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5. Metasurface-enhanced mid-infrared spectrochemical imaging of tissues

Author

Rosas, S., Schoeller, K. A., Chang, E., Mei, H., Kats, M. A., Eliceiri, K. W., Zhao, X., and Yesilkoy, F.

Subjects
Physics - Optics, Quantitative Biology - Tissues and Organs
Abstract

Label-free and nondestructive mid-infrared vibrational hyperspectral imaging is emerging as an important ex-vivo tissue analysis tool, providing spatially resolved biochemical information critical to understanding physiological and pathological processes. However, the chemically complex and spatially heterogeneous composition of tissue specimens and the inherently weak interaction of infrared light with biomolecules limit the analytical performance of infrared absorption spectroscopy. Here, we introduce an advanced mid-infrared spectrochemical tissue imaging modality using metasurfaces that support strong surface-localized electromagnetic fields to capture quantitative molecular maps of large-area murine brain-tissue sections. Our approach leverages polarization-multiplexed multi-resonance plasmonic metasurfaces to simultaneously detect many different functional biomolecules. The resulting surface-enhanced mid-infrared spectral imaging (SE-MIRSI) method eliminates the non-specific effects of bulk tissue morphology on the quantitative analysis of fingerprint spectra and improves the chemical selectivity. We show that the metasurface enhancement increases the retrieval of amide I and II absorption bands associated with secondary structures of proteins. Moreover, we demonstrate that plasmonic metasurfaces enhance the chemical contrast in infrared images and enable the detection of ultrathin tissue regions that are not otherwise visible to conventional mid-infrared spectral imaging. While we tested our approach on murine brain tissue sections, this chemical imaging method is well-suited for any tissue type, which significantly broadens the potential impacts of our method for both translational research and clinical histopathology.

Published
2023

12. XY sex determination in a cnidarian

Author

Chen, Ruoxu, Sanders, Steven M., Ma, Zhiwei, Paschall, Justin, Chang, E. Sally, Riscoe, Brooke M., Schnitzler, Christine E., Baxevanis, Andreas D., and Nicotra, Matthew L.

Published
2023
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15. Domain Adaptation Broad Learning System Based on Locally Linear Embedding

Author

Yuan, Chao and Ren, Chang-E

Subjects
Computer Science - Machine Learning
Abstract

Broad learning system (BLS) has been proposed for a few years. It demonstrates an effective learning capability for many classification and regression problems. However, BLS and its improved versions are mainly used to deal with unsupervised, supervised and semi-supervised learning problems in a single domain. As far as we know, a little attention is paid to the cross-domain learning ability of BLS. Therefore, we introduce BLS into the field of transfer learning and propose a novel algorithm called domain adaptation broad learning system based on locally linear embedding (DABLS-LLE). The proposed algorithm can learn a robust classification model by using a small part of labeled data from the target domain and all labeled data from the source domain. The proposed algorithm inherits the computational efficiency and learning capability of BLS. Experiments on benchmark dataset (Office-Caltech-10) verify the effectiveness of our approach. The results show that our approach can get better classification accuracy with less running time than many existing transfer learning approaches. It shows that our approach can bring a new superiority for BLS.

Published
2021

20. Metallic Ti3C2Tx MXene Gas Sensors with Ultrahigh Signal-to-Noise Ratio

Author

Joon Kim, Seon, primary, Koh, Hyeong-Jun, additional, Ren, Chang E., additional, Kwon, Ohmin, additional, Maleski, Kathleen, additional, Cho, Soo-Yeon, additional, Anasori, Babak, additional, Kim, Choong-Ki, additional, Choi, Yang-Kyu, additional, Kim, Jihan, additional, Gogotsi, Yury, additional, and Jung, Hee-Tae, additional

Published
2023
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22. Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial

Author

Guglielmetti, L, Ardizzoni, E, Atger, M, Baudin, E, Berikova, E, Bonnet, M, Chang, E, Cloez, S, Coit, JM, Cox, V, de Jong, BC, Delifer, C, Do, JM, Tozzi, D Dos Santos, Ducher, V, Ferlazzo, G, Gouillou, M, Khan, A, Khan, U, Lachenal, N, LaHood, AN, Lecca, L, Mazmanian, M, McIlleron, H, Moschioni, M, O’Brien, K, Okunbor, O, Oyewusi, L, Panda, S, Patil, SB, Phillips, PPJ, Pichon, L, Rupasinghe, P, Rich, ML, Saluhuddin, N, Seung, KJ, Tamirat, M, Trippa, L, Cellamare, M, Velásquez, GE, Wasserman, S, Zimetbaum, PJ, Varaine, F, and Mitnick, CD

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Antimicrobial Resistance, Biodefense, Rare Diseases, Clinical Trials and Supportive Activities, Orphan Drug, Infectious Diseases, Prevention, Emerging Infectious Diseases, Tuberculosis, Lung, Clinical Research, Vaccine Related, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, Antitubercular Agents, Bayes Theorem, Humans, Pharmaceutical Preparations, Randomized Controlled Trials as Topic, Rifampin, Tuberculosis, Multidrug-Resistant, Rifampin-resistant tuberculosis, Rifampicin-resistant tuberculosis, Bedaquiline, Delamanid, Linezolid, Clofazimine, Fluoroquinolone, Pyrazinamide, Treatment shortening, MDR-TB, Non-inferiority, Bayesian adaptive randomization, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, General & Internal Medicine, Clinical sciences, Epidemiology, Health services and systems
Abstract

BackgroundTreatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings.MethodsendTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations.DiscussionThe lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide.Trial registrationClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.

