46 results on '"Leung D."'
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2. Banach lattices with upper $p$-estimates: free and injective objects
- Author
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García-Sánchez, E., Leung, D. H., Taylor, M. A., and Tradacete, P.
- Subjects
Mathematics - Functional Analysis ,46B42, 06B25, 47B60 - Abstract
We study the free Banach lattice $FBL^{(p,\infty)}[E]$ with upper $p$-estimates generated by a Banach space $E$. Using a classical result of Pisier on factorization through $L^{p,\infty}(\mu)$ together with a finite dimensional reduction, it is shown that the spaces $\ell^{p,\infty}(n)$ witness the universal property of $FBL^{(p,\infty)}[E]$ isomorphically. As a consequence, we obtain a functional representation for $FBL^{(p,\infty)}[E]$. More generally, our proof allows us to identify the norm of any free Banach lattice over $E$ associated with a rearrangement invariant function space. After obtaining the above functional representation, we take the first steps towards analyzing the fine structure of $FBL^{(p,\infty)}[E]$. Notably, we prove that the norm for $FBL^{(p,\infty)}[E]$ cannot be isometrically witnessed by $L^{p,\infty}(\mu)$ and settle the question of characterizing when an embedding between Banach spaces extends to a lattice embedding between the corresponding free Banach lattices with upper $p$-estimates. To prove this latter result, we introduce a novel push-out argument, which when combined with the injectivity of $\ell^p$ allows us to give an alternative proof of the subspace problem for free $p$-convex Banach lattices. On the other hand, we prove that $\ell^{p,\infty}$ is not injective in the class of Banach lattices with upper $p$-estimates, elucidating one of many difficulties arising in the study of $FBL^{(p,\infty)}[E]$., Comment: 37 pages
- Published
- 2024
3. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection
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Marchal, A, Cirulli, E, Neveux, I, Bellos, E, Thwaites, R, Schiabor Barrett, K, Zhang, Y, Nemes-Bokun, I, Kalinova, M, Catchpole, A, Tangye, S, Spaan, A, Lack, J, Ghosn, J, Burdet, C, Gorochov, G, Tubach, F, Hausfater, P, Abel, L, Aiuti, A, Al-Muhsen, S, Al-Mulla, F, Amara, A, Anderson, M, Andreakos, E, Arias, A, Arkin, L, Feldman, H, Bastard, P, Belot, A, Biggs, C, Bogunovic, D, Bolze, A, Bondarenko, A, Borghesi, A, Bousfiha, A, Brodin, P, Bryceson, Y, Butte, M, Casanova, J, Casari, G, Christodoulou, J, Cobat, A, Colobran, R, Condino-Neto, A, Constantinescu, S, Cooper, M, Dalgard, C, Desai, M, Drolet, B, Duval, X, El Baghdadi, J, Eloy, P, Espinosa-Padilla, S, Fellay, J, Flores, C, Franco, J, Froidure, A, Gregersen, P, Grimbacher, B, Haerynck, F, Hagin, D, Halwani, R, Hammarstrom, L, Heath, J, Hsieh, E, Husebye, E, Imai, K, Itan, Y, Jouanguy, E, Kaja, E, Karamitros, T, Kisand, K, Ku, C, Lau, Y, Ling, Y, Lucas, C, Maniatis, T, Mansouri, D, Marodi, L, Mentre, F, Meyts, I, Milner, J, Mironska, K, Mogensen, T, Morio, T, Ng, L, Notarangelo, L, Novelli, A, Novelli, G, O'Farrelly, C, Okada, S, Okamoto, K, Ozcelik, T, Pan-Hammarstrom, Q, Pape, J, Perez de Diego, R, Perez-Tur, J, Perlin, D, Pesole, G, Planas, A, Prando, C, Pujol, A, Puel, A, Quintana-Murci, L, Ramaswamy, S, Renia, L, Resnick, I, Rodriguez-Gallego, C, Sancho-Shimizu, V, Sediva, A, Seppanen, M, Shahrooei, M, Shcherbina, A, Slaby, O, Snow, A, Soler-Palacin, P, Soumelis, V, Tancevski, I, Tayoun, A, Temel, S, Thorball, C, Tiberghien, P, Trouillet-Assant, S, Turvey, S, Uddin, K, Uddin, M, van de Beek, D, Vinh, D, von Bernuth, H, Wauters, J, Zatz, M, Zawadzki, P, Zhang, Q, Zhang, S, Bureau, S, Vacher, Y, Gysembergh-Houal, A, Demerville, L, Benleulmi-Chaachoua, A, Abad, S, Abassi, R, Abdellaoui, A, Abdelmalek, A, Abdoul, H, Abergel, H, Abeud, F, Abgrall, S, Abisror, N, Adechian, M, Aderdour, N, Admane, H, Adnet, F, Afritt, S, Agostini, H, Aguilar, C, Agut, S, Aiello, T, Kaci, M, Oufella, H, Ajeenthiravasan, G, 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R, Bonnet, N, Bonnouvrier, J, Botha, S, Boucenna, W, Bouchama, F, Bouchaud, O, Bouchghoul, H, Boudjebla, T, Boudjema, N, Bouffard, C, Bougle, A, Bouguerra, M, Bouras, L, Bourcier, A, Durand, A, Bourrier, A, Bouscarat, F, Bouvry, D, Bouziri, N, Bouzrara, O, Bribier, S, Brugier, D, Brunel, M, Bui, E, Buisson, A, Bukreyeva, I, Bureau, C, Cadranel, J, Cailhol, J, Calin, R, Vega, C, Canavaggio, P, Cancella, M, Cantin, D, Cao, A, Carbillon, L, Carlier, N, Cassard, C, Castor, G, Cauchy, M, Cha, O, Chaigne, B, Challal, S, Champion, K, Chariot, P, Chas, J, Chauveau, S, Chauvin, A, Chauvin, C, Chavarot, N, Chebbout, K, Cherai, M, Cherubini, I, Chevalier, A, Chiarabini, T, Chinet, T, Chocron, R, Choinier, P, Chommeloux, J, Choquet, C, Choupeaux, L, Chousterman, B, Ciocan, D, Clarke, A, Clavere, G, Clavier, F, Clement, K, Clerc, S, Cohen, Y, Cohen, F, Cohen, A, Coilly, A, Colboc, H, Colin, P, Collet, M, Comarmond, C, Combacon, E, Combes, A, Comparon, C, Constantin, J, Cordel, H, Cordier, A, 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U., Uzunhan Y., Vaittinadaayar P., Valent A., Valentian M., Valin N., Vallet H., Vaz M., Vazquezibarra M. -A., Vedie B., Velly L., Verstuyft C., Viallette C., Vicaut E., Vignes D., Vimpere D., Virlouvet M., Voiriot G., Voisot L., Weiss E., Weiss N., Winchenne A., Yordanov Y., Zafrani L., Zaidan M., Zaidi W., Zak C., Zarhrate-Ghoul A., Zatout O., Zeino S., Zeitouni M., Zemirli N., Zerah L., Zia O., Ziol M., Zolario O., Zuber J., Andrejak C., Angoulvant F., Bachelet D., Bartoli M., Basmaci R., Behillil S., Beluze M., Benkerrou D., Bhavsar K., Bouadma L., Bouchez S., Bouscambert M., Cervantes-Gonzalez M., Chair A., Chirouze C., Coelho A., Couffin-Cadiergues S., d'Ortenzio E., Debray M. -P., Deconinck L., Deplanque D., Descamps D., Desvallee M., Diallo A., Diouf A., Dorival C., Dubos F., Elharrar B., Enouf V., Esperou H., Esposito-Farese M., Devouge E. F., Gault N., Gaymard A., Gigante T., Gilg M., Guedj J., Hoctin A., Hoffmann I., Houas I., Hulot J. -S., Jaafoura S., Kaguelidou F., Kali S., Khalil A., Khan C., Laouenan C., Laribi S., Le M., Le Hingrat Q., Le Mestre S., Le Nagard H., Lescure F. -X., Letrou S., Levy Y., Lina B., Lingas G., Lucet J. -C., Malvy D., Mambert M., Meziane A., Mouquet H., Mullaert J., Neant N., Nguyen D., Noret M., Nseir S., Papadopoulos A., Paul C., Peiffer-Smadja N., Perpoint T., Petrov-Sanchez V., Peytavin G., Pham H., Picone O., Puechal O., Rabaud C., Rosa-Calatrava M., Rossignol B., Rossignol P., Roy C., Schneider M., Su R., Tardivon C., Tellier M. -C., Teoule F., Terrier O., Timsit J. -F., Tual C., van der Werf S., Vanel N., Veislinger A., Visseaux B., Wiedemann A., Yazdanpanah Y., Alavoine L., Charpentier C., Dechanet A., Ecobichon J. -L., Frezouls W., Houhou N., Lehacaut J., Manchon P., Nouroudine M., Quintin C., Thy M., Vignali V., Chahine A., Waucquier N., Migaud M. -C., Djossou F., Mergeay-Fabre M., Lucarelli A., Demar M., Bruneau L., Gerardin P., Maillot A., Payet C., Laviolle B., Laine F., Paris C., Desille-Dugast M., Fouchard J., Pistone T., Perreau P., Gissot V., Goas C. L. E., Montagne S., Richard L., Bouiller K., Desmarets M., Meunier A., Bourgeon M., Lefevre B., Jeulin H., Legrand