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270 results on '"Association pour la Recherche contre le Cancer (ARC)"'

1. TET2-mediated 5-hydroxymethylcytosine induces genetic instability and mutagenesis

Author: Lise Secardin, William Vainchenker, Olivier Bernard, Alexander A. Ishchenko, Murat Saparbaev, Emna Mahfoudhi, Philippe Rameau, Véronique Della Valle, Ibtissam Talhaoui, Isabelle Plo, Xenia Cabagnols, Salem Abbes, Hématopoïèse normale et pathologique (UMR 1170 ), Université Paris-Sud - Paris 11 (UP11) - Institut Gustave Roussy (IGR) - Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'hématologie moléculaire et cellulaire, institut Pasteur de Tunis, Institut Pasteur de Tunis - Réseau International des Instituts Pasteur, Institut Gustave Roussy (IGR), Réparation de l’ADN (CNRS UMR 8200), This work was supported by grants from Agence Nationale de la Recherche (ANR-Blanc 2013 GERMPN) to IP and [ANR Blanc 2010 Project ANR-10-BLAN-1617] to IP and MS, Association pour la Recherche contre le Cancer (ARC) (ARC libre 2012) to IP, Electricité de France (http://www.edf.fr) RB 2014-26 to MS and Fondation de France (http://www.fondationdefrance.org) [#2012 00029161] to AAI. Labex GR-Ex (IP, WV) is funded by the program 'Investissements d’avenir'. EM was funded by INSERM/DGRST then a grant from Institut Pasteur from Tunis, Tunisia. LS were supported by Ph.D grants from the Cancéropôle Région Ile de France (DIM cellule souche). XC was supported by Ph.D MENRT grant. IT was supported by postdoctoral fellowship from the Fondation ARC (http://www.arc-cancer.net) PDF20110603195., ANR-Blanc 2013 GERMPN, GERMPN, ANR-10-BLAN-1617, EPIGENOME, Formation, dynamics and epigenetic functions of 5-hydroxymethylcytosine residues in DNA.(2010), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tunis El Manar (UTM), Laboratoire d'hématologie moléculaire et cellulaire (LR11IPT07), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Plateforme imagerie et cytométrie (PFIC), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie, Institut Pasteur de Tunis, This work was supported by grants from Agence Nationale de la Recherche (ANR-Blanc 2013 GERMPN) to IP and [ANR Blanc 2010 Project ANR-10-BLAN-1617] to IP and MS, Association pour la Recherche contre le Cancer (ARC) (ARC libre 2012) to IP, Electricité de France (http://www.edf.fr) RB 2014-26 to MS and Fondation de France (http://www.fondationdefrance.org) [#2012 00029161] to AAI. Labex GR-Ex (IP, WV) is funded by the program 'Investissements d’avenir'. EM was funded by INSERM/DGRST then a grant from Institut Pasteur from Tunis, Tunisia. LS were supported by Ph.D grants from the Cancéropôle Région Ile de France (DIM cellule souche). XC was supported by Ph.D MENRT grant. IT was supported by postdoctoral fellowship from the Fondation ARC., We thank the cytometry platform of Gustave Roussy (Y. Lecluse)., ANR-10-BLAN-1617,EPIGENOME,Formation, dynamics and epigenetic functions of 5-hydroxymethylcytosine residues in DNA.(2010), ANR-13-JSV1-0007,GERMPN,Etude des cas familiaux de néoplasmes myéloproliférifs: recherche des anomalies génétiques et de leurs fonctions.(2013), Pasteur Tunis, Institut, BLANC - Formation, dynamics and epigenetic functions of 5-hydroxymethylcytosine residues in DNA. - - EPIGENOME2010 - ANR-10-BLAN-1617 - BLANC - VALID, Jeunes Chercheuses et Jeunes Chercheurs - Etude des cas familiaux de néoplasmes myéloproliférifs: recherche des anomalies génétiques et de leurs fonctions. - - GERMPN2013 - ANR-13-JSV1-0007 - JC - VALID, and Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, DNA Repair, Genetic instability, MESH: Fibroblasts/cytology, MESH: Tumor Suppressor Protein p53/metabolism, MESH: Fibroblasts/metabolism, MESH: Mutagenesis, MESH: Base Sequence, MESH: Thymine DNA Glycosylase/deficiency, Biochemistry, MESH: DNA Repair, Epigenesis, Genetic, S Phase, MESH: Thymine DNA Glycosylase/genetics, Mice, chemistry.chemical_compound, MESH: Genomic Instability, MESH: DNA-Binding Proteins/genetics, MESH: B-Lymphocytes/metabolism, MESH: Animals, MESH: Cytosine/metabolism, MESH: Epigenesis, Genetic, MESH: Megakaryocyte Progenitor Cells/cytology, MESH: B-Lymphocytes/cytology, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Cytosine/analogs & derivatives, MESH: S Phase, Base excision repair, DNA-Binding Proteins, MESH: Proto-Oncogene Proteins/genetics, 5-hmC, CpG site, 5-Methylcytosine, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cytosine, Guanine, MESH: Hydroxylation, TDG, Cell cycle, Biology, MESH: DNA-Binding Proteins/metabolism, Hydroxylation, Genomic Instability, Cell Line, Dioxygenases, 03 medical and health sciences, MESH: Tumor Suppressor Protein p53/genetics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Proto-Oncogene Proteins, Animals, Humans, MESH: Mice, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Megakaryocyte Progenitor Cells, MESH: 5-Methylcytosine/analogs & derivatives, 5-Hydroxymethylcytosine, TET2, MESH: Humans, Base Sequence, MESH: Proto-Oncogene Proteins/metabolism, Mutagenesis, MESH: 5-Methylcytosine/metabolism, Cell Biology, Fibroblasts, Molecular biology, Thymine DNA Glycosylase, MESH: Cell Line, 030104 developmental biology, DNA demethylation, chemistry, DNA glycosylase, MESH: Megakaryocyte Progenitor Cells/metabolism, Tumor Suppressor Protein p53
Abstract: International audience; The family of Ten-Eleven Translocation (TET) proteins is implicated in the process of active DNA demethy-lation and thus in epigenetic regulation. TET 1, 2 and 3 proteins are oxygenases that can hydroxylate 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) and further oxidize 5-hmC into 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). The base excision repair (BER) pathway removes the resulting 5-fC and 5-caC bases paired with a guanine and replaces them with regular cytosine. The question arises whether active modification of 5-mC residues and their subsequent elimination could affect the genomic DNA stability. Here, we generated two inducible cell lines (Ba/F3-EPOR, and UT7) over-expressing wild-type or catalytically inactive human TET2 proteins. Wild-type TET2 induction resulted in an increased level of 5-hmC and a cell cycle defect in S phase associated with higher level of phospho-rylated P53, chromosomal and centrosomal abnormalities. Furthermore, in a thymine-DNA glycosylase (Tdg) deficient context, the TET2-mediated increase of 5-hmC induces mutagenesis characterized by GC > AT transitions in CpG context suggesting a mutagenic potential of 5-hmC metabolites. Altogether, these data suggest that TET2 activity and the levels of 5-hmC and its derivatives should be tightly controlled to avoid genetic and chromosomal instabilities. Moreover, TET2-mediated active demethylation might be a very dangerous process if used to entirely demethylate the genome and might rather be used only at specific loci.
Published: 2016
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2. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

Author: Manfred B. Lutz, Roberto Labianca, Patrick Pessaux, Bert A. Bonsing, Benoist Chibaudel, David Malka, Claudio Bassi, Sophie Gourgou-Bourgade, Geertjan van Tienhoven, Pascal Hammel, Carine Bellera, Laeticia Dahan, Jean-Luc Van Laethem, Daniela Aust, Emmanuel Chamorey, Jean Robert Delpero, Josep Tabernero, Adelaide Dousseau, Teresa Macarulla, Franck Bonnetain, Julien Taieb, Karin Haustermans, Laurence Collette, Thomas Aparicio, François Lacaine, John P. Neoptolemos, Simone Mathoulin-Pélissier, Bengt Glimelius, Thierry Conroy, Paula Ghaneh, Alain Sauvanet, Erich Gerber, Christos Dervenis, Aurélien Latouche, Murielle Mauer, Michel Ducreux, Valérie Jooste, Virginie Berger, Jocelyn Gal, Alain Hendlisz, Aimery de Gramont, Emmanuel Mitry, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), UNICANCER, Leiden University Medical Center (LUMC), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Université Victor Segalen - Bordeaux 2, CHU Bordeaux [Bordeaux], Uppsala Universitet [Uppsala], University Hospitals Leuven [Leuven], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Carl Gustav Carus University (DRESDEN - CGCU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), G.B. Rossi Hospital, Verona University, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cooperator Multidisciplinary Oncology Group (GERCOR), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Agia Olga Hospital [Athènes] (Konstantopoulio ), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut für Radioonkologie, Royal Liverpool University Hospital, University of Liverpool-Royal Liverpool and Broadgreen University Hospital NHS Trust, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Institut Jules Bordet [Bruxelles], Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Azienda Ospedaleria Ospedali Riuniti di Bergamo, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CaritasKlinikum Saarbrücken, Vall d'Hebron University Hospital [Barcelona], European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Institut Curie [Paris], CRLCC René Huguenin, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Service d’Hépatologie [Hôpital Beaujon], Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Academisch Medisch Centrum bij, Universiteit van Amsterdam (UvA), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CHU Tenon [APHP], Hôpital Erasme (Bruxelles), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Carl Gustav Carus University ( DRESDEN - CGCU ), Technische Universität Dresden ( TUD ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, CRLCC Antoine Lacassagne, Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Cooperator Multidisciplinary Oncology Group ( GERCOR ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut Paoli Calmettes, Agia Olga Hospital [Athènes] ( Konstantopoulio ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Hôpital Beaujon, Institut Jules Bordet, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), European Organisation for Research and Treatment of Cancer [Bruxelles] ( EORTC ), European Cancer Organisation [Bruxelles] ( ECCO ), Institut Curie, L'Institut hospitalo-universitaire de Strasbourg ( IHU Strasbourg ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Universiteit van Amsterdam ( UvA ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Bergonié - CRLCC Bordeaux, Universiteit Leiden, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Verona = University of Verona (UNIVR), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)
Subjects: Oncology, Cancer Research, Pathology, Delphi Technique, MESH : Randomized Controlled Trials as Topic, MESH: Delphi Technique, MESH : Consensus, law.invention, Clinical trials, 0302 clinical medicine, Pancreatic cancer, Time to event end-point, Consensus, Guidelines, Methodology, Clinical trials, Randomized controlled trial, law, 030212 general & internal medicine, Time to event end-point, Randomized Controlled Trials as Topic, Event (probability theory), MESH: Endpoint Determination, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, 16. Peace & justice, 3. Good health, 030220 oncology & carcinogenesis, MESH : Disease-Free Survival, MESH : Endpoint Determination, MESH: Pancreatic Neoplasms, medicine.medical_specialty, Consensus, Endpoint Determination, Guidelines, Disease-Free Survival, 03 medical and health sciences, Internal medicine, Pancreatic cancer, medicine, Overall survival, Humans, MESH: Consensus, Distributed File System, neoplasms, MESH: Humans, End point, business.industry, MESH : Humans, Methodology, Cancer, medicine.disease, Pancreatic Neoplasms, Clinical trial, MESH: Randomized Controlled Trials as Topic, MESH : Delphi Technique, MESH: Disease-Free Survival, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Pancreatic Neoplasms
Abstract: International audience; BACKGROUND:Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer.METHODS:Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9).RESULTS:For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items.CONCLUSION:The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.
Published: 2014
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3. Robotic surgery: a time of change

Author: Marescaux, Jacques, Seeliger, Barbara, Institut de Recherche Contre les Cancers de l'Appareil Digestif-European Institute of Telesurgery (IRCAD/EITS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, CHU Strasbourg, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery
Abstract: International audience
Published: 2023
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4. A Role for the Serine/Arginine-Rich (SR) Protein B52/SRSF6 in Cell Growth and Myc Expression in Drosophila

Author: Fernando, Celine, Audibert, Agnes, Simon, Francoise, Tazi, Jamal, Juge, Francois, Cycle et détermination cellulaires = Cell cycle and cell determination (LBD-E04), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), European Alternative Splicing Network of Excellence (EURASNET, FP6 life sciences, genomics and biotechnology for health), Institut National du Cancer (Canceropole Ile-de-France), Association pour la Recherche contre le Cancer ARC [4894], Ministry of National Education, Research and Technology (M.E.N.R.T), Association pour la Recherche contre le Cancer (ARC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Developmental and Behavioral Genetics, Gene Expression Regulation, Developmental, Nuclear Proteins, Cell Differentiation, Cell Growth Processes, Myc, Investigations, Phosphoproteins, DNA-Binding Proteins, Proto-Oncogene Proteins c-myc, Drosophila melanogaster, Phenotype, genetic screen, Animals, Drosophila Proteins, cell growth, Cell Lineage, RNA Splicing Factors, SR protein, Mechanoreceptors, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Transcription Factors
Abstract: International audience; Serine-/arginine-rich (SR) proteins are RNA-binding proteins that are primarily involved in alternative splicing. Expression of some SR proteins is frequently upregulated in tumors, and previous reports have demonstrated that these proteins can directly participate in cell transformation. Identifying factors that can rescue the effects of SR overexpression in vivo is, therefore, of potential therapeutic interest. Here, we analyzed phenotypes induced by overexpression of the SR protein B52 during Drosophila development and identified several proteins that can rescue these phenotypes. Using the mechanosensory bristle lineage as a developmental model, we show that B52 expression level influences cell growth, but not differentiation, in this lineage. In particular, B52 overexpression increases cell growth, upregulates myc transcription, and gives rise to flies lacking thoracic bristles. Using a genetic screen, we identified several suppressors of the phenotypes induced by overexpression of B52 in vivo in two different organs. We show that upregulation of brain tumor (brat), a tumor suppressor and post-transcriptional repressor of myc, and downregulation of lilliputian (lilli), a subunit of the superelongation complex involved in transcription elongation, efficiently rescue the phenotypes induced by B52 overexpression. Our results demonstrate a role of this SR protein in cell growth and identify candidate proteins that may overcome the effects of SR protein overexpression in mammals.
Published: 2015
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5. Epstein–Barr virus encoded BALF1 gene is transcribed in Burkitt's lymphoma cell lines and in nasopharyngeal carcinoma's biopsies

