1,677 results on '"Gonzalez EM"'
Search Results
2. Primavera para as rosas negras: Lélia Gonzalez em primeira pessoa.
- Author
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Guimarães do Nascimento, Tamires
- Published
- 2019
3. BULLYING NA CONVIVÊNCIA ESCOLAR: UM ESTUDO DE CASO NOS 5os ANOS DO ENSINO FUNDAMENTAL NO COLÉGIO HERMESINDO ALONSO GONZALEZ EM TRÊS LAGOAS-MS
- Author
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Terezinha Bazé de Lima and Elizângela Barbosa de Oliveira Ferreira
- Subjects
General Medicine - Published
- 2020
4. BULLYING NA CONVIVÊNCIA ESCOLAR: UM ESTUDO DE CASO NOS 5os ANOS DO ENSINO FUNDAMENTAL NO COLÉGIO HERMESINDO ALONSO GONZALEZ EM TRÊS LAGOAS-MS
- Author
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Ferreira, Elizângela Barbosa de Oliveira, primary and Lima, Terezinha Bazé de, additional
- Published
- 2020
- Full Text
- View/download PDF
5. Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals
- Author
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Layo-Carris, DE, Lubin, EE, Sangree, AK, Clark, KJ, Durham, EL, Gonzalez, EM, Smith, S, Angireddy, R, Wang, XM, Weiss, E, Mendoza-Londono, R, Dupuis, L, Damseh, N, Velasco, D, Valenzuela, I, Codina-Sola, M, Ziats, C, Have, J, Clarkson, K, Steel, D, Kurian, M, Barwick, K, Carrasco, D, Dagli, AI, Nowaczyk, MJM, Hancarova, M, Bendova, S, Prchalova, D, Sedlacek, Z, Baxova, A, Nowak, CB, Douglas, J, Chung, WK, Longo, N, Platzer, K, Kloeckner, C, Averdunk, L, Wieczorek, D, Krey, I, Zweier, C, Reis, A, Balci, T, Simon, M, Kroes, HY, Wiesener, A, Vasileiou, G, Marinakis, NM, Veltra, D, Sofocleous, C, Kosma, K, Synodinos, JT, Voudris, KA, Vuillaume, M-L, Gueguen, P, Derive, N, Colin, E, Battault, C, Au, B, Delatycki, M, Wallis, M, Gallacher, L, Majdoub, F, Smal, N, Weckhuysen, S, Schoonjans, A-S, Kooy, RF, Meuwissen, M, Cocanougher, BT, Taylor, K, Pizoli, CE, McDonald, MT, James, P, Roeder, ER, Littlejohn, R, Borja, NA, Thorson, W, King, K, Stoeva, R, Suerink, M, Nibbeling, E, Baskin, S, Guyader, GLE, Kaplan, J, Muss, C, Carere, DA, Bhoj, EJK, Bryant, LM, Layo-Carris, DE, Lubin, EE, Sangree, AK, Clark, KJ, Durham, EL, Gonzalez, EM, Smith, S, Angireddy, R, Wang, XM, Weiss, E, Mendoza-Londono, R, Dupuis, L, Damseh, N, Velasco, D, Valenzuela, I, Codina-Sola, M, Ziats, C, Have, J, Clarkson, K, Steel, D, Kurian, M, Barwick, K, Carrasco, D, Dagli, AI, Nowaczyk, MJM, Hancarova, M, Bendova, S, Prchalova, D, Sedlacek, Z, Baxova, A, Nowak, CB, Douglas, J, Chung, WK, Longo, N, Platzer, K, Kloeckner, C, Averdunk, L, Wieczorek, D, Krey, I, Zweier, C, Reis, A, Balci, T, Simon, M, Kroes, HY, Wiesener, A, Vasileiou, G, Marinakis, NM, Veltra, D, Sofocleous, C, Kosma, K, Synodinos, JT, Voudris, KA, Vuillaume, M-L, Gueguen, P, Derive, N, Colin, E, Battault, C, Au, B, Delatycki, M, Wallis, M, Gallacher, L, Majdoub, F, Smal, N, Weckhuysen, S, Schoonjans, A-S, Kooy, RF, Meuwissen, M, Cocanougher, BT, Taylor, K, Pizoli, CE, McDonald, MT, James, P, Roeder, ER, Littlejohn, R, Borja, NA, Thorson, W, King, K, Stoeva, R, Suerink, M, Nibbeling, E, Baskin, S, Guyader, GLE, Kaplan, J, Muss, C, Carere, DA, Bhoj, EJK, and Bryant, LM
- Abstract
Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.
- Published
- 2024
6. Correction: Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals (vol 3, 2024, 59)
- Author
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Layo-Carris, DE, Lubin, EE, Sangree, AK, Clark, KJ, Durham, EL, Gonzalez, EM, Smith, S, Angireddy, R, Wang, XM, Weiss, E, Toutain, A, Mendoza-Londono, R, Dupuis, L, Damseh, N, Velasco, D, Valenzuela, I, Codina-Sola, M, Ziats, C, Have, J, Clarkson, K, Steel, D, Kurian, M, Barwick, K, Carrasco, D, Dagli, AI, Nowaczyk, MJM, Hancarova, M, Bendova, S, Prchalova, D, Sedlacek, Z, Baxova, A, Nowak, CB, Douglas, J, Chung, WK, Longo, N, Platzer, K, Klockner, C, Averdunk, L, Wieczorek, D, Krey, I, Zweier, C, Reis, A, Balci, T, Simon, M, Kroes, HY, Wiesener, A, Vasileiou, G, Marinakis, NM, Veltra, D, Sofocleous, C, Kosma, K, Synodinos, JT, Voudris, KA, Vuillaume, M-L, Gueguen, P, Derive, N, Colin, E, Battault, C, Au, B, Delatycki, M, Wallis, M, Gallacher, L, Majdoub, F, Smal, N, Weckhuysen, S, Schoonjans, A-S, Kooy, RF, Meuwissen, M, Cocanougher, BT, Taylor, K, Pizoli, CE, Mcdonald, MT, James, P, Roeder, ER, Littlejohn, R, Borja, NA, Thorson, W, King, K, Stoeva, R, Suerink, M, Nibbeling, E, Baskin, S, Guyader, GLE, Kaplan, J, Muss, C, Carere, DA, Bhoj, EJK, Bryant, LM, Layo-Carris, DE, Lubin, EE, Sangree, AK, Clark, KJ, Durham, EL, Gonzalez, EM, Smith, S, Angireddy, R, Wang, XM, Weiss, E, Toutain, A, Mendoza-Londono, R, Dupuis, L, Damseh, N, Velasco, D, Valenzuela, I, Codina-Sola, M, Ziats, C, Have, J, Clarkson, K, Steel, D, Kurian, M, Barwick, K, Carrasco, D, Dagli, AI, Nowaczyk, MJM, Hancarova, M, Bendova, S, Prchalova, D, Sedlacek, Z, Baxova, A, Nowak, CB, Douglas, J, Chung, WK, Longo, N, Platzer, K, Klockner, C, Averdunk, L, Wieczorek, D, Krey, I, Zweier, C, Reis, A, Balci, T, Simon, M, Kroes, HY, Wiesener, A, Vasileiou, G, Marinakis, NM, Veltra, D, Sofocleous, C, Kosma, K, Synodinos, JT, Voudris, KA, Vuillaume, M-L, Gueguen, P, Derive, N, Colin, E, Battault, C, Au, B, Delatycki, M, Wallis, M, Gallacher, L, Majdoub, F, Smal, N, Weckhuysen, S, Schoonjans, A-S, Kooy, RF, Meuwissen, M, Cocanougher, BT, Taylor, K, Pizoli, CE, Mcdonald, MT, James, P, Roeder, ER, Littlejohn, R, Borja, NA, Thorson, W, King, K, Stoeva, R, Suerink, M, Nibbeling, E, Baskin, S, Guyader, GLE, Kaplan, J, Muss, C, Carere, DA, Bhoj, EJK, and Bryant, LM
- Published
- 2024
7. Legume Nitrogen Utilization Under Drought Stress
- Author
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Castañeda, V., Gil-Quintana, E., Echeverria, A., González, EM., Shrawat, Ashok, editor, Zayed, Adel, editor, and Lightfoot, David A., editor
- Published
- 2018
- Full Text
- View/download PDF
8. Correction: Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.
- Author
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Layo-Carris DE, Lubin EE, Sangree AK, Clark KJ, Durham EL, Gonzalez EM, Smith S, Angireddy R, Wang XM, Weiss E, Toutain A, Mendoza-Londono R, Dupuis L, Damseh N, Velasco D, Valenzuela I, Codina-Solà M, Ziats C, Have J, Clarkson K, Steel D, Kurian M, Barwick K, Carrasco D, Dagli AI, Nowaczyk MJM, Hančárová M, Bendová Š, Prchalova D, Sedláček Z, Baxová A, Nowak CB, Douglas J, Chung WK, Longo N, Platzer K, Klöckner C, Averdunk L, Wieczorek D, Krey I, Zweier C, Reis A, Balci T, Simon M, Kroes HY, Wiesener A, Vasileiou G, Marinakis NM, Veltra D, Sofocleous C, Kosma K, Synodinos JT, Voudris KA, Vuillaume ML, Gueguen P, Derive N, Colin E, Battault C, Au B, Delatycki M, Wallis M, Gallacher L, Majdoub F, Smal N, Weckhuysen S, Schoonjans AS, Kooy RF, Meuwissen M, Cocanougher BT, Taylor K, Pizoli CE, McDonald MT, James P, Roeder ER, Littlejohn R, Borja NA, Thorson W, King K, Stoeva R, Suerink M, Nibbeling E, Baskin S, Guyader GLE, Kaplan J, Muss C, Carere DA, Bhoj EJK, and Bryant LM
- Published
- 2024
- Full Text
- View/download PDF
9. Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.
- Author
-
Layo-Carris DE, Lubin EE, Sangree AK, Clark KJ, Durham EL, Gonzalez EM, Smith S, Angireddy R, Wang XM, Weiss E, Toutain A, Mendoza-Londono R, Dupuis L, Damseh N, Velasco D, Valenzuela I, Codina-Solà M, Ziats C, Have J, Clarkson K, Steel D, Kurian M, Barwick K, Carrasco D, Dagli AI, Nowaczyk MJM, Hančárová M, Bendová Š, Prchalova D, Sedláček Z, Baxová A, Nowak CB, Douglas J, Chung WK, Longo N, Platzer K, Klöckner C, Averdunk L, Wieczorek D, Krey I, Zweier C, Reis A, Balci T, Simon M, Kroes HY, Wiesener A, Vasileiou G, Marinakis NM, Veltra D, Sofocleous C, Kosma K, Traeger Synodinos J, Voudris KA, Vuillaume ML, Gueguen P, Derive N, Colin E, Battault C, Au B, Delatycki M, Wallis M, Gallacher L, Majdoub F, Smal N, Weckhuysen S, Schoonjans AS, Kooy RF, Meuwissen M, Cocanougher BT, Taylor K, Pizoli CE, McDonald MT, James P, Roeder ER, Littlejohn R, Borja NA, Thorson W, King K, Stoeva R, Suerink M, Nibbeling E, Baskin S, L E Guyader G, Kaplan J, Muss C, Carere DA, Bhoj EJK, and Bryant LM
- Subjects
- Humans, Male, Female, Child, Neurodegenerative Diseases genetics, Neurodegenerative Diseases pathology, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders pathology, Child, Preschool, Adolescent, Adult, Intellectual Disability genetics, Intellectual Disability pathology, Phenotype, Histones genetics
- Abstract
Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
10. Enhancing the First-Pass Effect in Acute Stroke: The Impact of Stent Retriever Characteristics.
- Author
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Murias E, Puig J, Serna-Candel C, Gonzalez EM, Moreu M, Jiménez-Gómez E, SanRoman L, Aparici-Robles F, Terceño M, Martínez AM, Aixut S, Romero V, Mendez JC, Sagredo-Barra A, Aguilar Y, Espinosa de Rueda M, Blázquez MAC, Bashir S, Rodríguez Castro J, Lopez-Frías A, Jiménez JM, Chaviano J, Maestro V, Manso J, Lopez-Rueda A, Remollo S, Morales-Caba L, Comas-Cufí M, Vega P, and On Behalf Of Rossetti Registry Investigators
- Abstract
Introduction: Although stentrievers (SRs) have been a mainstay of mechanical thrombectomy (MT), and current guidelines recommend the use of SRs in the treatment of large vessel occlusion stroke (LVO), there is a paucity of studies in the literature comparing SRs directly against each other in terms of mechanical and functional properties. Timely access to endovascular therapy and the ability to restore intracranial flow in a safe, efficient, and efficacious manner have been critical to the success of MT. This study aimed to investigate the impact of contemporary SR characteristics, including model, brand, size, and length, on the first-pass effect (FPE) in patients with acute ischemic stroke. Methods: Consecutive patients with M1 occlusion treated with a single SR+BGC were recruited from the ROSSETTI registry. The primary outcome was the FPE that was defined as modified (mFPE) or true (tFPE) for the achievement of modified thrombolysis in cerebral infarction (mTICI) grades 2b-3 or 3 after a single device pass, respectively. We compared patients who achieved mFPE with those who achieved tFPE according to SR characteristics. Results: We included 610 patients (52.3% female and 47.7% male, mean age 75.1 ± 13.62 years). mFPE was achieved in 357 patients (58.5%), whereas tFPE was achieved in 264 (43.3%). There was no significant association between SR characteristics and mFPE or tFPE. Specifically, the SR size did not show a statistically significant relationship with improvement in FPE. Similarly, the length of the SR did not yield significant differences in the mFPE and tFPE, even when the data were grouped. Conclusions : Our data indicate that contemporary SR-mediated thrombectomy characteristics, including model, brand, size, and length, do not significantly affect the FPE.
- Published
- 2024
- Full Text
- View/download PDF
11. NeuroTri2-VISDOT: An open-access tool to harness the power of second trimester human single cell data to inform models of Mendelian neurodevelopmental disorders.
- Author
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Clark KJ, Lubin EE, Gonzalez EM, Sangree AK, Layo-Carris DE, Durham EL, Ahrens-Nicklas RC, Nomakuchi TT, and Bhoj EJ
- Abstract
Whole exome and genome sequencing, coupled with refined bioinformatic pipelines, have enabled improved diagnostic yields for individuals with Mendelian conditions and have led to the rapid identification of novel syndromes. For many Mendelian neurodevelopmental disorders (NDDs), there is a lack of pre-existing model systems for mechanistic work. Thus, it is critical for translational researchers to have an accessible phenotype- and genotype-informed approach for model system selection. Single-cell RNA sequencing data can be informative in such an approach, as it can indicate which cell types express a gene of interest at the highest levels across time. For Mendelian NDDs, such data for the developing human brain is especially useful. A valuable single-cell RNA sequencing dataset of the second trimester developing human brain was produced by Bhaduri et al in 2021, but access to these data can be limited by computing power and the learning curve of single-cell data analysis. To reduce these barriers for translational research on Mendelian NDDs, we have built the web-based tool, Neurodevelopment in Trimester 2 - VIsualization of Single cell Data Online Tool (NeuroTri2-VISDOT), for exploring this single-cell dataset, and we have employed it in several different settings to demonstrate its utility for the translational research community., Competing Interests: Conflict of Interest The authors declare no conflicts of interest.
- Published
- 2024
- Full Text
- View/download PDF
12. m6A-dependent circular RNA formation mediates tau-induced neurotoxicity.
