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1. 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.)

2. 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.
(Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

3. 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).)

4. The Kaiser Permanente Northern California Advance Alert Monitor Program: An Automated Early Warning System for Adults at Risk for In-Hospital Clinical Deterioration. [2022]

  • Martinez VA, Betts RK, Scruth EA, Buckley JD, Cadiz VR, Bertrand LD, Paulson SS, Dummett BA, Abhyankar SS, Reyes VM, Hatton JR, Sulit R, and Liu VX
  • Joint Commission journal on quality and patient safety [Jt Comm J Qual Patient Saf] 2022 Aug; Vol. 48 (8), pp. 370-375.
Subjects
Adult, Artificial Intelligence, Hospitals, Humans, Inpatients, Monitoring, Physiologic, and Clinical Deterioration
Abstract
Background: In-hospital deterioration among ward patients is associated with substantially increased adverse outcome rates. In 2013 Kaiser Permanente Northern California (KPNC) developed and implemented a predictive analytics-driven program, Advance Alert Monitor (AAM), to improve early detection and intervention for in-hospital deterioration. The AAM predictive model is designed to give clinicians 12 hours of lead time before clinical deterioration, permitting early detection and a patient goals-concordant response to prevent worsening.
Design of the Aam Intervention: Across the 21 hospitals of the KPNC integrated health care delivery system, AAM analyzes electronic health record (EHR) data for patients in medical/surgical and telemetry units 24 hours a day, 7 days a week. Patients identified as high risk by the AAM algorithm trigger an alert for a regional team of experienced critical care virtual quality nurse consultants (VQNCs), who then cascade validated, actionable information to rapid response team (RRT) nurses at local hospitals. RRT nurses conduct bedside assessments of at-risk patients and formulate interdisciplinary clinical responses with hospital-based physicians, bedside nurses, and supportive care teams to ensure a well-defined escalation plan that includes clarification of the patients' goals of care.
Success of the Intervention: Since 2019 the AAM program has been implemented at all 21 KPNC hospitals. The use of predictive modeling embedded within the EHR to identify high-risk patients has produced the standardization of monitoring workflows, clinical rescue protocols, and coordination to ensure that care is consistent with patients' individual goals of care. An evaluation of the program, using a staggered deployment sequence over 19 hospitals, demonstrates that the AAM program is associated with statistically significant decreases in mortality (9.8% vs. 14.4%), hospital length of stay, and ICU length of stay. Statistical analyses estimated that more than 500 deaths were prevented each year with the AAM program.
Lessons Learned: Unlocking the potential of predictive modeling in the EHR is the first step toward realizing the promise of artificial intelligence/machine learning (AI/ML) to improve health outcomes. The AAM program leveraged predictive analytics to produce highly reliable care by identifying at-risk patients, preventing deterioration, and reducing adverse outcomes and can be used as a model for how clinical decision support and inpatient population management can effectively improve care.
(Copyright © 2022 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

5. 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

6. 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

7. 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 Jul 21. Date of Electronic Publication: 2022 Jul 21.
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.
(Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

8. 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 Jul 13, pp. e14772. Date of Electronic Publication: 2022 Jul 13.

9. 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.)

10. 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 Jul 05. Date of Electronic Publication: 2022 Jul 05.

11. 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

12. 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 Jun 03. Date of Electronic Publication: 2022 Jun 03.

13. Decade-long disease, secondary malignancy, and brainstem injury outcomes in pediatric and young adult medulloblastoma patients treated with proton radiotherapy. [2022]

  • Baliga S, Gallotto S, Bajaj B, Lewy J, Weyman E, Lawell MP, Yeap BY, Ebb DE, Huang M, Caruso P, Perry A, Jones RM, MacDonald SM, Tarbell NJ, and Yock TI
  • Neuro-oncology [Neuro Oncol] 2022 Jun 01; Vol. 24 (6), pp. 1010-1019.
Subjects
Brain Stem, Child, Cohort Studies, Humans, Protons, Young Adult, Cerebellar Neoplasms drug therapy, and Medulloblastoma drug therapy
Abstract
Background: Survivors of pediatric medulloblastoma experience long-term morbidity associated with the toxic effects of postoperative radiotherapy (RT). Proton RT limits radiation dose to normal tissues thereby reducing side effects of treatment while maintaining high cure rates. However, long-term data on disease outcomes and long-term effects of proton RT remain limited.
Methods: One hundred seventy-eight pediatric medulloblastoma patients treated with proton RT between 2002 and 2016 at the Massachusetts General Hospital comprise the cohort of patients who were treated with surgery, radiation therapy, and chemotherapy. We evaluated event-free survival (EFS), overall survival (OS), and local control using the Kaplan-Meier method. The cumulative incidence of brainstem injury and secondary malignancies was assessed.
Results: Median follow-up was 9.3 years. One hundred fifty-nine patients (89.3%) underwent a gross total resection (GTR). The 10-year OS for the entire cohort, standard-risk (SR), and intermediate/high-risk (IR/HR) patients was 79.3%, 86.9%, and 68.9%, respectively. The 10-year EFS for the entire cohort, SR, and IR/HR cohorts was 73.8%, 79.5%, and 66.2%. The 10-year EFS and OS for patients with GTR/NTR were 75.3% and 81.0% vs 57.7% and 61.0% for subtotal resection (STR). On univariate analysis, IR/HR status was associated with inferior EFS, while both anaplastic histology and IR/HR status were associated with worse OS. The 10-year cumulative incidence of secondary tumors and brainstem injury was 5.6% and 2.1%, respectively.
Conclusions: In this cohort study of pediatric medulloblastoma, proton RT was effective, and disease outcomes were comparable to historically treated photon cohorts. The incidence of secondary malignancies and brainstem injury was low in this cohort with mature follow-up.
(© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

