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1. Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis

Author

Ryan J Collinson, Lynne Wilson, Darren Boey, Zi Yun Ng, Bob Mirzai, Hun S Chuah, Rebecca Howman, Carolyn S Grove, Jacques A J Malherbe, Michael F Leahy, Matthew D Linden, Kathryn A Fuller, Wendy N Erber, and Belinda B Guo

Subjects
Megakaryocyte, myelofibrosis, myeloproliferative neoplasms, next-generation sequencing, platelets, TCF3, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

AbstractTranscription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise de novo or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical “MF-like” morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of TCF3 in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.

Published
2024
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2. Single-Cell Profiling Identifies Key Pathways Expressed by iPSCs Cultured in Different Commercial Media

Author

Maciej Daniszewski, Quan Nguyen, Hun S. Chy, Vikrant Singh, Duncan E. Crombie, Tejal Kulkarni, Helena H. Liang, Priyadharshini Sivakumaran, Grace E. Lidgerwood, Damián Hernández, Alison Conquest, Louise A. Rooney, Sophie Chevalier, Stacey B. Andersen, Anne Senabouth, James C. Vickers, David A. Mackey, Jamie E. Craig, Andrew L. Laslett, Alex W. Hewitt, Joseph E. Powell, and Alice Pébay

Subjects
Science
Abstract

Summary: We assessed the pluripotency of human induced pluripotent stem cells (iPSCs) maintained on an automated platform using StemFlex and TeSR-E8 media. Analysis of transcriptome of single cells revealed similar expression of core pluripotency genes, as well as genes associated with naive and primed states of pluripotency. Analysis of individual cells from four samples consisting of two different iPSC lines each grown in the two culture media revealed a shared subpopulation structure with three main subpopulations different in pluripotency states. By implementing a machine learning approach, we estimated that most cells within each subpopulation are very similar between all four samples. The single-cell RNA sequencing analysis of iPSC lines grown in both media reports the molecular signature in StemFlex medium and how it compares to that observed in the TeSR-E8 medium. : Stem Cells Research; Transcriptomics; Automation Subject Areas: Stem Cells Research, Transcriptomics, Automation

Published
2018
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3. Transient naive reprogramming corrects hiPS cells functionally and epigenetically

Author

Buckberry, Sam, Liu, Xiaodong, Poppe, Daniel, Tan, Jia Ping, Sun, Guizhi, Chen, Joseph, Nguyen, Trung Viet, de Mendoza, Alex, Pflueger, Jahnvi, Frazer, Thomas, Vargas-Landín, Dulce B., Paynter, Jacob M., Smits, Nathan, Liu, Ning, Ouyang, John F., Rossello, Fernando J., Chy, Hun S., Rackham, Owen J. L., Laslett, Andrew L., Breen, James, Faulkner, Geoffrey J., Nefzger, Christian M., Polo, Jose M., and Lister, Ryan

Published
2023
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4. New Monoclonal Antibodies to Defined Cell Surface Proteins on Human Pluripotent Stem Cells

Author

O'Brien, Carmel M, Chy, Hun S, Zhou, Qi, Blumenfeld, Shiri, Lambshead, Jack W, Liu, Xiaodong, Kie, Joshua, Capaldo, Bianca D, Chung, Tung‐Liang, Adams, Timothy E, Phan, Tram, Bentley, John D, McKinstry, William J, Oliva, Karen, McMurrick, Paul J, Wang, Yu‐Chieh, Rossello, Fernando J, Lindeman, Geoffrey J, Chen, Di, Jarde, Thierry, Clark, Amander T, Abud, Helen E, Visvader, Jane E, Nefzger, Christian M, Polo, Jose M, Loring, Jeanne F, and Laslett, Andrew L

Subjects
Medical Biotechnology, Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Cancer, Stem Cell Research - Induced Pluripotent Stem Cell, Breast Cancer, Regenerative Medicine, Stem Cell Research - Embryonic - Human, Stem Cell Research, Biotechnology, 1.1 Normal biological development and functioning, Underpinning research, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Generic health relevance, Animals, Antibodies, Monoclonal, Antigens, Surface, Cell Culture Techniques, Cell Differentiation, Cell Self Renewal, Down-Regulation, Embryoid Bodies, Flow Cytometry, Hematopoietic Stem Cells, Humans, Membrane Proteins, Mice, Octamer Transcription Factor-3, Pluripotent Stem Cells, Pluripotency, Human embryonic stem cells, Human iPS cells, Naive, Breast, Colorectal, Cell surface markers, Monoclonal antibodies, Technology, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences
Abstract

The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterized monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here, we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures. These mAbs are immunoreactive to cell surface protein epitopes on both primed and naive state hPSCs, providing useful research tools to investigate the cellular mechanisms underlying human pluripotency and states of cellular reprogramming. In addition, we report that subsets of the seven new mAbs are also immunoreactive to human bone marrow-derived mesenchymal stem cells (MSCs), normal human breast subsets and both normal and tumorigenic colorectal cell populations. The mAbs reported here should accelerate the investigation of the nature of pluripotency, and enable development of robust cell separation and tracing technologies to enrich or deplete for hPSCs and other human stem and somatic cell types. Stem Cells 2017;35:626-640.

Published
2017

5. Imaging flow cytometric detection of del(17p) in bone marrow and circulating plasma cells in multiple myeloma.

Author

Mincherton, Thomas I., Lam, Stephanie J., Clarke, Sarah E., Hui, Henry Y. L., Malherbe, Jacques A. J., Chuah, Hun S., Sidiqi, M. Hasib, Fuller, Kathy A., and Erber, Wendy N.

Subjects
BLOOD testing, FLOW cytometry, MULTIPLE myeloma, BONE marrow, RESEARCH funding, CELL physiology, BLOOD collection, CHROMOSOME abnormalities, DESCRIPTIVE statistics, BLOOD plasma
Abstract

Background: Detection of del(17p) in myeloma is generally performed by fluorescence in situ hybridization (FISH) on a slide with analysis of up to 200 nuclei. The small cell sample analyzed makes this a low precision test. We report the utility of an automated FISH method, called "immuno‐flowFISH", to detect plasma cells with adverse prognostic risk del(17p) in bone marrow and blood samples of patients with myeloma. Methods: Bone marrow (n = 31) and blood (n = 19) samples from 35 patients with myeloma were analyzed using immuno‐flowFISH. Plasma cells were identified by CD38/CD138‐immunophenotypic gating and assessed for the 17p locus and centromere of chromosome 17. Cells were acquired on an AMNIS ImageStreamX MkII imaging flow cytometer using INSPIRE software. Results: Chromosome 17 abnormalities were identified in CD38/CD138‐positive cells in bone marrow (6/31) and blood (4/19) samples when the percent plasma cell burden ranged from 0.03% to 100% of cells. Abnormalities could be identified in 14.5%–100% of plasma cells. Conclusions: The "immuno‐flowFISH" imaging flow cytometric method could detect del(17p) in plasma cells in both bone marrow and blood samples of myeloma patients. This method was also able to detect gains and losses of chromosome 17, which are also of prognostic significance. The lowest levels of 0.009% (bone marrow) and 0.001% (blood) for chromosome 17 abnormalities was below the detection limit of current FISH method. This method offers potential as a new means of identifying these prognostically important chromosomal defects, even when only rare cells are present and for serial disease monitoring. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Transcription factor 3 is dysregulated in megakaryocytes in myelofibrosis

Author

Collinson, Ryan J, primary, Wilson, Lynne, additional, Boey, Darren, additional, Ng, Zi Yun, additional, Mirzai, Bob, additional, Chuah, Hun S, additional, Howman, Rebecca, additional, Grove, Carolyn S, additional, Malherbe, Jacques A J, additional, Leahy, Michael F, additional, Linden, Matthew D, additional, Fuller, Kathryn A, additional, Erber, Wendy N, additional, and Guo, Belinda B, additional

Published
2024
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8. Reprogramming roadmap reveals route to human induced trophoblast stem cells

Author

Liu, Xiaodong, Ouyang, John F., Rossello, Fernando J., Tan, Jia Ping, Davidson, Kathryn C., Valdes, Daniela S., Schröder, Jan, Sun, Yu B. Y., Chen, Joseph, Knaupp, Anja S., Sun, Guizhi, Chy, Hun S., Huang, Ziyi, Pflueger, Jahnvi, Firas, Jaber, Tano, Vincent, Buckberry, Sam, Paynter, Jacob M., Larcombe, Michael R., Poppe, Daniel, Choo, Xin Yi, O’Brien, Carmel M., Pastor, William A., Chen, Di, Leichter, Anna L., Naeem, Haroon, Tripathi, Pratibha, Das, Partha P., Grubman, Alexandra, Powell, David R., Laslett, Andrew L., David, Laurent, Nilsson, Susan K., Clark, Amander T., Lister, Ryan, Nefzger, Christian M., Martelotto, Luciano G., Rackham, Owen J. L., and Polo, Jose M.

Published
2020
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9. Single-Cell Profiling Identifies Key Pathways Expressed by iPSCs Cultured in Different Commercial Media

Author

Daniszewski, Maciej, Nguyen, Quan, Chy, Hun S., Singh, Vikrant, Crombie, Duncan E., Kulkarni, Tejal, Liang, Helena H., Sivakumaran, Priyadharshini, Lidgerwood, Grace E., Hernández, Damián, Conquest, Alison, Rooney, Louise A., Chevalier, Sophie, Andersen, Stacey B., Senabouth, Anne, Vickers, James C., Mackey, David A., Craig, Jamie E., Laslett, Andrew L., Hewitt, Alex W., Powell, Joseph E., and Pébay, Alice

Published
2018
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11. Comparison of Outcomes After Percutaneous Coronary Intervention for Chronic Total Occlusion Using Everolimus- Versus Sirolimus- Versus Paclitaxel-Eluting Stents (from the Korean National Registry of Chronic Total Occlusion Intervention)

Author

Lee, Min-Ho, Lee, Joo M., Kang, Si-Hyuck, Yoon, Chang-Hwan, Jang, Yangsoo, Yu, Cheol W., Park, Hun S., Lee, Seung-Hwan, Hur, Seung-Ho, Kim, Moo H., Rha, Seung-Woon, Gwon, Hyeon-Cheol, Chae, In-Ho, and Kim, Hyo-Soo

Published
2015
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12. Reprogramming roadmap reveals route to human induced trophoblast stem cells

Author

Anna L. Leichter, Carmel M. O’Brien, David R. Powell, Hun S. Chy, Jahnvi Pflueger, Ziyi Huang, Guizhi Sun, Amander T. Clark, Joseph Chen, Jacob M. Paynter, Andrew L. Laslett, Xin Yi Choo, Sam Buckberry, Christian M. Nefzger, Haroon Naeem, Jaber Firas, Pratibha Tripathi, John F. Ouyang, Vincent Tano, Daniela S. Valdes, Jia Ping Tan, Susan K. Nilsson, Michael R. Larcombe, Daniel Poppe, Di Chen, Fernando J. Rossello, Jan Schröder, Xiaodong Liu, Alexandra Grubman, Anja S Knaupp, Owen J. L. Rackham, Jose M. Polo, Ryan Lister, Yu Bo Yang Sun, Luciano G. Martelotto, Laurent David, William A. Pastor, Kathryn C. Davidson, and Partha Pratim Das

Subjects
Adult, Transcription, Genetic, Somatic cell, Induced Pluripotent Stem Cells, Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Ectoderm, medicine, Humans, Induced pluripotent stem cell, reproductive and urinary physiology, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Trophoblast, Fibroblasts, Cellular Reprogramming, Embryonic stem cell, Chromatin, Trophoblasts, Cell biology, medicine.anatomical_structure, Gene Expression Regulation, embryonic structures, Female, Stem cell, Reprogramming, 030217 neurology & neurosurgery
Abstract

The reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development 1–6. The molecular mechanism that underpins these reprogramming processes remains largely unexplored, which impedes our understanding and limits rational improvements to reprogramming protocols. Here, to address these issues, we reconstruct molecular reprogramming trajectories of human dermal fibroblasts using single-cell transcriptomics. This revealed that reprogramming into primed and naive pluripotency follows diverging and distinct trajectories. Moreover, genome-wide analyses of accessible chromatin showed key changes in the regulatory elements of core pluripotency genes, and orchestrated global changes in chromatin accessibility over time. Integrated analysis of these datasets revealed a role for transcription factors associated with the trophectoderm lineage, and the existence of a subpopulation of cells that enter a trophectoderm-like state during reprogramming. Furthermore, this trophectoderm-like state could be captured, which enabled the derivation of induced trophoblast stem cells. Induced trophoblast stem cells are molecularly and functionally similar to trophoblast stem cells derived from human blastocysts or first-trimester placentas 7. Our results provide a high-resolution roadmap for the transcription-factor-mediated reprogramming of human somatic cells, indicate a role for the trophectoderm-lineage-specific regulatory program during this process, and facilitate the direct reprogramming of somatic cells into induced trophoblast stem cells.

Published
2020

13. Decoding the Real-Time Neurobiological Properties of Incremental Semantic Interpretation

Author

Bingjiang Lyu, Lorraine K. Tyler, Hun S. Choi, William D. Marslen-Wilson, Billi Randall, Marslen-Wilson, William [0000-0003-0690-6308], Tyler, Lorraine [0000-0002-9943-118X], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Adolescent, Computer science, Cognitive Neuroscience, Semantic interpretation, Models, Neurological, Context (language use), computer.software_genre, Semantics, 050105 experimental psychology, representational similarity analysis, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Humans, Computer Simulation, 0501 psychology and cognitive sciences, Language, Computational model, Psycholinguistics, Interpretation (logic), AcademicSubjects/SCI01870, business.industry, Communication, incremental prediction, 05 social sciences, Magnetoencephalography, Bayes Theorem, Electroencephalography, Anticipation, Psychological, electro/magnetoencephalography, Original Article, Female, Artificial intelligence, Bayesian language modeling, Comprehension, business, computer, 030217 neurology & neurosurgery, Word (computer architecture), Natural language processing, Sentence, Spoken language
Abstract

Communication through spoken language is a central human capacity, involving a wide range of complex computations that incrementally interpret each word into meaningful sentences. However, surprisingly little is known about the spatiotemporal properties of the complex neurobiological systems that support these dynamic predictive and integrative computations. Here, we focus on prediction, a core incremental processing operation guiding the interpretation of each upcoming word with respect to its preceding context. To investigate the neurobiological basis of how semantic constraints change and evolve as each word in a sentence accumulates over time, in a spoken sentence comprehension study, we analyzed the multivariate patterns of neural activity recorded by source-localized electro/magnetoencephalography (EMEG), using computational models capturing semantic constraints derived from the prior context on each upcoming word. Our results provide insights into predictive operations subserved by different regions within a bi-hemispheric system, which over time generate, refine, and evaluate constraints on each word as it is heard.

Published
2020

14. DRG2 is required for surface localization of PD-L1 and the efficacy of anti-PD-1 therapy

Author

Seong Hee Choi, Muralidharan Mani, Jeonghwan Kim, Wha Ja Cho, Thomas F. J. Martin, Jee Hyun Kim, Hun Su Chu, Won Jin Jeong, Young-Wook Won, Byung Ju Lee, Byungyong Ahn, Junil Kim, Do Yong Jeon, and Jeong Woo Park

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Abstract More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells. However, it inhibited recycling of endosomal PD-L1 and reduced surface PD-L1 levels, which led to defects in interaction with PD-1. Anti-PD-1 did not expand effector-like T cells within DRG2-depleted tumors and failed to improve the survival of DRG2-depleted tumor-bearing mice. Cohort analysis revealed that patients bearing melanoma with low DRG2 protein levels were resistant to anti-PD-1 therapy. These findings identify DRG2 as a key regulator of recycling of endosomal PD-L1 and response to anti-PD-1 therapy and provide insights into how to increase the correlation between PD-L1 expression and response to anti-PD-1 therapy.

