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Full-Text Articles in Medicine and Health Sciences

Time-To-Event Analysis For Sports Injury Research Part 1: Time-Varying Exposures, Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Daniel Ramskov, Merete Møller, Adam Hulme, Daniel Theisen, Caroline F. Finch, Lauren Victoria Fortington, Mohammad Ali Mansournia, Erik Thorlund Parner Jan 2019

Time-To-Event Analysis For Sports Injury Research Part 1: Time-Varying Exposures, Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Daniel Ramskov, Merete Møller, Adam Hulme, Daniel Theisen, Caroline F. Finch, Lauren Victoria Fortington, Mohammad Ali Mansournia, Erik Thorlund Parner

ECU Publications Post 2013

BACKGROUND: ‘How much change in training load is too much before injury is sustained, among different athletes?’ is a key question in sports medicine and sports science. To address this question the investigator/practitioner must analyse exposure variables that change over time, such as change in training load. Very few studies have included time-varying exposures (eg, training load) and time-varying effect-measure modifiers (eg, previous injury, biomechanics, sleep/stress) when studying sports injury aetiology.

AIM: To discuss advanced statistical methods suitable for the complex analysis of time-varying exposures such as changes in training load and injury-related outcomes.

CONTENT: Time-varying exposures and ...


Time-To-Event Analysis For Sports Injury Research Part 2: Time-Varying Outcomes, Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Daniel Ramskov, Merete Møller, Adam Hulme, Daniel Theisen, Caroline F. Finch, Lauren Victoria Fortington, Mohammad Ali Mansournia, Erik Thorlund Parner Jan 2019

Time-To-Event Analysis For Sports Injury Research Part 2: Time-Varying Outcomes, Rasmus Oestergaard Nielsen, Michael Lejbach Bertelsen, Daniel Ramskov, Merete Møller, Adam Hulme, Daniel Theisen, Caroline F. Finch, Lauren Victoria Fortington, Mohammad Ali Mansournia, Erik Thorlund Parner

ECU Publications Post 2013

BACKGROUND: Time-to-event modelling is underutilised in sports injury research. Still, sports injury researchers have been encouraged to consider time-to-event analyses as a powerful alternative to other statistical methods. Therefore, it is important to shed light on statistical approaches suitable for analysing training load related key-questions within the sports injury domain.

CONTENT: In the present article, we illuminate: (i) the possibilities of including time-varying outcomes in time-to-event analyses, (ii) how to deal with a situation where different types of sports injuries are included in the analyses (ie, competing risks), and (iii) how to deal with the situation where multiple subsequent injuries ...


