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The paper presents a platform that provides deep learning-based tools that can perform basic organ segmentations in CT, which can then be used to automatically obtain the different measurement in the corresponding PET image. The RECOMIA platform is available on request at www.recomia.org for research purposes.We report a case of 33-year-old Japanese male who presented with a headache and visual disturbances. Magnetic resonance imaging revealed a large tumor in the left frontal lobe, measuring 7 cm in diameter, which was diagnosed as supratentorial anaplastic ependymoma accompanied by extensive desmoplasia. The patient underwent a gross total resection. Histologically, the tumor cells had oval or short, spindle-shaped nuclei, and proliferating cells in perivascular pseudorosettes with anucleate zones and mitotic figures. Desmoplasia with abundant collagen fibers among the tumor cells was detected at numerous sites, and perinuclear dot- or ring-like immunoreactivity for epithelial membrane antigen was identified. Five years and six months after the initial procedure, a small recurrent tumor was identified at the removal site. The patient underwent a second total resection. The histology of the resected tumor showed decreased collagen production and more apparent anaplastic features as compared to those of the initial tumor. In addition to the histological findings, molecular examinations revealed ependymoma, RELA fusion positive. Although not commonly observed, this case suggests that desmoplasia could be associated with ependymomas, including RELA fusion-positive variant. Moreover, our findings indicate that high-grade ependymoma requires careful, long-term follow-up even if gross total resection is performed.A small number of studies have described verbal selection deficits in Parkinson's disease (PD) when selection must occur among competing alternatives. However, these studies have largely focused on single-word processing, or have utilised sentence stems that carry high contextual constraint, thus reducing selection demands. The present study aimed to determine the influence of variable contextual constraint on the selection of a verbal response in PD. This was achieved using an adaption of the Hayling Sentence Completion Task whereby PD participants and matched controls were required to provide a single word to complete a cloze probability sentence stem that carried a low, medium, or high degree of contextual constraint. Results revealed no main effect of group in terms of response time or accuracy, though a group-by-condition interaction in accuracy was noted. This was characterised by a significant difference in accuracy between low and medium levels of constraint for control participants, but no significant difference for the PD group. Functional MRI data revealed marked between-group differences in underlying neural activity. The control group showed increased recruitment of the dorsal striatum and the vlPFC under conditions that placed greater demands upon selection (i.e. low and medium constraint), and greater activity overall in the left dlPFC and right vlPFC. However, in the PD group, behavioural performance appeared to be maintained despite underlying decreases in frontostriatal activity, suggesting other compensatory mechanisms that may include changes in functional connectivity or an over-medication effect in frontal networks in response to loss of signalling in cortico-subcortical pathways.Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.This study aims to evaluate the association of maternal DNA methylation (DNAm) during pregnancy and offspring birthweight. One hundred twenty-two newborn-mother dyads from the Isle of Wight (IOW) cohort were studied to identify differentially methylated cytosine-phosphate-guanine sites (CpGs) in maternal blood associated with offspring birthweight. Peripheral blood samples were drawn from mothers at 22-38 weeks of pregnancy for epigenome-wide DNAm assessment using the Illumina Infinium HumanMethylation450K array. Candidate CpGs were identified using a course of 100 repetitions of a training and testing process with robust regressions. CpGs were considered informative if they showed statistical significance in at least 80% of training and testing samples. Linear mixed models adjusting for covariates were applied to further assess the selected CpGs. The Swedish Born Into Life cohort was used to replicate our findings (n = 33). Eight candidate CpGs corresponding to the genes LMF1, KIF9, KLHL18, DAB1, VAX2, CD207, SCT, SCYL2, DEPDC4, NECAP1, and SFRS3 in mothers were identified as statistically significantly associated with their children's birthweight in the IOW cohort and confirmed by linear mixed models after adjusting for covariates. DFMO chemical structure Of these, in the replication cohort, three CpGs (cg01816814, cg23153661, and cg17722033 with p values = 0.06, 0.175, and 0.166, respectively) associated with four genes (LMF1, VAX2, CD207, and NECAP1) were marginally significant. Biological pathway analyses of three of the genes revealed cellular processes such as endocytosis (possibly sustaining an adequate maternal-fetal interface) and metabolic processes such as regulation of lipoprotein lipase activity (involved in providing substrates for the developing fetus). Our results contribute to an epigenetic understanding of maternal involvement in offspring birthweight. Measuring DNAm levels of maternal CpGs may in the future serve as a diagnostic tool recognizing mothers at risk for pregnancies ending with altered birthweights.
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