Published
2024
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15. Impaired autophagy in myeloid cells aggravates psoriasis-like skin inflammation through the IL-1β/CXCL2/neutrophil axis

Author

Jinju Lee, Mi-Yeon Kim, Hyo Jeong Kim, Woo Sun Choi, and Hun Sik Kim

Subjects
Psoriasis, Autophagy, Myeloid cells, IL-1β, IL-17, Neutrophilic inflammation, Biotechnology, TP248.13-248.65, Biology (General), QH301-705.5, Biochemistry, QD415-436
Abstract

Abstract Background Psoriasis is an inflammatory skin disease characterized by the hyperproliferative epidermal keratinocytes and significant immune cells infiltration, leading to cytokines production such as IL-1β, TNF-α, IL-23, and IL-17. Recent study highlights the critical role of IL-1β in the induction and activation of pathogenic Th17 and IL-17-producing γδ T cells, contributing to psoriasis. However, the mechanism underlying IL-1β dysregulation in psoriasis pathogenesis is unclear. Autophagy regulates IL-1β production and has a pleiotropic effect on inflammatory disorders. Previous studies showed controversial role of autophagy in psoriasis pathogenesis, either pro-inflammatory in autophagy-deficient keratinocyte or anti-inflammatory in pharmacologically autophagy-promoting macrophages. Thus, the direct role of autophagy and its therapeutic potential in psoriasis remains unclear. Methods We used myeloid cell-specific autophagy-related gene 7 (Atg7)-deficient mice and determined the effect of autophagy deficiency in myeloid cells on neutrophilia and disease pathogenesis in an imiquimod-induced psoriasis mouse model. We then assessed the pathogenic mechanism focusing on immune cells producing IL-1β and IL-17 along with gene expression profiles associated with psoriasis in mouse model and public database on patients. Moreover, therapeutic potential of IL-1β blocking in such context was assessed. Results We found that autophagy deficiency in myeloid cells exacerbated neutrophilic inflammation and disease pathogenesis in mice with psoriasis. This autophagy-dependent effect was associated with a significant increase in IL-1β production from myeloid cells, particularly macrophages, Cxcl2 expression, and IL-17 A producing T cells including γδ T cells. Supporting this, treatment with systemic IL-1 receptor blocking antibody or topical saccharin, a disaccharide suppressing pro-IL-1β expression, led to the alleviation of neutrophilia and psoriatic skin inflammation linked to autophagy deficiency. The pathophysiological relevance of this finding was supported by dysregulation of autophagy-related genes and their correlation with Th17 cytokines in psoriatic skin lesion from patients with psoriasis. Conclusions Our results suggest that autophagy dysfunction in myeloid cells, especially macrophages, along with IL-1β dysregulation has a causal role in neutrophilic inflammation and psoriasis pathogenesis.

Published
2024
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16. Neural dynamics of semantic composition

Author

Bingjiang Lyu, William D. Marslen-Wilson, Hun S. Choi, Lorraine K. Tyler, Billi Randall, Alex Clarke, Clarke, Alex [0000-0001-7768-5229], Apollo - University of Cambridge Repository, and Apollo-University Of Cambridge Repository

Subjects
Adult, Male, Speech perception, EEG/MEG, Adolescent, Computer science, speech, computational modelling, Object (grammar), Verb, computer.software_genre, Semantics, 050105 experimental psychology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, RSA, directed connectivity, Noun, Humans, 0501 psychology and cognitive sciences, Multidisciplinary, business.industry, 05 social sciences, Brain, Magnetoencephalography, Information flow, Electroencephalography, Linguistics, Semantic property, Biological Sciences, PNAS Plus, Psychological and Cognitive Sciences, FOS: Languages and literature, Auditory Perception, Speech Perception, Female, Artificial intelligence, Comprehension, business, computer, 030217 neurology & neurosurgery, Natural language processing, Utterance
Abstract

Significance The rapid comprehension of speech is a remarkable but poorly understood human capacity. Central to this process is the integration of the meaning of each word, as it is heard, into the listener’s interpretation of the utterance. Here we focus on the real-time flow of neural activity that underpins this combinatorial process, using multivariate pattern analysis and computational semantic models to discover the contextual constraints that are constructed as each word is heard, and to determine how these constraints guide the interpretation of future words in the utterance. This combination of methods reveals a continuous information flow across the left-hemisphere language system, strongly constraining the immediate activation of word meanings and providing a neural substrate for seamless real-time speech comprehension., Human speech comprehension is remarkable for its immediacy and rapidity. The listener interprets an incrementally delivered auditory input, millisecond by millisecond as it is heard, in terms of complex multilevel representations of relevant linguistic and nonlinguistic knowledge. Central to this process are the neural computations involved in semantic combination, whereby the meanings of words are combined into more complex representations, as in the combination of a verb and its following direct object (DO) noun (e.g., “eat the apple”). These combinatorial processes form the backbone for incremental interpretation, enabling listeners to integrate the meaning of each word as it is heard into their dynamic interpretation of the current utterance. Focusing on the verb-DO noun relationship in simple spoken sentences, we applied multivariate pattern analysis and computational semantic modeling to source-localized electro/magnetoencephalographic data to map out the specific representational constraints that are constructed as each word is heard, and to determine how these constraints guide the interpretation of subsequent words in the utterance. Comparing context-independent semantic models of the DO noun with contextually constrained noun models reflecting the semantic properties of the preceding verb, we found that only the contextually constrained model showed a significant fit to the brain data. Pattern-based measures of directed connectivity across the left hemisphere language network revealed a continuous information flow among temporal, inferior frontal, and inferior parietal regions, underpinning the verb’s modification of the DO noun’s activated semantics. These results provide a plausible neural substrate for seamless real-time incremental interpretation on the observed millisecond time scales.

Published
2019

17. HPK1 Dysregulation‐Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression

Author

Woo Seon Choi, Hyung‐Joon Kwon, Eunbi Yi, Haeun Lee, Jung Min Kim, Hyo Jin Park, Eun Ji Choi, Myoung Eun Choi, Young Hoon Sung, Chong Hyun Won, Chang Ohk Sung, and Hun Sik Kim

Subjects
HPK1, Dysfunction, Lung metastasis, Melanoma, Natural killer cell, Science
Abstract

Abstract Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1‐deficient mice are resistant to metastasis and further protected by combined immune‐checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF‐β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK‐target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.

Published
2024
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19. Transform-1: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, International Phase 3 Study of Navitoclax in Combination with Ruxolitinib Versus Ruxolitinib Plus Placebo in Patients with Untreated Myelofibrosis

Author

Pemmaraju, Naveen, Mead, Adam J, Somervaille, Tim CP, McCloskey, James K, Palandri, Francesca, Koschmieder, Steffen, Lavie, David, Leber, Brian, Yeh, Su-Peng, Gómez-Casares, Maria Teresa, Ammatuna, Emanuele, Shin, Ho-Jin, Kirito, Keita, Jourdan, Eric, Devos, Timothy, Chuah, Hun S, Radinoff, Atanas, Bogdanovic, Andrija, Moskal, Rastislav, Jiang, Qi, Chopra, Avijeet S, Papadopoulos, Elektra, Potluri, Jalaja, and Passamonti, Francesco

Published
2023
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20. Long‐term impact of angiotensin receptor‐neprilysin inhibitor based on short‐term treatment response in heart failure

Author

Hyuk Kyoon Park, Jong Sung Park, Myeong Seop Kim, Eunkyu Lee, Hyohun Choi, Yoon Jung Park, Bo Eun Park, Hong Nyun Kim, Namkyun Kim, Myung Hwan Bae, Jang Hoon Lee, Hun Sik Park, Yongkeun Cho, Se Yong Jang, and Dong Heon Yang

Subjects
Angiotensin receptor–neprilysin inhibitor, Heart failure with improved ejection fraction, Heart failure with reduced ejection fraction, Reverse remodelling, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Aims The long‐term effect of angiotensin receptor–neprilysin inhibitor (ARNI) remains uncertain in patients who have experienced improvements in left ventricular (LV) systolic function or significant LV reverse remodelling following a certain period of treatment. It is also unclear how ARNI performs in patients who have not shown these improvements. This study aimed to assess the impact of prolonged ARNI use compared with angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) in patients with and without significant treatment response after 1 year of heart failure (HF) treatment. Methods and results The present study enrolled patients with HF with reduced ejection fraction (HFrEF) who were treated with either ARNI or ACEIs/ARBs within 1 year of undergoing index echocardiography. After 1 year of treatment, patients were reclassified into the following groups: (i) patients with HF with improved ejection fraction and persistent HFrEF and (ii) patients with and without LV reverse remodelling based on the follow‐up echocardiography. The effect of ARNI versus that of ACEIs/ARBs in each group was assessed from the time of categorizing into new groups using the composite event of all‐cause mortality and HF hospitalization. A total of 671 patients with HFrEF (age, 66.4 ± 14.1 years; males, 66.8%) were included, and 133 (19.8%) composite events of death and rehospitalization for HF were observed during the follow‐up (median follow‐up, 44 [interquartile range, 34–51] months). ARNI had a significantly lower event rate than ACEIs/ARBs in patients with HF with improved ejection fraction (7.0% vs. 30.4%, P = 0.020) and those with persistent HFrEF (17.6% vs. 49.7%, P

Published
2023
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21. Exosomal miRNAs Differentiate Chronic Total Occlusion from Acute Myocardial Infarction

Author

Ji-Hye Son, Jeong Kyu Park, Ji-Hong Bang, Dongeon Kim, Inki Moon, Min Gyu Kong, Hyun-Woo Park, Hyung-Oh Choi, Hye-Sun Seo, Yoon Haeng Cho, Hun Soo Chang, and Jon Suh

Subjects
chronic total occlusion, acute myocardial infarction, exosome, microRNA, biomarker, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Although coronary artery occlusion can have a negative effect on the myocardium, chronic total occlusion (CTO) exhibits different clinical features from those of acute myocardial infarction (AMI). In this study, we identify the differential associations of exosomal miRNAs with CTO and AMI. Exosomes were isolated from the plasma obtained from coronary arteries of patients undergoing percutaneous coronary intervention to treat CTO (n = 29) and AMI (n = 24), followed by small RNA sequencing, target gene predictions, and functional enrichment analyses. Promising miRNA markers were validated using real-time PCR in 35 CTO, 35 AMI, and 10 normal subjects. A total of 205 miRNAs were detected in all subjects, and 20 and 12 miRNAs were upregulated and downregulated in CTO compared to AMI patients, respectively (|fold change| > 4, FDR q < 0.05). The target genes of miRNAs that were higher in CTO patients were associated with “regulation of cell cycle phase transition”, “cell growth”, and “apoptosis”. The target genes of miRNAs that were lower in CTO patients were enriched in terms such as “muscle cell differentiation”, “response to oxygen levels”, and “artery morphogenesis”. On qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p were significantly different between CTO and AMI patients. The miRNA expression levels accurately distinguished CTO from AMI patients with 79% specificity and 97% sensitivity. The miRNA contents of plasma exosomes were significantly different between CTO and AMI patients. The miRNAs may play important roles in CTO and AMI.

Published
2024
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22. Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression

Author

Nayoung Kim, Eunbi Yi, Eunbi Lee, Hyo Jin Park, and Hun Sik Kim

Subjects
natural killer cell, IL-2, NKp30, NKp46, acute myeloid leukemia, Immunologic diseases. Allergy, RC581-607
Abstract

Natural killer (NK) cells are key effectors in cancer immunosurveillance, eliminating a broad spectrum of cancer cells without major histocompatibility complex (MHC) specificity and graft-versus-host diseases (GvHD) risk. The use of allogeneic NK cell therapies from healthy donors has demonstrated favorable clinical efficacies in treating diverse cancers, particularly hematologic malignancies, but it requires cytokines such as IL-2 to primarily support NK cell persistence and expansion. However, the role of IL-2 in the regulation of activating receptors and the function of NK cells expanded for clinical trials is poorly understood and needs clarification for the full engagement of NK cells in cancer immunotherapy. Here, we demonstrated that IL-2 deprivation significantly impaired the cytotoxicity of primary expanded NK cells by preferentially downregulating NKp30 but not NKp46 despite their common adaptor requirement for expression and function. Using NK92 and IL-2-producing NK92MI cells, we observed that NKp30-mediated cytotoxicity against myeloid leukemia cells such as K562 and THP-1 cells expressing B7-H6, a ligand for NKp30, was severely impaired by IL-2 deprivation. Furthermore, IL-2 deficiency-mediated NK cell dysfunction was overcome by the ectopic overexpression of an immunostimulatory NKp30 isoform such as NKp30a or NKp30b. In particular, NKp30a overexpression in NK92 cells improved the clearance of THP-1 cells in vivo without IL-2 supplementation. Collectively, our results highlight the distinct role of IL-2 in the regulation of NKp30 compared to that of NKp46 and suggest NKp30 upregulation, as shown here by ectopic overexpression, as a viable modality to harness NK cells in cancer immunotherapy, possibly in combination with IL-2 immunocytokines.

Published
2024
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25. Comprehensive characterization of distinct states of human naive pluripotency generated by reprogramming

Author

Margeaux Hodgson-Garms, Ethan Ford, Joseph Chen, Jahnvi Pflueger, Jacob M. Paynter, Carmel M. O’Brien, Cheng Huang, Susan K. Nilsson, Ketan Mishra, Christian M. Nefzger, Andrew L. Laslett, Natasha Jansz, Xiaodong Liu, Sarah M. Williams, Fernando J. Rossello, Ralf B. Schittenhelm, Hun S. Chy, Anja S Knaupp, Marnie E. Blewitt, Jose M. Polo, Ryan Lister, and Jaber Firas

Subjects
Pluripotent Stem Cells, 0301 basic medicine, Somatic cell, Cellular differentiation, Cell Differentiation, Cell Biology, Computational biology, Fibroblasts, Biology, Cellular Reprogramming, Biochemistry, Web tool, Embryonic stem cell, Genomic Instability, Kruppel-Like Factor 4, 03 medical and health sciences, 030104 developmental biology, KLF4, Humans, Induced pluripotent stem cell, Molecular Biology, Cell potency, Reprogramming, Biotechnology
Abstract

Recent reports on the characteristics of naive human pluripotent stem cells (hPSCs) obtained using independent methods differ. Naive hPSCs have been mainly derived by conversion from primed hPSCs or by direct derivation from human embryos rather than by somatic cell reprogramming. To provide an unbiased molecular and functional reference, we derived genetically matched naive hPSCs by direct reprogramming of fibroblasts and by primed-to-naive conversion using different naive conditions (NHSM, RSeT, 5iLAF and t2iLGöY). Our results show that hPSCs obtained in these different conditions display a spectrum of naive characteristics. Furthermore, our characterization identifies KLF4 as sufficient for conversion of primed hPSCs into naive t2iLGöY hPSCs, underscoring the role that reprogramming factors can play for the derivation of bona fide naive hPSCs.

Published
2017

26. New Monoclonal Antibodies to Defined Cell Surface Proteins on Human Pluripotent Stem Cells

Author

Bianca D. Capaldo, Helen E. Abud, Qi Zhou, Shiri Blumenfeld, Karen Oliva, Paul J. McMurrick, Joshua Kie, Geoffrey J. Lindeman, Jane E. Visvader, Andrew L. Laslett, William J. McKinstry, Timothy E. Adams, Di Chen, Christian M. Nefzger, Jose M. Polo, Thierry Jarde, John D. Bentley, Jeanne F. Loring, Jack W. Lambshead, Yu-Chieh Wang, Xiaodong Liu, Tung Liang Chung, Fernando J. Rossello, Carmel M. O’Brien, Tram Phan, Amander T. Clark, and Hun S. Chy

Subjects
0301 basic medicine, Technology, Cellular differentiation, Cell Culture Techniques, Embryoid body, Medical and Health Sciences, Embryonic Stem Cells/Induced Pluripotent Stem Cells, Mice, Monoclonal, Cell surface markers, Breast, Cell Self Renewal, Naive, Induced pluripotent stem cell, Colorectal, Cancer, Antibodies, Monoclonal, Cell Differentiation, Biological Sciences, Flow Cytometry, Cell biology, Surface, Antigens, Surface, Molecular Medicine, Human embryonic stem cells, Stem cell, Reprogramming, Pluripotent Stem Cells, Pluripotency, Human iPS cells, Immunology, Down-Regulation, Biology, Antibodies, 03 medical and health sciences, Animals, Humans, Antigens, Cell potency, Embryoid Bodies, Mesenchymal stem cell, Membrane Proteins, Cell Biology, Hematopoietic Stem Cells, Molecular biology, Embryonic stem cell, 030104 developmental biology, Monoclonal antibodies, Octamer Transcription Factor-3, Developmental Biology
Abstract

The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterized monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here, we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures. These mAbs are immunoreactive to cell surface protein epitopes on both primed and naive state hPSCs, providing useful research tools to investigate the cellular mechanisms underlying human pluripotency and states of cellular reprogramming. In addition, we report that subsets of the seven new mAbs are also immunoreactive to human bone marrow-derived mesenchymal stem cells (MSCs), normal human breast subsets and both normal and tumorigenic colorectal cell populations. The mAbs reported here should accelerate the investigation of the nature of pluripotency, and enable development of robust cell separation and tracing technologies to enrich or deplete for hPSCs and other human stem and somatic cell types.

