110 results on '"Hilaire E"'
Search Results
2. P143 - Topic: AS09-Quality of life-Disease experiences: LONGITUDINAL TRAJECTORY OF QUALITY OF LIFE IN MDS AND IMPACT OF PATIENT-RELATED FACTORS
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Buckstein, R., Chodirker, L., Mozessohn, L., Geddes, M., Zhu, N., Trottier, A., Khalaf, D., Leber, B., St-Hilaire, E., Finn, N., Sabloff, M., Christou, G., Leitch, H., Shamy, A., Yee, K., Storring, J., Nevill, T., Elemary, M., Delage, R., Houston, B., Parmentier, A., Siddiqui, M., Mamedov, A., Zhang, L., and Abel, G.
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- 2023
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3. P025 - Topic: AS02-Epidemiology: EVALUATION OF INFECTIOUS COMPLICATIONS IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES: A PROSPECTIVE COHORT STUDY FROM THE CANADIAN MDS REGISTRY
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Mathur, S., Christou, G., Delage, R., Elemary, M., Finn, N., Geddes, M., Houston, D., Keating, M.-M., Khalaf, D., Leber, B., Leitch, H., Lother, S., Mozessohn, L., Nevill, T., Parmentier, A., Paulson, K., Rimmer, E., Sabloff, M., Shamy, A., St-Hilaire, E., Storring, J., Yee, K., Zhang, L., Zhu, N., Hay, A., Zarychanski, R., Buckstein, R., and Houston, B.
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- 2023
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4. P59 - Topic: AS08-Treatment/AS08j-Supportive care - Iron overload: MDS IRON ROAD: AN INTERNET-BASED ALGORITHM FOR THE DIAGNOSIS, WORKUP AND MANAGEMENT OF IRON OVERLOAD IN MDS FROM THE CANADIAN CONSORTIUM ON MDS (CCMDS)
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Leitch, H., Ezzat, H., Merkeley, H., Buckstein, R., Zhu, N., Nevill, T., Olney, H., Yee, K., Leber, B., Keating, M.-M., Hilaire, E. St., Kumar, R., Delage, R., Geddes, M., Storring, J., Shamy, A., Elemary, M., and Wells, R.
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- 2021
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5. P09 - Topic: AS02-Epidemiology: THE IMPACT OF GAINING OR LOSING TRANSFUSION INDEPENDENCE ON QUALITY OF LIFE IN MYELODYSPLASTIC SYNDROMES
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Brailovski, E., Mozessohn, L., Abel, G., Geddes, M., Zhu, N., Keating, M.-M., Sabloff, M., Christou, G., Leber, B., Khalaf, D., Leitch, H., Hilaire, E. St., Finn, N., Shamy, A., Yee, K., Storring, J., Nevill, T., Delage, R., Elemary, M., Banerji, V., Houston, B., Chodirker, L., Parmentier, A., Siddiqui, M., Mamedov, A., Zhang, L., and Buckstein, R.
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- 2021
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6. Description de deux crocodiles qui existent dans le Nil, comparés au crocodile de Saint-Domingue
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Saint-Hilaire, E Geoffroy and BioStor
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- 1807
7. Misoprostol coadministered with diclofenac for prevention of gastroduodenal ulcers: A one-year study
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Agrawal, Naurang M., van Kerckhove, Hilaire E. J. M., Erhardt, Lorri J., and Steven Geis, G.
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- 1995
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8. Vascular defense responses in rice: peroxidase accumulation in xylem parenchyma cells and xylem wall thickening
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Hilaire, E, Young, S. A, Willard, L. H, McGee, J. D, Sweat, T, Chittoor, J. M, Guikema, J. A, and Leach, J. E
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Life Sciences (General) - Abstract
The rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae is a vascular pathogen that elicits a defensive response through interaction with metabolically active rice cells. In leaves of 12-day-old rice seedlings, the exposed pit membrane separating the xylem lumen from the associated parenchyma cells allows contact with bacterial cells. During resistant responses, the xylem secondary walls thicken within 48 h and the pit diameter decreases, effectively reducing the area of pit membrane exposed for access by bacteria. In susceptible interactions and mock-inoculated controls, the xylem walls do not thicken within 48 h. Xylem secondary wall thickening is developmental and, in untreated 65-day-old rice plants, the size of the pit also is reduced. Activity and accumulation of a secreted cationic peroxidase, PO-C1, were previously shown to increase in xylem vessel walls and lumen. Peptide-specific antibodies and immunogold-labeling were used to demonstrate that PO-C1 is produced in the xylem parenchyma and secreted to the xylem lumen and walls. The timing of the accumulation is consistent with vessel secondary wall thickening. The PO-C1 gene is distinct but shares a high level of similarity with previously cloned pathogen-induced peroxidases in rice. PO-C1 gene expression was induced as early as 12 h during resistant interactions and peaked between 18 and 24 h after inoculation. Expression during susceptible interactions was lower than that observed in resistant interactions and was undetectable after infiltration with water, after mechanical wounding, or in mature leaves. These data are consistent with a role for vessel secondary wall thickening and peroxidase PO-C1 accumulation in the defense response in rice to X. oryzae pv. oryzae.
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- 2001
9. Growth in microgravity increases susceptibility of soybean to a fungal pathogen
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Ryba-White, M, Nedukha, O, Hilaire, E, Guikema, J. A, Kordyum, E, Leach, J. E, and Spooner, B. S
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Life Sciences (General) - Abstract
The influence of microgravity on the susceptibility of soybean roots to Phytophthora sojae was studied during the Space Shuttle Mission STS-87. Seedlings of soybean cultivar Williams 82 grown in spaceflight or at unit gravity were untreated or inoculated with the soybean root rot pathogen P. sojae. At 3, 6 and 7 d after launch while still in microgravity, seedlings were photographed and then fixed for subsequent microscopic analysis. Post-landing analysis of the seedlings revealed that at harvest day 7 the length of untreated roots did not differ between flight and ground samples. However, the flight-grown roots infected with P. sojae showed more disease symptoms (percentage of brown and macerated areas) and the root tissues were more extensively colonized relative to the ground controls exposed to the fungus. Ethylene levels were higher in spaceflight when compared to ground samples. These data suggest that soybean seedlings grown in microgravity are more susceptible to colonization by a fungal pathogen relative to ground controls.
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- 2001
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10. Plants, plant pathogens, and microgravity--a deadly trio
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Leach, J. E, Ryba-White, M, Sun, Q, Wu, C. J, Hilaire, E, Gartner, C, Nedukha, O, Kordyum, E, Keck, M, Leung, H, and Guikema, J. A
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Man/System Technology And Life Support - Abstract
Plants grown in spaceflight conditions are more susceptible to colonization by plant pathogens. The underlying causes for this enhanced susceptibility are not known. Possibly the formation of structural barriers and the activation of plant defense response components are impaired in spaceflight conditions. Either condition would result from altered gene expression of the plant. Because of the tools available, past studies focused on a few physiological responses or biochemical pathways. With recent advances in genomics research, new tools, including microarray technologies, are available to examine the global impact of growth in the spacecraft on the plant's gene expression profile. In ground-based studies, we have developed cDNA subtraction libraries of rice that are enriched for genes induced during pathogen infection and the defense response. Arrays of these genes are being used to dissect plant defense response pathways in a model system involving wild-type rice plants and lesion mimic mutants. The lesion mimic mutants are ideal experimental tools because they erratically develop defense response-like lesions in the absence of pathogens. The gene expression profiles from these ground-based studies will provide the molecular basis for understanding the biochemical and physiological impacts of spaceflight on plant growth, development and disease defense responses. This, in turn, will allow the development of strategies to manage plant disease for life in the space environment.
