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1. A saturated map of common genetic variants associated with human height

Author: Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, Hirschhorn, JN, Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, and Hirschhorn, JN
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022

2. Science forum: vision, challenges and opportunities for a Plant Cell Atlas

Author: Jha, SG, Borowsky, AT, Cole, BJ, Fahlgren, N, Farmer, A, Huang, S-SC, Karia, P, Libault, M, Provart, NJ, Rice, SL, Saura-Sanchez, M, Agarwal, P, Ahkami, AH, Anderton, CR, Briggs, SP, Brophy, JA, Denolf, P, Di Costanzo, LF, Exposito-Alonso, M, Giacomello, S, Gomez-Cano, F, Kaufmann, K, Ko, DK, Kumar, S, Malkovskiy, A, Nakayama, N, Obata, T, Otegui, MS, Palfalvi, G, Quezada-Rodriguez, EH, Singh, R, Uhrig, RG, Waese, J, Van Wijk, K, Wright, RC, Ehrhardt, DW, Birnbaum, KD, Rhee, SY, Royal Society, and The Royal Society
Subjects: Life Sciences & Biomedicine - Other Topics, chlamydomonas reinhardtii, Chloroplasts, DATABASE, Plant Development, maize, 0601 Biochemistry and Cell Biology, Zea mays, MECHANISMS, Plant Cells, cell biology, Image Processing, Computer-Assisted, Plant Cell Atlas Consortium, Biology, Science & Technology, Computational Biology, Agriculture, Plants, ARABIDOPSIS, GENE, C-4 PHOTOSYNTHESIS, Plant Cell Atlas, science forum, single-cell omics, translational research, VOCABULARY, A. thaliana, SYSTEMS BIOLOGY, PLASTIDS, location-to-function, Life Sciences & Biomedicine, 4D imaging, GENERATION
Abstract: With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.
Published: 2021

3. Carotid Atheromatic Plaque Is Commonly Associated with Hypopituitary Men.

Author: Hong, JW, primary, Kim, JY, additional, Rhee, SY, additional, Kim, CS, additional, Kim, DJ, additional, and Lee, EJ, additional
Published: 2010
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4. Liraglutide and Renal Outcomes in Type 2 Diabetes

Author: Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB, LEADER Steering Committee and Investigators. Bergenstal R, Daniels G, Moses AC, Nauck M, Nissen S, Pocock S, Steinberg W, Stockner M, Kristensen P, Ravn LS, Zychma M, Flyvbjerg A, Ford I, Kloos RT, Schactman MJ, Sleight P, Swedberg K, Tenner SM, Akalın S, Arechavaleta R, Bain S, Babkowski MC, Benroubi M, Berard L, Comlekci A, Czupryniak L, Eliasson B, Eriksson M, Fonseca V, Franek E, Gross J, Hafidh K, Haluzik M, Hayes F, Huang YY, Jacob S, Kaddaha G, Khalil A, Kilhovd B, Laakso M, Leiter L, Lalic N, Ji L, Luedemann J, Mannucci E, Marre M, Masmiquel L, Mota M, Omar M, O’Shea D, Pan C, Petrie J, Pieber T, Pratley R, Raz I, Rea R, Rutten G, Satman I, Shestakova M, Simpson R, Smith D, Tack C, Tarnow L, Thomas N, Van Gaal L, Travert F, Vidal J, Warren M, Yoon KH, Tuttle RM, Sheerman SI, Hegedüs L, Baerwald H, Bergenstal M, Celik S, Dias C, Eder M, Fitzgibbons S, Irvhage L, Kloluckova J, Kriulianski R, McDuffie R, Moen S, Paster A, Saalfeld RM, Sankar K, Shehaj E, Swierzewska P, Tiktin M, Tovey S, Gibson CM, Chakrabarti AK, Dashe JF, Hinchey J, Leary MC, Pride Y, Wiviott S, Allen S, Mehr AP, Mutter WP, Parikh S, Ray S, Cheifetz A, Leffler D, Sheth S, Alexander E, Gaglia JL, Goessling W, Mitzner LD, Rosenberg C, Snow KJ, Wagner A, Piazza G, Abell S, Davis T, D'Emden M, Ding SA, Gilfillan C, Greenaway T, Gunawan F, Ho J, Jackson R, Kalra B, Lau SL, Lin J, MacIsaac R, Makepeace A, Malabu U, Marjason J, McCallum R, McLean M, Moin N, Petersons C, Price S, Roberts A, Roberts D, Sangla K, Stranks S, Tan Y, Thynne T, Walters J, Ward G, Wen W, Zhang J, Brix J, Feder A, Höbaus C, Höllerl F, Höller V, Kotter T, Kratz E, Krzizek EC, Leb-Stoeger U, Mader J, Mras N, Novak E, Obendorf F, Peric S, Pesau G, Prager R, Ribitsch A, Schnack C, Schernthaner G, Wascher T, Batens AH, Benhalima K, De Block C, Ernest P, Fouckova A, Jandrain B, Lapauw B, Letiexhe M, Mathieu C, Neven S, Peiffer F, Ruige J, Scheen A, Taes Y, Van Boxelaer I, Vandistel G, Van Durme Y, Verhaegen A, Alencar E, Alencar R, Almeida AC, Alves B, Alves E, Alves G, Alves J, Araujo L, Arruda V, Augusto GA, Baggentoss R, Balestrassi L, Barbosa M, Barcelos I, Belem L, de Bem A, Betti RT, Bona R, Bosco A, Branda J, Bronstein M, Bueno T, Bulcão T, Caiado F, Camazzola F, Cambréa MF, Campos S, Canani L, Carra MK, Caruso S, Carvalho N, Casillo A, Castro D, Cavalcanti T, Cavichioli V, Cercato C, Chacra A, Challela W, Charchar HS, Chaves C, Chrisman C, Correia-Deur J, da Costa A Jr, Costa M, Costi B, Coutinho P, Coutinho W, Cunha MR, Daher J Jr, Davini E, Democh D Jr, Eliaschewitz F, Esmanhoto Facin G, Farias F, Felício J, Fernandes V, Filho CS, Filho FF, Filho M, Fontan D, Fontenele AP, Forti A, Franco D, Freire K, Fusaro A, Genestreti P, Gerchman F, Godi A, Gomes KF, Gonçalves P, Gonçalves R, Griz L, Grossman M, Gurgel MH, Vasconcellos Haddad AW, Halpern A, Hissa M, Inuy A, Jaime J, Jonasson T, Jorge JC, Malucelli FJ, Kohara S, Kramer C, Lacerda C, Ladeira S, Lana J, Lastebasse F, Leitão A, Leite S, Lerário AC, Lima D, Lima M, Lippi V, Lunardi M, Machado E, Maia F, Maia J, Maia KP, Mañas N, Marchisotti F, Marinho C, Martins C, Figueiredo de Medeiros F, Melo A, Melo F, Mendonca E, Mendonça P, Filho RM, Miguel M, Miléo K, Miyahara M, Montenegro AP, Moraes A, Moreira A, Ítalo Mota J, Mothe FS, Murro A, Nakatani V, Napoli TF, Neto BG, Neto OQ, Niclewicz E, Ohe LN, Oliveira F, Oliveira M, Panarotto D, Parente E, Parolin S, Pechmann L, Costa da Penha P, Perlamagna L, Perotta B, Pimentel L, Pinto M, Poço C, Ponte C, Prazeres P, Quintao E, Raduan R, Rassi DT, Rassi N, Reck L, Montenegro R Jr, Ribeiro R, Rodovalho S, Silveira Rodrigues G, Rollin G, Rossi S, Sabino C, Sales AP, Salles J, Sampaio CR, Santana L, Sato V, da Silva Santos M, Santos NL, Santos R, Saraiva J, Sartori C, Sena R, Sevilha M, Sgarbi J, Silva D, D'albuquerque Silva L, Silva ME, Siqueira K, Soares S, Sobreira W, Sousa B, Souza AC, Souza B, Tambascia M, Tarantino R, Tenor F, Tomarchio M, Triches C, Tristão LJ, Valenti A, Vasques E, Vencio S, Vianna A, Munhoz Vidotto T, Vieira 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E, Martinez G, Martinez-Miss S, Marx P, Massara L, Mastoor M, Matfin G, Maturu A, Maurides P, May M, Mayfield R, Maynard B, Mazza A, McCann K, McCoy J, McCoy T, McCullen MK, McDaniel C, McDaniel AM, McDermott M, McDonald A, McMasters B, McMurray C, Medlin T, Meinel M, Mendez I, Menefee J, Meredith M, Merriweather M, Mersey J, Messino C, Meyer S, Meyers L, Michael D, Midyett C, Miklius A, Milford E, Miller B, Miller H, Milligan M, Minor A, Miranda-Palma B, Mirarchi N, Mittadodla S, Mittle J, Moffat A, Mohaupt S, Mohiuddin K, Mokshagundam S, Monaco S, Monsaert R, Montano-Pereira C, Montgomery A, Moody K, Moon M, Moore D, Moore L, Morawski E, Moreau C, Morin D, Moscoa C, Motzkin C, Mueller R, Munoz C, Munoz M, Myneni A, Naderi B, Nagireddy P, Naidu J, Naidu R, Naik S, Naimark R, Nardicchi M, Ndukwu I, Neller C, Netten-Foster L, Neumiller J, New T, Newman S, Newton T, Nguyen B, Nicol B, Nicol P, Ninivaggi L, Niswender K, Norman L, Noworatzky G, Nyenwe E, O'Brien H, O'Connell T, Oden W, Odugbesan A, Oliver M, Oliver T, Olmeda C, O'Neil C, Oremus R, Ortega T, Ortiz-Santos S, Osborn T, Padmanabhan S, Papacostea O, Park I, Parker A, Parker K, Parker R, Patel C, Patel M, Patel R, Patino M, Patterson S, Paulson K, Paz A, Pemba R, Pepe C, Perez J, Perez T, Perry D, Phillips B, Phillips J, Pickett A, Pinson M, Pitzer R, Poduri M, Poehls J, Poteat T, Powell L, Prasad S, Prevost J, Price E, Priest D, Prieto L, Purewal T, Purighalla R, Purighalla U, Quadrel M, Qureshi A, Radhamma R, Rafla E, Rajab H, Ramalingam R, Ramirez A, Ramirez J, Ramirez K, Ramirez M, Randall M, Rangaraj U, Rao V, Rasmussen P, Rasouli N, Ray A, Reed J, Rems L, Renaud K, Reno M, Resnick M, Reusch J, Reynolds L, Rhoton K, Rhudy J, Ricci C, Rice L, Richardson A, Richardson L, Rickard H, Rickels M, Riff D, Rightenour N, Risser J, Rizvi A, Robertson J, Robinson A, Robinson R, Rockwell M, Rodriguez JP, Rodriguez M, Rojas M, Rojas W, Rooker-Morris L, Root C, Rose M, Rosenberg R, Rosenstock J, Roth M, Ruby R, Sachson R, Sack P, Sadler RK, Sahai S, Salazar J, Salgam M, Samal A, Samson A, Sanagorski R, Sanchez A, Sandberg J, Sanderson M, Sandoval J, Santiago E, Sapp T, Saunders J, Schill J, Schott C, Schreiman R, Schu D, Schuh K, Schutta M, Schwartz J, Schweppe L, Scofield H, Scribner A, Seal J, Sealock J, Seaton B, Sedlak-Hanslik T, Seekins K, Segal M, Seggelke S, Semenza S, Sentman P, Serra M, Seshadri P, Sevilla E, Shah S, Shaheen K, Shanik M, Shaw J, Sheets M, Shellabarger C, Sher J, Shippey J, Shivaswamy V, Shomali M, Shore D, Shroff P, Siddiqui T, Siegwald A, Silver R, Simmons D, Simons R, Sinan A, Singh M, Sirinvaravong S, Skero J, Slover-Zipf J, Small S, Smith B, Smith K, Smith M, Sohl J, Solarz SH, Soler D, Sood A, Sora N, Souchet A, Soule J, Sparks J, Spector L, Speicher R, Spillers L, Spivey T, Springer N, Sprouse H, St John J, Stacey A, Stacey H, Stafford M, Stagner E, Staples K, Steadman E, Steed R, Steeves G, Steinberg H, Stell C, Stirman E, Straub K, Strock E, Sue M, Suris O, Sutton T, Tabbah I, Talsania M, Tang R, Tapia J, Taylor K, Taylor-Hancher R, Teator R, Tekateka M, Temple B, Temple K, Teodori M, Tharp P, Thethi T, Theuma P, Thomas S, Thottan A, Thrasher J, Thrasher L, Tiemeyer M, Tinney I, Tobin T, Toma S, Tovar M, Townsend J, Trantow C, Traylor H, Trevino M, Troy M, Trumper D, Tryggestad J, Tucker C, Turner J, Turney R, Tuten C, Tyzack J, Ullo L, Underkofler C, Unger J, Urdanetta R, Valdivia V, Valenti S, Vanderheiden A, Vanderlinde-Wood M, Varma C, Vasquez E, Vazquez M, Vickery D, Villafuerte B, Villegas C, Vivar J, Vivekananthan K, Vo G, Vukojicic K, Wachter A, Wahl D, Waitmann J, Walker D, Walsh J, Walsh K, Walton A, Wang A, Wardell K, Watkins S, Watkinson J, Watts M, Watwe V, Weaver N, Weber R, Wedick C, Weeks D, Weeks L, Weindorff K, Weinstein R, Weiss S, Wenger K, Wentworth M, Werner A, West M, Whelan S, White B, White J, Whitmire M, Whittington R, Wical J, Wigley C, Wilkins F, Will K, Williams A, Wilson LE, Wince M, Wine S, Winkle P, Winner C, Wise J, Witte M, Wittenmyer J, Wood C, Wood R, Woodruff C, Worthington B, Wynn D, Wysham C, Xavier P, Yela S, Yenoby L, Young L, Younus N, Yourell V, Zaid M, Zubair I., Mann, Jfe, Ørsted, Dd, Brown-Frandsen, K, Marso, Sp, Poulter, Nr, Rasmussen, S, Tornøe, K, Zinman, B, Buse, Jb, Bergenstal R, LEADER Steering Committee and Investigators., Daniels, G, Moses, Ac, Nauck, M, Nissen, S, Pocock, S, Steinberg, W, Stockner, M, Kristensen, P, Ravn, L, Zychma, M, Flyvbjerg, A, Ford, I, Kloos, Rt, Schactman, Mj, Sleight, P, Swedberg, K, Tenner, Sm, Akalın, S, Arechavaleta, R, Bain, S, Babkowski, Mc, Benroubi, M, Berard, L, Comlekci, A, Czupryniak, L, Eliasson, B, Eriksson, M, Fonseca, V, Franek, E, Gross, J, Hafidh, K, Haluzik, M, Hayes, F, Huang, Yy, Jacob, S, Kaddaha, G, Khalil, A, Kilhovd, B, Laakso, M, Leiter, L, Lalic, N, Ji, L, Luedemann, J, Mannucci, E, Marre, M, Masmiquel, L, Mota, M, Omar, M, O’Shea, D, Pan, C, Petrie, J, Pieber, T, Pratley, R, Raz, I, Rea, R, Rutten, G, Satman, I, 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Resnick, M, Reusch, J, Reynolds, L, Rhoton, K, Rhudy, J, Ricci, C, Rice, L, Richardson, A, Richardson, L, Rickard, H, Rickels, M, Riff, D, Rightenour, N, Risser, J, Rizvi, A, Robertson, J, Robinson, A, Robinson, R, Rockwell, M, Rodriguez, Jp, Rodriguez, M, Rojas, M, Rojas, W, Rooker-Morris, L, Root, C, Rose, M, Rosenberg, R, Rosenstock, J, Roth, M, Ruby, R, Sachson, R, Sack, P, Sadler, Rk, Sahai, S, J, Salazar, Salgam, M, Samal, A, Samson, A, Sanagorski, R, Sanchez, A, Sandberg, J, Sanderson, M, Sandoval, J, Santiago, E, Sapp, T, Saunders, J, Schill, J, Schott, C, Schreiman, R, Schu, D, Schuh, K, Schutta, M, Schwartz, J, Schweppe, L, Scofield, H, Scribner, A, Seal, J, Sealock, J, Seaton, B, Sedlak-Hanslik, T, Seekins, K, Segal, M, Seggelke, S, Semenza, S, Sentman, P, Serra, M, Seshadri, P, Sevilla, E, Shah, S, Shaheen, K, Shanik, M, Shaw, J, Sheets, M, Shellabarger, C, Sher, J, Shippey, J, Shivaswamy, V, Shomali, M, Shore, D, Shroff, P, Siddiqui, T, Siegwald, A, Silver, R, Simmons, D, Simons, R, Sinan, A, Singh, M, Sirinvaravong, S, Skero, J, Slover-Zipf, J, Small, S, Smith, B, Smith, K, Smith, M, Sohl, J, Solarz, Sh, Soler, D, Sood, A, Sora, N, Souchet, A, Soule, J, Sparks, J, Spector, L, Speicher, R, Spillers, L, Spivey, T, Springer, N, Sprouse, H, St John, J, Stacey, A, Stacey, H, Stafford, M, Stagner, E, Staples, K, Steadman, E, Steed, R, Steeves, G, Steinberg, H, Stell, C, Stirman, E, Straub, K, Strock, E, Sue, M, Suris, O, Sutton, T, Tabbah, I, Talsania, M, Tang, R, Tapia, J, Taylor, K, Taylor-Hancher, R, Teator, R, Tekateka, M, Temple, B, Temple, K, Teodori, M, Tharp, P, Thethi, T, Theuma, P, Thomas, S, Thottan, A, Thrasher, J, Thrasher, L, Tiemeyer, M, Tinney, I, Tobin, T, Toma, S, Tovar, M, Townsend, J, Trantow, C, Traylor, H, Trevino, M, Troy, M, Trumper, D, Tryggestad, J, Tucker, C, Turner, J, Turney, R, Tuten, C, Tyzack, J, Ullo, L, Underkofler, C, Unger, J, Urdanetta, R, Valdivia, V, Valenti, S, Vanderheiden, A, Vanderlinde-Wood, M, Varma, C, Vasquez, E, Vazquez, M, Vickery, D, Villafuerte, B, Villegas, C, Vivar, J, Vivekananthan, K, Vo, G, Vukojicic, K, Wachter, A, Wahl, D, Waitmann, J, Walker, D, Walsh, J, Walsh, K, Walton, A, Wang, A, Wardell, K, Watkins, S, Watkinson, J, Watts, M, Watwe, V, Weaver, N, Weber, R, Wedick, C, Weeks, D, Weeks, L, Weindorff, K, Weinstein, R, Weiss, S, Wenger, K, Wentworth, M, Werner, A, West, M, Whelan, S, White, B, White, J, Whitmire, M, Whittington, R, Wical, J, Wigley, C, Wilkins, F, Will, K, Williams, A, Wilson, Le, Wince, M, Wine, S, Winkle, P, Winner, C, Wise, J, Witte, M, Wittenmyer, J, Wood, C, Wood, R, Woodruff, C, Worthington, B, Wynn, D, Wysham, C, Xavier, P, Yela, S, Yenoby, L, Young, L, Younus, N, Yourell, V, Zaid, M, Zubair, I., Mann J.F.E., Orsted D.D., Brown-Frandsen K., Marso S.P., Poulter N.R., Rasmussen S., Tornoe K., Zinman B., Buse J.B., and Buscemi S.
Subjects: Male, Settore MED/09 - Medicina Interna, Acute Kidney Injury, Aged, Albuminuria, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Follow-Up Studies, Glomerular Filtration Rate, Glucagon-Like Peptide 1, Humans, Hypoglycemic Agents, Intention to Treat Analysis, Kidney Failure, Chronic, Liraglutide, Middle Aged, Type 2 diabetes, 030204 cardiovascular system & hematology, urologic and male genital diseases, GLOMERULAR-FILTRATION-RATE, KIDNEY-FUNCTION, DISEASE, law.invention, Kidney Failure, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Chronic, RISK, Kidney, Acute kidney injury, 11 Medical And Health Sciences, General Medicine, medicine.anatomical_structure, TRIAL, liraglutide, randomized controlled trial, type 2 diabetes, renal outcomes, Life Sciences & Biomedicine, Type 2, medicine.drug, medicine.medical_specialty, Renal function, 030209 endocrinology & metabolism, CARDIOVASCULAR OUTCOMES, Follow-Up Studie, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Intensive care medicine, Science & Technology, business.industry, MORTALITY, medicine.disease, INTENSIVE GLUCOSE CONTROL, INDIVIDUALS, chemistry, Diabetic Nephropathie, LEADER Steering Committee and Investigators, business
Abstract: BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).
Published: 2017

5. Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

Author: Rhee, SY, Varghese, V, Holmes, SP, Van Zyl, GU, Steegen, K, Boyd, MA, Cooper, DA, Nsanzimana, S, Saravanan, S, Charpentier, C, de Oliveira, T, Etiebet, MAA, Garcia, F, Goedhals, D, Gomes, P, Gunthard, HF, Hamers, RL, Hoffmann, C J, Hunt, G, Jiamsakul, A, Kaleebu, P, Kanki, P, Kantor, R, Kerschberger, B, Marconi, V C, Ndahimana, JD, Ndembi, N, Ngo-Giang-Huong, N, Rokx, Casper, Santoro, MM, Schapiro, JM, Schmidt, D, Seu, L, Sigaloff, KCE, Sirivichayakul, S, Skhosana, L, Sunpath, H, Tang, M, Yang, CF, Carmona, S, Gupta, RK, Shafer, RW, Rhee, SY, Varghese, V, Holmes, SP, Van Zyl, GU, Steegen, K, Boyd, MA, Cooper, DA, Nsanzimana, S, Saravanan, S, Charpentier, C, de Oliveira, T, Etiebet, MAA, Garcia, F, Goedhals, D, Gomes, P, Gunthard, HF, Hamers, RL, Hoffmann, C J, Hunt, G, Jiamsakul, A, Kaleebu, P, Kanki, P, Kantor, R, Kerschberger, B, Marconi, V C, Ndahimana, JD, Ndembi, N, Ngo-Giang-Huong, N, Rokx, Casper, Santoro, MM, Schapiro, JM, Schmidt, D, Seu, L, Sigaloff, KCE, Sirivichayakul, S, Skhosana, L, Sunpath, H, Tang, M, Yang, CF, Carmona, S, Gupta, RK, and Shafer, RW
Published: 2017

6. HIV-1 fitness landscape models for indinavir treatment pressure using observed evolution in longitudinal sequence data are predictive for treatment failure

Author: Sangeda, RZ, Theys, K, Beheydt, G, Rhee, SY, Deforche, K, Vercauteren, J, Libin, P, Imbrechts, S, Grossman, Z, Camacho, RJ, Van Laethem, K, Pironti, A, Zazzi, M, Sonnerborg, A, Incardona, F, Luca, A, Torti, C, Ruiz, L, van de Vijver, David, Shafer, RW, Bruzzone, B, van Wijngaerden, E, Vandamme, AM, Sangeda, RZ, Theys, K, Beheydt, G, Rhee, SY, Deforche, K, Vercauteren, J, Libin, P, Imbrechts, S, Grossman, Z, Camacho, RJ, Van Laethem, K, Pironti, A, Zazzi, M, Sonnerborg, A, Incardona, F, Luca, A, Torti, C, Ruiz, L, van de Vijver, David, Shafer, RW, Bruzzone, B, van Wijngaerden, E, and Vandamme, AM
Abstract: We previously modeled the in vivo evolution of human immunodeficiency virus-1 (HIV-1) under drug selective pressure from cross-sectional viral sequences. These fitness landscapes (FLs) were made by using first a Bayesian network (BN) to map epistatic substitutions, followed by scaling the fitness landscape based on an HIV evolution simulator trying to evolve the sequences from treatment naive patients into sequences from patients failing treatment. In this study, we compared four FLs trained with different sequence populations. Epistatic interactions were learned from three different cross-sectional BNs, trained with sequence from patients experienced with indinavir (BNT), all protease inhibitors (PIs) (BNP) or all PI except indinavir (BND). Scaling the fitness landscape was done using cross-sectional data from drug naive and indinavir experienced patients (Fcross using BNT) and using longitudinal sequences from patients failing indinavir In pairwise FL comparisons we found significant correlation between fitness values for individual sequences, and this correlation improved after correcting for the subtype. Furthermore, FLs could predict the failing sequence under indinavir-containing combinations. At 12 and 48 weeks, all parameters from all FLs and indinavir GSS (both for Rega and HIVdb) were predictive of therapy outcome, except MR for FlongT and FlongP. The fitness landscapes have similar predictive power for treatment respon
Published: 2013

7. Drug Resistance Mutations for Surveillance of Transmitted HIV-1 Drug-Resistance: 2009 Update

Author: Bennett, DE, Camacho, RJ, Otelea, D, Kuritzkes, DR, Fleury, H, Kiuchi, M, Heneine, W, Kantor, R, Jordan, MR, Schapiro, JM, Vandamme, AM, Sandstrom, P, Boucher, Charles, van de Vijver, David, Rhee, SY, Liu, TF, Pilay, D, Shafer, RW, Bennett, DE, Camacho, RJ, Otelea, D, Kuritzkes, DR, Fleury, H, Kiuchi, M, Heneine, W, Kantor, R, Jordan, MR, Schapiro, JM, Vandamme, AM, Sandstrom, P, Boucher, Charles, van de Vijver, David, Rhee, SY, Liu, TF, Pilay, D, and Shafer, RW
Abstract: Programs that monitor local, national, and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs. To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance. In January 2007, we outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 RT and protease mutations meeting these criteria (surveillance drug resistance mutations; SDRMs). Since January 2007, several new drugs have been approved and several new drug-resistance mutations have been identified. In this paper, we follow the same procedures described previously to develop an updated list of SDRMs that are likely to be useful for ongoing and future studies of transmitted drug resistance. The updated SDRM list has 93 mutations including 34 NRTI-resistance mutations at 15 RT positions, 19 NNRTI-resistance mutations at 10 RT positions, and 40 PI-resistance mutations at 18 protease positions.
Published: 2009