Published
2017

27. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author

Deepak L Bhatt, Philippe Gabriel Steg, Shamir R Mehta, Lawrence A Leiter, Tabassome Simon, Kim Fox, Claes Held, Marielle Andersson, Anders Himmelmann, Wilhelm Ridderstråle, Jersey Chen, Yang Song, Rafael Diaz, Shinya Goto, Stefan K James, Kausik K Ray, Alexander N Parkhomenko, Mikhail N Kosiborod, Darren K McGuire, Robert A Harrington, Vladimir Santos, Ashit Jain, Irina Lendel, Michael Russo, W H Haught, Manuel Bouza, Harinder Gogia, Supratim Banerjee, George Kichura, Louis Kantaros, Francisco Padron, Rakesh Passi, Jay Stone, Michael Pursley, Michael D'Urso, Timothy Gardner, James Bennett, Khaled Nour, Satinder Saini, Wenwu Zhang, Dharam Kumbhani, Dustin Thomas, Dominick Angiolillo, Barry Bertolet, Amaury Roman-Miranda, Robert Black, Ramin Manshadi, Carlos Vaca, Antonio Blanco, Mark Napoli, David Brabham, Ayim Akyea-Djamson, Pratik Desai, Sudhir Prasada, Ajit Khaira, Leslie Forgosh, Ira Lieber, Guillermo Umpierrez, Dinesh Singal, Juan Londono, Neil Fraser, Jose Ruiz, Damaris Vega, Lilia Rodriguez, Christopher Brown, Faizullah Syed, Guarav Aggarwala, William Eaves, Michael Foster, Dinesh Gupta, David Avino, Wail Asfour, Glen Tonnessen, Xue-Qiao Zhao, Narendra Singh, Andrew Brockmyre, Norman Lepor, Nicolas Shammas, David Blick, Steven Hearne, John Prodafikas, Edgar Carell, Mark Izzo, Amin Karim, Bosh Zakhary, Mahmoud Atieh, Steven Leichter, Charles Meadows, David Hotchkiss, Mazen Abu-Fadel, Alan Wiseman, Jeffrey Bander, Mahesh Shah, Subhash Banerjee, Ricky Ganim, Karen Sopko, Misal Khan, Ramon Lloret, Troy Weirick, Rajendra Mehta, Udho Thadani, Anuj Bhargava, Mikhail Kosiborod, Jaynier Moya, Cezar Staniloae, Yamirka D Guerra, Anil Chhabra, Douglas Kosmicki, Wassim Shaheen, Akber Mohammed, J'Cinda Bitters, Jan Pattanayak, Julian Javier, Sunny Srivastava, Roland Phillips, Jessie Al-Amin, Michael Lillestol, Patrick Simpson, Lydie Hazan, Amit Amin, Gopi Shah, Denes Korpas, Bruce Platt, Jim Dickert, Orlando Puente, Louis Hiotis, Timothy Doyle, Raj Rajan, Alan Meholick, Christian Gring, Elie Hage-Korban, Robert Feldman, Harry Colfer, Samuel Butman, Malcolm Foster, Terence Hart, Randall Huling, Shervin Eshaghian, Ofsman Quintana, Deanna Cheung, Franklin Handel, Mara Rodriguez, David Suh, Paul Gordon, Gregg Pressman, Michael Bauer, William French, Mark Barettella, Sridhar Chatrathi, Damodhar Suresh, Ronald Goldberg, Mark Huth, Liwa Younis, Aref Rahman, Richard Mascolo, Michelle Welch, Randeep Suneja, Stephen Smith, Scott Shurmur, John Agaiby, Ahmad Jingo, Janice Johnston, Mary Beth, Anthony Vlastaris, Susan Kemp, Hamid Taheri, Edward Pereira, Michael Deyoung, Zafir Hawa, Ray Smith, Thomas Galski, Samer Garas, M Reddy, Susheel Sharma, Joeseph Hargrove, Charles Treasure, Ronald Emerson, Tariq Haddad, Kathryn Rohr, Larry Levinson, Raul Gaona, Barry Uretsky, Hiralal Maheshwari, Denny Lee, Stephanie Kinnaman, Robert Singal, Jeffrey Geohas, Osvaldo Gigliotti, Ajit Raisinghani, Charanjit Khurana, Brent Hella, Michael Kelberman, Steven Voyce, Sanjay Singh, Eric Lo, Pradeep Singh, Ross Goodfellow, Stuart Fischer, Richard Lorraine, Traci Turner, Jeffrey Shanes, Robert Busch, Robert Broker, Michelle Zaniewski, Kevin Pounds, Giselle Debs-Perez, Stephen Ong, Brad Frandsen, Douglas Fullington, Naseem Jaffrani, Ahtaram Khan, Marcus Lee, Joe Pouzar, George Revtyak, Julian Gonzalez, Samer Nakhle, Abel Murillo, Douglas Young, Sashi Makam, Mushtaq Syed, Kevin Woolf, Paul Grena, Sarab Alfata, Sharan Mahal, David Hoffman, Tinoy Kizhakekuttu, Joseph Deering, Janak Bhavsar, Scott Mikesell, William Wilson, Vance Wilson, Salah El, Francis Spinale, Vinod Kannarkat, Sunder Rao, Lenita Hanson, John Bertsch, Elena Gonzalez-Ortiz, Norma Severino, John Willis, Joel Schock, Ladan Bakhtari, Raul Gazmuri, Saadat Ansari, Jason Hall, Arvind Mehta, Neal Shealy, Stuart Zarich, Deovrat Singh, Kishor Vora, Nabil Andrawis, Darron Molter, David Maron, Jose Cardona, Ronald D'Agostino, Tamjeed Arshad, Rodney Samaan, David Jones, Dale Presser, John Heath, Sandy Green, George Bittar, Sheldon Henry, David Korn, John Schmedtje, Venkatesh Nadar, Bruce Graham, Ajay Labroo, Leonardo Clavijo, Hal Roseman, Gilbert Ledesma, Robert Rosen, Isaac Dor, William Kirby, Jennefer Sutton, Frank Eder, Bruce Iteld, Jose Gomez-Cortes, Maurice Buchbinder, Joseph Kasper, Antonio Terrelonge, Gustavo Torres, Ted Jagielo, Jose Alvarez, Yehuda Handelsman, Mario Guillen, Randall Richwine, Lorena Lewy-Alterbaum, Clinton Corder, Moogali Arvind, David Bolshoun, Magdy Mikhail, Stephen Minton, Odilon Alvarado, J Abbott, Brett Cauthen, Ryan Welter, Randy Mintz, John Cox, Annette Quick, Melvin Weiss, Johnny Dy, James Zebrack, Glenn Gandelman, Vinayak Hegde, Marc Silver, Michele DeGregorio, William Lawson, Christopher Paa, Anna Bortnick, Merrill Krolick, Rodolfo Sotolongo, Jorge Cheirif, Priya Kumar, Preetham Jetty, Ambar Patel, Mariusz Kruk, Iwona Kobielusz-Gembala, Barbara Rewerska, Adam Madrzejewski, Krzysztof Milewski, Jerzy Cygler, Joanna Petryka-Mazurkiewicz, Waldemar Jastrzebski, Janusz Korecki, Wojciech Fil, Janusz Prokopczuk, Anna Bochenek, Marek Wujkowski, Robert Witek, Piotr Konczakowski, Pawel Miekus, Marcin Szczasny, Wlodzimierz Musial, Krzysztof Cymerman, Jacek Lampart, Jacek Mikosinski, Slawomir Szynal, Issa Fares, Grzegorz Opolski, Stanislaw Mazur, Beata Wozakowska-Kaplon, Renata Bijata-Bronisz, Lukasz Wierucki, Beata Losa, Grzegorz Drelich, Marek Konieczny, Pawel Starczewski, Lidia Pawlowicz, Pawel Jesionowski, Jaroslaw Jurowiecki, Jacek Gniot, Mariusz Czyzycki, Karol Stania, Izabela Kucharczyk-Bauman, Benita Busz-Papiez, Agnieszka Karczmarczyk, Wanda Sudnik, Alina Koszek, Piotr Kolodziej, Bartosz Skwarna, Nicolás Jaramillo, Maciej Jankowski, Wojciech Czochra, Leszek Kinasz, Beata Miklaszewicz, Teresa Stasinska, Wladyslaw Pluta, Marcin Basiak, Teresa Rusicka, Izabela Niedbal-Yahfouf, Grazyna Popenda, Romuald Korzeniak, Agnieszka Mirek, Rafal Mariankowski, Lukasz Wojnowski, Marek Korol, Jacek Baszak, Piotr Podolec, Wojciech Piesiewicz, Aleksander Zurakowski, Carlos Luengas, Marek Skura, Piotr Pilecki, Piotr Majchrzak, Ewa Krzyzagórska, Marcin Drozd, Barbara Kaczmarek, Teresa Sliwinska, Katarzyna Zelazowska, Rafal Sztembis, Katarzyna Landa, Lidia Matyszczak-Toniak, Krzysztof Strojek, Marek Piepiorka, Robert Malinowski, Maria Górska, Edyta Stolarczyk-Sowa, Leszek Romanowski, Elzbieta Zinka, Zygfryd Reszka, Joanna Skierkowska, Anna Uzunow, Ewa Laskowska-Derlaga, Ekaterina Puntus, Elena D Kosmacheva, Natalia Koziolova, Prokhor Pavlov, Tatiana Supryadkina, Yury Didenko, Philipp Kopylov, Andrei Kazakov, Sergei Aksentiev, Elena Vishneva, Alexey Repin, Olga Smolenskaya, Olga Mantserova, Oleg Khrustalev, Elena Privalova, Vladimir Konstantinov, Svetlana Boldueva, Andrey Ezhov, Alexander Chernyavsky, Gadel Kamalov, Albert Galyavich, Galina Zubeeva, Galina Nechaeva, Sergey Shustov, Nino Dzhaiani, Tatiana Treshkur, Nataliya Osokina, Alexey Panov, Elena Shutemova, Valeriy Makukhin, Tatiana Kropotina, Larisa Tsyba, Yuri Karpov, J M Sizova, Marina Ballyuzek, Nikolay Tarasov, Elena Demchenko, Olga Barbarash, Valentin Moiseev, Valentin Markov, Vadim Kuznetsov, Inna Viktorova, Igor Sergienko, Lyudmila Ermoshkina, Niyaz Khasanov, Tatiana Khlevchuk, Andrey Baglikov, Sergey Shalaev, Elena Zonova, Elena Reznik, Larisa Haisheva, Tatyana Morugova, Nikita Lomakin, Alexander Vishnevsky, Yuri Shvarts, Olga Magnitskaya, Marina Mikhailusova, Elena Pavlysh, Igor Libov, Anna Zateyschikova, Victor Kostenko, Anton Edin, Yaroslava Khovaeva, Konstantin Zakharov, Raisa Stryuk, Vladimir Khirmanov, Sergey Kanorskiy, Sergey Yakushin, Anna Barabashkina, Hongwei Li, Qiang Zhao, Jian Zhang, Jianhua Ma, Yong He, Ming Luo, Aidong Zhang, Ningru Zhang, Yingru Chai, Genshan Ma, Hao Wang, Zhigang Liu, Lanjie He, Zhifang Song, Xiaolin Dong, Liang Tao, Zhanquan Li, Xi Su, Xiangqing Kong, Heping Niu, Junbo Ge, Zhurong Luo, Wenjun Huang, Daoquan Peng, Zuyi Yuan, Maria Milanova, Doncho Tenev, Antoni Gogov, Dimitar Karageorgiev, Todor Kolchev, Nikolay Rusev, Nikolina Georgieva, Rumen Kondov, Veselin Rusinov, Ivo Petrov, Georgi Stanchev, Mariana Konteva, Adriana Dincheva, Zdravka Yaneva, Ralitsa Vatova, Katya Ilieva, Nikolai Runev, Borislav Kolomanov, Ivan Petrov, Nikolay Iliev, Snezhanka Tisheva, Boryana Chompalova, Maria Tokmakova, Dimitar Raev, Kolyo Byanov, Dimitar Markov, Lenko Mihov, Atanas Mihov, Nora Milcheva, Milen Minchev, Mihail Mollov, Borislav Borisov, Tihomir Tihchev, Venelin Karakolev, Bojidar Dimov, Svetoslav Georgiev, Lachezar Smilov, Bon K Koo, Taehoon Ahn, Soon J Hong, Junghan Yoon, Seok K Oh, Myung H Jeong, Doo-Il Kim, Kiyuk Chang, Weon Kim, Joo-Yong Hahn, Kwang S Cha, Jung-Hee Lee, Si-Wan Choi, Chang-Wook Nam, In-Ho Chae, Yong H Park, Seung-Jea Tahk, Won-Yong Shin, Jei-Keon Chae, Byung J Kim, Jang-Whan Bae, Woo J Park, Seung W Rha, Young J Choi, Jin-Yong Hwang, Hun S Park, Luciano Baracioli, Fabio Guimaraes, Eduardo Vasconcellos, José Saraiva, Adamastor Pereira, Queulla Santos, Paulo Rossi, Lilia Maia, Miguel Madeira, Marcio Pereira, Roberto Botelho, Gilmar Reis, Freddy Eliaschewitz, Joao Borges, Carlos Nascimento, Jose A Fortes, Weimar de Souza, Pedro Pimentel, Miguel Hissa, Marcos Franchetti, Dalton Precoma, Costantino Ortiz, Mauro Hernandes, Wladmir Saporito, Fabio R dos Santos, Adrian Kormann, Fernando Neuenschwander, Oscar Dutra, Nelson Rassi, Luiz Tanajura, Juliana Souza, Delcio S Junior, Paulo Leaes, Adriana Forte, Teresa C Bonansea, Jose Marin, Bruno Machado, Maria J Cerqueira, Frederico Silva, Yorghos Michalaros, Euler Manenti, Cintia Cercato, Estevao Figueiredo, Ming-En Liu, Yi-Chih Wang, Tsung-Ming Lee, Chih Fang, Yen-Wen Wu, Kwo-Chang Ueng, Huey-Herng Sheu, Wen T Lai, I-Chang Hsieh, Zhih-Cherng Chen, Mu-Jang Lee, Chern Chiang, Kou-Gi Shyu, Chien-Hsun Hsia, Guang-Yuan Mar, Shih-Hung Chan, Chih-Cheng Wu, Wei-Kung Tseng, Kuan-Cheng Chang, Hung-I Yeh, Ji-Hung Wang, Charles Hou, Inna Sorokina, Maryna Dolzhenko, Olha Horoshko, Oleksandr Karpenko, Leonid Rudenko, Igor Vakaliuk, Anna Kulyk, Olena Levchenko, Oleksandr Prokhorov, Dmytro Reshotko, Mykhaylo Sorokivskyy, Nataliia Velichko, Valentyn Maslovskyi, Zinaida Teliatnikova, Sergiy Dotsenko, Olena Krakhmalova, Igor Kraiz, Viktoria Zharinova, Larysa Bula, Igor Kaydashev, Valeriy Molodtsov, Lesya Rasputina, Viktoriya Pidlisna, Olena Lysunets, Anatoliy Kravchenko, Liubomyr Glushko, Tetyana Khomazyuk, Yevgeniya Svyshchenko, Oleksandr Parkhomenko, Boris Mankovsky, Orest Abrahamovych, Andriy Yagensky, Mykola Stanislavchuk, Larisa Vasilyeva, Liubov Sokolova, Oleg Sychov, Vira Tseluyko, Igor Kyrychenko, Mykola Rishko, Sergiy Furkalo, Richard Gallo, Olivier Bertrand, Shamir Mehta, Christian Constance, Bruce Sussex, Remo Zadra, Simon Kouz, Raja Chehayeb, Amritanshu Pandey, Danielle Dion, Gordon Bailey, Laurie Hill, Krishnan Ramanathan, Micha Dorsch, Alykhan Nanji, Mohan Babapulle, Martine Montigny, Gilbert Gosselin, Payam Dehghani, Dennis Rupka, Michel Le May, Francis Pichette, Francois St-Maurice, Patrick Teefy, Samer Mansour, Saleem Kassam, Stephen Cheung, Anthony D Siega, Dennis O'Keefe, Eric Sabbah, Alan Bell, Guy Chouinard, Brian Wong, Mark Miller, Daniel Gaudet, Pierre Lachance, Iqbal Bata, Robert Petrella, Denis Gossard, Richard Dumas, Douglas Ing, Hagop Boyrazian, Ricardo Bessoudo, Thao T Huynh, Randy Hart, Jasmin Belle-Isle, Dinkar Shukla, Allan Kelly, Giuseppe Mazza, James Cha, Sam Henein, Andre Frechette, Saul Vizel, Joanne F Liutkus, Michael O'Mahony, Frank Halperin, Jacobus Kooy, John Graham, Allan Bailey, Ronald Wojcik, Igor Wilderman, Tibor Turi, Ákos Motyovszki, Béla Merkely, Csaba Király, Péter Andrássy, Zsolt Sárszegi, Tibor Fülöp, Zsolt Zilahi, István Édes, Andras Papp, Gábor Müller, Anna Czigány, Szilárd Zólyomi, László Korányi, János Takács, Ferenc Juhász, Bela Benczur, Sándor Kancz, András Földi, András C Nagy, Judit Bakai, István Greschik, László Püski, László Nagy, Róbert Kirschner, Roman Kuchar, Petr Hajek, Ladislav Busak, Daniel Michalik, Ivo Matyasek, Ivana Marusincova, Dusan Kucera, Ondrej Jerabek, Michaela Honkova, Vratislav Dedek, Ivan Rihacek, Pavel Kos, Josef Slaby, Martina Machkova, Eva Zidkova, Lubomir Elbl, Hana Grunfeldova, Jiri Carda, Vladimir Mrozek, Jiri Maly, Richard Milkovic, Jan Malecha, Hana Skalicka, Ivo Oral, Eva Krcova, Libor Lisa, Jan Belohlavek, Roman Miklik, Ondrej Cermak, Jana Bednarova, Zdenek Peroutka, Jindrich Spinar, Andreas Wilke, Karl-Friedrich Appel, Jens Taggeselle, Andreas Förster, Nicole Toursarkissian, Ekkehard Schmidt, Jochen Bott, Ayham Al-Zoebi, Dirk Hennig, Sabine Fischer, Norbert Schön, Joachim Sauter, Gregor Simonis, Ruth Nischik, Werner Rieker, Isabelle Schenkenberger, Thomas Behnke, Gerhard Klausmann, Michael Jeserich, Dietmar Trenk, Ingo Weigmann, Hannes Reuter, Reinhard Rummel, Candy von Münchhausen, Charlotte von Engelhardt, Eishun Horibe, Taro Shibasaki, Tomohiko Sato, Tsunekazu Kakuta, Ichiro Michishita, Michinao Tan, Ryoji Ishiki, Takahiko Aoyama, Shinichi Higashiue, Yawara Niijima, Akira Idogaki, Toru Hasegawa, Arihiro Kiyosue, Yoshiaki Tomobuchi, Katsunori Kawamitsu, Satsuki Kawasaki, Yoshiki Hata, Kazuki Fukui, Kozaburo Seki, Takashi Takenaka, Mitsuru Abe, Noriaki Utsu, Atsuyuki Oono, Kazuhisa Mitsuo, Atsushi Sueyoshi, Atsushi Hirohata, Mitsuru Tsujimoto, Osamu Ueda, Shinichi Takase, Masahiro Suzuki, Satoru Sakuragi, Fumi Yamamoto, Noritaka Fujimoto, Shigeo Kakinoki, Tatsushi Sugiura, Hiroshi Sugino, Toshihiro Nakamura, Toshiaki Kadokami, Hiroki Uehara, Masahiro Ono, Koichi Yokoya, Akihiro Koike, Sei Komatsu, Masahiro Sonoda, Hideki Ueno, Tomofumi Doi, Yuichiro Takagi, Kazuteru Fujimoto, Yutaka Eki, Munenori Okubo, Kenichiro Sasaki, Martijn van Eck, Eelko Ronner, Salem The, Ruud van de Wal, Pieter Nierop, Cornelis de Nooijer, Henri Werner, Iris Westendorp, Coen van der Zwaan, Hendrikus Crijns, Jan H Cornel, Sipke Strikwerda, Robert Bos, Edwin de Melker, Adrianus Kuijper, Hans Louwerenburg, Jacobus Plomp, Jan-Melle Dantzig, Francisco Prins, Henricus van Kesteren, Frank Willems, Giovanni Amoroso, Gabriela Carnero, Ernesto Duronto, Diego Besada, Carolina Chacon, Pedro Zangroniz, Silvana Solis, Alberto Liberman, Virginia Sernia, Andres Alvarisqueta, Laura Maffei, Oscar G Vilamajo, Celso García, Maximiliano Sicer, Juan Muntaner, Anselmo Bordonava, Juan Albisu, Alejandra Zanini, Lucas Rista, Miguel Hominal, José N Estrada, Aldo Prado, Diego M Gosparini, Beatriz Schiavi, Armando G Castillo, José G Ruíz, Guillermo R Martinez, Víctor G López, Enrique L Rosas, Gabriel R Lopez, Elias G Cantu, Manuel de los Ríos Ibarra, Francisco P Padilla, Jose P Carrasco, Luis V Carrillo, Joel D García, Alfredo N Askar, Carlos A Salinas, Marco A Gamba, Carlos G Sanchez, Arnulfo G Cantú, Raul V Sánchez, Jaime C Madrigal, Rafael H Urbano, Andrés Í Romo, José R González Juanatey, Paolo Racugno, Angel C Fillat, José M de la Torre Hernández, Juan A Peláez, Jorge B Cortada, Pablo G Pavia, Manuel J Navarro, Roberto M Asenjo, Francisco F Díaz, Eduard B Peligero, Fernando A Manterola, Antonio F Ortiz, Juan D Mediavilla García, Francisco M Ortuño, Tomás R Vera, Alfonso S González, Jaime A Viñas, Francisco J Fernández Portales, Petra S Mayordomo, Francisco B Ojeda, Antonio R Domínguez, Rosa S González, Diego B Guerrero, Juan M Ruiz Nodar, Xavier G Marimon, José G Margáez, Roberto M Aguilera, José F Díaz Fernández, José L Zamorano Gómez, Vicente B González, Bruno G del Blanco, Ignacio P Pérez, Mercé R Moreno, Ainhoa R Ereño, José A García Lledó, Juan Prieto, Alex Villablanca, Carlos Raffo, Christian Pincetti, Carlos Conejeros, Oscar Roman, Manuel Rodriguez, Paola Varleta, Cindy Goldberg, Jorge Sandoval, German Arriagada, Lucio Leon, Sergio Potthoff, Jorge Cobos, Christian Figueroa, Ellen Makotoko, Nyda Fourie, Lesley Burgess, Hendrik Nortje, Rust Theron, Perumal Pillai, Naresh Ranjith, Julien Trokis, Soobramoney Pillay, Jeevren Reddy, Theema Nunkoo, Cornelia Kapp, Dorothea Urbach, Lawrence Distiller, Adrian Horak, Louis van Zyl, Kathleen Coetzee, Zelda Punt, Junaid Bayat, Saleem Dawood, Ismail Mitha, Trevenesan Padayachee, Farzana Hoosen, Anthony Dalby, null Prabhavathi, Prakash Gowdaiah, Vimal Mehta, Milan Chag, Milind Gadkari, Kannaiyan Ramamurthee, Asit Das, Jitendra S Sawhney, Suvro Banerjee, Prachee Sathe, Srilakshmi Adhyapak, Tuan Nguyen, Vinh Pham, Huan Do, Anh Nguyen, Hien Nguyen, Binh Truong, Shahnaz Jamil-Copley, Chim Lang, Alastair Pell, Azfar Zaman, Robert Storey, Neil Swanson, Simon Smith, David Sharman, Denise Braganza, Peter Hammond, Andrew Moriarty, Stephen Bain, Maurice Pye, Andrew Sharp, Mark Blagden, Harpal Randeva, Timothy Myhill, Girish Viswanathan, Philip Keeling, Piers Clifford, Manish Saxena, Kristopher Lyons, John McMurray, Feeroz Jaafar, Clare Murphy, Simon Cartwright, Kamal Abouglila, Lubomir Antalik, Peter Krajci, Miroslav Urban, Frantisek Fazekas, Daniel Pella, Daniel Koleny, Tatiana Vykoukalova, Vladimir Macek, Daniela Vinanska, Livia Jamriskova, Slavomir Such, Peter Fulop, Stefan Farsky, Viliam Bugan, Jaroslava Strbova, Karol Micko, Juraj Palka Jr, Vladimir Sivak, Dalby Kristensen, Jens Refsgaard, Lene Holmvang, Ulrik Dixen, Henrik Nielsen, Kenneth Egstrup, Lisette O Jensen, Roman Sykulski, Ole Rasmussen, Alin Andries, Anders Luckow, Gitte Nielsen, Torben Sørensen, Chaiyasith Wongvipaporn, Noppadol Chamnarnphol, Suphot Srimahachota, Nakarin Sansanayudh, Srun Kuanprasert, Damras Tresukosol, Bancha Sookananchai, Mehmet Kanadasi, Turkay Ozcan, Murathan Kucuk, Zeki Ongen, Ertugrul Okuyan, Alev Arat, Sadik Acikel, Ahmet Yalcin, Umit Guray, Ceyhun Ceyhan, Necla Ozer, Sakir Arslan, Oskar Angerås, Nina Johnston, Ann-Charlotte Weiderman, Stellan Bandh, Ole Hansen, Hans Larnefeldt, Dawid Kusiak, Carl-Johan Lindholm, Anders Hedman, David Erlinge, Dan Curiac, Pia Lundman, Roberto Zucconi-Mazzini, Layth Aladellie, Jens Jensen, Jan Verwerft, Mathias Vrolix, Dirk Faes, Harry Striekwold, Peter Sinnaeve, Patrick Timmermans, Antoine Guedes, Marc Delforge, Jan Nimmegeers, Francis Stammen, Ian Buysschaert, Etienne Hoffer, Geert Hollanders, Geert Vervoort, Patrick Coussement, Stefan de Maeseneire, Luc Janssens, Stein A Gravdal, Knut Risberg, Lars Gullestad, Ola D Hofseth, Dennis Nilsen, Knut T Lappegård, Christian van den Heuvel, Charlotte Gibbs, Alamdar Khusrawi, Satish Arora, Tadeusz Tomala, Thorbjørn Kjærnli, Jan Berg-Johansen, Robert Hagemeier, Gunnar Skjelvan, David Colquhoun, John Amerena, Claire Morbey, Christopher Hammett, Anthony Dart, Ronald Lehman, Andrew Hamilton, Matthew Worthley, Peter Purnell, Alan Whelan, Richard MacIsaac, Ktut Arya, Sultan Linjawi, Joseph Proietto, Lakshman