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Veterinary Microbiology and Immunobiology Commons

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Leveraging Eco-Evolutionary Models For Gene Drive Risk Assessment, Matthew A. Combs, Andrew J. Golnar, Justin M. Overcash, Alun L. Lloyd, Keith R. Hayes, David A. O'Brochta, Kim M. Pepin 2023 NWRC, Fort Collins, CO

Leveraging Eco-Evolutionary Models For Gene Drive Risk Assessment, Matthew A. Combs, Andrew J. Golnar, Justin M. Overcash, Alun L. Lloyd, Keith R. Hayes, David A. O'Brochta, Kim M. Pepin

USDA Wildlife Services: Staff Publications

Engineered gene drives create potential for both widespread benefits and irreversible harms to ecosystems. CRISPR-based systems of allelic conversion have rapidly accelerated gene drive research across diverse taxa, putting field trials and their necessary risk assessments on the horizon. Dynamic processbased models provide flexible quantitative platforms to predict gene drive outcomes in the context of system-specific ecological and evolutionary features. Here, we synthesize gene drive dynamic modeling studies to highlight research trends, knowledge gaps, and emergent principles, organized around their genetic, demographic, spatial, environmental, and implementation features. We identify the phenomena that most significantly influence model predictions, discuss limitations of …


The Knowns And Unknowns Of Cardiac Autoimmunity In Viral Myocarditis, Kiruthiga Mone, Jay Reddy 2023 University of Nebraska‐Lincoln

The Knowns And Unknowns Of Cardiac Autoimmunity In Viral Myocarditis, Kiruthiga Mone, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis can result from various infectious and non‐infectious causes that can lead to dilated cardiomyopathy (DCM) and heart failure. Among the infectious causes, viruses are commonly suspected. But the challenge is our inability to demonstrate infectious viral particles during clinical presentations, partly because by that point, the viruses would have damaged the tissues and be cleared by the immune system. Therefore, viral signatures such as viral nucleic acids and virus-reactive antibodies may be the only readouts pointing to viruses as potential primary triggers of DCM. Thus, it becomes hard to explain persistent inflammatory infiltrates that might occur in individuals affected …


Evaluating Vaccine Management Strategies For Edwardsiella Ictaluri Infections In Zebrafish (Danio Rerio), Brandy Malbrough 2023 Louisiana State University at Baton Rouge

Evaluating Vaccine Management Strategies For Edwardsiella Ictaluri Infections In Zebrafish (Danio Rerio), Brandy Malbrough

LSU Master's Theses

Aquaculture is a globally important industry that faces significant challenges due to infectious diseases, which can result in substantial financial losses. In 2011, a new strain of Edwardsiella ictaluri emerged as a major pathogen affecting zebrafish in the ornamental fish industry, leading to high mortality rates and posing a severe threat to the sector. Vaccines provide potential benefits for disease prevention in aquaculture, particularly live-attenuated vaccines (LAVs), which induce strong host immune responses. Bacterial attenuation for vaccine development has evolved from serial passage to more targeted genetic modification techniques. However, regulatory constraints limit the availability of licensed LAVs for aquaculture. …


Naturally Occurring Highly Pathogenic Avian Influenza Virus H5n1 Clade 2.3.4.4b Infection In Three Domestic Cats In North America During 2023, Sarah J. Sillman, Mary Drozd, Duan S. Loy, Seth P. Harris 2023 University of Nebraska-Lincoln

Naturally Occurring Highly Pathogenic Avian Influenza Virus H5n1 Clade 2.3.4.4b Infection In Three Domestic Cats In North America During 2023, Sarah J. Sillman, Mary Drozd, Duan S. Loy, Seth P. Harris

School of Veterinary and Biomedical Sciences: Faculty Publications

The Eurasian strain of highly pathogenic avian influenza (HPAI) H5N1 is a devastating pathogen for birds that also has the capacity to infect mammals. This report describes the presentation, clinical case findings (including haemogram and serum biochemistry), gross and microscopic lesions and virus detection in three HPAI H5N1-infected domestic cats from the USA in 2023. All three cats presented with neurological abnormalities and were euthanized due to a poor prognosis within 2 days (two cats) or 10 days (one cat) of known clinical disease onset. Necropsy consistently revealed pulmonary congestion and oedema, and cerebrocortical malacia with haemorrhage was also seen …


