@article{LuekeHallerUtpateletal.2022, author = {L{\"u}ke, Florian and Haller, Florian and Utpatel, Kirsten and Krebs, Markus and Meidenbauer, Norbert and Scheiter, Alexander and Spoerl, Silvia and Heudobler, Daniel and Sparrer, Daniela and Kaiser, Ulrich and Keil, Felix and Schubart, Christoph and T{\"o}gel, Lars and Einhell, Sabine and Dietmaier, Wolfgang and Huss, Ralf and Dintner, Sebastian and Sommer, Sebastian and Jordan, Frank and Goebeler, Maria-Elisabeth and Metz, Michaela and Haake, Diana and Scheytt, Mithun and Gerhard-Hartmann, Elena and Maurus, Katja and Br{\"a}ndlein, Stephanie and Rosenwald, Andreas and Hartmann, Arndt and M{\"a}rkl, Bruno and Einsele, Hermann and Mackensen, Andreas and Herr, Wolfgang and Kunzmann, Volker and Bargou, Ralf and Beckmann, Matthias W. and Pukrop, Tobias and Trepel, Martin and Evert, Matthias and Claus, Rainer and Kerscher, Alexander}, title = {Identification of disparities in personalized cancer care — a joint approach of the German WERA consortium}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {20}, issn = {2072-6694}, doi = {10.3390/cancers14205040}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290311}, year = {2022}, abstract = {(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in W{\"u}rzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy.}, language = {en} } @article{MarenholzEsparzaGordilloRueschendorfetal.2015, author = {Marenholz, Ingo and Esparza-Gordillo, Jorge and R{\"u}schendorf, Franz and Bauerfeind, Anja and Strachan, David P. and Spycher, Ben D. and Baurecht, Hansj{\"o}rg and Magaritte-Jeannin, Patricia and S{\"a}{\"a}f, Annika and Kerkhof, Marjan and Ege, Markus and Baltic, Svetlana and Matheson, Melanie C. and Li, Jin and Michel, Sven and Ang, Wei Q. and McArdle, Wendy and Arnold, Andreas and Homuth, Georg and Demenais, Florence and Bouzigon, Emmanuelle and S{\"o}derh{\"a}ll, Cilla and Pershagen, G{\"o}ran and de Jongste, Johan C. and Postma, Dirkje S. and Braun-Fahrl{\"a}nder, Charlotte and Horak, Elisabeth and Ogorodova, Ludmila M. and Puzyrev, Valery P. and Bragina, Elena Yu and Hudson, Thomas J. and Morin, Charles and Duffy, David L. and Marks, Guy B. and Robertson, Colin F. and Montgomery, Grant W. and Musk, Bill and Thompson, Philip J. and Martin, Nicholas G. and James, Alan and Sleiman, Patrick and Toskala, Elina and Rodriguez, Elke and F{\"o}lster-Holst, Regina and Franke, Andre and Lieb, Wolfgang and Gieger, Christian and Heinzmann, Andrea and Rietschel, Ernst and Keil, Thomas and Cichon, Sven and N{\"o}then, Markus M. and Pennel, Craig E. and Sly, Peter D. and Schmidt, Carsten O. and Matanovic, Anja and Schneider, Valentin and Heinig, Matthias and H{\"u}bner, Norbert and Holt, Patrick G. and Lau, Susanne and Kabesch, Michael and Weidinger, Stefan and Hakonarson, Hakon and Ferreira, Manuel A. R. and Laprise, Catherine and Freidin, Maxim B. and Genuneit, Jon and Koppelman, Gerard H. and Mel{\´e}n, Erik and Dizier, Marie-H{\´e}l{\`e}ne and Henderson, A. John and Lee, Young Ae}, title = {Meta-analysis identifies seven susceptibility loci involved in the atopic march}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {8804}, doi = {10.1038/ncomms9804}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139835}, year = {2015}, abstract = {Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.}, language = {en} } @article{GrussWieserSchweinbergeretal.2012, author = {Gruss, L. Forest and Wieser, Matthias J. and Schweinberger, Stefan R. and Keil, Andreas}, title = {Face-evoked steady-state visual potentials: effects of presentation rate and face inversion}, series = {Frontiers in Human Neuroscience}, volume = {6}, journal = {Frontiers in Human Neuroscience}, number = {316}, doi = {10.3389/fnhum.2012.00316}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134399}, year = {2012}, abstract = {Face processing can be explored using electrophysiological methods. Research with event-related potentials has demonstrated the so-called face inversion effect, in which the N170 component is enhanced in amplitude and latency to inverted, compared to upright, faces. The present study explored the extent to which repetitive lower-level visual cortical engagement, reflected in flicker steady-state visual evoked potentials (ssVEPs), shows similar amplitude enhancement to face inversion. We also asked if inversion-related ssVEP modulation would be dependent on the stimulation rate at which upright and inverted faces were flickered. To this end, multiple tagging frequencies were used (5, 10, 15, and 20 Hz) across two studies (n=21, n=18). Results showed that amplitude enhancement of the ssVEP for inverted faces was found solely at higher stimulation frequencies (15 and 20 Hz). By contrast, lower frequency ssVEPs did not show this inversion effect. These findings suggest that stimulation frequency affects the sensitivity of ssVEPs to face inversion.