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"text": "\n171858\nGenetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.\n\nChauhan, G\n\nAdams, HHH\n\nSatizabal, CL\n\nBis, JC\n\nTeumer, A\n\nSargurupremraj, M\n\nHofer, E\n\nTrompet, S\n\nHilal, S\n\nSmith, AV\n\nJian, X\n\nMalik, R\n\nTraylor, M\n\nPulit, SL\n\nAmouyel, P\n\nMazoyer, B\n\nZhu, YC\n\nKaffashian, S\n\nSchilling, S\n\nBeecham, GW\n\nMontine, TJ\n\nSchellenberg, GD\n\nKjartansson, O\n\nGuðnason, V\n\nKnopman, DS\n\nGriswold, ME\n\nWindham, BG\n\nGottesman, RF\n\nMosley, TH\n\nSchmidt, R\n\nSaba, Y\n\nSchmidt, H\n\nTakeuchi, F\n\nYamaguchi, S\n\nNabika, T\n\nKato, N\n\nRajan, KB\n\nAggarwal, NT\n\nDe Jager, PL\n\nEvans, DA\n\nPsaty, BM\n\nRotter, JI\n\nRice, K\n\nLopez, OL\n\nLiao, J\n\nChen, C\n\nCheng, CY\n\nWong, TY\n\nIkram, MK\n\nvan der Lee, SJ\n\nAmin, N\n\nChouraki, V\n\nDeStefano, AL\n\nAparicio, HJ\n\nRomero, JR\n\nMaillard, P\n\nDeCarli, C\n\nWardlaw, JM\n\nHernández, MDCV\n\nLuciano, M\n\nLiewald, D\n\nDeary, IJ\n\nStarr, JM\n\nBastin, ME\n\nMuñoz Maniega, S\n\nSlagboom, PE\n\nBeekman, M\n\nDeelen, J\n\nUh, HW\n\nLemmens, R\n\nBrodaty, H\n\nWright, MJ\n\nAmes, D\n\nBoncoraglio, GB\n\nHopewell, JC\n\nBeecham, AH\n\nBlanton, SH\n\nWright, CB\n\nSacco, RL\n\nWen, W\n\nThalamuthu, A\n\nArmstrong, NJ\n\nChong, E\n\nSchofield, PR\n\nKwok, JB\n\nvan der Grond, J\n\nStott, DJ\n\nFord, I\n\nJukema, JW\n\nVernooij, MW\n\nHofman, A\n\nUitterlinden, AG\n\nvan der Lugt, A\n\nWittfeld, K\n\nGrabe, HJ\n\nHosten, N\n\nvon Sarnowski, B\n\nVölker, U\n\nLevi, C\n\nJimenez-Conde, J\n\nSharma, P\n\nSudlow, CLM\n\nRosand, J\n\nWoo, D\n\nCole, JW\n\nMeschia, JF\n\nSlowik, A\n\nThijs, V\n\nLindgren, A\n\nMelander, O\n\nGrewal, RP\n\nRundek, T\n\nRexrode, K\n\nRothwell, PM\n\nArnett, DK\n\nJern, C\n\nJohnson, JA\n\nBenavente, OR\n\nWasssertheil-Smoller, S\n\nLee, JM\n\nWong, Q\n\nMitchell, BD\n\nRich, SS\n\nMcArdle, PF\n\nGeerlings, MI\n\nvan der Graaf, Y\n\nde Bakker, PIW\n\nAsselbergs, FW\n\nSrikanth, V\n\nThomson, R\n\nMcWhirter, R\n\nMoran, C\n\nCallisaya, M\n\nPhan, T\n\nRutten-Jacobs, LCA\n\nBevan, S\n\nTzourio, C\n\nMather, KA\n\nSachdev, PS\n\nvan Duijn, CM\n\nWorrall, BB\n\nDichgans, M\n\nKittner, SJ\n\nMarkus, HS\n\nIkram, MA\n\nFornage, M\n\nLauner, LJ\n\nSeshadri, S\n\nLongstreth, WT\n\nDebette, S\n\nStroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer's Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium\n\nBeiträge in Fachzeitschriften\nISI:000462547500009\n30651383.0\n10.1212/WNL.0000000000006851\nPMC6369905\nTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.\n We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20, 49) from 5 ethnicities (3, 26 with BI, 2, 21 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6, 62; 1, 83 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.\n The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 × 10-25; p[SSBI] = 5.23 × 10-14 for hypertension), smoking (p[BI] = 4.4 × 10-10; p[SSBI] = 1.2 × 10-4), diabetes (p[BI] = 1.7 × 10-8; p[SSBI] = 2.8 × 10-3), previous cardiovascular disease (p[BI] = 1.0 × 10-18; p[SSBI] = 2.3 × 10-7), stroke (p[BI] = 3.9 × 10-69; p[SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p[BI] = 1.43 × 10-157; p[SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy.\n In this multiethnic GWAS meta-analysis, including over 20, 00 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.\n Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.\n\nHofer, Edith\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n181828\nEuropean Position Paper on Rhinosinusitis and Nasal Polyps 2020.\n\nFokkens, WJ\n\nLund, VJ\n\nHopkins, C\n\nHellings, PW\n\nKern, R\n\nReitsma, S\n\nToppila-Salmi, S\n\nBernal-Sprekelsen, M\n\nMullol, J\n\nAlobid, I\n\nTerezinha Anselmo-Lima, W\n\nBachert, C\n\nBaroody, F\n\nvon Buchwald, C\n\nCervin, A\n\nCohen, N\n\nConstantinidis, J\n\nDe Gabory, L\n\nDesrosiers, M\n\nDiamant, Z\n\nDouglas, RG\n\nGevaert, PH\n\nHafner, A\n\nHarvey, RJ\n\nJoos, GF\n\nKalogjera, L\n\nKnill, A\n\nKocks, JH\n\nLandis, BN\n\nLimpens, J\n\nLebeer, S\n\nLourenco, O\n\nMeco, C\n\nMatricardi, PM\n\nO'Mahony, L\n\nPhilpott, CM\n\nRyan, D\n\nSchlosser, R\n\nSenior, B\n\nSmith, TL\n\nTeeling, T\n\nTomazic, PV\n\nWang, DY\n\nWang, D\n\nZhang, L\n\nAgius, AM\n\nAhlstrom-Emanuelsson, C\n\nAlabri, R\n\nAlbu, S\n\nAlhabash, S\n\nAleksic, A\n\nAloulah, M\n\nAl-Qudah, M\n\nAlsaleh, S\n\nBaban, MA\n\nBaudoin, T\n\nBalvers, T\n\nBattaglia, P\n\nBedoya, JD\n\nBeule, A\n\nBofares, KM\n\nBraverman, I\n\nBrozek-Madry, E\n\nRichard, B\n\nCallejas, C\n\nCarrie, S\n\nCaulley, L\n\nChussi, D\n\nde Corso, E\n\nCoste, A\n\nEl Hadi, U\n\nElfarouk, A\n\nEloy, PH\n\nFarrokhi, S\n\nFelisati, G\n\nFerrari, MD\n\nFishchuk, R\n\nGrayson, W\n\nGoncalves, PM\n\nGrdinic, B\n\nGrgic, V\n\nHamizan, AW\n\nHeinichen, JV\n\nHusain, S\n\nPing, TI\n\nIvaska, J\n\nJakimovska, F\n\nJovancevic, L\n\nKakande, E\n\nKamel, R\n\nKarpischenko, S\n\nKariyawasam, HH\n\nKawauchi, H\n\nKjeldsen, A\n\nKlimek, L\n\nKrzeski, A\n\nKopacheva Barsova, G\n\nKim, SW\n\nLal, D\n\nLetort, JJ\n\nLopatin, A\n\nMahdjoubi, A\n\nMesbahi, A\n\nNetkovski, J\n\nNyenbue Tshipukane, D\n\nObando-Valverde, A\n\nOkano, M\n\nOnerci, M\n\nOng, YK\n\nOrlandi, R\n\nOtori, N\n\nOuennoughy, K\n\nOzkan, M\n\nPeric, A\n\nPlzak, J\n\nProkopakis, E\n\nPrepageran, N\n\nPsaltis, A\n\nPugin, B\n\nRaftopulos, M\n\nRombaux, P\n\nRiechelmann, H\n\nSahtout, S\n\nSarafoleanu, CC\n\nSearyoh, K\n\nRhee, CS\n\nShi, J\n\nShkoukani, M\n\nShukuryan, AK\n\nSicak, M\n\nSmyth, D\n\nSnidvongs, K\n\nSoklic Kosak, T\n\nStjarne, P\n\nSutikno, B\n\nSteinsvag, S\n\nTantilipikorn, P\n\nThanaviratananich, S\n\nTran, T\n\nUrbancic, J\n\nValiulius, A\n\nVasquez de Aparicio, C\n\nVicheva, D\n\nVirkkula, PM\n\nVicente, G\n\nVoegels, R\n\nWagenmann, MM\n\nWardani, RS\n\nWelge-Lussen, A\n\nWitterick, I\n\nWright, E\n\nZabolotniy, D\n\nZsolt, B\n\nZwetsloot, CP\n\nBeiträge in Fachzeitschriften\nISI:000595290600001\n32077450.0\n10.4193/Rhin20.600\nNone\nThe European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.\n\nTomazic, Peter Valentin\n\n\n"
},
{
"text": "\n187001\nAssociation of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.\n\nGenetics of Exfoliation Syndrome Partnership\n\nLi, Z\n\nWang, Z\n\nLee, MC\n\nZenkel, M\n\nPeh, E\n\nOzaki, M\n\nTopouzis, F\n\nNakano, S\n\nChan, A\n\nChen, S\n\nWilliams, SEI\n\nOrr, A\n\nNakano, M\n\nKobakhidze, N\n\nZarnowski, T\n\nPopa-Cherecheanu, A\n\nMizoguchi, T\n\nManabe, SI\n\nHayashi, K\n\nKazama, S\n\nInoue, K\n\nMori, Y\n\nMiyata, K\n\nSugiyama, K\n\nHigashide, T\n\nChihara, E\n\nIdeta, R\n\nIshiko, S\n\nYoshida, A\n\nTokumo, K\n\nKiuchi, Y\n\nOhashi, T\n\nSakurai, T\n\nSugimoto, T\n\nChuman, H\n\nAihara, M\n\nInatani, M\n\nMori, K\n\nIkeda, Y\n\nUeno, M\n\nGaston, D\n\nRafuse, P\n\nShuba, L\n\nSaunders, J\n\nNicolela, M\n\nChichua, G\n\nTabagari, S\n\nFounti, P\n\nSim, KS\n\nMeah, WY\n\nSoo, HM\n\nChen, XY\n\nChatzikyriakidou, A\n\nKeskini, C\n\nPappas, T\n\nAnastasopoulos, E\n\nLambropoulos, A\n\nPanagiotou, ES\n\nMikropoulos, DG\n\nKosior-Jarecka, E\n\nCheong, A\n\nLi, Y\n\nLukasik, U\n\nNongpiur, ME\n\nHusain, R\n\nPerera, SA\n\nÁlvarez, L\n\nGarcía, M\n\nGonzález-Iglesias, H\n\nFernández-Vega Cueto, A\n\nFernández-Vega Cueto, L\n\nMartinón-Torres, F\n\nSalas, A\n\nOguz, Ç\n\nTamcelik, N\n\nAtalay, E\n\nBatu, B\n\nIrkec, M\n\nAktas, D\n\nKasim, B\n\nAstakhov, YS\n\nAstakhov, SY\n\nAkopov, EL\n\nGiessl, A\n\nMardin, C\n\nHellerbrand, C\n\nCooke Bailey, JN\n\nIgo, RP\n\nHaines, JL\n\nEdward, DP\n\nHeegaard, S\n\nDavila, S\n\nTan, P\n\nKang, JH\n\nPasquale, LR\n\nKruse, FE\n\nReis, A\n\nCarmichael, TR\n\nHauser, M\n\nRamsay, M\n\nMossböck, G\n\nYildirim, N\n\nTashiro, K\n\nKonstas, AGP\n\nCoca-Prados, M\n\nFoo, JN\n\nKinoshita, S\n\nSotozono, C\n\nKubota, T\n\nDubina, M\n\nRitch, R\n\nWiggs, JL\n\nPasutto, F\n\nSchlötzer-Schrehardt, U\n\nHo, YS\n\nAung, T\n\nTam, WL\n\nKhor, CC\n\nBeiträge in Fachzeitschriften\nISI:000621957400024\n33620406.0\n10.1001/jama.2021.0507\nPMC7903258\nExfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness.\n To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function.\n A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome.\n Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function.\n The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses.\n The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome.\n In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.\n\n\n"
},
{
"text": "\n179733\nExaminations of Factors Influencing Survival of Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience From Budapest.\n\nPiros, L\n\nFehérvári, I\n\nGörög, D\n\nNemes, B\n\nSzabó, J\n\nGerlei, Z\n\nVégső, G\n\nKóbori, L\n\nMáthé, Z\n\nBeiträge in Fachzeitschriften\nISI:000361644000031\n26361680.0\n10.1016/j.transproceed.2015.07.026\nNone\nHepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Orthotopic liver transplantation (OLT) is the best therapy of choice for early, unresectable HCC. The Hungarian Liver Transplantation Program was launched in 1995 at the Department of Transplantation and Surgery, Semmelweis University, Budapest. From that time more than 60 patients underwent OLT for hepatic tumors, which in most cases were HCC. Our clinical examination was undertaken to analyze the possible influential factors of outcomes for our series of patients who received OLT for HCC.\n We performed a review of all patients who underwent OLT for HCC at our department from 1996 to October 1, 2013. Disease extent was determined by preoperative computed tomography or magnetic resonance images. All explants were examined and categorized based on tumor number, size, distribution, HCC histologic grade, and vascular invasion. Patients with HCC were classified as having tumors either meeting Milan criteria, beyond Milan criteria but within UCSF criteria, or exceeding UCSF criteria. OLT was performed using standard techniques including orthotopic implantation with cross-clamp technique or with the piggyback technique. Postoperative immunosuppression included a triple drug regimen of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone. mTOR inhibitors have been available since 2004.