K., Lomazzi S., Tardy B., Gagneux-Brunon A., Bertholon F., Botelho-Nevers E., Kouakam C., Nicolas L., Roufai L., Amat K., Hendou S., Foti G., Citerio G., Contro E., Pesci A., Valsecchi M. G., Cazzaniga M., Bellani G., Abad J., Accordino G., Angelini M., Aguilera-Albesa S., Aguilo-Cucurull A., Ozkan E. A., Darazam I. A., Roblero Albisures J. A., Aldave J. C., Ramos M. A., Khan T. A., Aliberti A., Nadji S. A., Alkan G., AlKhater S. A., Allardet-Servent J., Allende L. M., Alonso-Arias R., Alshahrani M. S., Alsina L., Amoura Z., Antoli A., Arrestier R., Aubart M., Auguet T., Avramenko I., Aytekin G., Azot A., Bahram S., Bajolle F., Baldanti F., Baldolli A., Ballester M., Barrou B., Barzaghi F., Basso S., Bayhan G. I., Bezrodnik L., Bilbao A., Blanchard-Rohner G., Blanco I., Blandinieres A., Blazquez-Gamero D., Bloomfield M., Bolivar-Prados M., Borie R., Botdhlo-Nevers E., Bousquet A., Boutolleau D., Bouvattier C., Boyarchuk O., Bravais J., Briones M. L., Brunner M. -E., Bruno R., Bueno M. R. P., Bukhari H., Bustamante J., Caceres Agra J. J., Capra R., Carapito R., Carrabba M., Casasnovas C., Caseris M., Cassaniti I., Castelle M., Castelli F., Castillo de Vera M., Castro M. V., Catherinot E., Celik J. B., Ceschi A., Chalumeau M., Charbit B., Boulanger C., Clave P., Clotet B., Codina A., Comoli P., Corsico A. G., Coskuner T., Cvetkovski A., Cyrus C., Dalmau D., Danion F., Darley D. R., Das V., Dauby N., Dauger S., De Munte P., de Pontual L., Dehban A., Delplancq G., Desguerre I., Di Sabatino A., Diehl J. -L., Dobbelaere S., Dominguez-Garrido E., Dubost C., Ekwall O., Bozdemir S. E., Elnagdy M. H., Emiroglu M., Endo A., Erdeniz E. H., Aytekin S. E., Etxart Lasa M. P., Euvrard R., Fabio G., Faivre L., Falck A., Fartoukh M., Faure M., Arquero M. F., Ferrer R., Ferreres J., Francois B., Fumado V., Fung K. S. C., Fusco F., Gagro A., Solis B. G., Garcon P., Gaussem P., Gayretli Z., Gil-Herrera J., Gilardin L., Gatineau A. G., Girona-Alarcon M., Cifuentes Godinez K. A., Goffard J. -C., Gonzales N., Gonzalez-Granado L. I., Gonzalez-Montelongo R., Guerder A., Gulhan B., Gumucio V. D., Hanitsch L. G., Gunst J., Gut M., Hadjadj J., Hancerli S., Hariyan T., Hatipoglu N., Heppekcan D., Hernandez-Brito E., Ho P. -K., Holanda-Pena M. S., Horcajada J. P., Hraiech S., Humbert L., Hung I. F. N., Iglesias A. D., Inigo-Campos A., Jamme M., Arranz M. J., Jimeno M. -T., Jordan I., Kanik-Yuksek S., Kara Y., Karahan A., Karbuz A., Yasar K. K., Kasapcopur O., Kashimada K., Keles S., Demirkol Y. K., Kido Y., Kizil C., Kilic A. O., Klocperk A., Koutsoukou A., Krol Z. J., Ksouri H., Kuentz P., Kwan A. M. C., Kwan Y. W. M., Kwok J. S. Y., Lagier J. -C., Lam D. S. Y., Lampropoulou V., Le Bourgeois F., Leo Y. -S., Lopez R. L., Leung D., Levin M., Levy M., Levy R., Li Z., Lilleri D., Adrian Bolanos Lima E. J., Linglart A., Lopez-Collazo E., Lorenzo-Salazar J. M., Louapre C., Lubetzki C., Lung K. -C., Luyt C. -E., Lye D. C., Magnone C., Marchioni E., Marioli C., Marjani M., Marques L., Pereira J. M., Martin-Nalda A., Pueyo D. M., Martinez-Picado J., Marzana I., Mata-Martinez C., Mathian A., Matos L. R. B., Matthews G. V., Mayaux J., McLaughlin-Garcia R., Meersseman P., Mege J. -L., Mekontso-Dessap A., Melki I., Meloni F., Meritet J. -F., Merlani P., Akcan O. M., Mezidi M., Migeotte I., Millereux M., Million M., Mirault T., Mircher C., Mirsaeidi M., Mizoguchi Y., Modi B. P., Mojoli F., Moncomble E., Melian A. M., Martinez A. M., Morandeira F., Morange P. -E., Mordacq C., Morelle G., Mouly S. J., Munoz-Barrera A., Nafati C., Nagashima S., Nakagama Y., Neven B., Neves J. F., Ng Y. -Y., Hubert Nielly, Medina Y. N., Cuadros E. N., Karabela S. N., Ocejo-Vinyals J. G., Oualha M., Ouedrani A., Ozkaya-Parlakay A., Pagani M., Papadaki M., Parola P., Pascreau T., Paul S., Paz-Artal E., Pedraza S., Gonzalez Pellecer N. C., Pellegrini S., Perez-Fernandez X. L., Philippe A., Philippot Q., Picod A., Pineton de Chambrun M., Piralla A., Planas-Serra L., Ploin D., Poissy J., Poncelet G., Poulakou G., Pouletty M. S., Pourshahnazari P., Qiu-Chen J. L., Quentric P., Rambaud T., Raoult D., Raoult V., Rebillat A. -S., Redin C., Resmini L., Ricart P., Richard J. -C., Rigo-Bonnin R., Rivet N., Riviere J. G., Rocamora-Blanch G., Rodero M. P., Rodrigo C., Rodriguez L. A., Rodriguez-Palmero A., Romero C. S., Rothenbuhler A., Roux D., Rovina N., Rozenberg F., Ruch Y., Ruiz M., Ruiz del Prado M. Y., Ruiz-Rodriguez J. C., Sabater-Riera J., Saks K., Salagianni M., Sanchez O., Sanchez-Montalva A., Sanchez-Ramon S., Schidlowski L., Schluter A., Schmidt J., Schmidt M., Schuetz C., Schweitzer C. E., Scolari F., Seijo L., Seminario A. G., Seng P., Senoglu S., Seppanen M., Llovich A. S., Siguret V., Siouti E., Smadja D. M., Smith N., Sobh A., Solanich X., Sole-Violan J., Soler C., Sozeri B., Stella G. M., Stepanovskiy Y., Stoclin A., Taccone F., Taupin J. -L., Tavernier S. J., Tello L. V., Terrier B., Thiery G., Thorn K., Thumerelle C., Tipu I., Tolstrup M., Tomasoni G., Toubiana J., Alvarez J. T., Triantafyllia V., Troya J., Tsang O. T. Y., Tserel L., Tso E. Y. K., Tucci A., Tuter Oz S. K., Ursini M. V., Utsumi T., Vabres P., Valencia-Ramos J., Van Den Rym A. M., Vandernoot I., Velez-Santamaria V., Zuniga Veliz S. P., Vidigal M. C., Viel S., Villain C., Vilaire-Meunier M. E., Villar-Garcia J., Vincent A., Van der Linden D., Volokha A., Vuotto F., Wauters E., Wu A. K. L., Wu T. -C., Yahsi A., Yesilbas O., Yildiz M., Young B. E., Yukselmis U., Zecca M., Zuccaro V., Van Praet J., Lambrecht B. N., Van Braeckel E., Bosteels C., Hoste L., Hoste E., Bauters F., De Clercq J., Heijmans C., Slabbynck H., Naesens L., Florkin B., Young M. -A., Willis A., Lapuente-Suanzes P., de Andres-Martin A., Berkell M., Carelli V., Malhotra S., Mattiaccio A., Pippucci T., Seri M., Tacconelli E., van Agtmael M., Algera A. G., Appelman B., van Baarle F., Bax D., Beudel M., Bogaard H. J., Bomers M., Bonta P., Bos L., Botta M., de Brabander J., de Bree G., de Bruin S., Buis D. T. P., Bugiani M., Bulle E., Chouchane O., Cloherty A., Dijkstra M., Dongelmans D. A., Dujardin R. W. G., Elbers P., Fleuren L., Geerlings S., Geijtenbeek T., Girbes A., Goorhuis B., Grobusch M. P., Hafkamp F., Hagens L., Hamann J., Harris V., Hemke R., Hermans S. M., Heunks L., Hollmann M., Horn J., Hovius J. W., de Jong M. D., Koning R., Lim E. H. T., van Mourik N., Nellen J., Nossent E. J., Paulus F., Peters E., Pina-Fuentes D. A. I., van der Poll T., Preckel B., Prins J. M., Raasveld J., Reijnders T., de Rotte M. C. F. J., Schinkel M., Schultz M. J., Schrauwen F. A. P., Schuurmans A., Schuurmans J., Sigaloff K., Slim M. A., Smeele P., Smit M., Stijnis C. S., Stilma W., Teunissen C., Thoral P., Tsonas A. M., Tuinman P. R., van der Valk M., Veelo D. P., Volleman C., de Vries H., Vught L. A., van Vugt M., Wouters D., Zwinderman A. H., Brouwer M. C., Wiersinga W. J., Vlaar A. P. J., Tompkins M. F., Alba C., Hupalo D. N., Rosenberger J., Sukumar G., Wilkerson M. D., Zhang X., Lack J., Oler A. J., Dobbs K., Delmonte O. M., Danielson J. J., Biondi A., Bettini L. R., D'Angio M., Beretta I., Imberti L., Sottini A., Quaresima V., Quiros-Roldan E., Rossi C., Castagnoli R., Montagna D., Licari A., Marseglia G. L., Chiu C., and Grzymski J. J.
