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The efficiency of a phenyl column compared with other stationary phases was also discussed. © 2020 Wiley Periodicals LLC.AIM Low anterior resection syndrome (LARS) is common after low anterior resection. Our aim was to evaluate the prevalence and bother of major LARS after one and two years, identify possible risk factors and relate the bowel function to a reference population. METHOD The QoLiRECT (Quality of Life in RECTal cancer) study is a Scandinavian prospective multicentre study including 1248 patients with rectal cancer of whom 552 had an anterior resection. Patient questionnaires were distributed at diagnosis and after one, two and five years. Data from the baseline, and at one and two years follow-up were included in this study. RESULTS LARS score was calculated for 309 patients at one year and 334 patients at two years. Prevalence was assessed by a generalised linear mixed effect model. Major LARS was 63% at one year and 56% at two years. Bother was 55% at one year and decreased to 46% at two years. Major LARS was most common among younger women (69%). Among younger patients, only marginal improvement was seen over time (63-59%), for older patients there was more improvement (62-52%). In the reference population, the highest prevalence of major LARS-like symptoms was noted in older women (12%). Preoperative radiotherapy, defunctioning stoma and tumour height were found to be associated with major LARS. CONCLUSION Major LARS is common and possibly persistent over time. Younger patients, especially women, are more affected and perhaps these patients should be prioritised for early stoma closure to improve the chance of a more normal bowel function. This article is protected by copyright. All rights reserved.Spontaneous necrosis is a defining feature of glioblastomas (GBMs), the most malignant glioma. Despite its strong correlations with poor prognosis, it remains unclear whether necrosis could be a possible cause or mere consequence of glioma progression. Here we isolated a particular fraction of necrotic products spontaneously arising from glioma cells, morphologically and biochemically defined as "autoschizis-like products (ALPs)." When administered to granulocyte macrophage colony-stimulating factor (GM-CSF)-primed bone marrow-derived macrophage/dendritic cells (Mφ/DCs), ALPs were found to be specifically engulfed by Mφs expressing a tumor-associated macrophage (TAM) marker CD204. ALPs from glioma stem cells (GSCs) had higher activity for the TAM development than those from non-GSCs. Of note, expression of the Il12b gene encoding a common subunit of IL-12/23 was upregulated in ALPs-educated Mφs. Furthermore, IL-12 protein evidently enhanced the sphere-forming activity of GBM patient-derived cells, although interestingly IL-12 is generally recognized as an antitumoral M1-Mφ marker. Finally, in silico analysis of The Cancer Genome Atlas (TCGA) transcriptome data of primary and recurrent GBMs revealed that higher expression of these IL-12 family genes was well correlated with more infiltration of M1-type TAMs and closely associated with poorer prognosis in recurrent GBMs. Our results highlight a role of necrosis in GSC-driven self-beneficial niche construction and glioma progression, providing important clues for developing new therapeutic strategies against gliomas. ©AlphaMed Press 2020.RATIONALE Mass spectrometry (MS) is an effective tool for the structural analysis of oligonucleotides. Currently, various modifications of oligonucleotides have been proposed to increase the efficacy and safety of oligonucleotide therapeutics. For MS-based structural characterization, the fragmentation behavior of modified oligonucleotides by MS must first be determined. METHODS The impact of the oligonucleotide structure on the in-source decay (ISD) of matrix-assisted laser desorption/ionization (MALDI) was examined using a new matrix and compared with collision-induced dissociation (CID) fragmentation behavior. RESULTS When a part of the oligonucleotide structure is replaced, an impact was observed at the 3' side of the replaced structure. Among the oligonucleotide components considered herein, nucleobases most significantly impacted both ISD and CID fragmentation patterns. CONCLUSIONS Compared with CID, ISD was less sensitive to structural differences. Because ISD fragmentation was less affected by various oligonucleotide modifications, MALDI is a useful and applicable method for the structural characterization or identification of various modified oligonucleotide therapeutics. This article is protected by copyright. All rights reserved.The cigarette beetle (CB; Lasioderma serricorne) is a pest on many stored products including tobacco. Fumigation is the common control method currently used. However, the options for controlling this pest are limited, due to resistance issues and phasing out of currently used chemical insecticides. Here, we evaluated RNA interference (RNAi) as a potential method for controlling the CB. RNA isolated from different stages was sequenced and assembled into a transcriptome. The CB RNA sequences showed the highest homology with those in the red flour beetle, Tribolium castaneum. Orthologs of proteins known to function in RNAi pathway were identified in the CB transcriptome, suggesting that RNAi may work well in this insect. Also, 32 P-labeled double-stranded RNA (dsRNA) injected into CB larvae and adults was processed to small interference RNAs. Selleckchem HDAC inhibitor We selected 12 genes that were shown to be the effective RNAi targets in T. castaneum and other insects and identified orthologs of them in the CB by searching its transcriptome. Injection of dsRNA targeting genes coding for GAWKY, Kinesin, Sec23, SNF7, and 26S proteasome subunit 6B into the CB larvae caused 100% mortality. Feeding dsRNA targeting SNF7 and 26S proteasome subunit 6B by sucrose droplet assay induced more than 90% mortality, which is 1.8 times higher