138 results on '"Lim EH"'
Search Results
2. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients
- Author
-
Ridker, P. M., Revkin, J., Amarenco, P., Brunell, R., Civeira, F., Flather, M., Glynn, R. J., Gregoire, J., Jukema, J. W., Karpov, Y., Kastelein, J. J. P., Koenig, W., Lorenzatti, A., Manga, P., Masiukiewicz, U., Miller, M., Mosterd, A., Murin, J., Nicolau, J. C., Nissen, S., Ponikowski, P., Santos, R. D., Schwartz, P. F., Soran, H., White, H., Wright, R. S., Vrablik, M., Yunis, C., Shear, C. L., Tardif, Conde D, J. -C., Colquhoun, D, Missault, L, Grégoire, J, Gao, R, Urina, M, Solar, M, Jensen, Hk, Grobbee, D, Savolainen, M, Schiele, Fn, Montalescot, G, Edes, I, Blake, G, Lotan, C, Maggioni, A, Savonitto, S, Lee, Cw, Leiva Pons JL, Dan, Ga, Cortada, Jb, Mellbin, L, Kahan, T, Noble, S, Hwang, Jj, Sritara, P, Tökgozoğlu, L, Tarasenko, L, Borer, Js, Black, H, Carmena, R, Furie, Kl, Mcmurray, J, Neaton, J, Zannad, F, O’Neill, B, Welty, F, Mcnamara, R, Chun, H, Abbott, Jd, Jacoby, D, Mcpherson, C, Jadbabaie, F, Pinto, D, Mccullough, L, Silverman, Ie, Sansing, Lh, Dearborn-Tomazos, J, Foody, J, Schindler, J, Piazza, G, Chakrabarti, A, Pride, Y, Gelfand, E, Baultrukonis, D, Chaudhuri, S, Frederich, R, Johnson, M, Mridha, K, Powell, C, Wang, E, Wei, C, Anderson, P, Buonanno, M, Epsley, C, Evans, B, Frolova, M, Goetsch, M, Hessinger, D, Ikehara, E, Ivanac, K, Kizko, J, Le, K, McNally-Dufort, C, Morocco, T, Nadkarni, S, Nissen, T, Nye, R, Pak, R, Pence, D, Redifer, P, Schwartz, W, Sattler, C, Schade, R, Sullivan, B, Wegner, J, Alvarez, Ca, Budassi, N, Vogel, Dr, Avaca, H, Conde, Dg, Estol, Cc, Gelersztein, E, Glenny, Ja, Hershson, Ar, Bruno, Rl, Maffei, Le, Soler, Jm, Zaidman, Cj, Carnero, Gs, Colombo, Hr, Jure, Ho, Luquez, Ha, Ramos, Hr, Resk, Jh, Rusculleda, Mm, Ulla, Mr, Caccavo, A, Farias, Ef, Wenetz, Lm, Cabella, Pr, Cuadrado, Ja, Chahin, M, Mackinnon, Ij, Zarandon, Rb, Schmidberg, J, Fernandez, Aa, Montana, O, Codutti, Or, Gorosito, Vm, Maldonado, N, Sala, J, De La Fuente RA, Casabella, Te, Di Gennaro JP, Guerrero, Ra, Alvarez, Ms, Berli, M, Botta, Ce, Montenegro, Ee, Vico, Ml, Begg, A, Lehman, R, Gilfillan, Cp, D'Emden, M, Markovic, Tp, Sullivan, D, Aroney, C, Stranks, Sn, Crimmins, Ds, Arstall, M, Van Gaal, W, Davis, T, Aylward, Pe, Amerena, J, William, M, Proietto, J, Purnell, Pw, Singh, B, Arya, Kw, Dart, Am, Thompson, P, Davis, Sm, Carroll, Pa, De Looze, F, Jayasinghe, R, Bhindi, R, Buysschaert, I, Sarens, T, van de Borne, P, Scott, Bp, Roosen, J, Cools, F, Missault, Lh, Debroye, C, Schoors, Df, Hollanders, G, Schroe, Hh, De Sutter, J, Hermans, K, Carlier, M, van Landegem, P, Verwerft, J, Mulleners, T, Delforge, Md, Soufflet, V, Elegeert, I, Descamps, Os, Janssens, S, Lemmens, Rc, Desfontaines, P, Scheen, A, Heijmans, S, Capiau, L, Vervoort, G, Carlier, Sg, Faes, D, Alzand, B, Keuleers, S, De Wolf, L, Thoeng, J, De Bruyne, L, de Santos MO, Felicio, Js, Areas, Ca, Figueiredo, El, Michalaros, Yl, Neuenschwander, Fc, Reis, G, Saad, Ja, Kormann, Ap, Nascimento, Cv, Precoma, Db, Abib, E Jr, dos Santos FR, Mello, Yg, Saraiva, Jf, Rech, Rl, Cerci, R, Fortes, Ja, Rossi, Pr, de Lima, e Silva FA, Hissa, M, Silva, Rp, de Souza WK, Guimarães Filho FV, Mangili, Oc, de Oliveira Paiva MS, Tumelero, R, Abrantes, Ja, Caramori, Pr, Dutra, Op, Leaes, Pe, Manenti, Er, Polanczyk, Ca, Bandeira, e Farias FA, de Moraes Junior JB, Russo, La, Alves AR Jr, Dracoulakis, Md, Ritt, Le, Saporito, Wf, Herdy, Ah, Maia, Ln, Sternieri, Mv, Ayoub, Jc, Bianco, Ht, da Costa FA, Eliaschewitz, Fg, Fonseca, Fa, Nakandakare, Er, Bonansea, Tc, Castro, Nm, de Barros, e Silva PG, Smith, P, Botelho, Rv, Resende, Es, Barbieri, Ds, Hernandes, Me, Bajaj, H, Beaudry, P, Berlingieri, Jc, Salter, Tj, Ajala, B, Anderson, Tj, Nanji, A, Ross, S, Pandey, S, Desrosiers, D, Gaudet, D, Moran, G, Csanadi, Ma, St-Amour, E, Cusimano, S, Halperin, Fa, Babapulle, M, Vizel, S, Petrella, J, Spence, Jd, Gupta, N, Tellier, G, Bourgeois, R, Gregóire, Jc, Wesson, T, Zadra, R, Twum-Barima, Dy, Cha, Jy, Hartleib, Mc, Bergeron, J, Chouinard, G, Mcpherson, Tp, Searles, G, Peterson, Sr, Mukherjee, A, Lepage, S, Conway, Jr, Kouz, Sm, Dion, D, Pesant, Y, Cheung, Ss, Goldenberg, Rm, Aronson, R, Gupta, Ak, O’Mahoney, M, Pliamm, L, Teitelbaum, I, Hoag, Gn, Nadra, Ij, Yared, Z, Yao, Lc, Nguyen, T, Saunders, Kk, Potthoff, S, Varleta, P, Assef, V, Godoy, Jg, Olivares, C, Roman, O, Vejar, M, Montecinos, H, Pincetti, C, Li, Y, Wang, D, Li, J, Yang, X, Du, Y, Wang, G, Yang, P, Zhang, X, Xu, P, Zhao, Y, Chen, J, Li, S, Li, W, Zhang, L, Zhu, Y, Zhang, Y, Zhou, C, Wang, Y, Liu, F, Ma, Y, Ti, Z, Zeng, X, Zhou, Y, Cui, G, Li, D, Xue, L, Jiang, J, Lian, Y, He, Y, Mendoza, Ja, Bonfanti, Ja, Dada, Fa, Urina-Triana, Ma, Rodriguez, Wr, Sanchez, Ml, Lozno, Hy, Triana, Eh, Arambula, Rm, Rico-Carrillo, Ae, Gallo, Hj, Catano, Js, Jattin, Fg, Plazas, Ja, Gomez, Je, Botero-Lopez, R, Gomez, Ni, Munoz, Cf, Pelaez, Sv, Eraso, Am, Goyes, Ar, Elbl, L, Fiserova, N, Vesely, J, Wasserburger, B, Blaha, V, Vojacek, J, Maskova, P, Hutyra, M, Vrkoc, J, Hala, T, Vodnansky, P, Bocek, P, Cifkova, R, Bufka, V, Ceska, R, Machkova, M, Zidkova, E, Lukac, M, Mikusova, T, Kellnerova, I, Kuchar, L, Ferkl, R, Cech, V, Zemek, S, Monhart, Z, Davidsen, F, Joensen, A, Lihn, As, Rasmussen, Tk, Wiggers, H, Lindgren, Lm, Schmidt, U, Galatius, S, Sillesen, H, Bronnum Schou, J, Thomsen, Kk, Urhammer, S, Jeppensen, J, Schou, M, May, O, Steffensen, R, Nielsen, Wb, Nielesen, T, Jepsen, Jm, Rai, A, Sykulski, R, Andersen, Lt, Rickers, H, Frost, L, Lomholdt, J, Egstrup, K, Wermuth, S, Klausen, L, Lassus, J, Palomaki, A, Khari, J, Tatlisumak, T, Kekki, S, Vanttinen, E, Strandberg, A, Valtonen, M, Sia, Sm, Nerg, O, Puhakka, M, Strand, J, Timonen, M, Levola, J, Arstila, L, Taurio, J, Kantola, I, Suomi, J, Humaloja, K, Askonen, K, Schiele, F, Sibon, I, Zemour, G, Goube, P, Petit, C, Chati, Z, Range, G, Rabahi, F, Rihani, R, Bergerot, C, Roubille, F, Boye, A, Probst, V, Ferrari, E, Cayla, G, Thouvenot, E, Delarche, N, Couffinhal, T, Coisne, D, Paillard, F, Elbaz, M, Decoulx, E, Angoulvant, D, Agraou, B, Caudmont, S, Berrouschot, J, Lauer, B, Schoell, I, Trenk, D, Derwahl, Km, Khariouzov, A, Proepper, F, Stawowy, P, Da Stephan, U, Stoessel, J, Voehringer, Hf, Dorsel, T, Stellbrink, C, Rinke, A, Northroff, J, Bourhaial, H, Stratmann, M, Wetzel, T, Axthelm, C, Guenzel, A, Weigmann, I, Faghih, M, Hagemann, D, Schaefer, A, Weber, D, Luedemann, J, Contzen, C, Kornmann, Mo, Winkelmann, B, Simon, J, Felix, S, Brauer, C, Laufs, U, Schmidt, E, Marten, I, Licka, M, Heisters, J, Appel, Kf, Kleinecke-Pohl, U, Klein, C, von Hodenberg EF, Maus, O, Sigal, H, Taeschner, H, Schwimmbeck, P, Lemke, B, Perings, C, Illies, G, Pfuetzner, A, Salbach, P, Hengstenberg, C, Kohler, A, Mudra, H, Behnke, T, Baar, M, Jeserich, M, Scholz, G, Naudts, I, Voller, H, Herrmann, Hj, von Engelhardt CB, Gerke, S, Pohlmeier, L, Schaufele, T, Woehrle, J, Al-Zoebi, A, Horacek, T, Peterfai, E, Kemeny, V, Lakatos, F, Bod, E, Andrassy, P, Andreka, P, Balo, T, Davidovits, Z, Laszlo, Z, Nagy, K, Papp, A, Somogyi, A, Toldy-Schedel, E, Vertes, A, Voros, P, Paragh, G, Martyin, T, Hajdu, C, Deak, L, Farago, K, Nagy, A, Kirschner, R, Koszegi, Z, Zilahi, Z, Toth, K, Wittmann, I, Bajcsi, D, Reiber, I, Toth, L, Benczur, B, Nagy, L, Sydo, T, Lupkovics, G, Oroszlan, T, Crean, P, Mahon, Ng, Mcadam, B, Macneill, B, Katz, A, Tsalihin, D, Vazan, A, Eitan, A, Lewis, Bs, Gavish, D, Wainstein, J, Mosenzon, O, Mosseri, M, Vishlitzky, V, Atar, S, Nseir, Wb, Brenner, H, Elis, A, Fuchs, S, Shimon, I, Solodky, A, Goldhaber, A, Tanne, D, Knobler, H, Kracoff, Oh, Hussein, O, Auriel, E, Chorin, E, Sharir, T, Bitzur, R, Shechter, M, Antonicelli, R, Franceschini, E, Porcu, M, Sesti, G, Maggiolini, S, Salvioni, A, Filardi, Pp, Trimarco, B, Averna, M, Pasqualini, L, Pirro, M, Pantaleoni, M, Piovaccari, G, Arca, M, Fedele, Francesco, Roncon, L, Anselmi, M, Sganzerla, P, Morocutti, G, Bonora, E, Dimas, Al, Esperon, Ga, Morales-Villegas, E, Isunza, Jm, Beltran, Lg, Molina, Ca, Garcia, Dk, Ruiz, La, Reyna, Ls, De los Rios Ibarra MO, Soto, Jr, Gonzalez-Ortiz, M, Herrera-Marmolejo, M, Ramos, Sa, Ramos-Lopez, Ga, Stobschinski, Ca, Aguilarsalinas, Ca, Alpizar-Salazar, M, Jimenez-Sanchez, M, Sanchez Mijangos JH, Elizondo Moreno ER, Garcia Castillo, A, Garcia Hernandez PA, Gonzalez-Gonzalez, Jg, Riojas Charles CM, Valdez Lopez HG, Nuriulu Escobar PL, Lechuga Martin del Campo, A, Castro Montes BE, Mendez Bucio, A, Rodriguez-Briones, I, Torre Amione, G, Violante Ortiz, R, Luna Ceballos RI, Lopez Rosas, E, Bax, Wa, Alhakim, M, van de Wiel, A, Liem, Ss, Groutars, Rg, Herrman, Jp, Hovingh, Gk, van de Wetering ML, van Royen, N, Groenemeijer, Be, Hoedemaker, G, Schaap, J, Ronner, E, Angun, M, Mairuhu, At, Van Alem AP, Martens, Fm, Heijmeriks, Ja, van Hal JM, Schoofs, Mw, den Hartog FR, Kentgens, S, Post, Jc, Louwerenburg, Jw, van Rossum, P, Viergever, Ep, Donders, Sh, Kamphuisen, Pw, van Beek, E, Nijmeijer, R, Lenderink, T, Schreuder, T, Kuijper, Af, The, Sh, Van het Hof-Wiersma JJ, Tichelaar, P, Westerndorp, I, Breedveld, Rw, Karalis, I, Romer, Tj, Bogaard, K, Van Koningsbruggen, P, Kroon, Aa, Hoogslag, Pa, Rensing, Bj, Cramer, E, Remmen, Jj, Riksen, Np, Bokern, Mj, Cabezas, Mc, Mulder, H, Nierop, Pr, van Kempen WW, Zoet-Nugteren, Sk, van Daele ME, Swart, Hp, van der Zwaan CT, Hermans, Wr, Magro, M, van de Wal RM, Hassink, Rj, Visseren, F, Veenendaal, A, De Nooijer, C, Troquay, Rp, Imholz, Bp, van der Meer, P, Visser, Rp, van Leendert