Genome-Wide Mega-Analysis Identifies 16 Loci And Highlights Diverse Biological Mechanisms In The Common Epilepsies., Bassel Abou-Khalil, Pauls Auce, Andreja Avbersek, Melanie Bahlo, David J. Balding, Thomas Bast, Larry Baum, Albert J. Becker, Felicitas Becker, Bianca Berghuis, Samuel F. Berkovic, Katja E. Boysen, Jonathan P. Bradfield, Lawrence C. Brody, Russell J. Buono, Ellen Campbell, Gregory D. Cascino, Claudia B. Catarino, Gianpiero L. Cavalleri, Stacey S. Cherny, Krishna Chinthapalli, Alison J. Coffey, Alastair Compston, Antonietta Coppola, Patrick Cossette, John J. Craig, Gerrit-Jan De Haan, Peter De Jonghe, Carolien G.F. De Kovel, Norman Delanty, Chantal Depondt, Orrin Devinsky, Dennis J. Dlugos, Colin P. Doherty, Christian E. Elger, Johan G. Eriksson, Thomas N. Ferraro, Martha Feuch, Ben Francis, Andre Franke, Jacqueline A. French, Saskia Freytag, Verena Gaus, Eric B. Geller, Christian Gieger, Tracy Glauser, Simon Glynn, David B. Goldstein, Hongsheng Gui, Youling Guo, Kevin F. Haas, Hakon Hakonarson, Kerstin Hallmann, Sheryl Haut, Erin L. Heinzen, Ingo Helbig, Christian Hengsbach, Helle Hjalgrim, Michele Iacomino, Andrés Ingason, Jennifer Jamnadas-Khoda, Michael R. Johnson, Reetta Kälviäinen, Anne-Mari Kantanen, Dalia Kasperavičiūte, Dorothee Kasteleijn-Nolst Trenite, Heidi E. Kirsch, Robert C. Knowlton, Bobby P.C. Koeleman, Roland Krause, Martin Krenn, Wolfram S. Kunz, Ruben Kuzniecky, Patrick Kwan, Dennis Lal, Yu-Lung Lau, Anna-Elina Lehesjoki, Holger Lerche, Costin Leu, Wolfgang Lieb, Dick Lindhout, Warren D. Lo, Iscia Lopes-Cendes, Daniel H. Lowenstein, Alberto Malovini, Anthony G. Marson, Thomas Mayer, Mark Mccormack, James L. Mills, Nasir Mirza, Martina Moerzinger, Rikke S. Møller, Anne M. Molloy, Hiltrud Muhle, Mark Newton, Ping-Wing Ng, Markus M. Nöthen, Peter Nürnberg, Terence J. O’Brien, Karen L. Oliver, Palotie Palotie, Faith Pangilinan, Sarah Peter, Slavé Petrovski, Annapurna Poduri, Michael Privitera, Rodney Radtke, Sarah Rau, Philipp S. Reif, Eva M. Reinthaler, Felix Rosenow, Josemir W. Sander, Thomas Sander, Theresa Scattergood, Steven C. Schachter, Christoph J. Schankin, Ingrid E. Scheffer, Bettina Schmitz, Susanne Schoch, Pak C. Sham, Jerry J. Shih, Graeme J. Sills, Sanjay M. Sisodiya, Lisa Slattery, Alexander Smith, David F. Smith, Michael C. Smith, Philip E. Smith, Anja C.M. Sonsma, Doug Speed, Michael R. Sperling, Bernhard J. Steinhoff, Ulrich Stephani, Remi Stevelink, Konstantin Strauch, Pasquale Striano, Hans Stroink, Rainer Surges, K. Meng Tan, Liu Lin Thio, G. Neil Thomas, Marian Todaro, Rossana Tozzi, Maria S. Vari, Ellen P.G. Vining, Frank Visscher, Sarah Von Spiczak, Nicole M. Walley, Yvonne G. Weber, Zhi Wei, Judith Weisenberg, Christopher D. Whelan, Peter Widdess-Walsh, Markus Wolff, Wolking Wolking, Wanling Yang, Federico Zara, Fritz Zimprich Dec 2018

Genome-Wide Mega-Analysis Identifies 16 Loci And Highlights Diverse Biological Mechanisms In The Common Epilepsies., Bassel Abou-Khalil, Pauls Auce, Andreja Avbersek, Melanie Bahlo, David J. Balding, Thomas Bast, Larry Baum, Albert J. Becker, Felicitas Becker, Bianca Berghuis, Samuel F. Berkovic, Katja E. Boysen, Jonathan P. Bradfield, Lawrence C. Brody, Russell J. Buono, Ellen Campbell, Gregory D. Cascino, Claudia B. Catarino, Gianpiero L. Cavalleri, Stacey S. Cherny, Krishna Chinthapalli, Alison J. Coffey, Alastair Compston, Antonietta Coppola, Patrick Cossette, John J. Craig, Gerrit-Jan De Haan, Peter De Jonghe, Carolien G.F. De Kovel, Norman Delanty, Chantal Depondt, Orrin Devinsky, Dennis J. Dlugos, Colin P. Doherty, Christian E. Elger, Johan G. Eriksson, Thomas N. Ferraro, Martha Feuch, Ben Francis, Andre Franke, Jacqueline A. French, Saskia Freytag, Verena Gaus, Eric B. Geller, Christian Gieger, Tracy Glauser, Simon Glynn, David B. Goldstein, Hongsheng Gui, Youling Guo, Kevin F. Haas, Hakon Hakonarson, Kerstin Hallmann, Sheryl Haut, Erin L. Heinzen, Ingo Helbig, Christian Hengsbach, Helle Hjalgrim, Michele Iacomino, Andrés Ingason, Jennifer Jamnadas-Khoda, Michael R. Johnson, Reetta Kälviäinen, Anne-Mari Kantanen, Dalia Kasperavičiūte, Dorothee Kasteleijn-Nolst Trenite, Heidi E. Kirsch, Robert C. Knowlton, Bobby P.C. Koeleman, Roland Krause, Martin Krenn, Wolfram S. Kunz, Ruben Kuzniecky, Patrick Kwan, Dennis Lal, Yu-Lung Lau, Anna-Elina Lehesjoki, Holger Lerche, Costin Leu, Wolfgang Lieb, Dick Lindhout, Warren D. Lo, Iscia Lopes-Cendes, Daniel H. Lowenstein, Alberto Malovini, Anthony G. Marson, Thomas Mayer, Mark Mccormack, James L. Mills, Nasir Mirza, Martina Moerzinger, Rikke S. Møller, Anne M. Molloy, Hiltrud Muhle, Mark Newton, Ping-Wing Ng, Markus M. Nöthen, Peter Nürnberg, Terence J. O’Brien, Karen L. Oliver, Palotie Palotie, Faith Pangilinan, Sarah Peter, Slavé Petrovski, Annapurna Poduri, Michael Privitera, Rodney Radtke, Sarah Rau, Philipp S. Reif, Eva M. Reinthaler, Felix Rosenow, Josemir W. Sander, Thomas Sander, Theresa Scattergood, Steven C. Schachter, Christoph J. Schankin, Ingrid E. Scheffer, Bettina Schmitz, Susanne Schoch, Pak C. Sham, Jerry J. Shih, Graeme J. Sills, Sanjay M. Sisodiya, Lisa Slattery, Alexander Smith, David F. Smith, Michael C. Smith, Philip E. Smith, Anja C.M. Sonsma, Doug Speed, Michael R. Sperling, Bernhard J. Steinhoff, Ulrich Stephani, Remi Stevelink, Konstantin Strauch, Pasquale Striano, Hans Stroink, Rainer Surges, K. Meng Tan, Liu Lin Thio, G. Neil Thomas, Marian Todaro, Rossana Tozzi, Maria S. Vari, Ellen P.G. Vining, Frank Visscher, Sarah Von Spiczak, Nicole M. Walley, Yvonne G. Weber, Zhi Wei, Judith Weisenberg, Christopher D. Whelan, Peter Widdess-Walsh, Markus Wolff, Wolking Wolking, Wanling Yang, Federico Zara, Fritz Zimprich

