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See detailIntegrated meta-omic analyses of the gastrointestinal tract microbiome in patients undergoing allogeneic hematopoietic stem cell transplantation.
Kaysen, Anne UL; Heintz-Buschart, Anna UL; Muller, Emilie UL et al

in Translational Research: the Journal of Laboratory and Clinical Medicine (2017)

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most ... [more ▼]

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or consequential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes during allo-HSCT and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies. These results revealed a major shift in the GIT microbiome after allo-HSCT including a marked reduction in bacterial diversity, accompanied by only limited changes in eukaryotes and archaea. An integrated analysis of metagenomic and metatranscriptomic data was performed on samples collected from a patient before and after allo-HSCT for acute myeloid leukemia. This patient developed severe GvHD, leading to death 9 months after allo-HSCT. In addition to drastically decreased bacterial diversity, the post-treatment microbiome showed a higher overall number and higher expression levels of antibiotic resistance genes (ARGs). One specific Escherichia coli strain causing a paravertebral abscess was linked to GIT dysbiosis, suggesting loss of intestinal barrier integrity. The apparent selection for bacteria expressing ARGs suggests that prophylactic antibiotic administration may adversely affect the overall treatment outcome. We therefore assert that such analyses including information about the selection of pathogenic bacteria expressing ARGs may assist clinicians in "personalizing" regimens for individual patients to improve overall outcomes. [less ▲]

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See detailMaking sense of big data in health research: Towards an EU action plan.
Auffray, Charles; Balling, Rudi UL; Barroso, Ines et al

in Genome medicine (2016), 8(1), 71

Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation ... [more ▼]

Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health and healthcare for all Europeans. [less ▲]

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See detailDynamic change of host gastrointestinal microbiome and immune status in relation to mucosal barrier effects during chemotherapy and immune ablative intervention in humans
Kaysen, Anne UL; Heintz-Buschart, Anna UL; Lebrun, Laura UL et al

Poster (2014, April)

The human gastrointestinal tract is colonized by communities of endogenous microbes, commonly referred to as the microbiome. Here, the microbiota are in close contact with the host intestinal mucosa and ... [more ▼]

The human gastrointestinal tract is colonized by communities of endogenous microbes, commonly referred to as the microbiome. Here, the microbiota are in close contact with the host intestinal mucosa and its innate and adaptive immune systems. The fact that certain stimuli induce an inflammatory response whereas others induce tolerance suggests, that the host immune system interacts with the microbiota and vice versa in different ways. However, the exact details of theses interactions remain largely unknown. It is known that cancer treatment can result in severe adverse effects like mucositis and in combination with allogeneic stem cell transplantation (Tx), in graft-versus host disease (GvHD). However, there is at present only sparse information available on the effects of chemotherapy on the intestinal microbiota and resulting changes in microbiome-immune system interactions. Almost no data exists on the effect of allogeneic stem cell Tx on the composition of the gastrointestinal microbiota. In this project, we are studying the complex interactions between the host and the intestinal microbiota after chemotherapy with or without allogeneic Tx and the occurrence of severe adverse side effects such as mucositis and GvHD. Using a systems biology approach including metagenomics and RNAseq, fecal samples and blood plasma samples from patients undergoing these treatments for malignancies will be analysed to identify the composition of the gastrointestinal microbiome and bacterial small RNAs. The main research hypothesis is that there are quantitative and qualitative changes in the gastrointestinal microbiome following chemotherapy and allogeneic Tx which are linked to the immune status of the patients and possible treatment side-effects, in particular mucositis and GvHD. We aim to provide knowledge on how the host's intestinal mucosa and immune system influence the gastrointestinal microbiome and on the role and involvement of the gastrointestinal microbiota in development in mucositis and GvHD. Importantly, this could help in the formulation of measures to prevent mucositis and GvHD development. [less ▲]

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See detailApplication of Shape Analysis on 3D Images - MRI of Renal Tumors
Schiltz, Jang UL; Giebel, Stefan; Graf, Norbert et al

in Journal of the Iranian Statistical Society (2012), 11(2), 131-146

The image recognotion and the classification of objects according to the images are more in focus of interests, especially in medicine. A mathematical procedure allows us, not only to evaluate the amount ... [more ▼]

The image recognotion and the classification of objects according to the images are more in focus of interests, especially in medicine. A mathematical procedure allows us, not only to evaluate the amount of data per se, but also ensures that each image is processed similarly. Here in this study, we propose the power of shape analysis, in conjunction with neural networks for reducing white noise instead of searching an optimal metric, to support the user in his evaluation of MRI of renal tumors. Therapy of renal tumors in childhood bases on therapy optimizing SIOP(Society of Pediatric Oncology and Hematology)-study protocols in Europe. The most frequent tumor is the nephroblastoma. Other tumor entities in the retroperitoneum are clear cell sarcoma, renal cell carcinoma and extrarenal tumors, especially neuroblastoma. Radiological diagnosis is produced with the help of cross sectional imaging methods (computertomography CT or Magnetic Resonance Images MRI). Our research is the first mathematical approach on MRI of retroperitoneal tumors (n=108). We use MRI in 3 planes and evaluate their potential to differentiate other types of tumor by Statistical Shape Analysis. Statistical shape Analysis is a methology for analyzing shapes in the presence of randomness. It allows to study two- or more dimensional objects, summarized according to key points called landmarks, with a possible correction of size and position of the object. To get the shape of an object without information about position and size, centralisation and standardisation procedures are used in some metric space. This approach provides an objective methodology for classification whereas even today in many applications the decision for classifying according to the appearance seems at most intuitive. We determine the key points or three dimensional landmarks of retroperitoneal tumors in childhood by using the edges of the platonic body (C60) and test the difference between the groups (nephroblastoma versus non-nephroblastoma). [less ▲]

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See detailFormanalyse in der Magnetresonanztomographie - Landmarken und Objektdifferenzierung bei retroperitonealen Tumoren im Kindesalter
Giebel, Stefan Markus; Schiltz, Jang UL; Graf, Norbert et al

in Bulletin de la Société des Sciences Médicales du Grand-Duché de Luxembourg (2010), 1

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