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2,659 results on '"Thomas, James D."'

1. pgMAP: a pipeline to enable guide RNA read mapping from dual-targeting CRISPR screens

Author

Parrish, Phoebe C. R., Groso, Daniel J., Thomas, James D., Bradley, Robert K., and Berger, Alice H.

Subjects
Quantitative Biology - Genomics
Abstract

We developed pgMAP, an analysis pipeline to map gRNA sequencing reads from dual-targeting CRISPR screens. pgMAP output includes a dual gRNA read counts table and quality control metrics including the proportion of correctly-paired reads and CRISPR library sequencing coverage across all time points and samples. pgMAP is implemented using Snakemake and is available open-source under the MIT license at https://github.com/fredhutch/pgmap_pipeline., Comment: 6 pages, 1 figure, code available at https://github.com/fredhutch/pgmap_pipeline

Published
2023

7. GLIDE Score: Scoring System for Prediction of Procedural Success in Tricuspid Valve Transcatheter Edge-to-Edge Repair

Author

Gerçek, Muhammed, Narang, Akhil, Körber, M. Isabel, Friedrichs, Kai P., Puthumana, Jyothy J., Ivannikova, Maria, Al-Kazaz, Mohamed, Cremer, Paul, Baldridge, Abigail S., Meng, Zhiying, Luedike, Peter, Thomas, James D., Rudolph, Tanja K., Geisler, Tobias, Rassaf, Tienush, Pfister, Roman, Rudolph, Volker, and Davidson, Charles J.

Published
2024
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9. Closing the Last Mile Gap in Access to Multimodality Imaging in Rural Settings: Design of the Imaging Core of the Risk Underlying Rural Areas Longitudinal Study

Author

Fazlalizadeh, Hooman, Khan, Muhammad Shahzeb, Fox, Ervin R., Douglas, Pamela S., Adams, David, Blaha, Michael J., Daubert, Melissa A., Dunn, Gary, van den Heuvel, Edwin, Kelsey, Michelle D., Martin, Randolph P., Thomas, James D., Thomas, Yngvil, Judd, Suzanne E., Vasan, Ramachandran S., Budoff, Matthew J., and Bloomfield, Gerald S.

Published
2024
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11. Deep Learning Algorithm for Automated Cardiac Murmur Detection via a Digital Stethoscope Platform

Author

Chorba, John S, Shapiro, Avi M, Le, Le, Maidens, John, Prince, John, Pham, Steve, Kanzawa, Mia M, Barbosa, Daniel N, Currie, Caroline, Brooks, Catherine, White, Brent E, Huskin, Anna, Paek, Jason, Geocaris, Jack, Elnathan, Dinatu, Ronquillo, Ria, Kim, Roy, Alam, Zenith H, Mahadevan, Vaikom S, Fuller, Sophie G, Stalker, Grant W, Bravo, Sara A, Jean, Dina, Lee, John J, Gjergjindreaj, Medeona, Mihos, Christos G, Forman, Steven T, Venkatraman, Subramaniam, McCarthy, Patrick M, and Thomas, James D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Bioengineering, Clinical Research, Heart Disease, Cardiovascular, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Algorithms, Cross-Sectional Studies, Deep Learning, Diagnosis, Computer-Assisted, Equipment Design, Female, Heart Auscultation, Heart Murmurs, Humans, Male, Middle Aged, Reproducibility of Results, Stethoscopes, Young Adult, auscultation, machine learning, neural networks, physical examination, valvular heart disease, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Abstract