Department of Neurology Faculty Papers

The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression ...


Emerging Themes In Food Security: Environmental Justice, Extended Families And The Multiple Roles Of Grandmothers., Ethel Alderete, Lauren Sonderegger, Eliseo J Pérez-Stable Sep 2018

Emerging Themes In Food Security: Environmental Justice, Extended Families And The Multiple Roles Of Grandmothers., Ethel Alderete, Lauren Sonderegger, Eliseo J Pérez-Stable

Journal Articles and Abstracts

BACKGROUND: Pre- and perinatal nutritional status defines the development of adult metabolism and energy balance in humans. Young children in poor households are disproportionately more vulnerable to food insecurity given the cumulative impact of chronic stress on susceptibility to chronic diseases as an adult. Qualitative studies focusing on the experience of food insecurity in Latin America are scarce. In Argentina, although socioeconomic indicators improved in the aftermath of the 2001ecomomic crisis, the disadvantaged provinces in the north continue to bear the burden of historical inequities. The study was conducted among Primary Health Care patients in the city of San Salvador ...


Pretty Peachy., Li-Anne Lim, Basil K. Williams, Carol L. Shields Sep 2018

Pretty Peachy., Li-Anne Lim, Basil K. Williams, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.


Voices For Food: Methodologies For Implementing A Multi-State Community-Based Intervention In Rural, High Poverty Communities., Suzanne Stluka, Lindsay Moore, Heather A Eicher-Miller, Lisa Franzen-Castle, Becky Henne, Donna Mehrle, Daniel Remley, Lacey Mccormack Aug 2018

Voices For Food: Methodologies For Implementing A Multi-State Community-Based Intervention In Rural, High Poverty Communities., Suzanne Stluka, Lindsay Moore, Heather A Eicher-Miller, Lisa Franzen-Castle, Becky Henne, Donna Mehrle, Daniel Remley, Lacey Mccormack

Health and Nutritional Sciences Faculty Publications

BACKGROUND: Rural communities experience unique barriers to food access when compared to urban areas and food security is a public health issue in rural, high poverty communities. A multi-leveled socio-ecological intervention to develop food policy councils (FPCs), and improve food security in rural communities was created. Methods to carry out such an intervention were developed and are described.
METHODS: A longitudinal, matched treatment and comparison study was conducted in 24 rural, high poverty counties in South Dakota, Indiana, Missouri, Michigan, Nebraska and Ohio. Counties were assigned to a treatment (n = 12) or comparison (n = 12) group. Intervention activities focus on ...


Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk., Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier A Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer Doherty, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, María Soler Artigas, Martin D Tobin, Louise V Wain, Fangyi Gu, Jinyoung Byun, Ahsan Kamal, Dakai Zhu, Rachel F Tyndale, Wei-Qi Wei, Stephen Chanock, Paul Brennan, Christopher I Amos Aug 2018

Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk., Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, Chu Chen, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier A Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher Haiman, Lynne Wilkens, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Erik H F M Van Der Heijden, Jin Hee Kim, Juncheng Dai, Zhibin Hu, Michael P A Davies, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Jennifer Doherty, Gary E Goodman, Angela Cox, Fiona Taylor, Penella Woll, Irene Brüske, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Kjell Grankvist, Mikael Johansson, Frances Shepherd, Ming-Sound Tsao, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Woon-Puay Koh, Yu-Tang Gao, Richard Houlston, John Mclaughlin, Victoria Stevens, David C Nickle, Ma'en Obeidat, Wim Timens, Bin Zhu, Lei Song, María Soler Artigas, Martin D Tobin, Louise V Wain, Fangyi Gu, Jinyoung Byun, Ahsan Kamal, Dakai Zhu, Rachel F Tyndale, Wei-Qi Wei, Stephen Chanock, Paul Brennan, Christopher I Amos

Journal Articles and Abstracts

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to ...


Drosophila Cav2 Channels Harboring Human Migraine Mutations Cause Synapse Hyperexcitability That Can Be Suppressed By Inhibition Of A Ca2+ Store Release Pathway, Douglas J Brusich, Ashlyn M Spring, Thomas D James, Catherine J Yeates, Timothy H Helms, C Andrew Frank Aug 2018

Drosophila Cav2 Channels Harboring Human Migraine Mutations Cause Synapse Hyperexcitability That Can Be Suppressed By Inhibition Of A Ca2+ Store Release Pathway, Douglas J Brusich, Ashlyn M Spring, Thomas D James, Catherine J Yeates, Timothy H Helms, C Andrew Frank

Department of Anatomy and Cell Biology Publications

Gain-of-function mutations in the human CaV2.1 gene CACNA1A cause familial hemiplegic migraine type 1 (FHM1). To characterize cellular problems potentially triggered by CaV2.1 gains of function, we engineered mutations encoding FHM1 amino-acid substitutions S218L (SL) and R192Q (RQ) into transgenes of Drosophila melanogaster CaV2/cacophony. We expressed the transgenes pan-neuronally. Phenotypes were mild for RQ-expressing animals. By contrast, single mutant SL- and complex allele RQ,SL-expressing animals showed overt phenotypes, including sharply decreased viability. By electrophysiology, SL- and RQ,SL-expressing neuromuscular junctions (NMJs) exhibited enhanced evoked discharges, supernumerary discharges, and an increase in the amplitudes and frequencies of ...


Assessing A Novel Point-Of-Care Ultrasound Training Program For Rural Healthcare Providers In Kenya, Grace W Wanjiku, Gregory Bell, Benjamin Wachira Aug 2018

Assessing A Novel Point-Of-Care Ultrasound Training Program For Rural Healthcare Providers In Kenya, Grace W Wanjiku, Gregory Bell, Benjamin Wachira

Department of Emergency Medicine Publications

A novel point-of-care ultrasound (PoCUS) training program was developed to train rural healthcare providers in Kenya on the Focused Assessment with Sonography for Trauma (FAST), thoracic ultrasound, basic echocardiography, and focused obstetric ultrasonography. The program includes a multimedia manual, pre-course testing, 1-day hands-on training, post-testing, 3-month post-course evaluation, and scheduled refresher training. This study evaluates the impact of the course on PoCUS knowledge and skills. Competency results were compared based on number of previous training/refresher sessions and time elapsed since prior training.


A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford Aug 2018

A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval ...


Co-Expression Of Cd39 And Cd103 Identifies Tumor-Reactive Cd8 T Cells In Human Solid Tumors., Thomas Duhen, Rebekka Duhen, Ryan Montler, Jake Moses, Tarsem Moudgil, Noel F De Miranda, Cheri P Goodall, Tiffany C Blair, Bernard A Fox, Jason E Mcdermott, Shu-Ching Chang, Gary Grunkemeier, Rom Leidner, Richard Bryan Bell, Andrew D Weinberg Jul 2018

Co-Expression Of Cd39 And Cd103 Identifies Tumor-Reactive Cd8 T Cells In Human Solid Tumors., Thomas Duhen, Rebekka Duhen, Ryan Montler, Jake Moses, Tarsem Moudgil, Noel F De Miranda, Cheri P Goodall, Tiffany C Blair, Bernard A Fox, Jason E Mcdermott, Shu-Ching Chang, Gary Grunkemeier, Rom Leidner, Richard Bryan Bell, Andrew D Weinberg

Journal Articles and Abstracts

Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies ...


