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1. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. [2023]

  • Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng WH, Zhou Y, Hoffman D, Harb JG, Potluri J, and Garcia-Manero G
  • American journal of hematology [Am J Hematol] 2023 Feb; Vol. 98 (2), pp. 272-281. Date of Electronic Publication: 2022 Nov 10.
Subjects
Aged, Humans, Male, Azacitidine therapeutic use, Leukemia, Myeloid, Acute drug therapy, Neutropenia chemically induced, Sulfonamides, Treatment Outcome, Female, Antineoplastic Combined Chemotherapy Protocols adverse effects, and Myelodysplastic Syndromes drug therapy
Abstract
Patients with relapsed/refractory (R/R) higher-risk myelodysplastic syndromes (MDS) have a dismal median overall survival (OS) after failing hypomethylating agent (HMA) treatment. There is no standard of care for patients after HMA therapy failure; hence, there is a critical need for effective therapeutic strategies. Herein, we present the safety and efficacy of venetoclax + azacitidine in patients with R/R MDS. This phase 1b, open-label, multicenter study enrolled patients ≥18 years. Patients were treated with escalating doses of oral venetoclax: 100, 200, or 400 mg daily for 14 days every 28-day cycle. Azacitidine was administered on Days 1-7 every cycle at 75 mg/m 2 /day intravenously/subcutaneously. Responses were assessed per modified 2006 International Working Group (IWG) criteria. Forty-four patients (male 86%, median age 74 years) received venetoclax + azacitidine treatment. Median follow-up was 21.2 months. Hematological adverse events of Grade ≥ 3 included febrile neutropenia (34%), thrombocytopenia (32%), neutropenia (27%), and anemia (18%). Pneumonia (23%) was the most common Grade ≥ 3 infection. Marrow responses were seen including complete remission (CR, n = 3, 7%) and marrow CR (mCR, n = 14, 32%); 36% (16/44) achieved transfusion independence (TI) for RBCs and/or platelets, and 43% (6/14) with mCR achieved hematological improvement (HI). The median time to CR/mCR was 1.2 months, and the median duration of response for CR + mCR was 8.6 months. Median OS was 12.6 months. Venetoclax + azacitidine shows activity in patients with R/R MDS following prior HMA therapy failure and provides clinically meaningful benefits, including HI and TI, and encouraging OS.
(© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

2. Transnational Trans Woman Inspires and Informs Evidence-Informed Interventions. [2023]

  • Cruzado-Quiñones J, Huibregtse RC, and Jordan AO
  • Journal of correctional health care : the official journal of the National Commission on Correctional Health Care [J Correct Health Care] 2023 Jan 25. Date of Electronic Publication: 2023 Jan 25.
Abstract
Transitional Care Coordination is an evidence-informed model program developed by New York City Correctional Health Services as a Health Resources and Services Administration Special Projects of National Significance Correctional Health Linkage Intervention. Using implementation science under this and subsequent demonstration projects, interventions were adapted and enhanced to address the transitional needs of people of Puerto Rican ancestry and to expand the network of care across the islands of Puerto Rico. These interventions were informed, in part, by a transnational trans woman of color of Puerto Rican ancestry living with HIV. A socioecological model framework and case study are used to illustrate how evidence-informed interventions are developed and adapted to address the needs of those served.

3. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group. [2023]

  • Groenewold NA, Bas-Hoogendam JM, Amod AR, Laansma MA, Van Velzen LS, Aghajani M, Hilbert K, Oh H, Salas R, Jackowski AP, Pan PM, Salum GA, Blair JR, Blair KS, Hirsch J, Pantazatos SP, Schneier FR, Talati A, Roelofs K, Volman I, Blanco-Hinojo L, Cardoner N, Pujol J, Beesdo-Baum K, Ching CRK, Thomopoulos SI, Jansen A, Kircher T, Krug A, Nenadić I, Stein F, Dannlowski U, Grotegerd D, Lemke H, Meinert S, Winter A, Erb M, Kreifelts B, Gong Q, Lui S, Zhu F, Mwangi B, Soares JC, Wu MJ, Bayram A, Canli M, Tükel R, Westenberg PM, Heeren A, Cremers HR, Hofmann D, Straube T, Doruyter AGG, Lochner C, Peterburs J, Van Tol MJ, Gur RE, Kaczkurkin AN, Larsen B, Satterthwaite TD, Filippi CA, Gold AL, Harrewijn A, Zugman A, Bülow R, Grabe HJ, Völzke H, Wittfeld K, Böhnlein J, Dohm K, Kugel H, Schrammen E, Zwanzger P, Leehr EJ, Sindermann L, Ball TM, Fonzo GA, Paulus MP, Simmons A, Stein MB, Klumpp H, Phan KL, Furmark T, Månsson KNT, Manzouri A, Avery SN, Blackford JU, Clauss JA, Feola B, Harper JC, Sylvester CM, Lueken U, Veltman DJ, Winkler AM, Jahanshad N, Pine DS, Thompson PM, Stein DJ, and Van der Wee NJA
  • Molecular psychiatry [Mol Psychiatry] 2023 Jan 19. Date of Electronic Publication: 2023 Jan 19.
Abstract
There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, p FWE  = 0.037; right: d = -0.104, p FWE  = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, p FWE  = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, p FWE  < 0.001; right: d = -0.158, p FWE  < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, p FWE  = 0.006; right: d = 0.099, p FWE  = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

4. PASC in Solid Organ Transplant Recipients With Self-reported SARS-CoV-2 Infection. [2023]

  • Alasfar S, Chiang TP, Snyder AJ, Ou MT, Boyarsky BJ, Abedon AT, Alejo JL, Cook S, Cochran W, Brigham E, Parker AM, Garonzik-Wang J, Massie AB, Brennan DC, Vannorsdall T, Segev DL, and Avery RK
  • Transplantation [Transplantation] 2023 Jan 01; Vol. 107 (1), pp. 181-191. Date of Electronic Publication: 2022 Sep 19.
Subjects
Humans, Self Report, SARS-CoV-2, Quality of Life, COVID-19 Testing, Transplant Recipients, Cough, Pain, COVID-19 epidemiology, and Organ Transplantation adverse effects
Abstract
Background: Postacute sequelae of SARS-CoV-2 infection (PASC) is an increasingly recognized phenomenon and manifested by long-lasting cognitive, mental, and physical symptoms beyond the acute infection period. We aimed to estimate the frequency of PASC symptoms in solid organ transplant (SOT) recipients and compared their frequency between those with SARS-CoV-2 infection requiring hospitalization and those who did not require hospitalization.
Methods: A survey consisting of 7 standardized questionnaires was administered to 111 SOT recipients with history of SARS-CoV-2 infection diagnosed >4 wk before survey administration.
Results: Median (interquartile range) time from SARS-CoV-2 diagnosis was 167 d (138-221). Hospitalization for SARS-CoV-2 infection was reported in 33 (30%) participants. Symptoms after the COVID episode were perceived as following: significant trauma (53%), cognitive decline (50%), fatigue (41%), depression (36%), breathing problems (35%), anxiety (23%), dysgeusia (22%), dysosmia (21%), and pain (19%). Hospitalized patients had poorer median scores in cognition (Quick Dementia Rating System survey score: 2.0 versus 0.5, P = 0.02), quality of life (Health-related Quality of Life survey: 2.0 versus 1.0, P = 0.015), physical health (Global physical health scale: 10.0 versus 11.0, P = 0.005), respiratory status (Breathlessness, Cough and Sputum Scale: 1.0 versus 0.0, P = 0.035), and pain (Pain score: 3 versus 0 out of 10, P = 0.003). Among patients with infection >6 mo prior, some symptoms were still present as following: abnormal breathing (42%), cough (40%), dysosmia (29%), and dysgeusia (34%).
Conclusions: SOT recipients reported a high frequency of PASC symptoms. Multidisciplinary approach is needed to care for these patients beyond the acute phase.
(Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

5. 6-month antibody kinetics and durability after four doses of a SARS-CoV-2 vaccine in solid organ transplant recipients. [2023]

  • Mitchell J, Chiang TP, Alejo JL, Kim JD, Chang A, Abedon AT, Avery RK, Tobian AAR, Levan ML, Warren DS, Garonzik-Wang JM, Segev DL, Massie AB, and Werbel WA
  • Clinical transplantation [Clin Transplant] 2023 Jan; Vol. 37 (1), pp. e14868. Date of Electronic Publication: 2022 Dec 07.
Subjects
Humans, COVID-19 Vaccines, Kinetics, SARS-CoV-2, Antibodies, Transplant Recipients, Antibodies, Viral, COVID-19 epidemiology, COVID-19 prevention control, and Organ Transplantation

6. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. [2022]

  • Kanoni S, Graham SE, Wang Y, Surakka I, Ramdas S, Zhu X, Clarke SL, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Yousri NA, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Hwu CM, Hung YJ, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Lamina C, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw E, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Vazquez-Moreno M, Feitosa MF, Wojczynski MK, Wang Z, Preuss MH, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Tsao NL, Verma A, Slieker RC, Lo KS, Zilhao NR, Le P, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Frank M, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Bayyana S, Stringham HM, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Nardone GG, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, Li X, Liang J, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Chen YI, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Kardia SLR, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Hunt SC, Walker M, Koistinen HA, Chandak GR, Mercader JM, Costanzo MC, Jang D, Burtt NP, Villalpando CG, Orozco L, Fornage M, Tai E, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Qu J, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, Hart LM', Elders PJM, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney LALM, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, van Dijk KW, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Chuang LM, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, Willemsen AHM, Cupples L, van Meurs JBJ, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen Y, Ho YL, Lynch JA, Rader DJ, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson PWF, Frayling TM, Hirschhorn JN, Kathiresan S, Mohlke KL, Sun YV, Morris AP, Boehnke M, Brown CD, Natarajan P, Deloukas P, Willer CJ, Assimes TL, and Peloso GM
  • Genome biology [Genome Biol] 2022 Dec 27; Vol. 23 (1), pp. 268. Date of Electronic Publication: 2022 Dec 27.
Subjects
Humans, Sex Characteristics, Phenotype, Lipids genetics, Polymorphism, Single Nucleotide, Genetic Pleiotropy, Genome-Wide Association Study, and Genetic Predisposition to Disease
Abstract
Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.
Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.
Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
(© 2022. The Author(s).)

