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6 results on '"Poling, Lara"'

1. Discovery and verification of extracellular microRNA biomarkers for diagnostic and prognostic assessment of preeclampsia at triage

Author

Morey, Robert, Poling, Lara, Srinivasan, Srimeenakshi, Martinez-King, Carolina, Anyikam, Adanna, Zhang-Rutledge, Kathy, To, Cuong, Hakim, Abbas, Mochizuki, Marina, Verma, Kajal, Mason, Antoinette, Tran, Vy, Meads, Morgan, Lamale-Smith, Leah, Roeder, Hilary, Horii, Mariko, Ramos, Gladys A, DeHoff, Peter, Parast, Mana M, Pantham, Priyadarshini, and Laurent, Louise C

Subjects
Medicinal and Biomolecular Chemistry, Chemical Sciences, Genetics, Clinical Research, Biotechnology, Prevention, Hypertension, Contraception/Reproduction, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Pregnancy, Female, Humans, MicroRNAs, Vascular Endothelial Growth Factor Receptor-1, Prognosis, Pre-Eclampsia, Triage, Biomarkers
Abstract

We report on the identification of extracellular miRNA (ex-miRNA) biomarkers for early diagnosis and prognosis of preeclampsia (PE). Small RNA sequencing of maternal serum prospectively collected from participants undergoing evaluation for suspected PE revealed distinct patterns of ex-miRNA expression among different categories of hypertensive disorders in pregnancy. Applying an iterative machine learning method identified three bivariate miRNA biomarkers (miR-522-3p/miR-4732-5p, miR-516a-5p/miR-144-3p, and miR-27b-3p/let-7b-5p) that, when applied serially, distinguished between PE cases of different severity and differentiated cases from controls with a sensitivity of 93%, specificity of 79%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 89%. In a small independent validation cohort, these ex-miRNA biomarkers had a sensitivity of 91% and specificity of 57%. Combining these ex-miRNA biomarkers with the established sFlt1:PlGF protein biomarker ratio performed better than either set of biomarkers alone (sensitivity of 89.4%, specificity of 91.3%, PPV of 95.5%, and NPV of 80.8%).

Published
2023

2. Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women.

Author

Srinivasan, Srimeenakshi, Treacy, Ryan, Herrero, Tiffany, Olsen, Richelle, Leonardo, Trevor R, Zhang, Xuan, DeHoff, Peter, To, Cuong, Poling, Lara G, Fernando, Aileen, Leon-Garcia, Sandra, Knepper, Katharine, Tran, Vy, Meads, Morgan, Tasarz, Jennifer, Vuppala, Aishwarya, Park, Soojin, Laurent, Clara D, Bui, Tony, Cheah, Pike See, Overcash, Rachael Tabitha, Ramos, Gladys A, Roeder, Hilary, Ghiran, Ionita, Parast, Mana, PAPR Study Consortium, Breakefield, Xandra O, Lueth, Amir J, Rust, Sharon R, Dufford, Max T, Fox, Angela C, Hickok, Durlin E, Burchard, Julja, Boniface, J Jay, and Laurent, Louise C

Subjects
PAPR Study Consortium
Abstract

Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.

Published
2020

3. Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women

Author

Boggess, Kim A., Saade, George R., Sullivan, Scott A., Markenson, Glenn R., Iams, Jay D., Coonrod, Dean V., Pereira, Leonardo M., Esplin, M. Sean, Cousins, Larry M., Lam, Garrett K., Hoffman, Matthew K., Srinivasan, Srimeenakshi, Treacy, Ryan, Herrero, Tiffany, Olsen, Richelle, Leonardo, Trevor R., Zhang, Xuan, DeHoff, Peter, To, Cuong, Poling, Lara G., Fernando, Aileen, Leon-Garcia, Sandra, Knepper, Katharine, Tran, Vy, Meads, Morgan, Tasarz, Jennifer, Vuppala, Aishwarya, Park, Soojin, Laurent, Clara D., Bui, Tony, Cheah, Pike See, Tabitha Overcash, Rachael, Ramos, Gladys A., Roeder, Hilary, Ghiran, Ionita, Parast, Mana, Breakefield, Xandra O., Lueth, Amir J., Rust, Sharon R., Dufford, Max T., Fox, Angela C., Hickok, Durlin E., Burchard, Julja, Boniface, J. Jay, and Laurent, Louise C.

