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1. Patterns of long-term survivorship following bevacizumab treatment for recurrent glioma: a case series

Author

Liang Yen Liu, Matthew S Ji, Nhung T Nguyen, Frances E Chow, Donna M Molaie, Sean T Pianka, Richard M Green, Linda M Liau, Benjamin M Ellingson, Phioanh L Nghiemphu, Timothy F Cloughesy, and Albert Lai

Subjects
bevacizumab, glioblastoma, glioma, long term, progression, recurrence, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Aim: Long-term survivors (LTS) after glioma recurrence while on bevacizumab (Bev) therapy are rarely reported in the current literature. The purpose of this case series is to confirm the existence of and describe a large cohort of recurrent glioma LTS treated with Bev (Bev-LTS). Patients & methods: We identified Bev-LTS as patients with post-Bev initiation survival times of ≥3 years among 1397 Bev treated recurrent glioma patients. Results: Among 962 grade-IV, 221 grade III, and 214 grade II Bev-treated glioma patients, we identified 28 (2.9%), 14 (6.3%) and 8 (3.7%) Bev-LTS patients, respectively. 45 Bev-LTS patients recurred on Bev, with 36 of those patients continuing therapy. Conclusion: Our study shows that a small portion of grade-IV, -III, and -II glioma patients can have long-term survival on Bev therapy even after Bev recurrence.

Published
2019
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2. Identification of molecular determinants that govern distinct STIM2 activation dynamics.

Author

Sisi Zheng, Guolin Ma, Lian He, Tian Zhang, Jia Li, Xiaoman Yuan, Nhung T Nguyen, Yun Huang, Xiaoyan Zhang, Ping Gao, Robert Nwokonko, Donald L Gill, Hao Dong, Yubin Zhou, and Youjun Wang

Subjects
Biology (General), QH301-705.5
Abstract

The endoplasmic reticulum (ER) Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2, which connect ER Ca2+ depletion with extracellular Ca2+ influx, are crucial for the maintenance of Ca2+ homeostasis in mammalian cells. Despite the recent progress in unraveling the role of STIM2 in Ca2+ signaling, the mechanistic underpinnings of its activation remain underexplored. We use an engineering approach to direct ER-resident STIMs to the plasma membrane (PM) while maintaining their correct membrane topology, as well as Förster resonance energy transfer (FRET) sensors that enabled in cellulo real-time monitoring of STIM activities. This allowed us to determine the calcium affinities of STIM1 and STIM2 both in cellulo and in situ, explaining the current discrepancies in the literature. We also identified the key structural determinants, especially the corresponding G residue in STIM1, which define the distinct activation dynamics of STIM2. The chimeric E470G mutation could switch STIM2 from a slow and weak Orai channel activator into a fast and potent one like STIM1 and vice versa. The systemic dissection of STIM2 activation by protein engineering sets the stage for the elucidation of the regulation and function of STIM2-mediated signaling in mammals.

Published
2018
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3. Correlation between electron-phonon coupling and superconductivity of Sn2+ ion irradiated MgB2-thin films

Author

Ha H. Pham, Tien Le, The Nghia Nguyen, Nguyen Hoang Nam, Nhung T. Nguyen, Min Kyun Sohn, Dae Joon Kang, Tuson Park, Jinyoung Yun, Yeonkyu Lee, Jeehoon Kim, Duc H. Tran, and Won Nam Kang

Subjects
Process Chemistry and Technology, Materials Chemistry, Ceramics and Composites, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials
Published
2023
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4. Supplementary Figures S1-S10 from D-2-Hydroxyglutarate Is Necessary and Sufficient for Isocitrate Dehydrogenase 1 Mutant–Induced MIR148A Promoter Methylation

Author

Albert Lai, Timothy F. Cloughesy, Phioanh L. Nghiemphu, Linda M. Liau, Harley I. Kornblum, Fei Liu, Sichen Li, Thomas J. Lai, HuyTram N. Nguyen, Nhung T. Nguyen, Byram H. Ozer, Christopher D. Cox, and Tie Li

Abstract

Supplementary Figure S1: Treatment with octyl-D-2-HG-induces MIR148A methylation; Supplementary Figure S2: Octyl-D-2-HG-induced MIR148A methylation status remains constant at late passages; Supplementary Figure S3: Octyl-D-2-HG induces CpG island methylation of the RBP1 promoter in 293T cells; Supplementary Figure S4: Octyl-D-2-HG induces CpG island methylation of the MIR148A promoter in normal human astrocytes (NHA); Supplementary Figure S5: MIR148A promoter CpG methylation in IDH1MUT-transfected 293T cells; Supplementary Figure S6: C227 prevents IDH1 mutant-induced MIR148A promoter methylation; Supplementary Figure S7: C227 prevents IDH1 mutant-induced RBP1 promoter methylation; Supplementary Figure S8: Schematic graph of MIR148A genomic location, CpG island, and promoter-reporter construct; Supplementary Figure S9: MIR148a expression is unchanged by octyl-D-2-HG treatment in early passages in 293T and NHA cells; Supplementary Figure S10: Octyl-D-2-HG withdrawal restores MIR148A promoter to an unmethylated state

Published
2023
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6. Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety

Author

Nhung T. Nguyen, Xin Liu, Ji Jing, Shaohai Fang, M. James You, Anjana Rao, Kai Huang, Hongxiang Zeng, Zixian Huang, Yun Huang, Joyce Chen, Rui Wang, Gang Han, and Yubin Zhou

Subjects
Male, Lymphoma, T-Lymphocytes, medicine.medical_treatment, T cell, Melanoma, Experimental, Biomedical Engineering, Bioengineering, Lymphocyte Activation, Immunotherapy, Adoptive, Jurkat Cells, Immune system, In vivo, Immunity, medicine, Animals, Humans, Nanotechnology, General Materials Science, Electrical and Electronic Engineering, Receptors, Chimeric Antigen, Cell Death, business.industry, Immunotherapy, Condensed Matter Physics, medicine.disease, Atomic and Molecular Physics, and Optics, Chimeric antigen receptor, Mice, Inbred C57BL, Optogenetics, Cytokine release syndrome, Cell killing, medicine.anatomical_structure, Cancer research, Female, business
Abstract

Chimeric antigen receptor (CAR) T cell-based immunotherapy, approved by the US Food and Drug Administration, has shown curative potential in patients with haematological malignancies. However, owing to the lack of control over the location and duration of the anti-tumour immune response, CAR T cell therapy still faces safety challenges arising from cytokine release syndrome and on-target, off-tumour toxicity. Herein, we present the design of light-switchable CAR (designated LiCAR) T cells that allow real-time phototunable activation of therapeutic T cells to precisely induce tumour cell killing. When coupled with imaging-guided, surgically removable upconversion nanoplates that have enhanced near-infrared-to-blue upconversion luminescence as miniature deep-tissue photon transducers, LiCAR T cells enable both spatial and temporal control over T cell-mediated anti-tumour therapeutic activity in vivo with greatly mitigated side effects. Our nano-optogenetic immunomodulation platform not only provides a unique approach to interrogate CAR-mediated anti-tumour immunity, but also sets the stage for developing precision medicine to deliver personalized anticancer therapy. While chimeric antigen receptor (CAR) T cell-based therapy has been approved for clinical use for certain types of blood cancers, it remains difficult to achieve precise spatiotemporal control of the elicited anti-tumour response. Here, the authors propose light-switchable CAR T cells that can be remotely activated by a nano-optogenetic approach, reducing unwanted side effects.

Published
2021
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7. Local structure and superconductivity in (Bi1.6Pb0.4Sr2Ca2Cu3O10+δ)1-x(Fe3O4)x compounds

Author

Won Nam Kang, Nguyen Khac Man, I-Jui Hsu, Duc H. Tran, Ha H. Pham, An T. Pham, Nguyen Hoang Nam, Nhung T. Nguyen, Dzung T. Tran, and Wantana Klysubun

Subjects
010302 applied physics, Superconductivity, Materials science, Valence (chemistry), Process Chemistry and Technology, Doping, Analytical chemistry, chemistry.chemical_element, 02 engineering and technology, Crystal structure, 021001 nanoscience & nanotechnology, 01 natural sciences, Copper, XANES, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Ion, Magnetization, chemistry, 0103 physical sciences, Materials Chemistry, Ceramics and Composites, 0210 nano-technology
Abstract

In this work, a close correlation between variations of critical temperature (Tc) and the hole concentration of (Bi1.6Pb0.4Sr2Ca2Cu3O10+δ)1-x(Fe3O4)x systems was studied. The (Bi1.6Pb0.4Sr2Ca2Cu3O10+δ)1-x(Fe3O4)x samples were fabricated using the solid-state reaction method, where x ranged from 0 to 0.2. The Tc values of the samples deduced from magnetization versus temperature measurement gradually decreased with increasing the Fe3O4 content (x). To investigate a possible reason for the observed decrease in the values of Tc in the samples, the valence state of copper (V) and the hole concentration (p) in all samples were examined by analyzing the Cu K-edge and Cu L2,3-edge X-ray absorption near edge structure (XANES) spectra. The values of V and p monotonously decreased with the increase in Fe3O4 doping content (x) and agreed with the behavior of Tc. The existence of Fe3+ was confirmed by analyzing Fe L2,3-edge XANES. Hence, Fe3+ ions possibly entered the lattice structure of the samples and filled the holes in CuO2 planes. The degradation of superconductivity in Fe3O4 doped samples was then explained.

Published
2021
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8. Circularly permuted LOV2 as a modular photoswitch for optogenetic engineering

Author

Lei Guo, Yun Huang, Nhung T. Nguyen, Junfeng Wang, Peng Tan, Yuhan Yang, Lian He, Zixian Huang, Ling Li, Kai Huang, Lei Zhu, Rui Wang, Gang Han, and Yubin Zhou

Subjects
Cell signaling, Phototropin, Computer science, Transgene, Mice, Transgenic, Computational biology, Optogenetics, Genome engineering, Mice, 03 medical and health sciences, Mice, Inbred NOD, Animals, Humans, Molecular Biology, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Photoswitch, Arabidopsis Proteins, Effector, 030302 biochemistry & molecular biology, Cell Biology, Photochemical Processes, Chimeric antigen receptor, DNA-Binding Proteins, Female, Genetic Engineering
Abstract

Plant-based photosensors, such as the light-oxygen-voltage sensing domain 2 (LOV2) from oat phototropin 1, can be modularly wired into cell signaling networks to remotely control protein activity and physiological processes. However, the applicability of LOV2 is hampered by the limited choice of available caging surfaces and its preference to accommodate the effector domains downstream of the C-terminal Jα helix. Here, we engineered a set of LOV2 circular permutants (cpLOV2) with additional caging capabilities, thereby expanding the repertoire of genetically encoded photoswitches to accelerate the design of optogenetic devices. We demonstrate the use of cpLOV2-based optogenetic tools to reversibly gate ion channels, antagonize CRISPR-Cas9-mediated genome engineering, control protein subcellular localization, reprogram transcriptional outputs, elicit cell suicide and generate photoactivatable chimeric antigen receptor T cells for inducible tumor cell killing. Our approach is widely applicable for engineering other photoreceptors to meet the growing need of optogenetic tools tailored for biomedical and biotechnological applications.

Published
2021
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9. Optogenetic approaches to control Ca2+-modulated physiological processes

Author

Nhung T. Nguyen, Guolin Ma, Yubin Zhou, and Ji Jing

Subjects
0301 basic medicine, biology, Physiology, Chemistry, Optogenetics, Receptor tyrosine kinase, 03 medical and health sciences, Synthetic biology, Upconversion nanoparticles, 030104 developmental biology, 0302 clinical medicine, Physiology (medical), biology.protein, Bioluminescence, Neuroscience, 030217 neurology & neurosurgery, Ion channel, G protein-coupled receptor, Calcium signaling
Abstract

As a versatile intracellular second messenger, calcium ion (Ca2+) regulates a plethora of physiological processes. To achieve precise control over Ca2+ signals in living cells and organisms, a set of optogenetic tools have recently been crafted by engineering photosensitive domains into intracellular signaling proteins, G-protein coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and Ca2+ channels. We highlight herein the optogenetic engineering strategies, kinetic properties, advantages and limitations of these genetically-encoded Ca2+ channel actuators (GECAs) and modulators. In parallel, we present exemplary applications in both excitable and non-excitable cells and tissues. Furthermore, we briefly discuss potential solutions for wireless optogenetics to accelerate the in vivo applications of GECAs under physiological conditions, with an emphasis on integrating near-infrared (NIR) light-excitable upconversion nanoparticles (UCNPs) and bioluminescence with optogenetics.

Published
2020
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10. Acetylation of CCAR2 Establishes a BET/BRD9 Acetyl Switch in Response to Combined Deacetylase and Bromodomain Inhibition

Author

Ying-Shiuan Chen, Laura M. Beaver, Gavin S. Johnson, Yun Huang, Deqiang Sun, Emily Ho, W. Mohaiza Dashwood, Shan Wang, Praveen Rajendran, Hon-Chiu Eastwood Leung, Nhung T. Nguyen, Ahmet M Ulusan, Roderick H. Dashwood, Kyle Chang, David A. Lieberman, Furkan U. Ertem, Jia Li, Eduardo Vilar, Li Li, Mutian Zhang, and Mark T. Bedford

Subjects
Male, 0301 basic medicine, Cancer Research, Mice, Nude, Article, Histone Deacetylases, Epigenesis, Genetic, Histones, BET inhibitor, Mice, Random Allocation, 03 medical and health sciences, 0302 clinical medicine, Isothiocyanates, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, Coactivator, Animals, Humans, Epigenetics, beta Catenin, Adaptor Proteins, Signal Transducing, Chemistry, Wnt signaling pathway, Proteins, Acetylation, Azepines, Triazoles, Cell cycle, HCT116 Cells, HDAC3, Xenograft Model Antitumor Assays, Bromodomain, Histone Deacetylase Inhibitors, 030104 developmental biology, Oncology, Sulfoxides, 030220 oncology & carcinogenesis, Cancer research, Colorectal Neoplasms, Transcription Factors
Abstract

There continues to be interest in targeting epigenetic “readers, writers, and erasers” for the treatment of cancer and other pathologies. However, a mechanistic understanding is frequently lacking for the synergy observed when combining deacetylase and bromodomain inhibitors. Here we identify cell cycle and apoptosis regulator 2 (CCAR2) as an early target for acetylation in colon cancer cells treated with sulforaphane. N-terminal acetylation of CCAR2 diminished its interactions with histone deacetylase 3 and β-catenin, interfering with Wnt coactivator functions of CCAR2, including in cells harboring genetically encoded CCAR2 acetylation. Protein domain arrays and pull-down assays identified acetyl “reader” proteins that recognized CCAR2 acetylation sites, including BRD9 and members of the bromodomain and extraterminal domain (BET) family. Treatment with the BET inhibitor JQ1 synergized with sulforaphane in colon cancer cells and suppressed tumor development effectively in a preclinical model of colorectal cancer. Studies with sulforaphane+JQ1 in combination implicated a BET/BRD9 acetyl switch and a shift in the pool of acetyl “reader” proteins in favor of BRD9-regulated target genes. Significance: These results highlight the competition that exists among the “readers” of acetylated histone and nonhistone proteins and provide a mechanistic basis for potential new therapeutic avenues involving epigenetic combination treatments.

