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2,810 results on '"CHAN, JONATHAN"'

103. Residual Disease Activity In Canadian Patients With Psoriatic Arthritis (PsA) Treated With Advanced Therapies: Results From A Multi-Registry Analysis (UNISON-PsA)

Author

Gladman, Dafna D., primary, Chandran, Vinod, additional, Rosen, Cheryl F., additional, Rohekar, Sherry, additional, Boyd, Tristan, additional, Eder, Lihi, additional, Rahman, Proton, additional, Dutz, Jan, additional, Chan, Jonathan, additional, Haydey, Richard P., additional, Barac, Snezana, additional, Laliberté, Marie-Claude, additional, Girard, Tanya, additional, Fournier, Pierre-André, additional, Sutton, Mitchell, additional, Pereira, Daniel, additional, Chim, Tina, additional, Coupal, Louis, additional, and Choquette, Denis, additional

Published
2024
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104. Effects of Cannabis Use During Pregnancy

Author

Nguyen, Han, primary, Chamanadjian, Christopher, additional, Chan, Jonathan, additional, Cannell, Ruslana, additional, Mandap, Joshua, additional, Cummings, Sydney, additional, Moffitt, Molly, additional, Alamdari, Danial, additional, Dong, Fanglong, additional, Siegler, David, additional, Challakere, Kedar, additional, and Ogunyemi, Dotun, additional

Published
2024
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111. In vitro clearance of doxorubicin with a DNA-based filtration device designed for intravascular use with intra-arterial chemotherapy

Author

Aboian, Mariam S, Yu, Jay F, Gautam, Ayushi, Sze, Chia-Hung, Yang, Jeffrey K, Chan, Jonathan, Lillaney, Prasheel V, Jordan, Caroline D, Oh, Hee-Jeung, Wilson, David M, Patel, Anand S, Wilson, Mark W, and Hetts, Steven W

Subjects
Cardiovascular, Cancer, Bioengineering, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Animals, Arteries, DNA, Doxorubicin, Equipment Design, Feasibility Studies, Filtration, Kinetics, Swine, Endovascular devices, Chemotherapy, Detoxification, Biomedical Engineering, Materials Engineering, Analytical Chemistry
Abstract

To report a novel method using immobilized DNA within mesh to sequester drugs that have intrinsic DNA binding characteristics directly from flowing blood. DNA binding experiments were carried out in vitro with doxorubicin in saline (PBS solution), porcine serum, and porcine blood. Genomic DNA was used to identify the concentration of DNA that shows optimum binding clearance of doxorubicin from solution. Doxorubicin binding kinetics by DNA enclosed within porous mesh bags was evaluated. Flow model simulating blood flow in the inferior vena cava was used to determine in vitro binding kinetics between doxorubicin and DNA. The kinetics of doxorubicin binding to free DNA is dose-dependent and rapid, with 82-96 % decrease in drug concentration from physiologic solutions within 1 min of reaction time. DNA demonstrates faster binding kinetics by doxorubicin as compared to polystyrene resins that use an ion exchange mechanism. DNA contained within mesh yields an approximately 70 % decrease in doxorubicin concentration from solution within 5 min. In the IVC flow model, there is a 70 % drop in doxorubicin concentration at 60 min. A DNA-containing ChemoFilter device can rapidly clear clinical doses of doxorubicin from a flow model in simple and complex physiological solutions, thereby suggesting a novel approach to reduce the toxicity of DNA-binding drugs.

Published
2016

112. The mTOR Complex Controls HIV Latency

Author

Besnard, Emilie, Hakre, Shweta, Kampmann, Martin, Lim, Hyung W, Hosmane, Nina N, Martin, Alyssa, Bassik, Michael C, Verschueren, Erik, Battivelli, Emilie, Chan, Jonathan, Svensson, J Peter, Gramatica, Andrea, Conrad, Ryan J, Ott, Melanie, Greene, Warner C, Krogan, Nevan J, Siliciano, Robert F, Weissman, Jonathan S, and Verdin, Eric

