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Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2019年第24期58卷 7972-7976页

作者： Kim, Beomsue Fukuda, Masahiro Lee, Jung-Yeol Su, Dongdong Sanu, Srikanta Silvin, Aymeric Khoo, Audrey T. T. Kwon, Taejoon Liu, Xiao Chi, Weijie Liu, Xiaogang Choi, Sejong Wan, Diana S. Y. Park, Sung-Jin Kim, Jin-Soo Ginhoux, Florent Je, H. Shawn Chang, Young-Tae Pohang Univ Sci & Technol Dept Chem Pohang 37673 South Korea ASTAR Singapore Bioimaging Consortium Singapore 138667 Singapore Duke NUS Med Sch Program Neurosci & Behav Disorders Singapore 169857 Singapore ASTAR Singapore Immunol Network Singapore 138648 Singapore Ulsan Natl Inst Sci & Technol Dept Biomed Engn Ulsan 44919 South Korea Inst for Basic Sci Korea Ctr Self Assembly & Complex Pohang 37673 South Korea Singapore Univ Technol & Design Singapore 487372 Singapore Seoul Natl Univ Dept Chem Seoul 08826 South Korea Inst for Basic Sci Korea Ctr Genome Engn Daejeon 34047 South Korea DGMIF New Drug Discovery Ctr Daegu 41061 South Korea

Microglia, the brain-resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resolution has been limited to transgenic mice. Efforts have therefore been dedicated to developing new methods for microglia detection and imaging. Using a thorough structure-activity relationships study, we developed CDr20, a high-performance fluorogenic chemical probe that enables the visualization of microglia both in vitro and in vivo. Using a genome-scale CRISPR-Cas9 knockout screen, the UDP-glucuronosyltransferase Ugt1a7c was identified as the target of CDr20. The glucuronidation of CDr20 by Ugt1a7c in microglia produces fluorescence.

关键词： biological activity fluorescent probes imaging agents microglia structure-activity relationships

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MRS demonstrates elevated brain glutathione in vascular mild cognitive impairment compared to cognitively normal coronary artery disease controls

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Alzheimer's and Dementia 2025年第5期21卷 e70230页

作者： Chen, Jinghan Jenny Kang, Yejin Gallagher, Damien Herrmann, Nathan Survilla, Kate Vieira, Danielle Mah, Ethan Graham, Simon J. Kiss, Alex Black, Sandra E. Ramirez, Joel Oh, Paul Marzolini, Susan Zukotynski, Katherine A. Kuo, Phillip H. Lanctôt, Krista L. Hurvitz Brain Sciences Program Sunnybrook Research Institute Toronto ON Canada Department of Pharmacology & Toxicology University of Toronto Toronto ON Canada Department of Psychiatry University of Toronto Toronto ON Canada Department of Medical Biophysics University of Toronto Toronto ON Canada Department of Research Design and Biostatistics Sunnybrook Research Institute Toronto ON Canada Dr. Sandra Black Centre for Brain Resilience and Recovery LC Campbell Cognitive Neurology Sunnybrook Hospital Toronto ON Canada Graduate Department of Psychological Clinical Science University of Toronto Scarborough Scarborough ON Canada Neurology Division Department of Medicine Sunnybrook Health Sciences Centre University of Toronto Toronto Canada KITE Toronto Rehabilitation Institute Toronto Rehabilitation Institute-University Health Network Toronto ON Canada Department of Medical Imaging McMaster University Hamilton ON Canada Department of Radiology City of Hope National Medical Center Duarte CA United States

INTRODUCTION: Oxidative stress (OS) is implicated in dementia. While elevated peripheral OS biomarkers were observed in vascular mild cognitive impairment (vMCI), the role of central antioxidants remains unclear. We assessed levels of the major brain antioxidant glutathione (GSH) in vMCI compared to cognitively normal coronary artery disease (CAD) controls (CN). METHODS: In vivo tissue-corrected GSH in the anterior cingulate cortex (ACC) and occipital cortex (OC) were quantified in persons with vMCI and CN using MEscher–GArwood Point RESolved magnetic resonance Spectroscopy. RESULTS: Among participants (vMCI, n = 22, age [mean ± SD] = 67.4 ± 7.3;CN, n = 21, age = 66.7 ± 7.8), ACC-GSH (i.u. ± SD) was higher in vMCI (4.42 ± 0.59) versus CN (3.72 ± 1.01) (Z = −2.5, p =.01), even after controlling for age and sex (B [SE] = 0.74 [0.26], p =.007). Increased ACC-GSH correlated with poorer executive function (EF) (B [SE] = −0.31 [0.14], p =.04). OC-GSH showed no effect. DISCUSSION: Higher ACC-GSH in vMCI may reflect a compensatory response to OS. ACC-GSH was negatively correlated with EF, suggesting a linkage between regional brain antioxidants and disease-relevant cognitive domains. Highlights: Brain GSH was measured in vascular MCI and matched controls using MEGA-PRESS. In contrast to GSH deficits in AD, anterior cingulate GSH was elevated in vMCI. Brain GSH was correlated with disease-relevant cognitive domains in vMCI. The GSH antioxidant system may be etiologically implicated in vMCI. © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

