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3. Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Study

Author

Lancaster, Lisa, primary, Cottin, Vincent, additional, Ramaswamy, Murali, additional, Wuyts, Wim A., additional, Jenkins, R. Gisli, additional, Scholand, Mary Beth, additional, Kreuter, Michael, additional, Valenzuela, Claudia, additional, Ryerson, Christopher J, additional, Goldin, Jonathan, additional, Kim, Grace Hyun J, additional, Jurek, Marzena, additional, Decaris, Martin, additional, Clark, Annie, additional, Turner, Scott, additional, Barnes, Chris N., additional, Achneck, Hardean E, additional, Cosgrove, Gregory, additional, Lefebvre, Éric A, additional, and Flaherty, Kevin R., additional

Published
2024
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4. Bexotegrast in people with idiopathic pulmonary fibrosis (IPF): a plain language summary of publication of the INTEGRIS-IPF study.

Author

Lancaster, Lisa, Cottin, Vincent, Ramaswamy, Murali, Wuyts, Wim A., Jenkins, R. Gisli, Scholand, Mary Beth, Kreuter, Michael, Valenzuela, Claudia, Ryerson, Christopher J., Goldin, Jonathan, Kim, Grace Hyun J., Jurek, Marzena, Decaris, Martin, Clark, Annie, Turner, Scott M., Barnes, Chris N., Achneck, Hardean E., Cosgrove, Gregory P., Lefebvre, Éric A., and Flaherty, Kevin R.

Abstract

What is this summary about? This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the American Journal of Respiratory and Critical Care Medicine in 2024. This study looked at a medicine called bexotegrast (beck-so-teh-grast) as a possible treatment for idiopathic pulmonary fibrosis (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). Bexotegrast is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment. IPF is a chronic, progressive lung disease that makes it hard to breathe and gets worse over time. There is no cure for IPF, treatment includes symptom management and consideration for the use of nintedanib or pirfenidone, which may decrease the pace of disease progression. The study compared bexotegrast to a placebo (a treatment that looks identical to the medicine but has no medicinal effect) to look at how well it works and how safe it is in treating people with IPF. Most people in the study also took one of two medicines that are already approved by the FDA for IPF, pirfenidone or nintedanib. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.

Author

Lancaster, Lisa, Cottin, Vincent, Ramaswamy, Murali, Wuyts, Wim A., Jenkins, R. Gisli, Scholand, Mary Beth, Kreuter, Michael, Valenzuela, Claudia, Ryerson, Christopher J., Goldin, Jonathan, Kim, Grace Hyun J., Jurek, Marzena, Decaris, Martin, Clark, Annie, Turner, Scott, Barnes, Chris N., Achneck, Hardean E., Cosgrove, Gregory P., Lefebvre, Éric A., and Flaherty, Kevin R.

Subjects
IDIOPATHIC pulmonary fibrosis, COUGH, CLINICAL trials, PULMONARY fibrosis, INVESTIGATIONAL drugs, DRUG development
Abstract

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease that causes progressive cough, exertional dyspnea, impaired quality of life, and death. Objectives: Bexotegrast (PLN-74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. Methods: This Phase-2a multicenter, clinical trial randomized participants with IPF to receive, orally and once daily, bexotegrast at 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included change from baseline in FVC, quantitative lung fibrosis (QLF) extent (%), and changes from baseline in fibrosis-related biomarkers. Measurements and Main Results: Bexotegrast was well tolerated, with similar rates of TEAEs in the pooled bexotegrast and placebo groups (62/89 [69.7%] and 21/31 [67.7%], respectively). Diarrhea was the most common TEAE; most participants with diarrhea also received nintedanib. Participants who were treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared with those who received placebo, with or without background therapy. A dose-dependent antifibrotic effect of bexotegrast was observed with QLF imaging, and a decrease in fibrosis-associated biomarkers was observed with bexotegrast versus placebo. Conclusions: Bexotegrast demonstrated a favorable safety and tolerability profile, up to 12 weeks for the doses studied. Exploratory analyses suggest an antifibrotic effect according to FVC, QLF imaging, and circulating levels of fibrosis biomarkers. Clinical trial registered with (NCT04396756). [ABSTRACT FROM AUTHOR]