7. Genetic diversity fuels gene discovery for tobacco and alcohol use [2022]

  • Saunders, Gretchen R. B., Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M., Addison, Clifton, Akiyama, Masato, Albert, Christine M., Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K., Ashley-Koch, Allison E., Ashrani, Aneel A., Barnes, Kathleen C., Barr, R. Graham, Bartz, Traci M., Becker, Diane M., Bielak, Lawrence F., Benjamin, Emelia J., Bis, Joshua C., Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R., Boardman, Jason D., Boerwinkle, Eric, Boomsma, Dorret I., Boorgula, Meher Preethi, Bowden, Donald W., Brody, Jennifer A., Cade, Brian E., Chasman, Daniel I., Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H., Choquet, Hélène, Cole, John W., Cornelis, Marilyn C., Cucca, Francesco, Curran, Joanne E., de Andrade, Mariza, Dick, Danielle M., Docherty, Anna R., Duggirala, Ravindranath, Eaton, Charles B., Ehringer, Marissa A., Esko, Tõnu, Faul, Jessica D., Fernandes Silva, Lilian, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I., Gabrielsen, Maiken E., Garrett, Melanie E., Gharib, Sina A., Gieger, Christian, Gillespie, Nathan, Glahn, David C., Gordon, Scott D., Gu, Charles C., Gu, Dongfeng, Gudbjartsson, Daniel F., Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E., Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K., Hickie, Ian, Hidalgo, Bertha, Hokanson, John E., Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J., Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R., Jee, Yon Ho, Johnson, Eric O., Joo, Yoonjung Y., Jorgenson, Eric, Justice, Anne E., Kamatani, Yoichiro, Kaplan, Robert C., Kaprio, Jaakko, Kardia, Sharon L. R., Keller, Matthew C., Kelly, Tanika N., Kooperberg, Charles, Korhonen, Tellervo, Kraft, Peter, Krauter, Kenneth, Kuusisto, Johanna, Laakso, Markku, Lasky-Su, Jessica, Lee, Wen-Jane, Lee, James J., Levy, Daniel, Li, Liming, Li, Kevin, Li, Yuqing, Lin, Kuang, Lind, Penelope A., Liu, Chunyu, Lloyd-Jones, Donald M., Lutz, Sharon M., Ma, Jiantao, Mägi, Reedik, Manichaikul, Ani, Martin, Nicholas G., Mathur, Ravi, Matoba, Nana, McArdle, Patrick F., McGue, Matt, McQueen, Matthew B., Medland, Sarah E., Metspalu, Andres, Meyers, Deborah A., Millwood, Iona Y., Mitchell, Braxton D., Mohlke, Karen L., Moll, Matthew, Montasser, May E., Morrison, Alanna C., Mulas, Antonella, Nielsen, Jonas B., North, Kari E., Oelsner, Elizabeth C., Okada, Yukinori, Orrù, Valeria, Palmer, Nicholette D., Palviainen, Teemu, Pandit, Anita, Park, S. Lani, Peters, Ulrike, Peters, Annette, Peyser, Patricia A., Polderman, Tinca J. C., Rafaels, Nicholas, Redline, Susan, Reed, Robert M., Reiner, Alex P., Rice, John P., Rich, Stephen S., Richmond, Nicole E., Roan, Carol, Rotter, Jerome I., Rueschman, Michael N., Runarsdottir, Valgerdur, Saccone, Nancy L., Schwartz, David A., Shadyab, Aladdin H., Shi, Jingchunzi, Shringarpure, Suyash S., Sicinski, Kamil, Skogholt, Anne Heidi, Smith, Jennifer A., Smith, Nicholas L., Sotoodehnia, Nona, Stallings, Michael C., Stefansson, Hreinn, Stefansson, Kari, Stitzel, Jerry A., Sun, Xiao, Syed, Moin, Tal-Singer, Ruth, Taylor, Amy E., Taylor, Kent D., Telen, Marilyn J., Thai, Khanh K., Tiwari, Hemant, Turman, Constance, Tyrfingsson, Thorarinn, Wall, Tamara L., Walters, Robin G., Weir, David R., Weiss, Scott T., White, Wendy B., Whitfield, John B., Wiggins, Kerri L., Willemsen, Gonneke, Willer, Cristen J., Winsvold, Bendik S., Xu, Huichun, Yanek, Lisa R., Yin, Jie, Young, Kristin L., Young, Kendra A., Yu, Bing, Zhao, Wei, Zhou, Wei, Zöllner, Sebastian, Zuccolo, Luisa, Batini, Chiara, Bergen, Andrew W., Bierut, Laura J., David, Sean P., Gagliano Taliun, Sarah A., Hancock, Dana B., Jiang, Bibo, Munafò, Marcus R., Thorgeirsson, Thorgeir E., Liu, Dajiang J., and Vrieze, Scott
  • Nature; December 2022, Vol. 612 Issue: 7941 p720-724, 5p
Abstract
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1–4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

8. Circulating adipose tissue proteins involved in atrial fibrillation: An explorative scoping review. [2022]

  • Meulendijks ER, Krul SPJ, Baalman SW, de Vries TAC, Wesselink R, Ernault AC, Kawasaki M, Al-Shama R, Neefs J, Limpens J, and de Groot JR
  • Trends in cardiovascular medicine [Trends Cardiovasc Med] 2022 Dec 17. Date of Electronic Publication: 2022 Dec 17.
Abstract
Obesity increases the risk of atrial fibrillation (AF), potentially through proteins secreted by adipose tissue (AT) that affect atrial electrical and structural remodeling. We aim to give a comprehensive overview of circulating AT proteins involved in inflammation and fibrosis, that are associated with prevalent AF (paroxysmal or persistent) and the risk on developing new-onset AF. These include adipokines, defined as proteins enriched in AT as adiponectin, but also proteins less specific to AT. We systematically performed an explorative search for studies reporting associations between proteins secreted from cells residing in the AT and AF, and additionally assessed the effect of obesity on these proteins by a secondary search. The AT proteins involved in inflammation were mostly increased in patients with prevalent and new-onset AF, and with obesity, while the AT enriched adipokines were mostly not associated with AF. This review provides insight into circulating adipose tissue proteins involved in AF substrate formation.
(Copyright © 2022. Published by Elsevier Inc.)

9. Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing. [2022]

  • Baliga S, Adams JA, Bajaj BVM, Van Benthuysen L, Daartz J, Gallotto SL, Lewy JR, DeNunzio N, Weyman EA, Lawell MP, Palmer JD, Yeap BY, Ebb DH, Huang MS, Perry AF, MacDonald SM, Jones RM, Tarbell NJ, and Yock TI
  • Cancer [Cancer] 2022 Dec 11. Date of Electronic Publication: 2022 Dec 11.
Abstract
Background: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB).
Methods and Materials: We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans.
Results: Thirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy.
Conclusions: Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB.
Plain Language Summary: In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.
(© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

10. PART is part of SNAP‐MCI. [2022]

  • Wisse, Laura EM, Xie, Long, Lyu, Xueying, Das, Sandhitsu R., de Flores, Robin, Lane, Jacqueline, Yushkevich, Paul A., Wolk, David A., and Initiative, Disease Neuroimaging
  • Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022 Supplement 6, Vol. 18 Issue 6, p1-4, 4p
Abstract
Background: Mild Cognitive Impairment with Suspected non‐Alzheimer's Pathophysiology (SNAP‐MCI) represents a group of patients with Alzheimer's disease (AD) like neurodegeneration without beta‐amyloid pathology. While this group likely has a heterogeneous etiology, tau pathology, as in Primary Age‐Related Tauopathy (PART), has been hypothesized to play a major role. We investigate tau positron emission tomography (PET) uptake in the medial temporal lobe (MTL) in SNAP‐MCI and the association of MTL Tau‐PET uptake with structural measures and delayed recall in beta‐amyloid negative (A‐) MCI patients. Method: 237 MCI patients and 301 A‐ controls with available beta‐amyloid and tau PET and magnetic resonance images (within 200 days) were included. Baseline hippocampal volume and entorhinal cortex (ERC) and Brodmann areas (BA)35 thickness were obtained using an in‐house developed pipeline and annualized atrophy rates were estimated in an unbiased fashion using follow‐up MRIs within 4.5 years. Βeta‐amyloid status (A+/‐) was determined by a standard cut‐off (Florbetapir: 1.11; Florbetaben: 1.08) and neurodegeneration status (N+/‐) by hippocampal volumes, corrected for intracranial volume, using the 90th percentile of A+ AD patients as the cut‐off. Tau‐PET standardized uptake value ratio (SUVR) in the ERC/BA35 was calculated. A composite z‐score of delayed recall at baseline and change over 2 years was obtained. Result: SNAP‐MCI had significantly higher ERC/BA35 Tau‐PET SUVR than A‐ controls (Table 1, corrected for age) and qualitatively higher than A‐N‐ MCI (p=0.10). ERC/BA35 Tau‐PET SUVR in A‐N‐ MCI was not significantly different from A‐ controls. In A‐ MCI patients, ERC/BA35 Tau‐PET SUVR was significantly associated with BA35 thickness and hippocampal, ERC and BA35 atrophy rates, corrected for beta‐amyloid PET SUVR (Table 2; Figure 1). MTL structural measures, but not ERC/BA35 Tau‐PET SUVR, were associated with cross‐sectional and longitudinal delayed recall measures (Table 3; Figure 2). Conclusion: SNAP‐MCI had elevated ERC/BA35 Tau‐PET SUVR and ERC/BA35 Tau‐PET SUVR was associated with MTL structural measures in A‐ MCI patients. This indicates that tau pathology might be an important driver of neurodegeneration in the absence of beta‐amyloid pathology, supporting the notion that PART contributes to SNAP‐MCI. Additionally, MTL structure was associated with memory performance, consistent with SNAP not being a benign condition. [ABSTRACT FROM AUTHOR]

