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4. TGFβ Drives Metabolic Perturbations during Epithelial Mesenchymal Transition in Pancreatic Cancer: TGFβ Induced EMT in PDAC

Author

Rajagopal, Meena U, Bansal, Shivani, Kaur, Prabhjit, Jain, Shreyans K, Altadil, Tatiana, Hinzman, Charles P, Li, Yaoxiang, Moulton, Joanna, Singh, Baldev, Bansal, Sunil, Chauthe, Siddheshwar Kisan, Singh, Rajbir, Banerjee, Partha P, Mapstone, Mark, Fiandaca, Massimo S, Federoff, Howard J, Unger, Keith, Smith, Jill P, and Cheema, Amrita K

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Cancer, Rare Diseases, Pancreatic Cancer, Aetiology, 2.1 Biological and endogenous factors, tumor microenvironment, pancreatic cancer, TGF beta, 9-cis retinoic acidPANC-1 cells, epithelial mesenchymal transition, Oncology and carcinogenesis
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy wherein a majority of patients present metastatic disease at diagnosis. Although the role of epithelial to mesenchymal transition (EMT), mediated by transforming growth factor beta (TGFβ), in imparting an aggressive phenotype to PDAC is well documented, the underlying biochemical pathway perturbations driving this behaviour have not been elucidated. We used high-resolution mass spectrometry (HRMS) based molecular phenotyping approach in order to delineate metabolic changes concomitant to TGFβ-induced EMT in pancreatic cancer cells. Strikingly, we observed robust changes in amino acid and energy metabolism that may contribute to tumor invasion and metastasis. Somewhat unexpectedly, TGFβ treatment resulted in an increase in intracellular levels of retinoic acid (RA) that in turn resulted in increased levels of extracellular matrix (ECM) proteins including fibronectin (FN) and collagen (COL1). These findings were further validated in plasma samples obtained from patients with resectable pancreatic cancer. Taken together, these observations provide novel insights into small molecule dysregulation that triggers a molecular cascade resulting in increased EMT-like changes in pancreatic cancer cells, a paradigm that can be potentially targeted for better clinical outcomes.