Published
2024
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6. Disease Severity and Quality of Life in Patients With Idiopathic Pulmonary Fibrosis: A Cross-Sectional Analysis of the IPF-PRO Registry

Author

Asi, Wael, Baker, Albert, Beegle, Scott, Belperio, John A., Condos, Rany, Cordova, Francis, Culver, Daniel A., de Andrade, Joao A.M., Dilling, Daniel, Flaherty, Kevin R., Glassberg, Marilyn, Gulati, Mridu, Guntupalli, Kalpalatha, Gupta, Nishant, Hajari Case, Amy, Hotchkin, David, Huie, Tristan, Kaner, Robert, Kim, Hyun, Kreider, Maryl, Lancaster, Lisa, Lasky, Joseph, Lederer, David, Lee, Doug, Liesching, Timothy, Lipchik, Randolph, Lobo, Jason, Mageto, Yolanda, Menon, Prema, Morrison, Lake, Namen, Andrew, Oldham, Justin, Raj, Rishi, Ramaswamy, Murali, Russell, Tonya, Sachs, Paul, Safdar, Zeenat, Sigal, Barry, Silhan, Leann, Strek, Mary, Suliman, Sally, Tabak, Jeremy, Walia, Rajat, Whelan, Timothy P., O’Brien, Emily C., Hellkamp, Anne S., Neely, Megan L., Swaminathan, Aparna, Bender, Shaun, Snyder, Laurie D., Conoscenti, Craig S., Todd, Jamie L., Palmer, Scott M., and Leonard, Thomas B.

Published
2020
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9. Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study

Author

Raghu, Ganesh, Flaherty, Kevin R, Lederer, David J, Lynch, David A, Colby, Thomas V, Myers, Jeffrey L, Groshong, Steve D, Larsen, Brandon T, Chung, Jonathan H, Steele, Mark P, Benzaquen, Sadia, Calero, Karel, Case, Amy H, Criner, Gerard J, Nathan, Steven D, Rai, Navdeep S, Ramaswamy, Murali, Hagmeyer, Lars, Davis, J Russell, Gauhar, Umair A, Pankratz, Daniel G, Choi, Yoonha, Huang, Jing, Walsh, P Sean, Neville, Hannah, Lofaro, Lori R, Barth, Neil M, Kennedy, Giulia C, Brown, Kevin K, and Martinez, Fernando J

Published
2019
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14. Differences in Patient Outcomes across the Pulmonary Fibrosis Foundation Care Center Network

Author

Boente, Ryan D., primary, White, Emily N., additional, Baxter, Caitlin M., additional, Shore, Jessica E., additional, Collard, Harold R., additional, Lee, Joyce S., additional, Abrencillo, Rodeo, additional, Bhatt, Nitin, additional, Boente, Ryan, additional, Farrand, Erica, additional, Glazer, Craig, additional, Huie, Tristan, additional, Kim, Hyun, additional, Ramaswamy, Murali, additional, Shah, Rupal, additional, Shore, Jessica, additional, and Thavarajah, Krishna, additional

Published
2023
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16. Disparities in Lung Transplant among Patients with Idiopathic Pulmonary Fibrosis: An Analysis of the IPF-PRO Registry