- Abstract
Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.
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- 2024
4. Abstract No. 177 ▪ FEATURED ABSTRACT A Comparison of Post-Procedural Hemoglobin in Catheter-Directed Thrombolysis vs. Large-Bore Aspiration Thrombectomy for Acute Pulmonary Embolism
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Ahmed, J., primary, Patel, K., additional, Ryan, W., additional, Leung, D., additional, and Graif, A., additional
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- 2024
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5. A novel machine learning-based model predicting lymph node metastasis at robotic assisted radical prostatectomy
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Fuligni, D., primary, Castellani, D., additional, Lucarelli, L., additional, Teoh, J.Y-C., additional, Leung, D., additional, Bugis, A., additional, Azhar, R.A., additional, Ghouse, S.M., additional, Gautam, G., additional, Gauhar, V., additional, Campobasso, D., additional, Campi, R., additional, Sakamoto, S., additional, Palagonia, E., additional, Bocciard, A.M., additional, Lee, H.Y., additional, Rubilotta, E., additional, Antonelli, A., additional, Pastore, A.L., additional, Vasdev, N., additional, Gómez Rivas, J., additional, Cormio, L., additional, Ferretti, S., additional, and Galosi, A.B., additional
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- 2024
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6. Bidirectional associations between IgE‐mediated food allergy and atopic dermatitis.
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Venter, C., Pickett‐Nairne, K., Glueck, D. H., Nevalainen, J., Greenhawt, M., Metsala, J., Sauder, K. A., Perng, W., Fleischer, D. M., Leung, D., and Dabelea, D.
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MEDICAL terminology ,MEDICAL personnel ,ELECTRONIC health records ,FOOD allergy ,MEDICAL history taking ,PEANUT allergy ,MILK allergy - Abstract
This document summarizes a study on the relationship between atopic dermatitis (AD) and IgE-mediated food allergy (FA) in children. The study found that children with AD were more likely to develop FA, and vice versa. However, the study had limitations, such as not assessing the severity of AD and having a small sample size for cases of FA. The findings suggest that AD and FA may be related and further research is needed to understand and address these conditions. [Extracted from the article]
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- 2024
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7. A64 HUMAN INTESINAL ORGANOIDS AS A MODEL FOR GASTROINTESTINAL FUNCTION AND TOXICITY SCREENING
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Stahl, M, primary, Leung, D, additional, Anderson, W, additional, Conlin, V, additional, Eaves, A, additional, Louis, S A, additional, and Conder, R K, additional
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- 2024
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8. A100 HEREDITARY HEMORRHAGIC TELANGIECTASIA: MORE THAN JUST ANOTHER RECTAL BLEED
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Leung, D, primary, Guo, J Y, additional, Zepeda-Gomez, S, additional, Wesilenko, S, additional, Halloran, B, additional, and Vethanayagam, D, additional
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- 2024
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9. 76P Utilization of g score in early oncology drug development: Impact on study design and early go/no-go decision
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He, P., primary, Gambhire, D., additional, Zhou, H., additional, Ma, X., additional, Emura, Y., additional, Laadem, A., additional, Leung, D., additional, Bates, S.E., additional, Fojo, A.T., additional, and Rixe, O., additional
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- 2024
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10. Optimising the acid–base ratio of Mg–Al layered double oxides to enhance CO2 capture performance: the critical role of calcination conditions
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Leung, D. W. Justin, primary, Laney, Katherine R., additional, Kenyon, Philip, additional, Rees, Nicholas H., additional, Buffet, Jean-Charles, additional, Chen, Chunping, additional, and O'Hare, Dermot, additional
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- 2024
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11. Optimising the acid-base ratio of Mg-Al layered double oxides to enhance CO2 capture performance: the critical role of calcination conditions.
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Leung, D. W. Justin, Laney, Katherine R., Kenyon, Philip, Rees, Nicholas H., Buffet, Jean-Charles, Chunping Chen, and O'Hare, Dermot
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SURFACE properties , *OXIDES , *SURFACE area - Abstract
The effect of calcination conditions (ramp rate, calcination temperature and time) on the formation of Mg2Al layered double oxides (Mg2Al LDOs) as well as their CO2 capture performance, has been systematically investigated. This study explores novel insights into the intricate relationship between these calcination conditions and the resulting surface characteristics, which play a vital role in CO2 capture efficiency. Notably, it is revealed that a rapid ramp rate (100 ℃ min-1) significantly increases surface area and hydroxyl concentration, leading to a 69% increase in CO2 capture efficiency compared to slower ramp rate. Conversely, short calcination times (1 h) and fast ramp rates (100 ℃ min-1) are observed to compromise CO2 adsorption due to the presence of dehydrated LDHs. A critical acid: base ratio of 0.37, achieved from a fast ramp rate (100 ℃ min-1) at 400 ℃ for 2 h, was found as a key threshold for optimising surface properties, effectively balancing favourable hydroxyl and less favourable strong acid sites, thereby maximizing CO2 capture performance. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Chinese family care partners of older adults in Canada have grit: A qualitative study.
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Leung, D. Y. L., Lee, C. T., Chu, S. Y. J., Ng, F., Wen, P., Fan, J., Cheung, D. S. K., Nielsen, L. Seto, Guruge, S., and Wong, J.
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HEALTH services accessibility , *COMMUNITY health services , *QUALITATIVE research , *RESEARCH funding , *SPOUSES , *INTERVIEWING , *FAMILY roles , *JUDGMENT sampling , *SOCIAL case work , *SOUND recordings , *THEMATIC analysis , *RESEARCH methodology , *DATA analysis software , *CAREGIVER attitudes - Abstract
Aim: To explain the process taken by Chinese family care partners of older adults in the Greater Toronto Area, Canada, to access health and social services in their communities. The research question was: What mechanisms and structures impact the agency of Chinese family care partners of older adults, in the process of assisting them to access health and social services? Design: This qualitative study was informed by critical realism. Methods: Chinese family care partners of older adults in the Greater Toronto Area, Canada, were interviewed from August 2020 to June 2021. Transcripts underwent thematic analysis. Findings: Twenty-eight Chinese family care partners expressed a firm commitment to maintain caregiving conditions and to judiciously access health and social services. Their commitment was made up of three parts: (a) legislative and cultural norms of family, work, and society; (b) their perseverance to fill gaps with limited social and financial resources; (c) the quality of their relationship to, and illness trajectory of the older adults. The social structures created tension in how Chinese family care partners made decisions, negotiated resources, and ultimately monitored and coordinated timely access with older adults. Conclusion: Participants' commitment and perseverance were conceptualized as "grit," central to their agency to conform to legislative and cultural norms. Moreover, findings support grit's power to motivate and sustain family caregiving, in order for older adults to age in place as long as possible with finite resources. Implications for the profession: This study highlights the importance of cultural awareness education for nurses, enabling continuity of care at a systems level and for a more resilient healthcare system. Impact: Family care partners' grit may be crucial for nurses to harness when together, they face limited access to culturally appropriate health and social services in a system grounded in values of equity and inclusion, as in Canada. Reporting method: When writing this manuscript, we adhered to relevant EQUATOR guidelines of the Consolidated Criteria for Reporting Qualitative Research (COREQ). Patient or public involvement and engagement: No patient or public involvement. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Glaucoma secondary to vascular changes in optic nerve head, retina, and choroid: abridged secondary publication.
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Tham, C. C. Y., Chan, P. P. M., Cheung, C. Y. L., Leung, D. Y. L., Chan, N. C. Y., and Chow, C. W. Y.
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- 2024
14. Establishing a Robotic-Assisted Percutaneous Coronary Intervention (R-PCI) Program: Initial Australian Experience
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Leung, J., Nguyen, C., Fares, S., French, J., Xu, J., Kachwalla, H., Kaddapu, K., Badie, T., Mussap, C., Rajaratnam, R., Leung, D., Lo, S., and Juergens, C.
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- 2024
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15. Additional Alert Burden Associated With the HeartLogic Multiparameter Algorithm in Patients With Cardiac Implanted Electronic Devices
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Ta, J., Assad, J., Hopkins, A., Leung, D., and Dimitri, H.
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- 2024
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16. Cognitive Impairment as a Factor to Influence Development of Heart Failure
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Huynh, Q., Haji, K., DePasquale, C., Hare, J., Leung, D., Stanton, T., and Marwick, T.
