259 results on '"N. Lynch"'
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2. Gas Chromatography--Mass Spectrometry Analysis of Cannabis: Undergraduate Organic Chemistry Laboratory Exercise
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Hailey N. Lynch, Claire Chaz Authement, Autumn Maczko, Miranda Parker, Kaylan Beaty, and Anuradha Liyana Pathiranage
- Abstract
In this laboratory teaching experiment, commercial cannabis oils were analyzed by undergraduate organic chemistry students using gas chromatography-mass spectrometry (GC-MS) to investigate three isomeric cannabinoids commonly found in cannabis products: cannabidiol (CBD), [delta][superscript 9]-tetrahydrocannabinol ([delta][superscript 9]-THC), and [delta][superscript 8]-tetrahydrocannabinol ([delta][superscript 8]-THC). The goal was to introduce GC-MS analysis through the relevant topic of product quality inspection, frequently used in various industries such as pharmaceuticals, cosmetics, etc. and which largely involves analyzing the chemical components of a sample. First, to better understand the cannabinoid analytes, students were taught the differences between these structural isomers, including bond locations, stereochemistry, and functional groups--factors which pertain to their pharmacology and drug classification. Finally, students were guided through the basics of GC-MS instrumentation and the process of analyzing GC-MS spectra through the characterization of CBD, [delta][superscript 8]-THC, and [delta][superscript 9]-THC present in oil samples.
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- 2023
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3. Triangulation of epidemiological evidence and risk of bias evaluation: A proposed framework and applied example using formaldehyde exposure and risk of myeloid leukemias
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Daniel J. Lauer, Anthony J. Russell, Heather N. Lynch, William J. Thompson, Kenneth A. Mundt, and Harvey Checkoway
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Triangulation ,Risk of bias ,Evidence synthesis ,Formaldehyde ,Myeloid leukemia ,Infectious and parasitic diseases ,RC109-216 - Abstract
Evidence triangulation may help identify the impact of study design elements on study findings and to tease out biased results when evaluating potential causal relationships; however, methods for triangulating epidemiologic evidence are evolving and have not been standardized. Building upon key principles of epidemiologic evidence triangulation and risk of bias assessment, and responding to the National Academies of Sciences, Engineering, and Medicine (NASEM) call for applied triangulation examples, the objective of this manuscript is to propose a triangulation framework and to apply it as an illustrative example to epidemiologic studies examining the possible relationship between occupational formaldehyde exposure and risk of myeloid leukemias (ML) including acute (AML) and chronic (CML) types.A nine-component triangulation framework for epidemiological evidence was developed incorporating study quality and ROB guidance from various federal health agencies (i.e., US EPA TSCA and NTP OHAT). Several components of the triangulation framework also drew from widely used epidemiological analytic tools such as stratified meta-analysis and sensitivity analysis. Regarding the applied example, fourteen studies were identified and assessed using the following primary study quality domains to explore potential key sources of bias: 1) study design and analysis; 2) study participation; 3) exposure assessment; 4) outcome assessment; and 5) potential confounding. Across studies, methodological limitations possibly contributing to biased results were observed within most domains. Interestingly, results from one study – often providing the largest and least-precise relative risk estimates, likely reflecting study biases, deviated from most primary study findings indicating no such associations. Triangulation of epidemiological evidence appears to be helpful in exploring inconsistent results for the identification of study results possibly reflecting various biases. Nonetheless, triangulation methodologies require additional development and application to real-world examples to enhance objectivity and reproducibility.
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- 2024
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4. The Impact of the NASA – Keck Observatory Partnership
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Ciara N. Lynch, Mario R. Perez, Peggi Kamisato, and Richard J. Howard
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Astronomy - Abstract
In the last thirty years, NASA Space Sciences and the W. M. Keck Observatory have established a partnership that has enabled both organizations to collaborate on scientific endeavors, some more successful than others. This ad-hoc relationship started with NASA participation in the Keck II construction around 1993 and it was formalized later in 1996 in the form of a Cooperative Agreement, a contractual vehicle which remains active until the present. The intention of documenting this partnership is to celebrate 30-years of Keck operations and for the benefit of future similar endeavors that could be established on protected lands. The value of lessons learned from these partnerships enables more effective ways to continue with future partnerships and agreements. In this document, we present the inception, evolution, and current status of this partnership by exploring four important past and current tasks or activities: Keck II development, Keck Interferometer and Outriggers, Keck Observatory Archive, and the continuous support of NASA space missions throughout the years. After diving into this sensitive and important topic, we offer some reflections on important points of the partnership and identify lessons that can be utilized in the future.
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- 2023
5. Long-Term Impact of Direct-Acting Antivirals on Liver Fibrosis and Survival in HCV-Infected Liver Transplant Recipients
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Martina Gambato, Chiara Manuli, Erica N. Lynch, Sara Battistella, Giacomo Germani, Marco Senzolo, Alberto Zanetto, Alberto Ferrarese, Alessandro Vitale, Enrico Gringeri, Umberto Cillo, Patrizia Burra, and Francesco Paolo Russo
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hepatitis C virus ,DAAs ,liver transplantation ,Microbiology ,QR1-502 - Abstract
(1) Background: Little is known about the long-term impact of sustained virological response (SVR) on fibrosis progression and patient survival in liver transplantation (LT) recipients treated with direct-acting antivirals (DAAs). We investigated liver fibrosis evolution and patient survival in hepatitis C virus (HCV)-infected patients receiving DAAs after LT. (2) Methods: All consecutive HCV-infected patients treated with DAAs after LT between May 2014 and January 2019 were considered. The clinical and virological features were registered at the baseline and during the follow-up. The liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at the baseline and at least 1 year after the end of treatment (EoT). (3) Results: A total of 136 patients were included. The SVR12 was 78% after the first treatment and 96% after retreatment. After the SVR12, biochemical tests improved at the EoT and remained stable throughout the 3-year follow-up. Liver fibrosis improved after the SVR12 (p < 0.001); nearly half of the patients with advanced liver fibrosis experienced an improvement of an F ≤ 2. The factors associated with lower survival in SVR12 patients were the baseline platelet count (p = 0.04) and creatinine level (p = 0.04). (4) Conclusions: The long-term follow-up data demonstrated that SVR12 was associated with an improvement in hepatic function, liver fibrosis, and post-LT survival, regardless of the baseline liver fibrosis. The presence of portal hypertension before the DAAs has an impact on patient survival, even after SVR12.
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- 2023
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6. Investigation of Cinnamaldehyde Derivatives as Potential Organic UV Filters
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Monica B. Pan, Chloe S. Hughes, Hailey N. Lynch, Marcia M. Schilling, and Anuradha Liyana Pathiranage
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Chemistry ,QD1-999 - Abstract
Long-term exposure to ultraviolet (UV) rays has been attributed to irreversible health defects at the cellular level. Most importantly, damage to DNA by UVA and UVB rays can result in uncontrolled cellular growth, leading to skin cancer. As a result, topical treatments have been developed over time to protect the skin from UVA and UVB rays. The active ingredients in sunscreens or sun creams are sometimes unsaturated, aromatic organic compounds capable of absorbing harmful UV photons at a great range of wavelengths. Absorption capabilities of these species depend on their degree of conjugation and their molar absorptivity. With this knowledge, two cinnamaldehyde derivatives were synthesized into five potential organic UV filters by the aldol condensation reaction. The products were identified using nuclear magnetic resonance (NMR) and attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopies, and ultraviolet-visible (UV-vis) spectroscopy was used to determine the UV absorption range and intensity of absorption for each compound. Since the compounds would hypothetically be utilized in topical ointments to aide in skin protection, these compounds were assessed in the presence of Pseudomonas aeruginosa, a representative bacterium of the skin’s natural flora. A time-course assay was conducted to detect growth effects of P. aeruginosa in the presence of the organic compounds. According to the spectroscopic and bacterial analyses of these UV-blocking compounds, three compounds were determined to be potential UV filters that cover UVA region while demonstrating no apparent harm to the natural skin bacteria P. aeruginosa, while the other two likely diminished bacterial growth by simple niche inhibition.