Recurrent Tumor-Specific Regulation Of Alternative Polyadenylation Of Cancer-Related Genes., Zhuyi Xue, René L Warren, Ewan A Gibb, Daniel Macmillan, Johnathan Wong, Readman Chiu, S Austin Hammond, Chen Yang, Ka Ming Nip, Catherine A Ennis, Abigail Hahn, Sheila Reynolds, Inanc Birol Jul 2018

Recurrent Tumor-Specific Regulation Of Alternative Polyadenylation Of Cancer-Related Genes., Zhuyi Xue, René L Warren, Ewan A Gibb, Daniel Macmillan, Johnathan Wong, Readman Chiu, S Austin Hammond, Chen Yang, Ka Ming Nip, Catherine A Ennis, Abigail Hahn, Sheila Reynolds, Inanc Birol

Journal Articles and Abstracts

BACKGROUND: Alternative polyadenylation (APA) results in messenger RNA molecules with different 3' untranslated regions (3' UTRs), affecting the molecules' stability, localization, and translation. APA is pervasive and implicated in cancer. Earlier reports on APA focused on 3' UTR length modifications and commonly characterized APA events as 3' UTR shortening or lengthening. However, such characterization oversimplifies the processing of 3' ends of transcripts and fails to adequately describe the various scenarios we observe.

RESULTS: We built a cloud-based targeted de novo transcript assembly and analysis pipeline that incorporates our previously developed cleavage site prediction tool, KLEAT. We applied this pipeline to ...


Direct Cell-To-Cell Transmission Of Respiratory Viruses: The Fast Lanes, Nicolás P. Cifuentes-Muñoz, Rebecca Ellis Dutch, Roberto Cattaneo Jun 2018

Direct Cell-To-Cell Transmission Of Respiratory Viruses: The Fast Lanes, Nicolás P. Cifuentes-Muñoz, Rebecca Ellis Dutch, Roberto Cattaneo

Molecular and Cellular Biochemistry Faculty Publications

Virus particles protect genomes from hostile environments within and outside the host, eventually delivering these genomes to target tissues to initiate infection. Complex processes requiring significant energy and time are necessary to assemble these virus particles, but only a small portion of released virus will successfully infect new target cells (Fig 1A). While the science of virology has developed based on the isolation and purification of viral particles, it is becoming increasingly clear that direct cell-to-cell transmission of viruses and/or viral components is also highly relevant [1,2].

Direct cell-to-cell spread of infections has several advantages. The first is ...


Altered Expression Of Genes Involved In Ganglioside Biosynthesis In Substantia Nigra Neurons In Parkinson's Disease., Jay S. Schneider Jun 2018

Altered Expression Of Genes Involved In Ganglioside Biosynthesis In Substantia Nigra Neurons In Parkinson's Disease., Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Reduced expression of GM1 and other major brain gangliosides GD1a, GD1b and GT1b have been reported in Parkinson's disease (PD) brain. Mechanisms underlying these changes are unclear but may be due to a deficit in the ganglioside biosynthetic process. The present study examined the extent to which deficits in gene expression of key biosynthetic enzymes involved in synthesis of GM1 and GD1b (B3galt4) and GD1a and GT1b (St3gal2) exist in neuromelanin-containing neurons in the PD substantia nigra (SN). In situ hybridization histochemistry was used to examine gene expression of B3GALT4 and ST3GAL2 in neuromelanin-containing neurons in the SN in ...


Can Capture Be Used To Identify Undiagnosed Patients With Mild-To-Moderate Copd Likely To Benefit From Treatment?, Nancy K. Leidy, Fernando J. Martinez, Karen G. Malley, David M. Mannino, Meilan K. Han, Elizabeth D. Bacci, Randall W. Brown, Julia F. Houfek, Wassim W. Labaki, Barry J. Make, Catherine A. Meldrum, Wilson Quezada, Stephen Rennard, Byron Thomashow, Barbara P. Yawn Jun 2018

Can Capture Be Used To Identify Undiagnosed Patients With Mild-To-Moderate Copd Likely To Benefit From Treatment?, Nancy K. Leidy, Fernando J. Martinez, Karen G. Malley, David M. Mannino, Meilan K. Han, Elizabeth D. Bacci, Randall W. Brown, Julia F. Houfek, Wassim W. Labaki, Barry J. Make, Catherine A. Meldrum, Wilson Quezada, Stephen Rennard, Byron Thomashow, Barbara P. Yawn

Preventive Medicine and Environmental Health Faculty Publications

Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC)11 60%–80% predicted) who may also benefit from diagnosis and treatment.

Methods: Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n ...