RJ, Gosselink, Ma, Baker, J, Benatar, Jr, Kerr, J, Pryke, Jr, Scott, Rs, Millar-Corte, Gd, Williams, M, Montgomery, B, Venter, Dj, Ternouth, If, Decaigney, Sc, Hart, Hh, Corin, A, Garden, Pi, Sheahan, D, Harding, Sa, Korecki, J, Supronik, J, Styczkiewicz, M, Bijata-Bronisz, R, Rusicka, T, Walczak, M, Krolikowski, Z, Ostrowski, J, Lukaszewicz, M, Przekwas-Jaruchowska, M, Zieba, B, Miekus, P, Orkwiszewska-Nalewajko, A, Piepiorka, M, Kubalski, P, Wychota, K, Blach, E, Ochala, A, Okopien, B, Wronska, D, Janion, M, Czarnecka, D, Kolodziejczyk, J, Konieczynska, M, Landa, K, Mirek-Bryniarska, E, Necki, M, Pasternak, Da, Rozpondek, P, Trebacz, J, Walczewska, J, Sidor, M, Broncel, M, Drozdz, J, Kosmider, M, Saryusz-Wolska, M, Kucharska, D, Opalinska, E, Pijanowski, Z, Wozniak, I, Banaszkiewicz, K, Klecha, A, Horodecki, M, Piskorz-Wapinska, J, Kobielusz-Gembala, I, Kim, Mh, Kim, Dk, Cho, Br, Kim, Ks, Her, Sh, Lee, Sy, Rhee, My, Kim, K, Kang, Wc, Kim, Dh, Cho, Ys, Kim, Sh, Rim, Sj, Tahk, Sj, Jeon, Hk, Yoon, J, Mociran, M, Pop, Cf, Minescu, B, Andrei, Ld, Radoi, M, Calin, A, Ciomag, Rm, Copaci, I, Fruntelata, Ag, Popescu, M, Tivadar, S, Roman, G, Avram, Ri, Mistodie, Cv, Morosanu, M, Popa, Ar, Popescu, Ml, Popoviciu, Ms, Tase, A, Busegeanu, M, Popescu, A, Szilagyi, I, Sitterli-Natea, Cn, Maximov, Dm, Munteanu, M, Negrisanu, Gd, Kuzin, A, Popov, D, Shapovalova, J, Vishneva, E, Shutemova, E, Pasechnik, E, Bogdanov, E, Khasanov, N, Barbarash, Ol, Shangina, Oa, Tarasov, N, Solonev, O, Kosmacheva, E, Chernyatina, Ma, Ginzburg, M, Blokhin, A, Bulanova, N, Drapkina, Om, Gordeev, Ig, Libov, Ia, Lomakin, N, Panchenko, E, Shogenov, Zs, Zateyshchikov, D, Klein, G, Motylev, I, Belenkiy, Di, Demin, A, Nikolaev, Ky, Oleynikov, V, Zrazhevskiy, K, Katelnitskiy, I, Khaisheva, L, Aksentiev, S, Nedoshivin, A, Popova, Vb, Agafina, As, Ballyuzek, M, Baranova, E, Burova, N, Eryshev, S, Filippov, A, Goloshchekin, Bm, Konstantinov, V, Kostenko, Va, Simanenkov, Vi, Volkova, A, Duplyakov, D, Reshetko, O, Shvarts, Y, Kuznetsov, Va, Samoylova, Yg, Tolkacheva, V, Shalaev, Sv, Khokhlov, Al, Malygin, A, Shilkina, Np, Yakusevich, Vv, Margoczy, R, Zubek, V, Dzupina, A, Dubrava, J, Dulkova, K, Fabryova, L, Gaspar, L, Kamensky, G, Kokles, M, Raslova, K, Soosova, I, Stevlik, J, Strbova, J, Sumbal, J, Uhliar, R, Micik, J, Truban, J, Fedacko, J, Pastrnakova, E, Pella, D, Fazekas, F, Ambrovicova, V, Kycina, P, Martinka, E, Nociar, J, Belicova, M, Banik, M, Kanderkova, D, Hranai, M, Duris, T, Krahulec, B, Benacka, J, Vinanska, D, Roskova, E, Skripova, D, Macek, V, Vohnout, B, Buganova, I, Engelbrecht, Jm, Pretorius, Mm, Ebrahim, Io, Bayat, J, Ganesh, S, Ranjith, N, Coetzer, Tf, Jacovides, A, Distiller, La, Hellig, Fs, Engelbrecht, Iv, Mahomed, Aa, Blignault, Sc, Burgess, Lj, Kotze, Hj, van Nieuwenhuizen, E, Musungaie, Db, Emanuel, S, van der Walt, E, Pretorius, Ce, Roos, Js, Roux, Sm, Badat, Ae, Fouche, L, Vahed, Ya, Jansen van Resburg, D, van Zyl LJ, Soto Gonzalez, A, Diaz, Jl, Segura, T, Botella Serrano, M, Botas Rodrigues, J, Molto-Jorda, Jm, Dominguez Escribano JR, Sogorb Garri, F, Blanco Coronado JL, Gaztambide Saenz MS, Brotons Cuixart, C, Bruguera Cortada, J, Garcia-Moll Marimon, X, Gonzalbez Morgaez JD, Maisterra Santos, O, Roquer Gonzalez, J, Sobrino-Martinez, J, Chueca Fernandez JE, Narejos, S, Suarez Garcia, S, Perez Martinez, P, Figueras Camos, R, Medrano Martinez, V, Bellido Guerrero, D, Martinez Deben, F, Vila Belmonte, A, Mediavilla Garcia JD, Romero Hinojosa JA, Martorell Mateu, E, Cequier Fillat AR, Pinto Sala, X, Adroer Martori, R, Bueno Diez, M, Lopez Cano, C, Worner Diz, F, Gonzalez Juanatey, C, Alvarez-Sala Walther LA, De Dios Garcia Diaz, J, Garcia Puig, J, Jodar Gimeno, E, Plaza Perez, I, Suarez-Fernandez, C, Tunon, J, Zamorano Gomez JL, Brito Sanfiel MA, Escudier Villa JM, de Mora Martin, M, Dominguez Lopez, M, Hernandez Garcia JM, Tinahones Madueno FJ, Perez Paredes, M, Aracil Villar, J, Barreda Gonzalez MJ, Ripoll Vera TV, Tofe Povedano, S, Sanchez Alvarez, J, Martinez Via, L, Robles Iniesta, A, Masana, L, Vinyoles Bargallo, E, Calvo Gomez, C, Gonzalez Juanatey JR, Cruz Fernandez JM, De La Cuesta Mayor, C, Duran Garcia, S, Jimenez Hernandez MD, Morales Portillo, C, Muniz Grijalvo, O, De Castro, R, Taverna Llaurado, E, Pons Amate JM, Terns Riera, M, Civeira Murillo, F, Linderfalk, C, Curiac, D, Saldeen-Nilehn, K, Koskinen, P, Khalili, P, Tortensson, I, Lindholm, Cj, Luts, A, Koskinen, Pt, Gottsater, A, Persson, Be, Mooe, T, Larnefeldt, H, Boman, K, Crisby, M, Rasmanis, G, Tengmark, Bo, Witt, N, Hagstrom, E, Viklund, J, Muller, C, Mach, F, Burnier, M, Nanchen, D, Wuerzner, G, Banyai, M, Moccetti, T, Miserez, Ar, Bilz, S, Weber, K, Lai, Wt, Chang, Kc, Ueng, Kc, Tsai, Wc, Chiang, Ce, Hou, C, Pei, D, Krittayaphong, R, Kiatchoosakun, S, Srimahachota, S, Boonyavarakul, A, Jintapakorn, W, Gullu, H, Onrat, E, Erkan, Af, Demirci, D, Sari, R, Ceyhan, C, Ari, H, Araz, M, Degertekin, M, Goktekin, O, Uresin, Ay, Yigit, Z, Akdeniz, B, Comlekci, A, Kayikcioglu, M, Sahin, T, Ozcan, T, Durakoglugil, E, Asamoah-Owusu, N, Reed, R, Bakhai, A, Dixon, L, Sharma, R, Avornyo, Aa, Jones, Af, Lip, G, Clark, R, Banerjee, M, Wakeling, J, Arden, C, Blagden, Md, Walukiewica, P, Marshall, A, Maxwell, Tg, Gunstone, Ae, Kadr, Hh, Patle, R, Arif, I, Jhund, Ps, Mckaig, G, Douglas, F, Mierzejewski, L, Turner, W, Sathyapalan, T, Ivan, P, Manoj, A, Rice, S, Collier, Dj, Nair, Dr, Thom, S, Fiore, G, De Belder, M, Price, D, Sobolewska, J, Martin, S, Takhar, A, Moriarty, A, Kondagunta, V, Myhill, T, Gibson, Jm, Cecil, Jt, Halcox, J, Annamalai, N, Gorog, Da, Mccormack, T, Pegge, N, Field, A, Adams, F, Klein, Jj, Busch, Rs, Bretton, Em, Jaffrani, N, Salacata, A, Assadourian, A, Gogia, Hs, Dyke, Ck, Rubenfire, M, Essandoh, Lk, Welker, Ja, Ledesma, G, Lupovitch, S, Delgado, Jp, Hendrix, El, Quyyumi, Aa, Riesenberg, Ra, Robertson, Dg, Weinstein, Dl, Weiss, R, Casaubon, L, Gammon, Rs, Brar, Hs, Bittar, Gd, Guarnieri, Tt, Ince CS Jr, Jrquraishi, Am, Saeed, S, Albert, M, Sotolongo, Rp, Bernard, Jv, Karlsbergg, Rp, Lepor, Ne, Kirby, We, Mclean, B, Miller, Ap, Ovalle, F, Townsend, Jc, Beckett, Pl, Eaves, Wb, West, Sh, Kosinski, Ej, Zarich, Sw, Mahal, Ss, Maw, K, Maynard, Km, Chen, Jc, Gelormini, J, Gottlieb, Dw, Gabra, Nw, Narayan, P, Sparks, J, Field, Jc, Willits, Vl, O’Steen, Mb, Pasquini, Ja, Sensebrenner, Jw, Yarows, Sa, Hiotis, L, Jagielo, Tj, Levinson, Dj, Diller, Pm, Kereiakes, Dj, Turner, Ta, Vincent, S, Camp, Ad, Denker, Ps, Manning, Mb, Rocco, Mb, Stamps, Hb, Strader, Jr, Uusinarkaus, Kt, Kennett, Jd, Leichter, Sb, Mcneil, Dl, Schumacher, Dr, Chang, Ar, Ellison, Hs, Updegrove, Jd, Hamroff, Gs, Kay, Js, Marar, Ie, Flores, E, Saini, S, Abdullah, S, Berk, Mr, Fordan, S, Joshi, Ph, Mccullough, Pa, Reynolds, Rd, Rosenstock, J, Sachson, Ra, Shammas, N, Fishbein, Gj, Randall, Wj, Henderson, Da, Nash, Ml, Barker, Ba, Cohen, Ss, Seidman, B, Odekirk, Ll, Grillo, Rs, Martinez, Lm, Multani, P, Alwine, Lk, Mcgarvey, Jf, Mollerus, Me, Miller, Ab, Kotek, Lw, Changlani, M, Zavaro, Sh, Munoz, F, Mehta, Pm, Helm, Rj, Farhat, Nz, Farsad, R, Raoof, Tj, Shultz, Jh, Geohas, Jg, Allaw, Ma, Dela Llana, A, Gutmann, Je, Inzerello, At, Alappat, P, George, Ar, Haddad, Tm, Lillestol, Mj, Grodman, R, Peniston, Jh, Wadud, K, Garcia, B, Hamilton, Me, Lerman, S, Perloff, De, Graff, A, Saxena, S, Alvarado, Op, Malik, A, Reddy, Rd, Kinzfogl, G, Cornett, Gm, Norwood, Pc, Gilbert, Jm, Willis, Jg, Mcgrew, F, Sharma, S, Castro, Ma, Cucher, Fh, Altafullah, Im, Khurana, S, Knutson, Tj, Kinnaman, Sj, Stuckey, T, Pudi, Kk, Mayfield, Rk, Funk, Gs, Nixon, Wa, Dor, I, Boyett, Be, Srivastava, S, Elosegui, Am, Isserman, Sm, Cheek, Hb, Promisloff, Sd, Tami, Lf, Zeig, S, fitz-Patrick, D, Dave, Kn, Ahmad, A, Arain, S, Ballantyne, Cm, Doshi, A, El Hafi SE, Feldman, J, Fragoso, Vg, Gilford, T, Hoffman, As, Pouzar, Je, Vivekananthan, K, Ansari, Sh, Strzinek, Ra, Crater, Ta, Robinson, Jg, Fulmer, Jj, Patel, Am, Pereira, Es, Stich, Ma, Sultan, S, Geskin, G, Ruoff, Ge, Gillespie, E, Bybee, Ka, Moriarty, Pm, Savin, V, Agaiby, Jm, Melucci, Mb, Jantzi, Cm, Davidson, E, Smith, Wb, Treasure, Cb, Wakefield, Ph, Deck, K, Edris, Ma, Gilmore, Rm, Seep, Mk, Andersen, Jl, Detweiler, Ro, Rosenfeld, Jc, Strobl, Dj, Steinhoff, Jp, Adams, A, Estevez, R, Molin, Cj, Kim, Cy, Dy, J, Fox, Ke, Farris, Nr, Wayne, Jd, Whitney, Rt, Randhawa, Pm, Mego, Dm, Macdolnald, L, Caputo, Rp, Rigolosi, R, Vannatta, B, Pacheco, Tr, El-Shahawy, M, Gonzalez, Ej, Guice, Mj, Cherlin, Rs, Bays, He, Shoukfeh, M, Morris, Fh, Loy, J, Vora, Sk, Staab, Pk, Frisoli, A, Kimmel, Ma, Cohen, Aj, Green, Cb, Whitlock, L, Butuk, Dj, Mccartney, Mj, Ables, Lr, Acosta, R, Alvarez, Jg, Barrera, Cm, Benitez, O, Berenguer, Ra, Breton, Cf, Chiong, R, Delgado, Mi, Dufreny, A, Fialkow, Ja, Franczek, S, Frias, Jj, Iglesias, C, Landron-Garcia, L, Llerena, Sn, Martinez, Rf, Miranda, Aa, Morytko, Ja, Rodriguez, Ij, Sotolongo, R, Suarez-Sarmiento, A, Terrelonge, Ae, Vaca, Ce, Venereo, Jm, Verdeza, C, Zeno, Ml, Chilka, S, Felten, Wr, Hartman, An, Shayani, Ss, Duprez, D, Knickelbine, T, Chambers, Jd, Cone, Cl, Broughton, R, Napoli, Mc, Seaton, Bl, Smith, Sk, Reedy, Ma, Kesani, Mk, Nicol, Pr, Stringam, So, Talano, Jv, Barnum, O, Desai, V, Montero, M, Jacks, Rk, Kostis, Jb, Owen, Jg, Makam, Sk, Grosman, I, Underberg, Ja, Masri, Be, Peters, Ss, Serje, J, Lenhard, Mj, Glover, R, Paraboschi, Cf, Lim, Eh, Connery, L, Kipgen, W, Bravo, P, Digiovanna, Mj, Tayoum, H, Gabriel, Jd, Ariani, Mk, Robinson, Mf, Clemens, Pc, Corder, Cn, Schifferdecker, B, Tahirkheli, Nk, Hurling, Rt, Rendell, Ms, Shivaswamy, V, Madu, Ij, Dahl, Cf, Ayesu, K, Kim, C, Barettella, Mb, Jamidar, Ha, Bloom, Sa, Vora, Kn, Ong, St, Aggarwala, G, Sack, G, Blaze, K, Krichmar, P, Murcia, A, Teltser, M, Villaman-Bencosme, Y, Fahdi, Ie, Williams, Dg, Lain, El, Garcia, Hl, Karim, Sn, Francyk, Dm, Gordon, Mb, Palchick, Ba, Mckenzie, Me, Gimness, Mp, Greiff, J, Ruiz-R, L, Vazquez-Tanus, Jb, Schlager, D, Connelly, T, Soroka, E, Hastings, Wl, O’Dea, Dj, Purdy, Da, Jackson, B, Arcanese, Ml, Strain, Je, Schmedtje