Author

Swaminathan, Aparna C., primary, Hellkamp, Anne S., additional, Neely, Megan L., additional, Bender, Shaun, additional, Paoletti, Luca, additional, White, Eric S., additional, Palmer, Scott M., additional, Whelan, Timothy P. M., additional, Dilling, Daniel F., additional, Baker, Albert, additional, Beegle, Scott, additional, Belperio, John A., additional, Condos, Rany, additional, Cordova, Francis, additional, Culver, Daniel A., additional, Fitzgerald, John, additional, Flaherty, Kevin R., additional, Gibson, Kevin, additional, Gulati, Mridu, additional, Guntupalli, Kalpalatha, additional, Gupta, Nishant, additional, Case, Amy Hajari, additional, Hotchkin, David, additional, Huie, Tristan J., additional, Kaner, Robert J., additional, Kim, Hyun J., additional, Lancaster, Lisa H., additional, Lasky, Joseph A., additional, Lee, Doug, additional, Liesching, Timothy, additional, Lipchik, Randolph, additional, Lobo, Jason, additional, Luckhardt, Tracy R., additional, Mageto, Yolanda, additional, Menon, Prema, additional, Morrison, Lake, additional, Namen, Andrew, additional, Oldham, Justin M., additional, Paul, Tessy, additional, Zhang, David, additional, Porteous, Mary, additional, Raj, Rishi, additional, Ramaswamy, Murali, additional, Russell, Tonya, additional, Sachs, Paul, additional, Safdar, Zeenat, additional, Shafazand, Shirin, additional, Siddiqi, Ather, additional, Sigal, Barry, additional, Strek, Mary E., additional, Suliman, Sally, additional, Tabak, Jeremy, additional, and Walia, Rajat, additional

Published
2022
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17. Practical management of suspected hypersensitivity reactions to anti-tuberculosis drugs

Author

William Hywel Bermingham, Rashmeet Bhogal, Sowmya Arudi Nagarajan, Leman Mutlu, Reham Mohamed El‐Shabrawy, Ramesh Madhan, Uma Maheswari Krishnaswamy, Mandakolathur Ramaswamy Murali, Sanath Thushara Kudagammana, Rajeev Shrestha, Stevent Sumantri, Devasahayam Jesudas Christopher, Padukudru Anand Mahesh, Martin Dedicoat, and Mamidipudi Thirumala Krishna

Subjects
Drug Hypersensitivity, SARS-CoV-2, Immunology, Antitubercular Agents, Immunology and Allergy, COVID-19, Humans, Anaphylaxis
Abstract

Tuberculosis (TB) is the commonest cause of death by a single infectious agent globally and ranks amongst the top ten causes of global mortality. The incidence of TB is highest in Low-Middle Income countries (LMICs). Prompt institution of, and compliance with, therapy are cornerstones for a favourable outcome in TB and to mitigate the risk of multiple drug resistant (MDR)-TB, which is challenging to treat. There is some evidence that adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) to anti-TB drugs occur in over 60% and 3%-4% of patients respectively. Both ADRs and HSRs represent significant barriers to treatment adherence and are recognised risk factors for MDR-TB. HSRs to anti-TB drugs are usually cutaneous and benign, occur within few weeks after commencement of therapy and are likely to be T-cell mediated. Severe and systemic T-cell mediated HSRs and IgE mediated anaphylaxis to anti-TB drugs are relatively rare, but important to recognise and treat promptly. T-cell-mediated HSRs are more frequent amongst patients with co-existing HIV infection. Some patients develop multiple sensitisation to anti-TB drugs. Whilst skin tests, patch tests and in vitro diagnostics have been used in the investigation of HSRs to anti-TB drugs, their predictive value is not established, they are onerous, require specialist input of an allergist and are resource-dependent. This is compounded by the global, unmet demand for allergy specialists, particularly in low-income countries (LICs)/LMICs and now the challenging circumstances of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This narrative review provides a critical analysis of the limited published evidence on this topic and proposes a cautious and pragmatic approach to optimise and standardise the management of HSRs to anti-TB drugs. This includes clinical risk stratification and a dual strategy involving sequential re-challenge and rapid drug desensitisation. Furthermore, a concerted international effort is needed to generate real-time data on ADRs, HSRs, safety and clinical outcomes of these interventions.