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- 2001
11. Plastid distribution in columella cells of a starchless Arabidopsis mutant grown in microgravity
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Hilaire, E, Paulsen, A. Q, Brown, C. S, Guikema, J. A, and Spooner, B. S
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Life Sciences (General) - Abstract
Wild-type and starchless Arabidopsis thaliana mutant seedlings (TC7) were grown and fixed in the microgravity environment of a U.S. Space Shuttle spaceflight. Computer image analysis of longitudinal sections from columella cells suggest a different plastid positioning mechanism for mutant and wild-type in the absence of gravity.
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- 1997
12. Clinorotation affects morphology and ethylene production in soybean seedlings
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Hilaire, E, Peterson, B. V, Guikema, J. A, Brown, C. S, and Sager, J. C
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Life Sciences (General) - Abstract
The microgravity environment of spaceflight influences growth, morphology and metabolism in etiolated germinating soybean. To determine if clinorotation will similarly impact these processes, we conducted ground-based studies in conjunction with two space experiment opportunities. Soybean (Glycine max [L.] Merr.) seeds were planted within BRIC (Biological Research In Canister) canisters and grown for seven days at 20 degrees C under clinorotation (1 rpm) conditions or in a stationary upright mode. Gas samples were taken daily and plants were harvested after seven days for measurement of growth and morphology. Compared to the stationary upright controls, plants exposed to clinorotation exhibited increased root length (125% greater) and fresh weight (42% greater), whereas shoot length and fresh weight decreased by 33% and 16% respectively. Plants grown under clinorotation produced twice as much ethylene as the stationary controls. Seedlings treated with triiodo benzoic acid (TIBA), an auxin transport inhibitor, under clinorotation produced 50% less ethylene than the untreated control subjected to the same gravity treatment, whereas a treatment with 2,4-D increased ethylene by five-fold in the clinorotated plants. These data suggest that slow clinorotation influences biomass partitioning and ethylene production in etiolated soybean plants.
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- 1996
13. Effects of clinorotation and microgravity on sweet clover columella cells treated with cytochalasin D
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Hilaire, E, Paulsen, A. Q, Brown, C. S, Guikema, J. A, and Spooner, B. S
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Life Sciences (General) - Abstract
The cytoskeleton of columella cells is believed to be involved in maintaining the developmental polarity of cells observed as a reproducible positioning of cellular organelles. It is also implicated in the transduction of gravitropic signals. Roots of sweet clover (Melilotus alba L.) seedlings were treated with a microfilament disrupter, cytochalasin D, on a slowly rotating horizontal clinostat (2 rpm). Electron micrographs of treated columella cells revealed several ultrastructural effects including repositioning of the nucleus and the amyloplasts and the formation of endoplasmic reticulum (ER) whorls. However, experiments performed during fast clinorotation (55 rpm) showed an accumulation (but no whorling) of a disorganized ER network at the proximal and distal pole and a random distribution of the amyloplasts. Therefore, formation of whorls depends upon the speed of clinorotation, and the overall impact of cytochalasin D suggests the necessity of microfilaments in organelle positioning. Interestingly, a similar drug treatment performed in microgravity aboard the US Space Shuttle Endeavour (STS-54, January 1993) caused a displacement of ER membranes and amyloplasts away from the distal plasma membrane. In the present study, we discuss the role of microfilaments in maintaining columella cell polarity and the utility of clinostats to simulate microgravity.
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- 1995
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14. Cortical microtubules in sweet clover columella cells developed in microgravity
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Hilaire, E, Paulsen, A. Q, Brown, C. S, Guikema, J. A, and Spooner, B. S
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Life Sciences (General) - Abstract
Electron micrographs of columella cells from sweet clover seedlings grown and fixed in microgravity revealed longitudinal and cross sectioned cortical microtubules. This is the first report demonstrating the presence and stability of this network in plants in microgravity.
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- 1995
15. Microgravity and clinorotation cause redistribution of free calcium in sweet clover columella cells
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Hilaire, E, Paulsen, A. Q, Brown, C. S, Guikema, J. A, and Spooner, B. S
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Life Sciences (General) - Abstract
In higher plants, calcium redistribution is believed to be crucial for the root to respond to a change in the direction of the gravity vector. To test the effects of clinorotation and microgravity on calcium localization in higher plant roots, sweet clover (Melilotus alba L.) seedlings were germinated and grown for two days on a slow rotating clinostat or in microgravity on the US Space Shuttle flight STS-60. Subsequently, the tissue was treated with a fixative containing antimonate (a calcium precipitating agent) during clinorotation or in microgravity and processed for electron microscopy. In root columella cells of clinorotated plants, antimonate precipitates were localized adjacent to the cell wall in a unilateral manner. Columella cells exposed to microgravity were characterized by precipitates mostly located adjacent to the proximal and lateral cell wall. In all treatments some punctate precipitates were associated with vacuoles, amyloplasts, mitochondria, and euchromatin of the nucleus. A quantitative study revealed a decreased number of precipitates associated with the nucleus and the amyloplasts in columella cells exposed to microgravity as compared to ground controls. These data suggest that roots perceive a change in the gravitational field, as produced by clinorotation or space flights, and respond respectively differently by a redistribution of free calcium.
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- 1995
16. Cytoskeleton-amyloplast interactions in sweet clover
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Guikema, J. A, Hilaire, E, Odom, W. R, and Spooner, B. S
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Life Sciences (General) - Abstract
The distribution of organelles within columella cells of sweet clover was examined by transmission electron microscopy following growth under static or clinorotating conditions. A developmentally conditioned polarity was observed, with a proximal location of the nucleus and a distal accumulation of the endoplasmic reticulum. This polarity was insensitive to clinorotation. In contrast, clinorotation altered the location of amyloplasts. Application of cytoskeletal poisons (colchicine, cytochalasin D, taxol, and phalloidin), especially during clinorotation, had interesting effects on the maintenance of columella cell polarity, with a profound effect on the extent, location, and structure of the endoplasmic reticulum. The site of cytoskeletal interactions with sedimenting amyloplasts is thought to be the amyloplast envelope. An envelope fraction, having over 17 polypeptides, was isolated using immobilized antibody technology, and will provide a means of assessing the role of specific peptides in cytoskeleton/amyloplast interactions.
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- 1993
17. Mapping responsible conduct in the uncharted field of research-creation: A scoping review.
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Voarino, N., Couture, V., Mathieu-Chartier, S., Bélisle-Pipon, J. C., St-Hilaire, E., Williams-Jones, B., Lapointe, F. J., Noury, C., Cloutier, M., and Gauthier, P.
