The lack of sensitive and specific biomarkers for the early detection of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is a major hurdle to improving patient management. A targeted, quantitative metabolomics approach using both 1H NMR and mass spectrometry was employed to investigate the performance of urine metabolites as potential biomarkers for MCI and AD. Correlation-based feature selection (CFS) and least absolute shrinkage and selection operator (LASSO) methods were used to develop biomarker panels tested using support vector machine (SVM) and logistic regression models for diagnosis of each disease state. Metabolic changes were investigated to identify which biochemical pathways were perturbed as a direct result of MCI and AD in urine. Using SVM, we developed a model with 94% sensitivity, 78% specificity, and 78% AUC to distinguish healthy controls from AD sufferers. Using logistic regression, we developed a model with 85% sensitivity, 86% specificity, and an AUC of 82% for AD diagnosis as compared to cognitively healthy controls. Further, we identified 11 urinary metabolites that were significantly altered to include glucose, guanidinoacetate, urocanate, hippuric acid, cytosine, 2- and 3-hydroxyisovalerate, 2-ketoisovalerate, tryptophan, trimethylamine N oxide, and malonate in AD patients, which are also capable of diagnosing MCI, with a sensitivity value of 76%, specificity of 75%, and accuracy of 81% as compared to healthy controls. This pilot study suggests that urine metabolomics may be useful for developing a test capable of diagnosing and distinguishing MCI and AD from cognitively healthy controls.
To interrogate the pathogenesis of intrauterine growth restriction (IUGR) and apply Artificial Intelligence (AI) techniques to multi-platform i.e. nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) based metabolomic analysis for the prediction of IUGR. MS and NMR based metabolomic analysis were performed on cord blood serum from 40 IUGR (birth weight < 10th percentile) cases and 40 controls. Three variable selection algorithms namely: Correlation-based feature selection (CFS), Partial least squares regression (PLS) and Learning Vector Quantization (LVQ) were tested for their diagnostic performance. For each selected set of metabolites and the panel consists of metabolites common in three selection algorithms so-called overlapping set (OL), support vector machine (SVM) models were developed for which parameter selection was performed busing 10-fold cross validations. Area under the receiver operating characteristics curve (AUC), sensitivity and specificity values were calculated for IUGR diagnosis. Metabolite set enrichment analysis (MSEA) was performed to identify which metabolic pathways were perturbed as a direct result of IUGR in cord blood serum. All selected metabolites and their overlapping set achieved statistically significant accuracies in the range of 0.78–0.82 for their optimized SVM models. The model utilizing all metabolites in the dataset had an AUC = 0.91 with a sensitivity of 0.83 and specificity equal to 0.80. CFS and OL (Creatinine, C2, C4, lysoPC.a.C16.1, lysoPC.a.C20.3, lysoPC.a.C28.1, PC.aa.C24.0) showed the highest performance with sensitivity (0.87) and specificity (0.87), respectively. MSEA revealed significantly altered metabolic pathways in IUGR cases. Dysregulated pathways include: beta oxidation of very long fatty acids, oxidation of branched chain fatty acids, phospholipid biosynthesis, lysine degradation, urea cycle and fatty acid metabolism. A systematically selected panel of metabolites was shown to accurately detect IUGR in newborn cord blood serum. Significant disturbance of hepatic function and energy generating pathways were found in IUGR cases.
This study explores how natural language processing (NLP) can supplement content analyses of political documents, particularly the manifestos of political parties. NLP is particularly useful for tasks such as: estimating the similarity between documents, identifying the topics discussed in documents (topic modeling), and sentiment analysis. This study applies each of these techniques to the study of political party manifestos. Document similarity may be used to gain some insight into the way parties change over time and which political parties are successful at bringing attention to their policy agenda. Categorizing text into topics may help objectively categorize and visualize the ideas political parties are discussing. Finally, sentiment analysis has the potential to show each political party’s attitude towards a policy area/topic. This study specifically applies these techniques to the manifestos produced by the political parties of New Zealand, from 1987 to 2017 (a period of significant party system change in New Zealand). It finds that NLP techniques provide valuable insights, although there is a need for significant fine-tuning.
Epilepsy not-otherwise-specified (ENOS) is one of the most common causes of chronic disorders impacting human health, with complex multifactorial etiology and clinical presentation. Understanding the metabolic processes associated with the disorder may aid in the discovery of preventive and therapeutic measures. Post-mortem brain samples were harvested from the frontal cortex (BA8/46) of people diagnosed with ENOS cases (n = 15) and age- and sex-matched control subjects (n = 15). We employed a targeted metabolomics approach using a combination of proton nuclear magnetic resonance (1H-NMR) and direct injection/liquid chromatography tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 72 metabolites using 1H-NMR and 159 using DI/LC-MS/MS. Among the 212 detected metabolites, 14 showed significant concentration changes between ENOS cases and controls (p < 0.05; q < 0.05). Of these, adenosine monophosphate and O-acetylcholine were the most commonly selected metabolites used to develop predictive models capable of discriminating between ENOS and unaffected controls. Metabolomic set enrichment analysis identified ethanol degradation, butyrate metabolism and the mitochondrial beta-oxidation of fatty acids as the top three significantly perturbed metabolic pathways. We report, for the first time, the metabolomic profiling of postmortem brain tissue form patients who died from epilepsy. These findings can potentially expand upon the complex etiopathogenesis and help identify key predictive biomarkers of ENOS.
Attribution of responsibility and blame are important topics in political science especially as individuals tend to think of political issues in terms of questions of responsibility, and as blame carries far more weight in voting behavior than that of credit. However, surprisingly, there is a paucity of studies on the attribution of responsibility and blame in the field of disaster research. In this work, we investigate the attribution of responsibility and blame through social media in the case of Flint water crisis. We form hypotheses based on social scientific theories in disaster research and then operationalize them on public responses available on social media rather than employing traditional data collection methods such as interviewing and surveying. In particular, we investigate the source for blame, the partisan predisposition, the concerned geographies, and the contagion of complaining by testing our hypotheses on data collected from Twitter. Our results demonstrate the utility of social media data in testing those hypotheses, which are rooted in sociology of disasters. Our findings are not only aligned with official reports listing the responsible officials for the source blame, but also reveal a partisan predisposition in regards to Democratic and Republican stances. We also confirm that closer geographies are more concerned and complaining seems contagious in social media conversations. This paper adds to the sociology of disasters research by exploiting a new, rarely used data source (the social web), and by employing new computational methods (such as sentiment analysis and retrospective cohort study design) on this new form of data. In this regard, this work can be seen as the first step toward drawing more challenging inferences on the sociology of disasters from “big social data”.
3 December 2022 in Journal of Computational Social Science