Published
2021

26. Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Author

Judge, PK, Staplin, N, Mayne, KJ, Wanner, C, Green, JB, Hauske, SJ, Emberson, JR, Preiss, D, Ng, SYA, Roddick, AJ, Sammons, E, Zhu, D, Hill, M, Stevens, W, Wallendszus, K, Brenner, S, Cheung, AK, Liu, ZH, Li, J, Hooi, LS, Liu, WJ, Kadowaki, T, Nangaku, M, Levin, A, Cherney, D, Maggioni, AP, Pontremoli, R, Deo, R, Goto, S, Rossello, X, Tuttle, KR, Steubl, D, Massey, D, Landray, MJ, Baigent, C, Haynes, R, Herrington, WG, Abat, S, Abd Rahman, R, Abdul Cader, R, Abdul Hafidz, MI, Abdul Wahab, MZ, Abdullah, NK, Abdul-Samad, T, Abe, M, Abraham, N, Acheampong, S, Achiri, P, Acosta, JA, Adeleke, A, Adell, V, Adewuyi-Dalton, R, Adnan, N, Africano, A, Agharazii, M, Aguilar, F, Aguilera, A, Ahmad, M, Ahmad, MK, Ahmad, NA, Ahmad, NH, Ahmad, NI, Ahmad Miswan, N, Ahmad Rosdi, H, Ahmed, I, Ahmed, S, Aiello, J, Aitken, A, AitSadi, R, Aker, S, Akimoto, S, Akinfolarin, A, Akram, S, Alberici, F, Albert, C, Aldrich, L, Alegata, M, Alexander, L, Alfaress, S, Alhadj Ali, M, Ali, A, Alicic, R, Aliu, A, Almaraz, R, Almasarwah, R, Almeida, J, Aloisi, A, Al-Rabadi, L, Alscher, D, Alvarez, P, Al-Zeer, B, Amat, M, Ambrose, C, Ammar, H, An, Y, Andriaccio, L, Ansu, K, Apostolidi, A, Arai, N, Araki, H, Araki, S, Arbi, A, Arechiga, O, Armstrong, S, Arnold, T, Aronoff, S, Arriaga, W, Arroyo, J, Arteaga, D, Asahara, S, Asai, A, Asai, N, Asano, S, Asawa, M, Asmee, MF, Aucella, F, Augustin, M, Avery, A, Awad, A, Awang, IY, Awazawa, M, Axler, A, Ayub, W, Azhari, Z, Baccaro, R, Badin, C, Bagwell, B, Bahlmann-Kroll, E, Bahtar, AZ, Bains, D, Bajaj, H, Baker, R, Baldini, E, Banas, B, Banerjee, D, Banno, S, Bansal, S, Barberi, S, Barnes, S, Barnini, C, Barot, C, Barrett, K, Barrios, R, Bartolomei Mecatti, B, Barton, I, Barton, J, Basily, W, Bavanandan, S, Baxter, A, Becker, L, Beddhu, S, Beige, J, Beigh, S, Bell, S, Benck, U, Beneat, A, Bennett, A, Bennett, D, Benyon, S, Berdeprado, J, Bergler, T, Bergner, A, Berry, M, Bevilacqua, M, Bhairoo, J, Bhandari, S, Bhandary, N, Bhatt, A, Bhattarai, M, Bhavsar, M, Bian, W, Bianchini, F, Bianco, S, Bilous, R, Bilton, J, Bilucaglia, D, Bird, C, Birudaraju, D, Biscoveanu, M, Blake, C, Bleakley, N, Bocchicchia, K, Bodine, S, Bodington, R, Boedecker, S, Bolduc, M, Bolton, S, Bond, C, Boreky, F, Boren, K, Bouchi, R, Bough, L, Bovan, D, Bowler, C, Bowman, L, Brar, N, Braun, C, Breach, A, Breitenfeldt, M, Brettschneider, B, Brewer, A, Brewer, G, Brindle, V, Brioni, E, Brown, C, Brown, H, Brown, L, Brown, R, Brown, S, Browne, D, Bruce, K, Brueckmann, M, Brunskill, N, Bryant, M, Brzoska, M, Bu, Y, Buckman, C, Budoff, M, Bullen, M, Burke, A, Burnette, S, Burston, C, Busch, M, Bushnell, J, Butler, S, Büttner, C, Byrne, C, Caamano, A, Cadorna, J, Cafiero, C, Cagle, M, Cai, J, Calabrese, K, Calvi, C, Camilleri, B, Camp, S, Campbell, D, Campbell, R, Cao, H, Capelli, I, Caple, M, Caplin, B, Cardone, A, Carle, J, Carnall, V, Caroppo, M, Carr, S, Carraro, G, Carson, M, Casares, P, Castillo, C, Castro, C, Caudill, B, Cejka, V, Ceseri, M, Cham, L, Chamberlain, A, Chambers, J, Chan, CBT, Chan, JYM, Chan, YC, Chang, E, Chant, T, Chavagnon, T, Chellamuthu, P, Chen, F, Chen, J, Chen, P, Chen, TM, Chen, Y, Cheng, C, Cheng, H, Cheng, MC, Ching, CH, Chitalia, N, Choksi, R, Chukwu, C, Chung, K, Cianciolo, G, Cipressa, L, Clark, S, Clarke, H, Clarke, R, Clarke, S, Cleveland, B, Cole, E, Coles, H, Condurache, L, Connor, A, Convery, K, Cooper, A, Cooper, N, Cooper, Z, Cooperman, L, Cosgrove, L, Coutts, P, Cowley, A, Craik, R, Cui, G, Cummins, T, Dahl, N, Dai, H, Dajani, L, D'Amelio, A, Damian, E, Damianik, K, Danel, L, Daniels, C, Daniels, T, Darbeau, S, Darius, H, Dasgupta, T, Davies, J, Davies, L, Davis, A, Davis, J, Davis, L, Dayanandan, R, Dayi, S, Dayrell, R, De