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- 2022
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7. Outcomes of gynecologic cancer surgery during the COVID-19 pandemic: an international, multicenter, prospective CovidSurg-Gynecologic Oncology Cancer study
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Nepogodiev, Dmitri, Siaw-Acheampong, Kwabena, Benson, Ruth A., Bywater, Edward, Chaudhry, Daoud, Dawson, Brett E., Evans, Jonathan P., Glasbey, James C., Gujjuri, Rohan R., Heritage, Emily, Jones, Conor S., Kamarajah, Sivesh K., Khatri, Chetan, Khaw, Rachel A., Keatley, James M., Knight, Andrew, Lawday, Samuel, Li, Elizabeth, Mann, Harvinder S., Marson, Ella J., McLean, Kenneth A., Mckay, Siobhan C., Mills, Emily C., Pellino, Gianluca, Picciochi, Maria, Taylor, Elliott H., Tiwari, Abhinav, Simoes, Joana FF., Trout, Isobel M., Venn, Mary L., Wilkin, Richard JW., Bhangu, Aneel, Abbott, Tom EF., Abukhalaf, Sadi, Adamina, Michel, Ademuyiwa, Adesoji O., Agarwal, Arnav, Akkulak, Murat, Alameer, Ehab, Alderson, Derek, Alakaloko, Felix, Albertsmeier, Markus, Alser, Osaid, Alshaar, Muhammad, Alshryda, Sattar, Arnaud, Alexis P., Augestad, Knut Magne, Ayasra, Faris, Azevedo, José, Bankhead-Kendall, Brittany K., Barlow, Emma, Beard, David, Blanco-Colino, Ruth, Brar, Amanpreet, Minaya-Bravo, Ana, Breen, Kerry A., Bretherton, Chris, Buarque, Igor Lima, Burke, Joshua, Caruana, Edward J., Chaar, Mohammad, Chakrabortee, Sohini, Christensen, Peter, Cox, Daniel, Cukier, Moises, Cunha, Miguel F., Davidson, Giana H., Desai, Anant, Di Saverio, Salomone, Drake, Thomas M., Edwards, John G., Elhadi, Muhammed, Emile, Sameh, Farik, Shebani, Fiore, Marco, Fitzgerald, J Edward, Ford, Samuel, Garmanova, Tatiana, Gallo, Gaetano, Ghosh, Dhruva, Ataíde Gomes, Gustavo Mendonça, Grecinos, Gustavo, Griffiths, Ewen A., Gruendl, Magdalena, Halkias, Constantine, Harrison, Ewen M., Hisham, Intisar, Hutchinson, Peter J., Hwang, Shelley, Isik, Arda, Jenkinson, Michael D., Jonker, Pascal, MA Kaafarani, Haytham, Keller, Debby, Kolias, Angelos, Kruijff, Schelto, Lawani, Ismail, Lederhuber, Hans, Leventoglu, Sezai, Litvin, Andrey, Loehrer, Andrew, Löffler, Markus W., Lorena, Maria Aguilera, Modolo, Maria Marta, Major, Piotr, Martin, Janet, Mashbari, Hassan N., Mazingi, Dennis, Metallidis, Symeon, Mohan, Helen M., Moore, Rachel, Moszkowicz, David, Moug, Susan, Ng-Kamstra, Joshua S., Maimbo, Mayaba, Negoi, Ionut, Niquen, Milagros, Ntirenganya, Faustin, Olivos, Maricarmen, Oussama, Kacimi, Outani, Oumaima, Parreno-Sacdalanm, Marie Dione, Pata, Francesco, Perez Rivera, Carlos Jose, Pinkney, Thomas D., van der Plas, Willemijn, Pockney, Peter, Qureshi, Ahmad, Radenkovic, Dejan, Ramos-De la Medina, Antonio, Richards, Toby, Roberts, Keith, Roslani, April C., Rutegård, Martin, Segura-Sampedro, Juan José, Santos, Irène, Satoi, Sohei, Sayyed, Raza, Schache, Andrew, Schnitzbauer, Andreas A., Seyi-Olajide, Justina O., Sharma, Neil, Shaw, Catherine A., Shaw, Richard, Shu, Sebastian, Soreide, Kjetil, Spinelli, Antonino, Stewart, Grant D., Sund, Malin, Sundar, Sudha, Tabiri, Stephen, Townend, Philip, Tsoulfas, Georgios, van Ramshorst, Gabrielle H., Vidya, Raghavan, Vimalachandran, Dale, Warren, Oliver J., Wedderburn, Duane, Wright, Naomi, Booth, Lesley, Barker, Neil, Cooke, Shirley, Doré, Suzanne, Horwood, Nigel, Runigamugabo, Emmy, Weir, Carrie Tierney, Dajti I, Albania, C, Allemand, LA, Boccalatte, M, Figari, M, Lamm, J, Larrañaga, C, Marchitelli, F, Noll, D, Odetto, M, Perrotta, J, Saadi, L, Zamora, Ballester, A.M., KE, Tapper, N, Zeff, JI, Valenzuela, C, Alurralde, J, Anastasio, Perez de Nucci A, Apas, EL, Caram, D, Eskinazi, JP, Mendoza, M, Usandivaras, R, Badra, A, Esteban, JS, García, PM, García, JI, Gerchunoff, Lucchini, S.M., NIgra, M.A., L, Vargas, T, Hovhannisyan, A, Stepanyan, CE, Vasey, EGR, Watson, C, Ip, J, Kealey, CSH, Lim, S, Sengupta, S, Ward, E, Wong, T, Gould, R, Gourlay, B, Griffiths, S, Gananadha, M, McLaren, J, Cecire, N, Joshi, S, Salindera, A, Sutherland, JH, Ahn, G, Charlton, S, Chen, N, Gauri, R, Hayhurst, S, Jang, F, Jia, C, Mulligan, W, Yang, G, Ye, H, Zhang, M, Ballal, D, Gibson, D, Hayne, H, McMillan, J, Moss, MJ, Pugliese, T, Richards, YTN, Seow, A, Thian, P, Viswambaram, UG, Vo, J, Bennetts, T, Bright, Brooke-Smith, M., R, Fong, B, Gricks, L, Huang, YH, Lam, A, Nathan, Ong, B.S., E, Ooi, M, Szpytma, D, Watson, K, Bagraith, S, Caird, E, Chan, C, Dawson, D, Ho, N, Hui, S, Izwan, E, Jeyarajan, S, Jordan, R, Liang, A, Lim, GJ, Nolan, A, Oar, D, Parker, H, Puhalla, A, Quennell, L, Rutherford, C, Sommerville, P, Townend, Papen M, Von, M, Wullschleger, AC, Dawson, A, Drane, A, Blatt, D, Cope, N, Egoroff, M, Fenton, J, Gani, N, Lott, P, Pockney, N, Shugg, M, Elliott, D, Phung, D, Phan, D, Townend, C, Bong, J, Gundara, A, Frankel, S, Bowman, GR, Guerra, N, Gerns, S, McGeorge, A, Riddell, M, Roberts, N, Rukin, J, Bolt, K, Buddingh, Dudi-Venkata, N.N., S, Jog, HM, Kroon, T, Sammour, R, Smith, C, Stranz, M, Batstone, K, Lah, W, McGahan, D, Mitchell, A, Morton, A, Pearce, G, Sheahan, B, Swinson, A, Waldron, P, Walker, N, Alam, S, Banting, L, Chong, P, Choong, S, Clatworthy, D, Foley, A, Fox, MW, Hii, B, Knowles, J, Mack, M, Read, A, Rowcroft, G, Wright, EWY, Lun, M, Lanner, J, Burtscher, Trivik-Barrientos, F., I, Königsrainer, M, Bauer, C, Freyschlag, M, Kafka, F, Messner, D, Öfner, I, Tsibulak, S, Holawe, M, Zimmermann, K, Emmanuel, M, Grechenig, R, Gruber, M, Harald, L, Öhlberger, J, Presl, A, Wimmer, İ, Namazov, E, Samadov, D, Barker, R, Boyce, S, Corbin, A, Doyle, A, Eastmond, R, Gill, A, Haynes, S, Millar, M, O’Shea, G, Padmore, N, Paquette, E, Phillips, John S, St., K, Walkes, J, Abeloos, Backer T, De, Ceulaer J, De, C, Dick, Diez-Fraile, A., P, Lamoral, C, Spaas, W, Ceelen, P, Pattyn, D, Van de putte, Nieuwenhove Y, Van, Ramshorst G, Van, Willaert, W., Bazzett-Matabele, L., SP, Chiyapo, Ramogola-Masire, D., G, Ramontshonyana, A, Seiphetlheng, P, Vuylsteke, EA, Abdallah, Júnior S, Aguiar, G, Baiocchi, GB, Carvalho, FJF, Coimbra, LP, Kowalski, F, Makdissi, N, Marques, T, Marques, Santos S, Soares Dos, Gonçalves B, Tirapelli, JG, Vartanian, Reis R, Dos, P, Camara, Lima RK, De, Giustina E, Della, PV, Hoffmann, A, Gatti, C, Nardi, R, Oliva, L, Nacif, Ferro C, Carvalho, Ataíde G, Gomes Mendonça, Buarque I, Lima, A, Lira dos Santos Leite, Pol-Fachin, L., Bezerra T, Santos, Ramos da Silva A, Maylson, de Araújo Silvestre D, Windson, Barros A, Vieira, L, Campbell, Cicco R, De, I, Cecconello, P, Gregorio, Lima L, Pontual, Junior U, Ribeiro, FR, Takeda, RM, Terra, Teixeira M, Faccini, Kulcsar, M.A.V., LL, Matos, KS, Nunes, G, Laporte, M, Salem, Awada J, Barakat, TR, Ijichi, NJ, Kim, A, Marreiro, B, Muller, R, Nunes, B, Bodanese, ER, Eidt, JC, Isoton, Vieira da Cunha M, Lemos, de Sampaio L, Regina, C, Vendrame, M, Zeni, JA, Zortéa, MR, Zortéa, M, Sokolov, B, Kidane, S, Srinathan, A, Munro, L, Helyer, D, McKeen, M, Boutros, NG, Caminsky, G, Ghitulescu, G, Jamjoum, J, Moon, J, Pelletier, T, Vanounou, S, Wong, D, Cheng, SD, MacNeil, J, Martin, S, Dumitra, A, Kouyoumdjian, S, Schmid, J, Spicer, A, Agarwal, A, Brar, J, Dada, A, Dare, U, Hameed, F, Osman, B, Johnston, C, Russell, G, Groot, A, Persad, H, Pham, M, Wood, M, Ko, L, Rajendran, S, Demyttenaere, R, Garfinkle, C, Brown, A, Karimuddin, N, Lee, J, Liu, Kia T, Madani, Phang, P.T., M, Raval, K, Tom, Abou-Khalil, J., A, Martel, C, Nessim, J, Stevenson, Riyami S, Al, K, Bali, D, Bigam, K, Dajani, A, Dell, MM, Modolo, Nieto P, Ramirez, R, Sepulveda, A, Molero, A, Bolbaran, I, Ruiz, F, Heredia, F, Bellolio, N, Besser, E, Grasset, JO, Guaman, M, Inzunza, MJ, Irarrázaval, C, Jarry, Martinic M, Quintana, Altamirano C, Riquoir, Manqui CA, Romero, Esquide M, Ruiz, Añazco C, Vargas, A, Almeciga, A, Fletcher, A, Merchan, T, Quijano, D, Sanabria, Arias-Amézquita, F., C, Cétares, Murgueitio N, Cortes, Gomez-Mayorga, J.L., Herrera-Almario, G., J, Rodriguez, P, Iglesias, LO, Puentes, JA, Calvache, Orozco-Chamorro, C.M., DA, Rojas, Sánchez-Gómez, A., M, Abadia, J, Acosta, Aristizabal J, Angel, A, Bonilla, L, Caicedo, Quiroz PH, Calderon, Bonilla S, Cervera, S, Diaz, H, Facundo, Mora M, Garcia, O, Guevara, L, Guzman, Mora DR, Herrera, Ramirez LJ, Jimenez, C, Lehmann, E, Manrique, I, Mariño, M, Medina, Morales RE, Pinilla, A, Puerto, Horta J, Puerto, M, Quintero, Ferro M, Rey, A, Saénz, D, Santana, W, Serrano, O, Suescun, Sanchez LM, Trujillo, Cuasquen BG, Velasquez, Quevedo J , Bogota, Mendoza, G, Bačić, D, Karlović, D, Kršul, M, Zelić, I, Luksic, M, Mamic, I, Bacic, B, Bakmaz, I, Ćoza, E, Dijan, Z, Katusic, J, Mihanovic, D, Morović, I, Rakvin, H, Almezghwi, K, Arslan, H, Besim, A, Özant, N, Özçay, K, Frantzeskou, N, Gouvas, G, Kokkinos, P, Papatheodorou, I, Pozotou, O, Stavrinidou, A, Yiallourou, L, Martinek, M, Skrovina, M, Straka, I, Szubota, M, Peteja, J, Žatecký, V, Javurkova, J, Klat, S, Antony, T, Avlund, KD, Berg, M, Borre, P, Christensen, MC, Elkjær, A, Ernst, SK, Fensman, M, Haldrup, JL, Harbjerg, LH, Iversen, Jensen, P.T., TD, Jeppesen, DW, Kjaer, HØ, Kristensen, N, Lund, Axelsen S, Maigaard, M, Mekhael, N, Mikic, EB, Ostenfeld, AL, Ebbehøj, P, Krarup, N, Schlesinger, H, Smith, S, Batista, A, Crespo, PJ, Díaz, R, Rivas, Rodriguez-Abreu, J., N, Tactuk, Kassas M, El, W, Omar, A, Tawheed, M, Talaat, A, Abdelsamed, AY, Azzam, H, Salem, A, Seleim, A, Abdelmajeed, M, Abdou, NE, Abosamak, Sayed M, A.L., F, Ashoush, R, Atta, E, Elazzazy, M, Elnemr, Hewalla ME, Elsayed, I, Elsherbini, E, Essam, M, Ewedah, I, Ghallab, E, Hassan, M, Ibrahim, M, Metwalli, M, Mourad, Qatora, M.S., M, Ragab, A, Sabry, H, Saifeldin, A, Samih, Abdelaal