- Author
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Atrian F, Ramirez P, De Mange J, Marquez M, Gonzalez EM, Minaya M, Karch CM, and Frost B
- Abstract
Circular RNAs (circRNAs), covalently closed RNA molecules that form due to back-splicing of RNA transcripts, have recently been implicated in Alzheimer's disease and related tauopathies. circRNAs are regulated by N
6 -methyladenosine (m6 A) RNA methylation, can serve as "sponges" for proteins and RNAs, and can be translated into protein via a cap-independent mechanism. Mechanisms underlying circRNA dysregulation in tauopathies and causal relationships between circRNA and neurodegeneration are currently unknown. In the current study, we aimed to determine whether pathogenic forms of tau drive circRNA dysregulation and whether such dysregulation causally mediates neurodegeneration. We identify circRNAs that are differentially expressed in the brain of a Drosophila model of tauopathy and in induced pluripotent stem cell (iPSC)-derived neurons carrying a tau mutation associated with autosomal dominant tauopathy. We leverage Drosophila to discover that depletion of circular forms of muscleblind ( circMbl) , a circRNA that is particularly abundant in brains of tau transgenic Drosophila , significantly suppresses tau neurotoxicity, suggesting that tau-induced circMbl elevation is neurotoxic. We detect a general elevation of m6 A RNA methylation and circRNA methylation in tau transgenic Drosophila and find that tau-induced m6 A methylation is a mechanistic driver of circMbl formation. Interestingly, we find that circRNA and m6 A RNA accumulate within nuclear envelope invaginations of tau transgenic Drosophila and in iPSC-derived cerebral organoid models of tauopathy. Taken together, our studies add critical new insight into the mechanisms underlying circRNA dysregulation in tauopathy and identify m6 A-modified circRNA as a causal factor contributing to neurodegeneration. These findings add to a growing literature implicating pathogenic forms of tau as drivers of altered RNA metabolism.- Published
- 2024
- Full Text
- View/download PDF
13. TBCK syndrome: a rare multi-organ neurodegenerative disease.
- Author
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Durham EL, Angireddy R, Black A, Melendez-Perez A, Smith S, Gonzalez EM, Navarro KG, Díaz A, Bhoj EJK, and Katsura KA
- Subjects
- Humans, Muscle Hypotonia genetics, Muscle Hypotonia pathology, Phenotype, Protein Serine-Threonine Kinases genetics, Neurodegenerative Diseases diagnosis, Neurodegenerative Diseases etiology
- Abstract
TBCK syndrome is an autosomal recessive disorder primarily characterized by global developmental delay, hypotonia, abnormal magnetic resonance imaging (MRI), and distinctive craniofacial phenotypes. High variability is observed among affected individuals and their corresponding variants, making clinical diagnosis challenging. Here, we discuss recent breakthroughs in clinical considerations, TBCK function, and therapeutic development., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
14. Genome-wide pooled CRISPR screening in neurospheres.
- Author
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Abid T, Goodale AB, Kalani Z, Wyatt M, Gonzalez EM, Zhou KN, Qian K, Novikov D, Condurat AL, Bandopadhayay P, Piccioni F, Persky NS, and Root DE
- Subjects
- Humans, CRISPR-Cas Systems, Genome, Cell Line, Clustered Regularly Interspaced Short Palindromic Repeats genetics, Neoplasms
- Abstract
Spheroid culture systems have allowed in vitro propagation of cells unable to grow in canonical cell culturing conditions, and may capture cellular contexts that model tumor growth better than current model systems. The insights gleaned from genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening of thousands of cancer cell lines grown in conventional culture conditions illustrate the value of such CRISPR pooled screens. It is clear that similar genome-wide CRISPR screens of three-dimensional spheroid cultures will be important for future biological discovery. Here, we present a protocol for genome-wide CRISPR screening of three-dimensional neurospheres. While many in-depth protocols and discussions have been published for more typical cell lines, few detailed protocols are currently available in the literature for genome-wide screening in spheroidal cell lines. For those who want to screen such cell lines, and particularly neurospheres, we provide a step-by-step description of assay development tests to be performed before screening, as well as for the screen itself. We highlight considerations of variables that make these screens distinct from, or similar to, typical nonspheroid cell lines throughout. Finally, we illustrate typical outcomes of neurosphere genome-wide screens, and how neurosphere screens typically produce slightly more heterogeneous signal distributions than more canonical cancer cell lines. Completion of this entire protocol will take 8-12 weeks from the initial assay development tests to deconvolution of the sequencing data., (© 2023. Springer Nature Limited.)
- Published
- 2023
- Full Text
- View/download PDF
15. PhytoOracle: Scalable, modular phenomics data processing pipelines.
- Author
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Gonzalez EM, Zarei A, Hendler N, Simmons T, Zarei A, Demieville J, Strand R, Rozzi B, Calleja S, Ellingson H, Cosi M, Davey S, Lavelle DO, Truco MJ, Swetnam TL, Merchant N, Michelmore RW, Lyons E, and Pauli D
- Abstract
As phenomics data volume and dimensionality increase due to advancements in sensor technology, there is an urgent need to develop and implement scalable data processing pipelines. Current phenomics data processing pipelines lack modularity, extensibility, and processing distribution across sensor modalities and phenotyping platforms. To address these challenges, we developed PhytoOracle (PO), a suite of modular, scalable pipelines for processing large volumes of field phenomics RGB, thermal, PSII chlorophyll fluorescence 2D images, and 3D point clouds. PhytoOracle aims to ( i ) improve data processing efficiency; ( ii ) provide an extensible, reproducible computing framework; and ( iii ) enable data fusion of multi-modal phenomics data. PhytoOracle integrates open-source distributed computing frameworks for parallel processing on high-performance computing, cloud, and local computing environments. Each pipeline component is available as a standalone container, providing transferability, extensibility, and reproducibility. The PO pipeline extracts and associates individual plant traits across sensor modalities and collection time points, representing a unique multi-system approach to addressing the genotype-phenotype gap. To date, PO supports lettuce and sorghum phenotypic trait extraction, with a goal of widening the range of supported species in the future. At the maximum number of cores tested in this study (1,024 cores), PO processing times were: 235 minutes for 9,270 RGB images (140.7 GB), 235 minutes for 9,270 thermal images (5.4 GB), and 13 minutes for 39,678 PSII images (86.2 GB). These processing times represent end-to-end processing, from raw data to fully processed numerical phenotypic trait data. Repeatability values of 0.39-0.95 (bounding area), 0.81-0.95 (axis-aligned bounding volume), 0.79-0.94 (oriented bounding volume), 0.83-0.95 (plant height), and 0.81-0.95 (number of points) were observed in Field Scanalyzer data. We also show the ability of PO to process drone data with a repeatability of 0.55-0.95 (bounding area)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gonzalez, Zarei, Hendler, Simmons, Zarei, Demieville, Strand, Rozzi, Calleja, Ellingson, Cosi, Davey, Lavelle, Truco, Swetnam, Merchant, Michelmore, Lyons and Pauli.)
- Published
- 2023
- Full Text
- View/download PDF
16. Poster session Wednesday 11 December all day display: 11/12/2013, 09: 30–16: 00Location: Poster area
- Author
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Sanchez Millan, P J, Cabeza Lainez, P, Castillo Ortiz, J, Chueca Gonzalez, EM, Gheorghe, L, Fernandez Garcia, P, Herruzo Rojas, MS, Del Pozo Contreras, R, Fernandez Garcia, M, and Vazquez Garcia, R
- Published
- 2013
17. Pan-cancer analysis of whole genomes
- Author
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Campbell, P. J. a., Abpemail, Author, Getz, G. b., C, D, Eemail, Author, Korbel, J. O. f., Gemail, Author, Stuart, hEmail Author, J. M., Jennings, J. L. i., Stein, J, L. D. k., Lemail, Author, Perry, M. D. m., Nahal-Bose, N, Ouellette, H. K. n., B. F. F. o., P, C. H. k., Li, Rheinbay, Q, E. b., E, Nielsen, R, Sgroi, G. P. r., D. C. r., Wu, C. -L. r., Faquin, W. C. r., Deshpande, V. r., Boutros, P. C. k., Q, S, Lazar, T, Hoadley, A. J. u., K. A. v., W, Louis, D. N. r., Dursi, L. J. k., Yung, X, Bailey, C. K. n., M. H. y., Z, Saksena, G. b., Raine, Abp, K. M., Buchhalter, Aa, I., Ab, Ac, Kleinheinz, Aa, K., Schlesner, Ac, Aa, M., Zhang, Ad, Wang, J. n., Ae, W., Wheeler, D. A., Af, Ding, Ag, L. y., Z, Simpson, Ah, J. T. k., Ai, O’Connor, B. D. n., Yakneen, Aj, Ellrott, S. g., Ak, K., Miyoshi, Al, N., Butler, Abp, A. P., Royo, Am, R., Shorser, S. I. k., Vazquez, Am, M., Rausch, An, Tiao, T. g., Waszak, G. b., Rodriguez-Martin, S. M. g., Ao, B., Ap, Aq, Shringarpure, Ar, S., D. -Y., As, Demidov, G. M., At, Au, Av, Delaneau, Aw, O., Ax, Ay, Hayashi, Al, S., Imoto, Habermann, N. g., Segre, A. V. b., Garrison, Az, Abp, E., Cafferkey, A. f., Alvarez, E. G., Ao, Heredia-Genestar, J. M., Ba, Muyas, At, F., Drechsel, At, O., Bruzos, Av, A. L., Ao, Temes, Ao, J., Zamora, Ap, Abp, Baez-Ortega, Bb, A., Kim, H. -L., Bc, Mashl, R. J. z., Bd, Ye, Be, K., Dibiase, Bf, Bg, A., Huang, K. -L. z., Letunic, Bh, Bi, I., Mclellan, M. D. y., Z, Ah, Newhouse, S. J. f., Shmaya, As, T., Kumar, Bj, S., Wedge, Bk, D. C., Bl, Abp, Bm, Wright, M. H., Ar, Yellapantula, V. D., Bn, Gerstein, Bo, Bj, M., Bk, Bp, Khurana, Bq, E., Br, Bs, Marques-Bonet, Bt, Bu, T., Bv, Bw, Navarro, Bx, Bu, A., Bustamante, C. D., Ar, Siebert, By, Bz, R., Nakagawa, Ca, Cb, H., Easton, D. F., Cc, Ossowski, Cd, At, S., Tubio, J. M. C., Ao, De La Vega, F. M., Ar, As, By, Estivill, At, X., Yuen, Ce, Mihaiescu, D. k., Omberg, G. L. n., Cf, L., Ferretti, V. n., Sabarinathan, Cg, Ch, R., Ci, Cj, Pich, Ch, O., Gonzalez-Perez, Cj, Ch, A., Taylor-Weiner, Cj, Ck, A., Fittall, M. W., Cl, Demeulemeester, Cl, J., Tarabichi, Cm, Cl, M., Abp, Roberts, Abp, N. D., Van, Loo, Cl, P., Cortés-Ciriano, Cm, Cn, I., Co, Cp, Urban, L. f., Park, G, Co, P., Zhu, Cp, Cq, B., Pitkänen, E. g., Abp, Y., Saini, Cr, N., Klimczak, L. J., Cs, Weischenfeldt, J. g., Ct, Cu, Sidiropoulos, Cu, N., Alexandrov, L. B., Cv, Abp, Rabionet, At, R., Av, Cw, Escaramis, At, G., Cx, Cy, Bosio, At, Av, Holik, A. Z., At, Susak, At, H., Prasad, Av, Av, A., Erkek, S. g., Calabrese, C. f., Raeder, G, Harrington, B. g., Cz, E., Mayes, Da, S., Turner, Da, D., Juul, Cz, S., Roberts, S. A., Db, Song, Cq, L., Koster, Dc, R., Mirabello, Hua, Cq, X., Tanskanen, T. J., Dd, Tojo, Aq, M., Chen, Bk, J., Aaltonen, De, L. A., Df, Rätsch, Dg, G., Dh, Di, Dj, Dk, Schwarz, Dl, R. F. f., Dm, Dn, Do, Butte, A. J., Dp, Brazma, A. f., Chanock, S. J., Cq, Chatterjee, Dq, N., Stegle, Dr, O. f., G, Harismendy, Ds, Dt, O., Bova, G. S., Du, Gordenin, D. A., Cr, Haan, D. h., Sieverling, Dv, L., Feuerbach, Dw, Chalmers, Dx, D., Joly, Dy, Y., Knoppers, Dy, B., Molnár-Gábor, Dz, F., Phillips, Dy, M., Thorogood, Dy, A., Townend, Dy, D., Goldman, Ea, M., Fonseca, N. A. f., Xiang, Eb, Craft, Q. n., Ea, B., Piñeiro-Yáñez, Ec, E., Muñoz, A. f., Petryszak, R. f., Füllgrabe, A. f., Al-Shahrour, Ec, F., Keays, M. f., Haussler, Ea, D., Weinstein, Ed, Ee, J., Huber, Ef, Valencia, W. g., Am, A., Papatheodorou, Bw, Zhu, I. f., Ea, J., Fan, Ae, Y., Torrents, Am, D., Bieg, Bw, Eg, M., Chen, Eh, Ei, K., Chong, Ej, Z., Cibulskis, K. b., Eils, Aa, R., Ac, Ek, Fulton, El, R. S. y., Z, Gelpi, Ah, J. L., Am, Gonzalez, Em, S. f., G, Gut, I. G., Av, Hach, Bu, En, F., Heinold, Eo, Ac, Hu, Ep, T., Huang, V. k., Hutter, Eh, B., Eq, Er, Jäger, Aa, N., Jung, Es, J., Ep, Y., Lalansingh, C. k., Leshchiner, I. b., Livitz, D. b., E. Z., Ep, Maruvka, Y. E. b., R, Et, Milovanovic, Nielsen, M. M., Eu, Paramasivam, Pedersen, Eh, J. S., Eu, Puiggròs, Ev, Sahinalp, S. C., Eo, Ew, Ex, Sarrafi, Eo, I., Stewart, Ex, Stobbe, C. b., M. D., Av, Wala, Bu, J. A. b., E, Wang, Ey, J. z., Be, Wendl, Ez, M. z., Fa, Werner, Fb, Aa, J., Fc, Wu, Ep, Z., Xue, Ep, H., Yamaguchi, T. N. k., Bn, V., Davis-Dusenbery, Bo, B. N., Fd, Grossman, R. L., Fe, Ff, Y., Heinold, Fg, M. C., Aa, Hinton, Ac, Abp, J., Jones, Abp, D. R., Menzies, Abp, A., Stebbings, Abp, L., Hess, J. M. b., Rosenberg, Et, M. b., R, Dunford, A. J. b., Gupta, M. b., Imielinski, Fh, M., Meyerson, Fi, M. b., E, Beroukhim, Ey, R. b., E, Reimand, Fj, J. k., Q, Dhingra, Br, P., Favero, Bt, Fk, F., Dentro, Bl, S., Abp, Cl, Wintersinger, Fl, J., Fm, Fn, Rudneva, V. g., Park, J. W., Fo, Hong, E. P., Fo, Heo, S. G., Fo, Kahles, Dg, A., Lehmann, K. -V., Dg, Di, Dj, Fp, Fq, Soulette, C. M., Aj, Shiraishi, Al, Y., Liu, Fr, F., Fs, He, Fr, Y., Demircioğlu, Ft, D., Davidson, Fu, N. R., Dg, Dl, Fp, Greger, L. f., Fv, S., Liu, Fw, Fv, D., Stark, Fw, S. G., Dj, Fp, Fx, Zhang, Fy, Amin, S. B., Fz, Ga, Gb, Bailey, Gc, P., Chateigner, A. n., Frenkel-Morgenstern, Gd, M., Hou, Fv, Y., Huska, Fw, M. R., Dm, Kilpinen, Ge, H., Lamaze, F. C. k., Fv, C., Fw, Li, Fv, X., Marin, Fw, M. G., Aj, Markowski, Dm, J., Nandi, Gf, T., Ojesina, A. I., Gg, Gh, Gi, Pan-Hammarström, Fv, Q., Park, Gj, P. J., Co, Pedamallu, Cp, C. S. b., E, Fj, Su, Fv, H., Tan, Fw, Gf, P., Gk, Gl, Teh, Gm, B. T., Gk, Gl, Gm, Gn, Go, Wang, Fv, J., Xiong, Fw, Ye, Yung, Fw, Zhang, C. n., Zheng, Fr, L., Zhu, Awadalla, Fw, P. k., L, Creighton, C. J., Gp, Fv, K., Yang, Fw, Göke, Ft, J., Zhang, Gq, Fr, Z., Brooks, Gr, A. N. b., Aj, Fittall, Ey, Martincorena, Abp, I., Rubio-Perez, Ch, C., Cj, Gs, Eu, M., Schumacher, S. b., Shapira, Gt, O. b., Ey, Tamborero, Ch, D., Mularoni, Cj, Ch, L., Hornshøj, Cj, Eu, H., Deu-Pons, Cj, J., Muiños, Gu, Ch, F., Bertl, Cj, Eu, J., Guo, Gv, Ev, Q., Gonzalez-Perez, Cj, Gw, Xiang, Gx, Q., Bazant, W. f., Barrera, E. f., Al-Sedairy, S. T., Gy, Aretz, Gz, A., Bell, Ha, C., Betancourt, Hb, M., Buchholz, Hc, C., Calvo, Hd, F., Chomienne, He, C., Dunn, Hf, M., Edmonds, Hg, S., Green, Hh, E., Gupta, Hi, S., C. M., Hh, Jegalian, Hj, K., Hk, N., Hl, Y., Hm, Hn, Nakagama, Ho, H., Nettekoven, Hp, G., Planko, Hp, L., Scott, Hk, D., Shibata, Hq, T., Shimizu, Hr, Hs, K., Stratton, Abp, M. R., Yugawa, Hs, T., Tortora, Ht, G., Vijayraghavan, Hu, Hi, K., Zenklusen, J. C., Hv, Hw, D., B. M., Dy, Aminou, B. n., Bartolome, Am, J., Boroevich, K. A., Cb, Boyce, Hx, Buchanan, R. f., Ak, A., Byrne, N. J. n., Hy, Z., Cho, Hz, S., Choi, Ia, W., Clapham, Abp, P., Dow, M. T., Hy, Eils, X, Ek, J., Farcas, El, Hy, C., Fayzullaev, N. n., Flicek, P. f., Heath, A. P., Ib, Hofmann, Ic, O., J. H., Id, Hudson, T. J., Ie, Hübschmann, If, Ac, D., Do, Ek, Ig, Ih, Ivkovic, Ii, S., Jeon, S. -H., Ia, Jiao, W. k., Kabbe, Dj, Fq, Kerssemakers, J. N. A., Aa, Ia, H., Ij, J., Koscher, Ik, M., Koures, Hy, A., Kovacevic, Ii, M., Lawerenz, El, C., Il, J., Mijalkovic, Mijalkovic-Lazic, A. M., Ii, Miyano, Nastic, Nicholson, Ocana, D. f., Ohi, Al, K., Ohno-Machado, Hy, L., Pihl, T. D., Im, Prinz, Radovic, Ii, P., Short, C. f., Sofia, H. J., Hh, Spring, Fe, J., Struck, A. J., Ak, Tijanic, Ii, N., Vicente, Hv, Z., Williams, Woo, Ia, Y., Wright, A. J. k., Yang, Hv, L., Hamilton, M. P., In, Johnson, T. A., Hx, Kahraman, Io, A., Ip, Iq, Kellis, M. b., Polak, Ir, P. b., C, Sallari, E, Sinnott-Armstrong, R. b., N. b., Ar, Von, Mering, Iq, C., Beltran, Is, Av, S., Gerhard, Bu, D. S., It, Av, M., Trotta, Bu, J. -R., Bu, Whalley, J. P., Bu, Niu, Iu, B., Espiritu, S. M. G. k., Gao, Ez, Y., Lalansingh, Iv, Teague, C. M. k., Abp, J. W., Wendl, M. C. z., Fa, Fb, Abascal, Abp, F., Bader, G. D. l., Bandopadhayay, P. b., Iw, Ix, Barenboim, J. k., Brunak, Iy, S., Carlevaro-Fita, Iz, Ja, J., Jb, Jc, Chakravarty, Jd, D., Chan, Je, C. W. Y., Aa, Choi, Dw, J. K., Jf, Diamanti, Jg, K., Fink, Frigola, Jh, Gu, J., Gambacorti-Passerini, Ji, C., Garsed, D. W., Jj, Haradhvala, N. J. b., Harmanci, R, A. O., Bk, Helmy, Jk, Fm, M., Herrmann, Aa, C., Ac, Jl, Hobolth, Ev, A., Hodzic, Gv, Ex, E., Dv, C., Isaev, Dw, K. k., Q, Izarzugaza, J. M. G., Iy, Jb, R., Juul, Jm, R. I., Eu, Kim, J. b., J. K., Jn, Jan, Komorowskijg, Lanzós, Jo, Jb, A., Jc, Jm, Larsson, Dg, E., Lee, Bk, D., Bk, S., Bk, X., Lin, Z. b., Liu, Jp, E. M., Br, Bt, Jq, Lochovsky, Bj, L., Bk, Gb, Lou, Madsen, Bk, Eu, T., Marchal, Jr, K., Martinez-Fundichely, Js, Br, A., Bs, Bt, Mcgillivray, P. D., Bj, Meyerson, Bk, W., Paczkowska, Jt, Park, M. k., Ju, K., Park, Jv, Jw, K., Pons, Jx, T., Pulido-Tamayo, Jr, S., Reyes-Salazar, Js, Ch, I., Reyna, M. A., Jy, Rubin, M. A., Jm, Jz, Ka, Kb, Kc, Salichos, Sander, Bk, Dg, C., Ey, Kd, Schumacher, Ke, S. E. b., Gt, Shackleton, Jj, M., Shen, Ke, C., Shrestha, Kf, Eo, R., Shuai, S. k., Tsunoda, L, Hx, T., Kg, Kh, Umer, Ki, H. M., Jg, Uusküla-Reimand, Kj, Kk, L., Verbeke, Kl, L. P. C., Js, Wadelius, Km, Kn, C., Wadi, L. k., Warrell, Bj, J., Bk, Wu, Ko, G., Kp, J., Zhang, Ez, X., Zhang, Kq, Bk, Y., Kr, Ks, Zhao, Kt, Z., Zou, Ku, L., Lawrence, M. S. b., R, Hx, Raphael, B. J., Jy, P. J., Gc, Craft, D. b., Goldman, Kv, M. J., Ea, Aburatani, Kw, H., Binder, Kx, H., Dinh, Ky, H. Q., Kz, S. C., Av, Hoffmann, Bu, Kx, S., Ky, La, Imbusch, Lb, C. D., Dv, Kretzmer, Ky, H., Laird, Lb, P. W., Lc, Martin-Subero, J. I., Bw, Nagae, Ld, Kw, G., Shen, Le, Lf, H., Ik, Q., Weichenhan, Lg, D., Zhou, Lf, W., Berman, B. P., Kz, Lh, Li, Brors, Dv, B., Er, Lj, Plass, Lg, C., Akdemir, K. C., Ei, Bowtell, D. D. L., Jj, Burns, K. H., Lk, Busanovich, Ll, J. b., Lm, Chan, Ln, K., Dueso-Barroso, Edwards, P. A., Lo, Etemadmoghadam, Lp, Jj, D., Haber, J. E., Lq, D. T. W., Lr, Ls, Ju, Y. S., Jf, Abp, Kazanov, M. D., Lt, Lu, Lv, Koh, Lw, Y., Kumar, Lx, Lee, K. b., E. A., Ly, J. J. -K., Co, Lynch, Cp, A. G., Lo, Lp, Lz, Macintyre, Lo, G., Markowetz, Lo, F., Navarro, Lp, F. C. P., Bj, Pearson, J. V., Ma, Rippe, Mb, Do, K., Scully, Mc, R., Villasante, Am, I., Waddell, Ma, N., Yang, Mb, Md, L., Yao, Fh, X., Yoon, Me, S. -S., Lx, C. -Z. b., E, Ey, Bergstrom, E. N., Mf, Boot, Gl, A., Covington, Mg, Ag, K., Fujimoto, Cb, A., M. N., Gl, Islam, Mg, S. M. A., Cv, Mcpherson, J. R., Gl, Morganella, Mg, Abp, S., Mustonen, Mh, V., Mi, Mj, A. W. T., Mk, Prokopec, S. D. k., Vázquez-García, Bn, I., Ml, Mm, Abp, Wu, Gl, Y., Yousif, Mg, F. k., Yu, Mn, W., Rozen, S. G., Gl, Gm, Mg, Rudneva, V. A. g., S. S., Ar, D. 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F., Jh, Thorne, Ok, H., Traficante, Ok, N., Vedururu, Ok, R., N. M., Mb, Waring, P. M., Os, Wood, Ma, S., Mb, Xu, Ma, Q., Defazio, Mb, Ot, A., Ou, Ov, Anderson, M. J., Jh, Antonello, Ow, D., Barbour, A. P., Ox, Bassi, Oy, Ow, C., Bersani, Oz, S., Cataldo, Oz, I., Chantrill, Pa, L. A., Mp, Chiew, Pb, Y. -E., Ot, Chou, Mp, A., Cingarlini, Pc, Ht, S., Cloonan, Pd, N., Corbo, Pa, V., Davi, Pe, M. V., Pf, Duthie, F. R., Gc, Gill, Pg, A. J., Mp, Graham, Pc, J. S., Gc, Harliwong, Ph, Jh, I., Jamieson, N. B., Gc, Nb, Pi, Johns, A. L., Mp, Kench, Or, J. G., Mp, Pc, Pj, Landoni, Ow, L., Lawlor, R. T., Pa, Mafficini, Pa, A., Merrett, N. D., Ow, Miotto, Pk, Ow, M., Musgrove, E. A., Gc, Nagrial, A. M., Mp, Oien, K. A., Os, Pajic, Pl, Mp, M., Pinese, Pm, M., Robertson, A. J., Jh, Rooman, Mp, I., Rusev, B. C., Pa, Samra, J. S., Ow, Scardoni, Pc, Oz, M., Scarlett, C. J., Mp, Scarpa, Pn, Sereni, Ow, E., Sikora, K. O., Pa, Simbolo, Pe, M., Taschuk, M. L. n., Toon, C. 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H., Qh, Kalimuthu, S. -B., Qn, Lungu, Qh, I., Luo, Qo, Mbabaali, X. k., If, F., T. A., Qk, J. K., If, Moore, M. J., Ql, Notta, Qh, F., Pasternack, Qp, If, D., Petersen, G. M., Qq, Roehrl, M. H. A. q., Qh, Qr, Qs, Qt, Sam, If, M., Selander, Qk, I., Serra, Os, S., Shahabi, Qn, S., Thayer, S. P., Qm, Timms, L. E., If, Wilson, G. W. k., Wilson, Qh, J. M., Qh, Wouters, B. G., Qu, J. D., If, Qh, Qv, Beck, T. A. n., Bhandari, Qw, Collins, V. k., C. C., Eo, Fleshner, N. E., Qx, Fox, N. S. k., Fraser, M. k., Heisler, L. E., Qy, Lalonde, E. k., Livingstone, J. k., Meng, Qz, A., Sabelnykova, V. Y. k., Shiah, Y. -J. k., Van der Kwast, Ra, T., Bristow, R. G. q., Rb, Rc, Rd, Re, Ding, Rf, S., Rg, D., Fv, L., Nie, Rg, Y., Xiao, Rh, Xing, Hm, R., Yang, Ri, Rj, Y., Banks, R. 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B., Morrison, Aag, Mose, Moser, L. E. w., C. D., Zg, Mungall, A. J., Yc, Yc, K., Mutch, Aah, D., Muzny, Aai, D. M., Myers, Aaj, J., Newton, Aj, Y., Noble, M. S. b., O’Donnell, Aak, P., Aal, B. P., Ochoa, Aam, J. -W., Parker, Aan, J. S., Pass, Aao, H., Pastore, Pennell, Aap, N. A., Perou, Aaq, C. M., Petrelli, Aar, N., Potapova, Aas, O., Rader, Aat, J. S., Ramalingam, Aau, S., Rathmell, Aav, W. K., Reuter, Sm, V., Reynolds, S. M., Zz, Ringel, Aaw, M., Roach, Aax, J., L. R., Zg, A. G., Yc, Sadeghi, Yc, S., Saller, Aay, C., Sanchez-Vega, Wt, F., Schadendorf, Yd, Eq, D., Aaz, Schein, J. E., Yc, Schmidt, H. K. z., Schultz, Yd, N., Seethala, Aba, R., Senbabaoglu, Dg, Y., Shelton, Yw, T., Shi, Y. w., Shih, J. b., Shmulevich, Fj, Zz, I., Shriver, Abb, C., Signoretti, Fj, S., Abc, Jb, Simons, J. V. w., Singer, Abd, Sipahimalani, Yc, P., Skelly, T. J. v., Smith-McCune, Socci, N. D., Dg, Soloway, Aan, M. G., Sood, Abe, A. K., Tam, Tan, D. v., Tarnuzzer, Hv, R., Thiessen, Abf, R. H., L. B., Xg, Tsao, Xe, M., Umbricht, Ye, Lk, C., Abg, Wv, Van Den Berg, D. J., Ym, Van, Meir, Abh, E. G., Veluvolu, U. v., Voet, D. b., Weinberger, Abi, P., Weisenberger, Wigle, Abj, D., Wilkerson, M. D. v., Wilson, R. K. z., Abk, Winterhoff, Abl, B., Wiznerowicz, Abm, M., Abn, Wong, T. z., Yc, Abo, W., Yau, Zhang, H. b., Yd, H., Hv, J., The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium View Correspondence (jump link), Medical Oncology, Pathology, IBM, Pharmacyclics, Novartis, Celgene, AstraZeneca, Bayer, Janssen Biotech, University of Chicago, Ipsen, Pfizer, Ono Pharmaceutical, Ariad Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Metamedica, Háskóli Íslands, University of Iceland, Faculty of Medicine, University of Helsinki, Department of Medical and Clinical Genetics, Research Programs Unit, Lauri Antti Aaltonen / Principal Investigator, ATG - Applied Tumor Genomics, Helsinki Institute of Life Science HiLIFE, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, STEMM - Stem Cells and Metabolism Research Program, Centre of Excellence in Stem Cell Metabolism, Genome-Scale Biology (GSB) Research Program, Department of Physics, HUS Helsinki and Uusimaa Hospital District, University of Zurich, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Apollo - University of Cambridge Repository, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Endocrinology, metabolism and nutrition, 