Quantitative Risk Assessment Of Oocyst Versus Bradyzoite Foodborne Transmission Of Toxoplasma Gondii In Brazil, Sophie Zhu, Elizabeth VanWormer, Beatriz Martínez-López, Lílian Maria Garcia Bahia-Oliveira, Renato Augusto DaMatta, Pedro Souto Rodrigues, Karen Shapiro 2023 University of California, Davis

Quantitative Risk Assessment Of Oocyst Versus Bradyzoite Foodborne Transmission Of Toxoplasma Gondii In Brazil, Sophie Zhu, Elizabeth Vanwormer, Beatriz Martínez-López, Lílian Maria Garcia Bahia-Oliveira, Renato Augusto Damatta, Pedro Souto Rodrigues, Karen Shapiro

School of Veterinary and Biomedical Sciences: Faculty Publications

Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental stage of T. gondii, oocysts, is an important source of infection in Brazil; however, no studies have quantified this risk relative to other parasite stages. We developed a Bayesian quantitative risk assessment (QRA) to estimate the relative attribution of the two primary parasite stages (bradyzoite and oocyst) that can be transmitted in foods to people in …


Mycobacterium Avium Subsp. Paratuberculosis Candidate Vaccine Strains Are Pro-Apoptotic In Raw264.7murinemacrophages, Raul G. Barletta, John P. Bannantine, Judith R. Stabel, Ezhumalai Muthukrishnan, Dirk Anderson, Enakshy Dutta, Vamsi Manthena, Mostafa Hanafy, Denise K. Zinniel 2023 University of Nebraska - Lincoln

Mycobacterium Avium Subsp. Paratuberculosis Candidate Vaccine Strains Are Pro-Apoptotic In Raw264.7murinemacrophages, Raul G. Barletta, John P. Bannantine, Judith R. Stabel, Ezhumalai Muthukrishnan, Dirk Anderson, Enakshy Dutta, Vamsi Manthena, Mostafa Hanafy, Denise K. Zinniel

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne’s disease, a severe gastroenteritis of ruminants. This study developed a model cell culture system to rapidly screen MAP mutants with vaccine potential for apoptosis. Two wild-type strains, a transposon mutant, and two deletion mutant MAP strains (MOI of 10 with 1.2 × 106 CFU) were tested in murine RAW 264.7 macrophages to determine if they induce apoptosis and/or necrosis. Both deletion mutants were previously shown to be attenuated and immunogenic in primary bovine macrophages. All strains had similar growth rates, but cell morphology indicated that both deletion mutants …


Design, Construction, And Testing Of Recombinant Dna-Based Vaccines For Protection Against Salmonella Enterica Subspecies Enterica Serovar Javiana, Ashley Edwards 2023 Louisiana State University

Design, Construction, And Testing Of Recombinant Dna-Based Vaccines For Protection Against Salmonella Enterica Subspecies Enterica Serovar Javiana, Ashley Edwards

LSU Doctoral Dissertations

In the United States, Salmonella Javiana is among the top 5 most common nontyphoidal Salmonella serotypes, with a 325% increase in infection rate since 1970. Globally, nontyphoidal Salmonella leads to approximately 93.8 million illnesses and 155,000 deaths annually, with disproportionate impacts in developing countries. In the United States alone, these infections lead to over $4 billion in costs, the majority of which are attributed to those expenses incurred from mortalities. The zoonotic nature of nontyphoidal Salmonellae and their ability to survive on and within vegetation mean huge economic burden potential for various agricultural industries as well, especially since some of …


Serological Prevalence Of Crimean–Congo Hemorrhagic Fever Virus Infection In Small Ruminants And Cattle In The Gambia, Jerusha Matthews, Arss Secka, David Scott McVey, Kimberly A. Dodd, Bonto Faburay 2023 United States Department of Agriculture

Serological Prevalence Of Crimean–Congo Hemorrhagic Fever Virus Infection In Small Ruminants And Cattle In The Gambia, Jerusha Matthews, Arss Secka, David Scott Mcvey, Kimberly A. Dodd, Bonto Faburay