Author: H. Melouli, Abdelmadjide Bouguermouh, D. Djennaoui, G. Cabras, G. Decaussin, Yué Zeng, P. Broully, Tadamasa Ooka, Virologie et pathogenèse virale (VPV), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Le centre hospitalier universitaire (CHU) Mustapha Pacha [Alger], Institut Pasteur d'Algérie, Réseau International des Instituts Pasteur (RIIP), This work was supported by Contract no. 3381 from the Association pour la Recherche contre le Cancer (ARC) and Ligue Nationale Contre le Cancer (Comité Rhône)., and We thank Dr. J. Nicholls (The University of Hong Kong) for a critical reading of the manuscript. We also thank Sylvie Fiorini for technical assistance. Scholarship from the Association pour la Recherche contre le Cancer (ARC) and Italian government to G.C.
Subjects: MESH: Burkitt Lymphoma/virology, Herpesvirus 4, Human, BALF1, Transcription, Genetic, MESH: 3T3 Cells, Biopsy, MESH: Nasopharyngeal Neoplasms/virology, medicine.disease_cause, Mice, MESH: Biopsy, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, hemic and lymphatic diseases, MESH: DNA, Viral/genetics, MESH: Animals, OCIS 000.1430, MESH: Transcription, Genetic, 0303 health sciences, Expression vector, MESH: Nasopharyngeal Neoplasms/genetics, Reverse Transcriptase Polymerase Chain Reaction, 3T3 Cells, Transfection, Burkitt Lymphoma, 3. Good health, MESH: Viral Proteins/genetics, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: Cell Division, MESH: RNA, Viral/genetics, NPC, Cell Division, DNA, Complementary, MESH: Cell Line, Tumor, MESH: DNA, Complementary/genetics, Nasopharyngeal neoplasm, Biology, Viral Proteins, 03 medical and health sciences, EBV, Cell Line, Tumor, Virology, BL, medicine, Animals, Humans, MESH: Mice, B cell, 030304 developmental biology, MESH: Humans, MESH: Transfection, MESH: Herpesvirus 4, Human/genetics, Nasopharyngeal Neoplasms, medicine.disease, Epstein–Barr virus, Molecular biology, MESH: Herpesvirus 4, Human/growth & development, Anti-apoptosis, Nasopharyngeal carcinoma, Cell culture, DNA, Viral, MESH: Burkitt Lymphoma/genetics, Burkitt's lymphoma
Abstract: Background: The Epstein–Barr virus (EBV) encodes two anti-apoptotic cellular Bcl2 homologs, BALF1 and BHRF1. BHRF1 has an antiapoptotic activity but is rarely expressed in nasopharyngeal carcinoma (NPC). However, BALF1 is not yet well characterized. Objectives: The objective of the study was to characterize BALF1gene. First, the search of its transcriptional expression in EBV-positive B cell lines, EBV-positive Burkitt’s lymphoma’s cell lines and nasopharyngeal carcinoma’s biopsies. Second, the examination of its anti-apoptotic activity in serum dependent assays. Study design: We first analysed the transcriptional expression of BALF1 by reverse transcriptase DNA polymerase chain reaction (RT-PCR) method. For the analysis of its anti-apoptotic activity, we transfected NIH3T3 cells with pBABE-BALF1 expression plasmid and studied serum dependence of these transfectants. Results: BALF1expression was detected in the latent stage and increased more significantly during the lytic phase in IgG-treated AKATA and TPA-SB-treated P3HR1-TK negative cell lines. As its expression was not affected by the inhibitor of viral DNA synthesis, this gene does not belong to late gene family. When analysed its transcription in Burkitt’s lymphoma (BL)-derived cell lines and NPC biopsies, all BL-derived cell lines and more than 80% of NPC biopsies transcribed this gene. The study of serum dependence of BALF1-transfected NIH3T3 cells showed: with 10% of serum, BALF1 transfectants grew significantly more higher cell density than vector alone transfected NIH3T3 cell lines and with 1% of serum, BALF1 transfectants were capable of growing, but with about 40% reduced rate in comparison with those with 10% serum, while vector alone transfected NIH3T3 cells could not almost grow. Conclusion: BALF1gene was transcribed in EBV-associated tumor cells. BALF1 could render cells to serum independent. These results suggest that BALF1 gene could play its role in EBV oncogenesis. © 2005 Elsevier B.V. All rights reserved.
Published: 2005
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6. Trackerless Volume Reconstruction from Intraoperative Ultrasound Images

Author: El Hadramy, Sidaty, Verde, Juan, Padoy, Nicolas, Cotin, Stéphane, Computational Anatomy and Simulation for Medicine (MIMESIS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, and Université de Strasbourg (UNISTRA)
Subjects: Volume Reconstruction, Intraoperative Ultrasound, Liver Surgery, [INFO]Computer Science [cs], Recurrent Neural Networks
Abstract: This paper proposes a method for trackerless ultrasound volume reconstruction in the context of minimally invasive surgery. It is based on a Siamese architecture, including a recurrent neural network that leverages the ultrasound image features and the optical flow to estimate the relative position of frames. Our method does not use any additional sensor and was evaluated on ex-vivo porcine data. It achieves translation and orientation errors of 0.449 ± 0.189 mm and 1.3 ± 1.5 degrees respectively for the relative pose estimation. In addition, despite the predominant non-linearity motion in our context, our method achieves a good reconstruction with final and average drift rates of 23.11% and 28.71% respectively. To the best of our knowledge, this is the first work to address volume reconstruction in the context of intravascular ultrasound. Code will be publicly released.
Published: 2023

7. Unraveling the role of the liver myeloid compartment during hepatitis C virus cure

Author: Emilie Crouchet, Thomas F. Baumert, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), ANR-10-LABX-0028,HepSys,Functional genomics of viral hepatitis and liver disease(2010), ANR-21-RHUS-0001,DELIVER,Deliver therapeuthic innovation for advanced hepatic diseases(2021), and ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017)
Subjects: interferon-stimulated genes, Hepatology, exhaustion, single cell RNA-Seq, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Direct-acting antivirals, innate immunity, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: No abstract available
Published: 2023
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8. Tumor microenvironment-derived serum markers as a new frontier of diagnostic and prognostic assessment in biliary tract cancers

Author: Romain Désert, Fabio Giannone, Catherine Schuster, Thomas F. Baumert, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), ANR-21-RHUS-0001,DELIVER,Deliver therapeuthic innovation for advanced hepatic diseases(2021), ANR-10-LABX-0028,HepSys,Functional genomics of viral hepatitis and liver disease(2010), ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), and ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017)
Subjects: Cancer Research, Oncology, [SDV.CAN]Life Sciences [q-bio]/Cancer, pathology, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Sciences du Vivant [q-bio]/Cancer
Abstract: editorial research support, n.i.h., extramural research support, non-u.s. gov't 2023 Mar 01 2022 12 01 imported
Published: 2023
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9. Inhibiting cell-to-cell transmission to reach HDV cure: The importance of IFN-α

Author: Julie Lucifora, Eloi R. Verrier, Thomas F. Baumert, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017), ANR-21-CE15-0035,DELTArget,Caractérisation de facteur cellulaires impliqués dans l'infection par le virus de l'hépatite D pour la caractérisation de nouvelles cibles antivirales(2021), European Project: 101021417,FIBCAN, and European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016)
Subjects: Hepatology, Interferon-alpha, Hepatitis Delta Virus, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: editorial research support, non-u.s. gov't 2022 Oct 2022 08 08 imported
Published: 2022
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10. Conventional and artificial intelligence-based imaging for biomarker discovery in chronic liver disease

Author: Jérémy Dana, Aïna Venkatasamy, Antonio Saviano, Joachim Lupberger, Yujin Hoshida, Valérie Vilgrain, Pierre Nahon, Caroline Reinhold, Benoit Gallix, Thomas F. Baumert, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, McGill University = Université McGill [Montréal, Canada], Pôle Hépato-digestif [Strasbourg], Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Harold C. Simmons Comprehensive Cancer Center [Dallas, TX, États-Unis], University of Texas Southwestern Medical Center [Dallas], Laboratory of Imaging Biomarkers, UMR1149, INSERM-University Paris-Diderot, Paris, AP-HP - Hôpitaux Universitaires Paris Seine-Saint-Denis (GHU 93), Augmented Intelligence and Precision Health Laboratory (AIPHL), Department of Radiology, McGill University, Montreal, QC H3G 1A4, Canada, ANR-10-LABX-0028,HepSys,Functional genomics of viral hepatitis and liver disease(2010), ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), and European Project: 667273,H2020,H2020-PHC-2015-two-stage,HEP-CAR(2016)
Subjects: Liver Cirrhosis, Chronic liver disease Histo-pathological features Pejorative evolution Quantitative biomarkers Elastography Machine learning Radiomics Deep learning, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Article, methods, Artificial Intelligence, Hypertension, Portal, Machine learning, Humans, Quantitative biomarkers, Histo-pathological features, diagnostic imaging, pathology, Radiomics, Hepatology, Liver Neoplasms, Chronic liver disease, Deep learning, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Magnetic Resonance Imaging, Fatty Liver, Liver, Pejorative evolution, Disease Progression, Elasticity Imaging Techniques, Elastography, Biomarkers
Abstract: Chronic liver diseases, resulting from chronic injuries of various causes, lead to cirrhosis with life-threatening complications including liver failure, portal hypertension, hepatocellular carcinoma. A key unmet medical need is robust non-invasive biomarkers to predict patient outcome, stratify patients for risk of disease progression and monitor response to emerging therapies. Quantitative imaging biomarkers have already been developed, for instance, liver elastography for staging fibrosis or proton density fat fraction on magnetic resonance imaging for liver steatosis. Yet, major improvements, in the field of image acquisition and analysis, are still required to be able to accurately characterize the liver parenchyma, monitor its changes and predict any pejorative evolution across disease progression. Artificial intelligence has the potential to augment the exploitation of massive multi-parametric data to extract valuable information and achieve precision medicine. Machine learning algorithms have been developed to assess non-invasively certain histological characteristics of chronic liver diseases, including fibrosis and steatosis. Although still at an early stage of development, artificial intelligence-based imaging biomarkers provide novel opportunities to predict the risk of progression from early-stage chronic liver diseases toward cirrhosis-related complications, with the ultimate perspective of precision medicine. This review provides an overview of emerging quantitative imaging techniques and the application of artificial intelligence for biomarker discovery in chronic liver disease. journal article review 2022 Jun 2022 02 09 imported
Published: 2022
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11. Consensus guidelines for the definition of time-to-event end points in image-guided tumor ablation

Author: Puijk, Robbert, Ahmed, Muneeb, Adam, Andreas, Arai, Yasuaki, Arellano, Ronald, de Baère, Thierry, Bale, Reto, Bellera, Carine, Binkert, Christoph, Brace, Christopher, Breen, David, Brountzos, Elias, Callstrom, Matthew, Carrafiello, Gianpaolo, Chapiro, Julius, de Cobelli, Francesco, Coupé, Veerle, Crocetti, Laura, Denys, Alban, Dupuy, Damian, Erinjeri, Joseph, Filippiadis, Dimitris, Gangi, Afshin, Gervais, Debra, Gillams, Alice, Greene, Tissy, Guiu, Boris, Helmberger, Thomas, Iezzi, Roberto, Kang, Tae Wook, Kelekis, Alexis, Kim, Hyun, Kröncke, Thomas, Kwan, Sharon, Lee, Min Woo, Lee, Fred, Lee, Edward, Liang, Ping, Lissenberg-Witte, Birgit, Lu, David, Madoff, David, Mauri, Giovanni, Meloni, Maria Franca, Morgan, Robert, Nadolski, Gregory, Narayanan, Govindarajan, Newton, Isabel, Nikolic, Boris, Orsi, Franco, Pereira, Philippe, Pua, Uei, Rhim, Hyunchul, Ricke, Jens, Rilling, William, Salem, Riad, Scheffer, Hester, Sofocleous, Constantinos, Solbiati, Luigi, Solomon, Stephen, Soulen, Michael, Sze, Daniel, Uberoi, Raman, Vogl, Thomas, Wang, David, Wood, Bradford, Goldberg, S Nahum, Meijerink, Martijn, Goldberg, S. Nahum, Amsterdam UMC - Amsterdam University Medical Center, Harvard Medical School [Boston] (HMS), Guy's and St Thomas' Hospital [London], National Cancer Center Hospital (NCCJ), Department of radiology (Massachusetts General Hospital), Massachusetts General Hospital [Boston], Institut Gustave Roussy (IGR), Imagerie thérapeutique (radiologie interventionnelle), Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Institut Bergonié [Bordeaux], UNICANCER, Kantonsspital Winterthur (KSW), University of Wisconsin School of Medicine and Public Health, University Hospital Southampton NHS Foundation Trust, National and Kapodistrian University of Athens (NKUA), Mayo Clinic [Rochester], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Yale University [New Haven], IRCCS Ospedale San Raffaele [Milan, Italy], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), University of Pisa - Università di Pisa, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Warren Alpert Medical School of Brown University, Memorial Sloan Kettering Cancer Center (MSKCC), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, The London Clinic cancer, Society of Interventional Oncology (SIO), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), and Kiel University
Subjects: Ablation Techniques, medicine.medical_specialty, Consensus, [SDV]Life Sciences [q-bio], MESH: Societies, Medical, MEDLINE, Outcome (game theory), Session (web analytics), Quality of life (healthcare), Humans, Neoplasms, Reproducibility of Results, Societies, Medical, Medical, medicine, MESH: Neoplasms, Radiology, Nuclear Medicine and imaging, Medical physics, ddc:610, MESH: Consensus, License, MESH: Humans, Health economics, business.industry, MESH: Ablation Techniques, Opinion leadership, MESH: Reproducibility of Results, Clinical trial, business, Societies
Abstract: International audience; There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.
Published: 2021
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12. Surgical Models of Liver Regeneration in Pigs: A Practical Review of the Literature for Researchers

Author: Lorenzo Cinelli, Edoardo Maria Muttillo, Emanuele Felli, Andrea Baiocchini, Fabio Giannone, Jacques Marescaux, Didier Mutter, Michel De Mathelin, Sylvain Gioux, Eric Felli, Michele Diana, Ospedale San Raffaele, l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), San Camillo Forlanini Hospital [Rome], Nouvel Hôpital Civil de Strasbourg, Université de Strasbourg (UNISTRA), Institut de Chirurgie guidée par l'Image, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), University of Bern, and ANR-18-CE19-0026,LiverSURG,Imagerie Optique Quantitative pour la Chirurgie du Foie(2018)
Subjects: hepatotoxicity, liver diseases, liver injury, liver regeneration, liver repair, 610 Medicine & health, General Medicine, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, surgery, physiology, pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The remarkable capacity of regeneration of the liver is well known, although the involved mechanisms are far from being understood. Furthermore, limits concerning the residual functional mass of the liver remain critical in both fields of hepatic resection and transplantation. The aim of the present study was to review the surgical experiments regarding liver regeneration in pigs to promote experimental methodological standardization. The Pubmed, Medline, Scopus, and Cochrane Library databases were searched. Studies evaluating liver regeneration through surgical experiments performed on pigs were included. A total of 139 titles were screened, and 41 articles were included in the study, with 689 pigs in total. A total of 29 studies (71% of all) had a survival design, with an average study duration of 13 days. Overall, 36 studies (88%) considered partial hepatectomy, of which four were an associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Remnant liver volume ranged from 10% to 60%. Only 2 studies considered a hepatotoxic pre-treatment, while 25 studies evaluated additional liver procedures, such as stem cell application, ischemia/reperfusion injury, portal vein modulation, liver scaffold application, bio-artificial, and pharmacological liver treatment. Only nine authors analysed how cytokines and growth factors changed in response to liver resection. The most used imaging system to evaluate liver volume was CT-scan volumetry, even if performed only by nine authors. The pig represents one of the best animal models for the study of liver regeneration. However, it remains a mostly unexplored field due to the lack of experiments reproducing the chronic pathological aspects of the liver and the heterogeneity of existing studies. journal article review research support, non-u.s. gov't 2023 Feb 13 2023 02 13 imported
Published: 2023
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13. Treatment of HCC with claudin-1-specific antibodies suppresses carcinogenic signaling and reprograms the tumor microenvironment

Author: Natascha Roehlen, Marion Muller, Zeina Nehme, Emilie Crouchet, Frank Jühling, Fabio Del Zompo, Sara Cherradi, Francois H.T. Duong, Nuno Almeida, Antonio Saviano, Mirian Fernández-Vaquero, Tobias Riedl, Houssein El Saghire, Sarah C. Durand, Clara Ponsolles, Marine A. Oudot, Romain Martin, Nicolas Brignon, Emanuele Felli, Patrick Pessaux, Antonin Lallement, Irwin Davidson, Simonetta Bandiera, Christine Thumann, Patrice Marchand, Solange Moll, Brandon Nicolay, Nabeel Bardeesy, Yujin Hoshida, Mathias Heikenwälder, Roberto Iacone, Alberto Toso, Markus Meyer, Greg Elson, Tamas Schweighoffer, Geoffrey Teixeira, Mirjam B. Zeisel, Patrice Laquerriere, Joachim Lupberger, Catherine Schuster, Laurent Mailly, Thomas F. Baumert, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nouvel Hôpital Civil de Strasbourg, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre médical universitaire de Genève (CMU), Harvard Medical School [Boston] (HMS), University of Texas Southwestern Medical Center, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
Subjects: tumor immune microenvironment, Hepatology, tight junction, Aucun, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, resistance, stemness, pharmacology, therapeutic use, CLDN1, plasticity, genetics, HCC, Liver cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Despite recent approvals, the response to treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) remain poor. Claudin-1 (CLDN1) is a membrane protein that is expressed at tight junctions, but it can also be exposed non-junctionally, such as on the basolateral membrane of the human hepatocyte. While CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 and its role as a therapeutic target in HCC remains unexplored. Using humanized monoclonal antibodies (mAbs) specifically targeting the extracellular loop of human non-junctional CLDN1 and a large series of patient-derived cell-based and animal model systems we aimed to investigate the role of CLDN1 as a therapeutic target for HCC. Targeting non-junctional CLDN1 markedly suppressed tumor growth and invasion in cell line-based models of HCC and patient-derived 3D ex vivo models. Moreover, the robust effect on tumor growth was confirmed in vivo in a large series of cell line-derived xenograft and patient-derived xenograft mouse models. Mechanistic studies, including single-cell RNA sequencing of multicellular patient HCC tumorspheres, suggested that CLDN1 regulates tumor stemness, metabolism, oncogenic signaling and perturbs the tumor immune microenvironment. Our results provide the rationale for targeting CLDN1 in HCC and pave the way for the clinical development of CLDN1-specific mAbs for the treatment of advanced HCC. Hepatocellular carcinoma (HCC) is associated with high mortality and unsatisfactory treatment options. Herein, we identified the cell surface protein Claudin-1 as a treatment target for advanced HCC. Monoclonal antibodies targeting Claudin-1 inhibit tumor growth in patient-derived ex vivo and in vivo models by modulating signaling, cell stemness and the tumor immune microenvironment. Given the differentiated mechanism of action, the identification of Claudin-1 as a novel therapeutic target for HCC provides an opportunity to break the plateau of limited treatment response. The results of this preclinical study pave the way for the clinical development of Claudin-1-specific antibodies for the treatment of advanced HCC. It is therefore of key impact for physicians, scientists and drug developers in the field of liver cancer and gastrointestinal oncology. journal article research support, non-u.s. gov't 2023 Feb 2022 10 27 imported
Published: 2023
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14. Deep Learning to Classify AL versus ATTR Cardiac Amyloidosis MR Images