11. Drug therapy, imaging, and other aspects of clinical management change after Alzheimer's biomarker testing in routine practice: Findings from the IMPACT‐AD BC study. [2022]

  • Yang, David, Best, John R., Chambers, Colleen, Feldman, Howard H., Pettersen, Jacqueline A, Henri‐Bhargava, Alexander, Lee, Philip E, Nygaard, Haakon B., Funnell, Clark R, Foti, Dean J, Hsiung, Ging‐Yuek Robin, and DeMarco, Mari L.
  • Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022 Supplement 6, Vol. 18 Issue 6, p1-2, 2p
Abstract
Background: While previous studies have demonstrated the effect of Alzheimer's disease (AD) CSF testing in changing diagnosis, we lack an understanding of how this testing affects clinical management. Therefore, we assessed changes in clinical management associated with AD CSF biomarker testing when ordered as part of routine clinical management. Method: The 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT‐AD BC) study (NCT05002699) is a longitudinal study examining the impact of AD CSF testing on clinical management, personal utility and health care economics in British Columbia, Canada. After AD CSF testing was ordered as part of routine care (where the clinical scenario met the appropriate use criteria), the patient and their physician were eligible to participate in the study. The primary outcome was the change in management (pre‐ v. post‐biomarker results) in a composite measure including 1) AD drug therapy, 2) other relevant drug therapy, 3) other diagnostic procedures, and 4) referral or counselling. Result: Participants (n = 129) had a median age of 63 (IQR:58‐68); 49% were female. Cognitive impairment at baseline consisted of 7% with subjective cognitive impairment, 53% with mild cognitive impairment, and 40% with dementia. CSF biomarker profiles were consistent with an amyloid‐beta pathology (i.e., A+) in 72% of cases. Changes in clinical management because of testing occurred in 83% of cases including: referrals and counseling (57%), imaging (47%) and other diagnostic procedures (e.g., neuropsychological testing) (42%), and use of AD drug therapies (40%). For those with a non‐AD pre‐biomarkers diagnosis, 42% were changed to AD post‐biomarkers; for those with an AD pre‐biomarkers diagnosis, 18% were changed to non‐AD post‐biomarkers. Conclusion: This study has revealed substantial changes in clinical management as a direct result of AD CSF biomarker testing in routine care. An understanding of the implications of biomarker testing will in turn help us: improve appropriate utilization, understand the broader impacts on persons living with dementia and on the health care system, and prepare for expanded use of this testing with the availability of disease‐modifying therapeutics. [ABSTRACT FROM AUTHOR]

12. Reply: Further Insights Into the Prognostic Value of Left Atrial Strain in Dilated Cardiomyopathy? [2022]

  • Raafs AG, Henkens MTHM, Vos JL, Nijveldt R, and Verdonschot JAJ
  • JACC. Cardiovascular imaging [JACC Cardiovasc Imaging] 2022 Dec; Vol. 15 (12), pp. 2156-2157.
Subjects
Humans, Prognosis, Predictive Value of Tests, Cardiomyopathy, Dilated diagnostic imaging, Atrial Fibrillation, and Atrial Appendage

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14. The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R): Real-World Data on Stage III Non-Small Cell Lung Cancer Patients Treated With Curative Chemoradiation. [2022]

  • Dieleman E, van der Woude L, van Os R, van Bockel L, Coremans I, van Es C, De Jaeger K, Knol HP, Kolff W, Koppe F, Pomp J, Reymen B, Schinagl D, Spoelstra F, Tissing-Tan C, van der Voort van Zyp N, van der Wel A, Wijsman R, Dielwart M, Wiegman E, Damhuis R, and Belderbos J
  • Clinical lung cancer [Clin Lung Cancer] 2022 Nov 25. Date of Electronic Publication: 2022 Nov 25.
Abstract
Introduction: Chemoradiotherapy (CRT) is the standard of care in inoperable non-small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe.
Methods: The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy.
Results: Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality.
Conclusion: In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

15. Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer. [2022]

  • Makhlin I, McAndrew NP, Wileyto EP, Clark AS, Holmes R, Bottalico LN, Mesaros C, Blair IA, Jeschke GR, Fox KR, Domchek SM, Matro JM, Bradbury AR, Feldman MD, Hexner EO, Bromberg JF, and DeMichele A
  • NPJ breast cancer [NPJ Breast Cancer] 2022 Nov 11; Vol. 8 (1), pp. 122. Date of Electronic Publication: 2022 Nov 11.
Abstract
Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective. Twenty-five subjects enrolled. The combination of ruxolitinib and exemestane was safe, though anemia requiring transfusion in 5/15 (33%) at the 25 mg dose in stage 1 led to a reduction to 15 mg twice daily in stage 2 (with no additional transfusions). Clinical benefit rate (CBR) in the overall study population was 24% (95% CI 9.4-45.1); 6/25 patients demonstrated stable disease for ≥6 months. Median progression-free survival was 2.8 months (95% CI 2.6-3.9). Exploratory biomarkers revealed high levels of systemic inflammation and 60% harbored a high-risk IL-6 genotype. Pharmacodynamics demonstrated modest on-target inhibition of phosphorylated-STAT3 by ruxolitinib at a tolerable dose. Thus, ruxolitinib combined with exemestane at a tolerable dose was safe but minimally active in AI-resistant tumors of patients with high levels of systemic inflammation. These findings highlight the need for more potent and specific therapies targeting inflammation in MBC.
(© 2022. The Author(s).)

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17. Patient and Healthcare Provider Perspectives on the Implementation of a Web-Based Clinical Communication System for Cancer: A Qualitative Study. [2022]

  • Petrovic B, O'Brien MA, Liddy C, Afkham A, McGee SF, Morgan SC, Segal R, Bender JL, Sussman J, Urquhart R, Fitch M, Schneider ND, and Grunfeld E
  • Current oncology (Toronto, Ont.) [Curr Oncol] 2022 Nov 03; Vol. 29 (11), pp. 8401-8414. Date of Electronic Publication: 2022 Nov 03.
Subjects
Male, Humans, Qualitative Research, Communication, Internet, Health Personnel, and Neoplasms
Abstract
Previous research has identified communication and care coordination problems for patients with cancer. Healthcare providers (HCPs) have reported communication issues due to the incompatibility of electronic medical records (EMR) software and not being consistently copied on patient reports. We evaluated an asynchronous web-based communication system ("eOncoNote") for primary care providers and cancer specialists to improve cancer care coordination. The objectives were to examine patients' perceptions of the role of eOncoNote in their healthcare, and HCPs' experiences of implementing eOncoNote. Qualitative interviews were conducted with patients with breast and prostate cancer, primary care providers, and cancer specialists. Eighteen patients and fourteen HCPs participated. Six themes were identified from the patient interviews focusing on HCP and patient roles related to care coordination and patient awareness of communication among their HCPs. Four themes were identified from HCP interviews related to the context of care coordination and experience with eOncoNote. Both patients and HCPs described the important role patients and caregivers play in care coordination. The results show that patients were often unaware of the communication between their HCPs and assumed they were communicating. HCPs encountered challenges incorporating eOncoNote into their workflow.

18. An innovative interprofessional education simulation for athletic training and prelicensure nursing students: Development, implementation, and student perspectives. [2022]

  • Vaughn J, Cunningham R, Schroeder LH, Waddill C, Peterson MJ, Gambacorta MR, and Sims S
  • Nursing forum [Nurs Forum] 2022 Nov; Vol. 57 (6), pp. 1373-1380. Date of Electronic Publication: 2022 Oct 29.
Subjects
Humans, Interprofessional Relations, Interprofessional Education, Learning, Attitude of Health Personnel, Patient Care Team, Students, Nursing, and Sports
Abstract
Background: The purpose of this article is to describe the development, implementation, and evaluation of a Simulation Interprofessional Education (Sim-IPE) activity for healthcare students from different disciplines (athletic training [AT] and nursing). The objective for the Sim-IPE activity was to engage AT and prelicensure nursing students in a realistic healthcare scenario to enhance knowledge about one another's profession, develop interprofessional skills, collaborate with one another, and communicate effectively as a team as they performed care.
Methods: This mixed methods study employed a one-time posttest design for a convenience sample of AT and prelicensure nursing students following a simulation intervention. Students completed the Student Perceptions of Interprofessional Clinical Education-Revised (SPICE-R) survey and answered open-ended response questions.
Results: Thirteen students (N = 13) from Cohort 1 and 12 students (N = 12) from Cohort 2 completed the SPICE-R survey. Most students strongly agreed/agreed for each of the SPICE-R survey questions. Qualitative findings indicated the students positively perceived the Sim-IPE activity as it helped them discover the value of interprofessional patient care.
Discussion: The quantitative findings indicated that the students found the Sim-IPE an effective learning methodology to achieve the objectives while the qualitative findings gave further insight into the students' perceptions of interprofessional teamwork and the value of the prebrief session conducted before the simulation. The findings will inform future Sim-IPE activities involving additional groups of healthcare students.
(© 2022 The Authors. Nursing Forum published by Wiley Periodicals LLC.)