关键词： antioxidant brain biomarker glutathione MEGA-PRESS mild cognitive impairment vascular cognitive impairment

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Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk

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BRITISH JOURNAL OF CANCER 2024年第10期130卷 1687-1696页

作者： Tian, Yu Lin, Yi Qu, Conghui Arndt, Volker Baurley, James W. Berndt, Sonja I. Bien, Stephanie A. Bishop, D. Timothy Brenner, Hermann Buchanan, Daniel D. Budiarto, Arif Campbell, Peter T. Carreras-Torres, Robert Casey, Graham Chan, Andrew T. Chen, Rui Chen, Xuechen Conti, David V. Diez-Obrero, Virginia Dimou, Niki Drew, David A. Figueiredo, Jane C. Gallinger, Steven Giles, Graham G. Gruber, Stephen B. Gunter, Marc J. Harlid, Sophia Harrison, Tabitha A. Hidaka, Akihisa Hoffmeister, Michael Huyghe, Jeroen R. Jenkins, Mark A. Jordahl, Kristina M. Joshi, Amit D. Keku, Temitope O. Kawaguchi, Eric Kim, Andre E. Kundaje, Anshul Larsson, Susanna C. Marchand, Loic Le Lewinger, Juan Pablo Li, Li Moreno, Victor Morrison, John Murphy, Neil Nan, Hongmei Nassir, Rami Newcomb, Polly A. Obon-Santacana, Mireia Ogino, Shuji Ose, Jennifer Pardamean, Bens Pellatt, Andrew J. Peoples, Anita R. Platz, Elizabeth A. Potter, John D. Prentice, Ross L. Rennert, Gad Ruiz-Narvaez, Edward A. Sakoda, Lori C. Schoen, Robert E. Shcherbina, Anna Stern, Mariana C. Su, Yu-Ru Thibodeau, Stephen N. Thomas, Duncan C. Tsilidis, Konstantinos K. van Duijnhoven, Franzel J. B. Van Guelpen, Bethany Visvanathan, Kala White, Emily Wolk, Alicja Woods, Michael O. Wu, Anna H. Peters, Ulrike Gauderman, W. James Hsu, Li Chang-Claude, Jenny Capital Med Univ Sch Publ Hlth Beijing Peoples R China German Canc Res Ctr Div Canc Epidemiol Heidelberg Germany Fred Hutchinson Canc Res Ctr Publ Hlth Sci Div Seattle WA 98109 USA German Canc Res Ctr Div Clin Epidemiol & Aging Res Heidelberg Germany Bina Nusantara Univ Bioinformat & Data Sci Res Ctr Jakarta Indonesia BioRealm LLC Walnut CA USA NCI Div Canc Epidemiol & Genet NIH Bethesda MD USA Univ Leeds Leeds Inst Canc & Pathol Leeds England Natl Ctr Tumor Dis NCT German Canc Res Ctr DKFZ Div Prevent Oncol Heidelberg Germany German Canc Res Ctr German Canc Consortium DKTK Heidelberg Germany Univ Melbourne Dept Clin Pathol Colorectal Oncogenom Grp Parkville Vic 3010 Australia Univ Melbourne Ctr Canc Res Victorian Comprehens Canc Ctr Parkville Vic 3010 Australia Royal Melbourne Hosp Genom Med & Family Canc Clin Parkville Vic Australia Albert Einstein Coll Med Dept Epidemiol & Populat Hlth Bronx NY USA Bellvitge Biomed Res Inst IDIBELL ONCOBELL Program Radiobiol & Canc Grp Barcelona Spain Catalan Inst Oncol Oncol Data Analyt Program Barcelona Spain Consortium Biomed Res Epidemiol & Publ Hlth CIBERE Madrid Spain Girona Biomed Res Inst Dr Josep Trueta IDIBGI Digest Dis & Microbiota Grp Girona 17190 Spain Univ Virginia Ctr Publ Hlth Genom Charlottesville VA USA Harvard Med Sch Massachusetts Gen Hosp Clin & Translat Epidemiol Unit Boston MA USA Harvard Med Sch Massachusetts Gen Hosp Div Gastroenterol Boston MA USA Harvard Med Sch Brigham & Womens Hosp Channing Div Network Med Boston MA USA Broad Inst Harvard & MIT Cambridge MA USA Harvard Univ Harvard TH Chan Sch Publ Hlth Dept Epidemiol Boston MA USA Harvard Univ Harvard TH Chan Sch Publ Hlth Dept Immunol & Infect Dis Boston MA USA Univ Southern Calif Keck Sch Med Dept Populat & Publ Hlth Sci Div Biostat Los Angeles CA USA Int Agcy Res Canc Nutr & Metab Branch Lyon France Cedars Sinai Med Ctr Samuel Oschin Comprehens Canc Inst Dept Med Los Angeles CA USA Univ Southern Cal