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Lochovsky, L, Lou, S, Madsen, T, Marchal, K, Martinez-Fundichely, A, Mcgillivray, P, Meyerson, W, Paczkowska, M, Park, K, Pons, T, Pulido-Tamayo, S, Reyes-Salazar, I, Reyna, M, Rubin, M, Salichos, L, Sander, C, Shackleton, M, Shen, C, Shrestha, R, Shuai, S, Tsunoda, T, Umer, H, Uuskula-Reimand, L, Verbeke, L, Wadelius, C, Wadi, L, Warrell, J, Wu, G, Yu, J, Zhang, Y, Zhao, Z, Zou, L, Lawrence, M, Raphael, B, Craft, D, Aburatani, H, Binder, H, Dinh, H, Heath, S, Hoffmann, S, Imbusch, C, Kretzmer, H, Laird, P, Martin-Subero, J, Nagae, G, Shen, H, Wang, Q, Weichenhan, D, Zhou, W, Berman, B, Brors, B, Plass, C, Akdemir, K, Bowtell, D, Burns, K, Busanovich, J, Chan, K, Dueso-Barroso, A, Edwards, P, Etemadmoghadam, D, Haber, J, Ju, Y, Kazanov, M, Koh, Y, Kumar, K, Lee, E, Lee, J, Lynch, A, Macintyre, G, Markowetz, F, Navarro, F, Pearson, J, Rippe, K, Scully, R, Villasante, I, Waddell, N, Yao, X, Yoon, S, Zhang, C, Bergstrom, E, Boot, A, Covington, K, Fujimoto, A, Huang, M, Islam, S, Mcpherson, J, Morganella, S, Mustonen, V, Ng, A, Prokopec, S, Vazquez-Garcia, I, Wu, Y, Yousif, F, Yu, W, Rozen, S, Xia, T, Atwal, G, Chang, D, Cooke, S, Faltas, B, Haider, S, Kaiser, V, Karlic, R, Kato, M, Kubler, K, Margolin, A, Martin, S, Nik-Zainal, S, P'Ng, C, Semple, C, Smith, J, Sun, R, Thai, K, Wright, D, Yuan, K, Biankin, A, Garraway, L, Grimmond, S, Adams, D, Anur, P, Cao, S, Christie, E, Cmero, M, Cun, Y, Dawson, K, Deshwar, A, Donmez, N, Drews, R, Gerstung, M, Ha, G, Haase, K, Jerman, L, Ji, Y, Jolly, C, Lee-Six, H, Malikic, S, Mitchell, T, Morris, Q, Oesper, L, Peifer, M, Peto, M, Rosebrock, D, Rubanova, Y, Salcedo, A, Sengupta, S, Shi, R, Shin, S, Spiro, O, Vembu, S, Yang, T, Yu, K, Zhu, H, Spellman, P, Chen, Y, Fujita, M, Han, L, Hasegawa, T, Komura, M, Li, J, Mizuno, S, Shimizu, E, Wang, Y, Xu, Y, Yamaguchi, R, Yang, F, Yang, Y, Yoon, C, Yuan, Y, Liang, H, Alawi, M, Borozan, I, Brewer, D, Cooper, C, Desai, N, Grundhoff, A, Iskar, M, Su, X, Zapatka, M, Lichter, P, Alsop, K, Bruxner, T, Christ, A, Cordner, S, Cowin, P, Drapkin, R, Fereday, S, George, J, Hamilton, A, Holmes, O, Hung, J, Kassahn, K, Kazakoff, S, Kennedy, C, Leonard, C, Mileshkin, L, Miller, D, Arnau, G, Mitchell, C, Newell, F, Nones, K, Patch, A, Quinn, M, Taylor, D, Thorne, H, Traficante, N, Vedururu, R, Waring, P, Wood, S, Xu, Q, Defazio, A, Anderson, M, Antonello, D, Barbour, A, Bassi, C, Bersani, S, Cataldo, I, Chantrill, L, Chiew, Y, Chou, A, Cingarlini, S, Cloonan, N, Corbo, V, Davi, M, Duthie, F, Gill, A, Graham, J, Harliwong, I, Jamieson, N, Johns, A, Kench, J, Landoni, L, Lawlor, R, Mafficini, A, Merrett, N, Miotto, M, Musgrove, E, Nagrial, A, Oien, K, Pajic, M, Pinese, M, Robertson, A, Rooman, I, Rusev, B, Samra, J, Scardoni, M, Scarlett, C, Scarpa, A, Sereni, E, Sikora, K, Simbolo, M, Taschuk, M, Toon, C, Vicentini, C, Wu, J, Zeps, N, Behren, A, Burke, H, Cebon, J, Dagg, R, De Paoli-Iseppi, R, Dutton-Regester, K, Field, M, Fitzgerald, A, Hersey, P, Jakrot, V, Johansson, P, Kakavand, H, Kefford, R, Lau, L, Long, G, Pickett, H, Pritchard, A, Pupo, G, Saw, R, Schramm, S, Shang, C, Shang, P, Spillane, A, Stretch, J, Tembe, V, Thompson, J, Vilain, R, Wilmott, J, Yang, J, Hayward, N, Mann, G, Scolyer, R, Bartlett, J, Bavi, P, Chadwick, D, Chan-Seng-Yue, M, Cleary, S, Connor, A, Czajka, K, Denroche, R, Dhani, N, Eagles, J, Gallinger, S, Grant, R, Hedley, D, Hollingsworth, M, Jang, G, Johns, J, Kalimuthu, S, Liang, S, Lungu, I, Luo, X, Mbabaali, F, Mcpherson, T, Miller, J, Moore, M, Notta, F, Pasternack, D, Petersen, G, Roehrl, M, Sam, M, Selander, I, Serra, S, Shahabi, S, Thayer, S, Timms, L, Wilson, G, Wilson, J, Wouters, B, Beck, T, Bhandari, V, Collins, C, Fleshner, N, Fox, N, Fraser, M, Heisler, L, Lalonde, E, Livingstone, J, Meng, A, Sabelnykova, V, Shiah, Y, Van der Kwast, T, Bristow, R, Ding, S, Fan, D, Li, L, Nie, Y, Xiao, X, Xing, R, Yang, S, Yu, Y, Zhou, Y, Banks, R, Bourque, G, Brennan, P, Letourneau, L, Riazalhosseini, Y, Scelo, G, Vasudev, N, Viksna, J, Lathrop, M, Tost, J, Ahn, S, Aparicio, S, Arnould, L, Aure, M, Bhosle, S, Birney, E, Borg, A, Boyault, S, Brinkman, A, Brock, J, Broeks, A, Borresen-Dale, A, Caldas, C, Chin, S, Davies, H, Desmedt, C, Dirix, L, Dronov, S, Ehinger, A, Eyfjord, J, Fatima, A, Foekens, J, Futreal, P, Garred, O, Giri, D, Glodzik, D, Grabau, D, Hilmarsdottir, H, Hooijer, G, Jacquemier, J, Jang, S, Jonasson, J, Jonkers, J, King, T, Knappskog, S, Kong, G, Krishnamurthy, S, Lakhani, S, Langerod, A, Larsimont, D, Lee, H, Lee, M, Lingjaerde, O, Macgrogan, G, Martens, J, O'Meara, S, Pauporte, I, Pinder, S, Pivot, X, Provenzano, E, Purdie, C, Ramakrishna, M, Ramakrishnan, K, Reis-Filho, J, Richardson, A, Ringner, M, Rodriguez, J, Rodriguez-Gonzalez, F, Romieu, G, Salgado, R, Sauer, T, Shepherd, R, Sieuwerts, A, Simpson, P, Smid, M, Sotiriou, C, Span, P, Stefansson, O, Stenhouse, A, Stunnenberg, H, Sweep, F, Tan, B, Thomas, G, Thompson, A, Tommasi, S, Treilleux, I, Tutt, A, Ueno, N, Van Laere, S, Van den Eynden, G, Vermeulen, P, Viari, A, Vincent-Salomon, A, Wong, B, Yates, L, Zou, X, van Deurzen, C, van de Vijver, M, van't Veer, L, Ammerpohl, O, Aukema, S, Bergmann, A, Bernhart, S, Borkhardt, A, Borst, C, Burkhardt, B, Claviez, A, Goebler, M, Haake, A, Haas, S, Hansmann, M, Hoell, J, Hummel, M, Karsch, D, Klapper, W, Kneba, M, Kreuz, M, Kube, D, Kuppers, R, Lenze, D, Loeffler, M, Lopez, C, Mantovani-Loffler, L, Moller, P, Ott, G, Radlwimmer, B, Richter, J, Rohde, M, Rosenstiel, P, Rosenwald, A, Schilhabel, M, Schreiber, S, Stadler, P, Staib, P, Stilgenbauer, S, Sungalee, S, Szczepanowski, M, Toprak, U, Trumper, L, Wagener, R, Zenz, T, Hovestadt, V, von Kalle, C, Kool, M, Korshunov, A, Landgraf, P, Lehrach, H, Northcott, P, Pfister, S, Reifenberger, G, Warnatz, H, Wolf, S, Yaspo, M, Assenov, Y, Gerhauser, C, Minner, S, Schlomm, T, Simon, R, Sauter, G, Sultmann, H, Biswas, N, Maitra, A, Majumder, P, Sarin, R, Barbi, S, Bonizzato, G, Cantu, C, Dei Tos, A, Fassan, M, Grimaldi, S, Luchini, C, Malleo, G, Marchegiani, G, Milella, M, Paiella, S, Pea, A, Pederzoli, P, Ruzzenente, A, Salvia, R, Sperandio, N, Arai, Y, Hama, N, Hiraoka, N, Hosoda, F, Nakamura, H, Ojima, H, Okusaka, T, Totoki, Y, Urushidate, T, Fukayama, M, Ishikawa, S, Katai, H, Katoh, H, Komura, D, Rokutan, H, Saito-Adachi, M, Suzuki, A, Taniguchi, H, Tatsuno, K, Ushiku, T, Yachida, S, Yamamoto, S, Aikata, H, Arihiro, K, Ariizumi, S, Chayama, K, Furuta, M, Gotoh, K, Hayami, S, Hirano, S, Kawakami, Y, Maejima, K, Nakamura, T, Nakano, K, Ohdan, H, Sasaki-Oku, A, Tanaka, H, Ueno, M, Yamamoto, M, Yamaue, H, Choo, S, Cutcutache, I, Khuntikeo, N, Ong, C, Pairojkul, C, Popescu, I, Ahn, K, Aymerich, M, Lopez-Guillermo, A, Lopez-Otin, C, Puente, X, Campo, E, Amary, F, Baumhoer, D, Behjati, S, Bjerkehagen, B, Myklebost, O, Pillay, N, Tarpey, P, Tirabosco, R, Zaikova, O, Flanagan, A, Boultwood, J, Bowen, D, Cazzola, M, Green, A, Hellstrom-Lindberg, E, Malcovati, L, Nangalia, J, Papaemmanuil, E, Vyas, P, Ang, Y, Barr, H, Beardsmore, D, Eldridge, M, Gossage, J, Grehan, N, Hanna, G, Hayes, S, Hupp, T, Khoo, D, Lagergren, J, Lovat, L, Macrae, S, O'Donovan, M, O'Neill, J, Parsons, S, Preston, S, Puig, S, Roques, T, Sanders, G, Sothi, S, Tavare, S, Tucker, O, Turkington, R, Underwood, T, Welch, I, Fitzgerald, R, Berney, D, De Bono, J, Cahill, D, Camacho, N, Dennis, N, Dudderidge, T, Edwards, S, Fisher, C, Foster, C, Ghori, M, Gill, P, Gnanapragasam, V, Gundem, G, Hamdy, F, Hawkins, S, Hazell, S, Howat, W, Isaacs, W, Karaszi, K, Kay, J, Khoo, V, Kote-Jarai, Z, Kremeyer, B, Kumar, P, Lambert, A, Leongamornlert, D, Livni, N, Luxton, H, Marsden, L, Massie, C, Matthews, L, Mayer, E, Mcdermott, U, Merson, S, Neal, D, Nicol, D, Ogden, C, Rowe, E, Shah, N, Thomas, S, Verrill, C, Visakorpi, T, Warren, A, Whitaker, H, Zhang, H, van As, N, Eeles, R, Abeshouse, A, Agrawal, N, Akbani, R, Al-Ahmadie, H, Albert, M, Aldape, K, Ally, A, Appelbaum, E, Armenia, J, Asa, S, Auman, J, Balasundaram, M, Balu, S, Barnholtz-Sloan, J, Bathe, O, Baylin, S, Benz, C, Berchuck, A, Berrios, M, Bigner, D, Birrer, M, Bodenheimer, T, Boice, L, Bootwalla, M, Bosenberg, M, Bowlby, R, Boyd, J, Broaddus, R, Brock, M, Brooks, D, Bullman, S, Caesar-Johnson, S, Carey, T, Carlsen, R, Cerfolio, R, Chandan, V, Chen, H, Cherniack, A, Chien, J, Cho, J, Chuah, E, Cibulskis, C, Cope, L, Cordes, M, Curley, E, Czerniak, B, Danilova, L, Davis, I, Defreitas, T, Demchok, J, Dhalla, N, Dhir, R, Doddapaneni, H, El-Naggar, A, Felau, I, Ferguson, M, Finocchiaro, G, Fong, K, Frazer, S, Friedman, W, Fronick, C, Fulton, L, Gabriel, S, Gao, J, Gehlenborg, N, Gershenwald, J, Ghossein, R, Giama, N, Gibbs, R, Gomez, C, Govindan, R, Hayes, D, Hegde, A, Heiman, D, Heins, Z, Hepperla, A, Holbrook, A, Holt, R, Hoyle, A, Hruban, R, Hu, J, Huntsman, D, Huse, J, Iacobuzio-Donahue, C, Ittmann, M, Jayaseelan, J, Jefferys, S, Jones, C, Jones, S, Juhl, H, Kang, K, Karlan, B, Kasaian, K, Kebebew, E, Korchina, V, Kundra, R, Lai, P, Lander, E, Le, X, Levine, D, Lewis, L, Ley, T, Li, H, Lin, P, Linehan, W, Lype, L, Ma, Y, Maglinte, D, Mardis, E, Marks, J, Marra, M, Matthew, T, Mayo, M, Mccune, K, Meier, S, Meng, S, Mieczkowski, P, Mikkelsen, T, Miller, C, Mills, G, Moore, R, Morrison, C, Mose, L, Moser, C, Mungall, A, Mungall, K, Mutch, D, Muzny, D, Myers, J, Newton, Y, Noble, M, O'Donnell, P, O'Neill, B, Ochoa, A, Parker, J, Pass, H, Pastore, A, Pennell, N, Perou, C, Petrelli, N, Potapova, O, Rader, J, Ramalingam, S, Rathmell, W, Reuter, V, Reynolds, S, Ringel, M, Roach, J, Roberts, L, Sadeghi, S, Saller, C, Sanchez-Vega, F, Schadendorf, D, Schein, J, Schmidt, H, Schultz, N, Seethala, R, Senbabaoglu, Y, Shelton, T, Shi, Y, Shih, J, Shmulevich, I, Shriver, C, Signoretti, S, Simons, J, Singer, S, Sipahimalani, P, Skelly, T, Smith-McCune, K, Socci, N, Soloway, M, Sood, A, Tam, A, Tan, D, Tarnuzzer, R, Thiessen, N, Thompson, R, Thorne, L, Tsao, M, Umbricht, C, Van Den Berg, D, Van Meir, E, Veluvolu, U, Voet, D, Wang, L, Weinberger, P, Weisenberger, D, Wigle, D, Wilkerson, M, Wilson, R, Winterhoff, B, Wiznerowicz, M, Wong, T, Wong, W, Xi, L, Yau, C, Consortium, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes, Demeulemeester, Jonas, Desmedt, Christine, Van Loo, Peter, Barcelona Supercomputing Center, Imperial College Healthcare NHS Trust- BRC Funding, Cancer Research UK, Basic (bio-) Medical Sciences, and Laboratory for Medical and Molecular Oncology
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Male ,tert promoter mutations ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,DNA Mutational Analysis ,Normal tissue ,systematic analysis ,Germline ,Transcriptome ,0302 clinical medicine ,Aetiology ,Càncer ,Cellular Senescence ,Cancer ,0303 health sciences ,dna-damage ,Massive parallel sequencing ,Pan cancer ,REARRANGEMENTS ,High-Throughput Nucleotide Sequencing ,Genomics ,Sciences bio-médicales et agricoles ,Telomere ,COMPREHENSIVE ,3. Good health ,TERT PROMOTER MUTATIONS ,signatures ,030220 oncology & carcinogenesis ,Science & Technology - Other Topics ,Erfðarannsóknir ,Human ,Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC] ,Evolution ,RNA Splicing ,Article ,Evolution, Molecular ,Structural variation ,RC0254 ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Genetic ,genomics ,SYSTEMATIC ANALYSIS ,Genetics ,Genomics--Databases ,Humans ,Genetic Testing ,Molecular Biology ,SIGNATURES ,Whole genome sequencing ,1000 Multidisciplinary ,Chromothripsis ,Science & Technology ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,Information Dissemination ,ResearchInstitutes_Networks_Beacons/mcrc ,Prevention ,Biology and Life Sciences ,Molecular ,Oncogenes ,Cloud Computing ,medicine.disease ,Genòmica ,Compute clouds ,Mutation ,570 Life sciences ,biology ,COMPREHENSIVE CHARACTERIZATION ,Genètica ,Whole Genome Sequencing--methods ,Background information ,Genetic / genetics ,Genome ,Germ-Line Mutation / genetics ,Human / genetics ,ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium ,Medizin ,Whole-genome ,Genome mapping ,Neoplasms ,2.1 Biological and endogenous factors ,Promoter Regions, Genetic ,Càncer -- Aspectes genètics ,Telomerase ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Multidisciplinary ,Manchester Cancer Research Centre ,genomics, cancer, profiling ,3rd-DAS ,10124 Institute of Molecular Life Sciences ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Multidisciplinary Sciences ,Parallel sequencing ,Female ,profiling ,Medical Genetics ,Engineering sciences. Technology ,Biotechnology ,General Science & Technology ,The Cancer Genome Atlas ,610 Medicine & health ,Computational biology ,QH426 Genetics ,Biology ,Consortium of the International Cancer Genome Consortium ,Promoter Regions ,Germline mutation ,Pan-cancer analysis ,Krabbameinsrannsóknir ,medicine ,cancer ,ddc:610 ,QH426 ,Germ-Line Mutation ,Medicinsk genetik ,Krabbamein ,030304 developmental biology ,Cell Proliferation ,LANDSCAPE ,Genome, Human ,comprehensive characterization ,Pan-cancer analysis of whole genomes ,Point mutation ,Human Genome ,Reproducibility of Results ,SOMATIC MUTATIONS ,EVOLUTION ,Cancer, sequencing, Chromothripsis, telomere ,DNA-DAMAGE ,Mutagenesis ,PATTERNS ,3111 Biomedicine ,CHARACTERIZATION - Abstract
