1,129 results on '"Aronow, Bruce J."'
Search Results
2. Pediatric cardiomyopathy illustrates the importance of reinterpreting the significance of genetic variants
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Lee, Teresa M., Miller, Erin, Sridhar, Arthi, Fan, Xiao, Dexheimer, Phillip J., Bansal, Neha, Godown, Justin, Hsu, Daphne T., Kantor, Paul, Kirmani, Sonya, Lal, Ashwin K., Rossano, Joseph W., Towbin, Jeffrey A., Webber, Steven A., Shi, Ling, Hamza, Taye H., Aronow, Bruce J., Bhatnaghar, Surbhi, Martin, Lisa J., Schubert, Jeffrey, Ware, Stephanie M., Chung, Wendy K., Wilkinson, James D., and Lipshultz, Steven E.
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- 2024
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3. Guided construction of single cell reference for human and mouse lung
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Guo, Minzhe, Morley, Michael P., Jiang, Cheng, Wu, Yixin, Li, Guangyuan, Du, Yina, Zhao, Shuyang, Wagner, Andrew, Cakar, Adnan Cihan, Kouril, Michal, Jin, Kang, Gaddis, Nathan, Kitzmiller, Joseph A., Stewart, Kathleen, Basil, Maria C., Lin, Susan M., Ying, Yun, Babu, Apoorva, Wikenheiser-Brokamp, Kathryn A., Mun, Kyu Shik, Naren, Anjaparavanda P., Clair, Geremy, Adkins, Joshua N., Pryhuber, Gloria S., Misra, Ravi S., Aronow, Bruce J., Tickle, Timothy L., Salomonis, Nathan, Sun, Xin, Morrisey, Edward E., Whitsett, Jeffrey A., and Xu, Yan
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- 2023
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4. Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer
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Bedard, Mary C., Chihanga, Tafadzwa, Carlile, Adrean, Jackson, Robert, Brusadelli, Marion G., Lee, Denis, VonHandorf, Andrew, Rochman, Mark, Dexheimer, Phillip J., Chalmers, Jeffrey, Nuovo, Gerard, Lehn, Maria, Williams, David E. J., Kulkarni, Aditi, Carey, Molly, Jackson, Amanda, Billingsley, Caroline, Tang, Alice, Zender, Chad, Patil, Yash, Wise-Draper, Trisha M., Herzog, Thomas J., Ferris, Robert L., Kendler, Ady, Aronow, Bruce J., Kofron, Matthew, Rothenberg, Marc E., Weirauch, Matthew T., Van Doorslaer, Koenraad, Wikenheiser-Brokamp, Kathryn A., Lambert, Paul F., Adam, Mike, Steven Potter, S., and Wells, Susanne I.
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- 2023
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5. International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality
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Weber, Griffin M, Hong, Chuan, Xia, Zongqi, Palmer, Nathan P, Avillach, Paul, L’Yi, Sehi, Keller, Mark S, Murphy, Shawn N, Gutiérrez-Sacristán, Alba, Bonzel, Clara-Lea, Serret-Larmande, Arnaud, Neuraz, Antoine, Omenn, Gilbert S, Visweswaran, Shyam, Klann, Jeffrey G, South, Andrew M, Loh, Ne Hooi Will, Cannataro, Mario, Beaulieu-Jones, Brett K, Bellazzi, Riccardo, Agapito, Giuseppe, Alessiani, Mario, Aronow, Bruce J, Bell, Douglas S, Benoit, Vincent, Bourgeois, Florence T, Chiovato, Luca, Cho, Kelly, Dagliati, Arianna, DuVall, Scott L, Barrio, Noelia García, Hanauer, David A, Ho, Yuk-Lam, Holmes, John H, Issitt, Richard W, Liu, Molei, Luo, Yuan, Lynch, Kristine E, Maidlow, Sarah E, Malovini, Alberto, Mandl, Kenneth D, Mao, Chengsheng, Matheny, Michael E, Moore, Jason H, Morris, Jeffrey S, Morris, Michele, Mowery, Danielle L, Ngiam, Kee Yuan, Patel, Lav P, Pedrera-Jimenez, Miguel, Ramoni, Rachel B, Schriver, Emily R, Schubert, Petra, Balazote, Pablo Serrano, Spiridou, Anastasia, Tan, Amelia LM, Tan, Byorn WL, Tibollo, Valentina, Torti, Carlo, Trecarichi, Enrico M, Wang, Xuan, Kohane, Isaac S, Cai, Tianxi, and Brat, Gabriel A
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Health Services and Systems ,Health Sciences ,Basic Behavioral and Social Science ,Behavioral and Social Science ,Good Health and Well Being ,Consortium for Clinical Characterization of COVID-19 by EHR ,Health services and systems - Abstract
Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach.
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- 2022
6. A roadmap for the Human Developmental Cell Atlas
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Haniffa, Muzlifah, Taylor, Deanne, Linnarsson, Sten, Aronow, Bruce J, Bader, Gary D, Barker, Roger A, Camara, Pablo G, Camp, J Gray, Chédotal, Alain, Copp, Andrew, Etchevers, Heather C, Giacobini, Paolo, Göttgens, Berthold, Guo, Guoji, Hupalowska, Ania, James, Kylie R, Kirby, Emily, Kriegstein, Arnold, Lundeberg, Joakim, Marioni, John C, Meyer, Kerstin B, Niakan, Kathy K, Nilsson, Mats, Olabi, Bayanne, Pe’er, Dana, Regev, Aviv, Rood, Jennifer, Rozenblatt-Rosen, Orit, Satija, Rahul, Teichmann, Sarah A, Treutlein, Barbara, Vento-Tormo, Roser, and Webb, Simone
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Medical Biotechnology ,Biomedical and Clinical Sciences ,Regenerative Medicine ,Stem Cell Research - Nonembryonic - Human ,Stem Cell Research ,Pediatric ,Stem Cell Research - Embryonic - Human ,Human Fetal Tissue ,Genetics ,Human Genome ,Good Health and Well Being ,Adult ,Animals ,Atlases as Topic ,Cell Culture Techniques ,Cell Movement ,Cell Survival ,Cell Tracking ,Cells ,Data Visualization ,Developmental Biology ,Embryo ,Mammalian ,Female ,Fetus ,Humans ,Imaging ,Three-Dimensional ,Information Dissemination ,Male ,Models ,Animal ,Organogenesis ,Organoids ,Stem Cells ,Human Cell Atlas Developmental Biological Network ,General Science & Technology - Abstract
The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.
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- 2021
7. Stratification of risk of progression to colectomy in ulcerative colitis via measured and predicted gene expression
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Mo, Angela, Nagpal, Sini, Gettler, Kyle, Haritunians, Talin, Giri, Mamta, Haberman, Yael, Karns, Rebekah, Prince, Jarod, Arafat, Dalia, Hsu, Nai-Yun, Chuang, Ling-Shiang, Argmann, Carmen, Kasarskis, Andrew, Suarez-Farinas, Mayte, Gotman, Nathan, Mengesha, Emebet, Venkateswaran, Suresh, Rufo, Paul A, Baker, Susan S, Sauer, Cary G, Markowitz, James, Pfefferkorn, Marian D, Rosh, Joel R, Boyle, Brendan M, Mack, David R, Baldassano, Robert N, Shah, Sapana, LeLeiko, Neal S, Heyman, Melvin B, Griffiths, Anne M, Patel, Ashish S, Noe, Joshua D, Davis Thomas, Sonia, Aronow, Bruce J, Walters, Thomas D, McGovern, Dermot PB, Hyams, Jeffrey S, Kugathasan, Subra, Cho, Judy H, Denson, Lee A, and Gibson, Greg
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Digestive Diseases ,Inflammatory Bowel Disease ,Human Genome ,Autoimmune Disease ,Clinical Research ,Genetics ,Patient Safety ,Biotechnology ,Prevention ,Generic health relevance ,Biological Specimen Banks ,Cohort Studies ,Colectomy ,Colitis ,Ulcerative ,Colon ,Crohn Disease ,Datasets as Topic ,Disease Progression ,Gene Expression Profiling ,Genome-Wide Association Study ,Humans ,Multifactorial Inheritance ,Prognosis ,Quantitative Trait Loci ,Risk Assessment ,Transcriptome ,United Kingdom ,cell-type-specific gene expression ,eQTLs ,predicted polygenic transcriptional risk scores ,prediction of disease progression ,transcriptional risk scores ,transcriptome-wide association studies ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.
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- 2021
8. Mucosal Inflammatory and Wound Healing Gene Programs Reveal Targets for Stricturing Behavior in Pediatric Crohn's Disease.