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Genetics, Infectious Diseases, Sexually Transmitted Infections, HIV/AIDS, Infection, Adaptor Proteins, Signal Transducing, CD4-Positive T-Lymphocytes, Cell Line, Clustered Regularly Interspaced Short Palindromic Repeats, Cyclin-Dependent Kinase 9, Gene Expression Regulation, Viral, Gene Knockdown Techniques, Genes, Viral, HIV Infections, HIV-1, Humans, K562 Cells, Phosphorylation, Positive Transcriptional Elongation Factor B, RNA, Small Interfering, Signal Transduction, TOR Serine-Threonine Kinases, Transcription, Genetic, Virus Latency, mTOR Associated Protein, LST8 Homolog, tat Gene Products, Human Immunodeficiency Virus, MTOR Associated Protein, LST8 Homolog, HIV LTR, HIV latency, HIV transcription, genome-wide shRNA screen, latency reversal, mTOR inhibition, reactivation from latency, Microbiology, Biochemistry and cell biology, Medical microbiology
Abstract

A population of CD4 T lymphocytes harboring latent HIV genomes can persist in patients on antiretroviral therapy, posing a barrier to HIV eradication. To examine cellular complexes controlling HIV latency, we conducted a genome-wide screen with a pooled ultracomplex shRNA library and in vitro system modeling HIV latency and identified the mTOR complex as a modulator of HIV latency. Knockdown of mTOR complex subunits or pharmacological inhibition of mTOR activity suppresses reversal of latency in various HIV-1 latency models and HIV-infected patient cells. mTOR inhibitors suppress HIV transcription both through the viral transactivator Tat and via Tat-independent mechanisms. This inhibition occurs at least in part via blocking the phosphorylation of CDK9, a p-TEFb complex member that serves as a cofactor for Tat-mediated transcription. The control of HIV latency by mTOR signaling identifies a pathway that may have significant therapeutic opportunities.

Published
2016

113. Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression

Author

Tang, Chih-Min, Lee, Tracy E, Syed, Sabriya A, Burgoyne, Adam M, Leonard, Stephanie Y, Gao, Fei, Chan, Jonathan C, Shi, Eileen, Chmielecki, Juliann, Morosini, Deborah, Wang, Kai, Ross, Jeffrey S, Kendrick, Michael L, Bardsley, Michael R, De Siena, Martina, Mao, Junhao, Harismendy, Olivier, Ordog, Tamas, and Sicklick, Jason K

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Rare Diseases, Digestive Diseases, Genetics, Cancer, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Antineoplastic Agents, Arsenic Trioxide, Arsenicals, Binding Sites, Cell Line, Tumor, Cell Survival, Cilia, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumors, Gene Expression Regulation, Neoplastic, Humans, Imatinib Mesylate, Interstitial Cells of Cajal, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Oxides, Promoter Regions, Genetic, Proto-Oncogene Proteins c-kit, RNA Interference, RNA, Messenger, Receptor, Platelet-Derived Growth Factor alpha, Signal Transduction, Transfection, Zinc Finger Protein GLI1, Zinc Finger Protein Gli2, Zinc Finger Protein Gli3, arsenic trioxide, GIST, GLI, ICC, imatinib-resistant, Oncology and carcinogenesis
Abstract

Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST.

Published
2016

120. MicroRNA-155 Reinforces HIV Latency*

Author

Ruelas, Debbie S, Chan, Jonathan K, Oh, Eugene, Heidersbach, Amy J, Hebbeler, Andrew M, Chavez, Leonard, Verdin, Eric, Rape, Michael, and Greene, Warner C

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Biotechnology, Sexually Transmitted Infections, HIV/AIDS, Infectious Diseases, Genetics, Infection, 3' Untranslated Regions, Amino Acid Motifs, Base Sequence, CD4-Positive T-Lymphocytes, Cell Death, Gene Silencing, Genes, Reporter, HIV-1, Humans, I-kappa B Proteins, Lentivirus, MicroRNAs, Molecular Sequence Data, NF-KappaB Inhibitor alpha, NF-kappa B, Sequence Homology, Nucleic Acid, Transcription Factors, Tripartite Motif Proteins, Ubiquitin, Ubiquitin-Protein Ligases, Virus Latency, Virus Replication, HIV-1 latency, IκBα, TRIM32, microRNA, molecular biology, viral transcription, virology, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