Prasad, Aldo Rodriguez, Armando Godoy, Victor Rodriguez, Percy Berrospi, Carlos Chavez, Sandra Negron, Javier Heredia, Felix Medina, Helard Manrique, Walter Cabrera, Fernando Cordova, Trinidad Quinteros, Jaime M Haro, Susana Regalado, Javier Guitton, Hugo Arbanil, Michel Pansieri, Eric Decoulx, Pascal Goube, Axel de Labriolle, Jean N Labeque, Gregoire Range, Yves Cottin, Gilles Montalescot, Guillaume Cayla, Nicolas Danchin, Denis Angoulvant, Emile Ferrario, Meyer Elbaz, Olivier Dubreuil, Philippe G Steg, Caroline Fontaine, Emmanuel Sorbets, Hafiz Omer, Shukri Al-Saif, Hussam Al-Faleh, Abdullah Al-Shehri, Halia Alshehri, Rasha Bazari, Pak Hei, Man Ying, Michael Chan, Michelle Wong, Ronald Ma, Shing C Siu, Chiu C Tsang, Maurizio Ferrario, Emilio Assanelli, Michele Senni, Piermarco Piatti, Paolo Calabrò, Stefano Urbinati, Massimo Michisanti, Ferdinando Varbella, Salvatore de Cosmo, Roberto Trevisan, Sandro Bellotti, Giuseppe Di Pasquale, Angelo S Bongo, Massimo Uguccioni, Edoardo Mannucci, Ciro Mauro, Mauro Ragonese, Claudio Fresco, Maurizio Turturo, Rossella Marcucci, Manuel J Lievano Triana, Camilo Arana, Jose Accini, Rodrigo Botero, Marlena Muzyk-Osikowicz, Fredy T Dada, Gregorio S Vallejo, Fernando Manzur, Daniel Isaza, Dora Molina, Juan G Mesa, Alvaro Quintero, Kai Nyman, Jyrki Mäkelä, Jorma Strand, Sakari Nieminen, Jyrki Taurio, Matti Kuusela, Timo Valle, Mikko Pietilä, Sakari Kekki, Timo Strandberg, Marc Klutstein, Gabriel Greenberg, Yoseph Rozenman, Ehud Chorin, Ariel Roguin, Basil Lewis, Amir Bashkin, Edgar Tan, Jose P Prado, Arthur Ferrolino, Noe Babilonia, Benny Barbas, Generoso Matiga, Raul M Coching, Heinz Drexel, Helmut Brath, Christoph Schnack, Ursula Hanusch, Evelyn Fließer-Görzer, Bernhard Paulweber, Christoph Ebenbichler, Rudolf Prager, Kurt Huber, Michael Wolzt, Johann Auer, Rudolf Berger, Gerit-Holger Schernthaner, Gabriela Stanciulescu, Mihai Creteanu, Marilena Spiridon, Viorica Dobreanu, Dragos Vinereanu, Laura C Iosipescu, Octavian Istratoaie, Ioan Coman, Constantin Militaru, Mircea Cinteza, Peter R Sinnaeve, José C Nicolau, José F Kerr Saraiva, Ramón Corbalán, Petr Widimský, Steen D Kristensen, Juha Hartikainen, Harald Darius, Hung F Tse, Robert G Kiss, Prem Pais, Eli Lev, Leonardo de Luca, Gabriel A Ramos López, Frederic Kontny, Noe A Babilonia, Dmitry A Zateyshchikov, Mikhail Ruda, Omer Elamin, František Kovář, Anthony J Dalby, Héctor Bueno, Chern-En Chiang, Alexander Parkhomenko, Tuan Q Nguyen, Maria Leonsson-Zachrisson, Herrada, Anthony, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Brompton Hospital, McMaster University [Hamilton, Ontario], Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], St. Michael's Hospital, University of Toronto, Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Uppsala University Hospital, Uppsala Universitet [Uppsala], AstraZeneca, Tokai University, Uppsala University, Imperial College London, Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of New South Wales [Sydney] (UNSW), University of Texas Southwestern Medical Center [Dallas], Stanford University, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Bhatt, D, Steg, P, Mehta, S, Leiter, L, Simon, T, Fox, K, Held, C, Andersson, M, Himmelmann, A, Ridderstrale, W, Chen, J, Song, Y, Diaz, R, Goto, S, James, S, Ray, K, Parkhomenko, A, Kosiborod, M, Mcguire, D, Harrington, R, Santos, V, Jain, A, Lendel, I, Russo, M, Haught, W, Bouza, M, Gogia, H, Banerjee, S, Kichura, G, Kantaros, L, Padron, F, Passi, R, Stone, J, Pursley, M, D'Urso, M, Gardner, T, Bennett, J, Nour, K, Saini, S, Zhang, W, Kumbhani, D, Thomas, D, Angiolillo, D, Bertolet, B, Roman-Miranda, A, Black, R, Manshadi, R, Vaca, C, Blanco, A, Napoli, M, Brabham, D, Akyea-Djamson, A, Desai, P, Prasada, S, Khaira, A, Forgosh, L, Lieber, I, Umpierrez, G, Singal, D, Londono, J, Fraser, N, Ruiz, J, Vega, D, Rodriguez, L, Brown, C, Syed, F, Aggarwala, G, Eaves, W, Foster, M, Gupta, D, Avino, D, Asfour, W, Tonnessen, G, Zhao, X, Singh, N, Brockmyre, A, Lepor, N, Shammas, N, Blick, D, Hearne, S, Prodafikas, J, Carell, E, Izzo, M, Karim, A, Zakhary, B, Atieh, M, Leichter, S, Meadows, C, Hotchkiss, D, Abu-Fadel, M, Wiseman, A, Bander, J, Shah, M, Ganim, R, Sopko, K, Khan, M, Lloret, R, Weirick, T, Mehta, R, Thadani, U, Bhargava, A, Moya, J, Staniloae, C, Guerra, Y, Chhabra, A, Kosmicki, D, Shaheen, W, Mohammed, A, Bitters, J, Pattanayak, J, Javier, J, Srivastava, S, Phillips, R, Al-Amin, J, Lillestol, M, Simpson, P, Hazan, L, Amin, A, Shah, G, Korpas, D, Platt, B, Dickert, J, Puente, O, Hiotis, L, Doyle, T, Rajan, R, Meholick, A, Gring, C, Hage-Korban, E, Feldman, R, Colfer, H, Butman, S, Hart, T, Huling, R, Eshaghian, S, Quintana, O, Cheung, D, Handel, F, Rodriguez, M, Suh, D, Gordon, P, Pressman, G, Bauer, M, French, W, Barettella, M, Chatrathi, S, Suresh, D, Goldberg, R, Huth, M, Younis, L, Rahman, A, Mascolo, R, Welch, M, Suneja, R, Smith, S, Shurmur, S, Agaiby, J, Jingo, A, Johnston, J, Beth, M, Vlastaris, A, Kemp, S, Taheri, H, Pereira, E, Deyoung, M, Hawa, Z, Smith, R, Galski, T, Garas, S, Reddy, M, Sharma, S, Hargrove, J, Treasure, C, Emerson, R, Haddad, T, Rohr, K, Levinson, L, Gaona, R, Uretsky, B, Maheshwari, H, Lee, D, Kinnaman, S, Singal, R, Geohas, J, Gigliotti, O, Raisinghani, A, Khurana, C, Hella, B, Kelberman, M, Voyce, S, Singh, S, Lo, E, Singh, P, Goodfellow, R, Fischer, S, Lorraine, R, Turner, T, Shanes, J, Busch, R, Broker, R, Zaniewski, M, Pounds, K, Debs-Perez, G, Ong, S, Frandsen, B, Fullington, D, Jaffrani, N, Khan, A, Lee, M, Pouzar, J, Revtyak, G, Gonzalez, J, Nakhle, S, Murillo, A, Young, D, Makam, S, Syed, M, Woolf, K, Grena, P, Alfata, S, Mahal, S, Hoffman, D, Kizhakekuttu, T, Deering, J, Bhavsar, J, Mikesell, S, Wilson, W, Wilson, V, El, S, Spinale, F, Kannarkat, V, Rao, S, Hanson, L, Bertsch, J, Gonzalez-Ortiz, E, Severino, N, Willis, J, Schock, J, Bakhtari, L, Gazmuri, R, Ansari, S, Hall, J, Mehta, A, Shealy, N, Zarich, S, Singh, D, Vora, K, Andrawis, N, Molter, D, Maron, D, Cardona, J, D'Agostino, R, Arshad, T, Samaan, R, Jones, D, Presser, D, Heath, J, Green, S, Bittar, G, Henry, S, Korn, D, Schmedtje, J, Nadar, V, Graham, B, Labroo, A, Clavijo, L, Roseman, H, Ledesma, G, Rosen, R, Dor, I, Kirby, W, Sutton, J, Eder, F, Iteld, B, Gomez-Cortes, J, Buchbinder, M, Kasper, J, Terrelonge, A, Torres, G, Jagielo, T, Alvarez, J, Handelsman, Y, Guillen, M, Richwine, R, Lewy-Alterbaum, L, Corder, C, Arvind, M, Bolshoun, D, Mikhail, M, Minton, S, Alvarado, O, Abbott, J, Cauthen, B, Welter, R, Mintz, R, Cox, J, Quick, A, Weiss, M, Dy, J, Zebrack, J, Gandelman, G, Hegde, V, Silver, M, Degregorio, M, Lawson, W, Paa, C, Bortnick, A, Krolick, M, Sotolongo, R, Cheirif, J, Kumar, P, Jetty, P, Patel, A, Kruk, M, Kobielusz-Gembala, I, Rewerska, B, Madrzejewski, A, Milewski, K, Cygler, J, Petryka-Mazurkiewicz, J, Jastrzebski, W, Korecki, J, Fil, W, Prokopczuk, J, Bochenek, A, Wujkowski, M, Witek, R, Konczakowski, P, Miekus, P, Szczasny, M, Musial, W, Cymerman, K, Lampart, J, Mikosinski, J, Szynal, S, Fares, I, Opolski, G, Mazur, S, Wozakowska-Kaplon, B, Bijata-Bronisz, R, Wierucki, L, Losa, B, Drelich, G, Konieczny, M, Starczewski, P, Pawlowicz, L, Jesionowski, P, Jurowiecki, J, Gniot, J, Czyzycki, M, Stania, K, Kucharczyk-Bauman, I, Busz-Papiez, B, Karczmarczyk, A, Sudnik, W, Koszek, A, Kolodziej, P, Skwarna, B, Jaramillo, N, Jankowski, M, Czochra, W, Kinasz, L, Miklaszewicz, B, Stasinska, T, Pluta, W, Basiak, M, Rusicka, T, Niedbal-Yahfouf, I, Popenda, G, Korzeniak, R, Mirek, A, Mariankowski, R, Wojnowski, L, Korol, M, Baszak, J, Podolec, P, Piesiewicz, W, Zurakowski, A, Luengas, C, Skura, M, Pilecki, P, Majchrzak, P, Krzyzagorska, E, Drozd, M, Kaczmarek, B, Sliwinska, T, Zelazowska, K, Sztembis, R, Landa, K, Matyszczak-Toniak, L, Strojek, K, Piepiorka, M, Malinowski, R, Gorska, M, Stolarczyk-Sowa, E, Romanowski, L, Zinka, E, Reszka, Z, Skierkowska, J, Uzunow, A, Laskowska-Derlaga, E, Puntus, E, Kosmacheva, E, Koziolova, N, Pavlov, P, Supryadkina, T, Didenko, Y, Kopylov, P, Kazakov, A, Aksentiev, S, Vishneva, E, Repin, A, Smolenskaya, O, Mantserova, O, Khrustalev, O, Privalova, E, Konstantinov, V, Boldueva, S, Ezhov, A, Chernyavsky, A, Kamalov, G, Galyavich, A, Zubeeva, G, Nechaeva, G, Shustov, S, Dzhaiani, N, Treshkur, T, Osokina, N, Panov, A, Shutemova, E, Makukhin, V, Kropotina, T, Tsyba, L, Karpov, Y, Sizova, J, Ballyuzek, M, Tarasov, N, Demchenko, E, Barbarash, O, Moiseev, V, Markov, V, Kuznetsov, V, Viktorova, I, Sergienko, I, Ermoshkina, L, Khasanov, N, Khlevchuk, T, Baglikov, A, Shalaev, S, Zonova, E, Reznik, E, Haisheva, L, Morugova, T, Lomakin, N, Vishnevsky, A, Shvarts, Y, Magnitskaya, O, Mikhailusova, M, Pavlysh, E, Libov, I, Zateyschikova, A, Kostenko, V, Edin, A, Khovaeva, Y, Zakharov, K, Stryuk, R, Khirmanov, V, Kanorskiy, S, Yakushin, S, Barabashkina, A, Li, H, Zhao, Q, Zhang, J, Ma, J, He, Y, Luo, M, Zhang, A, Zhang, N, Chai, Y, Ma, G, Wang, H, Liu, Z, He, L, Song, Z, Dong, X, Tao, L, Li, Z, Su, X, Kong, X, Niu, H, Ge, J, Luo, Z, Huang, W, Peng, D, Yuan, Z, Milanova, M, Tenev, D, Gogov, A, Karageorgiev, D, Kolchev, T, Rusev, N, Georgieva, N, Kondov, R, Rusinov, V, Petrov, I, Stanchev, G, Konteva, M, Dincheva, A, Yaneva, Z, Vatova, R, Ilieva, K, Runev, N, Kolomanov, B, Iliev, N, Tisheva, S, Chompalova, B, Tokmakova, M, Raev, D, Byanov, K, Markov, D, Mihov, L, Mihov, A, Milcheva, N, Minchev, M, Mollov, M, Borisov, B, Tihchev, T, Karakolev, V, Dimov, B, Georgiev, S, Smilov, L, Koo, B, Ahn, T, Hong, S, Yoon, J, Oh, S, Jeong, M, Kim, D, Chang, K, Kim, W, Hahn, J, Cha, K, Lee, J, Choi, S, Nam, C, Chae, I, Park, Y, Tahk, S, Shin, W, Chae, J, Kim, B, Bae, J, Park, W, Rha, S, Choi, Y, Hwang, J, Park, H, Baracioli, L, Guimaraes, F, Vasconcellos, E, Saraiva, J, Pereira, A, Santos, Q, Rossi, P, Maia, L, Madeira, M, Pereira, M, Botelho, R, Reis, G, Eliaschewitz, F, Borges, J, Nascimento, C, Fortes, J, de Souza, W, Pimentel, P, Hissa, M, Franchetti, M, Precoma, D, Ortiz, C, Hernandes, M, Saporito, W, dos Santos, F, Kormann, A, Neuenschwander, F, Dutra, O, Rassi, N, Tanajura, L, Souza, J, Junior, D, Leaes, P, Forte, A, Bonansea, T, Marin, J, Machado, B, Cerqueira, M, Silva, F, Michalaros, Y, Manenti, E, Cercato, C, Figueiredo, E, Liu, M, Wang, Y, Lee, T, Fang, C, Wu, Y, Ueng, K, Sheu, H, Lai, W, Hsieh, I, Chen, Z, Chiang, C, Shyu, K, Hsia, C, Mar, G, Chan, S, Wu, C, Tseng, W, Yeh, H, Wang, J, Hou, C, Sorokina, I, Dolzhenko, M, Horoshko, O, Karpenko, O, Rudenko, L, Vakaliuk, I, Kulyk, A, Levchenko, O, Prokhorov, O, Reshotko, D, Sorokivskyy, M, Velichko, N, Maslovskyi, V, Teliatnikova, Z, Dotsenko, S, Krakhmalova, O, Kraiz, I, Zharinova, V, Bula, L, Kaydashev, I, Molodtsov, V, Rasputina, L, Pidlisna, V, Lysunets, O, Kravchenko, A, Glushko, L, Khomazyuk, T, Svyshchenko, Y, Parkhomenko, O, Mankovsky, B, Abrahamovych, O, Yagensky, A, Stanislavchuk, M, Vasilyeva, L, Sokolova, L, Sychov, O, Tseluyko, V, Kyrychenko, I, Rishko, M, Furkalo, S, Gallo, R, Bertrand, O, Constance, C, Sussex, B, Zadra, R, Kouz, S, Chehayeb, R, Pandey, A, Dion, D, Bailey, G, Hill, L, Ramanathan, K, Dorsch, M, Nanji, A, Babapulle, M, Montigny, M, Gosselin, G, Dehghani, P, Rupka, D, Le May, M, Pichette, F, St-Maurice, F, Teefy, P, Mansour, S, Kassam, S, Cheung, S, Siega, A, O'Keefe, D, Sabbah, E, Bell, A, Chouinard, G, Wong, B, Miller, M, Gaudet, D, Lachance, P, Bata, I, Petrella, R, Gossard, D, Dumas, R, Ing, D, Boyrazian, H, Bessoudo, R, Huynh, T, Hart, R, Belle-Isle, J, Shukla, D, Kelly, A, Mazza, G, Cha, J, Henein, S, Frechette, A, Vizel, S, Liutkus, J, O'Mahony, M, Halperin, F, Kooy, J, Graham, J, Bailey, A, Wojcik, R, Wilderman, I, Turi, T, Motyovszki, A, Merkely, B, Kiss, R, Kiraly, C, Andrassy, P, Sarszegi, Z, Fulop, T, Zilahi, Z, Edes, I, Papp, A, Muller, G, Czigany, A, Zolyomi, S, Koranyi, L, Takacs, J, Juhasz, F, Benczur, B, Kancz, S, Foldi, A, Nagy, A, Bakai, J, Greschik, I, Puski, L, Nagy, L, Kirschner, R, Kuchar, R, Hajek, P, Busak, L, Michalik, D, Matyasek, I, Marusincova, I, Kucera, D, Jerabek, O, Honkova, M, Dedek, V, Rihacek, I, Kos, P, Slaby, J, Machkova, M, Zidkova, E, Elbl, L, Grunfeldova, H, Carda, J, Mrozek, V, Maly, J, Milkovic, R, Malecha, J, Skalicka, H, Oral, I, Krcova, E, Lisa, L, Belohlavek, J, Miklik, R, Cermak, O, Bednarova, J, Peroutka, Z, Spinar, J, Wilke, A, Appel, K, Taggeselle, J, Forster, A, Toursarkissian, N, Schmidt, E, Bott, J, Al-Zoebi, A, Hennig, D, Schon, N, Sauter, J, Simonis, G, Nischik, R, Rieker, W, Schenkenberger, I, Behnke, T, Klausmann, G, Jeserich, M, Trenk, D, Weigmann, I, Reuter, H, Rummel, R, von Munchhausen, C, von Engelhardt, C, Horibe, E, Shibasaki, T, Sato, T, Kakuta, T, Michishita, I, Tan, M, Ishiki, R, Aoyama, T, Higashiue, S, Niijima, Y, Idogaki, A, Hasegawa, T, Kiyosue, A, Tomobuchi, Y, Kawamitsu, K, Kawasaki, S, Hata, Y, Fukui, K, Seki, K, Takenaka, T, Abe, M, Utsu, N, Oono, A, Mitsuo, K, Sueyoshi, A, Hirohata, A, Tsujimoto, M, Ueda, O, Takase, S, Suzuki, M, Sakuragi, S, Yamamoto, F, Fujimoto, N, Kakinoki, S, Sugiura, T, Sugino, H, Nakamura, T, Kadokami, T, Uehara, H, Ono, M, Yokoya, K, Koike, A, Komatsu, S, Sonoda, M, Ueno, H, Doi, T, Takagi, Y, Fujimoto, K, Eki, Y, Okubo, M, Sasaki, K, van Eck, M, Ronner, E, The, S, van de Wal, R, Nierop, P, de Nooijer, C, Werner, H, Westendorp, I, van der Zwaan, C, Crijns, H, Cornel, J, Strikwerda, S, Bos, R, de Melker, E, Kuijper, A, Louwerenburg, H, Plomp, J, Dantzig, J, Prins, F, van Kesteren, H, Willems, F, Amoroso, G, Carnero, G, Duronto, E, Besada, D, Chacon, C, Zangroniz, P, Solis, S, Liberman, A, Sernia, V, Alvarisqueta, A, Maffei, L, Vilamajo, O, Garcia, C, Sicer, M, Muntaner, J, Bordonava, A, Albisu, J, Zanini, A, Rista, L, Hominal, M, Estrada, J, Prado, A, Gosparini, D, Schiavi, B, Castillo, A, Martinez, G, Lopez, V, Rosas, E, Lopez, G, Cantu, E, de los Rios Ibarra, M, Padilla, F, Carrasco, J, Carrillo, L, Garcia, J, Askar, A, Salinas, C, Gamba, M, Sanchez, C, Cantu, A, Sanchez, R, Madrigal, J, Urbano, R, Romo, A, Gonzalez Juanatey, J, Racugno, P, Fillat, A, de la Torre Hernandez, J, Pelaez, J, Cortada, J, Pavia, P, Navarro, M, Asenjo, R, Diaz, F, Peligero, E, Manterola, F, Ortiz, A, Mediavilla Garcia, J, Ortuno, F, Vera, T, Gonzalez, A, Vinas, J, Fernandez Portales, F, Mayordomo, P, Ojeda, F, Dominguez, A, Gonzalez, R, Guerrero, D, Ruiz Nodar, J, Marimon, X, Margaez, J, Aguilera, R, Diaz Fernandez, J, Zamorano Gomez, J, Gonzalez, V, del Blanco, B, Perez, I, Moreno, M, Ereno, A, Garcia Lledo, J, Prieto, J, Villablanca, A, Raffo, C, Pincetti, C, Conejeros, C, Roman, O, Varleta, P, Goldberg, C, Sandoval, J, Arriagada, G, Corbalan, R, Leon, L, Potthoff, S, Cobos, J, Figueroa, C, Makotoko, E, Fourie, N, Burgess, L, Nortje, H, Theron, R, Pillai, P, Ranjith, N, Trokis, J, Pillay, S, Reddy, J, Nunkoo, T, Kapp, C, Urbach, D, Distiller, L, Horak, A, van Zyl, L, Coetzee, K, Punt, Z, Bayat, J, Dawood, S, Mitha, I, Padayachee, T, Hoosen, F, Dalby, A, Prabhavathi, Gowdaiah, P, Mehta, V, Chag, M, Gadkari, M, Ramamurthee, K, Das, A, Sawhney, J, Sathe, P, Adhyapak, S, Nguyen, T, Pham, V, Do, H, Nguyen, A, Nguyen, H, Truong, B, Jamil-Copley, S, Lang, C, Pell, A, Zaman, A, Storey, R, Swanson, N, Sharman, D, Braganza, D, Hammond, P, Moriarty, A, Bain, S, Pye, M, Sharp, A, Blagden, M, Randeva, H, Myhill, T, Viswanathan, G, Keeling, P, Clifford, P, Saxena, M, Lyons, K, Mcmurray, J, Jaafar, F, Murphy, C, Cartwright, S, Abouglila, K, Antalik, L, Krajci, P, Urban, M, Fazekas, F, Pella, D, Koleny, D, Vykoukalova, T, Macek, V, Vinanska, D, Jamriskova, L, Such, S, Fulop, P, Farsky, S, Bugan, V, Strbova, J, Micko, K, Palka Jr, J, Sivak, V, Kristensen, D, Refsgaard, J, Holmvang, L, Dixen, U, Nielsen, H, Egstrup, K, Jensen, L, Sykulski, R, Rasmussen, O, Andries, A, Luckow, A, Nielsen, G, Sorensen, T, Wongvipaporn, C, Chamnarnphol, N, Srimahachota, S, Sansanayudh, N, Kuanprasert, S, Tresukosol, D, Sookananchai, B, Kanadasi, M, Ozcan, T, Kucuk, M, Ongen, Z, Okuyan, E, Arat, A, Acikel, S, Yalcin, A, Guray, U, Ceyhan, C, Ozer, N, Arslan, S, Angeras, O, Johnston, N, Weiderman, A, Bandh, S, Hansen, O, Larnefeldt, H, Kusiak, D, Lindholm, C, Hedman, A, Erlinge, D, Curiac, D, Lundman, P, Zucconi-Mazzini, R, Aladellie, L, Jensen, J, Verwerft, J, Vrolix, M, Faes, D, Striekwold, H, Sinnaeve, P, Timmermans, P, Guedes, A, Delforge, M, Nimmegeers, J, Stammen, F, Buysschaert, I, Hoffer, E, Hollanders, G, Vervoort, G, Coussement, P, de Maeseneire, S, Janssens, L, Gravdal, S, Risberg, K, Gullestad, L, Hofseth, O, Nilsen, D, Lappegard, K, van den Heuvel, C, Gibbs, C, Khusrawi, A, Arora, S, Tomala, T, Kjaernli, T, Berg-Johansen, J, Hagemeier, R, Skjelvan, G, Colquhoun, D, Amerena, J, Morbey, C, Hammett, C, Dart, A, Lehman, R, Hamilton, A, Worthley, M, Purnell, P, Whelan, A, Macisaac, R, Arya, K, Linjawi, S, Proietto, J, Prasad, L, Rodriguez, A, Godoy, A, Rodriguez, V, Berrospi, P, Chavez, C, Negron, S, Heredia, J, Medina, F, Manrique, H, Cabrera, W, Cordova, F, Quinteros, T, Haro, J, Regalado, S, Guitton, J, Arbanil, H, Pansieri, M, Decoulx, E, Goube, P, de Labriolle, A, Labeque, J, Range, G, Cottin, Y, Montalescot, G, Cayla, G, Danchin, N, Angoulvant, D, Ferrario, E, Elbaz, M, Dubreuil, O, Fontaine, C, Sorbets, E, Omer, H, Al-Saif, S, Al-Faleh, H, Al-Shehri, A, El-Amin, O, Alshehri, H, Bazari, R, Hei, P, Ying, M, Chan, M, Wong, M, Ma, R, Siu, S, Tsang, C, Ferrario, M, Assanelli, E, Senni, M, Piatti, P, Calabro, P, Urbinati, S, Michisanti, M, Varbella, F, de Cosmo, S, Trevisan, R, Bellotti, S, Di Pasquale, G, Bongo, A, Uguccioni, M, Mannucci, E, Mauro, C, Ragonese, M, Fresco, C, Turturo, M, Marcucci, R, Lievano Triana, M, Arana, C, Accini, J, Botero, R, Muzyk-Osikowicz, M, Dada, F, Vallejo, G, Manzur, F, Isaza, D, Molina, D, Mesa, J, Quintero, A, Nyman, K, Makela, J, Strand, J, Nieminen, S, Taurio, J, Kuusela, M, Valle, T, Pietila, M, Kekki, S, Strandberg, T, Klutstein, M, Greenberg, G, Rozenman, Y, Chorin, E, Roguin, A, Lewis, B, Bashkin, A, Tan, E, Prado, J, Ferrolino, A, Babilonia, N, Barbas, B, Matiga, G, Coching, R, Drexel, H, Brath, H, Schnack, C, Hanusch, U, Fliesser-Gorzer, E, Paulweber, B, Ebenbichler, C, Prager, R, Huber, K, Wolzt, M, Auer, J, Berger, R, Schernthaner, G, Stanciulescu, G, Creteanu, M, Spiridon, M, Dobreanu, V, Vinereanu, D, Iosipescu, L, Istratoaie, O, Coman, I, Militaru, C, Cinteza, M, Nicolau, J, Kerr Saraiva, J, Widimsky, P, Kristensen, S, Hartikainen, J, Darius, H, Tse, H, Pais, P, Lev, E, de Luca, L, Ramos Lopez, G, Kontny, F, Zateyshchikov, D, Ruda, M, Elamin, O, Kovar, F, Bueno, H, Leonsson-Zachrisson, M, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Royal Brompton and Harefield NHS Foundation Trust-Imperial College London