A, Samir, S, Shehata, K, Shenit, D, Attia, N, Kamal, N, Osman, Abbas, A.M., Elazeem HAS, Abd, Abd-Elkariem, A.Y., MM, Abdelkarem, S, Alaa, M, Ashraf, A, Ayman, MG, Azizeldine, H, Elkhayat, Mashhour A, Emad, M, Gaber, HM, Hamza, I, Hawal, HF, Hetta, Ali A, K., S, M.elghazaly, MM, Mohammed, FA, Monib, Nageh, M.A., A, Saad, MM, Saad, M, Shahine, EA, Yousof, A, Youssef, El-Deeb, M., M, Fawzy, G, Ghaly, M, Ibraheem, A, Eldaly, E, Esmail, M, ElFiky, A, Nabil, M, Alrahawy, A, Sakr, H, Soliman, H, Soltan, G, Amira, I, Sallam, M, Sherief, A, Sherif, A, Abdelrahman, H, Aboulkassem, R, Hamdy, A, Morsi, G, Sherif, H, Abdeldayem, Salama I, Abdelkader, M, Balabel, Y, Fayed, AE, Sherif, R, Elmorsi, S, Emile, B, Refky, S, Abd-elsalam, H, Badr, M, Elbahnasawy, M, Elzoghby, M, Essa, Badr S, Gamal, A, Ghoneim, O, Hamad, M, Hamada, M, Hammad, A, Hawila, Morsy, M.S., S, Salman, S, Sarsik, K, Bekele, JH, Kauppila, E, Sarjanoja, O, Helminen, H, Huhta, C, Beyrne, L, Jouffret, L, Lugans, Marie-Macron, L., E, Chouillard, Simone B, De, F, Fredon, A, Roux, J, Bettoni, S, Dakpé, B, Devauchelle, N, Lavagen, S, Testelin, S, Boucher, R, Breheret, A, Gueutier, A, Kahn, Kün-Darbois, J., A, Barrabe, Z, Lakkis, A, Louvrier, S, Manfredelli, P, Mathieu, A, Chebaro, V, Drubay, M, El amrani, C, Eveno, K, Lecolle, G, Legault, L, Martin, G, Piessen, FR, Pruvot, S, Truant, P, Zerbib, Q, Ballouhey, B, Barrat, L, Fourcade, J, Laloze, H, Salle, A, Taibi, J, Tricard, J, Usseglio, D, Bergeat, A, Merdrignac, Roy B, Le, LO, Perotto, A, Scalabre, H, Gornes, C, Vaysse, K, Vergriete, A, Aimé, A, Ezanno, B, Malgras, AP, Arnaud, E, Fustec, V, Lavoue, C, Tesson, P, Bouche, S, Tzedakis, E, Cotte, O, Glehen, J, Lifante, L, 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J, McGrath, A, McLennan, M, Ng, J, Pascoe, N, Rajaretnam, N, Angamuthu, S, Bulathsinhala, S, Chowdhury, B, Davidson, G, Fusai, J, Gilliland, C, Hart, Salinas C, Hidalgo, J, Knowles, N, Machairas, R, Mirnezami, T, Pissanou, JM, Pollok, DA, Raptis, F, Soggiu, H, Tzerbinis, M, Varcada, S, Xyda, A, Beamish, E, Davies, R, Foulkes, D, Magowan, H, Nassa, R, Ooi, C, Price, L, Smith, F, Solari, A, Tang, G, Williams, Kahar NN, Abd, Al-Tamimi, Y., A, Bacon, N, Beasley, J, Catto, LH, Chan, D, Chew, M, Crank, N, Ilenkovan, M, Macdonald, B, Narice, O, Rominiyi, S, Saad, S, Sinha, A, Thompson, I, Varley, P, Brennan, T, Drake, EM, Harrison, G, Linder, J, Mayes, R, McGregor, R, Pasricha, RJE, Skipworth, V, Zamvar, P, Hawkin, T, Raymond, O, Ryska, R, Baron, D, Dunne, S, Gahunia, C, Halloran, N, Howes, R, McKinney, F, McNicol, K, Rajput, J, Russ, R, Sutton, P, Szatmary, JR, Tan, P, Whelan, A, Anzak, A, Banerjee, O, Fuwa, F, Hughes, Jayasinghe, J.D., C, Knowles, HM, Kocher, Silva I, Leal, FS, Ledesma, A, Minicozzi, L, Navaratne, P, Patki, R, Rahman, R, Ramamoorthy, C, Sohrabi, C, Tanabalan, M, Thaha, B, Thakur, M, Venn, V, Yip, R, Baumber, J, Parry, S, Evans, L, Jeys, G, Morris, M, Parry, N, Ahmadi, G, Aresu, Barrett-Brown, Z.M., A, Coonar, Yates H, Durio, D, Gearon, J, Hogan, M, King, A, Peryt, IS, Pradeep, M, Adishesh, R, Atherton, K, Baxter, M, Brocklehurst, M, Chaudhury, N, Krishnamohan, J, McAleer, G, Owens, E, Parkin, P, Patkar, I, Phang, A, Aladeojebi, M, Ali, B, Barmayehvar, A, Gaunt, M, Gowda, E, Halliday, M, Kitchen, F, Mansour, P, Nanjaiah, D, Zakai, Abbassi-Ghadi, N., H, Assalaarachchi, A, Currie, M, Flavin, A, Frampton, M, Hague, C, Hammer, J, Hopper, J, Horsnell, S, Humphries, A, Kamocka, TK, Madhuri, S, Preston, P, Singh, J, Stebbing, A, Tailor, D, Walker, E, Coomber, S, Jaunoo, L, Kennedy, A, Airey, J, Bunni, R, Crowley, K, Fairhurst, J, Frost, R, George, S, Lee, S, Mitchell, J, Phull, S, Richards, F, Aljanadi, A, Campbell, A, Glass, I, Hraishawi, M, Jones, C, McIlmunn, S, McIntosh, P, Mhandu, C, O’Donnell, R, Turkington, Al-Ishaq, Z., S, Bhasin, AS, Bodla, A, Burahee, A, Crichton, El-Ghobashy, A., R, Fossett, N, Pigadas, E, Rahman, D, Snee, R, Vidya, N, Yassin, D, Fountain, Hasan, M.T., K, Karabatsou, R, Laurente, O, Pathmanaban, C, Barlow, D, Ding, J, Foster, L, Longstaff, Brett-Miller, C., FE, Buruiana, A, Al-mukhtar, J, Edwards, A, Giblin, C, Kelty, M, Lee, G, Lye, T, Newman, A, Sharkey, C, Steele, Shah N, Sureshkumar, E, Whitehall, J, Blair, A, Lakhiani, Parry-Smith, W., B, Sahu, R, Athwal, A, Baker, L, Jones, C, Konstantinou, S, Ramcharan, J, Vatish, R, Wilkin, A, Alzetani, K, Amer, A, Badran, HV, Colvin, M, Ethunandan, GK, Sekhon, Z, Shakoor, H, Shields, R, Singh, T, Talbot, F, Wensley, S, Lawday, A, Lyons, S, Newman, E, Chung, R, Hagger, A, Hainsworth, I, Hunt, A, Karim, H, Owen, A, Ramwell, G, Santhirakumaran, J, Smelt, C, Tan, P, Vaughan, K, Williams, C, Baker, A, Davies, J, Gossage, M, Kelly, W, Knight, S, Bromage, J, Hall, V, Kaushik, M, Rudic, N, Vallabh, Y, Zhang, G, Harris, G, James, C, Kang, DJ, Lin, AD, Rajgor, T, Royle, R, Scurrah, B, Steel, LJ, Watson, D, Choi, R, Hutchison, V, Luoma, HJ, Marcus, R, May, A, Menon, B, Pramodana, L, Webber, A, Hayes, R, Jones, G, Sivarajah, M, Smith, A, Smrke, D, Strauss, FAM, Abouelela, IA, Aneke, P, Asaad, B, Brown, J, Collis, S, Duff, A, Khan, F, Moura, M, Taylor, B, Wadham, H, Warburton, T, Elmoslemany, Jenkinson, M.D., CP, Millward, R, Zakaria, S, Mccluney, C, Parmar, S, Shah, J, Allison, Babar, M.S., J, Bowen, B, Collard, S, Goodrum, K, Lau, M, Sargent, R, Scott, E, Thomas, H, Whitmore, D, Balasubramaniam, B, Jayasankar, S, Kapoor, A, Ramachandran, C, Semple, A, Elhamshary, SMB, Imam, K, Kapriniotis, V, Kasivisvanathan, J, Lindsay, Rakhshani-Moghadam, S., N, Beech, M, Chand, L, Green, N, Kalavrezos, H, Kiconco, R, McEwen, C, Schilling, D, Sinha, J, Pereca, S, Chopra, D, Egbeare, R, Thomas, S, Arumugam, B, Ibrahim, K, Khan, T, Combellack, G, Hill, S, Jones, M, Kornaszewska, M, Mohammed, G, Tahhan, V, Valtzoglou, N, Blencowe, P, Eskander, K, Gash, L, Gourbault, M, Hanna, TA, Maccabe, B, Main, J, Olivier, C, Newton, S, Roswadowski, N, Ryan, E, Teh, D, West, H, Al-omishy, M, Baig, H, Bates, Taranto G, Di, K, Dickson, N, Dunne, C, Gill, D, Howe, D, Jeevan, A, Khajuria, Martin-Ucar, A., K, McEvoy, P, Naredla, S, Robertson, M, Sait, DR, Sarma, S, Shanbhag, T, Shortland, S, Simmonds, J, Skillman, N, Tewari, G, Walton, Akhtar, M.A., A, Brunt, J, McIntyre, K, Milne, MM, Rashid, A, Sgrò, KE, Stewart, A, Turnbull, Abou-Foul, A.K., G, Gossedge, S, O’Donnell, F, Oldfield, S, Thomson, Gonzalez M, Aguilar, S, Talukder, C, Boyle, D, Fernando, K, Gallagher, A, Laird, D, Tham, M, Bath, P, Basnyat, H, Davis, P, Montauban, A, Shrestha, K, Agarwal, T, Arif, C, Magee, T, Nambirajan, S, Powell, R, Vinayagam, I, Flindall, A, Hanson, V, Mahendran, S, Green, M, Lim, L, MacDonald, V, Miu, L, Onos, K, Sheridan, R, Young, F, Alam, O, Griffiths, C, Houlden, VS, Kolli, AK, Lala, S, Leeson, R, Peevor, Z, Seymour, E, Consorti, R, Gonzalez, R, Grolman, Kwan-Feinberg, R., T, Liu, O, Merzlikin, Francisco, San, A, Brown, Z, Cooper, S, Hirji, J, Jolissaint, D, Mahvi, B, Okafor, CP, Raut, V, Roxo, A, Salim, S, Bessen, L, Chen, L, Dagrosa, K, Fay, C, Fleischer, R, Hasson, E, Henderson, M, Leech, A, Loehrer, C, Markey, J, Paydarfar, K, Rosenkranz, K, Telma, N, Tocci, Wilkinson-Ryan, I., M, Bokenkamp, K, Brown, D, Fleming, C, Heron, C, Hill, H, Kay, E, Leede, K, McElhinney, KA, Olson, EC, Osterberg, C, Riley, P, Srikanth, J, Barbour, D, Blazer, GA, DiLalla, O, Fayanju, ES, Hwang, R, Kahmke, H, Kazaure, A, Lazarides, W, Lee, M, Lidsky, C, Menendez, D, Moris, J, Plichta, MC, Pradhan, L, Puscas, HE, Rice, D, Rocke, L, Rosenberger, R, Scheri, Smith, B.D., Stang, M.T., L, Tolnitch, K, Turnage, J, Visgauss, FS, Walton, T, Watts, S, Zani, J, Farma, K, Cardona, MC, Russell, J, Clark, D, Kwon, N, Goel, J, Kronenfeld, B, Bigelow, E, Etchill, Gabre-Kidan, A., H, Jenny, A, Kent, MR, Ladd, C, Long, H, Malapati, A, Margalit, S, Rapaport, J, Rose, K, Stevens, L, Tsai, D, Vervoort, P, Yesantharao, A, Dehal, D, Klaristenfeld, K, Huynh, H, Kaafarani, L, Naar, M, Qadan, L, Brown, I, Ganly, JE, Mullinax, N, Alpert, C, Gillezeau, Miles DDS MD, F.A.C.S.B.A., E, Taioli, DE, Cha, E, Gleeson, C, Horn, U, Sarpel, N, Gusani, J, Hazelton, J, Maines, JS, Oh, A, Ssentongo, P, Ssentongo, A, Bhama, K, Colling, M, Najarian, M, Azam, A, Choudhry, W, Marx, Y, Abedin, G, Arzumanov, R, Chokshi, S, Gabrilovich, N, Glass, E, Kalyoussef, Parvin-Nejad, F.P., D, Roden, J, Stein, Suarez-Ligon, A., G, Tsui, K, Zhao, J, Fleming, A, Fuson, J, Gigliotti, A, Ovaitt, Y, Ying, MK, Abel, V, Andaya, K, Bigay, Boeck, M.A., H, Chern, C, Corvera, El-Sayed, I., A, Glencer, P, Ha, Hamilton, B.C.S., C, Heaton, K, Hirose, Jablons, D.M., KS, Kirkwood, LZ, Kornblith, JR, Kratz, RH, Lee, PN, Miller, EK, Nakakura, Nunez-Garcia, B., RJ, O’Donnell, D, Ozgediz, P, Park, B, Robinson, A, Sarin, B, Sheu, MG, Varma, KC, Wai, R, Wustrack, MJ, Xu, M, Zimel, D, CA) Beswick, J, Goddard, J, Manor, J, Song, Springs/Loveland, Denver/Colorado, A, Cioci, W, Pavlis, K, Rakoczy, G, Ruiz, R, Saberi, T, Fullmer, C, Gaskill, N, Gross, K, Kiong, CL, Roland, SN, Zafar, M, Abdallah, A, Abouassi, E, Aigbivbalu, M, Almasri, J, Eid, B, George, G, Kulkarni, H, Marwan, M, Mehdi, Andrés M, San, J, Sundaresan, SG, Aoun, VS, Ban, HH, Batjer, K, Bosler, J, Caruso, B, Sumer, D, Abbott, A, Acher, T, Aiken, J, Barrett, E, Foley, PB, Schwartz, AT, Hawkins, A, Maiga, NM, Ruzgar, M, Sion, S, Ullrich, J, Laufer, S, Scasso, Al-Naggar, H., Al-Shehari, M., A, Almassaudi, M, Alsayadi, R, Alsayadi, M, Nahshal, S, Shream, S, AL-Ameri, M, Aldawbali, Fotopoulou, Christina, Khan, Tabassum, Bracinik, Juraj, Glasbey, James, Abu-Rustum, Nadeem, Chiva, Luis, Fagotti, Anna, Fujiwara, Keiichi, Ghebre, Rahel, Gutelkin, Murat, Konney, Thomas O., Ng, Joseph, Pareja, Rene, Kottayasamy Seenivasagam, Rajkumar, Sehouli, Jalid, Surappa, Shylasree T.S., and Leung, Elaine
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- 2022
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8. HPCMP CREATE-GV: Supporting Ground Vehicle Acquisition.