Published
2021

18. Effect of Antifibrotic Therapy on Survival in Patients with Idiopathic Pulmonary Fibrosis

Author

de Andrade, Joao Alberto, primary, Neely, Megan L., additional, Hellkamp, Anne S., additional, Culver, Daniel A., additional, Kim, Hyun J., additional, Liesching, Timothy, additional, Lobo, Leonard J., additional, Ramaswamy, Murali, additional, Safdar, Zeenat, additional, Bender, Shaun, additional, Conoscenti, Craig S., additional, Leonard, Thomas B., additional, Palmer, Scott M., additional, Snyder, Laurie D., additional, and Investigators, IPF-PRO Registry, additional

Published
2022
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19. Utility of a Molecular Classifier as a Complement to High-Resolution Computed Tomography to Identify Usual Interstitial Pneumonia

Author

Richeldi, Luca, Scholand, Mary Beth, Lynch, David A., Colby, Thomas, V, Myers, Jeffrey L., Groshong, Steve D., Chung, Jonathan H., Benzaquen, Sadia, Nathan, Steven D., Davis, J. Russell, Schmidt, Shelley L., Hagmeyer, Lars, Sonetti, David, Hetzel, Jurgen, Criner, Gerard J., Case, Amy H., Ramaswamy, Murali, Calero, Karel, Gauhar, Umair A., Patel, Nina M., Lancaster, Lisa, Choi, Yoonha, Pankratz, Daniel G., Walsh, P. Sean, Lofaro, Lori R., Huang, Jing, Bhorade, Sangeeta M., Kennedy, Giulia C., Martinez, Fernando J., Raghu, Ganesh, Richeldi, Luca, Scholand, Mary Beth, Lynch, David A., Colby, Thomas, V, Myers, Jeffrey L., Groshong, Steve D., Chung, Jonathan H., Benzaquen, Sadia, Nathan, Steven D., Davis, J. Russell, Schmidt, Shelley L., Hagmeyer, Lars, Sonetti, David, Hetzel, Jurgen, Criner, Gerard J., Case, Amy H., Ramaswamy, Murali, Calero, Karel, Gauhar, Umair A., Patel, Nina M., Lancaster, Lisa, Choi, Yoonha, Pankratz, Daniel G., Walsh, P. Sean, Lofaro, Lori R., Huang, Jing, Bhorade, Sangeeta M., Kennedy, Giulia C., Martinez, Fernando J., and Raghu, Ganesh

Abstract

Rationale: Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A molecular diagnosis of UIP in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP. Objectives: We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern. Methods: Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology. Measurements and Main Results: In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval [CI],78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%). Conclusions: In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.

Published
2021

20. Essential Components of an Interstitial Lung Disease Clinic

Author

Graney, Bridget A., primary, He, Christophe, additional, Marll, Michael, additional, Matson, Scott, additional, Bianchi, Pauline, additional, Cosgrove, Gregory P., additional, Lee, Joyce S., additional, Abrencillo, Rodeo, additional, Bascom, Rebecca, additional, Scholand, Mary Beth, additional, Bhatt, Nitin, additional, Case, Amy, additional, Chaudhary, Sachin, additional, Culver, Daniel, additional, Danoff, Sonye, additional, Desai, Alpa, additional, Dilling, Daniel, additional, Glazer, Craig, additional, Gulati, Mridu, additional, Gupta, Nishant, additional, Hamblin, Mark, additional, Hamzeh, Nabeel, additional, Huie, Tristan, additional, Kim, Hyun, additional, King, Christopher, additional, Kreider, Maryl, additional, Lacamera, Peter, additional, Lancaster, Lisa, additional, Luckhardt, Tracy, additional, Mageto, Yolanda, additional, Kottman, Robert Matthew, additional, McCormick, James, additional, Mehrad, Borna, additional, Menon, Prema, additional, Montesi, Sydney, additional, Mooney, Joshua, additional, Moore, Doug, additional, Moua, Teng, additional, Nambiar, Anoop, additional, Oldham, Justin, additional, Patel, Divya, additional, Paul, Tessy, additional, Perez, Rafael, additional, Podolanczuk, Anna, additional, Ramaswamy, Murali, additional, Roe, David, additional, Saad, Mohamed, additional, Sandbo, Nathan, additional, Schaumberg, Thomas, additional, Schmidt, Shelley, additional, Shea, Barry, additional, Shifren, Adrian, additional, Strek, Mary, additional, Thavarajah, Krishna, additional, Todd, Nevins, additional, Veeraraghavan, Srihari, additional, Weight, Stephen, additional, Wolters, Paul, additional, and Zibrak, Joseph, additional

