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  • 1
    In: Journal of Clinical Periodontology, Wiley, Vol. 44, No. 10 ( 2017-10), p. 962-970
    Abstract: The intronic variant rs4252120 in the plasminogen gene ( PLG ) is known to be associated with aggressive periodontitis (AgP) and atherosclerosis. Here, we examined the chromosomal region spanning PLG for associations with both chronic periodontitis (CP) and AgP. Materials and Methods The association of PLG candidate rs4252120 was tested in a German case–control sample of 1,419 CP cases using the genotyping assay hCV11225947 and 4,562 controls, genotyped with HumanOmni BeadChips. The German and Dutch sample of AgP cases ( N  = 851) and controls ( N  = 6,836) were genotyped with HumanOmni BeadChips. The North American CP sample ( N  = 2,681 cases, 1,823 controls) was previously genotyped on the Genome‐Wide Human SNP Array 6.0. Genotypes were imputed (software Impute v2), and association tests were performed using an additive genetic model adjusting for sex and smoking. Results Rs4252120 was not associated with CP. However, a haplotype block downstream of PLG and not in linkage disequilibrium with rs4252120 ( r 2  = .08) was associated with both AgP (rs1247559; p  =   .002, odds ratio [OR] = 1.33) and CP ( p  =   .02, OR = 1.15). That locus was also significantly associated with PLG expression in osteoblasts ( p  =   6.9 × 10 −5 ). Conclusions Our findings support a role of genetic variants in PLG in the aetiology of periodontitis.
    Type of Medium: Online Resource
    ISSN: 0303-6979 , 1600-051X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2026349-1
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  • 2
    In: Clinical and Translational Allergy, Wiley, Vol. 6, No. S1 ( 2016-11)
    Type of Medium: Online Resource
    ISSN: 2045-7022
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2630865-4
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  • 3
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 50, No. 5 ( 2019-09), p. 580-589
    Abstract: Single‐centre studies reported alterations of faecal microbiota in patients with primary sclerosing cholangitis (PSC). As regional factors may affect microbial communities, it is unclear if a microbial signature of PSC exists across different geographical regions. Aim To identify a robust microbial signature of PSC independent of geography and environmental influences. Methods We included 388 individuals (median age, 47 years; range, 15‐78) from Germany and Norway in the study, 137 patients with PSC (n = 75 with colitis), 118 with ulcerative colitis (UC) and 133 healthy controls. Faecal microbiomes were analysed by 16S rRNA gene sequencing (V1‐V2). Differences in relative abundances of single taxa were subjected to a meta‐analysis. Results In both cohorts, microbiota composition (beta‐diversity) differed between PSC patients and controls ( P   〈  0.001). Random forests classification discriminated PSC patients from controls in both geographical cohorts with an average area under the curve of 0.88. Compared to healthy controls, many new cohort‐spanning alterations were identified in PSC, such as an increase of Proteobacteria and the bile‐tolerant genus Parabacteroides , which were detected independent from geographical region. Associated colitis only had minor effects on microbiota composition, suggesting that PSC itself drives the faecal microbiota changes observed. Conclusion Compared to healthy controls, numerous microbiota alterations are reproducible in PSC patients across geographical regions, clearly pointing towards a microbiota composition that is shaped by the disease itself and not by environmental factors. These reproducibly altered microbial populations might provide future insights into the pathophysiology of PSC.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2003094-0
    SSG: 15,3
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  • 4
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 53, No. 2 ( 2021-01), p. 302-313