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Larry N. Lynch, Christopher Goodin, Kevin Walker, Jody D. Priddy, and Michael Puhr
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- 2017
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9. Metabolite Profiling of Unsaturated Fatty Acids in Bronchoalveolar Lavage in the Acute, Recovery and Convalescent Phases of SARS-CoV-2 Infection
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H. Wang, S. Gairhe, J.A. Huapaya, S.M. Kanth, J. Sun, D. Regenold, N. Lynch, J. Kovacs, P. Torabi-Parizi, A.F. Suffredini, and null COVID-ARC Study Group
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- 2023
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10. Changes in the Human Lung Extracellular Matrix Proteome After SARS-CoV-2 Infection
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J.A. Huapaya, S.M. Kanth, S. Gairhe, C. Demirkale, D. Regenold, N. Lynch, P. Torabi-Parizi, J. Kovacs, A.F. Suffredini, and null COVID-19ARC Natural History Team
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- 2023
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11. Longitudinal Evaluation of Blood Cellular Immune Markers and Lung Proteomics in Vaccinated Patients With SARS-CoV-2 Breakthrough Infections
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J.A. Huapaya, S.M. Kanth, S. Gairhe, C. Demirkale, D. Regenold, N. Lynch, P. Torabi-Parizi, J. Kovacs, A.F. Suffredini, and null COVID-19ARC Natural History Team
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- 2023
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12. Differences in the Longitudinal Blood Proteomic Profiles of Vaccinated and Unvaccinated SARS-CoV-2 Patients
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J.A. Huapaya, S. Gairhe, S.M. Kanth, C. demirkale, D. Regenold, J. Sun, N. Lynch, J.R. Strich, D. Chertow, J. Kovacs, P. Torabi-Parizi, A.F. Suffredini, and null COVIDA-ARC Study Group
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- 2023
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13. Supplementary Table 1 from Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
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Sarah J. Hill, Xiaole Shirley Liu, Myles Brown, Bo R. Rueda, Christopher P. Crum, Marisa R. Nucci, Ursula A. Matulonis, Ross S. Berkowitz, Michael J. Worley, Michael G. Muto, Colleen M. Feltmate, Neil S. Horowitz, Kevin M. Elias, Henry W. Long, Klothilda Lim, Paloma Cejas, Shengqing Gu, Dominique T. Zarrella, Rui Xu, Katherine N. Lynch, Karsten Boehnke, Suzan Lazo, Unnati M. Pandya, Linah F. Al-Alem, Han Dong, Matthew P. Keany, and Changxin Wan
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Table S1. Differential expression analysis for CD8 T cells.
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- 2023
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14. Supplementary Table 5 from Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
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Sarah J. Hill, Xiaole Shirley Liu, Myles Brown, Bo R. Rueda, Christopher P. Crum, Marisa R. Nucci, Ursula A. Matulonis, Ross S. Berkowitz, Michael J. Worley, Michael G. Muto, Colleen M. Feltmate, Neil S. Horowitz, Kevin M. Elias, Henry W. Long, Klothilda Lim, Paloma Cejas, Shengqing Gu, Dominique T. Zarrella, Rui Xu, Katherine N. Lynch, Karsten Boehnke, Suzan Lazo, Unnati M. Pandya, Linah F. Al-Alem, Han Dong, Matthew P. Keany, and Changxin Wan
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Table S5. List of Genes Used to Generate NK Cell Activation Scores.
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- 2023
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15. Supplementary Table 2 from Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
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Sarah J. Hill, Xiaole Shirley Liu, Myles Brown, Bo R. Rueda, Christopher P. Crum, Marisa R. Nucci, Ursula A. Matulonis, Ross S. Berkowitz, Michael J. Worley, Michael G. Muto, Colleen M. Feltmate, Neil S. Horowitz, Kevin M. Elias, Henry W. Long, Klothilda Lim, Paloma Cejas, Shengqing Gu, Dominique T. Zarrella, Rui Xu, Katherine N. Lynch, Karsten Boehnke, Suzan Lazo, Unnati M. Pandya, Linah F. Al-Alem, Han Dong, Matthew P. Keany, and Changxin Wan
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Table S2. Differential expression analysis for Treg CD4 T cells.
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- 2023
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16. Supplementary Table 3 from Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
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Sarah J. Hill, Xiaole Shirley Liu, Myles Brown, Bo R. Rueda, Christopher P. Crum, Marisa R. Nucci, Ursula A. Matulonis, Ross S. Berkowitz, Michael J. Worley, Michael G. Muto, Colleen M. Feltmate, Neil S. Horowitz, Kevin M. Elias, Henry W. Long, Klothilda Lim, Paloma Cejas, Shengqing Gu, Dominique T. Zarrella, Rui Xu, Katherine N. Lynch, Karsten Boehnke, Suzan Lazo, Unnati M. Pandya, Linah F. Al-Alem, Han Dong, Matthew P. Keany, and Changxin Wan
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Table S3. Differential expression analysis for non-Treg CD4 T cells.
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- 2023
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17. Data from Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
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Sarah J. Hill, Xiaole Shirley Liu, Myles Brown, Bo R. Rueda, Christopher P. Crum, Marisa R. Nucci, Ursula A. Matulonis, Ross S. Berkowitz, Michael J. Worley, Michael G. Muto, Colleen M. Feltmate, Neil S. Horowitz, Kevin M. Elias, Henry W. Long, Klothilda Lim, Paloma Cejas, Shengqing Gu, Dominique T. Zarrella, Rui Xu, Katherine N. Lynch, Karsten Boehnke, Suzan Lazo, Unnati M. Pandya, Linah F. Al-Alem, Han Dong, Matthew P. Keany, and Changxin Wan
- Abstract
Immune therapies have had limited efficacy in high-grade serous ovarian cancer (HGSC), as the cellular targets and mechanism(s) of action of these agents in HGSC are unknown. Here we performed immune functional and single-cell RNA sequencing transcriptional profiling on novel HGSC organoid/immune cell co-cultures treated with a unique bispecific anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody compared with monospecific anti-PD-1 or anti-PD-L1 controls. Comparing the functions of these agents across all immune cell types in real time identified key immune checkpoint blockade (ICB) targets that have eluded currently available monospecific therapies. The bispecific antibody induced superior cellular state changes in both T and natural killer (NK) cells. It uniquely induced NK cells to transition from inert to more active and cytotoxic phenotypes, implicating NK cells as a key missing component of the current ICB-induced immune response in HGSC. It also induced a subset of CD8 T cells to transition from naïve to more active and cytotoxic progenitor-exhausted phenotypes post-treatment, revealing the small, previously uncharacterized population of CD8 T cells responding to ICB in HGSC. These state changes were driven partially through bispecific antibody-induced downregulation of the bromodomain-containing protein BRD1. Small-molecule inhibition of BRD1 induced similar state changes in vitro and demonstrated efficacy in vivo, validating the co-culture results. Our results demonstrate that state changes in both NK and a subset of T cells may be critical in inducing an effective anti-tumor immune response and suggest that immune therapies able to induce such cellular state changes, such as BRD1 inhibitors, may have increased efficacy in HGSC.Significance:This study indicates that increased efficacy of immune therapies in ovarian cancer is driven by state changes of NK and small subsets of CD8 T cells into active and cytotoxic states.
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- 2023
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18. Supplementary Table 4 from Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
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Sarah J. Hill, Xiaole Shirley Liu, Myles Brown, Bo R. Rueda, Christopher P. Crum, Marisa R. Nucci, Ursula A. Matulonis, Ross S. Berkowitz, Michael J. Worley, Michael G. Muto, Colleen M. Feltmate, Neil S. Horowitz, Kevin M. Elias, Henry W. Long, Klothilda Lim, Paloma Cejas, Shengqing Gu, Dominique T. Zarrella, Rui Xu, Katherine N. Lynch, Karsten Boehnke, Suzan Lazo, Unnati M. Pandya, Linah F. Al-Alem, Han Dong, Matthew P. Keany, and Changxin Wan
- Abstract
Table S4. Differential expression analysis for NK cells.
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- 2023
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19. Supplementary Materials from Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
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Sarah J. Hill, Xiaole Shirley Liu, Myles Brown, Bo R. Rueda, Christopher P. Crum, Marisa R. Nucci, Ursula A. Matulonis, Ross S. Berkowitz, Michael J. Worley, Michael G. Muto, Colleen M. Feltmate, Neil S. Horowitz, Kevin M. Elias, Henry W. Long, Klothilda Lim, Paloma Cejas, Shengqing Gu, Dominique T. Zarrella, Rui Xu, Katherine N. Lynch, Karsten Boehnke, Suzan Lazo, Unnati M. Pandya, Linah F. Al-Alem, Han Dong, Matthew P. Keany, and Changxin Wan
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Supplementary Materials and Methods, Figures, and Figure and Table legends
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- 2023
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20. Gas Chromatography–Mass Spectrometric Analysis of Derivatives of Dibenzalacetone Aldol Products
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Austin H. Harnage, Hailey N. Lynch, and Anuradha Liyana Pathiranage
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Benzaldehyde ,chemistry.chemical_compound ,Aldol reaction ,Chemistry ,Mass spectrum ,Acetone ,Organic chemistry ,Aldol condensation ,General Chemistry ,Nuclear magnetic resonance spectroscopy ,Gas chromatography ,Mass spectrometry ,Education - Abstract
The aldol condensation reaction is one of the many synthesis reactions carried out in second semester organic chemistry laboratories. This reaction was integrated into a novel experiment requiring students to synthesize dibenzalacetone derivatives using the crossed-aldol condensation by reacting different types of benzaldehyde derivatives with acetone, followed by analyzing those products using spectrometric and spectroscopic methods, especially gas chromatography–mass spectrometry (GC–MS). The main objective of this 2 week lab experiment compared to other procedures in the literature was the analysis of the final aldol product using GC–MS methods rather than solely nuclear magnetic resonance (NMR) spectroscopic methods. During the first week’s 3 h laboratory period, students completed the reaction with a known benzaldehyde derivative and acetone to synthesize their aldol product. In the second week, students calculated the percent yield of their product, determined the product’s melting point range, and analyzed the product by thin-layer chromatography, NMR, and GC–MS methods. Students also strengthened their skills of spectral interpretation using NMR spectroscopy, especially distortionless enhancement by polarization transfer NMR, an NMR technique rarely covered in undergraduate organic laboratory sections. Students spent more classroom time during week two, analyzing GC–MS data. Students were shown how to use molecular model kits to understand the fragmentation of compounds in the mass spectrum. As a result, the students who performed this experiment increased their general knowledge of GC–MS spectrometric techniques, including identification of compounds based on their fragmentation pattern.
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- 2021
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21. A Case for MLP-Aware Cache Replacement.
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Moinuddin K. Qureshi, Daniel N. Lynch, Onur Mutlu, and Yale N. Patt
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- 2006
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22. Systematic review of the scientific evidence of the pulmonary carcinogenicity of talc
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Heather N. Lynch, Daniel J. Lauer, William J. Thompson, Olivia Leleck, Rachel D. Freid, Justin Collins, Kathleen Chen, A. Michael Ierardi, Ania M. Urban, Michael A. Cappello, Paolo Boffetta, and Kenneth A. Mundt
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Public Health, Environmental and Occupational Health - Abstract
We conducted a systematic review to assess the potential pulmonary carcinogenicity of inhaled talc in humans. Our systematic review methods adhere to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and incorporated aspects from the US Institute of Medicine (IOM) and several United States (US) Environmental Protection Agency (EPA) frameworks for systematic reviews. A comprehensive literature search was conducted. Detailed data abstraction and study quality evaluation, adapting the US Toxic Substances Control Act (TSCA) framework, were central to our analysis. The literature search and selection process identified 23 primary studies that assessed exposure to talc and pulmonary cancer risks in humans (n = 19) and animals (n = 3). Integrating all streams of evidence according to the IOM framework yielded classifications of suggestive evidence of no association between inhaled talc and lung cancer and pleural mesothelioma at human-relevant exposure levels.
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- 2022
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23. Rapid mobilisation of parent champions empowers vulnerable families on bronchiolitis
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A Lee, H Blackham, H Khalil, K Mlodawska, K Parry, K Sefton, N Lynch, B Carter, D Hawcutt, and I Sinha
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- 2022
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24. The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens
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Paolo Boffetta, H. N. Lynch, E. M. Beckett, Kenneth A. Mundt, W. J. Thompson, L. D. Dell, V. J. Desai, Cheng-Kuan Lin, Mundt K.A., Dell L.D., Boffetta P., Beckett E.M., Lynch H.N., Desai V.J., Lin C.K., and Thompson W.J.
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Oncology ,Myeloid ,Cancer Research ,medicine.medical_specialty ,1,3-butadiene ,Post hoc ,Epidemiology ,Myelodysplastic-Myeloproliferative Disease ,MPN ,Myelodysplastic Syndrome ,Review ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,AML ,Surgical oncology ,Internal medicine ,Formaldehyde ,hemic and lymphatic diseases ,Genetics ,MDS ,Medicine ,Humans ,CML ,Myeloproliferative Disorder ,Environmental Carcinogen ,Myeloproliferative Disorders ,business.industry ,Myeloid leukemia ,Cancer ,Benzene ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030210 environmental & occupational health ,Myelodysplastic-Myeloproliferative Diseases ,Carcinogens, Environmental ,Tobacco smoking ,Causality ,Epidemiologic Studies ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Myelodysplastic Syndromes ,Etiology ,business ,Human - Abstract
Introduction Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) – including chronic myeloid leukemia (CML) – and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. Methods We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes “myeloid malignancies.” Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. Results Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML – and not for MDS or MPN – but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. Conclusions Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing “myeloid malignancies,” the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc – where appropriate – always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.