Subjects
Male, Platelet Aggregation Inhibitors/therapeutic use, THEMIS Steering Committee and Investigators, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 030204 cardiovascular system & hematology, Coronary Angiography, Stroke/epidemiology, Coronary artery disease, DOUBLE-BLIND, 0302 clinical medicine, Hemorrhage/chemically induced, acetylsalicylic acid, antidiabetic agent, placebo, ticagrelor, Secondary Prevention, Medicine, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, Cardiovascular Diseases/mortality, 11 Medical and Health Sciences, OUTCOMES, Aspirin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Medicine, Middle Aged, Clopidogrel, 3. Good health, Ticagrelor/therapeutic use, DRUG-ELUTING STENTS, CLOPIDOGREL, Cardiology, PLATELET INHIBITION, Drug Therapy, Combination, Female, Life Sciences & Biomedicine, Ticagrelor, TIMI, medicine.drug, Coronary Artery Disease/complications, medicine.medical_specialty, Hypoglycemic Agents/therapeutic use, POOLED ANALYSIS, 03 medical and health sciences, Medicine, General & Internal, Percutaneous Coronary Intervention, Double-Blind Method, General & Internal Medicine, Internal medicine, Myocardial Infarction/epidemiology, Humans, Aged, Science & Technology, ANTIPLATELET THERAPY, business.industry, Diabetes Mellitus, Type 2/complications, ELEVATION MYOCARDIAL-INFARCTION, RIVAROXABAN, Percutaneous coronary intervention, medicine.disease, ASPIRIN, Coronary Stenosis/diagnostic imaging, Aspirin/therapeutic use, Conventional PCI, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p