Published
2021

5. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Author

Perkovic, Vlado, Mahaffey, Kenneth W., Agarwal, Rajiv, Bakris, George, Brenner, Barry M., Cannon, Christopher P., Charytan, David M., de Zeeuw, Dick, Greene, Tom, Jardine, Meg J., Heerspink, Hiddo J.L., Levin, Adeera, Meininger, Gary, Neal, Bruce, Pollock, Carol, Wheeler, David C., Zhang, Hong, Zinman, Bernard, Jardine, Meg, Li, Nicole, Kolesnyk, Inna, Aizenberg, Diego, Pecoits-Filho, Roberto, Cherney, David, Obrador, Gregorio, Chertow, Glenn, Chang, Tara, Hawley, Carmel, Ji, Linong, Wada, Takashi, Jha, Vivekanand, Lim, Soo Kun, Lim-Abrahan, Mary Anne, Santos, Florence, Chae, Dong-Wan, Hwang, Shang-Jyh, Vazelov, Evgueniy, Rychlík, Ivan, Hadjadj, Samy, Krane, Vera, Rosivall, László, De Nicola, Luca, Dreval, Alexander, Nowicki, Michał, Schiller, Adalbert, Distiller, Larry, Górriz, Jose L., Kolesnyk, Mykola, David, Wheeler, C., Guerrero, Rodolfo Andres Ahuad, Albisu, Juan Pablo, Alvarisqueta, Andres, Bartolacci, Ines, Berli, Mario Alberto, Bordonava, Anselmo, Calella, Pedro, Cantero, Maria Cecilia, Cartasegna, Luis Rodolfo, Cercos, Esteban, Coloma, Gabriela Cecilia, Colombo, Hugo, Commendatore, Victor, Cuadrado, Jesus, Cuneo, Carlos Alberto, Cusumano, Ana Maria, Douthat, Walter Guillermo, Dran, Ricardo Dario, Farias, Eduardo, Fernandez, Maria Florencia, Finkelstein, Hernan, Fragale, Guillermo, Fretes, Jose Osvaldo, Garcia, Nestor Horacio, Gastaldi, Anibal, Gelersztein, Elizabeth, Glenny, Jorge Archibaldo, Gonzalez, Joaquin Pablo, Colaso, Patricia del Carmen Gonzalez, Goycoa, Claudia, Greloni, Gustavo Cristian, Guinsburg, Adrian, Hermida, Sonia, Juncos, Luis Isaias, Klyver, Maria Isabel, Kraft, Florencia, Krynski, Fernando, Lanchiotti, Paulina Virginia, Leon de la Fuente, Ricardo Alfonso, Marchetta, Nora, Mele, Pablo, Nicolai, Silvia, Novoa, Pablo Antonio, Orio, Silvia Ines, Otreras, Fabian, Oviedo, Alejandra, Raffaele, Pablo, Resk, Jorge Hector, Rista, Lucas, Papini, Nelson Rodriguez, Sala, Jorgelina, Santos, Juan Carlos, Schiavi, Lilia Beatriz, Sessa, Horacio, Casabella, Tomas Smith, Ulla, Maria Rosa, Valdez, Maria, Vallejos, Augusto, Villarino, Adriana, Visco, Virginia Esther, Wassermann, Alfredo, Zaidman, Cesar Javier, Cheung, Ngai Wah, Droste, Carolyn, Fraser, Ian, Johnson, David, Mah, Peak Mann, Nicholls, Kathy, Packham, David, Proietto, Joseph, Roberts, Anthony, Roger, Simon, Tsang, Venessa, Raduan, Roberto Abrão, Costa, Fernando Augusto Alves da, Amodeo, Celso, Turatti, Luiz Alberto Andreotti, Bregman, Rachel, Sanches, Fernanda Cristina Camelo, Canani, Luis Henrique, Chacra, Antônio Roberto, Borges, João Lindolfo Cunha, Vêncio, Sérgio Alberto Cunha, Franco, Roberto Jorge da Silva, d’Avila, Domingos, Portes, Evandro de Souza, de Souza, Pedro, Deboni, Luciane Mônica, Fraige Filho, Fadlo, Neto, Bruno Geloneze, Gomes, Marcus, Kohara, Suely Keiko, Keitel, Elizete, Saraiva, Jose Francisco Kerr, Lisboa, Hugo Roberto Kurtz, Contieri, Fabiana Loss de Carvalho, Milagres, Rosângela, Junior, Renan Montenegro, de Brito, Claudia Moreira, Hissa, Miguel Nasser, Sabbag, Ângela Regina Nazario, Noronha, Irene, Panarotto, Daniel, Filho, Roberto Pecoits, Pereira, Márcio Antônio, Saporito, Wladmir, Scotton, Antonio Scafuto, Schuch, Tiago, de Almeida, Roberto Simões, Ramos, Cássio Slompo, Felício, João Soares, Thomé, Fernando, Hachmann, Jean Carlo Tibes, Yamada, Sérgio, Hayashida, Cesar Yoiti, Petry, Tarissa Beatrice Zanata, Zanella, Maria Teresa, Andreeva, Viktoria, Angelova, Angelina, Dimitrov, Stefan, Genadieva, Veselka, Genova-Hristova, Gabriela, Hristozov, Kiril, Kamenov, Zdravko, Koundurdjiev, Atanas, Lozanov, Lachezar, Margaritov, Viktor, Nonchev, Boyan, Rangelov, Rangel, Shinkov, Alexander, Temelkova, Margarita, Velichkova, Ekaterina, Yakov, Andrian, Aggarwal, Naresh, Aronson, Ronnie, Bajaj, Harpreet, Chouinard, Guy, Conway, James, Cournoyer, Serge, DaRoza, Gerald, De Serres, Sacha, Dubé, François, Goldenberg, Ronald, Gupta, Anil, Gupta, Milan, Henein, Sam, Khandwala, Hasnain, Leiter, Lawrence, Madore, François, McMahon, Alan, Muirhead, Norman, Pichette, Vincent, Rabasa-Lhoret, Remi, Steele, Andrew, Tangri, Navdeep, Torshizi, Ali, Woo, Vincent, Zalunardo, Nadia, Montenegro, María Alicia Fernández, Gonzalo Godoy Jorquera, Juan, Fariña, Marcelo Medina, Gajardo, Victor Saavedra, Vejar, Margarita, Chen, Nan, Chen, Qinkai, Gan, Shenglian, Kong, Yaozhong, Li, Detian, Li, Wenge, Li, Xuemei, Lin, Hongli, Liu, Jian, Lu, Weiping, Mao, Hong, Ren, Yan, Song, Weihong, Sun, Jiao, Sun, Lin, Tu, Ping, Wang, Guixia, Yang, Jinkui, Yin, Aiping, Yu, Xueqing, Zhao, Minghui, Zheng, Hongguang, Mendoza, Jose Luis Accini, Arcos, Edgar, Avendano, Jorge, Diaz Ruiz, Jorge Ernesto Andres, Ortiz, Luis Hernando Garcia, Gonzalez, Alexander, Triana, Eric Hernandez, Higuera, Juan Diego, Malaver, Natalia, de Salazar, Dora Inés Molina, Rosero, Ricardo, Alexandra Terront Lozano, Monica, Cometa, Luis Valderrama, Valenzuela, Alex, Vargas Alonso, Ruben Dario, Villegas, Ivan, Yupanqui, Hernan, Bartaskova, Dagmar, Barton, Petr, Belobradkova, Jana, Dohnalova, Lenka, Drasnar, Tomas, Ferkl, Richard, Halciakova, Katarina, Klokocnikova, Vera, Kovar, Richard, Lastuvka, Jiri, Lukac, Martin, Pesickova, Satu, Peterka, Karel, Pumprla, Jiri, Rychlik, Ivan, Saudek, Frantisek, Tesar, Vladimir, Valis, Martin, Weiner, Pavel, Zemek, Stanislav, Alamartine, Eric, Borot, Sophie, Cariou, Bertrand, Dussol, Bertrand, Fauvel, Jean-Pierre, Gourdy, Pierre, Klein, Alexandre, Le