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- 2024
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17. 470 Cutaneous CERS1 expression is a biomarker of staphylococcus aureus abundance and atopic dermatitis severity
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Kenney, H., Yoshida, T., Berdyshev, E., Calatroni, A., Gill, S., Simpson, E., Lussier, S., Boguniewicz, M., Hata, T., Fuxench, Z. C. Chiesa, De Benedetto, A., Ong, P., Ko, J., Davidson, W., David, G., Schlievert, P., Leung, D., and Beck, L.A.
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- 2024
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18. 280 Children with atopic dermatitis respond more rapidly to dupilumab treatment in comparison to adolescents and adults
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Berdyshev, E., Goleva, E., Danby, S., Bronoff, A., Agueusop, I., Zahn, J., Gloaguen, E., Bissonnette, R., Boguniewicz, M., Ong, P., Zhang, A., Cork, M., and Leung, D.
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- 2024
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19. 604 Frequency of hepatobiliary abnormalities in young children with CF before and after 6 months of elexacaftor/tezacaftor/ivacaftor: results from the BEGIN Study.
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Leung, D., O'Rourke, C., Russell, R., Heltshe, S., Buckingham, R., Ode, K. Larson, Zemanick, E., Hoffman, L., and Ramsey, B.
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HUMAN abnormalities - Published
- 2024
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20. Omalizumab for the Treatment of Multiple Food Allergies.
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Wood, R. A., Togias, A., Sicherer, S. H., Shreffler, W. G., Kim, E. H., Jones, S. M., Leung, D. Y. M., Vickery, B. P., Bird, J. A., Spergel, J. M., Iqbal, A., Olsson, J., Ligueros-Saylan, M., Uddin, A., Calatroni, A., Huckabee, C. M., Rogers, N. H., Yovetrch, N., Dantzer, J., and Mudd, K.
- Abstract
BACKGROUND Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose- limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose- limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. RESULTS Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 68% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. CONCLUSIONS In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTriaIs.gov number, NCT03881696.) [ABSTRACT FROM AUTHOR]
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- 2024
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21. 648 Using the TriNetX international database of rare disease: GI manifestations in children and young adults with cystic fibrosis before and after the highly effective triple modulator therapy era.
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Trocchia, C., Mosha, M., Mark, J., Leung, D., and Khalaf, R.
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YOUNG adults , *DATABASES , *CYSTIC fibrosis , *RARE diseases - Published
- 2024
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22. 600 Changes in fecal pancreatic elastase in children with CF with 6 months of highly effective modulator therapy: Results from the BEGIN study.
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Dutta, A., Pope, C., O'Rourke, C., Buckingham, R., Russell, R., Heltshe, S., Leung, D., Sullivan, J., Ode, K. Larson, Zemanick, E., Ramsey, B., and Hoffman, L.
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ELASTASES - Published
- 2024
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23. 635P Pain impacts quality of life, psychological disorders and exercise in a large international cohort of patients with facioscapulohumeral muscular dystrophy.
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Knox, R., Wang, L., Elsheikh, B., LoRusso, S., Zhao, S., Eichinger, K., Higgs, K., Lewis, L., Walker, M., Sansone, V., Leung, D., Sacconi, S., Mul, K., Shieh, P., Butterfield, R., Johnson, N., Bugiardini, E., McDermott, M., Tawil, R., and Statland, J.
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SLEEP interruptions , *MUSCULAR dystrophy , *RESISTANCE training , *SOCIAL participation , *PHYSICAL mobility , *FACIOSCAPULOHUMERAL muscular dystrophy - Abstract
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy. Although pain is common in FSHD, it has been less well characterized in the literature. This study aims to characterize pain in an international population of FSHD patients and to determine which factors are associated with pain and pain severity. We analyzed data from a prospective multicenter observational cohort of adult patients with FSHD, the ReSolve study, from 2018 to 2021. We compared patient-reported data, motor assessments, and the pharmacologic management of FSHD between patients with and without pain. Patient-Reported Outcome Measures Information System (PROMIS) 57 modules were analyzed for their association with pain. Of 219 patients, 83% reported pain, most commonly located in the lower back and shoulders. There were no significant regional differences in pain medication usage between patients in the USA and Europe. Analysis of PROMIS modules identified an association with the presence of pain and physical function, fatigue, and sleep disturbance. Linear regression modeling of the PROMIS scores revealed that pain intensity had a negative impact on physical function, social participation, depression, anxiety, and sleep interference. Additionally, univariate analysis found a significant association between pain and self-reported psychological problems and resistance exercise rates. Taken together, these data point to the significant impact of pain in FSHD patients and the importance of developing therapies to treat pain in FSHD. [ABSTRACT FROM AUTHOR]
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- 2024
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24. A0425 - A novel machine learning-based model predicting lymph node metastasis at robotic assisted radical prostatectomy.
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Fuligni, D., Castellani, D., Lucarelli, L., Teoh, J.Y-C., Leung, D., Bugis, A., Azhar, R.A., Ghouse, S.M., Gautam, G., Gauhar, V., Campobasso, D., Campi, R., Sakamoto, S., Palagonia, E., Bocciard, A.M., Lee, H.Y., Rubilotta, E., Antonelli, A., Pastore, A.L., and Vasdev, N.
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- *
LYMPHATIC metastasis , *RADICAL prostatectomy , *ROBOTICS , *FORECASTING , *MACHINERY - Published
- 2024
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25. Diagnostic accuracy of maternal diet measures for offspring allergy.
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Venter C, Pickett-Nairne K, Leung D, Fleischer D, O'Mahony L, Glueck DH, and Dabelea D
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- 2024
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26. Granulocyte colony stimulating factor promotes scarless tissue regeneration.
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Huang J, Sati S, Murphy C, Spencer CA, Rapp E, Prouty SM, Korte S, Ahart O, Sheng E, Jones P, Kersh AE, Leung D, and Leung TH
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- Animals, Humans, Male, Mice, Hair Follicle drug effects, Hair Follicle metabolism, Mice, Inbred C57BL, Mice, Knockout, Skin metabolism, Skin pathology, Skin drug effects, Cicatrix pathology, Cicatrix metabolism, Granulocyte Colony-Stimulating Factor pharmacology, Granulocyte Colony-Stimulating Factor metabolism, Macrophages metabolism, Macrophages drug effects, Receptors, Interleukin-8B metabolism, Regeneration drug effects, Wound Healing drug effects
- Abstract
Mammals typically heal with fibrotic scars, and treatments to regenerate human skin and hair without a scar remain elusive. We discovered that mice lacking C-X-C motif chemokine receptor 2 (CXCR2 knockout [KO]) displayed robust and complete tissue regeneration across three different injury models: skin, hair follicle, and cartilage. Remarkably, wild-type mice receiving plasma from CXCR2 KO mice through parabiosis or injections healed wounds scarlessly. A comparison of circulating proteins using multiplex ELISA revealed a 24-fold higher plasma level of granulocyte colony stimulating factor (G-CSF) in CXCR2 KO blood. Local injections of G-CSF into wild-type (WT) mouse wound beds reduced scar formation and increased scarless tissue regeneration. G-CSF directly polarized macrophages into an anti-inflammatory phenotype, and both CXCR2 KO and G-CSF-treated mice recruited more anti-inflammatory macrophages into injured areas. Modulating macrophage activation states at early time points after injury promotes scarless tissue regeneration and may offer a therapeutic approach to improve healing of human skin wounds., Competing Interests: Declaration of interests A provisional patent has been filed with the US Patent and Trademark Office regarding CXCR2, G-CSF, and NETosis on reducing scar formation and promoting tissue regeneration., (Published by Elsevier Inc.)
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- 2024
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27. Avian Influenza: Lessons from Past Outbreaks and an Inventory of Data Sources, Mathematical and AI Models, and Early Warning Systems for Forecasting and Hotspot Detection to Tackle Ongoing Outbreaks.
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Musa E, Nia ZM, Bragazzi NL, Leung D, Lee N, and Kong JD
- Abstract
Background/objectives: The ongoing avian influenza (H5N1) outbreak, one of the most widespread and persistent in recent history, has significantly impacted public health and the poultry and dairy cattle industries. This review covers lessons from past outbreaks, risk factors for transmission, molecular epidemiology, clinical features, surveillance strategies, and socioeconomic impacts. Since 1997, H5N1 has infected over 900 individuals globally, with a fatality rate exceeding 50%. Key factors influencing infection rates include demographic, socioeconomic, environmental, and ecological variables. The virus's potential for sustained human-to-human transmission remains a concern. The current outbreak, marked by new viral clades, has complicated containment efforts., Methods: This review discusses how to integrate technological advances, such as mathematical modeling and artificial intelligence (AI), to improve forecasting, hotspot detection, and early warning systems., Results: We provide inventories of data sources, covering both conventional and unconventional data streams, as well as those of mathematical and AI models, which can be vital for comprehensive surveillance and outbreak responses., Conclusion: In conclusion, integrating AI, mathematical models, and technological innovations into a One-Health approach is essential for improving surveillance, forecasting, and response strategies to mitigate the impacts of the ongoing avian influenza outbreak. Strengthening international collaboration and biosecurity measures will be pivotal in controlling future outbreaks and protecting both human and animal populations from this evolving global threat.
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- 2024
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28. Feasibility of Biology-guided Radiotherapy (BgRT) Targeting Fluorodeoxyglucose (FDG) avid liver metastases.