Background Clinicians vary markedly in their ability to detect murmurs during cardiac auscultation and identify the underlying pathological features. Deep learning approaches have shown promise in medicine by transforming collected data into clinically significant information. The objective of this research is to assess the performance of a deep learning algorithm to detect murmurs and clinically significant valvular heart disease using recordings from a commercial digital stethoscope platform. Methods and Results Using >34 hours of previously acquired and annotated heart sound recordings, we trained a deep neural network to detect murmurs. To test the algorithm, we enrolled 962 patients in a clinical study and collected recordings at the 4 primary auscultation locations. Ground truth was established using patient echocardiograms and annotations by 3 expert cardiologists. Algorithm performance for detecting murmurs has sensitivity and specificity of 76.3% and 91.4%, respectively. By omitting softer murmurs, those with grade 1 intensity, sensitivity increased to 90.0%. Application of the algorithm at the appropriate anatomic auscultation location detected moderate-to-severe or greater aortic stenosis, with sensitivity of 93.2% and specificity of 86.0%, and moderate-to-severe or greater mitral regurgitation, with sensitivity of 66.2% and specificity of 94.6%. Conclusions The deep learning algorithm's ability to detect murmurs and clinically significant aortic stenosis and mitral regurgitation is comparable to expert cardiologists based on the annotated subset of our database. The findings suggest that such algorithms would have utility as front-line clinical support tools to aid clinicians in screening for cardiac murmurs caused by valvular heart disease. Registration URL: https://clinicaltrials.gov; Unique Identifier: NCT03458806.

Published
2021

12. The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1

Author

Batra, Ranjan, Nelles, David A, Roth, Daniela M, Krach, Florian, Nutter, Curtis A, Tadokoro, Takahiro, Thomas, James D, Sznajder, Łukasz J, Blue, Steven M, Gutierrez, Haydee L, Liu, Patrick, Aigner, Stefan, Platoshyn, Oleksandr, Miyanohara, Atsushi, Marsala, Martin, Swanson, Maurice S, and Yeo, Gene W

Subjects
Engineering, Biomedical Engineering, Rare Diseases, Biotechnology, Muscular Dystrophy, Genetics, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Neurosciences, Myotonic Dystrophy, Adenoviridae, Animals, CRISPR-Associated Protein 9, CRISPR-Cas Systems, Disease Models, Animal, Female, Gene Editing, Genetic Vectors, Male, Mice, Transgenic, Muscle, Skeletal, Phenotype, RNA, Biomedical engineering
Abstract

Myotonic dystrophy type I (DM1) is a multisystemic autosomal-dominant inherited human disorder that is caused by CTG microsatellite repeat expansions (MREs) in the 3' untranslated region of DMPK. Toxic RNAs expressed from such repetitive sequences can be eliminated using CRISPR-mediated RNA targeting, yet evidence of its in vivo efficacy and durability is lacking. Here, using adult and neonatal mouse models of DM1, we show that intramuscular or systemic injections of adeno-associated virus (AAV) vectors encoding nuclease-dead Cas9 and a single-guide RNA targeting CUG repeats results in the expression of the RNA-targeting Cas9 for up to three months, redistribution of the RNA-splicing protein muscleblind-like splicing regulator 1, elimination of foci of toxic RNA, reversal of splicing biomarkers and amelioration of myotonia. The sustained reversal of DM1 phenotypes provides further support that RNA-targeting Cas9 is a viable strategy for treating DM1 and other MRE-associated diseases.

Published
2021

19. GLIDE Score

Author

Gerçek, Muhammed, primary, Narang, Akhil, additional, Körber, M. Isabel, additional, Friedrichs, Kai P., additional, Puthumana, Jyothy J., additional, Ivannikova, Maria, additional, Al-Kazaz, Mohamed, additional, Cremer, Paul, additional, Baldridge, Abigail S., additional, Meng, Zhiying, additional, Luedike, Peter, additional, Thomas, James D., additional, Rudolph, Tanja K., additional, Geisler, Tobias, additional, Rassaf, Tienush, additional, Pfister, Roman, additional, Rudolph, Volker, additional, and Davidson, Charles J., additional

Published
2024
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22. Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells

Author

North, Khrystyna, Benbarche, Salima, Liu, Bo, Pangallo, Joseph, Chen, Sisi, Stahl, Maximilian, Bewersdorf, Jan Philipp, Stanley, Robert F., Erickson, Caroline, Cho, Hana, Pineda, Jose Mario Bello, Thomas, James D., Polaski, Jacob T., Belleville, Andrea E., Gabel, Austin M., Udy, Dylan B., Humbert, Olivier, Kiem, Hans-Peter, Abdel-Wahab, Omar, and Bradley, Robert K.