Background Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC *** We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were *** The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 x 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 x 10-14);these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 x 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC *** MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

关键词： Cancer epidemiology Cancer genetics Colorectal cancer

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Scoping literature review to identify candidate domains for the OMERACT Systemic Lupus Erythematosus core outcome set

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SEMINARS IN ARTHRITIS AND RHEUMATISM 2025年 72卷 152684-152684页

作者： Nielsen, Wils Kharouf, Fadi Grajales, Carolina Munoz Thayaparan, Aarabi Anderson, Melanie Strand, Vibeke Simon, Lee Bonilla, Dennisse Morand, Eric Thumboo, Julian Aringer, Martin Mosca, Marta Bruce, Ian Papadopoulos, Elektra J. Torralba, Karina D. Whitall-Garcia, Laura Patricia Rosen, Cheryl F. Parodis, Ioannis Kim, Alfred Desai, Maya Enman, Yvonne Shea, Beverley Wallace, Daniel J. Chaichian, Yashaar Navarra, Sandra Aranow, Cynthia Mackay, Meggan Trotter, Kimberly Tayer-Shifman, Oshrat E. Duarte-Garcia, Ali Tam, Lai Shan Ugarte-Gil, Manuel F. Pons-Estel, Guillermo J. Reynolds, John A. Nikpour, Mandana Hoi, Alberta Romero-Diaz, Juanita Aggarwalqq, Amita Papachristos, Danae Mok, Chi Chiu Fujio, Keishi Ramsey-Goldman, Rosalind Legge, Alexandra Arnaud, Laurent Bultink, Irene E. M. Finzel, Stephanie Voll, Reinhard E. Ruiz-Irastorza, Guillermo Ines, Luis Sousa Appenzeller, Simone Dobrowolski, Chrisanna Clarke, Ann Elaine Kamen, Diane L. Barraclough, Michelle Tani, Chiara Gomez-Puerta, Jose A. Werth, Victoria P. Katz, Patti Askanase, Anca D. Bingham, Kathleen Gladman, Dafna D. Johnson, Sindhu Drucker, Aaron Nowrouzi-Kia, Behdin Touma, Zahi Univ Toronto Inst Med Sci Toronto ON Canada Univ Hlth Network Schroeder Arthrit Inst Krembil Res Inst Toronto ON Canada Univ Toronto Lupus Clin Toronto Western Hosp Ctr Prognosis Studies Rheumat Dis Toronto ON Canada Univ Hlth Network Toronto ON Canada Stanford Univ Sch Med Div Immunol Rheumatol Palo Alto CA 94305 USA SDG LLC Cambridge MA USA Monash Univ Ctr Inflammatory Dis Melbourne Vic Australia Singapore Gen Hosp Dept Rheumatol & Immunol Singapore Singapore Tech Univ Dresden Univ Med Ctr Dept Med 3 Div Rheumatol Dresden Germany Tech Univ Dresden Fac Med Dresden Germany Tech Univ Dresden Fac Med D-01307 Dresden Germany Univ Manchester Fac Biol Med & Hlth Ctr Musculoskeletal Res Div Musculoskeletal & Dermatol Sci Manchester England Manchester Univ NHS Fdn Trust NIHR Manchester Biomed Res Ctr Manchester Acad Hlth Sci Ctr Manchester England AbbVie Patient Ctr Outcomes Res Irvine CA USA Loma Linda Univ Patient Ctr Outcomes Res Sch Med Irvine CA USA Univ Calif Riverside Dept Med Div Rheumatol Riverside CA USA Amgen Inc Global Dev Inflammat Thousand Oaks CA USA Amgen Inc Dept Global Dev Thousand Oaks CA 91320 USA Toronto Western Hosp Div Dermatol Toronto ON Canada Karolinska Inst Dept Med Solna Div Rheumatol Stockholm Sweden Karolinska Inst Dept Gastroenterol Dermatol & Rheumatol Stockholm Sweden Karolinska Univ Hosp Dept Gastroenterol Dermatol & Rheumatol Stockholm Sweden Washington Univ Dept Med Div Rheumatol Sch Med St Louis MO USA OCAD Univ Fac Design Toronto ON Canada Swedish Rheumatism Assoc Stockholm Sweden Ottawa Hosp Res Inst Ctr Practice Changing Res Clin Epidemiol Program Knowledge Synth Grp 501 Smyth Rd Box 201 Ottawa ON K1H 8L6 Canada Univ Ottawa Fac Med Sch Epidemiol & Publ Hlth Ottawa ON Canada Cedars Sinai Dept Med Div Rheumatol Los Angeles CA USA UCLA Cedars Sinai Med Ctr David Geffen Sch Med Los Angeles CA USA Univ Santo Tomas Dept Med Sect Rheumatol Manila Philippines Feinstein Ins