19. Antibody response to a third dose of SARS-CoV-2 vaccine in heart and lung transplant recipients. [2022]

  • Alejo JL, Ruck JM, Chiang TPY, Abedon AT, Kim JD, Avery RK, Tobian AAR, Warren DS, Levan ML, Massie AB, Garonzik-Wang JM, Segev DL, and Werbel WA
  • Clinical transplantation [Clin Transplant] 2022 Nov; Vol. 36 (11), pp. e14818. Date of Electronic Publication: 2022 Sep 19.
Subjects
Humans, COVID-19 Vaccines, Antibody Formation, SARS-CoV-2, Transplant Recipients, Antibodies, Viral, COVID-19 epidemiology, COVID-19 prevention control, and Lung Transplantation

20. Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers. [2022]

  • Hakkaart C, Pearson JF, Marquart L, Dennis J, Wiggins GAR, Barnes DR, Robinson BA, Mace PD, Aittomäki K, Andrulis IL, Arun BK, Azzollini J, Balmaña J, Barkardottir RB, Belhadj S, Berger L, Blok MJ, Boonen SE, Borde J, Bradbury AR, Brunet J, Buys SS, Caligo MA, Campbell I, Chung WK, Claes KBM, Collonge-Rame MA, Cook J, Cosgrove C, Couch FJ, Daly MB, Dandiker S, Davidson R, de la Hoya M, de Putter R, Delnatte C, Dhawan M, Diez O, Ding YC, Domchek SM, Donaldson A, Eason J, Easton DF, Ehrencrona H, Engel C, Evans DG, Faust U, Feliubadaló L, Fostira F, Friedman E, Frone M, Frost D, Garber J, Gayther SA, Gehrig A, Gesta P, Godwin AK, Goldgar DE, Greene MH, Hahnen E, Hake CR, Hamann U, Hansen TVO, Hauke J, Hentschel J, Herold N, Honisch E, Hulick PJ, Imyanitov EN, Isaacs C, Izatt L, Izquierdo A, Jakubowska A, James PA, Janavicius R, John EM, Joseph V, Karlan BY, Kemp Z, Kirk J, Konstantopoulou I, Koudijs M, Kwong A, Laitman Y, Lalloo F, Lasset C, Lautrup C, Lazaro C, Legrand C, Leslie G, Lesueur F, Mai PL, Manoukian S, Mari V, Martens JWM, McGuffog L, Mebirouk N, Meindl A, Miller A, Montagna M, Moserle L, Mouret-Fourme E, Musgrave H, Nambot S, Nathanson KL, Neuhausen SL, Nevanlinna H, Yie JNY, Nguyen-Dumont T, Nikitina-Zake L, Offit K, Olah E, Olopade OI, Osorio A, Ott CE, Park SK, Parsons MT, Pedersen IS, Peixoto A, Perez-Segura P, Peterlongo P, Pocza T, Radice P, Ramser J, Rantala J, Rodriguez GC, Rønlund K, Rosenberg EH, Rossing M, Schmutzler RK, Shah PD, Sharif S, Sharma P, Side LE, Simard J, Singer CF, Snape K, Steinemann D, Stoppa-Lyonnet D, Sutter C, Tan YY, Teixeira MR, Teo SH, Thomassen M, Thull DL, Tischkowitz M, Toland AE, Trainer AH, Tripathi V, Tung N, van Engelen K, van Rensburg EJ, Vega A, Viel A, Walker L, Weitzel JN, Wevers MR, Chenevix-Trench G, Spurdle AB, Antoniou AC, and Walker LC
  • Communications biology [Commun Biol] 2022 Oct 06; Vol. 5 (1), pp. 1061. Date of Electronic Publication: 2022 Oct 06.
Subjects
BRCA1 Protein genetics, BRCA2 Protein genetics, DNA Copy Number Variations, Female, Genetic Predisposition to Disease, Heterozygote, Humans, RNA, Messenger, Breast Neoplasms genetics, and Breast Neoplasms pathology
Abstract
The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
(© 2022. The Author(s).)

21. Comprehensive Cardiovascular Magnetic Resonance-Derived Myocardial Strain Analysis Provides Independent Prognostic Value in Acute Myocarditis. [2022]

  • Vos JL, Raafs AG, van der Velde N, Germans T, Biesbroek PS, Roes K, Hirsch A, Heymans SRB, and Nijveldt R
  • Journal of the American Heart Association [J Am Heart Assoc] 2022 Oct 04; Vol. 11 (19), pp. e025106. Date of Electronic Publication: 2022 Sep 21.
Subjects
Arrhythmias, Cardiac, Contrast Media, Female, Gadolinium, Heart Atria, Humans, Magnetic Resonance Imaging, Cine methods, Magnetic Resonance Spectroscopy, Male, Predictive Value of Tests, Prognosis, Retrospective Studies, Stroke Volume, Ventricular Function, Left, Heart Failure, and Myocarditis diagnostic imaging
Abstract
Background Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life-threatening arrhythmias in acute myocarditis patients is limited. CMR-derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results In this multicenter retrospective study, patients with CMR-proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all-cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular-global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR-proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow-up of 5.5 (2.2-8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV-global longitudinal strain: hazard ratio [HR] 1.07, P =0.02; LV-global circumferential strain: HR 1.15, P =0.02; LV-global radial strain: HR 0.98, P =0.03), but right ventricular or left atrial strain did not predict outcome. Conclusions CMR-derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance.

22. Predicting a Positive Antibody Response After 2 SARS-CoV-2 mRNA Vaccines in Transplant Recipients: A Machine Learning Approach With External Validation. [2022]

  • Alejo JL, Mitchell J, Chiang TP, Chang A, Abedon AT, Werbel WA, Boyarsky BJ, Zeiser LB, Avery RK, Tobian AAR, Levan ML, Warren DS, Massie AB, Moore LW, Guha A, Huang HJ, Knight RJ, Gaber AO, Ghobrial RM, Garonzik-Wang JM, Segev DL, and Bae S
  • Transplantation [Transplantation] 2022 Oct 01; Vol. 106 (10), pp. e452-e460. Date of Electronic Publication: 2022 Jul 21.
Subjects
Antibodies, Viral, Antibody Formation, BNT162 Vaccine, Humans, Immunosuppressive Agents adverse effects, Machine Learning, Mycophenolic Acid, SARS-CoV-2, Vaccines, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention control, COVID-19 Vaccines adverse effects, and Transplant Recipients
Abstract
Background: Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations.
Methods: Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital.
Results: Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/ .
Conclusions: Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.
Competing Interests: D.L.S. has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific, Regeneron, and AstraZeneca. R.K.A. has grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, and Takeda/Shire. M.L.L. is the Social Media Editor for Transplantation and is a consultant for Takeda/Shire and Patients Like Me. The other authors declare no conflicts of interest.
(Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

23. Letter to the editor: Six-month antibody kinetics and durability in liver transplant recipients after two doses of SARS-CoV-2 mRNA vaccination. [2022]

  • Chang A, Strauss AT, Alejo JL, Chiang TP, Hernandez NF, Zeiser LB, Boyarsky BJ, Avery RK, Tobian AAR, Levan ML, Warren DS, Garonzik-Wang JM, Massie AB, Werbel WA, and Segev DL
  • Hepatology communications [Hepatol Commun] 2022 Oct; Vol. 6 (10), pp. 2990-2992. Date of Electronic Publication: 2022 Jul 05.
Subjects
Antibodies, Humans, Kinetics, RNA, Messenger, SARS-CoV-2 genetics, Vaccination, COVID-19 prevention control, and Liver Transplantation

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25. The impact of Mendelian sleep and circadian genetic variants in a population setting. [2022]

  • Weedon MN, Jones SE, Lane JM, Lee J, Ollila HM, Dawes A, Tyrrell J, Beaumont RN, Partonen T, Merikanto I, Rich SS, Rotter JI, Frayling TM, Rutter MK, Redline S, Sofer T, Saxena R, and Wood AR
  • PLoS genetics [PLoS Genet] 2022 Sep 22; Vol. 18 (9), pp. e1010356. Date of Electronic Publication: 2022 Sep 22 (Print Publication: 2022).
Subjects
Humans, Phenotype, Receptors, G-Protein-Coupled genetics, Sleep genetics, Circadian Rhythm genetics, and Sleep Wake Disorders genetics
Abstract
Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. No carriers for variants reported in NPSR1 or PER2 were identified. We found no association between variants analyzed and extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P = 4x10-8; and had a 57-minute earlier midpoint sleep, P = 5x10-7). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.
Competing Interests: The authors have declared that no competing interests exist.

26. Which drinkers have changed their alcohol consumption due to energy content concerns? An Australian survey. [2022]

  • Bowden J, Harrison NJ, Caruso J, Room R, Pettigrew S, Olver I, and Miller C
  • BMC public health [BMC Public Health] 2022 Sep 19; Vol. 22 (1), pp. 1775. Date of Electronic Publication: 2022 Sep 19.
Subjects
Adult, Australia epidemiology, Female, Humans, Male, Risk Factors, Surveys and Questionnaires, Alcohol Drinking epidemiology, and Diet
Abstract
Background: Alcohol is a discretionary, energy dense, dietary component. Compared to non-drinkers, people who consume alcohol report higher total energy intake and may be at increased risk of weight gain, overweight, and obesity, which are key preventable risk factors for illness. However, accurate consumer knowledge of the energy content in alcohol is low. To inform future behaviour change interventions among drinkers, this study investigated individual characteristics associated with changing alcohol consumption due to energy-related concerns.
Methods: An online survey was undertaken with 801 Australian adult drinkers (18-59 years, 50.2% female), i.e. who consumed alcohol at least monthly. In addition to demographic and health-related characteristics, participants reported past-year alcohol consumption, past-year reductions in alcohol consumption, frequency of harm minimisation strategy use (when consuming alcohol), and frequency of changing alcohol consumption behaviours because of energy-related concerns.
Results: When prompted, 62.5% of participants reported changing alcohol consumption for energy-related reasons at least 'sometimes'. Women, those aged 30-44 years, metropolitan residents, those with household income $80,001-120,000, and risky/more frequent drinkers had increased odds of changing consumption because of energy-related concerns, and unemployed respondents had reduced odds.
Conclusions: Results indicate that some sociodemographic groups are changing alcohol consumption for energy-related reasons, but others are not, representing an underutilised opportunity for health promotion communication. Further research should investigate whether messaging to increase awareness of alcohol energy content, including through systems-based policy actions such as nutritional/energy product labelling, would motivate reduced consumption across a broader range of drinkers.
(© 2022. The Author(s).)