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- 2021
25. Enhanced Efficacy of Simultaneous PD-1 and PD-L1 Immune Checkpoint Blockade in High-Grade Serous Ovarian Cancer
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Christopher P. Crum, Neil S. Horowitz, Katherine N. Lynch, Matthew P. Keany, Unnati M. Pandya, Klothilda Lim, Henry W. Long, Linah Al-Alem, Shengqing Gu, Kevin M. Elias, Ursula A. Matulonis, Han Dong, Xiaole Shirley Liu, Suzan Lazo, Myles Brown, Bo R. Rueda, Changxin Wan, Sarah J. Hill, Marisa R. Nucci, Michael J. Worley, Michael G. Muto, Karsten Boehnke, Colleen M. Feltmate, Dominique T. Zarrella, Paloma Cejas, Rui Xu, and Ross S. Berkowitz
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0301 basic medicine ,Cancer Research ,Cell type ,Programmed Cell Death 1 Receptor ,Population ,Apoptosis ,CD8-Positive T-Lymphocytes ,Article ,B7-H1 Antigen ,Mice ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,Downregulation and upregulation ,PD-L1 ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Animals ,Humans ,Cytotoxic T cell ,education ,Immune Checkpoint Inhibitors ,Cell Proliferation ,Ovarian Neoplasms ,education.field_of_study ,biology ,Xenograft Model Antitumor Assays ,Immune checkpoint ,Cystadenocarcinoma, Serous ,Gene Expression Regulation, Neoplastic ,Killer Cells, Natural ,Survival Rate ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Female ,Neoplasm Grading ,Antibody - Abstract
Immune therapies have had limited efficacy in high-grade serous ovarian cancer (HGSC), as the cellular targets and mechanism(s) of action of these agents in HGSC are unknown. Here we performed immune functional and single-cell RNA sequencing transcriptional profiling on novel HGSC organoid/immune cell co-cultures treated with a unique bispecific anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibody compared with monospecific anti-PD-1 or anti-PD-L1 controls. Comparing the functions of these agents across all immune cell types in real time identified key immune checkpoint blockade (ICB) targets that have eluded currently available monospecific therapies. The bispecific antibody induced superior cellular state changes in both T and natural killer (NK) cells. It uniquely induced NK cells to transition from inert to more active and cytotoxic phenotypes, implicating NK cells as a key missing component of the current ICB-induced immune response in HGSC. It also induced a subset of CD8 T cells to transition from naïve to more active and cytotoxic progenitor-exhausted phenotypes post-treatment, revealing the small, previously uncharacterized population of CD8 T cells responding to ICB in HGSC. These state changes were driven partially through bispecific antibody-induced downregulation of the bromodomain-containing protein BRD1. Small-molecule inhibition of BRD1 induced similar state changes in vitro and demonstrated efficacy in vivo, validating the co-culture results. Our results demonstrate that state changes in both NK and a subset of T cells may be critical in inducing an effective anti-tumor immune response and suggest that immune therapies able to induce such cellular state changes, such as BRD1 inhibitors, may have increased efficacy in HGSC. Significance: This study indicates that increased efficacy of immune therapies in ovarian cancer is driven by state changes of NK and small subsets of CD8 T cells into active and cytotoxic states.
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- 2021
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26. Support for populist candidates predicted by declining social capital and an increase in suicides
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R. Lynch, N. Lynch, S. N. Chapman, M. Briga, S. Helle, and E. Lynch
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- 2022
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27. Systematic review of the scientific evidence on ethylene oxide as a human carcinogen
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Heather N. Lynch, Jordan S. Kozal, Anthony J. Russell, William J. Thompson, Haley R. Divis, Rachel D. Freid, Edward J. Calabrese, and Kenneth A. Mundt
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Ethylene Oxide ,Carcinogens ,Animals ,Humans ,Breast Neoplasms ,Female ,General Medicine ,United States Environmental Protection Agency ,Toxicology ,United States ,Systematic Reviews as Topic - Abstract
Ethylene oxide is a highly reactive chemical primarily used as an intermediate in chemical production and as a sterilant of medical equipment and food products; it also is produced endogenously as a result of physiological processes. We conducted a systematic review of the potential carcinogenicity of inhaled ethylene oxide in humans using methods that adhere to PRIMSA guidelines and that incorporate aspects from the Institute of Medicine (IOM) (now the National Academy of Medicine) as well as several US Environmental Protection Agency (EPA) frameworks for systematic reviews. After a comprehensive literature search and selection process, study quality was evaluated following a method adapted from the EPA Toxic Substances Control Act (TSCA) framework. The literature screening and selection process identified 24 primary studies in animals or humans and more than 50 mechanistic studies. Integrating epidemiological, animal, and mechanistic literature on ethylene oxide and cancer according to the IOM framework yielded classifications of suggestive evidence of no association between ethylene oxide and stomach cancer, breast cancer and lymphohematopoietic malignancies at human relevant exposures. However, we acknowledge that there is additional uncertainty in the classification for lymphohematopoietic malignancies owing to a paucity of evidence for specific types of these tumors, each of which is a distinct disease entity of possibly unique etiology.
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- 2022
28. Mode of action assessment for propylene dichloride as a human carcinogen
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Jordan S. Kozal, Heather N. Lynch, Joanna Klapacz, Rita S. Schoeny, Paul A. Jean, and Andrew Maier
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General Medicine ,Toxicology - Published
- 2023
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29. Rehabilitation of severe hereditary gingival hyperplasia with virtual surgical planning and computer-assisted surgery
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I. Liau, P. Duke, N. Lynch, and A. Cheng
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Computer-assisted surgery ,medicine.medical_specialty ,Rehabilitation ,RD1-811 ,business.industry ,medicine.medical_treatment ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Hereditary gingival hyperplasia ,Hereditary gingival fibromatosis ,Craniomaxillofacial surgery ,General Medicine ,Hyperplasia ,medicine.disease ,Surgical planning ,RC31-1245 ,CAD/CAM ,Surgery ,Ablative case ,medicine ,business ,Virtual surgical planning ,Internal medicine ,ComputingMethodologies_COMPUTERGRAPHICS - Abstract
Virtual surgical planning and computer-assisted surgery have various applications and demonstrable benefits in craniomaxillofacial surgery. We report the complex rehabilitation of a severe case of hereditary gingival hyperplasia utilizing virtual surgical planning and computer-aided design and manufacturing (CAD/CAM) for the ablative, reconstructive and prosthetic components of the case.
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- 2021
30. OC-0617 Camera-based in-vivo dosimetry using dual-material 3D printed scintillator arrays
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N. Lynch, T. Monajemi, and J. Robar
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Oncology ,Radiology, Nuclear Medicine and imaging ,Hematology - Published
- 2022
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31. Literature review of the relative importance of household, community and social, and workplace settings on the probability of COVID-19 infection
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Heather N. Lynch, Evan M. Beckett, Lindsey L. Dobyns, William J. Thompson, Haley R. Divis, Eduardo Encina, Shannon H. Gaffney, and Kenneth A. Mundt
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Public Health, Environmental and Occupational Health ,Emergency Medicine - Published
- 2022
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32. Lost in the woods: Finding our way back to the scientific method in systematic review
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Heather N. Lynch, Kenneth A. Mundt, Dirk Pallapies, and Paolo F. Ricci
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Infectious Diseases ,Epidemiology ,Public Health, Environmental and Occupational Health - Published
- 2022
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33. 1101 Closed Traumatic Avulsion of Both Flexor Digitorum Tendons: A Novel Treatment Method
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J Woods, D Roisin, N Lynch, C Emma, C Cuggy, and J Natalie
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body regions ,Avulsion ,Novel treatment method ,medicine.medical_specialty ,business.industry ,Medicine ,Surgery ,musculoskeletal system ,business - Abstract
Case Report Closed tendon avulsion of both flexor tendons (Flexor Digitorum profundus [FDP] and Flexor Digitorum superficialais [FDS]) in the same finger is an extremely rare condition. We are proposing this subtype of injury be added as a type VI to the current Leddy and Packer classification for FDP avulsion injuries. The objective of this being an increase in awareness to avoid misdiagnosis and to aid in the subsequent management if encountered. We present the case of a 27-year-old male who presented with an avulsion of both flexor tendons from their respective insertions in the ring finger following a sporting injury causing hyperextension against an actively flexed distal interphalangeal joint. This condition has previously been reported twelve times in the literature. We propose a novel treatment method not described for previous cases and examine the successful method of treatment in this case.
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- 2021
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34. Lung physiology and controlled exposure study design
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Ammie N. Bachman, Julie E. Goodman, and Heather N. Lynch
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Pharmacology ,Chronic exposure ,Spirometry ,Acute effects ,medicine.medical_specialty ,Inhalation Exposure ,medicine.diagnostic_test ,business.industry ,Respiratory physiology ,Toxicology ,Affect (psychology) ,Human health ,Research Design ,medicine ,Humans ,Environmental Pollutants ,Chest tightness ,Intensive care medicine ,business ,Lung ,Lung function - Abstract
Controlled human inhalation exposure ( CHIE) studies provide a unique opportunity to conduct formal experiments to examine the human health effects of airborne pollutants. Lung function, easily measured using spirometry, is a common physiological variable often utilized in these studies. By design, CHIE studies only induce mild and reversible acute effects, which may or may not predict adverse effects that may develop under chronic exposure conditions. There is substantial inter- and intra-individual variability in functional capacity and symptoms such as chest tightness and dyspnea, which are complex variables that are affected by individual perception, physiological lung impairment, and other variables (e.g., concomitant health conditions, and level of conditioning/fitness). Thus, the design of the CHIE study and physiological and environmental factors of study participants can affect each CHIE study's results. Researchers can address many of these critical issues in the problem formulation phase of CHIE studies, utilizing existing information on the expected effects of the substance of interest and possible modes of action. Thoughtful design and interpretation of CHIE studies will increase their utility for evaluating and setting environmental health policy.
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- 2021
35. Financial aid award notification design
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Katherine N. Lynch
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- 2021
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36. Enhanced Efficacy of Aurora Kinase Inhibitors in G2/M Checkpoint Deficient TP53 Mutant Uterine Carcinomas Is Linked to the Summation of LKB1–AKT–p53 Interactions
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Mosammat Faria Afreen, Kin-Hoe Chow, Bo R. Rueda, Joyce F. Liu, Nikolas Kesten, Liping Yuan, Katherine N. Lynch, Ursula A. Matulonis, Michael J. Worley, Sarah J. Hill, Michael G. Muto, Christopher P. Crum, Colleen M. Feltmate, Whitfield B. Growdon, Ruiyang He, Neil S. Horowitz, Aniket Shetty, Ross S. Berkowitz, Lynch, Katherine N. [0000-0002-6842-7268], Hill, Sarah J. [0000-0002-9199-9459], Apollo - University of Cambridge Repository, Lynch, Katherine N [0000-0002-6842-7268], and Hill, Sarah J [0000-0002-9199-9459]
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0301 basic medicine ,p53 ,Cancer Research ,LKB1 ,Mutant ,Aurora inhibitor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Biology ,uterine cancer ,03 medical and health sciences ,Wee1 ,030104 developmental biology ,0302 clinical medicine ,Aurora kinase ,Oncology ,Downregulation and upregulation ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,G2/M cell cycle checkpoint ,Protein kinase B ,Mitosis ,RC254-282 - Abstract
Uterine carcinoma (UC) is the most common gynecologic malignancy in the United States. TP53 mutant UCs cause a disproportionate number of deaths due to limited therapies for these tumors and the lack of mechanistic understanding of their fundamental vulnerabilities. Here we sought to understand the functional and therapeutic relevance of TP53 mutations in UC. We functionally profiled targetable TP53 dependent DNA damage repair and cell cycle control pathways in a panel of TP53 mutant UC cell lines and patient-derived organoids. There were no consistent defects in DNA damage repair pathways. Rather, most models demonstrated dependence on defective G2/M cell cycle checkpoints and subsequent upregulation of Aurora kinase-LKB1-p53-AKT signaling in the setting of baseline mitotic defects. This combination makes them sensitive to Aurora kinase inhibition. Resistant lines demonstrated an intact G2/M checkpoint, and combining Aurora kinase and WEE1 inhibitors, which then push these cells through mitosis with Aurora kinase inhibitor-induced spindle defects, led to apoptosis in these cases. Overall, this work presents Aurora kinase inhibitors alone or in combination with WEE1 inhibitors as relevant mechanism driven therapies for TP53 mutant UCs. Context specific functional assessment of the G2/M checkpoint may serve as a biomarker in identifying Aurora kinase inhibitor sensitive tumors.
