that our proposal outperforms conventional RIS random and directional beam codebook designs in terms of PEB. We also illustrate the four beams allocated at the RIS (i.e., one directional beam, along with its derivatives with respect to space dimensions) and show how their relative weights according to the optimal solution can be practically implemented through time sharing (i.e., considering feasible beams sequentially)., Comment: 6 pages, 7 figures
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- 2022
12. Arbitrary Beam Pattern Approximation via RISs with Measured Element Responses
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Rahal, Moustafa, Denis, Benoît, Keykhosravi, Kamran, Keskin, Furkan, Uguen, Bernard, Alexandropoulos, George C., and Wymeersch, Henk
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Electrical Engineering and Systems Science - Signal Processing - Abstract
Smart radio environments (SREs) are seen as a key rising concept of next generation wireless networks, where propagation channels between transmitters and receivers are purposely controlled. One promising approach to achieve such channel flexibility relies on semipassive reflective Reconfigurable intelligent surfaces (RISs), which can shape the bouncing multipath signals for enhancing communication quality of service, making localization feasible in adverse operating conditions, or reducing unwanted electromagnetic emissions. This paper introduces a generic framework that aims at optimizing the end-to-end precoder controlled by RISs, so that arbitrary beam patterns can be generated, given a predefined lookup table of RIS element-wise complex reflection coefficients. This method is validated and illustrated for different targeted beam patterns in both the far-field and the near-field regimes, while considering the prior characterization of real-life RIS hardware prototypes. These results show how, and to which extent, RIS configuration optimization can approximate the desired beams under realistic hardware limitations and low-complexity implementation practicability, or conversely, which RIS elements' lookup tables would be more suitable. The latter can provide useful guidelines for future RIS hardware designs., Comment: 6 pages, 6 figures
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- 2022
13. Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma
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Julien Calderaro, Narmin Ghaffari Laleh, Qinghe Zeng, Pascale Maille, Loetitia Favre, Anaïs Pujals, Christophe Klein, Céline Bazille, Lara R. Heij, Arnaud Uguen, Tom Luedde, Luca Di Tommaso, Aurélie Beaufrère, Augustin Chatain, Delphine Gastineau, Cong Trung Nguyen, Hiep Nguyen-Canh, Khuyen Nguyen Thi, Viviane Gnemmi, Rondell P. Graham, Frédéric Charlotte, Dominique Wendum, Mukul Vij, Daniela S. Allende, Federico Aucejo, Alba Diaz, Benjamin Rivière, Astrid Herrero, Katja Evert, Diego Francesco Calvisi, Jérémy Augustin, Wei Qiang Leow, Howard Ho Wai Leung, Emmanuel Boleslawski, Mohamed Rela, Arnaud François, Anthony Wing-Hung Cha, Alejandro Forner, Maria Reig, Manon Allaire, Olivier Scatton, Denis Chatelain, Camille Boulagnon-Rombi, Nathalie Sturm, Benjamin Menahem, Eric Frouin, David Tougeron, Christophe Tournigand, Emmanuelle Kempf, Haeryoung Kim, Massih Ningarhari, Sophie Michalak-Provost, Purva Gopal, Raffaele Brustia, Eric Vibert, Kornelius Schulze, Darius F. Rüther, Sören A. Weidemann, Rami Rhaiem, Jean-Michel Pawlotsky, Xuchen Zhang, Alain Luciani, Sébastien Mulé, Alexis Laurent, Giuliana Amaddeo, Hélène Regnault, Eleonora De Martin, Christine Sempoux, Pooja Navale, Maria Westerhoff, Regina Cheuk-Lam Lo, Jan Bednarsch, Annette Gouw, Catherine Guettier, Marie Lequoy, Kenichi Harada, Pimsiri Sripongpun, Poowadon Wetwittayaklang, Nicolas Loménie, Jarukit Tantipisit, Apichat Kaewdech, Jeanne Shen, Valérie Paradis, Stefano Caruso, and Jakob Nikolas Kather
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Science - Abstract
Abstract Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.
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- 2023
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14. RIS-Enabled Localization Continuity Under Near-Field Conditions
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Rahal, Moustafa, Denis, Benoit, Keykhosravi, Kamran, Uguen, Bernard, and Wymeersch, Henk
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Electrical Engineering and Systems Science - Signal Processing - Abstract
Reconfigurable intelligent surfaces (RISs) have the potential to enable user localization in scenarios where traditional approaches fail. Building on prior work in single-antenna RIS-enabled localization, we investigate the potential to exploit wavefront curvature in geometric near-field conditions. Via a Fisher information analysis, we demonstrate that while near-field improves localization accuracy mostly at short distances when the line-of-sight (LoS) path is present, it could still provide reasonable performance when this path is blocked by relying on a single RIS reflection., Comment: 5 pages, 6 figures, SPAWC21 conference
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- 2021
15. Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma
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Calderaro, Julien, Ghaffari Laleh, Narmin, Zeng, Qinghe, Maille, Pascale, Favre, Loetitia, Pujals, Anaïs, Klein, Christophe, Bazille, Céline, Heij, Lara R., Uguen, Arnaud, Luedde, Tom, Di Tommaso, Luca, Beaufrère, Aurélie, Chatain, Augustin, Gastineau, Delphine, Nguyen, Cong Trung, Nguyen-Canh, Hiep, Thi, Khuyen Nguyen, Gnemmi, Viviane, Graham, Rondell P., Charlotte, Frédéric, Wendum, Dominique, Vij, Mukul, Allende, Daniela S., Aucejo, Federico, Diaz, Alba, Rivière, Benjamin, Herrero, Astrid, Evert, Katja, Calvisi, Diego Francesco, Augustin, Jérémy, Leow, Wei Qiang, Leung, Howard Ho Wai, Boleslawski, Emmanuel, Rela, Mohamed, François, Arnaud, Cha, Anthony Wing-Hung, Forner, Alejandro, Reig, Maria, Allaire, Manon, Scatton, Olivier, Chatelain, Denis, Boulagnon-Rombi, Camille, Sturm, Nathalie, Menahem, Benjamin, Frouin, Eric, Tougeron, David, Tournigand, Christophe, Kempf, Emmanuelle, Kim, Haeryoung, Ningarhari, Massih, Michalak-Provost, Sophie, Gopal, Purva, Brustia, Raffaele, Vibert, Eric, Schulze, Kornelius, Rüther, Darius F., Weidemann, Sören A., Rhaiem, Rami, Pawlotsky, Jean-Michel, Zhang, Xuchen, Luciani, Alain, Mulé, Sébastien, Laurent, Alexis, Amaddeo, Giuliana, Regnault, Hélène, De Martin, Eleonora, Sempoux, Christine, Navale, Pooja, Westerhoff, Maria, Lo, Regina Cheuk-Lam, Bednarsch, Jan, Gouw, Annette, Guettier, Catherine, Lequoy, Marie, Harada, Kenichi, Sripongpun, Pimsiri, Wetwittayaklang, Poowadon, Loménie, Nicolas, Tantipisit, Jarukit, Kaewdech, Apichat, Shen, Jeanne, Paradis, Valérie, Caruso, Stefano, and Kather, Jakob Nikolas
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- 2023
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16. Performance of RIS-aided near-field localization under beams approximation from real hardware characterization
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Rahal, Moustafa, Denis, Benoît, Keykhosravi, Kamran, Keskin, Musa Furkan, Uguen, Bernard, Alexandropoulos, George C., and Wymeersch, Henk
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- 2023
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17. Coupling imaging mass cytometry with Alcian blue histochemical staining for a single-slide approach
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Patrice Hemon, Danivanh Ben-Guigui, Margaux Geier, Marine Castillon, Corentin Paranthoen, Jacques-Olivier Pers, Marion Le Rochais, and Arnaud Uguen
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imaging mass cytometry ,Alcian blue ,digital pathology ,fixative ,histochemical staining ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Imaging mass cytometry (IMC) is a metal mass spectrometry-based method allowing highly multiplex immunophenotyping of cells within tissue samples. However, some limitations of IMC are its 1-µm resolution and its time and costs of analysis limiting respectively the detailed histopathological analysis of IMC-produced images and its application to small selected tissue regions of interest (ROI) of one to few square millimeters. Coupling on a single-tissue section, IMC and histopathological analyses could permit a better selection of the ROI for IMC analysis as well as co-analysis of immunophenotyping and histopathological data until the single-cell level. The development of this method is the aim of the present study in which we point to the feasibility of applying the IMC process to tissue sections previously Alcian blue-stained and digitalized before IMC tissue destructive analyses. This method could help to improve the process of IMC in terms of ROI selection, time of analysis, and the confrontation between histopathological and immunophenotypic data of cells.