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Haberman, Yael, Minar, Phillip, Karns, Rebekah, Dexheimer, Phillip J, Ghandikota, Sudhir, Tegge, Samuel, Shapiro, Daniel, Shuler, Brianne, Venkateswaran, Suresh, Braun, Tzipi, Ta, Allison, Walters, Thomas D, Baldassano, Robert N, Noe, Joshua D, Rosh, Joel, Markowitz, James, Dotson, Jennifer L, Mack, David R, Kellermayer, Richard, Griffiths, Anne M, Heyman, Melvin B, Baker, Susan S, Moulton, Dedrick, Patel, Ashish S, Gulati, Ajay S, Steiner, Steven J, LeLeiko, Neal, Otley, Anthony, Oliva-Hemker, Maria, Ziring, David, Gokhale, Ranjana, Kim, Sandra, Guthery, Stephen L, Cohen, Stanley A, Snapper, Scott, Aronow, Bruce J, Stephens, Michael, Gibson, Greg, Dillman, Jonathan R, Dubinsky, Marla, Hyams, Jeffrey S, Kugathasan, Subra, Jegga, Anil G, and Denson, Lee A
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Crohn's Disease ,Pediatric ,Clinical Research ,Genetics ,Digestive Diseases ,Inflammatory Bowel Disease ,Paediatric Crohn disease ,ileum ,small molecule ,surgery ,transcriptome ,pediatric Crohn Disease ,Clinical Sciences ,Gastroenterology & Hepatology - Abstract
Ileal strictures are the major indication for resective surgery in Crohn's disease (CD). We aimed to define ileal gene programs present at diagnosis linked with future stricturing behavior during five year follow-up, and to identify potential small molecules to reverse these gene signatures. Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicenter pediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behavior and for model testing to predict stricturing behavior. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied. 19 of the 249 patients developed isolated B2 stricturing behavior during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our prior report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix (ECM) gene expression in those who developed stricturing complications. We further computationally prioritize small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by year five after diagnosis (AUC (95th CI) = 0.82 (0.7-0.94)). An ileal gene program for macrophage and fibroblast activation is linked to stricturing complications in treatment naïve pediatric CD, and may inform novel small molecule therapeutic approaches.
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- 2021
9. Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortium
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Aaron, James R., Adam, Atif, Agapito, Giuseppe, Albayrak, Adem, Albi, Giuseppe, Alessiani, Mario, Alloni, Anna, Amendola, Danilo F., Angoulvant, François, Anthony, Li LLJ., Aronow, Bruce J., Ashraf, Fatima, Atz, Andrew, Avillach, Paul, Panickan, Vidul Ayakulangara, Azevedo, Paula S., Badenes, Rafael, Balshi, James, Batugo, Ashley, Beaulieu-Jones, Brendin R., Beaulieu-Jones, Brett K., Bell, Douglas S., Bellasi, Antonio, Bellazzi, Riccardo, Benoit, Vincent, Beraghi, Michele, Bernal-Sobrino, José Luis, Bernaux, Mélodie, Bey, Romain, Bhatnagar, Surbhi, Blanco-Martínez, Alvar, Boeker, Martin, Bonzel, Clara-Lea, Booth, John, Bosari, Silvano, Bourgeois, Florence T., Bradford, Robert L., Brat, Gabriel A., Bréant, Stéphane, Brown, Nicholas W., Bruno, Raffaele, Bryant, William A., Bucalo, Mauro, Bucholz, Emily, Burgun, Anita, Cai, Tianxi, Cannataro, Mario, Carmona, Aldo, Cattelan, Anna Maria, Caucheteux, Charlotte, Champ, Julien, Chen, Jin, Chen, Krista Y., Chiovato, Luca, Chiudinelli, Lorenzo, Cho, Kelly, Cimino, James J., Colicchio, Tiago K., Cormont, Sylvie, Cossin, Sébastien, Craig, Jean B., Cruz-Bermúdez, Juan Luis, Cruz-Rojo, Jaime, Dagliati, Arianna, Daniar, Mohamad, Daniel, Christel, Das, Priyam, Devkota, Batsal, Dionne, Audrey, Duan, Rui, Dubiel, Julien, DuVall, Scott L., Esteve, Loic, Estiri, Hossein, Fan, Shirley, Follett, Robert W., Ganslandt, Thomas, García-Barrio, Noelia, Garmire, Lana X., Gehlenborg, Nils, Getzen, Emily J., Geva, Alon, Goh, Rachel SJ., González, Tomás González, Gradinger, Tobias, Gramfort, Alexandre, Griffier, Romain, Griffon, Nicolas, Grisel, Olivier, Gutiérrez-Sacristán, Alba, Guzzi, Pietro H., Han, Larry, Hanauer, David A., Haverkamp, Christian, Hazard, Derek Y., He, Bing, Henderson, Darren W., Hilka, Martin, Ho, Yuk-Lam, Holmes, John H., Honerlaw, Jacqueline P., Hong, Chuan, Huling, Kenneth M., Hutch, Meghan R., Issitt, Richard W., Jannot, Anne Sophie, Jouhet, Vianney, Kainth, Mundeep K., Kate, Kernan F., Kavuluru, Ramakanth, Keller, Mark S., Kennedy, Chris J., Kernan, Kate F., Key, Daniel A., Kirchoff, Katie, Klann, Jeffrey G., Kohane, Isaac S., Krantz, Ian D., Kraska, Detlef, Krishnamurthy, Ashok K., L'Yi, Sehi, Leblanc, Judith, Lemaitre, Guillaume, Lenert, Leslie, Leprovost, Damien, Liu, Molei, Will Loh, Ne Hooi, Long, Qi, Lozano-Zahonero, Sara, Luo, Yuan, Lynch, Kristine E., Mahmood, Sadiqa, Maidlow, Sarah E., Makoudjou, Adeline, Makwana, Simran, Malovini, Alberto, Mandl, Kenneth D., Mao, Chengsheng, Maram, Anupama, Maripuri, Monika, Martel, Patricia, Martins, Marcelo R., Marwaha, Jayson S., Masino, Aaron J., Mazzitelli, Maria, Mazzotti, Diego R., Mensch, Arthur, Milano, Marianna, Minicucci, Marcos F., Moal, Bertrand, Ahooyi, Taha Mohseni, Moore, Jason H., Moraleda, Cinta, Morris, Jeffrey S., Morris, Michele, Moshal, Karyn L., Mousavi, Sajad, Mowery, Danielle L., Murad, Douglas A., Murphy, Shawn N., Naughton, Thomas P., Breda Neto, Carlos Tadeu, Neuraz, Antoine, Newburger, Jane, Ngiam, Kee Yuan, Njoroge, Wanjiku FM., Norman, James B., Obeid, Jihad, Okoshi, Marina P., Olson, Karen L., Omenn, Gilbert S., Orlova, Nina, Ostasiewski, Brian D., Palmer, Nathan P., Paris, Nicolas, Patel, Lav P., Pedrera-Jiménez, Miguel, Pfaff, Ashley C., Pfaff, Emily R., Pillion, Danielle, Pizzimenti, Sara, Priya, Tanu, Prokosch, Hans U., Prudente, Robson A., Prunotto, Andrea, Quirós-González, Víctor, Ramoni, Rachel B., Raskin, Maryna, Rieg, Siegbert, Roig-Domínguez, Gustavo, Rojo, Pablo, Romero-Garcia, Nekane, Rubio-Mayo, Paula, Sacchi, Paolo, Sáez, Carlos, Salamanca, Elisa, Samayamuthu, Malarkodi Jebathilagam, Sanchez-Pinto, L. Nelson, Sandrin, Arnaud, Santhanam, Nandhini, Santos, Janaina C.C., Sanz Vidorreta, Fernando J., Savino, Maria, Schriver, Emily R., Schubert, Petra, Schuettler, Juergen, Scudeller, Luigia, Sebire, Neil J., Serrano-Balazote, Pablo, Serre, Patricia, Serret-Larmande, Arnaud, Shah, Mohsin A., Hossein Abad, Zahra Shakeri, Silvio, Domenick, Sliz, Piotr, Son, Jiyeon, Sonday, Charles, South, Andrew M., Sperotto, Francesca, Spiridou, Anastasia, Strasser, Zachary H., Tan, Amelia LM., Tan, Bryce W.Q., Tan, Byorn W.L., Tanni, Suzana E., Taylor, Deanne M., Terriza-Torres, Ana I., Tibollo, Valentina, Tippmann, Patric, Toh, Emma MS., Torti, Carlo, Trecarichi, Enrico M., Vallejos, Andrew K., Varoquaux, Gael, Vella, Margaret E., Verdy, Guillaume, Vie, Jill-Jênn, Visweswaran, Shyam, Vitacca, Michele, Wagholikar, Kavishwar B., Waitman, Lemuel R., Wang, Xuan, Wassermann, Demian, Weber, Griffin M., Wolkewitz, Martin, Wong, Scott, Xia, Zongqi, Xiong, Xin, Ye, Ye, Yehya, Nadir, Yuan, William, Zachariasse, Joany M., Zahner, Janet J., Zambelli, Alberto, Zhang, Harrison G., Zöller, Daniela, Zuccaro, Valentina, Zucco, Chiara, Li, Xiudi, Rofeberg, Valerie N., Elias, Matthew D., Laird-Gion, Jessica, and Newburger, Jane W.