Publisher's version (útgefin grein), Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18., Competing interests Gad Getz receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig and POLYSOLVER. Hikmat Al-Ahmadie is consultant for AstraZeneca and Bristol-Myers Squibb. Samuel Aparicio is a founder and shareholder of Contextual Genomics. Pratiti Bandopadhayay receives grant funding from Novartis for an unrelated project. Rameen Beroukhim owns equity in Ampressa Therapeutics. Andrew Biankin receives grant funding from Celgene, AstraZeneca and is a consultant for or on advisory boards of AstraZeneca, Celgene, Elstar Therapeutics, Clovis Oncology and Roche. Ewan Birney is a consultant for Oxford Nanopore, Dovetail and GSK. Marcus Bosenberg is a consultant for Eli Lilly. Atul Butte is a cofounder of and consultant for Personalis, NuMedii, a consultant for Samsung, Geisinger Health, Mango Tree Corporation, Regenstrief Institute and in the recent past a consultant for 10x Genomics and Helix, a shareholder in Personalis, a minor shareholder in Apple, Twitter, Facebook, Google, Microsoft, Sarepta, 10x Genomics, Amazon, Biogen, CVS, Illumina, Snap and Sutro and has received honoraria and travel reimbursement for invited talks from Genentech, Roche, Pfizer, Optum, AbbVie and many academic institutions and health systems. Carlos Caldas has served on the Scientific Advisory Board of Illumina. Lorraine Chantrill acted on an advisory board for AMGEN Australia in the past 2 years. Andrew D. Cherniack receives research funding from Bayer. Helen Davies is an inventor on a number of patent applications that encompass the use of mutational signatures. Francisco De La Vega was employed at Annai Systems during part of the project. Ronny Drapkin serves on the scientific advisory board of Repare Therapeutics and Siamab Therapeutics. Rosalind Eeles has received an honorarium for the GU-ASCO meeting in San Francisco in January 2016 as a speaker, a honorarium and support from Janssen for the RMH FR meeting in November 2017 as a speaker (title: genetics and prostate cancer), a honorarium for an University of Chicago invited talk in May 2018 as speaker and an educational honorarium paid by Bayer & Ipsen to attend GU Connect ‘Treatment sequencing for mCRPC patients within the changing landscape of mHSPC’ at a venue at ESMO, Barcelona, on 28 September 2019. Paul Flicek is a member of the scientific advisory boards of Fabric Genomics and Eagle Genomics. Ronald Ghossein is a consultant for Veracyte. Dominik Glodzik is an inventor on a number of patent applications that encompass the use of mutational signatures. Eoghan Harrington is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Yann Joly is responsible for the Data Access Compliance Office (DACO) of ICGC 2009-2018. Sissel Juul is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Vincent Khoo has received personal fees and non-financial support from Accuray, Astellas, Bayer, Boston Scientific and Janssen. Stian Knappskog is a coprincipal investigator on a clinical trial that receives research funding from AstraZeneca and Pfizer. Ignaty Leshchiner is a consultant for PACT Pharma. Carlos López-Otín has ownership interest (including stock and patents) in DREAMgenics. Matthew Meyerson is a scientific advisory board chair of, and consultant for, OrigiMed, has obtained research funding from Bayer and Ono Pharma and receives patent royalties from LabCorp. Serena Nik-Zainal is an inventor on a number of patent applications that encompass the use of mutational signatures. Nathan Pennell has done consulting work with Merck, Astrazeneca, Eli Lilly and Bristol-Myers Squibb. Xose S. Puente has ownership interest (including stock and patents in DREAMgenics. Benjamin J. Raphael is a consultant for and has ownership interest (including stock and patents) in Medley Genomics. Jorge Reis-Filho is a consultant for Goldman Sachs and REPARE Therapeutics, member of the scientific advisory board of Volition RX and Paige.AI and an ad hoc member of the scientific advisory board of Ventana Medical Systems, Roche Tissue Diagnostics, InVicro, Roche, Genentech and Novartis. Lewis R. Roberts has received grant support from ARIAD Pharmaceuticals, Bayer, BTG International, Exact Sciences, Gilead Sciences, Glycotest, RedHill Biopharma, Target PharmaSolutions and Wako Diagnostics and has provided advisory services to Bayer, Exact Sciences, Gilead Sciences, GRAIL, QED Therapeutics and TAVEC Pharmaceuticals. Richard A. Scolyer has received fees for professional services from Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Dermpedia, Novartis Pharmaceuticals Australia, Myriad, NeraCare GmbH and Amgen. Tal Shmaya is employed at Annai Systems. Reiner Siebert has received speaker honoraria from Roche and AstraZeneca. Sabina Signoretti is a consultant for Bristol-Myers Squibb, AstraZeneca, Merck, AACR and NCI and has received funding from Bristol-Myers Squibb, AstraZeneca, Exelixis and royalties from Biogenex. Jared Simpson has received research funding and travel support from Oxford Nanopore Technologies. Anil K. Sood is a consultant for Merck and Kiyatec, has received research funding from M-Trap and is a shareholder in BioPath. Simon Tavaré is on the scientific advisory board of Ipsen and a consultant for Kallyope. John F. Thompson has received honoraria and travel support for attending advisory board meetings of GlaxoSmithKline and Provectus and has received honoraria for participation in advisory boards for MSD Australia and BMS Australia. Daniel Turner is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Naveen Vasudev has received speaker honoraria and/or consultancy fees from Bristol-Myers Squibb, Pfizer, EUSA pharma, MSD and Novartis. Jeremiah A. Wala is a consultant for Nference. Daniel J. Weisenberger is a consultant for Zymo Research. Dai-Ying Wu is employed at Annai Systems. Cheng-Zhong Zhang is a cofounder and equity holder of Pillar Biosciences, a for-profit company that specializes in the development of targeted sequencing assays. The other authors declare no competing interests.
- Published
- 2020
18. Editorial: Drought stress in legumes.
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Furlan AL, Gonzalez EM, Roy Choudhury S, and Signorelli S
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2022
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19. Tau LUM , an in vivo Drosophila sensor of tau multimerization, identifies neuroprotective interventions in tauopathy.
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Levy SA, Zuniga G, Gonzalez EM, Butler D, Temple S, and Frost B
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- Animals, Drosophila metabolism, tau Proteins genetics, Animals, Genetically Modified, Cell Death, Tauopathies drug therapy, Alzheimer Disease genetics
- Abstract
Tau protein aggregates are a defining neuropathological feature of "tauopathies," a group of neurodegenerative disorders that include Alzheimer's disease. In the current study, we develop a Drosophila split-luciferase-based sensor of tau-tau interaction. This model, which we term "tau
LUM ," allows investigators to quantify tau multimerization at individual time points or longitudinally in adult, living animals housed in a 96-well plate. TauLUM causes cell death in the adult Drosophila brain and responds to both pharmacological and genetic interventions. We find that transgenic expression of an anti-tau intrabody or pharmacological inhibition of HSP90 reduces tau multimerization and cell death in tauLUM flies, establishing the suitability of this system for future drug and genetic modifier screening. Overall, our studies position tauLUM as a powerful in vivo discovery platform that leverages the advantages of the Drosophila model organism to better understand tau multimerization., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)- Published
- 2022
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20. FOXR2 Is an Epigenetically Regulated Pan-Cancer Oncogene That Activates ETS Transcriptional Circuits.
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Tsai JW, Cejas P, Wang DK, Patel S, Wu DW, Arounleut P, Wei X, Zhou N, Syamala S, Dubois FPB, Crane A, Pelton K, Vogelzang J, Sousa C, Baguette A, Chen X, Condurat AL, Dixon-Clarke SE, Zhou KN, Lu SD, Gonzalez EM, Chacon MS, Digiacomo JJ, Kumbhani R, Novikov D, Hunter J, Tsoli M, Ziegler DS, Dirksen U, Jager N, Balasubramanian GP, Kramm CM, Nathrath M, Bielack S, Baker SJ, Zhang J, McFarland JM, Getz G, Aguet F, Jabado N, Witt O, Pfister SM, Ligon KL, Hovestadt V, Kleinman CL, Long H, Jones DTW, Bandopadhayay P, and Phoenix TN
- Subjects
- Adult, Carcinogenesis genetics, Cell Proliferation, Child, Epigenesis, Genetic, Humans, Male, Oncogenes genetics, Proto-Oncogene Proteins c-ets genetics, Proto-Oncogene Proteins c-ets metabolism, Transcriptional Activation, Forkhead Transcription Factors genetics, Neoplasms genetics
- Abstract
Forkhead box R2 (FOXR2) is a forkhead transcription factor located on the X chromosome whose expression is normally restricted to the testis. In this study, we performed a pan-cancer analysis of FOXR2 activation across more than 10,000 adult and pediatric cancer samples and found FOXR2 to be aberrantly upregulated in 70% of all cancer types and 8% of all individual tumors. The majority of tumors (78%) aberrantly expressed FOXR2 through a previously undescribed epigenetic mechanism that involves hypomethylation of a novel promoter, which was functionally validated as necessary for FOXR2 expression and proliferation in FOXR2-expressing cancer cells. FOXR2 promoted tumor growth across multiple cancer lineages and co-opted ETS family transcription circuits across cancers. Taken together, this study identifies FOXR2 as a potent and ubiquitous oncogene that is epigenetically activated across the majority of human cancers. The identification of hijacking of ETS transcription circuits by FOXR2 extends the mechanisms known to active ETS transcription factors and highlights how transcription factor families cooperate to enhance tumorigenesis., Significance: This work identifies a novel promoter that drives aberrant FOXR2 expression and delineates FOXR2 as a pan-cancer oncogene that specifically activates ETS transcriptional circuits across human cancers. See related commentary by Liu and Northcott, p. 2977., (©2022 The Authors; Published by the American Association for Cancer Research.)
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- 2022
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21. PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation.
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Khadka P, Reitman ZJ, Lu S, Buchan G, Gionet G, Dubois F, Carvalho DM, Shih J, Zhang S, Greenwald NF, Zack T, Shapira O, Pelton K, Hartley R, Bear H, Georgis Y, Jarmale S, Melanson R, Bonanno K, Schoolcraft K, Miller PG, Condurat AL, Gonzalez EM, Qian K, Morin E, Langhnoja J, Lupien LE, Rendo V, Digiacomo J, Wang D, Zhou K, Kumbhani R, Guerra Garcia ME, Sinai CE, Becker S, Schneider R, Vogelzang J, Krug K, Goodale A, Abid T, Kalani Z, Piccioni F, Beroukhim R, Persky NS, Root DE, Carcaboso AM, Ebert BL, Fuller C, Babur O, Kieran MW, Jones C, Keshishian H, Ligon KL, Carr SA, Phoenix TN, and Bandopadhayay P
- Subjects
- Adolescent, Adult, Animals, Brain Stem Neoplasms genetics, Carcinogenesis genetics, Cell Cycle, Child, Child, Preschool, DNA Damage, Disease Models, Animal, Female, HEK293 Cells, Humans, Infant, Male, Mice, Proto-Oncogene Proteins c-mdm2, Transcriptome, Tumor Suppressor Protein p53 genetics, Young Adult, Glioma genetics, Mutation, Oncogenes genetics, Protein Phosphatase 2C genetics
- Abstract
The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase the stability of its phosphatase are clonal driver events in 11% of Diffuse Midline Gliomas (DMGs) and are enriched in primary pontine tumors. Through the development of DMG mouse models, we show that PPM1D mutations potentiate gliomagenesis and that PPM1D phosphatase activity is required for in vivo oncogenesis. Finally, we apply integrative phosphoproteomic and functional genomics assays and find that oncogenic effects of PPM1D truncation converge on regulators of cell cycle, DNA damage response, and p53 pathways, revealing therapeutic vulnerabilities including MDM2 inhibition., (© 2022. The Author(s).)
- Published
- 2022
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22. Genome-wide association study and functional validation implicates JADE1 in tauopathy.