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- 2024
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18. Performance of RIS-aided near-field localization under beams approximation from real hardware characterization
- Author
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Moustafa Rahal, Benoît Denis, Kamran Keykhosravi, Musa Furkan Keskin, Bernard Uguen, George C. Alexandropoulos, and Henk Wymeersch
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Reconfigurable intelligent surfaces ,Nearfield localization ,Beam approximation ,Lookup table ,Hardware characterization ,Telecommunication ,TK5101-6720 ,Electronics ,TK7800-8360 - Abstract
Abstract The technology of reconfigurable intelligent surfaces (RISs) has been showing promising potential in a variety of applications relying on Beyond-5G networks. RIS can indeed provide fine channel flexibility to improve communication quality of service (QoS) or restore localization capabilities in challenging operating conditions, while conventional approaches fail (e.g., due to insufficient infrastructure, severe radio obstructions). In this paper, we tackle a general low-complexity approach for optimizing the precoders that control such reflective surfaces under hardware constraints. More specifically, it allows the approximation of any desired beam pattern using a pre-characterized lookup table of feasible complex reflection coefficients for each RIS element. The proposed method is first evaluated in terms of beam fidelity for several examples of RIS hardware prototypes. Then, by means of a theoretical bounds analysis, we examine the impact of RIS beams approximation on the performance of near-field downlink positioning in non-line-of-sight conditions, while considering several RIS phase profiles (including directional, random and localization-optimal designs). Simulation results in a canonical scenario illustrate how the introduced RIS profile optimization scheme can reliably produce the desired RIS beams under realistic hardware limitations. They also highlight its sensitivity to both the underlying hardware characteristics and the required beam kinds in relation to the specificity of RIS-aided localization applications.
- Published
- 2023
- Full Text
- View/download PDF
19. Coding and noncoding variants in EBF3 are involved in HADDS and simplex autism
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Padhi, Evin M, Hayeck, Tristan J, Cheng, Zhang, Chatterjee, Sumantra, Mannion, Brandon J, Byrska-Bishop, Marta, Willems, Marjolaine, Pinson, Lucile, Redon, Sylvia, Benech, Caroline, Uguen, Kevin, Audebert-Bellanger, Séverine, Le Marechal, Cédric, Férec, Claude, Efthymiou, Stephanie, Rahman, Fatima, Maqbool, Shazia, Maroofian, Reza, Houlden, Henry, Musunuri, Rajeeva, Narzisi, Giuseppe, Abhyankar, Avinash, Hunter, Riana D, Akiyama, Jennifer, Fries, Lauren E, Ng, Jeffrey K, Mehinovic, Elvisa, Stong, Nick, Allen, Andrew S, Dickel, Diane E, Bernier, Raphael A, Gorkin, David U, Pennacchio, Len A, Zody, Michael C, and Turner, Tychele N
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Biological Sciences ,Genetics ,Mental Health ,Human Genome ,Intellectual and Developmental Disabilities (IDD) ,Autism ,Pediatric ,Neurosciences ,Clinical Research ,Brain Disorders ,1.1 Normal biological development and functioning ,Underpinning research ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Neurological ,Autistic Disorder ,Enhancer Elements ,Genetic ,Exome ,Female ,Gene Regulatory Networks ,Genetic Predisposition to Disease ,Humans ,Male ,Muscle Hypotonia ,Mutation ,Neurodevelopmental Disorders ,Neurons ,Transcription Factors ,Neurodevelopmental disorder ,Enhancer ,Gene regulatory network ,EBF3 ,hs737 ,Genome ,Variant ,De novo ,Genetics & Heredity ,Biochemistry and cell biology - Abstract
BackgroundPrevious research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737.ResultsWe adapted the fitDNM statistical model to work in noncoding regions and tested enhancers for excess of DNVs in families with autism. We found only one enhancer (hs737) with nominal significance in the discovery (p = 0.0172), replication (p = 2.5 × 10-3), and combined dataset (p = 1.1 × 10-4). Each individual with a DNV in hs737 had shared phenotypes including being male, intact cognitive function, and hypotonia or motor delay. Our in vitro assessment of the DNVs showed they all reduce enhancer activity in a neuronal cell line. By epigenomic analyses, we found that hs737 is brain-specific and targets the transcription factor gene EBF3 in human fetal brain. EBF3 is genome-wide significant for coding DNVs in NDDs (missense p = 8.12 × 10-35, loss-of-function p = 2.26 × 10-13) and is widely expressed in the body. Through characterization of promoters bound by EBF3 in neuronal cells, we saw enrichment for binding to NDD genes (p = 7.43 × 10-6, OR = 1.87) involved in gene regulation. Individuals with coding DNVs have greater phenotypic severity (hypotonia, ataxia, and delayed development syndrome [HADDS]) in comparison to individuals with noncoding DNVs that have autism and hypotonia.ConclusionsIn this study, we identify DNVs in the hs737 enhancer in individuals with autism. Through multiple approaches, we find hs737 targets the gene EBF3 that is genome-wide significant in NDDs. By assessment of noncoding variation and the genes they affect, we are beginning to understand their impact on gene regulatory networks in NDDs.
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- 2021
20. HLA-DR expression in melanoma: from misleading therapeutic target to potential immunotherapy biomarker
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Karim Amrane, Coline Le Meur, Benjamin Besse, Patrice Hemon, Pierre Le Noac’h, Olivier Pradier, Christian Berthou, Ronan Abgral, and Arnaud Uguen
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melanoma ,MHC-II ,HLA-DR ,immunotherapy ,anti-PD1 ,BRAF ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Since the advent of anti-PD1 immune checkpoint inhibitor (ICI) immunotherapy, cutaneous melanoma has undergone a true revolution with prolonged survival, as available 5-year updates for progression-free survival and overall survival demonstrate a durable clinical benefit for melanoma patients receiving ICI. However, almost half of patients fail to respond to treatment, or relapse sooner or later after the initial response to therapy. Little is known about the reasons for these failures. The identification of biomarkers seems necessary to better understand this resistance. Among these biomarkers, HLA-DR, a component of MHC II and abnormally expressed in certain tumor types including melanoma for unknown reasons, seems to be an interesting marker. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on the potential interest of HLA-DR expression in melanoma as a predictive biomarker of ICI outcome.
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- 2024
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21. Beamwidth Optimization and Resource Partitioning Scheme for Localization Assisted mm-wave Communications
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Ghatak, Gourab, Koirala, Remun, De Domenico, Antonio, Denis, Benoit, Dardari, Davide, Uguen, Bernard, and Coupechoux, Marceau
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Electrical Engineering and Systems Science - Signal Processing - Abstract
We study a mm-wave wireless network deployed along the roads of an urban area, to support localization and communication services simultaneously for outdoor mobile users. In this network, we propose a mm-wave initial beam-selection scheme based on localization-bounds, which greatly reduces the initial access delay as compared to traditional initial access schemes for standalone mm-wave base station (BS). Then, we introduce a downlink transmission protocol, in which the radio frames are partitioned into three phases, namely, initial access, data, and localization, respectively. We establish a trade-off between the localization and communication performance of mm-wave systems, and show how enhanced localization can actually improve the data-communication performance. Our results suggest that dense BS deployments enable to allocate more resources to the data phase while still maintaining appreciable localization performance. Furthermore, for the case of sparse deployments and large beam dictionary size (i.e., with thinner beams), more resources must be allotted to the localization phase for optimizing the rate coverage. Based on our results, we provide several system design insights and dimensioning rules for the network operators that will deploy the first generation of mm-wave BSs.