\n HCC most commonly occurs in the presence of cirrhosis as a result of longstanding chronic liver disease. Most of our patients who underwent OLT for HCC are 56 to 60 years old, and most also had underlying HCV cirrhosis. As of October 1, 2013, 21 of 49 (42.85%) patients had died after OLT for HCC. The main cause was the recurrence of the HCC in 38%, followed by sepsis in 33%, and HCV recurrence in 19%. One death each (4.7% of the total number of deaths) was caused by primary nonfunction of the graft, acute myocardial infarct, and de novo malignancy, respectively. Overall survival for the entire group at 1, 3, and 5 years after transplantation was 73.48%, 65.2%, and 50.08%, respectively. Using pretransplant imaging, 34 tumors (69.3%) were within Milan criteria, 8 (16.3%) were beyond Milan but within UCSF criteria, and 7 (14.3%) exceeded UCSF criteria. Based on explant pathology, 30 tumors (61.2%) were within Milan criteria, 7 (14, %) were beyond Milan but within UCSF criteria, and 12 (24.3%) exceeded UCSF criteria. New onset, non-HCC malignant tumor developed in 2 cases (4%). There was no significant difference between the surgical techniques or the immunosuppressive strategies. Using the Cox analysis in our series, it can be seen that mortality was higher with tumors exceeding Milan criteria but within UCSF criteria compared with tumors within Milan criteria (Coef. = 0.5749 in Setting 1 and 0.1226 in Setting 2), and even higher with tumors beyond UCSF criteria compared with tumors within Milan criteria (Coef. = 0.7228 in Setting 1 and 0.1456 in Setting 2). Recurrence of the tumor causes higher mortality (Coef. = 1.709 in Setting 1 and 1.0256 in Setting 2). It seems that using an mTOR inhibitor has a beneficial impact on mortality (Coef. = -1.409 in Setting 1). Vascular invasion was associated with higher mortality (Coef. = 0.6581in Setting 1). Higher AFP levels correlated with higher mortality but not significantly (Coef. = 0.0002 in Setting 2). In our series, survival after OLT for HCC was best with tumors within Milan criteria comparing those exceeded Milan criteria (odds ratio = 4.000).\n According to our findings, the Milan criteria are still the safest criteria system; however, slightly expanded criteria do not have significantly worse results. Preoperative imaging methods sometimes show fewer or smaller tumors, and the explant histology reports the exact staging of HCC at the time of OLT. Histological examination especially of the lymphovascular invasion is mandatory to assess the estimated prognosis. Extremely high levels of AFP mean higher risk. HCC recurrence is an important factor on the outcome; therefore, continuous oncologic screening is mandatory. Immunosuppressant agents are chiefly responsible not just for higher risk of recurrence but for higher risk to develop de novo malignancies. Viral serology must be done periodically to catch HCV recurrence in time and begin adequate antiviral therapy. Potentially, mTOR inhibitors could be potent immunosuppressive agents after OLT for HCC due to this antiproliferative effect.\n Copyright © 2015 Elsevier Inc. All rights reserved.\n\n\n"
},
{
"text": "\n88112\nAnterior cruciate ligament reconstruction with semitendinosus tendon in children\n\nSchneider, FJ\n\nKraus, T\n\nLinhart, WE\n\nBeiträge in Fachzeitschriften\nISI:000262786200012\n19169783.0\n10.1007/s00064-008-1412-x\nNone\nTo present the technique of arthroscopy-assisted anterior cruciate ligament (ACL) reconstruction in children with complete ACL rupture. The indications for surgery are intraligamentous ruptures of the ACL with persistent signs and symptoms due to instability in spite of a minimum 6-month trial with conservative management and reduction of sports activities. Other decision-making factors for surgery include secondary injuries to the menisci or limitation of daily activities due to the instability produced by the ACL rupture. The indication for surgical intervention has to be judged individually and carefully in younger children. Poor compliance on the part of the patient to participate in postoperative rehabilitation. Overexpectations regarding the surgical outcome (ability to participate in professional sports without limitations). Younger age of the patient (Tanner stage 2 or younger maturity), without trial of conservative treatment over a period of 6 months. ACL rupture at the bone-ligament region (tibial or femoral), partial rupture or lengthening of the ACL without rupture; in these instances, the instability may improve with growth. Diagnostic arthroscopy to evaluate the knee joint and to identify associated or secondary injuries to the menisci and articular cartilage. If possible, these injuries should be addressed in the same surgical session. Preparation and stripping of the semitendinosus tendon using a tendon stripper. The technique used is transepiphyseal with extraosseous fixation. Depending on the thickness, the semitendinosus tendon is either tripled or quadrupled and prepared for transplantation. Single-canal technique. The diameter of the canal has to be selected depending on the size of the child's knee (usually between 6-8 mm). The tendon transplant is placed such that the canal is also filled with the tendon in the epiphyseal part (tendon transplant length usually 7 cm). Tibial canal entry medial to the tibial tuberosity, entering the joint at the level of the anterior horn of lateral meniscus in the intercondylar notch. Optimal positioning confirmed by an intraoperative negative impingement test of the guiding pin before drilling. Femoral canal entry placed at the 10:00-10:30 o'clock position on the right side, and 01:30-02:00 o'clock position on the left side. Care must be taken to avoid injury to the perichondral ring. In younger children (Tanner stage 3 or lower), avoidance of fixation material transfixing the epiphysis - femoral fixation performed using endobutton and tibial fixation with the Suture-disc. In older children (Tanner stage 4 or above) alternative fixation methods are possible (interference screw). The fixation of the ACL tendon transplant is such that reconstruction is in minimal tension in 30A degrees flexion. Postoperative treatment regimen in the first 6 weeks after surgery depends on the extent of additive surgeries (menisci, chondral injuries) performed in the same sitting. In the absence of associated injuries, weight bearing is gradually increased with the aim of achieving full weight bearing at the end of the 1st postoperative week. In case of additional meniscal sutures, knee flexion is restricted to 60A degrees maximum and non-weight bearing for 4 weeks is advised. Postoperative mobilization is performed using an adjustable knee orthesis. Between 4-6 weeks postoperatively, the permitted flexion is gradually increased to a maximum of 90A degrees and partial weight bearing is started. Full weight bearing and free movements with muscle training are started after 6 weeks. Avoidance of weight transmission on the flexed and rotated knee until 12 weeks postoperatively. Start with sports activities under supervision after 6 months, trial with professional sports activities after 9 months. 57 children with remaining growth potential around the knee underwent ACL reconstruction using the semitendinosus tendon at the Pediatric Orthopedic Unit, Department of Pediatric Surgery, Graz, Austria, between 2002-2007. 45 patients received ACL reconstruction with associated meniscal injuries. The described endobutton technique for fixation of the transplant has been performed since 2006. As the patients are under follow-up, the long-term effects of this technique on growth around the knee are, to date, not known. 30 patients were operated before 2006 using the bioresorbable interference screw for fixation by ACL reconstruction with the semtendinosus tendon. All these patients were at Tanner stage 4 or older. 15 of these cases were evaluated after completion of growth, and all showed a good to excellent outcome in Tegner, Lysholm and IKDC (International Knee Documentation Committee) Scores without any growth disturbances.\n\nKraus, Tanja\n\nLinhart, Wolfgang\n\n\n"
},
{
"text": "\n60006\nHLA Class I protein expression in the human placenta.\n\nBlaschitz, A\n\nHutter, H\n\nDohr, G\n\nBeiträge in Fachzeitschriften\nNone\n11753519.0\nNone\nNone\nThe maternal tolerance to the semiallogeneic fetus is still a central theme in reproductive immunology. During placentation, fetally-derived, genetically dissimilar tissue and cells come into close contact with maternal tissue and cells, thus forming the so-called feto-maternal interface. The most extensive contact between fetally-derived and maternal blood cells is formed by the villous trophoblastic barrier, where the syncytiotrophoblast surface permanently floats in maternal blood. Further contact is made by some extravillous cytotrophoblast cells, either located at villous tips, in so-called cell islands, or the endovascular trophoblast population within the uteroplacental spiral arteries. The third contact zone is the so-called junctional zone within the decidua where the invading extravillous trophoblast cells encounter all maternal tissue leukocytes, which are mainly NK cells, macrophages and T cells; this junctional zone extends at the edge of the placenta to the amnio-chorionic membranes where the chorionic laeve trophoblast has intimate contact with decidua tissue. It is worth mentioning that evidence has shown that even in healthy pregnancies fetal and maternal lymphoid cells are able to transgress the trophoblastic barrier, which, anatomically, seems completely impermeable. Because of this intimate contact of foreign cells to the foreign immune system it is important to define the antigenic status of the placental cells, in particular with respect to antigens of the Major Histocompatibility complex. The role of the highly polymorphic classical class I molecules HLA -A, -B, -C, which are expressed on almost all somatic cells, is the induction of a specific immune response