Published
2022
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25. Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease

Author

Hemnes, Anna R., Leopold, Jane A., Radeva, Milena K., Beck, Gerald J., Abidov, Aiden, Aldred, Micheala A., Barnard, John, Rosenzweig, Erika B., Borlaug, Barry A., Chung, Wendy K., Comhair, Suzy A.A., Desai, Ankit A., Dubrock, Hilary M., Erzurum, Serpil C., Finet, J. Emanuel, Frantz, Robert P., Garcia, Joe G.N., Geraci, Mark W., Gray, Michael P., Grunig, Gabriele, Hassoun, Paul M., Highland, Kristin B., Hill, Nicholas S., Hu, Bo, Kwon, Deborah H., Jacob, Miriam S., Jellis, Christine L., Larive, A. Brett, Lempel, Jason K., Maron, Bradley A., Mathai, Stephen C., McCarthy, Kevin, Mehra, Reena, Nawabit, Rawan, Newman, John H., Olman, Mitchell A., Park, Margaret M., Ramos, Jose A., Renapurkar, Rahul D., Rischard, Franz P., Sherer, Susan G., Tang, W.H. Wilson, Thomas, James D., Vanderpool, Rebecca R., Waxman, Aaron B., Wilcox, Jennifer D., Yuan, Jason X.-J., and Horn, Evelyn M.

Published
2022
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27. An autoregulatory poison exon in Smndc1 is conserved across kingdoms and influences organism growth.

Author

Belleville, Andrea E., Thomas, James D., Tonnies, Jackson, Gabel, Austin M., Borrero Rossi, Andrea, Singh, Priti, Queitsch, Christine, and Bradley, Robert K.

Subjects
*POISONS, *STOP codons, *RNA regulation, *HUMAN genome, *PHENOTYPES
Abstract

Many of the most highly conserved elements in the human genome are "poison exons," alternatively spliced exons that contain premature termination codons and permit post-transcriptional regulation of mRNA abundance through induction of nonsense-mediated mRNA decay (NMD). Poison exons are widely assumed to be highly conserved due to their presumed importance for organismal fitness, but this functional importance has never been tested in the context of a whole organism. Here, we report that a poison exon in Smndc1 is conserved across mammals and plants and plays a molecular autoregulatory function in both kingdoms. We generated mouse and A. thaliana models lacking this poison exon to find its loss leads to deregulation of SMNDC1 protein levels, pervasive alterations in mRNA processing, and organismal size restriction. Together, these models demonstrate the importance of poison exons for both molecular and organismal phenotypes that likely explain their extraordinary conservation. Author summary: Poison exons are highly conserved elements in the human genome and are known for their roles in regulating mRNA abundance. Despite their assumed importance for organismal fitness, their functional significance has not been tested in whole organisms. Our study focuses on a poison exon in the Smndc1 gene. We discovered that this poison exon is conserved between mammals and plants and sought to test its functional importance. We generated mouse and plant models lacking this specific poison exon. The loss of this exon led to dysregulated SMNDC1 protein levels and widespread disruptions in RNA processing. These molecular changes resulted in a noticeable reduction in organismal size, underscoring the physiological impact of poison exon loss. Our findings demonstrate that poison exons are crucial for maintaining proper protein levels and mRNA processing homeostasis, which may partially explain their remarkable evolutionary conservation. This study highlights the importance of poison exons in both molecular regulation and overall organismal health, providing insights into their conservation across diverse species. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Flow Convergence Area Estimation on In Vitro Color Flow Doppler Images Using Deep Learning

Author

Cheimariotis, Grigorios-Aris, Haris, Kostas, Lee, Jeesoo, White, Brent E., Katsaggelos, Aggelos K., Thomas, James D., Maglaveras, Nikolaos, Magjarevic, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Henriques, Jorge, editor, Neves, Nuno, editor, and de Carvalho, Paulo, editor