- Published
- 2020
22. 53BP1 interacts with the RNA primer from Okazaki fragments to support their processing during unperturbed DNA replication
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Melissa Leriche, Clara Bonnet, Jagannath Jana, Gita Chhetri, Sabrina Mennour, Sylvain Martineau, Vincent Pennaneach, Didier Busso, Xavier Veaute, Pascale Bertrand, Sarah Lambert, Kumar Somyajit, Patricia Uguen, and Stéphan Vagner
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CP: Molecular biology ,Biology (General) ,QH301-705.5 - Abstract
Summary: RNA-binding proteins (RBPs) are found at replication forks, but their direct interaction with DNA-embedded RNA species remains unexplored. Here, we report that p53-binding protein 1 (53BP1), involved in the DNA damage and replication stress response, is an RBP that directly interacts with Okazaki fragments in the absence of external stress. The recruitment of 53BP1 to nascent DNA shows susceptibility to in situ ribonuclease A treatment and is dependent on PRIM1, which synthesizes the RNA primer of Okazaki fragments. Conversely, depletion of FEN1, resulting in the accumulation of uncleaved RNA primers, increases 53BP1 levels at replication forks, suggesting that RNA primers contribute to the recruitment of 53BP1 at the lagging DNA strand. 53BP1 depletion induces an accumulation of S-phase poly(ADP-ribose), which constitutes a sensor of unligated Okazaki fragments. Collectively, our data indicate that 53BP1 is anchored at nascent DNA through its RNA-binding activity, highlighting the role of an RNA-protein interaction at replication forks.
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- 2023
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23. Discovery of hit compounds for methyl-lysine reader proteins from a target class DNA-encoded library
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Devan J. Shell, Justin M. Rectenwald, Peter H. Buttery, Rebecca L. Johnson, Caroline A. Foley, Shiva K.R. Guduru, Mélanie Uguen, Juanita Sanchez Rubiano, Xindi Zhang, Fengling Li, Jacqueline L. Norris-Drouin, Matthew Axtman, P. Brian Hardy, Masoud Vedadi, Stephen V. Frye, Lindsey I. James, and Kenneth H. Pearce
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DNA-encoded library ,Hit discovery ,Target class ,Chromatin ,Reader protein ,Methyl-lysine ,Medicine (General) ,R5-920 ,Biotechnology ,TP248.13-248.65 - Abstract
Methyl-lysine (Kme) reader domains are prevalent in chromatin regulatory proteins which bind post-translational modification sites to recruit repressive and activating factors; therefore, these proteins play crucial roles in cellular signaling and epigenetic regulation. Proteins that contain Kme domains are implicated in various diseases, including cancer, making them attractive therapeutic targets for drug and chemical probe discovery. Herein, we report on expanding the utility of a previously reported, Kme-focused DNA-encoded library (DEL), UNCDEL003, as a screening tool for hit discovery through the specific targeting of Kme reader proteins. As an efficient method for library generation, focused DELs are designed based on structural and functional features of a specific class of proteins with the intent of novel hit discovery. To broadly assess the applicability of our library, UNCDEL003 was screened against five diverse Kme reader protein domains (53BP1 TTD, KDM7B JmjC-PHD, CDYL2 CD, CBX2 CD, and LEDGF PWWP) with varying structures and functions. From these screening efforts, we identified hit compounds which contain unique chemical scaffolds distinct from previously reported ligands. The selected hit compounds were synthesized off-DNA and confirmed using primary and secondary assays and assessed for binding selectivity. Hit compounds from these efforts can serve as starting points for additional development and optimization into chemical probes to aid in further understanding the functionality of these therapeutically relevant proteins.
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- 2022
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24. Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis: stage I of a phase II trial
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Srdan Verstovsek, Lynda Foltz, Vikas Gupta, Robert Hasserjian, Taghi Manshouri, John Mascarenhas, Ruben Mesa, Olga Pozdnyakova, Ellen Ritchie, Ivo Veletic, Katia Gamel, Habib Hamidi, Lyrialle Han, Brian Higgins, Kerstin Trunzer, Marianne Uguen, Dao Wang, Tarec Christoffer El-Galaly, Boyan Todorov, and Jason Gotlib
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Pentraxin 2 (PTX-2; serum amyloid P component), a circulating endogenous regulator of the inflammatory response to tissue injury and fibrosis, is reduced in patients with myelofibrosis (MF). Zinpentraxin alfa (RO7490677, PRM-151) is a recombinant form of PTX-2 that has shown preclinical antifibrotic activity and no dose-limiting toxicities in phase I trials. We report results from stage 1 of a phase II trial of zinpentraxin alfa in patients with intermediate-1/2 or high-risk MF. Patients (n=27) received intravenous zinpentraxin α weekly (QW) or every 4 weeks (Q4W), as monotherapy or an additional therapy for patients on stable-dose ruxolitinib. The primary endpoint was overall response rate (ORR; investigatorassessed) adapted from International Working Group-Myeloproliferative Neoplasms Research and Treatment criteria. Secondary endpoints included modified Myeloproliferative Neoplasm-Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) change, bone marrow (BM) MF grade reduction, pharmacokinetics, and safety. ORR at week 24 was 33% (n=9/27) and varied across individual cohorts (QW: 38% [3/8]; Q4W: 14% [1/7]; QW+ruxolitinib: 33% [2/6]; Q4W+ruxolitinib: 50% [3/6]). Five of 18 evaluable patients (28%) experienced a ≥50% reduction in MPN-SAF TSS, and six of 17 evaluable patients (35%) had a ≥1 grade improvement from baseline in BM fibrosis at week 24. Most treatment-emergent adverse events (AE) were grade 1–2, most commonly fatigue. Among others, anemia and thrombocytopenia were infrequent (n=3 and n=1, respectively). Treatment-related serious AE occurred in four patients (15%). Overall, zinpentraxin alfa showed evidence of clinical activity and tolerable safety as monotherapy and in combination with ruxolitinib in this open-label, non-randomized trial (clinicaltrials gov. Identifier: NCT01981850).