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- 2023
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10. Characterization of long COVID temporal sub-phenotypes by distributed representation learning from electronic health record data: a cohort study
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Aaron, James R., Agapito, Giuseppe, Albayrak, Adem, Albi, Giuseppe, Alessiani, Mario, Alloni, Anna, Amendola, Danilo F., François Angoulvant, Anthony, Li L.L.J., Aronow, Bruce J., Ashraf, Fatima, Atz, Andrew, Avillach, Paul, Azevedo, Paula S., Balshi, James, Beaulieu-Jones, Brett K., Bell, Douglas S., Bellasi, Antonio, Bellazzi, Riccardo, Benoit, Vincent, Beraghi, Michele, Bernal-Sobrino, José Luis, Bernaux, Mélodie, Bey, Romain, Bhatnagar, Surbhi, Blanco-Martínez, Alvar, Bonzel, Clara-Lea, Booth, John, Bosari, Silvano, Bourgeois, Florence T., Bradford, Robert L., Brat, Gabriel A., Bréant, Stéphane, Brown, Nicholas W., Bruno, Raffaele, Bryant, William A., Bucalo, Mauro, Bucholz, Emily, Burgun, Anita, Cai, Tianxi, Cannataro, Mario, Carmona, Aldo, Caucheteux, Charlotte, Champ, Julien, Chen, Jin, Chen, Krista Y., Chiovato, Luca, Chiudinelli, Lorenzo, Cho, Kelly, Cimino, James J., Colicchio, Tiago K., Cormont, Sylvie, Cossin, Sébastien, Craig, Jean B., Cruz-Bermúdez, Juan Luis, Cruz-Rojo, Jaime, Dagliati, Arianna, Daniar, Mohamad, Daniel, Christel, Das, Priyam, Devkota, Batsal, Dionne, Audrey, Duan, Rui, Dubiel, Julien, DuVall, Scott L., Esteve, Loic, Estiri, Hossein, Fan, Shirley, Follett, Robert W., Ganslandt, Thomas, Barrio, Noelia García, Garmire, Lana X., Gehlenborg, Nils, Getzen, Emily J., Geva, Alon, Gradinger, Tobias, Gramfort, Alexandre, Griffier, Romain, Griffon, Nicolas, Grisel, Olivier, Gutiérrez-Sacristán, Alba, Han, Larry, Hanauer, David A., Haverkamp, Christian, Hazard, Derek Y., He, Bing, Henderson, Darren W., Hilka, Martin, Ho, Yuk-Lam, Holmes, John H., Hong, Chuan, Huling, Kenneth M., Hutch, Meghan R., Issitt, Richard W., Jannot, Anne Sophie, Jouhet, Vianney, Kavuluru, Ramakanth, Keller, Mark S., Kennedy, Chris J., Key, Daniel A., Kirchoff, Katie, Klann, Jeffrey G., Kohane, Isaac S., Krantz, Ian D., Kraska, Detlef, Krishnamurthy, Ashok K., L'Yi, Sehi, Le, Trang T., Leblanc, Judith, Lemaitre, Guillaume, Lenert, Leslie, Leprovost, Damien, Liu, Molei, Will Loh, Ne Hooi, Long, Qi, Lozano-Zahonero, Sara, Luo, Yuan, Lynch, Kristine E., Mahmood, Sadiqa, Maidlow, Sarah E., Makoudjou, Adeline, Malovini, Alberto, Mandl, Kenneth D., Mao, Chengsheng, Maram, Anupama, Martel, Patricia, Martins, Marcelo R., Marwaha, Jayson S., Masino, Aaron J., Mazzitelli, Maria, Mensch, Arthur, Milano, Marianna, Minicucci, Marcos F., Moal, Bertrand, Ahooyi, Taha Mohseni, Moore, Jason H., Moraleda, Cinta, Morris, Jeffrey S., Morris, Michele, Moshal, Karyn L., Mousavi, Sajad, Mowery, Danielle L., Murad, Douglas A., Murphy, Shawn N., Naughton, Thomas P., Breda Neto, Carlos Tadeu, Neuraz, Antoine, Newburger, Jane, Ngiam, Kee Yuan, Njoroge, Wanjiku F.M., Norman, James B., Obeid, Jihad, Okoshi, Marina P., Olson, Karen L., Omenn, Gilbert S., Orlova, Nina, Ostasiewski, Brian D., Palmer, Nathan P., Paris, Nicolas, Patel, Lav P., Pedrera-Jiménez, Miguel, Pfaff, Emily R., Pfaff, Ashley C., Pillion, Danielle, Pizzimenti, Sara, Prokosch, Hans U., Prudente, Robson A., Prunotto, Andrea, Quirós-González, Víctor, Ramoni, Rachel B., Raskin, Maryna, Rieg, Siegbert, Roig-Domínguez, Gustavo, Rojo, Pablo, Rubio-Mayo, Paula, Sacchi, Paolo, Sáez, Carlos, Salamanca, Elisa, Samayamuthu, Malarkodi Jebathilagam, Sanchez-Pinto, L. Nelson, Sandrin, Arnaud, Santhanam, Nandhini, Santos, Janaina C.C., Sanz Vidorreta, Fernando J., Savino, Maria, Schriver, Emily R., Schubert, Petra, Schuettler, Juergen, Scudeller, Luigia, Sebire, Neil J., Serrano-Balazote, Pablo, Serre, Patricia, Serret-Larmande, Arnaud, Shah, Mohsin, Hossein Abad, Zahra Shakeri, Silvio, Domenick, Sliz, Piotr, Son, Jiyeon, Sonday, Charles, South, Andrew M., Spiridou, Anastasia, Strasser, Zachary H., Tan, Amelia L.M., Tan, Bryce W.Q., Tan, Byorn W.L., Tanni, Suzana E., Taylor, Deanne M., Terriza-Torres, Ana I., Tibollo, Valentina, Tippmann, Patric, Toh, Emma M.S., Torti, Carlo, Trecarichi, Enrico M., Tseng, Yi-Ju, Vallejos, Andrew K., Varoquaux, Gael, Vella, Margaret E., Verdy, Guillaume, Vie, Jill-Jênn, Visweswaran, Shyam, Vitacca, Michele, Wagholikar, Kavishwar B., Waitman, Lemuel R., Wang, Xuan, Wassermann, Demian, Weber, Griffin M., Wolkewitz, Martin, Wong, Scott, Xia, Zongqi, Xiong, Xin, Ye, Ye, Yehya, Nadir, Yuan, William, Zambelli, Alberto, Zhang, Harrison G., Zo¨ller, Daniela, Zuccaro, Valentina, Zucco, Chiara, Mesa, Rebecca, and Verdy, Guillame
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- 2023
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11. Informative missingness: What can we learn from patterns in missing laboratory data in the electronic health record?
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Tan, Amelia L.M., Getzen, Emily J., Hutch, Meghan R., Strasser, Zachary H., Gutiérrez-Sacristán, Alba, Le, Trang T., Dagliati, Arianna, Morris, Michele, Hanauer, David A., Moal, Bertrand, Bonzel, Clara-Lea, Yuan, William, Chiudinelli, Lorenzo, Das, Priam, Zhang, Harrison G., Aronow, Bruce J., Avillach, Paul, Brat, Gabriel.A., Cai, Tianxi, Hong, Chuan, La Cava, William G., Hooi Will Loh, He, Luo, Yuan, Murphy, Shawn N., Yuan Hgiam, Kee, Omenn, Gilbert S., Patel, Lav P., Jebathilagam Samayamuthu, Malarkodi, Shriver, Emily R., Shakeri Hossein Abad, Zahra, Tan, Byorn W.L., Visweswaran, Shyam, Wang, Xuan, Weber, Griffin M., Xia, Zongqi, Verdy, Bertrand, Long, Qi, Mowery, Danielle L., and Holmes, John H.
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- 2023
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12. Genetic and Transcriptomic Variation Linked to Neutrophil Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Pediatric Crohn's Disease.
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Denson, Lee A, Jurickova, Ingrid, Karns, Rebekah, Shaw, Kelly A, Cutler, David J, Okou, David, Valencia, C Alexander, Dodd, Anne, Mondal, Kajari, Aronow, Bruce J, Haberman, Yael, Linn, Aaron, Price, Adam, Bezold, Ramona, Lake, Kathleen, Jackson, Kimberly, Walters, Thomas D, Griffiths, Anne, Baldassano, Robert N, Noe, Joshua D, Hyams, Jeffrey S, Crandall, Wallace V, Kirschner, Barbara S, Heyman, Melvin B, Snapper, Scott, Guthery, Stephen L, Dubinsky, Marla C, Leleiko, Neal S, Otley, Anthony R, Xavier, Ramnik J, Stevens, Christine, Daly, Mark J, Zwick, Michael E, and Kugathasan, Subra
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Genetics ,Autoimmune Disease ,Crohn's Disease ,Clinical Research ,Inflammatory Bowel Disease ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Adolescent ,Adult ,Case-Control Studies ,Child ,Child ,Preschool ,Crohn Disease ,Cytokine Receptor Common beta Subunit ,Female ,Follow-Up Studies ,Granulocyte-Macrophage Colony-Stimulating Factor ,Humans ,Infant ,Male ,Mutation ,Missense ,Neutrophils ,Prognosis ,Receptors ,Granulocyte-Macrophage Colony-Stimulating Factor ,Transcriptome ,Young Adult ,GM-CSF ,neutrophil ,pediatric inflammatory bowel disease ,RNA sequencing ,STAT5 ,whole-exome sequencing ,Clinical Sciences ,Gastroenterology & Hepatology - Abstract
BACKGROUND:Granulocyte-macrophage colony-stimulating factor auto-antibodies (GMAbs) suppress neutrophil-extrinsic GM-CSF signaling and increase risk for stricturing behavior in Crohn's disease (CD). We aimed to define clinical, genomic, and functional associations with neutrophil-intrinsic GM-CSF signaling. METHODS:Missense mutations in CSF2RA, CSF2RB, JAK2, STAT5A, and STAT5B were identified using whole-exome sequencing in 543 pediatric inflammatory bowel disease (IBD) patients. Neutrophil-intrinsic GM-CSF signaling was defined using the GM-CSF-induced STAT5 stimulation index (GMSI) in 180 pediatric IBD patients and 26 non-IBD controls. Reduced GM-CSF signaling (GMSI-Lo) was defined as the 20th percentile within the control group. Variation in neutrophil phospho-protein abundance, bacterial killing, and the global pattern of gene expression with the GMSI was determined. RESULTS:We validated 18 potentially damaging missense mutations in CSF2RA and CSF2RB. CSF2RA A17G carriage increased from 10% in those with intact neutrophil GMSI to 32% in those with low GMSI (P = 0.02). The frequency of reduced Staphylococcus aureus killing increased from 17% in those with intact neutrophil GMSI to 35% in GMSI-Lo neutrophils (P = 0.043). Crohn's disease neutrophils with low GMSI exhibited specific alterations in phospho-protein networks and genes regulating cytokine production, wound healing, and cell survival and proliferation. Stricturing behavior increased from 7% in patients with both low GMAb and intact GMSI to 64% in patients with both elevated GMAb and low GMSI (P < 0.0001). CONCLUSIONS:Low/normal neutrophil-intrinsic GM-CSF signaling is associated with CSF2RA missense mutations, alterations in gene expression networks, and higher rates of disease complications in pediatric CD.