JF Jr, Jrdavis, Mg, A, A, Prasada, S, Scott, Dl, Vukotic, G, Akhtar, N, Larsen, Dc, Rhudy, Jm, Zebrack, Js, Bailey, Sr, Grant, Dc, Mora, A, Perez, Ja, Reyes, Rg, Sutton, Jc, Brandon, Dm, First, Bp, Risser, Ja, Claudio, J, Figueroa-Cruz, Wl, Sosa-Padilla, Ma, Tan, Ae, Traboulssi, Ma, Morcos, Nc, Glaser, La, Bredlau, Ce, El Shahawy, M, Ramos, Mj, Kandath, Dd, Kaluski, E, Akright, L, Rictor, Kw, Pluto, Tm, Hermany, Pr, Bellingar, B, Clark, Gb, Herrod, Jn, Goisse, M, Hook, M, Barrington, P, Lentz, Jd, Singal, Dk, Gleason, Gp, Lipetz, Rs, Schuchard, Tn, Bonner, Jh, Forgosh, Lb, Lefebvre, Gc, Pierpoint, Be, Radin, Dm, Stoller, Sr, Segall, N, Shah, Sa, Ramstad, Ds, Nisnisan, Jm, Trippett, Jm, Benjamin, Sa, Labissiere, Jc, Nashed, An, Maaieh, M, Aslam, Aa, Mandviwala, M, Budoff, Mj, French, Wj, Vlach, Jj, Destefano, P, Bayron, Cj, Fraser, Nj, Sandberg, Jh, Fagan, Tc, Peart, Bc, Suryanarayana, Pg, Gupta, Dk, Lee, Mw, Bertolet, Bd, Hartley, Pa, Kelberman, M, Behmanesh, B, Buynak, Rj, Chochinov, Rh, Steinberg, Aa, Chandna, H, Bjasker, Kr, Perlman, Rl, Ball, Em, Pock, J, Singh, S, Baldari, D, Kaster, S, Lovell, Jp, Horowitz, Bs, Gorman, Ta, Pham, Dn, Landzberg, Js, Mootoo, Ki, Moon, E, Krawczyk, J, Alfieri, Ad, Janik, Mj, Herrington, Dm, Koilpillai, Rn, Waxler, Ar, Hoffman, Da, Sahul, Zh, Gumbiner, B, Cropp, A, Fujita, K, Garzone, P, Imai, K, Levisetti, M, Plowchalk, D, Sasson, S, Skaggs, J, Sweeney, K, Vincent, J., Curto, M, Ridker, P., Revkin, J., Amarenco, P., Brunell, R., Curto, M., Civeira, F., Flather, M., Glynn, R., Gregoire, J., Jukema, J., Karpov, Y., Kastelein, J., Koenig, W., Lorenzatti, A., Manga, P., Masiukiewicz, U., Miller, M., Mosterd, A., Murin, J., Nicolau, J., Nissen, S., Ponikowski, P., Santos, R., Schwartz, P., Soran, H., White, H., Wright, R., Vrablik, M., Yunis, C., Shear, C., Tardif, J., SPIRE Cardiovascular Outcome Investigators, Averna, M., Brigham and Women's Hospital [Boston], Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), RS: CARIM - R3.02 - Hypertension and target organ damage, MUMC+: MA Alg Interne Geneeskunde (9), Interne Geneeskunde, Ridker, P. M., Glynn, R. J., Jukema, J. W., Kastelein, J. J. P., Nicolau, J. C., Santos, R. D., Schwartz, P. F., Wright, R. S., Shear, C. L., Tardif, J. -C., SPIRE Cardiovascular Outcome Investigator, Perrone, Filardi, P, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
- Subjects
Male ,STATIN THERAPY ,Anticholesteremic Agents/adverse effects ,Antibodie ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Injections, Subcutaneous/adverse effects ,030204 cardiovascular system & hematology ,Bococizumab ,law.invention ,PCSK9 ,0302 clinical medicine ,Randomized controlled trial ,law ,Risk Factors ,GENETIC-VARIANTS ,Cardiovascular Disease ,Monoclonal ,Anticholesteremic Agent ,030212 general & internal medicine ,Myocardial infarction ,Treatment Failure ,Humanized ,Proprotein Convertase 9/antagonists & inhibitors ,Medicine(all) ,Antibodies ,Antibodies, Monoclonal, Humanized ,Anticholesteremic Agents ,Cardiovascular Diseases ,Cholesterol, LDL ,Double-Blind Method ,Female ,Follow-Up Studies ,Humans ,Hypercholesterolemia ,Injections, Subcutaneous ,Lipids ,Middle Aged ,Proprotein Convertase 9 ,Medicine (all) ,PCSK9 Inhibitors ,antibodies monoclonal humanized ,anticholesteremic agents ,cardiovascular diseases ,cholesterol, LDL ,double-blind method ,female ,follow-up studies ,humans ,hypercholesterolemia ,injections, subcutaneous ,lipids ,male ,middle aged ,proprotein convertase 9 ,risk factors ,treatment failure ,medicine (all) ,Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16] ,General Medicine ,Lipid ,3. Good health ,LDL/blood ,Multicenter Study ,Cholesterol ,TRIALS ,Cholesterol, LDL/blood ,Antibodies, Monoclonal, Humanized/adverse effects ,Randomized Controlled Trial ,subcutaneous ,lipids (amino acids, peptides, and proteins) ,Cardiovascular Diseases/prevention & control ,REDUCING LIPIDS ,Human ,medicine.medical_specialty ,animal structures ,Hypercholesterolemia/drug therapy ,Placebo ,Injections, Subcutaneou ,LDL ,Injections ,Follow-Up Studie ,EVENTS ,03 medical and health sciences ,Internal medicine ,medicine ,Journal Article ,Comparative Study ,METAANALYSIS ,Alirocumab ,business.industry ,Unstable angina ,Lipids/blood ,Risk Factor ,fungi ,Antibodies/blood ,ta3121 ,medicine.disease ,Surgery ,Evolocumab ,REDUCTION ,Humanized/adverse effects ,Subcutaneous/adverse effects ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Item does not contain fulltext BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P/=70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of >/=100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P
- Published
- 2017
3. Fingerless gloves for hand trauma cases
- Author
-
Lim Eh and Cole Rp
- Subjects
medicine.medical_specialty ,Tourniquet ,business.industry ,medicine.medical_treatment ,Letters and Comments ,technology, industry, and agriculture ,Hand surgery ,General Medicine ,Surgical Gloves ,equipment and supplies ,Surgery ,Finger injury ,body regions ,surgical procedures, operative ,Amputation ,Surgical site ,medicine ,business ,Toe surgery - Abstract
Tang and Bebbington have described a simple yet effective method of minimising contamination from adjacent surfaces during hand surgery with the use of a sterile surgical glove to isolate the surgical site. They also proposed the use of a rolled-down finger portion of the glove to be used as a finger tourniquet. The fact that this rolled-down finger tourniquet is not detached from the surgical glove may reduce the risk of leaving the tourniquet in situ after surgery. Iatrogenic digital ischaemic injuries may therefore be avoided. However, the use of a surgical glove as a digital tourniquet must be employed with great caution. The National Patient Safety Agency (NPSA) reported incidences of digital necrosis requiring subsequent amputation as a result of rubber or surgical glove finger tourniquets being left in situ.1 In reducing the risks of digital tourniquets being left after finger or toe surgery, the NPSA recommended that digital tourniquets should be brightly coloured and have a CE mark. The use of surgical gloves was also discouraged. The finger tourniquet described by Tang and Bebbington was highly visible as the rolled-down portion remained attached to the surgical glove. Nevertheless, the use of non-bright coloured surgical glove/rubber as a tourniquet will need to be exercised with caution.
- Published
- 2011
4. Fingerless gloves for hand trauma cases
- Author
-
Lim, EH, primary and Cole, RP, additional
- Published
- 2011
- Full Text
- View/download PDF
5. Role of FDG-PET in the Pre-Operative Evaluation of Surgical Resection of Hepatic Metastases from Colorectal Cancer
- Author
-
Garcia Ev, Hoffman J, Toro, Scott T. Grafton, Staley Ca, Lim Eh, and Raghuveer Halkar
- Subjects
Surgical resection ,medicine.medical_specialty ,Text mining ,Colorectal cancer ,business.industry ,General surgery ,medicine ,Cancer ,Radiology, Nuclear Medicine and imaging ,Radiology ,medicine.disease ,business ,Pre-operative evaluation - Published
- 1999
6. WiFi-Powered Sensor Integrated into a Smart Glove with a Fully Fabric Antenna for the Human-Machine Interface.
- Author
-
Lee KT, Lim EH, Tan CH, Low JH, Wong KL, Guan C, and Chee PS
- Subjects
- Humans, Wearable Electronic Devices, Fingers physiology, Man-Machine Systems, Textiles, Wireless Technology instrumentation
- Abstract
The integration of flexible sensors into human-machine interfaces (HMIs) is in increasing demand for intuitive and effective manipulation. Traditional glove-based HMIs, constrained by nonconformal rigid structures or the need for bulky batteries, face limitations in continuous operation. Addressing this, we introduce yarn-based bend sensors in our smart glove, which are wirelessly powered and harvest energy from a fully textile 5.8 GHz WiFi-band antenna receiver. These sensors exhibit a gauge factor (GF) of 5.60 for strains ranging from 0 to 10%. They show a consistent performance regardless of the straining frequency when being stretched and released at frequencies between 0.1 and 0.7 Hz. This reliability ensures that the sensor output is solely dependent on the yarn's elongation. Accurately detecting finger-bending movements from 0° to 90° in a virtual environment, the sensors enable enhanced degrees of freedom for human finger interaction. When integrated with advanced machine-learning techniques, the system achieves a classification accuracy of 98.75% for object recognition, demonstrating its potential for precise and accurate HMI. Unlike conventional near-field energy transfer methods that rely on magnetic flux and are limited by power loss over distance, our fully textile design effectively harvests microwave energy, showing no voltage deterioration up to 1 m away. This minimalist microwave-powered smart glove represents a significant advancement, offering a viable and practical solution for developing intuitive and reliable HMIs.
- Published
- 2024
- Full Text
- View/download PDF
7. Efficacy and safety of sacituzumab govitecan Trop-2-targeted antibody-drug conjugate in solid tumors and UGT1A1*28 polymorphism: a systematic review and meta-analysis.