Objective: To identify candidate Systemic Lupus Erythematosus (SLE) domains from the literature for consideration towards the development of the SLE Core Outcome Set. Methods: This was a comprehensive scoping literature review of SLE clinical trials and systematic reviews published since 2010. Studies were identified from 5 databases and were screened for eligibility. Candidate domains were extracted from the included studies. Candidate domains were winnowed and binned by the Outcome Measures in Rheumatology (OMERACT) SLE Advisory Group. Results: Of the 4063 studies identified, 507 met inclusion criteria and proceeded to data extraction. Multiple domains and items were extracted, which winnowing and binning reduced to 25 candidate domains. Conclusion: The 25 candidate domains cover the important aspects of SLE and the 4 core areas of disease impact according to OMERACT framework. The 25 candidate domains constitute a feasible and manageable number of domains to proceed with to the core domain consensus stage that covers the wide range of impact of SLE. The candidate domains will be supplemented by ongoing qualitative research with patients living with SLE to identify additional domains before proceeding to the consensus stage.

关键词： Systemic Lupus Erythematosus Core domain set Domains Literature Review

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Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells

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NATURE MICROBIOLOGY 2021年第8期6卷 991-+页

作者： Malleret, Benoit El Sahili, Abbas Tay, Matthew Zirui Carissimo, Guillaume Ong, Alice Soh Meoy Novera, Wisna Lin, Jianqing Suwanarusk, Rossarin Kosaisavee, Varakorn Chu, Trang T. T. Sinha, Ameya Howland, Shanshan Wu Fan, Yiping Gruszczyk, Jakub Tham, Wai-Hong Colin, Yves Maurer-Stroh, Sebastian Snounou, Georges Ng, Lisa F. P. Chan, Jerry Kok Yen Chacko, Ann-Marie Lescar, Julien Chandramohanadas, Rajesh Nosten, Francois Russell, Bruce Renia, Laurent ASTAR Singapore Immunol Network SIgN Singapore Singapore Natl Univ Singapore Yong Loo Lin Sch Med Dept Microbiol & Immunol Singapore Singapore Natl Univ Singapore Inst Life Sci Yong Loo Lin Sch Med Immunol Translat Res Programme Singapore Singapore Nanyang Technol Univ Sch Biol Sci Singapore Singapore Nanyang Technol Univ NTU Inst Struct Biol Singapore Singapore ASTAR A STAR ID Labs Singapore Singapore Duke NUS Med Sch Lab Translat & Mol Imaging Canc & Stem Cell Biol Programme Singapore Singapore Univ Otago Dept Microbiol & Immunol Dunedin New Zealand Mahidol Univ Fac Publ Hlth Dept Parasitol & Entomol Bangkok Thailand Singapore Univ Technol & Design Pillar Engn Product Dev Singapore Singapore KK Womens & Childrens Hosp Dept Reprod Med Singapore Singapore Natl Univ Singapore Yong Loo Lin Sch Med Dept Obstet & Gynecol Expt Fetal Med Grp Singapore Singapore Walter & Eliza Hall Inst Med Res Parkville Vic Australia Univ Melbourne Dept Med Biol Melbourne Vic Australia Univ Paris INSERM BIGR UMR S1134 Paris France Inst Natl Transfus Sanguine Paris France ASTAR Bioinformat Inst Singapore Singapore Natl Univ Singapore Dept Biol Sci Singapore Singapore Univ Paris Sud 11 CEA Immunol Viral Infect & Autoimmune Dis IMVA HB INSERMIBFJIDMIT DeptDRFU1184 Fontenay Aux Roses France Duke NUS Med Sch Acad Clin Program Obstet & Gynecol Singapore Singapore Mahidol Univ Fac Trop Med Mahidol Oxford Trop Med Res Unit Shoklo Malaria Res Unit Mae Sot Thailand Univ Oxford Nuffield Dept Med Ctr Trop Med Oxford England Nanyang Technol Univ Lee Kong Chian Sch Med Singapore Singapore