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- 2019
13. Genetic variants and pathways implicated in a pediatric inflammatory bowel disease cohort
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Shaw, Kelly A, Cutler, David J, Okou, David, Dodd, Anne, Aronow, Bruce J, Haberman, Yael, Stevens, Christine, Walters, Thomas D, Griffiths, Anne, Baldassano, Robert N, Noe, Joshua D, Hyams, Jeffrey S, Crandall, Wallace V, Kirschner, Barbara S, Heyman, Melvin B, Snapper, Scott, Guthery, Stephen, Dubinsky, Marla C, Shapiro, Jason M, Otley, Anthony R, Daly, Mark, Denson, Lee A, Kugathasan, Subra, and Zwick, Michael E
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Biological Sciences ,Genetics ,Clinical Research ,Biotechnology ,Autoimmune Disease ,Pediatric ,Inflammatory Bowel Disease ,Crohn's Disease ,Digestive Diseases ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Oral and gastrointestinal ,Inflammatory and immune system ,Adolescent ,Child ,Child ,Preschool ,Female ,Genome-Wide Association Study ,Humans ,Infant ,Inflammatory Bowel Diseases ,Male ,Polymorphism ,Genetic ,Exome Sequencing ,Immunology - Abstract
In the United States, approximately 5% of individuals with inflammatory bowel disease (IBD) are younger than 20 years old. Studies of pediatric cohorts can provide unique insights into genetic architecture of IBD, which includes Crohn's disease (CD) and ulcerative colitis (UC). Large genome-wide association studies have found more than 200 IBD-associated loci but explain a minority of disease variance for CD and UC. We sought to characterize the contribution of rare variants to disease development, comparing exome sequencing of 368 pediatric IBD patients to publicly available exome sequencing (dbGaP) and aggregate frequency data (ExAC). Using dbGaP data, we performed logistic regression for common variants and optimal unified association tests (SKAT-O) for rare, likely-deleterious variants. We further compared rare variants to ExAC counts with Fisher's exact tests. We did pathway enrichment analysis on the most significant genes from each comparison. Many variants overlapped with known IBD-associated genes (e.g. NOD2). Rare variants were enriched in CD-associated loci (p = 0.009) and showed suggestive enrichment in neutrophil function genes (p = 0.05). Pathway enrichment implicated immune-related pathways, especially cell killing and apoptosis. Variants in extracellular matrix genes also emerged as an important theme in our analysis.
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- 2019
14. Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response
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Haberman, Yael, Karns, Rebekah, Dexheimer, Phillip J, Schirmer, Melanie, Somekh, Judith, Jurickova, Ingrid, Braun, Tzipi, Novak, Elizabeth, Bauman, Laura, Collins, Margaret H, Mo, Angela, Rosen, Michael J, Bonkowski, Erin, Gotman, Nathan, Marquis, Alison, Nistel, Mason, Rufo, Paul A, Baker, Susan S, Sauer, Cary G, Markowitz, James, Pfefferkorn, Marian D, Rosh, Joel R, Boyle, Brendan M, Mack, David R, Baldassano, Robert N, Shah, Sapana, Leleiko, Neal S, Heyman, Melvin B, Grifiths, Anne M, Patel, Ashish S, Noe, Joshua D, Aronow, Bruce J, Kugathasan, Subra, Walters, Thomas D, Gibson, Greg, Thomas, Sonia Davis, Mollen, Kevin, Shen-Orr, Shai, Huttenhower, Curtis, Xavier, Ramnik J, Hyams, Jeffrey S, and Denson, Lee A
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Biological Sciences ,Biomedical and Clinical Sciences ,Immunology ,Nutrition ,Inflammatory Bowel Disease ,Clinical Research ,Autoimmune Disease ,Digestive Diseases ,Genetics ,Biotechnology ,4.1 Discovery and preclinical testing of markers and technologies ,Aetiology ,2.1 Biological and endogenous factors ,Detection ,screening and diagnosis ,Oral and gastrointestinal ,Good Health and Well Being ,Adolescent ,Adult ,Anti-Inflammatory Agents ,Non-Steroidal ,Child ,Colitis ,Ulcerative ,Feces ,Female ,Gene Expression Profiling ,Genes ,Mitochondrial ,Glucocorticoids ,Humans ,Integrins ,Intestinal Mucosa ,Male ,Mesalamine ,Microbiota ,Mitochondria ,Mitochondrial Diseases ,Precision Medicine ,Prospective Studies ,Rectum ,Remission Induction ,Sequence Analysis ,RNA ,Severity of Illness Index ,Transcriptome ,Treatment Outcome ,Tumor Necrosis Factor-alpha - Abstract
Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α4β7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches.
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- 2019
15. Cross-platform validation of neurotransmitter release impairments in schizophrenia patient-derived NRXN1 -mutant neurons
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Pak, ChangHui, Danko, Tamas, Mirabella, Vincent R., Wang, Jinzhao, Liu, Yingfei, Vangipuram, Madhuri, Grieder, Sarah, Zhang, Xianglong, Ward, Thomas, Huang, Yu-Wen Alvin, Jin, Kang, Dexheimer, Philip, Bardes, Eric, Mitelpunkt, Alexis, Ma, Junyi, McLachlan, Michael, Moore, Jennifer C., Qu, Pingping, Purmann, Carolin, Dage, Jeffrey L., Swanson, Bradley J., Urban, Alexander E., Aronow, Bruce J., Pang, Zhiping P., Levinson, Douglas F., Wernig, Marius, and Südhof, Thomas C.
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- 2021
16. International electronic health record-derived post-acute sequelae profiles of COVID-19 patients
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Zhang, Harrison G., Dagliati, Arianna, Shakeri Hossein Abad, Zahra, Xiong, Xin, Bonzel, Clara-Lea, Xia, Zongqi, Tan, Bryce W. Q., Avillach, Paul, Brat, Gabriel A., Hong, Chuan, Morris, Michele, Visweswaran, Shyam, Patel, Lav P., Gutiérrez-Sacristán, Alba, Hanauer, David A., Holmes, John H., Samayamuthu, Malarkodi Jebathilagam, Bourgeois, Florence T., L’Yi, Sehi, Maidlow, Sarah E., Moal, Bertrand, Murphy, Shawn N., Strasser, Zachary H., Neuraz, Antoine, Ngiam, Kee Yuan, Loh, Ne Hooi Will, Omenn, Gilbert S., Prunotto, Andrea, Dalvin, Lauren A., Klann, Jeffrey G., Schubert, Petra, Vidorreta, Fernando J. Sanz, Benoit, Vincent, Verdy, Guillaume, Kavuluru, Ramakanth, Estiri, Hossein, Luo, Yuan, Malovini, Alberto, Tibollo, Valentina, Bellazzi, Riccardo, Cho, Kelly, Ho, Yuk-Lam, Tan, Amelia L. M., Tan, Byorn W. L., Gehlenborg, Nils, Lozano-Zahonero, Sara, Jouhet, Vianney, Chiovato, Luca, Aronow, Bruce J., Toh, Emma M. S., Wong, Wei Gen Scott, Pizzimenti, Sara, Wagholikar, Kavishwar B., Bucalo, Mauro, Cai, Tianxi, South, Andrew M., Kohane, Isaac S., and Weber, Griffin M.