Author: Philippe Germain, Armine Vardazaryan, Aissam Labani, Nicolas Padoy, Catherine Roy, Soraya El Ghannudi, Nouvel Hôpital Civil de Strasbourg, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, and univOAK, Archive ouverte
Subjects: cardiac amyloidosis, light chain, transthyretine, deep learning, convolutional neural network, algorithm vs. human comparison, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine (miscellaneous), General Biochemistry, Genetics and Molecular Biology
Abstract: The aim of this work was to compare the classification of cardiac MR-images of AL versus ATTR amyloidosis by neural networks and by experienced human readers. Cine-MR images and late gadolinium enhancement (LGE) images of 120 patients were studied (70 AL and 50 TTR). A VGG16 convolutional neural network (CNN) was trained with a 5-fold cross validation process, taking care to strictly distribute images of a given patient in either the training group or the test group. The analysis was performed at the patient level by averaging the predictions obtained for each image. The classification accuracy obtained between AL and ATTR amyloidosis was 0.750 for cine-CNN, 0.611 for Gado-CNN and between 0.617 and 0.675 for human readers. The corresponding AUC of the ROC curve was 0.839 for cine-CNN, 0.679 for gado-CNN (p < 0.004 vs. cine) and 0.714 for the best human reader (p < 0.007 vs. cine). Logistic regression with cine-CNN and gado-CNN, as well as analysis focused on the specific orientation plane, did not change the overall results. We conclude that cine-CNN leads to significantly better discrimination between AL and ATTR amyloidosis as compared to gado-CNN or human readers, but with lower performance than reported in studies where visual diagnosis is easy, and is currently suboptimal for clinical practice.
Published: 2023
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15. Tight Junction Protein Signaling and Cancer Biology

Author: Zeina Nehme, Natascha Roehlen, Punita Dhawan, Thomas F. Baumert, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine II, University Hospital Freiburg, Buffet Cancer Center [Omaha, NE, USA], University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System, VA Nebraska-Western Iowa Health Care System [Omaha, NE, USA], L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), ANR-21-RHUS-0001,DELIVER,Deliver therapeuthic innovation for advanced hepatic diseases(2021), ANR-10-LABX-0028,HepSys,Functional genomics of viral hepatitis and liver disease(2010), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), European Project: 101021417,FIBCAN, European Project: 755460,PRELICAN, and European Project: 862551,HEPCAN
Subjects: tight junctions carcinogenesis signaling pathways therapeutic targets, tight junctions, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, therapeutic targets, metabolism, carcinogenesis, signaling pathways
Abstract: Tight junctions (TJs) are intercellular protein complexes that preserve tissue homeostasis and integrity through the control of paracellular permeability and cell polarity. Recent findings have revealed the functional role of TJ proteins outside TJs and beyond their classical cellular functions as selective gatekeepers. This is illustrated by the dysregulation in TJ protein expression levels in response to external and intracellular stimuli, notably during tumorigenesis. A large body of knowledge has uncovered the well-established functional role of TJ proteins in cancer pathogenesis. Mechanistically, TJ proteins act as bidirectional signaling hubs that connect the extracellular compartment to the intracellular compartment. By modulating key signaling pathways, TJ proteins are crucial players in the regulation of cell proliferation, migration, and differentiation, all of which being essential cancer hallmarks crucial for tumor growth and metastasis. TJ proteins also promote the acquisition of stem cell phenotypes in cancer cells. These findings highlight their contribution to carcinogenesis and therapeutic resistance. Moreover, recent preclinical and clinical studies have used TJ proteins as therapeutic targets or prognostic markers. This review summarizes the functional role of TJ proteins in cancer biology and their impact for novel strategies to prevent and treat cancer. journal article review research support, non-u.s. gov't research support, n.i.h., extramural research support, u.s. gov't, non-p.h.s. 2023 Jan 06 2023 01 06 imported
Published: 2023
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16. Scavenger receptor class B type I genetic variants associated with disease severity in chronic hepatitis C virus infection

Author: Victoria L. Arandhara, Charles Patrick McClure, Alexander W. Tarr, Sally Chappell, Kevin Morgan, Thomas F. Baumert, William L. Irving, Jonathan K. Ball, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), and European Project: 101021417,FIBCAN
Subjects: Infectious Diseases, complications, genetics, Virology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, metabolism
Abstract: Analysis of host genetic polymorphisms is an increasingly important tool for understanding and predicting pathogenesis and treatment response of viral diseases. The gene locus of scavenger receptor class B type I (SR-BI), encoding a cell entry factor and receptor for hepatitis C virus (HCV), contains several genetic polymorphisms. We applied a probe extension assay to determine the frequency of six single nucleotide polymorphisms (SNPs) within the SR-BI gene locus in 374 individuals with history of HCV infection. In addition, SR-BI messenger RNA (mRNA) levels were analyzed in liver biopsy specimens of chronically infected HCV subjects. The rs5888 variant allele T was present at a higher frequency in subjects with advanced fibrosis (χ journal article research support, non-u.s. gov't 2023 Jan imported
Published: 2023
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17. FUN-SIS: A Fully UNsupervised approach for Surgical Instrument Segmentation

Author: Luca Sestini, Benoit Rosa, Elena De Momi, Giancarlo Ferrigno, Nicolas Padoy, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Politecnico di Milano [Milan] (POLIMI), ANR-11-LABX-0004,CAMI,Gestes Médico-Chirurgicaux Assistés par Ordinateur(2011), univOAK, Archive ouverte, and Gestes Médico-Chirurgicaux Assistés par Ordinateur - - CAMI2011 - ANR-11-LABX-0004 - LABX - VALID
Subjects: FOS: Computer and information sciences, Radiological and Ultrasound Technology, Computer Vision and Pattern Recognition (cs.CV), Computer Science - Computer Vision and Pattern Recognition, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Health Informatics, Deep learning, Endoscopy, Computer Graphics and Computer-Aided Design, Unsupervised learning, Learning from noisy labels, Surgical instrument segmentation, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Radiology, Nuclear Medicine and imaging, Computer Vision and Pattern Recognition, Generative adversarial network
Abstract: Automatic surgical instrument segmentation of endoscopic images is a crucial building block of many computer-assistance applications for minimally invasive surgery. So far, state-of-the-art approaches completely rely on the availability of a ground-truth supervision signal, obtained via manual annotation, thus expensive to collect at large scale. In this paper, we present FUN-SIS, a Fully-UNsupervised approach for binary Surgical Instrument Segmentation. FUN-SIS trains a per-frame segmentation model on completely unlabelled endoscopic videos, by solely relying on implicit motion information and instrument shape-priors. We define shape-priors as realistic segmentation masks of the instruments, not necessarily coming from the same dataset/domain as the videos. The shape-priors can be collected in various and convenient ways, such as recycling existing annotations from other datasets. We leverage them as part of a novel generative-adversarial approach, allowing to perform unsupervised instrument segmentation of optical-flow images during training. We then use the obtained instrument masks as pseudo-labels in order to train a per-frame segmentation model; to this aim, we develop a learning-from-noisy-labels architecture, designed to extract a clean supervision signal from these pseudo-labels, leveraging their peculiar noise properties. We validate the proposed contributions on three surgical datasets, including the MICCAI 2017 EndoVis Robotic Instrument Segmentation Challenge dataset. The obtained fully-unsupervised results for surgical instrument segmentation are almost on par with the ones of fully-supervised state-of-the-art approaches. This suggests the tremendous potential of the proposed method to leverage the great amount of unlabelled data produced in the context of minimally invasive surgery.
Published: 2023
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18. TRandAugment: temporal random augmentation strategy for surgical activity recognition from videos

Author: Sanat Ramesh, Diego Dall’Alba, Cristians Gonzalez, Tong Yu, Pietro Mascagni, Didier Mutter, Jacques Marescaux, Paolo Fiorini, Nicolas Padoy, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Verona = University of Verona (UNIVR), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, CHU Strasbourg, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, and l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)
Subjects: Temporal convolutional networks, Data augmentation, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biomedical Engineering, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Health Informatics, General Medicine, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Computer Graphics and Computer-Aided Design, Computer Science Applications, Temporal augmentation, Surgical activity recognition, Gastric bypass procedures, Radiology, Nuclear Medicine and imaging, Surgery, Computer Vision and Pattern Recognition, Cataract procedures
Abstract: Purpose Automatic recognition of surgical activities from intraoperative surgical videos is crucial for developing intelligent support systems for computer-assisted interventions. Current state-of-the-art recognition methods are based on deep learning where data augmentation has shown the potential to improve the generalization of these methods. This has spurred work on automated and simplified augmentation strategies for image classification and object detection on datasets of still images. Extending such augmentation methods to videos is not straightforward, as the temporal dimension needs to be considered. Furthermore, surgical videos pose additional challenges as they are composed of multiple, interconnected, and long-duration activities. Methods This work proposes a new simplified augmentation method, called TRandAugment, specifically designed for long surgical videos, that treats each video as an assemble of temporal segments and applies consistent but random transformations to each segment. The proposed augmentation method is used to train an end-to-end spatiotemporal model consisting of a CNN (ResNet50) followed by a TCN. Results The effectiveness of the proposed method is demonstrated on two surgical video datasets, namely Bypass40 and CATARACTS, and two tasks, surgical phase and step recognition. TRandAugment adds a performance boost of 1–6% over previous state-of-the-art methods, that uses manually designed augmentations. Conclusion This work presents a simplified and automated augmentation method for long surgical videos. The proposed method has been validated on different datasets and tasks indicating the importance of devising temporal augmentation methods for long surgical videos.
Published: 2023
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19. Primary myelofibrosis and the 'bad seeds in bad soil' concept

Author: Marie-Caroline Le Bousse-Kerdilès, Les cellules souches : de leurs niches à leurs applications thérapeutiques, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Studies reported in this review was supported by grants from: the Association 'Nouvelles Recherches Biomédicales' (ANRB), Convention de Recherche INCa n°PL054 and n°R06031LP, the Association pour la Recherche contre le Cancer (ARC, 9806), 'Laurette Fugain' association (ALF/no. 06-06, project # R06067LL), the 'Contrat d'Interface' with Paul Brousse Hospital, the 'Groupement d'Intérêt Scientifique (GIS)-Institut des Maladies Rares 03/GIS/ PB/SJ/n°35, INCa (PL054 and 2007-1-PL5-Inserm 11-1), and the 'Ligue Contre le Cancer' (Equipe labellisée 'LA LIGUE 2010')., Le Bousse-Kerdilès, Marie-Caroline, the Association pour la Recherche contre le Cancer (ARC, 9806), 'Laurette Fugain' association (ALF/no. 06-06, project # R06067LL), the 'Contrat d'Interface' with Paul Brousse Hospital, the 'Groupement d'Intérêt Scientifique (GIS)-Institut des Maladies Rares 03/GIS/ PB/SJ/n°35, the European Union-EUMNET Project (QLRT-2001-01123), INCa (PL054 and 2007-1-PL5-Inserm 11-1), and the 'Ligue Contre le Cancer' (Equipe labellisée 'LA LIGUE 2010')., and BMC, Ed.
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Stromal cell, Medicine (miscellaneous), Dermatology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Osteosclerosis, 0302 clinical medicine, Polycythemia vera, Rheumatology, Stroma, Myeloproliferation, medicine, Myelofibrosis, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, 0303 health sciences, Hepatology, business.industry, Gastroenterology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, 3. Good health, Haematopoiesis, Proceedings, 030220 oncology & carcinogenesis, Immunology, Cancer research, Stem cell, business
Abstract: International audience; Primary Myelofibrosis (PMF) is a chronic myeloproliferative neoplasm characterized by a clonal myeloproliferation and a myelofibrosis. The concomitant presence of neoangiogenesis and osteosclerosis suggests a deregulation of medullar stem cell niches in which hematopoietic stem cells are engaged in a constant crosstalk with their stromal environment. Despite the recently discovered mutations including the JAK2Val617F mutation, the primitive molecular event responsible for the clonal hematopoietic proliferation is still unknown. We propose that the "specificity" of the pathological process that caracterizes PMF results from alterations in the cross talk between hematopoietic and stromal cells. These alterations contribute in creating a abnormal microenvironment that participates in the maintenance of the neoplasic clone leading to a misbalance disfavouring normal hematopoiesis; in return or simultaneously, stromal cells constituting the niches are modulated by hematopoietic cells resulting in stroma dysfunctions. Therefore, PMF is a remarkable "model" in which deregulation of the stem cell niche is of utmost importance for the disease development. A better understanding of the crosstalk between stem cells and their niches should imply new therapeutic strategies targeting not only intrinsic defects in stem cells but also regulatory niche-derived signals and, consequently, hematopoietic cell proliferation.
Published: 2012
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20. The MYST-containing protein Chameau is required for proper sensory organ specification during Drosophila thorax morphogenesis

Author: Hainaut, Matthieu, Sagnier, Thierry, Berenger, Hélène, Pradel, Jacques, Graba, Yacine, Miotto, Benoit, Imhof, Axel, Institut de Biologie du Développement de Marseille-Luminy (IBDML), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Centre National de la Recherche Scientifique (CNRS), grants from Association pour la Recherche contre le Cancer (ARC), CEntre Franco-Indien pour la Promotion de la Recherche Avancée (CEFIPRA) and Agence Nationale de la Recherche (ANR), and fellowships from Ministère de l’enseignement supérieur et de la Recherche (MRT) and l’Association pour la Recherche contre le cancer (ARC)., Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Miotto, Benoit
Subjects: Anatomy and Physiology, lcsh:Medicine, Gene Expression, Transcriptional control, medicine.disease_cause, MESH: Genotype, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, Molecular Cell Biology, MESH: Epistasis, Genetic, Morphogenesis, Drosophila Proteins, MESH: Animals, lcsh:Science, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH: Organ Specificity, Genetics, Regulation of gene expression, 0303 health sciences, Mutation, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Gene Expression Regulation, Developmental, Sense Organs, MESH: Transcription Factors, Animal Models, Thorax, Chromatin, Drosophila melanogaster, Phenotype, Organ Specificity, Epigenetics, Drosophila Protein, Research Article, MESH: Mutation, animal structures, Genotype, MESH: Drosophila Proteins, DNA transcription, Biology, Bristle, MESH: Phenotype, MESH: Thorax, Neurological System, MESH: Drosophila melanogaster, 03 medical and health sciences, Model Organisms, Acetyltransferases, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Animals, MESH: Sense Organs, Transcription factor, 030304 developmental biology, lcsh:R, fungi, Genetic interactions, MESH: Acetyltransferases, [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis, Epistasis, Genetic, biology.organism_classification, MESH: Morphogenesis, Gene regulation, lcsh:Q, Scute, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Transcription Factors, Developmental Biology
Abstract: International audience; The adult thorax of Drosophila melanogaster is covered by a stereotyped pattern of mechanosensory bristles called macrochaetes. Here, we report that the MYST containing protein Chameau (Chm) contributes to the establishment of this pattern in the most dorsal part of the thorax. Chm mutant pupae present extra-dorsocentral (DC) and scutellar (SC) macrochaetes, but a normal number of the other macrochaetes. We provide evidences that chm restricts the singling out of sensory organ precursors from proneural clusters and genetically interacts with transcriptional regulators involved in the regulation of achaete and scute in the DC and SC proneural cluster. This function of chm likely relies on chromatin structure regulation since a protein with a mutation in the conserved catalytic site fails to rescue the formation of supernumerary DC and SC bristles in chm mutant flies. This is further supported by the finding that mutations in genes encoding chromatin modifiers and remodeling factors, including Polycomb group (PcG) and Trithorax group (TrxG) members, dominantly modulate the penetrance of chm extra bristle phenotype. These data support a critical role for chromatin structure modulation in the establishment of the stereotyped sensory bristle pattern in the fly thorax.
Published: 2011
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21. Pareto front vs. Weighted sum for automatic trajectory planning of deep brain stimulation