by presenting peptide antigens to T cells. In contrast, the non-classical HLA class I molecules HLA-G and HLA-E are thought to be involved in the induction of immune tolerance by acting as ligands for inhibitory receptors present on NK cells and macrophages. The non-classical HLA-E is also expressed ubiquitously, but HLA-G expression is characterized by a unique tissue expression mainly in the human placenta. A further feature of HLA-G is that its mRNA has undergone alternative splicing, resulting in at least 6 different isoforms, encoding different proteins: 4 membrane-bound and 2 soluble forms, which could simultaneously maintain different functions depending on their molecular structure. In our immunohistochemical study we investigated the expression of classical and non-classical HLA class I proteins in human placenta using various mAbs, which were kindly provided by the groups of A. Ziegler, D. Geraghty, O. Genbacev, MT. McMaster, A. King, YW. Loke and Ph. Le Bouteiller. For HLA-A, B detection we used the antibody LA45; for detection of HLA-C, B mAbs Tü149 and HC10. HLA-C expression alone was detected with mAb L31. HLA-G expression was studied using antibodies 4H84, G233, 87G, 16G1 and BFL.1. For HLA-E staining we used antibodies DT9 and V16. The classical HLA class I proteins are expressed in all non-trophoblastic cells including the fetal and maternal cells. Comparison of HLA-A and HLA-B staining intensities within the villous stroma indicates that during first trimester of pregnancy the fetal HLA-B proteins are expressed before HLA-A appears. Among the trophoblast populations, the syncytiotrophoblast does not show any HLA class I staining, but the extravillous cells express high amounts of HLA-G together with HLA-C. King and co-workers have shown recently, using methods other than immunohistochemistry, that first trimester extravillous trophoblast cells are also likely to express HLA-E. By contrast we did not detect HLA-E in any trophoblasts with antibodies DT9 and V16. There is still an ongoing and also controversial discussion about which kinds of cells in the placenta, other than extravillous trophoblast, express which kind of the HLA-G isoforms. Depending on the antibodies and the different immunohistochemical techniques used, different results have been described: Antibody 16G1 specific for soluble HLA-G labels syncytiotrophoblast, antibody BFL.1 endothelial cells of chorionic fetal blood vessels and antibody 87G Hofbauer cells. All these HLA-G labelings, apart from extravillous trophoblasts, are in complete contrast to the reaction pattern (merely extravillous trophoblast) given by antibody 4H84, which recognizes all HLA-G isoforms -including the soluble ones- through an epitope located on the a 1-domain of HLA-G. Future studies employing isoform-specific antibodies, which are not yet available for all of the possible isoforms, will elucidate the function and expression pattern of HLA-G in the human placenta.\n\nDohr, Gottfried\n\nHutter, Heinz\n\n\n"
},
{
"text": "\n131213\nCommon variants associated with plasma triglycerides and risk for coronary artery disease.\n\nDo, R\n\nWiller, CJ\n\nSchmidt, EM\n\nSengupta, S\n\nGao, C\n\nPeloso, GM\n\nGustafsson, S\n\nKanoni, S\n\nGanna, A\n\nChen, J\n\nBuchkovich, ML\n\nMora, S\n\nBeckmann, JS\n\nBragg-Gresham, JL\n\nChang, HY\n\nDemirkan, A\n\nDen Hertog, HM\n\nDonnelly, LA\n\nEhret, GB\n\nEsko, T\n\nFeitosa, MF\n\nFerreira, T\n\nFischer, K\n\nFontanillas, P\n\nFraser, RM\n\nFreitag, DF\n\nGurdasani, D\n\nHeikkilä, K\n\nHyppönen, E\n\nIsaacs, A\n\nJackson, AU\n\nJohansson, A\n\nJohnson, T\n\nKaakinen, M\n\nKettunen, J\n\nKleber, ME\n\nLi, X\n\nLuan, J\n\nLyytikäinen, LP\n\nMagnusson, PK\n\nMangino, M\n\nMihailov, E\n\nMontasser, ME\n\nMüller-Nurasyid, M\n\nNolte, IM\n\nO'Connell, JR\n\nPalmer, CD\n\nPerola, M\n\nPetersen, AK\n\nSanna, S\n\nSaxena, R\n\nService, SK\n\nShah, S\n\nShungin, D\n\nSidore, C\n\nSong, C\n\nStrawbridge, RJ\n\nSurakka, I\n\nTanaka, T\n\nTeslovich, TM\n\nThorleifsson, G\n\nVan den Herik, EG\n\nVoight, BF\n\nVolcik, KA\n\nWaite, LL\n\nWong, A\n\nWu, Y\n\nZhang, W\n\nAbsher, D\n\nAsiki, G\n\nBarroso, I\n\nBeen, LF\n\nBolton, JL\n\nBonnycastle, LL\n\nBrambilla, P\n\nBurnett, MS\n\nCesana, G\n\nDimitriou, M\n\nDoney, AS\n\nDöring, A\n\nElliott, P\n\nEpstein, SE\n\nEyjolfsson, GI\n\nGigante, B\n\nGoodarzi, MO\n\nGrallert, H\n\nGravito, ML\n\nGroves, CJ\n\nHallmans, G\n\nHartikainen, AL\n\nHayward, C\n\nHernandez, D\n\nHicks, AA\n\nHolm, H\n\nHung, YJ\n\nIllig, T\n\nJones, MR\n\nKaleebu, P\n\nKastelein, JJ\n\nKhaw, KT\n\nKim, E\n\nKlopp, N\n\nKomulainen, P\n\nKumari, M\n\nLangenberg, C\n\nLehtimäki, T\n\nLin, SY\n\nLindström, J\n\nLoos, RJ\n\nMach, F\n\nMcArdle, WL\n\nMeisinger, C\n\nMitchell, BD\n\nMüller, G\n\nNagaraja, R\n\nNarisu, N\n\nNieminen, TV\n\nNsubuga, RN\n\nOlafsson, I\n\nOng, KK\n\nPalotie, A\n\nPapamarkou, T\n\nPomilla, C\n\nPouta, A\n\nRader, DJ\n\nReilly, MP\n\nRidker, PM\n\nRivadeneira, F\n\nRudan, I\n\nRuokonen, A\n\nSamani, N\n\nScharnagl, H\n\nSeeley, J\n\nSilander, K\n\nStančáková, A\n\nStirrups, K\n\nSwift, AJ\n\nTiret, L\n\nUitterlinden, AG\n\nvan Pelt, LJ\n\nVedantam, S\n\nWainwright, N\n\nWijmenga, C\n\nWild, SH\n\nWillemsen, G\n\nWilsgaard, T\n\nWilson, JF\n\nYoung, EH\n\nZhao, JH\n\nAdair, LS\n\nArveiler, D\n\nAssimes, TL\n\nBandinelli, S\n\nBennett, F\n\nBochud, M\n\nBoehm, BO\n\nBoomsma, DI\n\nBorecki, IB\n\nBornstein, SR\n\nBovet, P\n\nBurnier, M\n\nCampbell, H\n\nChakravarti, A\n\nChambers, JC\n\nChen, YD\n\nCollins, FS\n\nCooper, RS\n\nDanesh, J\n\nDedoussis, G\n\nde Faire, U\n\nFeranil, AB\n\nFerrières, J\n\nFerrucci, L\n\nFreimer, NB\n\nGieger, C\n\nGroop, LC\n\nGudnason, V\n\nGyllensten, U\n\nHamsten, A\n\nHarris, TB\n\nHingorani, A\n\nHirschhorn, JN\n\nHofman, A\n\nHovingh, GK\n\nHsiung, CA\n\nHumphries, SE\n\nHunt, SC\n\nHveem, K\n\nIribarren, C\n\nJärvelin, MR\n\nJula, A\n\nKähönen, M\n\nKaprio, J\n\nKesäniemi, A\n\nKivimaki, M\n\nKooner, JS\n\nKoudstaal, PJ\n\nKrauss, RM\n\nKuh, D\n\nKuusisto, J\n\nKyvik, KO\n\nLaakso, M\n\nLakka, TA\n\nLind, L\n\nLindgren, CM\n\nMartin, NG\n\nMärz, W\n\nMcCarthy, MI\n\nMcKenzie, CA\n\nMeneton, P\n\nMetspalu, A\n\nMoilanen, L\n\nMorris, AD\n\nMunroe, PB\n\nNjølstad, I\n\nPedersen, NL\n\nPower, C\n\nPramstaller, PP\n\nPrice, JF\n\nPsaty, BM\n\nQuertermous, T\n\nRauramaa, R\n\nSaleheen, D\n\nSalomaa, V\n\nSanghera, DK\n\nSaramies, J\n\nSchwarz, PE\n\nSheu, WH\n\nShuldiner, AR\n\nSiegbahn, A\n\nSpector, TD\n\nStefansson, K\n\nStrachan, DP\n\nTayo, BO\n\nTremoli, E\n\nTuomilehto, J\n\nUusitupa, M\n\nvan Duijn, CM\n\nVollenweider, P\n\nWallentin, L\n\nWareham, NJ\n\nWhitfield, JB\n\nWolffenbuttel, BH\n\nAltshuler, D\n\nOrdovas, JM\n\nBoerwinkle, E\n\nPalmer, CN\n\nThorsteinsdottir, U\n\nChasman, DI\n\nRotter, JI\n\nFranks, PW\n\nRipatti, S\n\nCupples, LA\n\nSandhu, MS\n\nRich, SS\n\nBoehnke, M\n\nDeloukas, P\n\nMohlke, KL\n\nIngelsson, E\n\nAbecasis, GR\n\nDaly, MJ\n\nNeale, BM\n\nKathiresan, S\n\nBeiträge in Fachzeitschriften\nISI:000326384100015\n24097064.0\n10.1038/ng.2795\nPMC3904346\nTriglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.\n\nMärz, Winfried\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n166768\nMultiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.\n\nMalik, R\n\nChauhan, G\n\nTraylor, M\n\nSargurupremraj, M\n\nOkada, Y\n\nMishra, A\n\nRutten-Jacobs, L\n\nGiese, AK\n\nvan der Laan, SW\n\nGretarsdottir, S\n\nAnderson, CD\n\nChong, M\n\nAdams, HHH\n\nAgo, T\n\nAlmgren, P\n\nAmouyel, P\n\nAy, H\n\nBartz, TM\n\nBenavente, OR\n\nBevan, S\n\nBoncoraglio, GB\n\nBrown, RD\n\nButterworth, AS\n\nCarrera, C\n\nCarty, CL\n\nChasman, DI\n\nChen, WM\n\nCole, JW\n\nCorrea, A\n\nCotlarciuc, I\n\nCruchaga, C\n\nDanesh, J\n\nde Bakker, PIW\n\nDeStefano, AL\n\nden Hoed, M\n\nDuan, Q\n\nEngelter, ST\n\nFalcone, GJ\n\nGottesman, RF\n\nGrewal, RP\n\nGudnason, V\n\nGustafsson, S\n\nHaessler, J\n\nHarris, TB\n\nHassan, A\n\nHavulinna, AS\n\nHeckbert, SR\n\nHolliday, EG\n\nHoward, G\n\nHsu, FC\n\nHyacinth, HI\n\nIkram, MA\n\nIngelsson, E\n\nIrvin, MR\n\nJian, X\n\nJiménez-Conde, J\n\nJohnson, JA\n\nJukema, JW\n\nKanai, M\n\nKeene, KL\n\nKissela, BM\n\nKleindorfer, DO\n\nKooperberg, C\n\nKubo, M\n\nLange, LA\n\nLangefeld, CD\n\nLangenberg, C\n\nLauner, LJ\n\nLee, JM\n\nLemmens, R\n\nLeys, D\n\nLewis, CM\n\nLin, WY\n\nLindgren, AG\n\nLorentzen, E\n\nMagnusson, PK\n\nMaguire, J\n\nManichaikul, A\n\nMcArdle, PF\n\nMeschia, JF\n\nMitchell, BD\n\nMosley, TH\n\nNalls, MA\n\nNinomiya, T\n\nO'Donnell, MJ\n\nPsaty, BM\n\nPulit, SL\n\nRannikmäe, K\n\nReiner, AP\n\nRexrode, KM\n\nRice, K\n\nRich, SS\n\nRidker, PM\n\nRost, NS\n\nRothwell, PM\n\nRotter, JI\n\nRundek, T\n\nSacco, RL\n\nSakaue, S\n\nSale, MM\n\nSalomaa, V\n\nSapkota, BR\n\nSchmidt, R\n\nSchmidt, CO\n\nSchminke, U\n\nSharma, P\n\nSlowik, A\n\nSudlow, CLM\n\nTanislav, C\n\nTatlisumak, T\n\nTaylor, KD\n\nThijs, VNS\n\nThorleifsson, G\n\nThorsteinsdottir, U\n\nTiedt, S\n\nTrompet, S\n\nTzourio, C\n\nvan Duijn, CM\n\nWalters, M\n\nWareham, NJ\n\nWassertheil-Smoller, S\n\nWilson, JG\n\nWiggins, KL\n\nYang, Q\n\nYusuf, S\n\nBis, JC\n\nPastinen, T\n\nRuusalepp, A\n\nSchadt, EE\n\nKoplev, S\n\nBjörkegren, JLM\n\nCodoni, V\n\nCivelek, M\n\nSmith, NL\n\nTrégouët, DA\n\nChristophersen, IE\n\nRoselli, C\n\nLubitz, SA\n\nEllinor, PT\n\nTai, ES\n\nKooner, JS\n\nKato, N\n\nHe, J\n\nvan der Harst, P\n\nElliott, P\n\nChambers, JC\n\nTakeuchi, F\n\nJohnson, AD\n\nSanghera, DK\n\nMelander, O\n\nJern, C\n\nStrbian, D\n\nFernandez-Cadenas, I\n\nLongstreth, WT\n\nRolfs, A\n\nHata, J\n\nWoo, D\n\nRosand, J\n\nPare, G\n\nHopewell, JC\n\nSaleheen, D\n\nStefansson, K\n\nWorrall, BB\n\nKittner, SJ\n\nSeshadri, S\n\nFornage, M\n\nMarkus, HS\n\nHowson, JMM\n\nKamatani, Y\n\nDebette, S\n\nDichgans, M\n\nMalik, R\n\nChauhan, G\n\nTraylor, M\n\nSargurupremraj, M\n\nOkada, Y\n\nMishra, A\n\nRutten-Jacobs, L\n\nGiese, AK\n\nvan der Laan, SW\n\nGretarsdottir, S\n\nAnderson, CD\n\nChong, M\n\nAdams, HHH\n\nAgo, T\n\nAlmgren, P\n\nAmouyel, P\n\nAy, H\n\nBartz, TM\n\nBenavente, OR\n\nBevan, S\n\nBoncoraglio, GB\n\nBrown, RD\n\nButterworth, AS\n\nCarrera, C\n\nCarty, CL\n\nChasman, DI\n\nChen, WM\n\nCole, JW\n\nCorrea, A\n\nCotlarciuc, I\n\nCruchaga, C\n\nDanesh, J\n\nde Bakker, PIW\n\nDeStefano, AL\n\nHoed, MD\n\nDuan, Q\n\nEngelter, ST\n\nFalcone, GJ\n\nGottesman, RF\n\nGrewal, RP\n\nGudnason, V\n\nGustafsson, S\n\nHaessler, J\n\nHarris, TB\n\nHassan, A\n\nHavulinna, AS\n\nHeckbert, SR\n\nHolliday, EG\n\nHoward, G\n\nHsu, FC\n\nHyacinth, HI\n\nIkram, MA\n\nIngelsson, E\n\nIrvin, MR\n\nJian, X\n\nJiménez-Conde, J\n\nJohnson, JA\n\nJukema, JW\n\nKanai, M\n\nKeene, KL\n\nKissela, BM\n\nKleindorfer, DO\n\nKooperberg, C\n\nKubo, M\n\nLange, LA\n\nLangefeld, CD\n\nLangenberg, C\n\nLauner, LJ\n\nLee, JM\n\nLemmens, R\n\nLeys, D\n\nLewis, CM\n\nLin, WY\n\nLindgren, AG\n\nLorentzen, E\n\nMagnusson, PK\n\nMaguire, J\n\nManichaikul, A\n\nMcArdle, PF\n\nMeschia, JF\n\nMitchell, BD\n\nMosley, TH\n\nNalls, MA\n\nNinomiya, T\n\nO'Donnell, MJ\n\nPsaty, BM\n\nPulit, SL\n\nRannikmäe, K\n\nReiner, AP\n\nRexrode, KM\n\nRice, K\n\nRich, SS\n\nRidker, PM\n\nRost, NS\n\nRothwell, PM\n\nRotter, JI\n\nRundek, T\n\nSacco, RL\n\nSakaue, S\n\nSale, MM\n\nSalomaa, V\n\nSapkota, BR\n\nSchmidt, R\n\nSchmidt, CO\n\nSchminke, U\n\nSharma, P\n\nSlowik, A\n\nSudlow, CLM\n\nTa ...