8. The Diabetes Technology Society Error Grid and Trend Accuracy Matrix for Glucose Monitors.

Author: Klonoff DC, Freckmann G, Pleus S, Kovatchev BP, Kerr D, Tse CC, Li C, Agus MSD, Dungan K, Voglová Hagerf B, Krouwer JS, Lee WA, Misra S, Rhee SY, Sabharwal A, Seley JJ, Shah VN, Tran NK, Waki K, Worth C, Tian T, Aaron RE, Rutledge K, Ho CN, Ayers AT, Adler A, Ahn DT, Aktürk HK, Al-Sofiani ME, Bailey TS, Baker M, Bally L, Bannuru RR, Bauer EM, Bee YM, Blanchette JE, Cengiz E, Chase JG, Y Chen K, Cherñavvsky D, Clements M, Cote GL, Dhatariya KK, Drincic A, Ejskjaer N, Espinoza J, Fabris C, Fleming GA, Gabbay MAL, Galindo RJ, Gómez-Medina AM, Heinemann L, Hermanns N, Hoang T, Hussain S, Jacobs PG, Jendle J, Joshi SR, Koliwad SK, Lal RA, Leiter LA, Lind M, Mader JK, Maran A, Masharani U, Mathioudakis N, McShane M, Mehta C, Moon SJ, Nichols JH, O'Neal DN, Pasquel FJ, Peters AL, Pfützner A, Pop-Busui R, Ranjitkar P, Rhee CM, Sacks DB, Schmidt S, Schwaighofer SM, Sheng B, Simonson GD, Sode K, Spanakis EK, Spartano NL, Umpierrez GE, Vareth M, Vesper HW, Wang J, Wright E, Wu AHB, Yeshiwas S, Zilbermint M, and Kohn MA
Subjects: Humans, Reproducibility of Results, Blood Glucose Self-Monitoring instrumentation, Blood Glucose Self-Monitoring standards, Blood Glucose analysis, Diabetes Mellitus blood, Diabetes Mellitus diagnosis
Abstract: Introduction: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs)., Methods: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy., Results: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose., Conclusion: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.C.K. is a consultant for Afon, Lifecare, Novo, Samsung, embecta, Glucotrack, SynchNeuro, and Thirdwayv. G.F. is CEO of IfDT. G.F./IfDT has/have received research support, speakers’ honoraria or consulting fees in the last three years from Abbott, Ascensia, Berlin Chemie, Boydsense, Dexcom, Glucoset, i-SENS, Lilly, Menarini, Novo Nordisk, Perfood, Pharmasens, Roche, Sinocare, Terumo, Ypsomed. S.P. is an employee of IfDT. B.P.K. declares patent royalties handled by UVA from: DexCom, J&J, Novo Nordisk, and Sanofi; and research support handled by UVA: Dexcom, Novo Nordisk, Tandem Diabetes Care. D.K. has received research support from Abbott Diabetes Care. M.S.D.A. is currently receiving in kind support (CGM devices) from Dexcom Inc for an investigator-initiated clinical study. K.D. receives research funding from Dexcom, Abbott, Sanofi, Viacyte, Insulet, consulting fees from Eli Lilly, Dexcom, Insulet, Oppenheimer, Elsevier, honoraria from Academy for Continued Healthcare Learning, Med Learning Group, Medscape, Impact Education, and royalties from UptoDate. S.M. is in receipt of an investigator-initiated grant from DexCom, has received speaker fees from Sanofi & Lilly, is funded by a Wellcome Trust (223024/Z/21/Z), and is supported by the NIHR Imperial Biomedical Research Centre. A.S. was supported by the NSF Engineering Research Center for Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP) (#1648451). V.N.S. reports receiving personal fees from Sanofi, Embecta, NovoNordisk, Dexcom, Insulet, Tandem Diabetes Care, Ascensia Diabetes Care, Genomelink and LumosFit for consulting, advising or speaking. N.K.T. is a consultant for Roche Diagnostics / Roche Molecular Systems / Radiometer. UC Davis is a Roche Diagnostics Center of Excellence. N.K.T. has received speaking honoraria for Roche Diagnostics, Nova Biomedical, Thermo Fisher, and Radiometer. N.K.T. is also Chair-Elect for the Association for Diagnostic and Laboratory Medicine (ADLM) Critical and Point-of-Care Testing Division, Co-Founder of the Machine Intelligene Learning Optimizer (MILO), Inc, and a member of the International Federation for Clinical Chemistry (IFCC) continuous glucose monitoring workgroup. T.T. is a consultant for Clinical ink. R.E.A. is a consultant for Clinical ink. D.T.A. has received speaker’s honoraria from Abbott, Ascensia Diabetes Care, Insulet, Lilly Diabetes, Mannkind, Novo Nordisk, and Xeris Pharmaceuticals. D.T.A. has received consulting fees from Ascensia Diabetes Care, Lilly Diabetes, and Senseonics. H.K.A. received research grants through University of Colorado from Dexcom, Tandem Diabetes, Medtronic, Mannkind, IM Therapeutics, IAFMS, and received honorarium through University of Colorado for consulting from Dexcom, Tandem Diabetes, and Medtronic. M.E.A.-S. has served on the advisory boards for Abbott, Medtronic, Insulet, VitalAire, Sanofi, Eli Lilly, and Dexcom; has received honoraria for speaking from Abbott, Eli Lilly, Medtronic, Novo Nordisk, Sanofi, VitalAire, and Eli Lilly; and received research support from Medtronic and Sanofi. T.S.B. has received research support from Abbott Rapid Diagnostics, Biolinq, Dexcom, Eli Lilly, Medtronic, Medtrum, Novo Nordisk, Sanofi, Senseonics, and vTv Therapeutics and consulting honoraria from Abbott Diabetes, Abbott Rapid Diagnostics, ACON, CeQur, HagarTech, Intuity Medical, Lifescan, Mannkind, Medtronic, Novo, Perspirion, Sanofi, Sequel Med Tech, and Ypsomed. M.B. currently participates on the Hospital Advisory board with Dexcom and has received research support from Dexcom. L.B. has received research/product support from Dexcom, Ypsomed, and Boehringer Ingelheim; speaker honoraria from Dexcom and Oviva; and participated in advisory boards of Dexcom, Novo Nordisk, Sanofi, Ypsomed, Oviva, and Roche Diabetes Care. Y.M.B. has received honoraria for lectures and scientific advisory from Roche and AstraZeneca in the past 12 months. J.E.B. is on the Speaker’s bureau for Insulet and on the Advisory Board for Cardinal Health and Lifescan. J.E.B. is a consultant for Embecta. J.E.B. receives research support from the Leona M. and Harry B. Helmsley Charitable Trust. E.C. is on the scientific advisory board for Novo Nordisk, Eli-Lilly, Adocia, Arecor, Proventionbio, Portal Insulin, and MannKind. D.C. was a Dexcom employee from August 2018 to May 2024. D.C. is a shareholder of Dexcom, Lilly, Abbott and Tandem. M.C. has received consulting fees from Glooko and research support from Dexcom and Abbott Diabetes Care. G.L.C. is a shareholder of BioTex, Inc., Basepair Biotechnologies Inc., Coordination Centric, Inc., and Shape Memory Medical, Inc. G.L.C. is supported by the NSF Engineering Research Center for Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP) (#1648451). K.K.D. has received honoraria, travel, or fees for advisory boards from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Abbott Diabetes, Menarini, and Sanofi in the last 12 months. J.E. receives federal funding from FDA, NIMHD, and NCATS and is a consultant for Sanofi. C.F. receives royalties from Dexcom and Novo Nordisk managed through her institution. G.A.F. is an advisor for 180 Life Sciences, 89bio, Adocia, Abbott, AdipoPharma, Aerami, Amolyt, Carthera, Catalyst, Cohen Global, CMC Magnetics, Diasome, Eleos, Entera Bio, Enterin, Glyscend, Hagar, Hogan Lovells, IM Therapeutics, Innoneo, Intarcia, Levicure, Lilly Asia Ventures, Lumos, Mars Symbioscience, Melior, metaLead Therapeutics, Microbiotix, MMD, Modular Medical, New Amsterdam, Northwestern, NuSirt, NuVox, Oramed, Pano, Pasithea, PhylloPharma, Pleiogenix, Recordati, Regor, Remodeless, Renaissance, RenovoRx, Rivus, RxMP, Sera Biopharma, Seraxis, Serpin, SFC Fluidics, Skinject, SROne, Stalicla, Surf Bio, TIXiMED, Veroscience, Verthermia, WaveBreak, Zealand Pharma, and Zucara. M.A.L.G. is a consultant for Abbott, Medtronic, Novonordisk, and Roche. R.J.G. received research support from Novo Nordisk, Dexcom and Eli Lilly and consulting fees/advisory fees from Abbott Diabetes Care, Aztra Zeneca, Bayer, Boehringer, Dexcom, Eli Lilly, Novo Nordisk, and Medtronic, outside of this work. R.J.G. is partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Numbers P30DK111024, K23DK123384, R03DK138255, and U2CD137135. A.M.G.-M. reports speaker fees from Novo Nordisk, Sanofi, Elli Lilly, Boehringer Ingelheim, Abbott, and Medtronic. L.H. is a consultant for a number of companies that are developing innovative solutions for the treatment of people with diabetes. N.H. reports Advisory Board member fees from Abbott Diabetes Care and Insulet as well as honoraria for lectures from Berlin-Chemie AG, Becton Dickenson, Sanofi Germany, Roche Diabetes Care, and Dexcom Germany. T.H. serves on the advisory board for Acella and Horizons Therapeutics (no financial compensation). S.H. has served on the advisory board for Tandem, Dexcom, and Medtronic, and received honoraria for nonpromotional educational and/or consultancy work from Abbott, Insulet, Dexcom, Roche, and Sanofi. P.G.J. is a shareholder of Pacific Diabetes Technologies Inc. and serves on the advisory board for Eli Lilly. P.G.J. received grant support from SFC Fluidics and research support from Eli Lilly and Dexcom. J.J. has received fees from lectures and or advisory boards from Abbott, Astra Zeneca, Boeringer Ingelheim, Eli Lilly, Medtronic, Nordic Infucare, Novo Nordisk, and Sanofi. S.R.J is a consultant for USV, Marico, Glenmark, Franco Indian, Twin Health, Biocon, and Zydus Lifesciences. S.R.J. received speaking honoraria from Abbott, Novo Nordisk, MSD, Sanofi, Boehringer Ingelheim, AstraZeneca, Lupin, Bayer Zydus, USV, DRL, Meyer Organics, Servier, Natco. R.A.L. is a consultant for Abbott Diabetes Care, Biolinq, Capillary Biomedical, Deep Valley Labs, Gluroo, PhysioLogic Devices, Portal Insulin, Sanofi, and Tidepool. R.A.L. has served on advisory boards for. ProventionBio and Lilly. R.A.L. receives research support through his institution from Insulet, Medtronic, Tandem, and Sinocare. L.A.L. has received research funding from, has provided CME on behalf of, and/or has acted as an advisor to Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Lexicon, Merck, Novo Nordisk, Pfizer, and Sanofi. M.L. has been a consultant or received honoraria from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Nordic InfuCare, and Novo Nordisk, and has received research grants from Eli Lilly and Novo Nordisk, all outside of the submitted work. J.K.M. is a member of advisory boards of Abbott Diabetes Care, Becton-Dickinson, Biomea Fusion, Eli Lilly, Embecta, Medtronic, NovoNordisk A/S, Roche Diabetes Care, Sanofi-Aventis, and Viatris and received speaker honoraria from A. Menarini Diagnostics, Abbott Diabetes Care, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Medtrust, MSD, NovoNordisk A/S, Roche Diabetes Care, Sanofi, Viatris, and Ypsomed. J.K.M. is a shareholder of decide Clinical Software GmbH and elyte Diagnostics. A.M. reports speaker fees from Novo Nordisk. M.M. has an existing research & development relationship with Scientific Bioprocessing, Inc and has been a consultant for Abbott. S.-J.M. is a consultant for Abbott, Curestream, Daewoong, EOFlow, G2e, Huons, iSense, Medtronic, Novo Nordisk, and Sanofi. D.N.O. has served on advisory boards for Abbott Laboratories, Medtronic, Merck Sharp & Dohme, Novo Nordisk, Roche, and Sanofi; received research support from Medtronic, Novo Nordisk, Roche, Eli Lilly and Company, and Sanofi; and received travel support from Novo Nordisk and Merck Sharp & Dohme. F.J.P. has received research support (to Emory University) from Dexcom, Insulet, Novo Nordisk, Tandem, and Ideal Medical Technologies, and has received consulting fees from Dexcom. A.L.P. is on the advisory board of Medscape, Vertex, and Lilly; receives research support from Insulin and Abbott; and has stock options in Omada Health. R.P.-B. receives grant support from Novo Nordisk, Lexicon Pharmaceuticals, and Medtronic and received consulting fees from Bayer, Lexicon Pharmaceuticals, Novo Nordisk, and Roche. C.M.R. has received honoraria and/or grant support from AstraZeneca, Dexcom, Fresenius, and Vifor. D.B.S. is supported by the Intramural Research Program of the National Institutes of Health. S.S. was a Novo Nordisk employee from 2022-2023. S.S. has served as advisor for Novo Nordisk and has received speaker fees from Novo Nordisk and Nordic Infucare within the past three years. G.D.S’s employer, nonprofit International Diabetes Center, HealthPartners Institute, has received educational grant funds from Abbott Diabetes Care, Medscape, and Sanofi-Aventis Groupe. G.D.S receives no personal income/honorarium from these activities. K.S. received grant supports from Arkray, Terumo, and Dexcom. E.K.S. is partly supported by the VA Merit Award (1I01CX001825) from the US Department of Veterans Affairs Clinical Sciences Research and has received unrestricted research support from Dexcom and Tandem Diabetes (to Baltimore VA Medical Center and to University of Maryland) for the conduction of clinical trials. N.L.S. received funding from Novo Nordisk for an investigator-initiated research grant unrelated to the current project. G.E.U. is partly supported by research grants from National Institutes of Health (NIH/NATS UL 3UL1TR002378-05S2) from the Clinical and Translational Science Award program, and from National Institutes of Health and National Center for Research Resources (NIH/NIDDK 2P30DK111024-06). G.E.U. has received research support (to Emory University) from Abbott, Bayer, and Dexcom; and has participated in advisory boards for Dexcom and GlyCare. E.W. has received consulting fees from Abbott Diabetes Care, Ascensia, Bayer, Boehringer, Ingelheim, Embecta, GlaxoSmithKline, Lilly, Medtronic, Renalytix, and Sanofi. E.W. has received honoraria from Abbott Diabetes Care, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Lilly, Medtronic, Renalytix, and Sanofi. E.W. is on the Speakers’ Bureau from Abbott Diabetes Care, Bayer, Boehringer, Ingelheim, GlaxoSmithKline, Lilly, Renalytix, and Sanofi. M.Z. is a consultant for DexCom, Inc. M.A.K. is Chief Medical Officer of QuesGen, Inc. C.T., C.L., B.V.H., J.S.K., W.A.L., S.Y.R., J.J.S., K.W., C.W., K.R., C.N.H., A.T.A., A.A., R.R.B., E.M.B., J.G.C., K.Y.C., A.D., N.E., S.K.K., U.M., N.M., C.M., J.H.N., A.P., P.R., S.M.S., B.S., M.V., H.W.V., J.W., A.H.B.W., and S.Y. have nothing to disclose.
Published: 2024
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9. Association between glucagon-like peptide-1 receptor agonists and risk of suicidality: A comprehensive analysis of the global pharmacovigilance database.

