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2. Maternal and neonatal outcomes after caesarean delivery in the African Surgical Outcomes Study: a 7-day prospective observational cohort study
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Abadagan, Hippolyte, Abbas, N, Abdelatif, A Ibrahim, Abdoulaye, Traoré, Abd-rouf, A, Abduljalil, A, Abdulrahman, A, Abdurazig, S, Abokris, A, Abozaid, W, Abugassa, SOA, Abuhdema, F, Abujanah, SA, Abusamra, R, Abushnaf, A, Abusnina, SA, Abuzalout, TS, Ackermann, HM, Adamu, YB, Addanfour, A, Adeleke, DM, Adigun, TA, Adisa, AO, Adjignon, Sèhivè Valéry, Adu-Aryee, NA, Afolabi, BB, Agaba, AFX, Agaba, PKA, Aghadi, K, Agilla, H, Ahmed, B, Ahmed, El-Z, Ahmed, Al-J, Ahmed, M, Ahossi, Rene, Aji, SA, Akanyun, S, Akhideno, I, Akhter, M, Akinyemi, OA, Akkari, M, Akodjenou, Joseph, AL Samateh, AL, al Shams, ES, Alagbe-Briggs, OT, Alakkari, EA, Alalem, RB, Alashhab, M, Alatise, OI, Alatresh, A, Alayeb Alayeb, MSI, Albakosh, BA, Albert, F, Alberts, ANJD, Aldarrat, AD, Alfari, A, Alfetore, A, Algbali, M, Algddar, A, Algedar, HA, Alghafoud, IA, Alghazali, A, Alhajj, M, Alhendery Alhendery, A, Alhoty, FFH, Ali, A, Ali, YA, Alioune, Beye Seïdina, Alkassem, MA, Alkchr, MA, Alkesa, TS, Alkilani, A, Alkobty Alkobty, F, Allaye, Thomas, Alleesaib, SBM, Alli, A, Allopi, K, Allorto, NL, Almajbery, A, Almesmary, R, Almisslati, SHA, Almoraid, F, Alobeidi, H, Alomami, MA, Alphonsus, Christella S, Alqawi, OA, Alraheem, AA, Alsabri, SA, Alsayed, A, Alsellabi, B, Al-Serksi, M, Alshareef, MSA, Altagazi, AA, Aluvale, JS, Alwahedi, HW, Alzahra, EA, Alzarouk, MA, Al-Zubaidy, K, Amadou, M, Amadou, Maiga, Amanor-Boadu, Simbo D, Amer, Al-A, Amisi, BT, Amuthenu, MA, Anabah, TWA, Anani, Felix, Anderson, PGR, Andriamampionona, AGB, Andrianina, L, Anele, A, Angelin, R, Anjar, N, Antùnez, O, Antwi-Kusi, Akwasi, Anyanwu, LJC, Aribi, AA, Arowolo, OA, Arrey, O, Ashebir, Daniel Zemenfes, Assefa, SB, Assoum, Guy, Athanse, V, Athombo, JS, Atiku, M, Atito-Narh, E, Atomabe, Anatole, Attia, A, Aungraheeta, M, Aurélia, DMA, Ayandipo, OO, Ayebale, AET, Azzaidey, HMZ, Babajee, NB, Badi, HB, Badianga, EK, Baghni, RB, Bahta, MT, Bai, M, Baitchu, Y, Baloyi, AM, Bamuza, KA, Bamuza, MI, Bangure, L, Bankole, OB, Barongo, ML, 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Cloete, Estie, Coltman, Megan, Conradie, W, Constance, N, Coulibaly, Youssouf, Cronje, L, Da Silva, MA, Daddy, H, Dahim, L, Daliri, D, Dambaki, MS, Dasrath, A, Davids, JG, Davies, Gareth L, De Lange, JT, de Wet, JB, Dedekind, B, Degaulle, MA, Dehal, V, Deka, PD, Delinikaytis, S, Desalu, IS, Dewanou, Hubert, Deye, MB Moussa, Dhege, C, Diale, BSG, Dibwe, DF, Diedericks, BJS, Dippenaar, JM, Dippenaar, L, Diyoyo, MP, Djessouho, Edith, Dlamini, SN, Dodiyi-Manuel, A, Dokolwana, BA, Domoyyeri, DP, Drummond, Leanne W, du Plessis, DE, du Plessis, WM, du Preez, LJ, Dube, K, Dube, NZ, Dullab, KD, Duvenhage, R, Echem, RC, Edaigbini, SA, Egote, AK, Ehouni, A, Ekwen, G, Ekwunife, NC, El Hensheri, M, Elfaghi, IE, Elfagieh, MA, Elfallah, S, Elfiky, Mahmoud, Elgelany, S, Elghallal, AM, Elghandouri, MG, Elghazal, ZS, Elghobashy, AM, Elharati, FT, Elkhogia, Abdulaziz M, Elkhwildi, RM, Ellis, S, Elmadani, L, Elmadany, HB, Elmehdawi, H, Elmgadmi, A, Eloi, H, Elrafifi, D, Elsaadi, G, Elsaity, RB, Elshikhy, 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LT, Kabongo, MD, Kady, N, Kafu, S, Kaggya, M, Kaholongo, BNK, Kairuki, PCK, Kakololo, SI, Kakudji, K, Kalisa, Amina, Kalisa, R, Kalufwelu, MR, Kalume, S, Kamanda, RJ, Kangili, MK, Kanoun, H, Kapesa, Kapp, P, Karanja, JK, Karar, M, Kariuki, K, Kaseke, K, Kashuupulwa, PNK, Kasongo, KJP, Kassa, SK, Kateregga, GK, Kathrada, MIS, Katompwa, PM, Katsukunya, L, Kavuma, KAM, Khalfallah, Khamajeet, A, Khetrish, SB, Kibandwa, Kibochi, W, Kilembe, AM, Kintu, AK, Kipng'etich, B, Kiprop, B, Kissoon, VMK, Kisten, Theroshnie K, Kiwanuka, JK, Kluyts, Hyla-Louise, Knox, MEK, Koledale, AK, Koller, VL, Kolotsi, MA, Kongolo, M, Konwuoh, ND, Koperski, WJ, Koraz, MYK, Kornilov, AA, Koto, M Zach, Kransingh, Samantha, Krick, D, Kruger, S, Kruse, C, Kuhn, W, Kuhn, WP, Kukembila, AM, Kule, KL, Kumar, M, Kusel, Belinda S, Kusweje, VK, Kuteesa, KJ, Kutor, YY, Labib, MA, Laksari, M, Lanos, F, Lawal, TA, Le Manach, Yannick, Lee, C, Lekoloane, RM, Lelo, SN, Lerutla, B, Lerutla, MT, Levin, AI, Likongo, TB, Limbajee, ML, Linyama, DM, Lionnet, C, Liwani, MM, Loots, E, Lopez, A Garrido, Lubamba, CLC, Lumbala, KF, Lumbamba, AJM, Lumona, John, Lushima, RF, Luthuli, L, Luweesi, HL, Lyimo, TSK, Maakamedi, HM, Mabaso, BM, Mabina, M, Maboya, ME, Macharia, I, Macheka, AM, Machowski, AZ, Madiba, Thandinkosi E, Madsen, ASM, Madzimbamuto, Farai, Madzivhe, LJ, Mafafo, SC, Maghrabi, M, Mahamane, Diango Djibo, Maharaj, A, Maharaj, AD, Mahmud, MR, Mahoko, M, Mahomedy, NA, Mahomva, O, Mahureva, TM, Maila, RK, Maimane, DM, Maimbo, M, Maina, SN, Maiwald, Dela A, Maiyalagan, MD, Majola, N, Makgofa, N, Makhanya, V, Makhaye, WP, Makhlouf, NM, Makhoba, S, Makopa, EK, Makori, O, Makupe, Alex M, Makwela, MA, Malefo, ME, Malongwe, SM, Maluleke, DM, Maluleke, MR, Mamadou, K Touré, Mamaleka, MP, Mampangula, Y, Mamy, RM, Mananjara, MNR, Mandarry, MTM, Mangoo, DM, Manirimbere, C, Manneh, A, Mansour, A, Mansour, I, Manvinder, M, Manyere, DV, Manzini, VT, Manzombi, JK, Mapanda, PM, Marais, LC, Maranga, O, Maritz, JPB, Mariwa, FK, Masela, RS, Mashamba, MM, Mashava, Doreen M, Mashile, MV, Mashoko, E, Masia, OR, Masipa, JN, Masiyambiri, ATM, Matenchi, MW, Mathangani, W, Mathe, RC, Matola, Christopher Y, Matondo, PM, Matos-Puig, R, Matoug, FFH, Matubatuba, JT, Mavesere, HP, Mavhungu, R, Maweni, S, Mawire, CJM, Mawisa, T, Mayeza, S, Mbadi, R, Mbayabu, M, Mbewe, N, Mbombo, WD, Mbuyi, T, Mbuyi, WMS, Mbuyisa, MW, Mbwele, Bernard, Mehyaoui, RM, Menkiti, ID, Mesarieki, LVM, Metali, A, Mewanou, Serge, Mgonja, L, Mgoqo, N, Mhatu, S, Mhlari, TM, Miima, S, Milod, IM, Minani, P, Mitema, F, Mlotshwa, A, Mmasi, JE, Mniki, T, Mofikoya, BO, Mogale, JO, Mohamed, A, Mohamed, S, Mohamed, TS, Mohamed, AM, Mohamed, P, Mohammed, I, Mohammed, FAM, Mohammed, M, Mohammed, NM, Mohlala, MP, Mokretar, R, Molokoane, FM, Mongwe, KN, Montenegro, L, Montwedi, OD, Moodie, QK, Moopanar, M, Morapedi, M, Morulana, TG, Moses, VL, Mossy, P, Mostafa, H, Motilall, SR, Motloutsi, SP, Moussa, Kanté, Moutari, M, Moyo, OM, Mphephu, PE, Mrara, Busi, Msadabwe, C, Mtongwe, VM, Mubeya, FK, Muchiri, K, Mugambi, J, Muguti, GIM, Muhammad, AB, Mukama, IF, Mukenga, MM, Mukinda, FK, Mukuna, PM, Mungherera, ARW, Munlemvo, Dolly M, Munyaradzi, TW, Munyika, AA, Muriithi, JM, Muroonga, MP, Murray, R, Mushangwe, VK, Mushaninga, M, Musiba, VEM, Musowoya, JM, Mutahi, S, Mutasiigwa, MGH, Mutizira, G, Muturi, A, Muzenda, T, Mvwala, KR, Mvwama, NM, Mwale, A, Mwaluka, CN, Mwamba, JD, Mwanga, HAM, Mwangi, CM, Mwansa, S, Mwenda, V, Mwepu, IM, Mwiti, TM, Mzezewa, SZ, Nabela, L, Nabukenya, MTN, Nabulindo, SM, Naicker, K, Naidoo, D, Naidoo, L, Naidoo, LC, Naidoo, N, Naidoo, R, Naidoo, RD, Naidoo, S, Naidoo, TD, Naidu, TK, Najat, NZ, Najm, Y, Nakandungile, F, Nakangombe, P, Namata, CN, Namegabe, ES, Nansook, A, Nansubuga, NP, Nantulu, C, Nascimento, Rodrigue, Naude, GT, Nchimunya, H, Ndaie, MA, Ndarukwa, PN, Ndasi, Henry, Ndayisaba, Gabriel, Ndegwa, D, Ndikumana, R, Ndonga, Andrew KN, Ndung'u, C, Neil, MC, Nel, MS, Neluheni, EV, Nesengani, DS, Nesengani, NT, Netshimboni, LE, Ngalala, AM, Ngari, BM, Ngari, NBM, Ngatia, E, Ngcobo, GK, Ngcobo, TS, Ngorora, D, Ngouane, D, Ngugi, K, Ngumi, Zipporah