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Chau B, Abuali T, Shirvani SM, Leung D, Al Feghali KA, Hui S, McGee H, Han C, Liu A, and Amini A
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- Humans, Female, Male, Middle Aged, Aged, Radiotherapy, Image-Guided methods, Aged, 80 and over, Retrospective Studies, Adult, Positron-Emission Tomography methods, Radiotherapy Planning, Computer-Assisted methods, Adenocarcinoma radiotherapy, Adenocarcinoma secondary, Adenocarcinoma diagnostic imaging, Positron Emission Tomography Computed Tomography methods, Prognosis, Liver Neoplasms secondary, Liver Neoplasms radiotherapy, Liver Neoplasms diagnostic imaging, Fluorodeoxyglucose F18, Feasibility Studies, Radiopharmaceuticals therapeutic use, Lung Neoplasms radiotherapy, Lung Neoplasms diagnostic imaging, Lung Neoplasms pathology
- Abstract
Introduction: Biology-guided radiotherapy (BgRT) is a novel radiation delivery approach utilizing fluorodeoxyglucose (FDG) activity on positron emission tomography (PET) imaging performed in real-time to track and direct RT. Our institution recently acquired the RefleXion X1 BgRT system and sought to assess the feasibility of targeting metastatic sites in various organs, including the liver. However, in order for BgRT to function appropriate, adequate contrast in FDG activity between the tumor and the background tissue, referred to as the normalized SUV (NSUV), is necessary for optimal functioning of BgRT., Methods: We reviewed the charts of 50 lung adenocarcinoma patients with liver metastases. The following variables were collected: SUVmax and SUVmean for each liver metastasis, SUVmean and SUVmax at 5 and 10 mm radially from the lesion, and NSUV at 5 mm and 10 mm (SUVmax of the liver metastasis divided by SUV mean at 5 mm at 10 mm respectively)., Results: 82 measurable liver metastases were included in the final analysis. The average SUVbackground of liver was 2.26 (95% confidence interval [CI] 2.17-2.35); average SUVmean for liver metastases was 5.31 (95% CI 4.87-5.75), and average SUVmax of liver metastases was 9.19 (95% CI 7.59-10.78). The average SUVmean at 5 mm and 10 mm radially from each lesion were 3.08 (95% CI 3.00-2.16) and 2.60 (95% CI 2.52-2.68), respectively. The mean NSUV at 5 mm and 10 mm were 3.13 (95% CI 2.53-3.73) and 3.69 (95% CI 3.00-4.41) respectively. Furthermore, 90% of lesions had NSUV greater than 1.45 at 5 mm and greater than 1.77 at 10 mm., Conclusions: This is the first study to comprehensively characterize FDG contrast between the liver tumor and background, referred to as NSUV. Due to the high background SUV normally found in the liver, this work will be valuable for guiding optimization of BgRT for treating liver metastases in the future using the RefleXion
® X1 and potentially other similar BgRT platforms., (© 2024. The Author(s).)- Published
- 2024
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29. Physicochemical and structural insights into lyophilized mRNA-LNP from lyoprotectant and buffer screenings.
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Fan Y, Rigas D, Kim LJ, Chang FP, Zang N, McKee K, Kemball CC, Yu Z, Winkler P, Su WC, Jessen P, Hura GL, Chen T, Koenig SG, Nagapudi K, Leung D, and Yen CW
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- Humans, Buffers, Leukocytes, Mononuclear, SARS-CoV-2, Cryoprotective Agents chemistry, Liposomes, Nanoparticles, Freeze Drying, RNA, Messenger, Excipients chemistry
- Abstract
The surge in RNA therapeutics has revolutionized treatments for infectious diseases like COVID-19 and shows the potential to expand into other therapeutic areas. However, the typical requirement for ultra-cold storage of mRNA-LNP formulations poses significant logistical challenges for global distribution. Lyophilization serves as a potential strategy to extend mRNA-LNP stability while eliminating the need for ultra-cold supply chain logistics. Although recent advancements have demonstrated the promise of lyophilization, the choice of lyoprotectant is predominately focused on sucrose, and there remains a gap in comprehensive evaluation and comparison of lyoprotectants and buffers. Here, we aim to systematically investigate the impact of a diverse range of excipients including oligosaccharides, polymers, amino acids, and various buffers, on the quality and performance of lyophilized mRNA-LNPs. From the screening of 45 mRNA-LNP formulations under various lyoprotectant and buffer conditions for lyophilization, we identified previously unexplored formulation compositions, e.g., polyvinylpyrrolidone (PVP) in Tris or acetate buffers, as promising alternatives to the commonly used oligosaccharides to maintain the physicochemical stability of lyophilized mRNA-LNPs. Further, we delved into how physicochemical and structural properties influence the functionality of lyophilized mRNA-LNPs. Leveraging high-throughput small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM), we showed that there is complex interplay between mRNA-LNP structural features and cellular translation efficacy. We also assessed innate immune responses of the screened mRNA-LNPs in human peripheral blood mononuclear cells (PBMCs), and showed minimal alterations of cytokine secretion profiles induced by lyophilized formulations. Our results provide valuable insights into the structure-activity relationship of lyophilized formulations of mRNA-LNP therapeutics, paving the way for rational design of these formulations. This work creates a foundation for a comprehensive understanding of mRNA-LNP properties and in vitro performance change resulting from lyophilization., Competing Interests: Declaration of competing interest Yuchen Fan, Diamanda Rigas, Nanzhi Zang, Kristina McKee, Christopher C. Kemball, Wan-Chih Su, Pierce Jessen, Tao Chen, Stefan G. Koenig, Karthik Nagapudi, Dennis Leung, and Chun-Wan Yen are employees of Genentech, Inc. Feng-Peng Chang, Zhixin Yu, and Pascal Winkler are former employees of Genentech, Inc. Lee Joon Kim and Greg L. Hura are employees of Lawrence Berkeley National Lab., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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30. Maternal allergy-preventive diet index, offspring infant diet diversity, and childhood allergic diseases.
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Venter C, Pickett-Nairne K, Leung D, Fleischer D, O'Mahony L, Glueck DH, and Dabelea D
- Abstract
Background: Studies of childhood diet diversity and allergic disease have not examined additional associations with an offspring allergy-linked maternal diet index during pregnancy. We studied both associations in a pre-birth cohort., Methods: Offspring allergic disease diagnoses were obtained from electronic medical records. Maternal and infant diet were self-reported. Adjusted parametric Weibull time-to-event models assessed associations between maternal diet index, infant diet diversity and time to development of allergic rhinitis, atopic dermatitis, asthma, wheeze, IgE-mediated food allergy, and a combined outcome of any allergic disease except for wheeze., Results: Infant diet diversity at 1 year was associated with the risk of the combined outcome between 1 and 4 years of age (p = .002). While both maternal diet index and infant diet diversity at 1 year were associated with the risk of the combined outcome between 1 and 4 years of age (both p < .05), infant diet diversity at 1 year did not modify the association between maternal diet index and the risk of the combined outcome between 1 and 4 years of age (p = .5). The group with the lowest risk of the combined allergy outcome had higher maternal diet index and higher infant diet diversity., Conclusions: The novel finding that both maternal diet index during pregnancy and infant diet diversity at 12 months are associated with the risk of a combined allergic disease outcome points to two targets for preventive interventions: maternal diet index scores during pregnancy and offspring diet diversity during infancy., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2024
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31. Clinical Staging of Prostaglandin-Associated Periorbitopathy Syndrome in Glaucoma: A Review from Asia.
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Liu C, Wong T, Leung D, Park HL, Aung T, Aihara M, Makornwattana M, Fang SK, Park KH, and Leung C
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- Humans, Intraocular Pressure physiology, Intraocular Pressure drug effects, Orbital Diseases chemically induced, Orbital Diseases diagnosis, Asia epidemiology, Syndrome, Prostaglandins, Synthetic adverse effects, Antihypertensive Agents adverse effects, Glaucoma drug therapy
- Abstract
Purpose: Topical prostaglandin analogues are commonly used to treat patients with glaucoma, but may cause periocular and periorbital complications known as prostaglandin-associated periorbitopathy syndrome (PAPS)., Methods: A literature review was conducted on PAPS. Given the lack of consensus on grading PAPS, glaucoma specialists from Asia convened to evaluate current PAPS grading systems and propose additional considerations in grading PAPS., Results: Existing grading systems are limited by the lack of specificity in defining grades and consideration for patients' subjective perception of symptoms. Patient-reported symptoms (e.g., via a self-assessment tool) and additional clinical assessments (e.g., exophthalmometry, lid laxity, differences between tonometry results, baseline measurements, and external ocular photographs) would be beneficial for grading PAPS systematically., Conclusions: Effective management of PAPS could be facilitated by a common clinical grading system to consistently and accurately diagnose and characterise symptoms. Further research is required to validate specific recommendations and approaches to stage and monitor PAPS.
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- 2024
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32. Oncology nurses' lived experience of caring for patients with advanced cancer in healthcare systems without palliative care services.