Published
2019
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11. Optogenetic Control of Non‐Apoptotic Cell Death: Optogenetic Control of Non‐Apoptotic Cell Death (Adv. Sci. 13/2021)

Author

Gang Han, Yubin Zhou, Xiaoli Cai, Ji Jing, Kai Huang, Nhung T. Nguyen, Rui Chen, Rui Wang, Joel R. Walker, Zixian Huang, Zhiquan Huang, Stefan Siwko, and Lian He

Subjects
Back Cover, General Chemical Engineering, Apoptotic cell death, General Engineering, General Physics and Astronomy, Medicine (miscellaneous), General Materials Science, Biology, Optogenetics, Biochemistry, Genetics and Molecular Biology (miscellaneous), Neuroscience
Abstract

In article number 2100424, Gang Han, Yubin Zhou, Ji Jing, and co‐workers introduce a set of optogenetic tools, designated LiPOPs, that enable photoswitchable control over key molecular steps involved in necroptosis or pyroptosis, including cell membrane perforation, extracellular ions influx, and cell suicide. LiPOPs are coupled with either upconversion nanoparticles (UCNPs) with NIR‐to‐blue emission (left corner) or NanoLuc‐catalyzed bioluminescence‐based optogenetic stimulation (NanoLOGS; right corner) to achieve wireless nano‐optogenetic or chemo‐optogenetic manipulation of cell fate with high spatiotemporal precision in living animals. LiPOPs open new avenues to study the role of non‐apoptotic cell death during microbial infection, inflammatory response and cancer immunotherapy. [Image: see text]

Published
2021

12. Optogenetic Control of Non-Apoptotic Cell Death

Author

Nhung T. Nguyen, Rui Chen, Zhiquan Huang, Lian He, Kai Huang, Joel R. Walker, Stefan Siwko, Rui Wang, Zixian Huang, Gang Han, Ji Jing, Yubin Zhou, and Xiaoli Cai

Subjects
Programmed cell death, Light, General Chemical Engineering, Necroptosis, Science, General Physics and Astronomy, Medicine (miscellaneous), necroptosis, Optogenetics, Biology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Upconversion nanoparticles, Mice, Immunity, Escherichia coli, Bioluminescence, Animals, Humans, General Materials Science, Research Articles, Leukemia, Cell Death, pyroptosis, General Engineering, Pyroptosis, Intracellular Signaling Peptides and Proteins, Phosphate-Binding Proteins, bioluminescence, Cell biology, upconversion nanoparticles, Cancer cell, Nanoparticles, Protein Kinases, HeLa Cells, Research Article
Abstract

Herein, a set of optogenetic tools (designated LiPOP) that enable photoswitchable necroptosis and pyroptosis in live cells with varying kinetics, is introduced. The LiPOP tools allow reconstruction of the key molecular steps involved in these two non‐apoptotic cell death pathways by harnessing the power of light. Further, the use of LiPOPs coupled with upconversion nanoparticles or bioluminescence is demonstrated to achieve wireless optogenetic or chemo‐optogenetic killing of cancer cells in multiple mouse tumor models. LiPOPs can trigger necroptotic and pyroptotic cell death in cultured prokaryotic or eukaryotic cells and in living animals, and set the stage for studying the role of non‐apoptotic cell death pathways during microbial infection and anti‐tumor immunity., A new class of genetically‐encoded actuators, designated LiPOPs, are designed to enable photoswitchable necroptosis or pyroptosis. LiPOPs are coupled with upconversion nanoparticles (UCNPs) or NanoLuc‐mediated luminescence‐aided optogenetic stimulation (NanoLOGS) to achieve wireless nano‐optogenetic or chemo‐optogenetic control of cell death in vivo with superior spatiotemporal precision. LiPOPs can also be exploited as safety switches to facilitate the development of safer cell‐based therapies.

Published
2021

13. Diffusion Magnetic Resonance Imaging Phenotypes Predict Overall Survival Benefit From Bevacizumab or Surgery in Recurrent Glioblastoma With Large Tumor Burden

Author

Timothy F. Cloughesy, Richard Everson, Kunal S. Patel, Jodi Goldman, Albert Lai, Caleb Tan, Jacob Schlossman, Phioanh L. Nghiemphu, Matthew Ji, Benjamin M. Ellingson, Catalina Raymond, Joseph Tsung, Linda M. Liau, Whitney B. Pope, Nhung T Nguyen, and Jingwen Yao

Subjects
Male, Imaging biomarker, Neurosurgical Procedures, Cohort Studies, Antineoplastic Agents, Immunological, 0302 clinical medicine, Computer-Assisted, Recurrent glioblastoma, Cancer, medicine.diagnostic_test, Brain Neoplasms, Middle Aged, Tumor Burden, Bevacizumab, Research—Human—Clinical Studies, Treatment Outcome, Phenotype, Immunological, Local, 030220 oncology & carcinogenesis, Cohort, Biomedical Imaging, Female, 6.4 Surgery, medicine.drug, Adult, medicine.medical_specialty, Clinical Sciences, Antineoplastic Agents, Diffusion MRI, 03 medical and health sciences, Rare Diseases, Clinical Research, Image Interpretation, Computer-Assisted, medicine, Overall survival, Effective diffusion coefficient, Humans, Image Interpretation, Retrospective Studies, Aged, ADC histogram analysis, Neurology & Neurosurgery, business.industry, T1 subtraction, Neurosciences, Evaluation of treatments and therapeutic interventions, Magnetic resonance imaging, Surgery, Brain Disorders, body regions, Brain Cancer, Neoplasm Recurrence, Diffusion Magnetic Resonance Imaging, Neurology (clinical), Neoplasm Recurrence, Local, business, Glioblastoma, 030217 neurology & neurosurgery
Abstract

BackgroundDiffusion magnetic resonance (MR) characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-vascular endothelial growth factor (VEGF) therapy; however, its use in large volume recurrence has not been evaluated.ObjectiveTo determine if diffusion MR characteristics can predict survival outcomes in patients with large volume recurrent glioblastoma treated with bevacizumab or repeat resection.MethodsA total of 32 patients with large volume (>20 cc or > 3.4 cm diameter) recurrent glioblastoma treated with bevacizumab and 35 patients treated with repeat surgery were included. Pretreatment tumor volume and apparent diffusion coefficient (ADC) histogram analysis were used to phenotype patients as having high (>1.24 μm2/ms) or low (

Published
2020

14. CRAC channel-based optogenetics

Author

Nhung T. Nguyen, Brendan D’Souza, Guolin Ma, Yubin Zhou, Ji Jing, Yun Huang, Eena Lin, and Lian He

Subjects
0301 basic medicine, Physiology, Neurotransmission, Optogenetics, Models, Biological, Article, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Animals, Humans, Molecular Biology, Ion channel, Chemistry, Tethering, Endoplasmic reticulum, STIM1, Cell Biology, Calcium Release Activated Calcium Channels, Cell biology, 030104 developmental biology, Cytoplasm, Calcium, Protein Multimerization, Reprogramming, 030217 neurology & neurosurgery
Abstract

Store-operated Ca(2+) entry (SOCE) constitutes a major Ca(2+) influx pathway in mammals to regulate a myriad of physiological processes, including muscle contraction, synaptic transmission, gene expression, and metabolism. In non-excitable cells, the Ca(2+) release-activated Ca(2+) (CRAC) channel, composed of ORAI and stromal interaction molecule (STIM), represents a prototypical example of SOCE to mediate Ca(2+) entry at specialized membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and the plasma membrane (PM). The key steps of SOCE activation include the oligomerization of the luminal domain of the ER-resident Ca(2+) sensor STIM1 upon Ca(2+) store depletion, subsequent signal propagation toward the cytoplasmic domain to trigger a conformational switch and overcome the intramolecular autoinhibition, and ultimate exposure of the minimal ORAI-activating domain to directly engage and gate ORAI channels in the plasma membrane. This exquisitely coordinated cellular event is also facilitated by the C-terminal polybasic domain of STIM1, which physically associates with negatively charged phosphoinositides embedded in the inner leaflet of the PM to enable efficient translocation of STIM1 into ER-PM MCSs. Here, we present recent progress in recapitulating STIM1-mediated SOCE activation by engineering CRAC channels with optogenetic approaches. These STIM1-based optogenetic tools make it possible to not only mechanistically recapture the key molecular steps of SOCE activation, but also remotely and reversibly control Ca(2+)-dependent cellular processes, inter-organellar tethering at MCSs, and transcriptional reprogramming when combined with CRISPR/Cas9-based genome-editing tools.

Published
2018
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15. Calcium store refilling and STIM activation in STIM- and Orai-deficient cell lines

Author

Nhung T. Nguyen, Tian Zhang, Jingguo Liu, Wanjie Li, Jindou Liu, Robert M. Nwokonko, Youjun Wang, Xiaoyan Zhang, Yandong Zhou, Jia Li, Fukuan Zhao, Guolin Ma, Sisi Zheng, Donald L. Gill, Lijuan Zhou, and Yun Huang

Subjects
0301 basic medicine, Orai1, Cell type, ORAI1 Protein, Signaling and Cell Physiology, STIM1, Physiology, Clinical Biochemistry, chemistry.chemical_element, Calcium, Endoplasmic Reticulum, 03 medical and health sciences, Physiology (medical), Humans, Calcium Signaling, Stromal Interaction Molecule 1, Receptor, ORAI1, Endoplasmic reticulum, Cell Membrane, Wild type, 2-APB, Cell biology, Protein Transport, HEK293 Cells, 030104 developmental biology, chemistry, Protein Multimerization, Homeostasis, SOCE
Abstract

Mediated through the combined action of STIM proteins and Orai channels, store-operated Ca2+ entry (SOCE) functions ubiquitously among different cell types. The existence of multiple STIM and Orai genes has made it difficult to assign specific roles of each STIM and Orai homolog in mediating Ca2+ signals. Using CRISPR/Cas9 gene editing tools, we generated cells with both STIM or all three Orai homologs deleted and directly monitored store Ca2+ and Ca2+ signals. We found that unstimulated, SOCE null KO cells still retain 50~70% of ER Ca2+ stores of wildtype (wt) cells. After brief exposure to store-emptying conditions, acute refilling of ER Ca2+ stores was totally blocked in KO cells. However, after 24 h in culture, stores were eventually refilled. Thus, SOCE is critical for immediate refilling of ER Ca2+ but is dispensable for the maintenance of long-term ER Ca2+ homeostasis. Using the Orai null background triple Orai-KO cells, we examined the plasma membrane translocation properties of a series of truncated STIM1 variants. FRET analysis reveals that, even though PM tethering of STIM1 expedites the activation of STIM1 by facilitating its oligomerization, migration, and accumulation in ER-PM junctions, it is not required for the conformational switch, oligomerization, and clustering of STIM1. Even without overt puncta formation at ER-PM junctions, STIM11–491 and STIM11–666 could still rescue SOCE when expressed in STIM KO cells. Thus, ER-PM trapping and clustering of STIM molecules only facilitates the process of SOCE activation, but is not essential for the activation of Orai channels. Electronic supplementary material The online version of this article (10.1007/s00424-018-2165-5) contains supplementary material, which is available to authorized users.

Published
2018
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16. Genetically encoded tags for real time dissection of protein assembly in living cells

Author

Shuzhong Liu, Yubin Zhou, Guolin Ma, Nhung T. Nguyen, Zuojiong Gong, Yun Huang, Lian He, and Qian Zhang

Subjects
0301 basic medicine, Protein structure and function, General Chemistry, Oligomer, 03 medical and health sciences, chemistry.chemical_compound, Cytosol, 030104 developmental biology, Monomer, chemistry, Microtubule, Fluorescence microscope, Biophysics, Protein quaternary structure
Abstract

Simple methods with straightforward readouts that enable real-time interrogation of protein quaternary structure are much needed to facilitate the physicochemical characterization of proteins at the single-cell level. After screening over a series of microtubule (MT) binders, we report herein the development of two genetically encoded tags (designated as “MoTags” for the monomer/oligomer detection tag) that can be conveniently fused to a given protein to probe its oligomeric state in cellulo when combined with routine fluorescence microscopy. In their monomeric form, MoTags are evenly distributed in the cytosol; whereas oligomerization enables MoTags to label MT or track MT tips in an oligomeric state-dependent manner. We demonstrate here the broad utility of engineered MoTags to aid the determination of protein oligomeric states, dissection of protein structure and function, and monitoring of protein–target interactions under physiological conditions in living cells.

Published
2018
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17. Integrated pipeline for inferring the evolutionary history of a gene family embedded in the species tree: a case study on the STIMATE gene family

Author

Kui Lin, Yubin Zhou, Youjun Wang, Sisi Zheng, Nhung T. Nguyen, and Jia Song

Subjects
0301 basic medicine, Pipeline (computing), Biology, lcsh:Computer applications to medicine. Medical informatics, Biochemistry, Genome, Coalescent theory, Evolution, Molecular, 03 medical and health sciences, Evolutionary history, STIMATE, Structural Biology, Gene Duplication, Gene family, Animals, Humans, Chordate, Molecular Biology, Gene, lcsh:QH301-705.5, Phylogeny, Likelihood Functions, Phylogenetic tree, Models, Genetic, Applied Mathematics, Membrane Proteins, Computer Science Applications, Tree (data structure), 030104 developmental biology, ComputingMethodologies_PATTERNRECOGNITION, lcsh:Biology (General), Evolutionary biology, Multigene Family, lcsh:R858-859.7, ComputingMethodologies_GENERAL, DNA microarray, Algorithms, Research Article
Abstract

Background Because phylogenetic inference is an important basis for answering many evolutionary problems, a large number of algorithms have been developed. Some of these algorithms have been improved by integrating gene evolution models with the expectation of accommodating the hierarchy of evolutionary processes. To the best of our knowledge, however, there still is no single unifying model or algorithm that can take all evolutionary processes into account through a stepwise or simultaneous method. Results On the basis of three existing phylogenetic inference algorithms, we built an integrated pipeline for inferring the evolutionary history of a given gene family; this pipeline can model gene sequence evolution, gene duplication-loss, gene transfer and multispecies coalescent processes. As a case study, we applied this pipeline to the STIMATE (TMEM110) gene family, which has recently been reported to play an important role in store-operated Ca2+ entry (SOCE) mediated by ORAI and STIM proteins. We inferred their phylogenetic trees in 69 sequenced chordate genomes. Conclusions By integrating three tree reconstruction algorithms with diverse evolutionary models, a pipeline for inferring the evolutionary history of a gene family was developed, and its application was demonstrated. Electronic supplementary material The online version of this article (10.1186/s12859-017-1850-2) contains supplementary material, which is available to authorized users.

Published
2017
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18. Targeted next-generation sequencing of 565 neuro-oncology patients at UCLA: A single-institution experience

Author

Stephanie Pan, Thomas J Lai, Matthew Ji, Frances Chow, Sean T Pianka, Phioanh L. Nghiemphu, Bryan Kevan, Linda M. Liau, Devin N Reeh, Christopher D Cox, Nhung T Nguyen, Regina Liu, Tie Li, William H. Yong, Timothy F. Cloughesy, Albert Lai, Blaine S C Eldred, Donna Molaie, and Gang Li

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Concordance, PALB2, Clinical Investigations, DNA sequencing, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, targeted next-generation sequencing, Clinical Research, Internal medicine, Glioma, glioma, medicine, CNS TUMORS, Medical diagnosis, Cancer, screening and diagnosis, Proportional hazards model, business.industry, Neurosciences, glioblastoma, CNS tumors, medicine.disease, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, 3. Good health, Brain Cancer, Detection, Good Health and Well Being, 030104 developmental biology, 030220 oncology & carcinogenesis, genomic profiling, business, 4.2 Evaluation of markers and technologies, Glioblastoma
Abstract

Background Targeted next-generation sequencing (NGS) is frequently obtained at the University of California, Los Angeles (UCLA) for clinical characterization of CNS tumors. In this study, we describe the diagnostic reliability of the Foundation Medicine (FM) targeted NGS platform and its ability to explore and identify tumor characteristics of prognostic significance in gliomas. Methods Neuro-oncology patients seen at UCLA who have received FM testing between August 2012 and March 2019 were included in this study, and all mutations from FM test reports were recorded. Initial tumor diagnoses and diagnostic markers found via standard clinical methods were obtained from pathology reports. With overall and progression-free survival data, elastic net regularized Cox regression and Cox proportional hazards models were used to determine whether any mutations of unknown significance detected by FM could predict patient outcome in glioblastoma (GBM). Results Six hundred and three samples tested by FM from 565 distinct patients were identified. Concordance of diagnostic markers was high between standard clinical testing methods and FM. Oligodendroglial markers detected via FM were highly correlated with 1p19q codeletion in IDH mutated gliomas. FM testing of multiple tumor samples from the same patient demonstrated temporal and spatial mutational heterogeneity. Mutations in BCORL1, ERBB4, and PALB2, which are mutations of unknown significance in GBM, were shown to be statistically significant in predicting patient outcome. Conclusions In our large cohort, we found that targeted NGS can both reliably and efficiently detect important diagnostic markers in CNS tumors.