- Author
-
Sultana R, Chen S, Lim EH, Dent R, and Chowbay B
- Abstract
Background: Sacituzumab govitecan (SG) is a promising Trop-2-targeted antibody-drug conjugate (ADC) approved for the treatment of metastatic triple-negative breast cancer (TNBC). Early phase clinical trials have demonstrated good clinical activity and safety profile of SG in various tumor types, albeit with differing response rates and durations. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy and toxicity of SG and the influence of UGT1A1*28 genotype in clinical trials involving solid tumors., Methods: A systematic review of the literature from publicly available databases was performed on February 15, 2024 whereby studies published till 15 February 2024 were retrieved according to PRISMA guidelines [PROSPERO #CRD42022359943]. Data extracted included tumor type, sample size, demographic information, SG dose, UGT1A1*28 status, toxicity events, duration of follow-up, response, and survival outcomes. Risks of bias analysis was refereed using the Joanna Briggs Institute quality assessment tool for the cohort and RCT studies using 11 and 13 parameters, respectively. Statistical analysis was performed using the DerSimonian and Laird inverse variance methods. Heterogeneity was assessed using the I
2 statistic and Χ2 tests. P value < 0.05 was considered as statistical significance., Results: Eleven eligible clinical trials comprised of 1578 patients harboring various tumor types including TNBC, lung, genitourinary and gastrointestinal malignancies were included in the systematic review and meta-analysis. Pooled incidences of severe adverse events were minimal at <10%, with the exception of grade 3-4 neutropenia at 37.4%. The median PFS and OS across all studies were 4.9 (95%CI: 4.0-5.8) months and 9.6 (95%CI: 7.6-11.6) months, respectively. Objective response rate across all studies evaluated was 17.1% (95%CI: 12.0-22.1)., Conclusion: Our systematic review and meta-analysis confirmed that SG confers good clinical activity in certain solid tumor types and was tolerable with minimal adverse events. The potential utility of UGT1A1*28 genotyping in predicting clinical response and outcomes could not be determined due to the limited number of studies with available UGT1A1 genotype data., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
8. Cost-minimization analysis comparing subcutaneous trastuzumab at home with intravenous trastuzumab for HER2-positive breast cancer in Singapore.
- Author
-
Ouyang Y, Lee HY, Leong FL, Tey HJ, Shih V, Lim EH, and Graves N
- Abstract
Background: Trastuzumab (Herceptin) can be administered intravenously (IV Herceptin) and subcutaneously, with similar efficacy and safety, but with differences in dosage and costs. Previous studies have evaluated the costs of both treatment approaches in the outpatient settings, but no study has compared the costs of IV Herceptin administered in outpatients with subcutaneous Herceptin administered at patients' homes (Homecare SC Herceptin)., Objectives: This study aimed to compare the per-patient costs of Homecare SC Herceptin versus IV Herceptin administered in a healthcare institution's outpatient setting in Singapore., Designs: We performed a model-based cost-minimization analysis to estimate and compare the per-patient annual costs associated with each treatment modality from a societal perspective., Methods: Direct cost comprised healthcare resources utilization: drug, consumables, manpower, facility and cardiac assessment. Indirect cost was valued using a human capital approach to account for productivity lost by patients. Monte Carlo simulations with 1000 iterations were performed to account for parameter uncertainties. Costs were reported in 2023 Singapore dollars., Results: The annual societal cost per patient receiving IV Herceptin ranged from S$64,194 to S$65,135, while for Homecare SC Herceptin, it ranged from S$25,865 to S$26,807. Homecare SC Herceptin reduced the annual cost burden by 58.8% and 59.7%, per non-metastatic and metastatic breast cancer patient, respectively. The primary cost contributor was drug therapy, comprising more than 90% of the total cost. Even when excluding the cost of drugs, Homecare SC Herceptin remained cheaper by S$1912 annually. The cost reduction is approximately 60% compared to IV Herceptin regardless of disease status, with a 100% probability that the decision to adopt Homecare SC Herceptin leads to cost savings in Singapore., Conclusion: Treatment of breast cancer with Homecare SC Herceptin is a cost-saving option compared to IV Herceptin., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)
- Published
- 2024
- Full Text
- View/download PDF
9. Combined aerobic and strength exercise training on biological ageing in Singaporean breast cancer patients: protocol for the Breast Cancer Exercise Intervention (BREXINT) Pilot Study.
- Author
-
Sitjar PHS, Tan SY, Wong M, Li J, Jalil RBA, Aw H, Lim EH, and Goh J
- Subjects
- Humans, Female, Pilot Projects, Singapore, Aging physiology, Muscle Strength physiology, Exercise Therapy methods, Middle Aged, Aged, Cardiorespiratory Fitness physiology, Adult, Breast Neoplasms rehabilitation, Breast Neoplasms therapy, Resistance Training methods, Quality of Life, Exercise physiology
- Abstract
Breast cancer (BC) is the most prominent cancer amongst women, but fortunately, early diagnosis and advances in multimodality treatments have improved patient survivability. Cancer survivors, however, experience increased biological ageing which may accelerate other co-morbidities. Exercise intervention is a promising clinical adjuvant approach to improve BC patients' physiological function, recovery from treatment, and quality of life. However, the effects of combined aerobic and strength exercise training on biological ageing in BC patients have not been studied. The Breast Cancer Exercise Intervention (BREXINT) Pilot Study will evaluate the effects of a 24-week combined aerobic and strength exercise intervention against usual care in 50 BC patients' post-treatment randomised to either group. The primary outcomes include changes in cardiorespiratory fitness, muscle strength, cancer-related symptoms, and rate of biological ageing following exercise intervention period. The secondary outcomes include habitual physical activity measured with tri-axial accelerometery and supporting questionnaires, including physical activity, food diary, and quality of life questionnaires. This study will identify the effects of combined aerobic exercise strength training on biological ageing in BC patients from Singapore. Results from this study could further support the implementation of regular exercise programmes as routine care for cancer patients., (© 2024. The Author(s), under exclusive licence to American Aging Association.)
- Published
- 2024
- Full Text
- View/download PDF
10. Deciphering tumour microenvironment and elucidating the origin of cancer cells in ovarian clear cell carcinoma.
- Author
-
Kamaraj US, Gautam P, Cheng T, Chin TS, Tay SK, Ho TH, Nadarajah R, Goh RCH, Wong SL, Mantoo S, Busmanis I, Li H, Le MT, Li QJ, Lim EH, and Loh YH
- Abstract
Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC's biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC., Competing Interests: Conflict of interest statement None declared.
- Published
- 2024
- Full Text
- View/download PDF
11. Regioselective Arylation of Amidoaryne Precursors via Ag-Mediated Intramolecular Oxy-Argentation.
- Author
-
Kwon YJ, Kong YJ, Lee MJ, Lim EH, Kwak J, and Kim WS
- Abstract
An unprecedented silver-mediated intramolecular oxy-argentation of 3-amidoaryne precursors that quickly generates a heteroarylsilver species is developed. AgF acts as both a stoichiometric fluoride source and a reagent for the formation of a benzoxazolylsilver intermediate via aryne generation. Pd-catalyzed coupling reactions of (hetero)aryl iodides with a silver species, generated in situ, allow for the synthesis of various C7-arylated benzoxazoles. As a result, an aryl group is selectively introduced into the meta-position of 3-amidobenzyne precursors. Mechanistic studies have indicated the presence of a benzoxazolylsilver intermediate and revealed that the reaction proceeds via an intramolecular oxy-argentation process, which is initiated by a direct fluoride attack on the silyl group., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF
12. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer.
- Author
-
Park KH, Loibl S, Sohn J, Park YH, Jiang Z, Tadjoedin H, Nag S, Saji S, Md Yusof M, Villegas EMB, Lim EH, Lu YS, Ithimakin S, Tseng LM, Dejthevaporn T, Chen TW, Lee SC, Galvez C, Malwinder S, Kogawa T, Bajpai J, Brahma B, Wang S, Curigliano G, Yoshino T, Kim SB, Pentheroudakis G, Im SA, Andre F, Ahn JB, and Harbeck N
- Subjects
- Humans, Female, Asia epidemiology, Medical Oncology standards, Practice Guidelines as Topic, Neoplasm Staging, Breast Neoplasms therapy, Breast Neoplasms diagnosis
- Abstract
The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
13. Cost-effectiveness analysis of add-on pertuzumab to trastuzumab biosimilar and chemotherapy as neoadjuvant treatment for human epidermal growth receptor 2-positive early breast cancer patients in Singapore.
- Author
-
Lim EH, Lim A, Khara JS, Cheong J, Fong J, Sivanesan S, Griffiths M, New E, and Lee SC
- Subjects
- Humans, Female, Neoadjuvant Therapy, Cost-Effectiveness Analysis, Singapore, Receptor, ErbB-2 metabolism, Cost-Benefit Analysis, Antineoplastic Combined Chemotherapy Protocols, Trastuzumab, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Biosimilar Pharmaceuticals, Antibodies, Monoclonal, Humanized
- Abstract
Objectives: The Asian PEONY trial showed that add-on pertuzumab to trastuzumab and chemotherapy significantly improved pathological complete response in the neoadjuvant treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC). This study evaluated the cost-effectiveness of pertuzumab as an add-on therapy to trastuzumab and chemotherapy for neoadjuvant treatment of patients with HER2+ EBC in Singapore., Methods: A six-state Markov model was developed from the Singapore healthcare system perspective, with a lifetime time horizon. Model outputs were: costs; life-years (LYs); quality-adjusted LYs (QALYs); incremental cost-effectiveness ratios (ICERs). Sensitivity/scenario analyses explored model uncertainties., Results: The base case projected the addition of pertuzumab to be associated with improved outcomes by 0.277 LYs and 0.271 QALYs, increased costs by S$1,387, and an ICER of S$5,121/QALY. The ICER was most sensitive to the pCR rate, and the probabilistic sensitivity analysis showed that add-on pertuzumab had an 81.3% probability of being cost-effective at a willingness-to-pay threshold of S$45,000/QALY gained., Conclusions: This model demonstrated that the long-term clinical impact of early pertuzumab use, particularly the avoidance of metastatic disease and thus avoidance of higher costs and mortality rates, make neoadjuvant pertuzumab a cost-effective option in the management of patients with HER2+ breast cancer in Singapore.
- Published
- 2024
- Full Text
- View/download PDF
14. Neuromuscular complications of the lower extremity after thrombectomy in a patient with superficial femoral artery occlusion: Case series.
- Author
-
Lim EH, Kim SY, Kim DS, Won YH, Park SH, Ko MH, Seo JH, and Kim GW
- Subjects
- Humans, Lower Extremity, Thrombectomy methods, Pain, Treatment Outcome, Femoral Artery surgery, Femoral Artery pathology, Rhabdomyolysis pathology
- Abstract
Background: Ischemia reperfusion (IR) injury may result in rhabdomyolysis and compartment syndrome when blood supply returns after thrombectomy for patients with acute limb ischemia., Objective: We highlight the value of early diagnosis and treatment in post-thrombectomy patients with IR injuries in their lower legs., Case Description: Two patients received thrombectomy due to left superficial femoral artery occlusion. Both patients complained of left calf pain during ambulation at the 1- and 3-day follow up post-thrombectomy, as well as a heating sensation, swelling, weakness, and sensory changes in the affected leg. For early diagnosis musculoskeletal ultrasounds were performed and in both cases revealed swelling and change of echogenicity in the left calf. To further diagnosis, magnetic resonance imaging of the left leg revealed limb IR-induced muscular injury and rhabdomyolysis, respectively. In both cases, an electrodiagnostic study revealed peripheral nerve injury in the left leg. Medications were provided for neuropathic pain control and early rehabilitation was performed to improve function. In both cases, patients reported during their follow-up that their pain and muscle weakness had improved., Conclusion: When post-thrombectomy calf pain occurs early evaluation and treatment should be performed to identify any potential IR injury.
- Published
- 2024
- Full Text
- View/download PDF
15. Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway.
- Author
-
Ho PJ, Khng AJ, Tan BK, Lim GH, Tan SM, Tan VKM, Tan RSYC, Lim EH, Iau PT, Chew YJ, Lim YY, Hartman M, Tan EY, and Li J
- Subjects
- Humans, Female, Olfactory Pathways, CpG Islands, DNA Methylation, Breast Neoplasms
- Abstract
Background: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients., Methods: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva)., Results: A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e-8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e-14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (p
paired-samples = 1.72e-9, psingle-timepoint-blood = 2.03e-15 and psingle-timepoint-saliva = 7.52e-56)., Conclusion: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
16. Assessment of Equine Influenza Virus Status in the Republic of Korea from 2020 to 2022.
- Author
-
Lim SI, Kim MJ, Kim MJ, Lee SK, Yang HS, Kwon M, Lim EH, Ouh IO, Kim EJ, Hyun BH, and Lee YH
- Subjects
- Animals, Horses, Republic of Korea epidemiology, Vaccination veterinary, Antibodies, Viral, Orthomyxoviridae Infections epidemiology, Orthomyxoviridae Infections veterinary, Influenza A Virus, H3N8 Subtype, Influenza Vaccines, Horse Diseases
- Abstract
Equine influenza virus (EIV) causes acute respiratory disease in horses and belongs to the influenza A virus family Orthomyxoviridae , genus Orthomyxovirus . This virus may have severe financial implications for the horse industry owing to its highly contagious nature and rapid transmission. In the Republic of Korea, vaccination against EIV has been practiced with the active involvement of the Korea Racing Authority since 1974. In this study, we monitored the viral RNA for EIV using PCR, as well as the antibody levels against 'A/equine/South Africa/4/03 (H3N8, clade 1)', from 2020 to 2022. EIV was not detected using RT-PCR. The seropositivity rates detected using a hemagglutination inhibition assay were 90.3% in 2020, 96.7% in 2021, and 91.8% in 2022. The geometric mean of antibody titer (GMT) was 83.4 in 2020, 135.7 in 2021, and 95.6 in 2022. Yearlings and two-year-olds in training exhibited lower positive rates (59.1% in 2020, 38.9% in 2021, and 44.1% in 2022) than the average. These younger horses may require more attention for vaccination and vaccine responses against EIV. Continuous surveillance of EIV should be performed to monitor the prevalence and spread of this disease.