Published
2020
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36. Pharmacologic modulation of RNA splicing enhances anti-tumor immunity

Author

Lu, Sydney X., De Neef, Emma, Thomas, James D., Sabio, Erich, Rousseau, Benoit, Gigoux, Mathieu, Knorr, David A., Greenbaum, Benjamin, Elhanati, Yuval, Hogg, Simon J., Chow, Andrew, Ghosh, Arnab, Xie, Abigail, Zamarin, Dmitriy, Cui, Daniel, Erickson, Caroline, Singer, Michael, Cho, Hana, Wang, Eric, Lu, Bin, Durham, Benjamin H., Shah, Harshal, Chowell, Diego, Gabel, Austin M., Shen, Yudao, Liu, Jing, Jin, Jian, Rhodes, Matthew C., Taylor, Richard E., Molina, Henrik, Wolchok, Jedd D., Merghoub, Taha, Diaz, Luis A., Jr., Abdel-Wahab, Omar, and Bradley, Robert K.

Published
2021
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38. Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9

Author

Batra, Ranjan, Nelles, David A, Pirie, Elaine, Blue, Steven M, Marina, Ryan J, Wang, Harrison, Chaim, Isaac A, Thomas, James D, Zhang, Nigel, Nguyen, Vu, Aigner, Stefan, Markmiller, Sebastian, Xia, Guangbin, Corbett, Kevin D, Swanson, Maurice S, and Yeo, Gene W

Subjects
Biological Sciences, Genetics, Rare Diseases, Myotonic Dystrophy, ALS, Neurodegenerative, Brain Disorders, Intellectual and Developmental Disabilities (IDD), Neurosciences, Muscular Dystrophy, Orphan Drug, Aetiology, 2.1 Biological and endogenous factors, Animals, COS Cells, Cell Line, Cells, Cultured, Chlorocebus aethiops, Clustered Regularly Interspaced Short Palindromic Repeats, Genetic Therapy, Microsatellite Repeats, Oligonucleotides, Antisense, RNA Splicing, Trinucleotide Repeat Expansion, CRISPR, Huntington’s disease, RNA-targeting Cas9, adeno-associated virus, gene therapy, microsatellite repeat expansion, minimal Cas9, myotonic dystrophy, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Microsatellite repeat expansions in DNA produce pathogenic RNA species that cause dominantly inherited diseases such as myotonic dystrophy type 1 and 2 (DM1/2), Huntington's disease, and C9orf72-linked amyotrophic lateral sclerosis (C9-ALS). Means to target these repetitive RNAs are required for diagnostic and therapeutic purposes. Here, we describe the development of a programmable CRISPR system capable of specifically visualizing and eliminating these toxic RNAs. We observe specific targeting and efficient elimination of microsatellite repeat expansion RNAs both when exogenously expressed and in patient cells. Importantly, RNA-targeting Cas9 (RCas9) reverses hallmark features of disease including elimination of RNA foci among all conditions studied (DM1, DM2, C9-ALS, polyglutamine diseases), reduction of polyglutamine protein products, relocalization of repeat-bound proteins to resemble healthy controls, and efficient reversal of DM1-associated splicing abnormalities in patient myotubes. Finally, we report a truncated RCas9 system compatible with adeno-associated viral packaging. This effort highlights the potential of RCas9 for human therapeutics.

Published
2017

39. Comparison of two-dimensional strain analysis using vendor-independent and vendor-specific software in adult and pediatric patients

Author

Anwar, Shafkat, Negishi, Kazuaki, Borowszki, Allen, Gladding, Patrick, Popović, Zoran B, Erenberg, Francine, and Thomas, James D

Subjects
Bioengineering, Biomedical Imaging, Clinical Research, Pediatric, Two-dimensional strain echocardiography, left ventricular function, cardiac deformation, Digital Imaging and Communications in Medicine, vendor-independent software
Abstract