Published
2020

19. Burden of injuries in Vietnam: emerging trends from a decade of economic achievement

Author

Nicholas L S Roberts, Thanh Huong Nguyen, Sonia Lewycka, Justin Beardsley, Quynh Anh P. Nguyen, Zichen Liu, Nhung T Nguyen, Bach Xuan Tran, Chi Linh Hoang, Thu Ha Nguyen, Spencer L. James, Zachary V Dingels, Khanh Bao Tran, Chris D Castle, Jack T Fox, Dillon O Sylte, Anh Kim Dang, Giang Thu Vu, Hai Quang Pham, Ali H. Mokdad, and Son Hoang Nguyen

Subjects
Poison control, burden of disease, Global Health, Suicide prevention, Occupational safety and health, Global Burden of Disease, 03 medical and health sciences, 0302 clinical medicine, Injury prevention, Humans, Medicine, Disabled Persons, 030212 general & internal medicine, Original Research, business.industry, Incidence, Incidence (epidemiology), Mortality rate, Public Health, Environmental and Occupational Health, Human factors and ergonomics, 030208 emergency & critical care medicine, global, economic development, Years of potential life lost, Vietnam, Wounds and Injuries, Quality-Adjusted Life Years, business, Demography
Abstract

BackgroundVietnam has been one of the fastest-growing world economies in the past decade. The burden of injuries can be affected by economic growth given the increased exposure to causes of injury as well as decreased morbidity and mortality of those that experience injury. It is of interest to evaluate the trends in injury burden that occurred alongside Vietnam’s economic growth in the past decade.MethodsResults from Global Burden of Disease 2017 were obtained and reviewed. Estimates of incidence, cause-specific mortality, years lived with disability, years of life lost, disability-adjusted life years were analysed and reported for 30 causes of injury in Vietnam from 2007 to 2017.ResultsBetween 2007 and 2017, the age-standardised incidence rate of all injuries increased by 14.6% (11.5%–18.2%), while the age-standardised mortality rate decreased by 11.6% (3.0%–20.2%). Interpersonal violence experienced the largest increase in age-standardised incidence (28.3% (17.6%–40.1%)), while exposure to forces of nature had the largest decrease in age-standardised mortality (47.1% (37.9%–54.6%)). The five leading causes of injury in both 2007 and 2017 were road injuries, falls, exposure to mechanical forces, interpersonal violence and other unintentional injuries, all of which increased in incidence from 2007 to 2017. Injury burden varied markedly by age and sex.ConclusionsThe rapid expansions of economic growth in Vietnam as well as improvements in the Sociodemographic Index have occurred alongside dynamic patterns in injury burden. These results should be used to develop and implement prevention and treatment programme.

Published
2020

20. Synthesis and anti-methicillin-resistant Staphylococcus aureus activity of 5,7-dibromo-2-benzoylbenzofurans alone and in combination with antibiotics

Author

Son N. Kim, Hong-Nhung T. Nguyen, Phuong-Thuy T. Phan, and Tuan-Anh N. Pham

Subjects
010405 organic chemistry, medicine.drug_class, Organic Chemistry, Antibiotics, biochemical phenomena, metabolism, and nutrition, 010402 general chemistry, Phenacyl, medicine.disease_cause, 01 natural sciences, Methicillin-resistant Staphylococcus aureus, Combinatorial chemistry, 0104 chemical sciences, chemistry.chemical_compound, chemistry, medicine, Benzofuran, Antibacterial activity
Abstract

A series of 5,7-dibromo-2-benzoylbenzofurans were synthesized by the Rap–Stoermer condensation of 5,7-dibromosalicylaldehyde with diverse phenacyl bromides and evaluated for in-vitro antibacterial activities against methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and MRSA ATCC 33591 by agar dilution method. The synergistic effects were determined by using the agar dilution checkerboard assay. The derivatives bearing carboxylic acid functional groups exhibited reasonable activity against MRSA strains with the best MIC = 32 µg/mL (9b, 9d). Moreover, the additive or synergistic interactions against MRSA strains was observed in six combinations (1b + cefuroxime/gentamicin, 1c + ciprofloxacin/gentamicin, 9b + gentamicin, and 9c + ciprofloxacin) with the fractional inhibitory concentration index (FICI) values in the range of 0.375–1.0. Significantly, the MICs of these antibiotics were reduced 2–4-fold. The results of the MTT assay illustrated the low mammalian cell cytotoxicity of these potent compounds.

Published
2020
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22. Single-Atom Fluorescence Switch: A General Approach toward Visible-Light-Activated Dyes for Biological Imaging

Author

Yubin Zhou, Kuan-Lin Wu, Han Xiao, Jingqi Pei, Juan Tang, Michael A. Robichaux, Theodore G. Wensel, and Nhung T. Nguyen

Subjects
Light, CHO Cells, 010402 general chemistry, Photochemistry, 01 natural sciences, Biochemistry, Catalysis, Fluorescence, Article, Colloid and Surface Chemistry, Cricetulus, Cricetinae, Atom, Microscopy, Adipocytes, Animals, Photoactivated localization microscopy, Sulfhydryl Compounds, Absorption (electromagnetic radiation), Cells, Cultured, Fluorescent Dyes, Chemistry, General Chemistry, 0104 chemical sciences, Microscopy, Fluorescence, Temporal resolution, Biological imaging, Visible spectrum
Abstract

Photoactivatable fluorophores afford powerful molecular tools to improve the spatial and temporal resolution of subcellular structures and dynamics. By performing a single sulfur-for-oxygen atom replacement within common fluorophores, we have developed a facile and general strategy to obtain photoactivatable fluorogenic dyes across a broad spectral range. Thiocarbonyl substitution within fluorophores results in significant loss of fluorescence via a photoinduced electron transfer-quenching mechanism as suggested by theoretical calculations. Significantly, upon exposure to air and visible light residing in their absorption regime (365-630 nm), thio-caged fluorophores can be efficiently desulfurized to their oxo derivatives, thus restoring strong emission of the fluorophores. The effective photoactivation makes thio-caged fluorophores promising candidates for super-resolution imaging, which was realized by photoactivated localization microscopy (PALM) with low-power activation light under physiological conditions in the absence of cytotoxic additives (e.g., thiols, oxygen scavengers), a feature superior to traditional PALM probes. The versatility of this thio-caging strategy was further demonstrated by multicolor super-resolution imaging of lipid droplets and proteins of interest.

Published
2019

23. Bevacizumab at first recurrence after standard radio-chemotherapy is associated with improved overall survival in glioblastoma patients with large tumor burden

Author

Laura Dovek, Timothy F. Cloughesy, Myung-Shin Sim, Albert Lai, Arliene Ravelo, Huy Tram N. Nguyen, Liang Yen Liu, Robert Harris, Byram Ozer, Daniel Lenchner, Richard M. Green, Nhung T Nguyen, Robert Elashoff, Benjamin M. Ellingson, Nicolas Sommer, and Phioanh L. Nghiemphu

Subjects
Oncology, medicine.medical_specialty, first recurrence, Bevacizumab, Large tumor, overall survival, Clinical Trials and Supportive Activities, Medicine (miscellaneous), bevacizumab, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Clinical Research, Internal medicine, Overall survival, Medicine, First Recurrence, Radio chemotherapy, Cancer, Tumor size, business.industry, tumor size, glioblastoma, Neurosciences, Lomustine, Original Articles, medicine.disease, Brain Disorders, Brain Cancer, 030220 oncology & carcinogenesis, 6.1 Pharmaceuticals, business, 030217 neurology & neurosurgery, medicine.drug, Glioblastoma
Abstract

Background Since its approval for use in recurrent glioblastoma (GBM), the survival benefit of bevacizumab (Bev) remains to be demonstrated. To address this issue, we retrospectively examined survival from first recurrence in patients treated with Bev, lomustine (CCNU), or Bev/CCNU. Methods We identified 168 primary GBM patients diagnosed at UCLA and Kaiser Permanente LA who received upfront radio-chemotherapy, followed by Bev and/or CCNU at first recurrence. Three patient groups, contemporaneously diagnosed from 2009 through 2015, were identified: (1) patients treated with Bev alone (n = 49), (2) CCNU alone (CCNU 09-15) (n = 36), and (3) Bev/CCNU (n = 53). Another CCNU control group (n = 30) diagnosed from 2001 through 2004 (CCNU 01-04) was also derived. We measured tumor size at first recurrence treatment initiation, using bidimensional (2D) and volumetric (3D) techniques, and analyzed overall survival (OS) from first recurrence. Results Among the entire cohort, larger tumor size at first recurrence was associated with poorer survival. The CCNU 01-04 group had similar tumor size as the Bev arms and low Bev crossover (7%). Treatment with Bev was associated with improved survival in patients with large tumor 2D measurements: Median OS for Bev and Bev/CCNU groups were 6.71 mo (n = 27) and 6.97 mo (n = 36) vs 4.03 mo (n = 10) in CCNU 01-04. Analysis by 3D measurement yielded similar results. Interestingly, the CCNU 09-15 group showed the highest survival, likely due to smaller tumor size and crossover to Bev (69%). Conclusion Survival advantage from Bev treatment was observed only among patients with large tumor burden as determined by either 2D or 3D measurement.

Published
2019

24. Abstract 2106: Combined deacetylase and bromodomain inhibition downregulates ERCC2 and suppresses growth of metastatic colon cancer cells

Author

Wan Mohaiza Dashwood, Trace Gustafson, Jorge Enrique Tovar Perez, Mutian Zhang, Nhung T. Nguyen, Jia Li, Sabeeta Kapoor, Roderick H. Dashwood, Praveen Rajendran, and Ying-Shiuan Chen

Subjects
Cancer Research, Global genome nucleotide-excision repair, DNA repair, Colorectal cancer, Cancer, Biology, medicine.disease, Bromodomain, Oncology, medicine, Cancer research, ERCC2, Epigenetics, Nucleotide excision repair
Abstract

DNA repair genes have potential clinical value in predicting cancer prognosis and treatment outcomes. Nucleotide excision repair (NER) proteins like ERCC2 play a critical role in maintaining genome integrity by recognizing and unwinding DNA at sites of damage1.Aberrant expression of ERCC2 alters NER capacity, influencing treatment outcomes2. The current investigation examined the expression of ERCC2 following epigenetic combination treatment in colorectal cancer (CRC) cells and preclinical models. Attention was drawn to ERCC2 based on three observations. First, from online databases, when ERCC2 was overexpressed in colon tumors the corresponding CRC patients had reduced overall survival3. Second, ERCC2 was the most highly downregulated gene when dietary histone deacetylase 3 (HDAC3) inhibitor sulforaphane (SFN) was combined withJQ1, an inhibitor of the bromodomain and extra terminal domain family, in human colon cancer cells and in colon polyps from the polyposis in rat colon (Pirc) model4. Third, as reported here for the first time, RNA-seq analyses of Pirc colon polyps from rats treated withJQ1 and the SFN analog 6-SFN5 identified Ercc2 as the most highly downregulated gene. RNA-seq data were corroborated by RT-qPCR and immunoblotting experiments. There is much interest in combination approaches that target epigenetic ‘readers, writers, and erasers' that are deregulated in cancer and other pathologies. The current work identified promising second-generation inhibitors with enhanced synergy and antitumor efficacy, especially in metastatic cells cultured in three-dimensions. Drug combinations decreased HDAC3, BRD4 and ERCC2 expression, while DNA damage and apoptosis markers were increased both in spheroids and in a mouse xenograft model. This investigation has potential clinical relevance for the identification of robust biomarkers that predict enhanced antitumor outcomes in CRC patients.1. Gillet LC, Schärer OD. Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem Rev 2006;106:253-76.2. Shuck SC, Short EA, Turchi JJ. Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology. Cell Res 2008;18:64-72.3. Liu J et al., The Differential Expression of Core Genes in Nucleotide Excision Repair Pathway Indicates Colorectal Carcinogenesis and Prognosis. Biomed Res Int 2018;2018:9651320.4. Rajendran P et al., Acetylation of CCAR2 establishes a BET/BRD9 acetyl switch in response to combined deacetylase and bromodomain inhibition. Cancer Res 2019;79:918-27.5. Rajendran Pet al., HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cell treated with sulforaphane and related dietary isothiocyanates. Epigenetics 2013;8:612-23. Citation Format: Sabeeta Kapoor, Trace Gustafson, Mutian Zhang, Ying-Shiuan Chen, Jia Li, Nhung Nguyen, Jorge Enrique Perez, Wan Mohaiza Dashwood, Praveen Rajendran, Roderick Dashwood. Combined deacetylase and bromodomain inhibition downregulates ERCC2 and suppresses growth of metastatic colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2106.

Published
2021
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25. Optical control of membrane tethering and interorganellar communication at nanoscales

Author

Qian Zhang, Ji Jing, Nhung T. Nguyen, Lei Zhu, Lian He, Yubin Zhou, Guolin Ma, Junfeng Wang, Peng Tan, and Yun Huang

Subjects
0303 health sciences, Cell signaling, Tethering, Endoplasmic reticulum, General Chemistry, Optogenetics, Biology, Subcellular localization, Cell biology, Cell membrane, Chemistry, 03 medical and health sciences, 0302 clinical medicine, Membrane, medicine.anatomical_structure, medicine, 030217 neurology & neurosurgery, Intracellular, 030304 developmental biology
Abstract

A light-controllable membrane tether to control protein subcellular localization and manipulate interorganellar contact sites at nanoscales., Endoplasmic reticulum (ER) forms an extensive intracellular membranous network in eukaryotes that dynamically connects and communicates with diverse subcellular compartments such as plasma membrane (PM) through membrane contact sites (MCSs), with the inter-membrane gaps separated by a distance of 10–40 nm. Phosphoinositides (PI) constitute an important class of cell membrane phospholipids shared by many MCSs to regulate a myriad of cellular events, including membrane trafficking, calcium homeostasis and lipid metabolism. By installing photosensitivity into a series of engineered PI-binding domains with minimal sizes, we have created an optogenetic toolkit (designated as ‘OptoPB’) to enable rapid and reversible control of protein translocation and inter-membrane tethering at MCSs. These genetically-encoded, single-component tools can be used as scaffolds for grafting lipid-binding domains to dissect molecular determinants that govern protein–lipid interactions in living cells. Furthermore, we have demonstrated the use of OptoPB as a versatile fusion tag to photomanipulate protein translocation toward PM for reprogramming of PI metabolism. When tethered to the ER membrane with the insertion of flexible spacers, OptoPB can be applied to reversibly photo-tune the gap distances at nanometer scales between the two organellar membranes at MCSs, and to gauge the distance requirement for the free diffusion of protein complexes into MCSs. Our modular optical tools will find broad applications in non-invasive and remote control of protein subcellular localization and interorganellar contact sites that are critical for cell signaling.