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- 2023
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25. Tracking Position and Orientation through Millimeter Wave Lens MIMO in 5G Systems
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Shahmansoori, Arash, Uguen, Bernard, Destino, Giuseppe, Seco-Granados, Gonzalo, and Wymeersch, Henk
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Computer Science - Information Theory - Abstract
Millimeter wave signals and large antenna arrays are considered enabling technologies for future 5G networks. Despite their benefits for achieving high data rate communications, their potential advantages for tracking of the location of the user terminals are largely undiscovered. In this paper, we propose a novel support detection-based channel training method for frequency selective millimeter-wave (mm-wave) multiple-input-multiple-output system with lens antenna arrays. We show that accurate position and orientation estimation and tracking is possible using signals from a single transmitter with lens antenna arrays. Particularly, the beamspace channel estimation is formulated as two sparse signal recovery problems in the downlink and uplink for the estimation of angle-of-arrival, angle-of-departure, and time-of-arrival. The proposed method offers a higher sparse detection probability compared to the compressed sensing based solutions. Finally, a joint heuristic beamformer design and user position and orientation tracking approach are proposed based on initial estimation of channel parameters obtained in the training phase., Comment: 30 pages, 8 figures, journal paper. Submitted to IEEE Transactions on Wireless Communications
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- 2018
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26. Positioning Data-Rate Trade-off in mm-Wave Small Cells and Service Differentiation for 5G Networks
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Ghatak, Gourab, Koirala, Remun, De Domenico, Antonio, Denis, Benoit, Dardari, Davide, and Uguen, Bernard
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Computer Science - Information Theory - Abstract
We analyze a millimeter wave network, deployed along the streets of a city, in terms of positioning and downlink data-rate performance, respectively. First, we present a transmission scheme where the base stations provide jointly positioning and data-communication functionalities. Accordingly, we study the trade-off between the localization and the data rate performance based on theoretical bounds. Then, we obtain an upper bound on the probability of beam misalignment based on the derived localization error bound. Finally, we prescribe the network operator a scheme to select the beamwidth and the power splitting factor between the localization and communication functions to address different quality of service requirements, while limiting cellular outage., Comment: IEEE VTC-Spring 2018, Porto, Portugal, 3-6 June 2018
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- 2018
27. Channel Whispering: a Protocol for Physical Layer Group Key Generation. Application to IR-UWB through Deconvolution
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Tunaru, Iulia, Denis, Benoît, Perrier, Régis, and Uguen, Bernard
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Computer Science - Cryptography and Security ,Computer Science - Information Theory - Abstract
As wireless ad hoc and mobile networks are emerging and the transferred data become more sensitive, information security measures should make use of all the available contextual resources to secure information flows. The physical layer security framework provides models, algorithms, and proofs of concept for generating pairwise symmetric keys over single links between two nodes within communication range. In this study, we focus on cooperative group key generation over multiple Impulse Radio - Ultra Wideband (IR-UWB) channels according to the source model. The main idea, proposed in previous work, consists in generating receiver-specific signals, also called s-signals, so that only the intended receiver has access to the non-observable channels corresponding to its non-adjacent links. Herein, we complete the analysis of the proposed protocol and investigate several signal processing algorithms to generate the s-signal expressed as a solution to a deconvolution problem in the case of IR-UWB. Our findings indicate that it is compulsory to add a parameterizable constraint to the searched s-signal and that the Expectation-Maximization algorithm can provide a stable self-parameterizable solution. Compared to physical layer key distribution methods, the proposed key generation protocol requires less traffic overhead for small cooperative groups while being robust at medium and high signal-to-noise ratios., Comment: 21 pages
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- 2018
28. Pathogenic variants in USP7 cause a neurodevelopmental disorder with speech delays, altered behavior, and neurologic anomalies
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Fountain, Michael D, Oleson, David S, Rech, Megan E, Segebrecht, Lara, Hunter, Jill V, McCarthy, John M, Lupo, Philip J, Holtgrewe, Manuel, Moran, Rocio, Rosenfeld, Jill A, Isidor, Bertrand, Le Caignec, Cédric, Saenz, Margarita S, Pedersen, Robert C, Morgan, Thomas M, Pfotenhauer, Jean P, Xia, Fan, Bi, Weimin, Kang, Sung-Hae L, Patel, Ankita, Krantz, Ian D, Raible, Sarah E, Smith, Wendy, Cristian, Ingrid, Torti, Erin, Juusola, Jane, Millan, Francisca, Wentzensen, Ingrid M, Person, Richard E, Küry, Sébastien, Bézieau, Stéphane, Uguen, Kévin, Férec, Claude, Munnich, Arnold, van Haelst, Mieke, Lichtenbelt, Klaske D, van Gassen, Koen, Hagelstrom, Tanner, Chawla, Aditi, Perry, Denise L, Taft, Ryan J, Jones, Marilyn, Masser-Frye, Diane, Dyment, David, Venkateswaran, Sunita, Li, Chumei, Escobar, Luis F, Horn, Denise, Spillmann, Rebecca C, Peña, Loren, Wierzba, Jolanta, Strom, Tim M, Parenti, Ilaria, Kaiser, Frank J, Ehmke, Nadja, and Schaaf, Christian P
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Biological Sciences ,Genetics ,Brain Disorders ,Neurosciences ,Behavioral and Social Science ,Clinical Research ,Pediatric ,Congenital Structural Anomalies ,Intellectual and Developmental Disabilities (IDD) ,Mental Health ,Autism ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Adolescent ,Autism Spectrum Disorder ,Child ,Child ,Preschool ,Chromosome Deletion ,DNA-Binding Proteins ,Genome ,Human ,Haploinsufficiency ,Humans ,Infant ,Infant ,Newborn ,Intellectual Disability ,Language Development Disorders ,Neurodevelopmental Disorders ,Nuclear Proteins ,Phenotype ,Problem Behavior ,Proteins ,Exome Sequencing ,USP7 ,neurodevelopment ,speech delay ,white matter paucity ,corpus callosum thinning ,Clinical Sciences ,Genetics & Heredity - Abstract
PurposeHaploinsufficiency of USP7, located at chromosome 16p13.2, has recently been reported in seven individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), seizures, and hypogonadism. Further, USP7 was identified to critically incorporate into the MAGEL2-USP7-TRIM27 (MUST), such that pathogenic variants in USP7 lead to altered endosomal F-actin polymerization and dysregulated protein recycling.MethodsWe report 16 newly identified individuals with heterozygous USP7 variants, identified by genome or exome sequencing or by chromosome microarray analysis. Clinical features were evaluated by review of medical records. Additional clinical information was obtained on the seven previously reported individuals to fully elucidate the phenotypic expression associated with USP7 haploinsufficiency.ResultsThe clinical manifestations of these 23 individuals suggest a syndrome characterized by DD/ID, hypotonia, eye anomalies,feeding difficulties, GERD, behavioral anomalies, and ASD, and more specific phenotypes of speech delays including a nonverbal phenotype and abnormal brain magnetic resonance image findings including white matter changes based on neuroradiologic examination.ConclusionThe consistency of clinical features among all individuals presented regardless of de novo USP7 variant type supports haploinsufficiency as a mechanism for pathogenesis and refines the clinical impact faced by affected individuals and caregivers.
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- 2019
29. Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability.
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Cogné, Benjamin, Ehresmann, Sophie, Beauregard-Lacroix, Eliane, Rousseau, Justine, Besnard, Thomas, Garcia, Thomas, Petrovski, Slavé, Avni, Shiri, McWalter, Kirsty, Blackburn, Patrick R, Sanders, Stephan J, Uguen, Kévin, Harris, Jacqueline, Cohen, Julie S, Blyth, Moira, Lehman, Anna, Berg, Jonathan, Li, Mindy H, Kini, Usha, Joss, Shelagh, von der Lippe, Charlotte, Gordon, Christopher T, Humberson, Jennifer B, Robak, Laurie, Scott, Daryl A, Sutton, Vernon R, Skraban, Cara M, Johnston, Jennifer J, Poduri, Annapurna, Nordenskjöld, Magnus, Shashi, Vandana, Gerkes, Erica H, Bongers, Ernie MHF, Gilissen, Christian, Zarate, Yuri A, Kvarnung, Malin, Lally, Kevin P, Kulch, Peggy A, Daniels, Brina, Hernandez-Garcia, Andres, Stong, Nicholas, McGaughran, Julie, Retterer, Kyle, Tveten, Kristian, Sullivan, Jennifer, Geisheker, Madeleine R, Stray-Pedersen, Asbjorg, Tarpinian, Jennifer M, Klee, Eric W, Sapp, Julie C, Zyskind, Jacob, Holla, Øystein L, Bedoukian, Emma, Filippini, Francesca, Guimier, Anne, Picard, Arnaud, Busk, Øyvind L, Punetha, Jaya, Pfundt, Rolph, Lindstrand, Anna, Nordgren, Ann, Kalb, Fayth, Desai, Megha, Ebanks, Ashley Harmon, Jhangiani, Shalini N, Dewan, Tammie, Coban Akdemir, Zeynep H, Telegrafi, Aida, Zackai, Elaine H, Begtrup, Amber, Song, Xiaofei, Toutain, Annick, Wentzensen, Ingrid M, Odent, Sylvie, Bonneau, Dominique, Latypova, Xénia, Deb, Wallid, CAUSES Study, Redon, Sylvia, Bilan, Frédéric, Legendre, Marine, Troyer, Caitlin, Whitlock, Kerri, Caluseriu, Oana, Murphree, Marine I, Pichurin, Pavel N, Agre, Katherine, Gavrilova, Ralitza, Rinne, Tuula, Park, Meredith, Shain, Catherine, Heinzen, Erin L, Xiao, Rui, Amiel, Jeanne, Lyonnet, Stanislas, Isidor, Bertrand, Biesecker, Leslie G, Lowenstein, Dan, Posey, Jennifer E, and Denommé-Pichon, Anne-Sophie
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CAUSES Study ,Deciphering Developmental Disorders study ,Humans ,Syndrome ,Adaptor Proteins ,Signal Transducing ,Nuclear Proteins ,Prognosis ,Autistic Disorder ,Amino Acid Sequence ,Sequence Homology ,Mutation ,Missense ,Adolescent ,Adult ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Young Adult ,Genetic Association Studies ,Intellectual Disability ,TRRAP ,autism spectrum disorder ,congenital malformations ,de novo variants ,histone acetylation ,intellectual disability ,neurodevelopmental disorders ,Intellectual and Developmental Disabilities (IDD) ,Pediatric ,Genetics ,Brain Disorders ,Neurosciences ,Mental Health ,Autism ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.
