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Estimating Under-recognized COVID-19 Deaths, United States, March 2020-May 2021 using an Excess Mortality Modelling Approach

A. Danielle Iuliano, Howard H. Chang, Neha N. Patel, Ryan Threlkel, Krista Kniss, Jeremy Reich, Molly Steele, Aron J. Hall, Alicia M. Fry, Carrie Reed,

<h4>Background</h4> In the United States, Coronavirus Disease 2019 (COVID-19) deaths are captured through the National Notifiable Disease Surveillance System and death certificates reported to the National Vital Statistics System (NVSS). However, not all COVID-19 deaths are recognized and reported because of limitations in testing, exacerbation of chronic health conditions that ... Read more >>

(The Lancet Regional Health - Americas)
[2021, :]

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Dynamic chromatin regulatory landscape of human CAR T cell exhaustion.

David G Gennert, Rachel C Lynn, Jeff M Granja, Evan W Weber, Maxwell R Mumbach, Yang Zhao, Zhana Duren, Elena Sotillo, William J Greenleaf, Wing H Wong, Ansuman T Satpathy, Crystal L Mackall, Howard Y Chang,

Dysfunction in T cells limits the efficacy of cancer immunotherapy. We profiled the epigenome, transcriptome, and enhancer connectome of exhaustion-prone GD2-targeting HA-28z chimeric antigen receptor (CAR) T cells and control CD19-targeting CAR T cells, which present less exhaustion-inducing tonic signaling, at multiple points during their ex vivo expansion. We found ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2021, 118(30):]

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Consequences of access to water from managed aquifer recharge systems for blood pressure and proteinuria in south-west coastal Bangladesh: a stepped-wedge cluster-randomized trial.

Abu Mohd Naser, Solaiman Doza, Mahbubur Rahman, Leanne Unicomb, Kazi M Ahmed, Shuchi Anand, Shahjada Selim, Mohammad Shamsudduha, Km Venkat Narayan, Howard Chang, Thomas F Clasen, Matthew O Gribble, Stephen P Luby,

<h4>Background</h4>Drinking-water salinity has been associated with high blood pressure (BP) among communities in south-west coastal Bangladesh. We evaluated whether access to water from managed aquifer recharge (MAR)-a hydrogeological intervention to lower groundwater salinity by infiltrating rainwater into the aquifers-can reduce community BP.<h4>Methods</h4>We conducted a stepped-wedge cluster-randomized trial with five monthly ... Read more >>

Int J Epidemiol (International journal of epidemiology)
[2021, 50(3):916-928]

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Macrophage inflammatory and regenerative response periodicity is programmed by cell cycle and chromatin state

Bence Daniel, Julia Belk, Stefanie Meier, Andy Chen, Katalin Sandor, Yanyan Qi, Hugo Kitano, Joshua Wheeler, Deshka Foster, Michael Januszyk, Michael Longaker, Howard Chang, Ansuman Satpathy,

<h4>Summary</h4> Cell cycle (CC) is a fundamental biological process with robust, cyclical gene expression programs to facilitate cell division. In the immune system, a productive immune response requires the expansion of pathogen-responsive cell types, but whether CC also confers unique gene expression programs that inform the subsequent immunological response remains ... Read more >>

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Personal regulome navigation of cancer.

Howard Y Chang,

Nat Rev Cancer (Nature reviews. Cancer)
[2021, :]

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Principles of ecDNA random inheritance drive rapid genome change and therapy resistance in human cancers

Joshua Lange, Celine Chen, Yuriy Pichugin, Liangqi Xie, Jun Tang, King Hung, Kathryn Yost, Quanming Shi, Marcella Erb, Utkrisht Rajkumar, Sihan Wu, Charles Swanton, Zhe Liu, Weini Huang, Howard Chang, Vineet Bafna, Anton Henssen, Benjamin Werner, Paul Mischel,

The foundational principles of Darwinian evolution are variation, selection, and identity by descent. Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumour growth, drug resistance, and shorter survival in patients 1-4 . Currently, the impact of non-chromosomal oncogene inheritance—random identity by descent—is not well understood. Neither ... Read more >>

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Profiling chromatin accessibility responses in human neutrophils with sensitive pathogen detection.