WW, Nibe, Z, Ninise, E, Niyondiko, JC, Njenga, PW, Njenga, MN, Njoroge, M, Njoroge, S, Njuguna, W, Njuki, PN, Nkesha, T, Nkuebe, TN, Nkuliyingoma, NP, Nkunjana, M, Nkwabi, Ernest, Nkwine, RN, Nnaji, C, Notoane, I, Nsalamba, Shaaban, Ntlhe, LM, Ntoto, C, Ntueba, B, Nyassi, MT, Nyatela-Akinrinmade, Z, Nyawanda, HO, Nyokabi, NN, Nziene, VN, Obadiah, S, Ochieng, OJP, Odia, PK, Oduor, OEO, Ogboli-Nwasor, EO, Ogendo, SWO, Ogunbode, O, Ogundiran, TO, Ogutu, O, Ojewola, RW, Ojujo, M, Ojuka, DO, Okelo, OS, Okiya, S, Okonu, N, Olang, PR, Omigbodun, Akinyinka O, Omoding, S, Omoshoro-Jones, J, Onyango, R, Onyegbule, A, Orjiako, O, Osazuwa, MO, Oscar, Kpatinvo, Osinaike, BB, Osinowo, AO, Othin, OM, Otman, FFH, Otokwala, J, Ouanes, F, Oumar, Ongoïba, Ousseini, AO, Padayachee, S, Pahlana, SM, Pansegrouw, J, Paruk, FP, Patel, MB, Patel-Mujajati, Ushmaben, Patience, AP, Pearse, Rupert M, Pembe, JD, Pengemale, GN, Perez, N, Perez, MF Aguilera, Peter, A Mallier, Phaff, M, Pheeha, RM, Pienaar, BH, Pillay, V, Pilusa, KA, Pochana, MP, Polishchuk, O, Porrill, Owen S, Post, EF, Prosper, A, Pupyshev, M, Rabemazava, A, Rabiou, MS, Rademan, L, Rademeyer, M, Raherison, RAR, Rajah, FR, Rajcoomar, MSR, Rakhda, Z, Rakotoarijaona, AHR, Rakotoarisoa, AHN, Rakotoarison, Sylvia R, Rakotoarison, RR, Rakotoniaina, François, Ramadan, L, Ramananasoa, MLR, Rambau, M, Ramchurn, TPR, Ramilson, HE, Ramjee, Rajesh J, Ramnarain, H, Ramos, R, Rampai, TJ, Ramphal, SR, Ramsamy, T, Ramuntshi, R, Randolph, R, Randriambololona, DMA, Ras, WAP, Rasolondraibe, RAF, Rasolonjatovo, JDLC, Rautenbach, RM, Ray, S, Rayne, Sarah R, Razanakoto, FAR, Reddy, SR, Reed, Anthony R, Rian, JR, Rija, FR, Rink, B, Robelie, AT, Roberts, CA, Rocher, AGL, Rocher, S, Rodseth, Reitze N, Rois, I, Rois, W, Rokhsi, S, Roos, J, Rorke, Nicolette F, Roura, H, Rousseau, FJ, Rousseau, N, Royas, L, Roytowski, D, Rungan, Devan, Rwehumbiza, SSR, Ryabchiy, BB, Ryndine, V, Saaiman, CR, Sabwa, HK, Sadat, S, Saed, SS, Salaheddin, E, Salaou, H, Saleh, M, Salisu-Kabara, HM, Sama, Hamza Doles, Samateh, Ahmadou L, Sam-Awortwi (Jnr), W, Samuel, N, Sanduku, DK, Sani, Chaibou M, Sanyang, LN, Sarah, HN, Sarkin-Pawa, A, Sathiram, R, Saurombe, T, Schutte, H, Sebei, MP, Sedekounou, MD, Segooa, MP, Semenya, EM, Semo, BO, Sendagire, CS, Senoga, SA, Senusi, FS, Serdyn, T, Seshibe, MD, Shah, GB, Shamamba, R, Shambare, CS, Shangase, TN, Shanin, SH, Shefren, IE, Sheshe, AA, Shittu, OB, Shkirban, AS, Sholadoye, T, Shubba, A, Sigcu, N, Sihope, SE, Sikazwe, DS, Sikombe, BS, Simaga Abdoul, K, Simo, WAG, Singata, K, Singh, AS, Singh, S, Singh, Usha, Sinoamadi, V, Sipuka, N, Sithole, NLM, Sitima, S, Skinner, David Lee, Skinner, GC, Smith, OI, Smits, CAG, Sofia, MSI, Sogoba, Gaoussou, Sohoub, A, Sookun, SS, Sosinska, O, Souhe, Rosalie, Souley, G, Souleymane, Thiam, Spicer, JM, Spijkerman, Sandra, Steinhaus, H, Steyn, A, Steyn, G, Steyn, HC, Stoltenkamp, Heidi L, Stroyer, S, Swaleh, A, Swayeb, E, Szpytko, AJ, Taiwo, NA, Tarhuni, A, Tarloff, D, Tchaou, Blaise, Tchegnonsi, Charles, Tchoupa, M, Teeka, MO, Thakoor, B, Theunissen, MM, Thomas, BP, Thomas, MB, Thotharam, A, Tobiko, O, Torborg, AM, Tshisekedi, SM, Tshisola, SK, Tshitangano, R, Tshivhula, F, Tshuma, HT, Tumukunde, Janat, Tun, M, Udo, IA, Uhuebor, DI, Umeh, KU, Usenbo, AO, Uwiteyimbabazi, JdD, Van der Merwe, DJ, van der Merwe, FH, van der Walt, JE, van Dyk, Dominique, Van Dyk, JG, van Niekerk, JJS, van Wyk, S, van Zyl, HA, Veerasamy, B, Venter, PJ, Vermeulen, AJ, Villarreal, R, Visser, J, Visser, L, Voigt, M, von Rahden, Richard P, Wafa, A, Wafula, A, Wambugu, PK, Waryoba, P, Waweru, EN, Weideman, M, Wise, Robert D, Wynne, EE, Yahya, AI, Yahya, AA, Yahya, R, Yakubu, Y, Yanga, JJ, Yangazov, YM, Yousef, O, Yousef, G, Youssouf, Coulibaly, Yunus, AA, Yusuf, AS, Zeiton, AZ, Zentuti, HZ, Zepharine, Henry, Zerihun, AB, Zhou, S, Zidan, A, Zié, Sanogo Zimogo, Zinyemba, CZ, Zo, A, Zomahoun, Lidwine, Zoobei, NZ, Zoumenou, Eugene, Zubia, NZ, Bishop, David, Dyer, Robert A, Maswime, Salome, Tumukunde, Janat T, Madzimbamuto, Farai D, Ndonga, Andrew K N, Ngumi, Zipporah W W, and Mehyaoui, Ryad
- Published
- 2019
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3. USP26 regulates TGF‐β signalling by deubiquitinating and stabilizing SMAD7; not applicable in glioblastoma
- Author
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Ware, Thomas MB and Zhu, Hong‐Jian
- Published
- 2020
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4. Scientists' warning on climate change and insects
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Harvey, JA, Tougeron, K, Gols, R, Heinen, R, Abarca, M, Abram, PK, Basset, Y, Berg, M, Boggs, C, Brodeur, J, Cardoso, P, de Boer, JG, De Snoo, GR, Deacon, C, Dell, JE, Desneux, N, Dillon, ME, Duffy, GA, Dyer, LA, Ellers, J, Espindola, A, Fordyce, J, Forister, ML, Fukushima, C, Gage, MJG, Garcia-Robledo, C, Gely, C, Gobbi, M, Hallmann, C, Hance, T, Harte, J, Hochkirch, A, Hof, C, Hoffmann, AA, Kingsolver, JG, Lamarre, GPA, Laurance, WF, Lavandero, B, Leather, SR, Lehmann, P, Le Lann, C, Lopez-Uribe, MM, Ma, C-S, Ma, G, Moiroux, J, Monticelli, L, Nice, C, Ode, PJ, Pincebourde, S, Ripple, WJ, Rowe, M, Samways, MJ, Sentis, A, Shah, AA, Stork, N, Terblanche, JS, Thakur, MP, Thomas, MB, Tylianakis, JM, Van Baaren, J, Van de Pol, M, Van der Putten, WH, Van Dyck, H, Verberk, WCEP, Wagner, DL, Weisser, WW, Wetzel, WC, Woods, HA, Wyckhuys, KAG, Chown, SL, Harvey, JA, Tougeron, K, Gols, R, Heinen, R, Abarca, M, Abram, PK, Basset, Y, Berg, M, Boggs, C, Brodeur, J, Cardoso, P, de Boer, JG, De Snoo, GR, Deacon, C, Dell, JE, Desneux, N, Dillon, ME, Duffy, GA, Dyer, LA, Ellers, J, Espindola, A, Fordyce, J, Forister, ML, Fukushima, C, Gage, MJG, Garcia-Robledo, C, Gely, C, Gobbi, M, Hallmann, C, Hance, T, Harte, J, Hochkirch, A, Hof, C, Hoffmann, AA, Kingsolver, JG, Lamarre, GPA, Laurance, WF, Lavandero, B, Leather, SR, Lehmann, P, Le Lann, C, Lopez-Uribe, MM, Ma, C-S, Ma, G, Moiroux, J, Monticelli, L, Nice, C, Ode, PJ, Pincebourde, S, Ripple, WJ, Rowe, M, Samways, MJ, Sentis, A, Shah, AA, Stork, N, Terblanche, JS, Thakur, MP, Thomas, MB, Tylianakis, JM, Van Baaren, J, Van de Pol, M, Van der Putten, WH, Van Dyck, H, Verberk, WCEP, Wagner, DL, Weisser, WW, Wetzel, WC, Woods, HA, Wyckhuys, KAG, and Chown, SL
- Abstract
Climate warming is considered to be among the most serious of anthropogenic stresses to the environment, because it not only has direct effects on biodiversity, but it also exacerbates the harmful effects of other human‐mediated threats. The associated consequences are potentially severe, particularly in terms of threats to species preservation, as well as in the preservation of an array of ecosystem services provided by biodiversity. Among the most affected groups of animals are insects—central components of many ecosystems—for which climate change has pervasive effects from individuals to communities. In this contribution to the scientists' warning series, we summarize the effect of the gradual global surface temperature increase on insects, in terms of physiology, behavior, phenology, distribution, and species interactions, as well as the effect of increased frequency and duration of extreme events such as hot and cold spells, fires, droughts, and floods on these parameters. We warn that, if no action is taken to better understand and reduce the action of climate change on insects, we will drastically reduce our ability to build a sustainable future based on healthy, functional ecosystems. We discuss perspectives on relevant ways to conserve insects in the face of climate change, and we offer several key recommendations on management approaches that can be adopted, on policies that should be pursued, and on the involvement of the general public in the protection effort.