Published
2017
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26. 18F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study

Author

Phioanh L. Nghiemphu, Catalina Raymond, Albert Lai, Elisa Fazzari, Benjamin M. Ellingson, Ararat Chakhoyan, Jasmine Manoukian, Huytram N. Nguyen, Timothy F. Cloughesy, Whitney B. Pope, Chirag B. Patel, Jingwen Yao, Johannes Czernin, and Nhung T Nguyen

Subjects
Male, Cancer Research, Neurology, Cross-sectional study, Contrast Media, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Cancer, screening and diagnosis, Tumor, Brain Neoplasms, Brain, Glioma, Middle Aged, Prognosis, Magnetic Resonance Imaging, Dihydroxyphenylalanine, 18F-FDOPA PET, Detection, Oncology, 030220 oncology & carcinogenesis, Preoperative Period, Biomarker (medicine), Biomedical Imaging, Female, MRI, 4.2 Evaluation of markers and technologies, Adult, medicine.medical_specialty, F-18-FDOPA PET, Adolescent, Oncology and Carcinogenesis, Malignancy, Article, 03 medical and health sciences, Young Adult, Rare Diseases, Clinical Research, medicine, Humans, Oncology & Carcinogenesis, Pathological, Retrospective Studies, Aged, Proportional hazards model, business.industry, Neurosciences, Biomarker, medicine.disease, Survival Analysis, Hyperintensity, Brain Disorders, Brain Cancer, Cross-Sectional Studies, Positron-Emission Tomography, Neurology (clinical), Radiopharmaceuticals, business, Nuclear medicine, Biomarkers
Abstract

INTRODUCTION: To report the potential value of pre-operative (18)F-FDOPA PET and anatomic MRI in diagnosis and prognosis of glioma patients. METHODS: Forty-five patients with a pathological diagnosis of glioma with pre-operative (18)F-FDOPA PET and anatomic MRI were retrospectively examined. The volume of contrast enhancement and T2 hyperintensity on MRI images along with the ratio of maximum (18)F-FDOPA SUV in tumor to normal tissue (T/N SUV(max)) were measured and used to predict tumor grade, molecular status, and overall survival (OS). RESULTS: A significant correlation was observed between WHO grade and: the volume of contrast enhancement (r=0.67), volume of T2 hyperintensity (r=0.42), and (18)F-FDOPA uptake (r=0.60)(P < 0.01 for each correlation). The volume of contrast enhancement and (18)F-FDOPA T/N SUV(max) were significantly higher in glioblastoma (WHO IV) compared with lower grade gliomas (WHO I–III), as well as for high-grade gliomas (WHO III–IV) compared with low-grade gliomas (WHO I–II). Receiver-operator characteristic (ROC) analyses confirmed the volume of contrast enhancement and (18)F-FDOPA T/N SUV(max) could each differentiate patient groups. No significant differences in (18)F-FDOPA uptake were observed by IDH or MGMT status. Multivariable Cox regression suggested age (HR = 1.16, P = 0.0001) and continuous measures of (18)F-FDOPA PET T/N SUV(max) (HR = 4.43, P = 0.016) were significant prognostic factors for OS in WHO I–IV gliomas. CONCLUSIONS: Current findings suggest a potential role for the use of pre-operative (18)F-FDOPA PET in suspected glioma. Increased (18)F-FDOPA uptake may not only predict higher glioma grade, but also worse OS.

Published
2018

27. Correlation of commercially available quantitative MGMT (O-6-methylguanine-DNA methyltransferase) promoter methylation scores and GBM patient survival

Author

Laura Dovek, Timothy F. Cloughesy, P Leia Nghiemphu, Nhung T Nguyen, Albert Lai, Linda M. Liau, Robert Elashoff, Richard M. Green, Ning Li, and Byram Ozer

Subjects
Oncology, medicine.medical_specialty, Temozolomide, Methyltransferase, Proportional hazards model, business.industry, Hazard ratio, Medicine (miscellaneous), O-6-methylguanine-DNA methyltransferase, Methylation, Original Articles, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Isocitrate dehydrogenase, 030220 oncology & carcinogenesis, Glioma, Internal medicine, medicine, business, neoplasms, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background Between 2011 and 2016, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation testing at University of California Los Angeles (UCLA) was performed through LabCorp, using a threshold of 2 to distinguish MGMT methylated from unmethylated tumors. In this study, we sought to determine whether the magnitude of the methylation score correlated with outcome. Methods We identified 165 newly diagnosed glioblastoma (GBM) isocitrate dehydrogenase (IDH) wild-type and temozolomide-treated upfront patients at UCLA and Kaiser Permanente Los Angeles with LabCorp-derived quantitative MGMT scores obtained on pretreatment tissue samples. Using LabCorp’s threshold, we found 102 unmethylated and 63 methylated patients. We then further substratified each group based on the magnitude of the score, and performed Kaplan-Meier and Cox regression analyses of overall survival (OS) and progression-free survival (PFS). Results We validated that the standard LabCorp threshold of 2 could separate our cohort by survival, showing longer OS and PFS for MGMT methylated patients vs unmethylated patients. Cox regression analysis confirmed that MGMT ( Conclusions The MGMT unmethylated group contains a partially methylated group (greater than 1) that shares survival benefits similar to the methylated group. However, we did not demonstrate an association of very high methylation scores with increased survival. These findings will require validation in additional independent clinical data sets.

Published
2018

28. D-2-Hydroxyglutarate is Necessary and Sufficient for Isocitrate Dehydrogenase 1 Mutant-induced MIR148A Promoter Methylation

Author

Christopher D Cox, Tie Li, Sichen Li, Fei Liu, Thomas J Lai, Huytram N. Nguyen, Phioanh L. Nghiemphu, Byram Ozer, Nhung T Nguyen, Timothy F. Cloughesy, Harley I. Kornblum, Linda M. Liau, and Albert Lai

Subjects
0301 basic medicine, Cancer Research, Mutant, Oncology and Carcinogenesis, RNA polymerase II, Article, Glutarates, 03 medical and health sciences, Rare Diseases, Transcription (biology), Genetics, Gene silencing, Humans, Oncology & Carcinogenesis, Molecular Biology, Cancer, biology, Chemistry, Promoter, Methylation, DNA Methylation, Molecular biology, Isocitrate Dehydrogenase, Brain Disorders, Brain Cancer, MicroRNAs, 030104 developmental biology, Isocitrate dehydrogenase, Oncology, DNA methylation, Mutation, biology.protein, Cancer research, Developmental Biology
Abstract

Mutant isocitrate dehydrogenase (IDH) 1/2 converts α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2-HG), a putative oncometabolite that can inhibit α-KG–dependent enzymes, including ten-eleven translocation methylcytosine dioxygenase (TET) DNA demethylases. We recently established that miRNAs are components of the IDH1 mutant–associated glioma CpG island methylator phenotype (G-CIMP) and specifically identified MIR148A as a tumor-suppressive miRNA within G-CIMP. However, the precise mechanism by which mutant IDH induces hypermethylation of MIR148A and other G-CIMP promoters remains to be elucidated. In this study, we demonstrate that treatment with exogenous D-2-HG induces MIR148A promoter methylation and transcriptional silencing in human embryonic kidney 293T (293T) cells and primary normal human astrocytes. Conversely, we show that the development of MIR148A promoter methylation in mutant IDH1–overexpressing 293T cells is abrogated via treatment with C227, an inhibitor of mutant IDH1 generation of D-2-HG. Using dot blot assays for global assessment of 5-hydroxymethylcytosine (5-hmC), we show that D-2-HG treatment reduces 5-hmC levels, whereas C227 treatment increases 5-hmC levels, strongly suggesting TET inhibition by D-2-HG. Moreover, we show that withdrawal of D-2-HG treatment reverses methylation with an associated increase in MIR148A transcript levels and transient generation of 5-hmC. We also demonstrate that RNA polymerase II binds endogenously to the predicted promoter region of MIR148A, validating the hypothesis that its transcription is driven by an independent promoter. Implications: Establishment of D-2-HG as a necessary and sufficient intermediate by which mutant IDH1 induces CpG island methylation of MIR148A will help with understanding the efficacy of selective mutant IDH1 inhibitors in the clinic. Mol Cancer Res; 16(6); 947–60. ©2018 AACR.

Published
2018

29. Rewiring Calcium Signaling for Precise Transcriptional Reprogramming

Author

Yun Huang, Yubin Zhou, Nhung T. Nguyen, Margarita Martinez-Moczygemba, and Lian He

Subjects
0301 basic medicine, Light, Transcription, Genetic, Biomedical Engineering, Gene regulatory network, Biology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Article, 03 medical and health sciences, Genome editing, Gene expression, CRISPR, Humans, Calcium Signaling, Cell Nucleus, Effector, Cas9, NFAT, General Medicine, Calcium Release Activated Calcium Channels, Cell biology, Optogenetics, Protein Transport, 030104 developmental biology, HEK293 Cells, Gene Expression Regulation, Calcium, Synthetic Biology, CRISPR-Cas Systems, Reprogramming, HeLa Cells
Abstract

Tools capable of modulating gene expression in living organisms are very useful for interrogating the gene regulatory network and controlling biological processes. The catalytically inactive CRISPR/Cas9 (dCas9), when fused with repressive or activating effectors, functions as a versatile platform to reprogram gene transcription at targeted genomic loci. However, without temporal control, the application of these reprogramming tools will likely cause off-target effects and lack strict reversibility. To overcome this limitation, we report herein the development of a chemical or light-inducible transcriptional reprogramming device that combines photoswitchable genetically encoded calcium actuators with dCas9 to control gene expression. By fusing an engineered Ca(2+)-responsive NFAT fragment with dCas9 and transcriptional coactivators, we harness the power of light to achieve photoinducible transcriptional reprogramming in mammalian cells. This synthetic system (designated CaRROT) can also be used to document calcium-dependent activity in mammals after exposure to ligands or chemicals that would elicit calcium response inside cells.