- Published
- 2023
- Full Text
- View/download PDF
17. Phylogenetic analysis of swine influenza A (H1N2) viruses isolated in Jinju City, Republic of Korea.
- Author
-
Kim M-J, Kwon M, Kim MJ, Lim EH, Hyun B-h, Lee Y-H, and Lim S-I
- Abstract
Genomic sequences of the swine influenza A (H1N2) viruses "A/Swine/South Korea/GN-1/2018" and "A/Swine/South Korea/GNJJ/2020" sampled from Jinju City, Republic of Korea, are reported here. The sequences of these viruses were 99% similar. These included eight genes from each of the H3N2pM, A(H1N1)2009pdm, and North American swine lineages., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
- Full Text
- View/download PDF
18. Exposure to low-level ambient air pollution and the relationship with lung and bladder cancer in older men, in Perth, Western Australia.
- Author
-
Lim EH, Franklin P, Trevenen ML, Nieuwenhuijsen M, Yeap BB, Almeida OP, Hankey GJ, Golledge J, Etherton-Beer C, Flicker L, Robinson S, and Heyworth J
- Subjects
- Male, Humans, Aged, Western Australia, Environmental Exposure, Australia, Particulate Matter, Lung, Air Pollutants, Air Pollution, Lung Neoplasms complications, Urinary Bladder Neoplasms, Environmental Pollutants
- Abstract
Background: Air pollution is a cause of lung cancer and is associated with bladder cancer. However, the relationship between air pollution and these cancers in regions of low pollution is unclear. We investigated associations between fine particulate matter (PM
2.5 ), nitrogen dioxide, and black carbon (BC), and both these cancers in a low-pollution city., Methods: A cohort of 11,679 men ≥65 years old in Perth (Western Australia) were followed from 1996-1999 until 2018. Pollutant concentrations, as a time-varying variable, were estimated at participants' residential addresses using land use regression models. Incident lung and bladder cancer were identified through the Western Australian Cancer Registry. Risks were estimated using Cox proportional-hazard models (age as the timescale), adjusting for smoking, socioeconomic status, and co-pollutants., Results: Lung cancer was associated with PM2.5 and BC in the adjusted single-pollutant models. A weak positive association was observed between ambient air pollution and squamous cell lung carcinoma but not lung adenocarcinoma. Positive associations were observed with bladder cancer, although these were not statistically significant. Associations were attenuated in two-pollutant models., Conclusion: Low-level ambient air pollution is associated with lung, and possibly bladder, cancer among older men, suggesting there is no known safe level for air pollution as a carcinogen., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
19. Breast cancer risk stratification using genetic and non-genetic risk assessment tools for 246,142 women in the UK Biobank.
- Author
-
Ho PJ, Lim EH, Hartman M, Wong FY, and Li J
- Subjects
- Female, Humans, Biological Specimen Banks, Genetic Predisposition to Disease, Risk Factors, Risk Assessment, United Kingdom epidemiology, Breast Neoplasms diagnosis, Breast Neoplasms genetics
- Abstract
Purpose: The benefit of using individual risk prediction tools to identify high-risk individuals for breast cancer (BC) screening is uncertain, despite the personalized approach of risk-based screening., Methods: We studied the overlap of predicted high-risk individuals among 246,142 women enrolled in the UK Biobank. Risk predictors assessed include the Gail model (Gail), BC family history (FH, binary), BC polygenic risk score (PRS), and presence of loss-of-function (LoF) variants in BC predisposition genes. Youden J-index was used to select optimal thresholds for defining high-risk., Results: In total, 147,399 were considered at high risk for developing BC within the next 2 years by at least 1 of the 4 risk prediction tools examined (Gail
2-year > 0.5%: 47%, PRS2-yea r > 0.7%: 30%, FH: 6%, and LoF: 1%); 92,851 (38%) were flagged by only 1 risk predictor. The overlap between individuals flagged as high-risk because of genetic (PRS) and Gail model risk factors was 30%. The best-performing combinatorial model comprises a union of high-risk women identified by PRS, FH, and, LoF (AUC2-year [95% CI]: 62.2 [60.8 to 63.6]). Assigning individual weights to each risk prediction tool increased discriminatory ability., Conclusion: Risk-based BC screening may require a multipronged approach that includes PRS, predisposition genes, FH, and other recognized risk factors., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
20. Development of Allison scanner to measure transverse emittance at low energy beam transport of rare-isotope accelerator complex for ON-line experiments.
- Author
-
Lim EH, Kwon JW, Chung YS, Woo HJ, Kim GD, and Kim ES
- Abstract
The Rare-isotope Accelerator complex for ON-line experiments is a heavy-ion accelerator facility that accelerates a stable or rare isotope beam up to 400 kW with an energy of 200 MeV/u. Various heavy-ion beams are generated from the Electron Cyclotron Resonance Ion Source, with an energy of 10 keV/u and separated according to A/Q at the first dipole magnet (DM). To measure beam transverse emittance at the Low Energy Beam Transport section, two Allison scanners are installed behind the DM for the X and Y directions. It consist of a servo motor for driving, a Faraday cup for current measurement, deflection plates, and electronic device. The measurable range of beam angle in of the Allison scanner is determined by the structure of the deflection plate and designed based on mathematical calculations. Experimental Physics and Industrial Control System (EPICS) is adopted to integrate and control a variety of devices. To control the complex measurement sequence of the Allison scanner, an EPICS sequencer module was used. Normalized emittance is calculated by python code with Pyepics module using phase space distribution data. In this paper, we present the detailed design of the Allison scanner, the configuration of the control system, and the experimental results using an Ar9+ 30 μA beam., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)
- Published
- 2023
- Full Text
- View/download PDF
21. Long-term exposure to low-concentration PM 2.5 and heart disease in older men in Perth, Australia: The Health in Men Study.
- Author
-
Jones JS, Nedkoff L, Heyworth JS, Almeida OP, Flicker L, Golledge J, Hankey GJ, Lim EH, Nieuwenhuijsen M, Yeap BB, and Trevenen ML
- Abstract
Exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM
2.5 ) is associated with increased risk of heart disease, but less is known about the relationship at low concentrations. This study aimed to determine the dose-response relationship between long-term PM2.5 exposure and risk of incident ischemic heart disease (IHD), incident heart failure (HF), and incident atrial fibrillation (AF) in older men living in a region with relatively low ambient air pollution., Methods: PM2.5 exposure was estimated for 11,249 older adult males who resided in Perth, Western Australia and were recruited from 1996 to 1999. Participants were followed until 2018 for the HF and AF outcomes, and until 2017 for IHD. Cox-proportional hazards models, using age as the analysis time, and adjusting for demographic and lifestyle factors were used. PM2.5 was entered as a restricted cubic spline to model nonlinearity., Results: We observed a mean PM2.5 concentration of 4.95 μg/m3 (SD 1.68 μg/m3 ) in the first year of recruitment. After excluding participants with preexisting disease and adjusting for demographic and lifestyle factors, PM2.5 exposure was associated with a trend toward increased incidence of IHD, HF, and AF, but none were statistically significant. At a PM2.5 concentration of 7 μg/m3 the hazard ratio for incident IHD was 1.04 (95% confidence interval [CI] = 0.86, 1.25) compared with the reference category of 1 μg/m3 ., Conclusions: We did not observe a significant association between long-term exposure to low-concentration PM2.5 air pollution and IHD, HF, or AF., Competing Interests: J.S.J. is a recipient of the Lawrence Scholarly Plus Award in Stroke Research. L.N. is funded by a National Heart Foundation Future Leader Fellowship. J.G. is supported by grants from the Queensland government, Medical Research Future Fund, National Health and Medical Research Council, Heart Foundation and Townsville Hospital and Health Services. The other authors declare that they have no conflicts of interest with regard to the content of this report. The Health in Men Study (HIMS) is supported by competitive projects grants from the National Health and Medical Research Council of Australia (NHMRC; 1128083, 1003589). Air pollution data that support the findings of this study are held by the Centre for Air pollution, energy and health Research (https://www.car-cre.org.au/cardatplatform) and are available from the corresponding author on reasonable request. The data derived from the Health in Men Study cannot be made publicly available due to confidentiality restrictions. Access to these data can be sought via application to the Health in Men Study investigators and will need to satisfy appropriate ethical requirements. The funding sources had no role in the design of the study, nor the collection, management, analysis or interpretation of data, nor had any input into the preparation of this manuscript., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
22. How Asian Breast Cancer Patients Experience Unequal Incidence of Chemotherapy Side Effects: A Look at Ethnic Disparities in Febrile Neutropenia Rates.
- Author
-
Lim ZL, Ho PJ, Hartman M, Tan EY, Riza NKBM, Lim EH, Nitar P, Joint Breast Cancer Registry Jbcr, Wong FY, and Li J
- Abstract
The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HR
Malay [95% CI]:2.04 [1.44-2.88], p < 0.001; HRIndian :1.88 [1.11-3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities' risk (HRMalay :1.29 [1.07-1.54], p = 0.006; HRIndian :1.50 [1.19-1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays ( p = 0.006) and Indians ( p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities.- Published
- 2023
- Full Text
- View/download PDF
23. Anthracycline-Free Protocol for Favorable-Risk Childhood ALL: A Noninferiority Comparison Between Malaysia-Singapore ALL 2003 and ALL 2010 Studies.
- Author
-
Ariffin H, Chiew EKH, Oh BLZ, Lee SHR, Lim EH, Kham SKY, Abdullah WA, Chan LL, Foo KM, Lam JCM, Chan YH, Lin HP, Quah TC, Tan AM, and Yeoh AEJ
- Subjects
- Child, Humans, Infant, Child, Preschool, Malaysia, Singapore, Neoplasm Recurrence, Local drug therapy, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antibiotics, Antineoplastic adverse effects, Disease-Free Survival, Treatment Outcome, Anthracyclines therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Purpose: To investigate whether, for children with favorable-risk B-cell precursor ALL (BCP-ALL), an anthracycline-free protocol is noninferior to a modified Berlin-Frankfurt-Muenster ALL-IC2002 protocol, which includes 120 mg/m
2 of anthracyclines., Patients and Methods: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts., Results: The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively ( P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% ± 0.7% ( P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively ( P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004)., Conclusion: In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.- Published
- 2023
- Full Text
- View/download PDF
24. First Detection of Influenza D Virus Infection in Cattle and Pigs in the Republic of Korea.
- Author
-
Lim EH, Lim SI, Kim MJ, Kwon M, Kim MJ, Lee KB, Choe S, An DJ, Hyun BH, Park JY, Bae YC, Jeoung HY, Lee KK, and Lee YH
- Abstract
Influenza D virus (IDV) belongs to the Orthomyxoviridae family, which also include the influenza A, B and C virus genera. IDV was first detected and isolated in 2011 in the United States from pigs with respiratory illness. IDV circulates in mammals, including pigs, cattle, camelids, horses and small ruminants. Despite the broad host range, cattle are thought to be the natural reservoir of IDV. This virus plays a role as a causative agent of the bovine respiratory disease complex (BRDC). IDV has been identified in North America, Europe, Asia and Africa. However, there has been no information on the presence of IDV in the Republic of Korea (ROK). In this study, we investigated the presence of viral RNA and seroprevalence to IDV among cattle and pigs in the ROK in 2022. Viral RNA was surveyed by the collection and testing of 999 cattle and 2391 pig nasal swabs and lung tissues using a real-time RT-PCR assay. IDV seroprevalence was investigated by testing 742 cattle and 1627 pig sera using a hemagglutination inhibition (HI) assay. The viral RNA positive rate was 1.4% in cattle, but no viral RNA was detected in pigs. Phylogenetic analysis of the hemagglutinin-esterase-fusion (HEF) gene was further conducted for a selection of samples. All sequences belonged to the D/Yamagata/2019 lineage. The seropositivity rates were 54.7% in cattle and 1.4% in pigs. The geometric mean of the antibody titer (GMT) was 68.3 in cattle and 48.5 in pigs. This is the first report on the detection of viral RNA and antibodies to IDV in the ROK.
- Published
- 2023
- Full Text
- View/download PDF
25. Compact conformal tattoo-polymer antenna for on-body wireless power transfer.
- Author
-
Chang XL, Chee PS, and Lim EH
- Abstract
This paper presents a 35.0 × 35.0 × 2.7 mm
3 compact, low-profile, and lightweight wearable antenna for on-body wireless power transfer. The proposed antenna can be easily printed on a piece of flexible tattoo paper and transformed onto a PDMS substrate, making the entire antenna structure conform to the human body for achieving a better user experience. Here, a layer of frequency selective surface (FSS) is inserted in between the antenna and human tissue, which has successfully reduced the loading effects of the tissue, with 13.8 dB improvement on the antenna gain. Also, the operating frequency of the rectenna is not affected much by deformation. To maximize the RF-DC conversion efficiency, a matching loop, a matching stub, and two coupled lines are integrated with the antenna for tuning the rectenna so that a wide bandwidth (~ 24%) can be achieved without the use of any external matching networks. Measurement results show that the proposed rectenna can achieve a maximum conversion efficiency of 59.0% with an input power of 5.75 μW/cm2 and can even exceed 40% for a low input power of 1.0 μW/cm2 with a 20 kΩ resistive load, while many other reported rectennas can only achieve a high PCE at a high power density level, which is not always practical for a wearable antenna., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF
26. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer.