Author: Claire Haegelen, Pierre Collet, Jimmy Voirin, Pierre Jannin, Noura Hamze, Caroline Essert, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, CHU Strasbourg, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], CHU Pontchaillou [Rennes], ANR 2010 BLAN 020901, ANR, Agence Nationale de la Recherche, Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Optimization, Weighted Sum, Mathematical optimization, Deep brain stimulation, Optimization problem, Computer science, Multi-objective optimization problem, medicine.medical_treatment, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [INFO.INFO-NE] Computer Science [cs]/Neural and Evolutionary Computing [cs.NE], Neurosurgery, Multiple constraint, [INFO.INFO-NE]Computer Science [cs]/Neural and Evolutionary Computing [cs.NE], Multi-objective optimization, Multi objective, 030218 nuclear medicine & medical imaging, Medical computing, 03 medical and health sciences, 0302 clinical medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Computer vision, Motion planning, Multiobjective optimization, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Trajectory Planning, Trajectory planning, Surgery, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Artificial intelligence, Medical imaging, business, Optimal solutions, Weighted sum approaches, 030217 neurology & neurosurgery
Abstract: International audience; Preoperative path planning for Deep Brain Stimulation (DBS) is a multi-objective optimization problem consisting in searching the best compromise between multiple placement constraints. Its automation is usually addressed by turning the problem into mono objective thanks to an aggregative approach. However,despite its intuitiveness,this approach is known for its incapacity to find all optimal solutions. In this work,we introduce an approach based on multi objective dominance to DBS path planning. We compare it to a classical aggregative weighted sum of the multiple constraints and to a manual planning thanks to a retrospective study performed by a neurosurgeon on 14 DBS cases. The results show that the dominance-based method is preferred over manual planning,and covers a larger choice of relevant optimal entry points than the traditional weighted sum approach which discards interesting solutions that could be preferred by surgeons. © Springer International Publishing AG 2016.
Published: 2022
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22. A Delphi consensus statement for digital surgery

Author: Kyle Lam, Michael D. Abràmoff, José M. Balibrea, Steven M. Bishop, Richard R. Brady, Rachael A. Callcut, Manish Chand, Justin W. Collins, Markus K. Diener, Matthias Eisenmann, Kelly Fermont, Manoel Galvao Neto, Gregory D. Hager, Robert J. Hinchliffe, Alan Horgan, Pierre Jannin, Alexander Langerman, Kartik Logishetty, Amit Mahadik, Lena Maier-Hein, Esteban Martín Antona, Pietro Mascagni, Ryan K. Mathew, Beat P. Müller-Stich, Thomas Neumuth, Felix Nickel, Adrian Park, Gianluca Pellino, Frank Rudzicz, Sam Shah, Mark Slack, Myles J. Smith, Naeem Soomro, Stefanie Speidel, Danail Stoyanov, Henry S. Tilney, Martin Wagner, Ara Darzi, James M. Kinross, Sanjay Purkayastha, Lam, Kyle [0000-0001-6407-4912], Abràmoff, Michael D [0000-0002-3490-0037], Fermont, Kelly [0000-0002-0733-8958], Neto, Manoel Galvao [0000-0003-4549-3606], Hager, Gregory D [0000-0002-6662-9763], Langerman, Alexander [0000-0003-0866-463X], Logishetty, Kartik [0000-0002-0469-9539], Mascagni, Pietro [0000-0001-7288-3023], Mathew, Ryan K [0000-0002-2609-9876], Neumuth, Thomas [0000-0001-6999-5024], Pellino, Gianluca [0000-0002-8322-6421], Shah, Sam [0000-0002-7743-8479], Wagner, Martin [0000-0002-9831-9110], Darzi, Ara [0000-0001-7815-7989], Kinross, James M [0000-0002-0427-7643], Purkayastha, Sanjay [0000-0003-0187-8328], Apollo - University of Cambridge Repository, Lam, Kyle, Abràmoff, Michael D, Balibrea, José M, Bishop, Steven M, Brady, Richard R, Callcut, Rachael A, Chand, Manish, Collins, Justin W, Diener, Markus K, Eisenmann, Matthia, Fermont, Kelly, Neto, Manoel Galvao, Hager, Gregory D, Hinchliffe, Robert J, Horgan, Alan, Jannin, Pierre, Langerman, Alexander, Logishetty, Kartik, Mahadik, Amit, Maier-Hein, Lena, Antona, Esteban Martín, Mascagni, Pietro, Mathew, Ryan K, Müller-Stich, Beat P, Neumuth, Thoma, Nickel, Felix, Park, Adrian, Pellino, Gianluca, Rudzicz, Frank, Shah, Sam, Slack, Mark, Smith, Myles J, Soomro, Naeem, Speidel, Stefanie, Stoyanov, Danail, Tilney, Henry S, Wagner, Martin, Darzi, Ara, Kinross, James M, Purkayastha, Sanjay, Imperial College London, University of Iowa [Iowa City], University College of London [London] (UCL), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Johns Hopkins University (JHU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Heidelberg University Hospital [Heidelberg], Universität Leipzig, Johns Hopkins University School of Medicine [Baltimore], Infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre (BRC). M.D.A. is supported in part by The Robert C. Watzke MD Professorship as well as Research to Prevent Blindness, Inc, New York, New York (unrestricted grant to the Department of Ophthalmology, and Visual Sciences, University of Iowa. M.E. receives funding from the Helmholtz Imaging Platform (HIP), a platform of the Helmholtz Incubator on Information and Data Science. R.J.H. receives funding from the Enid Linder Foundation & Royal College of Surgeons of England Chair in Trials in Surgery and is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. L.M.H. receives funding from the Federal Ministry for Economic Affairs and Energy (projects OP4·1 and pAItient), Germany. B.P.M.S. and M.W. receive funding from the German Federal Ministry of Health within project 'Surgomics'. SS receives funding from the German Research Foundation (DFG) as part of Germany’s Excellence Strategy - EXC2050/1 - Project ID 390696704 - Cluster of Excellence 'Centre for Tactile Internet with Human-in-the-Loop' (CeTI), and Imperial College Healthcare NHS Trust- BRC Funding
Subjects: [SDV]Life Sciences [q-bio], education, 8.1 Organisation and delivery of services, Medicine (miscellaneous), Health Informatics, and research governance, 8.3 Policy, 7.3 Management and decision making, 7.1 Individual care needs, Health Information Management, Clinical Research, 8.3 Policy, ethics, and research governance, 692/700/3935, 692/700/1538, 692/700/565/545, Science & Technology, article, 42 Health Sciences, 4203 Health Services and Systems, ethics, Computer Science Applications, Health Care Sciences & Services, Management of diseases and conditions, Patient Safety, Generic health relevance, 8 Health and social care services research, Life Sciences & Biomedicine, 7 Management of diseases and conditions, Medical Informatics, Health and social care services research
Abstract: The use of digital technology is increasing rapidly across surgical specialities, yet there is no consensus for the term ‘digital surgery’. This is critical as digital health technologies present technical, governance, and legal challenges which are unique to the surgeon and surgical patient. We aim to define the term digital surgery and the ethical issues surrounding its clinical application, and to identify barriers and research goals for future practice. 38 international experts, across the fields of surgery, AI, industry, law, ethics and policy, participated in a four-round Delphi exercise. Issues were generated by an expert panel and public panel through a scoping questionnaire around key themes identified from the literature and voted upon in two subsequent questionnaire rounds. Consensus was defined if >70% of the panel deemed the statement important and
Published: 2022
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23. Trachelectomy: How is it actually done? A review from FRANCOGYN group

Author: Lefebvre, A, Raimond, Emilie, Chauvet, Pauline, Touboul, Cyril, Canlorbe, Geoffroy, Lavoué, Vincent, Ouldamer, Lobna, Collinet, Pierre, Bendifallah, Sofiane, Carcopino, Xavier, Lecointre, Lise, Kerbage, Yohan, CHU Lille, Department of Obstetrics and Gynaecology, Institute Alix de Champagne University Hospital, Reims, France., CHU Clermont-Ferrand, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Fertility, [SDV.CAN] Life Sciences [q-bio]/Cancer, Trachelectomy, [SDV]Life Sciences [q-bio], Cervical cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Cerclage
Abstract: International audience; Because of the peak incidence of cervical cancer between the ages of 35 and 44 and the increasing age of first pregnancy, the issue of fertility preservation in cases of early-stage cervical cancer in women in this reproductive age category arises. Early-stage cervical cancer patients have a good prognosis and are surgically treated in cases of mildly aggressive human papillomavirus-related histological type (squamous cell carcinoma, adenocarcinoma), FIGO stage IA to IB1 (i.e.
Published: 2022
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24. Data Splits and Metrics for Method Benchmarking on Surgical Action Triplet Datasets

Author: Nwoye, Chinedu Innocent, Padoy, Nicolas, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), and Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ
Subjects: FOS: Computer and information sciences, ComputingMethodologies_PATTERNRECOGNITION, Action triplet, CholecT40, Surgical activity recognition, CholecT50, Computer Vision and Pattern Recognition (cs.CV), [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Computer Science - Computer Vision and Pattern Recognition, Tool-tissue interaction, CholecT45
Abstract: In addition to generating data and annotations, devising sensible data splitting strategies and evaluation metrics is essential for the creation of a benchmark dataset. This practice ensures consensus on the usage of the data, homogeneous assessment, and uniform comparison of research methods on the dataset. This study focuses on CholecT50, which is a 50 video surgical dataset that formalizes surgical activities as triplets of . In this paper, we introduce the standard splits for the CholecT50 and CholecT45 datasets and show how they compare with existing use of the dataset. CholecT45 is the first public release of 45 videos of CholecT50 dataset. We also develop a metrics library, ivtmetrics, for model evaluation on surgical triplets. Furthermore, we conduct a benchmark study by reproducing baseline methods in the most predominantly used deep learning frameworks (PyTorch and TensorFlow) to evaluate them using the proposed data splits and metrics and release them publicly to support future research. The proposed data splits and evaluation metrics will enable global tracking of research progress on the dataset and facilitate optimal model selection for further deployment., Comment: Official splits for the CholecT50 and CholecT45 datasets, 13 pages, 2 figures, 12 tables
Published: 2022
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25. Lumacaftor-ivacaftor effects on cystic fibrosis-related liver involvement in adolescents with homozygous F508 del-CFTR

Author: F. Chedevergne, David Drummond, Muriel Le Bourgeois, Jérémy Dana, Elena K Schneider-Futschik, Isabelle Sermet-Gaudelus, Thao Nguyen-Khoa, Laureline Berteloot, Muriel Girard, Mathieu Cornet, Dominique Debray, Céline Bailly-Botuha, Université Paris Cité (UPCité), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, CHU Necker - Enfants Malades [AP-HP], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and M C is supporterd by Fondation de la Recherche Médicale Grant. E.K.S.-F. is supported by a research grant from The University of Melbourne and the Australian National Health and Medical Research Council (NHMRC) as Biomedical Research Fellow
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Cirrhosis, Adolescent, Cystic Fibrosis, [SDV]Life Sciences [q-bio], Aminopyridines, Cystic Fibrosis Transmembrane Conductance Regulator, Hepatobiliary cirrhosis, Quinolones, Aminophenols, Gastroenterology, Cystic fibrosis, Pediatrics, Ivacaftor, Liver disease, chemistry.chemical_compound, Internal medicine, medicine, Humans, Benzodioxoles, Prospective Studies, Cystic-fibrosis liver disease, CFTR modulator, medicine.diagnostic_test, biology, business.industry, Lumacaftor, medicine.disease, Cystic fibrosis transmembrane conductance regulator, Liver enzymes, Drug Combinations, Liver, chemistry, Abdominal ultrasonography, Mutation, Pediatrics, Perinatology and Child Health, biology.protein, Portal hypertension, business, Biomarkers, medicine.drug
Abstract: Background The effects of lumacaftor-ivacaftor on cystic fibrosis transmembrane conductance regulator (CFTR)-associated liver disease remain unclear. The objective of the study was to describe the effect of this treatment on features of liver involvement in a cystic fibrosis (CF) adolescent population homozygous for F508del. Methods Clinical characteristics, liver blood tests, abdominal ultrasonography (US), and pancreas and liver proton density fat fraction (PDFF) by magnetic resonance imaging, were obtained at treatment initiation and at 12 months for all patients. Biomarkers of CFTR activity (sweat chloride test, nasal potential difference, and intestinal current measurement) were assessed at initiation and at 6 months therapy. Results Of the 37 patients who started ivacaftor/lumacaftor treatment, 28 were eligible for analysis. In this group, before treatment initiation, 4 patients were diagnosed with multinodular liver and portal hypertension, 19 with other forms of CF liver involvement, and 5 with no signs of liver involvement. During treatment, no hepatic adverse reactions were documented, and no patient developed liver failure. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) decreased significantly following initiation of lumacaftor-ivacaftor, and remained so after 12 months treatment. This was not correlated with changes in clinical status, liver and pancreas US and PDFF, fecal elastase, or lumacaftor-ivacaftor serum levels. The most “responsive” patients demonstrated a significant increase in biomarkers of CFTR activity. Conclusions These results may suggest a potential beneficial effect of CFTR modulators on CF liver disease and warrant further investigation in larger, prospective studies.
Published: 2022
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26. Hepatocellular carcinoma chemoprevention by targeting the angiotensin-converting enzyme and EGFR transactivation

Author: Emilie Crouchet, Shen Li, Mozhdeh Sojoodi, Simonetta Bandiera, Naoto Fujiwara, Hussein El Saghire, Shijia Zhu, Tongqi Qian, Fahmida Akter Rasha, Fabio Del Zompo, Stephen C. Barrett, Eugénie Schaeffer, Marine A. Oudot, Clara Ponsolles, Sarah C. Durand, Sarani Ghoshal, Gunisha Arora, Fabio Giannone, Raymond T. Chung, Nevena Slovic, Nicolaas Van Renne, Emanuele Felli, Patrick Pessaux, Joachim Lupberger, Nathalie Pochet, Catherine Schuster, Kenneth K. Tanabe, Yujin Hoshida, Bryan C. Fuchs, Thomas F. Baumert, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Harvard Medical School [Boston] (HMS), University of Texas Southwestern Medical Center [Dallas], Les Hôpitaux Universitaires de Strasbourg (HUS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Massachusetts General Hospital [Boston], Massachusetts Institute of Technology (MIT), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), European Project: 667273,H2020,H2020-PHC-2015-two-stage,HEP-CAR(2016), European Project: 862551,HEPCAN, European Project: 101021417,FIBCAN, and European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016)
Subjects: Liver Cirrhosis, Transcriptional Activation, Captopril, Carcinoma, Hepatocellular, Hepatology, Carcinogenesis, Liver Neoplasms, Angiotensin-Converting Enzyme Inhibitors, General Medicine, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Peptidyl-Dipeptidase A, Fibrosis, Chemoprevention, Rats, ErbB Receptors, Disease Progression, Animals, Liver cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Hepatocellular carcinoma (HCC) is a leading cause of death among cirrhotic patients, for which chemopreventive strategies are lacking. Recently, we developed a simple human cell-based system modeling a clinical prognostic liver signature (PLS) predicting liver disease progression and HCC risk. In a previous study, we applied our cell-based system for drug discovery and identified captopril, an approved angiotensin converting enzyme (ACE) inhibitor, as a candidate compound for HCC chemoprevention. Here, we explored ACE as a therapeutic target for HCC chemoprevention. Captopril reduced liver fibrosis and effectively prevented liver disease progression toward HCC development in a diethylnitrosamine (DEN) rat cirrhosis model and a diet-based rat model for nonalcoholic steatohepatitis–induced (NASH-induced) hepatocarcinogenesis. RNA-Seq analysis of cirrhotic rat liver tissues uncovered that captopril suppressed the expression of pathways mediating fibrogenesis, inflammation, and carcinogenesis, including epidermal growth factor receptor (EGFR) signaling. Mechanistic data in liver disease models uncovered a cross-activation of the EGFR pathway by angiotensin. Corroborating the clinical translatability of the approach, captopril significantly reversed the HCC high-risk status of the PLS in liver tissues of patients with advanced fibrosis. Captopril effectively prevents fibrotic liver disease progression toward HCC development in preclinical models and is a generic and safe candidate drug for HCC chemoprevention.
Published: 2022
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27. Surgical data science – from concepts toward clinical translation