Author: Kim TH, Lee K, Park S, Cho H, Park J, Jo H, Son Y, Kim S, Kang J, Smith L, Rahmati M, Fond G, Boyer L, Pizzol D, Lee H, Rhee SY, Hwang J, Sang H, and Yon DK
Subjects: Humans, Obesity epidemiology, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 epidemiology, Female, Male, Glucagon-Like Peptide-1 Receptor Agonists, Pharmacovigilance, Glucagon-Like Peptide-1 Receptor agonists, Adverse Drug Reaction Reporting Systems statistics & numerical data, Suicide statistics & numerical data, Hypoglycemic Agents adverse effects, Hypoglycemic Agents therapeutic use, Databases, Factual
Abstract: Aim: To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data., Materials and Methods: This study utilized the World Health Organization's pharmacovigilance database, encompassing adverse drug reaction reports from 1967 to 2023, from 170 countries (total reports, N = 131 255 418). We present the reported odds ratios (RORs) with 95% confidence intervals (CIs) and information component (IC) with IC 025 regarding the association between GLP-1RA use and suicidality., Results: Although reports of GLP-1RA-associated suicidality increased gradually from 2005 to 2023 (n = 332), no evidence of an association was observed (ROR 0.15 [95% CI 0.13 to 0.16]; IC -2.77 [IC 025 -2.95]). The lack of evidence of an association persisted regardless of whether GLP-1RAs were used for diabetes treatment (ROR 0.13 [95% CI 0.11 to 0.14]; IC -2.95 [IC 025 -3.14]) or obesity treatment (ROR 0.44 [95% CI 0.34 to 0.58]; IC -1.16 [IC 025 -1.62]). However, an association was found between suicidality and other diabetes medications excluding GLP-1RAs (ROR 1.13 [95% CI 1.10 to 1.15]; IC 0.17 [IC 025 0.13]). Similarly, the potential association with suicidality was observed in medications used to treat obesity excluding GLP-1RAs (ROR 1.08 [95% CI 1.01 to 1.14]; IC 0.10 [IC 025 0.01])., Conclusions: The suspected association between GLP-1RA use and suicidality, as raised by the European Medicines Agency, was not found in our global analysis. This indicates that the sporadic reports of GLP-1RA-associated suicidality are likely influenced by factors such as comorbidities present in the GLP-1RA user population., (© 2024 John Wiley & Sons Ltd.)
Published: 2024
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10. Trends in Antidiabetic Drug Use and Safety of Metformin in Diabetic Patients with Varying Degrees of Chronic Kidney Disease from 2010 to 2021 in Korea: Retrospective Cohort Study Using the Common Data Model.

Author: Joo SH, Yang S, Lee S, Park SJ, Park T, Rhee SY, Cha JM, Rhie SJ, Hwang HS, Kim YG, and Chung EK
Abstract: Background/objectives: This study aimed to investigate trends in antidiabetic drug use and assess the risk of metformin-associated lactic acidosis (MALA) in patients with chronic kidney disease (CKD)., Methods: A retrospective observational analysis based on the common data model was conducted using electronic medical records from 2010 to 2021. The patients included were aged ≥18, diagnosed with CKD and type 2 diabetes, and had received antidiabetic medications for ≥30 days. MALA was defined as pH ≤ 7.35 and arterial lactate ≥4 mmol/L., Results: A total of 8318 patients were included, with 6185 in CKD stages 1-2 and 2133 in stages 3a-5. Metformin monotherapy was the most prescribed regimen, except in stage 5 CKD. As CKD progressed, metformin use significantly declined; insulin and meglitinides were most frequently prescribed in end-stage renal disease. Over the study period, the use of SGLT2 inhibitors (13.3%) and DPP-4 inhibitors (24.5%) increased significantly, while sulfonylurea use decreased ( p < 0.05). Metformin use remained stable in earlier CKD stages but significantly decreased in stage 3b or worse. The incidence rate (IR) of MALA was 1.22 per 1000 patient-years, with a significantly increased IR in stage 4 or worse CKD ( p < 0.001)., Conclusions: Metformin was the most prescribed antidiabetic drug in CKD patients in Korea with a low risk of MALA. Antidiabetic drug use patterns varied across CKD stages, with a notable decline in metformin use in advanced CKD and a rise in SGLT2 inhibitor prescriptions, underscoring the need for further optimized therapy.
Published: 2024
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11. Worldwide burden of antidiabetic drug-induced sarcopenia: An international pharmacovigilance study.

Author: Kong J, Park S, Kim TH, Lee JE, Cho H, Oh J, Lee S, Jo H, Lee H, Lee K, Park J, Jacob L, Pizzol D, Rhee SY, Kim S, and Yon DK
Abstract: Background: Sarcopenia is a condition that poses a significant risk in the older population, with diabetes identified as a risk factor. Recent evidence suggests that GLP-1 RA, commonly used as antidiabetic treatments, may potentially induce sarcopenia. This study aimed to investigate the association between sarcopenia and various antidiabetic drugs, including GLP-1 RAs., Methods: This study analyzed reports from the World Health Organization international pharmacovigilance database, covering the period from 1967 to 2023 (total reports, n = 131,255,418). We analyzed the reported odds ratio (ROR) and information component (IC) to evaluate the association between sarcopenia and seven classes of antidiabetic drugs: DPP-4 inhibitors, GLP-1 RAs, insulin, metformin, SGLT2 inhibitors, sulfonylureas, and thiazolidinediones., Results: Reports of antidiabetic drugs-associated sarcopenia have gradually increased (n = 508; 258 males [50.79 %]). Overall, antidiabetic drugs showed significant associations with sarcopenia (ROR, 1.31 [95 % CI, 1.20-1.44]; IC, 0.38 [IC 025 , 0.24]). Among the individual drug classes, SGLT2 inhibitors showed the highest association (ROR, 2.49 [95 % CI, 1.93-3.22]; IC, 1.30 [IC 025 , 0.87]), followed by metformin (ROR, 1.86 [95 % CI, 1.43-2.41]; IC, 0.88 [IC 025 , 0.44]), DPP-4 inhibitors (ROR, 1.67 [95 % CI, 1.17-2.38]; IC, 0.72 [IC 025 , 0.12]), and insulin (ROR, 1.27 [95 % CI, 1.11-1.45]; IC, 0.34 [IC 025 , 0.11]). Despite the high number of reports for GLP-1 RAs, no significant association with sarcopenia was observed (n = 93; ROR, 1.06 [95 % CI, 0.86-1.29]; IC, 0.08 [IC 025 , -0.27])., Conclusions: Antidiabetic drugs showed significant associations with sarcopenia, with SGLT2 inhibitors exhibiting the strongest association. Notably, despite numerous reports, GLP-1 RAs did not show a significant association., Competing Interests: Declaration of competing interest All the authors declared no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)
Published: 2024
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12. National Trends in the Prevalence of Self-Perceived Overweight Among Adolescents Between 2005 and 2022: Nationwide Representative Study.

Author: Jeong J, Lee S, Lee K, Kim S, Park J, Son Y, Lee H, Lee H, Kang J, Rahmati M, Pizzol D, Smith L, López Sánchez GF, Dragioti E, Fond G, Boyer L, Woo S, Rhee SY, and Yon DK
Subjects: Humans, Adolescent, Female, Prevalence, Male, Republic of Korea epidemiology, Risk Factors, Self Concept, Surveys and Questionnaires, COVID-19 epidemiology, COVID-19 psychology, Overweight epidemiology, Overweight psychology
Abstract: Background: Despite several studies on self-evaluation of health and body shape, existing research on the risk factors of self-perceived overweight is insufficient, especially during the COVID-19 pandemic., Objective: This study aims to identify the risk factors affecting self-perceived overweight and examine how the prevalence of self-perceived overweight has changed before and during the COVID-19 pandemic. Specifically, we analyzed the impact of altered lifestyles due to COVID-19 on this phenomenon., Methods: The data used in the study were obtained from middle and high school students who participated in the Korean Youth Risk Behavior Web-based Survey (N=1,189,586). This survey was a 2-stage stratified cluster sampling survey representative of South Korean adolescents. We grouped the survey results by year and estimated the slope in the prevalence of self-perceived overweight before and during the pandemic using weighted linear regression, as well as the prevalence tendencies of self-perceived overweight according to various risk factors. We used prevalence ratios to identify the risk factors for self-perceived overweight. In addition, we conducted comparisons of risk factors in different periods to identify their associations with the COVID-19 pandemic., Results: The prevalence of self-perceived overweight was much higher than BMI-based overweight among 1,189,586 middle and high school participants (grade 7-12) from 2005 to 2022 (female participants: n=577,102, 48.51%). From 2005 to 2019 (prepandemic), the prevalence of self-perceived overweight increased (β=2.80, 95% CI 2.70-2.90), but from 2020 to 2022 (pandemic) it decreased (β=-0.53, 95% CI -0.74 to -0.33). During the pandemic, individuals with higher levels of stress or lower household economic status exhibited a more substantial decrease in the rate of self-perceived overweight. The prevalence of self-perceived overweight tended to be higher among individuals with poor academic performance, lower economic status, poorer subjective health, and a higher stress level., Conclusions: Our nationwide study, conducted over 18 years, indicated that self-perceived overweight decreased during the COVID-19 period while identifying low academic performance and economic status as risk factors. These findings suggest the need for policies and facilities to address serious dieting and body dissatisfaction resulting from self-perceived overweight by developing counseling programs for adolescents with risk factors such as lower school performance and economic status., (©Jinyoung Jeong, Seungjun Lee, Kyeongmin Lee, Seokjun Kim, Jaeyu Park, Yejun Son, Hyeri Lee, Hayeon Lee, Jiseung Kang, Masoud Rahmati, Damiano Pizzol, Lee Smith, Guillermo F López Sánchez, Elena Dragioti, Guillaume Fond, Laurent Boyer, Selin Woo, Sang Youl Rhee, Dong Keon Yon. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 09.10.2024.)
Published: 2024
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13. Machine Learning-Based Prediction of Neurodegenerative Disease in Patients With Type 2 Diabetes by Derivation and Validation in 2 Independent Korean Cohorts: Model Development and Validation Study.

Author: Sang H, Lee H, Park J, Kim S, Woo HG, Koyanagi A, Smith L, Lee S, Hwang YC, Park TS, Lim H, Yon DK, and Rhee SY
Subjects: Humans, Male, Middle Aged, Female, Cohort Studies, Republic of Korea, Aged, Diabetes Mellitus, Type 2 complications, Machine Learning, Neurodegenerative Diseases
Abstract: Background: Several machine learning (ML) prediction models for neurodegenerative diseases (NDs) in type 2 diabetes mellitus (T2DM) have recently been developed. However, the predictive power of these models is limited by the lack of multiple risk factors., Objective: This study aimed to assess the validity and use of an ML model for predicting the 3-year incidence of ND in patients with T2DM., Methods: We used data from 2 independent cohorts-the discovery cohort (1 hospital; n=22,311) and the validation cohort (2 hospitals; n=2915)-to predict ND. The outcome of interest was the presence or absence of ND at 3 years. We selected different ML-based models with hyperparameter tuning in the discovery cohort and conducted an area under the receiver operating characteristic curve (AUROC) analysis in the validation cohort., Results: The study dataset included 22,311 (discovery) and 2915 (validation) patients with T2DM recruited between 2008 and 2022. ND was observed in 133 (0.6%) and 15 patients (0.5%) in the discovery and validation cohorts, respectively. The AdaBoost model had a mean AUROC of 0.82 (95% CI 0.79-0.85) in the discovery dataset. When this result was applied to the validation dataset, the AdaBoost model exhibited the best performance among the models, with an AUROC of 0.83 (accuracy of 78.6%, sensitivity of 78.6%, specificity of 78.6%, and balanced accuracy of 78.6%). The most influential factors in the AdaBoost model were age and cardiovascular disease., Conclusions: This study shows the use and feasibility of ML for assessing the incidence of ND in patients with T2DM and suggests its potential for use in screening patients. Further international studies are required to validate these findings., (©Hyunji Sang, Hojae Lee, Jaeyu Park, Sunyoung Kim, Ho Geol Woo, Ai Koyanagi, Lee Smith, Sihoon Lee, You-Cheol Hwang, Tae Sun Park, Hyunjung Lim, Dong Keon Yon, Sang Youl Rhee. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.10.2024.)
Published: 2024
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14. Quantitative SPECT/CT Metrics in Early Prediction of [ 177 Lu]Lu-DOTATATE Treatment Response in Gastroenteropancreatic Neuroendocrine Tumor Patients.

Author: Tuncer O, Steinberger D, Steiner J, Hinojos M, Rhee SY, Humphrey B, Jafari F, and Cayci Z
Subjects: Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Treatment Outcome, Adult, Aged, 80 and over, Neuroendocrine Tumors radiotherapy, Neuroendocrine Tumors diagnostic imaging, Octreotide analogs & derivatives, Octreotide therapeutic use, Pancreatic Neoplasms radiotherapy, Pancreatic Neoplasms diagnostic imaging, Organometallic Compounds therapeutic use, Intestinal Neoplasms radiotherapy, Intestinal Neoplasms diagnostic imaging, Stomach Neoplasms diagnostic imaging, Stomach Neoplasms radiotherapy, Single Photon Emission Computed Tomography Computed Tomography
Abstract: Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [ 177 Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [ 177 Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (ΔTBS) and changes in normalized peak count (ΔnPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in ΔTBS second-first , ΔTBS third-first , and ΔTBS fourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [ 177 Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. -0.049, 0.08 vs. -0.116, and 0.109 vs. -0.123 [ P = 0.023, P = 0.002, and P < 0.001], respectively). ΔnPC second-first showed significant group differences (mean, -0.107 vs. -0.282; P = 0.033); ΔnPC third-first and ΔnPC fourth-first did not reach statistical significance (mean, -0.122 vs. -0.312 and -0.183 vs. -0.405 [ P = 0.117 and 0.067], respectively). At the optimal threshold, ΔTBS fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. ΔTBS second-first and ΔTBS third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. ΔnPC second-first , ΔnPC third-first , and ΔnPC fourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: ΔTBS and ΔnPC can predict [ 177 Lu]Lu-DOTATATE response by the second treatment session., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
Published: 2024
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15. Prenatal and infant exposure to antibiotics and subsequent risk of neuropsychiatric disorders in children: A nationwide birth cohort study in South Korea.