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- 2022
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17. Clinical and Genomic Correlates of Neutrophil Reactive Oxygen Species Production in Pediatric Patients With Crohn’s Disease
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Denson, Lee A, Jurickova, Ingrid, Karns, Rebekah, Shaw, Kelly A, Cutler, David J, Okou, David T, Dodd, Anne, Quinn, Kathryn, Mondal, Kajari, Aronow, Bruce J, Haberman, Yael, Linn, Aaron, Price, Adam, Bezold, Ramona, Lake, Kathleen, Jackson, Kimberly, Walters, Thomas D, Griffiths, Anne, Baldassano, Robert N, Noe, Joshua D, Hyams, Jeffrey S, Crandall, Wallace V, Kirschner, Barbara S, Heyman, Melvin B, Snapper, Scott, Guthery, Stephen L, Dubinsky, Marla C, Leleiko, Neal S, Otley, Anthony R, Xavier, Ramnik J, Stevens, Christine, Daly, Mark J, Zwick, Michael E, and Kugathasan, Subra
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Biomedical and Clinical Sciences ,Clinical Sciences ,Autoimmune Disease ,Pediatric ,Crohn's Disease ,Digestive Diseases ,Inflammatory Bowel Disease ,Clinical Research ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Adolescent ,Alleles ,Child ,Child ,Preschool ,Cohort Studies ,Crohn Disease ,Down-Regulation ,Female ,Gene Expression Profiling ,Glucose ,Humans ,Infant ,Male ,Mutation ,Missense ,NADPH Oxidases ,Neutrophils ,Phenotype ,Reactive Oxygen Species ,Sequence Analysis ,RNA ,Up-Regulation ,Exome Sequencing ,WES ,IBD ,Neutrophil Oxidative Burst ,Genetic Variant ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Background & aimsIndividuals with monogenic disorders of phagocyte function develop chronic colitis that resembles Crohn's disease (CD). We tested for associations between mutations in genes encoding reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, neutrophil function, and phenotypes of CD in pediatric patients.MethodsWe performed whole-exome sequence analysis to identify mutations in genes encoding NADPH oxidases (such as CYBA, CYBB, NCF1, NCF2, NCF4, RAC1, and RAC2) using DNA from 543 pediatric patients with inflammatory bowel diseases. Blood samples were collected from an additional 129 pediatric patients with CD and 26 children without IBD (controls); we performed assays for neutrophil activation, reactive oxygen species (ROS) production, and bacteria uptake and killing. Whole-exome sequence analysis was performed using DNA from 46 of the children with CD to examine associations with NADPH gene mutations; RNA sequence analyses were performed using blood cells from 46 children with CD to test for variations in neutrophil gene expression associated with ROS production.ResultsWe identified 26 missense mutations in CYBA, CYBB, NCF1, NCF2, and NCF4. Patients with CD who carried mutations in these genes were 3-fold more likely to have perianal disease (P = .0008) and stricturing complications (P = .002) than children with CD without these mutations. Among patients with CD with none of these mutations, 9% had undergone abdominal surgery; among patients with mutations in these NADPH oxidase genes, 31% had undergone abdominal surgery (P = .0004). A higher proportion of neutrophils from children with CD had low ROS production (47%) than from controls (15%) among the 129 patients tested for ROS (P = .002). Minor alleles of the NADPH genes were detected in 7% of children with CD whose neutrophils produced normal levels of ROS vs 38% of children whose neutrophils produced low levels of ROS (P = .009). Neutrophils that produced low levels of ROS had specific alterations in genes that regulate glucose metabolism and antimicrobial responses.ConclusionsWe identified missense mutations in genes that encode NADPH oxidases in children with CD; these were associated with a more aggressive disease course and reduced ROS production by neutrophils from the patients.
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- 2018
18. Whole-exome sequencing uncovers oxidoreductases DHTKD1 and OGDHL as linkers between mitochondrial dysfunction and eosinophilic esophagitis.
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Sherrill, Joseph D, Kc, Kiran, Wang, Xinjian, Wen, Ting, Chamberlin, Adam, Stucke, Emily M, Collins, Margaret H, Abonia, J Pablo, Peng, Yanyan, Wu, Qiang, Putnam, Philip E, Dexheimer, Phillip J, Aronow, Bruce J, Kottyan, Leah C, Kaufman, Kenneth M, Harley, John B, Huang, Taosheng, and Rothenberg, Marc E
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T-Lymphocytes ,Mitochondria ,Fibroblasts ,Epithelial Cells ,Humans ,Ketoglutarate Dehydrogenase Complex ,Oxidoreductases ,Ketone Oxidoreductases ,Oxidoreductases Acting on CH-CH Group Donors ,Proteins ,RNA ,Small Interfering ,Interleukin-13 ,Cytokines ,Up-Regulation ,Mutation ,Adult ,Child ,Female ,Male ,Eosinophilic Esophagitis ,Exome Sequencing ,Allergy ,Cellular immune response ,Immunology ,Inflammation ,Human Genome ,Food Allergies ,Clinical Research ,Genetics ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Whole Exome Sequencing - Abstract
Eosinophilic esophagitis (EoE) is an allergic inflammatory esophageal disorder with a complex underlying genetic etiology often associated with other comorbidities. Using whole-exome sequencing (WES) of 63 patients with EoE and 60 unaffected family members and family-based trio analysis, we sought to uncover rare coding variants. WES analysis identified 5 rare, damaging variants in dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1). Rare variant burden analysis revealed an overabundance of putative, potentially damaging DHTKD1 mutations in EoE (P = 0.01). Interestingly, we also identified 7 variants in the DHTKD1 homolog oxoglutarate dehydrogenase-like (OGDHL). Using shRNA-transduced esophageal epithelial cells and/or patient fibroblasts, we further showed that disruption of normal DHTKD1 or OGDHL expression blunts mitochondrial function. Finally, we demonstrated that the loss of DHTKD1 expression increased ROS production and induced the expression of viperin, a gene previously shown to be involved in production of Th2 cytokines in T cells. Viperin had increased expression in esophageal biopsies of EoE patients compared with control individuals and was upregulated by IL-13 in esophageal epithelial cells. These data identify a series of rare genetic variants implicating DHTKD1 and OGDHL in the genetic etiology of EoE and underscore a potential pathogenic role for mitochondrial dysfunction in EoE.
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- 2018
19. A Study on Gait Quality Assessment for Cerebral Palsy Using Unsupervised Deep Learning Model
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SUMI, Ginga, primary, KITAJIMA, Takumi, additional, KAWANAKA, Hiroharu, additional, IYER, Balaji, additional, SURYA PRASATH, V. B., additional, and ARONOW, Bruce J., additional
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- 2024
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20. LungMAP Portal Ecosystem: Systems-level Exploration of the Lung
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Gaddis, Nathan, primary, Fortriede, Joshua, additional, Guo, Minzhe, additional, Bardes, Eric E., additional, Kouril, Michal, additional, Tabar, Scott, additional, Burns, Kevin, additional, Ardini-Poleske, Maryanne E., additional, Loos, Stephanie, additional, Schnell, Daniel, additional, Jin, Kang, additional, Iyer, Balaji, additional, Du, Yina, additional, Huo, Bing-Xing, additional, Bhattacharjee, Anukana, additional, Korte, Jeff, additional, Munshi, Ruchi, additional, Smith, Victoria, additional, Herbst, Andrew, additional, Kitzmiller, Joseph A., additional, Clair, Geremy C., additional, Carson, James P., additional, Adkins, Joshua, additional, Morrisey, Edward E., additional, Pryhuber, Gloria S., additional, Misra, Ravi, additional, Whitsett, Jeffrey A., additional, Sun, Xin, additional, Heathorn, Trevor, additional, Paten, Benedict, additional, Prasath, V. B. Surya, additional, Xu, Yan, additional, Tickle, Tim, additional, Aronow, Bruce J., additional, and Salomonis, Nathan, additional
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- 2024
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21. An interactive single cell web portal identifies gene and cell networks in COVID-19 host responses
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Jin, Kang, Bardes, Eric E., Mitelpunkt, Alexis, Wang, Jake Y., Bhatnagar, Surbhi, Sengupta, Soma, Krummel, Daniel Pomeranz, Rothenberg, Marc E., and Aronow, Bruce J.
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- 2021
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22. AB569, a nontoxic chemical tandem that kills major human pathogenic bacteria
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McDaniel, Cameron T., Panmanee, Warunya, Winsor, Geoffrey L., Gill, Erin, Bertelli, Claire, Schurr, Michael J., Dongare, Prateek, Paul, Andrew T., Ko, Seung-Hyun B., Lau, Gee W., Dasgupta, Nupur, Bogue, Amy L., Miller, William E., Mortensen, Joel E., Haslam, David B., Dexheimer, Phillip, Muruve, Daniel A., Aronow, Bruce J., Forbes, Malcolm D. E., Danilczuk, Marek, Brinkman, Fiona S. L., Hancock, Robert E. W., Meyer, Thomas J., and Hassett, Daniel J.
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- 2020
23. Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease
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Marigorta, Urko M, Denson, Lee A, Hyams, Jeffrey S, Mondal, Kajari, Prince, Jarod, Walters, Thomas D, Griffiths, Anne, Noe, Joshua D, Crandall, Wallace V, Rosh, Joel R, Mack, David R, Kellermayer, Richard, Heyman, Melvin B, Baker, Susan S, Stephens, Michael C, Baldassano, Robert N, Markowitz, James F, Kim, Mi-Ok, Dubinsky, Marla C, Cho, Judy, Aronow, Bruce J, Kugathasan, Subra, and Gibson, Greg
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Biological Sciences ,Genetics ,Crohn's Disease ,Prevention ,Human Genome ,Autoimmune Disease ,Inflammatory Bowel Disease ,Digestive Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Age of Onset ,Alleles ,Child ,Crohn Disease ,Datasets as Topic ,Disease Progression ,Gene Expression Profiling ,Gene Expression Regulation ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Ileum ,Inflammatory Bowel Diseases ,Models ,Genetic ,Observational Studies as Topic ,Polymorphism ,Single Nucleotide ,Prognosis ,Quantitative Trait Loci ,RNA ,Messenger ,Risk Assessment ,Transcription ,Genetic ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease. We show that TRSs based on genes regulated by variants linked to inflammatory bowel disease (IBD) not only outperform genetic risk scores (GRSs) in distinguishing Crohn's disease from healthy samples, but also serve to identify patients who in time will progress to complicated disease. Our dissection of eQTL effects may be used to distinguish genes whose association with disease is through promotion versus protection, thereby linking statistical association to biological mechanism. The TRS approach constitutes a potential strategy for personalized medicine that enhances inference from static genotypic risk assessment.