Meur, Yannick, Penfornis, Alfred, Roussel, Ronan, Saulnier, Pierre-Jean, Thervet, Eric, Zaoui, Philippe, Burst, Volker, Faghih, Markus, Faulmann, Grit, Haller, Hermann, Jerwan-Keim, Reinhold, Maxeiner, Stephan, Paschen, Björn, Plassmann, Georg, Rose, Ludger, Gonzalez Orellana, Ronaldo Arturo, Haase, Franklin Paul, Moreira Diaz, Juan Pablo, Ramirez Roca, Luis Alberto, Sánchez Arenales, Jose Antonio, Sanchez Polo, José Vicente, Juarez, Erick Turcios, Csecsei, Gyongyi, Csiky, Botond, Danos, Peter, Deak, Laszlo, Dudas, Mihaly, Harcsa, Eleonora, Keltai, Katalin, Keresztesi, Sandor, Kiss, Krisztian, Konyves, Laszlo, Major, Lajos, Mileder, Margit, Molnar, Marta, Mucsi, Janos, Oroszlan, Tamas, Ory, Ivan, Paragh, Gyorgy, Peterfai, Eva, Petro, Gizella, Revesz, Katalin, Takacs, Robert, Vangel, Sandor, Vasas, Szilard, Zsom, Marianna, Abraham, Oomman, Bhushan, Raju Sree, Deepak, Dewan, Edwin, Fernando M., Gopalakrishnan, Natarajan, Gracious, Noble, Hansraj, Alva, Jain, Dinesh, Keshavamurthy, C.B., Khullar, Dinesh, Manisha, Sahay, Peringat, Jayameena, Prasad, Narayan, Satyanarayana, Rao K., Sreedhar, Reddy, Sreelatha, Melemadathil, Sudhakar, Bhimavarapu, Chandra Vyasam, Ramesh, Bonadonna, Riccardo, Castellino, Pietro, Ceriello, Antonio, Chiovato, Luca, De Cosmo, Salvatore, Derosa, Giuseppe, Di Carlo, Alberto, Di Cianni, Graziano, Frascà, Giovanni, Fuiano, Giorgio, Gambaro, Giovanni, Garibotto, Giacomo, Giorda, Carlo, Malberti, Fabio, Mandreoli, Marcora, Mannucci, Edoardo, Orsi, Emanuela, Piatti, Piermarco, Santoro, Domenico, Sasso, Ferdinando Carlo, Serviddio, Gaetano, Stella, Andrea, Trevisan, Roberto, Veronelli, Anna Maria, Zanoli, Luca, Akiyama, Hitoshi, Aoki, Hiromi, Asano, Akimichi, Iitsuka, Tadashi, Kajiyama, Shizuo, Kashine, Susumu, Kawada, Toshio, Kodera, Takamoto, Kono, Hiroshi, Koyama, Kazunori, Kumeda, Yasuro, Miyauchi, Shozo, Mizuyama, Kazuyuki, Niiya, Tetsuji, Oishi, Hiroko, Ota, Satoshi, Sakakibara, Terue, Takai, Masahiko, Tomonaga, Osamu, Tsujimoto, Mitsuru, Wakasugi, Masakiyo, Wakida, Yasushi, Watanabe, Takayuki, Yamada, Masayo, Yanagida, Kazuhiro, Yanase, Toshihiko, Yumita, Wataru, Gaupsiene, Egle, Kozloviene, Dalia, Navickas, Antanas, Urbanaviciene, Egle, Abdul Ghani, Rohana, Kadir, Khalid Abdul, Ali, Norsiah, Che Yusof, Mohd Daud, Gan, Chye Lee, Ismail, Mastura, Kong, Wei Yen, Lam, Swee Win, Lee, Li Yuan, Loh, Chek Loong, Manocha, Anita Bhajan, Ng, Kee Sing, Ahmad, Nik Nur Fatnoon Nik, Ratnasingam, Vanassa, Shudim, Saiful Shahrizal Bin, Vengadasalam, Paranthaman, Abraira Munoz, Luis David, Salazar, Melchor Alpizar, Cruz, Juan Baas, Soto, Mario Burgos, Ramos, Jose Chevaile, Wong, Alfredo Chew, Correa Rotter, Jose Ricardo, Escalante, Tonatiu Diaz, Enriquez Sosa, Favio Edmundo, Lozano, Fernando Flores, Flota Cervera, Luis Fernando, Baron, Paul Frenk, Ballesteros, Cecilia Garcia, Gomez Rangel, Jose David, Herrera Jimenez, Luis Enrique, Irizar Santana, Sergio Saul, Flores, Fernando Jimenez, Molina, Hugo Laviada, Luna Ceballos, Rosa Isela, del Campo Blanco, Belia Martin, Franco, Guadalupe Morales, Moreno Loza, Oscar Tarsicio, Rocha, Cynthia Mustieles, Vera, Gregorio Obrador, Castellanos, Ricardo Orozco, Calcaneo, Juan Peralta, Reyes Rosano, Miguel Angel, Pattzi, Hiromi Rodriguez, Guzman, Juan Rosas, Rucker Joerg, Isabel Erika, Saavedra Sanchez, Sandra Berenice, Sanchez Mijangos, Jose Hector, Sanson, Pablo Serrano, Tamayo y Orozco, Juan Alfredo, Chavez, Eloisa Tellez, Cepeda, Alejandro Valdes, Carrillo, Luis Venegas, Mesa, Juan Villagordoa, Escobedo, Rolando Zamarripa, Baker, John, Noonan, Paul, Scott, Russell, Walker, Robert, Watson, Edward, Williams, Michael, Young, Simon, Abejuela, Zaynab, Agra, Jeimeen, Aquitania, Grace, Caringal, Clodoaido, Comia, Rhea Severina, Santos, Lalaine Delos, Gomez, Olivert, Jimeno, Cecilia, Tan, Gerry, Tolentino, Marsha, Yao, Christy, Yap, Yvette Ethel, Lallaine Ygpuara, Ma. Dovie, Bijata-Bronisz, Renata, Hotlos, Lucyna, Januszewicz, Andrzej, Kaczmarek, Barbara, Kaminska, Anna, Lazuka, Lech, Madej, Andrzej, Mazur, Stanislaw, Mlodawska-Choluj, Dorota, Nowicki, Michal, Orlowska-Kowalik, Grazyna, Popenda, Grazyna, Rewerska, Barbara, Sowinski, Dariusz, Angelescu, Liliana Monica, Anghel, Veronica, Avram, Rodica-Ioana, Busegeanu, Mihaela-Magdalena, Cif, Adriana, Cosma, Dana, Crisan, Carmen, Demian, Luiza Despina, Ferariu, Ioana Emilia, Halmagyi, Ildiko, Hancu, Nicolae, Munteanu, Mircea, Negru, Doru, Onaca, Adriana Gabriela, Petrica, Ligia, Popa, Amorin Remus, Ranetti, Aurelian-Emil, Serafinceanu, Cristian, Toarba, Cristina, Agafyina, Alina, Barbarash, Olga, Barysheva, Olga, Chizhov, Daniil, Dobronravov, Vladimir, Glinkina, Irina, Grineva, Elena, Khirmanov, Vladimir, Kolmakova, Elena, Koroleva, Tatiana, Kvitkova, Liudmila, Marasaev, Viacheslav, Mkrtumyan, Ashot, Morugova, Tatiana, Nagibovich, Galina, Nagibovich, Oleg, Nedogoda, Sergei, Osipova, Irina, Raskina, Tatiana, Samoylova, Yulia, Sazonova, Olga, Shamkhalova, Minara, Shutemova, Elena, Shwartz, Yuriy, Uriasyev, Oleg, Vorobyev, Sergey, Zateyshchikova, Anna, Zateyshshikov, Dmitry, Zykova, Tatyana, Antic, Slobodan, Djordjevic, Miodrag, Kendereski, Aleksandra, Lalic, Katarina, Lalic, Nebojsa, Popovic-Radinovic, Vesna, Babikova, Jana, Benusova, Olga, Buganova, Ingrid, Culak, Jan, Dzupina, Andrej, Dzuponova, Jana, Fulop, Peter, Ilavska, Adriana, Martinka, Emil, Ochodnicka, Zuzana, Pella, Daniel, Smatanova, Iveta, Ahmed, Fayzal, Badat, Aysha, Breedt, Johannes, Distiller, Lawrence, Govender, Vimladhevi, Govender, Ravendran, Joshi, Mukesh, Jurgens, Jaco, Latiff, Gulam, Lombard, Landman, Mookadam, Mohamed, Ngcakani, Nomangesi, Nortje, Hendrik, Oosthuizen, Helena, Pillay-Ramaya, Larisha, Prozesky, Hans, Reddy, Jeevren, Rheeder, Paul, Seeber, Mary, Cho, Young