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- 2019
30. Deciphering the maturation of tertiary lymphoid structures in cancer and inflammatory diseases of the digestive tract using imaging mass cytometry
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Marion Le Rochais, Patrice Hémon, Danivanh Ben-guigui, Soizic Garaud, Christelle Le Dantec, Jacques-Olivier Pers, Divi Cornec, and Arnaud Uguen
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tertiary lymphoid structures ,imaging mass cytometry ,Hyperion ,cancer ,inflammation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Persistent inflammation can promote the development of tertiary lymphoid structures (TLS) within tissues resembling secondary lymphoid organs (SLO) such as lymph nodes (LN). The composition of TLS across different organs and diseases could be of pathophysiological and medical interest. In this work, we compared TLS to SLO in cancers of the digestive tract and in inflammatory bowel diseases. Colorectal and gastric tissues with different inflammatory diseases and cancers from the department of pathology of CHU Brest were analyzed based on 39 markers using imaging mass cytometry (IMC). Unsupervised and supervised clustering analyses of IMC images were used to compare SLO and TLS. Unsupervised analyses tended to group TLS per patient but not per disease. Supervised analyses of IMC images revealed that LN had a more organized structure than TLS and non-encapsulated SLO Peyer’s patches. TLS followed a maturation spectrum with close correlations between germinal center (GC) markers’ evolution. The correlations between organizational and functional markers made relevant the previously proposed TLS division into three stages: lymphoid-aggregates (LA) (CD20+CD21-CD23-) had neither organization nor GC functionality, non-GC TLS (CD20+CD21+CD23-) were organized but lacked GC’s functionality and GC-like TLS (CD20+CD21+CD23+) had GC’s organization and functionality. This architectural and functional maturation grading of TLS pointed to differences across diseases. TLS architectural and functional maturation grading is accessible with few markers allowing future diagnostic, prognostic, and predictive studies on the value of TLS grading, quantification and location within pathological tissues in cancers and inflammatory diseases.
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- 2023
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31. Women and health professionals’ perspectives on a conditional cash transfer programme to improve pregnancy follow-up: a qualitative analysis of the NAITRE randomised controlled study
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Celine Chauleur, Jacob Hannigsberg, Philippe Merviel, Marc Bardou, Franck Perrotin, Thomas Schmitz, Olivier Picone, Jeanne Sibiude, Karine Chemin, Dominique Dallay, Frédéric Coatleven, Loïc Sentilhes, Céline Brochot, Astrid Eckman-Lacroix, Elise Thellier, Frédérique Falchier, Philippe Deruelle, Muriel Doret, Xavier Carcopino-Tusoli, Nicolas Meunier-Beillard, Hervé Fernandez, Vincent Villefranque, Caroline Diguisto, Damien Subtil, Clémence Houssin, Philippe Gillard, Laurent Mandelbrot, Aurelie Godard-Marceau, Nathalie Lesavre, Claude Virtos, Elodie Debras, Aude Bourtembourg, Claire Toubin, Danièle Addes, Véronique Uguen, Cleo Tourbot, Caroline Lelievre, Christophe Tremouilhac, Anne-Hélène Saliou, Aurelie Derrieu, Stephanie Auget, Anne Legourrierec, Anne Leroux, Julie Fort-Jacquier, Marion Serclerat, Nathalie Laurenceau, Audrey Renouleau, Eliane Catteau, Julie Blanc, Candice Ronin, Laurence Piechon, Séverine Puppo, Fanny Greco, Sandrine Pettazzoni, Muriel Athlani, Amina Desvignes, Annie Petiteau, Amina El Yaakoubi, Valérie Bechadergue, Valérie Vaugirard, Marie-Emmanuelle Neveu, Caroline Geyl, Marie-Victoire Senat, Claire Colmant, Marie Houllier, Myriam Virlouet, Marion Mir, Yasmina Bejaoui, Hélène Le Cornu, Lauriane Nikel, Elodie Gustave, Amandine Stadler, Ahmad Mehdi, Tiphaine Barjat, Suzanne Lima, Thomas Corsini, Anne Genod, Charlotte Vermesch, Cécile Fanget, Marianne Perrot, Manuela Munoz, Sylvie Pitaval, Fanny Magand, Françoise Baldi, Stephanie Bret, Anne-Lise Verdier, Christelle Denis, Carine Arlicot, Jérôme Potin, Stéphanie Chretien, Julie Paternotte, Nathalie Trignol, Élisabeth Blin, Camille Mathieu, Anne Dubreuil, Anne Viallon Pelletier, Catherine Guerin, Chloé Arthuis, Christophe Vayssieres, Olivier Parant, Marion Groussolles, Maria Denis, M Mathieu Morin, Marie-Thérèse Bavoux, Juliette Pelloux, Anne-Claire Jambon, Madeleine Santraine, Veronique Lebuffe, Pascale Broux, Thierry Dzukou, Magloire Gnansounou, Didier Hubert, Claire Djazet, Ludivine Destoop, Marine Derue, Pierrick Theret, Dominique Delzenne, Stéphanie Daussin, Alice Fraissinet, Mélanie Vannerum, Cyril Faraguet, Laurence Landais, Mariana Radu, Anne Rouget, Sena Al Sudani, Bernard Guillon, Estelle Wucher, Véronique Selva, Sandrine Reviron, Francis Schwetterlé, Cécile Chassande, Véronique Grandin, Eliane Krtoliza, Patrick Becher, Marie Sarrau, Claire Lecoq, Elsa Lutringer, Denis Roux, Noémie Berge, Clémentine Barbier, Anne Heron, Audrey Farina-Bracquart, Marie-Paule Curtet, Evelyne Lefebure, Marie-Hélène Le Douarin, Hassan Al Rayes, Émilie Magne, Nathalie Destampes, Émilie Ricard, Pascale Ghezzi, Catherine Guillen, Fanny Alazard, Marie-Thé Campanaro, Florence Mojard, Magalie David-Reynard, Patricia Fuma, Remy De Montgolfier, Capucine Neel, Guillaume Legendre, Isabelle Andre, Sylvie Nordstrom, Brigitte Guionnet, Catherine Crenn Hebert, Chloé Dussaux, Karine Achaintre, Anne Wagner, Martine Werveake, Eloïse De Gouville, George Theresin, Marie Pierre Couetoux, Lydia Caillaud, Marie-Pierre Fernandez, Sabrina Bottet, M Alain Almodovar, Elisa Etienne, Véronique Guiteras, Angélique Torres, N. Roche, Myriam Nassef, Christine Abel-Faure, Marie Louvet, Carole Ettori, Guillaume Ducarme, Valérie Bonnenfant-Mezeray, Laurence Szezot-Renaudeau, Marie-Pierre Berte, Elodie Netier-Herault, Stéphanie Manson-Gallone, Franck Mauviel, Nathalie Agostini, Marine Mazeaud, Jean-Claude Dausset, Isabelle De Murcia, Emilie Alliot, Anne-Marie Bes, Magali Biferi Magali, Hélène Heckenroth, Sophie Morange, Gersende Chiuot, Audrey Gnisci, Annie Allegre, Laetitia Lecq, Eva Balenbois, Claire Tourette, Aude Figarella, Dio Andriamanjay, Pauline Vignoles, Catherine Cazelles, Véronique Lejeune Saada, Benafsheh Kashani, Isabelle Chevalier, Muriel Terrieres, Audrey Cointement, Valérie Benhaïm, Najat Lindoune, Anne-Sophie Maisonneuve, M Frédéric Daubercy, Guilia Mencattini, Vanessa Combaud, Isabelle Moya, Xavier-Côme Donato, Raoul Desbriere, Marie Lafon, and Véronique Baudet
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Medicine - Abstract