27. Incidence and Severity of COVID-19 Among Vaccinated Solid Organ Transplant Recipients During the Omicron Wave. [2022]

  • Alejo JL, Chiang TPY, Bowles Zeiser L, Kim JD, Mitchell J, Avery RK, Tobian AAR, Abedon RR, Levan ML, Warren DS, Garonzik-Wang JM, Massie AB, Segev DL, and Werbel WA
  • Transplantation [Transplantation] 2022 Sep 01; Vol. 106 (9), pp. e413-e415. Date of Electronic Publication: 2022 Jun 03.
Subjects
Humans, Incidence, Transplant Recipients, COVID-19 epidemiology, COVID-19 prevention control, and Organ Transplantation adverse effects
Abstract
Competing Interests: D.L.S. has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific, Regeneron, and AstraZeneca. R.K.A. is an associate editor of Transplantation and has grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, and Takeda/Shire. M.L.L. is a Social Media Editor for Transplantation and receives consulting honoraria that are not related to her authorship of the article from Takeda/Patients Like Me. The other authors declare no conflicts of interest.

28. Immunogenicity of Ad26.COV2.S prime and two subsequent doses of mRNA SARS-CoV-2 vaccines in solid organ transplant recipients: A case series. [2022]

  • Chang A, Mitchell J, Alejo JL, Chiang TPY, Abedon AT, Kim JD, Avery RK, Tobian AAR, Levan ML, Warren DS, Garonzik-Wang JM, Massie AB, Segev DL, and Werbel WA
  • Clinical transplantation [Clin Transplant] 2022 Sep; Vol. 36 (9), pp. e14772. Date of Electronic Publication: 2022 Jul 19.
Subjects
Ad26COVS1, Antibodies, Viral, COVID-19 Vaccines, Humans, RNA, Messenger, SARS-CoV-2 genetics, Transplant Recipients, COVID-19 epidemiology, COVID-19 prevention control, and Organ Transplantation adverse effects

29. Heterologous Ad.26.COV2.S versus homologous BNT162b2/mRNA-1273 as a third dose in solid organ transplant recipients seronegative after two-dose mRNA vaccination. [2022]

  • Chiang TP, Alejo JL, Mitchell J, Kim JD, Abedon AT, Karaba AH, Thomas L, Levan ML, Garonzik-Wang JM, Avery RK, Pekosz A, Clarke WA, Warren DS, Tobian AAR, Massie AB, Segev DL, and Werbel WA
  • American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2022 Sep; Vol. 22 (9), pp. 2254-2260. Date of Electronic Publication: 2022 May 03.
Subjects
Antibodies, Viral, COVID-19 Vaccines adverse effects, Humans, RNA, Messenger genetics, SARS-CoV-2, Transplant Recipients, Vaccination, 2019-nCoV Vaccine mRNA-1273 adverse effects, BNT162 Vaccine adverse effects, COVID-19 epidemiology, COVID-19 prevention control, Influenza Vaccines, and Organ Transplantation adverse effects
Abstract
Heterologous vaccination ("mixing platforms") for the third (D3) dose of SARS-CoV-2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA-1273; D3-mRNA) versus heterologous (Ad.26.COV2.S; D3-JJ) D3 among 377 SARS-CoV-2-infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti-spike titers and used weighted Poisson regression to evaluate seroconversion and development of high-titers, comparing D3-JJ to D3-mRNA, at 1-, 3-, and 6 month post-D3. 1-month post-D3, seroconversion (63% vs. 52%, p = .3) and development of high-titers (29% vs. 25%, p = .7) were comparable between D3-JJ and D3-mRNA recipients. 3 month post-D3, D3-JJ recipients were 1.4-fold more likely to seroconvert (80% vs. 57%, weighted incidence-rate-ratio: wIRR =  1.10 1.40 1.77 , p = .006) but not more likely to develop high-titers (27% vs. 22%, wIRR =  0.44 0.92 1.93 , p = .8). 6 month post-D3, D3-JJ recipients were 1.41-fold more likely to seroconvert (88% vs. 59%, wIRR =  1.04 1.41 1.93 , p = .029) and 2.63-fold more likely to develop high-titers (59% vs. 21%, wIRR =  1.38 2.63 5.00 , p = .003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3.
(© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

30. 210.5: Differential Immunogenicity of mRNA-1273 Versus BNT162b2 as a Third Vaccine Dose for Solid Organ Transplant Recipients Seronegative After Two BNT162b2 Doses. [2022]

  • Chang, Amy, Chiang, Teresa PY, Alejo, Jennifer L, Mitchell, Jonathan, Kim, Jake D, Abedon, Aura T, Avery, Robin K, Tobian, Aaron AR, Massie, Allan B, Levan, Macey L, Warren, Daniel S, Garonzik-Wang, Jacqueline M, Segev, Dorry L, and Werbel, William A
  • Transplantation; September 2022, Vol. 106 Issue: 9, Number 9 Supplement 1 pS3-S3, 1p

31. 230.6: Ad.26.COV2.S Versus BNT162b2 or mRNA-1273 as a Third Dose in Solid Organ Transplant Recipients Seronegative After 2-dose mRNA Vaccination [2022]

  • Chiang, Teresa Po-Yu, Alejo, Jennifer L, Mitchell, Jonathan, Kim, Jake D, Abedon, Aura T, Karaba, Andrew H, Thomas, Letitia, Levan, Macey L, Garonzik-Wang, Jacqueline M, Avery, Robin K, Pekosz, Andrew, Clarke, William A, Warren, Daniel S, Tobian, Aaron AR, Massie, Allan B, Segev, Dorry L, and Werbel, William A
  • Transplantation; September 2022, Vol. 106 Issue: 9, Number 9 Supplement 1 pS71-S72, 2p

32. 330.4: SARS-coV-2 Antibody Response to a Third Dose of Homologous mRNA Vaccination in Liver Transplant Recipients [2022]

  • Chang, Amy, Strauss, Alexandra T, Alejo, Jennifer L, Chiang, Teresa PY, Hernandez, Nicole F, Zeiser, Laura B, Boyarsky, Brian J, Avery, Robin K, Tobian, Aaron AR, Levan, Macey L, Warren, Daniel S, Massie, Allan B, Garonzik-Wang, Jacqueline M, Segev, Dorry L, and Werbel, William A
  • Transplantation; September 2022, Vol. 106 Issue: 9, Number 9 Supplement 1 pS262-S263, 2p

33. 330.5: A Prediction Model for Antibody Response to Three Vaccines Against SARS-CoV-2 Among Solid Organ Transplant Recipients [2022]

  • Alejo, Jennifer, Chiang, Teresa PY, Mitchell, Jonathan, Kim, Jake D, Abedon, Aura T, Avery, Robin K, Tobian, Aaron AR, Garonzik-Wang, Jacqueline M, Warren, Daniel S, Segev, Dorry L, Werbel, William A, and Bae, Sunjae
  • Transplantation; September 2022, Vol. 106 Issue: 9, Number 9 Supplement 1 pS263-S264, 2p

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35. Virtual Ontogeny of Cortical Growth Preceding Mental Illness. [2022]

  • Patel Y, Shin J, Abé C, Agartz I, Alloza C, Alnæs D, Ambrogi S, Antonucci LA, Arango C, Arolt V, Auzias G, Ayesa-Arriola R, Banaj N, Banaschewski T, Bandeira C, Başgöze Z, Cupertino RB, Bau CHD, Bauer J, Baumeister S, Bernardoni F, Bertolino A, Bonnin CDM, Brandeis D, Brem S, Bruggemann J, Bülow R, Bustillo JR, Calderoni S, Calvo R, Canales-Rodríguez EJ, Cannon DM, Carmona S, Carr VJ, Catts SV, Chenji S, Chew QH, Coghill D, Connolly CG, Conzelmann A, Craven AR, Crespo-Facorro B, Cullen K, Dahl A, Dannlowski U, Davey CG, Deruelle C, Díaz-Caneja CM, Dohm K, Ehrlich S, Epstein J, Erwin-Grabner T, Eyler LT, Fedor J, Fitzgerald J, Foran W, Ford JM, Fortea L, Fuentes-Claramonte P, Fullerton J, Furlong L, Gallagher L, Gao B, Gao S, Goikolea JM, Gotlib I, Goya-Maldonado R, Grabe HJ, Green M, Grevet EH, Groenewold NA, Grotegerd D, Gruber O, Haavik J, Hahn T, Harrison BJ, Heindel W, Henskens F, Heslenfeld DJ, Hilland E, Hoekstra PJ, Hohmann S, Holz N, Howells FM, Ipser JC, Jahanshad N, Jakobi B, Jansen A, Janssen J, Jonassen R, Kaiser A, Kaleda V, Karantonis J, King JA, Kircher T, Kochunov P, Koopowitz SM, Landén M, Landrø NI, Lawrie S, Lebedeva I, Luna B, Lundervold AJ, MacMaster FP, Maglanoc LA, Mathalon DH, McDonald C, McIntosh A, Meinert S, Michie PT, Mitchell P, Moreno-Alcázar A, Mowry B, Muratori F, Nabulsi L, Nenadić I, O'Gorman Tuura R, Oosterlaan J, Overs B, Pantelis C, Parellada M, Pariente JC, Pauli P, Pergola G, Piarulli FM, Picon F, Piras F, Pomarol-Clotet E, Pretus C, Quidé Y, Radua J, Ramos-Quiroga JA, Rasser PE, Reif A, Retico A, Roberts G, Rossell S, Rovaris DL, Rubia K, Sacchet M, Salavert J, Salvador R, Sarró S, Sawa A, Schall U, Scott R, Selvaggi P, Silk T, Sim K, Skoch A, Spalletta G, Spaniel F, Stein DJ, Steinsträter O, Stolicyn A, Takayanagi Y, Tamm L, Tavares M, Teumer A, Thiel K, Thomopoulos SI, Tomecek D, Tomyshev AS, Tordesillas-Gutiérrez D, Tosetti M, Uhlmann A, Van Rheenen T, Vazquez-Bourgón J, Vernooij MW, Vieta E, Vilarroya O, Weickert C, Weickert T, Westlye LT, Whalley H, Willinger D, Winter A, Wittfeld K, Yang TT, Yoncheva Y, Zijlmans JL, Hoogman M, Franke B, van Rooij D, Buitelaar J, Ching CRK, Andreassen OA, Pozzi E, Veltman D, Schmaal L, van Erp TGM, Turner J, Castellanos FX, Pausova Z, Thompson P, and Paus T
  • Biological psychiatry [Biol Psychiatry] 2022 Aug 15; Vol. 92 (4), pp. 299-313. Date of Electronic Publication: 2022 Mar 04.
Subjects
Cerebral Cortex, Child, Female, Humans, Infant, Newborn, Magnetic Resonance Imaging methods, Pregnancy, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder genetics, Autism Spectrum Disorder pathology, Bipolar Disorder, Depressive Disorder, Major pathology, and Premature Birth pathology
Abstract
Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.
Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.
Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.
Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
(Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

36. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids. [2022]

  • Ramdas S, Judd J, Graham SE, Kanoni S, Wang Y, Surakka I, Wenz B, Clarke SL, Chesi A, Wells A, Bhatti KF, Vedantam S, Winkler TW, Locke AE, Marouli E, Zajac GJM, Wu KH, Ntalla I, Hui Q, Klarin D, Hilliard AT, Wang Z, Xue C, Thorleifsson G, Helgadottir A, Gudbjartsson DF, Holm H, Olafsson I, Hwang MY, Han S, Akiyama M, Sakaue S, Terao C, Kanai M, Zhou W, Brumpton BM, Rasheed H, Havulinna AS, Veturi Y, Pacheco JA, Rosenthal EA, Lingren T, Feng Q, Kullo IJ, Narita A, Takayama J, Martin HC, Hunt KA, Trivedi B, Haessler J, Giulianini F, Bradford Y, Miller JE, Campbell A, Lin K, Millwood IY, Rasheed A, Hindy G, Faul JD, Zhao W, Weir DR, Turman C, Huang H, Graff M, Choudhury A, Sengupta D, Mahajan A, Brown MR, Zhang W, Yu K, Schmidt EM, Pandit A, Gustafsson S, Yin X, Luan J, Zhao JH, Matsuda F, Jang HM, Yoon K, Medina-Gomez C, Pitsillides A, Hottenga JJ, Wood AR, Ji Y, Gao Z, Haworth S, Mitchell RE, Chai JF, Aadahl M, Bjerregaard AA, Yao J, Manichaikul A, Lee WJ, Hsiung CA, Warren HR, Ramirez J, Bork-Jensen J, Kårhus LL, Goel A, Sabater-Lleal M, Noordam R, Mauro P, Matteo F, McDaid AF, Marques-Vidal P, Wielscher M, Trompet S, Sattar N, Møllehave LT, Munz M, Zeng L, Huang J, Yang B, Poveda A, Kurbasic A, Schönherr S, Forer L, Scholz M, Galesloot TE, Bradfield JP, Ruotsalainen SE, Daw EW, Zmuda JM, Mitchell JS, Fuchsberger C, Christensen H, Brody JA, Le P, Feitosa MF, Wojczynski MK, Hemerich D, Preuss M, Mangino M, Christofidou P, Verweij N, Benjamins JW, Engmann J, Noah TL, Verma A, Slieker RC, Lo KS, Zilhao NR, Kleber ME, Delgado GE, Huo S, Ikeda DD, Iha H, Yang J, Liu J, Demirkan A, Leonard HL, Marten J, Emmel C, Schmidt B, Smyth LJ, Cañadas-Garre M, Wang C, Nakatochi M, Wong A, Hutri-Kähönen N, Sim X, Xia R, Huerta-Chagoya A, Fernandez-Lopez JC, Lyssenko V, Nongmaithem SS, Sankareswaran A, Irvin MR, Oldmeadow C, Kim HN, Ryu S, Timmers PRHJ, Arbeeva L, Dorajoo R, Lange LA, Prasad G, Lorés-Motta L, Pauper M, Long J, Li X, Theusch E, Takeuchi F, Spracklen CN, Loukola A, Bollepalli S, Warner SC, Wang YX, Wei WB, Nutile T, Ruggiero D, Sung YJ, Chen S, Liu F, Yang J, Kentistou KA, Banas B, Morgan A, Meidtner K, Bielak LF, Smith JA, Hebbar P, Farmaki AE, Hofer E, Lin M, Concas MP, Vaccargiu S, van der Most PJ, Pitkänen N, Cade BE, van der Laan SW, Chitrala KN, Weiss S, Bentley AR, Doumatey AP, Adeyemo AA, Lee JY, Petersen ERB, Nielsen AA, Choi HS, Nethander M, Freitag-Wolf S, Southam L, Rayner NW, Wang CA, Lin SY, Wang JS, Couture C, Lyytikäinen LP, Nikus K, Cuellar-Partida G, Vestergaard H, Hidalgo B, Giannakopoulou O, Cai Q, Obura MO, van Setten J, He KY, Tang H, Terzikhan N, Shin JH, Jackson RD, Reiner AP, Martin LW, Chen Z, Li L, Kawaguchi T, Thiery J, Bis JC, Launer LJ, Li H, Nalls MA, Raitakari OT, Ichihara S, Wild SH, Nelson CP, Campbell H, Jäger S, Nabika T, Al-Mulla F, Niinikoski H, Braund PS, Kolcic I, Kovacs P, Giardoglou T, Katsuya T, de Kleijn D, de Borst GJ, Kim EK, Adams HHH, Ikram MA, Zhu X, Asselbergs FW, Kraaijeveld AO, Beulens JWJ, Shu XO, Rallidis LS, Pedersen O, Hansen T, Mitchell P, Hewitt AW, Kähönen M, Pérusse L, Bouchard C, Tönjes A, Ida Chen YD, Pennell CE, Mori TA, Lieb W, Franke A, Ohlsson C, Mellström D, Cho YS, Lee H, Yuan JM, Koh WP, Rhee SY, Woo JT, Heid IM, Stark KJ, Zimmermann ME, Völzke H, Homuth G, Evans MK, Zonderman AB, Polasek O, Pasterkamp G, Hoefer IE, Redline S, Pahkala K, Oldehinkel AJ, Snieder H, Biino G, Schmidt R, Schmidt H, Bandinelli S, Dedoussis G, Thanaraj TA, Peyser PA, Kato N, Schulze MB, Girotto G, Böger CA, Jung B, Joshi PK, Bennett DA, De Jager PL, Lu X, Mamakou V, Brown M, Caulfield MJ, Munroe PB, Guo X, Ciullo M, Jonas JB, Samani NJ, Kaprio J, Pajukanta P, Tusié-Luna T, Aguilar-Salinas CA, Adair LS, Bechayda SA, de Silva HJ, Wickremasinghe AR, Krauss RM, Wu JY, Zheng W, den Hollander AI, Bharadwaj D, Correa A, Wilson JG, Lind L, Heng CK, Nelson AE, Golightly YM, Wilson JF, Penninx B, Kim HL, Attia J, Scott RJ, Rao DC, Arnett DK, Walker M, Scott LJ, Koistinen HA, Chandak GR, Mercader JM, Villalpando CG, Orozco L, Fornage M, Tai ES, van Dam RM, Lehtimäki T, Chaturvedi N, Yokota M, Liu J, Reilly DF, McKnight AJ, Kee F, Jöckel KH, McCarthy MI, Palmer CNA, Vitart V, Hayward C, Simonsick E, van Duijn CM, Jin ZB, Lu F, Hishigaki H, Lin X, März W, Gudnason V, Tardif JC, Lettre G, T Hart LM, Elders PJM, Rader DJ, Damrauer SM, Kumari M, Kivimaki M, van der Harst P, Spector TD, Loos RJF, Province MA, Parra EJ, Cruz M, Psaty BM, Brandslund I, Pramstaller PP, Rotimi CN, Christensen K, Ripatti S, Widén E, Hakonarson H, Grant SFA, Kiemeney L, de Graaf J, Loeffler M, Kronenberg F, Gu D, Erdmann J, Schunkert H, Franks PW, Linneberg A, Jukema JW, Khera AV, Männikkö M, Jarvelin MR, Kutalik Z, Francesco C, Mook-Kanamori DO, Willems van Dijk K, Watkins H, Strachan DP, Grarup N, Sever P, Poulter N, Huey-Herng Sheu W, Rotter JI, Dantoft TM, Karpe F, Neville MJ, Timpson NJ, Cheng CY, Wong TY, Khor CC, Li H, Sabanayagam C, Peters A, Gieger C, Hattersley AT, Pedersen NL, Magnusson PKE, Boomsma DI, de Geus EJC, Cupples LA, van Meurs JBJ, Ikram A, Ghanbari M, Gordon-Larsen P, Huang W, Kim YJ, Tabara Y, Wareham NJ, Langenberg C, Zeggini E, Tuomilehto J, Kuusisto J, Laakso M, Ingelsson E, Abecasis G, Chambers JC, Kooner JS, de Vries PS, Morrison AC, Hazelhurst S, Ramsay M, North KE, Daviglus M, Kraft P, Martin NG, Whitfield JB, Abbas S, Saleheen D, Walters RG, Holmes MV, Black C, Smith BH, Baras A, Justice AE, Buring JE, Ridker PM, Chasman DI, Kooperberg C, Tamiya G, Yamamoto M, van Heel DA, Trembath RC, Wei WQ, Jarvik GP, Namjou B, Hayes MG, Ritchie MD, Jousilahti P, Salomaa V, Hveem K, Åsvold BO, Kubo M, Kamatani Y, Okada Y, Murakami Y, Kim BJ, Thorsteinsdottir U, Stefansson K, Zhang J, Chen YE, Ho YL, Lynch JA, Tsao PS, Chang KM, Cho K, O'Donnell CJ, Gaziano JM, Wilson P, Mohlke KL, Frayling TM, Hirschhorn JN, Kathiresan S, Boehnke M, Struan Grant, Natarajan P, Sun YV, Morris AP, Deloukas P, Peloso G, Assimes TL, Willer CJ, Zhu X, and Brown CD
  • American journal of human genetics [Am J Hum Genet] 2022 Aug 04; Vol. 109 (8), pp. 1366-1387.
Subjects
Chromatin genetics, Genomics, Humans, Lipids genetics, Genome-Wide Association Study, and Polymorphism, Single Nucleotide genetics
Abstract
A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
Competing Interests: Declaration of interests G.C.-P. is currently an employee of 23andMe Inc. M.J.C. is the Chief Scientist for Genomics England, a UK Government company. B.M. Psaty serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. G. Thorleifsson, A.H., D.F.G., H. Holm, U.T., and K.S. are employees of deCODE/Amgen Inc. V.S. has received honoraria for consultations from Novo Nordisk and Sanofi and has an ongoing research collaboration with Bayer Ltd. M. McCarthy has served on advisory panels for Pfizer, NovoNordisk, and Zoe Global and has received honoraria from Merck, Pfizer, Novo Nordisk, and Eli Lilly and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. M. McCarthy and A. Mahajan are employees of Genentech and holders of Roche stock. M.S. receives funding from Pfizer Inc. for a project unrelated to this work. M.E.K. is employed by SYNLAB MVZ Mannheim GmbH. W.M. has received grants from Siemens Healthineers, grants and personal fees from Aegerion Pharmaceuticals, grants and personal fees from AMGEN, grants from Astrazeneca, grants and personal fees from Sanofi, grants and personal fees from Alexion Pharmaceuticals, grants and personal fees from BASF, grants and personal fees from Abbott Diagnostics, grants and personal fees from Numares AG, grants and personal fees from Berlin-Chemie, grants and personal fees from Akzea Therapeutics, grants from Bayer Vital GmbH , grants from bestbion dx GmbH, grants from Boehringer Ingelheim Pharma GmbH Co KG, grants from Immundiagnostik GmbH, grants from Merck Chemicals GmbH, grants from MSD Sharp and Dohme GmbH, grants from Novartis Pharma GmbH, grants from Olink Proteomics, and other from Synlab Holding Deutschland GmbH, all outside the submitted work. A.V.K. has served as a consultant to Sanofi, Medicines Company, Maze Pharmaceuticals, Navitor Pharmaceuticals, Verve Therapeutics, Amgen, and Color Genomics; received speaking fees from Illumina and the Novartis Institute for Biomedical Research; received sponsored research agreements from the Novartis Institute for Biomedical Research and IBM Research, and reports a patent related to a genetic risk predictor (20190017119). S. Kathiresan is an employee of Verve Therapeutics and holds equity in Verve Therapeutics, Maze Therapeutics, Catabasis, and San Therapeutics. He is a member of the scientific advisory boards for Regeneron Genetics Center and Corvidia Therapeutics; he has served as a consultant for Acceleron, Eli Lilly, Novartis, Merck, Novo Nordisk, Novo Ventures, Ionis, Alnylam, Aegerion, Haug Partners, Noble Insights, Leerink Partners, Bayer Healthcare, Illumina, Color Genomics, MedGenome, Quest, and Medscape; and he reports patents related to a method of identifying and treating a person having a predisposition to or afflicted with cardiometabolic disease (20180010185) and a genetics risk predictor (20190017119). D.K. accepts consulting fees from Regeneron Pharmaceuticals. D.O.M.-K. is a part-time clinical research consultant for Metabolon, Inc. D. Saleheen has received support from the British Heart Foundation, Pfizer, Regeneron, Genentech, and Eli Lilly pharmaceuticals. P.N. reports investigator-initated grants from Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis, personal fees from Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Novartis, Roche / Genentech, is a co-founder of TenSixteen Bio, is a scientific advisory board member of Esperion Therapeutics, geneXwell, and TenSixteen Bio, and spousal employment at Vertex, all unrelated to the present work. The spouse of C.J.W. is employed by Regeneron.
(Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