\n\nBeiträge in Fachzeitschriften\nISI:000429529300013\n29531354.0\n10.1038/s41588-018-0058-3\nPMC5968830\nStroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521, 12 individuals (67, 62 cases and 454, 50 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n157075\nCan Multistate Modeling of Local Recurrence, Distant Metastasis, and Death Improve the Prediction of Outcome in Patients With Soft Tissue Sarcomas?\n\nPosch, F\n\nLeitner, L\n\nBergovec, M\n\nBezan, A\n\nStotz, M\n\nGerger, A\n\nPichler, M\n\nStöger, H\n\nLiegl-Atzwanger, B\n\nLeithner, A\n\nSzkandera, J\n\nBeiträge in Fachzeitschriften\nISI:000399195300025\n28083752.0\n10.1007/s11999-017-5232-x\nPMC5384928\nExploration of the complex relationship between prognostic indicators such as tumor grade and size and clinical outcomes such as local recurrence and distant metastasis in patients with cancer is crucial to guide treatment decisions. However, in patients with soft tissue sarcoma, there are many gaps in our understanding of this relationship. Multistate analysis may help us in gaining a comprehensive understanding of risk factor-outcome relationships in soft tissue sarcoma, because this methodology can integrate multiple risk factors and clinical endpoints into a single statistical model. To our knowledge, no study of this kind has been performed before in patients with soft tissue sarcoma.\n We implemented a multistate model of localized soft tissue sarcoma to statistically evaluate the relationship among baseline risk factors, recurrence, and death in patients with localized soft tissue sarcoma undergoing curative surgery.\n Between 1998 and 2015, our center treated 539 patients for localized soft tissue sarcoma with surgery as curative intent. Of those, 96 patients (18%) were not included in this single-center retrospective study owing to missing baseline histopathology data (n = 3), not yet observed followup (n = 80), or because a neoadjuvant treatment approach in the presence of synchronous distant metastasis was used (n = 13), leaving 443 patients (82%) for the current analysis, of which 40 were lost to followup during the first year after surgery. All patients had tumors of the stages I to III according to the American Joint Committee on Cancer Stages. The median age of the patients was 62 years (range, 16-96 years), and 217 patients (49%) were female. Three hundred-forty-six patients (78%) had tumors of high grade (Grades 2 and 3), and 310 (70%) tumors were greater than 5 cm in maximum diameter. Patients who had died during the first year of followup were included in this analysis. Median followup for the 443 study patients was 6 years, with 84%, 52%, and 23% of patients being followed for more than 1, 5, and 10 years, respectively. The 15-year cumulative incidences of local recurrence, distant metastasis, and death from any cause, using a competing risk analysis, were 16% (95% CI, 11%-22%), 21% (95% CI, 17%-26%), and 55% (95% CI, 44%-67%), respectively. Wide resection with a margin of 1 mm was the preferred treatment for all patients, except for those with Grade 1 liposarcoma where a marginal resection was considered adequate. Multistate models were implemented with the mstate library in R.\n In multistate analysis, patients who experienced a local recurrence were more likely to have distant metastasis develop (hazard ratio [HR] = 8.4; 95% CI, 4.3-16.5; p < 0.001), and to die (HR = 3.4; 95% CI, 2.1-5.6; p < 0.001). The occurrence of distant metastasis was associated with a strong increase in the risk of death (HR = 12.6; 95% CI, 8.7-18.3; p < 0.001). Distant metastasis occurring after a long tumor-free interval was not associated with a more-favorable prognosis with respect to mortality than distant metastasis occurring early after surgery (estimated relative decrease in the adverse effect of distant metastasis on mortality for 1-year delay in the occurrence of distant metastasis = 0.9; 95% CI, 0.7-1.1; p = 0.28). High-grade histology (Grades 2 and 3) was associated with a higher risk of overall recurrence (defined as a composite of local recurrence and distant metastasis, HR = 3.8; 95% CI, 1.8-7.8; p = 0.0003) and a higher risk of death after recurrence developed (HR = 4.4; 95% CI, 1.1-18.2; p = 0.04). Finally, the multistate model predicted distinct outcome patterns depending on baseline covariates and how long a patient has remained free from recurrence after surgery.\n In patients with localized soft tissue sarcoma undergoing resection, the occurrence of local recurrence and distant metastasis contributes to a dramatically impaired long-term survival outcome. Local recurrences are a substantial risk factor for distant metastasis. Multistate modeling is a very powerful approach for analysis of sarcoma cohorts, and may be used in the future to obtain highly personalized, dynamic predictions of outcomes in patients with localized soft tissue sarcoma.\n Level III, therapeutic study.\n\nBergovec, Marko\n\nGerger, Armin\n\nLeithner, Andreas\n\nLeitner, Lukas\n\nLiegl-Atzwanger, Bernadette\n\nPichler, Martin\n\nPosch, Florian\n\nStoeger, Herbert\n\nSzkandera, Joanna\n\nTerbuch, Angelika\n\n\n"
},
{
"text": "\n160650\nTransfer of innovation on allergic rhinitis and asthma multimorbidity in the elderly (MACVIA-ARIA) - EIP on AHA Twinning Reference Site (GARD research demonstration project).\n\nBousquet, J\n\nAgache, I\n\nAliberti, MR\n\nAngles, R\n\nAnnesi-Maesano, I\n\nAnto, JM\n\nArnavielhe, S\n\nAsayag, E\n\nBacci, E\n\nBedbrook, A\n\nBachert, C\n\nBaroni, I\n\nBarreto, BA\n\nBedolla-Barajas, M\n\nBergmann, KC\n\nBertorello, L\n\nBewick, M\n\nBieber, T\n\nBirov, S\n\nBindslev-Jensen, C\n\nBlua, A\n\nBochenska Marciniak, M\n\nBogus-Buczynska, I\n\nBosnic-Anticevich, S\n\nBosse, I\n\nBourret, R\n\nBucca, C\n\nBuonaiuto, R\n\nBurguete Cabanas, MT\n\nCaillaud, D\n\nCaimmi, DP\n\nCaiazza, D\n\nCamargos, P\n\nCanfora, G\n\nCardona, V\n\nCarriazo, AM\n\nCartier, C\n\nCastellano, G\n\nChavannes, NH\n\nCecci, L\n\nCiaravolo, MM\n\nCingi, C\n\nCiceran, A\n\nColas, L\n\nColgan, E\n\nColl, J\n\nConforti, D\n\nCorreia de Sousa, J\n\nCortés-Grimaldo, RM\n\nCorti, F\n\nCosta, E\n\nCourbis, AL\n\nCousein, E\n\nCruz, AA\n\nCustovic, A\n\nCvetkovski, B\n\nDario, C\n\nda Silva, J\n\nDauvilliers, Y\n\nDe Blay, F\n\nDedeu, T\n\nDe Feo, G\n\nDe Martino, B\n\nDemoly, P\n\nDe Vries, G\n\nDi Capua Ercolano, S\n\nDi Carluccio, N\n\nDoulapsi, M\n\nDray, G\n\nDubakiene, R\n\nEller, E\n\nEmuzyte, R\n\nEspinoza-Contreras, JG\n\nEstrada-Cardona, A\n\nFarrell, J\n\nFarsi, A\n\nFerrero, J\n\nFokkens, WJ\n\nFonseca, J\n\nFontaine, JF\n\nForti, S\n\nGálvez-Romero, JL\n\nGarcía-Cobas, CI\n\nGarcia Cruz, MH\n\nGemicioğlu, B\n\nGerth van Wijk, R\n\nGuidacci, M\n\nGómez-Vera, J\n\nGuldemond, NA\n\nGutter, Z\n\nHaahtela, T\n\nHajjam, J\n\nHellings, PW\n\nHernández-Velázquez, L\n\nIllario, M\n\nIvancevich, JC\n\nJares, E\n\nJoos, G\n\nJust, J\n\nKalayci, O\n\nKalyoncu, AF\n\nKarjalainen, J\n\nKeil, T\n\nKhaltaev, N\n\nKlimek, L\n\nKritikos, V\n\nKull, I\n\nKuna, P\n\nKvedariene, V\n\nKolek, V\n\nKrzych-Fałta, E\n\nKupczyk, M\n\nLacwik, P\n\nLa Grutta, S\n\nLarenas-Linnemann, D\n\nLaune, D\n\nLauri, D\n\nLavrut, J\n\nLessa, M\n\nLevato, G\n\nLewis, L\n\nLieten, I\n\nLipiec, A\n\nLouis, R\n\nLuna-Pech, JA\n\nMagnan, A\n\nMalva, J\n\nMaspero, JF\n\nMatta-Campos, JJ\n\nMayora, O\n\nMedina-Ávalos, MA\n\nMelén, E\n\nMenditto, E\n\nMillot-Keurinck, J\n\nModa, G\n\nMorais-Almeida, M\n\nMösges, R\n\nMota-Pinto, A\n\nMullol, J\n\nMuraro, A\n\nMurray, R\n\nNoguès, M\n\nNalin, M\n\nNapoli, L\n\nNeffen, H\n\nO'Hehir, RE\n\nOnorato, GL\n\nPalkonen, S\n\nPapadopoulos, NG\n\nPassalacqua, G\n\nPépin, JL\n\nPereira, AM\n\nPersico, M\n\nPfaar, O\n\nPozzi, AC\n\nProkopakis, E\n\nPugin, B\n\nRaciborski, F\n\nRimmer, J\n\nRizzo, JA\n\nRobalo-Cordeiro, C\n\nRodríguez-González, M\n\nRolla, G\n\nRoller-Wirnsberger, RE\n\nRomano, A\n\nRomano, M\n\nRomano, MR\n\nSalimäki, J\n\nSamolinski, B\n\nSerpa, FS\n\nShamai, S\n\nSierra, M\n\nSova, M\n\nSorlini, M\n\nStellato, C\n\nStelmach, R\n\nStrandberg, T\n\nStroetmann, V\n\nStukas, R\n\nSzylling, A\n\nTan, R\n\nTibaldi, V\n\nTodo-Bom, A\n\nToppila-Salmi, S\n\nTomazic, P\n\nTrama, U\n\nTriggiani, M\n\nValero, A\n\nValovirta, E\n\nValiulis, A\n\nvan Eerd, M\n\nVasankari, T\n\nVatrella, A\n\nVentura, MT\n\nVerissimo, MT\n\nViart, F\n\nWilliams, S\n\nWagenmann, M\n\nWanscher, C\n\nWestman, M\n\nWickman, M\n\nYoung, I\n\nYorgancioglu, A\n\nZernotti, E\n\nZuberbier, T\n\nZurkuhlen, A\n\nDe Oliviera, B\n\nSenn, A\n\nBeiträge in Fachzeitschriften\nISI:000418442300008\n28600902.0\n10.1111/all.13218\nNone\nThe overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.\n © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.\n\nRoller-Wirnsberger, Regina\n\nTomazic, Peter Valentin\n\n\n"
},
{