Published
2019

28. Development of Non-Invasive miRNA Markers for Assessing the Quality of Human Induced Pluripotent Stem Cell-Derived Retinal Organoids

Author

Hyo Song Park, Ji-Hong Bang, Wook Hyun Jung, Jin Young Yang, Hee Jeong Shin, Ji-Hye Son, Jung Woo Han, Si Hyung Lee, Kyung Hwun Chung, Kyunggon Kim, Hun Soo Chang, and Tae Kwann Park

Subjects
retinal organoids, exosomes, microRNA, differentiation, non-invasive, markers, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into ‘superior’ and ‘inferior’ groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods.

Published
2024
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29. Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

Author

Jung Woo Han, Hun Soo Chang, Sung Chul Park, Jin Young Yang, Ye Ji Kim, Jin Ha Kim, Hyo Song Park, Han Jeong, Junwon Lee, Chang Ki Yoon, Hyung Gon Yu, Se Joon Woo, Jungmook Lyu, and Tae Kwann Park

Subjects
induced pluripotent stem cells, organoids, retina, retinoschisis, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

Published
2024
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30. A mouse model of spinal and bulbar muscular atrophy

Author

McManamny, Patrick, Chy, Hun S., Finkelstein, David I., Craythorn, Rebecca G., Crack, Peter J., Kola, Ismail, Cheema, Surindar S., Horne, Malcolm K., Wreford, Nigel G., OʼBryan, Moira K., de Kretser, David M., and Morrison, John R.

Published
2002

31. Calcium ionophore-activated platelets induce eosinophil extracellular trap formation

Author

Myeong Seong Sim, Hye Jeong Kim, Ikhyeon Bae, Chun Kim, Hun Soo Chang, Youngwoo Choi, Dong-Hyun Lee, Hae-Sim Park, and Il Yup Chung

Subjects
Calcium ionophore, Eosinophil, Eosinophil extracellular trap, Platelet, Thrombin, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Platelets play a modulatory role in inflammatory response by secreting a vast array of granules and disintegrating into membrane-bound microparticles upon activation. The interplay between eosinophils and platelets is postulated to be implicated in the pathology of allergic airway inflammation. In this study, we investigated whether activated platelets can induce eosinophil extracellular trap (EET) formation, a cellular process by which activated eosinophils release net-like DNA fibers. Methods: Platelets were stimulated with the calcium ionophore, A23187, and the platelet agonists, thrombin and adenosine diphosphate (ADP). Platelet cultures were fractionated into conditioned medium (CM) and pellet, which were then overlaid on eosinophils to examine EET formation. Results: The CM and pellet from A23187-activated platelets stimulated eosinophils to generate EET, whereas those from thrombin- or ADP-activated platelets failed to induce such generation. The EET-inducing activity of the A23187-activated platelet culture was linearly proportional to the number of activated platelets. Interestingly, while EET formation induced by the direct stimulation of eosinophils with A23187 was NADPH oxidase (NOX)-dependent, EET formation induced by A23187-activated platelets was NOX-independent and significantly inhibited by necroptosis pathway inhibitors. Conclusions: Activated platelets and their products may induce EET formation, thereby potentiating their role in eosinophilic airway inflammation.

Published
2023
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32. Long-term clinical outcomes of image-guided percutaneous coronary intervention in acute myocardial infarction from the Korea Acute Myocardial Infarction Registry

Author

Youngjoon Kwon, Namkyun Kim, Chang-Yeon Kim, Do-Hoon Kim, Hyewon Shin, Min-Su Jung, Jong Sung Park, Yoon Jung Park, Bo Eun Park, Hong Nyun Kim, Se Yong Jang, Myung Hwan Bae, Jang Hoon Lee, Dong Heon Yang, Hun Sik Park, Yongkeun Cho, Kwang Soo Cha, Seung-Ho Hur, Jin-Yong Hwang, and Myung Ho Jeong

Subjects
Medicine, Science
Published
2024

34. Single-Cell Profiling Identifies Key Pathways Expressed by iPSCs Cultured in Different Commercial Media

Author

Damián Hernández, Anne Senabouth, Vikrant Singh, David A. Mackey, Tejal Kulkarni, Duncan E. Crombie, Helena Liang, Stacey B. Andersen, Andrew L. Laslett, Hun S. Chy, Joseph E. Powell, Sophie Chevalier, Maciej Daniszewski, Alex W. Hewitt, Grace E. Lidgerwood, James C. Vickers, Jamie E Craig, Louise A. Rooney, Priyadharshini Sivakumaran, Alison Conquest, Quan Nguyen, and Alice Pébay

Subjects
0301 basic medicine, Multidisciplinary, Cell, RNA, Biology, Regenerative medicine, Cell biology, Transcriptome, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, medicine, lcsh:Q, Copy-number variation, Human Induced Pluripotent Stem Cells, Induced pluripotent stem cell, lcsh:Science, Gene
Abstract

Summary: We assessed the pluripotency of human induced pluripotent stem cells (iPSCs) maintained on an automated platform using StemFlex and TeSR-E8 media. Analysis of transcriptome of single cells revealed similar expression of core pluripotency genes, as well as genes associated with naive and primed states of pluripotency. Analysis of individual cells from four samples consisting of two different iPSC lines each grown in the two culture media revealed a shared subpopulation structure with three main subpopulations different in pluripotency states. By implementing a machine learning approach, we estimated that most cells within each subpopulation are very similar between all four samples. The single-cell RNA sequencing analysis of iPSC lines grown in both media reports the molecular signature in StemFlex medium and how it compares to that observed in the TeSR-E8 medium. : Stem Cells Research; Transcriptomics; Automation Subject Areas: Stem Cells Research, Transcriptomics, Automation

Published
2018

35. Single Cell Profiling Identifies Key Pathways Expressed by iPSCs Cultured in Different Commercial Media

Author

Tejal Kulkarni, Helena Liang, Quan Nguyen, Duncan E. Crombie, Anne Senabouth, Alex W. Hewitt, Jamie E Craig, Hun S. Chy, Sophie Chevalier, Maciej Daniszewski, Andrew L. Laslett, Damián Hernández, Stacey B. Andersen, Grace E. Lidgerwood, James C. Vickers, Louise A. Rooney, David A. Mackey, Alice Pébay, Joseph E. Powell, Alison Conquest, and Vikrant Singh

Subjects
Transcriptome, medicine.anatomical_structure, Cell, medicine, RNA, Human Induced Pluripotent Stem Cells, Biology, Induced pluripotent stem cell, Gene, Cell biology
Abstract

We assessed the pluripotency of human induced pluripotent stem cells (iPSCs) maintained on an automated platform using StemFlexTM and TeSRTM-E8TM media. Analysis of transcriptome of single cells revealed similar expression of core pluripotency genes, as well as genes associated with naive and primed states of pluripotency. Analysis of individual cells from four samples consisting of two different iPSC lines each grown in the two culture media revealed a shared subpopulation structure with three main subpopulations different in pluripotency states. By implementing a machine-learning approach, we estimated that most cells within each subpopulation are very similar between all four samples. The single cell RNA sequencing analysis of iPSC lines grown in both media is the first report of the molecular signature of StemFlex medium and how it compares to that observed in TeSR-E8 medium.