}, language = {en} } @article{GrabenhenrichReichFischeretal.2014, author = {Grabenhenrich, Linus B. and Reich, Andreas and Fischer, Felix and Zepp, Fred and Forster, Johannes and Schuster, Antje and Bauer, Carl-Peter and Bergmann, Renate L. and Bergmann, Karl E. and Wahn, Ulrich and Keil, Thomas and Lau, Susanne}, title = {The Novel 10-Item Asthma Prediction Tool: External Validation in the German MAS Birth Cohort}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {12}, issn = {1932-6203}, doi = {10.1371/journal.pone.0115852}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114202}, pages = {e115852}, year = {2014}, abstract = {Background: A novel non-invasive asthma prediction tool from the Leicester Cohort, UK, forecasts asthma at age 8 years based on 10 predictors assessed in early childhood, including current respiratory symptoms, eczema, and parental history of asthma. Objective: We aimed to externally validate the proposed asthma prediction method in a German birth cohort. Methods: The MAS-90 study (Multicentre Allergy Study) recorded details on allergic diseases prospectively in about yearly follow-up assessments up to age 20 years in a cohort of 1,314 children born 1990. We replicated the scoring method from the Leicester cohort and assessed prediction, performance and discrimination. The primary outcome was defined as the combination of parent-reported wheeze and asthma drugs (both in last 12 months) at age 8. Sensitivity analyses assessed model performance for outcomes related to asthma up to age 20 years. Results: For 140 children parents reported current wheeze or cough at age 3 years. Score distribution and frequencies of later asthma resembled the Leicester cohort: 9\% vs. 16\% (MAS-90 vs. Leicester) of children at low risk at 3 years had asthma at 8 years, at medium risk 45\% vs. 48\%. Performance of the asthma prediction tool in the MAS-90 cohort was similar (Brier score 0.22 vs. 0.23) and discrimination slightly better than in the original cohort (area under the curve, AUC 0.83 vs. 0.78). Prediction and discrimination were robust against changes of inclusion criteria, scoring and outcome definitions. The secondary outcome 'physicians' diagnosed asthma at 20 years' showed the highest discrimination (AUC 0.89). Conclusion: The novel asthma prediction tool from the Leicester cohort, UK, performed well in another population, a German birth cohort, supporting its use and further development as a simple aid to predict asthma risk in clinical settings.}, language = {en} } @article{StegmannAndreattaPaulietal.2023, author = {Stegmann, Yannik and Andreatta, Marta and Pauli, Paul and Keil, Andreas and Wieser, Matthias J.}, title = {Investigating sustained attention in contextual threat using steady-state VEPs evoked by flickering video stimuli}, series = {Psychophysiology}, volume = {60}, journal = {Psychophysiology}, number = {5}, doi = {10.1111/psyp.14229}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312430}, year = {2023}, abstract = {Anxiety is characterized by anxious anticipation and heightened vigilance to uncertain threat. However, if threat is not reliably indicated by a specific cue, the context in which threat was previously experienced becomes its best predictor, leading to anxiety. A suitable means to induce anxiety experimentally is context conditioning: In one context (CTX+), an unpredictable aversive stimulus (US) is repeatedly presented, in contrast to a second context (CTX-), in which no US is ever presented. In this EEG study, we investigated attentional mechanisms during acquisition and extinction learning in 38 participants, who underwent a context conditioning protocol. Flickering video stimuli (32 s clips depicting virtual offices representing CTX+/-) were used to evoke steady-state visual evoked potentials (ssVEPs) as an index of visuocortical engagement with the contexts. Analyses of the electrocortical responses suggest a successful induction of the ssVEP signal by video presentation in flicker mode. Furthermore, we found clear indices of context conditioning and extinction learning on a subjective level, while cortical processing of the CTX+ was unexpectedly reduced during video presentation. The differences between CTX+ and CTX- diminished during extinction learning. Together, these results indicate that the dynamic sensory input of the video presentation leads to disruptions in the ssVEP signal, which is greater for motivationally significant, threatening contexts.