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Abu-Odah H, Leung D, Chan EA, Bayuo J, Su JJ, Ho KY, Lam KK, Yuen JW, Zhao IY, Allsop MJ, Al Zoubi FM, Al Khaldi MN, Krakauer EL, and Molassiotis A
- Subjects
- Humans, Adult, Female, Male, Middle Aged, Palliative Care, Qualitative Research, Adaptation, Psychological, Turkey, Interviews as Topic, Neoplasms nursing, Oncology Nursing
- Abstract
Background: Caring for patients with advanced cancer is complex and challenging, requiring varied expertise, including symptom management, communication skills, care coordination and emotional resilience. Within existing literature, the lived experiences of oncology nurses are poorly articulated in countries with a lower income where formal palliative care (PC) is absent., Aim: To explore the lived experiences of Gazan oncology nurses who provide care to patients with advanced cancer in healthcare systems, without formal palliative care infrastructure., Methods: A phenomenological approach was adopted. Semi-structured interviews were conducted between January and April 2022, in the Turkish Palestinian Friendship Hospital. Thematic analysis used the themes (corporeality, relationality, spatiality and temporality) to facilitate reflection on the meaning of participants' lived experiences., Results: Interviews were undertaken with 16 oncology nurses. The experience of the 'erosion of nurses' work when coping with anxious attachments to patients and families' was the overarching theme in nurses' views, characterised by five sub-themes: (1) inadequacy of PC training and resources, (2) serving humanity, (3) pride in their profession, (4) existential distress and the coping strategies used by nurses, and (5) reported stress and anxiety when caring for seriously ill patients and their families., Conclusions: The study sheds light on the challenges and powerful emotions experienced by oncology nurses who care for patients with advanced cancer, yet lack the necessary PC training and institutional resources. The findings indicate an urgent need for PC training for nurses within the Gazan healthcare system and other lower-income settings. Assessing nurses' emotions and relationships with patients and family caregivers is imperative to enable optimum care for patients with cancer and to foster resilience among their nurses.
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- 2024
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33. Feasibility of Saphenous Nerve Somatosensory-Evoked Potential Intraoperative Monitoring During Lumbar Spine Surgery: Early Results.
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Rucker S, Singh N, Mai E, Asada T, Shahi P, Mercado K, Leung D, Iyer S, Emerson R, and Qureshi SA
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- Humans, Retrospective Studies, Male, Female, Middle Aged, Adult, Aged, Monitoring, Intraoperative methods, Intraoperative Neurophysiological Monitoring methods, Tibial Nerve, Aged, 80 and over, Evoked Potentials, Somatosensory physiology, Lumbar Vertebrae surgery, Feasibility Studies
- Abstract
Study Design: Retrospective review., Objective: Assess the feasibility of saphenous nerve somatosensory evoked potentials (SN-SSEP) monitoring in lumbar spine surgeries., Background Context: SN-SSEPs have been proposed for detecting lumbar plexus and femoral nerve injury during lateral lumbar surgery where tibial nerve (TN) SSEPs alone are insufficient. SN-SSEPs may also be useful in other types of lumbar surgery, as stimulation of SN below the knee derives solely from the L4 root and provides a means of L4 monitoring, whereas TN-SSEPs often do not detect single nerve root injury. The feasibility of routine SN-SSEP monitoring has not been established., Methods: A total of 563 consecutive cases using both TN-SSEP and SN-SSEP monitoring were included. Anesthesia was at the discretion of the anesthesiologist, using an inhalant in 97.7% of procedures. SN stimulation was performed using 13 mm needle electrodes placed below the knee using 200-400 μsec pulses at 15 to 100 mA. Adjustments to stimulation parameters were made by the neurophysiology technician while obtaining baselines. Data were graded retrospectively for monitorability and cortical response amplitudes were measured by two independent reviewers., Results: Ninety-eight percent of TN-SSEPs and 92.5% of SN-SSEPs were monitorable at baseline, with a mean response amplitude of 1.35 μV for TN-SSEPs and 0.71 μV for SN-SSEPs. A significant difference between the stimulation parameters used to obtain reproducible TN and SN-SSEPs at baseline was observed, with SN-SSEPs requiring greater stimulation intensities. Body mass index is not associated with baseline monitorability. Out of 20 signal changes observed, 11 involved SN, while TN-SSEPs were unaffected., Conclusion: With adjustments to stimulation parameters, SN-SSEP monitoring is feasible within a large clinical cohort without modifications to the anesthetic plan. Incorporating SN into standard intraoperative neurophysiological monitoring protocols for lumbar spine procedures may expand the role of SSEP monitoring to include detecting injury to the lumbar plexus., Level of Evidence: 3., Competing Interests: S.Q.—AMOpportunities: Other financial or material support; Annals of Translational Medicine: Editorial or governing board; Association of Bone and Joint Surgeons: Board or committee member; Cervical Spine Research Society: Board or committee member; Contemporary Spine Surgery: Editorial or governing board; Globus Medical: IP royalties; Paid consultant; Paid presenter or speaker; Hospital Special Surgery Journal: Editorial or governing board; HS2, LLC: Stock or stock Options; International Society for the Advancement of Spine Surgery (ISASS) - Program Committee member: Board or committee member; Lifelink.com: Other financial or material support; Lumbar Spine Research Society: Board or committee member; Minimally Invasive Spine Study Group: Board or committee member; North American Spine Society: Board or committee member; Simplify Medical, Inc.: Other financial or material support; Society of Minimally Invasive Spine Surgery (SMISS) - Program Committee member: Board or committee member; Spinal Simplicity: Other financial or material support; SpineGuard, Inc.: Paid consultant; Stryker: IP royalties; Paid consultant; Surgalign: Paid consultant; Tissue Differentiation Intelligence: Stock or stock Options; Viseon, Inc.: Paid consultant; Research support; Clinical Spine Surgery: Editorial or governing board. S.I.—Globus Medical: Paid presenter or speaker; Stryker: Paid presenter or speaker; Vertebral Columns/International Society for the Advancement of Spine Surgery (ISASS): Editorial or governing board; HS2, LLC: Ownership/Equity/Investment; Innovasis: Research Support (either personally or through institution). The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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34. Fecal microbiota transplantation: current challenges and future landscapes.
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Yadegar A, Bar-Yoseph H, Monaghan TM, Pakpour S, Severino A, Kuijper EJ, Smits WK, Terveer EM, Neupane S, Nabavi-Rad A, Sadeghi J, Cammarota G, Ianiro G, Nap-Hill E, Leung D, Wong K, and Kao D
- Subjects
- Humans, Clostridium Infections therapy, Clostridium Infections microbiology, Inflammatory Bowel Diseases therapy, Inflammatory Bowel Diseases microbiology, Animals, Fecal Microbiota Transplantation methods, Gastrointestinal Microbiome
- Abstract
SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts. In this review, we outline clinical applications, efficacy, durability, and safety of FMT and provide a comprehensive assessment of its procedural and administration aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We focus on data from human studies in IBD in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics., Competing Interests: D.K. has received consulting fees from Ferring; E.M.T. and E.J.K. received an unrestricted research grant from Vedanta Biosciences; T.M.M. has received consulting fees from Takeda Pharmaceuticals and served as an advisor for CHAIN Biotechnology.
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- 2024
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35. Seroepidemiology of measles and rubella among Hong Kong young adults and the humoral responses of an MMR booster among participants with low antibody levels.
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Chan JCH, Leung D, Chan SM, Tam IYS, Lam JHY, Chan KW, Zhang K, Chiu TLH, Yeung THM, Chung GMH, Rosa Duque JS, and Lau YL
- Abstract
Background: Some individuals may not retain adequate immunity against measles and rubella years after two doses of measles, mumps, and rubella (MMR) vaccination due to vaccine failure. This study aimed to investigate the rates of vaccine failure and seroconversion by administering an MMR booster to young adults., Methods: We first assessed measles and rubella antibody levels using the Luminex multiplex assay, VIDAS IgG assay, and plaque reduction neutralization test (PRNT) among individuals aged 18-30 years old who had received two doses of MMR vaccine. Participants with low measles and/or rubella antibody levels as confirmed by VIDAS received an MMR booster. Antibody levels were measured at 1-month post-booster., Results: Among 791 participants, the measles and rubella seroprevalence rates were 94.7% (95% CI: 92.9%-96.0%) and 97.3% (95% CI: 96.0%-98.3%), respectively. Lower seroprevalence rates were observed among older participants. 113 participants who received an MMR booster acquired higher measles and rubella antibody levels at 1-month post-booster compared to baseline., Conclusions: Although measles and rubella vaccine failures were observed among 5.3% and 2.7% of young adults, respectively, an MMR booster triggered a significant antibody response., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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36. The Oncological and Functional Prognostic Value of Unconventional Histology of Prostate Cancer in Localized Disease Treated with Robotic Radical Prostatectomy: An International Multicenter 5-Year Cohort Study.