Nicola, L, Debnath, S, Deeb, W, Degenhardt, S, DeGoursey, K, Delaney, M, DeRaad, R, Derebail, V, Dev, D, Devaux, M, Dhall, P, Dhillon, G, Dienes, J, Dobre, M, Doctolero, E, Dodds, V, Domingo, D, Donaldson, D, Donaldson, P, Donhauser, C, Donley, V, Dorestin, S, Dorey, S, Doulton, T, Draganova, D, Draxlbauer, K, Driver, F, Du, H, Dube, F, Duck, T, Dugal, T, Dugas, J, Dukka, H, Dumann, H, Durham, W, Dursch, M, Dykas, R, Easow, R, Eckrich, E, Eden, G, Edmerson, E, Edwards, H, Ee, LW, Eguchi, J, Ehrl, Y, Eichstadt, K, Eid, W, Eilerman, B, Ejima, Y, Eldon, H, Ellam, T, Elliott, L, Ellison, R, Emberson, J, Epp, R, Er, A, Espino-Obrero, M, Estcourt, S, Estienne, L, Evans, G, Evans, J, Evans, S, Fabbri, G, Fajardo-Moser, M, Falcone, C, Fani, F, Faria-Shayler, P, Farnia, F, Farrugia, D, Fechter, M, Fellowes, D, Feng, F, Fernandez, J, Ferraro, P, Field, A, Fikry, S, Finch, J, Finn, H, Fioretto, P, Fish, R, Fleischer, A, Fleming-Brown, D, Fletcher, L, Flora, R, Foellinger, C, Foligno, N, Forest, S, Forghani, Z, Forsyth, K, Fottrell-Gould, D, Fox, P, Frankel, A, Fraser, D, Frazier, R, Frederick, K, Freking, N, French, H, Froment, A, Fuchs, B, Fuessl, L, Fujii, H, Fujimoto, A, Fujita, A, Fujita, K, Fujita, Y, Fukagawa, M, Fukao, Y, Fukasawa, A, Fuller, T, Funayama, T, Fung, E, Furukawa, M, Furukawa, Y, Furusho, M, Gabel, S, Gaidu, J, Gaiser, S, Gallo, K, Galloway, C, Gambaro, G, Gan, CC, Gangemi, C, Gao, M, Garcia, K, Garcia, M, Garofalo, C, Garrity, M, Garza, A, Gasko, S, Gavrila, M, Gebeyehu, B, Geddes, A, Gentile, G, George, A, George, J, Gesualdo, L, Ghalli, F, Ghanem, A, Ghate, T, Ghavampour, S, Ghazi, A, Gherman, A, Giebeln-Hudnell, U, Gill, B, Gillham, S, Girakossyan, I, Girndt, M, Giuffrida, A, Glenwright, M, Glider, T, Gloria, R, Glowski, D, Goh, BL, Goh, CB, Gohda, T, Goldenberg, R, Goldfaden, R, Goldsmith, C, Golson, B, Gonce, V, Gong, Q, Goodenough, B, Goodwin, N, Goonasekera, M, Gordon, A, Gordon, J, Gore, A, Goto, H, Gowen, D, Grace, A, Graham, J, Grandaliano, G, Gray, M, Greene, T, Greenwood, G, Grewal, B, Grifa, R, Griffin, D, Griffin, S, Grimmer, P, Grobovaite, E, Grotjahn, S, Guerini, A, Guest, C, Gunda, S, Guo, B, Guo, Q, Haack, S, Haase, M, Haaser, K, Habuki, K, Hadley, A, Hagan, S, Hagge, S, Haller, H, Ham, S, Hamal, S, Hamamoto, Y, Hamano, N, Hamm, M, Hanburry, A, Haneda, M, Hanf, C, Hanif, W, Hansen, J, Hanson, L, Hantel, S, Haraguchi, T, Harding, E, Harding, T, Hardy, C, Hartner, C, Harun, Z, Harvill, L, Hasan, A, Hase, H, Hasegawa, F, Hasegawa, T, Hashimoto, A, Hashimoto, C, Hashimoto, M, Hashimoto, S, Haskett, S, Hawfield, A, Hayami, T, Hayashi, M, Hayashi, S, Hazara, A, Healy, C, Hecktman, J, Heine, G, Henderson, H, Henschel, R, Hepditch, A, Herfurth, K, Hernandez, G, Hernandez Pena, A, Hernandez-Cassis, C, Herzog, C, Hewins, S, Hewitt, D, Hichkad, L, Higashi, S, Higuchi, C, Hill, C, Hill, L, Himeno, T, Hing, A, Hirakawa, Y, Hirata, K, Hirota, Y, Hisatake, T, Hitchcock, S, Hodakowski, A, Hodge, W, Hogan, R, Hohenstatt, U, Hohenstein, B, Hooi, L, Hope, S, Hopley, M, Horikawa, S, Hosein, D, Hosooka, T, Hou, L, Hou, W, Howie, L, Howson, A, Hozak, M, Htet, Z, Hu, X, Hu, Y, Huang, J, Huda, N, Hudig, L, Hudson, A, Hugo, C, Hull, R, Hume, L, Hundei, W, Hunt, N, Hunter, A, Hurley, S, Hurst, A, Hutchinson, C, Hyo, T, Ibrahim, FH, Ibrahim, S, Ihana, N, Ikeda, T, Imai, A, Imamine, R, Inamori, A, Inazawa, H, Ingell, J, Inomata, K, Inukai, Y, Ioka, M, Irtiza-Ali, A, Isakova, T, Isari, W, Iselt, M, Ishiguro, A, Ishihara, K, Ishikawa, T, Ishimoto, T, Ishizuka, K, Ismail, R, Itano, S, Ito, H, Ito, K, Ito, M, Ito, Y, Iwagaitsu, S, Iwaita, Y, Iwakura, T, Iwamoto, M, Iwasa, M, Iwasaki, H, Iwasaki, S, Izumi, K, Izumi, T, Jaafar, SM, Jackson, C, Jackson, Y, Jafari, G, Jahangiriesmaili, M, Jain, N, Jansson, K, Jasim, H, Jeffers, L, Jenkins, A, Jesky, M, Jesus-Silva, J, Jeyarajah, D, Jiang, Y, Jiao, X, Jimenez, G, Jin, B, Jin, Q, Jochims, J, Johns, B, Johnson, C, Johnson, T, Jolly, S, Jones, L, Jones, S, Jones, T, Jones, V, Joseph, M, Joshi, S, Judge, P, Junejo, N, Junus, S, Kachele, M, Kadoya, H, Kaga, H, Kai, H, Kajio, H, Kaluza-Schilling, W, Kamaruzaman, L, Kamarzarian, A, Kamimura, Y, Kamiya, H, Kamundi, C, Kan, T, Kanaguchi, Y, Kanazawa, A, Kanda, E, Kanegae, S, Kaneko, K, Kang, HY, Kano, T, Karim, M, Karounos, D, Karsan, W, Kasagi, R, Kashihara, N, Katagiri, H, Katanosaka, A, Katayama, A, Katayama, M, Katiman, E, Kato, K, Kato, M, Kato, N, Kato, S, Kato, T, Kato, Y, Katsuda, Y, Katsuno, T, Kaufeld, J, Kavak, Y, Kawai, I, Kawai, M, Kawase, A, Kawashima, S, Kazory, A, Kearney, J, Keith, B, Kellett, J, Kelley, S, Kershaw, M, Ketteler, M, Khai, Q, Khairullah, Q, Khandwala, H, Khoo, KKL, Khwaja, A, Kidokoro, K, Kielstein, J, Kihara, M, Kimber, C, Kimura, S, Kinashi, H, Kingston, H, Kinomura, M, Kinsella-Perks, E, Kitagawa, M, Kitajima, M, Kitamura, S, Kiyosue, A, Kiyota, M, Klauser, F, Klausmann, G, Kmietschak, W, Knapp, K, Knight, C, Knoppe, A, Knott, C, Kobayashi, M, Kobayashi, R, Kobayashi, T, Koch, M, Kodama, S, Kodani, N, Kogure, E, Koizumi, M, Kojima, H, Kojo, T, Kolhe, N, Komaba, H, Komiya, T, Komori, H, Kon, SP, Kondo, M, Kong, W, Konishi, M, Kono, K, Koshino, M, Kosugi, T, Kothapalli, B, Kozlowski, T, Kraemer, B, Kraemer-Guth, A, Krappe, J, Kraus, D, Kriatselis, C, Krieger, C, Krish, P, Kruger, B, Ku