Author: Hubertus Feussner, Swaroop Vedula, Ozanan R. Meireles, Nicolas Padoy, Carla M. Pugh, Russell H. Taylor, Duygu Sarikaya, Bernard Gibaud, Jan Goedeke, Pietro Mascagni, Pierre Jannin, Hirenkumar Nakawala, Toby Collins, Beat P. Müller-Stich, Teodor P. Grantcharov, Stamatia Giannarou, Ines Gockel, Gregory D. Hager, Dogu Teber, Doreen Heckmann-Nötzel, Justin W. Collins, Matthias Eisenmann, Lena Maier-Hein, Sinan Onogur, Anand Malpani, Frank Ückert, Hani J. Marcus, Germain Forestier, Luc Joyeux, Daniel R. Leff, Keno März, Daniel A. Hashimoto, Johannes Fallert, Thomas Neumuth, Minu D. Tizabi, Tobias Roß, Makoto Hashizume, Lars Mündermann, Kevin Cleary, Raphael Sznitman, Kyle Lam, Nassir Navab, Alexander Seitel, Martin Wagner, Amin Madani, Stefanie Speidel, Ron Kikinis, Adrian Park, Danail Stoyanov, Gabor Fichtinger, Hannes Kenngott, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg University, Gazi University, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Contre les Cancers de l'Appareil Digestif-European Institute of Telesurgery (IRCAD/EITS), Johns Hopkins University (JHU), La société Karl STORZ, Technische Universität München = Technical University of Munich (TUM), Imperial College London, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Università degli studi di Verona = University of Verona (UNIVR), Johns Hopkins University School of Medicine [Baltimore], Stanford University School of Medicine [CA, USA], University College of London [London] (UCL), Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington DC, Queen's University [Kingston, Canada], Institut de Recherche en Informatique Mathématiques Automatique Signal - IRIMAS - UR 7499 (IRIMAS), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Monash university, University of Toronto, Kyushu University, Heidelberg University Hospital [Heidelberg], Harvard Medical School [Boston] (HMS), University of Bern, Universität Leipzig, University Hospital Leipzig, Ludwig-Maximilians-Universität München (LMU), Massachusetts General Hospital [Boston], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Baylor College of Medicine (BCM), Baylor University, University Health Network, UCL Institute of Neurology, Queen Square [London], Universität Karlsruhe (TH), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), National Center for Tumor Diseases [Dresden] (NCT), Technische Universität Dresden = Dresden University of Technology (TU Dresden)-German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Helmholtz-Zentrum Dresden-Rossendorf (HZDR), This work was supported by the European Research Council (ERC) starting grant COMBIOSCOPY under the New Horizon Framework Programme grant agreement [ERC-2015-StG-637960], the Helmholtz Imaging Platform (HIP), a platform of the Helmholtz Incubator on Information and Data Science, the NCT Heidelberg, BPI France (project CONDOR), the Johns Hopkins Science of Learning Institute Research Grant, the National Institutes of Health [NIDCR R01 DE025265, P41 EB015902, P41 EB015898, R01 CA235589], the Surgical Oncology Program of the National Center for Tumor Diseases (NCT) Heidelberg, KARL STORZ SE & Co. KG, the Royal Society (UF140290) and NIHR Imperial BRC (Biomedical Research Centre), the ERC - H2020 Autonomous Robotic Surgery (ARS) grant agreement [ERC-2016-ADG-742671], the Surgical Metrics Project - American College of Surgeons (National Society Contract), the Quantified Physician - 7-SIGMA Simulation Systems, Minnesota, MN (Industry Contract), the Tourniquet Master Training - DOD SBIR Phase IIb - Continuation Award [W81XWH-13-C-0021], the Ontology for Human Motion and Psychomotor Performance - Stanford University Media-X, Motion Analysis for Microvascular Anastomosis - University of Wisconsin (Academic Contract), the Precision Learning Initiative - American Medical Association (National Society Grant), Quantifying the Metrics of Surgical Mastery: An Exploration in Data Science (NIH) [R01DK123445], the Wellcome/EPSRC Centre for Interventional and Surgical Sciences (WEISS) [203145Z/16/Z], Engineering and Physical Sciences Research Council (EPSRC) [EP/P027938/1, EP/R004080/1, EP/P012841/1], the Royal Academy of Engineering Chair in Emerging Technologies, the St. Michael’s Hospital, the University of Toronto, the Grant-in-Aid for Scientific Research on Innovative Area from MEXT, Japan, the National Cancer Data Ecosystem, contract number 19X037Q under Task Order HHSN26100071 from NCI, the project ProteCT [BMBF 16SV8568], the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft) as part of Germany’s Excellence Strategy - EXC 2050/1 - Project ID 390696704 - Cluster of Excellence 'Centre for Tactile Internet with Human-in-the-Loop' (CeTI), the Canada Research Chair in Computer Integrated Surgery, Natural Sciences and Engineering Research Council of Canada, the ANR with grants ANR-16-CE33-0009 (project DeepSurg), ANR-10-IAHU-02 (IHU Strasbourg) and ANR-20-CHIA-0029-01 (Chair AI4ORSafety), and the Federal Ministry of Economics and Energy (BMWi) and the German Aerospace Center (DLR) within the OP 4.1 project [BMWI 01MT17001C]., ANR-16-CE33-0009,DeepSurg,Apprentissage Profond à partir de Vidéos Chirurgicales Multi-vues et Multimodales pour Faciliter la Gestion du Bloc Opératoire(2016), ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), ANR-20-CHIA-0029,AI4ORSafety,Evaluation automatique des vues endoscopiques pour la validation des points de contrôle au bloc opératoire(2020), European Project: 637960,H2020,ERC-2014-STG,COMBIOSCOPY(2015), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Kyushu University [Fukuoka], Universität Leipzig [Leipzig], Institute of Neurology - UCL/Queen Square [London, UK] (IN-UCL-QS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), National Center for Tumor Diseases - Deutsches Krebsforschungszentrum [Heidelberg, Allemagne] (NCT / DKFZ), and Technische Universität Dresden = Dresden University of Technology (TU Dresden)
Subjects: FOS: Computer and information sciences, Computer Science - Machine Learning, Artificial intelligence, Surgical data science, Computer science, Computer Vision and Pattern Recognition (cs.CV), media_common.quotation_subject, Aucun, Delphi method, Computer Science - Computer Vision and Pattern Recognition, Health Informatics, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Field (computer science), Machine Learning (cs.LG), [SPI.AUTO]Engineering Sciences [physics]/Automatic, Machine Learning, 03 medical and health sciences, Computer Science - Computers and Society, 0302 clinical medicine, Computers and Society (cs.CY), Health care, FOS: Electrical engineering, electronic engineering, information engineering, Humans, Radiology, Nuclear Medicine and imaging, Quality (business), 030304 developmental biology, media_common, 0303 health sciences, Radiological and Ultrasound Technology, business.industry, Clinical translation, Image and Video Processing (eess.IV), Data Science, Deep learning, Electrical Engineering and Systems Science - Image and Video Processing, Computer aided surgery, Computer Graphics and Computer-Aided Design, Data science, 3. Good health, Current practice, 030220 oncology & carcinogenesis, Data analysis, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Computer Vision and Pattern Recognition, business, Data Annotation
Abstract: Recent developments in data science in general and machine learning in particular have transformed the way experts envision the future of surgery. Surgical Data Science (SDS) is a new research field that aims to improve the quality of interventional healthcare through the capture, organization, analysis and modeling of data. While an increasing number of data-driven approaches and clinical applications have been studied in the fields of radiological and clinical data science, translational success stories are still lacking in surgery. In this publication, we shed light on the underlying reasons and provide a roadmap for future advances in the field. Based on an international workshop involving leading researchers in the field of SDS, we review current practice, key achievements and initiatives as well as available standards and tools for a number of topics relevant to the field, namely (1) infrastructure for data acquisition, storage and access in the presence of regulatory constraints, (2) data annotation and sharing and (3) data analytics. We further complement this technical perspective with (4) a review of currently available SDS products and the translational progress from academia and (5) a roadmap for faster clinical translation and exploitation of the full potential of SDS, based on an international multi-round Delphi process.
Published: 2022
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28. Mesalazine initiates an anti-oncogenic β-catenin / MUCDHL negative feed-back loop in colon cancer cells by cell-specific mechanisms

Author: Emilie Bersuder, Chloe Terciolo, Mathilde Lechevrel, Elisabeth Martin, Celine Quesnelle, Jean-Noel Freund, Jean-Marie Reimund, Isabelle Gross, univOAK, Archive ouverte, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Fédération Hospitalo-Universitaire 'Digestive and OsteoARticular Remodeling/Inflammation/Immunomodulation/Metabolism in diseased ACEing' (FHU ARRIMAGE), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Les Hôpitaux Universitaires de Strasbourg (HUS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), and Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ
Subjects: Pharmacology, WNT pathway, Cadherin Related Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, 5-aminosalicylic acid, RM1-950, Cadherins, digestive system diseases, Colorectal neoplasm, [SDV.CAN] Life Sciences [q-bio]/Cancer, Colonic Neoplasms, Adhesion, Humans, Ulcerative Colitis, Therapeutics. Pharmacology, Colorectal Neoplasms, Mesalamine, Wnt Signaling Pathway, beta Catenin, CDHR5
Abstract: Chronic inflammation associated with intestinal architecture and barrier disruption puts patients with inflammatory bowel disease (IBD) at increased risk of developing colorectal cancer (CRC). Widely used to reduce flares of intestinal inflammation, 5-aminosalicylic acid derivatives (5-ASAs) such as mesalazine appear to also exert more direct mucosal healing and chemopreventive activities against CRC. The mechanisms underlying these activities are poorly understood and may involve the up-regulation of the cadherin-related gene MUCDHL (CDHR5). This atypical cadherin is emerging as a new actor of intestinal homeostasis and opposes colon tumorigenesis. Here, we showed that mesalazine increase mRNA levels of MUCDHL and of other genes involved in the intestinal barrier function in most intestinal cell lines. In addition, using gain / loss of function experiments (agonists, plasmid or siRNAs transfections), luciferase reporter genes and chromatin immunoprecipitation, we thoroughly investigated the molecular mechanisms triggered by mesalazine that lead to the up-regulation of MUCDHL expression. We found that basal transcription of MUCDHL in different CRC cell lines is regulated positively by CDX2 and negatively by β-catenin through a negative feed-back loop. However, mesalazine-stimulation of MUCDHL transcription is controlled by cell-specific mechanisms, involving either enhanced activation of CDX2 and PPAR-γ or repression of the β-catenin inhibitory effect. This work highlights the importance of the cellular and molecular context in the activity of mesalazine and suggests that its efficacy against CRC depends on the genetic alterations of transformed cells.
Published: 2022
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29. The Role of Virtual Reality, Telesurgery, and Teleproctoring in Robotic Surgery

Author: Barbara Seeliger, Justin W. Collins, Francesco Porpiglia, Jacques Marescaux, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Institut de Recherche Contre les Cancers de l'Appareil Digestif-European Institute of Telesurgery (IRCAD/EITS), Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery
Abstract: International audience
Published: 2022
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30. Proposal and multicentric validation of a laparoscopic Roux-en-Y gastric bypass surgery ontology

Author: Joël L. Lavanchy, Cristians Gonzalez, Hasan Kassem, Philipp C. Nett, Didier Mutter, Nicolas Padoy, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Bern University Hospital [Berne] (Inselspital), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Open access funding provided by University of Bern. Joël L. Lavanchy was supported by a grant of the Swiss National Science Foundation (P500PM_206724). This work was partially supported by French State Funds managed within the 'Plan Investissements d’Avenir'., ANR-10-IAHU-0002,MIX-Surg,Institut de Chirurgie Mini-Invasive guidée par l'Image(2010), and ANR-20-CHIA-0029,AI4ORSafety,Evaluation automatique des vues endoscopiques pour la validation des points de contrôle au bloc opératoire(2020)
Subjects: Surgery, 610 Medicine & health, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Phase and step annotation in surgical videos is a prerequisite for surgical scene understanding and for downstream tasks like intraoperative feedback or assistance. However, most ontologies are applied on small monocentric datasets and lack external validation. To overcome these limitations an ontology for phases and steps of laparoscopic Roux-en-Y gastric bypass (LRYGB) is proposed and validated on a multicentric dataset in terms of inter- and intra-rater reliability (inter-/intra-RR). Methods The proposed LRYGB ontology consists of 12 phase and 46 step definitions that are hierarchically structured. Two board certified surgeons (raters) with > 10 years of clinical experience applied the proposed ontology on two datasets: (1) StraBypass40 consists of 40 LRYGB videos from Nouvel Hôpital Civil, Strasbourg, France and (2) BernBypass70 consists of 70 LRYGB videos from Inselspital, Bern University Hospital, Bern, Switzerland. To assess inter-RR the two raters’ annotations of ten randomly chosen videos from StraBypass40 and BernBypass70 each, were compared. To assess intra-RR ten randomly chosen videos were annotated twice by the same rater and annotations were compared. Inter-RR was calculated using Cohen’s kappa. Additionally, for inter- and intra-RR accuracy, precision, recall, F1-score, and application dependent metrics were applied. Results The mean ± SD video duration was 108 ± 33 min and 75 ± 21 min in StraBypass40 and BernBypass70, respectively. The proposed ontology shows an inter-RR of 96.8 ± 2.7% for phases and 85.4 ± 6.0% for steps on StraBypass40 and 94.9 ± 5.8% for phases and 76.1 ± 13.9% for steps on BernBypass70. The overall Cohen’s kappa of inter-RR was 95.9 ± 4.3% for phases and 80.8 ± 10.0% for steps. Intra-RR showed an accuracy of 98.4 ± 1.1% for phases and 88.1 ± 8.1% for steps. Conclusion The proposed ontology shows an excellent inter- and intra-RR and should therefore be implemented routinely in phase and step annotation of LRYGB.
Published: 2022
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31. Preclinical Models for Acquired Resistance to Third-Generation EGFR Inhibitors in NSCLC: Functional Studies and Drug Combinations Used to Overcome Resistance