School of Veterinary and Biomedical Sciences: Faculty Publications

Crimean–Congo hemorrhagic fever virus (CCHFV) is a widely distributed tickborne zoonotic agent that infects a variety of host species. There is a lack of information on the true geographic distribution of the prevalence and risk of CCHFV in West Africa. A countrywide cross-sectional study involving 1413 extensively managed indigenous small ruminants and cattle at livestock sales markets and in village herds, respectively, was carried out in The Gambia. In sheep, an overall anti-CCHFV antibody prevalence of 18.9% (95% CI: 15.5–22.8%), goats 9.0% (95% CI: 6.7–11.7%), and cattle 59.9% (95% CI: 54.9–64.7%) was detected. Significant variation (p < 0.05) in the prevalence of anti-CCHFV antibodies at sites in the five administrative regions (sheep: 4.8–25.9%; goats: 1.8–17.1%) and three agroecological zones (sheep: 8.9–32.9%; goats: 4.1–18.0%) was also observed. Comparatively, higher anti-CCHFV antibody prevalence was detected in cattle (33.3–84.0%) compared to small ruminants (1.8–8.1%). This study represents the first countrywide investigation of the seroprevalence of CCHFV in The Gambia, and the results suggest potential circulation and endemicity of the virus in the country. These data provide critical information vital to the development of informed policies for the surveillance, diagnosis, and control of CCFHV infection in The Gambia and the region.


Feral Swine As Indirect Indicators Of Environmental Anthrax Contamination And Potential Mechanical Vectors Of Infectious Spores, Rachel M. Maison, Maggie R. Priore, Vienna R. Brown, Michael Bodenchuk, Bradley R. Borlee, Richard Bowen, Angela M. Bosco-Lauth 2023 Colorado State University - Fort Collins

Feral Swine As Indirect Indicators Of Environmental Anthrax Contamination And Potential Mechanical Vectors Of Infectious Spores, Rachel M. Maison, Maggie R. Priore, Vienna R. Brown, Michael Bodenchuk, Bradley R. Borlee, Richard Bowen, Angela M. Bosco-Lauth

USDA Wildlife Services: Staff Publications

U.S. government work


Optimal R&D Investment In The Management Of Invasive Species, William Haden Chomphosy, Dale T. Manning, Stephanie A. Shwiff, Stephan Weiler 2023 Hendrix College

Optimal R&D Investment In The Management Of Invasive Species, William Haden Chomphosy, Dale T. Manning, Stephanie A. Shwiff, Stephan Weiler

USDA Wildlife Services: Staff Publications

Invasive alien species (IAS) threaten world biodiversity, ecosystem services, and economic welfare. While existing literature has characterized the optimal control of an established IAS, it has not considered how research and development (R&D) into new removal methods or technologies can affect management decisions and costs over time. R&D can lower the costs of control in a management plan and creates an intertemporal trade-off between quick but costly control and gradual but cheaper removal over time. In this paper, we develop and solve a continuous time dynamic optimization model to study how investment in R&D influences the optimal control of an …


A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral And Cellular Immune Responses And Protects Mice From Lethal Virus Challenge, Aryamav Pattnaik, Bikash R. Sahoo, Lucas R. Struble, Gloria E. O. Borgstahl, You Zhou, Rodrigo Franco, Raul G. Barletta, Fernando A. Osorio, Thomas M. Petro, Asit K. Pattnaik 2023 University of Nebraska-Lincoln

A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral And Cellular Immune Responses And Protects Mice From Lethal Virus Challenge, Aryamav Pattnaik, Bikash R. Sahoo, Lucas R. Struble, Gloria E. O. Borgstahl, You Zhou, Rodrigo Franco, Raul G. Barletta, Fernando A. Osorio, Thomas M. Petro, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that …


Highly Pathogenic Avian Influenza A(H5n1) Virus Outbreak In New England Seals, United States, Wendy Puryear, Kaitlin Sawatzki, Nichola Hill, Alexa Foss, Jonathon J. Stone, Lynda Doughty, Dominique Walk, Katie Gilbert, Maureen Murray, Elena Cox, Priya Patel, Zak Mertz, Stephanie Ellis, Jennifer Taylor, Deborah Fauquier, Ainsley Smith, Robert A. DiGiovanni, Adriana van de Guchte, Ana Silvia Gonzalez-Reiche, Zain Khalil, Harm van Bakel, Mia K. Torchetti, Kristina Lantz, Julianna B. Lenoch, Jonathan Runstadler 2023 Cummings School of Veterinary Medicine