Md Razi, KR, Kuan, Y, Kubota, S, Kuhn, S, Kumar, P, Kume, S, Kummer, I, Kumuji, R, Küpper, A, Kuramae, T, Kurian, L, Kuribayashi, C, Kurien, R, Kuroda, E, Kurose, T, Kutschat, A, Kuwabara, N, Kuwata, H, La Manna, G, Lacey, M, Lafferty, K, LaFleur, P, Lai, V, Laity, E, Lambert, A, Langlois, M, Latif, F, Latore, E, Laundy, E, Laurienti, D, Lawson, A, Lay, M, Leal, I, Lee, AK, Lee, J, Lee, KQ, Lee, R, Lee, SA, Lee, YY, Lee-Barkey, Y, Leonard, N, Leoncini, G, Leong, CM, Lerario, S, Leslie, A, Lewington, A, Li, N, Li, X, Li, Y, Liberti, L, Liberti, ME, Liew, A, Liew, YF, Lilavivat, U, Lim, SK, Lim, YS, Limon, E, Lin, H, Lioudaki, E, Liu, H, Liu, J, Liu, L, Liu, Q, Liu, X, Liu, Z, Loader, D, Lochhead, H, Loh, CL, Lorimer, A, Loudermilk, L, Loutan, J, Low, CK, Low, CL, Low, YM, Lozon, Z, Lu, Y, Lucci, D, Ludwig, U, Luker, N, Lund, D, Lustig, R, Lyle, S, Macdonald, C, MacDougall, I, Machicado, R, MacLean, D, Macleod, P, Madera, A, Madore, F, Maeda, K, Maegawa, H, Maeno, S, Mafham, M, Magee, J, Mah, DY, Mahabadi, V, Maiguma, M, Makita, Y, Makos, G, Manco, L, Mangiacapra, R, Manley, J, Mann, P, Mano, S, Marcotte, G, Maris, J, Mark, P, Markau, S, Markovic, M, Marshall, C, Martin, M, Martinez, C, Martinez, S, Martins, G, Maruyama, K, Maruyama, S, Marx, K, Maselli, A, Masengu, A, Maskill, A, Masumoto, S, Masutani, K, Matsumoto, M, Matsunaga, T, Matsuoka, N, Matsushita, M, Matthews, M, Matthias, S, Matvienko, E, Maurer, M, Maxwell, P, Mazlan, N, Mazlan, SA, Mbuyisa, A, McCafferty, K, McCarroll, F, McCarthy, T, McClary-Wright, C, McCray, K, McDermott, P, McDonald, C, McDougall, R, McHaffie, E, McIntosh, K, McKinley, T, McLaughlin, S, McLean, N, McNeil, L, Measor, A, Meek, J, Mehta, A, Mehta, R, Melandri, M, Mené, P, Meng, T, Menne, J, Merritt, K, Merscher, S, Meshykhi, C, Messa, P, Messinger, L, Miftari, N, Miller, R, Miller, Y, Miller-Hodges, E, Minatoguchi, M, Miners, M, Minutolo, R, Mita, T, Miura, Y, Miyaji, M, Miyamoto, S, Miyatsuka, T, Miyazaki, M, Miyazawa, I, Mizumachi, R, Mizuno, M, Moffat, S, Mohamad Nor, FS, Mohamad Zaini, SN, Mohamed Affandi, FA, Mohandas, C, Mohd, R, Mohd Fauzi, NA, Mohd Sharif, NH, Mohd Yusoff, Y, Moist, L, Moncada, A, Montasser, M, Moon, A, Moran, C, Morgan, N, Moriarty, J, Morig, G, Morinaga, H, Morino, K, Morisaki, T, Morishita, Y, Morlok, S, Morris, A, Morris, F, Mostafa, S, Mostefai, Y, Motegi, M, Motherwell, N, Motta, D, Mottl, A, Moys, R, Mozaffari, S, Muir, J, Mulhern, J, Mulligan, S, Munakata, Y, Murakami, C, Murakoshi, M, Murawska, A, Murphy, K, Murphy, L, Murray, S, Murtagh, H, Musa, MA, Mushahar, L, Mustafa, R, Mustafar, R, Muto, M, Nadar, E, Nagano, R, Nagasawa, T, Nagashima, E, Nagasu, H, Nagelberg, S, Nair, H, Nakagawa, Y, Nakahara, M, Nakamura, J, Nakamura, R, Nakamura, T, Nakaoka, M, Nakashima, E, Nakata, J, Nakata, M, Nakatani, S, Nakatsuka, A, Nakayama, Y, Nakhoul, G, Naverrete, G, Navivala, A, Nazeer, I, Negrea, L, Nethaji, C, Newman, E, Ng, TJ, Ngu, LLS, Nimbkar, T, Nishi, H, Nishi, M, Nishi, S, Nishida, Y, Nishiyama, A, Niu, J, Niu, P, Nobili, G, Nohara, N, Nojima, I, Nolan, J, Nosseir, H, Nozawa, M, Nunn, M, Nunokawa, S, Oda, M, Oe, M, Oe, Y, Ogane, K, Ogawa, W, Ogihara, T, Oguchi, G, Ohsugi, M, Oishi, K, Okada, Y, Okajyo, J, Okamoto, S, Okamura, K, Olufuwa, O, Oluyombo, R, Omata, A, Omori, Y, Ong, LM, Ong, YC, Onyema, J, Oomatia, A, Oommen, A, Oremus, R, Orimo, Y, Ortalda, V, Osaki, Y, Osawa, Y, Osmond Foster, J, O'Sullivan, A, Otani, T, Othman, N, Otomo, S, O'Toole, J, Owen, L, Ozawa, T, Padiyar, A, Page, N, Pajak, S, Paliege, A, Pandey, A, Pandey, R, Pariani, H, Park, J, Parrigon, M, Passauer, J, Patecki, M, Patel, M, Patel, R, Patel, T, Patel, Z, Paul, R, Paulsen, L, Pavone, L, Peixoto, A, Peji, J, Peng, BC, Peng, K, Pennino, L, Pereira, E, Perez, E, Pergola, P, Pesce, F, Pessolano, G, Petchey, W, Petr, EJ, Pfab, T, Phelan, P, Phillips, R, Phillips, T, Phipps, M, Piccinni, G, Pickett, T, Pickworth, S, Piemontese, M, Pinto, D, 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2024
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27. Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial

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Staplin, N, Haynes, R, Judge, PK, Wanner, C, Green, JB, Emberson, J, Preiss, D, Mayne, KJ, Ng, SYA, Sammons, E, Zhu, D, Hill, M, Stevens, W, Wallendszus, K, Brenner, S, Cheung, AK, Liu, ZH, Li, J, Hooi, LS, Liu, WJ, Kadowaki, T, Nangaku, M, Levin, A, Cherney, D, Maggioni, AP, Pontremoli, R, Deo, R, Goto, S, Rossello, X, Tuttle, KR, Steubl, D, Petrini, M, Seidi, S, Landray, MJ, Baigent, C, Herrington, WG, Abat, S, Abd Rahman, R, Abdul Cader, R, Abdul Hafidz, MI, Abdul Wahab, MZ, Abdullah, NK, Abdul-Samad, T, Abe, M, Abraham, N, Acheampong, S, Achiri, P, Acosta, JA, Adeleke, A, Adell, V, Adewuyi-Dalton, R, Adnan, N, Africano, A, Agharazii, M, Aguilar, F, Aguilera, A, Ahmad, M, Ahmad, MK, Ahmad, NA, Ahmad, NH, Ahmad, NI, Ahmad Miswan, N, Ahmad Rosdi, H, Ahmed, I, Ahmed, S, Aiello, J, Aitken, A, AitSadi, R, Aker, S, Akimoto, S, Akinfolarin, A, Akram, S, Alberici, F, Albert, C, Aldrich, L, Alegata, M, Alexander, L, Alfaress, S, Alhadj Ali, M, Ali, A, Alicic, R, Aliu, A, Almaraz, R, 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W, Bianchini, F, Bianco, S, Bilous, R, Bilton, J, Bilucaglia, D, Bird, C, Birudaraju, D, Biscoveanu, M, Blake, C, Bleakley, N, Bocchicchia, K, Bodine, S, Bodington, R, Boedecker, S, Bolduc, M, Bolton, S, Bond, C, Boreky, F, Boren, K, Bouchi, R, Bough, L, Bovan, D, Bowler, C, Bowman, L, Brar, N, Braun, C, Breach, A, Breitenfeldt, M, Brettschneider, B, Brewer, A, Brewer, G, Brindle, V, Brioni, E, Brown, C, Brown, H, Brown, L, Brown, R, Brown, S, Browne, D, Bruce, K, Brueckmann, M, Brunskill, N, Bryant, M, Brzoska, M, Bu, Y, Buckman, C, Budoff, M, Bullen, M, Burke, A, Burnette, S, Burston, C, Busch, M, Bushnell, J, Butler, S, Büttner, C, Byrne, C, Caamano, A, Cadorna, J, Cafiero, C, Cagle, M, Cai, J, Calabrese, K, Calvi, C, Camilleri, B, Camp, S, Campbell, D, Campbell, R, Cao, H, Capelli, I, Caple, M, Caplin, B, Cardone, A, Carle, J, Carnall, V, Caroppo, M, Carr, S, Carraro, G, Carson, M, Casares, P, Castillo, C, Castro, C, Caudill, B, Cejka, V, Ceseri, M, Cham, L, Chamberlain, A, 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Ibrahim, FH, Ibrahim, S, Ihana, N, Ikeda, T, Imai, A, Imamine, R, Inamori, A, Inazawa, H, Ingell, J, Inomata, K, Inukai, Y, Ioka, M, Irtiza-Ali, A, Isakova, T, Isari, W, Iselt, M, Ishiguro, A, Ishihara, K, Ishikawa, T, Ishimoto, T, Ishizuka, K, Ismail, R, Itano, S, Ito, H, Ito, K, Ito, M, Ito, Y, Iwagaitsu, S, Iwaita, Y, Iwakura, T, Iwamoto, M, Iwasa, M, Iwasaki, H, Iwasaki, S, Izumi, K, Izumi, T, Jaafar, SM, Jackson, C, Jackson, Y, Jafari, G, Jahangiriesmaili, M, Jain, N, Jansson, K, Jasim, H, Jeffers, L, Jenkins, A, Jesky, M, Jesus-Silva, J, Jeyarajah, D, Jiang, Y, Jiao, X, Jimenez, G, Jin, B, Jin, Q, Jochims, J, Johns, B, Johnson, C, Johnson, T, Jolly, S, Jones, L, Jones, S, Jones, T, Jones, V, Joseph, M, Joshi, S, Judge, P, Junejo, N, Junus, S, Kachele, M, Kadoya, H, Kaga, H, Kai, H, Kajio, H, Kaluza-Schilling, W, Kamaruzaman, L, Kamarzarian, A, Kamimura, Y, Kamiya, H, Kamundi, C, Kan, T, Kanaguchi, Y, Kanazawa, A, Kanda, E, Kanegae, S, Kaneko, K, Kang, HY, Kano, T, Karim, M, 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Krish, P, Kruger, B, Ku Md Razi, KR, Kuan, Y, Kubota, S, Kuhn, S, Kumar, P, Kume, S, Kummer, I, Kumuji, R, Küpper, A, Kuramae, T, Kurian, L, Kuribayashi, C, Kurien, R, Kuroda, E, Kurose, T, Kutschat, A, Kuwabara, N, Kuwata, H, La Manna, G, Lacey, M, Lafferty, K, LaFleur, P, Lai, V, Laity, E, Lambert, A, Langlois, M, Latif, F, Latore, E, Laundy, E, Laurienti, D, Lawson, A, Lay, M, Leal, I, Lee, AK, Lee, J, Lee, KQ, Lee, R, Lee, SA, Lee, YY, Lee-Barkey, Y, Leonard, N, Leoncini, G, Leong, CM, Lerario, S, Leslie, A, Lewington, A, Li, N, Li, X, Li, Y, Liberti, L, Liberti, ME, Liew, A, Liew, YF, Lilavivat, U, Lim, SK, Lim, YS, Limon, E, Lin, H, Lioudaki, E, Liu, H, Liu, J, Liu, L, Liu, Q, Liu, X, Liu, Z, Loader, D, Lochhead, H, Loh, CL, Lorimer, A, Loudermilk, L, Loutan, J, Low, CK, Low, CL, Low, YM, Lozon, Z, Lu, Y, Lucci, D, Ludwig, U, Luker, N, Lund, D, Lustig, R, Lyle, S, Macdonald, C, MacDougall, I, Machicado, R, MacLean, D, Macleod, P, Madera, A, Madore, F, Maeda, K, Maegawa, H, Maeno, S, Mafham, M, Magee, J, Mah, DY, Mahabadi, V, Maiguma, M, Makita, Y, Makos, G, Manco, L, Mangiacapra, R, Manley, J, Mann, P, Mano, S, Marcotte, G, Maris, J, Mark, P, Markau, S, Markovic, M, Marshall, C, Martin, M, Martinez, C, Martinez, S, Martins, G, Maruyama, K, Maruyama, S, Marx, K, Maselli, A, Masengu, A, Maskill, A, Masumoto, S, Masutani, K, Matsumoto, M, Matsunaga, T, Matsuoka, N, Matsushita, M, Matthews, M, Matthias, S, Matvienko, E, Maurer, M, Maxwell, P, Mazlan, N, Mazlan, SA, Mbuyisa, A, McCafferty, K, McCarroll, F, McCarthy, T, McClary-Wright, C, McCray, K, McDermott, P, McDonald, C, McDougall, R, McHaffie, E, McIntosh, K, McKinley, T, McLaughlin, S, McLean, N, McNeil, L, Measor, A, Meek, J, Mehta, A, Mehta, R, Melandri, M, Mené, P, Meng, T, Menne, J, Merritt, K, Merscher, S, Meshykhi, C, Messa, P, Messinger, L, Miftari, N, Miller, R, Miller, Y, Miller-Hodges, E, Minatoguchi, M, Miners, M, Minutolo, R, Mita, T, Miura, Y, Miyaji, M, Miyamoto, S, Miyatsuka, T, Miyazaki, M, Miyazawa, I, Mizumachi, R, Mizuno, M, Moffat, S, Mohamad Nor, FS, Mohamad Zaini, SN, Mohamed Affandi, FA, Mohandas, C, Mohd, R, Mohd Fauzi, NA, Mohd Sharif, NH, Mohd Yusoff, Y, Moist, L, Moncada, A, Montasser, M, Moon, A, Moran, C, Morgan, N, Moriarty, J, Morig, G, Morinaga, H, Morino, K, Morisaki, T, Morishita, Y, Morlok, S, Morris, A, Morris, F, Mostafa, S, Mostefai, Y, Motegi, M, Motherwell, N, Motta, D, Mottl, A, Moys, R, Mozaffari, S, Muir, J, Mulhern, J, Mulligan, S, Munakata, Y, Murakami, C, Murakoshi, M, Murawska, A, Murphy, K, Murphy, L, Murray, S, Murtagh, H, Musa, MA, Mushahar, L, Mustafa, R, Mustafar, R, Muto, M, Nadar, E, Nagano, R, Nagasawa, T, Nagashima, E, Nagasu, H, Nagelberg, S, Nair, H, Nakagawa, Y, Nakahara, M, Nakamura, J, Nakamura, R, Nakamura, T, Nakaoka, M, Nakashima, E, Nakata, J, Nakata, M, Nakatani, S, Nakatsuka, A, Nakayama, Y, Nakhoul, G, Naverrete, G, Navivala, A, Nazeer, I, Negrea, L, Nethaji, C, Newman, E, Ng, TJ, Ngu, LLS, Nimbkar, T, Nishi, H, Nishi, M, Nishi, S, Nishida, Y, Nishiyama, A, Niu, J, Niu, P, Nobili, G, Nohara, N, Nojima, I, Nolan, J, Nosseir, H, Nozawa, M, Nunn, M, Nunokawa, S, Oda, M, Oe, M, Oe, Y, Ogane, K, Ogawa, W, Ogihara, T, Oguchi, G, Ohsugi, M, Oishi, K, Okada, Y, Okajyo, J, Okamoto, S, Okamura, K, Olufuwa, O, Oluyombo, R, Omata, A, Omori, Y, Ong, LM, Ong, YC, Onyema, J, Oomatia, A, Oommen, A, Oremus, R, Orimo, Y, Ortalda, V, Osaki, Y, Osawa, Y, Osmond