Author: Emna, Mahfoudhi, Charles, Ricordel, Gwendoline, Lecuyer, Cécile, Mouric, Hervé, Lena, Rémy, Pedeux, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], This work was funded by post-doctoral fellowship from Association pour la recherche contre le cancer (ARC), Ligue contre le cancer Grand Ouest, Institut National de la Santé et de la Recherche Médicale (INSERM)., and HAL UR1, Admin
Subjects: Cancer Research, 3rd G EGFR-TKI, [SDV.CAN]Life Sciences [q-bio]/Cancer, preclinical models, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, respiratory tract diseases, lung cancer, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, osimertinib, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, resistance mechanism
Abstract: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are currently recommended as first-line treatment for advanced non-small-cell lung cancer (NSCLC) with EGFR-activating mutations. Third-generation (3rd G) EGFR-TKIs, including osimertinib, offer an effective treatment option for patients with NSCLC resistant 1st and 2nd EGFR-TKIs. However, the efficacy of 3rd G EGFR-TKIs is limited by acquired resistance that has become a growing clinical challenge. Several clinical and preclinical studies are being carried out to better understand the mechanisms of resistance to 3rd G EGFR-TKIs and have revealed various genetic aberrations associated with molecular heterogeneity of cancer cells. Studies focusing on epigenetic events are limited despite several indications of their involvement in the development of resistance. Preclinical models, established in most cases in a similar manner, have shown different prevalence of resistance mechanisms from clinical samples. Clinically identified mechanisms include EGFR mutations that were not identified in preclinical models. Thus, NRAS genetic alterations were not observed in patients but have been described in cell lines resistant to 3rd G EGFR-TKI. Mainly, resistance to 3rd G EGFR-TKI in preclinical models is related to the activation of alternative signaling pathways through tyrosine kinase receptor (TKR) activation or to histological and phenotypic transformations. Yet, preclinical models have provided some insight into the complex network between dominant drivers and associated events that lead to the emergence of resistance and consequently have identified new therapeutic targets. This review provides an overview of preclinical studies developed to investigate the mechanisms of acquired resistance to 3rd G EGFR-TKIs, including osimertinib and rociletinib, across all lines of therapy. In fact, some of the models described were first generated to be resistant to first- and second-generation EGFR-TKIs and often carried the T790M mutation, while others had never been exposed to TKIs. The review further describes the therapeutic opportunities to overcome resistance, based on preclinical studies.
Published: 2022
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32. Organ-based estimation and minimization of clinician’s X-ray dose

Author: Alexandre Krebs, Jean-Paul Mazellier, Juan Verde, Cindy Rolland, Julien Bert, Nicolas Padoy, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and ANR-19-CE45-0011,SAMic,Microscopie intelligente autonome(2019)
Subjects: Biomedical Engineering, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Health Informatics, Radiology, Nuclear Medicine and imaging, Surgery, General Medicine, Computer Vision and Pattern Recognition, Computer Graphics and Computer-Aided Design, Computer Science Applications
Published: 2022
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33. Atorvastatin favorably modulates a clinical hepatocellular carcinoma risk gene signature

Author: Myung‐Ho Kim, Mi‐Young Kim, Shadi Salloum, Tongqi Qian, Lai Ping Wong, Min Xu, Yoojin Lee, Stuti G. Shroff, Ruslan I. Sadreyev, Kathleen E. Corey, Thomas F. Baumert, Yujin Hoshida, Raymond T. Chung, Massachusetts General Hospital [Boston], CHA Stem Cell Institute Seongnam-si, Republic of Korea], University of Texas Southwestern Medical Center [Dallas], Harvard Medical School [Boston] (HMS), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, and CHU Strasbourg
Subjects: Carcinoma, Hepatocellular, Hepatology, Non-alcoholic Fatty Liver Disease, Liver Neoplasms, Atorvastatin, Humans, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Sciences du Vivant [q-bio]/Cancer, Hepatitis C, Proto-Oncogene Proteins c-akt, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Lipophilic but not hydrophilic statins have been shown to be associated with reduced risk for hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis. We investigated differential actions of lipophilic and hydrophilic statins and their ability to modulate a clinical prognostic liver signature (PLS) predicting HCC risk in patients with liver disease. Hepatitis C virus (HCV)-infected Huh7.5.1 cells, recently developed as a model to screen HCC chemopreventive agents, were treated with lipophilic statins (atorvastatin and simvastatin) and hydrophilic statins (rosuvastatin and pravastatin), and then analyzed by RNA sequencing and PLS. Lipophilic statins, particularly atorvastatin, more significantly suppressed the HCV-induced high-risk pattern of PLS and genes in YAP and AKT pathway implicated in fibrogenesis and carcinogenesis, compared with the hydrophilic statins. While atorvastatin inhibited YAP activation through the mevalonate pathway, the distinctive AKT inhibition of atorvastatin was mediated by stabilizing truncated retinoid X receptor alpha, which has been known to enhance AKT activation, representing a target for HCC chemoprevention. In addition, atorvastatin modulated the high-risk PLS in an in vitro model of nonalcoholic fatty liver disease (NAFLD). Conclusion: Atorvastatin distinctively inhibits YAP and AKT activation, which are biologically implicated in HCC development, and attenuates a high-risk PLS in an in vitro model of HCV infection and NAFLD. These findings suggest that atorvastatin is the most potent statin to reduce HCC risk in patients with viral and metabolic liver diseases.
Published: 2022
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34. Visual Haptic Feedback for Training of Robotic Suturing

Author: François Jourdes, Brice Valentin, Jérémie Allard, Christian Duriez, Barbara Seeliger, InSimo, Deformable Robots Simulation Team (DEFROST ), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, CHU Strasbourg, l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), and univOAK, Archive ouverte
Subjects: [INFO.INFO-RB] Computer Science [cs]/Robotics [cs.RO], QA75.5-76.95, robotic surgery training, Computer Science Applications, knot-tying, haptics, Artificial Intelligence, Electronic computers. Computer science, TJ1-1570, virtual reality, [INFO.INFO-RB]Computer Science [cs]/Robotics [cs.RO], collision detection, Mechanical engineering and machinery, minimally invasive surgery, surgical simulation
Abstract: Current surgical robotic systems are teleoperated and do not have force feedback. Considerable practice is required to learn how to use visual input such as tissue deformation upon contact as a substitute for tactile sense. Thus, unnecessarily high forces are observed in novices, prior to specific robotic training, and visual force feedback studies demonstrated reduction of applied forces. Simulation exercises with realistic suturing tasks can provide training outside the operating room. This paper presents contributions to realistic interactive suture simulation for training of suturing and knot-tying tasks commonly used in robotically-assisted surgery. To improve the realism of the simulation, we developed a global coordinate wire model with a new constraint development for the elongation. We demonstrated that a continuous modeling of the contacts avoids instabilities during knot tightening. Visual cues are additionally provided, based on the computation of mechanical forces or constraints, to support learning how to dose the forces. The results are integrated into a powerful system-agnostic simulator, and the comparison with equivalent tasks performed with the da Vinci Xi system confirms its realism.
Published: 2022
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35. Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division

Author: Laurent Gagnoux, Serena Petracchini, Benoit Ladoux, Amel Mettouchi, Martial Balland, Mads Daugaard, Mukund Gupta, Emmanuel Lemichez, Francis Impens, Poul H. Sorensen, Sébastien Janel, Elisa Vitiello, Anne Doye, Frank Lafont, Florian Fage, Atef Asnacios, Teresa Mendes Maia, Daniel Hamaoui, Jerome Gilleron, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Equipe labellisée Ligue contre le Cancer, Matière et Systèmes Complexes (MSC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Cellular Microbiology and Physics of Infection Group [Lille] (CMPI), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Universiteit Gent = Ghent University (UGENT), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Vancouver Prostate Centre [Vancouver General Hospital] (VPC), Vancouver General Hospital, University of British Columbia (UBC), Toxines bactériennes - Bacterial Toxins, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This study was supported by institutional INSERM and Institut Pasteur fundings, 'Investments for the Future' LabEx SIGNALIFE ANR-11-LABX-0028-01 and grants from the Ligue Nationale contre le Cancer (LNCC labellisation and RS20/75-63), Association pour la Recherche contre le Cancer (ARC PJA20191209650), EPIC-XS, project number 823839, funded by the Horizon 2020 programme of the European Union (PRC-5074) and FRM-Piraud prize to E.L., Bio-SPC 'Contrat Doctoral' PhD fellowship to S.P., LNCC PhD fellowship to D.H., the Vancouver Prostate Centre to M.D., and Team Finn and The Ride to Concur Cancer to P.H.S., Fundings from ANR to A.A. ('ImmunoMeca' ANR-12-BSV5-0007-01, 'Initiatives d’excellence' Idex ANR-11-IDEX-0005-02, and 'Labex Who Am I?' ANR-11-LABX-0071)and to F.L. (ANR-10-EQPX-04-01), and from FEDER (12001407) to F.L. B.L. acknowledges financial supports from the Mechanobiology Institute, the European Research Council under the European Union's 7th Framework Programme (FP7/2007-2013) / ERC n° 617233 and NUS-USPC collaborative program., ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-12-BSV5-0007,ImmunoMeca,Caractérisation du rôle de la mécanique dans l'immunité: vers un modèle intégré de l'activation des cellules T(2012), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-11-LABX-0071,WHO AM I,Determinants de l'Identité : de la molécule à l'individu(2011), ANR-10-EQPX-0004,Imaginex BioMed,Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution(2010), European Project: 617233,EC:FP7:ERC,ERC-2013-CoG,DURACELL(2014), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université Nice Sophia Antipolis (... - 2019) (UNS), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), National University of Singapore (NUS), Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: rac1 GTP-Binding Protein, Integrins, Cell division, Mechanotransduction, Ubiquitin-Protein Ligases, [SDV]Life Sciences [q-bio], Integrin, General Physics and Astronomy, RAC1, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mechanotransduction, Cellular, General Biochemistry, Genetics and Molecular Biology, Extracellular matrix, Focal adhesion, Integrin signalling, 03 medical and health sciences, 0302 clinical medicine, Medicine and Health Sciences, Cyclin D1, 030304 developmental biology, Optineurin, 0303 health sciences, CNF1 toxin, Multidisciplinary, biology, Chemistry, Ubiquitination, Biology and Life Sciences, Cell migration, General Chemistry, Hostpathogen interaction, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell biology, E3 ubiquitin ligase, biology.protein, Rac1 GTPase, Cell Division, 030217 neurology & neurosurgery, Tumour suppressor
Abstract: Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behavior. Although the contribution of ECM compliance to the control of cell migration or division is extensively studied, little is reported regarding infectious processes. We study this phenomenon with the extraintestinal Escherichia coli pathogen UTI89. We show that UTI89 takes advantage, via its CNF1 toxin, of integrin mechanoactivation to trigger its invasion into cells. We identify the HACE1 E3 ligase-interacting protein Optineurin (OPTN) as a protein regulated by ECM stiffness. Functional analysis establishes a role of OPTN in bacterial invasion and integrin mechanical coupling and for stimulation of HACE1 E3 ligase activity towards the Rac1 GTPase. Consistent with a role of OPTN in cell mechanics, OPTN knockdown cells display defective integrin-mediated traction force buildup, associated with limited cellular invasion by UTI89. Nevertheless, OPTN knockdown cells display strong mechanochemical adhesion signalling, enhanced Rac1 activation and increased cyclin D1 translation, together with enhanced cell proliferation independent of ECM stiffness. Together, our data ascribe a new function to OPTN in mechanobiology. Uropathogenic strains of Escherichia coli (UPEC) are a leading cause of urinary tract infections (UTIs) and invasion involves Rho GTPase members, notably Rac1, to drive actin cytoskeleton rearrangement leading to engulfment. Here, Petracchini et al. provide evidence of an ECM stiffnessmodulated role of Optineurin (OPTN), which regulates HACE1-dependant Rac1 activity and thus controls integrinmediated mechanotransduction and bacterial invasion.
Published: 2022
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36. Augmented Reality and Image-Guided Robotic Liver Surgery

Author: Fabio Giannone, Emanuele Felli, Zineb Cherkaoui, Pietro Mascagni, Patrick Pessaux, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, and univOAK, Archive ouverte
Subjects: robotic, Cancer Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, image-guided surgery, Aucun, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Review, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, artificial intelligence, augmented reality, Oncology, liver surgery, RC254-282, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Simple Summary Robotic surgery has gained much attention in liver resection for its potential to increase surgical dexterity in a minimally invasive scenario. Different series are reported in the literature with promising results, although strong evidence is lacking. In addition, the robotic system presents the advantage of creating a hybrid interface in which pre- and intra-operative imaging tools could be exploited alone or together in order to guide surgical resection. These technologies have been developed with the aim of increasing surgical safety and improving oncological results. However, some drawbacks are still present, and the literature lacks data given the relatively recent distribution of the robotic platform and of some of these technologies. Abstract Artificial intelligence makes surgical resection easier and safer, and, at the same time, can improve oncological results. The robotic system fits perfectly with these more or less diffused technologies, and it seems that this benefit is mutual. In liver surgery, robotic systems help surgeons to localize tumors and improve surgical results with well-defined preoperative planning or increased intraoperative detection. Furthermore, they can balance the absence of tactile feedback and help recognize intrahepatic biliary or vascular structures during parenchymal transection. Some of these systems are well known and are already widely diffused in open and laparoscopic hepatectomies, such as indocyanine green fluorescence or ultrasound-guided resections, whereas other tools, such as Augmented Reality, are far from being standardized because of the high complexity and elevated costs. In this paper, we review all the experiences in the literature on the use of artificial intelligence systems in robotic liver resections, describing all their practical applications and their weaknesses.
Published: 2021
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37. Evaluation of an Innovative Care Pathway in the Diagnostic and Therapeutic Management of Hepatobiliary and Pancreatic Pathologies: 'One-Day Diagnosis'

Author: Zineb Cherkaoui, Barbara Seeliger, Vanina Faucher, Céline Biermann, Arne Kock, Patrick Pessaux, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: one-day diagnosis, value-based healthcare (VBHC), hepatobiliary and pancreatic diseases, care pathway, cancer, innovation, organization, Medicine (miscellaneous), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: “One-Day Diagnosis” (1DD) for hepatobiliary and pancreatic (HBP) diseases is an innovative care pathway that combines, on the same day, surgical consultation, medical imaging, anesthesia, diagnosis announcement, and therapeutic support consultations. The objective was to evaluate the length of the 1DD care pathway compared to a conventional one. The prospective “1DD care pathway” arm included 330 consecutive patients (January 2017–April 2019) vs. 152 (November 2014–November 2015) in the retrospective “conventional” one. In the 1DD group, diagnosis was made on the same day in 83% of consultations vs. 68.4% (p = 0.0005). Although there was no difference in overall time to diagnosis, diagnostic and therapeutic management was faster in the 1DD group (1 day vs. 15 days, p < 0.0004). In addition, 77% of patients who benefited from 1DD were very satisfied with their treatment overall. The mean cost of the 1DD consultation was EUR 176.8 +/− 149 (range: 50–546). The median cost of the overall program was similar (EUR 584 vs. EUR 563, p = 0.67). As an organizational innovation, the 1DD for HBP pathologies is a promising care pathway that optimizes diagnostic and therapeutic management, without creating medical overconsumption or additional costs. Given patient satisfaction, this model should be generalized to optimize cancer care by adapting it to the constraints of different healthcare structures.
Published: 2022
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38. Effect of emergency start and central venous catheter on outcomes in incident hemodialysis patients: a prospective observational cohort

Author: Cécile Couchoud, Thierry Hannedouche, Thierry Krummel, Erik-André Sauleau, Ulviyya Alizada, Isabelle Kazes, Olivier Moranne, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Université de Strasbourg (UNISTRA), Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: medicine.medical_specialty, Survival, Epidemiology, medicine.medical_treatment, Arteriovenous fistula, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, Nephrologists, Arteriovenous Shunt, Surgical, Renal Dialysis, Internal medicine, medicine, Risk of mortality, Central Venous Catheters, Humans, Survival rate, Data mining, Dialysis, Aged, business.industry, Hazard ratio, Middle Aged, equipment and supplies, medicine.disease, Survival Rate, Nephrology, Cohort, Kidney Failure, Chronic, Hemodialysis, business, Chronic hemodialysis, Central venous catheter
Abstract: International audience; Background: Unfavorable conditions at hemodialysis inception reduce the survival rate. However, the relative contribution to outcomes of predialysis follow-up, symptoms, emergency start or central venous catheter (CVC) is unknown.Methods: We analyzed the determinants of survival according to dialysis initiation conditions in the nationwide REIN registry, using two methods based either on clinical classification or data mining. We divided patients into four groups according to dialysis initiation (emergency vs planned, symptoms or not, previous follow-up). "Followed planned starters" began dialysis as outpatients and with an arteriovenous fistula (AVF). "Followed symptomatic non-urgent starters" were patients who started earlier because of any non-urgent symptomatic event. "Followed urgent starters" had seen a nephrologist before inception but started dialysis in an emergency condition. "Unknown urgent starters" were patients without any follow-up and who had a CVC at inception.Results: "Followed urgent" starters had the lowest 2-year survival rate (66.8%) compared to "followed planned" (77.3%), "followed symptomatic non urgent" (79.2%), and "unknown urgent" (71.7%). Compared to other groups, the risk of mortality was lower in followed symptomatic non urgent (HR 0.86 95% CI 0.75-0.99) and higher in followed urgent starters (HR 1.05 (95% CI 0.94-1.18). In data mining Classification And Regression Tree regrouping in five categories, the lowest 2-year survival (52.3%) was in over 70-year-old starters with a CVC. The survival was 93.2% in under 57-year-old patients without active cancer, 82.5% in 57-70-year-old individuals without cancer, 72.4% in over 70-year-old patients without CVC and 61.4% in under 70-year-old subjects with cancer. The hazard ratio of data mining categories varied between 2.12 (95% CI 1.73-2.60) in 57-70-year-old subjects without cancer and 4.42 (95% CI 3.64-5.37) in over 70-year-old patients with CVC. Therefore, regrouping incident patients into five data mining categories, identified by age, cancer, and CVC use, could discriminate the 2-year survival in patients starting hemodialysis.Conclusions: Although each classification captured different prognosis information, both analyses showed that starting hemodialysis on a CVC has more dramatic outcomes than emergency start per se.
Published: 2021
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39. Liver cell circuits and therapeutic discovery for advanced liver disease and cancer