"text": "\n177918\nGenetic architecture of subcortical brain structures in 38,851 individuals.\n\nSatizabal, CL\n\nAdams, HHH\n\nHibar, DP\n\nWhite, CC\n\nKnol, MJ\n\nStein, JL\n\nScholz, M\n\nSargurupremraj, M\n\nJahanshad, N\n\nRoshchupkin, GV\n\nSmith, AV\n\nBis, JC\n\nJian, X\n\nLuciano, M\n\nHofer, E\n\nTeumer, A\n\nvan der Lee, SJ\n\nYang, J\n\nYanek, LR\n\nLee, TV\n\nLi, S\n\nHu, Y\n\nKoh, JY\n\nEicher, JD\n\nDesrivières, S\n\nArias-Vasquez, A\n\nChauhan, G\n\nAthanasiu, L\n\nRentería, ME\n\nKim, S\n\nHoehn, D\n\nArmstrong, NJ\n\nChen, Q\n\nHolmes, AJ\n\nden Braber, A\n\nKloszewska, I\n\nAndersson, M\n\nEspeseth, T\n\nGrimm, O\n\nAbramovic, L\n\nAlhusaini, S\n\nMilaneschi, Y\n\nPapmeyer, M\n\nAxelsson, T\n\nEhrlich, S\n\nRoiz-Santiañez, R\n\nKraemer, B\n\nHåberg, AK\n\nJones, HJ\n\nPike, GB\n\nStein, DJ\n\nStevens, A\n\nBralten, J\n\nVernooij, MW\n\nHarris, TB\n\nFilippi, I\n\nWitte, AV\n\nGuadalupe, T\n\nWittfeld, K\n\nMosley, TH\n\nBecker, JT\n\nDoan, NT\n\nHagenaars, SP\n\nSaba, Y\n\nCuellar-Partida, G\n\nAmin, N\n\nHilal, S\n\nNho, K\n\nMirza-Schreiber, N\n\nArfanakis, K\n\nBecker, DM\n\nAmes, D\n\nGoldman, AL\n\nLee, PH\n\nBoomsma, DI\n\nLovestone, S\n\nGiddaluru, S\n\nLe Hellard, S\n\nMattheisen, M\n\nBohlken, MM\n\nKasperaviciute, D\n\nSchmaal, L\n\nLawrie, SM\n\nAgartz, I\n\nWalton, E\n\nTordesillas-Gutierrez, D\n\nDavies, GE\n\nShin, J\n\nIpser, JC\n\nVinke, LN\n\nHoogman, M\n\nJia, T\n\nBurkhardt, R\n\nKlein, M\n\nCrivello, F\n\nJanowitz, D\n\nCarmichael, O\n\nHaukvik, UK\n\nAribisala, BS\n\nSchmidt, H\n\nStrike, LT\n\nCheng, CY\n\nRisacher, SL\n\nPütz, B\n\nFleischman, DA\n\nAssareh, AA\n\nMattay, VS\n\nBuckner, RL\n\nMecocci, P\n\nDale, AM\n\nCichon, S\n\nBoks, MP\n\nMatarin, M\n\nPenninx, BWJH\n\nCalhoun, VD\n\nChakravarty, MM\n\nMarquand, AF\n\nMacare, C\n\nKharabian Masouleh, S\n\nOosterlaan, J\n\nAmouyel, P\n\nHegenscheid, K\n\nRotter, JI\n\nSchork, AJ\n\nLiewald, DCM\n\nde Zubicaray, GI\n\nWong, TY\n\nShen, L\n\nSämann, PG\n\nBrodaty, H\n\nRoffman, JL\n\nde Geus, EJC\n\nTsolaki, M\n\nErk, S\n\nvan Eijk, KR\n\nCavalleri, GL\n\nvan der Wee, NJA\n\nMcIntosh, AM\n\nGollub, RL\n\nBulayeva, KB\n\nBernard, M\n\nRichards, JS\n\nHimali, JJ\n\nLoeffler, M\n\nRommelse, N\n\nHoffmann, W\n\nWestlye, LT\n\nValdés Hernández, MC\n\nHansell, NK\n\nvan Erp, TGM\n\nWolf, C\n\nKwok, JBJ\n\nVellas, B\n\nHeinz, A\n\nOlde Loohuis, LM\n\nDelanty, N\n\nHo, BC\n\nChing, CRK\n\nShumskaya, E\n\nSingh, B\n\nHofman, A\n\nvan der Meer, D\n\nHomuth, G\n\nPsaty, BM\n\nBastin, ME\n\nMontgomery, GW\n\nForoud, TM\n\nReppermund, S\n\nHottenga, JJ\n\nSimmons, A\n\nMeyer-Lindenberg, A\n\nCahn, W\n\nWhelan, CD\n\nvan Donkelaar, MMJ\n\nYang, Q\n\nHosten, N\n\nGreen, RC\n\nThalamuthu, A\n\nMohnke, S\n\nHulshoff Pol, HE\n\nLin, H\n\nJack, CR\n\nSchofield, PR\n\nMühleisen, TW\n\nMaillard, P\n\nPotkin, SG\n\nWen, W\n\nFletcher, E\n\nToga, AW\n\nGruber, O\n\nHuentelman, M\n\nDavey Smith, G\n\nLauner, LJ\n\nNyberg, L\n\nJönsson, EG\n\nCrespo-Facorro, B\n\nKoen, N\n\nGreve, DN\n\nUitterlinden, AG\n\nWeinberger, DR\n\nSteen, VM\n\nFedko, IO\n\nGroenewold, NA\n\nNiessen, WJ\n\nToro, R\n\nTzourio, C\n\nLongstreth, WT\n\nIkram, MK\n\nSmoller, JW\n\nvan Tol, MJ\n\nSussmann, JE\n\nPaus, T\n\nLemaître, H\n\nSchroeter, ML\n\nMazoyer, B\n\nAndreassen, OA\n\nHolsboer, F\n\nDepondt, C\n\nVeltman, DJ\n\nTurner, JA\n\nPausova, Z\n\nSchumann, G\n\nvan Rooij, D\n\nDjurovic, S\n\nDeary, IJ\n\nMcMahon, KL\n\nMüller-Myhsok, B\n\nBrouwer, RM\n\nSoininen, H\n\nPandolfo, M\n\nWassink, TH\n\nCheung, JW\n\nWolfers, T\n\nMartinot, JL\n\nZwiers, MP\n\nNauck, M\n\nMelle, I\n\nMartin, NG\n\nKanai, R\n\nWestman, E\n\nKahn, RS\n\nSisodiya, SM\n\nWhite, T\n\nSaremi, A\n\nvan Bokhoven, H\n\nBrunner, HG\n\nVölzke, H\n\nWright, MJ\n\nvan 't Ent, D\n\nNöthen, MM\n\nOphoff, RA\n\nBuitelaar, JK\n\nFernández, G\n\nSachdev, PS\n\nRietschel, M\n\nvan Haren, NEM\n\nFisher, SE\n\nBeiser, AS\n\nFrancks, C\n\nSaykin, AJ\n\nMather, KA\n\nRomanczuk-Seiferth, N\n\nHartman, CA\n\nDeStefano, AL\n\nHeslenfeld, DJ\n\nWeiner, MW\n\nWalter, H\n\nHoekstra, PJ\n\nNyquist, PA\n\nFranke, B\n\nBennett, DA\n\nGrabe, HJ\n\nJohnson, AD\n\nChen, C\n\nva ...\n\nBeiträge in Fachzeitschriften\nISI:000494714300011\n31636452.0\n10.1038/s41588-019-0511-y\nPMC7055269\nSubcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40, 00 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.\n\nHofer, Edith\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n143273\nGenetic studies of body mass index yield new insights for obesity biology.\n\nLocke, AE\n\nKahali, B\n\nBerndt, SI\n\nJustice, AE\n\nPers, TH\n\nDay, FR\n\nPowell, C\n\nVedantam, S\n\nBuchkovich, ML\n\nYang, J\n\nCroteau-Chonka, DC\n\nEsko, T\n\nFall, T\n\nFerreira, T\n\nGustafsson, S\n\nKutalik, Z\n\nLuan, J\n\nMägi, R\n\nRandall, JC\n\nWinkler, TW\n\nWood, AR\n\nWorkalemahu, T\n\nFaul, JD\n\nSmith, JA\n\nZhao, JH\n\nZhao, W\n\nChen, J\n\nFehrmann, R\n\nHedman, ÅK\n\nKarjalainen, J\n\nSchmidt, EM\n\nAbsher, D\n\nAmin, N\n\nAnderson, D\n\nBeekman, M\n\nBolton, JL\n\nBragg-Gresham, JL\n\nBuyske, S\n\nDemirkan, A\n\nDeng, G\n\nEhret, GB\n\nFeenstra, B\n\nFeitosa, MF\n\nFischer, K\n\nGoel, A\n\nGong, J\n\nJackson, AU\n\nKanoni, S\n\nKleber, ME\n\nKristiansson, K\n\nLim, U\n\nLotay, V\n\nMangino, M\n\nLeach, IM\n\nMedina-Gomez, C\n\nMedland, SE\n\nNalls, MA\n\nPalmer, CD\n\nPasko, D\n\nPechlivanis, S\n\nPeters, MJ\n\nProkopenko, I\n\nShungin, D\n\nStančáková, A\n\nStrawbridge, RJ\n\nSung, YJ\n\nTanaka, T\n\nTeumer, A\n\nTrompet, S\n\nvan der Laan, SW\n\nvan Setten, J\n\nVan Vliet-Ostaptchouk, JV\n\nWang, Z\n\nYengo, L\n\nZhang, W\n\nIsaacs, A\n\nAlbrecht, E\n\nÄrnlöv, J\n\nArscott, GM\n\nAttwood, AP\n\nBandinelli, S\n\nBarrett, A\n\nBas, IN\n\nBellis, C\n\nBennett, AJ\n\nBerne, C\n\nBlagieva, R\n\nBlüher, M\n\nBöhringer, S\n\nBonnycastle, LL\n\nBöttcher, Y\n\nBoyd, HA\n\nBruinenberg, M\n\nCaspersen, IH\n\nChen, YI\n\nClarke, R\n\nDaw, EW\n\nde Craen, AJM\n\nDelgado, G\n\nDimitriou, M\n\nDoney, ASF\n\nEklund, N\n\nEstrada, K\n\nEury, E\n\nFolkersen, L\n\nFraser, RM\n\nGarcia, ME\n\nGeller, F\n\nGiedraitis, V\n\nGigante, B\n\nGo, AS\n\nGolay, A\n\nGoodall, AH\n\nGordon, SD\n\nGorski, M\n\nGrabe, HJ\n\nGrallert, H\n\nGrammer, TB\n\nGräßler, J\n\nGrönberg, H\n\nGroves, CJ\n\nGusto, G\n\nHaessler, J\n\nHall, P\n\nHaller, T\n\nHallmans, G\n\nHartman, CA\n\nHassinen, M\n\nHayward, C\n\nHeard-Costa, NL\n\nHelmer, Q\n\nHengstenberg, C\n\nHolmen, O\n\nHottenga, JJ\n\nJames, AL\n\nJeff, JM\n\nJohansson, Å\n\nJolley, J\n\nJuliusdottir, T\n\nKinnunen, L\n\nKoenig, W\n\nKoskenvuo, M\n\nKratzer, W\n\nLaitinen, J\n\nLamina, C\n\nLeander, K\n\nLee, NR\n\nLichtner, P\n\nLind, L\n\nLindström, J\n\nLo, KS\n\nLobbens, S\n\nLorbeer, R\n\nLu, Y\n\nMach, F\n\nMagnusson, PKE\n\nMahajan, A\n\nMcArdle, WL\n\nMcLachlan, S\n\nMenni, C\n\nMerger, S\n\nMihailov, E\n\nMilani, L\n\nMoayyeri, A\n\nMonda, KL\n\nMorken, MA\n\nMulas, A\n\nMüller, G\n\nMüller-Nurasyid, M\n\nMusk, AW\n\nNagaraja, R\n\nNöthen, MM\n\nNolte, IM\n\nPilz, S\n\nRayner, NW\n\nRenstrom, F\n\nRettig, R\n\nRied, JS\n\nRipke, S\n\nRobertson, NR\n\nRose, LM\n\nSanna, S\n\nScharnagl, H\n\nScholtens, S\n\nSchumacher, FR\n\nScott, WR\n\nSeufferlein, T\n\nShi, J\n\nSmith, AV\n\nSmolonska, J\n\nStanton, AV\n\nSteinthorsdottir, V\n\nStirrups, K\n\nStringham, HM\n\nSundström, J\n\nSwertz, MA\n\nSwift, AJ\n\nSyvänen, AC\n\nTan, ST\n\nTayo, BO\n\nThorand, B\n\nThorleifsson, G\n\nTyrer, JP\n\nUh, HW\n\nVandenput, L\n\nVerhulst, FC\n\nVermeulen, SH\n\nVerweij, N\n\nVonk, JM\n\nWaite, LL\n\nWarren, HR\n\nWaterworth, D\n\nWeedon, MN\n\nWilkens, LR\n\nWillenborg, C\n\nWilsgaard, T\n\nWojczynski, MK\n\nWong, A\n\nWright, AF\n\nZhang, Q\n\nLifeLines Cohort Study\n\nBrennan, EP\n\nChoi, M\n\nDastani, Z\n\nDrong, AW\n\nEriksson, P\n\nFranco-Cereceda, A\n\nGådin, JR\n\nGharavi, AG\n\nGoddard, ME\n\nHandsaker, RE\n\nHuang, J\n\nKarpe, F\n\nKathiresan, S\n\nKeildson, S\n\nKiryluk, K\n\nKubo, M\n\nLee, JY\n\nLiang, L\n\nLifton, RP\n\nMa, B\n\nMcCarroll, SA\n\nMcKnight, AJ\n\nMin, JL\n\nMoffatt, MF\n\nMontgomery, GW\n\nMurabito, JM\n\nNicholson, G\n\nNyholt, DR\n\nOkada, Y\n\nPerry, JRB\n\nDorajoo, R\n\nReinmaa, E\n\nSalem, RM\n\nSandholm, N\n\nScott, RA\n\nStolk, L\n\nTakahashi, A\n\nTanaka, T\n\nvan 't Hooft, FM\n\nVinkhuyzen, AAE\n\nWestra, HJ\n\nZheng, W\n\nZondervan, KT\n\nADIPOGen Consortium\n\nAGEN-BMI Working Group\n\nCARDIOGRAMplusC4D Consortium\n\nCKDGen Consortium\n\nGLGC\n\nICBP\n\nMAGIC Investigators\n\nMuTHER Consortium\n\nMIGen Consortium\n\nPAGE Consortium\n\nReproGen Consortium\n\nGENIE Consortium\n\nInternational Endogene Consort ...\n\nBeiträge in Fachzeitschriften\nISI:000349190300031\n25673413.0\n10.1038/nature14177\nPMC4382211\nObesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339, 24 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.\n\nMärz, Winfried\n\nPilz, Stefan\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n177809\nGuidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).