}, language = {en} } @article{WillekeJansonZinketal.2021, author = {Willeke, Kristina and Janson, Patrick and Zink, Katharina and Stupp, Carolin and Kittel-Schneider, Sarah and Bergh{\"o}fer, Anne and Ewert, Thomas and King, Ryan and Heuschmann, Peter U. and Zapf, Andreas and Wildner, Manfred and Keil, Thomas}, title = {Occurrence of mental illness and mental health risks among the self-employed: a systematic review}, series = {International Journal of Environmental Research and Public Health}, volume = {18}, journal = {International Journal of Environmental Research and Public Health}, number = {16}, issn = {1660-4601}, doi = {10.3390/ijerph18168617}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245085}, year = {2021}, abstract = {We aimed to systematically identify and evaluate all studies of good quality that compared the occurrence of mental disorders in the self-employed versus employees. Adhering to the Cochrane guidelines, we conducted a systematic review and searched three major medical databases (MEDLINE, Web of Science, Embase), complemented by hand search. We included 26 (three longitudinal and 23 cross-sectional) population-based studies of good quality (using a validated quality assessment tool), with data from 3,128,877 participants in total. The longest of these studies, a Swedish national register evaluation with 25 years follow-up, showed a higher incidence of mental illness among the self-employed compared to white-collar workers, but a lower incidence compared to blue-collar workers. In the second longitudinal study from Sweden the self-employed had a lower incidence of mental illness compared to both blue- and white-collar workers over 15 years, whereas the third longitudinal study (South Korea) did not find a difference regarding the incidence of depressive symptoms over 6 years. Results from the cross-sectional studies showed associations between self-employment and poor general mental health and stress, but were inconsistent regarding other mental outcomes. Most studies from South Korea found a higher prevalence of mental disorders among the self-employed compared to employees, whereas the results of cross-sectional studies from outside Asia were less consistent. In conclusion, we found evidence from population-based studies for a link between self-employment and increased risk of mental illness. Further longitudinal studies are needed examining the potential risk for the development of mental disorders in specific subtypes of the self-employed.}, language = {en} } @article{JansonWillekeZaibertetal.2022, author = {Janson, Patrick and Willeke, Kristina and Zaibert, Lisa and Budnick, Andrea and Bergh{\"o}fer, Anne and Kittel-Schneider, Sarah and Heuschmann, Peter U. and Zapf, Andreas and Wildner, Manfred and Stupp, Carolin and Keil, Thomas}, title = {Mortality, morbidity and health-related outcomes in informal caregivers compared to non-caregivers: a systematic review}, series = {International Journal of Environmental Research and Public Health}, volume = {19}, journal = {International Journal of Environmental Research and Public Health}, number = {10}, issn = {1660-4601}, doi = {10.3390/ijerph19105864}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275219}, year = {2022}, abstract = {A systematic overview of mental and physical disorders of informal caregivers based on population-based studies with good methodological quality is lacking. Therefore, our aim was to systematically summarize mortality, incidence, and prevalence estimates of chronic diseases in informal caregivers compared to non-caregivers. Following PRISMA recommendations, we searched major healthcare databases (CINAHL, MEDLINE and Web of Science) systematically for relevant studies published in the last 10 years (without language restrictions) (PROSPERO registration number: CRD42020200314). We included only observational cross-sectional and cohort studies with low risk of bias (risk scores 0-2 out of max 8) that reported the prevalence, incidence, odds ratio (OR), hazard ratio (HR), mean- or sum-scores for health-related outcomes in informal caregivers