Objectives Women of low socioeconomic status have been described as having suboptimal prenatal care, which in turn has been associated with poor pregnancy outcomes. Many types of conditional cash transfer (CCT) programmes have been developed, including programmes to improve prenatal care or smoking cessation during pregnancy, and their effects demonstrated. However, ethical critiques have included paternalism and lack of informed choice. Our objective was to determine if women and healthcare professionals (HPs) shared these concerns.Design Prospective qualitative research.Setting We included economically disadvantaged women, as defined by health insurance data, who participated in the French NAITRE randomised trial assessing a CCT programme during prenatal follow-up to improve pregnancy outcomes. The HP worked in some maternities participating in this trial.Participants 26 women, 14 who received CCT and 12 who did not, mostly unemployed (20/26), and - 7 HPs.Interventions We conducted a multicentre cross-sectional qualitative study among women and HPs who participated in the NAITRE Study to assess their views on CCT. The women were interviewed after childbirth.Results Women did not perceive CCT negatively. They did not mention feeling stigmatised. They described CCT as a significant source of aid for women with limited financial resources. HP described the CCT in less positive terms, for example, expressing concern about discussing cash transfer at their first medical consultation with women. Though they emphasised ethical concerns about the basis of the trial, they recognised the importance of evaluating CCT.Conclusions In France, a high-income country where prenatal follow-up is free, HPs were concerned that the CCT programme would change their relationship with patients and wondered if it was the best use of funding. However, women who received a cash incentive said they did not feel stigmatised and indicated that these payments helped them prepare for their baby’s birth.Trial registration number NCT02402855
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- 2023
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32. Stepwise use of genomics and transcriptomics technologies increases diagnostic yield in Mendelian disorders
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Estelle Colin, Yannis Duffourd, Martin Chevarin, Emilie Tisserant, Simon Verdez, Julien Paccaud, Ange-Line Bruel, Frédéric Tran Mau-Them, Anne-Sophie Denommé-Pichon, Julien Thevenon, Hana Safraou, Thomas Besnard, Alice Goldenberg, Benjamin Cogné, Bertrand Isidor, Julian Delanne, Arthur Sorlin, Sébastien Moutton, Mélanie Fradin, Christèle Dubourg, Magali Gorce, Dominique Bonneau, Salima El Chehadeh, François-Guillaume Debray, Martine Doco-Fenzy, Kevin Uguen, Nicolas Chatron, Bernard Aral, Nathalie Marle, Paul Kuentz, Anne Boland, Robert Olaso, Jean-François Deleuze, Damien Sanlaville, Patrick Callier, Christophe Philippe, Christel Thauvin-Robinet, Laurence Faivre, and Antonio Vitobello
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genome sequencing ,RNA-seq ,optical genome mapping ,long-read sequencing ,clinical diagnoses ,Biology (General) ,QH301-705.5 - Abstract
Purpose: Multi-omics offer worthwhile and increasingly accessible technologies to diagnostic laboratories seeking potential second-tier strategies to help patients with unresolved rare diseases, especially patients clinically diagnosed with a rare OMIM (Online Mendelian Inheritance in Man) disease. However, no consensus exists regarding the optimal diagnostic care pathway to adopt after negative results with standard approaches.Methods: In 15 unsolved individuals clinically diagnosed with recognizable OMIM diseases but with negative or inconclusive first-line genetic results, we explored the utility of a multi-step approach using several novel omics technologies to establish a molecular diagnosis. Inclusion criteria included a clinical autosomal recessive disease diagnosis and single heterozygous pathogenic variant in the gene of interest identified by first-line analysis (60%–9/15) or a clinical diagnosis of an X-linked recessive or autosomal dominant disease with no causative variant identified (40%–6/15). We performed a multi-step analysis involving short-read genome sequencing (srGS) and complementary approaches such as mRNA sequencing (mRNA-seq), long-read genome sequencing (lrG), or optical genome mapping (oGM) selected according to the outcome of the GS analysis.Results: SrGS alone or in combination with additional genomic and/or transcriptomic technologies allowed us to resolve 87% of individuals by identifying single nucleotide variants/indels missed by first-line targeted tests, identifying variants affecting transcription, or structural variants sometimes requiring lrGS or oGM for their characterization.Conclusion: Hypothesis-driven implementation of combined omics technologies is particularly effective in identifying molecular etiologies. In this study, we detail our experience of the implementation of genomics and transcriptomics technologies in a pilot cohort of previously investigated patients with a typical clinical diagnosis without molecular etiology.
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- 2023
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33. Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation
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Sala, Margaux, Allain, Nathalie, Moreau, Mélanie, Jabouille, Arnaud, Henriet, Elodie, Abou-Hammoud, Aya, Uguen, Arnaud, Di-Tommaso, Sylvaine, Dourthe, Cyril, Raymond, Anne-Aurélie, Dupuy, Jean-William, Gerard, Emilie, Dugot-Senant, Nathalie, Rousseau, Benoit, Merlio, Jean-Phillipe, Pham-Ledart, Anne, Vergier, Béatrice, Tartare-Deckert, Sophie, Moreau, Violaine, and Saltel, Frédéric
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- 2022
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34. PD-L1 expression in recurrent head and neck squamous cell carcinoma
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Delafoy, Alice, Uguen, Arnaud, Lemasson, Gilles, Conan-Charlet, Virginie, Pradier, Olivier, Lucia, François, and Schick, Ulrike
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- 2022
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35. The Histopathological 'Placentitis Triad' Is Specific for SARS-CoV-2 Infection, and Its Acute Presentation Can Be Associated with Poor Fetal Outcome
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Annabelle Remoué, Yurina Suazo, Marie Uguen, Arnaud Uguen, Pascale Marcorelles, and Claire de Moreuil
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placenta ,COVID-19 ,SARS-CoV-2 ,massive perivillous fibrin deposition ,intervillositis ,prematurity ,Science - Abstract
(1) Background: Placental histological lesions reported in relation with SARS-CoV-2 infection are various, with potential consequences such as fetal growth retardation, prematurity or stillbirth/neonatal death. We report here on a placental pathological association which could be specific for SARS-CoV-2 infection and associated with poor fetal outcome; (2) Methods: We collected all the placental pathological examinations performed in Brest University Hospital (France) since the beginning of COVID-19 pandemic with a known maternal SARS-CoV-2 infection and a poor pregnancy outcome. In these cases, we described the pathological lesions and we searched for these lesions in a large series of placentas collected and examined in the same institution before the SARS-CoV-2 pandemic; (3) Results: Three cases with severe fetal outcome (tardive abortion, prematurity, neonatal death), from the first to the third trimesters of pregnancy, were included. The three cases showed features of massive and acute “placentitis triad” consisting in massive perivillous fibrin deposition, sub-acute intervillositis and trophoblastic necrosis. This association was not encountered in any of 8857 placentas analyzed during the period between 2002 and 2012 in our institution; (4) Conclusions: The “placentitis triad” appears to be specific for SARS-CoV-2 infection and, in case of massive and acute presentation, could result in poor fetal outcome.
