TY - JOUR A1 - Werner, Rudolf A. A1 - Marcus, Charles A1 - Sheikhbahaei, Sara A1 - Solnes, Lilja B. A1 - Leal, Jeffrey P. A1 - Du, Yong A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. T1 - Visual and Semiquantitative Accuracy in Clinical Baseline 123I-Ioflupane SPECT/CT Imaging JF - Clinical Nuclear Medicine N2 - PURPOSE: We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists. METHODS: An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software. RESULTS: When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7%, ĸ = 0.75) compared to semiquantification (86.2%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found. CONCLUSIONS: In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment. KW - Single-Photon-Emissions-Computertomographie KW - SPECT KW - Parkinson’s disease KW - Parkinsonism KW - DaTscan KW - 123I-Ioflupane KW - SPECT KW - SPECT/CT Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168181 SN - 1536-0229 VL - 44 IS - 1 ER - TY - CHAP A1 - Werner, Rudolf A. A1 - Marcus, Charles A1 - Sheikhbahaei, Sara A1 - Higuchi, Takahiro A1 - Solnes, Lilja B. A1 - Rowe, Steven P. A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. T1 - The Impact of Ageing on Dopamine Transporter Imaging T2 - Journal of Nuclear Medicine N2 - No abstract available. KW - Parkinson-Krankheit KW - Parkinson KW - Parkinson Disease KW - DaTscan KW - Ioflupane KW - SPECT KW - molecular imaging KW - ageing Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162213 UR - http://jnm.snmjournals.org/content/59/supplement_1/1646.abstract SN - 0161-5505 N1 - This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. The Impact of Ageing on Dopamine Transporter Imaging. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:1646. © SNMMI. VL - 59 IS - Supplement No 1 SP - 1646 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Ordonez, Alvaro A. A1 - Sanchez-Bautista, Julian A1 - Marcus, Charles A1 - Lapa, Constantin A1 - Rowe, Steven P. A1 - Pomper, Martin G. A1 - Leal, Jeffrey P. A1 - Lodge, Martin A. A1 - Javadi, Mehrbod S. A1 - Jain, Sanjay K. A1 - Higuchi, Takahiro T1 - Novel functional renal PET imaging with 18F-FDS in human subjects JF - Clinical Nuclear Medicine N2 - The novel PET probe 2-deoxy-2-18F-fluoro-D-sorbitol (18F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in two human volunteers. 18F-FDS was produced by a simple one-step reduction from 18F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, 18F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from 18F-FDG, 18F-FDS is virtually available at any PET facility with radiochemistry infrastructure. KW - 2-deoxy-2-18F-fluoro-D-sorbitol KW - Positronen-Emissions-Tomografie KW - 18F-FDS KW - renal imaging KW - Positron-Emission Tomography KW - split renal function KW - kidney Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174634 SN - 0363-9762 VL - 44 IS - 5 ER - TY - JOUR A1 - Zannas, Anthony S. A1 - Arloth, Janine A1 - Carrillo-Roa, Tania A1 - Iurato, Stella A1 - Röh, Simone A1 - Ressler, Kerry J. A1 - Nemeroff, Charles B. A1 - Smith, Alicia K. A1 - Bradley, Bekh A1 - Heim, Christine A1 - Menke, Andreas A1 - Lange, Jennifer F. A1 - Brückl, Tanja A1 - Ising, Marcus A1 - Wray, Naomi R. A1 - Erhardt, Angelika A1 - Binder, Elisabeth B. A1 - Mehta, Divya T1 - Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling JF - Genome Biology N2 - Background Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. Results We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n = 392). This effect was primarily driven by personal life stressors, was more pronounced with advancing age, and was blunted in individuals with higher childhood abuse exposure. Hypothesizing that these epigenetic effects could be mediated by glucocorticoid signaling, we found