The presence of a small number of infected but transcriptionally dormant cells currently thwarts a cure for the more than 35 million individuals infected with HIV. Reactivation of these latently infected cells may result in three fates: 1) cell death due to a viral cytopathic effect, 2) cell death due to immune clearance, or 3) a retreat into latency. Uncovering the dynamics of HIV gene expression and silencing in the latent reservoir will be crucial for developing an HIV-1 cure. Here we identify and characterize an intracellular circuit involving TRIM32, an HIV activator, and miR-155, a microRNA that may promote a return to latency in these transiently activated reservoir cells. Notably, we demonstrate that TRIM32, an E3 ubiquitin ligase, promotes reactivation from latency by directly modifying IκBα, leading to a novel mechanism of NF-κB induction not involving IκB kinase activation.

Published
2015

123. A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

Author

See Hoe, Louise E., Wildi, Karin, Obonyo, Nchafatso G., Bartnikowski, Nicole, McDonald, Charles, Sato, Kei, Heinsar, Silver, Engkilde-Pedersen, Sanne, Diab, Sara, Passmore, Margaret R., Wells, Matthew A., Boon, Ai-Ching, Esguerra, Arlanna, Platts, David G., James, Lynnette, Bouquet, Mahe, Hyslop, Kieran, Shuker, Tristan, Ainola, Carmen, Colombo, Sebastiano M., Wilson, Emily S., Millar, Jonathan E., Malfertheiner, Maximillian V., Reid, Janice D., O’Neill, Hollier, Livingstone, Samantha, Abbate, Gabriella, Sato, Noriko, He, Ting, von Bahr, Viktor, Rozencwajg, Sacha, Byrne, Liam, Pimenta, Leticia P., Marshall, Lachlan, Nair, Lawrie, Tung, John-Paul, Chan, Jonathan, Haqqani, Haris, Molenaar, Peter, Li Bassi, Gianluigi, Suen, Jacky Y., McGiffin, David C., and Fraser, John F.

Published
2021
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130. Next Generation of Global Surgeons: Aligning Interest With Early Access to Global Surgery Education

Author

Acker, Rachael, Aharon, Shani, Alty, Isaac, Anyanwu, Chikamuche, Beck, Nicole, Brandt, Alyssa, Briggs, Logan, Caminita, Christena, Chaet, Alexis, Chan, Jonathan, Chiu, Lucinda, Cueto, Carmen, Daneshdoost, Shanaz, Edalatpour, Roya, Garba, Deen, Giles, Andrew E., Gualy, Sebastian, Haider, Ali, Hamilton, Charles, Hauser, Blake M., He, Puhan, Im, Chaewon, Jayaram, Anusha, Jhun, Ray, Joshi, Avina, Kahanu, Alexis, Kim, Na Eun, Kim, Raymond, Lauffer, Sam, McHargue, Cody, Meeks, Monica, Mehta, Ambar, Mendoza, Ardi, Miller, Matt, Nourian, Maziar, Ottesen, Taylor D., Patel, Prachi, Peck, Connor J., Pyarali, Monika, Ramirez, Adriana G., Rehman, Shahyan, Shankar, Bairavi, Stetson, Alyssa, Still, Megan E.H., Tutunjian, Alyssa, Yibrehu, Betel, Yu, Kristin E., Scott, Erin M., Fallah, Parisa N., Blitzer, David N., NeMoyer, Rachel E., Sifri, Ziad, Hanna, Joseph S., and Peck, Gregory L.