    Abstract: Primary sclerosing cholangitis (PSC) is associated with progressive liver disease and cholangiocarcinoma. Although risk stratification is crucial for making clinical decisions, it is hindered by a scarcity of proven prognostic markers. Aims To assess the value of novel anti‐glycoprotein 2 (anti‐GP2) and anti‐neutrophil cytoplasmic antibodies to serine proteinase 3 (PR3‐ANCA) in combination with PSC‐specific clinical and laboratory markers as predictors of quality of life, disease severity, and cholangiocarcinoma in two large, independent cohorts of PSC patients Methods Discovery (338 Polish patients) and validation (178 German patients) cohorts with PSC were evaluated. Anti‐GP2 (isoforms 1/4) was detected by ELISAs and PR3‐ANCA by chemiluminescence immunoassay. Clinical and laboratory data were collected and analysed. The outcome was defined as liver transplantation‐free survival and occurrence of cholangiocarcinoma during follow‐up. Results In the discovery group, anti‐GP2 1/4 IgA and PR3‐ANCA were associated with liver dysfunction, anti‐GP2 1/4 IgA with risk scores for PSC and anti‐GP2 4 IgA with cirrhosis. All cholangiocarcinoma patients were positive for PR3‐ANCA and/or anti‐GP2 4 IgA. The association between anti‐GP2 IgA and liver biochemistry, risk scores, cirrhosis, impaired survival, and cholangiocarcinoma was confirmed in the validation cohort. Cox proportional‐hazards regression indicated anti‐GP2 1 IgA as an independent variable of poor outcome in both study cohorts. Analysis of the combined data showed that anti‐GP2 4 IgA and PR3‐ANCA were independent predictors for cholangiocarcinoma, while anti‐GP2 1 IgA and PR3‐ANCA were indicators for poor survival. Conclusions Anti‐GP2 and PR3‐ANCA are prognostic antibodies in PSC as they identify patients at risk of severe disease, poor survival and biliary cancer.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2003094-0
    SSG: 15,3
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  • 5
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 51, No. 12 ( 2020-06), p. 1417-1428
    Abstract: The pathogenesis of autoimmune hepatitis (AIH) is poorly understood and little is known about enteric microbiota in AIH. Aim To investigate disease‐specific microbiome alterations in AIH. Methods The V1‐V2 variable regions of the 16S rRNA gene were sequenced in faecal samples from 347 patients with AIH and controls (AIH n = 72, healthy controls (HC) n = 95, primary biliary cholangitis (PBC) n = 99 and ulcerative colitis (UC) n = 81). Results Biodiversity (Shannon entropy) was decreased in AIH patients compared to HC ( P  = 0.016), which was partially reversed by azathioprine ( P  = 0.011). Regarding between‐sample diversity, AIH patients separated from HC, PBC and UC individuals (all P  = 0.001). Compared to HC, decreased relative abundance of anaerobic genera such as Faecalibacterium and an increase of Veillonella and the facultative anaerobic genera Streptococcus and Lactobacillus were detected. Importantly, a disease‐specific decline of relative abundance of Bifidobacterium was observed in AIH patients. Lack of Bifidobacterium was associated with failure to achieve remission of AIH ( P   〈  0.001). Of potential therapeutic implication, Bifidobacterium abundance correlated with average protein intake ( P   〈  0.001). Random forests classification between AIH and PBC on the microbiome signature yielded an area under receiver operating characteristic curve (AUC) of 0.787 in the training cohort, and an AUC of 0.849 in an external validation cohort. Conclusion Disease‐specific faecal microbial alterations were identified in patients with AIH. Intestinal dysbiosis in AIH was characterised by a decline of Bifidobacterium , which was associated with increased disease activity. These results point to the contribution of intestinal microbiota to AIH pathogenesis and to novel therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2003094-0
    SSG: 15,3
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  • 6
    In: ESC Heart Failure, Wiley, Vol. 4, No. 3 ( 2017-08), p. 282-290
    Abstract: In spite of current medical treatment approaches, mortality of chronic heart failure (HF) remains high and novel treatment modalities are thus urgently needed. A recent theory proposes a possible impact of the intestinal microbiome on the incidence and clinical course of heart failure. This study sought to systematically investigate, if there are specific changes of the intestinal microbiome in heart failure patients. Methods and results The intestinal microbiome of 20 patients with heart failure with reduced ejection fraction due to ischemic or dilated cardiomyopathy was investigated by applying high‐throughput sequencing of the bacterial 16S rRNA gene. Microbial profiles were compared to those of matched controls in which heart failure was ruled out by clinical assessment and NT‐proBNP serum levels ( n  = 20) . According to the Shannon diversity index (which measures the intra‐individual alpha‐diversity) based on the distribution of operational taxonomic units (OTUs), HF cases showed a nominally significantly lower diversity index compared to controls ( P nom.  = 0.01), and testing for genera abundance showed a tendency towards a decreased alpha diversity of HF patients. Beta‐diversity measures (inter‐individual diversity) revealed a highly significant separation of HF cases and controls, (e.g. P weighted UniFracv  = 0.004). Assessing the individual abundance of core measurable microbiota (CMM), a significant decrease of Coriobacteriaceae , Erysipelotrichaceae and Ruminococcaceae was observed on the family level. In line with that, Blautia , Collinsella , uncl. Erysipelotrichaceae and uncl. Ruminococcaceae showed a significant decrease in HF cases compared to controls on the genus level. Conclusions Heart failure patients showed a significantly decreased diversity of the intestinal microbiome as well as a downregulation of key intestinal bacterial groups. Our data point to an altered intestinal microbiome as a potential player in the pathogenesis and progression of heart failure.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2814355-3
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  • 7
    In: MicrobiologyOpen, Wiley, Vol. 11, No. 2 ( 2022-04)
    Abstract: The use of an adequate protocol that accurately extracts microbial DNA from bovine milk samples is of importance for downstream analysis such as 16S ribosomal RNA gene sequencing. Although sequencing platforms such as Illumina are very common, there are reservations concerning reproducibility in challenging samples that combine low bacterial loads with high amounts of host DNA. The objective of this study was to evaluate six different DNA extraction protocols applied to four different prototype milk samples (low/high level of colony‐forming units [cfu] and somatic cells). DNA extracts were sequenced on Illumina MiSeq with primers for the hypervariable regions V1V2 and V3V4. Different protocols were evaluated by analyzing the yield and purity of DNA extracts and the number of clean reads after sequencing. Three protocols with the highest median number of clean reads were selected. To assess reproducibility, these extraction replicates were resequenced in triplicates ( n  = 120). The most reproducible results for α‐ and β‐diversity were obtained with the modified DNeasy Blood & Tissue kit after a chemical pretreatment plus resuspension of the cream fraction. The unmodified QIAamp DNA Mini kit performed particularly weak in the sample representing unspecific mastitis. These results suggest that pretreatment in combination with the modified DNeasy Blood & Tissue kit is useful in extracting microbial DNA from challenging milk samples. To increase reproducibility, we recommend that duplicates, if not triplicates, should be sequenced. We showed that high counts of somatic cells challenged DNA extraction, which shapes the need to apply modified extraction protocols.
    Type of Medium: Online Resource
    ISSN: 2045-8827 , 2045-8827
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2661368-2
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  • 8
    Online Resource
    Online Resource
    Wiley ; 2016
    In:  Immunology & Cell Biology Vol. 94, No. 10 ( 2016-11), p. 943-948
    In: Immunology & Cell Biology, Wiley, Vol. 94, No. 10 ( 2016-11), p. 943-948
    Abstract: The November/December 2016 issue contains a Special Feature on Novel aspects of autoimmunity. Major scientific advances often arise at the interface of disciplines, or are made possible by transformative technological advances. Progress in our understanding of the basis of autoimmunity over recent years provides great examples of this, and we have selected four of these to highlight in this ICB Special Feature. Together these articles reveal how recent technological advances have revealed important mechanisms underlying autoimmune disease, mechanisms that can now be examined in humans as well as mouse models. Our increasing ability to conduct in‐depth studies in humans promises to continue to unlock the mysteries underlying autoimmunity, with inevitable benefits to patients with these diseases. Immunology & Cell Biology thanks the coordinators of this Special Feature ‐ Ken Smith and Arthur Kaser ‐ for their planning and input.