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- 2021
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37. Enhanced Efficacy of Aurora Kinase Inhibitors in G2/M Checkpoint Deficient
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Katherine N, Lynch, Joyce F, Liu, Nikolas, Kesten, Kin-Hoe, Chow, Aniket, Shetty, Ruiyang, He, Mosammat Faria, Afreen, Liping, Yuan, Ursula A, Matulonis, Whitfield B, Growdon, Michael G, Muto, Neil S, Horowitz, Colleen M, Feltmate, Michael J, Worley, Ross S, Berkowitz, Christopher P, Crum, Bo R, Rueda, and Sarah J, Hill
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p53 ,LKB1 ,G2/M cell cycle checkpoint ,Aurora kinase ,Article ,uterine cancer - Abstract
Simple Summary Cancers arising from the lining of the uterus, endometrial cancers, are the most common gynecologic malignancy in the United States. Once endometrial cancer escapes the uterus and grows in distant locations, there are limited therapeutic options. The most aggressive and lethal endometrial cancers carry alterations in the protein p53, which is a critical guardian of many cellular functions. The role of these p53 alterations in endometrial cancer is not well understood. The goal of this work was to use p53 altered models of endometrial cancer to understand which, if any, therapeutically targetable vulnerabilities these p53 alterations may confer in endometrial cancer. Here we show that many of these p53 altered cells have problems with cell division which can be targeted with novel single and combination therapies. These discoveries may lead to relevant new therapies for difficult to treat advanced stage endometrial cancers. Abstract Uterine carcinoma (UC) is the most common gynecologic malignancy in the United States. TP53 mutant UCs cause a disproportionate number of deaths due to limited therapies for these tumors and the lack of mechanistic understanding of their fundamental vulnerabilities. Here we sought to understand the functional and therapeutic relevance of TP53 mutations in UC. We functionally profiled targetable TP53 dependent DNA damage repair and cell cycle control pathways in a panel of TP53 mutant UC cell lines and patient-derived organoids. There were no consistent defects in DNA damage repair pathways. Rather, most models demonstrated dependence on defective G2/M cell cycle checkpoints and subsequent upregulation of Aurora kinase-LKB1-p53-AKT signaling in the setting of baseline mitotic defects. This combination makes them sensitive to Aurora kinase inhibition. Resistant lines demonstrated an intact G2/M checkpoint, and combining Aurora kinase and WEE1 inhibitors, which then push these cells through mitosis with Aurora kinase inhibitor-induced spindle defects, led to apoptosis in these cases. Overall, this work presents Aurora kinase inhibitors alone or in combination with WEE1 inhibitors as relevant mechanism driven therapies for TP53 mutant UCs. Context specific functional assessment of the G2/M checkpoint may serve as a biomarker in identifying Aurora kinase inhibitor sensitive tumors.
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- 2021
38. Additional file 1 of The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens
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Mundt, K. A., L. D. Dell, P. Boffetta, E. M. Beckett, H. N. Lynch, V. J. Desai, C. K. Lin, and W. J. Thompson
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Data_FILES - Abstract
Additional file 1.
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- 2021
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39. Elective cancer surgery in COVID-19–Free surgical pathways during the SARS-cov-2 pandemic: An international, multicenter, comparative cohort study
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James C Glasbey, Dmitri Nepogodiev, Joana Ff Simoes, Omar Omar, Elizabeth Li, Mary L Venn, Mohammad Abou Chaar, Vita Capizzi, Daoud Chaudhry, Anant Desai, Jonathan G Edwards, Jonathan P Evans, Marco Fiore, Jose Flavio Videria, Samuel J Ford, Ian Ganyli, Ewen A Griffiths, Rohan R Gujjuri, Angelos G Kolias, Haytham Ma Kaafarani, Ana Minaya-Bravo, Siobhan C McKay, Helen M Mohan, Keith Roberts, Carlos San Miguel-Méndez, Peter Pockney, Richard Shaw, Neil J Smart, Grant D Stewart, Sudha Sundar, Raghavan Vidya, Aneel A Bhangu, James C Glasbey, Omar Omar, Aneel A Bhangu, Kwabena Siaw-Acheampong, Ruth A Benson, Edward Bywater, Daoud Chaudhry, Brett E Dawson, Jonathan P Evans, James C Glasbey, Rohan R Gujjuri, Emily Heritage, Conor S Jones, Sivesh K Kamarajah, Chetan Khatri, Rachel A Khaw, James M Keatley, Andrew Knight, Samuel Lawday, Elizabeth Li, Harvinder S Mann, Ella J Marson, Kenneth A McLean, Siobhan C McKay, Emily C Mills, Dmitri Nepogodiev, Gianluca Pellino, Maria Picciochi, Elliott H Taylor, Abhinav Tiwari, Joana Ff Simoes, Isobel M Trout, Mary L Venn, Richard Jw Wilkin, Aneel A Bhangu, James C Glasbey, Neil J Smart, Ana Minaya-Bravo, Jonathan P Evans, Gaetano Gallo, Susan Moug, Francesco Pata, Peter Pockney, Salomone Di Saverio, Abigail Vallance, Dale Vimalchandran, Ewen A Griffiths, Sivesh K Kamarajah, Richard Pt Evans, Philip Townend, Keith Roberts, Siobhan McKay, John Isaac, Sohei Satoi, John Edwards, Aman S Coonar, Adrian Marchbank, Edward J Caruana, Georgia R Layton, Akshay Patel, Alessandro Brunelli, Samuel Ford, Anant Desai, Alessandro Gronchi, Marco Fiore, Max Almond, Fabio Tirotta, Sinziana Dumitra, Angelos Kolias, Stephen J Price, Daniel M Fountain, Michael D Jenkinson, Peter Hutchinson, Hani J Marcus, Rory J Piper, Laura Lippa, Franco Servadei, Ignatius Esene, Christian Freyschlag, Iuri Neville, Gail Rosseau, Karl Schaller, Andreas K Demetriades, Faith Robertson, Alex Alamri, Richard Shaw, Andrew G Schache, Stuart C Winter, Michael Ho, Paul Nankivell, Juan Rey Biel, Martin Batstone, Ian Ganly, Raghavan Vidya, Alex Wilkins, Jagdeep K Singh, Dinesh Thekinkattil, Sudha Sundar, Christina Fotopoulou, Elaine Leung, Tabassum Khan, Luis Chiva, Jalid Sehouli, Anna Fagotti, Paul Cohen, Murat Gutelkin, Rahel Ghebre, Thomas Konney, Rene Pareja, Rob Bristow, Sean Dowdy, T S Shylasree, R Kottayasamy Seenivasagam, Joe Ng, Keiiji Fujiwara, Grant D Stewart, Benjamin Lamb, Krishna Narahari, Alan McNeill, Alexandra Colquhoun, John McGrath, Steve Bromage, Ravi Barod, Veeru Kasivisvanathan, Tobias Klatte, Joana Ff Simoes, Tom Ef Abbott, Sadi Abukhalaf, Michel Adamina, Adesoji O Ademuyiwa, Arnav Agarwal, Murat Akkulak, Ehab Alameer, Derek Alderson, Felix Alakaloko, Markus Albertsmeiers, Osaid Alser, Muhammad Alshaar, Sattar Alshryda, Alexis P Arnaud, Knut Magne Augestad, Faris Ayasra, José Azevedo, Brittany K Bankhead-Kendall, Emma Barlow, David Beard, Ruth A Benson, Ruth Blanco-Colino, Amanpreet Brar, Ana Minaya-Bravo, Kerry A Breen, Chris Bretherton, Igor Lima Buarque, Joshua Burke, Edward J Caruana, Mohammad Chaar, Sohini Chakrabortee, Peter Christensen, Daniel Cox, Moises Cukier, Miguel F Cunha, Giana H Davidson, Anant Desai, Salomone Di Saverio, Thomas M Drake, John G Edwards, Muhammed Elhadi, Sameh Emile, Shebani Farik, Marco Fiore, J Edward Fitzgerald, Samuel Ford, Tatiana Garmanova, Gaetano Gallo, Dhruv Ghosh, Gustavo Mendonça Ataíde Gomes, Gustavo Grecinos, Ewen A Griffiths, Madalegna GrÜndl, Constantine Halkias, Ewen M Harrison, Intisar Hisham, Peter J Hutchinson, Shelley Hwang, Arda Isik, Michael D Jenkinson, Pascal Jonker, Haytham Ma Kaafarani, Debby Keller, Angelos Kolias, Schelto Kruijff, Ismail Lawani, Hans Lederhuber, Sezai Leventoglu, Andrey Litvin, Andrew Loehrer, Markus W Löffler, Maria Aguilera Lorena, Maria Marta Modolo, Piotr Major, Janet Martin, Hassan N Mashbari, Dennis Mazingi, Symeon Metallidis, Ana Minaya-Bravo, Helen M Mohan, Rachel Moore, David Moszkowicz, Susan Moug, Joshua S Ng-Kamstra, Mayaba Maimbo, Ionut Negoi, Milagros Niquen, Faustin Ntirenganya, Maricarmen Olivos, Kacimi Oussama, Oumaima Outani, Marie Dione Parreno-Sacdalanm, Francesco Pata, Carlos Jose Perez Rivera, Thomas D Pinkney, Willemijn van der Plas, Peter Pockney, Ahmad Qureshi, Dejan Radenkovic, Antonio Ramos-De la Medina, Keith Roberts, April C Roslani, Martin Rutegård, Juan José Segura-Sampedro, Irène Santos, Sohei Satoi, Raza Sayyed, Andrew Schache, Andreas A Schnitzbauer, Justina O Seyi-Olajide, Neil Sharma, Richard Shaw, Sebastian Shu, Kjetil Soreide, Antonino Spinelli, Grant D Stewart, Malin Sund, Sudha Sundar, Stephen Tabiri, Philip Townend, Georgios Tsoulfas, Gabrielle H van Ramshorst, Raghavan Vidya, Dale Vimalachandran, Oliver J Warren, Duane Wedderburn, Naomi Wright, C Allemand, L Boccalatte, M Figari, M Lamm, J Larrañaga, C Marchitelli, F Noll, D Odetto, M Perrotta, J Saadi, L Zamora, C Alurralde, E L Caram, D Eskinazi, J P Mendoza, M Usandivaras, R Badra, A Esteban, J S García, P M García, J I Gerchunoff, S M Lucchini, M A NIgra, L Vargas, T Hovhannisyan, A Stepanyan, T Gould, R Gourlay, B Griffiths, S Gananadha, M McLaren, J Cecire, N Joshi, S Salindera, A Sutherland, J H Ahn, G Charlton, S Chen, N Gauri, R Hayhurst, S Jang, F Jia, C Mulligan, W Yang, G Ye, H Zhang, M Ballal, D Gibson, D Hayne, J Moss, T Richards, P Viswambaram, U G Vo, J Bennetts, T Bright, M Brooke-Smith, R Fong, B Gricks, Y H Lam, B S Ong, M Szpytma, D Watson, K Bagraith, S Caird, E Chan, C Dawson, D Ho, E Jeyarajan, S Jordan, A Lim, G J Nolan, A Oar, D Parker, H Puhalla, A Quennell, L Rutherford, P Townend, M Von Papen, M Wullschleger, A Blatt, D Cope, N Egoroff, M Fenton, J Gani, N Lott, P Pockney, N Shugg, M Elliott, D Phung, D Phan, D Townend, C Bong, J Gundara, A Frankel, S Bowman, G R Guerra, J Bolt, K Buddingh, N N Dudi-Venkata, S Jog, H M Kroon, T Sammour, R Smith, C Stranz, M Batstone, K Lah, W McGahan, D Mitchell, A Morton, A Pearce, M Roberts, G Sheahan, B Swinson, N Alam, S Banting, L Chong, P Choong, S Clatworthy, D Foley, A Fox, M W Hii, B Knowles, J Mack, M Read, A Rowcroft, S Ward, G Wright, M Lanner, I Königsrainer, M Bauer, C Freyschlag, M Kafka, F Messner, D Öfner, I Tsibulak, K Emmanuel, M Grechenig, R Gruber, M Harald, L Öhlberger, J Presl, A Wimmer, I Namazov, E Samadov, D Barker, R Boyce, S Corbin, A Doyle, A Eastmond, R Gill, A Haynes, S Millar, M O'Shea, G Padmore, N Paquette, E Phillips, S St John, K Walkes, N Flamey, P Pattyn, W Oosterlinck, J