More than one-third of the world's population is exposed to Plasmodium vivax malaria, mainly in Asia(1). P. vivax preferentially invades reticulocytes (immature red blood cells)(2-4). Previous work has identified 11 parasite proteins involved in reticulocyte invasion, including erythrocyte binding protein 2 (ref. (5)) and the reticulocyte-binding proteins (PvRBPs)(6-10). PvRBP2b binds to the transferrin receptor CD71 (ref. (11)), which is selectively expressed on immature reticulocytes(12). Here, we identified CD98 heavy chain (CD98), a heteromeric amino acid transporter from the SLC3 family (also known as SLCA2), as a reticulocyte-specific receptor for the PvRBP2a parasite ligand using mass spectrometry, flow cytometry, biochemical and parasite invasion assays. We characterized the expression level of CD98 at the surface of immature reticulocytes (CD71(+)) and identified an interaction between CD98 and PvRBP2a expressed at the merozoite surface. Our results identify CD98 as an additional host membrane protein, besides CD71, that is directly associated with P. vivax reticulocyte tropism. These findings highlight the potential of using PvRBP2a as a vaccine target against P. vivax malaria.

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A glucose meter interface for point-of-care gene circuit-based diagnostics

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NATURE COMMUNICATIONS 2021年第1期12卷 1-10页

作者： Amalfitano, Evan Karlikow, Margot Norouzi, Masoud Jaenes, Katariina Cicek, Seray Masum, Fahim Mousavi, Peivand Sadat Guo, Yuxiu Tang, Laura Sydor, Andrew Ma, Duo Pearson, Joel D. Trcka, Daniel Pinette, Mathieu Ambagala, Aruna Babiuk, Shawn Pickering, Bradley Wrana, Jeff Bremner, Rod Mazzulli, Tony Sinton, David Brumell, John H. Green, Alexander A. Pardee, Keith Univ Toronto Leslie Dan Fac Pharm Toronto ON M5S 3M2 Canada Hosp Sick Children Peter Gilgan Ctr Res & Learning Program Cell Biol Toronto ON M5G 0A4 Canada Arizona State Univ Biodesign Ctr Mol Design & Biomimet Biodesign Inst Tempe AZ 85287 USA Arizona State Univ Sch Mol Sci Tempe AZ 85287 USA Sinai Hlth Syst Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp Toronto ON M5G 1X5 Canada Univ Toronto Dept Ophthalmol & Vis Sci Toronto ON M5T 3A9 Canada Univ Toronto Dept Lab Med & Pathobiol Toronto ON M5S 1A8 Canada Canadian Food Inspect Agcy Natl Ctr Foreign Anim Dis Winnipeg MB R3E 3M4 Canada Univ Manitoba Fac Med Dept Med Microbiol & Infect Dis Winnipeg MB R3E 0J9 Canada Iowa State Univ Coll Vet Med Dept Vet Microbiol & Prevent Med Ames IA 50011 USA Univ Toronto Dept Mol Genet Toronto ON M5S 1A8 Canada Univ Hlth Network Sinai Hlth Syst Dept Microbiol Toronto ON M5G 1X5 Canada Univ Toronto Dept Mech & Ind Engn Toronto ON M5S 3G8 Canada Univ Toronto Inst Med Sci Toronto ON M5S 1A8 Canada Hosp Sick Children SickKids IBD Ctr Toronto ON M5G 1X8 Canada Boston Univ Dept Biomed Engn Boston MA 02215 USA

Recent advances in cell-free synthetic biology have given rise to gene circuit-based sensors with the potential to provide decentralized and low-cost molecular diagnostics. However, it remains a challenge to deliver this sensing capacity into the hands of users in a practical manner. Here, we leverage the glucose meter, one of the most widely available point-of-care sensing devices, to serve as a universal reader for these decentralized diagnostics. We describe a molecular translator that can convert the activation of conventional gene circuit-based sensors into a glucose output that can be read by off-the-shelf glucose meters. We show the development of new glucogenic reporter systems, multiplexed reporter outputs and detection of nucleic acid targets down to the low attomolar range. Using this glucose-meter interface, we demonstrate the detection of a small-molecule analyte;sample-to-result diagnostics for typhoid, paratyphoid A/B;and show the potential for pandemic response with nucleic acid sensors for SARS-CoV-2. Getting synthetic biology circuit-based sensors into field applications is still a challenge. Here the authors combine a circuit sensor with a glucose meter for small analyte and nucleic acid detection.