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38. Reduced calcium levels and accumulation of abnormal insulin granules in stem cell models of HNF1A deficiency. [2022]

  • González BJ, Zhao H, Niu J, Williams DJ, Lee J, Goulbourne CN, Xing Y, Wang Y, Oberholzer J, Blumenkrantz MH, Chen X, LeDuc CA, Chung WK, Colecraft HM, Gromada J, Shen Y, Goland RS, Leibel RL, and Egli D
  • Communications biology [Commun Biol] 2022 Aug 02; Vol. 5 (1), pp. 779. Date of Electronic Publication: 2022 Aug 02.
Subjects
Calcium metabolism, Hepatocyte Nuclear Factor 1-alpha genetics, Hepatocyte Nuclear Factor 1-alpha metabolism, Humans, Insulin, Regular, Human, Stem Cells metabolism, Synaptotagmins, Diabetes Mellitus, Type 2 genetics, and Insulin metabolism
Abstract
Mutations in HNF1A cause Maturity Onset Diabetes of the Young (HNF1A-MODY). To understand mechanisms of β-cell dysfunction, we generated stem cell-derived pancreatic endocrine cells with hypomorphic mutations in HNF1A. HNF1A-deficient β-cells display impaired basal and glucose stimulated-insulin secretion, reduced intracellular calcium levels in association with a reduction in CACNA1A expression, and accumulation of abnormal insulin granules in association with SYT13 down-regulation. Knockout of CACNA1A and SYT13 reproduce the relevant phenotypes. In HNF1A deficient β-cells, glibenclamide, a sulfonylurea drug used in the treatment of HNF1A-MODY patients, increases intracellular calcium, and restores insulin secretion. While insulin secretion defects are constitutive in β-cells null for HNF1A, β-cells heterozygous for hypomorphic HNF1A (R200Q) mutations lose the ability to secrete insulin gradually; this phenotype is prevented by correction of the mutation. Our studies illuminate the molecular basis for the efficacy of treatment of HNF1A-MODY with sulfonylureas, and suggest promise for the use of cell therapies.
(© 2022. The Author(s).)

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40. Improved humoral immunogenicity with mRNA-1273 versus BNT162b2 as third vaccine dose among solid organ transplant recipients seronegative after two BNT162b2 doses. [2022]

  • Chang A, Chiang TP, Kim JD, Mitchell J, Alejo JL, Jefferis AA, Avery RK, Tobian AAR, Levan ML, Warren DS, Garonzik-Wang JM, Massie AB, Segev DL, and Werbel WA
  • Clinical transplantation [Clin Transplant] 2022 Aug; Vol. 36 (8), pp. e14738. Date of Electronic Publication: 2022 Jun 14.
Subjects
2019-nCoV Vaccine mRNA-1273, Antibodies, Viral, BNT162 Vaccine, Humans, Transplant Recipients, Influenza Vaccines, and Organ Transplantation adverse effects

41. Severe acute respiratory syndrome coronavirus 2 antibody response to a third dose of homologous messenger RNA vaccination in liver transplantation recipients. [2022]

  • Strauss AT, Chang A, Alejo JL, Chiang TP, Hernandez NF, Zeiser LB, Boyarsky BJ, Avery RK, Tobian AAR, Levan ML, Warren DS, Massie AB, Garonzik-Wang JM, Segev DL, and Werbel WA
  • Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society [Liver Transpl] 2022 Aug; Vol. 28 (8), pp. 1393-1396. Date of Electronic Publication: 2022 May 09.
Subjects
Antibodies, Viral, Antibody Formation, Humans, RNA, Messenger, SARS-CoV-2 genetics, Transplant Recipients, Vaccination, COVID-19 prevention control, and Liver Transplantation adverse effects

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43. Levels of Parental Drinking in the Presence of Children: An Exploration of Attitudinal Correlates. [2022]

  • Bowden JA, Delfabbro P, Room R, Miller CL, and Wilson C
  • Alcohol and alcoholism (Oxford, Oxfordshire) [Alcohol Alcohol] 2022 Jul 09; Vol. 57 (4), pp. 460-469.
Subjects
Adult, Australia epidemiology, Child, Cross-Sectional Studies, Female, Humans, Parents, Alcohol Drinking epidemiology, and Alcoholic Intoxication
Abstract
Aims: This study aimed to examine perceived social norms, the effect of parental drinking on these norms, alcohol use in front of children, and how norms and consumption vary based on child age and gender of the parent.
Methods: A cross-sectional online panel survey was undertaken with n = 1000 Australian adults (including 670 parents) aged 18-59 years. The survey assessed: alcohol consumption in front of children; normative attitudes towards drinking in the presence of children; and perceived social norms.
Results: Overall, 33.9% of parents reported drinking a glass of alcohol each day or a couple of times a week, 18.2% reported getting slightly drunk and 7.8% indicated getting visibly drunk each day or a couple of times a week with their children present. In total, 37.5% reported drinking in front of their children at least weekly. Fathers were more likely to drink in front of children than mothers. Most parents deemed drinking small amounts of alcohol in front of children as acceptable but did not accept drunkenness. Respondents were less concerned about a father drinking one or two drinks in front of their children than a mother. Social expectations were not related to child age, but norms related to others' perceived behaviour were.
Conclusions: Many parents, particularly fathers consume alcohol in front of their children. There is a need to target health promotion strategies to adults and parents consuming in excess of health guidelines, and to the many parents who are consuming alcohol at higher levels in front of their children.
(© The Author(s) 2021. Medical Council on Alcohol and Oxford University Press.)