Foster, J, O'Sullivan, A, Otani, T, Othman, N, Otomo, S, O'Toole, J, Owen, L, Ozawa, T, Padiyar, A, Page, N, Pajak, S, Paliege, A, Pandey, A, Pandey, R, Pariani, H, Park, J, Parrigon, M, Passauer, J, Patecki, M, Patel, M, Patel, R, Patel, T, Patel, Z, Paul, R, Paulsen, L, Pavone, L, Peixoto, A, Peji, J, Peng, BC, Peng, K, Pennino, L, Pereira, E, Perez, E, Pergola, P, Pesce, F, Pessolano, G, Petchey, W, Petr, EJ, Pfab, T, Phelan, P, Phillips, R, Phillips, T, Phipps, M, Piccinni, G, Pickett, T, Pickworth, S, Piemontese, M, Pinto, D, Piper, J, Plummer-Morgan, J, Poehler, D, Polese, L, Poma, V, Postal, A, Pötz, C, Power, A, Pradhan, N, Pradhan, R, Preiss, E, Preston, K, Prib, N, Price, L, Provenzano, C, Pugay, C, Pulido, R, Putz, F, Qiao, Y, Quartagno, R, Quashie-Akponeware, M, Rabara, R, Rabasa-Lhoret, R, Radhakrishnan, D, Radley, M, Raff, R, Raguwaran, S, Rahbari-Oskoui, F, Rahman, M, Rahmat, K, Ramadoss, S, Ramanaidu, S, Ramasamy, S, Ramli, R, Ramli, S, Ramsey, T, Rankin, A, Rashidi, A, Raymond, L, Razali, WAFA, Read, K, Reiner, H, Reisler, A, Reith, C, Renner, J, Rettenmaier, B, Richmond, L, Rijos, D, Rivera, R, Rivers, V, Robinson, H, Rocco, M, Rodriguez-Bachiller, I, Rodriquez, R, Roesch, C, Roesch, J, Rogers, J, Rohnstock, M, Rolfsmeier, S, Roman, M, Romo, A, Rosati, A, Rosenberg, S, Ross, T, Roura, M, Roussel, M, Rovner, S, Roy, S, Rucker, S, Rump, L, Ruocco, M, Ruse, S, Russo, F, Russo, M, Ryder, M, Sabarai, A, Saccà, C, Sachson, R, Sadler, E, Safiee, NS, Sahani, M, Saillant, A, Saini, J, Saito, C, Saito, S, Sakaguchi, K, Sakai, M, Salim, H, Salviani, C, Sampson, A, Samson, F, Sandercock, P, Sanguila, S, Santorelli, G, Santoro, D, Sarabu, N, Saram, T, Sardell, R, Sasajima, H, Sasaki, T, Satko, S, Sato, A, Sato, D, Sato, H, Sato, J, Sato, T, Sato, Y, Satoh, M, Sawada, K, Schanz, M, Scheidemantel, F, Schemmelmann, M, Schettler, E, Schettler, V, Schlieper, GR, Schmidt, C, Schmidt, G, Schmidt, U, Schmidt-Gurtler, H, Schmude, M, Schneider, A, Schneider, I, Schneider-Danwitz, C, Schomig, M, Schramm, T, Schreiber, A, Schricker, S, Schroppel, B, Schulte-Kemna, L, Schulz, E, Schumacher, B, Schuster, A, Schwab, A, Scolari, F, Scott, A, Seeger, W, Segal, M, Seifert, L, Seifert, M, Sekiya, M, Sellars, R, Seman, MR, Shah, S, Shainberg, L, Shanmuganathan, M, Shao, F, Sharma, K, Sharpe, C, Sheikh-Ali, M, Sheldon, J, Shenton, C, Shepherd, A, Shepperd, M, Sheridan, R, Sheriff, Z, Shibata, Y, Shigehara, T, Shikata, K, Shimamura, K, Shimano, H, Shimizu, Y, Shimoda, H, Shin, K, Shivashankar, G, Shojima, N, Silva, R, Sim, CSB, Simmons, K, Sinha, S, Sitter, T, Sivanandam, S, Skipper, M, Sloan, K, Sloan, L, Smith, R, Smyth, J, Sobande, T, Sobata, M, Somalanka, S, Song, X, Sonntag, F, Sood, B, Sor, SY, Soufer, J, Sparks, H, Spatoliatore, G, Spinola, T, Squyres, S, Srivastava, A, Stanfield, J, Staylor, K, Steele, A, Steen, O, Steffl, D, Stegbauer, J, Stellbrink, C, Stellbrink, E, Stevenson, A, Stewart-Ray, V, Stickley, J, Stoffler, D, Stratmann, B, Streitenberger, S, Strutz, F, Stubbs, J, Stumpf, J, Suazo, N, Suchinda, P, Suckling, R, Sudin, A, Sugamori, K, Sugawara, H, Sugawara, K, Sugimoto, D, Sugiyama, H, Sugiyama, T, Sullivan, M, Sumi, M, Suresh, N, Sutton, D, Suzuki, H, Suzuki, R, Suzuki, Y, Swanson, E, Swift, P, Syed, S, Szerlip, H, Taal, M, Taddeo, M, Tailor, C, Tajima, K, Takagi, M, Takahashi, K, Takahashi, M, Takahashi, T, Takahira, E, Takai, T, Takaoka, M, Takeoka, J, Takesada, A, Takezawa, M, Talbot, M, Taliercio, J, Talsania, T, Tamori, Y, Tamura, R, Tamura, Y, Tan, CHH, Tan, EZZ, Tanabe, A, Tanabe, K, Tanaka, A, Tanaka, N, Tang, S, Tang, Z, Tanigaki, K, Tarlac, M, Tatsuzawa, A, Tay, JF, Tay, LL, Taylor, J, Taylor, K, Te, A, Tenbusch, L, Teng, KS, Terakawa, A, Terry, J, Tham, ZD, Tholl, S, Thomas, G, Thong, KM, Tietjen, D, Timadjer, A, Tindall, H, Tipper, S, Tobin, K, Toda, N, Tokuyama, A, Tolibas, M, Tomita, A, Tomita, T, Tomlinson, J, Tonks, L, Topf, J, Topping, S, Torp, A, Torres, A, Totaro, F, Toth, P, Toyonaga, Y, Tripodi, F, Trivedi, K, Tropman, E, Tschope, D, Tse, J, Tsuji, K, Tsunekawa, S, Tsunoda, R, Tucky, B, Tufail, S, Tuffaha, A, Turan, E, Turner, H, Turner, J, Turner, M, Tye, YL, Tyler, A, Tyler, J, Uchi, H, Uchida, H, Uchida, T, Udagawa, T, Ueda, S, Ueda, Y, Ueki, K, Ugni, S, Ugwu, E, Umeno, R, Unekawa, C, Uozumi, K, Urquia, K, Valleteau, A, Valletta, C, van Erp, R, Vanhoy, C, Varad, V, Varma, R, Varughese, A, Vasquez, P, Vasseur, A, Veelken, R, Velagapudi, C, Verdel, K, Vettoretti, S, Vezzoli, G, Vielhauer, V, Viera, R, Vilar, E, Villaruel, S, Vinall, L, Vinathan, J, Visnjic, M, Voigt, E, von-Eynatten, M, Vourvou, M, Wada, J, Wada, T, Wada, Y, Wakayama, K, Wakita, Y, Walters, T, Wan Mohamad, WH, Wang, L, Wang, W, Wang, X, Wang, Y, Wanninayake, S, Watada, H, Watanabe, K, Watanabe, M, Waterfall, H, Watkins, D, Watson, S, Weaving, L, Weber, B, Webley, Y, Webster, A, Webster, M, Weetman, M, Wei, W, Weihprecht, H, Weiland, L, Weinmann-Menke, J, Weinreich, T, Wendt, R, Weng, Y, Whalen, M, Whalley, G, Wheatley, R, Wheeler, A, Wheeler, J, Whelton, P, White, K, Whitmore, B, Whittaker, S, Wiebel, J, Wiley, J, Wilkinson, L, Willett, M, Williams, A, Williams, E, Williams, K, Williams, T, Wilson, A, Wilson, P, Wincott, L, Wines, E, Winkelmann, B, Winkler, M, Winter-Goodwin, B, Witczak, J, Wittes, J, Wittmann, M, Wolf, G, Wolf, L, Wolfling, R, Wong, C, Wong, E, Wong, HS, Wong, LW, Wong, YH, Wonnacott, A, Wood, A, Wood, L, Woodhouse, H, Wooding, N, Woodman, A, Wren, K, Wu, J, Wu, P, Xia, S, Xiao, H, Xiao, X, Xie, Y, Xu, C, Xu, Y, Xue, H, Yahaya, H, Yalamanchili, H, Yamada, A, Yamada, N, Yamagata, K, Yamaguchi, M, Yamaji, Y, Yamamoto, A, Yamamoto, S, Yamamoto, T, Yamanaka, A, Yamano, T, Yamanouchi, Y, Yamasaki, N, Yamasaki, Y, Yamashita, C, Yamauchi, T, Yan, Q, Yanagisawa, E, Yang, F, Yang, L, Yano, S, Yao, S, Yao, Y, Yarlagadda, S, Yasuda, Y, Yiu, V, Yokoyama, T, Yoshida, S, Yoshidome, E, Yoshikawa, H, Young, A, Young, T, Yousif, V, Yu, H, Yu, Y, Yuasa, K, Yusof, N, Zalunardo, N, Zander, B, Zani, R, Zappulo, F, Zayed, M, Zemann, B, Zettergren, P, Zhang, H, Zhang, L, Zhang, N, Zhang, X, Zhao, J, Zhao, L, Zhao, S, Zhao, Z, Zhong, H, Zhou, N, Zhou, S, Zhu, L, Zhu, S, Zietz, M, Zippo, M, Zirino, F, and Zulkipli, FH