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- 2017
24. Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study
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Kugathasan, Subra, Denson, Lee A, Walters, Thomas D, Kim, Mi-Ok, Marigorta, Urko M, Schirmer, Melanie, Mondal, Kajari, Liu, Chunyan, Griffiths, Anne, Noe, Joshua D, Crandall, Wallace V, Snapper, Scott, Rabizadeh, Shervin, Rosh, Joel R, Shapiro, Jason M, Guthery, Stephen, Mack, David R, Kellermayer, Richard, Kappelman, Michael D, Steiner, Steven, Moulton, Dedrick E, Keljo, David, Cohen, Stanley, Oliva-Hemker, Maria, Heyman, Melvin B, Otley, Anthony R, Baker, Susan S, Evans, Jonathan S, Kirschner, Barbara S, Patel, Ashish S, Ziring, David, Trapnell, Bruce C, Sylvester, Francisco A, Stephens, Michael C, Baldassano, Robert N, Markowitz, James F, Cho, Judy, Xavier, Ramnik J, Huttenhower, Curtis, Aronow, Bruce J, Gibson, Greg, Hyams, Jeffrey S, and Dubinsky, Marla C
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Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Inflammatory Bowel Disease ,Prevention ,Autoimmune Disease ,Clinical Research ,Digestive Diseases ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Adalimumab ,Adolescent ,Anti-Inflammatory Agents ,Non-Steroidal ,Child ,Cohort Studies ,Crohn Disease ,Disease Progression ,Female ,Gastrointestinal Microbiome ,Humans ,Infliximab ,Intestinal Obstruction ,Male ,Prognosis ,Propensity Score ,Prospective Studies ,Risk Assessment ,Severity of Illness Index ,Tumor Necrosis Factor-alpha ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundStricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown.MethodsWe did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk.FindingsBetween Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51-82) and specificity of 63% (55-71), with a negative predictive value of 95% (94-97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10-0·89; p=0·0296) but not stricturing complication (1·13, 0·51-2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12-2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%.InterpretationOur findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy.FundingCrohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.
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- 2017
25. Computational Nuclei Segmentation Methods in Digital Pathology: A Survey
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Hayakawa, Tomohiro, Prasath, V. B. Surya, Kawanaka, Hiroharu, Aronow, Bruce J., and Tsuruoka, Shinji
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- 2021
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26. Integration of Molecular Analysis, Cutting-edge Mouse Genetic Models and Proton Therapy to Improve Outcomes for Glioma Patients
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Sengupta, Soma, primary, Pater, Luke E., additional, Krummel, Daniel Pomeranz, additional, Aronow, Bruce J., additional, Hirota, Yoshihisa, additional, Phoenix, Timothy N., additional, and Sasaki, Atsuo T., additional
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- 2021
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27. African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors associated with immunologic functions and environmental exposures
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Singh, Urminder, Hernandez, Kyle M., Aronow, Bruce J., and Wurtele, Eve Syrkin
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- 2021
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28. Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortium
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Sperotto, Francesca, primary, Gutiérrez-Sacristán, Alba, additional, Makwana, Simran, additional, Li, Xiudi, additional, Rofeberg, Valerie N., additional, Cai, Tianxi, additional, Bourgeois, Florence T., additional, Omenn, Gilbert S., additional, Hanauer, David A., additional, Sáez, Carlos, additional, Bonzel, Clara-Lea, additional, Bucholz, Emily, additional, Dionne, Audrey, additional, Elias, Matthew D., additional, García-Barrio, Noelia, additional, González, Tomás González, additional, Issitt, Richard W., additional, Kernan, Kate F., additional, Laird-Gion, Jessica, additional, Maidlow, Sarah E., additional, Mandl, Kenneth D., additional, Ahooyi, Taha Mohseni, additional, Moraleda, Cinta, additional, Morris, Michele, additional, Moshal, Karyn L., additional, Pedrera-Jiménez, Miguel, additional, Shah, Mohsin A., additional, South, Andrew M., additional, Spiridou, Anastasia, additional, Taylor, Deanne M., additional, Verdy, Guillaume, additional, Visweswaran, Shyam, additional, Wang, Xuan, additional, Xia, Zongqi, additional, Zachariasse, Joany M., additional, Newburger, Jane W., additional, Avillach, Paul, additional, Aaron, James R., additional, Adam, Atif, additional, Agapito, Giuseppe, additional, Albayrak, Adem, additional, Albi, Giuseppe, additional, Alessiani, Mario, additional, Alloni, Anna, additional, Amendola, Danilo F., additional, Angoulvant, François, additional, Anthony, Li LLJ., additional, Aronow, Bruce J., additional, Ashraf, Fatima, additional, Atz, Andrew, additional, Panickan, Vidul Ayakulangara, additional, Azevedo, Paula S., additional, Badenes, Rafael, additional, Balshi, James, additional, Batugo, Ashley, additional, Beaulieu-Jones, Brendin R., additional, Beaulieu-Jones, Brett K., additional, Bell, Douglas S., additional, Bellasi, Antonio, additional, Bellazzi, Riccardo, additional, Benoit, Vincent, additional, Beraghi, Michele, additional, Bernal-Sobrino, José Luis, additional, Bernaux, Mélodie, additional, Bey, Romain, additional, Bhatnagar, Surbhi, additional, Blanco-Martínez, Alvar, additional, Boeker, Martin, additional, Booth, John, additional, Bosari, Silvano, additional, Bradford, Robert L., additional, Brat, Gabriel A., additional, Bréant, Stéphane, additional, Brown, Nicholas W., additional, Bruno, Raffaele, additional, Bryant, William A., additional, Bucalo, Mauro, additional, Burgun, Anita, additional, Cannataro, Mario, additional, Carmona, Aldo, additional, Cattelan, Anna Maria, additional, Caucheteux, Charlotte, additional, Champ, Julien, additional, Chen, Jin, additional, Chen, Krista Y., additional, Chiovato, Luca, additional, Chiudinelli, Lorenzo, additional, Cho, Kelly, additional, Cimino, James J., additional, Colicchio, Tiago K., additional, Cormont, Sylvie, additional, Cossin, Sébastien, additional, Craig, Jean B., additional, Cruz-Bermúdez, Juan Luis, additional, Cruz-Rojo, Jaime, additional, Dagliati, Arianna, additional, Daniar, Mohamad, additional, Daniel, Christel, additional, Das, Priyam, additional, Devkota, Batsal, additional, Duan, Rui, additional, Dubiel, Julien, additional, DuVall, Scott L., additional, Esteve, Loic, additional, Estiri, Hossein, additional, Fan, Shirley, additional, Follett, Robert W., additional, Ganslandt, Thomas, additional, Garmire, Lana X., additional, Gehlenborg, Nils, additional, Getzen, Emily J., additional, Geva, Alon, additional, Goh, Rachel SJ., additional, Gradinger, Tobias, additional, Gramfort, Alexandre, additional, Griffier, Romain, additional, Griffon, Nicolas, additional, Grisel, Olivier, additional, Guzzi, Pietro H., additional, Han, Larry, additional, Haverkamp, Christian, additional, Hazard, Derek Y., additional, He, Bing, additional, Henderson, Darren W., additional, Hilka, Martin, additional, Ho, Yuk-Lam, additional, Holmes, John H., additional, Honerlaw, Jacqueline P., additional, Hong, Chuan, additional, Huling, Kenneth M., additional, Hutch, Meghan R., additional, Jannot, Anne Sophie, additional, Jouhet, Vianney, additional, Kainth, Mundeep K., additional, Kate, Kernan F., additional, Kavuluru, Ramakanth, additional, Keller, Mark S., additional, Kennedy, Chris J., additional, Key, Daniel A., additional, Kirchoff, Katie, additional, Klann, Jeffrey G., additional, Kohane, Isaac S., additional, Krantz, Ian D., additional, Kraska, Detlef, additional, Krishnamurthy, Ashok K., additional, L'Yi, Sehi, additional, Leblanc, Judith, additional, Lemaitre, Guillaume, additional, Lenert, Leslie, additional, Leprovost, Damien, additional, Liu, Molei, additional, Will Loh, Ne Hooi, additional, Long, Qi, additional, Lozano-Zahonero, Sara, additional, Luo, Yuan, additional, Lynch, Kristine E., additional, Mahmood, Sadiqa, additional, Makoudjou, Adeline, additional, Malovini, Alberto, additional, Mao, Chengsheng, additional, Maram, Anupama, additional, Maripuri, Monika, additional, Martel, Patricia, additional, Martins, Marcelo R., additional, Marwaha, Jayson S., additional, Masino, Aaron J., additional, Mazzitelli, Maria, additional, Mazzotti, Diego R., additional, Mensch, Arthur, additional, Milano, Marianna, additional, Minicucci, Marcos F., additional, Moal, Bertrand, additional, Moore, Jason H., additional, Morris, Jeffrey S., additional, Mousavi, Sajad, additional, Mowery, Danielle L., additional, Murad, Douglas A., additional, Murphy, Shawn N., additional, Naughton, Thomas P., additional, Breda Neto, Carlos Tadeu, additional, Neuraz, Antoine, additional, Newburger, Jane, additional, Ngiam, Kee Yuan, additional, Njoroge, Wanjiku FM., additional, Norman, James B., additional, Obeid, Jihad, additional, Okoshi, Marina P., additional, Olson, Karen L., additional, Orlova, Nina, additional, Ostasiewski, Brian D., additional, Palmer, Nathan P., additional, Paris, Nicolas, additional, Patel, Lav P., additional, Pfaff, Ashley C., additional, Pfaff, Emily R., additional, Pillion, Danielle, additional, Pizzimenti, Sara, additional, Priya, Tanu, additional, Prokosch, Hans U., additional, Prudente, Robson A., additional, Prunotto, Andrea, additional, Quirós-González, Víctor, additional, Ramoni, Rachel B., additional, Raskin, Maryna, additional, Rieg, Siegbert, additional, Roig-Domínguez, Gustavo, additional, Rojo, Pablo, additional, Romero-Garcia, Nekane, additional, Rubio-Mayo, Paula, additional, Sacchi, Paolo, additional, Salamanca, Elisa, additional, Samayamuthu, Malarkodi