Trevo Stent-Retriever Mechanical Thrombectomy For Acute Ischemic Stroke Secondary To Large Vessel Occlusion Registry., Osama O Zaidat, Alicia C Castonguay, Raul G Nogueira, Diogo C Haussen, Joey D English, Sudhakar R Satti, Jennifer Chen, Hamed Farid, Candace Borders, Erol Veznedaroglu, Mandy J Binning, Ajit Puri, Nirav A Vora, Ron F Budzik, Guilherme Dabus, Italo Linfante, Vallabh Janardhan, Amer Alshekhlee, Michael G Abraham, Randall Edgell, Muhammad Asif Taqi, Ramy El Khoury, Maxim Mokin, Aniel Q Majjhoo, Mouhammed R Kabbani, Michael T Froehler, Ira Finch, Sameer A Ansari, Roberta Novakovic, Thanh N Nguyen Jun 2018

Trevo Stent-Retriever Mechanical Thrombectomy For Acute Ischemic Stroke Secondary To Large Vessel Occlusion Registry., Osama O Zaidat, Alicia C Castonguay, Raul G Nogueira, Diogo C Haussen, Joey D English, Sudhakar R Satti, Jennifer Chen, Hamed Farid, Candace Borders, Erol Veznedaroglu, Mandy J Binning, Ajit Puri, Nirav A Vora, Ron F Budzik, Guilherme Dabus, Italo Linfante, Vallabh Janardhan, Amer Alshekhlee, Michael G Abraham, Randall Edgell, Muhammad Asif Taqi, Ramy El Khoury, Maxim Mokin, Aniel Q Majjhoo, Mouhammed R Kabbani, Michael T Froehler, Ira Finch, Sameer A Ansari, Roberta Novakovic, Thanh N Nguyen

Journal Articles and Abstracts

BACKGROUND: Recent randomized clinical trials (RCTs) demonstrated the efficacy of mechanical thrombectomy using stent-retrievers in patients with acute ischemic stroke (AIS) with large vessel occlusions; however, it remains unclear if these results translate to a real-world setting. The TREVO Stent-Retriever Acute Stroke (TRACK) multicenter Registry aimed to evaluate the use of the Trevo device in everyday clinical practice.

METHODS: Twenty-three centers enrolled consecutive AIS patients treated from March 2013 through August 2015 with the Trevo device. The primary outcome was defined as achieving a Thrombolysis in Cerebral Infarction (TICI) score of ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS ...


Phenotypical Characterization Of Human Rhinovirus Infections In Severely Premature Children, Geovanny F. Perez, Bassem Kurdi, Rosemary Megalaa, Krishna Pancham, Shehlanoor Huseni, Natalia Isaza, Carlos E. Rodriguez-Martinez, Dinesh Pillai, Gustavo Nino Jun 2018

Phenotypical Characterization Of Human Rhinovirus Infections In Severely Premature Children, Geovanny F. Perez, Bassem Kurdi, Rosemary Megalaa, Krishna Pancham, Shehlanoor Huseni, Natalia Isaza, Carlos E. Rodriguez-Martinez, Dinesh Pillai, Gustavo Nino

Pediatrics Faculty Publications

Background: Human Rhinovirus (HRV) has been identified as the most common cause of acute respiratory infections and hospitalizations in premature children. It is unclear if premature children are more susceptible to HRV due to their decreased pulmonary reserve or because they have enhanced lower airway reactivity to HRV.

Methods: We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HRV infections in full-term and premature children aged ≤ 3 years in our institution. Standardized respiratory distress scores were developed to examine lower airway obstruction (i.e., wheezing, hyperinflation, and sub-costal retractions) along with markers of decreased pulmonary reserve ...


Age Adjusted Hematopoietic Stem Cell Transplant Comorbidity Index Predicts Survival In A T-Cell Depleted Cohort, Hayder Saeed, Swati Yalamanchi, Meng Liu, Emily Van Meter, Zartash Gul, Gregory Monohan, Dianna Howard, Gerhard C. Hildebrandt, Roger Herzig Jun 2018

Age Adjusted Hematopoietic Stem Cell Transplant Comorbidity Index Predicts Survival In A T-Cell Depleted Cohort, Hayder Saeed, Swati Yalamanchi, Meng Liu, Emily Van Meter, Zartash Gul, Gregory Monohan, Dianna Howard, Gerhard C. Hildebrandt, Roger Herzig

Markey Cancer Center Faculty Publications

Objectives: Allogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria.

Methods: A retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was ...


In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian May 2018

In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian

Veterinary Science Faculty Publications

Background

The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define ...