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Farrell K, Kim S, Han N, Iida MA, Gonzalez EM, Otero-Garcia M, Walker JM, Richardson TE, Renton AE, Andrews SJ, Fulton-Howard B, Humphrey J, Vialle RA, Bowles KR, de Paiva Lopes K, Whitney K, Dangoor DK, Walsh H, Marcora E, Hefti MM, Casella A, Sissoko CT, Kapoor M, Novikova G, Udine E, Wong G, Tang W, Bhangale T, Hunkapiller J, Ayalon G, Graham RR, Cherry JD, Cortes EP, Borukov VY, McKee AC, Stein TD, Vonsattel JP, Teich AF, Gearing M, Glass J, Troncoso JC, Frosch MP, Hyman BT, Dickson DW, Murray ME, Attems J, Flanagan ME, Mao Q, Mesulam MM, Weintraub S, Woltjer RL, Pham T, Kofler J, Schneider JA, Yu L, Purohit DP, Haroutunian V, Hof PR, Gandy S, Sano M, Beach TG, Poon W, Kawas CH, Corrada MM, Rissman RA, Metcalf J, Shuldberg S, Salehi B, Nelson PT, Trojanowski JQ, Lee EB, Wolk DA, McMillan CT, Keene CD, Latimer CS, Montine TJ, Kovacs GG, Lutz MI, Fischer P, Perrin RJ, Cairns NJ, Franklin EE, Cohen HT, Raj T, Cobos I, Frost B, Goate A, White Iii CL, and Crary JF
- Subjects
- Aged, Aged, 80 and over, Aging pathology, Animals, Cohort Studies, Drosophila, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Homeodomain Proteins genetics, Tauopathies genetics, Tauopathies pathology, Tumor Suppressor Proteins genetics
- Abstract
Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) plaques. The pathogenesis of PART is not known, but evidence suggests an association with genes that promote tau pathology and others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n = 647) using Braak neurofibrillary tangle stage as a quantitative trait. We found some significant associations with candidate loci associated with AD (SLC24A4, MS4A6A, HS3ST1) and progressive supranuclear palsy (MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brains with four microtubule-binding domain repeats (4R) isoforms and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation in post-mortem human PART brain tissue revealed a specific binding of JADE1 protein to four repeat tau lacking N-terminal inserts (0N4R). Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model, as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a modifier of neurofibrillary degeneration., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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23. Realization of macroscopic ratchet effect based on nonperiodic and uneven potentials.
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Rollano V, Gomez A, Muñoz-Noval A, Velez M, de Ory MC, Menghini M, Gonzalez EM, and Vicent JL
- Abstract
Ratchet devices allow turning an ac input signal into a dc output signal. A ratchet device is set by moving particles driven by zero averages forces on asymmetric potentials. Hybrid nanostructures combining artificially fabricated spin ice nanomagnet arrays with superconducting films have been identified as a good choice to develop ratchet nanodevices. In the current device, the asymmetric potentials are provided by charged Néel walls located in the vertices of spin ice magnetic honeycomb array, whereas the role of moving particles is played by superconducting vortices. We have experimentally obtained ratchet effect for different spin ice I configurations and for vortex lattice moving parallel or perpendicular to magnetic easy axes. Remarkably, the ratchet magnitudes are similar in all the experimental runs; i. e. different spin ice I configurations and in both relevant directions of the vortex lattice motion. We have simulated the interplay between vortex motion directions and a single asymmetric potential. It turns out vortices interact with uneven asymmetric potentials, since they move with trajectories crossing charged Néel walls with different orientations. Moreover, we have found out the asymmetric pair potentials which generate the local ratchet effect. In this rocking ratchet the particles (vortices) on the move are interacting each other (vortex lattice); therefore, the ratchet local effect turns into a global macroscopic effect. In summary, this ratchet device benefits from interacting particles moving in robust and topological protected type I spin ice landscapes., (© 2021. The Author(s).)
- Published
- 2021
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24. In Vitro Antioxidant Capacity of Crude Extracts and Acetogenin Fraction of Soursop Fruit Pulp
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Gonzalez EM and Fernandez AEL
- Published
- 2016
25. Medicago sativa and Medicago truncatula Show Contrasting Root Metabolic Responses to Drought.
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Echeverria A, Larrainzar E, Li W, Watanabe Y, Sato M, Tran CD, Moler JA, Hirai MY, Sawada Y, Tran LP, and Gonzalez EM
- Abstract
Drought is an environmental stressor that affects crop yield worldwide. Understanding plant physiological responses to stress conditions is needed to secure food in future climate conditions. In this study, we applied a combination of plant physiology and metabolomic techniques to understand plant responses to progressive water deficit focusing on the root system. We chose two legume plants with contrasting tolerance to drought, the widely cultivated alfalfa Medicago sativa ( Ms ) and the model legume Medicago truncatula ( Mt ) for comparative analysis. Ms taproot (tapR) and Mt fibrous root (fibR) biomass increased during drought, while a progressive decline in water content was observed in both species. Metabolomic analysis allowed the identification of key metabolites in the different tissues tested. Under drought, carbohydrates, abscisic acid, and proline predominantly accumulated in leaves and tapRs, whereas flavonoids increased in fibRs in both species. Raffinose-family related metabolites accumulated during drought. Along with an accumulation of root sucrose in plants subjected to drought, both species showed a decrease in sucrose synthase (SUS) activity related to a reduction in the transcript level of SUS1 , the main SUS gene. This study highlights the relevance of root carbon metabolism during drought conditions and provides evidence on the specific accumulation of metabolites throughout the root system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Echeverria, Larrainzar, Li, Watanabe, Sato, Tran, Moler, Hirai, Sawada, Tran and Gonzalez.)
- Published
- 2021
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26. NGS of microRNAs Involved in Cardioprotection Induced by Sevoflurane Compared to Propofol in Myocardial Revascularization Surgery: The ACDHUVV-16 Clinical Trial.
- Author
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Orriach JLG, Belmonte JJE, Aliaga MR, Fernandez AR, Capitan MJR, Muñoz GQ, Ponferrada AR, Torres JA, Santiago-Fernandez C, Gonzalez EM, Navarro MR, Bautista R, Maldonado JG, Garrido-Sanchez L, and Mañas JC
- Subjects
- Humans, Myocardial Revascularization, Sevoflurane, Methyl Ethers, MicroRNAs genetics, Propofol therapeutic use
- Abstract
Background: Numerous studies have demonstrated that halogenated agents elicit myocardial conditioning effects when administered perioperatively in cardiac surgery. Recent evidence has been published on the benefits of maintaining exposure to halogenated agents during the early postoperative period. The enzymatic mechanisms by which this beneficial effect is exerted were explained recently., Objectives: Our study was performed to investigate whether this phenomenon is mediated by either the activation or suppression of miRNAs targeted by halogenated anesthetics., Methods: A double-blind, two-stage trial was conducted. The results of the first stage of the trial are presented in this paper. The sample was composed of patients undergoing off-pump myocardial revascularization surgery. Patients were randomized to receive either sevoflurane [S] or propofol [P] during the intraoperative and early postoperative period (during the first six hours after the intervention). Hemodynamics (heart rate, blood pressure, central venous pressure, cardiac index, systolic volume index, LVEF) and myocardial enzymes (troponin I) were monitored at six hour intervals during the first 48 hours. In the first stage of the trial, blood was drawn for gene sequencing from eight patients (four per group) at baseline and at 24 h. In the second stage of the study, a qPCR analysis was performed of the miRNAs identified as significant by gene sequencing. Levels of cardioprotective enzymes (serine/threonine protein kinase (Akt), tumor necrosis factor alpha (TNFα), extracellular regulated protein kinase (ERK 1/2), and caspase 3) were measured to assess their role in myocardial conditioning pathways. The purpose was to identify the miRNAs that play a major role in myocardial conditioning induced by halogenated agents. Concentrations of cardioprotective enzymes were higher in patients who received sevoflurane than the patients who were administered propofol., Results: NGS differences were observed between baseline and 24-h values in the two study groups. In group P, miRNA 197-3p was overexpressed, whereas miRNAs 4443 and 1294, 708-3p were underexpressed. In group S, miRNAs 615-3p, 4466, 29, 937-3p, 636, 197-3P, 184, 4685, 296-3p, 147b, 3199, 6815, 1294 and 3176 were underexpressed; whereas 708-3p was overexpressed. qPCR showed significant variations in miRNAs 197-3p, 4443, 708-3p and 1294 in the P group, and in miRNAs 937-3p, 636, 197- 3p, 296-3p and 708-3p in the S group., Conclusion: In the P Group, changes in the expression of some miRNAs were associated with lower concentrations of the enzymes involved in myocardial pre- and postconditioning. In contrast, in Group S, variations in miRNAs were associated with the activation of mediators of anesthetic-induced pre- and post-conditioning, a reduction in cell apoptosis, and a decrease in caspase and TnBF alpha concentrations. Changes in these miRNAs were associated with better prognosis in patients with ischemic heart disease. The main limitation of this study will be overcome in the second stage of the trial, where the specific role of each miRNA will be determined., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2021
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27. Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry
- Author
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Krawczyk, M, Grat, M, Adam, R, Polak, W, Klempnauer, J, Pinna, A, Di Benedetto, F, Filipponi, F, Senninger, N, Foss, A, Rufian-Pena, S, Bennet, W, Pratschke, J, Paul, A, Settmacher, U, Rossi, G, Salizzoni, M, Fernandez-Selles, C, de Rituerto, S, Gomez-Bravo, M, Pirenne, J, Detry, O, Majno, P, Nemec, P, Bechstein, W, Bartels, M, Nadalin, S, Pruvot, F, Mirza, D, Lupo, L, Colledan, M, Tisone, G, Ringers, J, Daniel, J, Torra, R, Gonzalez, E, Canizares, R, Martinez, V, Rodriguez, F, Yilmaz, S, Remiszewski, P, Krawczyk M, Grat M, Adam R, Polak WG, Klempnauer J, Pinna A, Di Benedetto F, Filipponi F, Senninger N, Foss A, Rufian-Pena S, Bennet W, Pratschke J, Paul A, Settmacher U, Rossi G, Salizzoni M, Fernandez-Selles C, de Rituerto STM, Gomez-Bravo MA, Pirenne J, Detry O, Majno PE, Nemec P, Bechstein WO, Bartels M, Nadalin S, Pruvot FR, Mirza DF, Lupo L, Colledan M, Tisone G, Ringers J, Daniel J, Torra RC, Gonzalez EM, Canizares RB, Martinez VCM, Rodriguez FSJ, Yilmaz S, Remiszewski P, Krawczyk, M, Grat, M, Adam, R, Polak, W, Klempnauer, J, Pinna, A, Di Benedetto, F, Filipponi, F, Senninger, N, Foss, A, Rufian-Pena, S, Bennet, W, Pratschke, J, Paul, A, Settmacher, U, Rossi, G, Salizzoni, M, Fernandez-Selles, C, de Rituerto, S, Gomez-Bravo, M, Pirenne, J, Detry, O, Majno, P, Nemec, P, Bechstein, W, Bartels, M, Nadalin, S, Pruvot, F, Mirza, D, Lupo, L, Colledan, M, Tisone, G, Ringers, J, Daniel, J, Torra, R, Gonzalez, E, Canizares, R, Martinez, V, Rodriguez, F, Yilmaz, S, Remiszewski, P, Krawczyk M, Grat M, Adam R, Polak WG, Klempnauer J, Pinna A, Di Benedetto F, Filipponi F, Senninger N, Foss A, Rufian-Pena S, Bennet W, Pratschke J, Paul A, Settmacher U, Rossi G, Salizzoni M, Fernandez-Selles C, de Rituerto STM, Gomez-Bravo MA, Pirenne J, Detry O, Majno PE, Nemec P, Bechstein WO, Bartels M, Nadalin S, Pruvot FR, Mirza DF, Lupo L, Colledan M, Tisone G, Ringers J, Daniel J, Torra RC, Gonzalez EM, Canizares RB, Martinez VCM, Rodriguez FSJ, Yilmaz S, and Remiszewski P
- Abstract
Background. Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. Methods. This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. Results. Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cutoff for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. Conclusions. Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.
- Published
- 2016
28. Little-Parks effect governed by magnetic nanostructures with out-of-plane magnetization.
- Author
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de Ory MC, Rollano V, Gomez A, Menghini M, Muñoz-Noval A, Gonzalez EM, and Vicent JL
- Abstract
Little-Parks effect names the oscillations in the superconducting critical temperature as a function of the magnetic field. This effect is related to the geometry of the sample. In this work, we show that this effect can be enhanced and manipulated by the inclusion of magnetic nanostructures with perpendicular magnetization. These magnetic nanodots generate stray fields with enough strength to produce superconducting vortex-antivortex pairs. So that, the L-P effect deviation from the usual geometrical constrictions is due to the interplay between local magnetic stray fields and superconducting vortices. Moreover, we compare our results with a low-stray field sample (i.e. with the dots in magnetic vortex state) showing how the enhancement of the L-P effect can be explained by an increment of the effective size of the nanodots.
- Published
- 2020
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29. Emerging roles of CCM genes during tumorigenesis with potential application as novel biomarkers across major types of cancers.
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Abou-Fadel J, Qu Y, Gonzalez EM, Smith M, and Zhang J
- Subjects
- Apoptosis Regulatory Proteins metabolism, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Carrier Proteins metabolism, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, KRIT1 Protein metabolism, Membrane Proteins metabolism, Neoplasm Grading, Neoplasms metabolism, Neoplasms pathology, Proto-Oncogene Proteins metabolism, Apoptosis Regulatory Proteins genetics, Carrier Proteins genetics, KRIT1 Protein genetics, Membrane Proteins genetics, Neoplasms genetics, Proto-Oncogene Proteins genetics
- Abstract
Cerebral cavernous malformations (CCMs) are microvascular anomalies in the brain that result in increased susceptibility to stroke. Three genes have been identified as causes of CCMs: cerebral cavernous malformations 1 [(CCM1) also termed Krev interaction trapped 1 (KRIT1)], cerebral cavernous malformation 2 [(CCM2) also termed MGC4607] and cerebral cavernous malformation 3 [(CCM3) also termed programmed cell death 10 (PDCD10)]. It has been demonstrated that both CCM1 and CCM3 bind to CCM2 to form a CCM signaling complex (CSC) with which to modulate multiple signaling cascades. CCM proteins have been reported to play major roles in microvascular angiogenesis in human and animal models. However, CCM proteins are ubiquitously expressed in all major tissues, suggesting an unseen broader role of the CSC in biogenesis. Recent evidence suggests the possible involvement of the CSC complex during tumorigenesis; however, studies concerning this aspect are limited. This is the first report to systematically investigate the expression patterns of CCM proteins in major human tumors using real‑time quantitative PCR, RNA‑fluorescence in situ hybridization, immunohistochemistry and multicolor immunofluorescence imaging. Our data demonstrated that differential expression patterns of the CSC complex are correlated with certain types and grades of major human cancers, indicating the potential application of CCM genes as molecular biomarkers for clinical oncology. Our data strongly suggest that more efforts are needed to elucidate the role of the CSC complex in tumorigenesis, which may have enormous clinical potential for cancer diagnostic, prognostic and therapeutic applications.
- Published
- 2020
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30. Climate and human water use diminish wetland networks supporting continental waterbird migration.