Min, Jeong, In-Kyung, Kim, Sin Gon, Kim, Yeong Hoon, Kwon, Hyuk-Sang, Kwon, Min Jeong, Lee, Byung-Wan, Lee, JungEun, Lee, Moon-Kyu, Nam, Moon-Suk, Oh, Kook-Hwan, Park, Cheol- Young, Park, Sun-Hee, Yoon, Kun Ho, Garcia, Pere Alvarez, Mercadal, Luis Asmarats, Barrios, Clara, Castro, Fernando Cereto, Guldris, Secundino Cigarran, Lopez, Marta Dominguez, Egido de los Rios, Jesus, Fresnedo, Gema Fernandez, Serrano, Antonio Galan, Garcia, Isabel, Gonzalez Martinez, Francisco Javier, Jodar Gimeno, Jose Esteban, Mendoza, Manuel Lopez, Marin, Tamara Malek, Portillo, Cristobal Morales, Munar Vila, Maria Antonia, Torres, Manuel Muñoz, Iglesias, Javier Nieto, Perez, Jonay Pantoja, Vera, Merce Perez, Portoles Perez, Jose M., Quesada Simón, María Angustias, Canonge, Rafael Simo, Gonzalez, Alfonso Soto, Riera, Manel Terns, Tinahones Madueno, Francisco Jose, Plaza, Mercedes Velo, Chang, Chwen-Tzuei, Chuang, Lee-Ming, Hsia, Te-Lin, Hsieh, Chang-Hsun, Lin, Chih-Ching, Lu, Yung- Chuan, Sheu, Wayne H-H, Barna, Olga, Bilyk, Svitlana D., Botsyurko, Volodymyr, Dudar, Iryna, Fushtey, Ivan, Godlevska, Olga, Golovchenko, Oleksandr, Gyrina, Olga, Kazmirchuk, Anatoliy, Komisarenko, Iuliia, Korzh, Oleksii, Kravchun, Nonna, Legun, Oleg, Mankovskyy, Borys, Martynyuk, Liliya, Mostovoy, Yuriy, Pashkovska, Nataliia, Pererva, Larysa, Pertseva, Tetyana, Samoylov, Oleksandr, Smirnov, Ivan, Svyshchenko, Yevgeniya, Tomashkevych, Halyna, Topchii, Ivan, Tryshchuk, Nadiya, Tseluyko, Vira, Vizir, Vadym, Vlasenko, Maryna, Zlova, Tetiana, Zub, Liliia, Abusnana, Salah, Railey, Mohamed, Abouglila, Kamal, Ainsworth, Paul, Ali, Zishan, Arutchelvam, Vijayaraman, Barnard, Maria, Bellary, Srikanth, Davies, Emyr, Davies, Mark, Davies, Simon, Dawson, Alison, El Kossi, Mohsen, English, Patrick, Fraser, Donald, Gnudi, Luigi, Gunstone, Anthony, Hall, Timothy, Hanif, Wasim, Jackson, Alan, Johnson, Andrew, Joseph, Franklin, Krishnan, Singhan, Kumwenda, Mick, MacDougall, Iain, Nixon, Paul, O'Hare, Joseph, Philip, Sam, Ramtoola, Shenaz, Saxena, Manish, Sennik, Davesh, Simon, Godwin, Singh, Baldev, Stephens, Jeffrey, Strzelecka, Anna, Symonds, Rehan, Turner, Wayne, Wahba, Mona, Wakeling, John, Wheeler, David, Winocour, Peter, Abdallah, Joseph, Abdullah, Raied, Abramowitz, Matthew, Acosta, Idalia, Aiello, Joseph, Akright, Laura, Akyea-Djamson, Ayim, Alappan, Rajendran, Alicic, Radica, Al-Karadsheh, Amer, Allison, Dale Crawford, Arauz-Pacheco, Carlos, Arfeen, Shahabul, Arif, Ahmed, Arvind, Moogali, Atray, Naveen, Awad, Ahmed, Barnhill, Peggy, Barranco, Elizabeth, Barrera, Carlos, Beacom, Matthew, Behara, Venkata, Belo, Diogo, Bentley-Lewis, Rhonda, Berenguer, Ramon, Bermudez, Lidia, Bernardo, Marializa, Biscoveanu, Mihaela, Bowman-Stroud, Cynthia, Brandon, Donald, Brusco, Osvaldo, Busch, Robert, Canaan, Yamil, Chilito, Alicia, Christensen, Tom, Christiano, Cynthia, Christofides, Elena, Chuateco, Caroucel, Cohen, Kenneth, Cohen, Robert, Cohen-Stein, Debbie, Cook, Charles, Coyne, Daniel, Daboul, Nizar, Darwish, Riad, Daswani, Adarsh, Deck, Kenneth, Desouza, Cyrus, Dev, Devasmita, Dhillon, Monika, Dua, Sohan, Eder, Frank, Elosegui, Ana Maria, El-Shahawy, Mohamed, Ervin, John, Esquenazi, Alberto, Evans, John, Fishbane, Steven, Frias, Juan, Galindo-Ramos, Eugenia, Galphin, Claude, Ghazi, Adline, Gonzalez, Enrique, Gorson, David, Gowda, Anupama, Greco, Barbara, Grubb, Stephen, Gulati, Rakesh, Hammoud, Jamal, Handelsman, Stuart, Hartman, Israel, Hershon, Kenneth, Hiser, Daniel, Hon, George, Jacob, Radu, Jaime, Maria, Jamal, Aamir, Kaupke, Charles, Keightley, Gerald, Kern, Elizabeth, Khanna, Rakhi, Khitan, Zeid, Kim, Sun, Kopyt, Nelson, Kovesdy, Csaba, Krishna, Gopal, Kropp, Jeffrey (Jay), Kumar, Amrendra, Kumar, Jayant, Kumar, Neil, Kusnir, Jorge, Lane, Wendy, Lawrence, Mary, Lehrner, Lawrence, Lentz, John, Levinson, Dennis, Lewis, Derek, Liss, Kenneth, Maddux, Andreas, Maheshwari, Hiralal, Mandayam, Sreedhar, Marar, Isam, Mehta, Bhasker, Middleton, John, Mordujovich, Jorge, Moreda, Ramon, Moustafa, Moustafa, Trenche, Samuel Mujica, Narayanan, Mohanram, Narvarte, Javier, Nassar, Tareq, Newman, George, Nichol, Brian, Nicol, Philip, Nisnisan, Josier, Nossuli, A. Kaldun, Obialo, Chamberlain, Olelewe, Sarah, Oliver, Michael, O'Shaughnessy, Andrew, Padron, John, Pankhaniya, Rohit, Parker, Reginald, Patel, Devesh, Patel, Gnyandev, Patel, Nina, Pavon, Humberto, Perez, Armando, Perez, Carlos, Perlman, Alan, Pettis, Karlton, Pharr, Walter, Phillips, Andrea, Purighalla, Raman, Quesada-Suarez, Luis, Ranjan, Rajiv, Rastogi, Sanjeev, Reddy, Jakkidi, Rendell, Marc, Rich, Lisa, Robinson, Michael, Rodriguez, Hector, Rosas, Sylvia, Saba, Fadi, Sankaram, Rallabhandi, Sarin, Ravi, Schreiman, Robert, Scott, David, Sekkarie, Mohamed, Sensenbrenner, John, Shakeel, Muhammad, Shanik, Michael, Shaw, Sylvia, Smith, Stephen, Solomon, Richard, Sprague, Amy, Spry, Leslie, Suchinda, Pusadee, Sultan, Senan, Surampudi, Prasanth, Sussman, Sherry, Tan, Anjanette, Terrelonge, Antonio, Thompson, Michael, Trespalacios, Fernando, Trippe, Bruce, Trueba, Pilar, Twahirwa, Marcel, Updegrove, John, Van Buren, Peter, Vannorsdall, Mark, Varghese, Freemu, Velasquez-Mieyer, Pedro, Ventrapragada, Sailaja, Vukotic, Goga, Wadud, Khurram, Warren, Mark, Watson, Henry, Watts, Ronald, Weiner, Daniel, Welker, James, Welsh, Jean, Williams, Shelley, Zaniewski-Singh, Michelle, Yi, Tae Won, Smyth, Brendan, Di Tanna, Gian Luca, Arnott, Clare, Cardoza, Kathryn, and Kang, Amy