Analysis Of The Immunological Biomarker Profile During Acute Zika Virus Infection Reveals The Overexpression Of Cxcl10, A Chemokine Linked To Neuronal Damage., Felipe Gomes Naveca, Gemilson Soares Pontes, Aileen Yu-Hen Chang, George Allan Villarouco Da Silva, Valdinete Alves Do Nascimento, Dana Cristina Da Silva Monteiro, +Several Additional Authors May 2018

Analysis Of The Immunological Biomarker Profile During Acute Zika Virus Infection Reveals The Overexpression Of Cxcl10, A Chemokine Linked To Neuronal Damage., Felipe Gomes Naveca, Gemilson Soares Pontes, Aileen Yu-Hen Chang, George Allan Villarouco Da Silva, Valdinete Alves Do Nascimento, Dana Cristina Da Silva Monteiro, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis.

OBJECTIVES: To define the immunologic biomarkers that correlate with acute ZIKV infection.

METHODS: We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining.

FINDINGS: ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite ...


Lost Seasonality And Overconsumption Of Plants: Risking Oxalate Toxicity, Sally K. Norton May 2018

Lost Seasonality And Overconsumption Of Plants: Risking Oxalate Toxicity, Sally K. Norton

Journal of Evolution and Health

In many plants, oxalate crystals are present. These relatively large microcrystals have the potential to inflict mechanical injury. On the other hand, ionic, soluble, and nano-crystal forms of oxalate are readily absorbed. Bioaccumulation in humans is well documented. Crystals and ionic oxalate are associated with pain and both functional and chronic disorders.

Today’s many health challenges have led people to select foods purported to be healthier, many of which are high in oxalate. Modern dietary approaches have placed great emphasis on the health benefits of vegetables, nuts, and spices. Many of these are high oxalate foods that are now ...


Exacerbation Recovery Patterns In Newly Diagnosed Or Maintenance Treatment-Naïve Patients With Copd: Secondary Analyses Of Ticari 1 Trial Data, David M. Mannino, Emmanuelle M. Clerisme-Beaty, Joanne Franceschina, Naitee Ting, Nancy K. Leidy May 2018

Exacerbation Recovery Patterns In Newly Diagnosed Or Maintenance Treatment-Naïve Patients With Copd: Secondary Analyses Of Ticari 1 Trial Data, David M. Mannino, Emmanuelle M. Clerisme-Beaty, Joanne Franceschina, Naitee Ting, Nancy K. Leidy

Preventive Medicine and Environmental Health Faculty Publications

Background: Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naïve patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI).

Methods: This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 µg maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naïve COPD patients with acute RTI symptoms for ≤7 days. Patients received standard care ...


Genome-Wide Association Meta-Analysis Of Circulating Odd-Numbered Chain Saturated Fatty Acids: Results From The Charge Consortium, Marcia C. De Oliveira Otto, Rozenn N. Lemaitre, Qi Sun, Irena B. King, Jason H. Y. Wu, Ani Manichaikul, Stephen S. Rich, Michael Y. Tsai, Y. D. Chen, Myriam Fornage, Guan Weihua, Stella Aslibekyan, Marguerite R. Irvin, Edmond K. Kabagambe, Donna K. Arnett, Majken K. Jensen, Barbara Mcknight, Bruce M. Psaty, Lyn M. Steffen, Caren E. Smith, Ulf Risérus, Lars Lind, Frank B. Hu, Eric B. Rimm, David S. Siscovick, Dariush Mozaffarian May 2018

Genome-Wide Association Meta-Analysis Of Circulating Odd-Numbered Chain Saturated Fatty Acids: Results From The Charge Consortium, Marcia C. De Oliveira Otto, Rozenn N. Lemaitre, Qi Sun, Irena B. King, Jason H. Y. Wu, Ani Manichaikul, Stephen S. Rich, Michael Y. Tsai, Y. D. Chen, Myriam Fornage, Guan Weihua, Stella Aslibekyan, Marguerite R. Irvin, Edmond K. Kabagambe, Donna K. Arnett, Majken K. Jensen, Barbara Mcknight, Bruce M. Psaty, Lyn M. Steffen, Caren E. Smith, Ulf Risérus, Lars Lind, Frank B. Hu, Eric B. Rimm, David S. Siscovick, Dariush Mozaffarian

Epidemiology Faculty Publications

Background

Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established.

Objective

To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA.

Design

We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0 ...


Neural Mechanisms Of The Rejection-Aggression Link, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall May 2018

Neural Mechanisms Of The Rejection-Aggression Link, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

Social rejection is a painful event that often increases aggression. However, the neural mechanisms of this rejection–aggression link remain unclear. A potential clue may be that rejected people often recruit the ventrolateral prefrontal cortex’s (VLPFC) self-regulatory processes to manage the pain of rejection. Using functional MRI, we replicated previous links between rejection and activity in the brain’s mentalizing network, social pain network and VLPFC. VLPFC recruitment during rejection was associated with greater activity in the brain’s reward network (i.e. the ventral striatum) when individuals were given an opportunity to retaliate. This retaliation-related striatal response was ...