Author: Oh J, Woo HG, Kim HJ, Park J, Lee M, Rahmati M, Rhee SY, Min C, Koyanagi A, Smith L, Fond G, Boyer L, Kim MS, Shin JI, Lee SW, and Yon DK
Subjects: Humans, Female, Republic of Korea epidemiology, Pregnancy, Male, Infant, Child, Birth Cohort, Adult, Child, Preschool, Cohort Studies, Mental Disorders epidemiology, Mental Disorders chemically induced, Infant, Newborn, Prenatal Exposure Delayed Effects epidemiology, Prenatal Exposure Delayed Effects chemically induced, Anti-Bacterial Agents adverse effects
Abstract: We aimed to assess the association between antibiotic exposure in fetal and postnatal life (within six months after birth) and the risk of neuropsychiatric disorders in childhood. A nationwide, population-based birth cohort study(infants, n = 3,163,206; paired mothers, n = 2,322,735) was conducted in South Korea, with a mean follow-up duration of 6.8 years, using estimates of hazard ratio [HR] and 95 % confidence intervals (CIs). Following propensity score matching including the baseline variables, antibiotic exposure in both fetal (HR,1.07 [95 % CI, 1.05-1.08]) and postnatal life (1.05 [1.03-1.07]) was associated with an increased risk of overall childhood neuropsychiatric disorders. A synergistic effect was observed with prenatal and postnatal exposures (1.12 [1.09-1.15]). The risk increases with the increasing number and duration of prescriptions. Significant associations were found for both common (1.06 [1.05-1.08]) and severe outcomes (1.17 [1.09-1.26]), especially for intellectual disability (1.12 [1.07-1.17]), ADHD (1.10 [1.07-1.13]), anxiety (1.06 [1.02-1.11]), mood (1.06 [1.00-1.12]), and autism (1.03 [1.01-1.07]). When comparing siblings with different exposure statuses to consider familial factors, prenatal and postnatal exposure risk increased to 10 % (95 % CI, 6-12) and 12 % (7-17), respectively. Similar results were observed in the unmatched and health screening cohort, which considers maternal obesity, smoking, and breastfeeding. Based on these findings, clinicians may consider potential long-term risks when assessing the risk-benefit of early-life antibiotic prescription., Competing Interests: Declaration of competing interest None reported., (Copyright © 2024 Elsevier B.V. All rights reserved.)
Published: 2024
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16. Real-World Risk of Gastrointestinal Bleeding for Direct Oral Anticoagulants and Warfarin Users: A Distributed Network Analysis Using a Common Data Model.

Author: Cha JM, Kim M, Jo HH, Seo WW, Rhee SY, Kim JH, Kim GH, and Park J
Subjects: Humans, Male, Female, Aged, Middle Aged, Pyridones adverse effects, Pyridones administration & dosage, Propensity Score, Factor Xa Inhibitors adverse effects, Administration, Oral, Risk Factors, Pyridines adverse effects, Thiazoles adverse effects, Aged, 80 and over, Rivaroxaban adverse effects, Risk Assessment, Warfarin adverse effects, Gastrointestinal Hemorrhage chemically induced, Gastrointestinal Hemorrhage epidemiology, Anticoagulants adverse effects, Pyrazoles adverse effects, Dabigatran adverse effects
Abstract: Background/aims: Early studies on direct oral anticoagulants (DOACs) reported a higher risk of gastrointestinal bleeding (GIB) compared with warfarin; however, recent studies have reported a reduced risk. Therefore, this study was designed to evaluate the risk of GIB in users of DOAC and warfarin., Methods: Using a common data model, we investigated the comparative risk of GIB in subjects from eight hospitals who were newly prescribed DOACs or warfarin. We excluded subjects who had a prior history of GIB or had been prescribed both medications. After propensity score matching, we analyzed 3,347 matched pairs of new DOAC and new warfarin users., Results: The risk of GIB in new DOAC users was comparable to that in new warfarin users (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.65 to 1.40; p=0.808). New DOAC users had a similar risk of GIB to new warfarin users among older patients >65 years (HR, 1.00; 95% CI, 0.69 to 1.52; p=0.997) and in older patients >75 years (HR, 1.21; 95% CI, 0.68 to 2.10; p=0.509). In addition, the risk of GIB was not significantly different between two groups according to sex. We also found that the risk of GIB in DOAC users was 26% lower in edoxaban or apixaban subgroups compared to rivaroxaban or dabigatran subgroups (HR, 0.74; 95% CI, 0.69 to 1.00; p=0.049)., Conclusions: In real-world practice, the risk of GIB in new DOAC users is comparable to that in new warfarin users. In DOAC users, the risk of GIB was lower in edoxaban or apixaban subgroups than rivaroxaban or dabigatran subgroups.
Published: 2024
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17. Global and regional prevalence of polypharmacy and related factors, 1997-2022: An umbrella review.

Author: Kim S, Lee H, Park J, Kang J, Rahmati M, Rhee SY, and Yon DK
Subjects: Humans, Prevalence, Aged, Risk Factors, Aged, 80 and over, Frail Elderly statistics & numerical data, Polypharmacy, Global Health statistics & numerical data
Abstract: Objective: Limited comprehensive evidence exists on the global prevalence of polypharmacy. This knowledge gap contributes to increased healthcare system costs and related public health concerns. Thus, we aimed to synthesize the current evidence on polypharmacy prevalence and associated factors in the general and older populations using an umbrella review., Methods: Our primary outcomes were global prevalence and related indicators of polypharmacy. We systematically searched Google Scholar, PubMed/MEDLINE, Embase, and CINAHL for studies published between the inception of each database until April 30, 2023., Results: Eleven meta-analyses incorporating 295 studies and 59,552,762 participants from 41 countries across six continents were identified. The global prevalence of polypharmacy in the general population is 37 %, with higher rates in older individuals (45 %), outpatients (48 %), and inpatients (52 %). North America showed a higher prevalence (52 %) than Asia (36 %) and Europe (36 %). Among frail elderly individuals, the prevalence of polypharmacy is 59 %, with the highest rates in Europe (68 %) and hospital settings (71 %)., Conclusion: The global prevalence of polypharmacy and its associated factors in older adults present a complex, multifaceted, and conflicting picture. Understanding the prevalence of polypharmacy and its associated factors may help reduce the number of multidrug prescriptions., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)
Published: 2024
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18. Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: a multi-nationwide cohort study from South Korea, Japan, and the UK.

Author: Lee K, Park J, Lee J, Lee M, Kim HJ, Son Y, Rhee SY, Smith L, Rahmati M, Kang J, Lee H, Ha Y, and Yon DK
Abstract: Background/aims: Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of long COVID in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary outcomes and other digestive abnormalities in various follow-up periods., Methods: We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years, including those with SARS-CoV-2 infection between 2020 and 2021 matched to non-infected control patients. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with contemporary controls., Results: The discovery cohort, consisting of 10,027,506 individuals (mean age 48.4 years; 49.9% female), revealed heightened risks of gastrointestinal diseases (HR: 1.15; 95% CI: 1.08-1.22), hepatobiliary diseases (1.30; 1.09-1.55), and other digestive abnormalities (1.05; 1.01-1.10) beyond the first 30 days after infection, following exposure-driven propensity score-matching. These results indicate a pronounced association as the severity of COVID-19 increases. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. Over time, the risk profile was most pronounced during the initial 3 months; however, it persisted for >6 months in validation cohorts, but not in the discovery cohort., Conclusions: The incidences of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.
Published: 2024
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19. Prevalence, Awareness, Treatment, and Control of Type 2 Diabetes in South Korea (1998 to 2022): Nationwide Cross-Sectional Study.

Author: Jang W, Kim S, Son Y, Kim S, Kim HJ, Jo H, Park J, Lee K, Lee H, Tully MA, Rahmati M, Smith L, Kang J, Woo S, Kim S, Hwang J, Rhee SY, and Yon DK
Subjects: Humans, Republic of Korea epidemiology, Male, Middle Aged, Female, Cross-Sectional Studies, Prevalence, Adult, Aged, Nutrition Surveys, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 therapy, COVID-19 epidemiology, Health Knowledge, Attitudes, Practice
Abstract: Background: Type 2 diabetes poses an increasing disease burden in South Korea. The development and management of type 2 diabetes are closely related to lifestyle and socioeconomic factors, which have undergone substantial changes over the past few decades, including during the COVID-19 pandemic., Objective: This study aimed to investigate long-term trends in type 2 diabetes prevalence, awareness, treatment, and control. It also aimed to determine whether there were substantial alterations in the trends during the pandemic and whether these changes were more pronounced within specific demographic groups., Methods: This study examined the prevalence, awareness, treatment, and control of type 2 diabetes in a representative sample of 139,786 South Koreans aged >30 years, using data from the National Health and Nutrition Examination Survey and covering the period from 1998 to 2022. Weighted linear regression and binary logistic regression were performed to calculate weighted β coefficients or odds ratios. Stratified analyses were performed based on sex, age, region of residence, obesity status, educational background, household income, and smoking status. β (difference) was calculated to analyze the trend difference between the prepandemic period and the COVID-19 pandemic. To identify groups more susceptible to type 2 diabetes, we estimated interaction terms for each factor and calculated weighted odds ratios., Results: From 1998 to 2022, a consistent increase in the prevalence of type 2 diabetes was observed among South Koreans, with a notable rise to 15.61% (95% CI 14.83-16.38) during the pandemic. Awareness followed a U-shaped curve, bottoming out at 64.37% (95% CI 61.79-66.96) from 2013 to 2015 before increasing to 72.56% (95% CI 70.39-74.72) during the pandemic. Treatment also increased over time, peaking at 68.33% (95% CI 65.95-70.71) during the pandemic. Control among participants with diabetes showed no substantial change, maintaining a rate of 29.14% (95% CI 26.82-31.47) from 2020 to 2022, while control among treated participants improved to 30.68% (95% CI 27.88-33.48). During the pandemic, there was a steepening of the curves for awareness and treatment. However, while the slope of control among participants being treated increased, the slope of control among participants with diabetes showed no substantial change during the pandemic. Older populations and individuals with lower educational level exhibited less improvement in awareness and control trends than younger populations and more educated individuals. People with lower income experienced a deceleration in prevalence during the pandemic., Conclusions: Over the recent decade, there has been an increase in type 2 diabetes prevalence, awareness, treatment, and control. During the pandemic, a steeper increase in awareness, treatment, and control among participants being treated was observed. However, there were heterogeneous changes across different population groups, underscoring the need for targeted interventions to address disparities and improve diabetes management for susceptible populations., (©Wonwoo Jang, Seokjun Kim, Yejun Son, Soeun Kim, Hyeon Jin Kim, Hyesu Jo, Jaeyu Park, Kyeongmin Lee, Hayeon Lee, Mark A Tully, Masoud Rahmati, Lee Smith, Jiseung Kang, Selin Woo, Sunyoung Kim, Jiyoung Hwang, Sang Youl Rhee, Dong Keon Yon. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 27.08.2024.)
Published: 2024
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20. National and Regional Trends in the Prevalence of Hypertension in South Korea Amid the Pandemic, 2009-2022: Nationwide Study of Over 3 Million Individuals.

Author: Lee H, Kim M, Woo S, Park J, Kim HJ, Kwon R, Koyanagi A, Smith L, Kim MS, López Sánchez GF, Dragioti E, Lee J, Lee H, Rahmati M, Rhee SY, Lee JH, Woo HG, and Yon DK
Subjects: Humans, Republic of Korea epidemiology, Prevalence, Middle Aged, Adult, Female, Male, Cross-Sectional Studies, Aged, Young Adult, Pandemics, Health Surveys, Hypertension epidemiology, COVID-19 epidemiology
Abstract: Background: Understanding the association between hypertension prevalence and socioeconomic and behavioral variables during a pandemic is essential, and this analysis should extend beyond short-term trends., Objective: This study aims to examine long-term trends in the prevalence of participants diagnosed with and receiving treatment for hypertension, using data collected by a nationally representative survey from 2009 to 2022, which includes the COVID-19 pandemic era., Methods: A nationwide, population-based, cross-sectional study used data collected from the South Korea Community Health Survey between 2009 and 2022. The study sample comprised 3,208,710 Korean adults over a period of 14 years. We aimed to assess trends in the prevalence of participants diagnosed with and receiving treatment for hypertension in the national population from 2009 to 2022, with a specific focus on the COVID-19 pandemic, using weighted linear regression models., Results: Among the included 3,072,546 Korean adults, 794,239 (25.85%) were aged 19-39 years, 1,179,388 (38.38%) were aged 40-59 years; 948,097 (30.86%) were aged 60-79 years, and 150,822 (4.91%) were aged 80 years or older. A total of 1,426,379 (46.42%) were men; 761,896 (24.80%) and 712,264 (23.18%) were diagnosed with and received treatment for hypertension, respectively. Although the overall prevalence over the 14-year period increased, the upward trends of patients diagnosed with and receiving treatment for hypertension decreased during the COVID-19 pandemic era compared with the prepandemic era (β difference for trend during vs before the pandemic -.101, 95% CI -0.107 to -0.094 vs -.133, 95% CI -0.140 to -0.127). Notably, the trends in prevalence during the pandemic were less pronounced in subgroups of older adults (≥60 years old) and individuals with higher alcohol consumption (≥5 days/month)., Conclusions: This nationwide representative study found that the national prevalence of participants diagnosed with and receiving treatment for hypertension increased during the prepandemic era. However, there was a marked decrease in these trends during the prepandemic era, compared with the pandemic era, particularly among specific subgroups at increased risk of negative outcomes. Future studies are needed to evaluate the factors associated with changes in the prevalence of hypertension during the COVID-19 pandemic., (©Hyeri Lee, Minji Kim, Selin Woo, Jaeyu Park, Hyeon Jin Kim, Rosie Kwon, Ai Koyanagi, Lee Smith, Min Seo Kim, Guillermo F López Sánchez, Elena Dragioti, Jinseok Lee, Hayeon Lee, Masoud Rahmati, Sang Youl Rhee, Jun Hyuk Lee, Ho Geol Woo, Dong Keon Yon. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 30.07.2024.)
Published: 2024
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21. Association of Soda Drinks and Fast Food with Allergic Diseases in Korean Adolescents: A Nationwide Representative Study.