14. 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.
(Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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

  • Dioverti MV, Gaston DC, Morris CP, Huff CA, Jain T, Jones R, Anders V, Lederman H, Saunders J, Mostafa HH, and Avery RK
  • Open forum infectious diseases [Open Forum Infect Dis] 2022 May 26; Vol. 9 (6), pp. ofac064. Date of Electronic Publication: 2022 May 26 (Print Publication: 2022).
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.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

16. Brain Imaging Abnormalities in Mixed Alzheimer's and Subcortical Vascular Dementia. [2022]

  • Lee H, Wiggermann V, Rauscher A, Kames C, Beg MF, Popuri K, Tam R, Lam K, Jacova C, Shahinfard E, Sossi V, Pettersen JA, and Hsiung GR
  • The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques [Can J Neurol Sci] 2022 May 26, pp. 1-14. Date of Electronic Publication: 2022 May 26.
Abstract
Background: A large proportion of Alzheimer's disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity.
Objective: To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD.
Methods: We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures.
Results: Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD).
Conclusion: These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

17. A novel air microfluidics-enabled soft robotic sleeve: Toward realizing innovative lymphedema treatment. [2022]

  • Gao RZ, Mai VNT, Levinski N, Kormylo JM, Murdock RW, Dickerson CR, and Ren CL
  • Biomicrofluidics [Biomicrofluidics] 2022 May 03; Vol. 16 (3), pp. 034101. Date of Electronic Publication: 2022 May 03 (Print Publication: 2022).
Abstract
A proof of concept of a novel air microfluidics-enabled soft robotic sleeve to enable lymphedema treatment is presented. Compression sleeves represent the current, suboptimal standard of care, and stationary pumps assist with lymph drainage; however, effective systems that are truly wearable while performing daily activities are very scarce. This problematic trade-off between performance and wearability requires a new solution, which is addressed by an innovative microfluidic device. Its novelty lies in the use of light, small, and inexpensive air microfluidic chips (35 × 20 × 5 mm 3 in size) that bring three major advantages compared to their traditional counterparts. First, each chip is designed with 16 fluidic channels with a cross-sectional area varying from 0.04 to 1 mm 2 , providing sequential inflation and uniform deflation capability to eight air bladders, thereby producing intentional gradient compression to the arm to facilitate lymph fluid circulation. The design is derived from the fundamentals of microfluidics, in particular, hydraulic resistance and paths of least resistance. Second, the air microfluidic chip enables miniaturization of at least eight bulky energy-consuming valves to two miniature solenoid valves for control increasing wearability. Third, the air microfluidic chip has no moving parts, which reduces the noise and energy needed. The cost, simplicity, and scale-up potential of developing methods for making the system are also detailed. The sequential inflation, uniform deflation, and pressure gradient are demonstrated, and the resulted compression and internal air bladder pressure were evaluated. This air microfluidics-enabled sleeve presents tremendous potential toward future improvements in self-care lymphedema management.
(© 2022 Author(s).)

18. Improved Antibody Response After a Fifth Dose of a SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series. [2022]

  • Abedon AT, Teles MS, Alejo JL, Kim JD, Mitchell J, Chiang TPY, Avery RK, Tobian AAR, Levan ML, Warren DS, Massie AB, Garonzik-Wang JM, Segev DL, and Werbel WA
  • Transplantation [Transplantation] 2022 May 01; Vol. 106 (5), pp. e262-e263. Date of Electronic Publication: 2022 Feb 15.
Subjects
Antibodies, Viral, Antibody Formation, COVID-19 Vaccines, Humans, SARS-CoV-2, Transplant Recipients, COVID-19 prevention control, and Organ Transplantation adverse effects

19. Humoral and Cellular Immune Response to a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients Taking Belatacept. [2022]

  • Mitchell J, Kim J, Alejo JL, Chiang TP, Karaba AH, Blankson JN, Aytenfisu TY, Chang A, Abedon AT, Avery RK, Tobian AA, Massie AB, Levan ML, Warren DS, Garonzik-Wang JM, Segev DL, and Werbel WA
  • Transplantation [Transplantation] 2022 May 01; Vol. 106 (5), pp. e264-e265. Date of Electronic Publication: 2022 Mar 14.
Subjects
Abatacept therapeutic use, Antibodies, Viral, COVID-19 Vaccines, Humans, Immunity, Cellular, SARS-CoV-2, Transplant Recipients, COVID-19 prevention control, and Kidney Transplantation adverse effects

20. Effect of Mycophenolate Mofetil Dosing on Antibody Response to SARS-CoV-2 Vaccination in Heart and Lung Transplant Recipients. [2022]

  • Mitchell J, Chiang TP, Alejo JL, 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 May 01; Vol. 106 (5), pp. e269-e270. Date of Electronic Publication: 2022 Mar 03.
Subjects
Antibodies, Viral, Antibody Formation, COVID-19 Vaccines, Humans, Immunosuppressive Agents adverse effects, Lung, Mycophenolic Acid, SARS-CoV-2, Vaccination, COVID-19 prevention control, and Transplant Recipients

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