Published
2019
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138. Unsupervised Deep Tensor Network for Hyperspectral–Multispectral Image Fusion

Author

Yang, Jingxiang, Xiao, Liang, Zhao, Yong-Qiang, and Chan, Jonathan Cheung-Wai

Abstract

Fusing low-resolution (LR) hyperspectral images (HSIs) with high-resolution (HR) multispectral images (MSIs) is a significant technology to enhance the resolution of HSIs. Despite the encouraging results from deep learning (DL) in HSI–MSI fusion, there are still some issues. First, the HSI is a multidimensional signal, and the representability of current DL networks for multidimensional features has not been thoroughly investigated. Second, most DL HSI–MSI fusion networks need HR HSI ground truth for training, but it is often unavailable in reality. In this study, we integrate tensor theory with DL and propose an unsupervised deep tensor network (UDTN) for HSI–MSI fusion. We first propose a tensor filtering layer prototype and further build a coupled tensor filtering module. It jointly represents the LR HSI and HR MSI as several features revealing the principal components of spectral and spatial modes and a sharing code tensor describing the interaction among different modes. Specifically, the features on different modes are represented by the learnable filters of tensor filtering layers, the sharing code tensor is learned by a projection module, in which a co-attention is proposed to encode the LR HSI and HR MSI and then project them onto the sharing code tensor. The coupled tensor filtering module and projection module are jointly trained from the LR HSI and HR MSI in an unsupervised and end-to-end way. The latent HR HSI is inferred with the sharing code tensor, the features on spatial modes of HR MSIs, and the spectral mode of LR HSIs. Experiments on simulated and real remote-sensing datasets demonstrate the effectiveness of the proposed method.

Published
2024
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139. Enhancing hypertension detection and control through a hypertension certification program for pharmacists: A cluster randomized trial (The RxPATH Study)

Author

Watson, Kaitlyn E., Chan, Jonathan C.H., Pan, Bo, Al Hamarneh, Yazid N., and Tsuyuki, Ross T.

Abstract

Importance: We designed an online educational program for primary care health care providers, the Hypertension Canada Professional Certification Program (HC-PCP), based upon its 2020 guidelines.Objective: The objective was to determine the effect of the HC-PCP, taken by pharmacists, on systolic blood pressure (BP) in patients with poorly controlled hypertension.Design: Stepped wedge cluster randomized trial (unit of randomization was the pharmacy).Participants: Patients with poorly controlled hypertension (BP >140/90 mmHg or >130/80 mmHg [diabetes]) in community pharmacies in Alberta, Canada, were recruited by their pharmacist.Intervention: Pharmacists completed the HC-PCP program, then provided care to their patients with poorly controlled hypertension according to what they learned in the course.Control: Pharmacists were given a copy of the Hypertension Canada guidelines and provided their usual care to their patients prior to undertaking the HC-PCP later.Main outcome and measure: The primary outcome was a difference in change in systolic BP at 3 months between groups, while the secondary outcome was patient satisfaction with using the Consultation Satisfaction Questionnaire.Results: We enrolled 890 patients from 59 pharmacies (including 104 pharmacists). Using a linear mixed-effect model with BP reduction as the dependent variable and independent variables of treatment allocation, baseline BP, site effect and patient effect, the intervention was associated with a 4.76 mmHg (95% confidence interval, 2.02–7.50, p< 0.0001) systolic BP reduction at 3 months. Patient satisfaction with using the Consultation Satisfaction Questionnaire was high at 75.9 (/90).Conclusion and relevance: Most educational programs are not evaluated at the patient care level. The HC-PCP taken by pharmacists resulted in a 4.76 mmHg systolic BP reduction in their patients over 3 months. This would have major implications for public health, reducing heart disease, stroke and kidney failure.

Published
2024
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140. Residual Disease Activity in Canadian Patients With Psoriatic Arthritis Treated With Advanced Therapies: Results From a Multiregistry Analysis (UNISON-PsA).

Author

Gladman, Dafna D., Chandran, Vinod, Rosen, Cheryl F., Rohekar, Sherry, Boyd, Tristan, Eder, Lihi, Rahman, Proton, Dutz, Jan, Chan, Jonathan, Haydey, Richard P., Barac, Snezana, Laliberté, Marie-Claude, Girard, Tanya, Fournier, Pierre-André, Sutton, Mitchell, Pereira, Daniel, Chim, Tina, Coupal, Louis, and Choquette, Denis

Published
2024
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143. National study of NAFLD management identifies variation in delivery of care in the UK between 2019 to 2022