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LITERATURE reviews ,EDUCATION research ,RESEARCH ethics - Abstract
This scoping review addresses the issues of responsible conduct of research (RCR) that can arise in the practice of research-creation (RC), an emergent, interdisciplinary, and heterogeneous field at the interface of academic research and creative activities. Little is yet known about the nature and scope of RCR issues in RC, so our study examined three questions: (1) What are the specific issues in RC in relation to RCR? (2) How does the specificity of RC influence the understanding and practice of RCR? (3) What recommendations could help address the issues highlighted in the literature? To answer these questions, we conducted a scoping review of the academic literature (n = 181 texts) dealing with RCR in RC. We found that researcher-creators faced some very different RCR challenges in comparison with their colleagues in the rest of academia. Addressing these issues is important for both the RCR and RC communities in order to ensure that the rapid development of this field occurs in line with the norms of RCR which, nonetheless, should be adapted to respect the particularities of RC and allow its contributions to the academic world. [ABSTRACT FROM AUTHOR]
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- 2019
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18. Compton imaging of prompt-gamma radiation in proton therapy: influence of the attenuation in the volume and of the detector performances
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Hilaire, E., Lojacono, X., Sarrut, D., Peyrin, F., Maxim, Voichita, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing - Abstract
National audience; In proton therapy cancer treatments, interactions between the beam and the patient's body lead to nuclear reactions that produce secondary prompt-γ radiation. It was shown that some correlation exists between the emission point of those photons and the Bragg peak position. Ongoing work aims to design imaging systems able to monitor the deposited dose by exploiting prompt-γ radiation, in particular the Compton camera. A 3D image of the prompt-γ cartography can be obtained with this device. The Compton camera detects a photon in two steps. The photon is scattered (at least once) in a first detector, then it is absorbed in a second detector. The hits, recorded with positions and energies, define an event. A Compton cone is defined for each event and the incoming path of the initial ray lies on its surface. The image of the source is then calculated by tomographic reconstruction from projections calculated on conical surfaces. However, several factors influence the quality of the reconstructed images. Because of the small extent and of the limited sensitivity of the camera, many photons are not detected. The spatial and energy resolutions of the detectors bring about measurement errors. Moreover, the image artifacts can be induced by random coincidences, uncertainties on the order of the photon interactions in the camera, incomplete absorptions. Other secondary particles emitted during the irradiation and the absorption in the volume, are also significant noise factors. In this study, we simulated the irradiation of a volume with a proton pencil beam. We modeled a Compton camera with geometry, spatial and energy resolutions inspired from the one currently developed at IPNL. All the secondary particles except γ-photons are withdrawn from the simulation. The photons are recorded one by one, in order to avoid random coincidences in the camera. Once the data are acquired, we reconstructed the 3D image using a list-mode MLEM (LM-MLEM) method where energy measurement errors could be considered. We compare the images obtained with and without attenuation in the patient with the true image of the simulated prompt-γ distribution. In both cases, we reconstruct the images with data acquired respectively with a perfect detector and with a realistic detector. The effects of the different noise sources on the ability to accurately detect displacements of the Bragg peak are showed. Preliminary results obtained in prompt-γ imaging are encouraging and will be further analyzed. However more effort has to be put in the development of the reconstruction algorithms in order to better account for the sources of noise in the images.
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- 2014
19. Data models for the Compton camera acquisition and their influence on the reconstructed images
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Maxim, Voichita, Dauvergne, D., Hilaire, E., Ley, J.-L., Lojacono, X., Testa, E., Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)
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[PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph] ,[PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det] - Abstract
International audience; SPECT imaging of prompt-gamma radiation with Compton cameras is currently investigated over the world as a relevant candidate to hadron therapy monitoring. The acquisition principle of the camera is based on Compton scattering of gamma photons on a first detector followed by absorption in the camera. The emitting point of a detected photon lies on the surface of the cone having its apex at the scattering point, the axis direction opposite to the direction of the scattered photon and the half-opening angle defined by the energies involved in the detection process. To date, several different approaches have been proposed for the modeling of the direct problem. In some models the Compton projections are integrals of the intensity of the source on conical surfaces. Weights are then given to the intensities upon the position of the point on the conical surface. In other models, the projections are the sum of the integrals of the intensity on the generatrices of the cone. Models also differ by the way they account for the measurement uncertainties. The reconstruction of the image of the source is then an important challenge which faces complexity of the model, memory load and computing time issues.
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- 2014
20. Compton imaging in proton therapy: reconstructed image of the simulated prompt-γ distribution
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Hilaire, E., Robert, C., Lojacono, X., Sarrut, D., Buvat, I., Peyrin, F., Maxim, Voichita, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Institut d'Imagerie BioMédicale (I2BM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, European Synchrotron Radiation Facility (ESRF), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)
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Astrophysics::High Energy Astrophysical Phenomena ,Physics::Medical Physics ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing - Abstract
International audience; Purpose: In proton therapy cancer treatments, interactions between the beam and the patient's body lead to nuclear reactions that produce secondary prompt-γ radiation. It was shown that some correlation exists between those photons and the Bragg peak position, and works are ongoing to design imaging systems in order to monitor the deposited dose by exploiting prompt-γ. Teams obtained encouraging results on the performance of the Compton camera for in vivo dosimetry in hadron therapy. The Compton camera detects a photon in two steps. The photon is scattered (at least once) in a first detector (in silicon in our case), then it is absorbed in a second detector (in LYSO). The hits, recorded with positions and energies, define an event. For each event, a Compton cone is defined and the incoming path of the initial ray lies on its surface. The image of the source is then calculated by tomographic reconstruction from projections calculated on conical surfaces. The goal of this work is to assess the ability of the reconstruction algorithms to faithfully calculate the image of the prompt-gamma distribution.
- Published
- 2014
21. PD-006 - Characterizations of DNA copy number variations and spatio-temporal intra tumor heterogeneity in liver metastasis from colorectal cancer patients
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Marques, M., Gambaro, K., du Tertre, M. Couetoux, Witcher, M., Samson, B., Lesperance, B., Ko, Y., Dalfen, R., St-Hilaire, E., Sideris, L., Couture, F., Tejpar, S., Burkes, R., Harb, M., Alcindor, T., Camlioglu, E., Gologan, A., Pelsser, V., McNamara, S., Kavan, P., Kleinman, C., and Batist, G.
