Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly ...defined GBM subtypes.
MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. IDH1 mutational and MGMT promoter methylation status were determined by DNA sequencing and methylation-specific PCR, respectively. Overall survival was determined by using a multivariate Cox model and the Kaplan-Meier method with a log rank test. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features.
MGMT promoter methylation and IDH1 mutation were associated with longer median survival. Edema levels stratified survival for methylated but not unmethylated tumors. Median survival for methylated tumors with little/no edema was 2476 days (95% CI, 795), compared with 586 days (95% CI, 507-654) for unmethylated tumors or tumors with edema. All IDH1 mutant tumors were nCET positive, and most (11/14, 79%) were located in the frontal lobe. Imaging features including larger tumor size and nCET could be used to determine IDH1 mutational status with 97.5% accuracy, but poorly predicted MGMT promoter methylation.
Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation. Edema stratifies survival in MGMT promoter methylated but not in unmethylated tumors; patients with methylated tumors with little or no edema have particularly long survival.
Particulate plastics in the terrestrial and aquatic environments are small plastic fragments or beads (i.e., 5 mm down to the nanometre range). They have been frequently referred to as ...‘micro-plastics’ or ‘nano-plastics’. Research has identified particulate plastics as a vector for toxic trace elements in the environment. The adsorption of toxic trace elements by particulate plastics may be facilitated by their high surface area and functionalized surfaces (e.g., through the attachment of natural organic matter). Other factors, such as environmental conditions (e.g., pH and water salinity), surface charge, and trace element oxidation status, also influence the adsorption of trace elements onto particulate plastics. Because of their small size and persistence, particulate plastics and the associated toxic trace elements are readily ingested and accumulated in many terrestrial and aquatic organisms. Thus, these plastics can have severe environmental consequences, such as the development of metal toxicity, within aquatic and terrestrial organisms. Humans could also become exposed to particulate plastics through food chain contamination and airborne ingestion. This review provides an overview of the sources of particulate plastics in the environment. To this end, we describe particulate plastics made of synthetic polymers, their origin, and characteristics with emphasis on how particulate plastics and associated toxic trace elements contaminate terrestrial and aquatic ecosystems. Future research needs and strategies are discussed to help reduce the environmental risks of particulate plastics as a potent vector for the transportation of toxic trace elements.
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•Particulate plastics include microplastics and nanoplastics.•The review covers the ecological and human health impacts of particulate plastics.•Trace-element-sorbed particulate plastics damage aquatic and terrestrial ecosystems.•Dissolved organic matter facilitates trace element sorption onto particulate plastics.•Particulate plastics pose human health threats by entering the food chain.
Background
The dermoscopic patterns of acral melanocytic nevi (AMNs) are crucial in differentiating them from acral melanoma. Several studies have reported the dermoscopic patterns of acquired acral ...melanocytic nevi (AAMNs). However, few have investigated the dermoscopic patterns of congenital acral melanocytic nevi (CAMNs).
Objective
To compare the clinical and dermoscopic features of CAMNs and AAMNs.
Methods
The present study included 43 patients with CAMNs and 40 with AAMNs. We reviewed their medical records as well as their clinical and dermoscopic findings.
Results
Congenital acral melanocytic nevis were more asymmetrical than AAMNs (P = 0.002) and presented more frequently as comma‐shaped (P = 0.005). Regarding dermoscopic findings, globular pattern (55.8%) was the most common feature of CAMNs, while parallel furrow pattern (37.5%) was the most common feature of AAMNs. The presence of fibrillar, globular, and parallel ridge patterns, and diffuse multi‐component pigmentation differed significantly between the groups (P < 0.05). Furthermore, CAMNs showed melanoma‐specific dermoscopic patterns, such as parallel ridge (18.6%) and diffuse multi‐component pigmentation (25.6%).
Conclusion
The dermoscopic patterns of CAMNs and AAMNs differed markedly. In terms of dermoscopic patterns, CAMNs resembled acral melanoma more often than AAMNs did.
Some patients with idiopathic pulmonary fibrosis experience acute exacerbations in their respiratory status leading to substantial morbidity and mortality. Occult aspiration of gastric contents has ...been proposed as one possible mechanism leading to these acute exacerbations. We sought to determine whether pepsin, a marker of gastric aspiration, is elevated in bronchoalveolar lavage fluid obtained from patients during acute exacerbation of idiopathic pulmonary fibrosis, compared with that obtained in stable disease. Lavage samples were obtained in a case-control study of well-characterised patients. Acute exacerbation was defined using standard criteria. Levels of lavage pepsin were compared in cases and controls, and were correlated with clinical features and disease course. 24 cases with acute exacerbations and 30 stable controls were identified. There were no significant differences in baseline demographics between the two groups. Pepsin level was an indicator of acute exacerbation status (p=0.04). On average, pepsin appeared higher in patients with acute exacerbations compared with stable controls. This difference was driven by a subgroup of eight patients (33%) with pepsin levels ≥70 ng·mL(-1). Pepsin level was not an independent predictor of survival time. These results suggest occult aspiration may play a role in some cases of acute exacerbation of idiopathic pulmonary fibrosis.
Detection of circulating tumor DNA can be limited due to their relative scarcity in circulation, particularly while patients are actively undergoing therapy. Exosomes provide a vehicle through which ...cancer-specific material can be enriched from the compendium of circulating non-neoplastic tissue-derived nucleic acids. We carried out a comprehensive profiling of the pancreatic ductal adenocarcinoma (PDAC) exosomal ‘surfaceome’ in order to identify surface proteins that will render liquid biopsies amenable to cancer-derived exosome enrichment for downstream molecular profiling.
