Unsupervised Context-Sensitive Spelling Correction of English and Dutch Clinical Free-Text with Word and Character N-Gram Embeddings

We present an unsupervised context-sensitive spelling correction method for clinical free-text that uses word and character n-gram embeddings. Our method generates misspelling replacement candidates and ranks them according to their semantic fit, by calculating a weighted cosine similarity between the vectorized representation of a candidate and the misspelling context. To tune the parameters of this model, we generate self-induced spelling error corpora. We perform our experiments for two languages. For English, we greatly outperform off-the-shelf spelling correction tools on a manually annotated MIMIC-III test set, and counter the frequency bias of a noisy channel model, showing that neural embeddings can be successfully exploited to improve upon the state-of-the-art. For Dutch, we also outperform an off-the-shelf spelling correction tool on manually annotated clinical records from the Antwerp University Hospital, but can offer no empirical evidence that our method counters the frequency bias of a noisy channel model in this case as well. However, both our context-sensitive model and our implementation of the noisy channel model obtain high scores on the test set, establishing a state-of-the-art for Dutch clinical spelling correction with the noisy channel model.Comment: Appears in volume 7 of the CLIN Journal, http://www.clinjournal.org/biblio/volum

Comparison of the chemical and technological characteristics of wholemeal flours obtained from amaranth (Amaranthus sp.), quinoa (Chenopodium quinoa) and buckwheat (Fagopyrum sp.) seeds

A sound fundamental knowledge of the seed and flour characteristics of pseudocereals is crucial to be able to promote their industrial use. As a first step towards a more efficient and successful application, this study focuses on the seed characteristics, chemical composition and technological properties of commercially available pseudocereals (amaranth, quinoa, buckwheat). The levels of starch, fat, dietary fiber and minerals were comparable for amaranth and quinoa seeds but the protein content is higher in amaranth. Due to the high amount of starch, buckwheat seeds are characterised by the lowest amounts of fat, dietary fibre and minerals. Its protein content ranged between that of amaranth and quinoa. Buckwheat seeds were larger but easily reduced in size. The lipid fraction of the pseudocereals mostly contained unsaturated fatty acids, with the highest prevalence of linoleic and oleic acid. Palmitic acid is the most abundant unsaturated fatty acid. Moreover, high levels of P, K and Mg were found in these pseudocereals. The highest phenolic content was found in buckwheat. Amaranth WMF (wholemeal flour) had a high swelling power but low shear stability. The pasting profile strongly varied among the different quinoa WMFs. Buckwheat WMFs showed high shear stability and rate of retrogradation

CRISPR/Cas9 screen in human iPSC‐derived cortical neurons identifies NEK6 as a novel disease modifier of C9orf72 poly(PR) toxicity

Introduction The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are hexanucleotide repeats in chromosome 9 open reading frame 72 (C9orf72). These repeats produce dipeptide repeat proteins with poly(PR) being the most toxic one. Methods We performed a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell (iPSC) -derived cortical neurons to identify modifiers of poly(PR) toxicity, and validated the role of candidate modifiers using in vitro, in vivo, and ex-vivo studies. Results Knock-down of NIMA-related kinase 6 (NEK6) prevented neuronal toxicity caused by poly(PR). Knock-down of nek6 also ameliorated the poly(PR)-induced axonopathy in zebrafish and NEK6 was aberrantly expressed in C9orf72 patients. Suppression of NEK6 expression and NEK6 activity inhibition rescued axonal transport defects in cortical neurons from C9orf72 patient iPSCs, at least partially by reversing p53-related DNA damage. Discussion We identified NEK6, which regulates poly(PR)-mediated p53-related DNA damage, as a novel therapeutic target for C9orf72 FTD/ALS

Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics

Liquid-liquid phase separation (LLPS) of RNA-binding proteins plays an important role in the formation of multiple membrane-less organelles involved in RNA metabolism, including stress granules. Defects in stress granule homeostasis constitute a cornerstone of ALS/FTLD pathogenesis. Polar residues (tyrosine and glutamine) have been previously demonstrated to be critical for phase separation of ALS-linked stress granule proteins. We now identify an active role for arginine-rich domains in these phase separations. Moreover, arginine-rich dipeptide repeats (DPRs) derived from C9orf72 hexanucleotide repeat expansions similarly undergo LLPS and induce phase separation of a large set of proteins involved in RNA and stress granule metabolism. Expression of arginine-rich DPRs in cells induced spontaneous stress granule assembly that required both eIF2α phosphorylation and G3BP. Together with recent reports showing that DPRs affect nucleocytoplasmic transport, our results point to an important role for arginine-rich DPRs in the pathogenesis of C9orf72 ALS/FTLD

Biplaire stoornis in de huisartsenpraktijk:: huisartsen volgen de evidence

status: publishe