Author: Thomas Baumert, Emilie Crouchet, Catherine Schuster, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Nouvel Hôpital Civil de Strasbourg, Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
Subjects: Carcinoma, Hepatocellular, business.industry, Hepatocellular carcinoma, Liver cell, Liver Neoplasms, Cancer, Epigenetic, General Medicine, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, medicine.disease, Chemoprevention, Fibrosis, Risk prediction, Liver disease, Cancer research, medicine, Hepatocytes, Gene signature, Humans, Obesity, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Hepatocellular carcinoma (HCC) is a major global health challenge with rising incidence. Despite the previous approval of several novel therapeutic approaches, HCC remains the second common cause of cancer-related death worldwide. The vast majority of HCCs arises in the context of chronic fibrotic liver diseases caused by viral or metabolic etiologies. In patients with advanced liver disease the risk of HCC persists even after viral cure or control of infection. Moreover, given the change in the lifestyle and increase of obesity and metabolic disorders, HCC incidence is predicted to drastically augment in the next decade. Early detection, improvement of the screening method in patient at-risk and development of chemopreventive strategies are therefore urgently needed to reduce HCC risk. This review summarizes the major challenges in the identification of patient at risk for HCC and the emergent strategies for HCC prevention to improve patients' outcome.Le carcinome hépatocellulaire (CHC) est un problème de santé mondial majeur dont l’incidence est en constante augmentation. Malgré l’approbation de plusieurs nouvelles approches thérapeutiques, le CHC demeure la deuxième cause de décès par cancer dans le monde. La grande majorité des CHC survient dans le contexte de maladies chroniques fibrotiques du foie causées par des étiologies virales ou métaboliques. Chez les patients présentant une maladie hépatique avancée, le risque de CHC persiste même après l’élimination du virus ou le contrôle de l’infection virale. En outre, compte tenu du changement de mode de vie et de l’augmentation de l’obésité et des troubles métaboliques, l’incidence du CHC devrait augmenter de façon spectaculaire au cours de la prochaine décennie. La détection précoce, l’amélioration des méthodes de dépistage chez les patients à risque et le développement de stratégies chimiopréventives sont donc nécessaires de toute urgence pour réduire le risque de CHC. Cette revue résume les principaux défis dans l’identification des patients à risque pour le CHC et les stratégies émergentes pour la prévention du CHC afin d’améliorer la prise en charge des patients.
Published: 2021
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40. Loss of hepatitis D virus infectivity upon farnesyl transferase inhibitor treatment associates with increasing RNA editing rates revealed by a new RT-ddPCR method

Author: Eloi R. Verrier, Anna Salvetti, Caroline Pons, Maud Michelet, Michel Rivoire, Thomas F. Baumert, David Durantel, Julie Lucifora, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Lucifora, Julie, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, ANR-21-CE15-0035,DELTArget,Caractérisation de facteur cellulaires impliqués dans l'infection par le virus de l'hépatite D pour la caractérisation de nouvelles cibles antivirales(2021), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), and ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pharmacology, Hepatitis delta Antigens, viruses, antiviral treatment, RT-ddPCR, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Virus Replication, Antiviral Agents, Hepatitis D virus, Transferases, Virology, FTI, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, RNA, Viral, hepatocytes, genetics, RNA Editing, pharmacology, Hepatitis Delta Virus, metabolism
Abstract: Chronic hepatitis D is the most severe form of chronic viral hepatitis and to date, efficient therapeutic approaches against hepatitis D virus (HDV) are limited. Among the antiviral molecules currently tested in clinical trials, the farnesyl transferase inhibitor (FTI) Lonafarnib inhibits the prenylation of the large delta antigen (L-HDAg), blocking virus assembly. Given the importance of L-HDAg in the virus life cycle, we hypothesized that Lonafarnib treatment may have side effects on virus replication. Here, we setup an innovative method for the quantification of HDV RNA allowing the independent quantification of edited and non-edited versions of the HDV genome upon infection. We demonstrated that FTI treatment of HBV/HDV co-infected dHepaRG or primary human hepatocytes leads to an accumulation of intracellular HDV RNAs and a marked increase in the levels of edited RNAs non only within the infected cells but also in the viral particles that are produced. Interestingly, these viral particles were less infectious, probably due to an enrichment in edited genomes that are packaged, leading to unproductive infection given the absence of S-HDAg synthesis after viral entry. Taken together, we setup an innovative quantification method allowing the investigation of RNA editing during HDV infection in a simple, fast, clinically-relevant assay and demonstrated for the first time the dual antiviral activity of FTI on HDV infection. journal article research support, non-u.s. gov't 2022 Feb 2022 01 17 imported
Published: 2021
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41. Prediction of In Vivo Laser-Induced Thermal Damage with Hyperspectral Imaging Using Deep Learning

Author: Annalisa Orrico, Paola Saccomandi, Richard Nkusi, Martina De Landro, Margherita Pizzicannella, Alexandre Hostettler, Michele Diana, Manuel Barberio, Eric Felli, Andrea Baiocchini, Toby Collins, Politecnico di Milano [Milan] (POLIMI), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, and ANR-18-CE19-0026,LiverSURG,Imagerie Optique Quantitative pour la Chirurgie du Foie(2018)
Subjects: Materials science, thermal damage, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, hyperspectral imaging, thermal damage prediction, convolutional neural network, 610 Medicine & health, TP1-1185, Biochemistry, Convolutional neural network, Article, 030218 nuclear medicine & medical imaging, Analytical Chemistry, law.invention, 03 medical and health sciences, remote sensing, 0302 clinical medicine, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], In vivo, law, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Electrical and Electronic Engineering, Instrumentation, Laser ablation, infrared imaging, business.industry, Deep learning, Lasers, Chemical technology, Hyperspectral imaging, deep learning, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Laser, in vivo experiments, Atomic and Molecular Physics, and Optics, 3. Good health, 030220 oncology & carcinogenesis, laser ablation, Thermal damage, Artificial intelligence, Laser Therapy, Neural Networks, Computer, Primary liver cancer, business, Biomedical engineering
Abstract: Thermal ablation is an acceptable alternative treatment for primary liver cancer, of which laser ablation (LA) is one of the least invasive approaches, especially for tumors in high-risk locations. Precise control of the LA effect is required to safely destroy the tumor. Although temperature imaging techniques provide an indirect measurement of the thermal damage, a degree of uncertainty remains about the treatment effect. Optical techniques are currently emerging as tools to directly assess tissue thermal damage. Among them, hyperspectral imaging (HSI) has shown promising results in image-guided surgery and in the thermal ablation field. The highly informative data provided by HSI, associated with deep learning, enable the implementation of non-invasive prediction models to be used intraoperatively. Here we show a novel paradigm “peak temperature prediction model” (PTPM), convolutional neural network (CNN)-based, trained with HSI and infrared imaging to predict LA-induced damage in the liver. The PTPM demonstrated an optimal agreement with tissue damage classification providing a consistent threshold (50.6 ± 1.5 °C) for the damage margins with high accuracy (~0.90). The high correlation with the histology score (r = 0.9085) and the comparison with the measured peak temperature confirmed that PTPM preserves temperature information accordingly with the histopathological assessment.
Published: 2021
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42. Oxidative Stress Triggers Selective tRNA Retrograde Transport in Human Cells during the Integrated Stress Response

Author: Schwenzer, Hagen, Jühling, Frank, Chu, Alexander, Pallett, Laura J., Baumert, Thomas F., Maini, Mala, Fassati, Ariberto, University College of London [London] (UCL), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nouvel Hôpital Civil de Strasbourg, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, and univOAK, Archive ouverte
Subjects: Cytoplasm, Aucun, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Article, RNA Transport, eIF-2 Kinase, RNA, Transfer, Humans, oxidative stress, tRNA, fluorescence in situ hybridization, lcsh:QH301-705.5, Cell Nucleus, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, TOR Serine-Threonine Kinases, nucleus, unfolded protein response, Pkr, retrograde transport, lcsh:Biology (General), Redd1, mTOR, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, HeLa Cells, Signal Transduction, Transcription Factors
Abstract: Summary In eukaryotes, tRNAs are transcribed in the nucleus and exported to the cytosol, where they deliver amino acids to ribosomes for protein translation. This nuclear-cytoplasmic movement was believed to be unidirectional. However, active shuttling of tRNAs, named tRNA retrograde transport, between the cytosol and nucleus has been discovered. This pathway is conserved in eukaryotes, suggesting a fundamental function; however, little is known about its role in human cells. Here we report that, in human cells, oxidative stress triggers tRNA retrograde transport, which is rapid, reversible, and selective for certain tRNA species, mostly with shorter 3′ ends. Retrograde transport of tRNASeC, which promotes translation of selenoproteins required to maintain homeostatic redox levels in cells, is highly efficient. tRNA retrograde transport is regulated by the integrated stress response pathway via the PERK-REDD1-mTOR axis. Thus, we propose that tRNA retrograde transport is part of the cellular response to oxidative stress., Graphical Abstract, Highlights • Oxidative stress triggers nuclear import of cytoplasmic tRNAs • Import is selective for certain tRNAs • Import requires activation of the unfolded protein response and inhibition of mTOR via REDD1 • tRNA nuclear import is a component of the integrated stress response, Schwenzer et. al discovered that oxidative stress induces nuclear import of cytoplasmic tRNAs. The authors found that this pathway is activated during the integrated stress response. tRNA nuclear import was selective to certain tRNA species and may contribute to the changes in protein translation known to protect cells from stress.
Published: 2019
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43. Quantitative dSTORM super-resolution microscopy localizes Aurora kinase A/AURKA in the mitochondrial matrix

Author: Giulia Bertolin, Charles Kervrann, Béatrice Durel, Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Space-timE RePresentation, Imaging and cellular dynamics of molecular COmplexes (SERPICO), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut Curie [Paris], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was supported by the Centre National de la Recherche Scientifique (CNRS), an intramural BIOSIT grant, grants from the Ligue Contre le Cancer Comités d'Ille et Vilaine, des Côtes d'Armor et du Finistère, the Fondation ARC pour la Recherche sur le Cancer, and an intramural technology-transfer grant from the Réseau Technologique Microscopie photonique de Fluorescence Multidimensionnelle (RTmfm) to G.B., ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), ANR-16-CE23-0005,DALLISH,Assimilation de Données et Microscopie à Feuille de Lumière Structurée pour la Modélisation des Voies d'Endocytose et d'Exocytose en Cellule Unique(2016), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), MRic is member of the national infrastructure France-BioImaging supported by the French National Research Agency (ANR-10-INBS-04). This work was supported by the Centre National de la Recherche Scientifique(CNRS), an intramural BIOSIT grant, grants from the Ligue Contre le Cancer Comités d’Ille et Vilaine, des Ĉotes d’Armor et du Finistère, the Association pour la Recherche Contre le Cancer (ARC), and an intramural technology-transfer grant from the Réseau Technologique de microscopie optique (RTmfm) toG.B., Chard-Hutchinson, Xavier, ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Bertolin, Giulia, and Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID
Subjects: [SDV]Life Sciences [q-bio], GcoPS, super-resolution, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Mitochondrion, colocalization, Mitochondrial Proteins, 03 medical and health sciences, 0302 clinical medicine, Organelle, Microscopy, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Aurora Kinase A, 0303 health sciences, AURKA, two-color dSTORM, Chemistry, Super-resolution microscopy, 030302 biochemistry & molecular biology, Colocalization, Cell Biology, General Medicine, Compartmentalization (psychology), Cell biology, [SDV] Life Sciences [q-bio], mitochondria, Mitochondrial matrix, Ultrastructure, 030217 neurology & neurosurgery
Abstract: International audience; Background information Mitochondria are dynamic organelles playing essential metabolic and signaling functions in cells. Their ultrastructure has largely been investigated with electron microscopy (EM) techniques. However, quantifying protein-protein proximities using EM is extremely challenging. Super-resolution microscopy techniques as direct stochastic optical reconstruction microscopy (dSTORM) now provide a fluorescent-based, quantitative alternative to EM. Recently, super-resolution microscopy approaches including dSTORM led to valuable advances in our knowledge of mitochondrial ultrastructure, and in linking it with new insights in organelle functions. Nevertheless, dSTORM is mostly used to image integral mitochondrial proteins, and there is little or no information on proteins transiently present at this compartment. The cancer-related Aurora kinase A/AURKA is a protein localized at various subcellular locations, including mitochondria. Results We first demonstrate that dSTORM coupled to GcoPS can resolve protein proximities within individual submitochondrial compartments. Then, we show that dSTORM provides sufficient spatial resolution to visualize and quantify the most abundant pool of endogenous AURKA in the mitochondrial matrix, as previously shown for overexpressed AURKA. In addition, we uncover a smaller pool of AURKA localized at the OMM, which could have a potential functional readout. We conclude by demonstrating that aldehyde-based fixatives are more specific for the OMM pool of the kinase instead. Conclusions Our results indicate that dSTORM coupled to GcoPS colocalization analysis is a suitable approach to explore the compartmentalization of non-integral mitochondrial proteins as AURKA, in a qualitative and quantitative manner. This method also opens up the possibility of analyzing the proximity between AURKA and its multiple mitochondrial partners with exquisite spatial resolution, thereby allowing novel insights into the mitochondrial functions controlled by AURKA. Significance Probing and quantifying the presence of endogenous AURKA - a cell cycle-related protein localized at mitochondria - in the different organelle subcompartments, using quantitative dSTORM super-resolution microscopy.
Published: 2021
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44. Nonlinear Robotics in Surgery

Author: Eduardo Parra-Davila, Deborah S. Keller, Sam Atallah, Rithvik Seela, Barbara Seeliger, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Institut de Recherche Contre les Cancers de l'Appareil Digestif-European Institute of Telesurgery (IRCAD/EITS), and Les Hôpitaux Universitaires de Strasbourg (HUS)
Subjects: medicine.medical_specialty, business.industry, Computer science, Deep learning, Soft robotics, Robotics, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Automation, Surgery, Nonlinear system, Tree (data structure), Transoral robotic surgery, medicine, Robot, Artificial intelligence, business
Abstract: The objective of robotics in surgery is evolving as systems are being redesigned to reach specific regions within specific organ systems. The next era for surgery will include reshaping and retooling robots to reach remote anatomic targets. While this includes the digitation of systems based on advancements in artificial intelligence, deep learning, and device automation, an important point of divergence from conventional laparoscopy and robotics will be the development and expansion of the role of nonlinear instruments to reach targets that are otherwise not possible to approach. This chapter explores the use of continuum and soft robotics via the major natural orifices, the bronchial tree, the cardiovascular system, and beyond.
Published: 2021
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45. Targeting the DNA damage response in immuno-oncology: developments and opportunities

