Adverse drug events constitute a major challenge for the success of clinical trials. Several computational strategies have been suggested to estimate the risk of adverse drug events in preclinical drug development. While these approaches have demonstrated high utility in practice, they are at the same time limited to specific information sources.
View Article and Find Full Text PDFParkinson's disease (PD) is a highly heterogeneous disease both with respect to arising symptoms and its progression over time. This hampers the design of disease modifying trials for PD as treatments which would potentially show efficacy in specific patient subgroups could be considered ineffective in a heterogeneous trial cohort. Establishing clusters of PD patients based on their progression patterns could help to disentangle the exhibited heterogeneity, highlight clinical differences among patient subgroups, and identify the biological pathways and molecular players which underlie the evident differences.
View Article and Find Full Text PDFPurpose: Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly targeting tumor cells that can survive, adapt, and subclonally expand under primary therapy.
Experimental Design: To identify candidate markers and to experimentally access dynamics of subclonal progression in glioblastoma, we established a discovery cohort of paired vital cell samples obtained before and after primary therapy.
Hydatid cyst is the larval form of the parasite, echinococcus granulosus. We operated upon a case of a giant hydatid cyst in the left cerebral hemisphere of a 10-year male child. The patient presented to us with a history of headache, vomiting, vertigo and difficulty in walking.
View Article and Find Full Text PDFNAR Genom Bioinform
September 2021
Many rare syndromes can be well described and delineated from other disorders by a combination of characteristic symptoms. These phenotypic features are best documented with terms of the Human Phenotype Ontology (HPO), which are increasingly used in electronic health records (EHRs), too. Many algorithms that perform HPO-based gene prioritization have also been developed; however, the performance of many such tools suffers from an over-representation of atypical cases in the medical literature.
View Article and Find Full Text PDFParkinson's disease (PD) is the second most common age-related neurodegenerative disease. Accumulating evidence demonstrates that alpha-synuclein (α-Syn), an apparently predominant neuronal protein, is a major contributor to PD pathology. As α-Syn is also highly abundant in blood, particularly in red blood cells (RBCs) and platelets, this in turn raises the question on the function of presumably dysfunctional α-Syn in "peripheral" cells and its putative effect on the other enclosed constituents.
View Article and Find Full Text PDFBackground: The protease inhibitor ritonavir (RTV) is a clinical-stage inhibitor of the human immunodeficiency virus. In a drug repositioning approach, we here exhibit the additional potential of RTV to augment current treatment of glioblastoma, the most aggressive primary brain tumour of adulthood.
Methods: We explored the antitumour activity of RTV and mechanisms of action in a broad spectrum of short-term expanded clinical cell samples from primary and recurrent glioblastoma and in a cohort of conventional cell lines and non-tumour human neural controls in vitro.
Over the last decade, a rapid rise in deaths due to liver disease has been observed especially amongst young people. Nowadays liver disease accounts for approximately 2 million deaths per year worldwide: 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma. Besides primary liver malignancies, almost all solid tumours are capable to spread metastases to the liver, in particular, gastrointestinal cancers, breast and genitourinary cancers, lung cancer, melanomas and sarcomas.
View Article and Find Full Text PDFBackground: Precision medicine requires a stratification of patients by disease presentation that is sufficiently informative to allow for selecting treatments on a per-patient basis. For many diseases, such as neurological disorders, this stratification problem translates into a complex problem of clustering multivariate and relatively short time series because (i) these diseases are multifactorial and not well described by single clinical outcome variables and (ii) disease progression needs to be monitored over time. Additionally, clinical data often additionally are hindered by the presence of many missing values, further complicating any clustering attempts.
View Article and Find Full Text PDFMotivation: Discovery of clinically relevant disease sub-types is of prime importance in personalized medicine. Disease sub-type identification has in the past often been explored in an unsupervised machine learning paradigm which involves clustering of patients based on available-omics data, such as gene expression. A follow-up analysis involves determining the clinical relevance of the molecular sub-types such as that reflected by comparing their disease progressions.
View Article and Find Full Text PDFParkinson's disease (PD) is a degenerative disorder of the nervous system and the cause of the majority of sporadic cases is unknown. Females are relatively protected from PD as compared with males and linkage studies suggested a PD susceptibility locus on the X chromosome. To determine a putative association of skewed X-chromosome inactivation (XCI) and PD, we examined XCI patterns using a human androgen receptor gene-based assay (HUMARA) and did not identify any association of skewed or random X inactivation with clinical heterogeneity among female PD patients.
View Article and Find Full Text PDFInferring the structure of molecular networks from time series protein or gene expression data provides valuable information about the complex biological processes of the cell. Causal network structure inference has been approached using different methods in the past. Most causal network inference techniques, such as Dynamic Bayesian Networks and ordinary differential equations, are limited by their computational complexity and thus make large scale inference infeasible.
View Article and Find Full Text PDFBackground: Increasing gene dosages of α-synuclein induce familial Parkinson's disease (PD); thus, the hypothesis has been put forward that regulation of gene expression, in particular altered α-synuclein gene methylation, might be associated with sporadic PD and could be used as a biological marker.
Methods: We performed a thorough analysis of α-synuclein methylation in bisulfite-treated DNA from peripheral blood of 490 sporadic PD patients and 485 healthy controls and in addition analyzed the effect of levodopa (L-dopa) on α-synuclein methylation and expression in cultured mononuclear cells.
Results: α-Synuclein was hypomethylated in sporadic PD patients, correlated with sex, age, and a polymorphism in the analyzed sequence stretch (rs3756063).