Published
2024
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37. POS0206 CLINICALLY AND MOLECULARLY DECIPHERING THE RAPIDLY PROGRESSIVE KNEE OSTEOARTHRITIS PHENOTYPE

Author

Rego-Perez, I., primary, Durán-Sotuela, A., additional, Ruiz-Romero, C., additional, De Andres, M. C., additional, Vázquez-García, J., additional, Lombardi, A. F., additional, Chang, E. Y., additional, Lane, N., additional, Relaño-Fernandez, S., additional, Lourido, L., additional, Calamia, V., additional, Paz González, R., additional, Quaranta, P., additional, Fernández Puente, P., additional, Oreiro, N., additional, Veronese, N., additional, Guma, M., additional, and Blanco, F. J., additional

Published
2024
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41. Medication Adherence and Healthcare Utilization in Relapsing-Remitting Multiple Sclerosis Patients Using Teriflunomide

Author

Greene N, Higuchi K, Bognar K, Chang E, and Broder MS

Subjects
administrative claims analysis, disease modifying therapies, medication compliance, percent of days covered, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Nupur Greene,1 Keiko Higuchi,1 Katalin Bognar,2 Eunice Chang,2 Michael S Broder2 1Neurology & Immunology (N&I), Sanofi, Cambridge, MA, USA; 2Real World Evidence, PHAR (Partnership for Health Analytic Research), Beverly Hills, CA, USACorrespondence: Nupur Greene, Global HEVA Business Partner, N&I, Sanofi, 450 Water Street, Cambridge, MA, USA, Tel +1 857 259 0037, Email Nupur.Greene@sanofi.comPurpose: Multiple sclerosis (MS) is a costly, immune-mediated disease of the central nervous system. Most patients have relapsing-remitting MS (RRMS) for which disease-modifying therapies (DMTs) provide an effective treatment option by reducing relapse rates. However, adherence to DMTs is suboptimal. This study examines the association between adherence to teriflunomide and clinical and healthcare utilization outcomes.Patients and Methods: Patients with RRMS who started treatment with teriflunomide between 1/1/2018 and 12/31/2019 were analyzed using IQVIA PharMetrics® Plus data. RRMS patients were identified via diagnosis codes and treatment types; the first prescription date for teriflunomide was the index date. Highly and poorly adherent patients were identified based on the proportion of days covered (PDC) post-index (PDC ≥ 0.8 and PDC ≤ 0.5, respectively). Patient demographics, clinical characteristics, healthcare utilization during the year pre- and post-index, and relapse rate post-index were reported descriptively. Outcomes were compared between highly and poorly adherent patients through logistic regression. Models were adjusted for demographics, comorbidities, and utilization measures during the baseline period.Results: Among the 922 RRMS patients identified, 534 (57.9%) were highly adherent to teriflunomide, while 249 (27.0%) had PDC ≤ 0.5. The two groups were not statistically different in terms of demographic characteristics and comorbidities; however, poorly adherent patients were more likely to have emergency department (ED) or inpatient visits during baseline (36.9% versus 26.8%, P=0.004; 17.3% versus 10.9%, P=0.013, respectively). Unadjusted results suggested lower likelihood of both relapses and utilization during follow-up among highly adherent patients compared to poorly adherent patients. Adjusted results confirmed that high adherence was associated with decreased likelihood of post-index relapses, ED utilization, and inpatient utilization (OR [95% CI]: 0.55 [0.39– 0.76], 0.49 [0.34– 0.71], and 0.51 [0.27– 0.97], respectively) even after controlling for baseline utilization.Conclusion: High adherence to teriflunomide was found to be associated with fewer relapses and lower healthcare utilization among patients with RRMS.Keywords: administrative claims analysis, disease modifying therapies, medication compliance, percent of days covered