Author: Christopher J. Lord, Philippe Pasero, Mathieu Rouanne, Roman M. Chabanon, Jean-Charles Soria, Sophie Postel-Vinay, Programme ATIP - Avenir, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], The institute of cancer research [London], Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), Université Paris-Saclay, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), AstraZeneca, Roche, Association pour la Recherche sur le Cancer, ARC: PGA1 RF 20190208576, Boehringer Ingelheim, Merck KGaA, Ligue Contre le Cancer: INCa-DGOS-INSERM_12551, Cancéropôle Ile de France: 2017-1-EMERG-72, Fondation Bettencourt Schueller, Fondation des Treilles, The authors thank Y. L. Lin and H. Técher for their careful reading of the manuscript and insightful comments. The work in the laboratory of S.P.-V. is supported by programme grants from ATIP-Avenir INSERM / La Ligue Nationale Contre le Cancer, SIRIC SOCRATE-2 (INCa-DGOS-INSERM_12551), Cancéropôle Ile-de-France (2017-1-EMERG-72) and Association pour la Recherche contre le Cancer (ARC PGA1 RF 20190208576). R.M.C. received funding from Fondation Bettencourt-Schueller, Fondation des Treilles, Fondation Philanthropia-Lombard Odier, Institut Servier, and Cancéropôle Ile-De-France., and R.M.C., M.R. and P.P. have no conflicts of interest or financial interests to disclose. C.J.L. is a named inventor on patents describing the use of DNA repair inhibitors and stands to gain from their use as part of the Institute of Cancer Research Rewards to Inventor scheme. C.J.L. has received research funding from AstraZeneca, Merck KGaA, Artios and Pfizer, has received consultancy and/or advisory fees from Astra Zeneca, Merck KGaA, Artios, Tango and GLG, and is a shareholder of OviBio and Tango. J.-C.S. has received consultancy fees from Relay Therapeutics, is a shareholder of AstraZeneca, Gritstone and Daiichi Sankyo, and is a member of the Hookipa board of directors. S.P.-V. has received research funding from Merck KGaA, Boehringer Ingelheim and Roche for unrelated research projects. As part of the Drug Development Department (DITEP), S.P.-V. is a principal investigator or a subinvestigator on clinical trials by Abbvie, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare AG, Bbb Technologies BV, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Eli Lilly, Exelixis, Forma, Gamamabs, Genentech Inc., Glaxosmithkline, H3 Biomedicine Inc., Hoffmann La Roche AG, Innate Pharma, Iris Servier, Janssen Cilag, Kyowa Kirin Pharmaceutical Development Inc., Loxo Oncology, Lytix Biopharma AS, Medimmune, Menarini Ricerche, Merck Sharp & Dohme-Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology NV, Oncoethix, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi Aventis, Taiho Pharma, Tesaro Inc. and Xencor. S.P.-V. has participated in advisory boards for Merck KGaA.
Subjects: Antigenicity, DNA damage, General Mathematics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cancer immunotherapy, Medical Oncology, Genomic Instability, 03 medical and health sciences, 0302 clinical medicine, Immune system, Targeted therapies, Immunity, Adjuvanticity, Neoplasms, medicine, Animals, Humans, 030304 developmental biology, 0303 health sciences, business.industry, Applied Mathematics, Immunogenicity, Immunotherapy, 3. Good health, 030220 oncology & carcinogenesis, Cancer research, Immunogenic cell death, Tumour immunology, business, DNA Damage
Abstract: International audience; Immunotherapy has revolutionized cancer treatment and substantially improved patient outcome with regard to multiple tumour types. However, most patients still do not benefit from such therapies, notably because of the absence of pre-existing T cell infiltration. DNA damage response (DDR) deficiency has recently emerged as an important determinant of tumour immunogenicity. A growing body of evidence now supports the concept that DDR-targeted therapies can increase the antitumour immune response by (1) promoting antigenicity through increased mutability and genomic instability, (2) enhancing adjuvanticity through the activation of cytosolic immunity and immunogenic cell death and (3) favouring reactogenicity through the modulation of factors that control the tumour–immune cell synapse. In this Review, we discuss the interplay between the DDR and anticancer immunity and highlight how this dynamic interaction contributes to shaping tumour immunogenicity. We also review the most innovative preclinical approaches that could be used to investigate such effects, including recently developed ex vivo systems. Finally, we highlight the therapeutic opportunities presented by the exploitation of the DDR–anticancer immunity interplay, with a focus on those in early-phase clinical development.
Published: 2021
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46. Hepatitis B virus compartmentalization and single-cell differentiation in hepatocellular carcinoma

Author: Jühling, Frank, Saviano, Antonio, Ponsolles, Clara, Heydmann, Laura, Crouchet, Emilie, Durand, Sarah C, El Saghire, Houssein, Felli, Emanuele, Lindner, Véronique, Pessaux, Patrick, Pochet, Nathalie, Schuster, Catherine, Verrier, Eloi R, Baumert, Thomas F, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Nouvel Hôpital Civil de Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), and ANR-10-LABX-0028,HepSys,Functional genomics of viral hepatitis and liver disease(2010)
Subjects: Adult, Gene Expression Regulation, Viral, Male, Hepatitis B virus, Carcinoma, Hepatocellular, viruses, genetic processes, Hepatitis B, Chronic, Cell Line, Tumor, Humans, natural sciences, Research Articles, Aged, Gene Expression Profiling, Liver Neoplasms, Cell Differentiation, Middle Aged, Viral Load, Cell Transformation, Viral, Hepatitis B, RNA, Viral, Female, Disease Susceptibility, Neoplasm Grading, Single-Cell Analysis, Transcriptome, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: Single-cell RNA-Seq unravels heterogeneity and compartmentalization of both hepatitis B virus and cancer identifying new candidate pathways for viral hepatocarcinogenesis., Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) world-wide. The molecular mechanisms of viral hepatocarcinogenesis are still partially understood. Here, we applied two complementary single-cell RNA-sequencing protocols to investigate HBV–HCC host cell interactions at the single cell level of patient-derived HCC. Computational analyses revealed a marked HCC heterogeneity with a robust and significant correlation between HBV reads and cancer cell differentiation. Viral reads significantly correlated with the expression of HBV-dependency factors such as HLF in different tumor compartments. Analyses of virus-induced host responses identified previously undiscovered pathways mediating viral carcinogenesis, such as E2F- and MYC targets as well as adipogenesis. Mapping of fused HBV–host cell transcripts allowed the characterization of integration sites in individual cancer cells. Collectively, single-cell RNA-Seq unravels heterogeneity and compartmentalization of both, virus and cancer identifying new candidate pathways for viral hepatocarcinogenesis. The perturbation of pro-carcinogenic gene expression even at low HBV levels highlights the need of HBV cure to eliminate HCC risk.
Published: 2021
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47. Cystic fibrosis-related liver disease: Clinical presentations, diagnostic and monitoring approaches in the era of CFTR modulator therapies

Author: Aurélie Beaufrère, Jérémy Dana, Thomas F. Baumert, Valérie Vilgrain, Sophie Hillaire, Laureline Berteloot, Monique Fabre, Dominique Debray, Caroline Reinhold, Department of Radiology, AP-HP, Beaujon University Hospital Paris Nord, F-92110 Clichy, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Pathologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], McGill University = Université McGill [Montréal, Canada], Research Institute of the McGill University Health Centre (RI-MUHC), McGill University Health Center [Montreal] (MUHC), and Service de radiologie pédiatrique [CHU Necker]
Subjects: Cystic Fibrosis Liver Disease, Pathology, medicine.medical_specialty, Cirrhosis, Cystic Fibrosis, medicine.medical_treatment, Cystic Fibrosis Transmembrane Conductance Regulator, Disease, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Liver transplantation, Cystic Fibrosis Liver Disease Focal Biliary Fibrosis Porto-sinusoidal Vascular Disease Noninvasive Diagnostic Radio-pathologic correlations, Cystic fibrosis, Severity of Illness Index, Focal Biliary Fibrosis, Liver disease, Noninvasive Diagnostic, Hypertension, Portal, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Humans, Pathological, Porto-sinusoidal Vascular Disease, Ultrasonography, methods, statistics & numerical data, Hepatology, business.industry, Vascular disease, Liver Diseases, Radio-pathologic correlations, diagnostic imaging, physiopathology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, antagonists & inhibitors, drug effects, therapeutic use, Liver, Portal hypertension, Elasticity Imaging Techniques, pathology, complications, business, etiology
Abstract: Cystic fibrosis (CF) is the most common autosomal recessive disease in the Caucasian population. Cystic fibrosis-related liver disease (CFLD) is defined as the pathogenesis related to the underlying CFTR defect in biliary epithelial cells. CFLD needs to be distinguished from other liver manifestations that may not have any pathological significance. The clinical/histological presentation and severity of CFLD vary. The main histological presentation of CFLD is focal biliary fibrosis, which is usually asymptomatic. Portal hypertension develops in a minority of cases (about 10%) and may require specific management including liver transplantation for end-stage liver disease. Portal hypertension is usually the result of the progression of focal biliary fibrosis to multilobular cirrhosis during childhood. Nevertheless, non-cirrhotic portal hypertension as a result of porto-sinusoidal vascular disease is now identified increasingly more frequently, mainly in young adults. To evaluate the effect of new CFTR modulator therapies on the liver, the spectrum of hepatobiliary involvement must first be precisely classified. This paper discusses the phenotypic features of CFLD, its underlying physiopathology and relevant diagnostic and follow-up approaches, with a special focus on imaging. journal article review 2022 Feb 2021 10 20 imported
Published: 2021
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48. Learning robotic needle steering from inverse finite element simulations

Author: Pedro Henrique Suruagy Perrusi, Anna Cazzaniga, Paul Baksic, Eleonora Tagliabue, Elena de Momi, Hadrien Courtecuisse, Automatique, Vision et Robotique [Strasbourg] (AVR), Laboratoire des Sciences de l'Image, de l'Informatique et de la Télédétection (LSIIT), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Computational Anatomy and Simulation for Medicine (MIMESIS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), ICube, CNRS, University of Strasbourg, France, L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Politecnico di Milano [Milan] (POLIMI), Department of Electronics, Information, and Bioengineering [Milano] (DEIB), Department of Computer Science [Verona] (UNIVR | DI), University of Verona (UNIVR), This work was supported by French National Research Agency (ANR)within the project SPERRY ANR-18-CE33-0007 and the Investissementsd’Avenir program (ANR-11-LABX-0004, Labex CAMI)., SOFA Framework, ANR-18-CE33-0007,SPERRY,CHIRURGIE ROBOTIQUE SUPERVISÉE - APPLICATION A L'ABLATION RADIOFREQUENCE DES TUMEURS DU FOIE(2018), ANR-11-LABX-0004,CAMI,Gestes Médico-Chirurgicaux Assistés par Ordinateur(2011), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), and Università degli studi di Verona = University of Verona (UNIVR)
Subjects: data-driven methods, machine learning, [INFO.INFO-AU]Computer Science [cs]/Automatic Control Engineering, percutaneous procedures, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, deformable needle steering, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: International audience; Tissue motion compensation during robotic needle steering is a challenging research topic. While the deformable non-linear coupling between needle and tissue is captured by simulation-based control strategies, they increase significantly the computational cost of the control. In this work, we rely on machine learning methods to enable autonomous robotic needle steering with very low computation times. We propose to use an Extreme Learning Machine (ELM) to learn an inverse model which accounts for needle-tissue interaction. The ELM trains with synthetic data generated from multiple needle insertions controlled by inverse finite-element simulations. Results indicate the method is able to achieve clinical compatible precision, and it's robust to previously unseen trajectory-shapes and variable tissue elasticity parameters, while using only a third of the computational time demanded for simulation-based methods.
Published: 2021

49. Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development

Author: Joachim Lupberger, Thomas Baumert, Alessia Virzì, Simona Tripon, Victor Gonzalez-Motos, univOAK, Archive ouverte, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, Nouvel Hôpital Civil de Strasbourg, Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
Subjects: lcsh:Medicine, Review, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Fibrosis, medicine, HBV, Epigenetics, HCC, 030304 developmental biology, risk, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, lcsh:R, biomarkers, General Medicine, medicine.disease, digestive system diseases, cure, 3. Good health, Chronic infection, Hepatocellular carcinoma, HCV, Cancer research, Biomarker (medicine), 030211 gastroenterology & hepatology, Signal transduction, business, Viral hepatitis, liver disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Despite breakthroughs in antiviral therapies, chronic viral hepatitis B and C are still the major causes of liver fibrosis and hepatocellular carcinoma (HCC). Importantly, even in patients with controlled infection or viral cure, the cancer risk cannot be fully eliminated, highlighting a persisting oncogenic pressure imposed by epigenetic imprinting and advanced liver disease. Reliable and minimally invasive biomarkers for early fibrosis and for residual HCC risk in HCV-cured patients are urgently needed. Chronic infection with HBV and/or HCV dysregulates oncogenic and profibrogenic signaling within the host, also displayed in the secretion of soluble factors to the blood. The study of virus-dysregulated signaling pathways may, therefore, contribute to the identification of reliable minimally invasive biomarkers for the detection of patients at early-stage liver disease potentially complementing existing noninvasive methods in clinics. With a focus on virus-induced signaling events, this review provides an overview of candidate blood biomarkers for liver disease and HCC risk associated with chronic viral hepatitis and epigenetic viral footprints.
Published: 2021
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50. Hepatotropic Peptides Grafted onto Maleimide-Decorated Nanoparticles: Preparation, Characterization and In Vitro Uptake by Human HepaRG Hepatoma Cells

Author: Clarisse Brossard, Manuel Vlach, Lucas Jacquet, Elise Vène, Vincent Dorcet, Pascal Loyer, Sandrine Cammas-Marion, Nicolas Lepareur, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Synthèse Caractérisation Analyse de la Matière (ScanMAT), Université de Rennes (UR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Rennes Angers, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), This work was funded by the Fondation pour la Recherche Médicale (FRM N°DCM20181039540), Cancéropôle Grand Ouest (CGO n° 17/028), Labex IRON (n° ANR-11-LABX-0018), Institut National de la Santé et de la Recherche Médicale (Inserm), l’Ecole Nationale Supérieure de Chimie de Rennes (ENSCR, France), the Centre National de la Recherche Scientifique (CNRS). Clarisse Brossard was recipient of a PhD fellowship from the Fondation pour la Recherche Médicale (FRM N°DCM20181039540) and Elise Vène received a 3-year PhD fellowship from the Association pour la Recherche contre le Cancer (ARC, France)., ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), Jonchère, Laurent, and Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID
Subjects: inorganic chemicals, Polymers and Plastics, poly(benzyl malate), biocompatible NPs, post-formulation modification, hepatotropic peptides, HepaRG cells, education, technology, industry, and agriculture, General Chemistry, respiratory system, [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, health care economics and organizations
Abstract: International audience; We recently demonstrated the strong tropism of George Baker (GB) Virus A (GBVA10-9) and Plasmodium circumsporozoite protein (CPB) derived synthetic peptides towards hepatoma cells. In a first approach, these peptides were covalently bound to poly(benzyl malate) (PMLABe(73)) and poly(ethylene glycol)-block-PMLABe(73) (PEG(62)-b-PMLABe(73)) (co)polymers, and corresponding peptide-decorated nanoparticles (NPs) were prepared by nanoprecipitation. We showed that peptide enhanced NPs internalization by hepatoma cells. In the present work, we set up a second strategy to functionalize NPs prepared from PMLABe(73) derivates. First, maleimide-functionalized PMLABe(73) (Mal-PMLABe(73)) and PEG(62)-b-PMLABe(73) (Mal-PEG(62)-b-PMLABe(73)) were synthesized and corresponding NPs were prepared by nanoprecipitation. Then, peptides (GBVA10-9, CPB and their scramble controls GBVA10-9scr and CPBscr) with a thiol group were engrafted onto the NPs’ maleimide groups using the Michael addition to obtain peptide functionalized NPs by post-formulation procedure. These peptide-modified NPs varied in diameter and dispersity depending on the considered peptides and/or (co)polymers but kept their spherical shape. The peptide-functionalized NPs were more efficiently internalized by HepaRG hepatoma cells than native and maleimide-NPs with various levels relying on the peptide’s nature and the presence of PEG. We also observed important differences in internalization of NPs functionalized by the maleimide-thiol-peptide reaction compared to that of NPs prepared from peptide-functionalized PMLABe(73) derivatives.
Published: 2022
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