- Author
-
Im SA, Gennari A, Park YH, Kim JH, Jiang ZF, Gupta S, Fadjari TH, Tamura K, Mastura MY, Abesamis-Tiambeng MLT, Lim EH, Lin CH, Sookprasert A, Parinyanitikul N, Tseng LM, Lee SC, Caguioa P, Singh M, Naito Y, Hukom RA, Smruti BK, Wang SS, Kim SB, Lee KH, Ahn HK, Peters S, Kim TW, Yoshino T, Pentheroudakis G, Curigliano G, and Harbeck N
- Subjects
- Humans, Female, Asia, India, Societies, Medical, Medical Oncology, Breast Neoplasms diagnosis, Breast Neoplasms therapy
- Abstract
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies., Competing Interests: Disclosure MLTAT declares consulting fees and honoraria from MSD, Roche, Novartis, Eli Lilly and AstraZeneca. HKA declares consulting fees from Daiichi Sankyo, Amgen, Yuhan and Novartis, and honoraria from Roche, BMS, MSD, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Menarini, Eisai, Pfizer, Boryung Pharmaceutical Company, Celtrion, Pharmobio Korea Inc. and Yuhan. GC has served as consultant or advisor for Roche, Eli Lilly and BMS; served on a speaker’s bureau for Roche, Pfizer and Eli Lilly; received travel funding from Pfizer and Roche; and received honoraria from Roche, Pfizer, Eli Lilly, Novartis, AstraZeneca and SeaGen, all outside the submitted work. THF declares honoraria from AstraZeneca Oncology Indonesia, Takeda Indonesia, Eisai Indonesia, Roche Oncology Indonesia, J & J Indonesia and Zueling Pharma Indonesia and role as head of division of Area Development for West Java, Indonesia for the Indonesian Society of Hematology and Medical Oncology. AG declares honoraria for advisory boards from AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Novartis, Pfizer and Roche; honoraria for lectures from Eisai and Eli Lilly and honoraria for expert testimony from Gentili. SG declares honoraria from Lupin, Roche, Novartis, Eli Lilly, Eisai, Cipla, CADILA, Intas and AstraZeneca; honoraria for being on committees of the Indian Council of Medical Research (Government of India), Council of Scientific and Industrial Research (Government of India), Department of Biotechnology (Government of India), India Alliance and institutional; honoraria from Novartis and AstraZeneca for participation in steering committees; leadership roles include President of Indian Society of Medical and Paediatric Oncology and General Secretary of Women’s Cancer Initiative - Tata Memorial Hospital, both roles unpaid. NH reports honoraria for lectures, advisory boards and/or personal fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz and SeaGen, and minority ownership interest in the West German Study Group. RAH declares honoraria from Roche, Novartis, MSD, Pfizer and Mylan, and support for attending meetings from Roche, MSD and Kalbe Pharma. SAI declares an institutional grant from AstraZeneca, Boryung Pharm, Daewoong Pharm, Eisai, Roche and Pfizer, and honoraria from AstraZeneca, Novartis, MSD, Roche, Pfizer; advisory role for AstraZeneca, Bertis, Daiichi Sankyo, Eisai, Hanmi, Lilly, MSD, Novartis, Roche and Pfizer. JHK declares an institutional grant from Ono Pharma Ltd., and honoraria from Novartis, MSD, Roche Pharma, Roche diagnostics, Pfizer, AstraZeneca, Eisai, Lilly, and Sanofi; fees for participation in data monitoring or advisory boards from Bixink, Eisai, Yuhan, Novartis, Daiichi Sankyo, Pfizer, Roche Pharma and Everest Medicines; institutional gifts from Eisai and Ono Pharma Ltd. SBK declares institutional funding from Novartis, Sanofi-Aventis and Dongkook Pharm Co.; consulting fees from Novartis, AstraZeneca, Lilly, DaeHwa Pharmaceutical Co Ltd., ISU Abxis, Beigene, OBI Pharma and Daiichi Sankyo; honoraria from Novartis, Pfizer, Lilly, OBI Pharma and Legochem Bioscience; participation on data safety monitoring or advisory boards for Novartis, AstraZeneca, MSD, Lilly and Daiichi Sankyo, and purchased stock in Genopeaks and Neogene TC. KHL declares honoraria from Pfizer, Novartis and Eli Lilly. SCL declares grants from Pfizer, Eisai, Taiho, ACT Genomics, MSD, Adagene and Epizyme; honoraria from Pfizer, Novartis, AstraZeneca, ACT Genomics, Eli Lilly, MSD and Roche and participation in data monitoring or advisory boards for Pfizer, Novartis, Eisai, Sanofi, Daiichi Sankyo, MSD and Roche. MYM declares institutional grants from MSD, Astella, Pfizer, Novartis, AstraZeneca, ARCUS, Amgen and honoraria from MSD, Amgen, Pfizer, Roche, Novartis, Zuelling Pharma, Specialised therapeutics, Eisai, GSK, Mundi Pharma, Eli Lilly and AstraZeneca. YN declares institutional grants from the Ministry of Health, Labour and Welfare, Abbvie, Ono, Daiichi Sankyo, Taiho, Pfizer, Boehringer Ingelheim, Eli Lilly, Eisai, AstraZeneca, Chugai, Bayer and honoraria from AstraZeneca, Eisai, Ono, Gardant, Takeda, Eli Lilly, Novartis, Pfizer, Chugai, Fuji Film Toyama Chemistry, Taiho, Mundi, Bristol, Shionogi. NP declares honoraria from AstraZeneca, Eisai, Roche, Eli Lilly, Novartis, Pfizer and MSD. YHP declares grants from AstraZeneca, Pfizer, Novartis, Roche and Gencurix, consulting fees from AstraZeneca, Pfizer, Novartis, Roche, Eisai, Daiichi Sankyo, MSD and Lilly, honoraria from Pfizer, MSD, Novartis and Roche, and participation on data monitoring boards and advisory boards for Roche, Eisai, Daiichi Sankyo, AstraZeneca, MSD and Novartis. SP declares fees for consultancy/advisory roles from Abbvie, Amgen, Arcus, AstraZeneca, Bayer, Beigene, Bio Invent, Biocartis, Blueprint Medicines, Boehringer Ingelheim, BMS, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-star, Foundation Medicine, Genzyme, Gilhead, GSK, Illumina, Incyte, IQIVIA, iTHeos, Janssen, Medscape, MSD, Merck Serono, Mirati, Novartis, Novocure, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Roche/Genentech, Sanofi, SeaGen, Takeda, Vaccibody, speaker roles for AstraZeneca, Boehringer Ingelheim, BMS, ecancer, Eli Lilly, Fishawack, Illumina, Imedex, Medscape, Mirati MSD, Novartis, OncologyEducation, PER, Pfizer, PRIME, RMEI, Roche/Genentech, RTP, Sanofi, Takeda and steering committee and trial chair roles as follows: AstraZeneca, coordinating PI, institutional, no financial interest, MERMAID-1; AstraZeneca, steering committee member, institutional, no financial interest, MERMAID-2, POSEIDON, MYSTIC; Beigene, steering committee member, institutional, no financial interest, BGB-A317-A1217-301/AdvanTIG-301; BMS, steering committee member, institutional, no financial interest, clinical trial steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451; BMS, steering committee member, institutional, no financial interest, RELATIVITY 095; GSK, trial chair, institutional, no financial interest, clinical trial chair ZEAL-1; iTeos, steering committee member, institutional, no financial interest, Phase 2 Inupadenant with chemo; Mirati, steering committee member, institutional, no financial interest, clinical trial steering committee SAPPHIRE; MSD, steering committee member, institutional, no financial interest, clinical trial steering committee PEARLS, MK-7684A; Pharma Mar, steering committee member, institutional, no financial interest, LAGOON; Phosplatin Therapeutics, steering committee member, institutional, no financial interest, phase 1/2 trials; Roche/Genentech, trial chair, institutional, no financial interest, clinical trial chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte. Also role as ESMO president, ETOP/EORTC/SAKK PI, involved in academic trials, ETOP/IBCSG partners officer. Council member and scientific chair, SAKK, vice-President Lung Group, SAMO, Vice President. BKS declares honoraria from Novartis and Eli Lilly. MS declares honoraria from AstraZeneca, MSD, Accord Health and Novartis, support for attending meetings from the Malaysia Urology Association and roles as an ex-committee member of the Malaysian Oncological Society and chairman of the Annual Scientific congress of the Malaysian Oncological Society. KT declares grants from Pfizer, Daiichi Sankyo, Eli Lilly, AstraZeneca, Eisai; honoraria from Daiichi Sankyo, Eli Lilly, Chugai, MSD; and data monitoring or advisory board fees from Daiichi Sankyo. SSW declares a grant from Pfizer and honoraria from Pfizer, Roche, AstraZeneca, Novartis, Daiichi Sankyo, Eli Lilly, MSD and Henrui. TY declares institutional grants from Amgen, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Genomedia, MSD, Ono, Pfizer, Sanofi, Sysmex and Taiho, and honoraria Bayer, Chugai, Merck biopharma, MSD and Ono. All other authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
27. Polarization-insensitive planar patch antenna with large embedded serial capacitance for on-metal tag design.
- Author
-
Murugesh M, Lim EH, Chee PS, and Bong FL
- Abstract
A polarization-insensitive planar patch antenna, which has a large embedded serial capacitance, is proposed for constructing a metal mountable tag by using merely a single radiator. The proposed antenna structure itself contains two flaps of patches, which are very closely overlapped, for generating a large capacitive reactance for reducing the resonant frequency of the tag. It has been found that the surface currents in the overlapped region are in the reverse direction as the large capacitance is virtually placed in series. This feature has been tactfully employed for producing a pair of orthogonal currents for designing the polarization-insensitive tag antenna and it can generate orthogonal fields in a unique way, making it readable from almost all directions at all points above the metal surface. For analyzing the impedance properties, an equivalent circuit was also constructed. This tag antenna is compact, and it can be read from ~ 15 m with 4W EIRP. Furthermore, the tag resonant frequency is shown to be unaffected much by its backing material. The proposed tag antenna is polarization-insensitve as it can be accessible from almost all directions on the metal., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
28. Importance of proper ventilator support and pulmonary rehabilitation in obese patients with heart failure: Two case reports.
- Author
-
Lim EH, Park SH, and Won YH
- Abstract
Background: The optimal treatment for heart failure (HF) is a combination of appropriate medications. Controlling the disease using only medical therapy is difficult in patients with HF, severe hypercapnia, and desaturation. These patients should first receive ventilator support followed by pulmonary rehabilitation (PR)., Case Summary: We report two cases in which arterial blood gas (ABG) improved and PR was possible with appropriate ventilator support. Two patients with extreme obesity complaining of worsening dyspnea-a 47-year-old woman and a 36-year-old man both diagnosed with HF-were hospitalized because of severe hypercapnia and hypoxia. Despite proper medical treatment, hypercapnia and desaturation resolved in neither case, and both patients were transferred to the rehabilitation department for PR. At the time of the first consultation, the patients were bedridden because of dyspnea. Oxygen demand was successfully reduced once noninvasive ventilation was initiated. As the patients' dyspnea gradually improved to the point where they could be weaned off the ventilator during the daytime, they started engaging in functional training and aerobic exercise. After 4 mo of follow-up, both patients were able to perform activities of daily living and maintain their lower body weight and normalized ABG levels., Conclusion: Symptoms of patients with obesity and HF may improve once ABG levels are normalized through ventilator support and implementation of PR., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
29. Will Absolute Risk Estimation for Time to Next Screen Work for an Asian Mammography Screening Population?
- Author
-
Ho PJ, Lim EH, Mohamed Ri NKB, Hartman M, Wong FY, and Li J
- Abstract
Personalized breast cancer risk profiling has the potential to promote shared decision-making and improve compliance with routine screening. We assessed the Gail model's performance in predicting the short-term (2- and 5-year) and the long-term (10- and 15-year) absolute risks in 28,234 asymptomatic Asian women. Absolute risks were calculated using different relative risk estimates and Breast cancer incidence and mortality rates (White, Asian-American, or the Singapore Asian population). Using linear models, we tested the association of absolute risk and age at breast cancer occurrence. Model discrimination was moderate (AUC range: 0.580-0.628). Calibration was better for longer-term prediction horizons (E/O
long-term ranges : 0.86-1.71; E/Oshort-term ranges :1.24-3.36). Subgroup analyses show that the model underestimates risk in women with breast cancer family history, positive recall status, and prior breast biopsy, and overestimates risk in underweight women. The Gail model absolute risk does not predict the age of breast cancer occurrence. Breast cancer risk prediction tools performed better with population-specific parameters. Two-year absolute risk estimation is attractive for breast cancer screening programs, but the models tested are not suitable for identifying Asian women at increased risk within this short interval.- Published
- 2023
- Full Text
- View/download PDF
30. Solitary Fibrous Tumour: A Rare Differential Diagnosis of Unilateral Nasal Mass.
- Author
-
Chew ZH, Lim EH, Sairin ME, and Wan Hamizan AK
- Abstract
Solitary fibrous tumors of the nasal cavity and paranasal sinuses are rarely encountered in clinical practice. These are unusual mesenchymal tumours initially described as primary spindle-cell neoplasms. Such tumours may manifest in pleural and extrapleural sites such as the liver, parapharyngeal space, sublingual and parotid glands, and thyroid but are seldom described in the nose and paranasal sinus region. Erosion of adjacent structures may occur, but the tumour itself does not metastasise. A young patient presented with a progressive unilateral nasal mass. The initial nasal biopsy reported it as a benign inflammatory nasal polyp. Imaging revealed a large, locally expansile mass within the right nasal cavity displacing the nasal septum. The patient underwent excision of the tumour and the diagnosis of solitary fibrous tumour was confirmed by immunohistochemistry staining. This case is intended to highlight the diagnosis and management of this rare tumour., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chew et al.)
- Published
- 2023
- Full Text
- View/download PDF
31. Effects of Home Based Serious Game Training (Brain Talk™) in the Elderly With Mild Cognitive Impairment: Randomized, a Single-Blind, Controlled Trial.