Published
2018

38. Comparison of Outcomes After Percutaneous Coronary Intervention for Chronic Total Occlusion Using Everolimus- Versus Sirolimus- Versus Paclitaxel-Eluting Stents (from the Korean National Registry of Chronic Total Occlusion Intervention)

Author

Yangsoo Jang, Hyo-Soo Kim, In Ho Chae, Seung Ho Hur, Seung Hwan Lee, Hun S. Park, Seung-Woon Rha, Min-Ho Lee, Si Hyuck Kang, Cheol Woong Yu, Moo H. Kim, Hyeon Cheol Gwon, Joo Myung Lee, and Chang Hwan Yoon

Subjects
Male, medicine.medical_specialty, Paclitaxel, medicine.medical_treatment, Population, Antineoplastic Agents, Coronary Angiography, Electrocardiography, Percutaneous Coronary Intervention, Internal medicine, Republic of Korea, medicine, Humans, Everolimus, Registries, cardiovascular diseases, Myocardial infarction, education, Retrospective Studies, Sirolimus, education.field_of_study, business.industry, Percutaneous coronary intervention, Stent, Drug-Eluting Stents, Retrospective cohort study, Middle Aged, medicine.disease, Survival Rate, Treatment Outcome, Coronary Occlusion, Chronic Disease, Cohort, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Immunosuppressive Agents, Mace, Follow-Up Studies, medicine.drug
Abstract

For the treatment of chronic total occlusion (CTO), the efficacy and safety of the everolimus-eluting stent (EES) remain less well defined. Also, there are limited data for the predictors of outcome after CTO intervention. The purpose of this study was to compare clinical outcomes of the EES with the first-generation drug-eluting stent (DES) in CTO intervention and to investigate the predictors of clinical outcome. The Korean National Registry of CTO Intervention is a retrospective cohort of 26 centers from the past 5 years. The primary end point was major adverse cardiovascular events (MACE) defined as a composite of cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Of the 1,754 all-comer patients, 1,509 patients (EES 311, sirolimus-eluting stent [SES] 642, paclitaxel-eluting stent 556) were finally analyzed after excluding 245 patients (mixed DESs in 46 and follow-up loss in 199). In the inverse probability weighting-adjusted population, the 1-year MACE rate of the EES was comparable with that of the SES (5.8% vs 3.4%, p = 0.796) and the paclitaxel-eluting stent (5.8% vs 6.9%, p = 0.740). Each component of MACE was also comparable among the 3 stents. Importantly, the independent predictors of MACE were diabetes mellitus, previous congestive heart failure, and left circumflex CTO. In conclusion, for the first time in the largest CTO cohort, the EES showed good 1-year clinical outcomes that were comparable with the SES. Independent predictors of MACE after CTO intervention were clinical factors (diabetes and congestive heart failure) and lesion location.

Published
2015

41. Real-time heart rate variability according to ambulatory glucose profile in patients with diabetes mellitus

Author

Sung Il Im, Soo Jin Kim, Su Hyun Bae, Bong Joon Kim, Jung Ho Heo, Su kyoung Kwon, Sung Pil Cho, Hun Shim, Jung Hwan Park, Hyun Su Kim, and Chul Ho Oak

Subjects
heart rate variability, glucose level, real-time monitoring, electrocadiography, autonomic dysfunction, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

BackgroundAutonomic neuropathy commonly occurs as a long-term complication of diabetes mellitus (DM) and can be diagnosed based on heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There are limited data on HRV using real-time ECG and ambulatory glucose monitoring in patients with DM. The aim of this study was to investigate real-time HRV according to ambulatory glucose levels in patients with DM.MethodsA total of 43 patients (66.3 ± 7.5 years) with DM underwent continuous real-time ECG monitoring (225.7 ± 107.3 h) for HRV and ambulatory glucose monitoring using a remote monitoring system. We compared the HRV according to the ambulatory glucose profile. Data were analyzed according to the target in glucose range (TIR).ResultsThere were no significant differences in the baseline characteristics of the patients according to the TIR. During monitoring, we checked ECG and ambulatory glucose levels (a total of 15,090 times) simultaneously for all patients. Both time- and frequency-domain HRVs were lower when the patients had poorly controlled glucose levels (TIR 70%). In addition, heart and respiratory rates increased with real-time glucose levels (P

Published
2023
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42. CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: A SUNFRAIL report

Author

Bousquet, J. Onorato, G.L. Bachert, C. Barbolini, M. Bedbrook, A. Bjermer, L. De Sousa, J.C. Chavannes, N.H. Cruz, A.A. De Manuel Keenoy, E. Devillier, P. Fonseca, J. Hun, S. Kostka, T. Hellings, P.W. Illario, M. Ivancevich, J.C. Larenas-Linnemann, D. Millot-Keurinck, J. Ryan, D. Samolinski, B. Sheikh, A. Yorgancioglu, A. Agache, I. Arnavielhe, S. Bewick, M. Annesi-Maesano, I. Anto, J.M. Bergmann, K.C. Bindslev-Jensen, C. Bosnic-Anticevich, S. Bouchard, J. Caimmi, D.P. Camargos, P. Canonica, G.W. Cardona, V. Carriazo, A.M. Cingi, C. Colgan, E. Custovic, A. Dahl, R. Demoly, P. De Vries, G. Fokkens, W.J. Fontaine, J.F. Gemicioǧlu, B. Guldemond, N. Gutter, Z. Haahtela, T. Hellqvist-Dahl, B. Jares, E. Joos, G. Just, J. Khaltaev, N. Keil, T. Klimek, L. Kowalski, M.L. Kull, I. Kuna, P. Kvedariene, V. Laune, D. Louis, R. Magnan, A. Malva, J. Mathieu-Dupas, E. Melén, E. Menditto, E. Morais-Almeida, M. Mösges, R. Mullol, J. Murray, R. Neffen, H. O'Hehir, R. Palkonen, S. Papadopoulos, N.G. Passalacqua, G. Pépin, J.L. Portejoie, F. Price, D. Pugin, B. Raciborski, F. Simons, F.E.R. Sova, M. Spranger, O. Stellato, C. Todo Bom, A. Tomazic, P.V. Triggiani, M. Valero, A. Valovirta, E. Vandenplas, O. Valiulis, A. Van Eerd, M. Ventura, M.T. Wickman, M. Young, I. Zuberbier, T. Zurkuhlen, A. Senn, A.

Abstract

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices. © 2017 The Author(s).

Published
2017

43. Recommendations for the use of serious games in neurodegenerative disorders: 2016 Delphi Panel

Author

Manera, V. Ben-Sadoun, G. Aalbers, T. Agopyan, H. Askenazy, F. Benoit, M. Bensamoun, D. Bourgeois, J. Bredin, J. Bremond, F. Crispim-Junior, C. David, R. Schutter, B.D. Ettore, E. Fairchild, J. Foulon, P. Gazzaley, A. Gros, A. Hun, S. Knoefel, F. Rikkert, M.O. Phan Tran, M.K. Politis, A. Rigaud, A.S. Sacco, G. Serret, S. Thümmler, S. Welter, M.L. Robert, P.

Abstract

The use of Serious Games (SG) in the health domain is expanding. In the field of neurodegenerative disorders (ND) such as Alzheimer's disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients' treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014). The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI) and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI). SG are more adapted for use with trained caregivers (both at home and in clinical settings), with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game), and should be personalized with the help of a clinician. © 2017 Manera, Ben-Sadoun, Aalbers, Agopyan, Askenazy, Benoit, Bensamoun, Bourgeois, Bredin, Bremond, Crispim-Junior, David, De Schutter, Ettore, Fairchild, Foulon, Gazzaley, Gros, Hun, Knoefel, Olde Rikkert, Phan Tran, Politis, Rigaud, Sacco, Serret, Thümmler, Welter and Robert.

Published
2017

44. CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: A SUNFRAIL report

Author

Bousquet, J. and Onorato, G.L. and Bachert, C. and Barbolini, M. and Bedbrook, A. and Bjermer, L. and De Sousa, J.C. and Chavannes, N.H. and Cruz, A.A. and De Manuel Keenoy, E. and Devillier, P. and Fonseca, J. and Hun, S. and Kostka, T. and Hellings, P.W. and Illario, M. and Ivancevich, J.C. and Larenas-Linnemann, D. and Millot-Keurinck, J. and Ryan, D. and Samolinski, B. and Sheikh, A. and Yorgancioglu, A. and Agache, I. and Arnavielhe, S. and Bewick, M. and Annesi-Maesano, I. and Anto, J.M. and Bergmann, K.C. and Bindslev-Jensen, C. and Bosnic-Anticevich, S. and Bouchard, J. and Caimmi, D.P. and Camargos, P. and Canonica, G.W. and Cardona, V. and Carriazo, A.M. and Cingi, C. and Colgan, E. and Custovic, A. and Dahl, R. and Demoly, P. and De Vries, G. and Fokkens, W.J. and Fontaine, J.F. and Gemicioǧlu, B. and Guldemond, N. and Gutter, Z. and Haahtela, T. and Hellqvist-Dahl, B. and Jares, E. and Joos, G. and Just, J. and Khaltaev, N. and Keil, T. and Klimek, L. and Kowalski, M.L. and Kull, I. and Kuna, P. and Kvedariene, V. and Laune, D. and Louis, R. and Magnan, A. and Malva, J. and Mathieu-Dupas, E. and Melén, E. and Menditto, E. and Morais-Almeida, M. and Mösges, R. and Mullol, J. and Murray, R. and Neffen, H. and O'Hehir, R. and Palkonen, S. and Papadopoulos, N.G. and Passalacqua, G. and Pépin, J.L. and Portejoie, F. and Price, D. and Pugin, B. and Raciborski, F. and Simons, F.E.R. and Sova, M. and Spranger, O. and Stellato, C. and Todo Bom, A. and Tomazic, P.V. and Triggiani, M. and Valero, A. and Valovirta, E. and Vandenplas, O. and Valiulis, A. and Van Eerd, M. and Ventura, M.T. and Wickman, M. and Young, I. and Zuberbier, T. and Zurkuhlen, A. and Senn, A., Contre les MAladies Chroniques Pour un VIeillissement, Actif en France Europ. Innov. Partnership on Active and Healthy Ageing Ref. Site, Montpellier, France, INSERM U 1168, VIMA, Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, UMR-S 1168, Montigny le Bretonneux, France, Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent, Belgium, Regione Emilia Romagna - Agenzia Sanitaria e Sociale, Reference Site of the European Innovation Partnership on Healthy and Active Ageing, Bologna, Italy, Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands, ProAR - Nucleo de Excelencia em Asma, Federal University of Bahia, Salvador, Brazil, GARD Executive Committee, Salvador, Brazil, Kronikgune, International Centre of Excellence in Chronicity Research Barakaldo, Bilbao Bizkaia, Spain, Laboratoire de Pharmacologie Respiratoire UPRES EA220, Pôle des Maladies Respiratoires, Hôpital Foch, Suresnes Université Versailles Saint-Quentin, Versailles, France, Center for Health Technology and Services Research- CINTESIS, Faculdade de Medicina, Universidade Do Porto, Porto, Portugal, Allergy Unit, CUF Porto Instituto and Hospital, Porto, Portugal, Public Health Agency Northern Ireland, Belfast, United Kingdom, Department of Geriatrics, Medical University of Lodz, Healthy Ageing Research Centre (HARC), Lodz, Poland, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Louvain, Belgium, Division for Health Innovation, Campania Region, Federico II University Hospital Naples, RandD and DISMET, Naples, Italy, Allergy and Immunology Department, Santa Isabel, Buenos Aires, Argentina, Clínica de Alergia, Asma y Pediatría, Hospital Médica sur, Mexico, Mexico, Caisse Assurance Retraite et Santé Au Travail Languedoc-Roussillon (CARSAT-LR), Montpellier, 34000, France, Allergy and Respiratory Research Group, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom, Department of Prevention of Envinronmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Asthma UK Centre for Applied Research, Centre of Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom, Department of Pulmonology, Celal Bayar University, Manisa, Turkey, GARD Executive Committee, Manisa, Turkey, Faculty of Medicine, Transylvania University, Brasov, Romania, Kyomed, Montpellier, France, IQ4U Consultants Ltd, London, United Kingdom, EPAR U707 INSERM, Paris and EPAR UMR-S UPMC, Paris VI, Paris, France, Centre for Research in Environmental Epidemiology (CREAL), ISGLoBAL, Barcelona, Spain, IMIM, Hospital Del Mar Research Institute), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, Comprehensive Allergy-Centre-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany, Global Allergy and Asthma European Network (GA2LEN), Berlin, Germany, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark, Woolcock Institute of Medical Research, University of Sydney and Sydney Local Health District, Glebe, NSW, Australia, Laval's University, Quebec City, Canada, Hôpital de la Malbaie, Quebec City, Canada, CHRU de Montpellier, Sorbonne Universités, UPMC Paris 06, UMR-S 1136, IPLESP, Equipe EPAR, Paris, 75013, France, Department of Respiratory Diseases, Montpellier University Hospital, Montpellier, France, Department of Pediatrics, Medical School, Federal University of Minas Gerais, Belo Horizonte, Brazil, Personalized Medicine Clinic Asthma and Allergy, Humanitas University, Humanitas Research Hospital, Rozzano Milan, Italy, Allergologia, S Medicina Interna, Hospital Vall d'Hebron, Barcelona, Spain, Regional Ministry of Health of Andalusia, Seville, Spain, ENT Department, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey, Department of Health, Social Services and Public Safety, Belfast, United Kingdom, Department of Pediatric, Imperial College London, London, United Kingdom, Peercode DV, Gerdermalsen, Netherlands, Department of Otorhinolaryngology, Academic Medical Centre, Amsterdam, Netherlands, Allergist, Reims, France, Department of Pulmonary Diseases, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, Institute of Health Policy and Management IBMG, Erasmus University, Rotterdam, Netherlands, University Hospital Olomouc, National EHealth Centre, Olomouc, Czech Republic, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland, Department of Respiratory Diseases, Odense University Hospital, Odense, Denmark, Libra Foundation, Buenos Aires, Argentina, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium, Allergology Department, Centre de l'Asthme et des Allergies Hôpital d'Enfants Armand-Trousseau (APHP), Paris, France, UPMC Univ Paris 06, UMR-S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Equipe EPAR, Sorbonne Universités, Paris, 75013, France, GARD, Geneva, Switzerland, Institute of Social Medicine, Epidemiology and Health Economics, Charité - Universitätsmedizin Berlin, Berlin, Germany, Institute for Clinical Epidemiology and Biometry, University of Wuerzburg, Würzburg, Germany, Center for Rhinology and Allergology, Wiesbaden, Germany, Department of Immunology Rheumatology and Allergy, Medical University of Lodz, HARC, Lodz, Poland, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet Stockholm, Stockholm, Sweden, Division of Internal Medicine Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Clinic of Infectious Chest Diseases, Dermatology and Allergology, Vilnius University, Vilnius, Lithuania, Department of Pulmonary Medicine, CHU Sart-Tilman, Liege, Belgium, Service de Pneumologie, UMR INSERM, UMR1087 and CNR 6291, L'Institut du Thorax, University of Nantes, Nantes, France, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal, Ageing at Coimbra EIP-AHA Reference Site, Coimbra, Portugal, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, CIRFF, Federico II University, Naples, Italy, Allergy and Clinical Immunology Department, Hospital CUF-Descobertas, Lisbon, Portugal, Institute of Medical Statistics, Informatics and Epidemiology, Medical Faculty, University of Cologne, Cologne, Germany, Clinical and Experimental Respiratory Immunoallergy, ENT Department, Hospital Clínic, IDIBAPS, CIBERES, Universitat de Barcelona, Barcelona, Spain, Medical Communications Consultant, MedScript Ltd, Dundalk Co Louth, Ireland, Argentina Center for Allergy and Immunology, Alassia Children's Hospital, Santa Fe, Santa Fe, Argentina, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Central Clinical School, Monash University, Melbourne, VIC, Australia, Department of Immunology, Monash University, Melbourne, VIC, Australia, EFA European Federation of Allergy and Airways Diseases Patients' Associations, Brussels, Belgium, Center for Pediatrics and Child Health, Institute of Human Development, Royal Manchester Children's Hospital, University of Manchester, Manchester, M13 9WL, United Kingdom, Allergy Department, 2nd Pediatric Clinic, Athens General Children's Hospital PandA Kyriakou, University of Athens, Athens, 11527, Greece, Allergy and Respiratory Diseases, IRCCS San Martino Hospital, IST-University of Genoa, Genoa, Italy, CHU Grenoble, La Tronche, France, Observational and Pragmatic Research Institute, Singapore, Singapore, Optimum Patient Care, Cambridge, United Kingdom, Academic Centre of Primary Care, University of Aberdeen, Aberdeen, United Kingdom, Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada, University Hospital Olomouc, Olomouc, Czech Republic, Global Allergy and Asthma Platform GAAPP, Altgasse 8-10, Vienna, 1130, Austria, Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana, University of Salerno, Salerno, Italy, Imunoalergologia, Centro Hospitalar Universitário de Coimbra, Faculty of Medicine, University of Coimbra, Coimbra, Portugal, Department of ENT, Medical University of Graz, Graz, Austria, Pneumology and Allergy Department Hospital Clínic, Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Department of Chest Medicine, Centre Hospitalier Universitaire UCL Namur, Université Catholique de Louvain, Yvoir, Belgium, Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy, Queen's University Belfast, Belfast, United Kingdom, Gesundheitsregion KölnBonn-HRCB Projekt GmbH, Kohln, Germany, EC-CNECT-H2, European Commission, Brussels, Belgium, and CHU Montpellier, 371 Avenue du Doyen Gaston Giraud, Montpellier Cedex 5, 34295, France

Abstract

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices. © 2017 The Author(s).