Published
2020
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4. Discovery and Verification of Extracellular microRNA Biomarkers for Diagnostic and Prognostic Assessment of Preeclampsia at Triage

Author

Morey, Robert, primary, Poling, Lara, additional, Srinivasan, Srimeenakshi, additional, Martinez-King, Carolina, additional, Anyikam, Adanna, additional, Zhang-Rutledge, Kathy, additional, Cuong, To, additional, Hakim, Abbas, additional, Mochizuki, Marina, additional, Verma, Kajal, additional, Mason, Antoinette, additional, Tran, Vy, additional, Meads, Morgan, additional, Lamale-Smith, Leah, additional, Horii, Mariko, additional, Ramos, Gladys A., additional, DeHoff, Peter, additional, Parast, Mana M., additional, Pantham, Priya, additional, and Laurent, Louise C., additional

Published
2023
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5. Performance of PCR/electrospray ionization-mass spectrometry on whole blood for detection of bloodstream microorganisms in patients with suspected sepsis

Author

Strålin, Kristoffer, Rothman, Richard E., Özenci, Volkan, Barkataki, Kieron, Brealey, David, Dhiman, Neelam, Poling, Lara, Kurz, Michael C., Limaye, Ajit P., LoVecchio, Frank, Lowery, Kristin, Miller, Loren G., Moran, Gregory J., Overcash, J. Scott, Parekh, Amisha, Peacock, W. Frank, Rivers, Emanuel P., Sims, Matthew, Stubbs, Amy M., Sundqvist, Martin, Ullberg, Måns, Carroll, Karen C., Strålin, Kristoffer, Rothman, Richard E., Özenci, Volkan, Barkataki, Kieron, Brealey, David, Dhiman, Neelam, Poling, Lara, Kurz, Michael C., Limaye, Ajit P., LoVecchio, Frank, Lowery, Kristin, Miller, Loren G., Moran, Gregory J., Overcash, J. Scott, Parekh, Amisha, Peacock, W. Frank, Rivers, Emanuel P., Sims, Matthew, Stubbs, Amy M., Sundqvist, Martin, Ullberg, Måns, and Carroll, Karen C.

Abstract

Blood culture (BC) often fails to detect bloodstream microorganisms in sepsis. However, molecular diagnostics hold great potential. The molecular method PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) can detect DNA from hundreds of different microorganisms in whole blood. The aim of the present study was to evaluate the performance of this method in a multicenter study including 16 teaching hospitals in the USA (n=13) and Europe (n=3). First, on 2,754 contrived whole blood samples, with or without spiked microorganisms, PCR/ESI-MS produced 99.1% true positive and 97.2% true negative results. Secondly, among 1,460 patients with suspected sepsis (sepsis-2 definition), BC and PCR/ESI-MS on whole blood were positive in 14.6% and 25.6% of cases, respectively, with the following result combinations: BC+/PCR/ESI-MS-, 4.3%; BC+/PCR/ESI-MS+, 10.3%; BC-/PCR/ESI-MS+, 15.3%; and BC-/PCR/ESI-MS-, 70.1%. Compared with BC, PCR/ESI-MS showed the following sensitivities (coagulase-negative staphylococci not included): Gram-positive bacteria, 58%; Gram-negative bacteria, 78%; and Candida species, 83%. The specificities were > 94% for all individual species. Patients treated with prior antimicrobial medications (n=603) had significantly increased PCR/ESI-MS positivity rates compared with patients without prior antimicrobial treatment, 31% vs 22% (p<0.0001), with pronounced differences for Gram-negative bacteria and Candida species. In conclusion, PCR/ESI-MS showed excellent performance on contrived samples. On clinical samples, it showed high specificities, moderately high sensitivities for Gram-negative bacteria and Candida species, and elevated positivity rates during antimicrobial treatment. These promising results encourage further development of molecular diagnostics on whole blood for detection of bloodstream microorganisms in sepsis., Funding Agencies:Ibis Biosciences, a division of Abbott Abbott LaboratoriesCepheid ContraFect Nabriva Therapeutics AG Lajolla Pharmaceuticals Alere Corporation Spectral Diagnostics Ferring Pharmaceuticals Inflammix VICTASm Sanofi Pasteur Inc. Curetis GmbH PfizerMerck & CompanyCidara Therapeutics Inc. Shire Aridis Pharmaceuticals Inc. Epigenomics Inc. Roche Holding GenentechFinch Therapeutics Seres Therapeutics Inc. Diasorin Molecular Janssen Research and Development NeuMoDx Molecular Iterum Therapeutics International

Published
2020
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6. Performance of PCR/Electrospray Ionization-Mass Spectrometry on Whole Blood for Detection of Bloodstream Microorganisms in Patients with Suspected Sepsis

Author

Strålin, Kristoffer, primary, Rothman, Richard E., additional, Özenci, Volkan, additional, Barkataki, Kieron, additional, Brealey, David, additional, Dhiman, Neelam, additional, Poling, Lara, additional, Kurz, Michael C., additional, Limaye, Ajit P., additional, LoVecchio, Frank, additional, Lowery, Kristin, additional, Miller, Loren G., additional, Moran, Gregory J., additional, Overcash, J. Scott, additional, Parekh, Amisha, additional, Peacock, W. Frank, additional, Rivers, Emanuel P., additional, Sims, Matthew, additional, Stubbs, Amy M., additional, Sundqvist, Martin, additional, Ullberg, Måns, additional, and Carroll, Karen C., additional

Published
2020
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