Author: Jeong J, Jo H, Son Y, Lee S, Lee K, Choi Y, Lee H, Kim S, Jacob L, Smith L, Lee JH, Rhee SY, Kim S, Kang J, Hwang J, Park J, Woo S, and Yon DK
Abstract: Introduction: A high consumption of carbonated soft drinks (i.e., soda drinks) and fast food is potentially associated with the observed global rise in adolescent allergic diseases. Thus, our study aimed to examine the potential associations between the consumption of soda drinks and fast food and allergic conditions, identifying specific relationships across subgroups and each allergic condition (asthma, allergic rhinitis, and atopic dermatitis)., Methods: This study uses large-scale data from the Korea Youth Risk Behavior Web-Based Survey (total n = 865,614). Soda drinks and fast food were defined by a self-reported questionnaire and allergic conditions by physician-diagnosed within 1 year. Multivariable logistic regression was used to analyze the weighted odds ratios (ORs), along with 95% confidence intervals (CIs), for allergic diseases associated with the intake of soda drinks and fast food., Results: Among 865,614 adolescents in grades 7-12 (male, 51.40%), patients with asthma, allergic rhinitis, and atopic dermatitis were 18,568 (2.15%), 153,536 (17.74%), and 59,014 (6.82%), respectively. Current asthma was associated with soda drinks (OR, 1.07; 95% CI, 1.03-1.12) and fast food consumption (1.25; 1.17-1.33). Interestingly, stronger associations were observed for female high schoolers, compared to male high schoolers and middle schoolers, in relation to the consumption of soda drinks (1.31; 1.19-1.44) and fast food (1.46; 1.26-1.69) with asthma. Current allergic rhinitis and atopic dermatitis had no significant association with fast food consumption and soda drinks., Conclusion: This first large-scale study suggests that fast food and soda drinks consumption are potentially associated with current asthma, with stronger associations observed in females than males, underscoring the need for sex-specific allergy prevention programs., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
Published: 2024
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22. 2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association.

Author: Moon JS, Kang S, Choi JH, Lee KA, Moon JH, Chon S, Kim DJ, Kim HJ, Seo JA, Kim MK, Lim JH, Song YJ, Yang YS, Kim JH, Lee YB, Noh J, Hur KY, Park JS, Rhee SY, Kim HJ, Kim HM, Ko JH, Kim NH, Kim CH, Ahn J, Oh TJ, Kim SK, Kim J, Han E, Jin SM, Bae J, Jeon E, Kim JM, Kang SM, Park JH, Yun JS, Cha BS, Moon MK, and Lee BW
Subjects: Humans, Republic of Korea epidemiology, Hypoglycemic Agents therapeutic use, Diabetes Mellitus, Type 2 therapy, Diabetes Mellitus, Type 2 epidemiology, Disease Management, Societies, Medical, Diabetes Mellitus therapy, Diabetes Mellitus epidemiology
Published: 2024
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23. Global burden of vaccine-associated hepatobiliary and gastrointestinal adverse drug reactions, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

Author: Lee S, Lee K, Park J, Jeong YD, Jo H, Kim S, Woo S, Son Y, Kim HJ, Lee K, Ha Y, Oh NE, Lee J, Rhee SY, Smith L, Kang J, Rahmati M, Lee H, and Yon DK
Subjects: Humans, Adverse Drug Reaction Reporting Systems statistics & numerical data, COVID-19 Vaccines adverse effects, Drug-Related Side Effects and Adverse Reactions epidemiology, COVID-19 prevention & control, COVID-19 epidemiology, Chemical and Drug Induced Liver Injury epidemiology, Chemical and Drug Induced Liver Injury etiology, Vaccines adverse effects, World Health Organization, Gastrointestinal Diseases chemically induced, Gastrointestinal Diseases epidemiology, Incidence, Global Health, Pharmacovigilance, Databases, Factual
Abstract: Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC 0.25 , the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC 0.25 ]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management., (© 2024 Wiley Periodicals LLC.)
Published: 2024
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24. Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

Author: Lee JE, Yu SH, Kim SR, Ahn KJ, Song KH, Lee IK, Shon HS, Kim IJ, Lim S, Kim DM, Chung CH, Lee WY, Lee SH, Kim DJ, Cho SR, Jung CH, Jeon HJ, Lee SH, Park KY, Rhee SY, Kim SG, Park SO, Kim DJ, Kim BJ, Lee SA, Kim YH, Kim KS, Seo JA, Nam-Goong IS, Lee CW, Kim DK, Kim SW, Cho CG, Kim JH, Kim YJ, Yoo JM, Min KW, and Lee MK
Subjects: Humans, Male, Female, Double-Blind Method, Middle Aged, Aged, Treatment Outcome, Adult, Atorvastatin therapeutic use, Atorvastatin administration & dosage, Metformin therapeutic use, Metformin administration & dosage, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 blood, Dyslipidemias drug therapy, Dyslipidemias blood, Drug Therapy, Combination, Glycated Hemoglobin analysis, Hypoglycemic Agents therapeutic use, Hypoglycemic Agents administration & dosage, Cholesterol, LDL blood
Abstract: Backgruound: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia., Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment., Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events., Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
Published: 2024
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25. Prediction model for cardiovascular disease in patients with diabetes using machine learning derived and validated in two independent Korean cohorts.

Author: Sang H, Lee H, Lee M, Park J, Kim S, Woo HG, Rahmati M, Koyanagi A, Smith L, Lee S, Hwang YC, Park TS, Lim H, Yon DK, and Rhee SY
Subjects: Humans, Female, Male, Middle Aged, Republic of Korea epidemiology, Aged, Cohort Studies, ROC Curve, Risk Factors, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Machine Learning, Diabetes Mellitus, Type 2 complications
Abstract: This study aimed to develop and validate a machine learning (ML) model tailored to the Korean population with type 2 diabetes mellitus (T2DM) to provide a superior method for predicting the development of cardiovascular disease (CVD), a major chronic complication in these patients. We used data from two cohorts, namely the discovery (one hospital; n = 12,809) and validation (two hospitals; n = 2019) cohorts, recruited between 2008 and 2022. The outcome of interest was the presence or absence of CVD at 3 years. We selected various ML-based models with hyperparameter tuning in the discovery cohort and performed area under the receiver operating characteristic curve (AUROC) analysis in the validation cohort. CVD was observed in 1238 (10.2%) patients in the discovery cohort. The random forest (RF) model exhibited the best overall performance among the models, with an AUROC of 0.830 (95% confidence interval [CI] 0.818-0.842) in the discovery dataset and 0.722 (95% CI 0.660-0.783) in the validation dataset. Creatinine and glycated hemoglobin levels were the most influential factors in the RF model. This study introduces a pioneering ML-based model for predicting CVD in Korean patients with T2DM, outperforming existing prediction tools and providing a groundbreaking approach for early personalized preventive medicine., (© 2024. The Author(s).)
Published: 2024
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26. A high-throughput behavioral screening platform for measuring chemotaxis by C. elegans.

Author: Fryer E, Guha S, Rogel-Hernandez LE, Logan-Garbisch T, Farah H, Rezaei E, Mollhoff IN, Nekimken AL, Xu A, Seyahi LS, Fechner S, Druckmann S, Clandinin TR, Rhee SY, and Goodman MB
Subjects: Animals, Smell physiology, Behavior, Animal drug effects, Behavior, Animal physiology, Software, Caenorhabditis elegans physiology, Caenorhabditis elegans drug effects, Chemotaxis, High-Throughput Screening Assays methods
Abstract: Throughout history, humans have relied on plants as a source of medication, flavoring, and food. Plants synthesize large chemical libraries and release many of these compounds into the rhizosphere and atmosphere where they affect animal and microbe behavior. To survive, nematodes must have evolved the sensory capacity to distinguish plant-made small molecules (SMs) that are harmful and must be avoided from those that are beneficial and should be sought. This ability to classify chemical cues as a function of their value is fundamental to olfaction and represents a capacity shared by many animals, including humans. Here, we present an efficient platform based on multiwell plates, liquid handling instrumentation, inexpensive optical scanners, and bespoke software that can efficiently determine the valence (attraction or repulsion) of single SMs in the model nematode, Caenorhabditis elegans. Using this integrated hardware-wetware-software platform, we screened 90 plant SMs and identified 37 that attracted or repelled wild-type animals but had no effect on mutants defective in chemosensory transduction. Genetic dissection indicates that for at least 10 of these SMs, response valence emerges from the integration of opposing signals, arguing that olfactory valence is often determined by integrating chemosensory signals over multiple lines of information. This study establishes that C. elegans is an effective discovery engine for determining chemotaxis valence and for identifying natural products detected by the chemosensory nervous system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fryer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2024
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27. GPT-4 performance on querying scientific publications: reproducibility, accuracy, and impact of an instruction sheet.

Author: Tao K, Osman ZA, Tzou PL, Rhee SY, Ahluwalia V, and Shafer RW
Subjects: Humans, Reproducibility of Results, PubMed, Publications statistics & numerical data, Publications standards, Information Storage and Retrieval methods, Information Storage and Retrieval standards, Software, HIV Infections drug therapy
Abstract: Background: Large language models (LLMs) that can efficiently screen and identify studies meeting specific criteria would streamline literature reviews. Additionally, those capable of extracting data from publications would enhance knowledge discovery by reducing the burden on human reviewers., Methods: We created an automated pipeline utilizing OpenAI GPT-4 32 K API version "2023-05-15" to evaluate the accuracy of the LLM GPT-4 responses to queries about published papers on HIV drug resistance (HIVDR) with and without an instruction sheet. The instruction sheet contained specialized knowledge designed to assist a person trying to answer questions about an HIVDR paper. We designed 60 questions pertaining to HIVDR and created markdown versions of 60 published HIVDR papers in PubMed. We presented the 60 papers to GPT-4 in four configurations: (1) all 60 questions simultaneously; (2) all 60 questions simultaneously with the instruction sheet; (3) each of the 60 questions individually; and (4) each of the 60 questions individually with the instruction sheet., Results: GPT-4 achieved a mean accuracy of 86.9% - 24.0% higher than when the answers to papers were permuted. The overall recall and precision were 72.5% and 87.4%, respectively. The standard deviation of three replicates for the 60 questions ranged from 0 to 5.3% with a median of 1.2%. The instruction sheet did not significantly increase GPT-4's accuracy, recall, or precision. GPT-4 was more likely to provide false positive answers when the 60 questions were submitted individually compared to when they were submitted together., Conclusions: GPT-4 reproducibly answered 3600 questions about 60 papers on HIVDR with moderately high accuracy, recall, and precision. The instruction sheet's failure to improve these metrics suggests that more sophisticated approaches are necessary. Either enhanced prompt engineering or finetuning an open-source model could further improve an LLM's ability to answer questions about highly specialized HIVDR papers., (© 2024. The Author(s).)
Published: 2024
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28. Risks of cutaneous immune-related adverse events in long COVID: Multinational cohort studies in South Korea, Japan, and the UK.

Author: Kim H, Kyung S, Park J, Lee H, Lee M, Smith L, Rahmati M, Shin JY, Kang J, Jacob L, Papadopoulos NG, Rhee SY, Lee J, Kim HJ, Lee H, and Yon DK
Subjects: Humans, Middle Aged, Male, Female, Republic of Korea epidemiology, United Kingdom epidemiology, Japan epidemiology, Adult, Aged, Cohort Studies, SARS-CoV-2 immunology, COVID-19 Vaccines adverse effects, COVID-19 Vaccines immunology, Risk Factors, Proportional Hazards Models, Young Adult, Skin Diseases epidemiology, COVID-19 epidemiology, COVID-19 immunology
Abstract: Previous research has not investigated the persistent cutaneous immune-related adverse events (cirAEs) related to long COVID to investigate the long-term sequelae. This multinational study, using a propensity-matched overlap weighting method, utilizes large national claims-based cohorts, using ICD-10 code diagnosis, focusing on patients aged ≥20 years from three countries: South Korean, Japanese, and the British cohorts. To estimate the risk of cirAEs in long COVID, the persistence or emergence of cirAEs occurring 4 weeks after the initial SARS-CoV-2 infection, we employed a Cox proportional hazard regression model. The Korean cohort (n = 5,937,373; mean age 49.2 years [SD: 13.2]), the Japanese cohort (n = 4,307,587; 42.5 years [13.6]), and the UK cohort (n = 395,435; 71.0 years [8.07]) were presented. An increased risk of cirAEs in long COVID was observed (HR, 1.10; 95% CI, 1.06-1.14) in Korean cohort, while a similar association was observed in Japanese and UK cohorts. The long-term risk of cirAEs in long COVID was higher in more severe COVID-19 cases (1.31; 1.22-1.39). Unlike the increased risk of cirAEs in long COVID, COVID-19 vaccination attenuated the risk, especially with two or more doses (1.03; 0.95-1.11) or heterologous regimens (0.98; 0.76-1.27). The time attenuation effect indicated a sustained risk for up to 6 months postinfection (<3 months: 1.13 [1.07-1.19]; 3-6 months: 1.14 [1.06-1.22]). SARS-CoV-2 infection is associated with an increased risk of cirAEs in the aspect of long COVID. Vaccination might reduce this risk, highlighting the need for preventive strategies in long COVID management., (© 2024 Wiley Periodicals LLC.)
Published: 2024
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29. A reference-free algorithm discovers regulation in the plant transcriptome.

Author: Meyer E, Saldivar EV, Kokot M, Xue B, Deorowicz S, Rhee SY, and Salzman J
Abstract: Most plant genomes and their regulation remain unknown. We used SPLASH - a new, reference-genome free sequence variation detection algorithm - to analyze transcriptional and post-transcriptional regulation from RNA-seq data. We discovered differential homolog expression during maize pollen development, and imbibition-dependent cryptic splicing in Arabidopsis seeds. SPLASH enables discovery of novel regulatory mechanisms, including differential regulation of genes from hybrid parental haplotypes, without the use of alignment to a reference genome.
Published: 2024
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30. Comparison of Finasteride and Dutasteride on Risk of Prostate Cancer in Patients with Benign Prostatic Hyperplasia: A Pooled Analysis of 15 Real-world Databases.

