Restoration of the striatal circuitry: from developmental aspects toward clinical applications

In the basal ganglia circuitry, the striatum is a highly complex structure coordinating motor and cognitive functions and it is severely affected in Huntington's disease (HD) patients. Transplantation of fetal ganglionic eminence (GE) derived precursor cells aims to restore neural circuitry in the degenerated striatum of HD patients. Pre-clinical transplantation in genetic and lesion HD animal models has increased our knowledge of graft vs. host interactions, and clinical studies have been shown to successfully reduce motor and cognitive effects caused by the disease. Investigating the molecular mechanisms of striatal neurogenesis is a key research target, since novel strategies aim on generating striatal neurons by differentiating embryonic stem cells or by reprogramming somatic cells as alternative cell source for neural transplantation

Environmental housing and duration of exposure affect striatal graft morphology in a rodent model of Huntington's disease

Clinical trials of cell replacement therapy in Huntington's disease have shown its safety, feasibility, and potentially long-lasting effects. However, more needs to be known regarding the conditions that stimulate plasticity and compensation achieved by neural grafts to maximize posttransplantation recovery of such neurorehabilitative therapies. The effects of enriched environment (EE), behavioral experience, and transplantation can each separately influence neuronal plasticity and recovery of function after brain damage, and the mechanisms by which these factors interact to modify the survival, integration, or function of grafted tissues are at present unknown. To investigate the effects of variable housing conditions and duration on morphological and cellular changes within embryonic striatal transplants, rats received unilateral excitotoxic lesions of the striatum, followed by E15 whole-ganglionic eminence suspension grafts. The rats were divided into three groups according to housing: full-time EE, 1 h/day exposure to EE, or standard laboratory cages. The experimental design included “early” (7 weeks postgrafting) and “late” (13 weeks postgrafting) survival time points to explore the effects of exposure lengths to the three housing conditions. The morphological and cellular effects on the grafts were analyzed using immunohistochemistry, cell morphology, image analysis, and enzyme-linked immunoassay. Both the duration of the exposure and the housing conditions were seen to influence multiple parameters of grafted cell morphology. The factors acted either independently (e.g., on graft size), complementarily (e.g., on spine density), or had no distinctive effect (e.g., on lesion size) on graft development. Features of embryonic striatal grafts and their trophic milieu were influenced both by the complexity of the environmental conditions and by the length of exposure to them. The data suggest that neurorehabilitation should be a feature of clinical trials of cell transplantation in order to exploit the underlying mechanisms that promote anatomical integration of the grafted cells and maximize transplant-mediated functional recovery

Investigating Sub-Word Embedding Strategies for the Morphologically Rich and Free Phrase-Order Hungarian

For morphologically rich languages, word embeddings provide less consistent semantic representations due to higher variance in word forms. Moreover, these languages often allow for less constrained word order, which further increases variance. For the highly agglutinative Hungarian, semantic accuracy of word embeddings measured on word analogy tasks drops by 50-75% compared to English. We observed that embeddings learn morphosyntax quite well instead. Therefore, we explore and evaluate several sub-word unit based embedding strategies – character n-grams, lemmatization provided by an NLP-pipeline, and segments obtained in unsupervised learning (morfessor) – to boost semantic consistency in Hungarian word vectors. The effect of changing embedding dimension and context window size have also been considered. Morphological analysis based lemmatization was found to be the best strategy to improve embeddings’ semantic accuracy, whereas adding character n-grams was found consistently counterproductive in this regard

State of vulnerable populations in the techquity framework in Hungary

Digital health solutions could alleviate the needs of vulnerable populations in the recent period of the permacrisis, however, there are several barriers that limit their use for certain individuals. We use the four-pillar model of the novel concept of techquity to provide original evidence of the discrepancy in the willingness to try and the ability to harness healthtech in Hungary. We identified three underserved segments of society: older adults, people with long-term activity-limiting conditions, and people experiencing homelessness who could greatly benefit from digital technologies and yet use them less than the general population. We also discuss potential strategic considerations in order to promote techquity and digital inclusion among people living in vulnerable situations