Author

Li, Wenhao, primary, Sheridan, David, additional, McPherson, Stuart, additional, Alazawi, William, additional, Abeysekera, Kush, additional, Marjot, Tom, additional, Brennan, Paul, additional, Mahgoub, Sara, additional, Cacciottolo, Tessa, additional, Hydes, Theresa, additional, Hardy, Tim, additional, McGinty, Gio, additional, Tavabie, Oliver, additional, Cathcart, Jennifer, additional, Premathilaka, Chirantha, additional, Mukhopadhya, Ashis, additional, Bhat, Arshiya, additional, Begum, Shahnaz, additional, Abushaban, Bashar, additional, Bhuva, Meha, additional, Sinclair, Sophie, additional, Leith, Damien, additional, McCulloch, Cullen, additional, Leithead, Joanna, additional, Fox, Richard, additional, Shah, Muhammad Haris, additional, Campbell, Eugene, additional, Brown, Edward, additional, Mansour, Dina, additional, Shah, Fatma, additional, Allison, Michael, additional, Chan, Jonathan, additional, Roberts, Victoria, additional, Appanna, Gautham, additional, Mandour, Mandour Omer, additional, Slee, Georgina, additional, Wong, Vicki, additional, Kotha, Sreelakshmi, additional, Pekarska, Katrina, additional, Parker, Richard, additional, Sieberhagen, Cyril, additional, Ngan, Thomas, additional, Asilmaz, Esra, additional, Miller, Hamish, additional, Cobbold, Jeremy, additional, Crocombe, Dom, additional, Tsochatzis, Manolis, additional, Tanwar, Sudeep, additional, Dias, Aruna, additional, Singh, Gurmit, additional, Agrawal, Swastik, additional, Chhabra, Puneet, additional, Gurung, Amrita, additional, Veettil, Rajesh, additional, Abeles, Robin Daniel, additional, Chatterjee, Devnandan, additional, Carbonell, Michael, additional, Mohamed, Zameer, additional, El-Sayed, Ahmed, additional, Johnson, Amy, additional, Barclay, Stephen, additional, Kelly, Katherine, additional, Munonye, Joshua, additional, Coates, Dominic, additional, Bamidele, Opeyemi, additional, Johnston, Thomas, additional, Samuel, David, additional, Ball, Belinda, additional, Arscott-Samuel, Rebecca, additional, Hams, Pamela, additional, Armstrong, Matthew, additional, Elkhol, Ayman, additional, Shailesh, Karanth, additional, Bains, Vikram, additional, Manousou, Pinelopi, additional, Gupta, Tarun, additional, Than, Sophia, additional, Unitt, Esther, additional, Gordon, Victoria, additional, Wakefield, Alice, additional, Gilchrist, Sian, additional, Cozma, Ioana, additional, Saeed, Sohaib, additional, Umrani, Salman, additional, and Olsen, Kathryn, additional

Published
2023
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146. Resting echocardiographic parameters can exclude significant coronary artery disease: A comparison with coronary computed tomography angiography

Author

Jinno, Shinji, primary, Yamada, Akira, additional, Sugimoto, Kunihiko, additional, Chan, Jonathan, additional, Nakashima, Chihiro, additional, Funato, Yusuke, additional, Hoshino, Naoki, additional, Hoshino, Meiko, additional, Takada, Kayoko, additional, Sato, Yoshihiro, additional, Kawai, Hideki, additional, Sarai, Masayoshi, additional, Ito, Hiroyasu, additional, and Izawa, Hideo, additional

Published
2023
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147. A novel speckle‐tracking echocardiography parameter assessing left ventricular afterload

Author

Sato, Kei, primary, Wildi, Karin, additional, Chan, Jonathan, additional, Palmieri, Chiara, additional, Obonyo, Nchafatso G., additional, Heinsar, Silver, additional, Liu, Keibun, additional, Livingstone, Samantha, additional, Sato, Noriko, additional, Ainola, Carmen, additional, Abbate, Gabriella, additional, Bouquet, Mahé, additional, Wilson, Emily, additional, Passmore, Margaret, additional, Hyslop, Kieran, additional, Platts, David G., additional, Suen, Jacky, additional, Bassi, Gianluigi Li, additional, and Fraser, John F., additional

Published
2023
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