关键词： Assay systems Diagnostic markers Expression systems Molecular engineering Synthetic biology

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Distinct Genetic Pathways Define Leukemia Predisposition Versus Adaptive Clonal Hematopoiesis in Shwachman-Diamond Syndrome

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BLOOD 2020年 136卷 35-36页

作者： Kennedy, Alyssa L. Myers, Kasiani C. Bowman, James Gibson, Christopher J. Muscato, Gwen M. Klein, Robert Ballotti, Kaitlyn Camarda, Nicholas Furutani, Elissa M. Harris, Chad E. Liu, Shanshan Galvin, Ashley Malsch, Maggie Dale, David C. Gansner, John M. Nakano, Taizo A. Bertuch, Alison A. Vlachos, Adrianna Lipton, Jeff H. Castillo, Paul Connelly, James Edwards, John Hijiya, Nobuko Ho, Richard Hofmann, Inga Huang, James N. Keel, Sioban B. Lamble, Adam J. Lau, Bonnie W. Walkovich, Kelly J. Norkin, Maxim Stock, Wendy Boettcher, Steffen Brendel, Christian Stieglitz, Elliot Fleming, Mark D. Davies, Stella M. Weller, Edie A. Bahl, Chris Carter, Scott L. Shimamura, Akiko Lindsley, R. Coleman Dana-Farber Cancer Institute Boston MA Department of Pediatrics Division of Bone Marrow Transplantation and Immune Deficieny Cincinnati Children's Hospital Cincinnati OH Institute for Protein Innovation Boston MA Department of Medical Oncology Dana-Farber Cancer Institute Chestnut Hill MA Boston Children's Hospital Boston MA Boston Children's Cancer and Blood Disorders Center Boston Children's Hospital Boston MA Division of Hematology and Oncology and Biostatistics and Research Design Center Institutional Centers for Clinical and Translational Research Boston Children's Hospital Boston MA Department of Medicine University of Washington Seattle WA Hematology Division Brigham and Women's Hospital Newton MA Children's Hospital Colorado University of Colorado School of Medicine Denver CO Baylor College of Medicine Houston TX Feinstein Institute of Medical Research Cohen Children's Medical Center Manhasset NY Blood and Marrow Transplant Program Department of Medical Oncology and Hematology Princess Margaret Cancer Centre University Health Network Toronto Canada Shand's Children's Hospital Department of Pediatrics Division of Pediatric Hematology Oncology University of Florida Gainesville FL Department of Medical Oncology Dana-Farber Cancer Institute Boston MA

Background: Shwachman-Diamond Syndrome (SDS) is a bone marrow failure disorder caused by impaired removal of EIF6 from the nascent 60S ribosome subunit, resulting in defective ribosome assembly. SDS patients have a high risk of myeloid neoplasms (MN) and the prognosis of those that develop MN is poor. Knowledge of the kinetics and functional consequences of somatic mutation acquisition in SDS may offer insight into mechanism of transformation and the potential for therapuetic intervention. Methods: We performed whole exome sequencing of 45 samples from 30 patients, and validated recurrent somatically mutated genes using targeted sequencing with error suppression in prospectively collected samples from 110 patients in the North American SDS Registry. We correlated mutation status with clinical outcome and performed functional studies to understand the consequence of somatic mutations in SDS. Results: We detected somatic mutations in 74 of 98 (76%) patients with germline biallelic SBDS mutations (median 2 mutations/patient, range 0-21). We found no mutations in patients with SDS-like disease; those who have clinical features of SDS without disease defining mutations. Of the 83 patients with SDS without a MN diagnosis, 60 (72%) had detectable clonal hematopoiesis (CH), 40 of whom had more than one mutation (median 3, range 1-21). The most frequently mutated genes were EIF6 ( 60/98, 61%), TP53 ( 44/98, 45% ) , PRPF8 (12/98, 12%), and CSNK1A1 (6/98, 6%). Among SDS patients with TP53 mutated CH, 90.9% (30 of 33) had concurrent EIF6 mutations. To determine whether EIF6 and TP53 mutations occur in the same or different clones, we performed single cell DNA sequencing. Among the 47 clones identified with either EIF6 or TP53 mutations, 24 had a sole EIF6 mutation, and 21 had a sole TP53 mutation, showing that these mutations arise in separate clones. To study the functional consequences of EIF6 missense mutations, we cloned 7 patient-derived mutations and generated cell lines