IntroductionTwo-dimensional strain analysis is a powerful analysis modality, however, clinical utilization has been limited by variability between different analysis systems and operators. We compared strain in adults and children using vendor-specific and vendor-independent software to evaluate variability.MethodsOne hundred and ten subjects (50/110 pediatric, 80/110 normal left ventricular function) had echocardiograms with a General Electric ultrasound scanner between September 2010 and January 2012. Left ventricular longitudinal strain was derived with EchoPAC (General Electric, v10.8.1), a vendor-specific software, and Velocity Vector Imaging (Siemens, v3.5), which is vendor-independent. Three independent readers analyzed all the echocardiograms yielding 330 datasets.ResultsMean left ventricular global longitudinal Lagrangian strain was -18.1 ± SD 4.4% for EchoPAC and -15.3 ± SD 4.1% for Velocity Vector Imaging. Velocity Vector Imaging yielded lower absolute global longitudinal Lagrangian strain by mean 2.9 (±SD 2.7, p 3-5 strain points on repeat measurements. Strain values between the systems are not interchangeable.

Published
2017

40. Echocardiographic Parameters Associated With Less Reverse Left Ventricular Remodeling After Transcatheter Aortic Valve Implant in Subjects With Prosthesis Patient Mismatch

Author

Peters, Andrew C., Gong, Fei Fei, Ramesh, Ashvita, Andrei, Adin, Jankowski, Madeline, Cantey, Eric, Chen, Vincent, Thomas, James D., Flaherty, James D., Malaisrie, S. Christopher, Maganti, Kameswari, Peters, Andrew C., Gong, Fei Fei, Ramesh, Ashvita, Andrei, Adin, Jankowski, Madeline, Cantey, Eric, Chen, Vincent, Thomas, James D., Flaherty, James D., Malaisrie, S. Christopher, and Maganti, Kameswari

Abstract

BACKGROUND: Transaortic valve implant (TAVI) is the treatment of choice for severe aortic stenosis (AS). Some patients develop prosthesis patient mismatch (PPM) after TAVI. It is challenging to determine which patients are at risk for clinical deterioration. METHODS: We retrospectively measured echocardiographic parameters of left ventricular (LV) morphology and function, prosthetic aortic valve effective orifice area (iEOA) and hemodynamics in 313 patients before and 1 year after TAVI. Our objective was to compare the change in echocardiographic parameters associated with left ventricular reverse modeling in subjects with and without PPM. Our secondary objective was to evaluate echo parameters associated with PPM and the relationship to patient functional status and survival post-TAVI. RESULTS: We found that 82 (26.2%) of subjects had moderate and 37 (11.8%) had severe PPM post-TAVI. There was less relative improvement in LVEF with PPM (1.9 ± 21.3% vs. 8.2 + 30.1%, p = .045). LV GLS also exhibited less relative improvement in those with PPM (13.4 + 34.1% vs. 30.9 + 73.3%, p = .012). NYHA functional class improved in 84.3% of subjects by one grade or more. Echocardiographic markers of PPM were worse in those without improvement in NYHA class (mean AT/ET was .29 vs. .27, p = .05; DVI was .46 vs. .51, p = .021; and iEOA was .8 cm/m CONCLUSIONS: There was no improvement in LVEF and less improvement in LV GLS in those with PPM post-TAVI. Echocardiographic markers of PPM were present in those with lack of improvement in NYHA functional class.

Published
2024

42. Cardiac Structural and Functional Remodeling After Transcatheter Mitral Valve in Valve Implantation: Early Changes and Prognostic Significance

Author

Ayuba, Gloria, primary, Meng, Zhiying, additional, Baldridge, Abigail S., additional, Goyal, Ansh, additional, Tilkens, Blair, additional, Shrivastav, Rishi, additional, Safder, Taimur, additional, Malaisrie, Chris S., additional, Flaherty, James, additional, McCarthy, Patrick M., additional, Thomas, James D., additional, Davidson, Charles, additional, Puthumana, Jyothy, additional, and Narang, Akhil, additional

Published
2023
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44. Obituary: Arthur E. Weyman, 1941–2024.