Nikhil Ram-Mohan, Simone A Thair, Ulrike M Litzenburger, Steven Cogill, Nadya Andini, Xi Yang, Howard Y Chang, Samuel Yang,

Sepsis, sequela of bloodstream infections and dysregulated host responses, is a leading cause of death globally. Neutrophils tightly regulate responses to pathogens to prevent organ damage. Profiling early host epigenetic responses in neutrophils may aid in disease recognition. We performed assay for transposase-accessible chromatin (ATAC)-seq of human neutrophils challenged with ... Read more >>

Life Sci Alliance (Life science alliance)
[2021, 4(8):]

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Author Correction: ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis.

Jeffrey M Granja, M Ryan Corces, Sarah E Pierce, S Tansu Bagdatli, Hani Choudhry, Howard Y Chang, William J Greenleaf,

Nat Genet (Nature genetics)
[2021, 53(6):935]

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Invariant Natural Killer T Cell Subsets Have Diverse Graft-Versus-Host-Disease-Preventing and Anti-Tumor Effects.

Kristina Maas-Bauer, Juliane K Lohmeyer, Toshihito Hirai, Teresa Lopes Ramos, Furqan Muhammad Fazal, Ulrike M Litzenburger, Kathryn E Yost, Jessica V Ribado, Neeraja Kambham, Arielle Wenokur, Po-Yu Lin, Maite Alvarez, Melissa Mavers, Jeanette Baker, Ami S Bhatt, Howard Chang, Federico Simonetta, Robert S Negrin,

Invariant Natural Killer T (iNKT) cells are a T cell subset with potent immunomodulatory properties. Experimental evidence in mice and observational studies in humans indicate that iNKT cells have antitumor potential as well as the ability to suppress acute and chronic Graft-versus-Host-Disease (GvHD). Murine iNKT cells differentiate during thymic development ... Read more >>

Blood (Blood)
[2021, :]

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Cardiovascular disease risk and pathophysiology in South Asians: can longitudinal multi-omics shed light?

Yan Sun, Chang Liu, Lisa Staimez, Mohammed Ali, Howard Chang, Dimple Kondal, Shivani Patel, Dean Jones, Viswanathan Mohan, Nikhil Tandon, Dorairaj Prabhakaran, Arshed Quyyumi, Venkat Narayan, Anurag Agrawal,

Cardiovascular disease (CVD) is the leading cause of mortality in South Asia, with rapidly increasing prevalence of hypertension, type 2 diabetes (T2DM) and hyperlipidemia over the last two decades. Atherosclerotic CVD (ASCVD) affects South Asians earlier in life and at lower body weights, which is not fully explained by differential ... Read more >>

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Is the severity of the Great Recession's aftershocks correlated with changes in access to the combined prevention environment among people who inject drugs?

Akilah Wise, Behzad Kianian, Howard H Chang, Sabriya Linton, Mary E Wolfe, Justin Smith, Barbara Tempalski, Don Des Jarlais, Zev Ross, Salaam Semaan, Cyprian Wejnert, Dita Broz, Hannah L F Cooper,

<h4>Background</h4>The 2008 Recession was a global event that led to funding cuts for programs and services in the United States; though this recession officially ended in 2009, its aftershocks continued through 2012. We evaluated the relationship between the severity of the Great Recession's aftermath and spatial access to combined prevention ... Read more >>

Int J Drug Policy (The International journal on drug policy)
[2021, 95:103264]

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Imperfect adherence in real life: a prevention-effective perspective on adherence to daily and event-driven HIV pre-exposure prophylaxis among men who have sex with men - a prospective cohort study in Taiwan.

Huei-Jiuan Wu, Stephane Wen-Wei Ku, Howard H Chang, Chia-Wen Li, Nai-Ying Ko, Carol Strong,

<h4>Introduction</h4>Both daily and event-driven (ED) pre-exposure prophylaxis (PrEP) have been demonstrated to be highly effective among men who have sex with men (MSM). Prevention-effective adherence proposes that PrEP adherence should be aligned with the risk of HIV, which could be applied to both daily and ED PrEP adherence measurement. The ... Read more >>

J Int AIDS Soc (Journal of the International AIDS Society)
[2021, 24(5):e25733]

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Clonal inactivation of telomerase promotes accelerated stem cell differentiation

Kazuteru Hasegawa, Yang Zhao, Alina Garbuzov, Ryan Corces, Lu Chen, Peggie Cheung, Yuning Wei, Howard Chang, Steven Artandi,

<h4>Summary</h4> Telomerase is intimately associated with stem cells and upregulated in cancer, where it serves essential roles through its catalytic action in elongating telomeres, nucleoprotein caps that protect chromosome ends 1 . Overexpression of the telomerase reverse transcriptase (TERT) enhances cell proliferation through telomere-independent means, yet definitive evidence for such ... Read more >>

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Using logic regression to characterize extreme heat exposures and their health associations: a time-series study of emergency department visits in Atlanta.