Published
2023
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6. Audit and Analysis of Docker Tools for Vulnerability Detection and Tasks Execution in Secure Environment

Author

Jain, Vipin, Singh, Baldev, Choudhary, Nilam, Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Prates, Raquel Oliveira, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Balas, Valentina E., editor, Sinha, G. R., editor, Agarwal, Basant, editor, Sharma, Tarun Kumar, editor, Dadheech, Pankaj, editor, and Mahrishi, Mehul, editor

Published
2022
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15. Genetic Upregulation of Activated Protein C Mitigates Delayed Effects of Acute Radiation Exposure in the Mouse Plasma

Author

Bansal, Shivani, primary, Li, Yaoxiang, additional, Bansal, Sunil, additional, Klotzbier, William, additional, Singh, Baldev, additional, Jayatilake, Meth, additional, Sridharan, Vijayalakshmi, additional, Fernández, José A, additional, Griffin, John H, additional, Weiler, Hartmut, additional, Boerma, Marjan, additional, and Cheema, Amrita K, additional

Published
2024
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17. Associations of antidiabetic drugs with diabetic retinopathy in people with type 2 diabetes: an umbrella review and meta-analysis

Author

Tan, Luyuan, primary, Wang, Zhaonan, additional, Okoth, Kelvin, additional, Toulis, Konstantinos A., additional, Denniston, Alastair K., additional, Singh, Baldev M., additional, Crowe, Francesca L., additional, Sainsbury, Christopher, additional, Wang, Jingya, additional, and Nirantharakumar, Krishnarajah, additional

Published
2024
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18. Machine Learning for Flipped Teaching in Higher Education—A Reflection

Author

Naidu, Vikas Rao, Singh, Baldev, Farei, Khadija Al, Suqri, Noor Al, Pisello, Anna Laura, Editorial Board Member, Hawkes, Dean, Editorial Board Member, Bougdah, Hocine, Editorial Board Member, Rosso, Federica, Editorial Board Member, Abdalla, Hassan, Editorial Board Member, Boemi, Sofia-Natalia, Editorial Board Member, Mohareb, Nabil, Editorial Board Member, Mesbah Elkaffas, Saleh, Editorial Board Member, Bozonnet, Emmanuel, Editorial Board Member, Pignatta, Gloria, Editorial Board Member, Mahgoub, Yasser, Editorial Board Member, De Bonis, Luciano, Editorial Board Member, Kostopoulou, Stella, Editorial Board Member, Pradhan, Biswajeet, Editorial Board Member, Abdul Mannan, Md., Editorial Board Member, Alalouch, Chaham, Editorial Board Member, O. Gawad, Iman, Editorial Board Member, Nayyar, Anand, Editorial Board Member, Amer, Mourad, Series Editor, Al-Masri, Ahmed N., editor, and Al-Assaf, Yousef, editor

Published
2020
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19. A Review: Emerging Trends of Big Data in Higher Educational Institutions

Author

Hasan, Raza, Palaniappan, Sellappan, Mahmood, Salman, Naidu, Vikas Rao, Agarwal, Aparna, Singh, Baldev, Sarker, Kamal Uddin, Abbas, Ali, Sattar, Mian Usman, Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Sharma, Devendra Kumar, editor, Balas, Valentina Emilia, editor, Son, Le Hoang, editor, Sharma, Rohit, editor, and Cengiz, Korhan, editor

Published
2020
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23. Genetic Upregulation of Activated Protein C Mitigates Delayed Effects of Acute Radiation Exposure in the Mouse Plasma.

Author

Bansal, Shivani, Li, Yaoxiang, Bansal, Sunil, Klotzbier, William, Singh, Baldev, Jayatilake, Meth, Sridharan, Vijayalakshmi, Fernández, José A., Griffin, John H., Weiler, Hartmut, Boerma, Marjan, and Cheema, Amrita K.

Subjects
PROTEIN C, GENETIC regulation, TRANSGENIC mice, RADIATION injuries, MICE, RADIATION exposure, IONIZING radiation
Abstract

Exposure to ionizing radiation, accidental or intentional, may lead to delayed effects of acute radiation exposure (DEARE) that manifest as injury to organ systems, including the kidney, heart, and brain. This study examines the role of activated protein C (APC), a known mitigator of radiation-induced early toxicity, in long-term plasma metabolite and lipid panels that may be associated with DEARE in APCHi mice. The APCHi mouse model used in the study was developed in a C57BL/6N background, expressing the D168F/N173K mouse analog of the hyper-activatable human D167F/D172K protein C variant. This modification enables increased circulating APC levels throughout the mouse's lifetime. Male and female cohorts of C57BL/6N wild-type and APCHi transgenic mice were exposed to 9.5 Gy γ-rays with their hind legs shielded to allow long-term survival that is necessary to monitor DEARE, and plasma was collected at 6 months for LC-MS-based metabolomics and lipidomics. We observed significant dyslipidemia, indicative of inflammatory phenotype, upon radiation exposure. Additionally, observance of several other metabolic dysregulations was suggestive of gut damage, perturbations in TriCarboxylic Acid (TCA) and urea cycles, and arginine metabolism. We also observed gender- and genotype-modulated metabolic perturbations post radiation exposure. The APCHi mice showed near-normal abundance for several lipids. Moreover, restoration of plasma levels of some metabolites, including amino acids, citric acid, and hypoxanthine, in APCHi mice is indicative of APC-mediated protection from radiation injuries. With the help of these findings, the role of APC in plasma molecular events after acute γ-radiation exposure in a gender-specific manner can be established for the first time. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Cloud Concept for Implementing Multimedia Based Learning in Higher Education