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- 2023
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36. An alternative D. melanogaster 7SK snRNP
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Duy Nguyen, Nicolas Buisine, Olivier Fayol, Annemieke A. Michels, Olivier Bensaude, David H. Price, and Patricia Uguen
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7SK snRNA ,Drosophila ,P-TEFb ,Long non-coding RNA ,Cytology ,QH573-671 - Abstract
Abstract Background The 7SK small nuclear RNA (snRNA) found in most metazoans is a key regulator of P-TEFb which in turn regulates RNA polymerase II elongation. Although its primary sequence varies in protostomes, its secondary structure and function are conserved across evolutionary distant taxa. Results Here, we describe a novel ncRNA sharing many features characteristic of 7SK RNAs, in D. melanogaster. We examined the structure of the corresponding gene and determined the expression profiles of the encoded RNA, called snRNA:7SK:94F, during development. It is probably produced from the transcription of a lncRNA which is processed into a mature snRNA. We also addressed its biological function and we show that, like dm7SK, this alternative 7SK interacts in vivo with the different partners of the P-TEFb complex, i.e. HEXIM, LARP7 and Cyclin T. This novel RNA is widely expressed across tissues. Conclusion We propose that two distinct 7SK genes might contribute to the formation of the 7SK snRNP complex in D. melanogaster.
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- 2021
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37. The prognostic significance of PD-L1 expression on tumor and immune cells in Merkel cell carcinoma
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Guénolé, Morgan, Bénigni, Paolo, Bourbonne, Vincent, Lucia, François, Legoupil, Delphine, Pradier, Olivier, Misery, Laurent, Uguen, Arnaud, and Schick, Ulrike
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- 2021
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38. Untreated bleeds in people with hemophilia A in a noninterventional study and intrapatient comparison after initiating emicizumab in HAVEN 1–3
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Michael U. Callaghan, Elina Asikanius, Michaela Lehle, Johannes Oldenburg, Johnny Mahlangu, Marianne Uguen, Sammy Chebon, Rebecca Kruse‐Jarres, Víctor Jiménez‐Yuste, Midori Shima, Peter Trask, Christine L. Kempton, Craig M. Kessler, Gallia G. Levy, and Flora Peyvandi
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bleeding ,factor VIII ,hemophilia A ,hemostasis ,prophylaxis ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Background Bleeding in people with hemophilia A can be life threatening, and intra‐articular bleeds can result in joint damage. Most clinical studies focus on treated bleeds, while bleeds not treated with coagulation factor(s) (untreated bleeds) are underreported. Objectives We assessed the incidence of untreated bleeds during a noninterventional study (NIS) wherein people with hemophilia A, with or without factor VIII (FVIII) inhibitors, were managed according to standard practice. Patients/Methods Using the Bleed and Medication Questionnaire, we prospectively collected data from three cohorts: Cohort A, adults/adolescents (age ≥12 years) with FVIII inhibitors; Cohort B, children (aged
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- 2022
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39. Coding and noncoding variants in EBF3 are involved in HADDS and simplex autism
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Evin M. Padhi, Tristan J. Hayeck, Zhang Cheng, Sumantra Chatterjee, Brandon J. Mannion, Marta Byrska-Bishop, Marjolaine Willems, Lucile Pinson, Sylvia Redon, Caroline Benech, Kevin Uguen, Séverine Audebert-Bellanger, Cédric Le Marechal, Claude Férec, Stephanie Efthymiou, Fatima Rahman, Shazia Maqbool, Reza Maroofian, Henry Houlden, Rajeeva Musunuri, Giuseppe Narzisi, Avinash Abhyankar, Riana D. Hunter, Jennifer Akiyama, Lauren E. Fries, Jeffrey K. Ng, Elvisa Mehinovic, Nick Stong, Andrew S. Allen, Diane E. Dickel, Raphael A. Bernier, David U. Gorkin, Len A. Pennacchio, Michael C. Zody, and Tychele N. Turner
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Autism ,Neurodevelopmental disorder ,Enhancer ,Gene regulatory network ,EBF3 ,hs737 ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. Results We adapted the fitDNM statistical model to work in noncoding regions and tested enhancers for excess of DNVs in families with autism. We found only one enhancer (hs737) with nominal significance in the discovery (p = 0.0172), replication (p = 2.5 × 10−3), and combined dataset (p = 1.1 × 10−4). Each individual with a DNV in hs737 had shared phenotypes including being male, intact cognitive function, and hypotonia or motor delay. Our in vitro assessment of the DNVs showed they all reduce enhancer activity in a neuronal cell line. By epigenomic analyses, we found that hs737 is brain-specific and targets the transcription factor gene EBF3 in human fetal brain. EBF3 is genome-wide significant for coding DNVs in NDDs (missense p = 8.12 × 10−35, loss-of-function p = 2.26 × 10−13) and is widely expressed in the body. Through characterization of promoters bound by EBF3 in neuronal cells, we saw enrichment for binding to NDD genes (p = 7.43 × 10−6, OR = 1.87) involved in gene regulation. Individuals with coding DNVs have greater phenotypic severity (hypotonia, ataxia, and delayed development syndrome [HADDS]) in comparison to individuals with noncoding DNVs that have autism and hypotonia. Conclusions In this study, we identify DNVs in the hs737 enhancer in individuals with autism. Through multiple approaches, we find hs737 targets the gene EBF3 that is genome-wide significant in NDDs. By assessment of noncoding variation and the genes they affect, we are beginning to understand their impact on gene regulatory networks in NDDs.
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- 2021
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40. N3 (> 6 cm) squamous cell carcinoma of the head and neck: outcomes and predictive factors in 104 patients
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Selima Sellami, Jean Christophe Leclere, François Lucia, Yves Gobel, Arnaud Uguen, Jean Rousset, Dominique Gouders, Olivier Pradier, Rémi Marianowski, Ronan Abgral, and Ulrike Schick
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Otorhinolaryngology ,RF1-547 - Published
- 2021
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41. Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior
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Harris, Holly K., Nakayama, Tojo, Lai, Jenny, Zhao, Boxun, Argyrou, Nikoleta, Gubbels, Cynthia S., Soucy, Aubrie, Genetti, Casie A., Suslovitch, Victoria, Rodan, Lance H., Tiller, George E., Lesca, Gaetan, Gripp, Karen W., Asadollahi, Reza, Hamosh, Ada, Applegate, Carolyn D., Turnpenny, Peter D., Simon, Marleen E. H., Volker-Touw, Catharina M. L., Gassen, Koen L. I. van, Binsbergen, Ellen van, Pfundt, Rolph, Gardeitchik, Thatjana, Vries, Bert B. A. de, Immken, LaDonna L., Buchanan, Catherine, Willing, Marcia, Toler, Tomi L., Fassi, Emily, Baker, Laura, Vansenne, Fleur, Wang, Xiadong, Ambrus, Jr., Julian L., Fannemel, Madeleine, Posey, Jennifer E., Agolini, Emanuele, Novelli, Antonio, Rauch, Anita, Boonsawat, Paranchai, Fagerberg, Christina R., Larsen, Martin J., Kibaek, Maria, Labalme, Audrey, Poisson, Alice, Payne, Katelyn K., Walsh, Laurence E., Aldinger, Kimberly A., Balciuniene, Jorune, Skraban, Cara, Gray, Christopher, Murrell, Jill, Bupp, Caleb P., Pascolini, Giulia, Grammatico, Paola, Broly, Martin, Küry, Sébastien, Nizon, Mathilde, Rasool, Iqra Ghulam, Zahoor, Muhammad Yasir, Kraus, Cornelia, Reis, André, Iqbal, Muhammad, Uguen, Kevin, Audebert-Bellanger, Severine, Ferec, Claude, Redon, Sylvia, Baker, Janice, Wu, Yunhong, Zampino, Guiseppe, Syrbe, Steffan, Brosse, Ines, Jamra, Rami Abou, Dobyns, William B., Cohen, Lilian L., Blomhoff, Anne, Mignot, Cyril, Keren, Boris, Courtin, Thomas, Agrawal, Pankaj B., Beggs, Alan H., and Yu, Timothy W.