- Author
-
Lim EH, Kim DS, Won YH, Park SH, Seo JH, Ko MH, and Kim GW
- Abstract
Mild cognitive impairment (MCI) increases with aging society. Serious games may be effective in improving cognitive function in patients with MCI; however, research on their effects remains insufficient. This study aimed to confirm the efficacy and safety of cognitive rehabilitation training using a serious game (Brain Talk™) for the elderly with MCI. Twenty-four elderly individuals with MCI were randomized into study and control groups. The study group received 12 training sessions (30 min/session, 3 times/week), whereas the control group did not receive training. Blinded evaluations were conducted before and after the training and four weeks after the training. The primary outcome measures were the Korean Mini-Mental State Examination (K-MMSE) and K-MoCA (Korean Montreal Cognitive Assessment). Secondary outcome measures were the Semantic Verbal Fluency Task (SVFT), Trail-Making Test-B, and 2-back test. In the study group, the K-MMSE, K-MoCA, and SVFT scores after finishing the training and 4 weeks after training showed a significant increase; however, there was no significant change in the control group. No significant differences were observed between the two groups. Cognitive function significantly improved in the study group after training. Home-based serious games are considered helpful in improving cognitive function., Competing Interests: Conflict of Interest: The authors have no potential conflicts of interest to disclose., (Copyright © 2023. Korean Society for Neurorehabilitation.)
- Published
- 2023
- Full Text
- View/download PDF
32. Ironing out exercise on immuno-oncological outcomes.
- Author
-
Soh J, Lim ZX, Lim EH, Kennedy BK, and Goh J
- Subjects
- Exercise, Humans, Immunotherapy, Iron metabolism, Neoplasms pathology, Tumor Microenvironment
- Abstract
Despite accumulating evidence that supports the beneficial effects of physical exercise in inhibiting cancer progression, whether exercise modulates its effects through systemic and cellular changes in iron metabolism and immune-tumor crosstalk is unknown. Cancer cells have greater metabolic requirements than normal cells, with their survival and proliferation depending largely on iron bioavailability. Although iron is an essential mineral for mitogenesis, it also participates in a form of iron-dependent programmed cell death termed ferroptosis. In this short hypothesis paper, we speculate that modulating iron bioavailability, transport and metabolism with regular exercise can have significant implications for tumor and stromal cells in the tumor microenvironment, by affecting multiple tumor-autonomous and stromal cell responses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
- Full Text
- View/download PDF
33. Anti-Inflammatory Effects of Phlebia sp. Extract in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages.
- Author
-
Lim EH, Mun SK, Kim JJ, Chang DJ, and Yee ST
- Subjects
- Animals, Cytokines metabolism, Dinoprostone metabolism, Lipopolysaccharides, Macrophages metabolism, Mice, NF-kappa B metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase Type II metabolism, RAW 264.7 Cells, Anti-Inflammatory Agents pharmacology, Biological Products pharmacology, Polyporales chemistry, Transcription Factor AP-1 metabolism
- Abstract
Lichens are a life form in which algae and fungi have a symbiotic relationship and have various biological activities, including anti-inflammatory and antiproliferative activities. This is the first study to investigate the anti-inflammatory activity of a Phlebia sp. fungal extract (PSE) isolated from Peltigera neopolydactyla in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage. PSE reduced the production of the proinflammatory cytokine (tumor necrosis factor- α , interleukin-6, and interleukin-1 β ), chemokine (granulocyte-macrophage colony-stimulating factor), nitric oxide, and prostaglandin E2 in the LPS-stimulated RAW264.7 macrophages. Especially, PSE inhibits the phosphorylation of activator protein-1 (AP-1) signaling (c-Fos and c-Jun) and their upstream mitogen-activated protein kinase kinases/mitogen-activated protein kinases (MKK/MAPKs: MKK4, MKK7, and JNK) and finally reduced the production of the inflammatory cytokines. The inhibitory effects mainly act via suppressing JNK-mediated AP-1 rather than the NF- κ B pathway. Furthermore, PSE inhibited the production of final inflammatory effector molecules involved in AP-1 signaling, including nitric oxide (NO) and prostaglandin E2 (PGE2). Here, we report that PSE has the potential to be developed as an anti-inflammatory agent., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Eui Hyeon Lim et al.)
- Published
- 2022
- Full Text
- View/download PDF
34. Digital PCR for Minimal Residual Disease Quantitation Using Immunoglobulin/T-Cell Receptor Gene Rearrangements in Acute Lymphoblastic Leukemia: A Proposed Analytic Algorithm.
- Author
-
Lu Y, Li Z, Lim EH, Huan PT, Kham SKY, and Yeoh AE
- Subjects
- Algorithms, Child, Genes, T-Cell Receptor, Humans, Immunoglobulins genetics, Neoplasm, Residual diagnosis, Neoplasm, Residual genetics, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
In minimal residual disease (MRD), where there are exceedingly low target copy numbers, digital PCR (dPCR) can improve MRD quantitation. However, standards for dPCR MRD interpretation in acute lymphoblastic leukemia are lacking. Here, for immunoglobulin/T-cell receptor-based MRD, we propose an objective, statistics-based analytic algorithm. In 161 postinduction samples from 79 children with acute lymphoblastic leukemia, MRD was performed by dPCR and real-time quantitative PCR (qPCR) using the same markers and primer-probe sets. The dPCR raw data were analyzed by using an automated algorithm. dPCR and qPCR results were highly concordant (P < 0.0001): 98% (50 of 51) of qPCR positive were positive by dPCR, whereas 95% (61 of 64) of qPCR negative results were also negative by dPCR. For MRD quantitation, both qPCR and dPCR were tightly correlated (R
2 = 0.94). Using more DNA (1 μg × 7 versus 630 ng × 3), dPCR improved sensitivity of MRD quantitation by one log10 (median MRD positive cutoff 1.6 × 10-5 ). With dPCR, 83% (29 of 35) of positive-not-quantifiable results by qPCR could be assigned positive/negative MRD status. Seven replicates of tested samples and negative controls were optimal. Compared with qPCR, dPCR could improve MRD sensitivity by one log10 . We proposed an automatable, statistics-based algorithm that minimized interoperator variance for dPCR MRD., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
35. Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results.
- Author
-
Ong SS, Ho PJ, Khng AJ, Lim EH, Wong FY, Tan BK, Lim SH, Tan EY, Tan SM, Tan VKM, Dent R, Tan TJY, Ngeow J, Madhukumar P, Hamzah JLB, Sim Y, Lim GH, Pang JS, Alcantara VS, Chan PMY, Chen JJC, Kuah S, Seah JCM, Buhari SA, Tang SW, Ng CWQ, Li J, and Hartman M
- Abstract
Background: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients., Methods: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia. A continuous PRS was calculated by summing weighted risk alleles associated with overall, estrogen receptor- (ER-) positive, and ER-negative BC risk. PRS distributions neutropenia or FNc cases were compared to controls who did not develop neutropenia using two-sample t -tests. Odds ratios (OR) and corresponding 95% confidence intervals were estimated for the associations between PRS (quartiles and per standard deviation (SD) increase) and neutropenia-related outcomes compared to controls., Results: PRS distributions were not significantly different in any of the comparisons. Higher PRS
overall quartiles were negatively correlated with neutropenia or FNc. However, the associations were not statistically significant (PRS per SD increase OR neutropenia: 0.91 [0.79-1.06]; FNc: 0.87 [0.73-1.03]). No dose-dependent trend was observed for the ER-positive weighted PRS (PRSER-pos ) and ER-negative weighted PRS (PRSER-neg )., Conclusion: BC PRS was not strongly associated with chemotherapy-induced neutropenia or FNc.- Published
- 2022
- Full Text
- View/download PDF
36. Multi-center evaluation of artificial intelligent imaging and clinical models for predicting neoadjuvant chemotherapy response in breast cancer.
- Author
-
Qi TH, Hian OH, Kumaran AM, Tan TJ, Cong TRY, Su-Xin GL, Lim EH, Ng R, Yeo MCR, Tching FLLW, Zewen Z, Hui CYS, Xin WR, Ooi SKG, Leong LCH, Tan SM, Preetha M, Sim Y, Tan VKM, Yeong J, Yong WF, Cai Y, and Nei WL
- Subjects
- Breast pathology, Female, Humans, Prognosis, Retrospective Studies, Breast Neoplasms diagnostic imaging, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Neoadjuvant Therapy
- Abstract
Background: Neoadjuvant chemotherapy (NAC) plays an important role in the management of locally advanced breast cancer. It allows for downstaging of tumors, potentially allowing for breast conservation. NAC also allows for in-vivo testing of the tumors' response to chemotherapy and provides important prognostic information. There are currently no clearly defined clinical models that incorporate imaging with clinical data to predict response to NAC. Thus, the aim of this work is to develop a predictive AI model based on routine CT imaging and clinical parameters to predict response to NAC., Methods: The CT scans of 324 patients with NAC from multiple centers in Singapore were used in this study. Four different radiomics models were built for predicting pathological complete response (pCR): first two were based on textural features extracted from peri-tumoral and tumoral regions, the third model based on novel space-resolved radiomics which extract feature maps using voxel-based radiomics and the fourth model based on deep learning (DL). Clinical parameters were included to build a final prognostic model., Results: The best performing models were based on space-resolved and DL approaches. Space-resolved radiomics improves the clinical AUCs of pCR prediction from 0.743 (0.650 to 0.831) to 0.775 (0.685 to 0.860) and our DL model improved it from 0.743 (0.650 to 0.831) to 0.772 (0.685 to 0.853). The tumoral radiomics model performs the worst with no improvement of the AUC from the clinical model. The peri-tumoral combined model gives moderate performance with an AUC of 0.765 (0.671 to 0.855)., Conclusions: Radiomics features extracted from diagnostic CT augment the predictive ability of pCR when combined with clinical features. The novel space-resolved radiomics and DL radiomics approaches outperformed conventional radiomics techniques., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
37. Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification.
- Author
-
Ho PJ, Ho WK, Khng AJ, Yeoh YS, Tan BK, Tan EY, Lim GH, Tan SM, Tan VKM, Yip CH, Mohd-Taib NA, Wong FY, Lim EH, Ngeow J, Chay WY, Leong LCH, Yong WS, Seah CM, Tang SW, Ng CWQ, Yan Z, Lee JA, Rahmat K, Islam T, Hassan T, Tai MC, Khor CC, Yuan JM, Koh WP, Sim X, Dunning AM, Bolla MK, Antoniou AC, Teo SH, Li J, and Hartman M
- Subjects
- Asian People, Female, Genetic Predisposition to Disease genetics, Humans, Risk Assessment, Breast Neoplasms diagnosis, Breast Neoplasms epidemiology, Breast Neoplasms genetics
- Abstract
Background: Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear., Methods: In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%., Results: Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history., Conclusions: Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
38. An AI-Assisted and Self-Powered Smart Robotic Gripper Based on Eco-EGaIn Nanocomposite for Pick-and-Place Operation.
- Author
-
Goh QL, Chee PS, Lim EH, and Ng DW
- Abstract
High compliance and muscle-alike soft robotic grippers have shown promising performance in addressing the challenges in traditional rigid grippers. Nevertheless, a lack of control feedback (gasping speed and contact force) in a grasping operation can result in undetectable slipping and false positioning. In this study, a pneumatically driven and self-powered soft robotic gripper that can recognize the grabbed object is reported. We integrated pressure (P-TENG) and bend (B-TENG) triboelectric sensors into a soft robotic gripper to transduce the features of gripped objects in a pick-and-place operation. Both the P-TENG and B-TENG sensors are fabricated using a porous structure made of soft Ecoflex and Euthethic Gallium-Indium nanocomposite (Eco-EGaIn). The output voltage of this porous setup has been improved by 63%, as compared to the non-porous structure. The developed soft gripper successfully recognizes three different objects, cylinder, cuboid, and pyramid prism, with a good accuracy of 91.67% and has shown its potential to be beneficial in the assembly lines, sorting, VR/AR application, and education training.
- Published
- 2022
- Full Text
- View/download PDF
39. Special Histologic Type and Rare Breast Tumors - Diagnostic Review and Clinico-Pathological Implications.
- Author
-
Tan BY, Lim EH, and Tan PH
- Subjects
- Breast pathology, Diagnosis, Differential, Female, Humans, Breast Neoplasms diagnosis, Breast Neoplasms genetics, Breast Neoplasms pathology, Carcinoma pathology
- Abstract
Breast cancer is the most common malignant tumor in females. While most carcinomas are categorized as invasive carcinoma, no special type (NST), a diverse group of tumors with distinct pathologic and clinical features is also recognized, ranging in incidence from relatively more common to rare. So-called "special histologic type" tumors display more than 90% of a specific, distinctive histologic pattern, while a spectrum of tumors more often encountered in the salivary gland may also arise in the breast. Metaplastic carcinomas can present diagnostic challenges. Some uncommon tumors harbor pathognomonic genetic alterations. This article provides an overview of the key diagnostic points and differential diagnoses for this group of disparate lesions, as well as the salient clinical characteristics of each entity., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
40. Facial Nerve Palsy Secondary to Parotid Abscess: Report of a Rare Case and Review of the Literature.
- Author
-
Chew ZH, Lim EH, Lum SG, and Teo DSHM
- Abstract
A parotid lesion with facial nerve involvement almost always indicates malignancy. Facial nerve palsy as a complication of parotid abscess is extremely rare. The postulated mechanisms include ischaemic neuropathy secondary to the compression of the facial nerve by the parotid swelling, local toxic effect and perineuritis from the inflammatory process. Here, we present our experience in managing a case of facial nerve palsy due to a parotid abscess in an otherwise healthy 44-year-old female. The abscess was drained surgically and the facial nerve function returned to normal at two months. Histopathological examination of the parotid tissue showed no features of malignancy. The severity of facial nerve impairment varied from grade II to total palsy. The mainstay of treatment of a parotid abscess is surgical drainage along with medical therapy including broad-spectrum antibiotics, adequate hydration and sialogogues., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Chew et al.)