44. Antibody Response to a Fourth Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: An Update. [2022]

  • Mitchell J, Alejo JL, Chiang TPY, Kim J, Chang A, Abedon AT, Avery RK, Tobian AAR, Massie AB, Levan ML, Warren DS, Garonzik-Wang JM, Segev DL, and Werbel WA
  • Transplantation [Transplantation] 2022 Jul 01; Vol. 106 (7), pp. e338-e340. Date of Electronic Publication: 2022 Apr 15.
Subjects
Antibodies, Viral, Antibody Formation, COVID-19 Vaccines, Humans, SARS-CoV-2, Transplant Recipients, COVID-19 prevention control, and Organ Transplantation adverse effects
Abstract
Competing Interests: D.L.S. has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific, Regeneron, and AstraZeneca. R.K.A. has study/grant support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, Takeda/Shire, and Vir/GSK and is an Associate Reviewer for Transplantation. M.L.L. is the Social Media Editor for Transplantation. The other authors declare no conflicts of interest.

45. Levels of Parental Drinking in the Presence of Children: An Exploration of Attitudinal Correlates. [2022]

  • Bowden, Jacqueline A, Delfabbro, Paul, Room, Robin, Miller, Caroline L, and Wilson, Carlene
  • Alcohol & Alcoholism. Jul2022, Vol. 57 Issue 4, p460-469. 10p.
Subjects
MOTHERS, PARENT attitudes, SOCIAL norms, AGE distribution, CROSS-sectional method, INTERNET, FATHERS, SEX distribution, PARENTING, ALCOHOL drinking, DESCRIPTIVE statistics, PARENT-child relationships, and PARENTS
Abstract
Aims This study aimed to examine perceived social norms, the effect of parental drinking on these norms, alcohol use in front of children, and how norms and consumption vary based on child age and gender of the parent. Methods A cross-sectional online panel survey was undertaken with n  = 1000 Australian adults (including 670 parents) aged 18–59 years. The survey assessed: alcohol consumption in front of children; normative attitudes towards drinking in the presence of children; and perceived social norms. Results Overall, 33.9% of parents reported drinking a glass of alcohol each day or a couple of times a week, 18.2% reported getting slightly drunk and 7.8% indicated getting visibly drunk each day or a couple of times a week with their children present. In total, 37.5% reported drinking in front of their children at least weekly. Fathers were more likely to drink in front of children than mothers. Most parents deemed drinking small amounts of alcohol in front of children as acceptable but did not accept drunkenness. Respondents were less concerned about a father drinking one or two drinks in front of their children than a mother. Social expectations were not related to child age, but norms related to others' perceived behaviour were. Conclusions Many parents, particularly fathers consume alcohol in front of their children. There is a need to target health promotion strategies to adults and parents consuming in excess of health guidelines, and to the many parents who are consuming alcohol at higher levels in front of their children. [ABSTRACT FROM AUTHOR]

46. New Directions in Feminism and Global Race Studies: A Book Conversation. [2022]

  • Florvil, Tiffany N., Glover, Kaiama L., Joseph-Gabriel, Annette K., Marino, Katherine M., Mitchell, Robin, Mogoué, Jacqueline-Bethel, and Pinto, Samantha
  • Signs: Journal of Women in Culture & Society. Summer2022, Vol. 47 Issue 4, p1013-1040. 28p.
Subjects
BLACK feminism, HISTORY of feminism, FEMINISM, BLACK feminists, WORLD history, CONVERSATION, and RACISM
Abstract
This roundtable stems from a Zoom event, "New Directions in Feminism and Global Race Studies (a Book Conversation)" with authors Tiffany N. Florvil, Kaiama L. Glover, Annette K. Joseph-Gabriel, Katherine M. Marino, Robin Mitchell, and Jacqueline-Bethel Tchouta Mougoué, hosted by Samantha Pinto. These scholars discussed their recently published books, which expand how we think about transnational feminism and global Black feminisms in the Americas, the Caribbean, Africa, and Europe. The lightly edited transcript of the conversation explores how putting Black women at the center of histories of global feminisms and race studies transforms these fields and the questions that are usually asked. The authors also discussed navigating research challenges and confronting racism in the sources and in the archives. The conversation underscores the importance of intellectual community, as well as the relevance and urgency of Black feminist scholarship today. [ABSTRACT FROM AUTHOR]

47. Left Atrial Strain Has Superior Prognostic Value to Ventricular Function and Delayed-Enhancement in Dilated Cardiomyopathy. [2022]

  • Raafs AG, Vos JL, Henkens MTHM, Slurink BO, Verdonschot JAJ, Bossers D, Roes K, Gerretsen S, Knackstedt C, Hazebroek MR, Nijveldt R, and Heymans SRB
  • JACC. Cardiovascular imaging [JACC Cardiovasc Imaging] 2022 Jun; Vol. 15 (6), pp. 1015-1026. Date of Electronic Publication: 2022 May 11.
Subjects
Contrast Media, Female, Gadolinium, Heart Atria, Humans, Magnetic Resonance Imaging, Cine, Male, Middle Aged, Predictive Value of Tests, Prognosis, Stroke Volume, Ventricular Function, Left, Cardiomyopathy, Dilated, and Ventricular Dysfunction, Left
Abstract
Background: The left atrium is an early sensor of left ventricular (LV) dysfunction. Still, the prognostic value of left atrial (LA) function (strain) on cardiac magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown.
Objectives: The goal of this study was to evaluate the prognostic value of CMR-derived LA strain in DCM.
Methods: Patients with DCM from the Maastricht Cardiomyopathy Registry with available CMR imaging were included. The primary endpoint was the combination of sudden or cardiac death, heart failure (HF) hospitalization, or life-threatening arrhythmias. Given the nonlinearity of continuous variables, cubic spline analysis was performed to dichotomize.
Results: A total of 488 patients with DCM were included (median age: 54 [IQR: 46-62] years; 61% male). Seventy patients (14%) reached the primary endpoint (median follow-up: 6 [IQR: 4-9] years). Age, New York Heart Association (NYHA) functional class >II, presence of late gadolinium enhancement (LGE), LV ejection fraction (LVEF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.02). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, NYHA functional class >II, and LGE remained associated in the multivariable model (LA conduit strain HR: 3.65 [95% CI: 2.01-6.64; P < 0.001]; NYHA functional class >II HR: 1.81 [95% CI: 1.05-3.12; P = 0.033]; and LGE HR: 2.33 [95% CI: 1.42-3.85; P < 0.001]), whereas age, N-terminal pro-B-type natriuretic peptide, LVEF, left atrial ejection fraction, LAVI, and LV GLS were not. Adding LA conduit strain to other independent predictors (NYHA functional class and LGE) significantly improved the calibration, accuracy, and reclassification of the prediction model (P < 0.05).
Conclusions: LA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV GLS, LVEF, and LAVI and incremental to LGE. Including LA conduit strain in DCM patient management should be considered to improve risk stratification.
Competing Interests: Funding Support and Author Disclosures This study was supported by the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON She-PREDICTS, grant 2017-21, CVON-DCVA Double Dosis 2021. Dr Heymans has provided current and previous scientific advice to AstraZeneca, CellProthera, Novo Nordisk, Bayer, Pfizer, CSL Behring, and Merck on heart failure and cardiomyopathies. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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49. Combination Therapy With Casirivimab/Imdevimab and Remdesivir for Protracted SARS-CoV-2 Infection in B-cell-Depleted Patients. [2022]

  • Dioverti, M Veronica, Gaston, David C, Morris, C Paul, Huff, Carol Ann, Jain, Tania, Jones, Richard, Anders, Viki, Lederman, Howard, Saunders, Jacqueline, Mostafa, Heba H, and Avery, Robin K
  • Open Forum Infectious Diseases. Jun2022, Vol. 9 Issue 6, p1-5. 5p.
Subjects
COVID-19, SARS-CoV-2, and REMDESIVIR
Abstract
Profoundly B-cell-depleted patients can have prolonged severe acute respiratory syndrome coronavirus 2 infections with evidence of active viral replication, due to inability to mount an adequate humoral response to clear the virus. We present 3 B-cell-depleted patients with prolonged coronavirus disease 2019 infection who were successfully treated with a combination of casirivimab/imdevimab and remdesivir. [ABSTRACT FROM AUTHOR]

50. Should we "just stick to the facts"? The benefit of controversial conversations in classrooms. [2022]

  • Kraatz, Elizabeth, von Spiegel, Jacqueline, Sayers, Robin, and Brady, Anna C.
  • Theory Into Practice. Summer2022, Vol. 61 Issue 3, p312-324. 13p. 1 Chart.
Subjects
TEACHERS, TEACHING of controversial topics, STUDENTS, DISCUSSION in education, and SOCIAL conditions of students
Abstract
Controversial topics may be uncomfortable for teachers to include in their in-class discussions. However, there are considerable cognitive and social-emotional benefits to engagement in controversial conversations, or classroom discussion about controversial topics. It is critical that teachers support students in respectful discussion to help them develop skills such as problem solving, critical thinking, and the ability to consider issues from multiple perspectives. These skills can enable students to meet larger educational goals such as engaged citizenship. The goal of this article is to highlight the benefits of controversial conversations in the classroom and describe teaching approaches that facilitate effective controversial conversations. First, we identify important factors for teachers' consideration in supporting effective and beneficial controversial conversations. Second, we provide examples of topics of conversations that may be appropriate for students of varying ages. Third, we review how the structure of conversation, scaffolding, classroom context, relationships, and students' individual differences can shape controversial conversations. [ABSTRACT FROM AUTHOR]

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