ParkinsoNET: Estimation of UPDRS Score using Hubness-aware Feed-Forward Neural Networks

Parkinson’s disease is a worldwide frequent neurodegenerative disorder with increasing incidence. Speech disturbance appears during the progression of the disease. UPDRS is a gold standard tool for diagnostic and follow up of the disease. We aim at estimating the UPDRS score based on biomedical voice recordings. In this paper, we study the hubness phenomenon in context of the UPDRS score estimation and propose hubness-aware error correction for feed-forward neural networks in order to increase the accuracy of estimation. We perform experiments on publicly available datasets derived form real voice data and show that the proposed technique systematically increases the accuracy of various feed-forward neural networks

Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease – a combined tissue microarray, in vitro and in vivo study

BACKGROUND: Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. METHODS: mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. RESULTS: The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic effect of chemotherapeutic agents. CONCLUSIONS: Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response

Mitochondrial dysfunction and autism: Comprehensive genetic analyses of children with autism and mtDNA deletion

Additional file 1: Table S1. Investigated genes responsible for mtDNA maintenance (intergenomic NGS panel)

Deep Brain Stimulation or Thalamotomy in Fragile X-Associated Tremor/Ataxia Syndrome? Case Report

We present the case of a 66 -year -old man who has been treated for essential tremor since the age of 58. He developed mild cerebellar gait ataxia seven years after tremor onset . M oderate, global brain atrophy was identified on MRI scans . At the age of 68, only temporary tremor relief could be achieved by bilateral deep brain stimulation of the ventral intermedius nucleus of the thalamus . B ilateral stimulation of the subthalamic nucleus also resulted only in transie nt improvement. In the meantime, progressive gait ataxia and tetraataxia developed accompanied by other cerebellar symptoms, such as nystagmus and scanning speech. These correlat ed with progressive development of bilateral symmetric hyperintensity of the middle cerebellar peduncles on T2 weighted MRI scans. Genetic testing revealed premutation of the FMR1 gene , establishing the diagnosis of fragile X -associated tremor/ataxia syndrome. Although this is a rare disorder, it should be taken into consideration during preoperative evaluation of essential tremor. P ostural tremor ceased two years later after thalamotomy on the left side, while kinetic tremor of the right hand also improved