Published
2018

30. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013

Author

Yong Zhao, Hadi Danawi, Bach Xuan Tran, Gene Bukhman, Vasiliki Stathopoulou, Taavi Tillmann, Nelson Alvis-Guzman, Yongmei Li, Jerry Puthenpurakal Abraham, Sudan Prasad Neupane, Jack Caravanos, Ben Schöttker, Rafael Lozano, Damian G Hoy, Yoshihiro Kokubo, Nicholas J K Breitborde, Sergey Soshnikov, Yukito Shinohara, Randall V. Martin, Michael Brainin, Fernando Perez-Ruiz, Yingfeng Zheng, Santosh Mishra, Julio Cesar Montañez Hernandez, Michael Phillips, Belinda J. Gabbe, Hebe N. Gouda, Ziad A. Memish, Rupert R A Bourne, Guoqing Hu, Emmanuel A. Ameh, Abigail McLain, Michelle L. Bell, Christopher Margono, Marissa Iannarone, Wilkister N. Moturi, Donald H. Silberberg, Carl Abelardo T. Antonio, Nataliya Foigt, Anand Dayama, Yanping Wang, Amanda J. Mason-Jones, Bolajoko O. Olusanya, Monica S. Vavilala, Katherine B Gibney, David Tanne, Sidibe S Kany Roseline, Marcella Montico, Abhishek Singh, Sarah Derrett, Alireza Esteghamati, Seok Jun Yoon, Corine Karema, Rakhi Dandona, David M. Pereira, Kazem Rahimi, Gitanjali M. Singh, Vivekanand Jha, John Hornberger, Anne M. Riederer, Kathryn H. Jacobsen, Andrea Pedroza, Lily Alexander, Fiona M. Blyth, Tommi Vasankari, Kyle J Foreman, Rana J. Asghar, Tilahun Nigatu Haregu, Yousef Khader, Rafael Alfonso-Cristancho, Suzanne Barker-Collo, Lydia S. Atkins, Simerjot K. Jassal, Mohammad Ali Sahraian, Peter Scarborough, Hans W. Hoek, E. Ray Dorsey, Muluken Dessalegn, David C. Schwebel, Gavin Shaddick, Thomas D. Fleming, Mohammad Tavakkoli, Dorairaj Prabhakaran, Mohammad H. Forouzanfar, Christopher C. Mapoma, Jost B. Jonas, Erin C Mullany, Gene F. Kwan, Johanna M. Geleijnse, Antonio Luiz Pinho Ribeiro, Roberto Tchio Talongwa, Tolesa Bekele, Jed D. Blore, Gunn Marit Aasvang, Philimon Gona, Miguel Angel Alegretti, Babak Eshrati, Mitsuru Mukaigawara, Richard F. Gillum, Odgerel Chimed-Ochir, Ubai Alsharif, Richard C. Franklin, Felix Masiye, Richard T. Burnett, Sanjay Krishnaswami, Martin McKee, John J Huang, Lucía Cuevas-Nasu, Wagner Marcenes, Walid Ammar, Knud Juel, Joseph R. Zunt, Martha M Téllez Rojo, Mamta Swaroop, Noela M Prasad, Azmeraw T. Amare, Tim Driscoll, Michael Kravchenko, Heresh Amini, Amir Sapkota, Theo Vos, Charlotte Watts, Dennis Odai Laryea, D. Alex Quistberg, Justin Beardsley, Cheng Huang, Adnan M. Durrani, Sarah V Thackway, Rita Van Dingenen, Manami Inoue, Martha Híjar, Honglei Chen, Amany H. Refaat, Yichong Li, Vineet K. Chadha, Wenzhi Wang, Louisa Degenhardt, Kingsley N. Ukwaja, Nayu Ikeda, James D. Wilkinson, Linh N Bui, Maria Hagströmer, Gonghuan Yang, Ann Kristin Knudsen, David J. Margolis, Soewarta Kosen, Hans Kromhout, Atsushi Goto, Man Mohan Mehndiratta, Thomas N. Williams, Michael Soljak, Yun Jin Kim, Hideaki Toyoshima, Jeyaraj D Pandian, Borja del Pozo-Cruz, Soufiane Boufous, Ivy Shiue, Anders Larsson, Guilherme V. Polanczyk, John Powles, Yara A. Halasa, Robin Room, Ratilal Lalloo, Carolina Batis Ruvalcaba, Panniyammakal Jeemon, Elisabete Weiderpass, Jürgen Rehm, Ejaz Ahmad Khan, Alicia Aleman, Zacharie Tsala Dimbuene, Elena Alvarez, Rachelle Buchbinder, Randah R. Hamadeh, Bryan Hubbell, Sadaf G. Sepanlou, Farhad Islami, Costas A. Christophi, Heidi Stöckl, Ismael R. Campos-Nonato, Nigel Bruce, Edward J Mills, Samuel A L Perry, Taavi Lai, Baffour Awuah, Mete Saylan, Karen J. Courville, Arindam Basu, Vanessa De la Cruz-Góngora, Teresita González de Cosío, Naohiro Yonemoto, Frida Namnyak Ngalesoni, Muluken Azage Yenesew, Atte Meretoja, Michael Brauer, Cyrus Cooper, Giorgia Giussani, Valentina S. Arsic Arsenijevic, Vasiliy Victorovich Vlassov, André Karch, Leilei Duan, Matthew M Coates, Omid Ameli, Gelin Xu, Matthias Endres, Ganesan Karthikeyan, Ione Jayce Ceola Schneider, Mohamed Hsairi, Palwasha Anwari, Mazin J. Al Khabouri, Dariush Mozaffarian, Juan R. Sanabria, Pablo M. Lavados, Sumeet S. Chugh, Johan Ärnlöv, Ivo Rakovac, Maurice Giroud, Haidong Kan, Ibrahim Abdelmageem Mohamed Ginawi, José Luis Texcalac-Sangrador, Luigi Naldi, Erica Leigh Slepak, Deena Alasfoor, James E. Saunders, Richard Matzopoulos, Talal Bakfalouni, Stein Emil Vollset, Andrea Werdecker, Lennert J. Veerman, Lorenzo Monasta, Henrica A. F. M. Jansen, Reyna A Gutiérrez, Brittany Wurtz, Luz Maria Sanchez, Lijing L. Yan, M. Patrice Lindsay, Michele Meltzer, Sanjay Basu, Steven van de Vijver, Alaa Badawi, Thomas Claßen, Young-Ho Khang, Brett M. Kissela, Jun Zhu, In-Hwan Oh, Fiona J Charlson, Maria Cecilia Bahit, Dinorah González-Castell, Rosario Cárdenas, Dan Poenaru, Sayed Saidul Alam, Mitchell T. Wallin, Harish Chander Gugnani, James Leigh, Ferrán Catalá-López, Lidia Morawska, Jim van Os, Stephanie J. London, Kaire Innos, Isabelle Romieu, Fiorella Cavalleri, Adrian Davis, Hwee Pin Phua, Chakib Nejjari, Héctor Gómez Dantés, Boris I. Pavlin, Karen Sliwa, Lynne Gaffikin, Constance D. Pond, Michael F. MacIntyre, Blake Thomson, Norberto Perico, Ronny Westerman, Samantha M. Colquhoun, Michael H. Criqui, Ana Maria Nogales Vasconcelos, Wubegzier Mekonnen, Bulat Idrisov, Ana Basto-Abreu, Andrew G. M. Bulloch, Jasvinder A. Singh, Vinod K. Paul, Emin Murat Tuzcu, Svetlana Popova, Hmwe H Kyu, Richard L. Guerrant, Mohammed I. Albittar, Srikanth Mangalam, Steven E. Lipshultz, Lela Sturua, Semaw Ferede Abera, Eduardo Bernabé, George D. Thurston, Bruno F. Sunguya, Tiffany Ku, Alejandra G. Contreras, Abdullah Sulieman Terkawi, Charles Atkinson, Ashkan Afshin, Heidi J. Larson, Abdullatif Husseini, Jose C. Adsuar, Reza Assadi, Ademola Lukman Adelekan, Joshua A. Salomon, Yousef M. Elshrek, Gokalp Kadri Yentur, Devina Nand, Narayanaswamy Venketasubramanian, Graça Maria Ferreira De Lima, Maheswar Satpathy, Fotis Topouzis, Traolach S. Brugha, Hywel C Williams, Coen H. Van Gool, Andrew H. Kemp, Awoke Misganaw, Amado D Quezada, Norito Kawakami, Bert Brunekreef, Peter Burney, Tati S. Warouw, Jongmin Lee, Inga Dora Sigfusdottir, Marcel Tanner, Solveig A. Cunningham, Benjamin O. Anderson, Tariku Jibat Beyene, Lars Barregard, Xia Wan, Giuseppe Remuzzi, Bernadette Thomas, Lilia S Pedraza, Massimo Cirillo, Alina Rodriguez, Ricky Leung, Farshad Pourmalek, K. Srinath Reddy, Charles D.A. Wolfe, Ulrich O Mueller, Neeraj Bedi, Al Artaman, Lucia Hernandez, Itamar S. Santos, C. Arden Pope, Norlinah Mohamed Ibrahim, Carlo Irwin A. Panelo, Selen Begüm Uzun, Miltiadis K. Tsilimbaris, Anwar Rafay, Daniel Dicker, Melvin Barrientos Marzan, Sajjad Ur Rahman, Mohammed O. Basulaiman, Edgar P. Simard, Mohammad T Mashal, Maysaa El Sayed Zaki, Shiwei Liu, Don C. Des Jarlais, Bo Norrving, Salvador Villalpando, Miia Kivipelto, Yang Liu, Carolina Maria Teixeira, Catalina Medina, Sudha Jayaraman, Josep Maria Haro, Diego De Leo, Angel J Paternina Caicedo, Abigail C. McKay, Eric L. Ding, Mukesh Dherani, Ljiljana Pejin Stokic, Vinay Nangia, Sukanta Saha, Juan Liang, Elisabeth Cardis, Zourkaleini Younoussi, José R Nogueira, Braden Te Ao, Vasco Manuel Pedro Machado, Lionel Racapé, Ting Wu Chuang, Shahab Khatibzadeh, E Filipa de Castro, Barthelemy Kuate Defo, Ulises Trujillo, Alan D. Lopez, Soraya Seedat, Lope H Barrero, Linhong Wang, Daniel Pope, Alexandra Brazinova, Faris Lami, Valentina Colistro, G Anil Kumar, Derek F J Fay, Haidong Wang, Hwashin H. Shin, Raimundas Lunevicius, Suzanne Polinder, Dietrich Plass, David Rojas-Rueda, Stephen S Lim, Tania G Sánchez-Pimienta, K.M. Venkat Narayan, Yuantao Hao, Jung-Chen Chang, Corina Benjet, Seyed-Mohammad Fereshtehnejad, Luciano A. Sposato, Stan Biryukov, Kunihiro Matsushita, Beth E. Ebel, Cleusa P. Ferri, Soumya Swaminathan, K. Ryan Wessells, Gustavo Velasquez-Melendez, Leslie T. Cooper, David O. Carpenter, Nancy Lopez, Bryan L. Sykes, Sandra Nolte, Murray B. Stein, Paul N. Jensen, Fabiola Mejía-Rodríguez, Xiaonong Zou, Bradford D. Gessner, Dhruv S. Kazi, Dragos Virgil Davitoiu, Alejandra Jáuregui, Pouria Heydarpour, Megan Bohensky, Harvey Whiteford, Berrak Bora Basara, Zhengming Chen, Gregory R. Wagner, Paul I. Dargan, Hermann Brenner, Nima Hafezi-Nejad, John Nelson Opio, Scott Weichenthal, Deborah Salvo, Jun She, Tea Lallukka, Carolyn C. Gotay, Stephen G. Waller, Christian Kieling, Shivanthi Balalla, Valery L. Feigin, Qing Lan, Matias Trillini, Adam D M Briggs, Sungroul Kim, Niveen M E Abu-Rmeileh, Renata Micha, Sergey Petrovich Ermakov, Ole Frithjof Norheim, Zulfiqar A Bhutta, Paul S. F. Yip, Grant Nguyen, Ralph L. Sacco, Biju Abraham, Ken Takahashi, Jixiang Ma, Peter A. Meaney, Ayse Abbasoglu Ozgoren, Kimberly Cooperrider, M Rifat Kose, Shams Eldin Ali Hassan Khalifa, Rasmus Havmoeller, Alize J. Ferrari, Kebede Deribe, Nadim E. Karam, George A. Mensah, Bongani M. Mayosi, Konrad Pesudovs, Joanna Moschandreas, Ziad Nahas, James Damsere-Derry, Nsanzimana Sabin, Tonatiuh Barrientos-Gutiérrez, Ying Jiang, Andre Pascal Kengne, Peter Allebeck, Jonas Minet Kinge, Shankuan Zhu, Guy B. Marks, Daniel C Casey, Marco A Avila, Anna Roca, Lalit Dandona, Ami R. Moore, Adansi A. Amankwaa, David Gunnell, Andre Keren, Yohannes Adama Melaku, Nhung T Nguyen, Anthony D. Woolf, Mayuree Rao, Peter J. Allen, Christina Papachristou, Karzan Abdulmuhsin Mohammad, Ravi Kumar Balu, Marie Ng, Marcello Tonelli, Maziar Moradi-Lakeh, Maigeng Zhou, Emmanuela Gakidou, Mohammed K. Ali, Amanda W Pain, Dan J. Stein, Kawkab Shishani, Fortuné Gbètoho Gankpé, Howard J. Hoffman, James Scott, Nadine Steckling, Samia Alhabib, Deborah Jarvis, Kara Estep, Arsène Kouablan Adou, Ricardo Orozco, Holly Hagan, K. C. Astha, Reza Malekzadeh, Klara Dokova, Aliya Naheed, Ernst J. Kuipers, Valeria Caso, Derrick A Bennett, Andrea B. Feigl, Uche S. Uchendu, Holly E. Erskine, Shireen Sindi, Arjun Lakshmana Balaji, Francesco Saverio Violante, Monika Sawhney, Alejandra Cantoral, Ketevan Goginashvili, Raghib Ali, Fan Jiang, Robert G. Weintraub, Homie Razavi, Myriam Tobollik, Howard Hu, Emerito Jose A. Faraon, Irma Khonelidze, Patricia M. Riccio, Eun-Kee Park, Julio Cesar Campuzano, Ibrahim Abubakar, Jürgen C Schmidt, Konstantinos Stroumpoulis, Aref A. Bin Abdulhak, Graeme J. Hankey, Natan M. Bornstein, Mouhanad Hammami, Lee Richardson, Rintaro Mori, Alanur Çavlin, Ruth W Kimokoti, Samir Soneji, Mark J. Nieuwenhuijsen, John Q. Wong, Joseph Frostad, Tom Achoki, Rahman Shiri, Ashish Bhalla, Kurt Straif, Simon I. Hay, Scott B. Patten, Kalpana Balakrishnan, Awoke Misganaw Temesgen, Chandrashekhar T Sreeramareddy, Ryan M Barber, Rosana E. Norman, JianLi Wang, Siyi Shangguan, Luke Nyakarahuka, Kovin Naidoo, Charles D. H. Parry, Mercedes Colomar, H. Ross Anderson, Carlos Magis-Rodriguez, Joan M. Nolla, Muhammad Imran Nisar, Karen Devries, Andrew L. Thorne-Lyman, Denis Nash, Marape Marape, Rajiv Chowdhury, Dima M. Qato, Luca Ronfani, Nobhojit Roy, Daniel Kim, Yuichiro Yano, Luke D. Knibbs, Margaret Robinson, Hilda L Harb, Rogelio Pérez-Padilla, Janet L Leasher, Jonathan L. Wright, Peter Brooks, Cristiana Abbafati, Belinda K Lloyd, Victor Aboyans, Nikhil Tandon, Charles R. Newton, Simón Barquera, Ted R. Miller, Kinnari S. Murthy, Habib Benzian, Glen Mola, Paulo A. Lotufo, Burcu Kucuk Bicer, Peggy Pei-Chia Chiang, Alexander Kraemer, Solomon Meseret Woldeyohannes, Saman Fahimi, Lesley Rushton, Kim Moesgaard Iburg, Vafa Rahimi-Movaghar, Logan Sandar, Bruce Neal, Teresa Shamah Levy, Karen M. Tabb, Jeffrey A. Towbin, Christopher J L Murray, Ramesh Sahathevan, Aaron Cohen, Chanda Kulkarni, Van C. Lansingh, François Alla, Tasara T. Mazorodze, Murugesan Raju, Saeid Shahraz, Uchechukwu K.A. Sampson, Rajeev Gupta, Neil Pearce, Mustafa Z. Younis, Veena S. Kulkarni, Francisco A García-Guerra, Amanda G. Thrift, Stefan Ma, Samaya Ismayilova, Evariste Gasana, Amitava Banerjee, Aslam Pervaiz, Emilie Agardh, Abraham D. Flaxman, Farshad Farzadfar, Peter W. Gething, Ileana Heredia-Pi, Boris Bikbov, Wanqing Chen, Saad B. Omer, Ruben Castro, Neeraj Bhala, Sara Sheikhbahaei, Hilton Lam, Urbano Fra Paleo, Lidia Sanchez-Riera, Alicia Elena Beatriz Lawrynowicz, Kristen Delwiche, Richard G. Ellenbogen, Max Petzold, Yuri Y Varakin, Guilherme Borges, Guohong Jiang, Francis Guillemin, Kyle R. Heuton, Yohannes Kinfu, Victoria F Bachman, Joseph A Wagner, Carlos A Castañeda-Orjuela, Leonardo Trasande, Abbas Ali Mahdi, Josef Coresh, Chuanhua Yu, Kenji Shibuya, Berrin Serdar, Laetitia Huiart, Xiaofeng Liang, Jean de Dieu Ngirabega, Takayoshi Ohkubo, Natalie Stephens, Francis Apolinary Mhimbira, Jefferson Traebert, Amiran Gamkrelidze, Kjetil Søreide, Samath D Dharmaratne, Robert P. Dellavalle, George Mugambage Ruhago, Lakshmi Vijayakumar, Joannie Lortet-Tieulent, Dipan Bose, Tania C Aburto, Saleem M Rana, Miriam Levi, Mohammad Taghi Hedayati, Rodolfo S Pagcatipunan, Ron T. Gansevoort, H. D. Hosgood, Michael Burch, Mohsen Naghavi, Vegard Skirbekk, Ayfer Pekericli, Walter Mendoza, Pengpeng Ye, Gabrielle deVeber, Ali H. Mokdad, David M. Broday, Koranteng Adofo, Zewdie Aderaw Alemu, Shifalika Goenka, Carrie Beth Peterson, Nicolas J. C. Stapelberg, Edson Serván-Mori, Anil Kaul, Foad Abd-Allah, Marek Majdan, Rahul Gupta, Giancarlo Logroscino, Kardiyoloji, Peterson, Carrie B., Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Wisconsin Division of Public Health, Laboratoire de psychologie sociale et de psychologie cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Erosion torrentielle neige et avalanches (UR ETGR (ETNA)), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), London South Bank University, Metropolitan Police Service, Hong Kong Baptist University (HKBU), Institut für Informatik [München/Munich] (LMU), Ludwig-Maximilians-Universität München (LMU), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Insight Centre for Data Analytics [Galway] (INSIGHT), National University of Ireland [Galway] (NUI Galway), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Karolinska Institute, karolinska institute, Department of Molecular Biosciences, Department of Molecular Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Centro de Estudios Avanzados en Zonas Aridas (CEAZA), Ecole Polytechnique Fédérale de Lausanne (EPFL), Regional Genetic Service, St Mary's Hospital, Manchester, Laboratoire d'Ingénierie des Matériaux (LIM), Centre National de la Recherche Scientifique (CNRS), Computer Science Department [Bristol], University of Bristol [Bristol], Universität Mannheim [Mannheim], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) (SRI-B), Computational Science and Engineering Department [Daresbury] (STFC), Science & Technologie Facilities Council, Multimedia Research Center (MRC), University of Alberta, Division of Biostatistics (Biostat - MINNEAPOLIS), University of Minnesota [Twin Cities], University of Minnesota System-University of Minnesota System, University of Southampton, Imperial College London, Neurology Department, Ichilov Medical Center, Interactions, transferts, ruptures artistiques et culturels - EA 6301 (InTRu), Université de Tours, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Risk Assessment Sciences Institute, Utrecht University [Utrecht], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Respiratory Epidemiology and Public Health, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], CIBER de Epidemiología y Salud Pública (CIBERESP), STAR laboratory, Stanford University [Stanford], Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Tennent Institute of Ophthalmology, National University of Singapore (NUS), Centre de Robotique (CAOR), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Multidisciplinary Nanotechnology Centre, Swansea University, Cyprus International Institute for the Environment and Public Health, Harvard School of Public Health, Genomics Research Center, Academia Sinica, Neuro Rehab Services LLP [New Delhi], Department of Signal Theory and Communications (TSC), Univ. Politec. de Catalunya, King‘s College London, Dept. Mat. Engn. De Ma, Sao Carlos, Fed. Univ. Sao Carlos UFSCar, RESPEC (RESPEC), RESPEC, Advanced Laboratories on Embedded Systems [Roma] (ALES), Department of Biology [Miami], University of Miami [Coral Gables], Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Department of Nephrology, University Medical Center, University of Groningen, Division of Human Nutrition, Wageningen University and Research Centre [Wageningen] (WUR), Spatial Ecology and Epidemiology Group, University of Oxford [Oxford], College of Medicine, University of Hail, Saudi Arabia, Laboratory of Neurologic Diseases, Mario Negri Institute, Milan, Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], GEMMA — Environmental Engineering and Microbiology Research Group, Department of Hydraulic, Maritime and Environmental Engineering, Universitat Politècnica de Catalunya [Barcelona] (UPC), Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Institut National de Recherche et d'Analyse Physico-Chimique (INRAP), Institut National de Recherche et d'Analyse Physico-chimique (Ariana, Tunisie) (INRAP), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University-Shahid Beheshti University, Center for Applied Medical Research (CIMA), University of Tehran, Secretariat of the Pacific Community, Public Health Division, Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), College of Precision Instrument and Optoelectronics Engineering, Tianjin University, George Washington University (GW), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent [Ghent], Washington State University (WSU), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, School of Computer Science - China University of Geosciences (China University of Geosciences (East Area)), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Fachbereich Physik [Berlin], Freie Universität Berlin, Div Cyclotron & Radiopharmaceut Sci (DRDO, INMAS), Univ New Delhi, School of Physics and Astronomy, University of St Andrews [Scotland], University of Cape Town, Department of Neuroscience, Department of Computer Science and Engineering [Daejeon] (Chungnam National University), Lawrence University, Gastroenterology & Hepatology, Tata Research Development and Design Center (TRDDC), TCS Innovation Labs, University of Helsinki, Google Inc [Mountain View], Research at Google, Swedish Defense Research Agency (FOI), Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Novartis Pharmaceutical Corporation, Laboratoire de glaciologie et géophysique de l'environnement (LGGE), Observatoire des Sciences de l'Univers de Grenoble [1985-2015] (OSUG [1985-2015]), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Department of Mechanical and Automation Engineering (CAD Laboratory), The Chinese University of Hong Kong [Hong Kong], Università degli studi di Bari, Department of Health and Human Services, National Institutes of Health [Bethesda] (NIH), Centre d'études et de recherche en informatique et communications (CEDRIC), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] (Heudiasyc), Université de Technologie de Compiègne (UTC)-Centre National de la Recherche Scientifique (CNRS), College of Information and Electrical Engineering [Beijing] (CIEE), China Agricultural University (CAU), Thales Research and Technology [Palaiseau], THALES, Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Centre d'économie de la Sorbonne (CES), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Paris School of Economics (PSE), École supérieure du professorat et de l'éducation - Académie de Grenoble [2013-2019] (ESPE Grenoble [2013-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Mathematics, University of Iowa [Iowa City], College of Medicine, Alfaisal University, Saudi Ministry of Health, Institut national des recherches