that a high number (n = 85) of epigenetic clock CpG sites were located within glucocorticoid response elements. We further examined the functional effects of glucocorticoids on epigenetic clock CpGs in an independent sample with genome-wide DNA methylation (n = 124) and gene expression data (n = 297) before and after exposure to the glucocorticoid receptor agonist dexamethasone. Dexamethasone induced dynamic changes in methylation in 31.2 % (110/353) of these CpGs and transcription in 81.7 % (139/170) of genes neighboring epigenetic clock CpGs. Disease enrichment analysis of these dexamethasone-regulated genes showed enriched association for aging-related diseases, including coronary artery disease, arteriosclerosis, and leukemias. Conclusions Cumulative lifetime stress may accelerate epigenetic aging, an effect that could be driven by glucocorticoid-induced epigenetic changes. These findings contribute to our understanding of mechanisms linking chronic stress with accelerated aging and heightened disease risk. KW - aging KW - DNA methylation KW - gene expression KW - glucocorticoids KW - psychological stress KW - aging-related disease KW - epigenetics Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149865 VL - 16 IS - 266 ER - TY - JOUR A1 - Iyengar, Sudha K. A1 - Sedor, John R. A1 - Freedman, Barry I. A1 - Kao, W. H. Linda A1 - Kretzler, Matthias A1 - Keller, Benjamin J. A1 - Abboud, Hanna E. A1 - Adler, Sharon G. A1 - Best, Lyle G. A1 - Bowden, Donald W. A1 - Burlock, Allison A1 - Chen, Yii-Der Ida A1 - Cole, Shelley A. A1 - Comeau, Mary E. A1 - Curtis, Jeffrey M. A1 - Divers, Jasmin A1 - Drechsler, Christiane A1 - Duggirala, Ravi A1 - Elston, Robert C. A1 - Guo, Xiuqing A1 - Huang, Huateng A1 - Hoffmann, Michael Marcus A1 - Howard, Barbara V. A1 - Ipp, Eli A1 - Kimmel, Paul L. A1 - Klag, Michael J. A1 - Knowler, William C. A1 - Kohn, Orly F. A1 - Leak, Tennille S. A1 - Leehey, David J. A1 - Li, Man A1 - Malhotra, Alka A1 - März, Winfried A1 - Nair, Viji A1 - Nelson, Robert G. A1 - Nicholas, Susanne B. A1 - O’Brien, Stephen J. A1 - Pahl, Madeleine V. A1 - Parekh, Rulan S. A1 - Pezzolesi, Marcus G. A1 - Rasooly, Rebekah S. A1 - Rotimi, Charles N. A1 - Rotter, Jerome I. A1 - Schelling, Jeffrey R. A1 - Seldin, Michael F. A1 - Shah, Vallabh O. A1 - Smiles, Adam M. A1 - Smith, Michael W. A1 - Taylor, Kent D. A1 - Thameem, Farook A1 - Thornley-Brown, Denyse P. A1 - Truitt, Barbara J. A1 - Wanner, Christoph A1 - Weil, E. Jennifer A1 - Winkler, Cheryl A. A1 - Zager, Philip G. A1 - Igo, Jr, Robert P. A1 - Hanson, Robert L. A1 - Langefeld, Carl D. T1 - Genome-wide association and trans-ethnic meta-analysis for advanced diabetic kidney disease: Family Investigation of Nephropathy and Diabetes (FIND) JF - PLoS Genetics N2 - Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10\(^{−9}\)). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10\(^{−8}\)), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD. KW - diabetic kidney disease KW - genome-wide association study KW - Family Investigation of Nephropathy and Diabetes Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180545 VL - 11 IS - 8 ER - TY - JOUR A1 - Morton, Charles Oliver A1 - Fliesser, Mirjam A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Bauer, Ruth A1 - Kneitz, Susanne A1 - Hope, William A1 - Rogers, Thomas Richard A1 - Einsele, Hermann A1 - Löffler, Jürgen T1 - Gene Expression Profiles of Human Dendritic Cells Interacting with Aspergillus fumigatus in a Bilayer Model of the Alveolar Epithelium/Endothelium Interface N2 - The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549) and endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and myeloid DC (mDC), were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA. KW - aspergillus