\n\nCossarizza, A\n\nChang, HD\n\nRadbruch, A\n\nAcs, A\n\nAdam, D\n\nAdam-Klages, S\n\nAgace, WW\n\nAghaeepour, N\n\nAkdis, M\n\nAllez, M\n\nAlmeida, LN\n\nAlvisi, G\n\nAnderson, G\n\nAndrä, I\n\nAnnunziato, F\n\nAnselmo, A\n\nBacher, P\n\nBaldari, CT\n\nBari, S\n\nBarnaba, V\n\nBarros-Martins, J\n\nBattistini, L\n\nBauer, W\n\nBaumgart, S\n\nBaumgarth, N\n\nBaumjohann, D\n\nBaying, B\n\nBebawy, M\n\nBecher, B\n\nBeisker, W\n\nBenes, V\n\nBeyaert, R\n\nBlanco, A\n\nBoardman, DA\n\nBogdan, C\n\nBorger, JG\n\nBorsellino, G\n\nBoulais, PE\n\nBradford, JA\n\nBrenner, D\n\nBrinkman, RR\n\nBrooks, AES\n\nBusch, DH\n\nBüscher, M\n\nBushnell, TP\n\nCalzetti, F\n\nCameron, G\n\nCammarata, I\n\nCao, X\n\nCardell, SL\n\nCasola, S\n\nCassatella, MA\n\nCavani, A\n\nCelada, A\n\nChatenoud, L\n\nChattopadhyay, PK\n\nChow, S\n\nChristakou, E\n\nČičin-Šain, L\n\nClerici, M\n\nColombo, FS\n\nCook, L\n\nCooke, A\n\nCooper, AM\n\nCorbett, AJ\n\nCosma, A\n\nCosmi, L\n\nCoulie, PG\n\nCumano, A\n\nCvetkovic, L\n\nDang, VD\n\nDang-Heine, C\n\nDavey, MS\n\nDavies, D\n\nDe Biasi, S\n\nDel Zotto, G\n\nDela Cruz, GV\n\nDelacher, M\n\nDella Bella, S\n\nDellabona, P\n\nDeniz, G\n\nDessing, M\n\nDi Santo, JP\n\nDiefenbach, A\n\nDieli, F\n\nDolf, A\n\nDörner, T\n\nDress, RJ\n\nDudziak, D\n\nDustin, M\n\nDutertre, CA\n\nEbner, F\n\nEckle, SBG\n\nEdinger, M\n\nEede, P\n\nEhrhardt, GRA\n\nEich, M\n\nEngel, P\n\nEngelhardt, B\n\nErdei, A\n\nEsser, C\n\nEverts, B\n\nEvrard, M\n\nFalk, CS\n\nFehniger, TA\n\nFelipo-Benavent, M\n\nFerry, H\n\nFeuerer, M\n\nFilby, A\n\nFilkor, K\n\nFillatreau, S\n\nFollo, M\n\nFörster, I\n\nFoster, J\n\nFoulds, GA\n\nFrehse, B\n\nFrenette, PS\n\nFrischbutter, S\n\nFritzsche, W\n\nGalbraith, DW\n\nGangaev, A\n\nGarbi, N\n\nGaudilliere, B\n\nGazzinelli, RT\n\nGeginat, J\n\nGerner, W\n\nGherardin, NA\n\nGhoreschi, K\n\nGibellini, L\n\nGinhoux, F\n\nGoda, K\n\nGodfrey, DI\n\nGoettlinger, C\n\nGonzález-Navajas, JM\n\nGoodyear, CS\n\nGori, A\n\nGrogan, JL\n\nGrummitt, D\n\nGrützkau, A\n\nHaftmann, C\n\nHahn, J\n\nHammad, H\n\nHämmerling, G\n\nHansmann, L\n\nHansson, G\n\nHarpur, CM\n\nHartmann, S\n\nHauser, A\n\nHauser, AE\n\nHaviland, DL\n\nHedley, D\n\nHernández, DC\n\nHerrera, G\n\nHerrmann, M\n\nHess, C\n\nHöfer, T\n\nHoffmann, P\n\nHogquist, K\n\nHolland, T\n\nHöllt, T\n\nHolmdahl, R\n\nHombrink, P\n\nHouston, JP\n\nHoyer, BF\n\nHuang, B\n\nHuang, FP\n\nHuber, JE\n\nHuehn, J\n\nHundemer, M\n\nHunter, CA\n\nHwang, WYK\n\nIannone, A\n\nIngelfinger, F\n\nIvison, SM\n\nJäck, HM\n\nJani, PK\n\nJávega, B\n\nJonjic, S\n\nKaiser, T\n\nKalina, T\n\nKamradt, T\n\nKaufmann, SHE\n\nKeller, B\n\nKetelaars, SLC\n\nKhalilnezhad, A\n\nKhan, S\n\nKisielow, J\n\nKlenerman, P\n\nKnopf, J\n\nKoay, HF\n\nKobow, K\n\nKolls, JK\n\nKong, WT\n\nKopf, M\n\nKorn, T\n\nKriegsmann, K\n\nKristyanto, H\n\nKroneis, T\n\nKrueger, A\n\nKühne, J\n\nKukat, C\n\nKunkel, D\n\nKunze-Schumacher, H\n\nKurosaki, T\n\nKurts, C\n\nKvistborg, P\n\nKwok, I\n\nLandry, J\n\nLantz, O\n\nLanuti, P\n\nLaRosa, F\n\nLehuen, A\n\nLeibundGut-Landmann, S\n\nLeipold, MD\n\nLeung, LYT\n\nLevings, MK\n\nLino, AC\n\nLiotta, F\n\nLitwin, V\n\nLiu, Y\n\nLjunggren, HG\n\nLohoff, M\n\nLombardi, G\n\nLopez, L\n\nLópez-Botet, M\n\nLovett-Racke, AE\n\nLubberts, E\n\nLuche, H\n\nLudewig, B\n\nLugli, E\n\nLunemann, S\n\nMaecker, HT\n\nMaggi, L\n\nMaguire, O\n\nMair, F\n\nMair, KH\n\nMantovani, A\n\nManz, RA\n\nMarshall, AJ\n\nMartínez-Romero, A\n\nMartrus, G\n\nMarventano, I\n\nMaslinski, W\n\nMatarese, G\n\nMattioli, AV\n\nMaueröder, C\n\nMazzoni, A\n\nMcCluskey, J\n\nMcGrath, M\n\nMcGuire, HM\n\nMcInnes, IB\n\nMei, HE\n\nMelchers, F\n\nMelzer, S\n\nMielenz, D\n\nMiller, SD\n\nMills, KHG\n\nMinderman, H\n\nMjösberg, J\n\nMoore, J\n\nMoran, B\n\nMoretta, L\n\nMosmann, TR\n\nMüller, S\n\nMulthoff, G\n\nMuñoz, LE\n\nMünz, C\n\nNakayama, T\n\nNasi, M\n\nNeumann, K\n\nNg, LG\n\nNiedobitek, A\n\nNourshargh, S\n\nNúñez, G\n\nO'Connor, JE\n\nOchel, A\n\nOja, A\n\nOrdonez, D\n\nOrfao, A\n\nOrlowski-Oliver, E\n\nOuyang, W\n\nOxenius, A\n\nPalankar, R\n\nPanse, I\n\nPattanapanyasat ...\n\nBeiträge in Fachzeitschriften\nISI:000491166500003\n31633216.0\n10.1002/eji.201970107\nPMC7350392\nThese guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.\n © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.\n\nKroneis, Thomas\n\n\n"
},
{
"text": "\n187327\nSwitching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial.\n\nHoeper, MM\n\nAl-Hiti, H\n\nBenza, RL\n\nChang, SA\n\nCorris, PA\n\nGibbs, JSR\n\nGrünig, E\n\nJansa, P\n\nKlinger, JR\n\nLangleben, D\n\nMcLaughlin, VV\n\nMeyer, GMB\n\nOta-Arakaki, J\n\nPeacock, AJ\n\nPulido, T\n\nRosenkranz, S\n\nVizza, CD\n\nVonk-Noordegraaf, A\n\nWhite, RJ\n\nChang, M\n\nKleinjung, F\n\nMeier, C\n\nParaschin, K\n\nGhofrani, HA\n\nSimonneau, G\n\nREPLACE investigators\n\nBeiträge in Fachzeitschriften\nNone\n33773120.0\n10.1016/S2213-2600(20)30532-4\nNone\nRiociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality.\n Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) was an open-label, randomised controlled trial in 81 hospital-based pulmonary hypertension centres in 22 countries. The study enrolled patients aged 18-75 years with symptomatic PAH at intermediate risk of 1-year mortality (based on the European Society for Cardiology-European Respiratory Society guideline thresholds for WHO functional class and 6-min walk distance [6MWD]) who were receiving treatment with a PDE5i with or without an endothelin receptor antagonist for at least 6 weeks before randomisation. Patients were excluded if they had been previously treated with riociguat, had used prostacyclin analogues or prostacyclin receptor agonists within 30 days before randomisation, had clinically significant restrictive or obstructive parenchymal lung disease, or had left heart disease. Patients were randomly assigned (1:1) to remain on PDE5i treatment (oral sildenafil [≥60 mg per day] or oral tadalafil [20-40 mg per day]; the PDE5i group) or to switch to oral riociguat (up to 2·5 mg three times per day; the riociguat group), using an interactive voice and web response system, stratified by cause of PAH. The primary endpoint was clinical improvement by week 24, defined as an absence of clinical worsening and prespecified improvements in at least two of three variables (6MWD, WHO functional class, and N-terminal prohormone of brain natriuretic peptide), analysed using last observation carried forward in all randomly assigned patients with observed values at baseline and week 24 who received at least one dose of study medication (the full analysis set). Secondary endpoints included clinical worsening events. The trial has been completed and is registered with ClinicalTrials.gov, NCT02891850.\n Between Jan 11, 2017, and July 31, 2019, 293 patients were screened, of which 226 patients were randomly assigned to the riociguat group (n=111) or to the PDE5i group (n=115). 211 patients completed the study and 14 patients discontinued (seven in each group). One patient assigned to the PDE5i group did not receive treatment, so 225 patients were included in the safety analysis, and one further patient in the PDE5i group had missing components of the composite primary endpoint at baseline, so 224 patients were included in the full analysis set. The primary endpoint was met by 45 (41%) of 111 patients in the riociguat group and 23 (20%) of 113 patients in the PDE5i group; odds ratio [OR] 2·78 (95% CI 1·53-5·06; p=0·0007). Clinical worsening events occurred in one (1%) of 111 patients in the riociguat group (hospitalisation due to worsening PAH) and 10 (9%) of 114 patients in the PDE5i group (hospitalisation due to worsening PAH [n=9]; disease progression [n=1]; OR 0·10 [0·01-0·73]; p=0·0047). The most frequently occurring adverse events were hypotension (15 [14%]), headache (14 [13%]), and dyspepsia (10 [9%]) in the riociguat group, and headache (eight [7%]), cough (seven [6%]), and upper respiratory tract infection (seven [6%]) in the PDE5i group. Serious adverse events were reported in eight (7%) of 111 patients in the riociguat group and 19 (17%) of 114 patients in the PDE5i group. During the study, four patients died in the PDE5i group, one of them during the safety follow-up period.\n Switching to riociguat from PDE5i treatment, both of which act via the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway, could be a strategic option for treatment escalation in patients with PAH at intermediate risk of 1-year mortality.\n Bayer AG, Merck Sharp & Dohme.\n Copyright © 2021 Elsevier Ltd. All rights reserved.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n143257\nNew genetic loci link adipose and insulin biology to body fat distribution.\n\nShungin, D\n\nWinkler, TW\n\nCroteau-Chonka, DC\n\nFerreira, T\n\nLocke, AE\n\nMägi, R\n\nStrawbridge, RJ\n\nPers, TH\n\nFischer, K\n\nJustice, AE\n\nWorkalemahu, T\n\nWu, JMW\n\nBuchkovich, ML\n\nHeard-Costa, NL\n\nRoman, TS\n\nDrong, AW\n\nSong, C\n\nGustafsson, S\n\nDay, FR\n\nEsko, T\n\nFall, T\n\nKutalik, Z\n\nLuan, J\n\nRandall, JC\n\nScherag, A\n\nVedantam, S\n\nWood, AR\n\nChen, J\n\nFehrmann, R\n\nKarjalainen, J\n\nKahali, B\n\nLiu, CT\n\nSchmidt, EM\n\nAbsher, D\n\nAmin, N\n\nAnderson, D\n\nBeekman, M\n\nBragg-Gresham, JL\n\nBuyske, S\n\nDemirkan, A\n\nEhret, GB\n\nFeitosa, MF\n\nGoel, A\n\nJackson, AU\n\nJohnson, T\n\nKleber, ME\n\nKristiansson, K\n\nMangino, M\n\nLeach, IM\n\nMedina-Gomez, C\n\nPalmer, CD\n\nPasko, D\n\nPechlivanis, S\n\nPeters, MJ\n\nProkopenko, I\n\nStančáková, A\n\nSung, YJ\n\nTanaka, T\n\nTeumer, A\n\nVan Vliet-Ostaptchouk, JV\n\nYengo, L\n\nZhang, W\n\nAlbrecht, E\n\nÄrnlöv, J\n\nArscott, GM\n\nBandinelli, S\n\nBarrett, A\n\nBellis, C\n\nBennett, AJ\n\nBerne, C\n\nBlüher, M\n\nBöhringer, S\n\nBonnet, F\n\nBöttcher, Y\n\nBruinenberg, M\n\nCarba, DB\n\nCaspersen, IH\n\nClarke, R\n\nDaw, EW\n\nDeelen, J\n\nDeelman, E\n\nDelgado, G\n\nDoney, AS\n\nEklund, N\n\nErdos, MR\n\nEstrada, K\n\nEury, E\n\nFriedrich, N\n\nGarcia, ME\n\nGiedraitis, V\n\nGigante, B\n\nGo, AS\n\nGolay, A\n\nGrallert, H\n\nGrammer, TB\n\nGräßler, J\n\nGrewal, J\n\nGroves, CJ\n\nHaller, T\n\nHallmans, G\n\nHartman, CA\n\nHassinen, M\n\nHayward, C\n\nHeikkilä, K\n\nHerzig, KH\n\nHelmer, Q\n\nHillege, HL\n\nHolmen, O\n\nHunt, SC\n\nIsaacs, A\n\nIttermann, T\n\nJames, AL\n\nJohansson, I\n\nJuliusdottir, T\n\nKalafati, IP\n\nKinnunen, L\n\nKoenig, W\n\nKooner, IK\n\nKratzer, W\n\nLamina, C\n\nLeander, K\n\nLee, NR\n\nLichtner, P\n\nLind, L\n\nLindström, J\n\nLobbens, S\n\nLorentzon, M\n\nMach, F\n\nMagnusson, PK\n\nMahajan, A\n\nMcArdle, WL\n\nMenni, C\n\nMerger, S\n\nMihailov, E\n\nMilani, L\n\nMills, R\n\nMoayyeri, A\n\nMonda, KL\n\nMooijaart, SP\n\nMühleisen, TW\n\nMulas, A\n\nMüller, G\n\nMüller-Nurasyid, M\n\nNagaraja, R\n\nNalls, MA\n\nNarisu, N\n\nGlorioso, N\n\nNolte, IM\n\nOlden, M\n\nRayner, NW\n\nRenstrom, F\n\nRied, JS\n\nRobertson, NR\n\nRose, LM\n\nSanna, S\n\nScharnagl, H\n\nScholtens, S\n\nSennblad, B\n\nSeufferlein, T\n\nSitlani, CM\n\nSmith, AV\n\nStirrups, K\n\nStringham, HM\n\nSundström, J\n\nSwertz, MA\n\nSwift, AJ\n\nSyvänen, AC\n\nTayo, BO\n\nThorand, B\n\nThorleifsson, G\n\nTomaschitz, A\n\nTroffa, C\n\nvan Oort, FV\n\nVerweij, N\n\nVonk, JM\n\nWaite, LL\n\nWennauer, R\n\nWilsgaard, T\n\nWojczynski, MK\n\nWong, A\n\nZhang, Q\n\nZhao, JH\n\nBrennan, EP\n\nChoi, M\n\nEriksson, P\n\nFolkersen, L\n\nFranco-Cereceda, A\n\nGharavi, AG\n\nHedman, ÅK\n\nHivert, MF\n\nHuang, J\n\nKanoni, S\n\nKarpe, F\n\nKeildson, S\n\nKiryluk, K\n\nLiang, L\n\nLifton, RP\n\nMa, B\n\nMcKnight, AJ\n\nMcPherson, R\n\nMetspalu, A\n\nMin, JL\n\nMoffatt, MF\n\nMontgomery, GW\n\nMurabito, JM\n\nNicholson, G\n\nNyholt, DR\n\nOlsson, C\n\nPerry, JR\n\nReinmaa, E\n\nSalem, RM\n\nSandholm, N\n\nSchadt, EE\n\nScott, RA\n\nStolk, L\n\nVallejo, EE\n\nWestra, HJ\n\nZondervan, KT\n\nADIPOGen Consortium\n\nCARDIOGRAMplusC4D Consortium\n\nCKDGen Consortium\n\nGEFOS Consortium\n\nGENIE Consortium\n\nGLGC\n\nICBP\n\nInternational Endogene Consortium\n\nLifeLines Cohort Study\n\nMAGIC Investigators\n\nMuTHER Consortium\n\nPAGE Consortium\n\nReproGen Consortium\n\nAmouyel, P\n\nArveiler, D\n\nBakker, SJ\n\nBeilby, J\n\nBergman, RN\n\nBlangero, J\n\nBrown, MJ\n\nBurnier, M\n\nCampbell, H\n\nChakravarti, A\n\nChines, PS\n\nClaudi-Boehm, S\n\nCollins, FS\n\nCrawford, DC\n\nDanesh, J\n\nde Faire, U\n\nde Geus, EJ\n\nDörr, M\n\nErbel, R\n\nEriksson, JG\n\nFarrall, M\n\nFerrannini, E\n\nFerrières, J\n\nForouhi, NG\n\nForrester, T\n\nFranco, OH\n\nGansevoort, RT\n\nGieger, C\n\nGudnason, V\n\nHaiman, CA\n\nHarris, TB\n\nHattersley, AT\n\nHeliövaara, M\n\nHicks, AA\n\nHingorani, AD\n\nHoffmann, W\n\nHofman, A\n\nHomuth, G\n\nHumphries, SE\n\nHyppönen, E\n\nIllig, T\n\nJarvelin, MR\n\nJohansen, B\n\nJousilahti ...