agricoles du Bénin, Centre de Recherches agricoles du Sud, Departments of Epidemiology and Nutrition, Unit of Human Nutrition, Agricultural University of Athens, Department of Animal Science, Pennsylvania State University (Penn State), Penn State System-Penn State System, University of Virginia, University of Virginia [Charlottesville], Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS ‘‘Burlo Garofolo', Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], American University of Beirut [Beyrouth] (AUB), Department of Chemistry, Scientific Computing Research Unit, Department of dermatology, Milano University-Azienda Ospedaleria Ospedali Riuniti di Bergamo, Mailman School of Public Health, Columbia University [New York], The Georges Institute for International Health, The University of Sydney, Department of epidemiology and Public Health, Faculty of Medicine, Département Optique (OPT), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona], Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université de la Méditerranée - Aix-Marseille 2, Department of Neurology Lunds University Hospital Lund, Unit of Functional Bionanomaterials, School of Biosciences, University of Birmingham [Birmingham], Electrical Engineering and Computer Science Department - Case Western Reserve University, Case Western Reserve University [Cleveland], World Health Organization, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Nordic School of Public Health, The James Hutton Institute, Horia Hulubei National Institute for Physics and Nuclear Engineering, Department of Pediatrics, University of Washington [Seattle], Institute of Public Health, Department of Physics, Clarendon Laboratory, Center for TeleInFrastruktur (CTIF), Aalborg University [Denmark] (AAU), Physikalisches Institut [Freiburg], Albert-Ludwigs-Universität Freiburg, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Dept.of Computer Science, Indian Institute of Technology Madras (IIT Madras), Istituto Mario Negri Bergamo, Centro Ricerche e Trapianti Villa Camozzi, Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Laboratoire de Génie Informatique et Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut geològic de Catalunya (IGC), Institut Geològic de Catalunya-IGC, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Politecnico di Milano [Milan] (POLIMI), Symantec, University of Oviedo, European Microsoft Innovation Center (EMIC), Microsoft Corporation [Redmond, Wash.], Technion - Israel Institute of Technology [Haifa], Laboratoire de Mécanique, Physique et Géosciences (LMPG), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Department of Physics, Cavendish Laboratory, University of Cambridge [UK] (CAM), Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Departments of Applied Physics [New Haven], Yale University [New Haven], Center for Mathematical Modeling (CMM), Department of Global Health and Development, London School of Hygiene and Tropical Medicine (LSHTM), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Department of Computer Science and Engineering [New Delhi], Indian Institute of Technology Delhi (IIT Delhi), Institut de Recherche sur les Phénomènes Hors Equilibre (IRPHE), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), GlaxoSmithKline, Imperial College London-Clinical Imaging Center, Universidade Federal de Pernambuco [Recife] (UFPE), Maclean Building, Benson Lane, Crowmarsh Gifford, Centre for Ecology and Hydrology, Nanoscience Institute (NEST), Dipartimento di Fisica, Università di Pisa, Aristotle University of Thessaloniki, Laboratory Of Immune Cell Biology (LICB), JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC), Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] (LNCC / MCT), Occupational Health Unit, Bologna University Hospital-Sant'Orsola-Malpighi Polyclinic, Royal Institute of Technology [Stockholm] (KTH ), NICTA [Eveleigh], National ICT Australia [Sydney] (NICTA), Division of Solid Mechanics, Lund University [Lund], University of Calgary, BioWare Corp, Manchester Academic Health Sciences Centre, Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Ghent University [Belgium] (UGENT), Imaging Sciences and Biomedical Engineering Division [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia], Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Neurorestoration Group, Wolfson Centre for Age-related Diseases-King‘s College London, Electronic Navigation Research Institute (ENRI), Ministry of Land, Infrastructure, Transport and Tourism, Department of Computer Science [KAIST] (CS), Korea Advanced Institute of Science and Technology (KAIST), Centre for Undergraduate Studies, University of the Punjab, Siemens Corporate Research, Siemens AG [Munich], University of Massachusetts [Boston] (UMass Boston), University of Massachusetts System (UMASS), Department of Materials Science, Sichuan University [Chengdu] (SCU), Natl Engn Res Ctr Vegetables, Key Lab Biol & Genet Improvement Hort Crops N Chi, Beijing Acad Agr & Forestry Sci, University Hospital Puerta de Hierro, Madrid, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Shahid Beheshti University of Medical Sciences, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), MOLTECH-ANJOU (MOLTECH-ANJOU), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH)-Universidad del Desarrollo, Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), École supérieure du professorat et de l'éducation - Académie de Grenoble (ESPE Grenoble), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), California Institute of Technology (CALTECH)-NASA, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Santiago de Chile [Santiago] (USACH), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), King‘s College London-Wolfson Centre for Age-related Diseases, Sichuan University, Universitat de Barcelona, Interne Geneeskunde, Medische Sociologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), Psychiatrie & Neuropsychologie, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Mines-Télécom [Paris] (IMT)-Télécom Bretagne-Université européenne de Bretagne - European University of Brittany (UEB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), RS: MHeNs - R2 - Mental Health, Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de psychologie sociale et de psychologie cognitive ( LAPSCO ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ), Erosion torrentielle neige et avalanches ( UR ETGR ), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture ( IRSTEA ), Hong Kong Baptist University ( HKBU ), Institut für Informatik [München/Munich] ( LMU ), Ludwig-Maximilians-Universität München, Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Insight Centre for Data Analytics (National University of Ireland Galway (NUIG)) ( INSIGHT ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Oslo ( UiO ) -University of Oslo ( UiO ), Centro de Estudios Avanzados en Zonas Aridas ( CEAZA ), Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Laboratoire d'Ingénierie des Matériaux ( LIM ), Centre National de la Recherche Scientifique ( CNRS ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Samsung Research &Development Institute India - Bangalore (Groupe Samsung) ( SRI-B ), Computational Science and Engineering Department [Daresbury] ( STFC ), Multimedia Research Center ( MRC ), University of Alberta [Edmonton], Division of Biostatistics ( Biostat - MINNEAPOLIS ), University of Minnesota [Minneapolis], University of Southampton [Southampton], Interactions, transferts, ruptures artistiques et culturels - EA 6301 ( InTRu ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University Medical Center Utrecht, Biologie Fonctionnelle et Adaptative ( BFA ), Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), National University of Singapore ( NUS ), Centre de Robotique ( CAOR ), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University ( PSL ), Department of Signal Theory and Communications ( TSC ), RESPEC ( RESPEC ), Advanced Laboratories on Embedded Systems [Roma] ( ALES ), Wageningen University and Research Centre [Wageningen] ( WUR ), Universitat Politècnica de Catalunya [Barcelona] ( UPC ), Institut National de Recherche et d'Analyse Physico-Chimique ( INRAP ), Institut National de Recherche et d'Analyse Physico-chimique (INRAP-Tunisie), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ), Tehran University, Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Washington State University ( WSU ), Laboratoire de Physique de l'ENS Lyon ( Phys-ENS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en informatique de Toulouse ( IRIT ), Institut National Polytechnique [Toulouse] ( INP ) -Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Freie Universität Berlin [Berlin], Div Cyclotron & Radiopharmaceut Sci ( DRDO, INMAS ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Tata Research Development and Design Center ( TRDDC ), Laboratoire MOLTECH-Anjou [Angers] ( MOLTECH ANJOU ), Université d'Angers ( UA ) -Centre National de la Recherche Scientifique ( CNRS ), University of Helsinki [Helsinki], Swedish Defense Research Agency ( FOI ), Servicio de Neurologia ( SANTIAGO - Neurologie ), Universidad de Santiago de Chile [Santiago] ( USACH ) -Universidad del Desarrollo, Novartis Pharmaceutical Corp., East Hanover NJ 07936, USA, Laboratoire de glaciologie et géophysique de l'environnement ( LGGE ), Observatoire des Sciences de l'Univers de Grenoble ( OSUG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mechanical and Automation Engineering ( CAD Laboratory ), National Institutes of Health ( NIH ), Centre d'étude et de recherche en informatique et communications ( CEDRIC ), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise ( ENSIIE ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Heuristique et Diagnostic des Systèmes Complexes [Compiègne] ( Heudiasyc ), Université de Technologie de Compiègne ( UTC ) -Centre National de la Recherche Scientifique ( CNRS ), College of Information and Electrical Engineering [Beijing] ( CIEE ), China Agricultural University ( CAU ), Queen Mary University of London ( QMUL ), Centre d'économie de la Sorbonne ( CES ), Université Panthéon-Sorbonne ( UP1 ) -Centre National de la Recherche Scientifique ( CNRS ), Paris School of Economics ( PSE ), École supérieure du professorat et de l'éducation - Académie de Grenoble ( ESPE Grenoble ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Université Grenoble Alpes ( UGA ), PennState University [Pennsylvania] ( PSU ), Jet Propulsion Laboratory ( JPL ), NASA-California Institute of Technology ( CALTECH ), American University of Beirut [Beyrouth], The University of Sydney [Sydney], Département Optique ( OPT ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Laboratoire des signaux et systèmes ( L2S ), Université Paris-Sud - Paris 11 ( UP11 ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Center for Research in Environmental Epidemiology ( CREAL ), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for TeleInFrastruktur ( CTIF ), Aalborg University [Denmark] ( AAU ), Savoirs, Textes, Langage (STL) - UMR 8163 ( STL ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Indian Institute of Technology Madras ( IIT Madras ), Universidade Estadual Paulista Júlio de Mesquita ( UNESP ), Laboratoire de Génie Informatique et Ingénierie de Production ( LGI2P ), IMT - Mines Alès Ecole Mines - Télécom ( IMT - MINES ALES ), Institut geològic de Catalunya ( IGC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physiologie et Génomique des Poissons ( LPGP ), Institut National de la Recherche Agronomique ( INRA ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Politecnico di Milano [Milan], European Microsoft Innovation Center ( EMIC ), Laboratoire de Mécanique, Physique et Géosciences ( LMPG ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ), University of Cambridge [UK] ( CAM ), Laboratoire de Probabilités et Modèles Aléatoires ( LPMA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Center for Mathematical Modeling ( CMM ), Universidad de Santiago de Chile [Santiago] ( USACH ), London School of Hygiene and Tropical Medicine ( LSHTM ), University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Indian Institute of Technology Delhi ( IIT Delhi ), Institut de Recherche sur les Phénomènes Hors Equilibre ( IRPHE ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Universidade Federal de Pernambuco [Recife] ( UFPE ), Nanoscience Institute ( NEST ), Laboratory Of Immune Cell Biology ( LICB ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ), Bonn Universität [Bonn], Laboratorio Nacional de Computação Cientifica [Rio de Janeiro] ( LNCC / MCT ), Royal Institute of Technology [Stockholm] ( KTH ), National ICT Australia [Sydney] ( NICTA ), Institut d'Histoire et de Philosophie des Sciences et des Techniques ( IHPST ), Université Panthéon-Sorbonne ( UP1 ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Ghent University [Belgium] ( UGENT ), Children’s Hospital of Philadelphia ( CHOP ), Univeristy of Pennsylvania Medical School, Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique ( LHEEA ), École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Génie Civil et Mécanique ( GeM ), Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Medical College of Georgia, Electronic Navigation Research Institute ( ENRI ), Department of Computer Science [KAIST] ( CS ), Korea Advanced Institute of Science and Technology ( KAIST ), Laboratoire de l'Accélérateur Linéaire ( LAL ), University of Massachusetts [Boston] ( UMass Boston ), Forouzanfar, Mohammad H, Alexander, Lily, Anderson, H. Ro, Bachman, Victoria F, Biryukov, Stan, Brauer, Michael, Burnett, Richard, Casey, Daniel, Coates, Matthew M, Cohen, Aaron, Delwiche, Kristen, Estep, Kara, Frostad, Joseph J, Kc, Astha, Kyu, Hmwe H, Moradi Lakeh, Maziar, Ng, Marie, Slepak, Erica Leigh, Thomas, Bernadette A, Wagner, Joseph, Aasvang, Gunn Marit, Abbafati, Cristiana, Ozgoren, Ayse Abbasoglu, Abd Allah, Foad, Abera, Semaw F, Aboyans, Victor, Abraham, Biju, Abraham, Jerry Puthenpurakal, Abubakar, Ibrahim, Abu Rmeileh, Niveen M. E, Aburto, Tania C, Achoki, Tom, Adelekan, Ademola, Adofo, Koranteng, Adou, Arsène K, Adsuar, José C, Afshin, Ashkan, Agardh, Emilie E, Al Khabouri, Mazin J, Al Lami, Faris H, Alam, Sayed Saidul, Alasfoor, Deena, Albittar, Mohammed I, Alegretti, Miguel A, Aleman, Alicia V, Alemu, Zewdie A, Alfonso Cristancho, Rafael, Alhabib, Samia, Ali, Raghib, Ali, Mohammed K, Alla, Françoi, Allebeck, Peter, Allen, Peter J, Alsharif, Ubai, Alvarez, Elena, Alvis Guzman, Nelson, Amankwaa, Adansi A, Amare, Azmeraw T, Ameh, Emmanuel A, Ameli, Omid, Amini, Heresh, Ammar, Walid, Anderson, Benjamin O, Antonio, Carl Abelardo T, Anwari, Palwasha, Cunningham, Solveig Argeseanu, Arnlöv, Johan, Arsenijevic, Valentina S. Arsic, Artaman, Al, Asghar, Rana J, Assadi, Reza, Atkins, Lydia S, Atkinson, Charle, Avila, Marco A, Awuah, Baffour, Badawi, Alaa, Bahit, Maria C, Bakfalouni, Talal, Balakrishnan, Kalpana, Balalla, Shivanthi, Balu, Ravi Kumar, Banerjee, Amitava, Barber, Ryan M, Barker Collo, Suzanne L, Barquera, Simon, Barregard, Lar, Barrero, Lope H, Barrientos Gutierrez, Tonatiuh, Basto Abreu, Ana C, Basu, Arindam, Basu, Sanjay, Basulaiman, Mohammed O, Ruvalcaba, Carolina Bati, Beardsley, Justin, Bedi, Neeraj, Bekele, Tolesa, Bell, Michelle L, Benjet, Corina, Bennett, Derrick A, Benzian, Habib, Bernabé, Eduardo, Beyene, Tariku J, Bhala, Neeraj, Bhalla, Ashish, Bhutta, Zulfiqar A, Bikbov, Bori, Abdulhak, Aref A. Bin, Blore, Jed D, Blyth, Fiona M, Bohensky, Megan A, Başara, Berrak Bora, Borges, Guilherme, Bornstein, Natan M, Bose, Dipan, Boufous, Soufiane, Bourne, Rupert R, Brainin, Michael, Brazinova, Alexandra, Breitborde, Nicholas J, Brenner, Hermann, Briggs, Adam D. M, Broday, David M, Brooks, Peter M, Bruce, Nigel G, Brugha, Traolach S, Brunekreef, Bert, Buchbinder, Rachelle, Bui, Linh N, Bukhman, Gene, Bulloch, Andrew G, Burch, Michael, Burney, Peter G. J, Campos Nonato, Ismael R, Campuzano, Julio C, Cantoral, Alejandra J, Caravanos, Jack, Cárdenas, Rosario, Cardis, Elisabeth, Carpenter, David O, Caso, Valeria, Castañeda Orjuela, Carlos A, Castro, Ruben E, Catalá López, Ferrán, Cavalleri, Fiorella, Çavlin, Alanur, Chadha, Vineet K, Chang, Jung Chen, Charlson, Fiona J, Chen, Honglei, Chen, Wanqing, Chen, Zhengming, Chiang, Peggy P, Chimed Ochir, Odgerel, Chowdhury, Rajiv, Christophi, Costas A, Chuang, Ting Wu, Chugh, Sumeet S, Cirillo, Massimo, Claßen, Thomas Kd, Colistro, Valentina, Colomar, Mercede, Colquhoun, Samantha M, Contreras, Alejandra G, Cooper, Cyru, Cooperrider, Kimberly, Cooper, Leslie T, Coresh, Josef, Courville, Karen J, Criqui, Michael H, Cuevas Nasu, Lucia, Damsere Derry, Jame, Danawi, Hadi, Dandona, Lalit, Dandona, Rakhi, Dargan, Paul I, Davis, Adrian, Davitoiu, Dragos V, Dayama, Anand, de Castro, E. Filipa, De la Cruz Góngora, Vanessa, De Leo, Diego, de Lima, Graça, Degenhardt, Louisa, Del Pozo Cruz, Borja, Dellavalle, Robert P, Deribe, Kebede, Derrett, Sarah, Jarlais, Don C. De, Dessalegn, Muluken, Deveber, Gabrielle A, Devries, Karen M, Dharmaratne, Samath D, Dherani, Mukesh K, Dicker, Daniel, Ding, Eric L, Dokova, Klara, Dorsey, E. Ray, Driscoll, Tim R, Duan, Leilei, Durrani, Adnan M, Ebel, Beth E, Ellenbogen, Richard G, Elshrek, Yousef M, Endres, Matthia, Ermakov, Sergey P, Erskine, Holly E, Eshrati, Babak, Esteghamati, Alireza, Fahimi, Saman, Faraon, Emerito Jose A, Farzadfar, Farshad, Fay, Derek F. 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Subjects
Male, Fine particulate matter, Nutrition and Disease, MESH : Sanitation, Health Behavior, Diseases, MESH: Metabolic Diseases, MESH: Global Health, 030204 cardiovascular system & hematology, MESH: Risk Assessment, Global Health, MESH : Nutritional Status, MESH: Occupational Exposure, 0302 clinical medicine, Unsafe Sex, MESH: Risk Factors, Risk Factors, Voeding en Ziekte, Medicine, Air-pollution, MESH : Female, 030212 general & internal medicine, MESH : Risk Assessment, Sanitation, Wasting, 2. Zero hunger, Factors de risc en les malalties, Medicine (all), [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, MESH : Occupational Diseases, MESH: Nutritional Status, All-cause mortality, MESH : Risk Factors, humanities, Environmental Exposure, Female, Humans, Metabolic Diseases, Nutritional Status, Occupational Diseases, Occupational Exposure, Risk Assessment, Tobacco smoking, 3. Good health, Nutritional Statu, MESH : Occupational Exposure, MESH : Metabolic Diseases, Cohort, medicine.symptom, Risk assessment, Blood-pressure, Human, MESH: Occupational Diseases, Risk factors in diseases, Coronary-heart-disease, MESH : Male, MESH: Health Behavior, MESH: Environmental Exposure, Population health, Body-mass index, 03 medical and health sciences, Household cooking, Cardiovascular-disease, Environmental health, General & Internal Medicine, parasitic diseases, Life Science, MESH: Sanitation, Risk factor, MESH : Health Behavior, VLAG, GBD2013, MESH: Humans, business.industry, Risk Factor, Global Burden of Disease Study, 79 behavioural, environmental and occupational, and metabolic risks, Long-term exposure, MESH : Humans, CAUSE-SPECIFIC MORTALITY, MESH: Male, Metabolic Disease, Occupational Disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, MALE BRITISH DOCTORS, Years of potential life lost, Relative risk, Malalties, MESH : Global Health, OUTDOOR AIR-POLLUTION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Environmental Exposure, MESH: Female
Abstract