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Leung D, Castellani D, Nicoletti R, Dilme RV, Sierra JM, Serni S, Franzese C, Chiacchio G, Galosi AB, Mazzucchelli R, Palagonia E, Dell'Oglio P, Galfano A, Bocciardi AM, Zhao X, Ng CF, Lee HY, Sakamoto S, Vasdev N, Rivas JG, Campi R, and Teoh JY
- Subjects
- Humans, Male, Retrospective Studies, Middle Aged, Aged, Prognosis, Cohort Studies, Treatment Outcome, Time Factors, Internationality, Prostatic Neoplasms surgery, Prostatic Neoplasms pathology, Prostatic Neoplasms radiotherapy, Prostatectomy methods, Robotic Surgical Procedures
- Abstract
Background and Objective: The impact of prostate cancer of unconventional histology (UH) on oncological and functional outcomes after robot-assisted radical prostatectomy (RARP) and adjuvant radiotherapy (aRT) receipt is unclear. We compared the impact of cribriform pattern (CP), ductal adenocarcinoma (DAC), and intraductal carcinoma (IDC) in comparison to pure adenocarcinoma (AC) on short- to mid-term oncological and functional results and receipt of aRT after RARP., Methods: We retrospectively collected data for a large international cohort of men with localized prostate cancer treated with RARP between 2016 and 2020. The primary outcomes were biochemical recurrence (BCR)-free survival, erectile and continence function. aRT receipt was a secondary outcome. Kaplan-Meier survival and Cox regression analyses were performed., Key Findings and Limitations: A total of 3935 patients were included. At median follow-up of 2.8 yr, the rates for BCR incidence (AC 10.7% vs IDC 17%; p < 0.001) and aRT receipt (AC 4.5% vs DAC 6.3% [p = 0.003] vs IDC 11.2% [p < 0.001]) were higher with UH. The 5-yr BCR-free survival rate was significantly poorer for UH groups, with hazard ratios of 1.67 (95% confidence interval [CI] 1.16-2.40; p = 0.005) for DAC, 5.22 (95% CI 3.41-8.01; p < 0.001) for IDC, and 3.45 (95% CI 2.29-5.20; p < 0.001) for CP in comparison to AC. Logistic regression analysis revealed that the presence of UH doubled the risk of new-onset erectile dysfunction at 1 yr, in comparison to AC (grade group 1-3), with hazard ratios of 2.13 (p < 0.001) for DAC, 2.14 (p < 0.001) for IDC, and 2.01 (p = 0.011) for CP. Moreover, CP, but not IDC or DAC, was associated with a significantly higher risk of incontinence (odds ratio 1.97; p < 0.001). The study is limited by the lack of central histopathological review and relatively short follow-up., Conclusions and Clinical Implications: In a large cohort, UH presence was associated with worse short- to mid-term oncological outcomes after RARP. IDC independently predicted a higher rate of aRT receipt. At 1-yr follow-up after RP, patients with UH had three times higher risk of erectile dysfunction post RARP; CP was associated with a twofold higher incontinence rate., Patient Summary: Among patients with prostate cancer who undergo robot-assisted surgery to remove the prostate, those with less common types of prostate cancer have worse results for cancer control, erection, and urinary continence and a higher probability of receiving additional radiotherapy after surgery., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
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- 2024
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37. Unlocking the Potential of 2D MoS 2 Cathodes for High-Performance Aqueous Al-Ion Batteries: Deciphering the Intercalation Mechanisms.
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Pan W, Zhang Y, Leong KW, Zhang Y, Mao J, Wang Y, Zhao X, Luo S, and Leung DYC
- Abstract
In recent years, there have been significant advancements in Al-ion battery development, resulting in high voltage and capacity. Traditionally, only carbon-based materials with layered structures and strong bonding capabilities can deliver superior performance. However, most other materials exhibited low discharge voltages of 1.4 V, especially in aqueous Al-ion battery systems lacking anion intercalation. Thus, the development of high-voltage cathode materials has become crucial. This study introduces 2D MoS
2 as a high-performance cathode for aqueous Al-ion batteries. The material's interlayer structure enables the intercalation of AlCl4 - anions, resulting in high-voltage intercalation. The resulting battery achieved a high voltage of 1.8 V with a capacity of 750 mAh g-1 , contributing to a high energy density of 890 Wh kg-1 and an impressive retention rate of ≈100% after 200 cycles. This research not only sheds light on the high-voltage anion-intercalation mechanism of MoS2 but also paves the way for the further development of advanced cathode materials in the field of Al-ion batteries. By demonstrating the potential of using 2D MoS2 as a cathode material, this finding can lead to the development of more efficient and innovative energy storage technologies, ultimately contributing to a sustainable and green energy future., (© 2023 The Authors. Small Methods published by Wiley‐VCH GmbH.)- Published
- 2024
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38. Practical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients.
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Ranjan S, Leung D, Ghiaseddin AP, Taylor JW, Lobbous M, Dhawan A, Budhu JA, Coffee E, Melnick K, Chowdhary SA, Lu-Emerson C, Kurz SC, Burke JE, Lam K, Patel MP, Dunbar EM, Mohile NA, and Peters KB
- Subjects
- Humans, Anticoagulants adverse effects, Hemorrhage, Prospective Studies, Neoplasm Recurrence, Local drug therapy, Administration, Oral, Venous Thromboembolism epidemiology, Neoplasms drug therapy, Brain Neoplasms complications, Brain Neoplasms drug therapy
- Abstract
Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro-oncology experts convened to provide practical clinical guidance for the off-label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low-molecular-weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT., (© 2024 American Cancer Society.)
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- 2024
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39. Single-cell image-based genetic screens systematically identify regulators of Ebola virus subcellular infection dynamics.
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Carlson RJ, Patten JJ, Stefanakis G, Soong BY, Radhakrishnan A, Singh A, Thakur N, Amarasinghe GK, Hacohen N, Basler CF, Leung D, Uhler C, Davey RA, and Blainey PC
- Abstract
Ebola virus (EBOV) is a high-consequence filovirus that gives rise to frequent epidemics with high case fatality rates and few therapeutic options. Here, we applied image-based screening of a genome-wide CRISPR library to systematically identify host cell regulators of Ebola virus infection in 39,085,093 million single cells. Measuring viral RNA and protein levels together with their localization in cells identified over 998 related host factors and provided detailed information about the role of each gene across the virus replication cycle. We trained a deep learning model on single-cell images to associate each host factor with predicted replication steps, and confirmed the predicted relationship for select host factors. Among the findings, we showed that the mitochondrial complex III subunit UQCRB is a post-entry regulator of Ebola virus RNA replication, and demonstrated that UQCRB inhibition with a small molecule reduced overall Ebola virus infection with an IC50 of 5 μM. Using a random forest model, we also identified perturbations that reduced infection by disrupting the equilibrium between viral RNA and protein. One such protein, STRAP, is a spliceosome-associated factor that was found to be closely associated with VP35, a viral protein required for RNA processing. Loss of STRAP expression resulted in a reduction in full-length viral genome production and subsequent production of non-infectious virus particles. Overall, the data produced in this genome-wide high-content single-cell screen and secondary screens in additional cell lines and related filoviruses (MARV and SUDV) revealed new insights about the role of host factors in virus replication and potential new targets for therapeutic intervention., Competing Interests: P.C.B. is a consultant to or holds equity in 10X Genomics, General Automation Lab Technologies/Isolation Bio, Celsius Therapeutics, Next Gen Diagnostics, Cache DNA, Concerto Biosciences, Stately, Ramona Optics, Bifrost Biosystems, and Amber Bio. His laboratory receives research funding from Calico Life Sciences, Merck, and Genentech for work related to genetic screening. N.H. holds equity in and advises Danger Bio/Related Sciences, owns equity in BioNtech and receives research funding from Bristol Myers Squibb. C.U. serves on the Scientific Advisory Board of Immunai, Relation Therapeutics and Focal Biosciences, and receives research funding from AstraZeneca and Janssen Pharmaceuticals. The Broad Institute and MIT may seek to commercialize aspects of this work, and related applications for intellectual property have been filed. A.S. is an employee at Genentech and R.J.C. is an employee at Flagship Pioneering.
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- 2024
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40. Effectiveness of inactivated COVID-19 vaccine CoronaVac in children aged less than 3 years old during Omicron wave in Hong Kong.
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Wong WHS, Leung DL, Yip KM, So HK, Rosa Duque JS, and Lau YL
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- Child, Humans, Child, Preschool, Hong Kong epidemiology, Pandemics, COVID-19 Vaccines, COVID-19 prevention & control, Vaccines, Inactivated
- Abstract
The COVID-19 pandemic has affected people of all ages worldwide. However, there is still no information on the vaccine effectiveness (VE) of inactivated COVID-19 vaccines in children aged less than 3 years old. This study highlighted that 2 doses of CoronaVac were effective in preventing COVID-19, with a VE of 83.1 %., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hong Kong Special Administrative Region Government. All other authors declare no competing interests]., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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41. Optimising the acid-base ratio of Mg-Al layered double oxides to enhance CO 2 capture performance: the critical role of calcination conditions.
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Leung DWJ, Laney KR, Kenyon P, Rees NH, Buffet JC, Chen C, and O'Hare D
- Abstract
The effect of calcination conditions (ramp rate, calcination temperature and time) on the formation of Mg
2 Al layered double oxides (Mg2 Al LDOs) as well as their CO2 capture performance, has been systematically investigated. This study explores novel insights into the intricate relationship between these calcination conditions and the resulting surface characteristics, which play a vital role in CO2 capture efficiency. Notably, it is revealed that a rapid ramp rate (100 °C min-1 ) significantly increases surface area and hydroxyl concentration, leading to a 69% increase in CO2 capture efficiency compared to slower ramp rate. Conversely, short calcination times (1 h) and fast ramp rates (100 °C min-1 ) are observed to compromise CO2 adsorption due to the presence of dehydrated LDHs. A critical acid : base ratio of 0.37, achieved from a fast ramp rate (100 °C min-1 ) at 400 °C for 2 h, was found as a key threshold for optimising surface properties, effectively balancing favourable hydroxyl and less favourable strong acid sites, thereby maximizing CO2 capture performance.- Published
- 2024
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42. Robotic Assisted Percutaneous Coronary Intervention: Initial Australian Experience.