and non-caregivers. For a thorough methodological quality assessment, we used a validated checklist. The synthesis of the results was conducted by grouping outcomes. We included 22 studies, which came predominately from the USA and Europe. Informal caregivers had a significantly lower mortality than non-caregivers. Regarding chronic morbidity outcomes, the results from a large longitudinal German health-insurance evaluation showed increased and statistically significant incidences of severe stress, adjustment disorders, depression, diseases of the spine and pain conditions among informal caregivers compared to non-caregivers. In cross-sectional evaluations, informal caregiving seemed to be associated with a higher occurrence of depression and of anxiety (ranging from 4 to 51\% and 2 to 38\%, respectively), pain, hypertension, diabetes and reduced quality of life. Results from our systematic review suggest that informal caregiving may be associated with several mental and physical disorders. However, these results need to be interpreted with caution, as the cross-sectional studies cannot determine temporal relationships. The lower mortality rates compared to non-caregivers may be due to a healthy-carer bias in longitudinal observational studies; however, these and other potential benefits of informal caregiving deserve further attention by researchers.}, language = {en} } @article{GrabenhenrichTrendelenburgBellachetal.2020, author = {Grabenhenrich, Linus and Trendelenburg, Val{\´e}rie and Bellach, Johanna and Y{\"u}rek, Song{\"u}l and Reich, Andreas and Fiandor, Ana and Rivero, Daniela and Sigurdardottir, Sigurveig and Clausen, Michael and Papadopoulos, Nikolaos G. and Xepapadaki, Paraskevi and Sprikkelman, Aline B. and Dontje, Bianca and Roberts, Graham and Grimshaw, Kate and Kowalski, Marek L. and Kurowski, Marcin and Dubakiene, Ruta and Rudzeviciene, Odilija and Fern{\´a}ndez-Rivas, Montserrat and Couch, Philip and Versteeg, Serge A. and van Ree, Ronald and Mills, Clare and Keil, Thomas and Beyer, Kirsten}, title = {Frequency of food allergy in school-aged children in eight European countries—The EuroPrevall-iFAAM birth cohort}, series = {Allergy}, volume = {75}, journal = {Allergy}, number = {9}, doi = {10.1111/all.14290}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214746}, pages = {2294 -- 2308}, year = {2020}, abstract = {Background The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. Methods A follow-up assessment at age 6-10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). Results A total of 6105 children participated in this school-age follow-up (57.8\% of 10 563 recruited at birth). For 982 of 6069 children (16.2\%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4\%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4\% (88 related to all 6105 participants of this follow-up) and 3.8\% (88 related to 2289 with completed eligibility assessment). Interpretation In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons.}, language = {en} } @article{TanoeyBaechleBrenneretal.2022, author = {Tanoey, Justine and Baechle, Christina and Brenner, Hermann and Deckert, Andreas and Fricke, Julia and G{\"u}nther, Kathrin and Karch, Andr{\´e} and Keil, Thomas and Kluttig, Alexander and Leitzmann, Michael and Mikolajczyk, Rafael and Obi, Nadia and Pischon, Tobias and Schikowski, Tamara and Schipf, Sabine M. and Schulze, Matthias B. and Sedlmeier, Anja and Moreno Vel{\´a}squez, Ilais and Weber, Katharina S. and V{\"o}lzke, Henry and Ahrens, Wolfgang and Gastell, Sylvia and Holleczek, Bernd and J{\"o}ckel, Karl-Heinz and Katzke, Verena and Lieb, Wolfgang and Michels, Karin B. and Schmidt, B{\"o}rge and Teismann, Henning and Becher, Heiko}, title = {Birth order, Caesarean section, or daycare attendance in relation to child- and adult-onset type 1 diabetes: results from the German National Cohort}, series = {International Journal of Environmental Research and Public Health}, volume = {19}, journal = {International Journal of Environmental Research and Public Health}, number = {17}, issn = {1660-4601}, doi = {10.3390/ijerph191710880}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286216}, year = {2022}, abstract = {(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to "only-children", HRs for second- or later-born individuals were 0.70 (95\% CI = 0.50-0.96) and 0.65 (95\% CI = 0.45-0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults' T1D risk assessment for early detection.}, language = {en} }