Patients with R/M HNSCC treated with palliative first-line therapy at Hannover Medical School between October 2005 and December 2016 have been included to show changes in survival following broad utilization of cetuximab. Treatment periods were defined from 10/2005 to 12/2008 (Period A) and 01/2009 to 12/2016. Overall survival did not improve over time. However, in subgroup analysis cetuximab utilized at any time vs. never showed a significant improve of overall survival (11.3 vs. 6.3 months,...

Supplementary Material 1. Representative flow cytometry dot plots are displayed for different DC and T cell populations within each organ analyzed. First, total lymphocytes were gated. Then, DC and T cell frequencies were determined according to their specific marker combinations

Histological changes in somalian patients with autoimmune hepatitis.

Histological changes in somalian patients with autoimmune hepatitis.

Histological changes in somalian patients with autoimmune hepatitis.

Additional file 2: Fig. S2. Differential methylation of CpG loci in the SOCS3 promoter in T-LGL samples. Comparison of CpG methylation (beta-value) for CpGs in the SOCS3 promoter between CD8+ memory cells (CD8mem) and T-LGLL samples (LGL). On top, adjusted p val of differential methylation analysis (dmpFDR, top left) and adjusted p value of differential variability analysis (dmVar, top right).

Additional file 4: Fig. S3A. Gene Ontology analysis of genes hyper- (A) and hypomethylated (B) of T-LGL patients. Significant Biological processes (GO database) enriched in genes associated with significantly differentially methylated CpG loci in T-LGL. Enrichment represented as odds ratio. Point size represents the gene count of each pathway. Enrichment p value obtained by overrepresentation analysis [30], represented by point color. A Gene Ontology analysis of hypermethylated genes in T-LGL.

Additional file 5: Fig. S3B. Gene Ontology analysis of genes hyper- (A) and hypomethylated (B) of T-LGL patients. Significant Biological processes (GO database) enriched in genes associated with significantly differentially methylated CpG loci in T-LGL. Enrichment represented as odds ratio. Point size represents the gene count of each pathway. Enrichment p value obtained by overrepresentation analysis [30], represented by point color. B Gene Ontology analysis of hypomethylated genes in T-LGL.

Additional file 7: Fig. S5A. (A and B): Location of differentially methylated CpG loci in the genes BCL11B and C14orf64 (LINC01550). A Significant differentially methylated CpGs in BCL11B (T-LGLL compared to CD8+. memory T cells) were located in the gene body and assigned as enhancers by ENCODE, which match as enhancers in CD8-positive memory cells.

Additional file 8: Fig. S5B. (A and B): Location of differentially methylated CpG loci in the genes BCL11B and C14orf64 (LINC01550). B Significant differentially methylated CpGs in C14orf64 (LINC01550) (T-LGL compared to CD8 pos. memory T cells).

Additional file 10: Fig. S6. Expression correlation between BCL11B & C14ORF64 (LINC01550). Expression correlation between BCL11B & C14ORF64 (LINC01550) in 426 human datasets with 42563 samples from R2: Genomics analysis and visualization platform (https://hgserver1.amc.nl/cgi-bin/r2/main.cgi).

Supplementary Material 1. Representative flow cytometry dot plots are displayed for different DC and T cell populations within each organ analyzed. First, total lymphocytes were gated. Then, DC and T cell frequencies were determined according to their specific marker combinations

Additional file 4: Fig. S3A. Gene Ontology analysis of genes hyper- (A) and hypomethylated (B) of T-LGL patients. Significant Biological processes (GO database) enriched in genes associated with significantly differentially methylated CpG loci in T-LGL. Enrichment represented as odds ratio. Point size represents the gene count of each pathway. Enrichment p value obtained by overrepresentation analysis [30], represented by point color. A Gene Ontology analysis of hypermethylated genes in T-LGL.

Additional file 6: Fig. S4. Differential gene expression of IL6 between T-LGL and healthy donor-derived CD8+ memory T cells. Differential gene expression for IL6 was measured by qPCR. Bulk CD8+ cells from two healthy donors were used for comparison. In line with previous publications, the T-LGLL cohort analyzed exhibits a higher IL6 expression compared to healthy donor-derived C8+ cells. HD Healthy donor.