Summary Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation. Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the fi rst of a series of annual updates of the GBD. Risk factor quantifi cation, particularly of modifi able risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the fi rst level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular fi ltration rate. For most risks, data for exposure were synthesised with a Bayesian metaregression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5−89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. Funding Bill & Melinda Gates Foundation.

Published
2015
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31. GENE-41. EPIGENETIC DOWN-REGULATION OF THE METALLOTHIONEIN FAMILY IN ISOCITRATE DEHYDROGENASE (IDH) MUTANT GLIOMAS

Author

Albert Lai, Linda M. Liau, Yvonne T. Bui, Reshmi Chowdhury, Nhung T Nguyen, Tie Li, Timothy F. Cloughesy, Phioanh L. Nghiemphu, Byram Ozer, and William H. Yong

Subjects
Cancer Research, Mutant, Biology, medicine.disease, Molecular biology, Abstracts, Isocitrate dehydrogenase, Oncology, Glioma, Gene expression, DNA methylation, medicine, Metallothionein, Neurology (clinical), Epigenetics, Gene
Published
2017

32. Phase 2 Study of Bortezomib Combined With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

Author

Whitney B. Pope, Yoon Jeong Choi, Andrew B. Lassman, Linda M. Liau, Stacey Green, William H. Yong, Richard M. Green, Xiao-Tang Kong, Huytram N. Nguyen, Guicheng Zhang, Albert Lai, Timothy F. Cloughesy, P Leia Nghiemphu, Nhung T Nguyen, Tania Kaprealian, and Emese Filka

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_treatment, Phases of clinical research, Bortezomib, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Cancer, Radiation, Brain Neoplasms, Chemoradiotherapy, Middle Aged, Progression-Free Survival, Other Physical Sciences, Local, 030220 oncology & carcinogenesis, 6.1 Pharmaceuticals, Female, medicine.drug, Adult, medicine.medical_specialty, Clinical Trials and Supportive Activities, Clinical Sciences, Oncology and Carcinogenesis, Article, Maintenance Chemotherapy, 03 medical and health sciences, Rare Diseases, Clinical Research, Internal medicine, medicine, Temozolomide, Humans, Radiology, Nuclear Medicine and imaging, Progression-free survival, Oncology & Carcinogenesis, Adverse effect, Aged, business.industry, Neurosciences, Evaluation of treatments and therapeutic interventions, Confidence interval, Brain Disorders, Radiation therapy, Clinical trial, Brain Cancer, 030104 developmental biology, Neoplasm Recurrence, Neoplasm Recurrence, Local, business, Glioblastoma
Abstract

PURPOSE:To assess the safety and efficacy of upfront treatment using bortezomib combined with standard radiation therapy (RT) and temozolomide (TMZ), followed by adjuvant bortezomib and TMZ for ≤24 cycles, in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS:Twenty-four patients with newly diagnosed GBM were enrolled. The patients received standard external beam regional RT with concurrent TMZ beginning 3 to 6weeks after surgery, followed by adjuvant TMZ and bortezomib for ≤24 cycles or until tumor progression. During RT, bortezomib was given at 1.3mg/m2 on days 1, 4, 8, 11, 29, 32, 36, and 39. After RT, bortezomib was given at 1.3mg/m2 on days 1, 4, 8, and 11 every 4weeks. RESULTS:No unexpected adverse events occurred from the addition of bortezomib. The efficacy analysis showed a median progression-free survival (PFS) of 6.2months (95% confidence interval [CI] 3.7-8.8), with promising PFS rates at ≥18months compared with historical norms (25.0% at 18 and 24months; 16.7% at 30months). In terms of overall survival (OS), the median OS was 19.1months (95% CI 6.7-31.4), with improved OS rates at ≥12months (87.5% at 12, 50.0% at 24, 34.1% at 36-60months) compared with the historical norms. The median PFS was 24.7months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61months (95% CI upper bound not reached) in the methylated and 16.4months (95% CI 11.8-21.0) in the unmethylated patients. CONCLUSIONS:The addition of bortezomib to current standard radiochemotherapy in newly diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising, with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.

Published
2017

33. Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as Antibacterial Agents

Author

Tuan-Anh N. Pham, Dong C. Tran, Bao-Khanh N. Le, Thu-Trang T. Nguyen, Phuong-Thuy T. Phan, Hong-Nhung T. Nguyen, and Thao T. Vu

Subjects
Methicillin-Resistant Staphylococcus aureus, Stereochemistry, Carboxylic acid, Pharmaceutical Science, Microbial Sensitivity Tests, MRSA, 010402 general chemistry, medicine.disease_cause, Phenacyl, 01 natural sciences, Article, Analytical Chemistry, lcsh:QD241-441, chemistry.chemical_compound, antibacterial activity, lcsh:Organic chemistry, Drug Discovery, Enterococcus faecalis, Escherichia coli, medicine, Agar diffusion test, Physical and Theoretical Chemistry, Benzofuran, 2-salicyloylbenzofuran, Benzofurans, Antibacterial agent, Rap–Stoermer condensation, chemistry.chemical_classification, 010405 organic chemistry, Organic Chemistry, benzofuran, Salicylates, Anti-Bacterial Agents, 0104 chemical sciences, Williamson synthesis, chemistry, Chemistry (miscellaneous), Staphylococcus aureus, Molecular Medicine, Antibacterial activity
Abstract

In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and Streptococcus faecalis (S. faecalis) ATCC 29212) and one Gram-(−) strain (Escherichia coli (E. coli) ATCC 25922). The 2-salicyloylbenzofuran heterocycles were generated by Rap–Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse O-ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+) bacterial strains including S. faecalis, MSSA and MRSA with the most potent antibacterial agent 8h (MICs = 0.06–0.12 mM). Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM (8f) and 0.12 mM (8h). Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities.

Published
2017

34. Abstract 2614: CCAR2 acetylation establishes a BET/BRD9 acetyl switch in response to combined deacetylase and bromodomain inhibition

Author

Deqiang Sun, Hon-Chiu Eastwood Leung, Gavin S. Johnson, Shan Wang, Roderick H. Dashwood, Ahmet M Ulusan, Kyle Chang, W. Mohaiza Dashwood, Mark T. Bedford, Ying-Shiuan Chen, Mutian Zhang, Nhung T. Nguyen, Praveen Rajendran, Eduardo Vilar, Laura M. Beaver, Yun Huang, Li Li, Emily Ho, David A. Lieberman, and Furkan U. Ertem

Subjects
Cancer Research, Chemistry, Wnt signaling pathway, Cancer, medicine.disease, HDAC3, Bromodomain, BET inhibitor, Oncology, Acetylation, Coactivator, Cancer research, medicine, Epigenetics
Abstract

There continues to be interest in targeting epigenetic ‘readers, writers and erasers’ for the treatment of cancer and other pathologies. A mechanistic understanding is frequently lacking, however, for the synergy observed when combining deacetylase and bromodomain inhibitors. We identified cell cycle and apoptosis regulator 2 (CCAR2) as an early target for acetylation in colon cancer cells treated with sulforaphane (SFN). N-terminal acetylation of CCAR2 diminished its interactions with histone deacetylase 3 (HDAC3) and β-catenin, interfering with Wnt coactivator functions of CCAR2, including in cells harboring genetically encoded CCAR2 acetylation. Protein domain arrays and pull-down assays identified acetyl ‘reader’ proteins that recognized CCAR2 acetylation sites, including BRD9 and members of the bromodomain and extraterminal domain (BET) family. The BET inhibitor JQ1 synergized with SFN in colon cancer cells, and suppressed tumor development effectively in a preclinical model of colorectal cancer. Studies with SFN+JQ1 in combination implicated a BET/BRD9 acetyl switch, and a shift in the pool of acetyl ‘reader’ proteins in favor of BRD9 regulated target genes. These results highlight the competition that exists among the ‘readers’ of acetylated histone and non-histone proteins, and provide a mechanistic basis for potential new therapeutic avenues involving epigenetic combination treatments. Citation Format: Gavin S. Johnson, Praveen Rajendran, Li Li, Ying-Shiuan Chen, W. Mohaiza Dashwood, Nhung Nguyen, Ahmet M. Ulusan, Furkan Ertem, Mutian Zhang, Deqiang Sun, Yun Huang, Shan Wang, Hon-Chiu E. Leung, David Lieberman, Laura M. Beaver, Emily Ho, Mark T. Bedford, Kyle Chang, Eduardo Vilar, Roderick H. Dashwood. CCAR2 acetylation establishes a BET/BRD9 acetyl switch in response to combined deacetylase and bromodomain inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2614.

Published
2019
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35. Patterns of long-term survivorship following bevacizumab treatment for recurrent glioma: a case series

Author

Albert Lai, Benjamin M. Ellingson, Frances Chow, Matthew Ji, Richard M. Green, Phioanh L. Nghiemphu, Linda M. Liau, Sean T Pianka, Donna Molaie, Liang Yen Liu, Nhung T Nguyen, and Timothy F. Cloughesy

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Long Term Survivorship, recurrence, Bevacizumab, Angiogenesis Inhibitors, bevacizumab, Recurrent Glioma, California, Cohort Studies, Young Adult, Rare Diseases, glioma, Internal medicine, Glioma, medicine, Humans, Case Series, Survivors, Retrospective Studies, Aged, Cancer, relapse, Series (stratigraphy), business.industry, glioblastoma, Neurosciences, General Medicine, Middle Aged, medicine.disease, Brain Disorders, Large cohort, Brain Cancer, Neoplasm Recurrence, Treatment Outcome, Local, survivor, Female, long term, lipids (amino acids, peptides, and proteins), progression, Neoplasm Recurrence, Local, business, medicine.drug, Glioblastoma
Abstract

Aim: Long-term survivors (LTS)after glioma recurrence while on bevacizumab (Bev)therapy are rarely reported in the current literature. The purpose of this case series is to confirm the existence of and describe a large cohort of recurrent glioma LTS treated with Bev (Bev-LTS). Patients & methods: We identified Bev-LTS as patients with post-Bev initiation survival times of ≥3 years among 1397 Bev treated recurrent glioma patients. Results: Among 962 grade-IV,221 grade III, and214 grade II Bev-treated glioma patients, we identified 28 (2.9%),14 (6.3%) and8(3.7%)Bev-LTS patients, respectively. 45Bev-LTS patients recurred on Bev, with 36 of those patients continuing therapy.Conclusion: Our study shows that a small portion of grade-IV, -III,and -II glioma patients can have long-term survival on Bev therapy even after Bev recurrence.

Published
2019
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36. A review of allergoid immunotherapy: is cat allergy a suitable target?

Author

Ralph Mösges, Kija Shah-Hosseini, Esther Raskopf, G Zadoyan, and Nhung T Nguyen

Subjects
0301 basic medicine, Risk, Allergen immunotherapy, Allergy, Polymers, medicine.medical_treatment, Injections, Subcutaneous, Immunology, Polymerization, 03 medical and health sciences, 0302 clinical medicine, Allergoids, Hypersensitivity, Immunology and Allergy, Medicine, Animals, Humans, Sublingual immunotherapy, Asthma, Sublingual Immunotherapy, business.industry, Plant Extracts, Immunogenicity, Specific immunotherapy, Immunotherapy, Allergens, medicine.disease, Allergoid, 030104 developmental biology, 030228 respiratory system, Oncology, Desensitization, Immunologic, Cats, business
Abstract

To modify the course of allergy, different types of specific allergen immunotherapy have been developed such as sublingual immunotherapy and subcutaneous immunotherapy with native allergens or subcutaneous immunotherapy with polymerized allergoids. However, the optimal specific immunotherapy, especially for cat allergy, remains undetermined. Few studies investigating immunotherapy in cat allergy have been published, and the risk of serious adverse reactions and systemic reactions has often been an important issue. Monomeric allergoids have lower allergenic potential while their immunogenicity remains constant, resulting in excellent safety with notable efficacy. Specific immunotherapy with monomeric allergoids could, therefore, be of high value, especially in cat allergy as well as other types of allergy, and bring relief to a great community of patients.

Published
2016

37. Moral Awareness in Business Ethics Education

Author

M. Tom Basuray, Donald McCulloh, Nhung T. Nguyen, and Donald Kopka

Subjects
Economics and Econometrics, medicine.medical_specialty, Normative ethics, Nursing ethics, Meta-ethics, Philosophy of business, Applied ethics, Education, Philosophy, Information ethics, medicine, Business, Management and Accounting (miscellaneous), Military medical ethics, Engineering ethics, Sociology, Business and International Management, Business ethics, Social psychology
Published
2012
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38. The ubiquity of common method variance: The case of the Big Five

Author

Christopher J. L. Cunningham, Nhung T. Nguyen, Michael D. Biderman, and Nima Ghorbani

Subjects
Social Psychology, International Personality Item Pool, media_common.quotation_subject, Statistics, Personality, Sample (statistics), Common-method variance, Psychology, General Psychology, Confirmatory factor analysis, media_common
Abstract

The factor structures of the International Personality Item Pool (IPIP) and NEO-FFI Big Five questionnaires were examined via confirmatory factor analyses. Analyses of IPIP data for five samples and NEO data for one sample showed that a CFA model with three method bias factors, one influencing all items, one influencing negatively worded items, and one influencing positively worded items fit the data significantly better than models without method factors or models with only one method factor . With the method factors estimated, our results indicated that the Big Five dimensions may be more nearly orthogonal than previously demonstrated. Implications of the presence of method variance in Big Five scales are discussed.