Jebathilagam, additional, Sanchez-Pinto, L. Nelson, additional, Sandrin, Arnaud, additional, Santhanam, Nandhini, additional, Santos, Janaina C.C., additional, Sanz Vidorreta, Fernando J., additional, Savino, Maria, additional, Schriver, Emily R., additional, Schubert, Petra, additional, Schuettler, Juergen, additional, Scudeller, Luigia, additional, Sebire, Neil J., additional, Serrano-Balazote, Pablo, additional, Serre, Patricia, additional, Serret-Larmande, Arnaud, additional, Hossein Abad, Zahra Shakeri, additional, Silvio, Domenick, additional, Sliz, Piotr, additional, Son, Jiyeon, additional, Sonday, Charles, additional, Sperotto, Francesca, additional, Strasser, Zachary H., additional, Tan, Amelia LM., additional, Tan, Bryce W.Q., additional, Tan, Byorn W.L., additional, Tanni, Suzana E., additional, Terriza-Torres, Ana I., additional, Tibollo, Valentina, additional, Tippmann, Patric, additional, Toh, Emma MS., additional, Torti, Carlo, additional, Trecarichi, Enrico M., additional, Vallejos, Andrew K., additional, Varoquaux, Gael, additional, Vella, Margaret E., additional, Vie, Jill-Jênn, additional, Vitacca, Michele, additional, Wagholikar, Kavishwar B., additional, Waitman, Lemuel R., additional, Wassermann, Demian, additional, Weber, Griffin M., additional, Wolkewitz, Martin, additional, Wong, Scott, additional, Xiong, Xin, additional, Ye, Ye, additional, Yehya, Nadir, additional, Yuan, William, additional, Zahner, Janet J., additional, Zambelli, Alberto, additional, Zhang, Harrison G., additional, Zöller, Daniela, additional, Zuccaro, Valentina, additional, and Zucco, Chiara, additional
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- 2023
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29. Bering:joint cell segmentation and annotation for spatial transcriptomics with transferred graph embeddings
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Jin, Kang, primary, Zhang, Zuobai, additional, Zhang, Ke, additional, Viggiani, Francesca, additional, Callahan, Claire, additional, Tang, Jian, additional, Aronow, Bruce J., additional, and Shu, Jian, additional
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- 2023
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30. What Every Reader Should Know About Studies Using Electronic Health Record Data but May Be Afraid to Ask
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Kohane, Isaac S, Aronow, Bruce J, Avillach, Paul, Beaulieu-Jones, Brett K, Bellazzi, Riccardo, Bradford, Robert L, Brat, Gabriel A, Cannataro, Mario, Cimino, James J, García-Barrio, Noelia, Gehlenborg, Nils, Ghassemi, Marzyeh, Gutiérrez-Sacristán, Alba, Hanauer, David A, Holmes, John H, Hong, Chuan, Klann, Jeffrey G, Loh, Ne Hooi Will, Luo, Yuan, Mandl, Kenneth D, Daniar, Mohamad, Moore, Jason H, Murphy, Shawn N, Neuraz, Antoine, Ngiam, Kee Yuan, Omenn, Gilbert S, Palmer, Nathan, Patel, Lav P, Pedrera-Jiménez, Miguel, Sliz, Piotr, South, Andrew M, Tan, Amelia Li Min, Taylor, Deanne M, Taylor, Bradley W, Torti, Carlo, Vallejos, Andrew K, Wagholikar, Kavishwar B, Weber, Griffin M, and Cai, Tianxi
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Public aspects of medicine ,RA1-1270 - Abstract
Coincident with the tsunami of COVID-19–related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field.
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- 2021
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31. Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis
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Wen, Ting, Aronow, Bruce J., Rochman, Yrina, Rochman, Mark, Kiran, K.C., Dexheimer, Phil J., Putnam, Philip, Mukkada, Vincent, Foote, Heather, Rehn, Kira, Darko, Sam, Douek, Daniel, and Rothenberg, Marc E.
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Esophagitis -- Genetic aspects -- Research ,RNA sequencing -- Research ,T cells -- Research ,Lymphocytes ,Inflammation ,B cells ,Allergy ,Fatty acids ,RNA ,Phenotypes ,Health care industry - Abstract
T cell heterogeneity is highly relevant to allergic disorders. We resolved the heterogeneity of human tissue [CD3.sup.+] T cells during allergic inflammation, focusing on a tissue-specific allergic disease, eosinophilic esophagitis (EoE). We investigated 1088 single T cells derived from patients with a spectrum of disease activity. Eight disparate tissue T cell subtypes (designated T1-T8) were identified, with T7 and T8 enriched in the diseased tissue. The phenotypes of T7 and T8 resemble putative Treg ([FOXP3.sup.+]) and effector Th2-like ([GATA3.sup.+]) cells, respectively. Prodigious levels of IL-5 and IL-13 were confined to [HPGDS.sup.+] [CRTH2.sup.+][IL-17RB.sup.+][FFAR3.sup.+][CD4.sup.+] T8 effector Th2 cells. EoE severity closely paralleled a lipid/fatty acid-induced activation node highlighted by the expression of the short-chain fatty acid receptor FFAR3. Ligands for FFAR3 induced Th2 cytokine production from human and murine T cells, including in an in vivo allergy model. Therefore, we elucidated the defining characteristics of tissue-residing [CD3.sup.+] T cells in EoE, a specific enrichment of [CD4.sup.+] Treg and effector Th2 cells, confinement of type 2 cytokine production to the [CD4.sup.+] effector population, a highly likely role for FFAR3 in amplifying local Th2 responses in EoE, and a resource to further dissect tissue lymphocytes and allergic responses., Introduction Substantial heterogeneity of [CD3.sup.+] T cells exist, starting grossly with [CD4.sup.+] and [CD8.sup.+] cells, which are involved in helper and cytotoxic responses, respectively. [CD4.sup.+] T helper (Th) cells, as [...]
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- 2019
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32. MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors
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Jessen, Walter J, Miller, Shyra J, Jousma, Edwin, Wu, Jianqiang, Rizvi, Tilat A, Brundage, Meghan E, Eaves, David, Widemann, Brigitte, Kim, Mi-Ok, Dombi, Eva, Sabo, Jessica, Dudley, Atira Hardiman, Niwa-Kawakita, Michiko, Page, Grier P, Giovannini, Marco, Aronow, Bruce J, Cripe, Timothy P, and Ratner, Nancy
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Pediatric ,Cancer ,Neurofibromatosis ,Biotechnology ,Neurosciences ,Animals ,Benzamides ,Child ,Child ,Preschool ,Diphenylamine ,Extracellular Signal-Regulated MAP Kinases ,Female ,Humans ,Male ,Mice ,Mice ,Mutant Strains ,Mitogen-Activated Protein Kinase Kinases ,Neoplasm Transplantation ,Neurofibromatosis 1 ,Oncogene Protein p21(ras) ,Peripheral Nervous System Neoplasms ,Transcriptome ,Transplantation ,Heterologous ,Xenograft Model Antitumor Assays ,raf Kinases ,Medical and Health Sciences ,Immunology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating the effects of hyperactive Ras in NF1 tumors are unknown. We performed cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs and identified global negative feedback of genes that regulate Ras/Raf/MEK/ERK signaling in both species. Nonetheless, ERK activation was sustained in mouse and human neurofibromas and MPNST. We used a highly selective pharmacological inhibitor of MEK, PD0325901, to test whether sustained Ras/Raf/MEK/ERK signaling contributes to neurofibroma growth in a neurofibromatosis mouse model (Nf1(fl/fl);Dhh-Cre) or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in more than 80% of mice tested. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide a strong rationale for testing MEK inhibitors in NF1 clinical trials.
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- 2013
33. Cancer Informatics for Cancer Centers: Scientific Drivers for Informatics, Data Science, and Care in Pediatric, Adolescent, and Young Adult Cancer
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Kerlavage, Anthony R., Kirchhoff, Anne C., Guidry Auvil, Jaime M., Sharpless, Norman E., Davis, Kara L., Reilly, Karlyne, Reaman, Gregory, Penberthy, Lynne, Deapen, Dennis, Hwang, Amie, Durbin, Eric B., Gallotto, Sara L., Aplenc, Richard, Volchenboum, Samuel L., Heath, Allison P., Aronow, Bruce J., Zhang, Jinghui, Vaske, Olena, Alonzo, Todd A., Nathan, Paul C., Poynter, Jenny N., Armstrong, Greg, Hahn, Erin E., Wernli, Karen J., Greene, Casey, DiGiovanna, Jack, Resnick, Adam C., Shalley, Eve R., Nadaf, Sorena, and Kibbe, Warren A.
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- 2021
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34. Bridging the gap between systems biology and medicine
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Clermont, Gilles, Auffray, Charles, Moreau, Yves, Rocke, David M, Dalevi, Daniel, Dubhashi, Devdatt, Marshall, Dana R, Raasch, Peter, Dehne, Frank, Provero, Paolo, Tegner, Jesper, Aronow, Bruce J, Langston, Michael A, and Benson, Mikael
- Abstract
Abstract Systems biology has matured considerably as a discipline over the last decade, yet some of the key challenges separating current research efforts in systems biology and clinically useful results are only now becoming apparent. As these gaps are better defined, the new discipline of systems medicine is emerging as a translational extension of systems biology. How is systems medicine defined? What are relevant ontologies for systems medicine? What are the key theoretic and methodologic challenges facing computational disease modeling? How are inaccurate and incomplete data, and uncertain biologic knowledge best synthesized in useful computational models? Does network analysis provide clinically useful insight? We discuss the outstanding difficulties in translating a rapidly growing body of data into knowledge usable at the bedside. Although core-specific challenges are best met by specialized groups, it appears fundamental that such efforts should be guided by a roadmap for systems medicine drafted by a coalition of scientists from the clinical, experimental, computational, and theoretic domains.