Author: Yang DY, Seo WW, Park RW, Rhee SY, Cha JM, Hah YS, Jeong CW, Kim KJ, Yang HJ, Kim DK, and Ha JY
Abstract: Purpose: Finasteride and dutasteride are used to treat benign prostatic hyperplasia (BPH) and reduce the risk of developing prostate cancer. Finasteride blocks only the type 2 form of 5-alpha-reductase, whereas dutasteride blocks both type 1 and 2 forms of the enzyme. Previous studies suggest the possibility that dutasteride may be superior to finasteride in preventing prostate cancer. We directly compared the effects of finasteride and dutasteride on the risk of prostate cancer in patients with BPH using a pooled analysis of 15 real-world databases., Materials and Methods: We conducted a multicenter, cohort study of new-users of finasteride and dutasteride. We include patients who were prescribed 5 mg finasteride or dutasteride for the first time to treat BPH and had at least 180 days of prescription. We excluded patients with a history of prostate cancer or a prostate-specific antigen level ≥ 4 ng/mL before the study drug prescription. Cox regression analysis was performed to examine the hazard ratio (HR) for prostate cancer after propensity score (PS) matching., Results: A total of 8,284 patients of new-users of finasteride and 8,670 patients of new-users of dutasteride were included across the 15 databases. In the overall population, compared to dutasteride, finasteride was associated with a lower risk of prostate cancer in both on-treatment and intent-to-treat time-at-risk periods. After 1:1 PS matching, 4,897 patients using finasteride and 4,897 patients using dutasteride were enrolled in the present study. No significant differences were observed for risk of prostate cancer between finasteride and dutasteride both on-treatment (HR=0.66, 95% confidence interval [CI]: 0.44-1.00; p=0.051) and intent-to-treat time-at-risk periods (HR=0.87, 95% CI: 0.67-1.14; p=0.310)., Conclusions: Using real-world databases, the present study demonstrated that dutasteride was not associated with a lower risk of prostate cancer than finasteride in patients with BPH., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)
Published: 2024
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31. Research on the Multiple Small Target Detection Methodology in Remote Sensing.

Author: Zou C, Jeon WS, and Rhee SY
Abstract: This study focuses on advancing the field of remote sensing image target detection, addressing challenges such as small target detection, complex background handling, and dense target distribution. We propose solutions based on enhancing the YOLOv7 algorithm. Firstly, we improve the multi-scale feature enhancement (MFE) method of YOLOv7, enhancing its adaptability and precision in detecting small targets and complex backgrounds. Secondly, we design a modified YOLOv7 global information DP-MLP module to effectively capture and integrate global information, thereby improving target detection accuracy and robustness, especially in handling large-scale variations and complex scenes. Lastly, we explore a semi-supervised learning model (SSLM) target detection algorithm incorporating unlabeled data, leveraging information from unlabeled data to enhance the model's generalization ability and performance. Experimental results demonstrate that despite the outstanding performance of YOLOv7, the mean average precision (MAP) can still be improved by 1.9%. Specifically, under testing on the TGRS-HRRSD-Dataset, the MFE and DP-MLP models achieve MAP values of 93.4% and 93.1%, respectively. Across the NWPU VHR-10 dataset, the three models achieve MAP values of 93.1%, 92.1%, and 92.2%, respectively. Significant improvements are observed across various metrics compared to the original model. This study enhances the adaptability, accuracy, and generalization of remote sensing image object detection.
Published: 2024
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32. Efficacy of information and communication technology interventions for the management of diabetes mellitus: An umbrella review and evidence map.

Author: Park S, Lee H, Cho W, Woo HG, Lim H, Kim S, Rhee SY, and Yon DK
Subjects: Humans, Pregnancy, Diabetes, Gestational therapy, Diabetes Mellitus therapy, Randomized Controlled Trials as Topic, Female, Diabetes Mellitus, Type 2 therapy
Abstract: Introduction: We validated the quality of evidence and potential benefits of information and communication technology interventions on diabetes-related health outcomes., Methods: We systematically searched PubMed/MEDLINE, Embase, Google Scholar, and CINAHL and manually searched the reference lists of the retrieved review articles from each database's inception to October 2022. Randomized controlled trials were included to determine the benefits of information and communication technology interventions on diabetes outcomes., Results: Ten meta-analyses of randomized controlled trials were included, with 37 unique outcomes encompassing 379 studies and >70,000 participants across 47 countries and six continents. Information and communication technology intervention was associated with reduced HbA1c levels in patients with type 1 (moderate certainty), type 2 (moderate certainty), and gestational diabetes (low certainty) and showed potential benefits for type 2 diabetes, demonstrating a reduction in systolic blood pressure (high certainty), low-density lipoprotein cholesterol (low certainty), and body weight (low certainty), whereas those for gestational diabetes demonstrated a reduction in fasting (low certainty) and 2-h postprandial blood glucose levels (low certainty)., Conclusion: This umbrella review and evidence map revealed varying evidence on the potential benefits of information and communication technology interventions for diabetes-related outcomes. Our results demonstrate these interventions to be novel treatment options for policymakers and physicians to establish personalized health strategies., (© 2024 World Obesity Federation.)
Published: 2024
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33. An efficient behavioral screening platform classifies natural products and other chemical cues according to their chemosensory valence in C. elegans .

Author: Fryer E, Guha S, Rogel-Hernandez LE, Logan-Garbisch T, Farah H, Rezaei E, Mollhoff IN, Nekimken AL, Xu A, Selin Seyahi L, Fechner S, Druckmann S, Clandinin TR, Rhee SY, and Goodman MB
Abstract: Throughout history, humans have relied on plants as a source of medication, flavoring, and food. Plants synthesize large chemical libraries and release many of these compounds into the rhizosphere and atmosphere where they affect animal and microbe behavior. To survive, nematodes must have evolved the sensory capacity to distinguish plant-made small molecules (SMs) that are harmful and must be avoided from those that are beneficial and should be sought. This ability to classify chemical cues as a function of their value is fundamental to olfaction, and represents a capacity shared by many animals, including humans. Here, we present an efficient platform based on multi-well plates, liquid handling instrumentation, inexpensive optical scanners, and bespoke software that can efficiently determine the valence (attraction or repulsion) of single SMs in the model nematode, Caenorhabditis elegans . Using this integrated hardware-wetware-software platform, we screened 90 plant SMs and identified 37 that attracted or repelled wild-type animals, but had no effect on mutants defective in chemosensory transduction. Genetic dissection indicates that for at least 10 of these SMs, response valence emerges from the integration of opposing signals, arguing that olfactory valence is often determined by integrating chemosensory signals over multiple lines of information. This study establishes that C. elegans is an effective discovery engine for determining chemotaxis valence and for identifying natural products detected by the chemosensory nervous system., Competing Interests: Competing interests Authors declare that they have no competing interests.
Published: 2024
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34. Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK.

Author: Oh J, Lee M, Kim M, Kim HJ, Lee SW, Rhee SY, Koyanagi A, Smith L, Kim MS, Lee H, Lee J, and Yon DK
Subjects: Humans, Female, Middle Aged, Male, Japan epidemiology, COVID-19 Vaccines, SARS-CoV-2, Cohort Studies, United Kingdom epidemiology, COVID-19 epidemiology, Asthma, Rhinitis, Allergic epidemiology, Rhinitis, Allergic diagnosis
Abstract: As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020-2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13-1.27), notably in asthma (HR, 2.25; 95% CI, 1.80-2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15-1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68-0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts., (© 2024. The Author(s).)
Published: 2024
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35. Weight Management Health Note, a Mobile Health Platform for Obesity Management Developed by the Korean Society for the Study of Obesity.

Author: Lee Y, Sang H, Kim S, Choi DA, and Rhee SY
Abstract: The Weight Management Health Note application, developed by the Korean Society for the Study of Obesity (KSSO), was designed to assist individuals in weight management and enhance overall well-being. The Committee of IT-Convergence Treatment of Metabolic Syndrome of the KSSO designed this application. Committee members reviewed and supervised the application's underlying driving algorithms and scientific rationale. A healthcare-specific application developer subsequently finalized the application. This application encompasses a myriad of features, including a comprehensive food diary, an exercise tracker, and tailor-made lifestyle recommendations aligned with individual needs and aspirations. Moreover, it facilitates connections within a community of like-minded individuals endeavoring to manage their weight, fostering mutual support and motivation. Importantly, the application is rich in evidence-based health content curated by the KSSO, ensuring users access accurate information for effective obesity management. Looking ahead, the KSSO is committed to orchestrating diverse academic research endeavors linked to this application and refining its functionalities through continuous feedback from users. The KSSO aspires for this application to serve as a valuable resource for individuals striving to manage their health and enhance their quality of life.
Published: 2024
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36. Obesity in Children and Adolescents: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

Author: Kang E, Hong YH, Kim J, Chung S, Kim KK, Haam JH, Kim BT, Kim EM, Park JH, Rhee SY, Kang JH, and Rhie YJ
Abstract: The prevalence of obesity in children and adolescents has been gradually increasing in recent years and has become a major health problem. Childhood obesity can readily progress to adult obesity. It is associated with obesity-related comorbidities, such as type 2 diabetes mellitus, hypertension, obstructive sleep apnea, non-alcoholic fatty liver disease, and the risk factor for cardiovascular disease. It is important to make an accurate assessment of overweight and obesity in children and adolescents with consideration of growth and development. Childhood obesity can then be prevented and treated using an appropriate treatment goal and safe and effective treatment strategies. This article summarizes the clinical practice guidelines for obesity in children and adolescents that are included in the 8th edition of the Clinical Practice Guidelines for Obesity of the Korean Society for the Study of Obesity.
Published: 2024
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37. Non-destructive, whole-plant phenotyping reveals dynamic changes in water use efficiency, photosynthesis, and rhizosphere acidification of sorghum accessions under osmotic stress.

Author: Ginzburg DN, Cox JA, and Rhee SY
Abstract: Noninvasive phenotyping can quantify dynamic plant growth processes at higher temporal resolution than destructive phenotyping and can reveal phenomena that would be missed by end-point analysis alone. Additionally, whole-plant phenotyping can identify growth conditions that are optimal for both above- and below-ground tissues. However, noninvasive, whole-plant phenotyping approaches available today are generally expensive, complex, and non-modular. We developed a low-cost and versatile approach to noninvasively measure whole-plant physiology over time by growing plants in isolated hydroponic chambers. We demonstrate the versatility of our approach by measuring whole-plant biomass accumulation, water use, and water use efficiency every two days on unstressed and osmotically stressed sorghum accessions. We identified relationships between root zone acidification and photosynthesis on whole-plant water use efficiency over time. Our system can be implemented using cheap, basic components, requires no specific technical expertise, and should be suitable for any non-aquatic vascular plant species., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)
Published: 2024
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38. Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.

Author: Chu C, Tao K, Kouamou V, Avalos A, Scott J, Grant PM, Rhee SY, McCluskey SM, Jordan MR, Morgan RL, and Shafer RW
Subjects: Humans, Cross-Sectional Studies, Prevalence, Lamivudine therapeutic use, Heterocyclic Compounds, 3-Ring therapeutic use, Heterocyclic Compounds, 3-Ring pharmacology, Mutation, HIV Infections drug therapy, HIV Infections epidemiology, HIV Integrase Inhibitors therapeutic use, HIV Integrase Inhibitors pharmacology, Anti-HIV Agents therapeutic use, Oxazines, Piperazines, Pyridones
Abstract: Background: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART., Methods: We performed a PubMed search using the term "Dolutegravir", last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART., Results: Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details., Conclusions: In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.
Published: 2024
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39. Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19 : A Binational Cohort Study.

Author: Kim MS, Lee H, Lee SW, Kwon R, Rhee SY, Lee JA, Koyanagi A, Smith L, Fond G, Boyer L, Lee J, Rahmati M, Shin JY, Min C, Shin JI, and Yon DK
Subjects: Male, Humans, Middle Aged, Female, Cohort Studies, SARS-CoV-2, Longitudinal Studies, COVID-19 epidemiology, Influenza, Human
Abstract: Background: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings., Objective: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods., Design: Binational, longitudinal, propensity-matched cohort study., Setting: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort)., Participants: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients., Measurements: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients., Results: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort., Limitations: Referral bias due to the pandemic; residual confounding., Conclusion: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19., Primary Funding Source: National Research Foundation of Korea., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1831.
Published: 2024
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40. Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study.

Author: Yang YS, Kim NH, Baek JH, Ko SH, Son JW, Lee SH, Rhee SY, Kim SK, Sohn TS, Jun JE, Jeong IK, Kim CH, Song K, Rhee EJ, Noh J, and Hur KY
Subjects: Adult, Humans, Male, Aged, Hypoglycemic Agents pharmacology, Retrospective Studies, Republic of Korea epidemiology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 epidemiology, Cardiovascular Diseases complications, Cardiovascular Diseases epidemiology, Cardiovascular Diseases chemically induced
Abstract: Backgruound: Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD., Methods: We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study., Results: Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users., Conclusion: The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.
Published: 2024
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41. National Trends in the Prevalence of Screen Time and Its Association With Biopsychosocial Risk Factors Among Korean Adolescents, 2008-2021.

Author: Oh J, Kim M, Rhee SY, Rahmati M, Koyanagi A, Smith L, Kim MS, Fond G, Boyer L, Kim S, Shin JI, and Yon DK
Subjects: Humans, Adolescent, Female, Prevalence, Screen Time, Risk Factors, Republic of Korea epidemiology, Pandemics, COVID-19
Abstract: Purpose: Prior studies suggested an increase in screen time among adolescents during the COVID-19 pandemic; however, due to limited sample size and a short-term observation period, these associations are inconclusive and inconsistent. Thus, we aimed to compare screen time during the pandemic and the long-term trend through a Korean large-scale and long-term study of one million adolescents., Methods: Data from 2008 to 2021 on 913,191 Korean adolescents aged 12-18 years were obtained via a nationwide, large-scale, and serial study. We investigated the change of screen time use over time and the change in trend before and during the pandemic (2008-2019 vs. 2020-2021) by using weighted linear regression model with estimates of β-coefficients and 95% confidence intervals (CIs). Moreover, we analyzed the differences in vulnerability of biopsychosocial factor before and during the pandemic., Results: A total of 913,191 adolescents were included in this analysis. During the pandemic, the overall screen time of Korean adolescents significantly increased compared to the expected based on the prepandemic period during the pre-COVID-19 period (weighted screen time before the pandemic [133.24 min/day; 95% CI, 132.08-134.40] vs. during the pandemic [303.66 min/day; 95% CI, 300.59-306.73]; β diff 0.331; 95% CI, 0.311-0.351). Comparing before and during the pandemic, potential risk factors associated with screen exposure included female sex, sadness, suicidal thoughts, alcohol consumption, low educational level of parents, low level of vigorous physical activity, middle school students, and low household income., Discussion: Through large-scale nationwide study, this study described the 14-year trend of screen time among Korean adolescents. In the era of COVID-19, the prevalence of screen exposure has been increasing more rapidly than before at the population level. Also, the pandemic amplified the differences in screen time across grade, sex, sadness, suicidal thoughts, smoking, alcohol consumption, education level of parents, physical activity, and household income groups., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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42. Arabidopsis thaliana RHAMNOSE 1 condensate formation drives UDP-rhamnose synthesis.