- Published
- 2018
- Full Text
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22. Tomographic reconstruction for Compton imaging in proton beam therapy
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Hilaire, E., Lojacono, X., Prost, R., Maxim, Voichita, Peyrin, F., Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles, and European Synchrotron Radiation Facility (ESRF)
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[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2013
23. Imagerie Compton en protonthérapie : de la simulation GATE à la reconstruction d'images
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Hilaire, E., Robert, Cédric, Lojacono, X., Lartizien, C., Buvat, I., Maxim, Voichita, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 4 - Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), and 2 - Images et Modèles
- Subjects
[ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2013
24. Image reconstruction for the Compton camera: calculation of the system matrix
- Author
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Lojacono, X., Hilaire, E., Maxim, Voichita, Prost, R., Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Images et Modèles
- Subjects
[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2013
25. Compton imaging in proton beam therapy: from GATE simulations to image reconstruction
- Author
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Hilaire, E., Robert, Cédric, Lojacono, X., Lartizien, C., Buvat, I., Maxim, Voichita, 4 - Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Imagerie et Modélisation en Neurobiologie et Cancérologie ( IMNC ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), 2 - Images et Modèles, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,ComputingMilieux_MISCELLANEOUS ,[ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging - Abstract
International audience
- Published
- 2013
26. Algorithmes LM-MLEM pour la reconstruction d'images pour caméra Compton
- Author
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Lojacono, X., Hilaire, E., Prasad, R., Maxim, Voichita, Prost, R., Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Images et Modèles
- Subjects
[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
- Published
- 2012
27. 283 - Improved Survival from Transfusion Dependence in Lower-Risk MDS Receiving Iron Chelation, Adjusting for MDS and Patient Characteristics: An MDS-Can Analysis
- Author
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Leitch, H.A., Wells, R.A., Chodirker, L., Zhu, N., Nevill, T.J., Yee, K.W.L., Leber, B., Keating, M.M., Sabloff, M., Hilaire, E. St., Kumar, R., Delage, R., Geddes, M., Storring, J.M., Shamy, A., Elemary, M., Lenis, M., Francis, J., Zhang, L., and Buckstein, R.
- Published
- 2017
- Full Text
- View/download PDF
28. Dietary Risk Factors for Cardiovascular Disease among Low-Income Haitian Adults: Findings from a Population-Based Cohort
- Author
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Adrienne Clermont, Rodney Sufra, Jean Lookens Pierre, Michelle Nour Mourra, Elizabeth L. Fox, Vanessa Rouzier, Eliezer Dade, Stephano St-Preux, Joseph Inddy, Hilaire Erline, Fleurijean Pierre Obed, Lily D. Yan, Miranda Metz, Myung Hee Lee, Daniel W. Fitzgerald, Marie Marcelle Deschamps, Jean W. Pape, and Margaret L. McNairy
- Subjects
nutrition ,Haiti ,cardiovascular disease ,noncommunicable disease ,dietary habits ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Poor diets are responsible for a large burden of noncommunicable disease (NCD). The prevalence of modifiable dietary risk factors is rising in lower-income countries such as Haiti, along with increasing urbanization and shifts to diets high in sugar, salt, and fat. We describe self-reported dietary patterns (intake of fruits, vegetables, fried food, sugar-sweetened beverages, and added salt and oil) among a population-based cohort of low-income adults in Port-au-Prince and assess for associated sociodemographic factors (age, sex, income, education, body mass index). Among 2989 participants, the median age was 40 years, and 58.0% were women. Less than 1% met the World Health Organization recommendation of at least five servings/day of fruits and vegetables. Participants consumed fried food on average 1.6 days/week and sugar-sweetened beverages on average 4.7 days/week; young males of low socioeconomic status were the most likely to consume these dietary risk factors. The vast majority of participants reported usually or often consuming salt (87.1%) and oil (86.5%) added to their meals eaten at home. Our findings underscore the need for public health campaigns, particularly those targeting young males and household cooks preparing family meals at home, to improve dietary patterns in Haiti in order to address the growing NCD burden.
- Published
- 2022
- Full Text
- View/download PDF
29. 134: Data models for the Compton camera acquisition and their influence on the reconstructed images
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Maxim, V., Dauvergne, D., Hilaire, E., Ley, J.L., Lojacono, X., and Testa, E.
- Published
- 2014
- Full Text
- View/download PDF
30. 87: Compton imaging in proton therapy: reconstructed images compared to simulated prompt-γ distribution
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Hilaire, E., Robert, C., Lojacono, X., Sarrut, D., Buvat, I., Peyrin, F., and Maxim, V.
- Published
- 2014
- Full Text
- View/download PDF
31. XLIX. Memoir on a new genus of mammalia called hydromis.
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Geoffroi(Saint-Hilaire), E.
- Published
- 1805
- Full Text
- View/download PDF
32. L'homme aux pommes de terre : (fin)
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Marco de Saint-Hilaire, E.
- Published
- 1878
- Full Text
- View/download PDF
33. O-020 - Copy number variation in longitudinal liver metastases biopsies in colorectal cancer identifies biomarker candidates of resistance to standard chemotherapy.
- Author
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Gambaro, K., Marques, M., McNamara, S., du Tertre, M. Couetoux, Hoffert, C., Srivastava, A., Samson, B., Lesperance, B., Ko, Y., Dalfen, R., St-Hilaire, E., Sideris, L., Couture, F., Burkes, R., Harb, M., Camlioglu, E., Gologan, A., Pelsser, V., Tejpar, S., and Kavan, P.
- Subjects
- *
COLORECTAL liver metastasis , *BIOMARKERS , *CANCER chemotherapy - Published
- 2019
- Full Text
- View/download PDF
34. SMARCAL1 ubiquitylation controls its association with RPA-coated ssDNA and promotes replication fork stability.
- Author
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Yates M, Marois I, St-Hilaire E, Ronato DA, Djerir B, Brochu C, Morin T, Hammond-Martel I, Gezzar-Dandashi S, Casimir L, Drobetsky E, Cappadocia L, Masson JY, Wurtele H, and Maréchal A
- Subjects
- Humans, Replication Protein A genetics, Replication Protein A metabolism, Protein Binding, Ubiquitination, DNA Damage, Genomic Instability, DNA Helicases genetics, DNA Helicases metabolism, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, DNA, Single-Stranded genetics, DNA Replication genetics
- Abstract
Impediments in replication fork progression cause genomic instability, mutagenesis, and severe pathologies. At stalled forks, RPA-coated single-stranded DNA (ssDNA) activates the ATR kinase and directs fork remodeling, 2 key early events of the replication stress response. RFWD3, a recently described Fanconi anemia (FA) ubiquitin ligase, associates with RPA and promotes its ubiquitylation, facilitating late steps of homologous recombination (HR). Intriguingly, RFWD3 also regulates fork progression, restart and stability via poorly understood mechanisms. Here, we used proteomics to identify putative RFWD3 substrates during replication stress in human cells. We show that RFWD3 interacts with and ubiquitylates the SMARCAL1 DNA translocase directly in vitro and following DNA damage in vivo. SMARCAL1 ubiquitylation does not trigger its subsequent proteasomal degradation but instead disengages it from RPA thereby regulating its function at replication forks. Proper regulation of SMARCAL1 by RFWD3 at stalled forks protects them from excessive MUS81-mediated cleavage in response to UV irradiation, thereby limiting DNA replication stress. Collectively, our results identify RFWD3-mediated SMARCAL1 ubiquitylation as a novel mechanism that modulates fork remodeling to avoid genome instability triggered by aberrant fork processing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yates et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
- Full Text
- View/download PDF
35. Third-line treatment patterns in HER2-positive metastatic breast cancer: a retrospective analysis of real-world data in Canada.