Additional file 7: Fig. S5A. (A and B): Location of differentially methylated CpG loci in the genes BCL11B and C14orf64 (LINC01550). A Significant differentially methylated CpGs in BCL11B (T-LGLL compared to CD8+. memory T cells) were located in the gene body and assigned as enhancers by ENCODE, which match as enhancers in CD8-positive memory cells.

Additional file 8: Fig. S5B. (A and B): Location of differentially methylated CpG loci in the genes BCL11B and C14orf64 (LINC01550). B Significant differentially methylated CpGs in C14orf64 (LINC01550) (T-LGL compared to CD8 pos. memory T cells).

Poster presented at European Conference on Rare Disease (ECRD), 2022. A new approach of conducting expert interviews to create 11 clinical vignettes on lysosomal storage diseases (LSDs) which were then used to update Ada’s condition models. 15 LSD patients and 9 LSD experts will rate both new and old disease models in Ada to compare efficacy. This novel approach can potentially shorten the ‘time to diagnosis’ for rare diseases.

Poster presented at European Conference on Rare Disease (ECRD), 2022. A new approach of conducting expert interviews to create 11 clinical vignettes on lysosomal storage diseases (LSDs) which were then used to update Ada’s condition models. 15 LSD patients and 9 LSD experts will rate both new and old disease models in Ada to compare efficacy. This novel approach can potentially shorten the ‘time to diagnosis’ for rare diseases.

Patients with R/M HNSCC treated with palliative first-line therapy at Hannover Medical School between October 2005 and December 2016 have been included to show changes in survival following broad utilization of cetuximab. Treatment periods were defined from 10/2005 to 12/2008 (Period A) and 01/2009 to 12/2016. Overall survival did not improve over time. However, in subgroup analysis cetuximab utilized at any time vs. never showed a significant improve of overall survival (11.3 vs. 6.3 months,...

Additional file 2: Fig. S2. Differential methylation of CpG loci in the SOCS3 promoter in T-LGL samples. Comparison of CpG methylation (beta-value) for CpGs in the SOCS3 promoter between CD8+ memory cells (CD8mem) and T-LGLL samples (LGL). On top, adjusted p val of differential methylation analysis (dmpFDR, top left) and adjusted p value of differential variability analysis (dmVar, top right).

Additional file 3: Fig. S2. Differential methylation of CpG loci in the SOCS3 promoter in T-LGL samples. Comparison of CpG methylation (beta-value) for CpGs in the SOCS3 promoter between CD8+ memory cells (CD8mem) and T-LGLL samples (LGL). On top, adjusted p val of differential methylation analysis (dmpFDR, top left) and adjusted p value of differential variability analysis (dmVar, top right).

Additional file 6: Fig. S4. Differential gene expression of IL6 between T-LGL and healthy donor-derived CD8+ memory T cells. Differential gene expression for IL6 was measured by qPCR. Bulk CD8+ cells from two healthy donors were used for comparison. In line with previous publications, the T-LGLL cohort analyzed exhibits a higher IL6 expression compared to healthy donor-derived C8+ cells. HD Healthy donor.

Additional file 9: Fig. S1. Correlation of bisulfite Pyrosequencing (BPS) and methylation Array DNA methylation levels. The correlation matrix shows the Pearson correlation coefficient (r: 1 (red) to − 1 (blue) among all CpG loci analyzed by BPS. The candidate genes LINC01550 and BCL11B contained multiple CpG sites. Columns and rows represent one CpG loci of the listed candidate gene.

Additional file 9: Fig. S1. Correlation of bisulfite Pyrosequencing (BPS) and methylation Array DNA methylation levels. The correlation matrix shows the Pearson correlation coefficient (r: 1 (red) to − 1 (blue) among all CpG loci analyzed by BPS. The candidate genes LINC01550 and BCL11B contained multiple CpG sites. Columns and rows represent one CpG loci of the listed candidate gene.

Histological changes in somalian patients with autoimmune hepatitis.