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- 2023
5. Dissecting the conformational complexity and mechanism of a bacterial heme transporter
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Wu, Di, Mehdipour, Ahmad R, Finke, Franziska, Goojani, Hojjat G, Groh, Roan R, Grund, Tamara M, Reichhart, Thomas MB, Zimmermann, Rita, Welsch, Sonja, Bald, Dirk, Shepherd, Mark, Hummer, Gerhard, Safarian, Schara, Wu, Di, Mehdipour, Ahmad R, Finke, Franziska, Goojani, Hojjat G, Groh, Roan R, Grund, Tamara M, Reichhart, Thomas MB, Zimmermann, Rita, Welsch, Sonja, Bald, Dirk, Shepherd, Mark, Hummer, Gerhard, and Safarian, Schara
- Abstract
Iron-bound cyclic tetrapyrroles (hemes) are redox-active cofactors in bioenergetic enzymes. However, the mechanisms of heme transport and insertion into respiratory chain complexes remain unclear. Here, we used cellular, biochemical, structural and computational methods to characterize the structure and function of the heterodimeric bacterial ABC transporter CydDC. We provide multi-level evidence that CydDC is a heme transporter required for functional maturation of cytochrome bd, a pharmaceutically relevant drug target. Our systematic single-particle cryogenic-electron microscopy approach combined with atomistic molecular dynamics simulations provides detailed insight into the conformational landscape of CydDC during substrate binding and occlusion. Our simulations reveal that heme binds laterally from the membrane space to the transmembrane region of CydDC, enabled by a highly asymmetrical inward-facing CydDC conformation. During the binding process, heme propionates interact with positively charged residues on the surface and later in the substrate-binding pocket of the transporter, causing the heme orientation to rotate 180°.
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- 2023
6. Myeloablative conditioning with total body irradiation for AML: Balancing survival and pulmonary toxicity
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Sarah J. Stephens, MD, Samantha Thomas, MB, David A. Rizzieri, MD, Mitchell E. Horwitz, MD, Nelson J. Chao, MD, Ashley M. Engemann, PharmD, Martha Lassiter, MSN, and Chris R. Kelsey, MD
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Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Purpose: The purpose of this study was to compare leukemia-free survival (LFS) and other clinical outcomes in patients with acute myelogenous leukemia who underwent a myeloablative allogeneic stem cell transplant with and without total body irradiation (TBI). Methods and materials: Adult patients with acute myelogenous leukemia undergoing myeloablative allogeneic stem cell transplant at Duke University Medical Center between 1995 and 2012 were included. The primary endpoint was LFS. Secondary outcomes included overall survival (OS), nonrelapse mortality, and the risk of pulmonary toxicity. Kaplan-Meier survival estimates and Cox proportional hazards multivariate analyses were performed. Results: A total of 206 patients were evaluated: 90 received TBI-based conditioning regimens and 116 received chemotherapy alone. Median follow-up was 36 months. For all patients, 2-year LFS and OS were 36% (95% confidence interval [CI], 29-43) and 39% (95% CI, 32-46), respectively. After adjusting for known prognostic factors using a multivariate analysis, TBI was associated with improved LFS (hazard ratio: 0.63; 95% CI: 0.44-0.91) and OS (hazard ratio: 0.63; 95% CI, 0.43-0.91). There was no difference in nonrelapse mortality between cohorts, but pulmonary toxicity was significantly more common with TBI (2-year incidence 42% vs 12%, P < .001). High-grade pulmonary toxicity predominated with both conditioning strategies (70% and 93% of cases were grade 3-5 with TBI and chemotherapy alone, respectively). Conclusions: TBI-based regimens were associated with superior LFS and OS but at the cost of increased pulmonary toxicity.
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- 2016
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7. Dissecting the conformational complexity and flipping mechanism of bacterial heme transport
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Wu, Di, Mehdipour, Ahmed R., Finke, Franziska, Goojani, Hojjat G, Groh, Roan R, Grund, Tamara M, Reichhart, Thomas MB, Zimmerman, Rita, Welsch, Sonja, Bald, Dirk, Shepherd, Mark, Hummer, Gerhard, and Safarian, Schara
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- 2022
8. Dissecting the conformational complexity and flipping mechanism of a prokaryotic heme transporter
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Di Wu, Ahmad R Mehdipour, Franziska Finke, Hojjat G Goojani, Roan R Groh, Tamara N Grund, Thomas MB Reichhart, Rita Zimmermann, Sonja Welsch, Dirk Bald, Mark Shepherd, Gerhard Hummer, and Schara Safarian
- Abstract
Iron-bound cyclic tetrapyrroles (hemes) are key redox-active cofactors in membrane-integrated oxygen reductases and other bioenergetic enzymes. However, the mechanisms of heme transport and insertion into respiratory chain complexes remain unclear. Here, we used a combination of cellular, biochemical, structural and computational methods to resolve ongoing controversies around the function of the heterodimeric bacterial ABC transporter CydDC. We provide multi-level evidence that CydDC is a heme transporter required for assembly and functional maturation of cytochrome bd, a pharmaceutically relevant drug target. Our systematic single-particle cryo-EM approach combined with atomistic molecular dynamics simulations provides detailed insight into the conformational landscape of CydDC during substrate binding and occlusion. Our simulations reveal that heme binds laterally from the membrane space to the transmembrane region of CydDC, enabled by a highly asymmetrical inward-facing CydDC conformation. During the binding process, heme propionates interact with positively charged residues on the surface and later in the substrate-binding pocket of the transporter, causing the heme orientation to flip 180 degrees. The membrane-accessible heme entry site of CydDC is primarily controlled by the conformational plasticity of CydD transmembrane helix 4, the extended cytoplasmic segment of which also couples heme confinement to a rotational movement of the CydC nucleotide-binding domain. Our cryo-EM data highlight that this signal transduction mechanism is necessary to drive conformational transitions toward occluded and outward-facing states.One Sentence SummaryThe heterodimeric bacterial ABC transporter CydDC is a heme flippase essential for the functional maturation of cytochrome bd.
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- 2022
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9. Intracellular delivery of doxorubicin encapsulated in novel pH-responsive chitosan/heparin nanocapsules
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Thomas MB, Radhakrishnan K, Gnanadhas DP, Chakravortty D, and Raichur AM
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Medicine (General) ,R5-920 - Abstract
Midhun B Thomas,1,* Krishna Radhakrishnan,1,* Divya P Gnanadhas,2,* Dipshikha Chakravortty,2 Ashok M Raichur1,31Department of Materials Engineering, 2Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India; 3Department of Applied Chemistry, University of Johannesburg, Doornfontein, South Africa*These authors contributed equally to this workAbstract: A novel polyelectrolyte nanocapsule system composed of biopolymers, chitosan and heparin has been fabricated by the layer-by-layer technique on silica nanoparticles followed by dissolution of the silica core. The nanocapsules were of the size range 200 ± 20 nm and loaded with the positively charged anticancer drug doxorubicin with an efficiency of 89%. The loading of the drug into the capsule happens by virtue of the pH-responsive property of the capsule wall, which is determined by the pKa of the polyelectrolytes. As the pH is varied, about 64% of the drug is released in acidic pH while 77% is released in neutral pH. The biocompatibility, efficiency of drug loading, and enhanced bioavailability of the capsule system was confirmed by MTT assay and in vivo biodistribution studies.Keywords: drug delivery, layer-by-layer, electrostatic interaction, biocompatible
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- 2013
10. Dissecting the conformational complexity and flipping mechanism of a prokaryotic heme transporter
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Wu, Di, primary, Mehdipour, Ahmad R, additional, Finke, Franziska, additional, Goojani, Hojjat G, additional, Groh, Roan R, additional, Grund, Tamara N, additional, Reichhart, Thomas MB, additional, Zimmermann, Rita, additional, Welsch, Sonja, additional, Bald, Dirk, additional, Shepherd, Mark, additional, Hummer, Gerhard, additional, and Safarian, Schara, additional
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- 2022
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11. Associations between cognition and white matter microstructure in first-episode antipsychotic-naive patients with schizophrenia and healthy controls: A multivariate pattern analysis
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Thomas, MB, Raghava, JM, Pantelis, C, Rostrup, E, Nielsen, MO, Jensen, MH, Glenthoj, BY, Mandl, RCW, Ebdrup, BH, Fagerlund, B, Thomas, MB, Raghava, JM, Pantelis, C, Rostrup, E, Nielsen, MO, Jensen, MH, Glenthoj, BY, Mandl, RCW, Ebdrup, BH, and Fagerlund, B
- Abstract
BACKGROUND: Cognitive functions have been associated with white matter (WM) microstructure in schizophrenia, but most studies are limited by examining only select cognitive measures and single WM tracts in chronic, medicated patients. It is unclear if the cognition-WM relationship differs between antipsychotic-naïve patients with schizophrenia and healthy controls, as differential associations have not been directly examined. Here we examine if there are differential patterns of associations between cognition and WM microstructure in first-episode antipsychotic-naïve patients with schizophrenia and healthy controls, and we characterize reliable contributors to the pattern of associations across multiple cognitive domains and WM regions, in order to elucidate white matter contribution to the neural underpinnings of cognitive deficits. METHODS: Thirty-six first-episode antipsychotic-naïve patients with schizophrenia and 52 matched healthy controls underwent cognitive tests and diffusion-weighted imaging on a 3T Magnetic Resonance Imaging scanner. Using a multivariate partial least squares correlation analysis, we included 14 cognitive variables and mean fractional anisotropy values of 48 WM regions. RESULTS: Initial analyses showed significant group differences in both measures of WM and cognition. There was no group interaction effect in the pattern of associations between cognition and WM microstructure. The combined analysis of patients and controls lead to a significant pattern of associations (omnibus test p = .015). Thirty-four regions and seven cognitive functions contributed reliably to the associations. CONCLUSIONS: The lack of an interaction effect suggests similar associations in first-episode antipsychotic-naïve patients with schizophrenia and healthy controls. This, together with the differences in both WM and cognitive measurements, supports the involvement of WM in cognitive deficits in schizophrenia. Our findings add to the field by showing a coherent
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- 2021
12. Reactivation of BMP signaling by suboptimal concentrations of MEK inhibitor and FK506 reduces organ-specific breast cancer metastasis
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Josephine Iaria, Thomas Mb Ware, Peter ten Dijke, Hong-Jian Zhu, Jiang Ren, and Yanhong Wang
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0301 basic medicine ,Cancer Research ,U0126 ,FK506 ,Metastasis ,Mice ,0302 clinical medicine ,Neoplasm Metastasis ,Zebrafish ,Breast cancer metastasis ,MEK inhibitor ,Bone metastasis ,Drug Synergism ,Extravasation ,Gene Expression Regulation, Neoplastic ,Oncology ,Organ Specificity ,030220 oncology & carcinogenesis ,embryonic structures ,Bone Morphogenetic Proteins ,MCF-7 Cells ,Female ,Signal Transduction ,animal structures ,Cell Survival ,Breast Neoplasms ,Tacrolimus ,03 medical and health sciences ,Breast cancer ,TGF beta ,Cell Line, Tumor ,TGF beta signaling pathway ,Nitriles ,medicine ,Butadienes ,BMP ,Animals ,Humans ,Protein Kinase Inhibitors ,Cell Proliferation ,Flavonoids ,business.industry ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,030104 developmental biology ,Cancer cell ,Cancer research ,NIH 3T3 Cells ,business - Abstract
TGF beta-SMAD3 signaling is a major driving force for cancer metastasis, while BMP-SMAD1/5 signaling can counteract this response. Analysis of gene expression profiles revealed that an increased TGF beta-SMAD3 and a reduced BMP-SMAD1/5 targeted gene expression signature correlated with shortened distant metastasis free survival and overall survival of patients. At molecular levels, we discovered that TGF beta abolished BMP-induced SMAD1/5 activation in the highly-invasive breast cancer MDA-MB-231 cells, but to a less extent in the non-invasive cancer and normal breast cells. This suggests an inverse correlation between BMP signaling and invasiveness of tumor cells and TGF beta signaling acts in a double whammy fashion in driving cancer invasion and metastasis. Sustained ERK activation by TGF beta was specifically observed in MDA-MB-231 cells, and MEK inhibitor (MEKi) treatment restored BMP-SMAD1/5 signaling while not affecting SMAD2/3 activation. FK506 potently activated BMP, but not TGF beta signaling in breast cancer cells. MEKi or FK506 alone inhibited MDA-MB-231 extravasation in a zebrafish xenograft cancer model. Importantly, when administrated at suboptimal concentrations MEKi and FK506 strongly synergized in promoting BMP-SMAD1/5 signaling and inhibiting cancer cell extravasation. Furthermore, this combination of suboptimal concentrations treatment in a mouse tumor model resulted in real-time reduction of BMP-SMAD1/5 signaling in live tumors, and consequently potently inhibited tumor self-seeding, liver and bone metastasis, but not lung and brain metastasis. Mechanistically, it is the first time to identify BMP-SMAD1/5 signaling as an underlying molecular driver for organ-specific metastasis. Combining of MEKi and FK506, or their analogues, may be explored for clinical development of breast cancer.
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- 2020
13. USP26 regulates TGF-β signalling by deubiquitinating and stabilizing SMAD7; not applicable in glioblastoma
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Thomas Mb Ware and Hong-Jian Zhu
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Cysteine Endopeptidases ,education ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Biochemistry ,USP26 ,Smad7 Protein ,03 medical and health sciences ,0302 clinical medicine ,Transforming Growth Factor beta ,Correspondence ,Genetics ,medicine ,Humans ,Tgf β signalling ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,integumentary system ,biology ,Chemistry ,Transforming growth factor beta ,medicine.disease ,humanities ,Cell biology ,biology.protein ,Smad7 protein ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Signal transduction ,Glioblastoma ,030217 neurology & neurosurgery ,Transforming growth factor ,Signal Transduction - Abstract
Comment on “USP26 regulates TGF‐β signaling by deubiquitinating and stabilizing SMAD7” by Kit Leng Lui et al. [Image: see text]
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- 2019
14. USP26 regulates TGF‐β signalling by deubiquitinating and stabilizing SMAD7; not applicable in glioblastoma
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Ware, Thomas MB, primary and Zhu, Hong‐Jian, additional
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- 2019
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15. Defining the essential function of FBP/KSRP proteins: Drosophila Psi interacts with the mediator complex to modulate MYC transcription and tissue growth
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Ross D. Hannan, Rodney B. Luwor, Naomi C Mitchell, Linda M. Parsons, Olga Zaysteva, David Levens, Leonie M. Quinn, Jue Er Amanda Lee, Thomas Mb Ware, Gretchen Poortinga, Zuqin Nie, and Linna Guo
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0301 basic medicine ,Transcription, Genetic ,RNA polymerase II ,RNA-binding protein ,DNA-binding protein ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,Mediator ,Transcription (biology) ,Genetics ,Morphogenesis ,Animals ,Drosophila Proteins ,Humans ,Promoter Regions, Genetic ,Transcription factor ,Mediator Complex ,biology ,Gene regulation, Chromatin and Epigenetics ,Nuclear Proteins ,RNA-Binding Proteins ,KH domain ,Cell biology ,Protein Subunits ,030104 developmental biology ,Drosophila melanogaster ,Gene Knockdown Techniques ,biology.protein ,RNA Polymerase II ,HeLa Cells ,Protein Binding - Abstract
Despite two decades of research, the major function of FBP-family KH domain proteins during animal development remains controversial. The literature is divided between RNA processing and transcriptional functions for these single stranded nucleic acid binding proteins. Using Drosophila, where the three mammalian FBP proteins (FBP1-3) are represented by one ortholog, Psi, we demonstrate the primary developmental role is control of cell and tissue growth. Co-IP-mass spectrometry positioned Psi in an interactome predominantly comprised of RNA Polymerase II (RNA Pol II) transcriptional machinery and we demonstrate Psi is a potent transcriptional activator. The most striking interaction was between Psi and the transcriptional mediator (MED) complex, a known sensor of signaling inputs. Moreover, genetic manipulation of MED activity modified Psi-dependent growth, which suggests Psi interacts with MED to integrate developmental growth signals. Our data suggest the key target of the Psi/MED network in controlling developmentally regulated tissue growth is the transcription factor MYC. As FBP1 has been implicated in controlling expression of the MYC oncogene, we predict interaction between MED and FBP1 might also have implications for cancer initiation and progression.
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- 2016
16. Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
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Hong-Jian Zhu, Hao Chen, Thomas Mb Ware, and Josephine Iaria
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0301 basic medicine ,Cell signaling ,General Immunology and Microbiology ,biology ,General Chemical Engineering ,General Neuroscience ,Cellular homeostasis ,Transforming growth factor beta ,Transfection ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Live cell imaging ,In vivo ,TGF beta signaling pathway ,biology.protein ,Signal transduction - Abstract
Transforming Growth Factor β (TGF-β) signaling regulates many important functions required for cellular homeostasis and is commonly found overexpressed in many diseases, including cancer. TGF-β is strongly implicated in metastasis during late stage cancer progression, activating a subset of migratory and invasive tumor cells. Current methods for signaling pathway analysis focus on endpoint models, which often attempt to measure signaling post-hoc of the biological event and do not reflect the progressive nature of the disease. Here, we demonstrate a novel adenovirus reporter system specific for the TGF-β/Smad3 signaling pathway that can detect transcriptional activation in live cells. Utilizing an Ad-CAGA12-Td-Tom reporter, we can achieve a 100% infection rate of MDA-MB-231 cells within 24 h in vitro. The use of a fluorescent reporter allows for imaging of live single cells in real-time with direct identification of transcriptionally active cells. Stimulation of infected cells with TGF-β displays only a subset of cells that are transcriptionally active and involved in specific biological functions. This approach allows for high specificity and sensitivity at a single cell level to enhance understanding of biological functions related to TGF-β signaling in vitro. Smad3 transcriptional activity can also be reported in vivo in real-time through the application of an Ad-CAGA12-Luc reporter. Ad-CAGA12-Luc can be measured in the same manner as traditional stably transfected luciferase cell lines. Smad3 transcriptional activity of cells implanted in vivo can be analyzed through conventional IVIS imaging and monitored live during tumor progression, providing unique insight into the dynamics of the TGF-β signaling pathway. Our protocol describes an advantageous reporter delivery system allowing for quick high-throughput imaging of live cell signaling pathways both in vitro and in vivo. This method can be expanded to a range of image based assays and presents as a sensitive and reproducible approach for both basic biology and therapeutic development.
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- 2018
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17. Transmission traits of malaria parasites within the mosquito: Genetic variation, phenotypic plasticity, and consequences for control
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Lefevre, T, Ohm, J, Dabiré, KR, Cohuet, A, Choisy, M, Thomas, MB, Cator, L, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Laboratoire mixte international sur les vecteurs [Bobo Dioulasso, Burkina Faso] (LAMIVECT), Institut de Recherche pour le Développement (IRD), Pennsylvania State University (Penn State), Penn State System, Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Imperial College London, and ANR-16-CE35-0007,STORM,Stratégies de transmission des parasites à vecteur : variation génétique, plasticité phénotypique et conséquences pour les mesures de contrôle(2016)
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lcsh:Evolution ,malaria ,transmission ,mosquito ,[SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology ,host-parasite interactions ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Perspective ,parasitic diseases ,host–parasite interactions ,lcsh:QH359-425 ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,[SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis - Abstract
International audience; Evaluating the risk of emergence and transmission of vector-borne diseases requires knowledge of the genetic and environmental contributions to pathogen transmission traits. Compared to the significant effort devoted to understanding the biology of malaria transmission from vertebrate hosts to mosquito vectors, the strategies that malaria parasites have evolved to maximize transmission from vectors to vertebrate hosts have been largely overlooked. While determinants of infection success within the mosquito host have recently received attention, the causes of variability for other key transmission traits of malaria, namely the duration of parasite development and its virulence within the vector, as well as its ability to alter mosquito behavior, remain largely unknown. This important gap in our knowledge needs to be bridged in order to obtain an integrative view of the ecology and evolution of malaria transmission strategies. Associations between transmission traits also need to be characterized, as they trade-offs and constraints could have important implications for understanding the evolution of parasite transmission. Finally, theoretical studies are required to evaluate how genetic and environmental influences on parasite transmission traits can shape malaria dynamics and evolution in response to disease control.
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- 2018
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18. Glioblastoma treatment: Where to now?
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Hong-Jian Zhu and Thomas Mb Ware
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,medicine.disease ,Glioblastoma - Published
- 2018
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19. Mouse models of glioma
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Thomas Mb Ware, Fiona H Tan, Andrew H. Kaye, Rodney B. Luwor, and Stanley S. Stylli
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Oncology ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,Central nervous system ,Mice ,Physiology (medical) ,Internal medicine ,Glioma ,Parenchyma ,medicine ,Animals ,Pathological ,Brain Neoplasms ,business.industry ,General Medicine ,medicine.disease ,Disease Models, Animal ,medicine.anatomical_structure ,Neurology ,Surgery ,Neurology (clinical) ,Stem cell ,business ,Adjuvant ,Median survival ,Glioblastoma - Abstract
Gliomas are the most common primary tumour in the central nervous system in adults. The pathological hallmark of gliomas is their propensity for extensive infiltration into the surrounding brain parenchyma which results in tumour recurrence. Despite the use of optimal surgical removal and adjuvant therapies the most aggressive of these tumours, glioblastoma multiforme, has a poor patient prognosis, with median survival of less than 15 months. In this review, we discuss mouse glioma models that have been utilised to advance our basic knowledge of the processes involved in gliomagenesis and their use in the testing of novel therapies and treatment regimens in the preclinical setting.
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- 2015
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20. Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib
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Ramin Shayan, Bo Li, Lipi Shukla, Lucia Paradiso, Stanley S. Stylli, Nicole C. Harris, Thomas Mb Ware, Andrew H. Kaye, Zammam Areeb, Rodney B. Luwor, and Andrew P. Morokoff
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0301 basic medicine ,Cancer Research ,Antineoplastic Agents ,Pharmacology ,Bortezomib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Growth factor receptor ,Cell Movement ,Cell Line, Tumor ,Medicine ,Humans ,Viability assay ,neoplasms ,Cell Proliferation ,business.industry ,Cell growth ,Brain Neoplasms ,Cell migration ,Hematology ,General Medicine ,Carfilzomib ,030104 developmental biology ,Oncology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Matrix Metalloproteinase 2 ,Stem cell ,Drug Screening Assays, Antitumor ,business ,Glioblastoma ,Oligopeptides ,Proteasome Inhibitors ,medicine.drug - Abstract
Glioblastoma multiforme is the most aggressive and lethal tumor of the central nervous system with limited treatment strategies on offer, and as such the identification of effective novel therapeutic agents is paramount. To examine the efficacy of proteasome inhibitors, we tested bortezomib, carfilzomib, nafamostat mesylate, gabexate mesylate and acetylsalicylic acid on glioblastoma cell viability, migration and invasion. Both bortezomib and carfilzomib produced significant reduction of cell viability, while nafamostat mesylate, gabexate mesylate and acetylsalicylic acid did not. Subsequent testing showed that carfilzomib significantly reduced cell viability at nM concentrations. Carfilzomib also reduced cell migration, secretion and activation of MMP2 and also cell invasion of all four glioblastoma cells tested. In summary, carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme.
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- 2016
21. The evidence base for clinical governance
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Matt Thomas Mb Chb Mrcp
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Clinical governance ,Service quality ,Quality management ,business.industry ,Health Policy ,media_common.quotation_subject ,Public Health, Environmental and Occupational Health ,MEDLINE ,Assertion ,Evidence-based medicine ,Public relations ,Nursing ,Health care ,Medicine ,Quality (business) ,business ,media_common - Abstract
RATIONALE, AIMS AND OBJECTIVES Clinical governance has been advanced as a mechanism for continuous quality improvement within the UK National Health Service (NHS). This study aimed to assess whether evidence exists to support this claim. METHODS A Medline search for evidence to link the introduction of clinical governance to improvements in the quality of health care was conducted. RESULTS Of the 335 papers retrieved initially, 114 were potentially relevant to the question, but only 10 attributed changes in quality to clinical governance directly. Of these, only three attempted to provide data to support the assertion. CONCLUSION No sound evidence currently exists to support the claim that clinical governance will increase service quality and moves towards its implementation must therefore be questioned.
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- 2002
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22. Abstract B38: Quiescence as a marker of treatment resistance and malignancy in GBM
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Atkins, Ryan J., primary, Stylli, Stanley S., additional, Luwor, Rodney B., additional, Ware, Thomas MB, additional, Kaye, Andrew H., additional, and Hovens, Christopher M., additional
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- 2016
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23. Abstract B38: Quiescence as a marker of treatment resistance and malignancy in GBM
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Stanley S. Stylli, Thomas Mb Ware, Ryan J. Atkins, Christopher M. Hovens, Andrew H. Kaye, and Rodney B. Luwor
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Cancer Research ,education.field_of_study ,Temozolomide ,Cell division ,Population ,Cancer ,Biology ,medicine.disease ,Stem cell marker ,Oncology ,Cancer stem cell ,Glioma ,medicine ,Cancer research ,Stem cell ,education ,Molecular Biology ,medicine.drug - Abstract
Glioblastoma multiforme (GBM) is a World Health Organization grade IV astrocytic tumor, and is the most common primary brain malignancy. GBM is characterized as being highly malignant and rapidly progressive with a high mitotic index, diffuse invasion, microvascular proliferation and pseudopalisading necrosis. Current best treatment for GBM involves maximal safe surgical resection, with radiotherapy (XRT) and temozolomide (TMZ), but even with this regime patients survive for an average of only ~15 months. GBM’s position within the brain and diffuse progression profile prevents a surgical cure, and the cells left behind following surgery contain a quiescent, treatment-resistant subpopulation of cells with a stem-like capacity for self-renewal which survive chemoradiotherapy and cause relapse. These resistant cells have been referred to as cancer stem cells, but while stem cell markers have been useful in enriching stem populations in some cancers, a marker that reliably defines the glioma stem cell has remained elusive. The critical feature that allows these resistant cells to survive treatment is their slow division rate, which helps them to avoid chemoradiotherapy-induced cell death by virtue of their condensed chromatin and reduced requirement for DNA replication. In the present study we use a pulse-chase assay to ubiquitously label glioma cell lines with the fluorescent dye Oregon Green and observe the label dilution as an indicator of cell division. Based on their slower division rates, quiescent cells retain the dye longer than rapidly-dividing cells and are easily identified by fluorescence imaging and FACS analysis. Once such a population is isolated it can then be compared to a rapidly-dividing (Oregon Green-diluting) subpopulation of cells to analyze differences in treatment resistance, migration, invasion, and gene expression between the two populations. It is hoped that by elucidating the molecular mechanisms that drive treatment resistance and migration/invasion we will be able to inform novel GBM treatments that improve patient outcomes. We have shown that quiescent cells are innately resistant to the current gold standard GBM treatments and display more malignant features in vitro than rapidly dividing cells. We have developed a platform for quick, easy, and reliable isolation of this quiescent fraction of cells to facilitate its interrogation. This method has the potential to identify future treatment targets, and could, in principle, be extended to other malignancies. Citation Format: Ryan J. Atkins, Stanley S. Stylli, Rodney B. Luwor, Thomas MB Ware, Andrew H. Kaye, Christopher M. Hovens. Quiescence as a marker of treatment resistance and malignancy in GBM. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr B38.
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- 2016
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24. Perioperative patient outcomes in the African Surgical Outcomes Study: a 7-day prospective observational cohort study
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Biccard, Bruce M, Madiba, Thandinkosi E, Kluyts, Hyla-Louise, Munlemvo, Dolly M, Madzimbamuto, Farai D, Basenero, Apollo, Gordon, Christina S, Youssouf, Coulibaly, Rakotoarison, Sylvia R, Gobin, Veekash, Samateh, Ahmadou L, Sani, Chaibou M, Omigbodun, Akinyinka O, Amanor-Boadu, Simbo D, Tumukunde, Janat T, Esterhuizen, Tonya M, Manach, Yannick Le, Forget, Patrice, Elkhogia, Abdulaziz M, Mehyaoui, Ryad M, Zoumeno, Eugene, Ndayisaba, Gabriel, Ndasi, Henry, Ndonga, Andrew K N, Ngumi, Zipporah W W, Patel, Ushmah P, Ashebir, Daniel Zemenfes, Antwi-Kusi, Akwasi A K, Mbwele, Bernard, Sama, Hamza Doles, Elfiky, Mahmoud, Fawzy, Maher A, Pearse, Rupert M, Abadagan, Hippolyte, Abbas, N, Abdelatif, A Ibrahim, Abdoulaye, Traoré, Abd-rouf, A, Abduljalil, A, Abdulrahman, A, Abdurazig, S, Abokris, A, Abozaid, W, Abugassa, SOA, Abuhdema, F, Abujanah, SA, Abusamra, R, Abushnaf, A, Abusnina, SA, Abuzalout, TS, Ackermann, HM, Adamu, YB, Addanfour, A, Adeleke, DM, Adigun, TA, Adisa, AO, Adjignon, Sèhivè 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PM, Katsukunya, L, Kavuma, KAM, Khalfallah, Khamajeet, A, Khetrish, SB, Kibandwa, Kibochi, W, Kilembe, AM, Kintu, AK, Kipng'etich, B, Kiprop, B, Kissoon, VMK, Kisten, Theroshnie K, Kiwanuka, JK, Kluyts, Hyla-Louise, Knox, MEK, Koledale, AK, Koller, VL, Kolotsi, MA, Kongolo, M, Konwuoh, ND, Koperski, WJ, Koraz, MYK, Kornilov, AA, Koto, M Zach, Kransingh, Samantha, Krick, D, Kruger, S, Kruse, C, Kuhn, W, Kuhn, WP, Kukembila, AM, Kule, KL, Kumar, M, Kusel, Belinda S, Kusweje, VK, Kuteesa, KJ, Kutor, YY, Labib, MA, Laksari, M, Lanos, F, Lawal, TA, Le Manach, Yannick, Lee, C, Lekoloane, RM, Lelo, SN, Lerutla, B, Lerutla, MT, Levin, AI, Likongo, TB, Limbajee, ML, Linyama, DM, Lionnet, C, Liwani, MM, Loots, E, Lopez, A Garrido, Lubamba, CLC, Lumbala, KF, Lumbamba, AJM, Lumona, John, Lushima, RF, Luthuli, L, Luweesi, HL, Lyimo, TSK, Maakamedi, HM, Mabaso, BM, Mabina, M, Maboya, ME, Macharia, I, Macheka, AM, Machowski, AZ, Madiba, Thandinkosi E, Madsen, ASM, Madzimbamuto, Farai, Madzivhe, LJ, 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SK, Tshitangano, R, Tshivhula, F, Tshuma, HT, Tumukunde, Janat, Tun, M, Udo, IA, Uhuebor, DI, Umeh, KU, Usenbo, AO, Uwiteyimbabazi, JdD, Van der Merwe, DJ, van der Merwe, FH, van der Walt, JE, van Dyk, Dominique, Van Dyk, JG, van Niekerk, JJS, van Wyk, S, van Zyl, HA, Veerasamy, B, Venter, PJ, Vermeulen, AJ, Villarreal, R, Visser, J, Visser, L, Voigt, M, von Rahden, Richard P, Wafa, A, Wafula, A, Wambugu, PK, Waryoba, P, Waweru, EN, Weideman, M, Wise, Robert D, Wynne, EE, Yahya, AI, Yahya, AA, Yahya, R, Yakubu, Y, Yanga, JJ, Yangazov, YM, Yousef, O, Yousef, G, Youssouf, Coulibaly, Yunus, AA, Yusuf, AS, Zeiton, AZ, Zentuti, HZ, Zepharine, Henry, Zerihun, AB, Zhou, S, Zidan, A, Zié, Sanogo Zimogo, Zinyemba, CZ, Zo, A, Zomahoun, Lidwine, Zoobei, NZ, Zoumenou, Eugene, and Zubia, NZ
- Abstract
There is a need to increase access to surgical treatments in African countries, but perioperative complications represent a major global health-care burden. There are few studies describing surgical outcomes in Africa.
- Published
- 2018
- Full Text
- View/download PDF
25. Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds.
- Author
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Bovine Hap Map, Consortium, Gibbs, Ra, Taylor, Jf, Van Tassel, Cp, Barendse, W, Eversole, Ka, Gill, Ca, Green, Rd, Hamernik, Dl, Kappes, Sm, Lien, S, Matukumalli, Lk, Mcevan, Jc, Mazareth, Lv, Schnabel, Rd, Weinstock, Gm, Wheeler, Da, Ajmone Marsan, Paolo, Boettcher, Pj, Caetano, Ar, Garcia, Jf, Hanotte, O, Mariani, P, Skow, Lc, Sonstegard, T, Williams, Jl, Diallo, B, Hailemariam, L, Martinez, Ml, Morris, Ca, Silva, Lo, Spelman, Rj, Malatu, W, Zhao, K, Abbey, Ca, Agaba, M, Araujo, Fr, Bunch, Rj, Burton, J, Gorni, C, Olivier, H, Harrison, Be, Luff, B, Machado, Ma, Mwakaya, J, Plastow, G, Sim, W, Smith, T, Thomas, Mb, Valentini, A, Williams, P, Womack, J, Wolliams, Ja, Liu, Y, Qin, X, Worley, Kc, Gao, C, Jiang, H, Moore, S, Ren, Y, Song, Xz, Bustamante, Cd, Hernandez, Rd, Muzny, Dm, Patil, S, San Lucas, A, Fu, Q, Kent, Mp, Vega, R, Matukumalli, A, Mcwilliam, S, Sclep, G, Bryc, K, Choi, J, Gao, H, Grefenstette, Jj, Murdoch, B, Stella, A, Villa Angulo, R, Wright, M, Aerts, J, Jann, O, Negrini, Riccardo, Goddard, Me, Hayes, Bj, Bradley, Dg, Lau, Lp, Liu, Ge, Lynn, Dj, Panzitta, F, Dodds, Kg, Ajmone Marsan, Paolo (ORCID:0000-0003-3165-4579), Negrini, Riccardo (ORCID:0000-0002-8735-0286), Bovine Hap Map, Consortium, Gibbs, Ra, Taylor, Jf, Van Tassel, Cp, Barendse, W, Eversole, Ka, Gill, Ca, Green, Rd, Hamernik, Dl, Kappes, Sm, Lien, S, Matukumalli, Lk, Mcevan, Jc, Mazareth, Lv, Schnabel, Rd, Weinstock, Gm, Wheeler, Da, Ajmone Marsan, Paolo, Boettcher, Pj, Caetano, Ar, Garcia, Jf, Hanotte, O, Mariani, P, Skow, Lc, Sonstegard, T, Williams, Jl, Diallo, B, Hailemariam, L, Martinez, Ml, Morris, Ca, Silva, Lo, Spelman, Rj, Malatu, W, Zhao, K, Abbey, Ca, Agaba, M, Araujo, Fr, Bunch, Rj, Burton, J, Gorni, C, Olivier, H, Harrison, Be, Luff, B, Machado, Ma, Mwakaya, J, Plastow, G, Sim, W, Smith, T, Thomas, Mb, Valentini, A, Williams, P, Womack, J, Wolliams, Ja, Liu, Y, Qin, X, Worley, Kc, Gao, C, Jiang, H, Moore, S, Ren, Y, Song, Xz, Bustamante, Cd, Hernandez, Rd, Muzny, Dm, Patil, S, San Lucas, A, Fu, Q, Kent, Mp, Vega, R, Matukumalli, A, Mcwilliam, S, Sclep, G, Bryc, K, Choi, J, Gao, H, Grefenstette, Jj, Murdoch, B, Stella, A, Villa Angulo, R, Wright, M, Aerts, J, Jann, O, Negrini, Riccardo, Goddard, Me, Hayes, Bj, Bradley, Dg, Lau, Lp, Liu, Ge, Lynn, Dj, Panzitta, F, Dodds, Kg, Ajmone Marsan, Paolo (ORCID:0000-0003-3165-4579), and Negrini, Riccardo (ORCID:0000-0002-8735-0286)
- Published
- 2009
26. The effect of liver transplantation (LT) on hepatic osteodystrophy in children
- Author
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D'Antiga, L, Dhawan, A, Moniz, C, Thomas, M, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, D'Antiga L, Dhawan A, Moniz C, Thomas MB, Abraha H, Baker AJ, Heaton ND, Rela M, Mieli-Vergani G, D'Antiga, L, Dhawan, A, Moniz, C, Thomas, M, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, D'Antiga L, Dhawan A, Moniz C, Thomas MB, Abraha H, Baker AJ, Heaton ND, Rela M, and Mieli-Vergani G
- Published
- 2000
27. Cyanide poisoning in cattle from Dysphania glomulifera (red crumbweed): using the internet for rapid plant identification and diagnostic advice
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McKenzie, RA, primary, Burren, BG, additional, Noble, JW, additional, and Thomas, MB, additional
- Published
- 2007
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28. Biochemical markers of bone metabolism and bone mineral density (BMD) in children before and after liver transplantation
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D'Antiga, L, Dhawan, A, Moniz, C, Thomas, M, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, D'Antiga L, Dhawan A, Moniz C, Thomas MB, Abraha H, Baker AJ, Heaton ND, Rela M, Mieli-Vergani G, D'Antiga, L, Dhawan, A, Moniz, C, Thomas, M, Abraha, H, Baker, A, Heaton, N, Rela, M, Mieli-Vergani, G, D'Antiga L, Dhawan A, Moniz C, Thomas MB, Abraha H, Baker AJ, Heaton ND, Rela M, and Mieli-Vergani G
- Published
- 1999
29. The evidence base for clinical governance
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Thomas MB ChB, MRCP, Matt, primary
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- 2002
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30. Phase I and pharmacokinetic study of 3'-C-ethynylcytidine (TAS-106), an inhibitor of RNA polymerase I, II and III,in patients with advanced solid malignancies.
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Hammond-Thelin LA, Thomas MB, Iwasaki M, Abbruzzese JL, Lassere Y, Meyers CA, Hoff P, de Bono J, Norris J, Matsushita H, Mita A, and Rowinsky EK
- Published
- 2012
31. Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma.
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Thomas MB, Morris JS, Chadha R, Iwasaki M, Kaur H, Lin E, Kaseb A, Glover K, Davila M, and Abbruzzese J
- Published
- 2009
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32. Targeted therapies for cancer of the gallbladder.
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Thomas MB
- Published
- 2008
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33. Systemic therapy for hepatocellular carcinoma.
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Thomas MB
- Abstract
Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer-related death. Eighty percent of new cases occur in developing countries, but the incidence is rising in economically developed regions including Japan, Western Europe, and the United States. More than 80% of patients present with advanced or unresectable disease, and for those patients who do undergo resection, the recurrence rates can be as high as 50% at 2 years. Thus, a large number of patients will seek systemic therapy. Systemic cytotoxic chemotherapy is largely ineffective and can have significant toxicity in patients with underlying liver dysfunction. Newer biologic agents that target molecular abnormalities common to HCC may improve the clinical outcome in patients with HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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34. Theoretical approaches for investigating patient safety.
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Thomas MB and Houston S
- Abstract
Patient safety and freedom from accidental injury is an issue that is promoting the search for excellence among healthcare providers, payers, and consumers. The issue is complex and multifaceted, providing many avenues for analysis, quality enhancement, and research. Several models exist that may assist in exploring patient safety issues and the relationships between error and safety. Three models are discussed and research questions are generated that with further investigation will help us to understand the complexity of error management and the promotion of patient safety. Because of their leadership role and guardianship in managing patient care, clinical nurse specialists understand and promote models that improve safety for their patients. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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35. Stemming the tide of hepatitis B virus related hepatocellular carcinoma?
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Thomas MB, Davila M, and Abbruzzese JL
- Published
- 2008
36. Study examines working hours and feelings of fatigue by reported nurses.
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Thomas MB
- Published
- 2005
37. Lessons from agriculture for the sustainable management of malaria vectors.
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Thomas MB, Godfray HC, Read AF, van den Berg H, Tabashnik BE, van Lenteren JC, Waage JK, Takken W, Thomas, Matthew B, Godfray, H Charles J, Read, Andrew F, van den Berg, Henk, Tabashnik, Bruce E, van Lenteren, Joop C, Waage, Jeff K, and Takken, Willem
- Published
- 2012
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38. From the guest editors.
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Thomas MB and Lawrence TS
- Published
- 2008
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39. Global threat to agriculture from invasive species
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Paini, DR, Sheppard, AW, Cook, DC, De Barro, PJ, Worner, SP, and Thomas, MB
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40. Biological control for One Health.
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Schaffner U, Heimpel GE, Mills NJ, Muriithi BW, Thomas MB, Gc YD, and Wyckhuys KAG
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- Humans, Animals, Pest Control, Biological methods, Conservation of Natural Resources methods, Biodiversity, Ecosystem, Agriculture methods, One Health
- Abstract
Biological control has been effectively exploited by mankind since 300 CE. By promoting the natural regulation of pests, weeds, and diseases, it produces societal benefits at the food-environment-health nexus. Here we scrutinize biological control endeavours and their social-ecological outcomes through a holistic 'One-Health' lens, recognizing that the health of humans, animals, plants, and the wider environment are linked and interdependent. Evidence shows that biological control generates desirable outcomes within all One Health dimensions, mitigating global change issues such as chemical pollution, biocide resistance, biodiversity loss, and habitat destruction. Yet, its cross-disciplinary achievements remain underappreciated. To remedy this, we advocate a systems-level, integrated approach to biological control research, policy, and practice. Framing biological control in a One Health context helps to unite medical and veterinary personnel, ecologists, conservationists and agricultural professionals in a joint quest for solutions to some of the most pressing issues in planetary health., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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41. Analyzing the impact of the Coronavirus disease 2019 pandemic on initial oncologic presentation and treatment of non-small cell lung cancer in the United States.
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Dyas AR, Bronsert MR, Stuart CM, Thomas MB, Schulick RD, Franco SR, Gleisner A, Randhawa SK, David EA, Mitchell JD, and Meguid RA
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- Humans, Male, Female, Retrospective Studies, United States epidemiology, Aged, Middle Aged, Neoplasm Staging, SARS-CoV-2, Pandemics, Pneumonectomy statistics & numerical data, COVID-19 epidemiology, COVID-19 therapy, Carcinoma, Non-Small-Cell Lung therapy, Carcinoma, Non-Small-Cell Lung epidemiology, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms therapy, Lung Neoplasms epidemiology, Lung Neoplasms pathology
- Abstract
Background: A significantly lower rate of non-small cell lung cancer (NSCLC) screening, greater health care avoidance, and changes to oncologic recommendations were some consequences of the Coronavirus disease 2019 (COVID-19) pandemic affecting the medical environment. We sought to determine how the health care environment during the COVID-19 pandemic affected the oncologic treatment of patients diagnosed with non-small cell lung cancer (NSCLC)., Methods: This was a retrospective cohort study evaluating patients with NSCLC in the National Cancer Database (2019-2020). Patients were divided into prepandemic (2019) and pandemic (2020) cohorts, and patient, oncologic, and treatment variables were compared. Multivariable logistic regression was performed to control for the impact of demographic characteristics on oncologic variables and the impact of oncologic variables on treatment variables., Results: The study population comprised 250,791 patients, including 114,533 patients (45.7%) in the pandemic cohort. There were 15% fewer new NSCLC diagnoses during the pandemic compared with prepandemic. Patients diagnosed during the pandemic had more advanced clinical TNM stage on presentation (P < .0001) and were more likely to have tumors in overlapping lobes or in a main bronchus (P = .0002). They were less likely to receive cancer treatment (P < .0001) and to undergo primary resection (P < .0001) and more likely to receive adjuvant systemic therapy (P = .004) and a combination of palliative treatment regimens (P < .0001). After risk adjustment, all these differences remained statistically significant (P < .05)., Conclusions: The COVID-19 pandemic was associated with increased clinical stage at presentation for patients with NSCLC, which impacted subsequent treatment strategies. However, treatment differed minimally when controlling for cancer stage. Future studies will examine the impact of these differences on overall survival and cancer-free survival., Competing Interests: Conflict of Interest Statement E.A.D. reports honoraria from Astra Zeneca. R.A.M. reports consulting fees from Medtronic (payments made to institution). The other authors have no conflicts of interest to report. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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42. The Characterization of Violent Deaths Among Asian and Pacific Islander Americans.
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Tran W, Thomas MB, Garofalo D, Patten M, Graham R, Estrella J, Dickinson K, Carmichael H, Velopulos CG, and Myers QWO
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- Humans, Cause of Death, Population Surveillance, United States, Homicide, Native Hawaiian or Other Pacific Islander, Suicide, Violence
- Abstract
Introduction: Health disparities in the Asian and Pacific Islander Americans (APIAs) community have not been well described, unlike non-Hispanic Black and Hispanic communities. However, there has been a rise in violence against the APIA community. This study explores and characterizes violent death by incident (e.g., homicide, suicide), weapon (e.g., firearm, strangulation), and location types among APIAs as they compare with other racial or ethnic groups., Methods: We used the National Violent Death Reporting System from 2003 to 2018 to characterize violent deaths among APIA and compared them to all other races. We compared these racial categories in two ways. First, we compared all races as a categorical variable that included six non-Hispanic racial categories including "Other or unspecified" and "two or more races. We then created a binary variable of APIA versus All Other Races for analysis. We explored the incident type of death, substance abuse disorders, mental health history, and gang involvement among other variables. We used Chi-square tests for categorical variables and Mann-Whitney U-tests for continuous variables., Results: Overall, APIAs had a unique pattern of violent death. APIAs were more likely to commit suicide (71.74%-62.21%, P<0.001) and less likely to die of homicide than other races (17.56%-24.31%, P<0.001). In the cases of homicide, APIAs were more likely to have their deaths precipitated by another crime (40.87% versus 27.87%, P < 0.001). APIAs were more than twice as likely to die of strangulation than other races (39.93%-18.06%, P<0.001). Conversely, APIAs were less likely to die by firearm than other races (29.69-51.51, P<0.001)., Conclusions: APIAs have a unique pattern of violence based on analysis of data from the National Violent Death Reporting System. Our data reveal a significant difference in the incident, weapon and location type as compared to Americans of other races, which begs further inquiry into the patterns of change in time and factors that contribute to inter-racial differences in death patterns., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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43. Estimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum.
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Suh E, Stopard IJ, Lambert B, Waite JL, Dennington NL, Churcher TS, and Thomas MB
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- Animals, Humans, Kenya epidemiology, Climate Change, Female, Plasmodium falciparum physiology, Malaria, Falciparum transmission, Malaria, Falciparum parasitology, Malaria, Falciparum epidemiology, Anopheles parasitology, Temperature, Mosquito Vectors parasitology
- Abstract
Despite concern that climate change could increase the human risk to malaria in certain areas, the temperature dependency of malaria transmission is poorly characterized. Here, we use a mechanistic model fitted to experimental data to describe how Plasmodium falciparum infection of the African malaria vector, Anopheles gambiae, is modulated by temperature, including its influences on parasite establishment, conversion efficiency through parasite developmental stages, parasite development rate, and overall vector competence. We use these data, together with estimates of the survival of infected blood-fed mosquitoes, to explore the theoretical influence of temperature on transmission in four locations in Kenya, considering recent conditions and future climate change. Results provide insights into factors limiting transmission in cooler environments and indicate that increases in malaria transmission due to climate warming in areas like the Kenyan Highlands, might be less than previously predicted., (© 2024. The Author(s).)
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- 2024
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44. Biodegradable Nanocomposite of ZnS(Mn) Quantum Dots Immobilized Graphene Oxide for Bioimaging Applications.
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Kurungottu P, Thomas MB, Lalitha MM, Ganesh P, Gnanadhas DP, Chakravortty D, Raichur AM, and Kurapati R
- Subjects
- Humans, HeLa Cells, Quantum Dots chemistry, Graphite chemistry, Nanocomposites chemistry
- Abstract
Developing a biocompatible and biodegradable graphene-based fluorescent nanoprobe with the ability to visualize live cells could be interesting for intracellular imaging and monitoring the efficiency of chemotherapy. Herein, we report a biodegradable and biocompatible hybrid fluorescent graphene oxide (GO)-ZnS(Mn) composite synthesized via in situ growth of ZnS(Mn) quantum dots (QDs) on the surface of GO in the aqueous medium. The prepared 'GO-ZnS(Mn)' composite was characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and high-resolution transmission electron microscopy (HR-TEM) along with selected area electron diffraction (SAED). Further, the fluorescence properties of the GO-ZnS(Mn) composite were studied using fluorescence emission spectroscopy. The composite material exhibited a strong and broad visible light fluorescence from 500 to 600 nm by excitation with 365 nm (UV) light. The cytotoxic experiments of folic acid (FA) conjugated GO-ZnS(Mn) using MTT [(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)] assay revealed that the composite had excellent biocompatibility even at higher concentrations up to 200 µg/mL in HeLa cell lines. Next, the bioimaging experiments carried out using confocal fluorescence laser scanning microscopy (CLSM) revealed that GO-ZnS(Mn) composite was taken up by the HeLa cells effectively within 12 h of incubation via receptor (folate) mediated endocytosis with strong fluorescence throughout the cell surface. Finally, the biodegradability of GO-ZnS(Mn) composite was studied by treating it with human myeloperoxidase enzyme (hMPO) isolated from the primary immune cells, neutrophils, which is important to understand the in vivo fate of GO-Zns(Mn). The HR-TEM and Raman analyses confirmed the biodegradation of GO-ZnS(Mn) within 15 h of hMPO treatment. Thus, the biodegradable GO-ZnS (Mn) composite could be helpful for chemotherapy and bioimaging applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2024
- Full Text
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45. Phenotypic adaptation to temperature in the mosquito vector, Aedes aegypti.
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Dennington NL, Grossman MK, Ware-Gilmore F, Teeple JL, Johnson LR, Shocket MS, McGraw EA, and Thomas MB
- Subjects
- Animals, Mosquito Vectors physiology, Temperature, Aedes physiology, Zika Virus Infection, Zika Virus
- Abstract
Most models exploring the effects of climate change on mosquito-borne disease ignore thermal adaptation. However, if local adaptation leads to changes in mosquito thermal responses, "one size fits all" models could fail to capture current variation between populations and future adaptive responses to changes in temperature. Here, we assess phenotypic adaptation to temperature in Aedes aegypti, the primary vector of dengue, Zika, and chikungunya viruses. First, to explore whether there is any difference in existing thermal response of mosquitoes between populations, we used a thermal knockdown assay to examine five populations of Ae. aegypti collected from climatically diverse locations in Mexico, together with a long-standing laboratory strain. We identified significant phenotypic variation in thermal tolerance between populations. Next, to explore whether such variation can be generated by differences in temperature, we conducted an experimental passage study by establishing six replicate lines from a single field-derived population of Ae. aegypti from Mexico, maintaining half at 27°C and the other half at 31°C. After 10 generations, we found a significant difference in mosquito performance, with the lines maintained under elevated temperatures showing greater thermal tolerance. Moreover, these differences in thermal tolerance translated to shifts in the thermal performance curves for multiple life-history traits, leading to differences in overall fitness. Together, these novel findings provide compelling evidence that Ae. aegypti populations can and do differ in thermal response, suggesting that simplified thermal performance models might be insufficient for predicting the effects of climate on vector-borne disease transmission., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
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46. Economic Burden of Accidents and Injuries in India: What Does 75 th Round of National Sample Survey Imply?