Author

Naidu, Vikas Rao, Bhat, Anjum Zameer, Singh, Baldev, Abdalla, Hassan, Editorial Board Member, Abdul Mannan, Md., Editorial Board Member, Alalouch, Chaham, Editorial Board Member, Boemi, Sofia Natalia, Editorial Board Member, Bougdah, Hocine, Editorial Board Member, Bozonnet, Emmanuel, Editorial Board Member, De Bonis, Luciano, Editorial Board Member, Hawkes, Dean, Editorial Board Member, Kostopoulou, Stella, Editorial Board Member, Mahgoub, Yasser, Editorial Board Member, Mesbah Elkaffas, Saleh, Editorial Board Member, Mohareb, Nabil, Editorial Board Member, O. Gawad, Iman, Editorial Board Member, Oostra, Mieke, Editorial Board Member, Pignatta, Gloria, Editorial Board Member, Pisello, Anna Laura, Editorial Board Member, Rosso, Federica, Editorial Board Member, Pradhan, Biswajeet, Editorial Board Member, Amer, Mourad, Series Editor, Al-Masri, Ahmed, editor, and Curran, Kevin, editor

Published
2019
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25. Multimedia Cloud for Higher Education Establishments: A Reflection

Author

Bhat, Anjum Zameer, Naidu, Vikas Rao, Singh, Baldev, Kacprzyk, Janusz, Series Editor, Pal, Nikhil R., Advisory Editor, Bello Perez, Rafael, Advisory Editor, Corchado, Emilio S., Advisory Editor, Hagras, Hani, Advisory Editor, Kóczy, László T., Advisory Editor, Kreinovich, Vladik, Advisory Editor, Lin, Chin-Teng, Advisory Editor, Lu, Jie, Advisory Editor, Melin, Patricia, Advisory Editor, Nedjah, Nadia, Advisory Editor, Nguyen, Ngoc Thanh, Advisory Editor, Wang, Jun, Advisory Editor, Rathore, Vijay Singh, editor, Worring, Marcel, editor, Mishra, Durgesh Kumar, editor, Joshi, Amit, editor, and Maheshwari, Shikha, editor

Published
2019
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30. Withania somnifera

Author

Sharma, Indu, primary, Kumar, Rahul, additional, Sharma, Vikas, additional, Singh, Baldev, additional, Pati, Pratap Kumar, additional, and Sharma, Ashutosh, additional

Published
2021
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31. Meaningful and Measurable Health Domains in Huntington’s Disease: Large-Scale Validation of the Huntington’s Disease Health-Related Quality of Life Questionnaire Across Severity Stages

Author

Downie, Lorna, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A., Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza (Keylock), Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Wright, Abigail, Barker, Roger A., O’Keefe, Deidre, Gerrtiz (nee Di Pietro), Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Mason, Sarah, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Callaghan, Jenny, Dunnett, Stephen, Clenaghan, Catherine, Fullam, Ruth, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Minster, Sara, Owen, Michael, Price, Kathleen, Townhill, Jenny, Rosser, Anne, Goudie, David, Buchanan, Lindsay, McFadyen, Paula, Tonner, Alison, Taylor, Anne-Marie, Edwards, Maureen, Ho, Carrie, McGill, Marie, Porteous, Mary, Pearson, Pauline, Harrower, Timothy, Irvine, Sarah, Brockie, Peter, Foster, Jillian, Johns, Nicola, McKenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Deith, Catherine, Ireland, Jane, Ritchie, Stuart, Brown, Pauline, Burrows, Liz, Fletcher, Amy, Harding, Alison, Harrison, Kaye, Laver, Fiona, Silva, Mark, Thomson, Aileen, Chu, Carol, Evans, Carole, Gallentree, Deena, Hamer, Stephanie, Kraus, Alison, Markova, Ivana, Raman, Ashok, Rowett, Liz, Andrew, Alyson, Frost, Julie, Noad, Rupert, Cosgrove, Jeremy, Gallantree, Deena, Hobson, Emma, Jamieson, Stuart, Longthorpe, Mandy, Musgrave, Hannah, Peacy, Caroline, Toscano, Jean, Wild, Sue, Yardumian, Pam, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Hallam, Caroline, Middleton, Julia, Alusi, Sundus, Davies, Rhys, Foy, Kevin, Gerrans, Emily, Pate, Louise, Anjum, Uruj, Coebergh, Jan, Eddy, Charlotte, Lahiri, Nayana, McEntagart, Meriel, Patton, Michael, Peterson, Maria, Rose, Sarah, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Gosling (nee Brown), Stefanie, Bruno, Stefania, Chu, Elvina, Doherty, Karen, Haider, Salman, Hensman, Davina, Lewis, Monica, Novak, Marianne, Patel, Aakta, Robertson, Nicola, Rosser, Elisabeth, Tabrizi, Sarah, Taylor, Rachel, Warner, Thomas, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Krishnamoorthy, Ashok, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iris, Verstraelen (formerly Ritchie), Nichola, Westmoreland, Leann, Cass, Ginette, Davidson, Lynn, Davison, Jill, Fullerton, Neil, Holmes, Katrina, Komati, Suresh, McDonnell, Sharon, Mohammed, Zeid, Morgan, Karen, Savage, Lois, Singh, Baldev, Wood, Josh, Nemeth, Andrea H., Siuda, Gill, Valentine, Ruth, Dixon, Kathryn, Armstrong, Richard, Burn, John, Weekes, Rebecca, Craven, Janet, Bailey, Wendy, Coleman, Caroline, Haig-Brown, Diane, Simpson, Steve, Majeed, Tahir, Verstraelen (Ritchie), Nicola, Barrett, Wendy, Ho, Aileen, Bandmann, Oliver, Bradbury, Alyson, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Gill, Paul, Kazoka, Mbombe, O’Donovan, Kirsty, Nevitt, Louise, Peppa, Nadia, Quarrell, Oliver, Taylor, Cat, Tidswell, Katherine, Kipps, Christopher, MacKinnon, Lesley, Agarwal, Veena, Hayward, Elaine, Gunner, Kerry, Harris, Kayla, Anderson, Mary, Heywood, Melanie, Keys, Liane, Smalley, Sarah, El-Nimr, George, Duffell, Allison, Wood, Sue, Kennedy (nee Smith), Karen, Gowers, Lesley, Powell, Kingsley, Bethwaite, Pamela, Edwards, Rachel, Fuller, Kathleen, Phillips, Michelle, Bucher, Walter, de Schepper, Beatrice, Eden, John, Hendrikx, Victor, Hughes, Alis, King, Diana, Kleibrink, Ursula, Kuttruff-Wilschut, Rita, Lenon-Bird, Anne, Lohkamp, Christiane, Perrousseaux, Marie-Odile, Martinez, Asuncion, Rapaille, Lilliane, Santini, Helen, Sasinkova, Pavla, Soltysiak, Beverley, Smith, Steve, van der Leer, Hans, van der Meer, Lucienne, Wooldridge, Michael, Zinzi, Paola, Ho, Aileen K., Horton, Mike C., Landwehrmeyer, G. Bernhard, Burgunder, Jean-Marc, and Tennant, Alan

