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Clark Kristoffersen posted an update 3 days, 4 hours ago
042) tumour-infiltrating lymphocytes in LGG. sPD-L1 is correlated with neutrophil counts (r=-0.318, p=0.045) and C reactive protein levels (r=-0.363, p=0.008) in GBM. sPD-L1+ patients had longer overall survival in GBM (p=0.006) and worse OS in LGG (p=0.028).
sPD-L1 is detectable in a fraction of patients with brain tumour. Although it is not correlated with tissue PD-L1 expression, correlations with other local and systemic inflammation parameters could be detected in LGG and GBM.
sPD-L1 is detectable in a fraction of patients with brain tumour. Although it is not correlated with tissue PD-L1 expression, correlations with other local and systemic inflammation parameters could be detected in LGG and GBM.
To establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS).
We long-listed licensed drugs with evidence of human safety, blood-brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review.
From a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine.
We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.
We report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.The near-haploid human cell line HAP1 recently became a popular subject for CRISPR/Cas9 editing, since only one allele requires modification. Through the gene-editing service at Horizon Discovery, there are at present more than 7500 edited cell lines available and the number continuously increases. The haploid nature of HAP1 is unstable as cultures become diploid with time. Here, we demonstrated some fundamental differences between haploid and diploid HAP1 cells, hence underlining the need for taking control over ploidy status in HAP1 cultures prior to phenotyping. Consequently, we optimized a procedure to determine the ploidy of HAP1 by flow cytometry in order to obtain diploid cultures and avoid ploidy status as an interfering variable in experiments. Furthermore, in order to facilitate this quality control, we validated a size-based cell sorting procedure to obtain the diploid culture more rapidly. Hence, we provide here two streamlined protocols for quality controlling the ploidy of HAP1 cells and document their validity and necessity.This article has an associated First Person interview with the co-first authors of the paper.Auxin is an endogenous small molecule with an incredibly large impact on growth and development in plants. Movement of auxin between cells, due to its negative charge at most physiological pHs, strongly relies on families of active transporters. These proteins import auxin from the extracellular space or export it into the same. Selleckchem TGFbeta inhibitor Mutations in these components have profound impacts on biological processes. Another transport route available to auxin, once the substance is inside the cell, are plasmodesmata connections. These small channels connect the cytoplasms of neighbouring plant cells and enable flow between them. Interestingly, the biological significance of this latter mode of transport is only recently starting to emerge with examples from roots, hypocotyls and leaves. The existence of two transport systems provides opportunities for reciprocal cross-regulation. Indeed, auxin levels influence proteins controlling plasmodesmata permeability, while cell-cell communication affects auxin biosynthesis and transport. In an evolutionary context, transporter driven cell-cell auxin movement and plasmodesmata seem to have evolved around the same time in the green lineage. This highlights a co-existence from early on and a likely functional specificity of the systems. Exploring more situations where auxin movement via plasmodesmata has relevance for plant growth and development, and clarifying the regulation of such transport, will be key aspects in coming years.This article has an associated Future Leader to Watch interview with the author of the paper.
Since the emergence in 1997 of the Wellness Recovery Action Plan, a number of other tools developed by users and/or ex-users of mental health services have been published and implemented. All these tools aim to promote self-determination in mental health recovery processes. A scoping review will be carried out in order to (1) identify existing tools, (2) describe their distinctive characteristics and (3) examine how they have been implemented and evaluated.
The scoping review will be guided by the methodological framework proposed by Arksey and O’Malley and expanded by Levac
. It will involve, primarily, a literature search of the following electronic databases Cochrane database, Cumulative Index to Nursing and Allied Health Literature, PsycInfo, PsycArticles, Scopus, PubMed and Web of Science. In addition, the search process will consider grey literature databases. Users, ex-users and survivors organisations and networks will be contacted in order to identify any relevant material. The reference lists be disseminated through an article submitted for publication to a scientific journal and presented at relevant conferences. The results will also be shared in future workshops and seminars as part of continuing education programmes for mental health professionals.
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a well-established treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high incidence of complications. Moreover, relative studies have indicated that traditional laboratory testing is insufficient to demonstrate the overall haemostatic physiology of CRS/HIPEC. Thromboelastography (TEG), administered by monitoring dynamic changes in haemostasis, has been shown to contribute to reducing transfusion requirements and improving survival. However, there is no evidence to verify whether TEG can be applied to guide transfusion strategies during CRS/HIPEC. Therefore, we aim to investigate whether TEG-guided blood product transfusion (TEG-BT) therapy is superior to traditional blood product transfusion (T-BT) therapy for guiding perioperative blood transfusion treatment and improving the prognosis of patients undergoing CRS/HIPEC.
The TEG-BT versus T-BT study is a single-centre, randomised, blinded outcome assessment clinical trial of 162 patients with PC, aged 18-64 years and undergoing CRS/HIPEC.