Highly Pathogenic Avian Influenza A(H5n1) Virus Outbreak In New England Seals, United States, Wendy Puryear, Kaitlin Sawatzki, Nichola Hill, Alexa Foss, Jonathon J. Stone, Lynda Doughty, Dominique Walk, Katie Gilbert, Maureen Murray, Elena Cox, Priya Patel, Zak Mertz, Stephanie Ellis, Jennifer Taylor, Deborah Fauquier, Ainsley Smith, Robert A. Digiovanni, Adriana Van De Guchte, Ana Silvia Gonzalez-Reiche, Zain Khalil, Harm Van Bakel, Mia K. Torchetti, Kristina Lantz, Julianna B. Lenoch, Jonathan Runstadler

USDA Wildlife Services: Staff Publications

We report the spillover of highly pathogenic avian influenza A(H5N1) into marine mammals in the northeastern United States, coincident with H5N1 in sympatric wild birds. Our data indicate monitoring both wild coastal birds and marine mammals will be critical to determine pandemic potential of influenza A viruses.


Time And Temperature Stability Of Tritrichomonas Foetus In Phosphate-Buffered Saline As Evaluated By A Reverse Transcription Real-Time Pcr Assay And Field Analysis, Duan S. Loy, Renata Spuri Gomes, Enakshy Dutta, Bruce W. Brodersen, John Dustin Loy 2023 University of Nebraska-Lincoln

Time And Temperature Stability Of Tritrichomonas Foetus In Phosphate-Buffered Saline As Evaluated By A Reverse Transcription Real-Time Pcr Assay And Field Analysis, Duan S. Loy, Renata Spuri Gomes, Enakshy Dutta, Bruce W. Brodersen, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Tritrichomonas foetus (TF) is a significant reproductive pathogen of cattle, and sample collection, handling, transport, and testing are significant hurdles to surveillance programs. Recent methods have been developed that allow for the direct detection of TF using a reverse transcription real-time PCR (direct RT-qPCR) approach. To evaluate these methods, a comparative analysis was conducted to assess the technical performance of this assay with a commercially available real- time PCR (qPCR) assay. In addition, the evaluation of two types of collection media (PBS and TF transport tube) was conducted that evaluated sample stability from 0 to 3 days when stored at …


Association Of IsvSa3 With Multidrug Resistance In Salmonella Enterica Isolates From Cattle (Bos Taurus), Gentry L. Lewis, Robert J. Fenton, Etsuko Moriyama, John Dustin Loy, Rodney A. Moxley 2023 University of Nebraska-Lincoln

Association Of IsvSa3 With Multidrug Resistance In Salmonella Enterica Isolates From Cattle (Bos Taurus), Gentry L. Lewis, Robert J. Fenton, Etsuko Moriyama, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Salmonella enterica is, globally, an important cause of human illness with beef being a significant attributable source. In the human patient, systemic Salmonella infection requires antibiotic therapy, and when strains are multidrug resistant (MDR), no effective treatment may be available. MDR in bacteria is often associated with the presence of mobile genetic elements (MGE) that mediate horizontal spread of antimicrobial resistance (AMR) genes. In this study, we sought to determine the potential relationship of MDR in bovine Salmonella isolates with MGE. The present study involved 111 bovine Salmonella isolates obtained collectively from specimens derived from healthy cattle or their environments …


Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. McKeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker 2023 Iowa State University

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker

School of Veterinary and Biomedical Sciences: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …


Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. McKeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker 2023 Iowa State University

Comparison Of Two Diagnostic Assays For The Detection Of Serum Neutralizing Antibody To Porcine Epidemic Diarrhea Virus, Justin Brown, Korakrit Poonsuk, Ting-Yu Cheng, Chris Rademacher, Erin Kalkwarf, Liying Tian, Lauren A. Mckeen, Chong Wang, Luis Gimenez-Lirola, David Baum, Locke A. Karriker

School of Veterinary and Biomedical Sciences: Faculty Publications

Lactogenic immunity is important for the protection of piglets against many pathogens including porcine epidemic diarrhea virus. Circulating neutralizing antibodies levels in sow sera may help determine if a detectable immune response could confer protection to piglets. Neutralizing antibodies can be detected through various diagnostic assays. This study evaluated the diagnostic characteristics of two neutralizing antibody assays for porcine epidemic diarrhea virus neutralizing antibodies in serum of challenged gilts. Four treatment groups, control, non-vaccinated, vaccinated prior to challenge, and vaccinated following challenge, were comprised of 20 gilts. Serum sample were collected from each gilt prior to and following challenge with …