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- 2009
35. Transcriptome Signature of Irreversible Senescence in Human Papillomavirus-Positive Cervical Cancer Cells
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Wells, Susanne I., Aronow, Bruce J., Wise, Trisha M., Williams, Sarah S., Couget, Jennifer A., and Howley, Peter M.
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- 2003
36. Clusterin Promotes Amyloid Plaque Formation and is Critical for Neuritic Toxicity in a Mouse Model of Alzheimer's Disease
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DeMattos, Ronald B., O'dell, Mark A., Parsadanian, Maia, Taylor, Jennie W., Bales, Kelly R., Paul, Steven M., Aronow, Bruce J., and Holtzman, David M.
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- 2002
37. Automatic disease stage classification of glioblastoma multiforme histopathological images using deep convolutional neural network
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Yonekura, Asami, Kawanaka, Hiroharu, Prasath, V. B. Surya, Aronow, Bruce J., and Takase, Haruhiko
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- 2018
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38. The Genetic Landscape of Hypoplastic Left Heart Syndrome
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Yagi, Hisato, Liu, Xiaoqin, Gabriel, George C., Wu, Yijen, Peterson, Kevin, Murray, Stephen A., Aronow, Bruce J., Martin, Lisa J., Benson, D. Woodrow, and Lo, Cecilia W.
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- 2018
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39. Spatial transcriptome profiling uncovers metabolic regulation of left-right patterning
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Yagi, Hisato, primary, Cui, Cheng, additional, Saydmohammed, Manush, additional, Gabriel, George, additional, Baker, Candice, additional, Devine, William, additional, Wu, Yijen, additional, Lin, Jiuann-huey, additional, Malek, Marcus, additional, Bais, Abha, additional, Murray, Stephen, additional, Aronow, Bruce J, additional, Tsang, Michael J, additional, Kostka, Dennis, additional, and Lo, Cecilia W, additional
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- 2023
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40. Editor's Note: Activator Protein-1 Transcription Factors Are Associated with Progression and Recurrence of Prostate Cancer
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Ouyang, Xuesong, primary, Jessen, Walter J., additional, Al-Ahmadie, Hikmat, additional, Serio, Angel M., additional, Lin, Yong, additional, Shih, Weichung-Joseph, additional, Reuter, Victor E., additional, Scardino, Peter T., additional, Shen, Michael M., additional, Aronow, Bruce J., additional, Vickers, Andrew J., additional, Gerald, William L., additional, and Abate-Shen, Cory, additional
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- 2023
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41. Data from Gene Expression Analysis Identifies Potential Biomarkers of Neurofibromatosis Type 1 Including Adrenomedullin
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Hummel, Trent R., primary, Jessen, Walter J., primary, Miller, Shyra J., primary, Kluwe, Lan, primary, Mautner, Victor F., primary, Wallace, Margaret R., primary, Lázaro, Conxi, primary, Page, Grier P., primary, Worley, Paul F., primary, Aronow, Bruce J., primary, Schorry, Elizabeth K., primary, and Ratner, Nancy, primary
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- 2023
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42. Supplementary Figures 2 - 4 from Ras-Driven Transcriptome Analysis Identifies Aurora Kinase A as a Potential Malignant Peripheral Nerve Sheath Tumor Therapeutic Target
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Patel, Ami V., primary, Eaves, David, primary, Jessen, Walter J., primary, Rizvi, Tilat A., primary, Ecsedy, Jeffrey A., primary, Qian, Mark G., primary, Aronow, Bruce J., primary, Perentesis, John P., primary, Serra, Eduard, primary, Cripe, Timothy P., primary, Miller, Shyra J., primary, and Ratner, Nancy, primary
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- 2023
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43. Supplement 1 from Gene Expression Analysis Identifies Potential Biomarkers of Neurofibromatosis Type 1 Including Adrenomedullin
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Hummel, Trent R., primary, Jessen, Walter J., primary, Miller, Shyra J., primary, Kluwe, Lan, primary, Mautner, Victor F., primary, Wallace, Margaret R., primary, Lázaro, Conxi, primary, Page, Grier P., primary, Worley, Paul F., primary, Aronow, Bruce J., primary, Schorry, Elizabeth K., primary, and Ratner, Nancy, primary
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- 2023
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44. Supplementary Figure 1 from Ras-Driven Transcriptome Analysis Identifies Aurora Kinase A as a Potential Malignant Peripheral Nerve Sheath Tumor Therapeutic Target
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Patel, Ami V., primary, Eaves, David, primary, Jessen, Walter J., primary, Rizvi, Tilat A., primary, Ecsedy, Jeffrey A., primary, Qian, Mark G., primary, Aronow, Bruce J., primary, Perentesis, John P., primary, Serra, Eduard, primary, Cripe, Timothy P., primary, Miller, Shyra J., primary, and Ratner, Nancy, primary
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- 2023
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45. Supplementary Figure 4 from Credentialing a Preclinical Mouse Model of Alveolar Rhabdomyosarcoma
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Nishijo, Koichi, primary, Chen, Qing-Rong, primary, Zhang, Lei, primary, McCleish, Amanda T., primary, Rodriguez, Andrea, primary, Cho, Min Jung, primary, Prajapati, Suresh I., primary, Gelfond, Jonathan A.L., primary, Chisholm, Gary B., primary, Michalek, Joel E., primary, Aronow, Bruce J., primary, Barr, Frederic G., primary, Randall, R. Lor, primary, Ladanyi, Marc, primary, Qualman, Stephen J., primary, Rubin, Brian P., primary, LeGallo, Robin D., primary, Wang, Chiayeng, primary, Khan, Javed, primary, and Keller, Charles, primary
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- 2023
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46. MIAME Microarry Data URL from Activator Protein-1 Transcription Factors Are Associated with Progression and Recurrence of Prostate Cancer
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Ouyang, Xuesong, primary, Jessen, Walter J., primary, Al-Ahmadie, Hikmat, primary, Serio, Angel M., primary, Lin, Yong, primary, Shih, Weichung-Joseph, primary, Reuter, Victor E., primary, Scardino, Peter T., primary, Shen, Michael M., primary, Aronow, Bruce J., primary, Vickers, Andrew J., primary, Gerald, William L., primary, and Abate-Shen, Cory, primary
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- 2023
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47. Supplementary Figures 1-5 and 7 from The SWI/SNF ATPase Brm Is a Gatekeeper of Proliferative Control in Prostate Cancer
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Shen, Hui, primary, Powers, Nathan, primary, Saini, Nitin, primary, Comstock, Clay E.S., primary, Sharma, Ankur, primary, Weaver, Katherine, primary, Revelo, Monica P., primary, Gerald, William, primary, Williams, Erin, primary, Jessen, Walter J., primary, Aronow, Bruce J., primary, Rosson, Gary, primary, Weissman, Bernard, primary, Muchardt, Christian, primary, Yaniv, Moshe, primary, and Knudsen, Karen E., primary
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- 2023
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48. Supplementary Tables 1-7 from Credentialing a Preclinical Mouse Model of Alveolar Rhabdomyosarcoma
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Nishijo, Koichi, primary, Chen, Qing-Rong, primary, Zhang, Lei, primary, McCleish, Amanda T., primary, Rodriguez, Andrea, primary, Cho, Min Jung, primary, Prajapati, Suresh I., primary, Gelfond, Jonathan A.L., primary, Chisholm, Gary B., primary, Michalek, Joel E., primary, Aronow, Bruce J., primary, Barr, Frederic G., primary, Randall, R. Lor, primary, Ladanyi, Marc, primary, Qualman, Stephen J., primary, Rubin, Brian P., primary, LeGallo, Robin D., primary, Wang, Chiayeng, primary, Khan, Javed, primary, and Keller, Charles, primary
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- 2023
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49. Supplementary Figures 1-3, Tables 1-4 from Activator Protein-1 Transcription Factors Are Associated with Progression and Recurrence of Prostate Cancer
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Ouyang, Xuesong, primary, Jessen, Walter J., primary, Al-Ahmadie, Hikmat, primary, Serio, Angel M., primary, Lin, Yong, primary, Shih, Weichung-Joseph, primary, Reuter, Victor E., primary, Scardino, Peter T., primary, Shen, Michael M., primary, Aronow, Bruce J., primary, Vickers, Andrew J., primary, Gerald, William L., primary, and Abate-Shen, Cory, primary
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- 2023
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50. Supplementary Figure 1 from Credentialing a Preclinical Mouse Model of Alveolar Rhabdomyosarcoma
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Nishijo, Koichi, primary, Chen, Qing-Rong, primary, Zhang, Lei, primary, McCleish, Amanda T., primary, Rodriguez, Andrea, primary, Cho, Min Jung, primary, Prajapati, Suresh I., primary, Gelfond, Jonathan A.L., primary, Chisholm, Gary B., primary, Michalek, Joel E., primary, Aronow, Bruce J., primary, Barr, Frederic G., primary, Randall, R. Lor, primary, Ladanyi, Marc, primary, Qualman, Stephen J., primary, Rubin, Brian P., primary, LeGallo, Robin D., primary, Wang, Chiayeng, primary, Khan, Javed, primary, and Keller, Charles, primary
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- 2023
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