Shan Jiang, Joshua L Warren, Noah Scovronick, Shannon E Moss, Lyndsey A Darrow, Matthew J Strickland, Andrew J Newman, Yong Chen, Stefanie T Ebelt, Howard H Chang,

<h4>Background</h4>Short-term associations between extreme heat events and adverse health outcomes are well-established in epidemiologic studies. However, the use of different exposure definitions across studies has limited our understanding of extreme heat characteristics that are most important for specific health outcomes or subpopulations.<h4>Methods</h4>Logic regression is a statistical learning method for constructing ... Read more >>

BMC Med Res Methodol (BMC medical research methodology)
[2021, 21(1):87]

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Acute associations between heatwaves and preterm and early-term birth in 50 US metropolitan areas: a matched case-control study.

Mengjiao Huang, Matthew J Strickland, Megan Richards, Heather A Holmes, Andrew J Newman, Joshua V Garn, Yan Liu, Joshua L Warren, Howard H Chang, Lyndsey A Darrow,

<h4>Background</h4>The effect of heatwaves on adverse birth outcomes is not well understood and may vary by how heatwaves are defined. The study aims to examine acute associations between various heatwave definitions and preterm and early-term birth.<h4>Methods</h4>Using national vital records from 50 metropolitan statistical areas (MSAs) between 1982 and 1988, singleton ... Read more >>

Environ Health (Environmental health : a global access science source)
[2021, 20(1):47]

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Integrated spatial multi-omics reveals fibroblast fate during tissue repair

Deshka Foster, Michael Januszyk, Malini Chinta, Kathryn Yost, Gunsagar Gulati, Alan Nguyen, Austin Burcham, Ankit Salhotra, Chase Ransom, Dominic Henn, Kellen Chen, Shamik Mascharak, Karen Tolentino, Ashley Titan, Ellen Jones, Oscar da Silva, Tripp Leavitt, Clement Marshall, Heather desJardins-Park, Michael Hu, Derrick Wan, Gerlinde Wernig, Dhananjay Wagh, John Coller, Jeffrey Norton, Geoffrey Gurtner, Aaron Newman, Howard Chang, Michael Longaker,

In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a ... Read more >>

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Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing.

James K Nuñez, Jin Chen, Greg C Pommier, J Zachery Cogan, Joseph M Replogle, Carmen Adriaens, Gokul N Ramadoss, Quanming Shi, King L Hung, Avi J Samelson, Angela N Pogson, James Y S Kim, Amanda Chung, Manuel D Leonetti, Howard Y Chang, Martin Kampmann, Bradley E Bernstein, Volker Hovestadt, Luke A Gilbert, Jonathan S Weissman,

A general approach for heritably altering gene expression has the potential to enable many discovery and therapeutic efforts. Here, we present CRISPRoff-a programmable epigenetic memory writer consisting of a single dead Cas9 fusion protein that establishes DNA methylation and repressive histone modifications. Transient CRISPRoff expression initiates highly specific DNA methylation ... Read more >>

Cell (Cell)
[2021, 184(9):2503-2519.e17]

Cited: 3 times

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Dynamic chromatin regulatory landscape of human CAR T cell exhaustion

David Gennert, Rachel Lynn, Jeff Granja, Evan Weber, Maxwell Mumbach, Yang Zhao, Zhana Duren, Elena Sotillo, William Greenleaf, Wing Wong, Ansuman Satpathy, Crystal Mackall, Howard Chang,

<h4>ABSTRACT</h4> Dysfunction in T cells limits the efficacy of cancer immunotherapy 1–6 . We profiled the epigenome, transcriptome, and enhancer connectome of exhaustion-prone GD2-targeting HA-28z chimeric antigen receptor (CAR) T cells and control CD19-targeting CAR T cells, which present less exhaustion-inducing tonic signaling, at multiple points during their ex vivo ... Read more >>

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Recruiting T cells in cancer immunotherapy.

Kathryn E Yost, Howard Y Chang, Ansuman T Satpathy,

Science (Science (New York, N.Y.))
[2021, 372(6538):130-131]

Cited: 1 time

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Place-Based Correlates of Exchange Sex Among People Who Inject Drugs in 19 U.S. Metropolitan Areas, 2012.

