Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We perform a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we consider locus-specific TEs as distinct molecular features during stratification. Here, we identify three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.

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Introduction: The dysregulation of cortisol secretion has been associated with a number of mental health and mood disorders. However, diagnostics for mental health and mood disorders are behavioral and lack biological contexts. Objectives: The goal of this work is to identify volatile metabolites capable of predicting changes in total urinary cortisol across the diurnal cycle for long-term stress monitoring in psychological disorders. Methods: We applied comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry to sample the urinary volatile metabolome using an untargeted approach across three time points in a single day for 60 subjects. Results: The finalized multiple regression model includes 14 volatile metabolites and 7 interaction terms. A review of the selected metabolites suggests pyrrole, 6-methyl-5-hepten-2-one and 1-iodo-2-methylundecane may originate from endogenous metabolic mechanisms influenced by glucocorticoid signaling mechanisms. Conclusion: This analysis demonstrated the feasibility of using specific volatile metabolites for the prediction of secreted cortisol across time.

The development of cell-specific photoacoustic (PA) contrast agents within systems of fluidic flow provides opportunities for the accurate detection of early stage cancer metastasis. Despite the promise of exogenous contrast agents for use in clinical settings, applications are currently limited by both material biocompatibility and target specificity. In this study, folic acid functionalized copper sulfide nanoparticles (FA-CuS NPs) are synthesized to enable ovarian-cancer-specific binding and PA detection in a custom flow system. Folate receptors, known to be overexpressed on the surface of ovarian cancer cells, have remained an ideal candidate for specific targeting through functionalization on nanoparticles and other contrast agents. In combination with copper sulfide nanoparticles’ strong absorbance in the near-infrared (NIR), these FA-CuS NPs are an ideal contrast agent capable of being detected by photoacoustic flow cytometry. For the first time, this study shows a potential PA contrast agent to accurately identify ovarian circulating tumor cells in flow.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We performed a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we considered locus-specific TEs as distinct molecular features during stratification. We identified three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.