Published
2011
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39. The Relationship of Reliability and Validity of Personality Tests to Frame-of-Reference Instructions and Within-Person Inconsistency

Author

Michael D. Biderman, Nhung T. Nguyen, and Craig M. Reddock

Subjects
Measure (data warehouse), Strategy and Management, media_common.quotation_subject, Wonderlic test, Applied psychology, Cognition, Conscientiousness, General Business, Management and Accounting, Management of Technology and Innovation, Personality, Big Five personality traits, Psychology, Incremental validity, Social psychology, General Psychology, Applied Psychology, Reliability (statistics), media_common
Abstract

The efficacy of both frame-of-reference (FOR) instructions and a measure of within-person inconsistency in predicting grade point average was investigated. The IPIP Big Five personality questionnaire was given to 329 students with generic instructions and ‘at school’ FOR instructions. The Wonderlic Personnel Test was also administered. A measure of within-person inconsistency was created based on the standard deviations of responses to items within the same Big Five dimension. The validity of conscientiousness was greater when FOR instructions were given. The measure of within-person inconsistency provided incremental validity over that of conscientiousness and cognitive ability. Additionally, within-person inconsistency moderated the relationship between conscientiousness and performance for the participants without the FOR instructions. Practical implications are discussed.

Published
2011
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40. Identification of molecular determinants that govern distinct STIM2 activation dynamics

Author

Yubin Zhou, Tian Zhang, Xiaoyan Zhang, Youjun Wang, Robert M. Nwokonko, Sisi Zheng, Hao Dong, Guolin Ma, Lian He, Xiaoman Yuan, Nhung T. Nguyen, Yun Huang, Donald L. Gill, Jia Li, and Ping Gao

Subjects
0301 basic medicine, Yellow fluorescent protein, Science and Technology Workforce, Cell Membranes, Cultured tumor cells, Endoplasmic Reticulum, Careers in Research, Protein Engineering, Biochemistry, Fluorophotometry, Spectrum Analysis Techniques, 0302 clinical medicine, Fluorescence Resonance Energy Transfer, Homeostasis, Biology (General), Macromolecular Engineering, Secretory Pathway, General Neuroscience, STIM1, STIM2, Neoplasm Proteins, Cell biology, Professions, Spectrophotometry, Cell Processes, Membrane topology, Engineering and Technology, Cell lines, Synthetic Biology, Cellular Structures and Organelles, Biological cultures, General Agricultural and Biological Sciences, Research Article, Yellow Fluorescent Protein, Science Policy, QH301-705.5, Bioengineering, Biology, Research and Analysis Methods, General Biochemistry, Genetics and Molecular Biology, Protein–protein interaction, 03 medical and health sciences, Humans, Calcium Signaling, Stromal Interaction Molecule 1, HeLa cells, Stromal Interaction Molecule 2, General Immunology and Microbiology, Endoplasmic reticulum, Cell Membrane, HEK 293 cells, Membrane Proteins, Biology and Life Sciences, Proteins, Engineers, Cell Biology, Cell cultures, Luminescent Proteins, HEK293 Cells, 030104 developmental biology, Förster resonance energy transfer, Synthetic Bioengineering, People and Places, Signal Processing, biology.protein, Calcium, Population Groupings, Calcium Channels, 030217 neurology & neurosurgery
Abstract

The endoplasmic reticulum (ER) Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2, which connect ER Ca2+ depletion with extracellular Ca2+ influx, are crucial for the maintenance of Ca2+ homeostasis in mammalian cells. Despite the recent progress in unraveling the role of STIM2 in Ca2+ signaling, the mechanistic underpinnings of its activation remain underexplored. We use an engineering approach to direct ER-resident STIMs to the plasma membrane (PM) while maintaining their correct membrane topology, as well as Förster resonance energy transfer (FRET) sensors that enabled in cellulo real-time monitoring of STIM activities. This allowed us to determine the calcium affinities of STIM1 and STIM2 both in cellulo and in situ, explaining the current discrepancies in the literature. We also identified the key structural determinants, especially the corresponding G residue in STIM1, which define the distinct activation dynamics of STIM2. The chimeric E470G mutation could switch STIM2 from a slow and weak Orai channel activator into a fast and potent one like STIM1 and vice versa. The systemic dissection of STIM2 activation by protein engineering sets the stage for the elucidation of the regulation and function of STIM2-mediated signaling in mammals., Author summary Calcium ions play a major regulatory role in the physiology and biochemistry of the cell, and thus their levels and activities should be tightly regulated. The stromal interaction molecules (STIMs) are sensors of the calcium levels within the endoplasmic reticulum (ER)—which serves as a major intracellular calcium store—to mediate communication between the ER and the plasma membrane and are regarded as ubiquitous central players of calcium signaling in mammalian cells. STIM2 acts as a slow and weak activator of Orai1 calcium channels on the plasma membrane by direct binding; however, the affinity of STIMs for calcium or how Orai1 channels are activated remain unclear. In this study, we systematically analyzed the molecular determinants that govern the activation of STIM proteins. Adopting protein engineering approaches that enable the relocation of ER-resident STIM proteins at the plasma membrane, we determined the calcium affinities of STIMs under physiological conditions in mammalian cells. We identified a critical position within STIMs, which defines their distinct resting states and activation kinetics, as well as the efficacy to activate Orai1 channels. These findings shed new light on how STIM2 can efficiently respond to small changes within the ER lumen to regulate calcium homeostasis and signaling in mammalian cells.

Published
2018
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41. A validation study of the Cross-Cultural Adaptability Inventory

Author

Nhung T. Nguyen, Lisa D. McNary, and Michael D. Biderman

Subjects
Organizational Behavior and Human Resource Management, Validation study, media_common.quotation_subject, Factor structure, Confirmatory factor analysis, Adaptability, Education, Cross-cultural, Psychological resilience, Common-method variance, Psychology, Social psychology, Reliability (statistics), media_common
Abstract

Despite the claims made about the effectiveness of crosscultural training programs, few studies have examined the reliability and validity of the instruments used in these training programs. In this study, the authors examine the factor structure of the Cross-Cultural Adaptability Inventory (CCAI) via a confirmatory factor analytic approach. A series of confirmatory factor analysis (CFA) models was tested and applied at the item level to both the CCAI and Goldberg’s Big Five Inventory. A CFA model in which a method factor was estimated fits the data significantly better than a model without such a method effect. Further, the method factor suppressed substantive relationships such that the two CCAI factors of emotional resilience and personal autonomy became significant correlates with self-reported number of international job assignments after accounting for method variance. Implications for research and practice are discussed.

Published
2010
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42. Exploring the impact of personality on performance: How time-on-task moderates the mediation by self-efficacy

Author

Tom Basuray, Filiz Tabak, Nhung T. Nguyen, and William P. Darrow

Subjects
Mediation (statistics), Extraversion and introversion, media_common.quotation_subject, Conscientiousness, Moderation, Hierarchical structure of the Big Five, Developmental psychology, Moderated mediation, Personality, Big Five personality traits, Psychology, Social psychology, General Psychology, media_common
Abstract

Despite the widely acknowledged impact of dispositional traits on performance, little is known about how personality affects performance. We address this gap by investigating the relationships between the Big Five personality traits, self-efficacy, and academic performance in a moderated mediation model using time-on-task as the moderating variable. Results indicate that self-efficacy partially mediates the conscientiousness–performance relationship and that time-on-task moderates the mediating effect of self-efficacy. Time-on-task moderates the indirect effect of conscientiousness on course performance through self-efficacy such that the indirect effect is not significant at low levels of time-on-task, but becomes significant and stronger at higher levels of time-on-task.

Published
2009
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43. Ethics Perception: Does Teaching Make a Difference?

Author

Nhung T. Nguyen, William P. Smith, Donald Kopka, Donald McCulloh, and M. Tom Basuray

Subjects
medicine.medical_specialty, ComputingMilieux_THECOMPUTINGPROFESSION, Nursing ethics, media_common.quotation_subject, Applied psychology, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Meta-ethics, Applied ethics, Education, Contractualism, Perception, medicine, ComputingMilieux_COMPUTERSANDSOCIETY, Business, Management and Accounting (miscellaneous), Business ethics, Psychology, Social psychology, Social cognitive theory, Relativism, media_common
Abstract

The present study examined student learning in business ethics, particularly ethical judgment, using R. E. Reidenbach and D. P. Robin's (1990) Multidimensional Ethics Scale (MES). The authors asked 262 undergraduate students to provide ethical judgment rating, first at the beginning of the semester and again at the end of the semester. Students judged 3 moral issues in the MES—labeled sales, auto, and retail—using 3 ethics theories: moral equity, relativism, and contractualism. Ethics learning was only significant in contractualism ethics for the auto scenario. Further, ethics learning significantly predicted ethical behavioral intent, supporting A. Bandura's (1986) social cognitive theory. The authors provide theoretical and practical implications based on the study's findings.

Published
2008
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44. Subgroup Differences in Situational Judgment Test Performance: A Meta-Analysis

Author

Deborah L. Whetzel, Michael A. McDaniel, and Nhung T. Nguyen

Subjects
Agreeableness, Situational judgement test, Organizational Behavior and Human Resource Management, media_common.quotation_subject, White test, Cognition, Conscientiousness, Test (assessment), Developmental psychology, Personality, Psychology, General Psychology, Applied Psychology, Cognitive load, media_common
Abstract

In this article, we describe a systematic review of mean race and sex differences in situational judgment test (SJT) performance. On average, White test takers perform better on SJTs than Black, Hispanic, and Asian test takers. Female examinees perform slightly better than male test takers on SJTs. We investigate two moderators of these differences: loading of g or personality on the SJT, and response instructions. Mean race differences between Black, Hispanic, Asian and White examinees in SJT performance are largely explained by the cognitive loading of the SJT such that the larger the cognitive load, the larger the mean race differences. Regarding the effect of personality loadings of SJTs on race differences, Black–White and Asian–White differences are smaller to the extent that the SJT is correlated with emotional stability and Hispanic–White differences are smaller to the extent that SJTs are correlated with conscientiousness and agreeableness. Cognitive loading has minimal effect on male–female SJT ...

Published
2008
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45. Time-on-task mediates the conscientiousness–performance relationship

Author

Michael D. Biderman, Nhung T. Nguyen, and Jennifer Sebren

Subjects
Mediation (statistics), media_common.quotation_subject, Cognition, Context (language use), Conscientiousness, Time on task, Hierarchical structure of the Big Five, Developmental psychology, Personality, Common-method variance, Psychology, Social psychology, General Psychology, media_common
Abstract

The relationships between conscientiousness, time-on-task, and academic performance were investigated in a mediation model. When simple summated conscientiousness scores were analyzed, relationships with performance and time-on-task were not significant. When factor scores estimated in the context of a model assuming common method bias were analyzed, conscientiousness was a significant predictor of test performance, and time-on-task fully mediated the conscientiousness–performance relationship. The relationships held for conscientiousness alone and for conscientiousness controlling for cognitive ability.

Published
2008
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46. Studying Ethical Judgments and Behavioral Intentions Using Structural Equations: Evidence from the Multidimensional Ethics Scale*

Author

Nhung T. Nguyen and Michael D. Biderman

Subjects
Economics and Econometrics, Equity (finance), Sample (statistics), Latent variable, General Business, Management and Accounting, Structural equation modeling, Confirmatory factor analysis, Contractualism, Arts and Humanities (miscellaneous), Business and International Management, Business ethics, Psychology, Law, Social psychology, Relativism
Abstract

The linkage between ethical judgment and ethical behavioral intention was investigated. The Multidimensional Ethics Scale (MES) was used to measure ethical judgment ratings of hypothetical behaviors in retail, sales, and automobile repair scenarios. Confirmatory factor analysis on a sample of 300 undergraduate business students showed that a model with three latent variables representing three correlated ethical dimensions of moral equity, relativism, and contractualism, three correlated scenario latent variables, and correlated residuals presented a good fit to the data. Further, structural models of the relationship of ethical judgment to behavioral intentions revealed that behavioral intentions were more highly related to the scenario factors than to the ethical dimensions across three scenarios. Adding a method factor to the model improved goodness-of-fit and changed some structural model conclusions.

Published
2008
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47. Moral Issues and Gender Differences in Ethical Judgment using Reidenbach and Robin’s (1990) Multidimensional Ethics Scale: Implications in Teaching of Business Ethics

Author

Donald Kopka, William P. Smith, M. Tom Basuray, Nhung T. Nguyen, and Donald McCulloh

Subjects
Economics and Econometrics, Equity (economics), Multidimensional ethics scale, Interpretation (philosophy), Role theory, General Business, Management and Accounting, Contractualism, Arts and Humanities (miscellaneous), Sociology, Business and International Management, Business ethics, Law, Female students, Social psychology, Relativism
Abstract

In this study, we examined moral issues and gender differences in ethical judgment using Reidenbach and Robin’s [Journal of Business Ethics 9 (1990) 639) multidimensional ethics scale (MES). A total of 340 undergraduate students were asked to provide ethical judgment by rating three moral issues in the MES labeled: ‚sales’, ‚auto’, and ‚retail’ using three ethics theories: moral equity, relativism, and contractualism. We found that female students’ ratings of ethical judgment were consistently higher than that of male students across two out of three moral issues examined (i.e., sales and retails) and ethics theories; providing support for Eagly’s [1987, Sex Differences in Social Behavior: A Social-role Interpretation. (Lawrence Erlbaum Associates, Inc, Hillsdale, NJ, England)] social role theory. After controlling for moral issues, women’s higher ratings of ethical judgment over men’s became statistically non-significant. Theoretical and practical implications based on the study’s findings are provided.

Published
2007
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48. Recruiters' Assessment and Use of Social Capital in Résumé Screening1

Author

Charles L. Allen, R. Lynn Godkin, and Nhung T. Nguyen

Subjects
Social Psychology, business.industry, media_common.quotation_subject, Context (language use), Public relations, Human capital, Friendship, Human resources, business, Employee selection, Psychology, Social psychology, Social capital, media_common
Abstract

An experiment was conducted with undergraduate business students to investigate how human resource (HR) recruiters use social capital conceptualized as friendship between applicants and the recruiter in screening resumes. Results showed that social capital influenced recruiters' assessment of applicants above and beyond human capital. In addition, the influence of friendship ties in applicant assessment was more prominent among female HR recruiters than among male recruiters. Implications for researchers and practitioners are discussed in the context of employee selection.

Published
2006
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49. Effects of Response Instructions on Faking a Situational Judgment Test

Author

Nhung T. Nguyen, Michael D. Biderman, and Michael A. McDaniel

Subjects
Situational judgment test, Management of Technology and Innovation, Strategy and Management, Cognition, Big Five personality traits, Psychology, General Business, Management and Accounting, Social psychology, General Psychology, Applied Psychology, Test (assessment)
Abstract

A situational judgment test (SJT) and a Big 5 personality test were administered to 203 participants under instructions to respond honestly and to fake good using a within-subjects design. Participants indicated both the best and worst response (i.e., Knowledge) and the most likely and least likely response (i.e., Behavioral Tendency) to each situation. Faking effect size for the SJT Behavioral Tendency response format was (d=.34) when participants responded first under honest instructions and (d=.15) when they responded first under faking instructions. Those for the Big 5 dimensions ranged from d=.26 to d=1.0. For the Knowledge response format results were inconsistent. Honest condition Knowledge SJT scores were more highly correlated with cognitive ability (r=.56) than were Behavioral Tendency SJT scores (r=.38). Implications for researchers and practitioners are discussed.

Published
2005
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50. PATH-17. CORRELATION OF COMMERCIALLY-AVAILABLE QUANTITATIVE MGMT (O-6-METHYLGUANINE-DNA METHYLTRANSFERASE) METHYLATION SCORES AND OVERALL GBM PATIENT SURVIVAL

Author

Nhung T Nguyen, Linda M. Liau, Phioanh L. Nghiemphu, Timothy F. Cloughesy, Albert Lai, Byram Ozer, and Laura Dovek

Subjects
0301 basic medicine, Cancer Research, DNA repair, law.invention, Correlation, Abstracts, 03 medical and health sciences, 0302 clinical medicine, law, Medicine, Polymerase chain reaction, Genetics, Temozolomide, business.industry, O-6-methylguanine-DNA methyltransferase, Patient survival, Methylation, medicine.disease, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Neurology (clinical), business, Glioblastoma, medicine.drug
Published
2017
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