Published
2022

42. Measuring the Orbital Parameters of Radial Velocity Systems in Mean Motion Resonance---a Case Study of HD 200964

Author

Rosenthal, M. M., Jacobson-Galan, W., Nelson, B., Murray-Clay, R. A., Burt, J. A., Holden, B., Chang, E., Kaaz, N., Yant, J., Butler, R. P., and Vogt, S. S.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

The presence of mean motion resonances (MMRs) complicates analysis and fitting of planetary systems observed through the radial velocity (RV) technique. MMR can allow planets to remain stable in regions of phase space where strong planet-planet interactions would otherwise destabilize the system. These stable orbits can occupy small phase space volumes, allowing MMRs to strongly constrain system parameters, but making searches for stable orbital parameters challenging. Furthermore, libration of the resonant angle and dynamical interaction between the planets introduces another, long period variation into the observed RV signal, complicating analysis of the periods of the planets in the system. We discuss this phenomenon using the example of HD 200964. By searching through parameter space and numerically integrating each proposed set of planetary parameters to test for long term stability, we find stable solutions in the 7:5 and 3:2 MMRs in addition to the originally identified 4:3 MMR. The 7:5 configuration provides the best match to the data, while the 3:2 configuration provides the most easily understood formation scenario. In reanalysis of the originally published shorter-baseline data, we find fits in both the 4:3 and 3:2 resonances, but not the 7:5. Because the time baseline of the data is less than the resonant libration period, the current best fit to the data may not reflect the actual resonant configuration. In the absence of a full sample of the longer libration period, we find that it is of paramount importance to incorporate long term stability when fitting for the system's orbital configuration., Comment: 26 pages, 23 figures

Published
2019
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45. Surface complexation model of rare earth element adsorption onto bacterial surfaces with lanthanide binding tags

Author

Chang, E, Brewer, AW, Park, DM, Jiao, Y, and Lammers, LN

Subjects
Surface complexation modeling, Rare earth elements, REE, Biosorption, Bioadsorption, Surface complexation, Lanthanide binding tag, Geochemistry & Geophysics, Geochemistry, Environmental Science and Management
Abstract

Lanthanide binding tags (LBTs) have been engineered onto the cell surface of E. coli to enhance biosorption and recovery of rare earth elements (REEs). The protonation behavior of the bacterial surfaces before and after LBT-display was compared by modeling acid-base titration data. A multiple discrete site, constant capacitance surface complexation model was constructed to examine rare earth (Tb) binding to cell surface functional groups, comparing wild type and LBT-engineered surfaces. Our acid-base titrations show similar pKa values between the two strains, suggesting induction of LBTs does not significantly alter cell surface protonation behavior. Tb sorption onto the wild type cell surface can be captured by a one-site carboxyl model. The LBT strain exhibited a higher metal loading that can be explained by the increase of sorption sites in the form of lanthanide binding tags. Furthermore, carboxyl site concentrations between wild type and LBT-induced cells were statistically indistinguishable. We thus attribute the engineered strains’ increase in Tb adsorption capacity and affinity to the addition of lanthanide binding tags to the cell surface. The Tb stability constant with the LBT site is two orders of magnitude higher than that with the carboxyl functional group. As a result, at low metal loading 10 μM, a more abundant but low affinity functional group becomes the main source of adsorption that results in an overall higher sorption capacity. This work demonstrates how surface complexation modeling can be implemented for bacterial surfaces engineered with a known protein tag to optimize REE recovery from fluids with variable pH and metal loadings.

Published
2020

49. Biologic Initiation Rate in Systemic-Naïve Psoriatic Arthritis Patients Starting Treatment with Apremilast vs Methotrexate: 1-Year Retrospective Analysis of a US Claims Database

Author

Husni ME, Chang E, Broder MS, Paydar C, Bognar K, Desai P, Klyachkin Y, and Khilfeh I

Subjects
psoriatic arthritis, oral small molecules, biologics, systemic treatment initiation, administrative claims analysis, Diseases of the musculoskeletal system, RC925-935
Abstract

M Elaine Husni,1 Eunice Chang,2 Michael S Broder,2 Caleb Paydar,2 Katalin Bognar,2 Pooja Desai,3 Yuri Klyachkin,3 Ibrahim Khilfeh3 1Cleveland Clinic, Cleveland, OH, USA; 2Partnership for Health Analytic Research, LLC, Beverly Hills, CA, USA; 3Amgen Inc., Thousand Oaks, CA, USACorrespondence: Michael S Broder, Partnership for Health Analytic Research, LLC, 280 S. Beverly Drive, Suite 404, Beverly Hills, CA, 90212, USA, Tel +1 310 858 9555, Fax +1 310 858 9552, Email mbroder@pharllc.comPurpose: To compare the rate of biologic initiation after commencing treatment with apremilast (APR) vs methotrexate (MTX), in systemic-naïve patients with psoriatic arthritis (PsA).Patients and Methods: Systemic-naïve patients with PsA who started treatment with either APR or MTX between 01/01/2015 and 12/31/2018 were analyzed using claims data from the IBM® MarketScan® Commercial and Medicare Supplemental databases (2014– 2019). PsA patients were identified via diagnosis codes; the first prescription date for APR or MTX was the index date. Patient demographics, clinical characteristics, healthcare utilization during the year pre-index (baseline) and the year post-index (follow-up), and median time to biologic initiation were reported descriptively. The rates and risk of biologic initiation during follow-up were compared between APR and MTX users by logistic and Cox regressions, respectively. Models were adjusted for demographics, clinical and utilization measures during the baseline period.Results: A total of 2116 patients with PsA newly treated with APR (n = 534) or MTX (n = 1582) were identified. Mean age was similar (50.5 vs 50.4; P = 0.938), and proportion of females was higher for APR vs MTX users (59.4% vs 54.0%; P = 0.031). Mean time to biologic initiation among patients who initiated during follow-up was 194.1 vs 138.7 days between APR vs MTX users (P < 0.001). After adjusting for confounders, the likelihood of biologic initiation was 58% lower (OR, 0.42 [95% CI, 0.32– 0.54]; P < 0.001) with APR, with a significantly lower predicted rate of biologic initiation among APR users when compared to MTX users during follow-up (20.0% [95% CI, 16.6– 23.9%] vs 37.5% [95% CI, 35.0– 40.1%]). Additionally, APR users had a lower risk of biologic initiation than MTX users (HR, 0.46 [95% CI, 0.37– 0.57]; P < 0.001) during the 1-year follow-up.Conclusion: Systemic-naïve patients with PsA have a lower rate of, and longer time to, biologic initiation over one-year following APR initiation, compared to those initiating MTX.Keywords: psoriatic arthritis, oral small molecules, biologics, systemic treatment initiation, administrative claims analysis

Published
2022

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