- Published
- 2022
- Full Text
- View/download PDF
41. Challenges in Diagnosing Foreign Body Aspiration in Children.
- Author
-
Goh PL, Lim EH, Teo DSHM, and Sairin ME
- Abstract
Foreign body aspiration in children is a medical emergency that is associated with significant morbidity and requires medical intervention. The variability of clinical presentations results in delayed diagnosis and treatment. Hence, a high index of clinical suspicion and a thorough examination is needed to expedite the management. We report the case of a toddler girl who aspirated a piece of peanut and was diagnosed as having bronchopneumonia upon presentation with respiratory symptoms for six days. Rigid bronchoscopy was performed and the foreign body was removed successfully without any complications. We aim to highlight the importance of considering the diagnosis of airway foreign body in children with unexplained respiratory distress in our case study., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Goh et al.)
- Published
- 2022
- Full Text
- View/download PDF
42. The Role of the Extracellular Matrix and Tumor-Infiltrating Immune Cells in the Prognostication of High-Grade Serous Ovarian Cancer.
- Author
-
Belotti Y, Lim EH, and Lim CT
- Abstract
Ovarian cancer is the eighth global leading cause of cancer-related death among women. The most common form is the high-grade serous ovarian carcinoma (HGSOC). No further improvements in the 5-year overall survival have been seen over the last 40 years since the adoption of platinum- and taxane-based chemotherapy. Hence, a better understanding of the mechanisms governing this aggressive phenotype would help identify better therapeutic strategies. Recent research linked onset, progression, and response to treatment with dysregulated components of the tumor microenvironment (TME) in many types of cancer. In this study, using bioinformatic approaches, we identified a 19-gene TME-related HGSOC prognostic genetic panel (19 prognostic genes ( PLXNB2 , HMCN2 , NDNF , NTN1 , TGFBI , CHAD , CLEC5A , PLXNA1 , CST9 , LOXL4 , MMP17 , PI3 , PRSS1 , SERPINA10 , TLL1 , CBLN2 , IL26 , NRG4, and WNT9A ) by assessing the RNA sequencing data of 342 tumors available in the TCGA database. Using machine learning, we found that specific patterns of infiltrating immune cells characterized each risk group. Furthermore, we demonstrated the predictive potential of our risk score across different platforms and its improved prognostic performance compared with other gene panels.
- Published
- 2022
- Full Text
- View/download PDF
43. Distinct clinical characteristics of DUX4- and PAX5-altered childhood B-lymphoblastic leukemia.
- Author
-
Li Z, Lee SHR, Chin WHN, Lu Y, Jiang N, Lim EH, Coustan-Smith E, Chiew KH, Oh BLZ, Koh GS, Chen Z, Kham SKY, Quah TC, Lin HP, Tan AM, Ariffin H, Yang JJ, and Yeoh AE
- Subjects
- Child, Humans, Neoplasm, Residual, PAX5 Transcription Factor genetics, Prognosis, Vincristine, Lymphoma, Non-Hodgkin, Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Abstract
Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
44. Germline breast cancer susceptibility genes, tumor characteristics, and survival.
- Author
-
Ho PJ, Khng AJ, Loh HW, Ho WK, Yip CH, Mohd-Taib NA, Tan VKM, Tan BK, Tan SM, Tan EY, Lim SH, Jamaris S, Sim Y, Wong FY, Ngeow J, Lim EH, Tai MC, Wijaya EA, Lee SC, Chan CW, Buhari SA, Chan PMY, Chen JJC, Seah JCM, Lee WP, Mok CW, Lim GH, Woo E, Kim SW, Lee JW, Lee MH, Park SK, Dunning AM, Easton DF, Schmidt MK, Teo SH, Li J, and Hartman M
- Subjects
- BRCA1 Protein genetics, Female, Genetic Predisposition to Disease, Genetic Testing, Germ Cells, Germ-Line Mutation, Humans, Odds Ratio, Breast Neoplasms pathology
- Abstract
Background: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent., Methods: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease., Results: PTV
9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28])., Conclusions: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions., (© 2021. The Author(s).)- Published
- 2021
- Full Text
- View/download PDF
45. Breast cancer risk stratification for mammographic screening: A nation-wide screening cohort of 24,431 women in Singapore.
- Author
-
Ho PJ, Wong FY, Chay WY, Lim EH, Lim ZL, Chia KS, Hartman M, and Li J
- Subjects
- Aged, Breast Neoplasms, Cohort Studies, Female, Humans, Middle Aged, Risk Assessment, Singapore, Early Detection of Cancer methods, Mammography methods
- Abstract
Background: Breast cancer incidence is increasing in Asia. However, few women in Singapore attend routine mammography screening. We aim to identify women at high risk of breast cancer who will benefit most from regular screening using the Gail model and information from their first screen (recall status and mammographic density)., Methods: In 24,431 Asian women (50-69 years) who attended screening between 1994 and 1997, 117 developed breast cancer within 5 years of screening. Cox proportional hazard models were used to study the associations between risk classifiers (Gail model 5-year absolute risk, recall status, mammographic density), and breast cancer occurrence. The efficacy of risk stratification was evaluated by considering sensitivity, specificity, and the proportion of cancers identified., Results: Adjusting for information from first screen attenuated the hazard ratios (HR) associated with 5-year absolute risk (continuous, unadjusted HR [95% confidence interval]: 2.3 [1.8-3.1], adjusted HR: 1.9 [1.4-2.6]), but improved the discriminatory ability of the model (unadjusted AUC: 0.615 [0.559-0.670], adjusted AUC: 0.703 [0.653-0.753]). The sensitivity and specificity of the adjusted model were 0.709 and 0.622, respectively. Thirty-eight percent of all breast cancers were detected in 12% of the study population considered high risk (top five percentile of the Gail model 5-year absolute risk [absolute risk ≥1.43%], were recalled, and/or mammographic density ≥50%)., Conclusion: The Gail model is able to stratify women based on their individual breast cancer risk in this population. Including information from the first screen can improve prediction in the 5 years after screening. Risk stratification has the potential to pick up more cancers., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
46. Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer.
- Author
-
Loo SY, Toh LP, Xie WH, Pathak E, Tan W, Ma S, Lee MY, Shatishwaran S, Yeo JZZ, Yuan J, Ho YY, Peh EKL, Muniandy M, Torta F, Chan J, Tan TJ, Sim Y, Tan V, Tan B, Madhukumar P, Yong WS, Ong KW, Wong CY, Tan PH, Yap YS, Deng LW, Dent R, Foo R, Wenk MR, Lee SC, Ho YS, Lim EH, and Tam WL
- Abstract
Cell state transitions control the functional behavior of cancer cells. Epithelial-to-mesenchymal transition (EMT) confers cancer stem cell-like properties, enhanced tumorigenicity and drug resistance to tumor cells, while mesenchymal-epithelial transition (MET) reverses these phenotypes. Using high-throughput chemical library screens, retinoids are found to be potent promoters of MET that inhibit tumorigenicity in basal-like breast cancer. Cell state transitions are defined by reprogramming of lipid metabolism. Retinoids bind cognate nuclear receptors, which target lipid metabolism genes, thereby redirecting fatty acids for β-oxidation in the mesenchymal cell state towards lipid storage in the epithelial cell state. Disruptions of key metabolic enzymes mediating this flux inhibit MET. Conversely, perturbations to fatty acid oxidation (FAO) rechannel fatty acid flux and promote a more epithelial cell phenotype, blocking EMT-driven breast cancer metastasis in animal models. FAO impinges on the epigenetic control of EMT through acetyl-CoA-dependent regulation of histone acetylation on EMT genes, thus determining cell states.
- Published
- 2021
- Full Text
- View/download PDF
47. Practical Considerations for Using RNA Sequencing in Management of B-Lymphoblastic Leukemia: Malaysia-Singapore Acute Lymphoblastic Leukemia 2020 Implementation Strategy.
- Author
-
Ni Chin WH, Li Z, Jiang N, Lim EH, Suang Lim JY, Lu Y, Chiew KH, Yin Kham SK, Zhi Oh BL, Tan AM, Ariffin H, Yang JJ, and Eng-Juh Yeoh A
- Subjects
- Child, Data Accuracy, Genotyping Techniques methods, Humans, Karyotyping methods, Malaysia epidemiology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma epidemiology, Prospective Studies, Reproducibility of Results, Singapore epidemiology, Exome Sequencing methods, Methyltransferases genetics, Mutation, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Pyrophosphatases genetics, RNA-Seq methods, Tumor Suppressor Protein p53 genetics
- Abstract
Despite the immense genetic heterogeneity of B-lymphoblastic leukemia [or precursor B-cell acute lymphoblastic leukemia (B-ALL)], RNA sequencing (RNA-Seq) could comprehensively interrogate its genetic drivers, assigning a specific molecular subtype in >90% of patients. However, study groups have only started to use RNA-Seq. For broader clinical use, technical, quality control, and appropriate performance validation are needed. We describe the development and validation of an RNA-Seq workflow for subtype classification, TPMT/NUDT15/TP53 variant discovery, and immunoglobulin heavy chain (IGH) disease clone identification for Malaysia-Singapore acute lymphoblastic leukemia (ALL) 2020. We validated this workflow in 377 patients in our preceding Malaysia-Singapore ALL 2003/Malaysia-Singapore ALL 2010 studies and proposed the quality control measures for RNA quality, library size, sequencing, and data analysis using the International Organization for Standardization 15189 quality and competence standard for medical laboratories. Compared with conventional methods, we achieved >95% accuracy in oncogene fusion identification, digital karyotyping, and TPMT and NUDT15 variant discovery. We found seven pathogenic TP53 mutations, confirmed with Sanger sequencing, which conferred a poorer outcome. Applying this workflow prospectively to the first 21 patients in Malaysia-Singapore ALL 2020, we identified the genetic drivers and IGH disease clones in >90% of patients with concordant TPMT, NUDT15, and TP53 variants using PCR-based methods. The median turnaround time was 12 days, which was clinically actionable. In conclusion, RNA-Seq workflow could be used clinically in management of B-cell ALL patients., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
48. Artificial Intelligence-Assisted Throat Sensor Using Ionic Polymer-Metal Composite (IPMC) Material.
- Author
-
Lee JH, Chee PS, Lim EH, and Tan CH
- Abstract
Throat sensing has received increasing demands in recent years, especially for oropharyngeal treatment applications. The conventional videofluoroscopy (VFS) approach is limited by either exposing the patient to radiation or incurring expensive costs on sophisticated equipment as well as well-trained speech-language pathologists. Here, we propose a smart and non-invasive throat sensor that can be fabricated using an ionic polymer-metal composite (IPMC) material. Through the cation's movement inside the IPMC material, the sensor can detect muscle movement at the throat using a self-generated signal. We have further improved the output responses of the sensor by coating it with a corrosive-resistant gold material. A support vector machine algorithm is used to train the sensor in recognizing the pattern of the throat movements, with a high accuracy of 95%. Our proposed throat sensor has revealed its potential to be used as a promising solution for smart healthcare devices, which can benefit many practical applications such as human-machine interactions, sports training, and rehabilitation.
- Published
- 2021
- Full Text
- View/download PDF
49. Combination of Rescue Stenting and Antiplatelet Infusion Improved Outcomes for Acute Intracranial Atherosclerosis-Related Large-Vessel Occlusion.
- Author
-
Baek JH, Jung C, Kim BM, Heo JH, Kim DJ, Nam HS, Kim YD, Lim EH, Kim JH, Kim JY, and Kim JH
- Abstract
Background and Purpose: Intracranial atherosclerosis-related large-vessel occlusion caused by in situ thrombo-occlusion (ICAS-LVO) has been regarded an important reason for refractoriness to mechanical thrombectomy (MT). To achieve better outcomes for ICAS-LVO, different endovascular strategies should be explored. We aimed to investigate an optimal endovascular strategy for ICAS-LVO. Methods: We retrospectively reviewed three prospective registries of acute stroke underwent endovascular treatment. Among them, patients with ICAS-LVO were assigned to four groups based on their endovascular strategy: (1) MT alone , (2) rescue intracranial stenting after MT failure ( MT-RS ), (3) glycoprotein IIb/IIIa inhibitor infusion after MT failure ( MT-GPI ), and (4) a combination of MT-RS and MT-GPI ( MT-RS + GPI ). Baseline characteristics and outcomes were compared among the groups. To evaluate whether the endovascular strategy resulted in favorable outcome, multivariable analysis was also performed. Results: A total of 184 patients with ICAS-LVO were included. Twenty-four patients (13.0%) were treated with MT alone, 25 (13.6%) with MT-RS, 84 (45.7%) with MT-GPI, and 51 (27.7%) with MT-RS+GPI. The MT-RS+GPI group showed the highest recanalization efficiency (98.0%). Frequency of patent arteries on follow-up (98.0%, p < 0.001) and favorable outcome (84.3%, p < 0.001) were higher in the MT-RS+GPI group than other groups. The MT-RS+GPI strategy remained an independent factor for favorable outcome (odds ratio, 20.4; 95% confidence interval, 1.97-211.4; p = 0.012). Conclusion: Endovascular strategy was significantly associated with procedural and clinical outcomes in acute stroke by ICAS-LVO. A combination of RS and GPI infusion might be an optimal rescue modality when frontline MT fails., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baek, Jung, Kim, Heo, Kim, Nam, Kim, Lim, Kim, Kim and Kim.)
- Published
- 2021
- Full Text
- View/download PDF
50. Role of transcriptome sequencing in clinical diagnosis of B-cell acute lymphoblastic leukemia.
- Author
-
Li Z, Jiang N, Lim EH, Chin WHN, and Yeoh AE
- Subjects
- Biomarkers, Tumor genetics, Gene Expression Profiling methods, Humans, Exome Sequencing methods, B-Lymphocytes pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Transcriptome genetics
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.