Machine learning identifies phenotypic profile alterations of human dopaminergic neurons exposed to bisphenols and perfluoroalkyls.

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by the loss of midbrain dopaminergic neurons. Endocrine disrupting chemicals (EDCs) are active substances that interfere with hormonal signaling. Among EDCs, bisphenols (BPs) and perfluoroalkyls (PFs) are chemicals leached from plastics and other household products, and humans are unavoidably exposed to these xenobiotics. Data from animal studies suggest that EDCs exposure may play a role in PD, but data about the effect of BPs and PFs on human models of the nervous system are lacking. Previous studies demonstrated that machine learning (ML) applied to microscopy data can classify different cell phenotypes based on image features. In this study, the effect of BPs and PFs at different concentrations within the real-life exposure range (0.01, 0.1, 1, and 2 µM) on the phenotypic profile of human stem cell-derived midbrain dopaminergic neurons (mDANs) was analyzed. Cells exposed for 72 h to the xenobiotics were stained with neuronal markers and evaluated using high content microscopy yielding 126 different phenotypic features. Three different ML models (LDA, XGBoost and LightGBM) were trained to classify EDC-treated versus control mDANs. EDC treated mDANs were identified with high accuracies (0.88-0.96). Assessment of the phenotypic feature contribution to the classification showed that EDCs induced a significant increase of alpha-synuclein (αSyn) and tyrosine hydroxylase (TH) staining intensity within the neurons. Moreover, microtubule-associated protein 2 (MAP2) neurite length and branching were significantly diminished in treated neurons. Our study shows that human mDANs are adversely impacted by exposure to EDCs, causing their phenotype to shift and exhibit more characteristics of PD. Importantly, ML-supported high-content imaging can identify concrete but subtle subcellular phenotypic changes that can be easily overlooked by visual inspection alone and that define EDCs effects in mDANs, thus enabling further pathological characterization in the future.

Association between spontaneous intracranial epidural hematoma and craniofacial infections: A systematic literature review.

Background: Spontaneous and nontraumatic epidural hematoma (SEDH) is a rare entity. Etiology is various, including vascular malformations of the dura mater, hemorrhagic tumors, and coagulation defects. The association between SEDH and craniofacial infections is rather unusual. Methods: We performed a systematic review of the available literature using the PubMed, Cochrane Library, and Scopus research databases. Literature research was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We exclusively included studies reporting demographic and clinical data, published until October 31, 2022. We also report one case from our experience. Results: A total of 18 scientific publications, corresponding to 19 patients, met the inclusion criteria for the qualitative and quantitative analysis. Patients were mostly adolescents, with a clear male predominance. SEDHs frequently occurred in the frontal area, usually near the site of the infection. Surgical evacuation was the treatment of choice with good postoperative outcomes. Endoscopy of the involved paranasal sinus should be achieved as soon as possible to remove the cause of the SEDH. Conclusion: SEDH may occur as a rare and life-threatening complication of craniofacial infections; therefore, prompt recognition and treatment are mandatory.