than the mortality induced by dsGFP control (53%). These data demonstrate an efficient RNAi response in CB, suggesting that RNAi could be developed as an efficient method to control this pest. © 2020 Wiley Periodicals, Inc.BACKGROUND AND PURPOSE To assess the frequency of plateaus in Amyotrophic Lateral Sclerosis (ALS) progression using a large population-based cohort. METHODS Data from the Piemonte and Valle d'Aosta ALS register (PARALS) were used. Patients who were diagnosed between 2007 and 2014 were considered. Follow-up period was extended until 31st December 2018. Visits after tracheostomy were excluded. A plateau was defined as a stable ALSFRS revised score lasting at least 6, 12 or 18 months. RESULTS Out of 1214 patients, 200 (16.5%), 93 (7.7%) and 52 (4.3%) showed at least one plateau lasting a minimum of 6, 12 and 18 months, respectively. Plateaus occurred mostly at high ALSFRSr scores and were more frequent during the initial phases of the disease course. Spinal onset (OR 1.83, 95% CI 1.16 - 2.95, p-value = 0.01) and predominant upper motor neuron phenotype (OR 2.18, 95% CI 1.36 - 3.48, p-value = 0.001) conferred a higher risk for the subsequent appearance of plateaus; conversely, older age at diagnosis (OR 0.25, 95% CI 0.11 - 0.54, p-value = 0.002 for >75 age class) reduced this risk. CONCLUSIONS Plateaus in ALS progression lasting at least 6 months appear in about one out of six patients and could last even 12, 18 months or more in a smaller subgroup of patients. Plateaus occurrence should not lead the neurologist to automatically reconsider ALS diagnosis and should be considered for future clinical trials design. This article is protected by copyright. All rights reserved.Treatment selection markers are generally sought for when the benefit of an innovative treatment in comparison with a reference treatment is considered, and this benefit is suspected to vary according to the characteristics of the patients. Classically, such quantitative markers are detected through testing a marker-by-treatment interaction in a parametric regression model. Most alternative methods rely on modeling the risk of event occurrence in each treatment arm or the benefit of the innovative treatment over the marker values, but with assumptions that may be difficult to verify. Herein, a simple non-parametric approach is proposed to detect and assess the general capacity of a quantitative marker for treatment selection when no overall difference in efficacy could be demonstrated between two treatments in a clinical trial. This graphical method relies on the area between treatment-arm-specific receiver operating characteristic curves (ABC), which reflects the treatment selection capacity of the marker. A simulation study assessed the inference properties of the ABC estimator and compared them with other parametric and non-parametric indicators. The simulations showed that the estimate of the ABC had low bias, power comparable to parametric indicators, and that its confidence interval had a good coverage probability (better than the other non-parametric indicator in some cases). Thus, the ABC is a good alternative to parametric indicators. The ABC method was applied to data of the PETACC-8 trial that investigated FOLFOX4 versus FOLFOX4 + cetuximab in stage III colon adenocarcinoma. It enabled the detection of a treatment selection marker the DDR2 gene. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The potential role of home literacy environment (HLE) in children's language development has been widely studied. However, data on the HLE of children with familial risk (FR) of dyslexia are limited. In this longitudinal study, we examined (a) whether amount of book exposure and reading interest at age 4 were different in samples of Norwegian FR and no FR-children, respectively, (b) whether these home literacy-related factors exerted different effects depending on family-risk status on vocabulary and grammar skills at school entry age (6 years) and (c) whether they contributed independently to language outcomes at age 6, after controlling for the 4;6-year language skills. Results showed no significant between-group differences in book exposure and reading interest. Furthermore, while interest in reading did not affect vocabulary and grammar in either group, book exposure contributed to vocabulary skills only in the FR-group by school entry. However, this longitudinal association was mediated by lexical skills at age 4;6, implying that the HLE has a positive indirect effect on later language development through its effect on early language. Thus, these findings can be taken to suggest that early intervention including exposure to various book-reading activities for pre-school FR-children with poor expressive vocabulary is worth considering. © 2020 The Authors. Dyslexia published by John Wiley & Sons Ltd.Recently developed stem-cell-based in vitro models of morphogenesis can help shed light on the mechanisms involved in embryonic patterning. These models are showcased using traditional cell culture platforms and materials, which allow limited control over the biological system and usually do not support high-content imaging. In contrast, using advanced microengineered tools can help in microscale control, long-term culture, and real-time data acquisition from such biological models and aid in elucidating the underlying mechanisms. Here, a new culturing, manipulation and analysis platform is described to study in vitro morphogenesis using thin polycarbonate film-based microdevices. A pipeline consisting of open-source software to quantify 3D cell movement using 4D image acquisition is developed to analyze cell migration within the multicellular clusters. It is shown that the platform can be used to control and study morphogenesis in non-adherent cultures of the P19C5 mouse stem cell line and mouse embryonic stem cells (mESCs) that show symmetry breaking and axial elongation events similar to early embryonic development.