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- 2021
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42. Location-Quality-aware Policy Optimisation for Relay Selection in Mobile Networks
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Nielsen, Jimmy J., Olsen, Rasmus L., Madsen, Tatiana K., Uguen, Bernard, and Schwefel, Hans-Peter
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Computer Science - Networking and Internet Architecture - Abstract
Relaying can improve the coverage and performance of wireless access networks. In presence of a localisation system at the mobile nodes, the use of such location estimates for relay node selection can be advantageous as such information can be collected by access points in linear effort with respect to number of mobile nodes (while the number of links grows quadratically). However, the localisation error and the chosen update rate of location information in conjunction with the mobility model affect the performance of such location-based relay schemes; these parameters also need to be taken into account in the design of optimal policies. This paper develops a Markov model that can capture the joint impact of localisation errors and inaccuracies of location information due to forwarding delays and mobility; the Markov model is used to develop algorithms to determine optimal location-based relay policies that take the aforementioned factors into account. The model is subsequently used to analyse the impact of deployment parameter choices on the performance of location-based relaying in WLAN scenarios with free-space propagation conditions and in an measurement-based indoor office scenario., Comment: Accepted for publication in ACM/Springer Wireless Networks
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- 2015
43. Review on radiomic analysis in 18F-fluorodeoxyglucose positron emission tomography for prediction of melanoma outcomes.
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Amrane, Karim, Meur, Coline Le, Thuillier, Philippe, Berthou, Christian, Uguen, Arnaud, Deandreis, Désirée, Bourhis, David, Bourbonne, Vincent, and Abgral, Ronan
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- 2024
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44. Application of High-Throughput Imaging Mass Cytometry Hyperion in Cancer Research
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Marion Le Rochais, Patrice Hemon, Jacques-Olivier Pers, and Arnaud Uguen
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imaging mass cytometry ,hyperion ,cancer research ,biomarker ,tumoral microenvironment ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Imaging mass cytometry (IMC) enables the in situ analysis of in-depth-phenotyped cells in their native microenvironment within the preserved architecture of a single tissue section. To date, it permits the simultaneous analysis of up to 50 different protein- markers targeted by metal-conjugated antibodies. The application of IMC in the field of cancer research may notably help 1) to define biomarkers of prognostic and theragnostic significance for current and future treatments against well-established and novel therapeutic targets and 2) to improve our understanding of cancer progression and its resistance mechanisms to immune system and how to overcome them. In the present article, we not only provide a literature review on the use of the IMC in cancer-dedicated studies but we also present the IMC method and discuss its advantages and limitations among methods dedicated to deciphering the complexity of cancer tissue.
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- 2022
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45. Modelling of the packet delivery rate in an actual LoRaWAN network
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Ahmed Abdelghany, Bernard Uguen, Christophe Moy, and Dominique Lemur
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Computer communications ,Other topics in statistics ,Other computer networks ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
Abstract The Internet of things (IoT) paradigm is paving the way to ensure connectivity and monitoring within different market fields. Thus, it is critical to understand the packet transmission performance in Low Power Wide Area Network (LPWAN), especially LoRaWAN. Packet delivery rate (PDR) is considered as a dominant factor of the network performance and its dependency on the signal power. However, previous works do not model the PDR as a function of the received signal power. An in‐depth investigation of the PDR is done by performing an outdoor measurement campaign in the area of the Campus Beaulieu in Rennes. For each received LoRa packet, the effective signal power (ESP) values are obtained as well as their high influence on PDR is proven. With the given results, modelling the PDR using an ESP‐parameterized beta distribution function is proposed. Feasibility of the proposed model is assured by simulating PDR against ESP, hence, the simulated PDR values follow the distribution of the measured ones well. This PDR model gives important guidelines for future LoRaWAN network regulation and optimization.
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- 2021
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46. An alternative D. melanogaster 7SK snRNP
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Nguyen, Duy, Buisine, Nicolas, Fayol, Olivier, Michels, Annemieke A., Bensaude, Olivier, Price, David H., and Uguen, Patricia
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- 2021
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47. Case Report: Nasal Cavity Epithelial-Myoepithelial Carcinoma With High Fluoro-D-Glucose Uptake on Positron Emission Tomography/Computed Tomography
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Jacques Dzuko Kamga, Jean-Christophe Leclere, Arnaud Uguen, Karim Amrane, and Ronan Abgral
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nasal cavity ,high grade ,high avidity ,18FDG-PET/CT ,epithelial-myoepithelial carcinoma (EMC) ,Medicine (General) ,R5-920 - Abstract
Epithelial-myoepithelial carcinoma (EMC) is a rare malignant neoplasm arising most frequently in the salivary glands and exceptionally in the nasal cavity. EMC accounts for ~1–2% of salivary gland tumors. Even if the nodal and distant metastasis rates are low, tumor staging remains indicated. Here, the authors present the 2-deoxy-2-[18F]fluoro-D-glucose PET-CT (18F-FDG-PET/CT) study of a very rare case of biopsy-proven EMC of the left nasal cavity. This 18F-FDG-PET/CT was performed to stage this tumor and guide the therapeutic strategy due to an atypical high-grade presentation in immunohistochemistry. To our knowledge, this is the first case reporting such high 18F-FDG avidity of EMC of the nasal cavity in PET/CT.
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- 2021
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48. Lymphocytes and Neutrophil-to-Lymphocyte Ratio Variations After Selective Internal Radiation Treatment for HCC: A Retrospective Cohort Study
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Estrade, Florian, Lescure, Céline, Muzellec, Léa, Pedrono, Maud, Palard, Xavier, Pracht, Marc, Le Sourd, Samuel, Rolland, Yan, Uguen, Thomas, Garin, Etienne, and Edeline, Julien
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- 2020
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49. Pitolisant, a wake‐promoting agent devoid of psychostimulant properties: Preclinical comparison with amphetamine, modafinil, and solriamfetol
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Stéphane Krief, Isabelle Berrebi‐Bertrand, Isabelle Nagmar, Martin Giret, Simon Belliard, David Perrin, Marilyne Uguen, Philippe Robert, Jeanne‐Marie Lecomte, Jean‐Charles Schwartz, Olivier Finance, and Xavier Ligneau
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behavior ,modafinil ,neurochemistry ,pitolisant ,psychostimulants ,rodents ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Several therapeutic options are currently available to treat excessive daytime sleepiness (EDS) in patients suffering from narcolepsy or obstructive sleep apnea. However, there are no comparisons between the various wake‐promoting agents in terms of mechanism of action, efficacy, or safety. The goal of this study was to compare amphetamine, modafinil, solriamfetol, and pitolisant at their known primary pharmacological targets, histamine H3 receptors (H3R), dopamine, norepinephrine, and serotonin transporters, and in various in vivo preclinical models in relation to neurochemistry, locomotion, behavioral sensitization, and food intake. Results confirmed that the primary pharmacological effect of amphetamine, modafinil, and solriamfetol was to increase central dopamine neurotransmission, in part by inhibiting its transporter. Furthermore, solriamfetol increased levels of extracellular dopamine in the nucleus accumbens, and decreased the 3,4‐dihydroxyphenyl acetic acid (DOPAC)/DA ratio in the striatum, as reported for modafinil and amphetamine. All these compounds produced hyperlocomotion, behavioral sensitization, and hypophagia, which are common features of psychostimulants and of compounds with abuse potential. In contrast, pitolisant, a selective and potent H3R antagonist/inverse agonist that promotes wakefulness, had no effect on striatal dopamine, locomotion, or food intake. In addition, pitolisant, devoid of behavioral sensitization by itself, attenuated the hyperlocomotion induced by either modafinil or solriamfetol. Therefore, pitolisant presents biochemical, neurochemical, and behavioral profiles different from those of amphetamine and other psychostimulants such as modafinil or solriamfetol. In conclusion, pitolisant is a differentiated therapeutic option, when compared with psychostimulants, for the treatment of EDS, as this agent does not show any amphetamine‐like properties within in vivo preclinical models.
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- 2021
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50. Spatial-frequency-domain hyperspectral microscopy
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Georgakoudi, Irene, Georges, Marc P., Verrier, Nicolas, Uguen, Lisa, Piedevache, Ronan, Russias, Gaspard, Helmer, Sofian, Fournier, Antoine, Tregoat, Denis, and Perrin, Stéphane
- Published
- 2024
- Full Text
- View/download PDF
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