fumigatus KW - gene expression KW - immune receptors KW - immune response KW - denritic cells KW - B cell receptors KW - gene regulation KW - RNA extraction Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112893 ER - TY - CHAP A1 - Werner, Rudolf A. A1 - Marcus, Charles A1 - Sheikhbahaei, Sara A1 - Higuchi, Takahiro A1 - Solnes, Lilja B. A1 - Rowe, Steven P. A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. T1 - Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method T2 - Journal of Nuclear Medicine N2 - No abstract available. KW - Parkinson-Krankheit KW - SPECT KW - Parkinson KW - Parkinson Disease KW - DaTscan KW - Ioflupane KW - molecular imaging Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162208 UR - http://jnm.snmjournals.org/content/59/supplement_1/626.abstract SN - 0161-5505 N1 - This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:626. © SNMMI. VL - 59 IS - Supplement No. 1 SP - 626 ER - TY - JOUR A1 - Postema, Merel C. A1 - Hoogman, Martine A1 - Ambrosino, Sara A1 - Asherson, Philip A1 - Banaschewski, Tobias A1 - Bandeira, Cibele E. A1 - Baranov, Alexandr A1 - Bau, Claiton H.D. A1 - Baumeister, Sarah A1 - Baur‐Streubel, Ramona A1 - Bellgrove, Mark A. A1 - Biederman, Joseph A1 - Bralten, Janita A1 - Brandeis, Daniel A1 - Brem, Silvia A1 - Buitelaar, Jan K. A1 - Busatto, Geraldo F. A1 - Castellanos, Francisco X. A1 - Cercignani, Mara A1 - Chaim‐Avancini, Tiffany M. A1 - Chantiluke, Kaylita C. A1 - Christakou, Anastasia A1 - Coghill, David A1 - Conzelmann, Annette A1 - Cubillo, Ana I. A1 - Cupertino, Renata B. A1 - de Zeeuw, Patrick A1 - Doyle, Alysa E. A1 - Durston, Sarah A1 - Earl, Eric A. A1 - Epstein, Jeffery N. A1 - Ethofer, Thomas A1 - Fair, Damien A. A1 - Fallgatter, Andreas J. A1 - Faraone, Stephen V. A1 - Frodl, Thomas A1 - Gabel, Matt C. A1 - Gogberashvili, Tinatin A1 - Grevet, Eugenio H. A1 - Haavik, Jan A1 - Harrison, Neil A. A1 - Hartman, Catharina A. A1 - Heslenfeld, Dirk J. A1 - Hoekstra, Pieter J. A1 - Hohmann, Sarah A1 - Høvik, Marie F. A1 - Jernigan, Terry L. A1 - Kardatzki, Bernd A1 - Karkashadze, Georgii A1 - Kelly, Clare A1 - Kohls, Gregor A1 - Konrad, Kerstin A1 - Kuntsi, Jonna A1 - Lazaro, Luisa A1 - Lera‐Miguel, Sara A1 - Lesch, Klaus‐Peter A1 - Louza, Mario R. A1 - Lundervold, Astri J. A1 - Malpas, Charles B A1 - Mattos, Paulo A1 - McCarthy, Hazel A1 - Namazova‐Baranova, Leyla A1 - Nicolau, Rosa A1 - Nigg, Joel T. A1 - Novotny, Stephanie E. A1 - Oberwelland Weiss, Eileen A1 - O'Gorman Tuura, Ruth L. A1 - Oosterlaan, Jaap A1 - Oranje, Bob A1 - Paloyelis, Yannis A1 - Pauli, Paul A1 - Picon, Felipe A. A1 - Plessen, Kerstin J. A1 - Ramos‐Quiroga, J. Antoni A1 - Reif, Andreas A1 - Reneman, Liesbeth A1 - Rosa, Pedro G.P. A1 - Rubia, Katya A1 - Schrantee, Anouk A1 - Schweren, Lizanne J.S. A1 - Seitz, Jochen A1 - Shaw, Philip A1 - Silk, Tim J. A1 - Skokauskas, Norbert A1 - Soliva Vila, Juan C. A1 - Stevens, Michael C. A1 - Sudre, Gustavo A1 - Tamm, Leanne A1 - Tovar‐Moll, Fernanda A1 - van Erp, Theo G.M. A1 - Vance, Alasdair A1 - Vilarroya, Oscar A1 - Vives‐Gilabert, Yolanda A1 - von Polier, Georg G. A1 - Walitza, Susanne A1 - Yoncheva, Yuliya N. A1 - Zanetti, Marcus V. A1 - Ziegler, Georg C. A1 - Glahn, David C. A1 - Jahanshad, Neda A1 - Medland, Sarah E. A1 - Thompson, Paul M. A1 - Fisher, Simon E. A1 - Franke, Barbara A1 - Francks, Clyde T1 - Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets JF - Journal of Child Psychology and Psychiatry N2 - Objective Some studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait. KW - attention‐deficit KW - hyperactivity disorder KW - brain asymmetry KW - brain laterality KW - structural MRI KW - large‐scale data Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239968 VL - 62 IS - 10 SP - 1202 EP - 1219 ER -