Van den Eynde, R Van den Eynde, A Gatti, C Nardi, R Oliva, R De Cicco, I Cecconello, P Gregorio, L Pontual Lima, U Ribeiro Junior, F Takeda, R M Terra, M Sokolov, B Kidane, S Srinathan, M Boutros, N Caminsky, G Ghitulescu, G Jamjoum, J Moon, J Pelletier, T Vanounou, S Wong, M Boutros, S Dumitra, A Kouyoumdjian, B Johnston, C Russell, M Boutros, S Demyttenaere, R Garfinkle, J Abou-Khalil, C Nessim, J Stevenson, F Heredia, A Almeciga, A Fletcher, A Merchan, L O Puentes, J Mendoza Quevedo, G Bacic, D Karlovic, D Krsul, M Zelic, I Luksic, M Mamic, B Bakmaz, I Coza, E Dijan, Z Katusic, J Mihanovic, I Rakvin, K Frantzeskou, N Gouvas, G Kokkinos, P Papatheodorou, I Pozotou, O Stavrinidou, A Yiallourou, L Martinek, M Skrovina, I Szubota, J Žatecký, V Javurkova, J Klat, T Avlund, P Christensen, J L Harbjerg, L H Iversen, D W Kjaer, Hø Kristensen, M Mekhael, A L Ebbehøj, P Krarup, N Schlesinger, H Smith, A Abdelsamed, A Y Azzam, H Salem, A Seleim, A Abdelmajeed, M Abdou, N E Abosamak, M Al Sayed, F Ashoush, R Atta, E Elazzazy, M Elhoseiny, M Elnemr, M S Elqasabi, M E Elsayed Hewalla, I Elsherbini, E Essam, M Eweda, I Ghallab, E Hassan, M Ibrahim, M Metwalli, M Mourad, M S Qatora, M Ragab, A Sabry, H Saifeldin, M Saleh Mesbah Mohamed Elkaffas, A Samih, A Samir Abdelaal, S Shehata, K Shenit, D Attia, N Kamal, N Osman, A M Abbas, Has Abd Elazeem, M M Abdelkarem, S Alaa, A K Ali, A Ayman, M G Azizeldine, H Elkhayat, S M Elghazaly, F A Monib, M A Nageh, M M Saad, M Salah, M Shahine, E A Yousof, A Youssef, A 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J R Tan, A Thomas, P Whelan, A Anzak, A Banerjee, O Fuwa, F Hughes, J D Jayasinghe, C Knowles, H Kocher, I Leal Silva, F S Ledesma, A Minicozzi, L Navaratne, R Rahman, R Ramamoorthy, C Sohrabi, M Thaha, B Thakur, M Venn, V Yip, R Baumber, J Parry, S Evans, L Jeys, G Morris, M Parry, J Stevenson, N Ahmadi, G Aresu, Z M Barrett-Brown, A S Coonar, H Durio Yates, D Gearon, J Hogan, M King, A Peryt, I S Pradeep, C Smith, M Adishesh, R Atherton, K Baxter, M Brocklehurst, M Chaudhury, N Krishnamohan, J McAleer, G Owens, E Parkin, P Patkar, I Phang, A Aladeojebi, M Ali, B Barmayehvar, A Gaunt, M Gowda, E Halliday, M Kitchen, F Mansour, M Thomas, D Zakai, N Abbassi-Ghadi, H Assalaarachchi, A Currie, M Flavin, A Frampton, M Hague, C Hammer, J Hopper, J Horsnell, S Humphries, A Kamocka, T K Madhuri, S Preston, P Singh, J Stebbing, A Tailor, D Walker, F Aljanadi, M Jones, P Mhandu, C O'Donnell, R Turkington, Z Al-Ishaq, S Bhasin, A S Bodla, A Burahee, A Crichton, R Fossett, N Pigadas, S Pickford, E Rahman, D Snee, R Vidya, N Yassin, F Colombo, D Fountain, M T Hasan, K Karabatsou, R Laurente, O Pathmanaban, A Al-Mukhtar, S Brown, J Edwards, A Giblin, C Kelty, M Lee, G Lye, T Newman, A Sharkey, C Steele, N Sureshkumar Shah, E Whitehall, R Athwal, A Baker, L Jones, C Konstantinou, S Ramcharan, S Singh, J Vatish, R Wilkin, M Ethunandan, G K Sekhon, H Shields, R Singh, F Wensley, S Lawday, A Lyons, T Abbott, S Anwar, K Ghufoor, C Sohrabi, E Chung, R Hagger, A Hainsworth, A Karim, H Owen, A Ramwell, K Williams, C Baker, A Davies, J Gossage, M Kelly, W Knight, J Hall, G Harris, G James, C Kang, D J Lin, A D Rajgor, T Royle, R Scurrah, B Steel, L J Watson, D Choi, R Hutchison, A Jain, V Luoma, H Marcus, R May, A Menon, B Pramodana, L Webber, I A Aneke, P Asaad, B Brown, J Collis, S Duff, A Khan, F Moura, B Wadham, H Warburton, T Elmoslemany, M Jenkinson, C Millward, R Zakaria, S Mccluney, C Parmar, S Shah, J Allison, M S Babar, B Collard, S Goodrum, K Lau, A Patel, R Scott, E Thomas, H Whitmore, D Balasubramaniam, B Jayasankar, S Kapoor, A Ramachandran, A Elhamshary, Smb Imam, K Kapriniotis, V Kasivisvanathan, J Lindsay, S Rakhshani-Moghadam, N Beech, M Chand, L Green, N Kalavrezos, H Kiconco, R McEwen, C Schilling, D Sinha, J Pereca, J Singh, S Chopra, D Egbeare, R Thomas, T Combellack, Sef Jones, M Kornaszewska, M Mohammed, A Sharma, G Tahhan, V Valtzoglou, J Williams, P Eskander, K Gash, L Gourbault, M Hanna, T Maccabe, C Newton, J Olivier, S Rozwadowski, E Teh, D West, H Al-Omishy, M Baig, H Bates, G Di Taranto, K Dickson, N Dunne, C Gill, D Howe, D Jeevan, A Khajuria, K Martin-Ucar AMcEvoy, P Naredla, V Ng, S Robertson, M Sait, D R Sarma, S Shanbhag, T Shortland, S Simmonds, J Skillman, N Tewari, G Walton, M A Akhtar, A Brunt, J McIntyre, K Milne, M M Rashid, A Sgro, K E Stewart, A Turnbull, M Aguilar Gonzalez, S Talukder, C Boyle, D Fernando, K Gallagher, A Laird, D Tham, M Bath, P Patki, C Sohrabi, C Tanabalan, T Arif, C Magee, T Nambirajan, S Powell, R Vinayagam, I Flindall, A Hanson, V Mahendran, S Green, M Lim, L MacDonald, V Miu, L Onos, K Sheridan, R Young, F Alam, O Griffiths, C Houlden, R Jones, V S Kolli, A K Lala, S Leeson, R Peevor, Z Seymour, L Chen, E Henderson, A Loehrer, K Brown, D Fleming, A Haynes, C Heron, C Hill, H Kay, E Leede, K McElhinney, K Olson, E C Osterberg, C Riley, P Srikanth, M Thornhill, D Blazer, G DiLalla, E S Hwang, W Lee, M Lidsky, J Plichta, L Rosenberger, R Scheri, K Shah, K Turnage, J Visgauss, S Zani, J Farma, J Clark, D Kwon, E Etchill, H E Gabre-Kidan AJenny, A Kent, M Ladd, C Long, H Malapati, A Margalit, S Rapaport, J Rose, K Stevens, L Tsai, D Vervoort, P Yesantharao, A Dehal, D Klaristenfeld, K Huynh, L Brown, I Ganly, J Mullinax, N Gusani, J Hazelton, J Maines, J S Oh, A Ssentongo, P Ssentongo, M Azam, A Choudhry, W Marx, J Fleming, A Fuson, J Gigliotti, A Ovaitt, Y Ying, M K Abel, V Andaya, K Bigay, M A Boeck, L Chen, H Chern, C Corvera, I El-Sayed, A Glencer, P Ha, Bcs Hamilton, C Heaton, K Hirose, D M Jablons, K Kirkwood, L Z Kornblith, J R Kratz, R Lee, P N Miller, E Nakakura, B Nunez-Garcia, R O'Donnell, D Ozgediz, P Park, B Robinson, A Sarin, B Sheu, M Varma, K Wai, R Wustrack, M J Xu, D Beswick, J Goddard, J Manor, J Song, T Fullmer, C Gaskill, N Gross, K Kiong, C L Roland, S N Zafar, M Abdallah, A Abouassi, M Almasri, G Kulkarni, H Marwan, M Mehdi, S Aoun, V S Ban, H H Batjer, J Caruso, D Abbott, A Acher, T Aiken, J Barrett, E Foley, P Schwartz, S N Zafar, A Hawkins, A Maiga, J Laufer, S Scasso
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Aged, 80 and over ,Male ,Critical Care ,SARS-CoV-2 ,International Cooperation ,COVID-19 ,Middle Aged ,Cohort Studies ,Logistic Models ,Postoperative Complications ,Elective Surgical Procedures ,Neoplasms ,Outcome Assessment, Health Care ,Humans ,Female ,Epidemics ,Aged - Abstract
PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
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- 2021
40. Abstract 568: A novel memory-like NK cell CAR targeting proximal mesothelin domain shows promising preclinical activity in ovarian cancer using cell lines and patient derived organoids
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Mubin Tarannum, Juliana A. Vergara, Yasmin Abdulhamid, Khanhlinh Dinh, Katherine N. Lynch, Sarah Hill, and Rizwan Romee
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Cancer Research ,Oncology - Abstract
Epithelial ovarian cancer (OVC) is the leading cause of death among gynecological malignancies. Natural killer (NK) cells are an attractive platform for immunotherapy owing to their superior safety, multiple mechanisms of target killing, and reduced risk of alloreactivity. Recently, paradigm-shifting studies have shown that brief activation of NK cells with inflammatory cytokines induces differentiation into cytokine induced memory-like (CIML) NK cells. CIML NK cells have demonstrated potent anti-leukemia activity in preclinical settings and in recent clinical trials and therefore represent a novel platform for genetically modified chimeric antigen receptor (CAR) cells for OVC therapy. Mesothelin (MSLN) is expressed in around 82% of OVCs and its expression is corelated with chemoresistance, increased metastasis, and poor overall survival in patients. We hypothesize arming CIML NK cells with a CAR targeting the proximal mesothelin domain will enhance their antitumor responses. We designed and tested anti-MSLN CAR CIML NK cells for their anti-cancer functionality against OVC cell lines and patient-derived organoids (PDOs). We first validated the mesothelin expression in 13 OVC patient samples which, based on pathological scoring showed high mesothelin in 8, moderate in 3, and low in 2 patient samples. PDOs also showed high expression of mesothelin, confirming it as an attractive candidate for CAR cells. We designed the aMSLN-CAR using an ScFv sequence against the proximal domain of the protein with 4-1BB and CD3ζ as co-stimulatory domains. Primary NK cells were purified from peripheral blood, activated using IL-12, IL-18, and IL-15 to afford CIML NK cells. The CAR gene was transduced into CIML NK cells via our optimized baboon lentiviral system to achieve a high transduction efficiency of 40-60%. The direct cytotoxic effect of these NK cells was tested against OVC cell lines. OVC cell lines were co-cultured with NK cells at various effector:target (E:T) ratios for 6 hours and analyzed using apoptotic markers. Compared to CIML NK cells, aMSLN-CAR CIML NK cells showed enhanced cytotoxicity against OVCAR3 (47.9% vs 14.8%), SKOV3 (29.3% vs 8.0%) and OVCAR8 (60.7% vs 39.8%) at 10:1 ratio. To test the therapeutic potential of CAR CIML NK cells in vitro, three different PDOs were used. Cytotoxicity was determined by evaluating apoptotic EpCAM+ cancer cells amongst the organoid cell population after 18-hour co-culture with NK cells. The aMSLN-CAR CIML NK cells were shown to cause increased apoptosis in cells from PDOs compared to CIML NK cells; 58.2% vs 11.0%, 4.5% vs 61.0%, and 10.5% vs 32.0%. We are currently evaluating the in vivo functionality of aMSLN-CAR CIML NK cells in a xenograft mouse model using OVC cell lines and PDOs. The successful application of CAR CIML-NK cells will pave way for the use of NK cell platforms for other solid tumors. Citation Format: Mubin Tarannum, Juliana A. Vergara, Yasmin Abdulhamid, Khanhlinh Dinh, Katherine N. Lynch, Sarah Hill, Rizwan Romee. A novel memory-like NK cell CAR targeting proximal mesothelin domain shows promising preclinical activity in ovarian cancer using cell lines and patient derived organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 568.