    Type of Medium: Online Resource
    ISSN: 0818-9641 , 1440-1711
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2011707-3
    SSG: 12
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  • 9
    In: Global Ecology and Biogeography, Wiley, Vol. 28, No. 5 ( 2019-05), p. 576-587
    Abstract: Animal movement is an important determinant of individual survival, population dynamics and ecosystem structure and function. Nonetheless, it is still unclear how local movements are related to resource availability and the spatial arrangement of resources. Using resident bird species and migratory bird species outside the migratory period, we examined how the distribution of resources affects the movement patterns of both large terrestrial birds (e.g., raptors, bustards and hornbills) and waterbirds (e.g., cranes, storks, ducks, geese and flamingos). Location Global. Time period 2003–2015. Major taxa studied Birds. Methods We compiled GPS tracking data for 386 individuals across 36 bird species. We calculated the straight‐line distance between GPS locations of each individual at the 1‐hr and 10‐day time‐scales. For each individual and time‐scale, we calculated the median and 0.95 quantile of displacement. We used linear mixed‐effects models to examine the effect of the spatial arrangement of resources, measured as enhanced vegetation index homogeneity, on avian movements, while accounting for mean resource availability, body mass, diet, flight type, migratory status and taxonomy and spatial autocorrelation. Results We found a significant effect of resource spatial arrangement at the 1‐hr and 10‐day time‐scales. On average, individual movements were seven times longer in environments with homogeneously distributed resources compared with areas of low resource homogeneity. Contrary to previous work, we found no significant effect of resource availability, diet, flight type, migratory status or body mass on the non‐migratory movements of birds. Main conclusions We suggest that longer movements in homogeneous environments might reflect the need for different habitat types associated with foraging and reproduction. This highlights the importance of landscape complementarity, where habitat patches within a landscape include a range of different, yet complementary resources. As habitat homogenization increases, it might force birds to travel increasingly longer distances to meet their diverse needs.
    Type of Medium: Online Resource
    ISSN: 1466-822X , 1466-8238
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1479787-2
    detail.hit.zdb_id: 2021283-5
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Wiley ; 2017
    In:  Journal of Clinical Periodontology Vol. 44, No. 4 ( 2017-04), p. 382-393
    In: Journal of Clinical Periodontology, Wiley, Vol. 44, No. 4 ( 2017-04), p. 382-393
    Abstract: The objective of this systematic review was to systematically investigate whether there is an association between inflammatory bowel disease ( IBD ) and oral health. Methods Literature searches for randomized and non‐randomized studies were performed up to January 2017. Risk of bias within studies was assessed with the Downs and Black checklist. Across‐studies risk of bias was assessed with the GRADE framework. Quantitative synthesis was conducted with random‐effects meta‐analyses. Results A total of 9 cross‐sectional studies including 1297 patients were included. IBD was associated with increased risk of periodontitis (332 more patients per 1000 patients; 95% confidence interval (CI): 257–388 patients; p   〈  0.001) compared to non‐ IBD patients. Additionally, the Decayed‐Missing‐Filled‐Teeth index of IBD patients was significantly worse than non‐ IBD patients (mean difference: 3.85; 95% CI : 2.36–5.34; p  = 0.005). Patients with ulcerative colitis had considerably worse oral health for most of the assessed factors, while the quality of overall evidence ranged from high to low, due to the observational nature of contributing studies. Conclusions Inflammatory bowel disease was associated with significantly higher risk of periodontitis and worse oral health compared to non‐ IBD patients. However, longitudinal studies are needed in order to establish a causality link between IBD and periodontal disease.
    Type of Medium: Online Resource
    ISSN: 0303-6979 , 1600-051X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2026349-1
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