Published
2017

45. A taxonomic re-assessment of Oligodon cinereus (Günther, 1864) (Squamata, Serpentes, Colubridae) populations from southern Indochina

Author

Platon V. Yushchenko, Justin L. Lee, Thy Neang, Hun Seiha, Nguyen Van Tan, Gernot Vogel, and Nikolay A. Poyarkov Jr.

Subjects
Zoology, QL1-991
Abstract

The ashy kukri snake Oligodon cinereus (Günther, 1864) is a widely distributed and morphologically variable species found throughout mainland Southeast Asia. In this paper, we re-assessed the taxonomic status of O. cinereus populations found in southern Indochina (southern Vietnam, Cambodia, and southern Laos), including the recently described Cat Tien kukri snake Oligodon cattienensis Vassilieva et al., 2013, which was previously confused with this species. Phylogenetic analyses using mitochondrial DNA from the 12S–16S ribosomal subunit and cytochrome b gene revealed that O. cattienensis is embedded in a mixed clade containing samples of the subspecies O. cinereus pallidocinctus, which bears a dorsal color pattern with white crossbars and black edges. This clade forms a strongly supported sister group with a topotypic sample of O. cinereus cinereus, representing populations bearing a uniform dorsal color pattern and slight reticulate markings, however the genetic divergence between the two clades is very low. The morphological characters used to distinguish O. cattienensis from O. cinereus sensu lato broadly overlap and supposed differences in hemipenial morphology between the two taxa are due to outdated terminologies used to describe the organ. We relegate both O. cattienensis and O. cinereus pallidocinctus to the junior synonymy of O. cinereus and consider all color patterns of this species found near the type locality in Cambodia, southern Laos, and southern Vietnam to represent O. cinereus sensu stricto. Future integrative investigations across the range of O. cinereus sensu lato are needed to resolve the status of the remaining subspecies and synonyms associated with this taxon. Problems associated with hemipenial morphology and Oligodon systematics are also discussed.

Published
2023
Full Text
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46. Self-efficacy and positive thinking as predictors of health-related quality of life in women with stress urinary incontinence

Author

Ching Hui Chien, Xuan Yi Huang, Shu Pen Hsu, Yi Hua Yen, Hun Shan Pan, and Feng Chu Yen

Subjects
Stress urinary incontinence, Positive thinking, Self-efficacy, Quality of life, Gynecology and obstetrics, RG1-991, Public aspects of medicine, RA1-1270
Abstract

Highlights • General quality of life was influenced by positive thinking in women with SUI. • Health-related QOL was influenced by self-efficacy in women with SUI. • Symptom distress was a predictor of urinary incontinence-specific QOL. • Multi-element programs are needed to improve the health-related QOL of women with SUI.

Published
2022
Full Text
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47. Recommendations for the Use of Serious Games in Neurodegenerative Disorders: 2016 Delphi Panel

Author

Manera, V., Ben-Sadoun, G., Aalbers, T., Agopyan, H., Askenazy, F., Benoit, M., Bensamoun, D., Bourgeois, J., Bredin, J., Bremond, F., Crispim-Junior, C., David, R., Schutter, B. De, Ettore, E., Fairchild, J., Foulon, P., Gazzaley, A., Gros, A., Hun, S., Knoefel, F., Olde Rikkert, M.G.M., Tran, M.K.P., Politis, A., Rigaud, A.S., Sacco, G., Serret, S., Thummler, S., Welter, M.L., Robert, P., Manera, V., Ben-Sadoun, G., Aalbers, T., Agopyan, H., Askenazy, F., Benoit, M., Bensamoun, D., Bourgeois, J., Bredin, J., Bremond, F., Crispim-Junior, C., David, R., Schutter, B. De, Ettore, E., Fairchild, J., Foulon, P., Gazzaley, A., Gros, A., Hun, S., Knoefel, F., Olde Rikkert, M.G.M., Tran, M.K.P., Politis, A., Rigaud, A.S., Sacco, G., Serret, S., Thummler, S., Welter, M.L., and Robert, P.

Abstract

Contains fulltext : 177188.pdf (publisher's version ) (Open Access), The use of Serious Games (SG) in the health domain is expanding. In the field of neurodegenerative disorders (ND) such as Alzheimer's disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients' treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014). The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI) and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI). SG are more adapted for use with trained caregivers (both at home and in clinical settings), with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game), and should be personalized with the help of a clinician.

Published
2017

48. Recommendations for the use of serious games in neurodegenerative disorders: 2016 Delphi Panel

Author

Manera, V. (Valeria), Ben-Sadoun, G. (Grégory), Aalbers, T. (Teun), Agopyan, H. (Hovannes), Askenazy, F. (Florence), Benoit, M. (Michel), Bensamoun, D. (David), Bourgeois, J. (Jérémy), Bredin, J. (Jonathan), Bremond, F. (Francois), Crispim-Junior, C. (Carlos), David, R. (Renaud), Schutter, B.D. (Bob De), Ettore, E. (Eric), Fairchild, J. (Jennifer), Foulon, P. (Pierre), Gazzaley, A. (Adam), Gros, A. (Auriane), Hun, S. (Stéphanie), Knoefel, F. (Frank), Rikkert, M.O. (Marcel Olde), Phan Tran, M.K. (Minh K.), Politis, A. (Antonios), Rigaud, A.S. (Anne S.), Sacco, G. (Guillaume), Serret, S. (Sylvie), Thümmler, S. (Susanne), Welter, M.L. (Marie L.), Robert, P. (Philippe), Manera, V. (Valeria), Ben-Sadoun, G. (Grégory), Aalbers, T. (Teun), Agopyan, H. (Hovannes), Askenazy, F. (Florence), Benoit, M. (Michel), Bensamoun, D. (David), Bourgeois, J. (Jérémy), Bredin, J. (Jonathan), Bremond, F. (Francois), Crispim-Junior, C. (Carlos), David, R. (Renaud), Schutter, B.D. (Bob De), Ettore, E. (Eric), Fairchild, J. (Jennifer), Foulon, P. (Pierre), Gazzaley, A. (Adam), Gros, A. (Auriane), Hun, S. (Stéphanie), Knoefel, F. (Frank), Rikkert, M.O. (Marcel Olde), Phan Tran, M.K. (Minh K.), Politis, A. (Antonios), Rigaud, A.S. (Anne S.), Sacco, G. (Guillaume), Serret, S. (Sylvie), Thümmler, S. (Susanne), Welter, M.L. (Marie L.), and Robert, P. (Philippe)

Abstract

The use of Serious Games (SG) in the health domain is expanding. In the field of neurodegenerative disorders (ND) such as Alzheimer's disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients' treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014). The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI) and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI). SG are more adapted for use with trained caregivers (both at home and in clinical settings), with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game), and should be personalized with the help of a clinician.

Published
2017
Full Text
View/download PDF

49. CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report.

Author

UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet, J, Onorato, G L, Bachert, C, Barbolini, M, Bedbrook, A, Bjermer, L, de Sousa, J Correia, Chavannes, N H, Cruz, A A, De Manuel Keenoy, E, Devillier, P, Fonseca, J, Hun, S, Kostka, T, Hellings, P W, Illario, M, Ivancevich, J C, Larenas-Linnemann, D, Millot-Keurinck, J, Ryan, D, Samolinski, B, Sheikh, A, Yorgancioglu, A, Agache, I, Arnavielhe, S, Bewick, M, Annesi-Maesano, I, Anto, J M, Bergmann, K C, Bindslev-Jensen, C, Bosnic-Anticevich, S, Bouchard, J, Caimmi, D P, Camargos, P, Canonica, G W, Cardona, V, Carriazo, A M, Cingi, C, Colgan, E, Custovic, A, Dahl, R, Demoly, P, De Vries, G, Fokkens, W J, Fontaine, J F, Gemicioğlu, B, Guldemond, N, Gutter, Z, Haahtela, T, Hellqvist-Dahl, B, Jares, E, Joos, G, Just, J, Khaltaev, N, Keil, T, Klimek, L, Kowalski, M L, Kull, I, Kuna, P, Kvedariene, V, Laune, D, Louis, R, Magnan, A, Malva, J, Mathieu-Dupas, E, Melén, E, Menditto, E, Morais-Almeida, M, Mösges, R, Mullol, J, Murray, R, Neffen, H, O'Hehir, R, Palkonen, S, Papadopoulos, N G, Passalacqua, G, Pépin, J L, Portejoie, F, Price, D, Pugin, B, Raciborski, F, Simons, F E R, Sova, M, Spranger, O, Stellato, C, Todo Bom, A, Tomazic, P V, Triggiani, M, Valero, A, Valovirta, E, VandenPlas, Olivier, Valiulis, A, van Eerd, M, Ventura, M T, Wickman, M, Young, I, Zuberbier, T, Zurkuhlen, A, Senn, A, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet, J, Onorato, G L, Bachert, C, Barbolini, M, Bedbrook, A, Bjermer, L, de Sousa, J Correia, Chavannes, N H, Cruz, A A, De Manuel Keenoy, E, Devillier, P, Fonseca, J, Hun, S, Kostka, T, Hellings, P W, Illario, M, Ivancevich, J C, Larenas-Linnemann, D, Millot-Keurinck, J, Ryan, D, Samolinski, B, Sheikh, A, Yorgancioglu, A, Agache, I, Arnavielhe, S, Bewick, M, Annesi-Maesano, I, Anto, J M, Bergmann, K C, Bindslev-Jensen, C, Bosnic-Anticevich, S, Bouchard, J, Caimmi, D P, Camargos, P, Canonica, G W, Cardona, V, Carriazo, A M, Cingi, C, Colgan, E, Custovic, A, Dahl, R, Demoly, P, De Vries, G, Fokkens, W J, Fontaine, J F, Gemicioğlu, B, Guldemond, N, Gutter, Z, Haahtela, T, Hellqvist-Dahl, B, Jares, E, Joos, G, Just, J, Khaltaev, N, Keil, T, Klimek, L, Kowalski, M L, Kull, I, Kuna, P, Kvedariene, V, Laune, D, Louis, R, Magnan, A, Malva, J, Mathieu-Dupas, E, Melén, E, Menditto, E, Morais-Almeida, M, Mösges, R, Mullol, J, Murray, R, Neffen, H, O'Hehir, R, Palkonen, S, Papadopoulos, N G, Passalacqua, G, Pépin, J L, Portejoie, F, Price, D, Pugin, B, Raciborski, F, Simons, F E R, Sova, M, Spranger, O, Stellato, C, Todo Bom, A, Tomazic, P V, Triggiani, M, Valero, A, Valovirta, E, VandenPlas, Olivier, Valiulis, A, van Eerd, M, Ventura, M T, Wickman, M, Young, I, Zuberbier, T, Zurkuhlen, A, and Senn, A

Abstract

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.

Published
2017

50. CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report

Author

Bousquet, J. (Jean), Onorato, G.L., Bachert, C. (Claus), Barbolini, M., Bedbrook, A. (Anna), Bjermer, L. (Leif), de Sousa, JC, Chavannes, N.H. (Nicolas), Cruz, A.A. (Alvaro), Keenoy, ED, Devillier, P. (Philippe), Fonseca, J, Hun, S., Kostka, T., Hellings, P.W. (Peter), Illario, M., Ivancevich, J.C. (Juan), Larenas-Linnemann, D. (Désirée), Millot-Keurinck, J., Ryan, D. (Dermot), Samolinski, B. (Boleslaw), Sheikh, A. (Aziz), Yorgancioglu, A., Agache, I., Arnavielhe, S, Bewick, M, Annesi-Maesano, I. (Isabella), Anto, JM, Bergmann, K.-C. (Karl-Christian), Bindslev-Jensen, C. (Carsten), Bosnic-Anticevich, S, Bouchard, J. (Jacques), Caimmi, D. P., Camargos, P., Canonica, G.W., Cardona, V, Carriazo, A.M., Cingi, C., Colgan, E., Custovic, A. (Adnan), Dahl, R., Demoly, P., Vries, G. (Gerard) de, Fokkens, WJ, Fontaine, J.F., Gemicioglu, B, Guldemond, N. (Nick), Gutter, Z., Haahtela, T. (Tari), Hellqvist-Dahl, B., Jares, E., Joos, G.F. (Guy), Just, P.M., Khaltaev, N., Keil, M. (Mark), Klimek, L., Kowalski, M.L., Kull, C.A. (Christian), Kuna, P. (Piotr), Kvedariene, V. (Violeta), Laune, D, Louis, R, Magnan, A, Malva, J., Mathieu-Dupas, E., Melén, E. (Erik), Menditto, E., Morais-Almeida, M. (Mario), Mosges, R, Mullol, J., Murray, R., Neffen, H, O'Hehir, R, Palkonen, S., Papadopoulos, N., Passalacqua, G. (Giovanni), Pepin, J.L., Portejoie, F, Price, D., Pugin, B., Raciborski, F, Simons, F.E.R., Sova, M., Spranger, O., Stellato, C., Bom, AT, Tomazic, P.V., Triggiani, M. (M.), Valero, A., Valovirta, E. (Erkka), Vandenplas, O. (Olivier), Valiulis, A. (Arunas), Eerd, M. (Maarten) van, Ventura, M. T., Wickman, M., Young, I, Zuberbier, T. (Torsten), Zurkuhlen, A., Senn, A., Bousquet, J. (Jean), Onorato, G.L., Bachert, C. (Claus), Barbolini, M., Bedbrook, A. (Anna), Bjermer, L. (Leif), de Sousa, JC, Chavannes, N.H. (Nicolas), Cruz, A.A. (Alvaro), Keenoy, ED, Devillier, P. (Philippe), Fonseca, J, Hun, S., Kostka, T., Hellings, P.W. (Peter), Illario, M., Ivancevich, J.C. (Juan), Larenas-Linnemann, D. (Désirée), Millot-Keurinck, J., Ryan, D. (Dermot), Samolinski, B. (Boleslaw), Sheikh, A. (Aziz), Yorgancioglu, A., Agache, I., Arnavielhe, S, Bewick, M, Annesi-Maesano, I. (Isabella), Anto, JM, Bergmann, K.-C. (Karl-Christian), Bindslev-Jensen, C. (Carsten), Bosnic-Anticevich, S, Bouchard, J. (Jacques), Caimmi, D. P., Camargos, P., Canonica, G.W., Cardona, V, Carriazo, A.M., Cingi, C., Colgan, E., Custovic, A. (Adnan), Dahl, R., Demoly, P., Vries, G. (Gerard) de, Fokkens, WJ, Fontaine, J.F., Gemicioglu, B, Guldemond, N. (Nick), Gutter, Z., Haahtela, T. (Tari), Hellqvist-Dahl, B., Jares, E., Joos, G.F. (Guy), Just, P.M., Khaltaev, N., Keil, M. (Mark), Klimek, L., Kowalski, M.L., Kull, C.A. (Christian), Kuna, P. (Piotr), Kvedariene, V. (Violeta), Laune, D, Louis, R, Magnan, A, Malva, J., Mathieu-Dupas, E., Melén, E. (Erik), Menditto, E., Morais-Almeida, M. (Mario), Mosges, R, Mullol, J., Murray, R., Neffen, H, O'Hehir, R, Palkonen, S., Papadopoulos, N., Passalacqua, G. (Giovanni), Pepin, J.L., Portejoie, F, Price, D., Pugin, B., Raciborski, F, Simons, F.E.R., Sova, M., Spranger, O., Stellato, C., Bom, AT, Tomazic, P.V., Triggiani, M. (M.), Valero, A., Valovirta, E. (Erkka), Vandenplas, O. (Olivier), Valiulis, A. (Arunas), Eerd, M. (Maarten) van, Ventura, M. T., Wickman, M., Young, I, Zuberbier, T. (Torsten), Zurkuhlen, A., and Senn, A.

Abstract

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life da

Published
2017
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