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Call for transparency of COVI D-19 models

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SCIENCE 2020年第6490期368卷 482-483页

作者： Barton, C. Michael Alberti, Marina Ames, Daniel Atkinson, Jo-An Bales, Jerad Burke, Edmund Chen, Min Diallo, Saikou Y. Earn, David J. D. Fath, Brian Feng, Zhilan Gibbons, Christopher Hammond, Ross Heffernan, Jane Houser, Heather Hovmand, Peter S. Kopainsky, Birgit Mabry, Patricia L. Mair, Christina Meier, Petra Niles, Rebecca Nosek, Brian Osgood, Nathaniel Pierce, Suzanne Polhill, J. Gareth Prosser, Lisa Robinson, Erin Rosenzweig, Cynthia Sankaran, Shankar Stange, Kurt Tucker, Gregory Network Computat Modeling Social & Ecol Sci Tempe AZ USA Urban Eco Evolutionary Res Network Seattle WA USA Int Environm Modelling & Software Soc Manno Ticino Switzerland Comp Simulat & Adv Res Technol Sydney NSW Australia Univ Sydney Syst Modeling & Simulat Brain & Mind Ctr Sydney NSW Australia Consortium Univ Adv Hydrol Sci Inc Cambridge MA USA Operat Res Soc Birmingham W Midlands England Nanjing Normal Univ Open Geog Modeling & Simulat Nanjing Jiangsu Peoples R China Soc Modeling & Simulat Int Suffolk VA USA Soc Math Biol Math Epidemiol Subgrp Governing Comm W Lafayette IN USA Int Soc Ecol Modeling Severna Pk MD USA Business Intelligence Team City Sheffield Sheffield S Yorkshire England Brookings Inst Ctr Social Dynam & Policy Washington DC USA Univ Texas Austin Planet Texas 2050 Bridging Barriers Program Austin TX 78712 USA Washington Univ Social Syst Design Lab St Louis MO 63110 USA Univ Bergen Syst Dynam Grp Bergen Norway HealthPartners Inst Minneapolis MN USA Univ Pittsburgh Ctr Social Dynam & Community Hlth Pittsburgh PA USA Syst Sci Publ Hlth & Hlth Econ Res Consortium Sheffield S Yorkshire England Syst Dynam Soc Albany NY USA Ctr Open Sci Charlottesville VA USA Univ Saskatchewan Computat Epidemiol & Publ Hlth Informat Saskatoon SK Canada Syst Sci Hlth Saskatoon SK Canada Intelligent Syst & Geosci Res Coordinat Network Austin TX USA European Social Simulat Assoc Zurich Switzerland Soc Med Decis Making Bridgewater NJ USA Earth Sci Informat Partners Boulder CO USA Agr Model Intercomparison & Improvement Project New York NY USA Int Soc Syst Sci Ashland KY USA Case Western Reserve Univ Ctr Community Hlth Integrat Cleveland OH 44106 USA Community Surface Dynam Modeling Syst Boulder CO USA

A hallmark of science is the open exchange of knowledge. At this time of crisis, it is more important than ever for scientists around the world to openly share their knowledge, expertise, tools, and technology. Scientific models are critical tools for anticipating, predicting, and responding to complex biological, social, and environmental crises, including pandemics. They are essential for guiding regional and national governments in designing health, social, and economic policies to manage the spread of disease and lessen its impacts. However, presenting modeling results alone is not enough. Scientists must also openly share their model code so that the results can be replicated and evaluated.