Physiologically Based Pharmacokinetic Modeling Of Nanoceria Systemic Distribution In Rats Suggests Dose- And Route-Dependent Biokinetics, Ulrika Carlander, Tshepo Paulsen Moto, Anteneh Assefa Desalegn, Robert A. Yokel, Gunnar Johanson May 2018

Physiologically Based Pharmacokinetic Modeling Of Nanoceria Systemic Distribution In Rats Suggests Dose- And Route-Dependent Biokinetics, Ulrika Carlander, Tshepo Paulsen Moto, Anteneh Assefa Desalegn, Robert A. Yokel, Gunnar Johanson

Pharmaceutical Sciences Faculty Publications

Background: Cerium dioxide nanoparticles (nanoceria) are increasingly being used in a variety of products as catalysts, coatings, and polishing agents. Furthermore, their antioxidant properties make nanoceria potential candidates for biomedical applications. To predict and avoid toxicity, information about their biokinetics is essential. A useful tool to explore such associations between exposure and internal target dose is physiologically based pharmacokinetic (PBPK) modeling. The aim of this study was to test the appropriateness of our previously published PBPK model developed for intravenous (IV) administration when applied to various sizes of nanoceria and to exposure routes relevant for humans.

Methods: Experimental biokinetic data ...


Digitizing Omics Profiles By Divergence From A Baseline., Wikum Dinalankara, Qian Ke, Yiran Xu, Lanlan Ji, Nicole Pagane, Anching Lien, Tejasvi Matam, Elana J Fertig, Nathan D Price, Laurent Younes, Luigi Marchionni, Donald Geman May 2018

Digitizing Omics Profiles By Divergence From A Baseline., Wikum Dinalankara, Qian Ke, Yiran Xu, Lanlan Ji, Nicole Pagane, Anching Lien, Tejasvi Matam, Elana J Fertig, Nathan D Price, Laurent Younes, Luigi Marchionni, Donald Geman

Journal Articles and Abstracts

Data collected from omics technologies have revealed pervasive heterogeneity and stochasticity of molecular states within and between phenotypes. A prominent example of such heterogeneity occurs between genome-wide mRNA, microRNA, and methylation profiles from one individual tumor to another, even within a cancer subtype. However, current methods in bioinformatics, such as detecting differentially expressed genes or CpG sites, are population-based and therefore do not effectively model intersample diversity. Here we introduce a unified theory to quantify sample-level heterogeneity that is applicable to a single omics profile. Specifically, we simplify an omics profile to a digital representation based on the omics profiles ...


Population-Specific Genetic Modification Of Huntington's Disease In Venezuela., Michael J Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C Wheeler, Hong Li, Jared C Roach, Leroy Hood, Nancy S Wexler, Laura B Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, Marcy E Macdonald, James F Gusella, Jong-Min Lee May 2018

Population-Specific Genetic Modification Of Huntington's Disease In Venezuela., Michael J Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C Wheeler, Hong Li, Jared C Roach, Leroy Hood, Nancy S Wexler, Laura B Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, Marcy E Macdonald, James F Gusella, Jong-Min Lee

Journal Articles and Abstracts

Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a ...


Tat Controls Transcriptional Persistence Of Unintegrated Hiv Genome In Primary Human Macrophages., Beatrix Meltzer, Deemah Dabbagh, Jia Guo, Fatah Kashanchi, Mudit Tyagi, Yuntao Wu May 2018

Tat Controls Transcriptional Persistence Of Unintegrated Hiv Genome In Primary Human Macrophages., Beatrix Meltzer, Deemah Dabbagh, Jia Guo, Fatah Kashanchi, Mudit Tyagi, Yuntao Wu

Medicine Faculty Publications

In HIV infected macrophages, a large population of viral genomes persists as the unintegrated form (uDNA) that is transcriptionally active. However, how this transcriptional activity is controlled remains unclear. In this report, we investigated whether Tat, the viral transactivator of transcription, is involved in uDNA transcription. We demonstrate that de novo Tat activity is generated from uDNA, and this uDNA-derived Tat (uTat) transactivates the uDNA LTR. In addition, uTat is required for the transcriptional persistence of uDNA that is assembled into repressive episomal minichromatin. In the absence of uTat, uDNA minichromatin is gradually silenced, but remains highly inducible by HDAC ...


Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi Apr 2018

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.


Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu Apr 2018

Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu

Markey Cancer Center Faculty Publications

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce ...