Author: "Chen WM" - Searchworks@Jio Institute Digital Library Search Results

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1,388 results on '"Chen WM"'

1. Clinical Characteristics and Risk Factors for Pleural Effusion in Patients with Multiple Myeloma

Author: Kang Y, Hou ZL, Yang GZ, Wang XJ, Chen WM, and Shi HZ
Subjects: pleural effusion, multiple myeloma, incidence, risk factors, overall survival, Medicine (General), R5-920
Abstract: Yu Kang,1 Zi-Liang Hou,2 Guang-Zhong Yang,3 Xiao-Juan Wang,1 Wen-Ming Chen,3 Huan-Zhong Shi4 1Department of Internal Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Huan-Zhong Shi; Wen-Ming Chen Email shihuanzhong@sina.com; 13910107759@163.comPurpose: Pleural effusion (PE) is prevalent in “real-life” populations of multiple myeloma (MM), a common hematologic malignancy. Development of PE likely has prognostic implications. The aim of this study was to investigate the characteristics and identify risk factors for occurrence of PE in MM.Patients and Methods: We reviewed electronic medical records of 907 patients diagnosed with MM.Results: Incidence of PE in MM patients was 42.7%. Small and bilateral PE in most cases. PE developed in all MM subtypes, the median time from diagnosis of multiple myeloma to pleural effusion was 6.8 months (range 0.8– 33.6 months). Patients with PE showed worse survival than those without PE (unadjusted hazard ratio with 95% confidence interval: 2.249 [1.774– 2.852]). No difference in survival was found between patients with small PE and those with moderate to large PE (unadjusted HR, 1.402; 95% CI, 1.037– 1.896). Plasma cell proportion (OR, 1.373; 95% CI, 1.153– 1.634; P = 0.009) and amyloidosis (OR, 1.791; 95% CI, 1.408– 2.279; P = 0.024) were risk factors for the occurrence of PE at the initial diagnosis of MM. Plasma cell proportion (OR, 1.853; 95% CI, 1.451– 2.368; P = 0.038), pneumonia (OR, 1.309; 95% CI, 1.143– 1.498; P = 0.008) and heart failure (OR, 1.815; 95% CI, 1.387– 2.374; P = 0.031) were risk factors for the occurrence of PE at relapse of MM.Conclusion: The incidence of PE in MM patients is notable and PE can occur in all MM subtypes. PE indicates a poor prognosis, even small amounts of effusion. PE is a problem worthy of attention, especially in patients with high plasma cell proportion, amyloidosis or complicated with pneumonia and heart failure.Keywords: pleural effusion, multiple myeloma, incidence, risk factors, overall survival
Published: 2021

2. Design and prediction of new anticoagulants as a selective Factor IXa inhibitor via three-dimensional quantitative structure-property relationships of amidinobenzothiophene derivatives

Author: Gao JS, Tong XP, Chang YQ, He YX, Mei YD, Tan PH, Guo JL, Liao GC, Xiao GK, Chen WM, Zhou SF, and Sun PH
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Jia-Suo Gao,1* Xu-Peng Tong,2* Yi-Qun Chang,1 Yu-Xuan He,1 Yu-Dan Mei,1 Pei-Hong Tan,1 Jia-Liang Guo,1 Guo-Chao Liao,3 Gao-Keng Xiao,1 Wei-Min Chen,1 Shu-Feng Zhou,4 Ping-Hua Sun1 1Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China; 2College of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3Department of Chemistry, Wayne State University, Detroit, Michigan, USA; 4College of Pharmacy, University of South Florida, Tampa, FL, USA *These authors contributed equally to this work Abstract: Factor IXa (FIXa), a blood coagulation factor, is specifically inhibited at the initiation stage of the coagulation cascade, promising an excellent approach for developing selective and safe anticoagulants. Eighty-four amidinobenzothiophene antithrombotic derivatives targeting FIXa were selected to establish three-dimensional quantitative structure–activity relationship (3D-QSAR) and three-dimensional quantitative structure–selectivity relationship (3D-QSSR) models using comparative molecular field analysis and comparative similarity indices analysis methods. Internal and external cross-validation techniques were investigated as well as region focusing and bootstrapping. The satisfactory q2 values of 0.753 and 0.770, and r2 values of 0.940 and 0.965 for 3D-QSAR and 3D-QSSR, respectively, indicated that the models are available to predict both the inhibitory activity and selectivity on FIXa against Factor Xa, the activated status of Factor X. This work revealed that the steric, hydrophobic, and H-bond factors should appropriately be taken into account in future rational design, especially the modifications at the 2'-position of the benzene and the 6-position of the benzothiophene in the R group, providing helpful clues to design more active and selective FIXa inhibitors for the treatment of thrombosis. On the basis of the three-dimensional quantitative structure–property relationships, 16 new potent molecules have been designed and are predicted to be more active and selective than Compound 33, which has the best activity as reported in the literature. Keywords: CoMFA, CoMSIA, 3D-QSAR, 3D-QSSR, benzothiophene antithrombosis
Published: 2015

3. Synthesis and antibacterial activities of acylide derivatives bearing an aryl-tetrazolyl chain

Author: Shan LX, Sun PH, Guo BQ, Xu XJ, Li ZQ, Sun JZ, Zhou SF, and Chen WM
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Ling-Xing Shan,1 Ping-Hua Sun,1,2 Bao-Qin Guo,1 Xing-Jun Xu,1 Zhi-Qiang Li,1 Jia-Zhi Sun,2 Shu-Feng Zhou,2 Wei-Min Chen1 1Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, People's Republic of China; 2College of Pharmacy, University of South Florida, Tampa, FL, USA Abstract: Seventeen acylides bearing an aryl-tetrazolyl alkyl-substituted side chain were synthesized, starting from clarithromycin, via several reactions including hydrolysis, acetylating, esterification, carbamylation, and Michael addition. The structures of all new compounds were confirmed by 1H nuclear magnetic resonance spectroscopy, 13C nuclear magnetic resonance spectroscopy, and mass spectrometry. All these synthesized acylides were evaluated for in vitro antimicrobial activities against gram-positive pathogens (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative pathogens (Pseudomonas aeruginosa, Escherichia coli), using the broth microdilution method. Results showed that compounds 10e, 10f, 10g, 10 h, 10o have good antibacterial activities. Keywords: acylide, clarithromycin, synthesis, antibacterial activity
Published: 2014

4. Role of Temperature in the Growth of Silver Nanoparticles Through a Synergetic Reduction Approach

Author: Jiang XC, Chen WM, Chen CY, Xiong SX, and Yu AB
Subjects: Silver nanoparticles, Nanoplates, Reaction temperature, Thermodynamics effect, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract: Abstract This study presents the role of reaction temperature in the formation and growth of silver nanoparticles through a synergetic reduction approach using two or three reducing agents simultaneously. By this approach, the shape-/size-controlled silver nanoparticles (plates and spheres) can be generated under mild conditions. It was found that the reaction temperature could play a key role in particle growth and shape/size control, especially for silver nanoplates. These nanoplates could exhibit an intensive surface plasmon resonance in the wavelength range of 700–1,400 nm in the UV–vis spectrum depending upon their shapes and sizes, which make them useful for optical applications, such as optical probes, ionic sensing, and biochemical sensors. A detailed analysis conducted in this study clearly shows that the reaction temperature can greatly influence reaction rate, and hence the particle characteristics. The findings would be useful for optimization of experimental parameters for shape-controlled synthesis of other metallic nanoparticles (e.g., Au, Cu, Pt, and Pd) with desirable functional properties.
Published: 2011

5. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, and Gravel, S
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
Published: 2022

6. Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

Author: Valdes-Marquez, E, Parish, S, Clarke, R, Stari, T, Worrall, BB, Hopewell, JC, Hofman, Bert, Ikram, Arfan, Chen, WM, Cheng, CY (Ching-Yu), and Epidemiology
Published: 2019

7. Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

Author: Larsson, SC, Traylor, M, Burgess, S, Boncoraglio, GB, Jern, C, Michaëlsson, K, Markus, HS, Malik, R, Chauhan, G, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, AK, Van Der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, RM, Benavente, OR, Bevan, S, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, De Bakker, PIW, Destefano, AL, Hoed, MD, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, Gudnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, FC, Hyacinth, HI, Ikram, MA, Ingelsson, E, Irvin, MR, Jian, X, Jiménez-Conde, J, Johnson, JA, Jukema, JW, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, JM, Lemmens, R, Leys, D, Lewis, CM, Lin, WY, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O'Donnell, MJ, Psaty, BM, Pulit, SL, Rannikmäe, K, Reiner, AP, Rexrode, KM, Rice, K, Rich, SS, Ridker, PM, Rost, NS, Rothwell, PM, Larsson, SC, Traylor, M, Burgess, S, Boncoraglio, GB, Jern, C, Michaëlsson, K, Markus, HS, Malik, R, Chauhan, G, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, AK, Van Der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, RM, Benavente, OR, Bevan, S, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, De Bakker, PIW, Destefano, AL, Hoed, MD, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, Gudnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, FC, Hyacinth, HI, Ikram, MA, Ingelsson, E, Irvin, MR, Jian, X, Jiménez-Conde, J, Johnson, JA, Jukema, JW, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, JM, Lemmens, R, Leys, D, Lewis, CM, Lin, WY, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O'Donnell, MJ, Psaty, BM, Pulit, SL, Rannikmäe, K, Reiner, AP, Rexrode, KM, Rice, K, Rich, SS, Ridker, PM, Rost, NS, and Rothwell, PM
Abstract: © 2019 American Academy of Neurology. ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.
Published: 2019

8. Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study

Author: Larsson, SC, Traylor, M, Burgess, S, Boncoraglio, GB, Jern, C, Michaëlsson, K, Markus, HS, Malik, R, Chauhan, G, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, AK, Van Der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, RM, Benavente, OR, Bevan, S, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, De Bakker, PIW, Destefano, AL, Hoed, MD, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, Gudnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, FC, Hyacinth, HI, Ikram, MA, Ingelsson, E, Irvin, MR, Jian, X, Jiménez-Conde, J, Johnson, JA, Jukema, JW, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, JM, Lemmens, R, Leys, D, Lewis, CM, Lin, WY, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O'Donnell, MJ, Psaty, BM, Pulit, SL, Rannikmäe, K, Reiner, AP, Rexrode, KM, Rice, K, Rich, SS, Ridker, PM, Rost, NS, and Rothwell, PM
Subjects: Stroke, Neurology & Neurosurgery, Intracranial Embolism, Humans, Calcium, Magnesium, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Brain Ischemia
Abstract: © 2019 American Academy of Neurology. ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.
Published: 2018

9. Publisher correction: Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes(Nature Genetics, (2018) 50, 4, (524-537), 10.1038/s41588-018-0058-3)

Author: Malik, R, Chauhan, G, Traylor, M, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, AK, van der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, TM, Benavente, OR, Bevan, S, Boncoraglio, GB, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, de Bakker, PIW, Destefano, AL, Den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, Gudnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, FC, Hyacinth, HI, Arfan Ikram, M, Ingelsson, E, Irvin, MR, Jian, X, Jiménez-Conde, J, Johnson, JA, Wouter Jukema, J, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, JM, Lemmens, R, Leys, D, Lewis, CM, Lin, WY, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O’donnell, MJ, Psaty, BM, Pulit, SL, Rannikmäe, K, Reiner, AP, Rexrode, KM, Rice, K, Rich, SS, Ridker, PM, Rost, NS, Rothwell, PM, Rotter, JI, Rundek, T, Sacco, RL, Sakaue, S, and Sale, MM
Subjects: Developmental Biology
Abstract: © 2019, Nature Publishing Group. All rights reserved. In the HTML version of this article initially published, the author groups ‘AFGen Consortium’, ‘Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium’, ‘International Genomics of Blood Pressure (iGEN-BP) Consortium’, ‘INVENT Consortium’, ‘STARNET’, ‘BioBank Japan Cooperative Hospital Group’, ‘COMPASS Consortium’, ‘EPIC-CVD Consortium’, ‘EPIC-InterAct Consortium’, ‘International Stroke Genetics Consortium (ISGC)’, ‘METASTROKE Consortium’, ‘Neurology Working Group of the CHARGE Consortium’, ‘NINDS Stroke Genetics Network (SiGN)’, ‘UK Young Lacunar DNA Study’ and ‘MEGASTROKE Consortium’ appeared at the end of the author list but should have appeared earlier in the list. In addition, the author group ‘MEGASTROKE Consortium’ was duplicated, and its members were not displayed in the ‘Author information’ section. The errors have been corrected in the HTML version of the article.
Published: 2018

10. Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations

Author: Marquez, A, Kerick, M, Zhernakova, A, Gutierrez-Achury, J, Chen, W, Onengut-Gumuscu, S, Gonzalez-Alvaro, I, Rodriguez-Rodriguez, L, Rios-Fernandez, R, Gonzalez-Gay, M, Mayes, M, Raychaudhuri, S, Rich, S, Wijmenga, C, Martin, J, Barisani, D, Chen, WM, Gonzalez-Gay, MA, Mayes, MD, Rich, SS, Marquez, A, Kerick, M, Zhernakova, A, Gutierrez-Achury, J, Chen, W, Onengut-Gumuscu, S, Gonzalez-Alvaro, I, Rodriguez-Rodriguez, L, Rios-Fernandez, R, Gonzalez-Gay, M, Mayes, M, Raychaudhuri, S, Rich, S, Wijmenga, C, Martin, J, Barisani, D, Chen, WM, Gonzalez-Gay, MA, Mayes, MD, and Rich, SS
Abstract: Background: In recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. The objective of this study was to further investigate this shared genetic component. Methods: For this purpose, we performed a cross-disease meta-analysis of Immunochip data from 37,159 patients diagnosed with a seropositive autoimmune disease (11,489 celiac disease (CeD), 15,523 rheumatoid arthritis (RA), 3477 systemic sclerosis (SSc), and 6670 type 1 diabetes (T1D)) and 22,308 healthy controls of European origin using the R package ASSET. Results: We identified 38 risk variants shared by at least two of the conditions analyzed, five of which represent new pleiotropic loci in autoimmunity. We also identified six novel genome-wide associations for the diseases studied. Cell-specific functional annotations and biological pathway enrichment analyses suggested that pleiotropic variants may act by deregulating gene expression in different subsets of T cells, especially Th17 and regulatory T cells. Finally, drug repositioning analysis evidenced several drugs that could represent promising candidates for CeD, RA, SSc, and T1D treatment. Conclusions: In this study, we have been able to advance in the knowledge of the genetic overlap existing in autoimmunity, thus shedding light on common molecular mechanisms of disease and suggesting novel drug targets that could be explored for the treatment of the autoimmune diseases studied
Published: 2018

11. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author: Malik, R, Chauhan, G, Traylor, M, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, AK, Van Der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, TM, Benavente, OR, Bevan, S, Boncoraglio, GB, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, De Bakker, PIW, Destefano, AL, Den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, Gudnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, FC, Hyacinth, HI, Ikram, MA, Ingelsson, E, Irvin, MR, Jian, X, Jiménez-Conde, J, Johnson, JA, Jukema, JW, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, JM, Lemmens, R, Leys, D, Lewis, CM, Lin, WY, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O'Donnell, MJ, Psaty, BM, Pulit, SL, Rannikmäe, K, Reiner, AP, Rexrode, KM, Rice, K, Rich, SS, Ridker, PM, Rost, NS, Rothwell, PM, Rotter, JI, Rundek, T, Sacco, RL, Sakaue, S, Sale, MM, Malik, R, Chauhan, G, Traylor, M, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, AK, Van Der Laan, SW, Gretarsdottir, S, Anderson, CD, Chong, M, Adams, HHH, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, TM, Benavente, OR, Bevan, S, Boncoraglio, GB, Brown, RD, Butterworth, AS, Carrera, C, Carty, CL, Chasman, DI, Chen, WM, Cole, JW, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, De Bakker, PIW, Destefano, AL, Den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gottesman, RF, Grewal, RP, Gudnason, V, Gustafsson, S, Haessler, J, Harris, TB, Hassan, A, Havulinna, AS, Heckbert, SR, Holliday, EG, Howard, G, Hsu, FC, Hyacinth, HI, Ikram, MA, Ingelsson, E, Irvin, MR, Jian, X, Jiménez-Conde, J, Johnson, JA, Jukema, JW, Kanai, M, Keene, KL, Kissela, BM, Kleindorfer, DO, Kooperberg, C, Kubo, M, Lange, LA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, JM, Lemmens, R, Leys, D, Lewis, CM, Lin, WY, Lindgren, AG, Lorentzen, E, Magnusson, PK, Maguire, J, Manichaikul, A, McArdle, PF, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Ninomiya, T, O'Donnell, MJ, Psaty, BM, Pulit, SL, Rannikmäe, K, Reiner, AP, Rexrode, KM, Rice, K, Rich, SS, Ridker, PM, Rost, NS, Rothwell, PM, Rotter, JI, Rundek, T, Sacco, RL, Sakaue, S, and Sale, MM
Abstract: © 2018 The Author(s). Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.
Published: 2018

12. Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African ancestry anthropometry genetics consortium

Author: Ng, MCY, Graff, M, Lu, Y, Justice, AE, Mudgal, P, Liu, CT, Young, K, Yanek, LR, Feitosa, MF, Wojczynski, MK, Rand, K, Brody, JA, Cade, BE, Dimitrov, L, Duan, Q, Guo, X, Lange, LA, Nalls, MA, Okut, H, Tajuddin, SM, Tayo, BO, Vedantam, S, Bradfield, JP, Chen, G, Chen, WM, Chesi, A, Irvin, MR, Padhukasahasram, B, Smith, JA, Zheng, W, Allison, MA, Ambrosone, CB, Bandera, EV, Bartz, TM, Berndt, SI, Bernstein, L, Blot, WJ, Bottinger, EP, Carpten, J, Chanock, SJ, Chen, YDI, Conti, DV, Cooper, RS, Fornage, M, Freedman, BI, Garcia, M, Goodman, PJ, Hsu, YHH, Hu, J, Huff, CD, Ingles, SA, John, EM, Kittles, R, Klein, E, Li, J, McKnight, B, Nayak, U, Nemesure, B, Ogunniyi, A, Olshan, A, Press, MF, Rohde, R, Rybicki, BA, Salako, B, Sanderson, M, Shao, Y, Siscovick, DS, Stanford, JL, Stevens, VL, Stram, A, Strom, SS, Vaidya, D, Witte, JS, Yao, J, Zhu, X, Ziegler, RG, Zonderman, AB, Adeyemo, A, Ambs, S, Cushman, M, Faul, JD, Hakonarson, H, Levin, AM, Nathanson, KL, and Ware, EB
Abstract: © 2017 Public Library of Science. All rights reserved. Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMIfrom the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMIand eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMIin African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMIwhen combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI(SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (
Published: 2017
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13. A FRAILTY SCALE PREDICTS OUTCOMES IN TRANSPLANT-INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH CONTINUOUS LENALIDOMIDE PLUS LOW-DOSE DEXAMETHASONE IN THE FIRST (MM-020) TRIAL

Author: Facon, T Hulin, C Dimopoulos, MA Belch, A Meuleman, N Mohty, M Chen, WM Kim, K Zamagni, E Rodriguez-Otero, P others
Subjects: Health Sciences, Επιστήμες Υγείας
Published: 2016

14. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib:A multicenter international myeloma working group study

Author: Kumar S. K., Lee J. H., Lahuerta J. J., Morgan G., Richardson P. G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S. K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J. S., Orlowski R., Palumbo A., Sezer O., Rajkumar S. V., Durie B. G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Chanan Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., CAVO, MICHELE, Kumar S.K., Lee J.H., Lahuerta J.J., Morgan G., Richardson P.G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S.K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J.S., Orlowski R., Palumbo A., Sezer O., Rajkumar S.V., Durie B.G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet-Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben-Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Cavo M, Chanan-Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García-Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., and Hematology
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, NATURAL HISTORY, Antineoplastic Agents, Context (language use), RELAPSE, Article, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Elotuzumab, Survival analysis, Multiple myeloma, Aged, Aged, 80 and over, Isatuximab, Bortezomib, business.industry, Hematology, Middle Aged, Pomalidomide, medicine.disease, Survival Analysis, Surgery, Regimen, SURVIVAL, Disease Progression, Female, Multiple Myeloma, business, medicine.drug
Abstract: Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T-0). The median age at diagnosis was 58 years, and time from diagnosis to T-0 was 3.3 years. Following T-0, 213 (74%) patients had a treatment recorded with one or more regimens (median = 1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including >= partial response in 69 (32%). The median overall survival and event-free survival from T-0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. Leukemia (2012) 26, 149-157; doi:10.1038/leu.2011.196; published online 29 July 2011
Published: 2012
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15. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

Author: Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M, CAVO, MICHELE, Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M, Cavo M, Hematology, and Radiology & Nuclear Medicine
Subjects: Cancer Research, medicine.medical_specialty, Myeloma protein, health care facilities, manpower, and services, education, Asymptomatic, Monoclonal Gammopathy of Undetermined Significance, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, immune system diseases, Internal medicine, hemic and lymphatic diseases, medicine, AL amyloidosis, Humans, Risk factor, Multiple myeloma, health care economics and organizations, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, business.industry, Macroglobulinemia, Hematology, medicine.disease, Prognosis, 3. Good health, Surgery, Oncology, 030220 oncology & carcinogenesis, Serum protein electrophoresis, Practice Guidelines as Topic, Disease Progression, medicine.symptom, business, Multiple Myeloma, Monoclonal gammopathy of undetermined significance
Abstract: International Myeloma Working Group22.-- et al., Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein
Published: 2010

16. Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

Author: Ng, MCY, Shriner, D, Chen, BH, Li, J, Chen, WM, Guo, X, Liu, J, Bielinski, SJ, Yanek, LR, Nalls, MA, Comeau, ME, Rasmussen-Torvik, LJ, Jensen, RA, Evans, DS, Sun, YV, An, P, Patel, SR, Lu, Y, Long, J, Armstrong, LL, Wagenknecht, L, Yang, L, Snively, BM, Palmer, ND, Mudgal, P, Langefeld, CD, Keene, KL, Freedman, BI, Mychaleckyj, JC, Nayak, U, Raffel, LJ, Goodarzi, MO, Chen, YDI, Taylor, HA, Correa, A, Sims, M, Couper, DJ, Pankow, JS, Boerwinkle, E, Adeyemo, A, Doumatey, A, Chen, G, Mathias, RA, Vaidya, D, Singleton, AB, Zonderman, AB, Igo, RP, Sedor, JR, Zondervan, KT, Kabagambe, EK, Siscovick, DS, McKnight, B, Rice, K, Liu, Y, Hsueh, WC, Zhao, W, Bielak, LF, Kraja, A, Province, MA, Bottinger, EP, Gottesman, O, Cai, Q, Zheng, W, Blot, WJ, Lowe, WL, Pacheco, JA, Crawford, DC, Yang, TP, Wilk, A, Grundberg, E, Tsoka, S, Rich, SS, Hayes, MG, Shu, XO, and Loos, RJF
Subjects: endocrine system diseases
Abstract: © 2014. Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10−94
Published: 2014
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17. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

Author: Traylor, M, Farrall, M, Holliday, EG, Sudlow, C, Hopewell, JC, Cheng, YC, Fornage, M, Ikram, MA, Malik, R, Bevan, S, Thorsteinsdottir, U, Nalls, MA, Longstreth, WT, Wiggins, KL, Yadav, S, Parati, EA, DeStefano, AL, Worrall, BB, Kittner, SJ, Khan, MS, Reiner, AP, Helgadottir, A, Achterberg, S, Fernandez-Cadenas, I, Abboud, S, Schmidt, R, Walters, M, Chen, WM, Ringelstein, EB, O'Donnell, M, Ho, WK, Pera, J, Lemmens, R, Norrving, B, Higgins, P, Benn, M, Sale, M, Kuhlenbäumer, G, Doney, ASF, Vicente, AM, Delavaran, H, Algra, A, Davies, G, Oliveira, SA, Palmer, CNA, Deary, I, Schmidt, H, Pandolfo, M, Montaner, J, Carty, C, de Bakker, PIW, Kostulas, K, Ferro, JM, van Zuydam, NR, Valdimarsson, E, Nordestgaard, BG, Lindgren, A, Thijs, V, Slowik, A, Saleheen, D, Paré, G, Berger, K, Thorleifsson, G, Hofman, A, Mosley, TH, Mitchell, BD, Furie, K, Clarke, R, Levi, C, Seshadri, S, Gschwendtner, A, Boncoraglio, GB, Sharma, P, Bis, JC, Gretarsdottir, S, Psaty, BM, Rothwell, PM, Rosand, J, Radiology & Nuclear Medicine, Cardiology, and Epidemiology
Subjects: musculoskeletal diseases, medicine.medical_specialty, Neurology, endocrine system diseases, infarction, Population, Clinical Neurology, MEDLINE, population, Genome-wide association study, Disease, Bioinformatics, Article, diseases, Brain Ischemia, Doenças Cardio e Cérebro-vasculares, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, map, Databases, Genetic, Humans, Medicine, Genetic Predisposition to Disease, education, Stroke, 030304 developmental biology, Genetic association, sequence variants, 0303 health sciences, education.field_of_study, common, business.industry, prkch, nutritional and metabolic diseases, medicine.disease, 3. Good health, Meta-analysis, loci, Neurology (clinical), business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Background: Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. Methods: We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. Findings: We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10-16) and ZFHX3 (p=2·28×10-8), and for large-vessel stroke at a 9p21 locus (p=3·32×10-5) and HDAC9 (p=2·03×10-12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p
Published: 2012
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18. Knowledge, attitudes and practices regarding human papillomavirus vaccination among young women attending a tertiary institution in Singapore

Author: Zhuang, QY, primary, Wong, RX, additional, Chen, WM, additional, and Guo, XX, additional
Published: 2015
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19. The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement

Author: Hussein, Ma, Vrionis, Fd, Allison, R, Berenson, J, Berven, S, Erdem, E, Giralt, S, Jagannath, S, Kyle, Ra, Legrand, S, Pflugmacher, R, Raje, N, Rajkumar, Sv, Randall, Rl, Roodman, D, Siegel, D, Vescio, R, Zonder, J, Durie, Bg, Alexanian R, International Myeloma Working G. r. o. u. p., Anderson, K, Attal, M, Avet Loiseau, H, Badros, A, Bergsagel, L, Bladé, J, Barlogie, B, Batille, R, Beksac, M, Belch, A, Bensinger, B, Boccadoro, M, Cavo, M, Chen, Wm, Child, T, Chim, J, Comenzo, R, Crowley, J, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimipoulous, M, Dispenzieri, A, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, Gertz, M, Gibson, J, Goldschmidt, H, Greipp, P, Hajek, R, Hardan, I, Harousseau, Jl, Hata, H, Hattori, Y, Ho, J, Hungria, V, Hussein, M, Ida, S, Jacobs, P, Jian, H, Joshua, D, Kawano, M, Kumar, S, Kyle, R, Lahuerta, J, Lee, Jh, Lokhorst, H, Ludwig, H, Leleu, X, Maiolino, A, Mehta, J, Merlini, G, Moreau, P, Morgan, G, Munshi, N, Palumbo, Antonio, Pavlovsky, S, Niesvizky, R, Novis, Y, Nouel, A, Powles, R, Pilarski, L, Reece, D, Reiman, T, Richardson, P, Morales, Ar, Sezer, O, Shaughnessy, J, Shimizu, K, Tricot, G, San Miguel, J, Singhal, S, Sonneveld, P, Shustik, C, Spencer, A, Stewart, K, Tosi, P, Turesson, I, Van Ness, B, Van Riet, I, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, Yehuda, Db, and Zonder, J.
Published: 2008

20. Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

Author: Liu, CT, Monda, KL, Taylor, KC, Lange, L, Demerath, EW, Palmas, W, Wojczynski, MK, Ellis, JC, Vitolins, MZ, Liu, S, Papanicolaou, GJ, Irvin, MR, Xue, L, Griffin, PJ, Nalls, MA, Adeyemo, A, Liu, J, Li, G, Ruiz-Narvaez, EA, Chen, WM, Chen, F, Henderson, BE, Millikan, RC, Ambrosone, CB, Strom, SS, Guo, X, Andrews, JS, Sun, YV, Mosley, TH, Yanek, LR, Shriner, D, Haritunians, T, Rotter, JI, Speliotes, EK, Smith, M, Rosenberg, L, Mychaleckyj, J, Nayak, U, Spruill, I, Garvey, WT, Pettaway, C, Nyante, S, Bandera, EV, Britton, AF, Zonderman, AB, Rasmussen-Torvik, LJ, Chen, YDI, Ding, J, Lohman, K, Kritchevsky, SB, Zhao, W, Peyser, PA, Kardia, SLR, Kabagambe, E, Broeckel, U, Chen, G, Zhou, J, Wassertheil-Smoller, S, Neuhouser, ML, Rampersaud, E, Psaty, B, Kooperberg, C, Manson, JAE, Kuller, LH, Ochs-Balcom, HM, Johnson, KC, Sucheston, L, Ordovas, JM, Palmer, JR, Haiman, CA, McKnight, B, Howard, BV, Becker, DM, Bielak, LF, Liu, Y, Allison, MA, Grant, SFA, Burke, GL, Patel, SR, Schreiner, PJ, Borecki, IB, Evans, MK, Taylor, H, Sale, MM, Howard, V, Carlson, CS, Rotimi, CN, Cushman, M, Harris, TB, Reiner, AP, Cupples, LA, North, KE, Fox, CS, Liu, CT, Monda, KL, Taylor, KC, Lange, L, Demerath, EW, Palmas, W, Wojczynski, MK, Ellis, JC, Vitolins, MZ, Liu, S, Papanicolaou, GJ, Irvin, MR, Xue, L, Griffin, PJ, Nalls, MA, Adeyemo, A, Liu, J, Li, G, Ruiz-Narvaez, EA, Chen, WM, Chen, F, Henderson, BE, Millikan, RC, Ambrosone, CB, Strom, SS, Guo, X, Andrews, JS, Sun, YV, Mosley, TH, Yanek, LR, Shriner, D, Haritunians, T, Rotter, JI, Speliotes, EK, Smith, M, Rosenberg, L, Mychaleckyj, J, Nayak, U, Spruill, I, Garvey, WT, Pettaway, C, Nyante, S, Bandera, EV, Britton, AF, Zonderman, AB, Rasmussen-Torvik, LJ, Chen, YDI, Ding, J, Lohman, K, Kritchevsky, SB, Zhao, W, Peyser, PA, Kardia, SLR, Kabagambe, E, Broeckel, U, Chen, G, Zhou, J, Wassertheil-Smoller, S, Neuhouser, ML, Rampersaud, E, Psaty, B, Kooperberg, C, Manson, JAE, Kuller, LH, Ochs-Balcom, HM, Johnson, KC, Sucheston, L, Ordovas, JM, Palmer, JR, Haiman, CA, McKnight, B, Howard, BV, Becker, DM, Bielak, LF, Liu, Y, Allison, MA, Grant, SFA, Burke, GL, Patel, SR, Schreiner, PJ, Borecki, IB, Evans, MK, Taylor, H, Sale, MM, Howard, V, Carlson, CS, Rotimi, CN, Cushman, M, Harris, TB, Reiner, AP, Cupples, LA, North, KE, and Fox, CS
Abstract: Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10-6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10-8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10-8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10-8; RREB1: p = 5.7×10-8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distr
Published: 2013

21. Genome-wide analysis of blood pressure variability and ischemic stroke

Author: Yadav, S, Cotlarciuc, I, Munroe, PB, Khan, MS, Nalls, MA, Bevan, S, Cheng, YC, Chen, WM, Malik, R, Mccarthy, NS, Holliday, EG, Speed, D, Hasan, N, Pucek, M, Rinne, PE, Sever, P, Stanton, A, Shields, DC, Maguire, JM, Mcevoy, M, Scott, RJ, Ferrucci, L, Macleod, MJ, Attia, J, Markus, HS, Sale, MM, Worrall, BB, Mitchell, BD, Dichgans, M, Sudlow, C, Meschia, JF, Rothwell, PM, Caulfield, M, Sharma, P, Yadav, S, Cotlarciuc, I, Munroe, PB, Khan, MS, Nalls, MA, Bevan, S, Cheng, YC, Chen, WM, Malik, R, Mccarthy, NS, Holliday, EG, Speed, D, Hasan, N, Pucek, M, Rinne, PE, Sever, P, Stanton, A, Shields, DC, Maguire, JM, Mcevoy, M, Scott, RJ, Ferrucci, L, Macleod, MJ, Attia, J, Markus, HS, Sale, MM, Worrall, BB, Mitchell, BD, Dichgans, M, Sudlow, C, Meschia, JF, Rothwell, PM, Caulfield, M, and Sharma, P
Abstract: Background and Purpose-Visit-to-visit variability in blood pressure (vBP) is associated with ischemic stroke. We sought to determine whether such variability has genetic causes and whether genetic variants associated with BP variability are also associated with ischemic stroke. Methods-A Genome Wide Association Study (GWAS) for loci influencing BP variability was undertaken in 3802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study, in which long-term visit-to-visit and within-visit BP measures were available. Because BP variability is strongly associated with ischemic stroke, we genotyped the sentinel single nucleotide polymorphism in an independent ischemic stroke population comprising 8624 cases and 12 722 controls and in 3900 additional (Scandinavian) participants from the ASCOT study to replicate our findings. Results-The ASCOT discovery GWAS identified a cluster of 17 correlated single nucleotide polymorphisms within the NLGN1 gene (3q26.31) associated with BP variability. The strongest association was with rs976683 (P=1.4×10-8). Conditional analysis of rs976683 provided no evidence of additional independent associations at the locus. Analysis of rs976683 in patients with ischemic stroke found no association for overall stroke (odds ratio, 1.02; 95% CI, 0.97-1.07; P=0.52) or its subtypes: cardioembolic (odds ratio, 1.07; 95% CI, 0.97-1.16; P=0.17), large vessel disease (odds ratio, 0.98; 95% CI, 0.89-1.07; P=0.60), and small vessel disease (odds ratio, 1.07; 95% CI, 0.97-1.17; P=0.19). No evidence for association was found between rs976683 and BP variability in the additional (Scandinavian) ASCOT participants (P=0.18). Conclusions-We identified a cluster of single nucleotide polymorphisms at the NLGN1 locus showing significant association with BP variability. Follow-up analyses did not support an association with risk of ischemic stroke and its subtypes. © 2013 American Heart Association, Inc.
Published: 2013

22. Strain relaxation in GaNxP1-x alloy: Effect on optical properties

Author: Buyanova, IA, Chen, WM, Goldys, EM, Phillips, MR, Xin, HP, and Tu, CW
Subjects: General Physics
Abstract: By using scanning electron microscopy and cathodoluminescence (CL), a decrease in radiative efficiency of GaNP alloy with increasing N content is seen due to the formation of structural defects. The defect formation is attributed to relaxation of tensile strain in the GaNP layer, which is lattice mismatched to GaP substrate. Several types of extended defects including dislocations, microcracks and pits are revealed in partly relaxed GaNxP1-x epilayers with x≥1.9%, whereas coherently strained layers exhibit high crystalline quality for x up to 4%. According to the CL measurements, all extended defects act as competing, non-radiative channels leading to the observed strong decrease in the radiative efficiency. From CL mapping experiments, non-uniformity of strain distribution around the extended defects is partly responsible for the broadening of the photoluminescence (PL) spectra recorded in the macro-PL experiments. © 2001 Elsevier Science B.V. All rights reserved.
Published: 2001

23. Evaluation of 15 functional candidate genes for association with chronic otitis media with effusion and/or recurrent otitis media (COME/ROM)

Author: Sale, MM, Chen, WM, Weeks, DE, Mychaleckyj, JC, Hou, X, Marion, M, Segade, F, Casselbrant, ML, Mandel, EM, Ferrell, RE, Rich, SS, Daly, KA, Sale, MM, Chen, WM, Weeks, DE, Mychaleckyj, JC, Hou, X, Marion, M, Segade, F, Casselbrant, ML, Mandel, EM, Ferrell, RE, Rich, SS, and Daly, KA
Abstract: DNA sequence variants in genes involved in the innate immune response and secondary response to infection may confer susceptibility to chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). We evaluated single nucleotide polymorphisms (SNPs) in 15 functional candidate genes. A total of 99 SNPs were successfully genotyped on the Sequenom platform in 142 families (618 subjects) from the Minnesota COME/ROM Family Study. Data were analyzed for association with COME/ROM using the Generalized Disequilibrium Test (GDT). Sex and age at exam were adjusted as covariates, relatedness was accounted for, and genotype differences from all phenotypically discordant relative pairs were utilized to measure the evidence of association between COME/ROM and each SNP. SNP rs2735733 in the region of the mucin 5, subtypes A/C gene (MUC5AC) exhibited nominal evidence for association with COME/ROM (P = 0.002). Two additional SNPs from this region had P values<0.05. Other variants exhibiting associations with COME/ROM at P<0.05 included the SCN1B SNP rs8100085 (P = 0.013), SFTPD SNP rs1051246 (P = 0.039) and TLR4 SNP rs2770146 (P = 0.038). However, none of these associations replicated in an independent sample of COME/ROM families. The candidate gene variants examined do not appear to make a major contribution to COME/ROM susceptibility, despite a priori evidence from functional or animal model studies for a role in COME/ROM pathology. © 2011 Sale et al.
Published: 2011

24. Distribution of culturable endophytic bacteria in aquatic plants and their potential for bioremediation in polluted waters

Author: Chen, WM, primary, Tang, YQ, additional, Mori, K, additional, and Wu, XL, additional
Published: 2012
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25. Fuzzy intelligent control of automotive vibration via magneto-rheological damper

Author: Li, R, Chen, WM, Yu, M, Liu, DK, Li, R, Chen, WM, Yu, M, and Liu, DK
Abstract: Based on analyses of characteristics of Magneto-Theological (MR) damper, a hierarchical fuzzy intelligent controller is proposed for vibration control of an automotive vehicle with MR dampers. This controller consists of control level and coordination level. In the control level, a semi-active fuzzy logic controller is designed for each MR suspension system based on a hybrid control strategy of sky-hook control and ground-hook control. In the coordination level, a coordination controller is designed to coordinate the four independent semi-active fuzzy logic controllers by adjusting their output parameters according to the system feedback. To validate the results of hierarchical fuzzy intelligent control, a MR semi-active suspension control and test system is set up and is implemented on a mini bus, which is equipped with four controllable MR dampers. Test results indicate that the hierarchical fuzzy intelligent controller can effectively reduce the vertical vibration and improve the ride comfort and handle stability of automobile.
Published: 2004

26. Clinical trials of TCM and Parkinson's disease in China

Author: Lim, D, primary, Chen, WM, additional, and Lian, XF, additional
Published: 2010
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27. Role of Temperature in the Growth of Silver Nanoparticles Through a Synergetic Reduction Approach

Author: Jiang, XC, primary, Chen, WM, additional, Chen, CY, additional, Xiong, SX, additional, and Yu, AB, additional
Published: 2010
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28. 20-Hydroxyecdysone attenuates TGF-β1-induced renal cellular fibrosis in proximal tubule cells.

Author: Hung TJ, Chen WM, Liu SF, Liao TN, Lee TC, Chuang LY, Guh JY, Hung CY, Hung YJ, Chen PY, Hsieh PF, Yang YL, Hung, Tsung-Jen, Chen, Wei-Ming, Liu, Shu-Fen, Liao, Tung-Nan, Lee, Tao-Chen, Chuang, Lea-Yea, Guh, Jinn-Yuh, and Hung, Chien-Ya
Abstract: Unlabelled: Renal fibrosis progresses to end stage of diabetes kidney disease, which causes irreversible progressive proximal tubular injury. In a previous study, 20-hydroxyecdysterone (20-HE), a phytoecdysteroid, attenuated renal injury in diabetes models. However, the fibrosis regulatory role remains to be investigated. Methods: The proximal tubular epithelial cells (designated as HK-2) were treated for 48 h with TGF-β1 (5 ng/ml) in different concentrations of 20-HE (0 to 500 nM/ml) in the last 24 h of culture. The extracellular fibronectin was measured by ELISA assay. Western blot and immunofluorescence were used to evaluate the expression of TGF-β1/Smads transducer (including Smad2/3, 4, and 7), epithelial and mesenchymal markers (e.g. E-cadherin and α-smooth muscle actin) and Snail (transcriptional regulators for EMT). Results: 20-HE reverses TGF-β1-induced increase in fibronectin (both intracellular and extracellular fibronectin). Simultaneously, 20-HE reverses TGF-β1-induced down-regulation of Smad7. In addition, 20-HE significantly attenuates TGF-β1-induced upregulation of Smad2/3 and pSmad2/3, and downregulation of E-Cadherin. Moreover, 20-HE dramatically suppresses TGF-β1-induced increases in the expression of Snail. Conclusion: We propose that 20-HE is a potential fibrosis antagonist for renal proximal tubule cells. 20-HE might act through suppressing post-receptor signaling of TGF-β1 and restoring tubule epithelial character by blocking the expression of Snail. [ABSTRACT FROM AUTHOR]
Published: 2012
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29. Clinical comparison of valgus and varus deformities in primary total knee arthroplasty following midvastus approach.

Author: Chou PH, Chen WM, Chen CF, Chiang CC, Liu CL, and Chen TH
Published: 2012

30. Are myocardial infarction--associated single-nucleotide polymorphisms associated with ischemic stroke?

Author: Cheng YC, Anderson CD, Bione S, Keene K, Maguire JM, Nalls M, Rasheed A, Zeginigg M, Attia J, Baker R, Barlera S, Biffi A, Bookman E, Brott TG, Brown RD Jr, Chen F, Chen WM, Ciusani E, Cole JW, and Cortellini L
Published: 2012
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31. Transcobalamin 2 variant associated with poststroke homocysteine modifies recurrent stroke risk.

Author: Hsu FC, Sides EG, Mychaleckyj JC, Worrall BB, Elias GA, Liu Y, Chen WM, Coull BM, Toole JF, Rich SS, Furie KL, Sale MM, Hsu, F-C, Sides, E G, Mychaleckyj, J C, Worrall, B B, Elias, G A, Liu, Y, Chen, W-M, and Coull, B M
Published: 2011
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32. Tests for genetic interactions in type 1 diabetes: linkage and stratification analyses of 4,422 affected sib-pairs.

Author: Morahan G, Mehta M, James I, Chen WM, Akolkar B, Erlich HA, Hilner JE, Julier C, Nerup J, Nierras C, Pociot F, Todd JA, Rich SS, Type 1 Diabetes Genetics Consortium, Morahan, Grant, Mehta, Munish, James, Ian, Chen, Wei-Min, Akolkar, Beena, and Erlich, Henry A
Abstract: Objective: Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1 diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions.Research Design and Methods: To address this issue, the Type 1 Diabetes Genetics Consortium recruited 3,892 families, including 4,422 affected sib-pairs. After genotyping 6,090 markers, linkage analyses of these families were performed, using a novel method and taking into account factors such as genotype at known susceptibility loci.Results: Evidence for linkage was robust at the HLA and INS loci, with logarithm of odds (LOD) scores of 398.6 and 5.5, respectively. There was suggestive support for five other loci. Stratification by other risk factors (including HLA and age at diagnosis) identified one convincing region on chromosome 6q14 showing linkage in male subjects (corrected LOD = 4.49; replication P = 0.0002), a locus on chromosome 19q in HLA identical siblings (replication P = 0.006), and four other suggestive loci.Conclusions: This is the largest linkage study reported for any disease. Our data indicate there are no major type 1 diabetes subtypes definable by linkage analyses; susceptibility is caused by actions of HLA and an apparently random selection from a large number of modest-effect loci; and apart from HLA and INS, there is no important susceptibility factor discoverable by linkage methods. [ABSTRACT FROM AUTHOR]
Published: 2011
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33. The prognosis for patients with osteosarcoma who have received prior manipulative therapy.

Author: Wu PK, Chen WM, Lee OK, Chen CF, Huang CK, and Chen TH
Published: 2010
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34. Iatrogenic radial nerve palsy after operative management of humeral shaft fractures.

Author: Wang JP, Shen WJ, Chen WM, Huang CK, Shen YS, and Chen TH
Published: 2009
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35. Periprosthetic femoral supracondylar fracture after total knee arthroplasty with navigation system.

Author: Li CH, Chen TH, Su YP, Shao PC, Lee KS, and Chen WM
Published: 2008

36. Effects of norepinephrine in the presence of adrenergic antagonists and different ionic media upon the mechanical and 86 rubidium efflux responses in vascular smooth muscle

Author: Sunahara Fa and Chen Wm
Subjects: medicine.medical_specialty, Contraction (grammar), Vascular smooth muscle, Cell Membrane Permeability, Membrane permeability, Physiology, Guinea Pigs, chemistry.chemical_element, Propranolol, Calcium, In Vitro Techniques, Membrane Potentials, Norepinephrine, Phentolamine, Mesenteric Veins, Physiology (medical), Internal medicine, medicine, Animals, Pharmacology, Radioisotopes, Dose-Response Relationship, Drug, Chemistry, Portal Vein, Muscle, Smooth, General Medicine, Rubidium, Endocrinology, Potassium, Sympatholytics, Efflux, medicine.symptom, medicine.drug, Muscle contraction, Muscle Contraction
Abstract: The action of norepinephrine (NE) on the isolated guinea pig mesenteric–portal vein was studied in relation to its mechanical and 86rubidium (86Rb) efflux responses using a continuous flow technique. NE (1 × 10−8 to 2 × 10−6 g/ml) produced dose-dependent increases in both contraction and 86Rb efflux. Phentolamine but not propranolol inhibited both responses to NE. In high potassium medium the 86Rb efflux response was more markedly depressed than the mechanical response. In calcium-deficient medium the NE-induced contraction was abolished but the 86Rb efflux response was potentiated and in high calcium medium there was a significant depression of the mechanical response but no significant difference in the 86Rb efflux response. There seems to be an optimal calcium ion concentration at 2.5 mM for the mechanical responses to NE. These experiments suggest that contraction correlates strongly with an increase in membrane permeability, calcium is required for vascular muscle contraction, and contraction can be initiated by a mechanism independent of changes in membrane potential.
Published: 1972

37. In situ contact analysis of the prosthesis components of Prodisc-L in lumbar spine following total disc replacement.

Author: Chen WM, Park C, Lee K, and Lee S
Abstract: STUDY DESIGN: A three-dimensional, nonlinear finite element analysis was performed to predict the in situ contact interaction of prosthesis components of the Prodisc-L in a multisegmental lumbar model following total disc replacement (TDR). OBJECTIVE: Efforts were made to investigate how the TDR implant contact characteristics could affect the 3-dimensional kinematics, facet loads of the lumbar spine following TDR. SUMMARY OF BACKGROUND DATA: Although spinal motion analyses of human lumbar cadaveric models after Prodisc TDR have been widely studied, the interaction of the disc prosthesis, particularly its in situ contact mechanics, is never known. METHODS: A validated intact multisegmental lumbar finite element model L2-L4 was altered to accommodate the TDR prosthesis through anterior approach. At L3-L4 disc space, the Prodisc-L of 6 degrees lordosis angle was implanted centrally. The model was subjected to compressive preload and pure moments to create flexion, extension, lateral bending, and axial rotation motion in physiologic range. The contact interaction between the superior component of Prodisc-L and the UHMWPE inlay were assessed in terms of contact region (CR), contact area (CA), and contact pressure (CP). Parameters of range of motion (ROM) and facet loading transfer were simultaneously analyzed and compared with those of the intact model. RESULTS: The predicted contact area was 3.5 times larger in flexion than that observed in extension, whereas the maximum contact pressure in the disc articulation was very similar with 15.1 MPa for flexion and 14.5 MPa for extension. Joint surface incongruence was developed in extension motion. The implanted model exhibited a 91.4% increase in ROM accompanied by a 150.6% rising in facet force during extension, while the flexion motion showed the least effects of TDR. In lateral bending and axial rotation, the abnormal joint 'lift off' was not seen. CONCLUSION: The in situ function of the TDR prosthesis was highly dependent on how well the device could incorporate itself into the mechanical environment in the disc space, which has been determined by the rest of the spinal structures, including the retained disc anulus, articular facets, ligaments, vertebrae, and muscular stabilizers. The different contact interaction of the artificial disc components revealed here could be attributed to the violation of this mechanical environment which, in turn, may bring adverse effects to those spinal elements. [ABSTRACT FROM AUTHOR]
Published: 2009
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38. On the Origin of Seebeck Coefficient Inversion in Highly Doped Conducting Polymers

Author: Kai Xu, Tero‐Petri Ruoko, Morteza Shokrani, Dorothea Scheunemann, Hassan Abdalla, Hengda Sun, Chi‐Yuan Yang, Yuttapoom Puttisong, Nagesh B. Kolhe, José Silvestre Mendoza Figueroa, Jonas O. Pedersen, Thomas Ederth, Weimin M. Chen, Magnus Berggren, Samson A. Jenekhe, Daniele Fazzi, Martijn Kemerink, Simone Fabiano, Tampere University, Materials Science and Environmental Engineering, Xu K, Ruoko TP, Shokrani M, Scheunemann D, Abdalla H, Sun HD, Yang CY, Puttisong Y, Kolhe NB, Figueroa JSM, Pedersen JO, Ederth T, Chen WM, Berggren M, Jenekhe SA, Fazzi D, Kemerink M, and Fabiano S
Subjects: 218 Environmental engineering, Seebeck coefficient, Condensed Matter Physics, Electronic, Optical and Magnetic Materials, thermoelectric application, Biomaterials, Condensed Matter::Materials Science, organic electrochemical transistor, 216 Materials engineering, Condensed Matter::Superconductivity, Electrochemistry, thermoelectric, DFT, spectroscopy, electrochemistry, spin, polarons, conducting polymers, Den kondenserade materiens fysik
Abstract: A common way of determining the majority charge carriers of pristine and doped semiconducting polymers is to measure the sign of the Seebeck coefficient. However, a polarity change of the Seebeck coefficient has recently been observed to occur in highly doped polymers. Here, it is shown that the Seebeck coefficient inversion is the result of the density of states filling and opening of a hard Coulomb gap around the Fermi energy at high doping levels. Electrochemical n-doping is used to induce high carrier density (>1 charge/monomer) in the model system poly(benzimidazobenzophenanthroline) (BBL). By combining conductivity and Seebeck coefficient measurements with in situ electron paramagnetic resonance, UV-vis-NIR, Raman spectroelectrochemistry, density functional theory calculations, and kinetic Monte Carlo simulations, the formation of multiply charged species and the opening of a hard Coulomb gap in the density of states, which is responsible for the Seebeck coefficient inversion and drop in electrical conductivity, are uncovered. The findings provide a simple picture that clarifies the roles of energetic disorder and Coulomb interactions in highly doped polymers and have implications for the molecular design of next-generation conjugated polymers. Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [2020-03243]; Olle Engkvists Stiftelse [204-0256]; European CommissionEuropean CommissionEuropean Commission Joint Research Centre [GA-955837, GA-799477]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [SFO-Mat-LiU 2009-00971]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanys Excellence Strategy via the Excellence Cluster 3D Matter Made to OrderGerman Research Foundation (DFG) [EXC-2082/1-390761711]; Carl Zeiss Foundation; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [FA 1502/1-1]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [52173156]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [ITM17-0316]
Published: 2022

39. Serum magnesium and calcium levels in relation to ischemic stroke Mendelian randomization study

Author: Susanna C. Larsson, Matthew Traylor, Stephen Burgess, Giorgio B. Boncoraglio, Christina Jern, Karl Michaëlsson, Hugh S. Markus, Rainer Malik, Ganesh Chauhan, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab HH Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, raci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown, Adam S Butterworth, Caty Carrera, Cara L Carty, Daniel I Chasman, Wei-Min Chen, John W Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul IW de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Vilmundur Gudnason, Stefan Gustafsson, Jeffrey Haessler, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Susan R Heckbert, Elizabeth G Holliday, George Howard, Fang-Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei-Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Toshiharu Ninomiya, Martin J O'Donnell, Bruce M Psaty, Sara L Pulit, Kristiina Rannikmäe, Alexander P Reiner, Kathryn M Rexrode, Kenneth Rice, Stephen S Rich, Paul M Ridker, Natalia S Rost, Peter M Rothwell, Jerome I Rotter, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie LM Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D Taylor, Vincent NS Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Christophe Tzourio, Cornelia M van Duijn, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil-Smoller, James G Wilson, Kerri L Wiggins, Qiong Yang, Salim Yusuf, Najaf Amin, Hugo S Aparicio, Donna K Arnett, John Attia, Alexa S Beiser, Claudine Berr, Julie E Buring, Mariana Bustamante, Valeria Caso, Yu-Ching Cheng, Seung Hoan Choi, Ayesha Chowhan, Natalia Cullell, Jean-François Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dörr, Gunnar Engström, Ian Ford, Wander S Gurpreet, Anders Hamsten, Laura Heitsch, Atsushi Hozawa, Laura Ibanez, Andreea Ilinca, Martin Ingelsson, Motoki Iwasaki, Rebecca D Jackson, Katarina Jood, Pekka Jousilahti, Sara Kaffashian, Lalit Kalra, Masahiro Kamouchi, Takanari Kitazono, Olafur Kjartansson, Manja Kloss, Peter J Koudstaal, Jerzy Krupinski, Daniel L Labovitz, Cathy C Laurie, Christopher R Levi, Linxin Li, Lars Lind, Cecilia M Lindgren, Vasileios Lioutas, Yong Mei Liu, Oscar L Lopez, Hirata Makoto, Nicolas Martinez-Majander, Koichi Matsuda, Naoko Minegishi, Joan Montaner, Andrew P Morris, Elena Muiño, Martina Müller-Nurasyid, Bo Norrving, Soichi Ogishima, Eugenio A Parati, Leema Reddy Peddareddygari, Nancy L Pedersen, Joanna Pera, Markus Perola, Alessandro Pezzini, Silvana Pileggi, Raquel Rabionet, Iolanda Riba-Llena, Marta Ribasés, Jose R Romero, Jaume Roquer, Anthony G Rudd, Antti-Pekka Sarin, Ralhan Sarju, Chloe Sarnowski, Makoto Sasaki, Claudia L Satizabal, Mamoru Satoh, Naveed Sattar, Norie Sawada, Gerli Sibolt, Ásgeir Sigurdsson, Albert Smith, Kenji Sobue, Carolina Soriano-Tárraga, Tara Stanne, O Colin Stine, David J Stott, Konstantin Strauch, Takako Takai, Hideo Tanaka, Kozo Tanno, Alexander Teumer, Liisa Tomppo, Nuria P Torres-Aguila, Emmanuel Touze, Shoichiro Tsugane, Andre G Uitterlinden, Einar M Valdimarsson, Sven J van der Lee, Henry Völzke, Kenji Wakai, David Weir, Stephen R Williams, Charles DA Wolfe, Quenna Wong, Huichun Xu, Taiki Yamaji, Dharambir K Sanghera, Olle Melander, Daniel Strbian, Israel Fernandez-Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C Hopewell, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Sudha Seshadri, Myriam Fornage, Hugh S Markus, Joanna MM Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans, Berr, Claudine, Unit of Cardiovascular and Nutritional Epidemiology [Stockholm, Sweden], Karolinska Institutet [Stockholm]-Institute of Environmental Medicine [Stockholm, Sweden], Stroke Research Group [London, UK] (Department of Brain Repair and Rehabilitation), University of London - UCL [London, UK], MRC Biostatistics Unit [Cambridge, UK], University of Cambridge [UK] (CAM), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Section of Clinical Immunology [Uppsala, Sweden] (Department of Immunology, Genetics and Pathology), Uppsala University, Department of Surgical Sciences [Uppsala, Sweden], This work was supported by the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Swedish Research Council. Hugh Markus is supported by an NIHR Senior Investigator award. His and Matthew Traylor’s work is supported by infrastructural support from the Cambridge University Hospitals Trust NIHR Biomedical Research Centre., MEGASTROKE project of the International Stroke Genetics Consortium : Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson CD, Chong M, Adams HH, Ago T, Almgren P, Amouyel P, Ay H, Bartz RM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD Jr, Butterworth AS, Carrera C, Carty CL, Chasman DI, Chen WM, Cole JW, Correa A, Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PI, DeStefano AL, Hoed MD, Duan Q, Engelter ST, Falcone GJ, Gottesman RF, Grewal RP, Gudnason V, Gustafsson S, Haessler J, Harris TB, Hassan A, Havulinna AS, Heckbert SR, Holliday EG, Howard G, Hsu FC, Hyacinth HI, Ikram MA, Ingelsson E, Irvin MR, Jian X, Jiménez-Conde J, Johnson JA, Jukema JW, Kanai M, Keene KL, Kissela BM, Kleindorfer DO, Kooperberg C, Kubo M, Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lee JM, Lemmens R, Leys D, Lewis CM, Lin WY, Lindgren AG, Lorentzen E, Magnusson PK, Maguire J, Manichaikul A, McArdle PF, Meschia JF, Mitchell BD, Mosley TH, Nalls MA, Ninomiya T, O'Donnell MJ, Psaty BM, Pulit SL, Rannikmäe K, Reiner AP, Rexrode KM, Rice K, Rich SS, Ridker PM, Rost NS, Rothwell PM, Rotter JI, Rundek T, Sacco RL, Sakaue S, Sale MM, Salomaa V, Sapkota BR, Schmidt R, Schmidt CO, Schminke U, Sharma P, Slowik A, Sudlow CL, Tanislav C, Tatlisumak T, Taylor KD, Thijs VN, Thorleifsson G, Thorsteinsdottir U, Tiedt S, Trompet S, Tzourio C, van Duijn CM, Walters M, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL, Yang Q, Yusuf S, Amin N, Aparicio HS, Arnett DK, Attia J, Beiser AS, Berr C, Buring JE, Bustamante M, Caso V, Cheng YC, Choi SH, Chowhan A, Cullell N, Dartigues JF, Delavaran H, Delgado P, Dörr M, Engström G, Ford I, Gurpreet WS, Hamsten A, Heitsch L, Hozawa A, Ibanez L, Ilinca A, Ingelsson M, Iwasaki M, Jackson RD, Jood K, Jousilahti P, Kaffashian S, Kalra L, Kamouchi M, Kitazono T, Kjartansson O, Kloss M, Koudstaal PJ, Krupinski J, Labovitz DL, Laurie CC, Levi CR, Li L, Lind L, Lindgren CM, Lioutas V, Liu YM, Lopez OL, Makoto H, Martinez-Majander N, Matsuda K, Minegishi N, Montaner J, Morris AP, Muiño E, Müller-Nurasyid M, Norrving B, Ogishima S, Parati EA, Peddareddygari LR, Pedersen NL, Pera J, Perola M, Pezzini A, Pileggi S, Rabionet R, Riba-Llena I, Ribasés M, Romero JR, Roquer J, Rudd AG, Sarin AP, Sarju R, Sarnowski C, Sasaki M, Satizabal CL, Satoh M, Sattar N, Sawada N, Sibolt G, Sigurdsson Á, Smith A, Sobue K, Soriano-Tárraga C, Stanne T, Stine OC, Stott DJ, Strauch K, Takai T, Tanaka H, Tanno K, Teumer A, Tomppo L, Torres-Aguila NP, Touze E, Tsugane S, Uitterlinden AG, Valdimarsson EM, van der Lee SJ, Völzke H, Wakai K, Weir D, Williams SR, Wolfe CD, Wong Q, Xu H, Yamaji T, Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Longstreth WT Jr, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell JC, Saleheen D, Stefansson K, Worrall BB, Kittner SJ, Seshadri S, Fornage M, Markus HS, Howson JM, Kamatani Y, Debette S, Dichgans M., Larsson, Susanna C [0000-0003-0118-0341], Apollo - University of Cambridge Repository, and Neurology
Subjects: medicine.medical_specialty, Neurology, Heredity, Neurologi, [SDV]Life Sciences [q-bio], chemistry.chemical_element, Calcium, Polymorphism, Single Nucleotide, Gastroenterology, Article, Brain Ischemia, Brain ischemia, 03 medical and health sciences, 0302 clinical medicine, Human genetics, Internal medicine, Mendelian randomization, Medicine, Humans, Magnesium, 030212 general & internal medicine, Stroke, Herència (Biologia), Genètica humana, business.industry, Neurosciences, Mendelian Randomization Analysis, Odds ratio, medicine.disease, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], Intracranial Embolism, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, 030217 neurology & neurosurgery, Neurovetenskaper
Abstract: Comment inThe yin and yang of magnesium and calcium: New genetic insights for stroke? [Neurology. 2019]; International audience; Objective To determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach. Methods Analyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases). Results In standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10 −4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10 −4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype. Conclusions This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.
Published: 2019
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40. A genome-wide association study of anorexia nervosa

Author: Boraska, V., Franklin, C. S., Floyd, J. A. B., Thornton, L. M., Huckins, L. M., Southam, L., Rayner, N. W., Tachmazidou, I., Klump, K. L., Treasure, J., Lewis, C. M., Schmidt, U., Tozzi, F., Kiezebrink, K., Hebebrand, J., Gorwood, P., Adan, R. A. H., Kas, M. J. H., Favaro, Angela, Santonastaso, Paolo, Fernández Aranda, F., Gratacos, M., Rybakowski, F., Dmitrzak Weglarz, M., Kaprio, J., Keski Rahkonen, A., Raevuori, A., Van Furth, E. F., Slof Op 't Landt, M. C. T., Hudson, J. I., Reichborn Kjennerud, T., Knudsen, G. P. S., Monteleone, P., Kaplan, A. S., Karwautz, A., Hakonarson, H., Berrettini, W. H., Guo, Y., Li, D., Schork, N. J., Komaki, G., Ando, T., Inoko, H., Esko, T., Fischer, K., Männik, K., Metspalu, A., Baker, J. H., Cone, R. D., Dackor, J., Desocio, J. E., Hilliard, C. E., O'Toole, J. K., Pantel, J., Szatkiewicz, J. P., Taico, C., Zerwas, S., Trace, S. E., Davis, O. S. P., Helder, S., Bühren, K., Burghardt, R., de Zwaan, M., Egberts, K., Ehrlich, S., Herpertz Dahlmann, B., Herzog, W., Imgart, H., Scherag, A., Scherag, S., Zipfel, S., Boni, C., Ramoz, N., Versini, A., Brandys, M. K., Danner, U. N., de Kovel, C., Hendriks, J., Koeleman, B. P. C., Ophoff, R. A., Strengman, E., van Elburg, A. A., Bruson, Alice, Clementi, Maurizio, Degortes, Daniela, Forzan, Monica, Tenconi, Elena, Docampo, E., Escaramís, G., Jiménez Murcia, S., Lissowska, J., Rajewski, A., Szeszenia Dabrowska, N., Slopien, A., Hauser, J., Karhunen, L., Meulenbelt, I., Slagboom, P. E., Tortorella, A., Maj, M., Dedoussis, G., Dikeos, D., Gonidakis, F., Tziouvas, K., Tsitsika, A., Papezova, H., Slachtova, L., Martaskova, D., Kennedy, J. L., Levitan, R. D., Yilmaz, Z., Huemer, J., Koubek, D., Merl, E., Wagner, G., Lichtenstein, P., Breen, G., Cohen Woods, S., Farmer, A., Mcguffin, P., Cichon, S., Giegling, I., Herms, S., Rujescu, D., Schreiber, S., Wichmann, H. E., Dina, C., Sladek, R., Gambaro, G., Soranzo, N., Julia, A., Marsal, S., Rabionet, R., Gaborieau, V., Dick, D. M., Palotie, A., Ripatti, S., Widén, E., Andreassen, O. A., Espeseth, T., Lundervold, A., Reinvang, I., Steen, V. M., Le Hellard, S., Mattingsdal, M., Ntalla, I., Bencko, V., Foretova, L., Janout, V., Navratilova, M., Gallinger, S., Pinto, D., Scherer, S. W., Aschauer, H., Carlberg, L., Schosser, A., Alfredsson, L., Ding, B., Klareskog, L., Padyukov, L., Courtet, P., Guillaume, S., Jaussent, I., Finan, C., Kalsi, G., Roberts, M., Logan, D. W., Peltonen, L., Ritchie, G. R. S., Barrett, J. C., Anderson, Carl A., Barrett, Jeffrey C., Floyd, James A. B., Franklin, Christopher S., Ralph, Mcginnis, Nicole, Soranzo, Eleftheria, Zeggini, Jennifer, Sambrook, Jonathan, Stephens, Ouwehand, Willem H., Mcardle, Wendy L., Ring, Susan M., Strachan, David P., Graeme, Alexander, Bulik, Cynthia M., Collier, David A., Conlon, Peter J., Anna, Dominiczak, Audrey, Duncanson, Adrian, Hill, Cordelia, Langford, Graham, Lord, Maxwell, Alexander P., Linda, Morgan, Leena, Peltonen, Sandford, Richard N., Neil, Sheerin, Vannberg, Fredrik O., Hannah, Blackburn, Wei Min Chen, Sarah, Edkins, Mathew, Gillman, Emma, Gray, Hunt, Sarah E., Suna Onengut Gumuscu, Simon, Potter, Rich, Stephen S., Douglas, Simpkin, Pamela, Whittaker, Estivill, X., Hinney, A., Sullivan, P. F., Collier, D. A., Zeggini, E., Bulik, C. M., Boraska, V., Franklin, Christopher S., Floyd, James A. B., Thornton, L. M., Huckins, L. M., Southam, L., Rayner, N. W., Tachmazidou, I., Klump, K. L., Treasure, J., Lewis, C. M., Schmidt, U., Tozzi, F., Kiezebrink, K., Hebebrand, J., Gorwood, P., Adan, R. A. H., Kas, M. J. H., Favaro, A., Santonastaso, P., Fernández-Aranda, F., Gratacos, M., Rybakowski, F., Dmitrzak-Weglarz, M., Kaprio, J., Keski-Rahkonen, A., Raevuori, A., Van Furth, E. F., Slof-Op 't Landt, M. C. T., Hudson, J. I., Reichborn-Kjennerud, T., Knudsen, G. P. S., Monteleone, P., Kaplan, A. S., Karwautz, A., Hakonarson, H., Berrettini, W. H., Guo, Y., Li, D., Schork, N. J., Komaki, G., Ando, T., Inoko, H., Esko, T., Fischer, K., Männik, K., Metspalu, A., Baker, J. H., Cone, R. D., Dackor, J., Desocio, J. E., Hilliard, C. E., O'Toole, J. K., Pantel, J., Szatkiewicz, J. P., Taico, C., Zerwas, S., Trace, S. E., Davis, O. S. P., Helder, S., Bühren, K., Burghardt, R., De Zwaan, M., Egberts, K., Ehrlich, S., Herpertz-Dahlmann, B., Herzog, W., Imgart, H., Scherag, A., Scherag, S., Zipfel, S., Boni, C., Ramoz, N., Versini, A., Brandys, M. K., Danner, U. N., De Kovel, C., Hendriks, J., Koeleman, B. P. C., Ophoff, R. A., Strengman, E., Van Elburg, A. A., Bruson, A., Clementi, M., Degortes, D., Forzan, M., Tenconi, E., Docampo, E., Escaramís, G., Jiménez-Murcia, S., Lissowska, J., Rajewski, A., Szeszenia-Dabrowska, N., Slopien, A., Hauser, J., Karhunen, L., Meulenbelt, I., Slagboom, P. E., Tortorella, A., Maj, M., Dedoussis, G., Dikeos, D., Gonidakis, F., Tziouvas, K., Tsitsika, A., Papezova, H., Slachtova, L., Martaskova, D., Kennedy, J. L., Levitan, R. D., Yilmaz, Z., Huemer, J., Koubek, D., Merl, E., Wagner, G., Lichtenstein, P., Breen, G., Cohen-Woods, S., Farmer, A., Mcguffin, P., Cichon, S., Giegling, I., Herms, S., Rujescu, D., Schreiber, S., Wichmann, H. -E., Dina, C., Sladek, R., Gambaro, G., Soranzo, Nicole, Julia, A., Marsal, S., Rabionet, R., Gaborieau, V., Dick, D. M., Palotie, A., Ripatti, S., Widén, E., Andreassen, O. A., Espeseth, T., Lundervold, A., Reinvang, I., Steen, V. M., Le Hellard, S., Mattingsdal, M., Ntalla, I., Bencko, V., Foretova, L., Janout, V., Navratilova, M., Gallinger, S., Pinto, D., Scherer, S. W., Aschauer, H., Carlberg, L., Schosser, A., Alfredsson, L., Ding, B., Klareskog, L., Padyukov, L., Courtet, P., Guillaume, S., Jaussent, I., Finan, C., Kalsi, G., Roberts, M., Logan, D. W., Peltonen, Leena, Ritchie, G. R. S., Barrett, Jeffrey C., Anderson, Carl A., Mcginnis, Ralph, Zeggini, Eleftheria, Sambrook, Jennifer, Stephens, Jonathan, Ouwehand, Willem H., Mcardle, Wendy L., Ring, Susan M., Strachan, David P., Alexander, Graeme, Bulik, C. M., Collier, David A., Conlon, Peter J., Dominiczak, Anna, Duncanson, Audrey, Hill, Adrian, Langford, Cordelia, Lord, Graham, Maxwell, Alexander P., Morgan, Linda, Sandford, Richard N., Sheerin, Neil, Vannberg, Fredrik O., Blackburn, Hannah, Chen, Wei-Min, Edkins, Sarah, Gillman, Mathew, Gray, Emma, Hunt, Sarah E., Onengut-Gumuscu, Suna, Potter, Simon, Rich, Stephen S., Simpkin, Dougla, Whittaker, Pamela, Estivill, X., Hinney, A., Sullivan, P. F., Martaskova D., Wellcome Trust Case Control Consortium 3, Anderson, CA., Barrett, JC., Floyd, JA., Franklin, CS., McGinnis, R., Soranzo, N., Zeggini, E., Sambrook, J., Stephens, J., Ouwehand, WH., McArdle, WL., Ring, SM., Strachan, DP., Alexander, G., Bulik, CM., Collier, DA., Conlon, PJ., Dominiczak, A., Duncanson, A., Hill, A., Langford, C., Lord, G., Maxwell, AP., Morgan, L., Peltonen, L., Sandford, RN., Sheerin, N., Vannberg, FO., Blackburn, H., Chen, WM., Edkins, S., Gillman, M., Gray, E., Hunt, SE., Onengut-Gumuscu, S., Potter, S., Rich, SS., Simpkin, D., and Whittaker, P.
Subjects: Male, Candidate gene, Anorexia Nervosa, Medizin, Genome-wide association study, anorexia nervosa, body mass index, eating disorders, genome-wide association study, GWAS, metabolic, Japan, Settore MED/14 - NEFROLOGIA, Guanine Nucleotide Exchange Factors, genome wide association study, Nuclear Protein, Genetics, Calcineurin, Eating disorder, Anorèxia nerviosa, Nuclear Proteins, Genomics, Cullin Proteins, 3. Good health, Anorexia, VDP::Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714, Anorexia nervosa (differential diagnoses), Psychiatry and Mental Health, Female, Case-Control Studie, Human, Asian Continental Ancestry Group, European Continental Ancestry Group, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, Cellular and Molecular Neuroscience, Asian People, Meta-Analysis as Topic, Genetic linkage, Humans, Genotyping, Molecular Biology, anorexia nervosa, body mass index, eating disorders, genome wide association study, GWAS, metabolic, Cullin Protein, Case-control study, Anorexia nervosa, VDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, Guanine Nucleotide Exchange Factor, Genòmica, Case-Control Studies, Carrier Protein, Carrier Proteins, Body mass index, Genome-Wide Association Study
Abstract: Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P = 3.01 x 10(-7)) in SOX2OT and rs17030795 (P = 5.84 x 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P = 5.76 x 10(-6)) between CUL3 and FAM124B and rs1886797 (P = 8.05 x 10(-6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4x10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.
Published: 2014

41. Cyclic Diguanylate G-Quadruplex Inducer-Quorum Sensing Inhibitor Hybrids as Bifunctional Anti-biofilm and Anti-virulence Agents Against Pseudomonas aeruginosa .

Author: Liu JJ, Liu J, Huang YS, Chen WM, and Lin J
Subjects: Animals, Virulence drug effects, Microbial Sensitivity Tests, Pseudomonas Infections drug therapy, Pseudomonas Infections microbiology, Pseudomonas aeruginosa drug effects, Biofilms drug effects, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents chemical synthesis, Quorum Sensing drug effects, Cyclic GMP analogs & derivatives, Cyclic GMP metabolism, Caenorhabditis elegans microbiology, G-Quadruplexes drug effects
Abstract: The release of virulence factors and biofilm formation by Pseudomonas aeruginosa are pivotal drivers of its severe pathogenicity and antibiotic resistance. Based on our prior findings, cyclic di-GMP (c-di-GMP) G-quadruplex inducers are promising biofilm inhibitors and that quorum sensing systems are central regulators of virulence, we aimed to design and synthesize c-di-GMP G-quadruplex inducer-quorum sensing inhibitor hybrids. These hybrids were envisioned as bifunctional agents with both antibiofilm and antivirulence capabilities. Hybrids A7 and A11 , characterized by their quinoline and 3-indole rings, emerged as potent inhibitors. They achieve this dual action by inducing c-di-GMP G-quadruplex formation and disrupting the las and pqs signaling system. Additionally, hybrids A7 and A11 attenuated virulence factors and inhibited the motility phenotypes of P. aeruginosa . Furthermore, when tested in in vivo Caenorhabditis elegans infection models, these hybrids, in combination with antibiotics such as tetracycline, improved survival rates, all while maintaining a favorable biosafety profile.
Published: 2024
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42. Statin Use During Concurrent Chemoradiotherapy for Advanced Nasopharyngeal Cancer.

Author: Yu JM, Chang CL, Lin KC, Chen WM, Shia BC, and Wu SY
Subjects: Humans, Female, Male, Middle Aged, Aged, Adult, Taiwan epidemiology, Neoplasm Staging, Treatment Outcome, Prognosis, Propensity Score, Nasopharyngeal Carcinoma therapy, Nasopharyngeal Carcinoma mortality, Nasopharyngeal Carcinoma pathology, Chemoradiotherapy methods, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Nasopharyngeal Neoplasms therapy, Nasopharyngeal Neoplasms mortality, Nasopharyngeal Neoplasms pathology
Abstract: Background: The objective of this study was to assess the impact of statin use on overall survival (OS) and nasopharyngeal cancer (NPC)-specific survival in patients with advanced NPC who underwent standard concurrent chemoradiotherapy (CCRT)., Patients and Methods: This propensity score matched cohort study used data from the Taiwan Cancer Registry Database and National Health Insurance Research Database to examine the impact of statin use during CCRT on both OS and NPC-specific survival., Results: Statin use during CCRT demonstrated significant and independent prognostic value for both OS and NPC-specific survival. The adjusted hazard ratio for all-cause mortality in the statin group compared with the nonstatin group was 0.48 (95% CI, 0.34-0.68; P<.0001). Similarly, the adjusted hazard ratio for NPC-specific mortality in the statin group compared with the nonstatin group was 0.43 (95% CI, 0.29-0.65; P<.0001). Rosuvastatin, atorvastatin, and lovastatin demonstrated significant efficacy in improving NPC-specific survival outcomes. Moreover, our findings indicate a dose-response relationship, with higher cumulative defined daily doses and greater daily intensity of statin use associated with reduced mortality., Conclusions: This study suggests an association between statin use during the CCRT period for NPC and potential enhancements in both OS and NPC-specific survival. Our findings indicate a possible survival benefit of rosuvastatin, atorvastatin, and lovastatin for patients with NPC undergoing CCRT. The observed dose-response relationship underscores the potential importance of higher statin use in mitigating NPC-specific mortality, but further research is needed to establish a definitive causal relationship.
Published: 2024
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43. Leg length discrepancy risk differs between fit-and-fill and taper wedge stems across Dorr types.

Author: Hung YT, Chang CY, Lee KH, Chang WL, Tsai SW, Chen CF, Wu PK, and Chen WM
Subjects: Humans, Female, Male, Middle Aged, Aged, Femur surgery, Retrospective Studies, Postoperative Complications epidemiology, Incidence, Risk Factors, Adult, Leg Length Inequality etiology, Arthroplasty, Replacement, Hip methods, Hip Prosthesis, Prosthesis Design
Abstract: Introduction: The comparison between the cementless taper wedge stem and fit-and-fill stem in total hip arthroplasty (THA) for various proximal femoral morphological types has not been thoroughly assessed. This study aimed to compare the risk of leg length discrepancy (LLD) ≥ 10 mm between these two stem types in Dorr type A, B, and C femurs., Materials and Methods: From April 2015 through April 2021, we analyzed 1178 unilateral primary cementless THA procedures. We categorized all procedures into three groups: Dorr type A (N = 220, 18.7%), B (N = 875, 74.3%), and C (N = 83, 7.0%). Within each Dorr type, we compared the incidence and risk of postoperative LLD ≥ 10 mm between the two stem types. The factors considered in the multivariate regression analyses included stem type, age, sex, body mass index, diagnosis, canal flare index, femoral cortical index and stem alignment., Results: The taper wedge stem group had a higher overall incidence of LLD ≥ 10 mm (12.8% vs. 7.4%, P = 0.012) and in Dorr type A femurs (22.2% vs. 7.6%, P = 0.014), compared with the fit-and-fill stem group. In multivariate analysis, the taper wedge stem exhibited an increased risk of LLD ≥ 10 mm only in Dorr type A femurs (aOR: 3.449, 95% CI: 1.325-8.794). The incidence and risk of LLD ≥ 10 mm were not different between the two stems in Dorr type B and C femurs., Conclusions: The taper wedge stem demonstrated an elevated risk of LLD ≥ 10 mm in Dorr type A femurs compared with the fit-and-fill stem, necessitating meticulous preoperative templating and intraoperative femoral canal preparation., Competing Interests: Declarations. Compliance with ethical standards: The ethics committee and institutional review board of Taipei Veterans General Hospital approved this study (2023-011-001BC). The requirement for informed consent was waived due to the retrospective nature of the study. The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Published: 2024
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44. Dynamic high-pressure microfluidization assisted with galactooligosaccharide-modified whey protein isolate: Investigating its effect on relieving intestinal barrier damage.

Author: Mao JH, Chen WM, Wang Y, Shao YH, Liu J, Wang XM, and Tu ZC
Subjects: Animals, Mice, Mice, Inbred BALB C, Pressure, Gastrointestinal Microbiome drug effects, Male, Rats, Cell Line, Whey Proteins pharmacology, Whey Proteins chemistry, Oligosaccharides pharmacology, Oligosaccharides chemistry, Intestinal Mucosa metabolism, Intestinal Mucosa drug effects
Abstract: The study aimed to investigating the mechanisms of relieved intestinal barrier damage by dynamic high-pressure microfluidization assisted with galactooligosaccharide- glycated whey protein isolate. The modifications changed the multi-structure, and the modified whey protein isolate could promote the proliferation of IEC-6 cells and contributed to the restoration of LPS-induced occludin damage in IEC-6 cells. Also, it could repair cyclophosphamide-induced ileal villus rupture and crypt destruction in BALB/c mice, significantly altered the abundance of dominant bacteria, which were associated with propionic acid, butyric acid, isovaleric acid, and valeric acid. Ileum transcriptomics revealed that the modified whey protein isolate significantly regulate of the levels of Cstad, Cyp11a1, and Hs6st2 genes, relating to the increase of propionic acid, isovaleric acid, and valeric acid. In conclusion, galactooligosaccharide- modified whey protein isolate could regulate the level of Cstad, Cyp11a1 and Hs6st2 genes by altering the gut microbial structure and the level of SCFAs, thereby repairing the intestinal barrier., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
Published: 2024
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45. QSOX1 facilitates dormant esophageal cancer stem cells to evade immune elimination via PD-L1 upregulation and CD8 T cell exclusion.

Author: Wei JR, Zhang B, Zhang Y, Chen WM, Zhang XP, Zeng TT, Li Y, Zhu YH, Guan XY, and Li L
Subjects: Humans, Animals, Mice, Oxidoreductases Acting on Sulfur Group Donors metabolism, Oxidoreductases Acting on Sulfur Group Donors genetics, Up-Regulation drug effects, Tumor Escape drug effects, Cell Line, Tumor, Organoselenium Compounds pharmacology, Gene Expression Regulation, Neoplastic drug effects, Reactive Oxygen Species metabolism, CD8-Positive T-Lymphocytes immunology, B7-H1 Antigen metabolism, B7-H1 Antigen genetics, Esophageal Neoplasms immunology, Esophageal Neoplasms metabolism, Esophageal Neoplasms pathology, Neoplastic Stem Cells immunology, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells drug effects
Abstract: Dormant cancer stem cells (DCSCs) exhibit characteristics of chemotherapy resistance and immune escape, and they are a crucial source of tumor recurrence and metastasis. However, the underlying mechanisms remain unrevealed. We demonstrate that enriched Gzmk + CD8 + T cells within the niche of esophageal DCSCs restrict the outgrowth of tumor mass. Nonetheless, DCSCs can escape immune elimination by enhancing PD-L1 signaling, thereby maintaining immune equilibrium. Quiescent fibroblast-derived quiescin sulfhydryl oxidase 1 (QSOX1) promotes the expression of PD-L1 and its own expression in DCSCs by elevating the level of reactive oxygen species. Additionally, high QSOX1 in the dormant tumor niche contributes to the exclusion of CD8 + T cells. Conversely, blocking QSOX1 with Ebselen in combination with anti-PD-1 and chemotherapy can effectively eradicate residual DCSCs by reducing PD-L1 expression and promoting CD8 + T cell infiltration. Clinically, high expression of QSOX1 predicts a poor response to anti-PD-1 treatment in patients with esophageal cancer. Thus, our findings reveal a mechanism whereby QSOX1 promotes PD-L1 upregulation and T cell exclusion, facilitating the immune escape of DCSCs, and QSOX1 inhibition, combined with immunotherapy and chemotherapy, represents a promising therapeutic approach for eliminating DCSCs and preventing recurrence., Competing Interests: Competing interests statement:L.L. and J.-R.W. are inventors on a pending patent related to this work (patentee: Sun Yat-sen Memorial Hospital, 11 June 2024; Application No.: 202410743238.7). The other authors declare that they have no other competing interests.
Published: 2024
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46. Evaluating the Effectiveness of a Structural Allograft in Medial Open Wedge High Tibial Osteotomy in Patients With and Without a Lateral Hinge Fracture.

Author: Hung YT, Lee KH, Chang WL, Tsai SW, Chen CF, Wu PK, and Chen WM
Abstract: Background: A lateral hinge fracture is a common complication in medial open wedge high tibial osteotomy (MOWHTO) and is associated with delayed union or nonunion. A comparison of outcomes between patients with or without a lateral hinge fracture after MOWHTO with a structural allograft has not been investigated., Purpose: To validate the outcomes of MOWHTO with a structural allograft, especially in the presence of a lateral hinge fracture., Study Design: Case series; Level of evidence, 4., Methods: We conducted a single-surgeon cohort study at a tertiary referral hospital between April 2017 and August 2022 and included patients who had undergone MOWHTO with a structural allograft for isolated medial compartment osteoarthritis with genu varum. We compared the incidence of delayed union or nonunion events and functional scores between patients with a lateral hinge fracture and those without using the Fisher exact test and independent t test., Results: A total of 88 MOWHTO procedures (77 patients) were analyzed. The overall incidence of lateral hinge fractures was 29.5% (n = 26), including type I (n = 20 [22.7%]) and type II (n = 6 [6.8%]). Notably, 42.3% (n = 11) of these fractures had not been detected intraoperatively but during the follow-up visits. The overall Knee Society Score (KSS), Knee Society Score-Function (KSS-F), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were 90.0 ± 10.0, 93.4 ± 10.8, and 93.8 ± 7.1 points, respectively. None of the patients had delayed union or nonunion, and none underwent a reoperation because of bony union problems. The functional scores (KSS, KSS-F, and WOMAC) were not different between patients who had a lateral hinge fracture and those who did not ( P > .05)., Conclusion: The routine use of a structural allograft was associated with satisfactory outcomes after MOWHTO, regardless of whether there was a lateral hinge fracture., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)
Published: 2024
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47. Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.

Author: Huang YJ, Lin JA, Chen WM, Shia BC, and Wu SY
Subjects: Humans, Female, Middle Aged, Retrospective Studies, Radiotherapy, Adjuvant adverse effects, Taiwan epidemiology, Aged, Breast Neoplasms radiotherapy, Incidence, Mastectomy, Segmental, Registries, Risk Assessment, Radiation Injuries epidemiology, Radiation Injuries prevention & control, Radiation Injuries etiology, Adult, Carcinoma, Ductal, Breast radiotherapy, Risk Factors, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Cardiotoxicity
Abstract: Background: To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy., Methods and Results: A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%)., Conclusions: Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.
Published: 2024
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48. High dose chemotherapy with autologous stem cell rescue in children and young adults with high-risk Ewing sarcoma: A single institute experience in Taiwan.

Author: Lee CY, Yen HJ, Hou MH, Hung GY, Ho CY, Yu TY, Wu PK, Chen CM, Yen CC, Shiau CY, Chen PC, Wu HH, Wu CL, and Chen WM
Abstract: Background: A combination treatment of surgery, chemotherapy, and radiotherapy can improve the survivals of pediatric patients with Ewing sarcoma (ES). However, prognosis remains poor for patients with metastatic disease at diagnosis or recurrence. Other high-risk (HR) features include large tumor burden, tumors of the axial skeleton and poor histologic response. Several studies have documented high dose chemotherapy with autologous stem cell rescue (HDC-ASCR) to be effective in such patients. In this retrospective study, we present the results of HDC-ASCR for high-risk Ewing sarcoma in children and young adults in a single institute., Methods: From March 2004 to March 2021, patients with ES, Ewing-like sarcoma, or round cell sarcoma received HDC-ASCR as part of treatment were included. The patients' characteristics, disease status, stem cell dose, engraftment status, post-transplant complications, and outcomes were analyzed., Results: Twenty patients receiving HDC-ASCR at complete response (n = 6), partial response (n = 13), and stable disease (n = 1) were enrolled. The male to female ratio was 11:9. Median age at diagnosis and transplant was 15.6 years old (range: 3.3-28.9) and 16.2 (range: 4.2-29.9), respectively. The conditioning regimens included ifosfamide-based in two and melphalan-based in 19. All patients achieved successful engraftment without tansplant-related mortality. The 5-year progression-free and overall survival (OS) rate were 35% and 54.5%, respectively. The causes of death (n = 8) were all contributed to disease progression. Patients in the complete response group or with localized HRES exhibited a higher 5-year OS (p = 0.047 and 0.05, respectively). Compared to the historical cohort without HDC-ASCR as part of primary treatment, the current cohort had a significantly better 5-year OS (p = 0.018)., Conclusion: HDC-ASCR seems promising as an alternative treatment for HRES in improving OS in this retrospective study with limited case number., Competing Interests: Conflicts of interest: Dr. Po-Kuei Wu and Dr. Wei-Ming Chen, editorial board member at the Journal of the Chinese Medical Association, had no role in the peer review process or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)
Published: 2024
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49. Metformin Use and Risk of Delirium in Older Adults With Type 2 Diabetes.

Author: Sun M, Wang X, Lu Z, Yang Y, Lv S, Miao M, Chen WM, Wu SY, and Zhang J
Abstract: Objective: Delirium is a precursor and risk factor for dementia, emphasizing the urgency of effective prevention and management strategies in older adults with type 2 diabetes (T2D). Identifying long-term, safe, and effective medications to prevent diabetes-related delirium is crucial because of its significant impact on this population. This study aimed to evaluate the protective effects of metformin against delirium in older adults with T2D, using a competing risk analysis of death to provide a more accurate assessment., Research Design and Methods: Metformin users were compared with a cohort of nonusers. Multivariable Cox regression and Fine and Gray methods were used to assess the risk of delirium and mortality., Results: Our study included 66,568 metformin users and 66,568 nonusers, matched by propensity score. The use of metformin was associated with a significantly lower risk of delirium, with adjusted hazard ratios ranging from 0.77 to 0.81. A dose-response relationship was observed, indicating that higher cumulative and daily doses of metformin were associated with greater reductions in delirium risk., Conclusions: Metformin use is associated with a reduced risk of delirium in older adults with T2D, with higher doses offering greater protection., (© 2024 by the American Diabetes Association.)
Published: 2024
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50. Galacto-oligosaccharides modified whey protein isolate ameliorates cyclophosphamide-induced immunosuppression.

Author: Mao JH, Wang Y, Chen WM, Wang XM, Liu J, Shao YH, and Tu ZC
Subjects: Animals, Mice, RAW 264.7 Cells, Immunosuppression Therapy, Gastrointestinal Microbiome drug effects, Signal Transduction drug effects, Male, TOR Serine-Threonine Kinases metabolism, Cyclophosphamide pharmacology, Oligosaccharides pharmacology, Oligosaccharides chemistry, Whey Proteins chemistry, Whey Proteins pharmacology, NF-kappa B metabolism
Abstract: The effect of whey protein isolate (WPI)- galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS) conjugates on RAW264.7 cells, and further the effect of WPI-GOS conjugates on CTX-induced immunosuppressed mice were investigated. Compared to WPI-FOS conjugates, WPI-GOS conjugates exhibited deeper glycation extent, more pronounced structural unfolding and helix-destabilizing, and obviously improved functional indicators of RAW264.7 macrophages. In addition, WPI-GOS conjugates also repaired immune organ and intestinal barrier and increased IL-1β and IFN-γ levels in immunosuppressed mice. The alteration of gut microbiota induced by WPI-GOS conjugates changed the serum metabolites, causing the activation of NFκB pathway, which strengthens the immune system. The activation of NFκB pathway maybe associated with the mTOR signal pathway and ABC transporters. However, the precise mechanisms by which NFκB pathway interacts with mTOR signal pathway and ABC transporters to modulate the immune response need for further research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
Published: 2024
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