Akilah Wise, Behzad Kianian, Howard Chang, Sabriya Linton, Mary E Wolfe, Justin Smith, Barbara Tempalski, Don Des Jarlais, Zev Ross, Salaam Semaan, Cyprian Wejnert, Dita Broz, Hannah Cooper,

This study examined overall and gender-specific associations between place-based characteristics and opposite-sex exchange sex among people who inject drugs (PWID) in the U.S. PWID were recruited from 19 metropolitan statistical areas (MSAs) for the Centers for Disease Control and Prevention's 2012 National HIV Behavioral Surveillance. Administrative data were used to ... Read more >>

Arch Sex Behav (Archives of sexual behavior)
[2021, :]

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LKB1 inactivation modulates chromatin accessibility to drive metastatic progression

Sarah Pierce, Jeffrey Granja, Ryan Corces, Jennifer Brady, Min Tsai, Aubrey Pierce, Rui Tang, Pauline Chu, David Feldser, Howard Chang, Michael Bassik, William Greenleaf, Monte Winslow,

Metastasis is the leading cause of cancer-related deaths, enabling cancer cells to expand to secondary sites and compromise organ function 1 . Given that primary tumors and metastases often share the same constellation of driver mutations 2–4 , the mechanisms driving their distinct phenotypes are unclear. Here, we show that ... Read more >>

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BABEL enables cross-modality translation between multiomic profiles at single-cell resolution.

Kevin E Wu, Kathryn E Yost, Howard Y Chang, James Zou,

Simultaneous profiling of multiomic modalities within a single cell is a grand challenge for single-cell biology. While there have been impressive technical innovations demonstrating feasibility-for example, generating paired measurements of single-cell transcriptome (single-cell RNA sequencing [scRNA-seq]) and chromatin accessibility (single-cell assay for transposase-accessible chromatin using sequencing [scATAC-seq])-widespread application of joint ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2021, 118(15):]

Cited: 2 times

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Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling.

Evan W Weber, Kevin R Parker, Elena Sotillo, Rachel C Lynn, Hima Anbunathan, John Lattin, Zinaida Good, Julia A Belk, Bence Daniel, Dorota Klysz, Meena Malipatlolla, Peng Xu, Malek Bashti, Sabine Heitzeneder, Louai Labanieh, Panayiotis Vandris, Robbie G Majzner, Yanyan Qi, Katalin Sandor, Ling-Chun Chen, Snehit Prabhu, Andrew J Gentles, Thomas J Wandless, Ansuman T Satpathy, Howard Y Chang, Crystal L Mackall,

T cell exhaustion limits immune responses against cancer and is a major cause of resistance to chimeric antigen receptor (CAR)-T cell therapeutics. Using murine xenograft models and an in vitro model wherein tonic CAR signaling induces hallmark features of exhaustion, we tested the effect of transient cessation of receptor signaling, ... Read more >>

Science (Science (New York, N.Y.))
[2021, 372(6537):]

Cited: 1 time

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B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells.

Bingfei Yu, Yanyan Qi, Rui Li, Quanming Shi, Ansuman T Satpathy, Howard Y Chang,

The long non-coding RNA (lncRNA) XIST establishes X chromosome inactivation (XCI) in female cells in early development and thereafter is thought to be largely dispensable. Here, we show XIST is continually required in adult human B cells to silence a subset of X-linked immune genes such as TLR7. XIST-dependent genes ... Read more >>

Cell (Cell)
[2021, 184(7):1790-1803.e17]

Cited: 1 time

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RNA-Binding Proteins Direct Myogenic Cell Fate Decisions

Joshua Wheeler, Oscar Whitney, Thomas Vogler, Eric Nguyen, Bradley Pawlikowski, Evan Lester, Alicia Cutler, Tiffany Elston, Nicole Dalla Betta, Kevin Parker, Kathryn Yost, Hannes Vogel, Thomas Rando, Howard Chang, Aaron Johnson, Roy Parker, Bradley Olwin,

<h4>ABSTRACT</h4> RNA-binding proteins (RBPs) are essential for skeletal muscle regeneration and RBP dysfunction causes muscle degeneration and neuromuscular disease. How ubiquitously expressed RBPs orchestrate complex tissue regeneration and direct cell fate decisions in skeletal muscle remains poorly understood. Single cell RNA-sequencing of regenerating skeletal muscle reveals that RBP expression, including ... Read more >>

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