Author: Field S, Dorone Y, Dwyer WP, Cox JA, Raba D, Froehlich J, Blea M, Carmo OMS, Wallace IS, Hastings R, Boeynaems S, and Rhee SY
Abstract: Rhamnose is an essential component of the plant cell wall and is synthesized from uridine diphosphate (UDP)-glucose by the RHAMNOSE1 (RHM1) enzyme. RHM1 localizes to biomolecular condensates in plants, but their identity, formation, and function remain elusive. Combining live imaging, genetics, and biochemical approaches in Arabidopsis and heterologous systems, we show that RHM1 alone is sufficient to form enzymatically active condensates, which we name rhamnosomes. Rhamnosome formation is required for UDP-rhamnose synthesis and organ development. Overall, our study demonstrates a novel role for biomolecular condensation in metabolism and organismal development, and provides further support for how organisms have harnessed this biophysical process to regulate small molecule metabolism.
Published: 2024
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43. Efficacy of Crataegus Extract Mixture on Body Fat and Lipid Profiles in Overweight Adults: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

Author: Song J, Kim DY, Lee HS, Rhee SY, and Lim H
Subjects: Adult, Humans, Leptin pharmacology, Body Weight, Obesity drug therapy, Adipose Tissue, Body Mass Index, Lipids, Double-Blind Method, Overweight drug therapy, Crataegus, Plant Extracts
Abstract: A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20-60 years with body mass indexes between 25 and 30 kg/m 2 . Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks, the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals., Competing Interests: The authors declare no conflict of interest. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Published: 2024
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44. Variability in drought gene expression datasets highlight the need for community standardization.

Author: VanBuren R, Nguyen A, Marks RA, Mercado C, Pardo A, Pardo J, Schuster J, Aubin BS, Wilson ML, and Rhee SY
Abstract: Physiologically relevant drought stress is difficult to apply consistently, and the heterogeneity in experimental design, growth conditions, and sampling schemes make it challenging to compare water deficit studies in plants. Here, we re-analyzed hundreds of drought gene expression experiments across diverse model and crop species and quantified the variability across studies. We found that drought studies are surprisingly uncomparable, even when accounting for differences in genotype, environment, drought severity, and method of drying. Many studies, including most Arabidopsis work, lack high-quality phenotypic and physiological datasets to accompany gene expression, making it impossible to assess the severity or in some cases the occurrence of water deficit stress events. From these datasets, we developed supervised learning classifiers that can accurately predict if RNA-seq samples have experienced a physiologically relevant drought stress, and suggest this can be used as a quality control for future studies. Together, our analyses highlight the need for more community standardization, and the importance of paired physiology data to quantify stress severity for reproducibility and future data analyses.
Published: 2024
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45. Perioperative adverse cardiac events and mortality after non-cardiac surgery: a multicenter study.

Author: Choi B, Oh AR, Park J, Lee JH, Yang K, Lee DY, Rhee SY, Kang SS, Lee SD, Lee SH, Jeong CW, Park B, Seol S, Park RW, and Lee S
Subjects: Adolescent, Adult, Humans, Male, Network Meta-Analysis, Heart Arrest, Myocardial Infarction
Abstract: Background: Perioperative adverse cardiac events (PACE), a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health records., Methods: Data from 7 hospitals, converted to Observational Medical Outcomes Partnership Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta‑analysis., Results: After 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta‑analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In subgroup analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk)., Conclusions: A nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger in high-risk surgery, older, male, and chronic kidney disease subgroups. Further studies to improve mortality associated with PACE are needed.
Published: 2024
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46. National prevalence and trends in food labeling awareness, comprehension, usage, and COVID-19 pandemic-related factors in South Korea, 2014-2022.

Author: Choi Y, Kim HJ, Park J, Lee SW, Rahmati M, Koyanagi A, Smith L, Kim MS, López Sánchez GF, Dragioti E, Lee J, Rhee SY, Kim S, Lim H, and Yon DK
Subjects: Adult, Humans, Male, Female, Prevalence, Food Labeling, Comprehension, Nutrition Surveys, Republic of Korea epidemiology, Pandemics, COVID-19 epidemiology
Abstract: Although food labeling on food packages is crucial for promoting a healthy diet, limited research has been conducted on how the COVID-19 pandemic (hereinafter "the pandemic") has affected food labeling awareness. Therefore, this study aims to analyze the changes in trends in food labeling awareness, comprehension, and usage in South Korea during the pandemic. We utilized a nationwide, large-scale, and long-term dataset provided by the Korea Community Health Survey (KCHS) from 2014 to 2022 (total = 1,756,847 participants). This allowed the researchers to assess the long-term trends in the prevalence of food labeling awareness, comprehension, and usage. Furthermore, we investigated the factors associated with awareness specifically related to the pandemic. In total, 1,756,847 adults (54.19% women) participated in this study. The upward slope in overall food labeling awareness became less pronounced and even exhibited a downward slope during the pandemic (βdiff - 1.759; 95% CI - 1.874 to - 1.644). The upward slope in food labeling comprehension and usage became more pronounced during the pandemic (comprehension: βdiff 0.535; 95% CI 0.436-0.634; usage: βdiff 0.693; 95% CI 0.601-0.785). The vulnerability factors associated with lower food labeling awareness during the pandemic included older age, male, obesity, residing in rural areas, lower household income, lower educational level, smoking, and increased alcohol consumption. This study analyzed the 9-year trend in the prevalence of food labeling awareness, comprehension, and usage based on nationally representative data of adults in South Korea from 2014 to 2022. Our findings suggest that personalized nutrition strategies are needed to recognize vulnerable groups with risk factors and improve food labeling awareness among Korean adults during the pandemic., (© 2024. The Author(s).)
Published: 2024
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47. Clinical characteristics and outcomes of patients with mpox during the 2022 mpox outbreak compared with those before the outbreak: A systematic review and meta-analysis.

Author: Cho W, Park S, Kim HJ, Lee M, Choi YS, Yeo SG, Lee J, Koyanagi A, Jacob L, Smith L, Rahmati M, Ahmad S, Fond G, Boyer L, Rhee SY, Lee SW, Shin JI, Woo HG, and Yon DK
Subjects: Humans, Disease Outbreaks, Public Health, Fever, Mpox (monkeypox), Exanthema, HIV Seropositivity, HIV-1
Abstract: On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that caused the outbreak was classified as clade IIb, which belongs to the West African clade. However, the relationship between MPXV clades and symptoms, as well as the severity of mpox outcomes, is not fully understood. Thus, we aimed to investigate the global mpox prevalence and the differences in clinical manifestations and outcomes among patients with mpox between pre-outbreak (2003-2021) and the current mpox outbreak. In this systematic review and meta-analysis, PubMed/MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were searched using the keyword "monkeypox" and "mpox" up to 13 October 2022. A random effects model was used to obtain the pooled prevalence and 95% confidence intervals. This study included 27 articles, and 5698 patients with mpox with 19 distinctive features from 19 countries across five continents were assessed. Patients with mpox during the 2022 mpox outbreak showed mild clinical manifestations and outcomes compared with those before the 2022 mpox outbreak: mild rash (relative ratio [RR]: 5.09, 95% confidence interval [CI]: 1.52-17.08), fever (0.68, 0.49-0.94), pruritus (0.25, 0.19-0.32), myalgia (0.50, 0.31-0.81), headache (0.56, 0.35-0.88), skin ulcer (0.32, 0.17-0.59), abdominal symptom (0.29, 0.20-0.42), pharyngitis (0.32, 0.18-0.58), nausea or vomiting (0.15, 0.02-0.93), conjunctivitis (0.11, 0.03-0.38), concomitant infection with HIV (1.70, 0.95-3 0.04), and death (0.02, 0.001-0.31). MPXV clade IIb exhibited higher infectivity but may cause mild disease symptoms and low mortality rate. It is important to consider MPXV infection in patients with mpox-related features and/or a history of sexual transmission to prevent the spread of the disease and recognise the current pandemic threat., (© 2024 John Wiley & Sons Ltd.)
Published: 2024
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48. National Trends in Allergic Rhinitis and Chronic Rhinosinusitis and COVID-19 Pandemic-Related Factors in South Korea, from 1998 to 2021.

Author: Lee H, Park J, Lee M, Kim HJ, Kim M, Kwon R, Lee SW, Koyanagi A, Smith L, Kim MS, Rhee SY, Cho JK, Kim S, Rahmati M, and Yon DK
Subjects: Adult, Male, Humans, Middle Aged, Female, Pandemics, Nutrition Surveys, Risk Factors, Chronic Disease, Republic of Korea epidemiology, Prevalence, Rhinitis epidemiology, Rhinosinusitis, COVID-19 epidemiology, Rhinitis, Allergic epidemiology, Sinusitis epidemiology
Abstract: Introduction: Existing studies provide insights into the prevalence and environmental factors associated with allergic rhinitis (AR) and chronic rhinosinusitis (CRS) globally. However, limitations still persist in these studies, particularly regarding cohort sizes and the duration of follow-up periods, indicating a need for more comprehensive and long-term research in these fields. Our study aimed to investigate the prevalence, long-term trends, and underlying factors of these conditions in the general population of adult participants (≥19 years) in Korea., Method: We analyzed data from adult participants (≥19 years) from the Korea National Health and Nutrition Examination Survey (KNHANES) study to determine the prevalence of AR and CRS from 1998 to 2021. To analyze prevalence trends before and during the COVID-19 pandemic, we employed a weighted linear regression model and obtained β-coefficients with 95% confidence intervals (CI)., Results: Between 1998 and 2021, over a span of 24 years, the comprehensive KNHANES study included 146,264 adult participants (mean age: 47.80 years, standard deviation: 16.49 years; 66,177, 49.3% men). The prevalence of AR and CRS increased from 1998 to 2021, with AR prevalence rising from 5.84% (95% CI, 5.57-6.10) in 1998-2005 to 8.99% (8.09-9.91) in 2021 and CRS from 1.84% (1.70-1.97) in 1998-2005 to 3.70% (3.18-4.23) in 2021. However, the increasing trend has slowed down during the COVID-19 pandemic era., Conclusions: The significance of continuous monitoring and focused interventions for AR and CRS is underscored by this study. The observed deceleration in the rising prevalence of AR and CRS during the pandemic indicates the possibility of beneficial impacts from lifestyle modifications triggered by the pandemic. These findings call for additional research to explore potential protective effects in greater depth., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
Published: 2024
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49. National long-term trends in health-related quality of life using EQ-5D-3L in South Korea, 2008-2021, including the COVID-19 pandemic: a representative serial study of 2.8 million people.

Author: Kim H, Kim M, Rhee SY, Koyanagi A, Smith L, Kim MS, Fond G, Boyer L, Kim S, Shin JI, Jacob L, Lee J, Rahmati M, Yeo SG, and Yon DK
Subjects: Young Adult, Humans, Aged, Pandemics, Surveys and Questionnaires, Health Surveys, Health Status, Quality of Life, COVID-19 epidemiology
Abstract: Objective: There is a scarcity of literature investigating the impact of the coronavirus disease 2019 (COVID-19) pandemic on long-term trends in health-related quality of life (HrQoL) using large-scale and representative data. Thus, we aimed to investigate the nationwide and long-term trends in quality of life (QoL) using the European Quality of Life- 5 dimensions, 3-level version (EQ-5D-3L) from a Korean representative serial study of 2.8 million people, 2008-2021., Subjects and Methods: This Korean study used data on adults between 2008 and 2021 who participated in the Community Health Survey. Timeframes were categorized as COVID-19 mid-pandemic (2021) and pre-pandemic (2008-2019). The mean EQ-5D-3L index for the whole population and subgroups stratified by demographic characters was evaluated for each timeframe, and differences between before and during the COVID-19 pandemic were also analyzed., Results: 2,827,240 adults who responded to the survey, 2008-2021, were eligible for this study. Overall EQ-5D index persistently decreased from 2008-2016, then minimally decreased during the pandemic, still being much higher than forecasted before the COVID-19 pandemic. The reduction in the rate of decline in QoL after the COVID-19 outbreak was especially marked in white-collared, young adults, people with 'good' or 'very good' subjective health, and college-educated or above group. On the other hand, the previously increasing trend of QoL in the elderly group has decelerated during the pandemic, and QoL of the 'very bad' subjective health group recorded the lowest in the whole study period., Conclusions: The present study investigated the long-term trend of QoL in Korean adults using serial data over the past 14 years, with a special emphasis on comparing the pre- and mid-COVID-19 pandemic periods.
Published: 2024
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50. A Micrometric Transformer: Compositional Nanoshell Transformation of Fe 3+ -Trimesic-Acid Complex with Concomitant Payload Release in Cell-in-Catalytic-Shell Nanobiohybrids.

Author: Park J, Kim N, Han SY, Rhee SY, Nguyen DT, Lee H, and Choi IS
Subjects: Phosphates, Nanoshells
Abstract: Nanoencapsulation of living cells within artificial shells is a powerful approach for augmenting the inherent capacity of cells and enabling the acquisition of extrinsic functions. However, the current state of the field requires the development of nanoshells that can dynamically sense and adapt to environmental changes by undergoing transformations in form and composition. This paper reports the compositional transformation of an enzyme-embedded nanoshell of Fe 3+ -trimesic acid complex to an iron phosphate shell in phosphate-containing media. The cytocompatible transformation allows the nanoshells to release functional molecules without loss of activities and biorecognition, while preserving the initial shell properties, such as cytoprotection. Demonstrations include the lysis and killing of Escherichia coli by lysozyme, and the secretion of interleukin-2 by Jurkat T cells in response to paracrine stimulation by antibodies. This work on micrometric Transformers will benefit the creation of cell-in-shell nanobiohybrids that can interact with their surroundings in active and adaptive ways., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Published: 2024
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