- Author
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Donnelly JP, King SL, Silverman NL, Collins DP, Carrera-Gonzalez EM, Lafón-Terrazas A, and Moore JN
- Abstract
Migrating waterbirds moving between upper and lower latitudinal breeding and wintering grounds rely on a limited network of endorheic lakes and wetlands when crossing arid continental interiors. Recent drying of global endorheic water stores raises concerns over deteriorating migratory pathways, yet few studies have considered these effects at the scale of continental flyways. Here, we investigate the resiliency of waterbird migration networks across western North America by reconstructing long-term patterns (1984-2018) of terminal lake and wetland surface water area in 26 endorheic watersheds. Findings were partitioned regionally by snowmelt- and monsoon-driven hydrologies and combined with climate and human water-use data to determine their importance in predicting surface water trends. Nonlinear patterns of lake and wetland drying were apparent along latitudinal flyway gradients. Pervasive surface water declines were prevalent in northern snowmelt watersheds (lakes -27%, wetlands -47%) while largely stable in monsoonal watersheds to the south (lakes -13%, wetlands +8%). Monsoonal watersheds represented a smaller proportion of total lake and wetland area, but their distribution and frequency of change within highly arid regions of the continental flyway increased their value to migratory waterbirds. Irrigated agriculture and increasing evaporative demands were the most important drivers of surface water declines. Underlying agricultural and wetland relationships however were more complex. Approximately 7% of irrigated lands linked to flood irrigation and water storage practices supported 61% of all wetland inundation in snowmelt watersheds. In monsoonal watersheds, small earthen dams, meant to capture surface runoff for livestock watering, were a major component of wetland resources (67%) that supported networks of isolated wetlands surrounding endorheic lakes. Ecological trends and human impacts identified herein underscore the importance of assessing flyway-scale change as our model depictions likely reflect new and emerging bottlenecks to continental migration., (© 2020 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)
- Published
- 2020
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31. Topologically protected superconducting ratchet effect generated by spin-ice nanomagnets.
- Author
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Rollano V, Muñoz-Noval A, Gomez A, Valdes-Bango F, Martin JI, Velez M, Osorio MR, Granados D, Gonzalez EM, and Vicent JL
- Abstract
We have designed, fabricated and tested a robust superconducting ratchet device based on topologically frustrated spin ice nanomagnets. The device is made of a magnetic Co honeycomb array embedded in a superconducting Nb film. This device is based on three simple mechanisms: (i) the topology of the Co honeycomb array frustrates in-plane magnetic configurations in the array yielding a distribution of magnetic charges which can be ordered or disordered with in-plane magnetic fields, following spin ice rules; (ii) the local vertex magnetization, which consists of a magnetic half vortex with two charged magnetic Néel walls; (iii) the interaction between superconducting vortices and the asymmetric potentials provided by the Néel walls. The combination of these elements leads to a superconducting ratchet effect. Thus, superconducting vortices driven by alternating forces and moving on magnetic half vortices generate a unidirectional net vortex flow. This ratchet effect is independent of the distribution of magnetic charges in the array.
- Published
- 2019
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32. Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma.
- Author
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Bandopadhayay P, Piccioni F, O'Rourke R, Ho P, Gonzalez EM, Buchan G, Qian K, Gionet G, Girard E, Coxon M, Rees MG, Brenan L, Dubois F, Shapira O, Greenwald NF, Pages M, Balboni Iniguez A, Paolella BR, Meng A, Sinai C, Roti G, Dharia NV, Creech A, Tanenbaum B, Khadka P, Tracy A, Tiv HL, Hong AL, Coy S, Rashid R, Lin JR, Cowley GS, Lam FC, Goodale A, Lee Y, Schoolcraft K, Vazquez F, Hahn WC, Tsherniak A, Bradner JE, Yaffe MB, Milde T, Pfister SM, Qi J, Schenone M, Carr SA, Ligon KL, Kieran MW, Santagata S, Olson JM, Gokhale PC, Jaffe JD, Root DE, Stegmaier K, Johannessen CM, and Beroukhim R
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors drug effects, Basic Helix-Loop-Helix Transcription Factors metabolism, CRISPR-Cas Systems, Cell Cycle Proteins drug effects, Cell Cycle Proteins metabolism, Cell Line, Tumor, Cell Lineage, Cerebellar Neoplasms genetics, Cyclin D2 drug effects, Cyclin D2 metabolism, Cyclin-Dependent Kinase 4 antagonists & inhibitors, Cyclin-Dependent Kinase 6 antagonists & inhibitors, Drug Resistance, Neoplasm, Gene Expression Profiling, Humans, Medulloblastoma genetics, Mice, Neural Stem Cells drug effects, Neural Stem Cells metabolism, Proto-Oncogene Proteins c-myc genetics, S Phase drug effects, Azepines pharmacology, Cell Cycle drug effects, Cerebellar Neoplasms drug therapy, Medulloblastoma drug therapy, Neurogenesis drug effects, Proteins antagonists & inhibitors, Triazoles pharmacology
- Abstract
BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. However, the mechanisms for its action, and ultimately for resistance, have not been fully defined. Here, using a combination of expression profiling, genome-scale CRISPR/Cas9-mediated loss of function and ORF/cDNA driven rescue screens, and cell-based models of spontaneous resistance, we identify bHLH/homeobox transcription factors and cell-cycle regulators as key genes mediating BETi's response and resistance. Cells that acquire drug tolerance exhibit a more neuronally differentiated cell-state and expression of lineage-specific bHLH/homeobox transcription factors. However, they do not terminally differentiate, maintain expression of CCND2, and continue to cycle through S-phase. Moreover, CDK4/CDK6 inhibition delays acquisition of resistance. Therefore, our data provide insights about the mechanisms underlying BETi effects and the appearance of resistance and support the therapeutic use of combined cell-cycle inhibitors with BETi in MYC-amplified medulloblastoma.
- Published
- 2019
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33. Gallbladder Carcinoma: Radical Surgery?
- Author
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Gonzalez Em
- Subjects
Reoperation ,medicine.medical_specialty ,medicine.medical_treatment ,MEDLINE ,lcsh:Surgery ,Neoplasm Recurrence ,medicine ,Carcinoma ,Hepatectomy ,Humans ,Radical surgery ,lcsh:RC799-869 ,Neoplasm Staging ,Hepatology ,business.industry ,Gallbladder ,General surgery ,lcsh:RD1-811 ,Surgical procedures ,medicine.disease ,medicine.anatomical_structure ,Surgical Procedures, Operative ,Surgery ,lcsh:Diseases of the digestive system. Gastroenterology ,Gallbladder Neoplasms ,Gallbladder Neoplasm ,Neoplasm Recurrence, Local ,business ,Research Article - Published
- 1990
34. Magnetic order and disorder in nanomagnets probed by superconducting vortices.
- Author
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Rollano V, Del Valle J, Gomez A, Velez M, Alvarez-Prado LM, Quiros C, Martin JI, Osorio MR, Granados D, Gonzalez EM, and Vicent JL
- Abstract
We have studied two nanomagnet systems with strong (Co/Pd multilayers) and weak (NdCo alloy films) stray magnetic fields by probing the out-of-plane magnetic states with superconducting vortices. The hybrid samples are made of array of nanomagnets embedded in superconducting Nb thin films. The vortex motion detects relevant magnetic state features, since superconducting vortices are able to discriminate between different magnetic stray field strengths and directions. The usual matching effect between the superconducting vortex lattice and the periodic pinning array can be quenched by means of disorder magnetic potentials with strong stray fields at random. Ordered stray fields retrieve the matching effect and yield asymmetry and shift in the vortex dissipation signal. Furthermore vortices can discriminate the sizes of the nanomagnet magnetic domains, detecting magnetic domain sizes as small as 70 nm. In addition, we observe that the vortex cores play the crucial role instead of the supercurrents around the vortex.
- Published
- 2018
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35. 3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome
- Author
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UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - MD/CHIR - Département de chirurgie, Burroughs, AK, Sabin, CA, Rolles, K, Delvart, V., Karam, V., Buckels, J., O'Grady, JG, Castaing, D., Klempnauer, J., Jamieson, N., Neuhaus, P., Lerut, Jan, de Ville de Goyet, J., Pollard, S., Salizzoni, M., Rogiers, X, Muhlbacher, F, Valdecasas, JCG, Broelsch, C, Jaeck, D, Berenguer, J, Gonzalez, EM, Adam, R., UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - MD/CHIR - Département de chirurgie, Burroughs, AK, Sabin, CA, Rolles, K, Delvart, V., Karam, V., Buckels, J., O'Grady, JG, Castaing, D., Klempnauer, J., Jamieson, N., Neuhaus, P., Lerut, Jan, de Ville de Goyet, J., Pollard, S., Salizzoni, M., Rogiers, X, Muhlbacher, F, Valdecasas, JCG, Broelsch, C, Jaeck, D, Berenguer, J, Gonzalez, EM, and Adam, R.
- Abstract
Background Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation. Methods We analysed data from 34 664 first adult liver transplants from the European Liver Transplant Registry to identify factors associated with mortality at 3-months (n=21 605 in training dataset) and 12-months (n=18 852 in training dataset) after transplantation. We used multivariable logistic regression models to generate mortality scores for each individual, and assessed model discrimination and calibration on an independent validation dataset (n=9489 for 3-month model and n=8313 for 12-month model). Findings 2540 of 21 605 (12%) individuals in the 3-month training sample had died by 3 months. Compared with those transplanted in 2000-03, those transplanted earlier had a higher risk of death. increased mortality at 3-months post- transplantation was associated with acute liver failure (adjusted odds ratio 1.61), donor age older than 60 years (1.16), compatible (1.22) or incompatible (2.07) donor-recipient blood group, older recipient age (1.12 per 5 years), split or reduced graft (1.96), total ischaemia time of longer than 13 h (1.38), and low United Network for Organ Sharing score (score 1: 2.43; score 2: 1.67). However, cirrhosis with hepatocellular carcinoma, alcohol cirrhosis, hepatitis C or primary biliary cirrhosis, donor age 40 years or younger, or less, hepatitis B, and larger size of transplant Centre (>= 70 transplants per year) were associated with improved early outcomes. The 3-month mortality score discriminated well between those who did and did not die in the validation sample (C statistic=0.688). We noted similar findings for 12-month mortality, although deaths were generally underestimated at this timepoint. Interpretation The 3-month and 12-month mortality models can be effectively used to assess outcomes both within and between ce
- Published
- 2006
36. Evolution of liver transplantation in Europe: Report of the European liver transplant registry
- Author
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UCL - MD/CHIR - Département de chirurgie, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Adam, René, Lerut, Jan, McMaster, P, O'Grady, JG, Castaing, D., Klempnauer, JL, Jamieson, N., Neuhaus, P., Salizzoni, M., Pollard, S., Muhlbacher, F, Rogiers, X, Valdecasas, JCG, Berenguer, J, Jaeck, D, Gonzalez, EM, UCL - MD/CHIR - Département de chirurgie, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Adam, René, Lerut, Jan, McMaster, P, O'Grady, JG, Castaing, D., Klempnauer, JL, Jamieson, N., Neuhaus, P., Salizzoni, M., Pollard, S., Muhlbacher, F, Rogiers, X, Valdecasas, JCG, Berenguer, J, Jaeck, D, and Gonzalez, EM
- Abstract
The European Liver Transplant Registry (ELTR) currently allows for the analysis of 44,286 liver transplantations (LTs) performed on 39,196 patients in a 13-year period. After an exponential increase, the number of Us is plateauing due to a lack of organs. To cope with this, alternatives to cadaveric LT, such as split LT, domino LT, or living-related LT (LRLT) are being used increasingly. They now account for 11% of all procedures. One of the most important findings in the evolution of LT is the considerable improvement of results along time with, for the mean time, a one-year survival of 83%, all indications confounded. The improvement is particularly significant for cancers. This improvement is mainly represented by hepatocellular carcinoma, with a gain of 17% for 5-year survival rate from 1990 to 2000. Increasingly, older donors are used to augment the donor pool and older recipients are transplanted due to improved results and a better selection of patients. More than two thirds of deaths and three quarters of retransplantations occurred within the first year of transplantation. Retransplantation is associated with much less optimal results than first LT. One of the prominent features of recent years is the development of LRLT. LRLT is now performed by almost half of the European centers. As with split LT or domino LT, LRLT aims to provide more patients to be transplanted. Special attention is paid to reducing the risk for the donor, which is now estimated to be 0.5% mortality and 21% postoperative morbidity.
- Published
- 2003
37. Dosimetry and first human experience with 89 Zr-panitumumab.
- Author
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Lindenberg L, Adler S, Turkbey IB, Mertan F, Ton A, Do K, Kummar S, Gonzalez EM, Bhattacharyya S, Jacobs PM, and Choyke P
- Abstract
89 Zr-panitumumab is a novel immuno-PET radiotracer. A fully humanized IgG2 antibody, panitumumab binds with high affinity to the extracellular ligand binding domain of EGFR. Immuno-PET with radiolabeled panitumumab is a non-invasive method that could characterize EGFR expression in tumors and metastatic lesions. It might also assist in selecting patients likely to benefit from targeted therapy as well as monitor response and drug biodistribution for dosing guidance. Our objective was to calculate the maximum dosing for effective imaging with minimal radiation exposure in a small subset. Three patients with metastatic colon cancer were injected with approximately 1 mCi (37 MBq) of89 Zr-panitumumab IV. Whole body static images were then obtained at 2-6 hours, 1-3 days and 5-7 days post injection. Whole organ contours were applied to the liver, kidneys, spleen, stomach, lungs, bone, gut, heart, bladder and psoas muscle. From these contours, time activity curves were derived and used to calculate mean resident times which were used as input into OLINDA 1.1 software for dosimetry estimates. The whole body effective dose was estimated between 0.264 mSv/MBq (0.97 rem/mCi) and 0.330 mSv/MBq (1.22 rem/mCi). The organ which had the highest dose was the liver which OLINDA estimated between 1.9 mGy/MBq (7.2 rad/mCi) and 2.5 mGy/MBq (9 rad/mCi). The effective dose is within range of extrapolated estimates from mice studies.89 Zr-panitumumab appears safe and dosimetry estimates are reasonable for clinical imaging., Competing Interests: None.- Published
- 2017
38. Prediction of Response to Immune Checkpoint Inhibitor Therapy Using Early-Time-Point 18 F-FDG PET/CT Imaging in Patients with Advanced Melanoma.
- Author
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Cho SY, Lipson EJ, Im HJ, Rowe SP, Gonzalez EM, Blackford A, Chirindel A, Pardoll DM, Topalian SL, and Wahl RL
- Subjects
- Adult, Aged, Female, Humans, Male, Melanoma immunology, Melanoma pathology, Middle Aged, Treatment Outcome, Fluorodeoxyglucose F18, Melanoma diagnostic imaging, Melanoma therapy, Positron Emission Tomography Computed Tomography, Signal Transduction drug effects, Signal Transduction immunology
- Abstract
The purpose of this study was to evaluate
18 F-FDG PET/CT scanning as an early predictor of response to immune checkpoint inhibitors (ICIs) in patients with advanced melanoma. Methods: Twenty patients with advanced melanoma receiving ICI prospectively underwent18 F-FDG PET/CT at 3 scan intervals: before treatment initiation (SCAN-1), at days 21-28 (SCAN-2), and at 4 mo (SCAN-3). This study was approved by the institutional review board, and informed consent was received from all patients who were enrolled between April 2012 and December 2013. Tumor response at each posttreatment time point was assessed according to RECIST 1.1, immune-related response criteria, PERCIST (PERCIST 1.0), and European Organization for Research and Treatment of Cancer (EORTC) criteria. Performance characteristics of each metric to predict best overall response (BOR) at ≥ 4 mo were assessed. Results: Twenty evaluable patients were treated with ipilimumab ( n = 16), BMS-936559 ( n = 3), or nivolumab ( n = 1). BOR at ≥ 4 mo included complete response ( n = 2), partial response ( n = 2), stable disease ( n = 1), and progressive disease ( n = 15). Response evaluations at SCAN-2 using RECIST 1.1, immune-related response criteria, PERCIST, and EORTC criteria demonstrated accuracies of 75%, 70%, 70%, and 65%, respectively, to predict BOR at ≥ 4 mo. Interestingly, the optimal PERCIST and EORTC threshold values at SCAN-2 to predict BOR were >15.5% and >14.7%, respectively. By combining anatomic and functional imaging data collected at SCAN-2, we developed criteria to predict eventual response to ICI with 100% sensitivity, 93% specificity, and 95% accuracy. Conclusion: Combining functional and anatomic imaging parameters from18 F-FDG PET/CT scans performed early in ICI appears predictive for eventual response in patients with advanced melanoma. These findings require validation in larger cohorts., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2017
- Full Text
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39. Utility of 18 F-fluoroestradiol ( 18 F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.