Surface exosomal proteins were profiled in 13 human PDAC and 2 non-neoplastic cell lines by liquid chromatography–mass spectrometry. A total of 173 prospectively collected blood samples from 103 PDAC patients underwent exosome isolation. Droplet digital PCR was used on 74 patients (136 total exosome samples) to determine baseline KRAS mutation call rates while patients were on therapy. PDAC-specific exosome capture was then carried out on additional 29 patients (37 samples) using an antibody cocktail directed against selected proteins, followed by droplet digital PCR analysis. Exosomal DNA in a PDAC patient resistant to therapy were profiled using a molecular barcoded, targeted sequencing panel to determine the utility of enriched nucleic acid material for comprehensive molecular analysis.
Proteomic analysis of the exosome ‘surfaceome’ revealed multiple PDAC-specific biomarker candidates: CLDN4, EPCAM, CD151, LGALS3BP, HIST2H2BE, and HIST2H2BF. KRAS mutations in total exosomes were detected in 44.1% of patients undergoing active therapy compared with 73.0% following exosome capture using the selected biomarkers. Enrichment of exosomal cargo was amenable to molecular profiling, elucidating a putative mechanism of resistance to PARP inhibitor therapy in a patient harboring a BRCA2 mutation.
Exosomes provide unique opportunities in the context of liquid biopsies for enrichment of tumor-specific material in circulation. We present a comprehensive surfaceome characterization of PDAC exosomes which allows for capture and molecular profiling of tumor-derived DNA.
Heat shock factor 1 (HSF1) is a transcription factor for heat shock proteins (HSPs) expression that enhances the survival of cancer cells exposed to various stresses. HSF1 knockout suppresses ...carcinogen-induced cancer induction in mice. Therefore, HSF1 is a promising therapeutic and chemopreventive target. We performed cell-based screening with a natural compound collection and identified fisetin, a dietary flavonoid, as a HSF1 inhibitor. Fisetin abolished heat shock-induced luciferase activity with an IC50 of 14 μM in HCT-116 cancer cells. The treatment of HCT-116 with fisetin inhibited proliferation with a GI50 of 23 μM. When the cells were exposed to heat shock in the presence of fisetin, the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 (Bcl-2-associated athanogene domain 3), were inhibited. HSP70/BAG3 complexes protect cancer cells from apoptosis by stabilizing anti-apoptotic Bcl-2 family proteins. The downregulation of HSP70/BAG3 by fisetin significantly reduced the amounts of Bcl-2, Bcl-xL and Mcl-1 proteins, subsequently inducing apoptotic cell death. Chromatin immunoprecipitation assays showed that fisetin inhibited HSF1 activity by blocking the binding of HSF1 to the hsp70 promoter. Intraperitoneal treatment of nude mice with fisetin at 30mg/kg resulted in a 35.7% (P < 0.001) inhibition of tumor growth.
The objectives of this tutorial are as follows: 1) to help students and researchers develop a basic understanding of how pulsed-power systems are used to create high-energy-density (HED) matter; 2) ...to develop a basic understanding of a new, compact, and efficient pulsed-power technology called linear transformer drivers (LTDs); 3) to understand why LTDs are an attractive technology for driving HED physics (HEDP) experiments; 4) to contrast LTDs with the more traditional Marx-generator/pulse-forming-line approach to driving HEDP experiments; and 5) to briefly review the history of LTD technology as well as some of the LTD-driven HEDP research presently underway at universities and research laboratories across the globe. This invited tutorial is part of the Mini-Course on Charged Particle Beams and High-Powered Pulsed Sources, held in conjunction with the 44th International Conference on Plasma Science in May of 2017.
Fusiform aneurysms and ultrawide-neck circumferential aneurysms are still some of the most challenging lesions. The aim of this study was to investigate the efficacy and feasibility of the use of ...multiple overlapping Enterprise stents with coiling for the treatment of fusiform or ultrawide-neck circumferential aneurysms.
Twelve consecutive patients (9 men and 3 women; mean age, 56 years) with fusiform (n = 5) or ultrawide-neck circumferential (n = 7) aneurysms were treated with 2-3 overlapping Enterprise stents and coiling. The feasibility of this procedure and the clinical and angiographic outcomes of this technique were retrospectively evaluated.
All patients were successfully treated by using this technique without any complications. Posttreatment angiographic results revealed grade 4 occlusion of the aneurysm in 6, grade 3 in 4, and grade 2 in 2 patients. Clinical follow-up was performed in all patients (mean, 16 months; range, 5-24 months). Nine patients had an mRS score of 0. Two had an mRS score of 1, one of whom had an initial mRS score of 2 due to the mass effect of a giant aneurysm; the other had a recurrent aneurysm presenting with SAH 5 years after clipping. Angiographic follow-up was performed in 10 patients at 6-20 months posttreatment. Nine had stable or improved occlusion, while 1 had a minor recurrence.
In this small series, multiple overlapping Enterprise stents with coiling were a feasible and effective option for the treatment of fusiform and ultrawide-neck circumferential aneurysms. Further experience and follow-up are required to document the long-term efficacy of this treatment.
Pruritus in epithelial tumours of the face Lee, H.‐J.; Kim, G.‐W.; Kim, H.‐S. ...
Journal of the European Academy of Dermatology and Venereology,
November 2017, 2017-Nov, 2017-11-00, 20171101, Letnik:
31, Številka:
11
Journal Article
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