- Author
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Gambaro K, Groleau M, McNamara S, Awan A, Salem M, Abdelsalam M, St-Hilaire E, Vincent F, Carrier J, MacKay H, Provencher L, Boudreau D, Hamilou Z, Saad F, Ferrario C, Batist G, and Marques M
- Subjects
- Humans, Female, Lapatinib therapeutic use, Retrospective Studies, Receptor, ErbB-2 analysis, Receptor, ErbB-2 therapeutic use, Canada, Ado-Trastuzumab Emtansine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices., Competing Interests: Author MG was employed by company Knight Therapeutics Inc. This study received funding from Knight Therapeutics Inc. Knight Therapeutics had the following involvement with the study: CR cohort patient selection design and review of the manuscript., (Copyright © 2023 Gambaro, Groleau, McNamara, Awan, Salem, Abdelsalam, St-Hilaire, Vincent, Carrier, MacKay, Provencher, Boudreau, Hamilou, Saad, Ferrario, Batist and Marques.)
- Published
- 2023
- Full Text
- View/download PDF
36. A Rapid and Efficient Method for the Extraction of Histone Proteins.
- Author
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Homsi C, Rajan RE, Minati R, St-Hilaire E, Bonneil E, Dufresne SF, Wurtele H, Verreault A, and Thibault P
- Subjects
- Animals, Protein Processing, Post-Translational, Histone Code, Mammals metabolism, Histones metabolism, Saccharomyces cerevisiae metabolism
- Abstract
Current protocols used to extract and purify histones are notoriously tedious, especially when using yeast cells. Here, we describe the use of a simple filter-aided sample preparation approach enabling histone extraction from yeast and mammalian cells using acidified ethanol, which not only improves extraction but also inactivates histone-modifying enzymes. We show that our improved method prevents N-terminal clipping of H3, an artifact frequently observed in yeast cells using standard histone extraction protocols. Our method is scalable and provides efficient recovery of histones when extracts are prepared from as few as two million yeast cells. We further demonstrate the application of this approach for the analysis of histone modifications in fungal clinical isolates available in a limited quantity. Compared with standard protocols, our method enables the study of histones and their modifications in a faster, simpler, and more robust manner.
- Published
- 2023
- Full Text
- View/download PDF
37. A genome-wide screen reveals that Dyrk1A kinase promotes nucleotide excision repair by preventing aberrant overexpression of cyclin D1 and p21.
- Author
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Bélanger F, Roussel C, Sawchyn C, St-Hilaire E, Gezzar-Dandashi S, Kimenyi Ishimwe AB, Mallette FA, Wurtele H, and Drobetsky E
- Subjects
- Humans, DNA Damage radiation effects, HeLa Cells, Fibroblasts enzymology, Fibroblasts metabolism, Fibroblasts pathology, Fibroblasts radiation effects, S Phase, G1 Phase, Melanoma genetics, Melanoma pathology, Cells, Cultured, Ultraviolet Rays adverse effects, Carcinogenesis genetics, Carcinogenesis pathology, Carcinogenesis radiation effects, Dyrk Kinases, Cyclin D1 genetics, Cyclin D1 metabolism, Cyclin-Dependent Kinase Inhibitor p21 genetics, Cyclin-Dependent Kinase Inhibitor p21 metabolism, DNA Repair, Protein-Tyrosine Kinases metabolism, Protein Serine-Threonine Kinases metabolism
- Abstract
Nucleotide excision repair (NER) eliminates highly genotoxic solar UV-induced DNA photoproducts that otherwise stimulate malignant melanoma development. Here, a genome-wide loss-of-function screen, coupling CRISPR/Cas9 technology with a flow cytometry-based DNA repair assay, was used to identify novel genes required for efficient NER in primary human fibroblasts. Interestingly, the screen revealed multiple genes encoding proteins, with no previously known involvement in UV damage repair, that significantly modulate NER uniquely during S phase of the cell cycle. Among these, we further characterized Dyrk1A, a dual specificity kinase that phosphorylates the proto-oncoprotein cyclin D1 on threonine 286 (T286), thereby stimulating its timely cytoplasmic relocalization and proteasomal degradation, which is required for proper regulation of the G1-S phase transition and control of cellular proliferation. We demonstrate that in UV-irradiated HeLa cells, depletion of Dyrk1A leading to overexpression of cyclin D1 causes inhibition of NER uniquely during S phase and reduced cell survival. Consistently, expression/nuclear accumulation of nonphosphorylatable cyclin D1 (T286A) in melanoma cells strongly interferes with S phase NER and enhances cytotoxicity post-UV. Moreover, the negative impact of cyclin D1 (T286A) overexpression on repair is independent of cyclin-dependent kinase activity but requires cyclin D1-dependent upregulation of p21 expression. Our data indicate that inhibition of NER during S phase might represent a previously unappreciated noncanonical mechanism by which oncogenic cyclin D1 fosters melanomagenesis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
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38. The burden of red blood cell transfusions in patients with lower-risk myelodysplastic syndromes and ring sideroblasts: an analysis of the prospective MDS-CAN registry.
- Author
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Buckstein R, Chodirker L, Yee KWL, Geddes M, Leitch HA, Christou G, Banerji V, Leber B, Khalaf D, St-Hilaire E, Finn N, Nevill T, Keating MM, Storring J, Parmentier A, Thambipillai A, Tang D, Westcott C, Cameron C, and Spin P
- Subjects
- Humans, Quality of Life, Prospective Studies, Registries, Erythrocyte Transfusion adverse effects, Myelodysplastic Syndromes drug therapy
- Abstract
Many patients with lower-risk myelodysplastic syndromes (LR MDS) require long-term red blood cell (RBC) transfusions to manage anemia. The consequences of RBC transfusions in LR MDS with ring sideroblasts (LR MDS-RS) are not well known. We estimated the association between cumulative RBC dose density and clinical and patient-reported outcomes using data from the MDS-CAN registry for patients enrolled between January 2008 and December 2018. Outcomes included overall survival, hospitalization, and health-related quality of life (HRQoL). A total of 145 enrolled patients with LR MDS and RS ≥5% had a median follow-up time of 27.1 months; 45 had no transfusions during follow-up, 51 had <1 transfusion per month, and 49 had ≥1 transfusion per month. The cumulative density of RBC transfusions was associated with significantly greater mortality, hospitalization, and inferior HRQoL, suggesting that exposure to RBC transfusion may constitute a significant treatment burden in patients with LR MDS-RS.