Published
2019
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33. Associations of antidiabetic drugs with diabetic retinopathy in people with type 2 diabetes: an umbrella review and meta-analysis.

Author

Luyuan Tan, Zhaonan Wang, Okoth, Kelvin, Toulis, Konstantinos A., Denniston, Alastair K., Singh, Baldev M., Crowe, Francesca L., Sainsbury, Christopher, Jingya Wang, and Nirantharakumar, Krishnarajah

Subjects
TYPE 2 diabetes, EXENATIDE, METFORMIN, DIABETIC retinopathy, GLUCAGON-like peptide-1 receptor, HYPOGLYCEMIC agents, GLUCAGON-like peptide-1 agonists, LARGE scale systems
Abstract

Background: Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes. Methods: A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Randomeffects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052). Results: With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99). Conclusion: Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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35. A prediction algorithm to improve the accuracy of the Gold Standard Framework Surprise Question end-of-life prognostic categories in an acute hospital admission cohort-controlled study. The Proactive Risk-Based and Data-Driven Assessment of Patients at the End of Life (PRADA)

Author

Singh, Baldev, primary, Kumari-Dewat, Nisha, additional, Ryder, Adam, additional, Klaire, Vijay, additional, Bennion, Gemma, additional, Jennens, Hannah, additional, Matthews, Dawn, additional, Rayner, Sophie, additional, Ritzenthaler, Benoit, additional, Shears, Jean, additional, Ahmed, Kamran, additional, Sidhu, Mona, additional, Viswanath, Ananth, additional, Warren, Kate, additional, and Parry, Emma, additional

Published
2023
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39. GP assessment of unmet need in a complex multimorbid population using a data-driven and clinical triage system: a prospective cohort study

Author

Parry, Emma, primary, Ahmed, Kamran, additional, Evans, Simon, additional, Guest, Elizabeth, additional, Klaire, Vijay, additional, Koodaruth, Abdool, additional, Labutale, Prasadika, additional, Matthews, Dawn, additional, Lampitt, Jonathan, additional, Pickavance, Gillian, additional, Sidhu, Mona, additional, Warren, Kate, additional, and Singh, Baldev, additional

Published
2023
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40. ROLE OF TRIPLE EXAMINATION CONSISTING OF CLINICAL EXAMINATION, RADIOLOGICAL EXAMINATION AND EXTENDED FOCUSSED ASSESSMENT WITH SONOGRAPHY IN TRAUMA (eFAST) IN EARLY DIAGNOSIS OF VISCERAL INJURIES IN TORSO TRAUMA.

Author

Singh, Baldev, Ohri, Poonam, Alhan, Priya, Sharma, Sanjeev, Singh, Bhupinder, Kohli, Manasi, and Kohli, Parushi

Subjects
*TORSO, *ULTRASONIC imaging, *RIB fractures, *WOUNDS & injuries, *COMPUTED tomography
Abstract

BACKGROUND AND AIM: Trauma is a major cause of global suffering and death. Timely management is thought to be a critical predictor of outcomes for patients with acute traumatic injuries. The present study evaluates the role of triple examination in early diagnosis of visceral injuries in trauma. METHODS: This study included 50 patients with torso trauma admitted to emergency surgical wards at Guru Nanak Dev Hospital, Amritsar after written informed consent. The patients underwent clinical assessment, resuscitation and stabilization followed by eFAST scan and X-ray chest and abdomen. Once patients were hemodynamically stabilized, they underwent CT scan torso to confirm the findings of triple examination. The data collected was later suitably tabulated and statistically analysed to achieve the following results. RESULTS: Triple examination proved to be comparable to the gold standard CT torso in detecting haemoperitoneum with a sensitivity and specificity of 100%. Triple examination was able to diagnose rib fractures, pneumothorax, haemothorax, pneumoperitoneum and visceral injuries with a sensitivity of 92%, 95%, 100%, 83.33%, 97.30% and a specificity of 96%, 90%, 89.7%, 93.18%, 53.85% respectively. CONCLUSION: Triple examination is a cost effective, non-invasive and time saving protocol for early diagnosis of visceral injuries in torso trauma patients. It can be easily undertaken alongside hemodynamic resuscitation without withholding necessary care to the patient. [ABSTRACT FROM AUTHOR]

Published
2023

43. A Hybrid Model for Real-Time Docker Container Threat Detection and Vulnerability Analysis

Author

Jain, Vipin, Singh, Baldev, Choudhary, Nilam, and Yadav, Praveen Kumar

Subjects
Docker, Vulnerability, Cloud, Container, Threat
Abstract

Computer attacks are becoming more sophisticated and difficult to detect, the large volume of information in security records generated by network devices, servers and applications does not allow an adequate analysis due to the complexity of the data produced, and this leads to not taking measures timely in the event of gaps or security incidents. In spite of the fact that containers are widely accepted as a standardized way of deploying micro services and play a vital role in emerging areas of cloud computing such as service meshes. A survey has revealed that container security is the common concern and barrier to adoption for most organizations. This paper aims to conduct a review of the existing literature on container security and solutions. The time that elapses between the occurrences of an incident until its discovery should be as short as possible in order to determine the scope of the incident and compromised systems in a timely and efficient manner. The main objective of this paper is to deploy a solution using open source tools in a Docker container based environment to allow analysis of security anomalies. Therefore, relevant information must be collected, processed, and presented through dashboard displays in order to identify or detect security incidents in real time in a timely manner.