\n\nBeiträge in Fachzeitschriften\nISI:000349190300030\n25673412.0\n10.1038/nature14132\nPMC4338562\nBody fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224, 59 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n152724\nGenome-wide association study identifies 74 loci associated with educational attainment.\n\nOkbay, A\n\nBeauchamp, JP\n\nFontana, MA\n\nLee, JJ\n\nPers, TH\n\nRietveld, CA\n\nTurley, P\n\nChen, GB\n\nEmilsson, V\n\nMeddens, SF\n\nOskarsson, S\n\nPickrell, JK\n\nThom, K\n\nTimshel, P\n\nde Vlaming, R\n\nAbdellaoui, A\n\nAhluwalia, TS\n\nBacelis, J\n\nBaumbach, C\n\nBjornsdottir, G\n\nBrandsma, JH\n\nPina Concas, M\n\nDerringer, J\n\nFurlotte, NA\n\nGalesloot, TE\n\nGirotto, G\n\nGupta, R\n\nHall, LM\n\nHarris, SE\n\nHofer, E\n\nHorikoshi, M\n\nHuffman, JE\n\nKaasik, K\n\nKalafati, IP\n\nKarlsson, R\n\nKong, A\n\nLahti, J\n\nvan der Lee, SJ\n\ndeLeeuw, C\n\nLind, PA\n\nLindgren, KO\n\nLiu, T\n\nMangino, M\n\nMarten, J\n\nMihailov, E\n\nMiller, MB\n\nvan der Most, PJ\n\nOldmeadow, C\n\nPayton, A\n\nPervjakova, N\n\nPeyrot, WJ\n\nQian, Y\n\nRaitakari, O\n\nRueedi, R\n\nSalvi, E\n\nSchmidt, B\n\nSchraut, KE\n\nShi, J\n\nSmith, AV\n\nPoot, RA\n\nSt Pourcain, B\n\nTeumer, A\n\nThorleifsson, G\n\nVerweij, N\n\nVuckovic, D\n\nWellmann, J\n\nWestra, HJ\n\nYang, J\n\nZhao, W\n\nZhu, Z\n\nAlizadeh, BZ\n\nAmin, N\n\nBakshi, A\n\nBaumeister, SE\n\nBiino, G\n\nBønnelykke, K\n\nBoyle, PA\n\nCampbell, H\n\nCappuccio, FP\n\nDavies, G\n\nDe Neve, JE\n\nDeloukas, P\n\nDemuth, I\n\nDing, J\n\nEibich, P\n\nEisele, L\n\nEklund, N\n\nEvans, DM\n\nFaul, JD\n\nFeitosa, MF\n\nForstner, AJ\n\nGandin, I\n\nGunnarsson, B\n\nHalldórsson, BV\n\nHarris, TB\n\nHeath, AC\n\nHocking, LJ\n\nHolliday, EG\n\nHomuth, G\n\nHoran, MA\n\nHottenga, JJ\n\nde Jager, PL\n\nJoshi, PK\n\nJugessur, A\n\nKaakinen, MA\n\nKähönen, M\n\nKanoni, S\n\nKeltigangas-Järvinen, L\n\nKiemeney, LA\n\nKolcic, I\n\nKoskinen, S\n\nKraja, AT\n\nKroh, M\n\nKutalik, Z\n\nLatvala, A\n\nLauner, LJ\n\nLebreton, MP\n\nLevinson, DF\n\nLichtenstein, P\n\nLichtner, P\n\nLiewald, DC\n\nLifeLines Cohort Study\n\nLoukola, A\n\nMadden, PA\n\nMägi, R\n\nMäki-Opas, T\n\nMarioni, RE\n\nMarques-Vidal, P\n\nMeddens, GA\n\nMcMahon, G\n\nMeisinger, C\n\nMeitinger, T\n\nMilaneschi, Y\n\nMilani, L\n\nMontgomery, GW\n\nMyhre, R\n\nNelson, CP\n\nNyholt, DR\n\nOllier, WE\n\nPalotie, A\n\nPaternoster, L\n\nPedersen, NL\n\nPetrovic, KE\n\nPorteous, DJ\n\nRäikkönen, K\n\nRing, SM\n\nRobino, A\n\nRostapshova, O\n\nRudan, I\n\nRustichini, A\n\nSalomaa, V\n\nSanders, AR\n\nSarin, AP\n\nSchmidt, H\n\nScott, RJ\n\nSmith, BH\n\nSmith, JA\n\nStaessen, JA\n\nSteinhagen-Thiessen, E\n\nStrauch, K\n\nTerracciano, A\n\nTobin, MD\n\nUlivi, S\n\nVaccargiu, S\n\nQuaye, L\n\nvan Rooij, FJ\n\nVenturini, C\n\nVinkhuyzen, AA\n\nVölker, U\n\nVölzke, H\n\nVonk, JM\n\nVozzi, D\n\nWaage, J\n\nWare, EB\n\nWillemsen, G\n\nAttia, JR\n\nBennett, DA\n\nBerger, K\n\nBertram, L\n\nBisgaard, H\n\nBoomsma, DI\n\nBorecki, IB\n\nBültmann, U\n\nChabris, CF\n\nCucca, F\n\nCusi, D\n\nDeary, IJ\n\nDedoussis, GV\n\nvan Duijn, CM\n\nEriksson, JG\n\nFranke, B\n\nFranke, L\n\nGasparini, P\n\nGejman, PV\n\nGieger, C\n\nGrabe, HJ\n\nGratten, J\n\nGroenen, PJ\n\nGudnason, V\n\nvan der Harst, P\n\nHayward, C\n\nHinds, DA\n\nHoffmann, W\n\nHyppönen, E\n\nIacono, WG\n\nJacobsson, B\n\nJärvelin, MR\n\nJöckel, KH\n\nKaprio, J\n\nKardia, SL\n\nLehtimäki, T\n\nLehrer, SF\n\nMagnusson, PK\n\nMartin, NG\n\nMcGue, M\n\nMetspalu, A\n\nPendleton, N\n\nPenninx, BW\n\nPerola, M\n\nPirastu, N\n\nPirastu, M\n\nPolasek, O\n\nPosthuma, D\n\nPower, C\n\nProvince, MA\n\nSamani, NJ\n\nSchlessinger, D\n\nSchmidt, R\n\nSørensen, TI\n\nSpector, TD\n\nStefansson, K\n\nThorsteinsdottir, U\n\nThurik, AR\n\nTimpson, NJ\n\nTiemeier, H\n\nTung, JY\n\nUitterlinden, AG\n\nVitart, V\n\nVollenweider, P\n\nWeir, DR\n\nWilson, JF\n\nWright, AF\n\nConley, DC\n\nKrueger, RF\n\nDavey Smith, G\n\nHofman, A\n\nLaibson, DI\n\nMedland, SE\n\nMeyer, MN\n\nYang, J\n\nJohannesson, M\n\nVisscher, PM\n\nEsko, T\n\nKoellinger, PD\n\nCesarini, D\n\nBenjamin, DJ\n\nBeiträge in Fachzeitschriften\nISI:000376443100042\n27225129.0\n10.1038/nature17671\nPMC4883595\nEducational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101, 69 individuals to 293, 23 individuals, and a replication study in an independent sample of 111, 49 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.\n\nHofer, Edith\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n162523\nHistory of ophthalmic oncology at the Department of Ophthalmology, Medical University Graz (MUG)\n\nLangmann, G\n\nWackernagel, W\n\nMayer, C\n\nTarmann, L\n\nSchwab, C\n\nWedrich, A\n\nBeiträge in Fachzeitschriften\nISI:000409029600011\nNone\n10.1007/s00717-017-0369-2\nNone\nThe beginning of eye-preserving therapy at the Department of Ophthalmology, Medical University Graz (MUG) dates back to 1985 with the introduction of Ruthenium 106 applicators (Lommatzsch, Vormun). The author sketches in chronological order the introduction and development of different types of gobe-preserving therapies and ends with new treatment modalities of retinoblastoma and metastasizing choroidal melanoma. The former heads of the Department of Ophthalmolgy, beginning with Hofmann, supported the paradigm shift from a radical-surgical concept (enucleation) of intraocular tumors to an globe-preserving therapy despite the absence of large studies with high evidence. Assigning ophthalmologists were justifiably in doubt about the meaningfulness of these new therapeutic concepts, but with their patients' assignments they have been supporting the new paradigm shift to the present day. Uveal melanoma: In 1985, the eye-preserving therapy was introduced by means of Ruthenium 106 applicators in Graz for small and medium-sized choroidal melanomas with aequatorial and anterior localisations. Between 1992 and 2011 the Gamma Knife Radiosurgery was used as an alternative to proton and photon therapy at the Univ. Clinic for Neurosurgery in Graz. Radiosurgery was developed with contributions from other tumor centers for the treatment of large choroidal melanomas or those with posterior localization. Transpupillary thermotherapy (TTT): Transpupillary thermotherapy (TTT) was developed in an animal model in 1995 in Leiden by Osterhuis and Journ, de Korver for the treatment of flat posterior localized melanomas. The therapy has been discredited and neglected due to an increased rate of recurrences in individual tumor centers, but should be evaluated again on the basis of good personal experience. Endoresection: Uveal melanomas are going to be resected after pre-irradiation because of the large tumor volume or a persisting retinal detachment by means of vitrectomy techniques. The Leksell Gamma Knife (LGK) was used as an irradiation technology in Graz and in Essen. Biopsy: Biopsies either with a transvitral or transscleral approach have been carried out for several years for histopathological, genetic and microbiological studies. New microbiological findings will hopefully lead to the development of promising new systemic therapeutic concepts. Retinoblastoma: In contrast to choroidal melanoma, adjuvant chemotherapy is highly effective in chemoreduction of retinoblastomas prior globe preserving therapy. Brachytherapy with Ruthenium 106 applicators, triple freeze/thaw cryotherapy and laser therapy have been used for decades at the deparment. TTT with or without simultaneous chemotherapy (chemothermotherapy) was recently introduced. New therapy concepts such as intrabulbar chemotherapy (already in use) as well as intraarterial chemotherapy (shortly before implementation) are already in routine. Since 2003, retinoblastomas have been treated in Graz for the first time in a therapy optimising study. So called RBA2003 was developed by the Department of Paediatric Hematology/Oncology in Graz together with the Department of Ophthalmology. The University Clinicum Graz establishes itself as a reference center for retinoblastomas and pseudoretinoblastomas in Austria and surrounding countries and has been receiving inquiries and patient assignments from the Alps Adria countries, Switzerland, Bulgaria, Czech Republic, Romania and Russia. Wedrich, currently chairman of the Department of Ophthalmology, Medical University Graz, promoted the development of the retinoblastoma competence center in terms of personnel, instrumentation and logistical aspects. In 2015, the Univ. Clinicum Essen developed an expanded international protocol based on the protocol RBA2003, according to which patients from Graz and Essen are now treated and evaluated together. This protocol, in turn, is considered in an EU application initiated by Chandada (Buenos Aires, Barcelona) for an uniform treatment of retinoblastomas in Europe. In 2003 the NGO, Light for the World, asked the Ophthalmic Oncology group Graz to examine the framework conditions for the establishment of a retinoblastoma center in Mozambique/Africa. Recently the Ophthalmic Oncology group of the Department of Ophthalmology was integrated into the Comprehensive Cancer Center (CCC) of the LKH Univ. Clinicum Graz. The concept of globe-preserving therapy established at the Department of Ophthalmology was confirmed 32 years after our introduction by the largest multicentric study (COMS study) in the USA, according to which no difference in survival between enucleation and globe-retaining therapy (Iodine 125) was found in small and medium-sized choroid melanomas. The unchanged (sometimes very bad) prognosis for over 30 years may possibly be improved in due time by new treatment concepts. The basis for these encouraging developments are cutting-edge findings from cytogenetic and molecular biological research.\n\nLangmann, Gerald\n\nMayer-Xanthaki, Christoph\n\nSchwab, Christoph\n\nWedrich, Andreas\n\n\n"