Published
2021
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21. Utility of a Molecular Classifier as a Complement to High-Resolution Computed Tomography to Identify Usual Interstitial Pneumonia

Author

Richeldi, Luca, primary, Scholand, Mary Beth, additional, Lynch, David A., additional, Colby, Thomas V., additional, Myers, Jeffrey L., additional, Groshong, Steve D., additional, Chung, Jonathan H., additional, Benzaquen, Sadia, additional, Nathan, Steven D., additional, Davis, J. Russell, additional, Schmidt, Shelley L., additional, Hagmeyer, Lars, additional, Sonetti, David, additional, Hetzel, Jurgen, additional, Criner, Gerard J., additional, Case, Amy H., additional, Ramaswamy, Murali, additional, Calero, Karel, additional, Gauhar, Umair A., additional, Patel, Nina M., additional, Lancaster, Lisa, additional, Choi, Yoonha, additional, Pankratz, Daniel G., additional, Walsh, P. Sean, additional, Lofaro, Lori R., additional, Huang, Jing, additional, Bhorade, Sangeeta M., additional, Kennedy, Giulia C., additional, Martinez, Fernando J., additional, and Raghu, Ganesh, additional

Published
2021
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22. COMBINING RADIOLOGY AND ENVISIA, A MOLECULAR CLASSIFIER, TO IMPROVE USUAL INTERSTITIAL PNEUMONIA (UIP) DIAGNOSIS

Author

Benzaquen, Sadia, Chung, Jonathan, Lynch, David, Lederer, David, Flaherty, Kevin, Colby, Thomas, Myers, Jeffrey, Groshong, Steve, Larsen, Brandon, Steele, Mark, Calero, Karel, Case, Amy, Criner, Gerard, Nathan, Steven, Rai, Navdeep, Ramaswamy, Murali, Hagmeyer, Lars, Gauhar, Umair, Pankratz, Daniel, Choi, Yoonha, Huang, Jing, Neville, Hannah, Lofaro, Lori, Kennedy, Giulia, Brown, Kevin, Raghu, Ganesh, Martinez, Fernando, Davis, John, Barth, Neil, and Walsh, Patric

Published
2019
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23. EVALUATING CLINICAL UTILITY OF A UIP GENOMIC CLASSIFIER IN SUBJECTS WITH AND WITHOUT A HRCT PATTERN OF UIP

Author

Chung, Jonathan, Lynch, David, Lederer, David, Flaherty, Kevin, Colby, Thomas, Myers, Jeffrey, Groshong, Steve, Larsen, Brandon, Steele, Mark, Benzaquen, Sadia, Calero, Karel, Case, Amy, Criner, Gerard, Nathan, Steven, Rai, Navdeep, Ramaswamy, Murali, Hagmeyer, Lars, Davis, John, Gauhar, Umair, Barth, Neil, Pankratz, Daniel, Choi, Yoonha, Huang, Jing, Walsh, Patric, Neville, Hannah, Lofaro, Lori, Kennedy, Giulia, Brown, Kevin, Raghu, Ganesh, and Martinez, Fernando

Published
2019
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24. Antifibrotic Drug Use in Patients with Idiopathic Pulmonary Fibrosis. Data from the IPF-PRO Registry