An Evaluation Of Avian Influenza Virus Whole-Genome Sequencing Approaches Using Nanopore Technology, Hon S. Ip, Sarah Uhm, Mary Lea Killian, Mia K. Torchetti 2023 USGS National Wildlife Health Center

An Evaluation Of Avian Influenza Virus Whole-Genome Sequencing Approaches Using Nanopore Technology, Hon S. Ip, Sarah Uhm, Mary Lea Killian, Mia K. Torchetti

USDA Wildlife Services: Staff Publications

As exemplified by the global response to the SARS-CoV-2 pandemic, whole-genome sequencing played an important role in monitoring the evolution of novel viral variants and provided guidance on potential antiviral treatments. The recent rapid and extensive introduction and spread of highly pathogenic avian influenza virus in Europe, North America, and elsewhere raises the need for similarly rapid sequencing to aid in appropriate response and mitigation activities. To facilitate this objective, we investigate a next-generation sequencing platform that uses a portable nanopore sequencing device to generate and present data in real time. This platform offers the potential to extend in-house sequencing …


Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu 2023 Harvard T.H. Chan School of Public Health

Displaying And Delivering Viral Membrane Antigens Via Ww Domain–Activated Extracellular Vesicles, Sengjin Choi, Zhiping Yang, Qiyu Wang, Zhi Qiao, Maoyun Sun, Joshua Wiggins, Shi-Hua Xiang, Quan Lu

School of Veterinary and Biomedical Sciences: Faculty Publications

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle–based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain–activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral …


Vaccines Against Group B Coxsackieviruses And Their Importance, Kiruthiga Mone, Ninaad Lasrado, Meghna Sur, Jay Reddy 2023 University of Nebraska-Lincoln

Vaccines Against Group B Coxsackieviruses And Their Importance, Kiruthiga Mone, Ninaad Lasrado, Meghna Sur, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The group B coxsackieviruses (CVBs) exist in six serotypes (CVB1 to CVB6). Disease associations have been reported for most serotypes, and multiple serotypes can cause similar diseases. For example, CVB1, CVB3, and CVB5 are generally implicated in the causation of myocarditis, whereas CVB1 and CVB4 could accelerate the development of type 1 diabetes (T1D). Yet, no vaccines against these viruses are currently available. In this review, we have analyzed the attributes of experimentally tested vaccines and discussed their merits and demerits or limitations, as well as their impact in preventing infections, most importantly myocarditis and T1D.


Personalized Matched Targeted Therapy In Advanced Pancreatic Cancer: A Pilot Cohort Analysis, Justin Shaya, Shumei Kato, Jacob J. Adashek, Hitendra Patel, Paul T. Fanta, Gregory P. Botta, Jason K. Sicklick, Razelle Kurzrock 2023 University of California San Diego Moores Cancer Center

Personalized Matched Targeted Therapy In Advanced Pancreatic Cancer: A Pilot Cohort Analysis, Justin Shaya, Shumei Kato, Jacob J. Adashek, Hitendra Patel, Paul T. Fanta, Gregory P. Botta, Jason K. Sicklick, Razelle Kurzrock

School of Veterinary and Biomedical Sciences: Faculty Publications

Despite progress, 2-year pancreatic cancer survival remains dismal. We evaluated a biomarker-driven, combination/N-of-one strategy in 18 patients (advanced/metastatic pancreatic cancer) (from Molecular Tumor Board). Targeted agents administered/ patient = 2.5 (median) (range, 1–4); first-line therapy (N = 5); second line, (N = 13). Comparing patients (high versus low degrees of matching) (matching score ≥50% versus <50%; reflecting number of alterations matched to targeted agents divided by number of pathogenic alterations), survival was significantly longer (hazard ratio [HR] 0.24 (95% confidence interval [CI], 0.078–0.76, P = 0.016); clinical benefit rates (CBR) (stable disease ≥6 months/partial/complete response) trended higher (45.5 vs 0.0%, P = 0.10); progression-free survival, HR, 95% CI, 0.36 (0.12–1.10) (p = 0.075). First versus ≥2nd-line therapy had higher CBRs (80.0 vs 7.7%, P = …


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