- Published
- 2023
- Full Text
- View/download PDF
39. High transferrin saturation predicts inferior clinical outcomes in patients with myelodysplastic syndromes.
- Author
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Teichman J, Geddes M, Zhu N, Keating MM, Sabloff M, Christou G, Leber B, Khalaf D, St-Hilaire E, Finn N, Shamy A, Yee KWL, Storring JM, Nevill TJ, Delage R, Elemary M, Banerji V, Houston B, Mozessohn L, Chodirker L, Zhang L, Siddiqui M, Parmentier A, Leitch HA, and Buckstein RJ
- Subjects
- Humans, Aged, Canada, Ferritins, Transferrins, Transferrin, Iron, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes therapy
- Abstract
Iron overload (IO) reflected by elevated ferritin is associated with increased mortality in myelodysplastic syndromes (MDS), however, ferritin is an imperfect metric. Elevated labile plasma iron correlates with clinical outcomes and transferrin saturation (TSAT) >80%, but is not readily measurable. The trajectory of TSAT, and its association with clinical outcomes remain undefined. Canadian MDS registry patients were evaluated. Mean TSAT, mean ferritin and transfusion dose density (TDD) were determined. Survival was evaluated by TSAT and ferritin (<50%, 50-80%, >80%), (≤500 μg/L, 501-800 μg/L, >800 μg/L). In 718 patients, median age was 74 years; 12%, 31%, 29%, 15% and 13% were IPSS-R very low, low, intermediate, high and very high. TSAT and ferritin were moderately correlated (r=0.63, P<0.0001). TSAT increased over time in transfusion- dependent patients (P=0.006). Higher TSAT and ferritin were associated with inferior 5-year overall (OS), progression- free (PFS), and leukemia-free survival (LFS) (P≤0.008) and higher TDD with inferior 5-year OS. TSAT >80% trended with inferior cardiac death-free survival (P=0.053). In univariate analysis, age, IPSS-R, blast percentage by Eastern Cooperative Oncology Group Performance Status, frailty, Charlson Comorbidity Index, iron chelation (Y/N), TDD, TSAT and ferritin were significantly associated with inferior OS. By multivariable analysis, TSAT >80% (P=0.007) remained significant for OS (R2 30.3%). In MDS, TSAT >80% and ferritin >800 μg/L portended inferior OS, PFS and LFS. TSAT may indicate the presence of oxidative stress, and is readily measurable in a clinical setting. The relationship between TSAT and cardiac death-free survival warrants further study.
- Published
- 2023
- Full Text
- View/download PDF
40. A natural history of lower-risk myelodysplastic syndromes with ring sideroblasts: an analysis of the MDS-CAN registry.
- Author
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Buckstein R, Chodirker L, Mozessohn L, Yee KWL, Geddes M, Zhu N, Shamy A, Leitch HA, Christou G, Banerji V, Brian L, Khalaf D, St-Hilaire E, Finn N, Nevill T, Keating MM, Storring J, Delage R, Parmentier A, Thambipillai A, Siddiqui M, Westcott C, Cameron C, Mamedov A, Spin P, and Tang D
- Subjects
- Humans, Chelation Therapy, Prognosis, Quality of Life, Registries, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes epidemiology, Myelodysplastic Syndromes therapy
- Abstract
Patients with lower-risk (LR) myelodysplastic syndromes (MDS) with ring sideroblasts (RS) have better prognosis than those without RS, but how they fare over time is not fully understood. This study's objective was to assess the natural history of LR MDS with RS ≥5% using MDS-CAN registry individual data. Kaplan-Meier estimates and generalized linear mixed models were used to describe time-to-event outcomes and continuous outcomes, respectively. One hundred and thirty-eight patients were enrolled; median times from diagnosis to enrollment and follow-up were 6.6 and 39.6 months, respectively. Within 5 years of enrollment, 65% of patients had ≥1 red blood cell transfusion dependence episode. Within 5 years of diagnosis, 59% developed iron overload, 38% received iron chelation therapy, 14% progressed to acute myeloid leukemia, and 42% died. Patients exhibited inferior health-related quality of life trends. These first real-world data in LR MDS-RS in Canada indicate a high level of morbidity and mortality over a 5-year period. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02537990.
- Published
- 2022
- Full Text
- View/download PDF
41. A genome-wide screen identifies SCAI as a modulator of the UV-induced replicative stress response.
- Author
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Lemay JF, St-Hilaire E, Ronato DA, Gao Y, Bélanger F, Gezzar-Dandashi S, Kimenyi Ishimwe AB, Sawchyn C, Lévesque D, McQuaid M, Boisvert FM, Mallette FA, Masson JY, Drobetsky EA, and Wurtele H
- Subjects
- Humans, Ultraviolet Rays adverse effects, DNA Replication genetics, Chromatin, DNA, Mutagens, Replication Protein A genetics, Replication Protein A metabolism, DNA, Single-Stranded genetics
- Abstract
Helix-destabilizing DNA lesions induced by environmental mutagens such as UV light cause genomic instability by strongly blocking the progression of DNA replication forks (RFs). At blocked RF, single-stranded DNA (ssDNA) accumulates and is rapidly bound by Replication Protein A (RPA) complexes. Such stretches of RPA-ssDNA constitute platforms for recruitment/activation of critical factors that promote DNA synthesis restart. However, during periods of severe replicative stress, RPA availability may become limiting due to inordinate sequestration of this multifunctional complex on ssDNA, thereby negatively impacting multiple vital RPA-dependent processes. Here, we performed a genome-wide screen to identify factors that restrict the accumulation of RPA-ssDNA during UV-induced replicative stress. While this approach revealed some expected "hits" acting in pathways such as nucleotide excision repair, translesion DNA synthesis, and the intra-S phase checkpoint, it also identified SCAI, whose role in the replicative stress response was previously unappreciated. Upon UV exposure, SCAI knock-down caused elevated accumulation of RPA-ssDNA during S phase, accompanied by reduced cell survival and compromised RF progression. These effects were independent of the previously reported role of SCAI in 53BP1-dependent DNA double-strand break repair. We also found that SCAI is recruited to UV-damaged chromatin and that its depletion promotes nascent DNA degradation at stalled RF. Finally, we (i) provide evidence that EXO1 is the major nuclease underlying ssDNA formation and DNA replication defects in SCAI knockout cells and, consistent with this, (ii) demonstrate that SCAI inhibits EXO1 activity on a ssDNA gap in vitro. Taken together, our data establish SCAI as a novel regulator of the UV-induced replicative stress response in human cells., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
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42. Catheter ablation of ventricular tachycardia in patients with postinfarction left ventricular aneurysm.
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Amin M, Farwati M, Hilaire E, Siontis KC, Madhavan M, Kapa S, Mulpuru SK, Deshmukh AJ, Cha YM, Friedman PA, Munger T, Asirvatham SJ, and Killu AM
- Subjects
- Adolescent, Aged, Heart Ventricles diagnostic imaging, Heart Ventricles surgery, Humans, Male, Middle Aged, Recurrence, Treatment Outcome, Catheter Ablation adverse effects, Heart Aneurysm diagnostic imaging, Heart Aneurysm etiology, Myocardial Infarction complications, Myocardial Infarction diagnostic imaging, Myocardial Infarction surgery, Tachycardia, Ventricular diagnostic imaging, Tachycardia, Ventricular etiology
- Abstract
Background: While ventricular tachycardia (VT) in the setting of postmyocardial infarction left ventricular aneurysms (LVA) is not uncommonly encountered, there is a scarcity of data regarding the safety, efficacy, and outcomes of ablation of VT in this subset of patients., Methods: Our study included consecutive patients aged 18 years or older with postmyocardial infarction LVA who presented to Mayo Clinic for catheter ablation of VT between 2002 and 2018., Results: Of 34 patients, the mean age was 70.4 ± 9.1 years; 91% were male. Mean LVEF was 29 ± 9.7% and left ventricular end-diastolic dimension was 64.9 ± 6.6 mm. The site of the LVA was apical in 21 patients (62%). Fifteen patients (44%) presented with electrical storm or incessant VT. Nine patients (26%) had a history of intracardiac thrombus. All except for one patient had at least one VT originating from the aneurysm. The mean number of VTs was 2.9 ± 1.7. All patients underwent ablation at the site of the aneurysm. Ablation outside the aneurysm was performed in 13 patients (38%). Low-voltage fractionated potentials and/or late potentials at the aneurysmal site were present in all cases. Complete elimination of all VTs was achieved in 18 (53%), while the elimination of the clinical VT with continued inducibility of nonclinical VTs was achieved in a further 11 patients (32%). Two patients developed cardiac tamponade requiring pericardiocentesis. During a mean follow-up period of 2.3 ± 2.4 years, 11 patients (32%) experienced VT recurrence. Freedom from all-cause mortality at 1-year follow-up was 94%., Conclusion: Radiofrequency catheter ablation targeting the aneurysmal site is a feasible and reasonably effective management strategy for clinical VTs in patients with postinfarction LVA., (© 2021 Wiley Periodicals LLC.)