- Author
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Lin FI, Gonzalez EM, Kummar S, Do K, Shih J, Adler S, Kurdziel KA, Ton A, Turkbey B, Jacobs PM, Bhattacharyya S, Chen AP, Collins JM, Doroshow JH, Choyke PL, and Lindenberg ML
- Subjects
- Adult, Aged, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms, Male drug therapy, Breast Neoplasms, Male genetics, Estrogen Antagonists therapeutic use, Female, Genital Neoplasms, Female drug therapy, Genital Neoplasms, Female genetics, Humans, Male, Middle Aged, Receptors, Estrogen antagonists & inhibitors, Receptors, Estrogen genetics, Tamoxifen analogs & derivatives, Tamoxifen therapeutic use, Breast Neoplasms diagnostic imaging, Breast Neoplasms, Male diagnostic imaging, Estradiol analogs & derivatives, Genital Neoplasms, Female diagnostic imaging, Positron Emission Tomography Computed Tomography, Radiopharmaceuticals
- Abstract
Background: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6.
18 F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes18 F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen., Methods: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with18 F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with18 F-FES 1-5 days post administration of Z-endoxifen., Results: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration., Conclusion: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.- Published
- 2017
- Full Text
- View/download PDF
40. ANG1005 for breast cancer brain metastases: correlation between 18 F-FLT-PET after first cycle and MRI in response assessment.
- Author
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O'Sullivan CC, Lindenberg M, Bryla C, Patronas N, Peer CJ, Amiri-Kordestani L, Davarpanah N, Gonzalez EM, Burotto M, Choyke P, Steinberg SM, Liewehr DJ, Figg WD, Fojo T, Balasubramaniam S, and Bates SE
- Subjects
- Adult, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Biomarkers, Biomarkers, Tumor, Brain Neoplasms diagnosis, Breast Neoplasms diagnosis, Breast Neoplasms metabolism, Combined Modality Therapy, Female, Fluorodeoxyglucose F18, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Magnetic Resonance Imaging, Middle Aged, Paclitaxel administration & dosage, Paclitaxel adverse effects, Paclitaxel therapeutic use, Peptides administration & dosage, Peptides adverse effects, Positron-Emission Tomography, Treatment Outcome, Antineoplastic Agents therapeutic use, Brain Neoplasms drug therapy, Brain Neoplasms secondary, Breast Neoplasms pathology, Paclitaxel analogs & derivatives, Peptides therapeutic use
- Abstract
Purpose: Improved therapies and imaging modalities are needed for the treatment of breast cancer brain metastases (BCBM). ANG1005 is a drug conjugate consisting of paclitaxel covalently linked to Angiopep-2, designed to cross the blood-brain barrier. We conducted a biomarker substudy to evaluate
18 F-FLT-PET for response assessment., Methods: Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m2 IV every 21 days. Before and after cycle 1, patients underwent PET imaging with18 F-FLT, a thymidine analog, retention of which reflects cellular proliferation, for comparison with gadolinium-contrast magnetic resonance imaging (Gd-MRI) in brain metastases detection and response assessment. A 20 % change in uptake after one cycle of ANG1005 was deemed significant., Results: Thirty-two target and twenty non-target metastatic brain lesions were analyzed. The median tumor reduction by MRI after cycle 1 was -17.5 % (n = 10 patients, lower, upper quartiles: -25.5, -4.8 %) in target lesion size compared with baseline. Fifteen of twenty-nine target lesions (52 %) and 12/20 nontarget lesions (60 %) showed a ≥20 % decrease post-therapy in FLT-PET SUV change (odds ratio 0.71, 95 % CI: 0.19, 2.61). The median percentage change in SUVmax was -20.9 % (n = 29 lesions; lower, upper quartiles: -42.4, 2.0 %), and the median percentage change in SUV80 was also -20.9 % (n = 29; lower, upper quartiles: -49.0, 0.0 %). Two patients had confirmed partial responses by PET and MRI lasting 6 and 18 cycles, respectively. Seven patients had stable disease, receiving a median of six cycles., Conclusions: ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and18 F-FLT-PET imaging.- Published
- 2016
- Full Text
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41. Evidence for a rhizobia-induced drought stress response strategy in Medicago truncatula.
- Author
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Staudinger C, Mehmeti-Tershani V, Gil-Quintana E, Gonzalez EM, Hofhansl F, Bachmann G, and Wienkoop S
- Subjects
- Medicago truncatula metabolism, Medicago truncatula microbiology, Plant Proteins metabolism, Rhizobium, Stress, Physiological
- Abstract
Drought stress hampers plant energy and biomass production; however it is still unknown how internal C:N balance and rhizobial symbiosis impact on plant response to water limitation. Here, the effect of differential optimal nitrogen nutrition and root nodule symbiosis on drought stress and rehydration responses of Medicago truncatula was assessed. Two groups of plants were nodulated with Sinorhizobium medicae or Sinorhizobium meliloti--differing in the performance of N fixation; the third group grew in a rhizobia-free medium and received mineral nitrogen fertilizer. In addition to growth analyses, physiological and molecular responses of the two systems were studied using ionomic, metabolomic and proteomic techniques. We found a significant delay in drought-induced leaf senescence in nodulated relative to non-nodulated plants, independent of rhizobial strain and uncoupled from initial leaf N content. The major mechanisms involved are increased concentrations of potassium and shifts in the carbon partitioning between starch and sugars under well-watered conditions, as well as the enhanced allocation of reserves to osmolytes during drought. Consequently, nodulated plants recovered more effectively from drought, relative to non-nodulated M. truncatula. Proteomic data suggest that phytohormone interactions and enhanced translational regulation play a role in increased leaf maintenance in nodulated plants during drought., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
42. Superconducting/magnetic Three-state Nanodevice for Memory and Reading Applications.
- Author
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del Valle J, Gomez A, Gonzalez EM, Osorio MR, Granados D, and Vicent JL
- Abstract
We present a simple nanodevice that can operate in two modes: i) non-volatile three-state memory and ii) reading device. The nanodevice can retain three well defined states -1, 0 and +1 and can operate in a second mode as a sensor for external magnetic fields. The nanodevice is fabricated with an array of ordered triangular-shaped nanomagnets embedded in a superconducting thin film gown on Si substrates. The device runs based on the combination of superconducting vortex ratchet effect (superconducting film) with the out of plane magnetization (nanomagnets). The input signals are ac currents and the output signal are dc voltages. The memory mode is realized without applying a magnetic field and the nanomagnet stray magnetic fields govern the effect. In the sensor mode an external magnetic field is applied. The main characteristic of this mode is that the output signal is null for a precise value of the external magnetic field that only depends on the fabrication characteristics of the nanodevice.
- Published
- 2015
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43. Altered microRNA composition in the uterine lumen fluid in cattle (Bos taurus) pregnancies initiated by artificial insemination or transfer of an in vitro produced embryo.
- Author
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Biase, Fernando H., Moorey, Sarah E., Schnuelle, Julie G., Rodning, Soren, Ortega, Martha Sofia, and Spencer, Thomas E.
- Subjects
CATTLE pregnancy ,NON-coding RNA ,MESSENGER RNA ,REPRODUCTIVE technology ,CATTLE ,TROPHOBLAST - Abstract
Background: MicroRNAs (miRNAs) are presented in the uterine lumen of many mammals, and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions. Our aim was to identify and contrast the miRNAs present in extracellular vesicles (EVs) in the uterine lumen fluid (ULF) at the onset of attachment in cattle pregnancies (gestation d 18) initiated by artificial insemination (AI) or by the transfer of an in vitro-produced blastocyst (IVP-ET). A third group had no conceptus after the transfer of an IVP embryo. Results: The abundance of 263 annotated miRNAs was quantified in the EVs collected from ULF. There was an increase in the transcript abundance of 20 miRNAs in the ULF EVs from the AI pregnant group, while 4 miRNAs had a lower abundance relative to the group not containing a conceptus. Additionally, 4 miRNAs were more abundant in ULF EVs in the AI pregnant group relative to IVP-ET group (bta-mir-17, bta-mir-7-3, MIR7-1, MIR18A). Specific miRNAs in the ULF EVs were co-expressed with messenger RNAs expressed in extra-embryonic tissues and endometrium, including genes that are known to be their targets. Conclusions: The results provide biological insights into the participation of miRNAs in the regulation of trophoblast proliferation and differentiation, as well as in endometrium receptivity. The knowledge that in vitro cultured embryos can contribute to the altered abundance of specific miRNAs in the uterine lumen can lead to the development of corrective approaches to reduce conceptus losses during the first month of pregnancy in cattle. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. Colonização, patriarcado e racismo: uma análise feminista e antirracista de um Brasil oculto e pungente.
- Author
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Cisne Alvaro, Mirla
- Subjects
EQUALITY ,RACE ,COLONIZATION ,ANTI-racism ,RACISM - Abstract
Copyright of O Social em Questão is the property of Faculdades Catolicas - Pontificia Universidade Catolica do Rio de Janeiro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2024
- Full Text
- View/download PDF
45. Role of quantitative imaging biomarkers in an early FDG-PET/CT for detection of immune-related adverse events in melanoma patients: a prospective study.
- Author
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Hribernik, Nezka, Strasek, Katja, Huff, Daniel T, Studen, Andrej, Zevnik, Katarina, Skalic, Katja, Jeraj, Robert, and Rebersek, Martina
- Subjects
RADIOPHARMACEUTICALS ,MELANOMA ,RESEARCH funding ,RECEIVER operating characteristic curves ,DEOXY sugars ,POSITRON emission tomography computed tomography ,CANCER patients ,LUNGS ,GASTROINTESTINAL system ,METASTASIS ,IMMUNE checkpoint inhibitors ,LONGITUDINAL method ,THYROID gland ,ARTIFICIAL neural networks ,BIOMARKERS - Abstract
To evaluate the role of the novel quantitative imaging biomarker (QIB) SUV
X% of18 F-FDG uptake extracted from early18 F-FDG-PET/CT scan at 4 weeks for the detection of immune-related adverse events (rAE) in a cohort of patients with metastatic melanoma (mM) patients receiving immune-checkpoint inhibitors (ICI). In this prospective non-interventional, one-centre clinical study, patients with mM, receiving ICI treatment, were regularly followed by18 F-FDG PET/CT. Patients were scanned at baseline, early point at week four (W4), week sixteen (W16) and week thirty-two (W32) after ICI initiation. A convolutional neural network (CNN) was used to segment three organs: lung, bowel, thyroid. QIB of irAE - SUVX% - was analyzed within the target organs and correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. A total of 24218 F-FDG PET/CT images of 71 mM patients were prospectively collected and analysed. The early W4 scan showed improved detection only for the thyroid gland compared to W32 scan (p=0.047). The AUROC for detection of irAE in the three target organs was highest when SUVX% was extracted from W16 scan and was 0.76 for lung, 0.53 for bowel and 0.81 for thyroid. SUVX% extracted from W4 scan did not improve detection of irAE compared to W16 scan (lung: p = 0.54, bowel: p = 0.75, thyroid: p = 0.3, DeLong test), as well as compared to W32 scan in lungs (p = 0.32) and bowel (p = 0.3). Early time point18 F-FDG PET/CT at W4 did not lead to statistically significant earlier detection of irAE. However, organ18 F-FDG uptake as quantified by SUVX% proved to be a consistent QIB of irAE. To better assess the role of18 F-FDG PET/CT in irAE detection, the time evolution of18 F-FDG PET/CT quantifiable inflammation would be of essence, only achievable in multi centric studies. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
46. A branquitude posta em cheque: uma análise histórica de Que horas ela volta? (2015)
- Author
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Lucas Xavier Anselmo
- Subjects
branquitude ,cinema brasileiro ,lélia gonzalez ,History (General) ,D1-2009 ,Latin America. Spanish America ,F1201-3799 - Abstract
Este artigo tem como principal proposta a realização de uma análise cinematográfica do longa-metragem Que horas ela volta? (2015), de Anna Muylaert, com ênfase na presença da branquitude. Como principal texto de apoio, utilizamos o Racismo e sexismo na cultura brasileira (1984), de Lélia Gonzalez, em que a intelectual analisa o imaginário social brasileiro sobre a mulher negra através do engendramento das figuras da “mulata”, da “mucama” e da “mãe preta”. Tal exercício nos ajuda a compreender como esse grupo denominado de “branquitude”, usando desse aparato de imagens caricaturais, é representado de maneira crítica, ao mesmo tempo que também não deixa de ser reforçado, em alguns dos seus aspectos, como hegemônico por esse filme de 2015.
- Published
- 2024
- Full Text
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47. A 6-day-old male infant with linear band of skin-colored papules. Incontinentia pigmenti.
- Author
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Gonzalez EM, DeKlotz CC, and Eichenfield LF
- Subjects
- Diagnosis, Differential, Exanthema etiology, Humans, Infant, Newborn, Male, Exanthema diagnosis, Incontinentia Pigmenti diagnosis
- Published
- 2014
- Full Text
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48. Beta blockers: an innovation in the treatment of infantile hemangiomas.
- Author
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Admani S, Feldstein S, Gonzalez EM, and Friedlander SF
- Abstract
Infantile hemangiomas are benign vascular tumors seen in 4.5 percent of neonates and infants. While most infantile hemangiomas can be managed with active nonintervention, a subset of patients will require more aggressive management. Here the authors review the use of beta-blockers in the treatment of infantile hemangiomas, including oral, topical, and multimodal treatment options. They discuss the latest data on propranolol, including criteria for patient selection, dosing recommendations, and appropriate monitoring for side effects and efficacy. Lastly, they review indications for topical timolol treatment and the potential benefits of concomitant laser therapy.
- Published
- 2014
49. Water-deficit effects on carbon and nitrogen metabolism of pea nodules.
- Author
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Gonzalez, EM, Aparicio-Tejo, PM, Gordon, AJ, Minchin, FR, Royuela, M, and Arrese-Igor, C
- Subjects
- *
EFFECT of water levels on plants , *PLANT metabolism , *PEAS - Abstract
Investigates the effect of water-deficit stress on carbon and nitrogen metabolism of Pisum sativum nodules. Factors involved in the decline of sucrose synthase activity; Enzymes involved in nitrogen assimilation; Alterations in nodule metabolic activity.
- Published
- 1998
- Full Text
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50. Glioblastoma arising in a patient with Mayer-Rokitansky-Küster-Hauser syndrome.
- Author
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Gonzalez EM and Prayson RA
- Subjects
- Adult, Female, Humans, 46, XX Disorders of Sex Development etiology, Congenital Abnormalities etiology, Glioblastoma complications, Mullerian Ducts abnormalities, Ovarian Neoplasms complications
- Abstract
Mayer-Rokitansky-Küster-Hauser syndrome is a rare developmental disorder marked by the congenital absence of the uterus and vagina. The syndrome has been associated with tumors of the female reproductive system, but rarely in other organ systems and to our knowledge, never in the brain. We report a glioblastoma in a 34-year-old patient with Mayer-Rokitansky-Küster-Hauser syndrome., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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