Author

Salisbury, Margaret L., primary, Conoscenti, Craig S., additional, Culver, Daniel A., additional, Yow, Eric, additional, Neely, Megan L., additional, Bender, Shaun, additional, Hartmann, Nadine, additional, Palmer, Scott M., additional, Leonard, Thomas B., additional, Baker, Albert, additional, Beegle, Scott, additional, Belperio, John, additional, Condos, Rany, additional, Cordova, Francis, additional, Dilling, Daniel, additional, Fitzgerald, John, additional, Flaherty, Kevin R., additional, Gibson, Kevin, additional, Gulati, Mridu, additional, Guntupalli, Kalpalatha, additional, Gupta, Nishant, additional, Case, Amy Hajari, additional, Hotchkin, David, additional, Huie, Tristan, additional, Kaner, Robert, additional, Kim, Hyun, additional, Lancaster, Lisa, additional, Lasky, Joseph A., additional, Lee, Doug, additional, Liesching, Timothy, additional, Lipchik, Randolph, additional, Lobo, Jason, additional, Luckhardt (formerly Joao de Andrade), Tracy, additional, Mageto, Yolanda, additional, Malik, Numaan, additional, Menon, Prema, additional, Morrison, Lake, additional, Namen, Andrew, additional, Oldham, Justin, additional, Paul, Tessy, additional, Podolanczuk, Anna, additional, Porteous, Mary, additional, Raj, Rishi, additional, Ramaswamy, Murali, additional, Russell, Tonya, additional, Sachs, Paul, additional, Safdar, Zeenat, additional, Shafazand, Shirin, additional, Siddiqi, Ather, additional, Sigal, Barry, additional, Strek, Mary, additional, Suliman, Sally, additional, Tabak, Jeremy, additional, Walia, Rajat, additional, and Whelan, Timothy, additional

Published
2020
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25. Disease Severity and Quality of Life in Patients With Idiopathic Pulmonary Fibrosis

Author

O’Brien, Emily C., primary, Hellkamp, Anne S., additional, Neely, Megan L., additional, Swaminathan, Aparna, additional, Bender, Shaun, additional, Snyder, Laurie D., additional, Culver, Daniel A., additional, Conoscenti, Craig S., additional, Todd, Jamie L., additional, Palmer, Scott M., additional, Leonard, Thomas B., additional, Asi, Wael, additional, Baker, Albert, additional, Beegle, Scott, additional, Belperio, John A., additional, Condos, Rany, additional, Cordova, Francis, additional, de Andrade, Joao A.M., additional, Dilling, Daniel, additional, Flaherty, Kevin R., additional, Glassberg, Marilyn, additional, Gulati, Mridu, additional, Guntupalli, Kalpalatha, additional, Gupta, Nishant, additional, Hajari Case, Amy, additional, Hotchkin, David, additional, Huie, Tristan, additional, Kaner, Robert, additional, Kim, Hyun, additional, Kreider, Maryl, additional, Lancaster, Lisa, additional, Lasky, Joseph, additional, Lederer, David, additional, Lee, Doug, additional, Liesching, Timothy, additional, Lipchik, Randolph, additional, Lobo, Jason, additional, Mageto, Yolanda, additional, Menon, Prema, additional, Morrison, Lake, additional, Namen, Andrew, additional, Oldham, Justin, additional, Raj, Rishi, additional, Ramaswamy, Murali, additional, Russell, Tonya, additional, Sachs, Paul, additional, Safdar, Zeenat, additional, Sigal, Barry, additional, Silhan, Leann, additional, Strek, Mary, additional, Suliman, Sally, additional, Tabak, Jeremy, additional, Walia, Rajat, additional, and Whelan, Timothy P., additional

Published
2020
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28. It is not just the work - It is also the words

Author

Ramaswamy, Murali

Subjects
Plagiarism -- Ethical aspects -- Analysis -- Risk factors, Medical students -- Beliefs, opinions and attitudes -- Ethical aspects, Health
Abstract

Byline: Murali. Ramaswamy Definition of Plagiarism Plagiarism is an ethical issue. I personally became aware of the concept of plagiarism seven years ago when I was a pulmonary fellow. A [...]