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- 2021
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43. Abortion-related morbidity in six Latin American and Caribbean countries: findings of the WHO/HRP multi-country survey on abortion (MCS-A).
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Romero M, Gomez Ponce de Leon R, Baccaro LF, Carroli B, Mehrtash H, Randolino J, Menjivar E, Estevez Saint-Hilaire E, Huatuco MDP, Hernandez Muñoz R, Garcia Camacho G, Thwin SS, Campodonico L, Abalos E, Giordano D, Gamerro H, Kim CR, Ganatra B, Gülmezoglu M, Tuncalp Ö, and Carroli G
- Subjects
- Caribbean Region, Cross-Sectional Studies, Female, Humans, Infant, Latin America epidemiology, Morbidity, Pregnancy, World Health Organization, Abortion, Induced adverse effects
- Abstract
Introduction: Abortion-related complications are a significant cause of morbidity and mortality among women in many Latin American and Caribbean (LAC) countries. The objective of this study was to characterise abortion-related complication severity, describe the management of these complications and report women's experiences with abortion care in selected countries of the Americas region., Methods: This is a cross-sectional study of 70 health facilities across six countries in the region. We collected data on women's characteristics including socio-demographics, obstetric history, clinical information, management procedures and using Audio Computer-Assisted Self-Interviewing (ACASI) survey the experience of abortion care. Descriptive bivariate analysis was performed for women's characteristics, management of complications and reported experiences of abortion care by severity of complications, organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Generalised linear estimation models were used to assess the association between women's characteristics and severity of complications., Results: We collected data on 7983 women with abortion-related complications. Complications were classified as mild (46.3%), moderate (49.5%), potentially life-threatening (3.1%), near-miss cases (1.1%) and deaths (0.2%). Being single, having a gestational age of ≥13 weeks and having expelled products of conception before arrival at the facility were significantly associated with experiencing severe maternal outcomes compared with mild complications.Management of abortion-related complications included both uterotonics and uterine evacuation for two-thirds of the women while one-third received uterine evacuation only. Surgical uterine evacuation was performed in 93.2% (7437/7983) of women, being vacuum aspiration the most common one (5007/7437, 67.4%).Of the 327 women who completed the ACASI survey, 16.5% reported having an induced abortion, 12.5% of the women stated that they were not given explanations regarding their care nor were able to ask questions during their examination and treatment with percentages increasing with the severity of morbidity., Conclusions: This is one of the first studies using a standardised methodology to measure severity of abortion-related complications and women's experiences with abortion care in LAC. Results aim to inform policies and programmes addressing sexual and reproductive rights and health in the region., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)
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- 2021
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44. Patient-reported fatigue refines prognosis in higher-risk myelodysplastic syndromes (MDS): a MDS-CAN study.
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Amitai I, Geddes M, Zhu N, Keating MM, Sabloff M, Christou G, Leber B, Khalaf D, Leitch HA, St-Hilaire E, Finn N, Shamy A, Yee K, Storring J, Nevill T, Delage R, Elemary M, Banerji V, Chodirker L, Mozessohn L, Parmentier A, Siddiqui M, Mamedov A, Zhang L, and Buckstein R
- Subjects
- Adult, Aged, Aged, 80 and over, Canada epidemiology, Fatigue diagnosis, Fatigue epidemiology, Female, Humans, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes epidemiology, Patient Reported Outcome Measures, Prognosis, Quality of Life, Registries, Fatigue complications, Myelodysplastic Syndromes complications
- Abstract
The incorporation of patient-reported outcomes with traditional disease risk classification was found to strengthen survival prediction in patients with myelodysplastic syndromes (MDS). In the present Canadian MDS registry analysis, we validate a recently reported prognostic model, the Fatigue-International Prognostic Scoring System among higher-risk patients [FA-IPSS(h)], which incorporates patients' reported fatigue, assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30), with a threshold of ≥45 points, in higher IPSS score, stratifying them into distinct subgroups with different survival outcomes. We further validated this concept, using the Revised IPSS >3·5 as cut-off for the definition of higher-risk MDS, and patients' reported fatigue according to Edmonton Symptom Self-Assessment Scale (ESAS) Global Fatigue Scale (GFS), a single-item fatigue rating scale, which is easier to deploy. This emphasises the power of self-reported fatigue at refining overall survival predictions in higher-risk MDS and further bolsters the importance of considering patient-related outcomes in global assessments., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2021
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45. Copy number and transcriptome alterations associated with metastatic lesion response to treatment in colorectal cancer.
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Gambaro K, Marques M, McNamara S, Couetoux du Tertre M, Diaz Z, Hoffert C, Srivastava A, Hébert S, Samson B, Lespérance B, Ko YJ, Dalfen R, St-Hilaire E, Sideris L, Couture F, Burkes R, Harb M, Camlioglu E, Gologan A, Pelsser V, Constantin A, Greenwood CMT, Tejpar S, Kavan P, Kleinman CL, and Batist G
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Bevacizumab therapeutic use, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Drug Resistance, Neoplasm genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms secondary, Male, Middle Aged, Progression-Free Survival, Exome Sequencing, Colorectal Neoplasms genetics, DNA Copy Number Variations genetics, Transcriptome genetics
- Abstract
Background: Therapeutic resistance is the main cause of death in metastatic colorectal cancer. To investigate genomic plasticity, most specifically of metastatic lesions, associated with response to first-line systemic therapy, we collected longitudinal liver metastatic samples and characterized the copy number aberration (CNA) landscape and its effect on the transcriptome., Methods: Liver metastatic biopsies were collected prior to treatment (pre, n = 97) and when clinical imaging demonstrated therapeutic resistance (post, n = 43). CNAs were inferred from whole exome sequencing and were correlated with both the status of the lesion and overall patient progression-free survival (PFS). We used RNA sequencing data from the same sample set to validate aberrations as well as independent datasets to prioritize candidate genes., Results: We identified a significantly increased frequency gain of a unique CN, in liver metastatic lesions after first-line treatment, on chr18p11.32 harboring 10 genes, including TYMS, which has not been reported in primary tumors (GISTIC method and test of equal proportions, FDR-adjusted p = 0.0023). CNA lesion profiles exhibiting different treatment responses were compared and we detected focal genomic divergences in post-treatment resistant lesions but not in responder lesions (two-tailed Fisher's Exact test, unadjusted p ≤ 0.005). The importance of examining metastatic lesions is highlighted by the fact that 15 out of 18 independently validated CNA regions found to be associated with PFS in this study were only identified in the metastatic lesions and not in the primary tumors., Conclusion: This investigation of genomic-phenotype associations in a large colorectal cancer liver metastases cohort identified novel molecular features associated with treatment response, supporting the clinical importance of collecting metastatic samples in a defined clinical setting., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)
- Published
- 2021
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46. Revised 15-item MDS-specific frailty scale maintains prognostic potential.