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- 2022
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41. Critique of the ACGIH 2016 derivation of toluene diisocyanate Threshold Limit Values
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Heather N. Lynch, Robyn L. Prueitt, and Julie E. Goodman
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Threshold limit value ,Air Pollutants, Occupational ,010501 environmental sciences ,Toxicology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Occupational hygiene ,Occupational Exposure ,Environmental health ,medicine ,Animals ,Humans ,Asthma, Occupational ,Threshold Limit Values ,Occupational Health ,Lung function ,0105 earth and related environmental sciences ,Asthma ,Toluene diisocyanate ,business.industry ,General Medicine ,medicine.disease ,030210 environmental & occupational health ,respiratory tract diseases ,chemistry ,Toluene 2,4-Diisocyanate ,business ,Occupational asthma - Abstract
In 2016, the American Conference of Governmental Industrial Hygienists (ACGIH) lowered the 8-hr Threshold Limit Value - time-weighted average (TLV-TWA) for toluene diisocyanate (TDI) from 5 ppb to 1 ppb, and the 15-min short-term exposure limit (STEL) from 20 ppb to 5 ppb. We evaluated ACGIH's basis for lowering these values. It is our opinion that the ACGIH's evaluation of the evidence for occupational asthma and respiratory effects from TDI exposure does not fully integrate the results of all the available human and animal studies. We found that some studies reported occupational asthma cases at TWAs less than 5 ppb, but these cases were likely caused by peak exposures above 20 ppb. Advances in industrial hygiene have reduced peak exposures and the incidence of upset conditions, such as spills and accidents, in modern TDI facilities. Taken together, the human evidence indicates that adherence to the previous 8-hr TLV-TWA and 15-min STEL (5 ppb and 20 ppb, respectively) prevents most, if not all, cases of occupational asthma, and eliminates or reduces the risk of lung function decrements and other respiratory effects. While limited, the animal literature supports the human evidence and indicates that TDI-induced asthma is a threshold phenomenon. We conclude that ACGIH's decision to lower the TLV-TWA and STEL values for TDI is not adequately supported.
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- 2018
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42. De strafmaat voor jeugdige daders van ernstige gewelds- en zedenmisdrijven in internationaal perspectief
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J.J. Asscher, Y.N. van den Brink, H.E. Creemers, E. Huls, E.K. van Logchem, N. Lynch, Stephanie Rap, J.J. Asscher, Y.N. van den Brink, H.E. Creemers, E. Huls, E.K. van Logchem, N. Lynch, and Stephanie Rap
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- Juvenile justice, Administration of, Violent offenders, At-risk youth--Rehabilitation
- Abstract
De sanctionering van jeugdigen die zich schuldig maken aan een ernstig gewelds- of zedenmisdrijf is in Nederland al langere tijd onderwerp van politieke en maatschappelijke discussie. In dit onderzoek wordt in kaart gebracht welke sancties Nederland en andere Europese landen – België (Vlaanderen), Duitsland, Engeland en Wales, Ierland en Zweden – hanteren voor minderjarigen en jongvolwassenen (tot 23 jaar) die een ernstig gewelds- of zedenmisdrijf hebben gepleegd. Ook wordt onderzocht wat de effectiviteit van deze sancties is en hoe de diverse sanctiestelsels zich verhouden tot internationale en Europese kinder- en mensenrechten. Vervolgens wordt gereflecteerd op de vraag in hoeverre de bevindingen van dit onderzoek aanleiding geven tot aanpassing van de Nederlandse strafrechtelijke aanpak van jeugdigen die worden veroordeeld voor een ernstig gewelds- of zedenmisdrijf. Uiteindelijk resulteert het onderzoek in een aantal concrete aandachtspunten voor wetgeving en beleid en suggesties voor ver volgonderzoek die de wetgever en beleidsmakers beogen te ondersteunen bij het maken van goed geïnformeerde, weloverwogen en wetenschappelijk onderbouwde beslissingen omtrent dit vraagstuk. Hiermee legt dit onderzoek een belangrijke wetenschappelijke basis voor het ontwikkelen van een effectief en kinder- en mensenrechtenconform sanctiestelsel voor jeugdigen die zich schuldig maken aan een ernstig gewelds- of zedenmisdrijf in Nederland en daarbuiten.
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- 2021
43. PO-1335: Characterization of novel 3D printed plastic scintillation dosimeters
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James Robar, N. Lynch, and T. Monajemi
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3d printed ,Scintillation ,Materials science ,Dosimeter ,Oncology ,business.industry ,Optoelectronics ,Radiology, Nuclear Medicine and imaging ,Hematology ,business ,Characterization (materials science) - Published
- 2020
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44. Target sites: skin
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Heather N. Lynch and Julie E. Goodman
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- 2020
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45. Critical review of the evidence for a causal association between exposure to asbestos and esophageal cancer
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Michael K Peterson, Anna M Engel, Thuy Lam, Isaac Mohar, Heather N. Lynch, and Travis J Cook
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Oncology ,medicine.medical_specialty ,Esophageal Neoplasms ,010501 environmental sciences ,Toxicology ,medicine.disease_cause ,01 natural sciences ,Hazardous Substances ,Asbestos ,03 medical and health sciences ,Internal medicine ,Epidemiology ,Animals ,Humans ,Medicine ,Mesothelioma ,Lung cancer ,Carcinogen ,030304 developmental biology ,0105 earth and related environmental sciences ,0303 health sciences ,business.industry ,Environmental Exposure ,Esophageal cancer ,medicine.disease ,Causal association ,Causal link ,business - Abstract
Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM’s findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.
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- 2020
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46. List of Contributors
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Martins O. Ainerua, Iris An, Charles C. Barton, Sol Bobst, Marie Bourgeois, Megan Branson, Bruce Busby, Brenda Carito, Clark Carrington, Grace A. Chappell, Guang-Di Chen, Debra Cherry, Karen Chou, Joseph A. Cichocki, Louis Anthony Cox, Yuri Bruinen de Bruin, Aisha S. Dickerson, David C. Dorman, Ruth A. Etzel, Allan S. Felsot, Jeremy A. Freeman, Katie Frevert, Elizabeth Friedman, Shayne Gad, Victoria Gifford, Steven G. Gilbert, Julie E. Goodman, Anshul Gupta, Kevin Guth, Axel Hahn, Raymond D. Harbison, Esther M. Haugabrooks, A. Wallace Hayes, Antoinette Hayes, Stacey Herriage, Richard C. Hertzberg, Stephanie Holmgren, Tamara House-Knight, Sara T. Humes, Devin Hunt, William Irwin, Maryam Zare Jeddi, Samantha J. Jones, James E. Klaunig, Cecile M. Krejsa, Meredith G. Lassiter, Abby A. Li, Edward P. Locke, Heather N. Lynch, Andrew Maier, Stacey Mantooth, M. Elizabeth Marder, Asish Mohapatra, Virginia Moser, M. Moiz Mumtaz, Lewis S. Nelson, Kenneth J. Olivier, Amanda S. Persad, Mark Pershouse, Rebekah Petroff, Carey Pope, Elizabeth Putnam, Gary O. Rankin, Glenn E. Rice, Tara Sabo-Attwood, Cynthia Santos, Barbara B. Saunders-Price, Johanna E. Schaaper, Dietrich (Dieter) Schwela, Jane Ellen Simmons, Gregory J. Smith, Kenneth R. Still, Frederick W. Stoss, Dexter W. Sullivan, Michele R. Sullivan, Alicia A. Taylor, Greet B.A. Teuns, Karen Tilmant, Monica A. Valentovic, Sander Van Der Linden, Nina Ching Y. Wang, Katherine D. Watson, Eleanor Weston, Philip Wexler, Catherine F. Wise, James T.F. Wise, John Pierce Wise, John P. Wise, Jamie L. Young, and Robert R. Young
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- 2020
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47. Simulating the Mobility of Wheeled Ground Vehicles with Mercury
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Jody D. Priddy, Jeremy Mange, Sara Pace, Christopher Goodin, Thomas Skorupa, Daniel Kedziorek, and Larry N. Lynch
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0209 industrial biotechnology ,020303 mechanical engineering & transports ,020901 industrial engineering & automation ,0203 mechanical engineering ,chemistry ,Environmental engineering ,chemistry.chemical_element ,Environmental science ,02 engineering and technology ,General Medicine ,Ground vehicles ,Mercury (element) - Published
- 2017
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48. Improving the International Agency for Research on Cancer's consideration of mechanistic evidence
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Heather N. Lynch and Julie E. Goodman
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0301 basic medicine ,Pharmacology ,Biomedical Research ,Study quality ,Computer science ,Standardized approach ,Decision Making ,International Agencies ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Hazard ,Scientific evidence ,03 medical and health sciences ,030104 developmental biology ,Risk analysis (engineering) ,Biological significance ,Neoplasms ,Carcinogens ,Humans ,Relevance (law) ,Human cancer ,0105 earth and related environmental sciences ,International agency - Abstract
Background The International Agency for Research on Cancer (IARC) recently developed a framework for evaluating mechanistic evidence that includes a list of 10 key characteristics of carcinogens. This framework is useful for identifying and organizing large bodies of literature on carcinogenic mechanisms, but it lacks sufficient guidance for conducting evaluations that fully integrate mechanistic evidence into hazard assessments. Objectives We summarize the framework, and suggest approaches to strengthen the evaluation of mechanistic evidence using this framework. Discussion While the framework is useful for organizing mechanistic evidence, its lack of guidance for implementation limits its utility for understanding human carcinogenic potential. Specifically, it does not include explicit guidance for evaluating the biological significance of mechanistic endpoints, inter- and intra-individual variability, or study quality and relevance. It also does not explicitly address how mechanistic evidence should be integrated with other realms of evidence. Because mechanistic evidence is critical to understanding human cancer hazards, we recommend that IARC develop transparent and systematic guidelines for the use of this framework so that mechanistic evidence will be evaluated and integrated in a robust manner, and concurrently with other realms of evidence, to reach a final human cancer hazard conclusion. Conclusions IARC does not currently provide a standardized approach to evaluating mechanistic evidence. Incorporating the recommendations discussed here will make IARC analyses of mechanistic evidence more transparent, and lead to assessments of cancer hazards that reflect the weight of the scientific evidence and allow for scientifically defensible decision-making.
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- 2017
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49. Novel copolymers of styrene. 4. Halogen ring-substituted propyl 2-cyano-3-phenyl-2-propenoates
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Gregory B. Kharas, Valeria A. Sloan-Lyon, Jason D. Grannum, Mark B. Gudger, Mirlinda L. Isai, Lauren A. Kopczynski, Cameron N. Lynch, Haley M. Meyer, Brandon A. Roman, Sean R. Schaefer, and Lucas F. Welk
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Polymers and Plastics ,Materials Chemistry ,Ceramics and Composites ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,0210 nano-technology ,01 natural sciences ,0104 chemical sciences - Published
- 2016
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50. First Report of Soybean Rust Caused by Phakopsora pachyrhizi on Phaseolus spp. in the United States
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Philip F. Harmon, M. R. Miles, T. N. Lynch, Glen L. Hartman, David L. Wright, Carrie L. Harmon, and James J. Marois
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food.ingredient ,biology ,Plant Science ,biology.organism_classification ,Rust ,Kudzu ,Aphis ,Horticulture ,food ,Agronomy ,Phakopsora pachyrhizi ,Pueraria montana ,Phaseolus coccineus ,Phaseolus ,Soybean rust ,Agronomy and Crop Science - Abstract
Phakopsora pachyrhizi Syd. & P. Syd., the cause of soybean rust, was first observed in the continental United States in November 2004 (2). During the growing season of 2005, P. pachyrhizi was confirmed on soybean (Glycine max) and/or kudzu (Pueraria montana) in nine states in the southern United States. It is known that P. pachyrhizi has a much larger host range within the Fabaceae family. On 29 September 2005 in Quincy, FL, 45 entries of mostly large-seeded legumes were planted next to soybeans that were infected with P. pachyrhizi. Several seeds of each entry were planted on one hill. Soybean plants growing adjacent to these potential hosts had 15 to 25% of the leaf area affected, 95% incidence, and 73% defoliation on 16 November. On 7 December 2005, all the plants of Phaseolus coccineus L. (scarlet runner bean, PI311827), Phaseolus lunatus L. (lima bean, PI583558), and two Phaseolus vulgaris L. (kidney bean) cvs. Red Hawk and California Early Light Red Kidney (CELRK) were found to have leaves with suspected rust lesions. These plants were at physiological maturity but had not senesced. None of the hosts had been inoculated other than from spores produced by the adjacent rust-infected soybean plants or from unknown locations. On the basis of microscopic examination, suspected infected leaves from plants of the Phaseolus spp. had rust pustules characteristic of P. pachyrhizi uredinia. Uredinia were counted within a randomly selected 2-cm2 area of one leaf of each sample. The mean and range of uredinia per lesion for Phaseolus coccineus was 29 uredinia with a range of 0 to 3 uredinia per lesion, Phaseolus lunatus had 2 uredinia with 0 to 1 uredinium per lesion, Phaseolus vulgaris cv. Red Hawk had 22 uredinia with 0 to 5 uredinia per lesion, and Phaseolus vulgaris cv. CELRK had 43 uredinia with 0 to 4 uredinia per lesion. Polymerase chain reactions using two sets of primers (Ppa1/Ppa2 and Pme1/Pme2) were performed on DNA extracted from leaves of the three species with sporulating rust pustules (1). The results of these tests and further tests conducted by the USDA/APHIS confirmed that P. pachyrhizi was the causal organism for the observed rust. References: (1) P. F. Harmon et al. On-line publication. doi:10.1094/PHP-2005-0613-01-RS. Plant Health Progress, 2005. (2) R. W. Schneider et al. Plant Dis. 89:774, 2005.
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- 2019
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