Published
2007

29. Random access with large propagation delay

Author

Ramaswamy Murali and Brian L. Hughes

Subjects
Computer Science::Computer Science and Game Theory, Computer Networks and Communications, Network packet, Computer science, business.industry, ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS, Throughput, Propagation delay, Topology, Computer Science Applications, Computer Science::Performance, Channel capacity, Packet switching, Aloha, Computer Science::Networking and Internet Architecture, Forward error correction, Electrical and Electronic Engineering, business, Software, Random access, Computer Science::Information Theory, Computer network
Abstract

Random access to a packet broadcast channel with large propagation delay is investigated. A protocol is presented that combines slotted ALOHA random access with the use of forward-error-correction (FEC) across transmitted packets. Expressions for the throughput, delay, and drift of this protocol are derived. Numerical studies and asymptotic analyses of the drift indicate that the protocol has a maximum throughput of e/sup -1/ and exhibits bistability and saturation behavior similar to that of slotted ALOHA with immediate feedback. However, unlike ALOHA, bistability and saturation in the code protocol can be eliminated with the proper choice of protocol parameters without increasing the packet delay. It is further shown that, when compared to slotted ALOHA, the code protocol typically achieves a higher throughput and lower delay at system equilibrium with no loss in maximum throughput.

Published
1997

41. Nonstructural proteins of respiratory syncytial virus suppress premature apoptosis by an NF-kappaB-dependent, interferon-independent mechanism and facilitate virus growth.

Author

Bitko V, Shulyayeva O, Mazumder B, Musiyenko A, Ramaswamy M, Look DC, and Barik S

Subjects
Animals, Cell Line, Chlorocebus aethiops, Down-Regulation, ErbB Receptors physiology, Humans, Proteasome Endopeptidase Complex, Protein Kinases metabolism, Proteins metabolism, Respiratory Syncytial Viruses physiology, Vero Cells, Virus Replication, Apoptosis, Interferons physiology, NF-kappa B physiology, Respiratory Syncytial Virus Infections virology, Respiratory Syncytial Viruses pathogenicity, Viral Nonstructural Proteins metabolism
Abstract

The two nonstructural (NS) proteins NS1 and NS2 of respiratory syncytial virus (RSV) are abundantly expressed in the infected cell but are not packaged in mature progeny virions. We found that both proteins were expressed early in infection, whereas the infected cells underwent apoptosis much later. Coincident with NS protein expression, a number of cellular antiapoptotic factors were expressed or activated at early stages, which included NF-kappaB and phosphorylated forms of protein kinases AKT, phosphoinositide-dependent protein kinase, and glycogen synthase kinase. Using specific short interfering RNAs (siRNAs), we achieved significant knockdown of one or both NS proteins in the infected cell, which resulted in abrogation of the antiapoptotic functions and led to early apoptosis. NS-dependent suppression of apoptosis was observed in Vero cells that are naturally devoid of type I interferons (IFN). The siRNA-based results were confirmed by the use of NS-deleted RSV mutants. Early activation of epidermal growth factor receptor (EGFR) in the RSV-infected cell did not require NS proteins. Premature apoptosis triggered by the loss of NS or by apoptosis-promoting drugs caused a severe reduction of RSV growth. Finally, recombinantly expressed NS1 and NS2, individually and together, reduced apoptosis by tumor necrosis factor alpha, suggesting an intrinsic antiapoptotic property of both. We conclude that the early-expressed nonstructural proteins of RSV boost viral replication by delaying the apoptosis of the infected cell via a novel IFN- and EGFR-independent pathway.

Published
2007
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