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Wan BA, Nazha A, Starkman R, Alibhai S, Wells RA, Geddes M, Zhu N, Keating MM, Leber B, Chodirker L, Sabloff M, Christou G, Leitch HA, St-Hilaire E, Finn N, Shamy A, Yee KWL, Storring J, Nevill TJ, Delage R, Elemary M, Banerji V, Parmentier A, Siddiqui M, Kirubananthaan A, Mamedov A, Zhang L, and Buckstein R
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- Humans, Prognosis, Risk Factors, Frailty diagnosis, Myelodysplastic Syndromes diagnosis
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- 2020
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47. Chapitre 3. Horizontal Exchange, Relations, and Resistance in Bioart and Practice-based Research.
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Hey M, Hunter W, and St-Hilaire E
- Abstract
Bioart sits at the intersection of two relatively elite fields of knowledge specialization and production: Biotechnology and Art. These specializations occupy different strata of the academic hierarchy, requiring credentials and disciplinary rigour that, historically, have tended to validate delineated specificities instead of similarities in research; in turn, these areas of expertise privilege credentialed mastery over other ways of knowing. With its overlap of the arts and the sciences, how might bioart function to flatten existing hierarchies and foster more horizontally collaborative methods towards a shared and critical understanding of bioethics? This paper builds on the notion of horizontal collaboration theorized by Couture et al. (2017), critically attending to the ruptures and resistances (real, perceived, and constructed) that occur when working transversally within verticalized institutions. Combining theoretical interventions with practice-based case studies that deconstruct spaces of bio-artistic inquiry - from the lab or studio to kitchens, classrooms, and galleries - this paper aims to build 'good' relations according to Joanna Zylinska's definition of a body compounding it's relation to another, thereby increasing the power of both.
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- 2020
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48. Iron overload in myelodysplastic syndromes: Evidence based guidelines from the Canadian consortium on MDS.
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Leitch HA, Buckstein R, Zhu N, Nevill TJ, Yee KWL, Leber B, Keating MM, St Hilaire E, Kumar R, Delage R, Geddes M, Storring JM, Shamy A, Elemary M, and Wells RA
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- Canada, Female, Humans, Male, Multicenter Studies as Topic, Practice Guidelines as Topic, Iron Overload diagnosis, Iron Overload metabolism, Iron Overload pathology, Iron Overload therapy, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes metabolism, Myelodysplastic Syndromes pathology, Myelodysplastic Syndromes therapy
- Abstract
In 2008 the first evidence-based Canadian consensus guideline addressing the diagnosis, monitoring and management of transfusional iron overload in patients with myelodysplastic syndromes (MDS) was published. The Canadian Consortium on MDS, comprised of hematologists from across Canada with a clinical and academic interest in MDS, reconvened to update these guidelines. A literature search was updated in 2017; topics reviewed include mechanisms of iron overload induced cellular damage, evidence for clinical endpoints impacted by iron overload including organ dysfunction, infections, marrow failure, overall survival, acute myeloid leukemia progression, and endpoints around hematopoietic stem-cell transplant. Evidence for an impact of iron reduction on the same endpoints is discussed, guidelines are updated, and areas identified where evidence is suboptimal. The guidelines address common questions around the diagnosis, workup and management of iron overload in clinical practice, and take the approach of who, when, why and how to treat iron overload in MDS. Practical recommendations for treatment and monitoring are made. Evidence levels and grading of recommendations are provided for all clinical endpoints examined., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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49. Eastern Canadian Colorectal Cancer Consensus Conference 2017.
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McGee SF, AlGhareeb W, Ahmad CH, Armstrong D, Babak S, Berry S, Biagi J, Booth C, Bossé D, Champion P, Colwell B, Finn N, Goel R, Gray S, Green J, Harb M, Hyde A, Jeyakumar A, Jonker D, Kanagaratnam S, Kavan P, MacMillan A, Muinuddin A, Patil N, Porter G, Powell E, Ramjeesingh R, Raza M, Rorke S, Seal M, Servidio-Italiano F, Siddiqui J, Simms J, Smithson L, Snow S, St-Hilaire E, Stuckless T, Tate A, Tehfe M, Thirlwell M, Tsvetkova E, Valdes M, Vickers M, Virik K, Welch S, Marginean C, and Asmis T
- Subjects
- Canada, Consensus, History, 21st Century, Humans, Colorectal Neoplasms pathology
- Abstract
The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in radiation oncology, medical oncology, surgical oncology, and cancer genetics who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of gastric, rectal, and colon cancer, including ■ identification and management of hereditary gastric and colorectal cancer (crc);■ palliative systemic therapy for metastatic gastric cancer;■ optimum duration of preoperative radiation in rectal cancer-that is, short- compared with long-course radiation;■ management options for peritoneal carcinomatosis in crc;■ implications of tumour location for treatment and prognosis in crc; and■ new molecular markers in crc.
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- 2018
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50. A predictive model of response to erythropoietin stimulating agents in myelodysplastic syndrome: from the Canadian MDS patient registry.
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Houston BL, Jayakar J, Wells RA, Lenis M, Zhang L, Zhu N, Leitch HA, Nevill TJ, Yee KWL, Leber B, Sabloff M, St-Hilaire E, Kumar R, Geddes M, Shamy A, Storring JM, Keating MM, Elemary M, Delage R, Mamedov A, and Buckstein R
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- Canada, Female, Ferritins blood, Humans, Infant, Infant, Newborn, L-Lactate Dehydrogenase blood, Male, Prospective Studies, Erythropoietin blood, Hematinics administration & dosage, Models, Biological, Myelodysplastic Syndromes blood, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes mortality, Registries
- Abstract
Prediction of response to erythropoietin stimulating agents (ESAs) in anemic MDS patients is often based on the Nordic score. We wished to validate the Nordic score (IWG 2006 response criteria) in a larger cohort and determine if other variables such as IPSS/IPSS-R, ferritin, LDH, and a novel European ESA response score (Santini 2013) were of prognostic importance. We analyzed 208 ESA-treated MDS patients (WHO 2008 criteria) from a prospective registry. Ninety-four and 93% had lower risk scores by IPSS (low/int - 1) and IPSS-R (low/very low), respectively. Erythroid response was achieved in 94 patients (47%); responses were similar with erythropoietin (50%) and darbepoetin (39%; p = 0.2). The Nordic and European scores were both validated on univariate analysis. Variables independently predictive of response in multivariate analysis were low-risk IPSS score (OR 0.1, p = 0.0016) and serum EPO level < 100 mIU/mL (OR 8.7, p < 0.0001). We propose a new ESA response score, consisting of (a) IPSS low score (1 point) and (b) serum EPO levels < 100 mIU/ml (2 points), yielding scores ranging from 0 to 3, with response rates varying from 17 to 81%. The Nordic score has validity but we observed lower than the expected response rates in the best risk group. Our proposed scoring system appears more discriminating but needs validation.
- Published
- 2017
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