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The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is an intronic GC repeat expansion in C9orf72. The repeats undergo bidirectional transcription to produce sense and antisense repeat RNA species, which are translated into dipeptide repeat proteins (DPRs). As toxicity has been associated with both sense and antisense repeat-derived RNA and DPRs, targeting both strands may provide the most effective therapeutic strategy.
View Article and Find Full Text PDFDisseminated enterovirus infection treated with intravenous immunoglobulin in a patient on maintenance ocrelizumab for multiple sclerosis.
BMJ Case Rep
January 2025
Infectious Diseases, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
We present a case of a woman in her 40s with disseminated enterovirus infection in the setting of maintenance therapy with ocrelizumab for relapsing-remitting multiple sclerosis. The patient originally presented with fever, bilateral lower limb swelling and hypoalbuminaemia. She subsequently developed a productive cough and diarrhoea, and a viral respiratory multiplex panel detected rhino/enterovirus.
View Article and Find Full Text PDFA data-driven model of disability progression in progressive multiple sclerosis.
Brain Commun
December 2024
Department of Health Sciences (DISSAL), Università di Genova, 16132 Genoa, Italy.
This study applies the Gaussian process progression model, a Bayesian data-driven disease progression model, to analyse the evolution of primary progressive multiple sclerosis. Utilizing data from 1521 primary progressive multiple sclerosis participants collected within the International Progressive Multiple Sclerosis Alliance Project, the analysis includes 18 581 longitudinal time-points (average follow-up time: 28.2 months) of disability assessments including the expanded disability status scale, symbol digit modalities, timed 25-foot-walk, 9-hole-peg test and of MRI metrics such as T1 and T2 lesion volume and normalized brain volume.
View Article and Find Full Text PDFAdvanced whole transcriptome sequencing and artificial intelligence/machine learning (AI/ML) in imiquimod-induced psoriasis-like inflammation of human keratinocytes.
Biomedicine (Taipei)
December 2024
Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
Introduction: Although the HaCaT keratinocyte model has been used in previous research to study the effects of antipsoriatic agents, there is still a lack of comprehensive understanding of the mechanism of imiquimod (IMQ)-induced proliferation and signal transduction in psoriasis-like keratinocytes.
Objectives: This study aimed to investigate the molecular mechanisms and pathways associated with psoriasis-like inflammation caused by IMQ in human keratinocytes.
Materials And Methods: HaCaT cells were exposed to different concentrations of IMQ to induce inflammation similar to that observed in psoriasis.
A 50-year data-driven model of disability and lesion load trajectories in progressive multiple sclerosis.
Brain Commun
December 2024
UCL Hawkes Institute and UCL Queen Square Institute of Neurology, University College London, London, UK.
This scientific commentary refers to 'A data-driven model of disability progression in progressive multiple sclerosis', by Garbarino . (https://doi.org/10.
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