Author

Flachskampf, Frank A, Bertrand, Philippe B, Neskovic, Aleksandar N, Schwammenthal, Ehud, Vandervoort, Pieter, Thomas, James D, and Picard, Michael H

Subjects
SERIAL publications, OCCUPATIONAL achievement, AWARDS, CARDIOLOGISTS, VOCATIONAL guidance
Published
2024
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45. Integrative oncogene-dependency mapping identifies RIT1 vulnerabilities and synergies in lung cancer

Author

Vichas, Athea, Riley, Amanda K., Nkinsi, Naomi T., Kamlapurkar, Shriya, Parrish, Phoebe C. R., Lo, April, Duke, Fujiko, Chen, Jennifer, Fung, Iris, Watson, Jacqueline, Rees, Matthew, Gabel, Austin M., Thomas, James D., Bradley, Robert K., Lee, John K., Hatch, Emily M., Baine, Marina K., Rekhtman, Natasha, Ladanyi, Marc, Piccioni, Federica, and Berger, Alice H.

Published
2021
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48. List of Contributors

Author

Andersen, Øyvind Senstad, primary, Anderson, Bonita A., additional, Appleton, Christopher P., additional, Asher, Craig R., additional, Aurigemma, Gerard P., additional, Baicu, Catalin F., additional, Beyer, Ruxandra, additional, Bhat, Pavan, additional, Bianco, Christopher Michael, additional, Borlaug, Barry A., additional, Bradshaw, Amy D., additional, Burstow, Darryl J., additional, Carasso, Shemy, additional, Cerqueira, Manuel D., additional, Chetrit, Michael, additional, Collier, Patrick, additional, DeLeon-Pennell, Kristine Y., additional, Dokainish, Hisham, additional, Flachskampf, Frank A., additional, Friedberg, Mark K., additional, Furlani, Andrea C., additional, Garcia, Mario J., additional, Gorodeski, Eiran Z., additional, Gregory, Stephen H., additional, Grimm, Richard A., additional, Ha, Jong-Won, additional, Habib, Manhal, additional, Harb, Serge C., additional, Herrera, Cesar J., additional, Hoit, Brian D., additional, Imazio, Massimo, additional, Inoue, Katsuji, additional, Jaber, Wael A., additional, Kane, Garvan C., additional, Klein, Allan L., additional, Kovell, Lara C., additional, Kwon, Deborah H., additional, Lambert, Cameron T., additional, Levine, Benjamin D., additional, LeWinter, Martin M., additional, MacNamara, James P., additional, Makkiya, Mohammed, additional, Maragiannis, Dimitrios, additional, Melenovsky, Vojtech, additional, Menick, Donald R., additional, Miranda, William R., additional, Murthy, Sandhya, additional, Nagueh, Sherif F., additional, Nakatani, Satoshi, additional, Nambiar, Lakshmi, additional, Negishi, Kazuaki, additional, Obokata, Masaru, additional, Oh, Jae K., additional, Piña, Ileana, additional, Popović, Zoran B., additional, Quinones, Miguel A., additional, Rakowski, Harry, additional, Reddy, Yogesh N.V., additional, Rodriguez, Leonardo, additional, Sarma, Satyam, additional, Schenone, Aldo L., additional, Sengupta, Partho, additional, Smiseth, Otto A., additional, Starling, Randall C., additional, Stugaard, Marie, additional, Swaminathan, Madhav, additional, Tam, Edlira, additional, Tang, W.H. Wilson, additional, Thakkar, Harsh V., additional, Thomas, James D., additional, Williams, Lynne, additional, Yaranov, Dmitry M., additional, Young, Laura, additional, and Zile, Michael R., additional

Published
2021
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50. 2019 ACC/AHA/ASE Key Data Elements and Definitions for Transthoracic Echocardiography: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards) and the American Society of Echocardiography

Author

Douglas, Pamela S., Carabello, Blase A., Lang, Roberto M., Lopez, Leo, Pellikka, Patricia A., Picard, Michael H., Thomas, James D., Varghese, Paul, Wang, Tracy Y., Weissman, Neil J., and Wilgus, Rebecca

Published
2019
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