},
{
"text": "\n184687\nMonogenic variants in dystonia: an exome-wide sequencing study.\n\nZech, M\n\nJech, R\n\nBoesch, S\n\nŠkorvánek, M\n\nWeber, S\n\nWagner, M\n\nZhao, C\n\nJochim, A\n\nNecpál, J\n\nDincer, Y\n\nVill, K\n\nDistelmaier, F\n\nStoklosa, M\n\nKrenn, M\n\nGrunwald, S\n\nBock-Bierbaum, T\n\nFečíková, A\n\nHavránková, P\n\nRoth, J\n\nPříhodová, I\n\nAdamovičová, M\n\nUlmanová, O\n\nBechyně, K\n\nDanhofer, P\n\nVeselý, B\n\nHaň, V\n\nPavelekova, P\n\nGdovinová, Z\n\nMantel, T\n\nMeindl, T\n\nSitzberger, A\n\nSchröder, S\n\nBlaschek, A\n\nRoser, T\n\nBonfert, MV\n\nHaberlandt, E\n\nPlecko, B\n\nLeineweber, B\n\nBerweck, S\n\nHerberhold, T\n\nLangguth, B\n\nŠvantnerová, J\n\nMinár, M\n\nRamos-Rivera, GA\n\nWojcik, MH\n\nPajusalu, S\n\nÕunap, K\n\nSchatz, UA\n\nPölsler, L\n\nMilenkovic, I\n\nLaccone, F\n\nPilshofer, V\n\nColombo, R\n\nPatzer, S\n\nIuso, A\n\nVera, J\n\nTroncoso, M\n\nFang, F\n\nProkisch, H\n\nWilbert, F\n\nEckenweiler, M\n\nGraf, E\n\nWestphal, DS\n\nRiedhammer, KM\n\nBrunet, T\n\nAlhaddad, B\n\nBerutti, R\n\nStrom, TM\n\nHecht, M\n\nBaumann, M\n\nWolf, M\n\nTelegrafi, A\n\nPerson, RE\n\nZamora, FM\n\nHenderson, LB\n\nWeise, D\n\nMusacchio, T\n\nVolkmann, J\n\nSzuto, A\n\nBecker, J\n\nCremer, K\n\nSycha, T\n\nZimprich, F\n\nKraus, V\n\nMakowski, C\n\nGonzalez-Alegre, P\n\nBardakjian, TM\n\nOzelius, LJ\n\nVetro, A\n\nGuerrini, R\n\nMaier, E\n\nBorggraefe, I\n\nKuster, A\n\nWortmann, SB\n\nHackenberg, A\n\nSteinfeld, R\n\nAssmann, B\n\nStaufner, C\n\nOpladen, T\n\nRůžička, E\n\nCohn, RD\n\nDyment, D\n\nChung, WK\n\nEngels, H\n\nCeballos-Baumann, A\n\nPloski, R\n\nDaumke, O\n\nHaslinger, B\n\nMall, V\n\nOexle, K\n\nWinkelmann, J\n\nBeiträge in Fachzeitschriften\nISI:000581121200023\n33098801.0\n10.1016/S1474-4422(20)30312-4\nNone\nDystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia.\n For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow.\n We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism.\n In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations.\n Else Kröner-Fresenius-Stiftung, Technische Universität München, Helmholtz Zentrum München, Medizinische Universität Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.\n Copyright © 2020 Elsevier Ltd. All rights reserved.\n\nPlecko, Barbara\n\n\n"
},
{
"text": "\n123284\nResearch needs in allergy: an EAACI position paper, in collaboration with EFA.\n\nPapadopoulos, NG\n\nAgache, I\n\nBavbek, S\n\nBilo, BM\n\nBraido, F\n\nCardona, V\n\nCustovic, A\n\nDemonchy, J\n\nDemoly, P\n\nEigenmann, P\n\nGayraud, J\n\nGrattan, C\n\nHeffler, E\n\nHellings, PW\n\nJutel, M\n\nKnol, E\n\nLötvall, J\n\nMuraro, A\n\nPoulsen, LK\n\nRoberts, G\n\nSchmid-Grendelmeier, P\n\nSkevaki, C\n\nTriggiani, M\n\nVanree, R\n\nWerfel, T\n\nFlood, B\n\nPalkonen, S\n\nSavli, R\n\nAllegri, P\n\nAnnesi-Maesano, I\n\nAnnunziato, F\n\nAntolin-Amerigo, D\n\nApfelbacher, C\n\nBlanca, M\n\nBogacka, E\n\nBonadonna, P\n\nBonini, M\n\nBoyman, O\n\nBrockow, K\n\nBurney, P\n\nButers, J\n\nButiene, I\n\nCalderon, M\n\nCardell, LO\n\nCaubet, JC\n\nCelenk, S\n\nCichocka-Jarosz, E\n\nCingi, C\n\nCouto, M\n\nDejong, N\n\nDel Giacco, S\n\nDouladiris, N\n\nFassio, F\n\nFauquert, JL\n\nFernandez, J\n\nRivas, MF\n\nFerrer, M\n\nFlohr, C\n\nGardner, J\n\nGenuneit, J\n\nGevaert, P\n\nGroblewska, A\n\nHamelmann, E\n\nHoffmann, HJ\n\nHoffmann-Sommergruber, K\n\nHovhannisyan, L\n\nHox, V\n\nJahnsen, FL\n\nKalayci, O\n\nKalpaklioglu, AF\n\nKleine-Tebbe, J\n\nKonstantinou, G\n\nKurowski, M\n\nLau, S\n\nLauener, R\n\nLauerma, A\n\nLogan, K\n\nMagnan, A\n\nMakowska, J\n\nMakrinioti, H\n\nMangina, P\n\nManole, F\n\nMari, A\n\nMazon, A\n\nMills, C\n\nMingomataj, E\n\nNiggemann, B\n\nNilsson, G\n\nOllert, M\n\nO'Mahony, L\n\nO'Neil, S\n\nPala, G\n\nPapi, A\n\nPassalacqua, G\n\nPerkin, M\n\nPfaar, O\n\nPitsios, C\n\nQuirce, S\n\nRaap, U\n\nRaulf-Heimsoth, M\n\nRhyner, C\n\nRobson-Ansley, P\n\nAlves, RR\n\nRoje, Z\n\nRondon, C\n\nRudzeviciene, O\n\nRuëff, F\n\nRukhadze, M\n\nRumi, G\n\nSackesen, C\n\nSantos, AF\n\nSantucci, A\n\nScharf, C\n\nSchmidt-Weber, C\n\nSchnyder, B\n\nSchwarze, J\n\nSenna, G\n\nSergejeva, S\n\nSeys, S\n\nSiracusa, A\n\nSkypala, I\n\nSokolowska, M\n\nSpertini, F\n\nSpiewak, R\n\nSprikkelman, A\n\nSturm, G\n\nSwoboda, I\n\nTerreehorst, I\n\nToskala, E\n\nTraidl-Hoffmann, C\n\nVenter, C\n\nVlieg-Boerstra, B\n\nWhitacker, P\n\nWorm, M\n\nXepapadaki, P\n\nAkdis, CA\n\nBeiträge in Fachzeitschriften\nNone\n23121771.0\n10.1186/2045-7022-2-21\nPMC3539924\nIn less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.\n\nSturm, Gunter\n\n\n"
},
{
"text": "\n157489\nNovel genetic loci associated with hippocampal volume.\n\nHibar, DP\n\nAdams, HHH\n\nJahanshad, N\n\nChauhan, G\n\nStein, JL\n\nHofer, E\n\nRenteria, ME\n\nBis, JC\n\nArias-Vasquez, A\n\nIkram, MK\n\nDesrivières, S\n\nVernooij, MW\n\nAbramovic, L\n\nAlhusaini, S\n\nAmin, N\n\nAndersson, M\n\nArfanakis, K\n\nAribisala, BS\n\nArmstrong, NJ\n\nAthanasiu, L\n\nAxelsson, T\n\nBeecham, AH\n\nBeiser, A\n\nBernard, M\n\nBlanton, SH\n\nBohlken, MM\n\nBoks, MP\n\nBralten, J\n\nBrickman, AM\n\nCarmichael, O\n\nChakravarty, MM\n\nChen, Q\n\nChing, CRK\n\nChouraki, V\n\nCuellar-Partida, G\n\nCrivello, F\n\nDen Braber, A\n\nDoan, NT\n\nEhrlich, S\n\nGiddaluru, S\n\nGoldman, AL\n\nGottesman, RF\n\nGrimm, O\n\nGriswold, ME\n\nGuadalupe, T\n\nGutman, BA\n\nHass, J\n\nHaukvik, UK\n\nHoehn, D\n\nHolmes, AJ\n\nHoogman, M\n\nJanowitz, D\n\nJia, T\n\nJørgensen, KN\n\nKarbalai, N\n\nKasperaviciute, D\n\nKim, S\n\nKlein, M\n\nKraemer, B\n\nLee, PH\n\nLiewald, DCM\n\nLopez, LM\n\nLuciano, M\n\nMacare, C\n\nMarquand, AF\n\nMatarin, M\n\nMather, KA\n\nMattheisen, M\n\nMcKay, DR\n\nMilaneschi, Y\n\nMuñoz Maniega, S\n\nNho, K\n\nNugent, AC\n\nNyquist, P\n\nLoohuis, LMO\n\nOosterlaan, J\n\nPapmeyer, M\n\nPirpamer, L\n\nPütz, B\n\nRamasamy, A\n\nRichards, JS\n\nRisacher, SL\n\nRoiz-Santiañez, R\n\nRommelse, N\n\nRopele, S\n\nRose, EJ\n\nRoyle, NA\n\nRundek, T\n\nSämann, PG\n\nSaremi, A\n\nSatizabal, CL\n\nSchmaal, L\n\nSchork, AJ\n\nShen, L\n\nShin, J\n\nShumskaya, E\n\nSmith, AV\n\nSprooten, E\n\nStrike, LT\n\nTeumer, A\n\nTordesillas-Gutierrez, D\n\nToro, R\n\nTrabzuni, D\n\nTrompet, S\n\nVaidya, D\n\nVan der Grond, J\n\nVan der Lee, SJ\n\nVan der Meer, D\n\nVan Donkelaar, MMJ\n\nVan Eijk, KR\n\nVan Erp, TGM\n\nVan Rooij, D\n\nWalton, E\n\nWestlye, LT\n\nWhelan, CD\n\nWindham, BG\n\nWinkler, AM\n\nWittfeld, K\n\nWoldehawariat, G\n\nWolf, C\n\nWolfers, T\n\nYanek, LR\n\nYang, J\n\nZijdenbos, A\n\nZwiers, MP\n\nAgartz, I\n\nAlmasy, L\n\nAmes, D\n\nAmouyel, P\n\nAndreassen, OA\n\nArepalli, S\n\nAssareh, AA\n\nBarral, S\n\nBastin, ME\n\nBecker, DM\n\nBecker, JT\n\nBennett, DA\n\nBlangero, J\n\nvan Bokhoven, H\n\nBoomsma, DI\n\nBrodaty, H\n\nBrouwer, RM\n\nBrunner, HG\n\nBuckner, RL\n\nBuitelaar, JK\n\nBulayeva, KB\n\nCahn, W\n\nCalhoun, VD\n\nCannon, DM\n\nCavalleri, GL\n\nCheng, CY\n\nCichon, S\n\nCookson, MR\n\nCorvin, A\n\nCrespo-Facorro, B\n\nCurran, JE\n\nCzisch, M\n\nDale, AM\n\nDavies, GE\n\nDe Craen, AJM\n\nDe Geus, EJC\n\nDe Jager, PL\n\nDe Zubicaray, GI\n\nDeary, IJ\n\nDebette, S\n\nDeCarli, C\n\nDelanty, N\n\nDepondt, C\n\nDeStefano, A\n\nDillman, A\n\nDjurovic, S\n\nDonohoe, G\n\nDrevets, WC\n\nDuggirala, R\n\nDyer, TD\n\nEnzinger, C\n\nErk, S\n\nEspeseth, T\n\nFedko, IO\n\nFernández, G\n\nFerrucci, L\n\nFisher, SE\n\nFleischman, DA\n\nFord, I\n\nFornage, M\n\nForoud, TM\n\nFox, PT\n\nFrancks, C\n\nFukunaga, M\n\nGibbs, JR\n\nGlahn, DC\n\nGollub, RL\n\nGöring, HHH\n\nGreen, RC\n\nGruber, O\n\nGudnason, V\n\nGuelfi, S\n\nHåberg, AK\n\nHansell, NK\n\nHardy, J\n\nHartman, CA\n\nHashimoto, R\n\nHegenscheid, K\n\nHeinz, A\n\nLe Hellard, S\n\nHernandez, DG\n\nHeslenfeld, DJ\n\nHo, BC\n\nHoekstra, PJ\n\nHoffmann, W\n\nHofman, A\n\nHolsboer, F\n\nHomuth, G\n\nHosten, N\n\nHottenga, JJ\n\nHuentelman, M\n\nHulshoff Pol, HE\n\nIkeda, M\n\nJack, CR\n\nJenkinson, M\n\nJohnson, R\n\nJönsson, EG\n\nJukema, JW\n\nKahn, RS\n\nKanai, R\n\nKloszewska, I\n\nKnopman, DS\n\nKochunov, P\n\nKwok, JB\n\nLawrie, SM\n\nLemaître, H\n\nLiu, X\n\nLongo, DL\n\nLopez, OL\n\nLovestone, S\n\nMartinez, O\n\nMartinot, JL\n\nMattay, VS\n\nMcDonald, C\n\nMcIntosh, AM\n\nMcMahon, FJ\n\nMcMahon, KL\n\nMecocci, P\n\nMelle, I\n\nMeyer-Lindenberg, A\n\nMohnke, S\n\nMontgomery, GW\n\nMorris, DW\n\nMosley, TH\n\nMühleisen, TW\n\nMüller-Myhsok, B\n\nNalls, MA\n\nNauck, M\n\nNichols, TE\n\nNiessen, WJ\n\nNöthen, MM\n\nNyberg, L\n\nOhi, K\n\nOlvera, RL\n\nOphoff, RA\n\nPandolfo, M\n\nPaus, T\n\nPausova, Z\n\nPenninx, BWJH\n\nPike, GB\n\nPotkin, SG\n\nPsaty, BM\n\nReppermund, S\n\nRietschel, M\n\nRoffman, JL\n\nRomanczuk-Seiferth, N\n\nRotter, JI\n\nRyten, M\n\nSacco, RL\n\nSachdev, PS\n\nSaykin, AJ\n\n...\n\nBeiträge in Fachzeitschriften\nISI:000392154900001\n28098162.0\n10.1038/ncomms13624\nPMC5253632\nThe hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33, 36 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.\n\nEnzinger, Christian\n\nHofer, Edith\n\nPirpamer, Lukas\n\nRopele, Stefan\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
}
]
}