Published
2023

46. The relationship between DNA double-strand breaks and mutation induction following treatment with X-rays and restriction endonucleases

Author

Singh, Baldev and Bryant, Peter Edward

Subjects
572.8, QP623.S5, RNA
Abstract

DNA double-strand breaks (dsb) are thought to be major radiation-induced lesions in biological end-points such as cell lethality and chromosome aberrations. Based on this notion, this project aimed to extend further the investigation of the role of dsb in radiation-induced mutagenesis. The initial part of the project involved optimising conditions for the mutation assay so as to select for 'true' tk-mutants in Chinese hamster cells, following treatment with X-rays. This was important, due to the insufficient previous mutation data involving this locus in Chinese hamster cells. Furthermore, the choice of the tk locus over the more commonly used hprt locus was based on existing evidence of its higher sensitivity, as found in mutation experiments with the L5178Y mouse lymphoma cell line (Evans et al, 1986). An Initial comparative study was carried out to measure the induced mutation frequency following X-ray irradiation in both the parent Chinese hamster Ovary (CHO KI) cell line and its X-ray- sensitive mutant (xrs 5) cell line. This mutant line was chosen because of its characteristic marked deficiency in dsb repair, yet normal ability to rejoin single-strand breaks (Kemp et al, 1984., Costa and Bryant, 1988). This allowed the study of the role of dsb in mutation induction. The enhanced mutation induction observed in xrs 5 over that in CHO KI cells suggested the Importance of dsb in radiation-induction mutagenesis. The next experimental strategy adopted involved the use of the DNA synthesis inhibitor, 9-D-arabinofuranosyladenine (ara A). The choice of this drug was based on previous work by Bryant and Blocher (1982) and Iliakis and Bryant (1983) who, using DNA unwinding and neutral velocity sedimentation, showed ara A to strongly inhibit dsb repair, Plateau-phase CHO KI cells were exposed to X-rays alone or in combination width ara A , the latter treatment showing an increased induction of mutations. This suggested the possible existence of dsb which are fixed as mutations in the absence of DNA polymerization, suggesting a sub-class of dsb which may be critical in the steps leading to the induction of a mutation. XV The third approach was to use restriction endonucleases (RE) which were introduced into cells by electroporation. This method unlike ionising radiation, induced 'pure' dsb. The use of this method was based on the work of Bryant (1984), who used RE to mimic radiation-induced damage in the induction of chromosomal aberrations. Two different types of RE were used: those which produce blunt- and those which produce cohesive-ended dsb. In all mutation experiments with these enzymes, blunt-ended dsb were found to be more effective in generating mutations compared to cohesive-ended dsb. This suggests a possible further resolution of type(s) of dsb that would be induced by radiation in the ability to induce mutations i.e dependent on the end-structure of the induced dsb. Blunt-ended dsb may thus represent the major type of critical pre-mutational lesions which may be fixed as a mutation, as a result of misrepair. Cohesive- ended dsb may be of lesser importance. Finally, a RE (Pvu II) which generates blunt-ended dsb was used to induce mutations at the hprt locus in Chinese hamster (V79) cells. DNA from mutant cells was analysed using Southern blot and PCR analysis of 3 exons in the hprt gene. Some of the mutants (5/15) showed large deletions (representing complete loss of the gene), a change similar to that observed in mutants Induced following treatment with ionising radiation (e.g. Thacker, 1986). However, the percentage of large deletion mutants (70%) observed in radiation- induced mutants was higher than that (~34%) obtained with RE- induced mutation data. This preliminary data on the analysis of RE- induced mutations suggests that blunt-ended dsb mimics radiation- induced pre-mutational lesions, resulting in some large genomic changes (e.g. large deletions). However, a larger number of RE- induced mutants would have to be analysed before a more accurate comparison between RE and ionising mutation data can be made. In summary, this study provides evidence for dsb as a major pre-mutational lesion in cells exposed to ionising radiation, and suggests the existence of a sub-class of dsb in relation to mutation induction. In addition, RE offer the possibility of gaining further understanding of the role of dsb in the origin of mutations such as those caused by deletions.

Published
1992

47. A PROSPECTIVE STUDY TO EVALUATE THE ROLE OF MULTIDETECTOR COMPUTED TOMOGRAPHY IN BOWEL LESIONS.

Author

Ohri, Poonam, Kaur, Manreet, Singh, Baldev, Kohli, Manasi, and Kohli, Parushi

Subjects
MULTIDETECTOR computed tomography, TUBERCULOSIS, LARGE intestine, INTESTINAL diseases, LONGITUDINAL method
Abstract

Aims and objectives: 1) To study the role of MDCT in the evaluation of clinically suspected bowel pathologies. 2) To study the imaging characteristics of various bowel pathologies and narrow down the differential diagnosis using MDCT. 3) To correlate the imaging findings with operative findings/ cytohistopathology/ clinical outcomes if any. 4) To determine the sensitivity, specificity and accuracy of MDCT in the evaluation of bowel pathologies. Material and Methods: 50 patients with suspected bowel pathologies who were referred to the Department of Radiodiagnosis were included in this study. Results: The study had 60% males and 40% females This study showed male predominance. All the 50 patients in the study presented with abdominal pain. Weight loss, fever, vomiting and diarrhoea/constipation were the other complaints by the patients. The predominant wall enhancement pattern was homogenous. We observed that mucosa was affected in maximum number of cases. Based on the length of the bowel maximum cases in our study showed focal involvement. The cases in our study showed equal proportion of the large and small bowel involvement. Maximum cases in our study showed moderate mural thickness. Ascites was present in 88% cases in the present study. Necrotic and non-necrotic nodes were observed in 42% and 38% cases respectively. Pulmonary tuberculosis, liver microabscesses, metastases, peritoneal abscess, diverticulae and ovarian malignancy were the associated abnormalities in our study. On MDCT, tuberculosis followed by the malignancy were the maximum number of cases reported. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MDCT on diagnosis of tuberculosis was found to be 91.67%, 92.11%, 78.57%, 97.22% and 92.00% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MDCT on diagnosis of malignancy found to be 66.67%, 97.56%, 85.71%, 93.02% and 92.00% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MDCT on diagnosis of other cases was found to be 100% each. Conclusion: The present study confirms the high diagnostic accuracy of MDCT in bowel diseases. MDCT is a powerful diagnostic tool for the study of bowel disorders, including inflammatory disease, neoplasms, and mechanical obstruction. MDCT enterography is a dedicated technique that allows proper visualization of the entire bowel wall to detect abnormal mural thickening and analyse its type, length, and pattern of enhancement. [ABSTRACT FROM AUTHOR]

Published
2023

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