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Leung J, French J, Xu J, Kachwalla H, Kaddapu K, Badie T, Mussap C, Rajaratnam R, Leung D, Lo S, and Juergens C
- Subjects
- Humans, Male, Female, Aged, Australia, Coronary Angiography, Middle Aged, Treatment Outcome, Coronary Artery Disease surgery, Follow-Up Studies, Percutaneous Coronary Intervention methods, Robotic Surgical Procedures methods
- Abstract
Background & Aim: Robotic-assisted percutaneous coronary intervention (R-PCI) has been increasingly performed overseas. Initial observations have demonstrated its clinical efficacy and safety with additional potential benefits of more accurate lesion assessment and stent deployment, with reduced radiation exposure to operators and patients. However, data from randomised controlled trials or clinical experience from Australia are lacking., Methods: This was a single-centre experience of all patients undergoing R-PCI as part of the run-in phase for an upcoming randomised clinical trial (ACTRN12623000480684). All R-PCI procedures were performed using the CorPath GRX robot (Corindus Vascular Robotics, Waltham, Massachusetts, USA). Key inclusion criteria included patients with obstructive coronary disease requiring percutaneous coronary intervention. Major exclusion criteria included ST-elevation myocardial infarction, cardiogenic shock or lesions deemed unsuitable for R-PCI by the operator. Clinical success was defined as residual stenosis <30% without in-hospital major adverse cardiovascular events (MACE). Technical success was defined as the completion of the R-PCI procedure without unplanned manual conversion. Procedural characteristics were compared between early (cases 1-3) and later (cases 4-21) cases., Results: Twenty-one (21) patients with a total of 24 lesions were analysed. The mean age of patients was 66.5 years, and 66% of cases were male. Radial access was used in 18 cases (86%). Most lesions were American Heart Association/American College of Cardiology class B2/C (66%). Clinical success was achieved in 100% with manual conversion required in four cases (19%). No procedural complications or in-hospital MACE occurred. Compared to the early cases, later cases had a statistically significantly shorter fluoroscopy time (44.0mins vs 25.2mins, p<0.007), dose area product (967.3 dGy.cm
2 vs 361.0dGy.cm2 , p=0.01) and air kerma (2484.3mGy vs 797.4mGy, p=0.009) with no difference in contrast usage (136.7mL vs 131.4mL, p=0.88)., Conclusions: We present the first clinical experience of R-PCI in Australia using the Corindus CorPath GRX robot. We achieved clinical success in all patients and technical success in the majority of cases with no procedural complications or in-hospital MACE. With increasing operator and staff experience, cases required shorter fluoroscopy time and less radiation exposure but similar contrast usage., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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43. Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents.
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Rosa Duque JS, Cheng SMS, Cohen CA, Leung D, Wang X, Mu X, Chung Y, Lau TM, Wang M, Zhang W, Zhang Y, Wong HHW, Tsang LCH, Chaothai S, Kwan TC, Li JKC, Chan KCK, Luk LLH, Ho JCH, Li WY, Lee AMT, Lam JHY, Chan SM, Wong WHS, Tam IYS, Mori M, Valkenburg SA, Peiris M, Tu W, and Lau YL
- Subjects
- Adolescent, Child, Female, Humans, Male, Antibodies, Viral immunology, Antibodies, Viral blood, Immunogenicity, Vaccine, Injections, Intradermal, Injections, Intramuscular, SARS-CoV-2 immunology, Vaccines, Inactivated, COVID-19 prevention & control, COVID-19 immunology, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, T-Lymphocytes immunology
- Abstract
Background: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents., Methods: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively., Results: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)
+ CD4+ , SNM-specific IL-2+ CD8+ , S-specific IL-2+ CD8+ , N-specific IL-2+ CD4+ , N-specific IL-2+ CD8+ and M-specific IL-2+ CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+ CD4+ , interferon-γ+ CD8+ and IL-2+ CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions., Conclusion: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines., (© 2023. The Author(s).)- Published
- 2024
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44. A protein-proximity screen reveals Ebola virus co-opts the mRNA decapping complex through the scaffold protein EDC4.
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Davey R, Donahue C, Kesari A, Thakur N, Wang L, Hulsey-Stubbs S, Williams C, Kirby C, Leung D, Aryal U, Basler C, and LaCount D
- Abstract
The interaction of host and Ebola virus (EBOV) proteins is required for establishing infection of the cell. To identify protein binding partners, a proximity-dependent protein interaction screen was performed for six EBOV proteins. Hits were computationally mapped onto a human protein-protein interactome and then annotated with viral proteins to reveal known and previously undescribed EBOV-host protein interactions and processes. Importantly, this approach efficiently arranged proteins into functional complexes associated with single viral proteins. Focused characterization of interactions between EBOV VP35 and the mRNA decapping complex demonstrated that VP35 binds the scaffold protein EDC4 through the C-terminal subdomain, with each protein found associated in EBOV-infected cells. Mechanistically, depletion of three components of the complex each similarly inhibited viral replication by reducing early viral RNA synthesis. Overall, we demonstrate successful identification of EBOV protein interaction with entire cellular machines, providing a deeper understanding of replication mechanism for therapeutic intervention.
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- 2024
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45. Cell-type differential targeting of SETDB1 prevents aberrant CTCF binding, chromatin looping, and cis-regulatory interactions.
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Tam PLF, Cheung MF, Chan LY, and Leung D
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- Animals, Mice, DNA Methylation, Retroelements, Regulatory Sequences, Nucleic Acid, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase metabolism, Histones metabolism, Chromatin
- Abstract
SETDB1 is an essential histone methyltransferase that deposits histone H3 lysine 9 trimethylation (H3K9me3) to transcriptionally repress genes and repetitive elements. The function of differential H3K9me3 enrichment between cell-types remains unclear. Here, we demonstrate mutual exclusivity of H3K9me3 and CTCF across mouse tissues from different developmental timepoints. We analyze SETDB1 depleted cells and discover that H3K9me3 prevents aberrant CTCF binding independently of DNA methylation and H3K9me2. Such sites are enriched with SINE B2 retrotransposons. Moreover, analysis of higher-order genome architecture reveals that large chromatin structures including topologically associated domains and subnuclear compartments, remain intact in SETDB1 depleted cells. However, chromatin loops and local 3D interactions are disrupted, leading to transcriptional changes by modifying pre-existing chromatin landscapes. Specific genes with altered expression show differential interactions with dysregulated cis-regulatory elements. Collectively, we find that cell-type specific targets of SETDB1 maintain cellular identities by modulating CTCF binding, which shape nuclear architecture and transcriptomic networks., (© 2024. The Author(s).)
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- 2024
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46. Relative anemia and perioperative stroke in children with moyamoya.
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Gatti JR, Ahmad SA, Gardner Yelton S, DiGiusto M, Leung D, Xu R, Cohen AR, Gottesman RF, and Sun LR
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- Child, Humans, Retrospective Studies, Treatment Outcome, Hemoglobins, Postoperative Complications epidemiology, Postoperative Complications etiology, Cerebral Revascularization adverse effects, Stroke etiology, Stroke complications, Anemia, Sickle Cell complications, Ischemic Stroke complications, Moyamoya Disease complications, Moyamoya Disease diagnostic imaging, Moyamoya Disease surgery
- Abstract
Objectives: Surgical revascularization for moyamoya arteriopathy decreases long-term stroke risk but carries a risk of perioperative ischemic complications. We aimed to evaluate modifiable stroke risk factors in children undergoing surgical revascularization for moyamoya., Materials and Methods: In this exploratory, single-center, retrospective cohort study, medical records of pediatric patients undergoing surgical revascularization for moyamoya arteriopathy at our center between 2003 and 2021 were reviewed. Candidate modifiable risk factors were analyzed for association with perioperative stroke, defined as ischemic stroke ≤7 days after surgery., Results: We analyzed 53 surgeries, consisting of 39 individual patients undergoing indirect surgical revascularization of 74 hemispheres. Perioperative ischemic stroke occurred following five surgeries (9.4%). There were no instances of hemorrhagic stroke. Larger pre-to-postoperative decreases in hemoglobin (OR 3.90, p=0.017), hematocrit (OR 1.69, p=0.012) and blood urea nitrogen (OR 1.83, p=0.010) were associated with increased risk of perioperative ischemic stroke. Weight-adjusted intraoperative blood loss was not associated with risk of perioperative ischemic stroke (OR 0.94, p=0.796). Among children with sickle cell disease, all of whom underwent exchange transfusion within one week prior to surgery, none experienced perioperative stroke., Conclusions: Decreases in hemoglobin, hematocrit, and blood urea nitrogen between the preoperative and postoperative periods are associated with increased risk of perioperative stroke. These novel findings suggest that dilutional anemia, possibly due to standardly administered hyperhydration, may increase the risk of perioperative stroke in some children with moyamoya. Further work optimizing both mean arterial pressure and oxygen-carrying capacity in these patients, including consideration of alternative blood transfusion thresholds, is necessary., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2024
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