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Consensus on nomenclature for clinical staging models in bipolar disorder: A narrative review from the International Society for Bipolar Disorders (ISBD) Staging Task Force

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BIPOLAR DISORDERS 2021年第7期23卷 659-678页

作者： Kupka, Ralph Duffy, Anne Scott, Jan Almeida, Jorge Balanza-Martinez, Vicent Birmaher, Boris Bond, David J. Brietzke, Elisa Chendo, Ines Frey, Benicio N. Grande, Iria Hafeman, Danella Hajek, Tomas Hillegers, Manon Kauer-Sant'Anna, Marcia Mansur, Rodrigo B. van der Markt, Afra Post, Robert Tohen, Mauricio Tremain, Hailey Vazquez, Gustavo Vieta, Eduard Yatham, Lakshmi N. Berk, Michael Alda, Martin Kapczinski, Flavio Vrije Univ Dept Psychiat Amsterdam UMC Amsterdam Publ Mental HlthRes Inst Oldenaller 1 NL-1081 HJ Amsterdam Netherlands Queens Univ Cote Sharp Student Wellness Ctr Dept Psychiat Div Student Mental Hlth Kingston ON Canada Univ Oxford Dept Psychiat Oxford England Newcastle Univ Inst Neurosci Newcastle Upon Tyne Tyne & Wear England Univ Sydney Brain & Mind Ctr Sydney NSW Australia Univ Texas Austin Dell Med Sch Dept Psychiat & Behav Sci Austin TX USA Univ Valencia Dept Med Teaching Unit Psychiat & Psychol Med CIBERSAM Valencia Spain Univ Pittsburgh Med Ctr Pittsburgh PA USA Univ Minnesota Dept Psychiat & Behav Sci Sch Med Minneapolis MN USA Queens Univ Dept Psychiat Sch Med Kingston ON Canada Queens Univ Ctr Neurosci Studies Kingston ON Canada Hosp Santa Maria Psychiat Dept Dept Neurosci Lisbon Portugal Univ Lisbon Clin Univ Psiquiatria Fac Med Lisbon Portugal McMaster Univ Dept Psychiat & Behav Neurosci Hamilton ON Canada St Josephs Healthcare Hamilton Mood Disorders Program & Womens Hlth Concerns Cli Hamilton ON Canada Univ Barcelona Hosp Clin Inst Neurosci IDIBAPSCIBERSAMBarcelona Bipolar Disorders & De Barcelona Spain Univ Pittsburgh Sch Med Dept Psychiat Pittsburgh PA USA Dalhousie Univ Dept Psychiat Halifax NS Canada Erasmus MC Dept Child & Adolescent Psychiat Psychol Sophia Childrens Hosp Rotterdam Netherlands Univ Fed Rio Grande Sul UFRGS Hosp Clin Porto Alegre HCPA Fac Med Dept Psychiat Porto Alegre RS Brazil Univ Hlth Network Mood Disorders Psychopharmacol Unit Toronto ON Canada Univ Toronto Dept Psychiat Toronto ON Canada George Washington Univ Sch Med Washington DC USA Bipolar Collaborat Network Bethesda MD USA Univ New Mexico Dept Psychiat & Behav Sci Hlth Sci Ctr Albuquerque NM USA Swinburne Univ Fac Hlth Arts & Design Ctr Mental Hlth Melbourne Vic Australia Natl Ctr Excellence Youth Mental Hlth Orygen Parkville Vic Australia Queens Univ Dept Psychiat Kingston ON Canada Univ Barcelona

Objectives Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions;in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking. Methods Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders. Results Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at-risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed. Conclusion The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.

关键词： bipolar disorders clinical staging nomenclature

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An Advertisement Effect Simulator for Single Source Data and Its Experimental Evaluation

An Advertisement Effect Simulator for Single Source Data and...

引用

International IEEE Conference on Signal-Image Technologies and Internet-Based System

作者： Yutaro Hara Yoshitaka Sakurai Setsuo Tsuruta Eriko Sakurai Network Design Program Graduate School of Advanced Mathematical Sciences Nakano Tokyo Japan Tokyo Denki University School of Information Environment Inzai Japan Faculty of Service Management Bunri University of Hospitality Sayama Japan

ISBN: (纸本)9781538693865;9781538693858

In the past, advertisements commercial advertisements in TV, Newspapers and Radio broadcasts were very common in Japan and most other countries in the world. Meanwhile, the contact situation to the media has been changing due to recent changes in lifestyles and the spread of smartphones and tablet-type devices worldwide. Therefore, when a company would like to announce their own product, cross media advertisement has become important. However, when announcing products, it is quite costly to advertise on various media. Hence, there are some problems how should company decide, what method of advertisement is the best. In this research, based on the single source data, Nomura Research Institute Ltd. investigates and provides, we create a simulator to estimate advertisement effect in each media. This simulation is based on data. Therefore, the precision of the simulation is affected by the number of data. The objective of this research is to find a relation between the number of data and the precision of the advertising effectiveness. For this purpose, we conducted experiments to observe changes in advertisement effectiveness when changing the number of consumers using a simulator, and the results are summarized.

关键词： Media Advertising TV Internet Companies Data models Smart phones

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