- Author
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Thomas MB, Pandey AK, Gautam D, Gopinathan S, and Panolan S
- Abstract
Background: Accidents and injuries constitute a sizable share of mortality and morbidity in low- and middle-income countries. This affects the most productive age group and increases disability-adjusted life years (DALYs). It results in a substantial financial burden on the households. To explore the economic burden of accidents and Injuries on Indian households and to find how the catastrophic health expenditure (CHE) from accidents and injuries affects the population. Another objective is to explore Catastrophic out-of-pocket expenditures (OOPE) patterns and distressed financing of households in India., Materials and Methods: The study used data from the 75
th round of nationally representative surveys, that is, the National Sample Survey (NSS). Authors have analyzed the data using descriptive binary logistic regression analysis to estimate the rate and average days of hospitalization, average OOPE, and share of the population experiencing the catastrophic impact from the health expenditure separately from the public and private healthcare institutions., Results: The study observed that hospitalization in the private sector imposes 72% of households incur CHE at more than 10% cut-off and 41% at more than 25% cut-off. In comparison, it is less in the public sector, with 22% of households incurring CHE at more than 10% of annual per capita household income and 9% at more than 25%., Conclusion: The increasing incidence of road traffic accidents (RTA) is a concern for the overstretched health system. The government should provide better healthcare facilities and universal health insurance coverage to ensure patients' speedy recovery and financial security., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Community Medicine.)- Published
- 2024
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47. Global malaria predictors at a localized scale.
- Author
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Skinner EB, Childs ML, Thomas MB, Cook J, Sternberg ED, Koffi AA, N'Guessan R, Wolie RZ, Oumbouke WA, Ahoua Alou LP, Brice S, and Mordecai EA
- Abstract
Malaria is a life-threatening disease caused by Plasmodium parasites transmitted by Anopheles mosquitoes. In 2021, more than 247 million cases of malaria were reported worldwide, with an estimated 619,000 deaths. While malaria incidence has decreased globally in recent decades, some public health gains have plateaued, and many endemic hotspots still face high transmission rates. Understanding local drivers of malaria transmission is crucial but challenging due to the complex interactions between climate, entomological and human variables, and land use. This study focuses on highly climatically suitable and endemic areas in Côte d'Ivoire to assess the explanatory power of coarse climatic predictors of malaria transmission at a fine scale. Using data from 40 villages participating in a randomized controlled trial of a household malaria intervention, the study examines the effects of climate variation over time on malaria transmission. Through panel regressions and statistical modeling, the study investigates which variable (temperature, precipitation, or entomological inoculation rate) and its form (linear or unimodal) best explains seasonal malaria transmission and the factors predicting spatial variation in transmission. The results highlight the importance of temperature and rainfall, with quadratic temperature and all precipitation models performing well, but the causal influence of each driver remains unclear due to their strong correlation. Further, an independent, mechanistic temperature-dependent R
0 model based on laboratory data aligns well with observed malaria incidence rates, emphasizing the significance and predictability of temperature suitability across scales. By contrast, entomological variables, such as entomological inoculation rate, were not strong predictors of human incidence in this context. Finally, the study explores the predictors of spatial variation in malaria, considering land use, intervention, and entomological variables. The findings contribute to a better understanding of malaria transmission dynamics at local scales, aiding in the development of effective control strategies in endemic regions.- Published
- 2023
- Full Text
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48. Attractive targeted sugar bait: the pyrrole insecticide chlorfenapyr and the anti-malarial pharmaceutical artemether-lumefantrine arrest Plasmodium falciparum development inside wild pyrethroid-resistant Anopheles gambiae s.s. mosquitoes.
- Author
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N'Guessan R, Camara S, Rowland M, Ahoua Alou LP, Wolie RZ, Zoh MG, N'Guessan B, Tia IZ, Oumbouke WA, Thomas MB, and Koffi AA
- Subjects
- Animals, Female, Humans, Male, Sugars pharmacology, Plasmodium falciparum, Mosquito Control methods, Artemether, Lumefantrine Drug Combination pharmacology, Mosquito Vectors, Artemether, Carbohydrates, Insecticide Resistance, Insecticides pharmacology, Antimalarials pharmacology, Anopheles, Malaria prevention & control, Pyrethrins pharmacology, Malaria, Falciparum prevention & control
- Abstract
Background: Attractive targeted sugar bait (ATSB) is a novel approach to vector control, offering an alternative mode of insecticide delivery via the insect alimentary canal, with potential to deliver a variety of compounds new to medical entomology and malaria control. Its potential to control mosquitoes was recently demonstrated in major field trials in Africa. The pyrrole chlorfenapyr is an insecticide new to malaria vector control, and through its unique mode of action-disruption of ATP mediated energy transfer in mitochondria-it may have direct action on energy transfer in the flight muscle cells of mosquitoes. It may also have potential to disrupt mitochondrial function in malarial parasites co-existing within the infected mosquito. However, little is known about the impact of such compounds on vector competence in mosquitoes responsible for malaria transmission., Methods: In this study, ATSBs containing chlorfenapyr insecticide and, as a positive control, the anti-malarial drugs artemether/lumefantrine (A/L) were compared for their effect on Plasmodium falciparum development in wild pyrethroid-resistant Anopheles gambiae sensu stricto (s.s.) and for their capacity to reduce vector competence. Female mosquitoes were exposed to ATSB containing either sublethal dose of chlorfenapyr (CFP: 0.025%) or concentrations of A/L ranging from 0.4/2.4 mg/ml to 2.4/14.4 mg/ml, either shortly before or after taking infective blood meals. The impact of their component compounds on the prevalence and intensity of P. falciparum infection were compared between treatments., Results: Both the prevalence and intensity of infection were significantly reduced in mosquitoes exposed to either A/L or chlorfenapyr, compared to unexposed negative control mosquitoes. The A/L dose (2.4/14.4 mg/ml) totally erased P. falciparum parasites: 0% prevalence of infection in female mosquitoes exposed compared to 62% of infection in negative controls (df = 1, χ
2 = 31.23 p < 0.001). The dose of chlorfenapyr (0.025%) that killed < 20% females in ATSB showed a reduction in oocyte density of 95% per midgut (0.18/3.43 per midgut)., Conclusion: These results are evidence that chlorfenapyr, in addition to its direct killing effect on the vector, has the capacity to block Plasmodium transmission by interfering with oocyte development inside pyrethroid-resistant mosquitoes, and through this dual action may potentiate its impact under field conditions., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
49. Prioritizing rapid COVID-19 testing in emergency general surgery patients decreases burden of inpatient hospital admission.
- Author
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Thomas MB, Carmichael H, Harrison M, Abbitt D, Moore A, Myers QWO, and Velopulos CG
- Abstract
Objectives: The COVID-19 pandemic has changed delivery of emergency general surgery (EGS) and contributed to widespread bed shortages. At our institution, rapid testing is not routinely approved for EGS patients. We examined common EGS conditions (appendicitis and acute cholecystitis), hypothesizing that necessity of testing for COVID-19 significantly delayed operative intervention., Methods: We performed a prepost study to examine a 2-month timeframe, or historical control, prior to COVID-19 testing (January 1, 2020-March 1, 2020) as well as a 2-month timeframe during the COVID-19 era (January 1, 2021-March 1, 2021). We chose conditions that are frequently treated surgically as outpatient or observation status. We examined time for COVID-19 test to result, and associated time to operative intervention (operating room (OR)) and need for admission., Results: Median time to COVID-19 test results was 7.4 hours (IQR 5.8-13.1). For appendectomy, time to surgical consultation or case request did not differ between cohorts. Time to OR after case request was significantly longer (12.5 vs 1.9 hours, p<0.001) and patients more frequently required admission prior to operative intervention if receiving treatment in the COVID-19 timeframe. Similarly, for cholecystectomy there were no differences in time to surgical consultation or case request, but time to OR after case request was longer in the COVID-19 era (21.1 vs 9.0 hours, p<0.001)., Conclusion: While COVID-19 positivity rates have declined, the purpose of this study was to reflect on one element of our hospital system's response to the COVID-19 pandemic. Based on our institutional experience, waiting for COVID-19 test results directly impacts time to surgery, as well as the need for admission for a historically outpatient procedure. In the future, if the healthcare system is asked to respond to another pandemic or similar situation, expediting time to OR to eliminate unnecessary time in the hospital and non-critical admissions should be paramount., Level of Evidence: Level III, prognostic/epidemiological., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
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50. Emergency thoracic surgery patients have worse risk-adjusted outcomes than non-emergency patients.
- Author
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Dyas AR, Thomas MB, Bronsert MR, Madsen HJ, Colborn KL, Henderson WG, David EA, Velopulos CG, and Meguid RA
- Subjects
- Humans, Retrospective Studies, Postoperative Complications epidemiology, Postoperative Complications etiology, Postoperative Complications surgery, Herniorrhaphy adverse effects, Treatment Outcome, Thoracic Surgery, Hernia, Hiatal surgery, Hernia, Hiatal etiology, Thoracic Surgical Procedures adverse effects, Laparoscopy adverse effects
- Abstract
Background: Outcomes for patients undergoing emergency thoracic operations have not been well described. This study was designed to compare postoperative outcomes among patients undergoing emergency versus nonemergency thoracic operations., Methods: We retrospectively analyzed the American College of Surgeons National Surgical Quality Improvement Program database (2005-2018). We identified patients who underwent emergency thoracic operations using current procedural technology codes. Patients were then sorted into 1 of 4 cohorts: lung and chest wall, hiatal hernia, esophagus, and pericardium. Emergency versus nonemergency outcomes were compared. Univariate logistic regression was performed with "emergency status" as the independent variable and 30-day postoperative outcomes as the dependent variables. Multiple logistic regression models were performed to control for preoperative factors., Results: Of 90,398 thoracic operations analyzed, 4,044 (4.5%) were emergency. Common emergency operations were pericardial window (n = 580, 10.2%), laparoscopic hiatal hernia repair (n = 366, 8.9%), thoracoscopic partial lung decortication (n = 334, 8.1%), thoracoscopic wedge resection (n = 301, 7.3%), thoracoscopic total lung decortication (n = 256, 6.2%), and open repair of hiatal hernia without mesh (n = 254, 6.2%). In all 4 cohorts, 30-day postoperative complications occurred more frequently after emergency surgery. After controlling for patient characteristics, 8 complications were more frequent after emergency lung and chest wall surgery, 5 complications were more frequent after emergency hiatal hernia surgery, and 3 complications were more frequent after emergency pericardium surgery. Risk-adjusted complications were not different after emergency esophageal surgery., Conclusion: Patients undergoing emergency thoracic operations have worse risk-adjusted outcomes than those undergoing nonemergency thoracic operations. Subset analysis is needed to determine what factors contribute to increased adverse outcomes in specific patient populations., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
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