Evaluation of a Novel Rapid Test System for the Detection of Specific IgE to Hymenoptera Venoms

Background. The Allergy Lateral Flow Assay (ALFA) is a novel rapid assay for the detection of sIgE to allergens. The objective of this study is the evaluation of ALFA for the detection of sIgE to bee venom (BV) and wasp venom (WV) in insect venom allergic patients. Methods. Specific IgE to BV and WV was analyzed by ALFA, ALLERG-O-LIQ, and ImmunoCAP in 80 insect venom allergic patients and 60 control sera. Sensitivity and specificity of ALFA and correlation of ALFA and ImmunoCAP results were calculated. Results. The sensitivity/specificity of ALFA to the diagnosis was 100%/83% for BV and 82%/97% for WV. For insect venom allergic patients, the Spearman correlation coefficient for ALFA versus ImmunoCAP was 0.79 for BV and 0.80 for WV. However, significant differences in the negative control groups were observed. Conclusion. ALFA represents a simple, robust, and reliable tool for the rapid detection of sIgE to insect venoms

Distribution of enteric glia and GDNF during gut inflammation

<p>Abstract</p> <p>Background</p> <p>The enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD). Enteric glia cells (EGCs) are the major source of glial-derived neurotrophic factor (GDNF), which regulates apoptosis of enterocytes. The aim of the study was to determine the distribution of EGCs and GDNF during gut inflammation and to elucidate a possible diminished enteric glia network in IBD.</p> <p>Methods</p> <p>The expression of glial fibrillary acidic protein (GFAP) in colonic biopsies of patients with IBD, controls and patients with infectious colitis was detected by immunohistochemistry and Western blot. Tissue GDNF levels were measured by ELISA.</p> <p>Results</p> <p>The expression of GFAP and GDNF in the mucosal plexus is highly increased in the inflamed colon of patients with ulcerative colitis (UC) and infectious colitis. Although the GDNF and GFAP content are increased in Crohn's disease (CD), it is significantly less. Additionally the non-inflamed colon of CD patients showed a reduced GFAP and no GDNF expression compared to controls and the non-inflamed colon of UC patients.</p> <p>Conclusions</p> <p>GFAP and GDNF as signs of activated EGCs are increased in the inflamed mucosa of patients with UC and infectious colitis, which underline an unspecific role of EGC in the regulation of intestinal inflammation. The reduced GFAP and GDNF content in the colon of CD patients suggest a diminished EGC network in this disease. This might be a part of the pathophysiological puzzle of CD.</p

Early Computer Science Education. Goals and Success Criteria for Pre-Primary and Primary Education

“Scientific Studies on the Work of the ‘Haus der kleinen Forscher’ Foundation” is a regularly published series of scientific reports authored by distinguished experts from the field of early education. This series serves to pursue professional dialogue between the Foundation, academia and practice, with the aim of lending sound support to all child-care centres, after-school care centres and primary schools in Germany in their educational mission. This ninth volume of the series, with a foreword by Ilan Chabay, deals with the goals and requirements of computer science education in the elementary and primary sector. In their expert report, Nadine Bergner, Hilde Köster, Johannes Magenheim, Kathrin Müller, Ralf Romeike, Ulrik Schroeder and Carsten Schulte specify the pedagogical and content-related goal dimensions of computer science education at child-care centres and primary schools. In addition to establishing a theoretical basis for various goal dimensions, the authors discuss the success criteria for effective and efficient early computer science education in practice. They also provide recommendations for the further development of the Foundation’s offerings and scientific accompaniment of the work of the Foundation in the field of computer science. In their expert recommendation, Nadine Bergner and Kathrin Müller describe a selection of informatics systems for children at child-care centres and primary schools and offer suggestions for particularly suitable systems and their use in elementary and primary education based on professional criteria. The final chapter of the volume describes the implementation of these professional recommendations in the programmes of the “Haus der kleinen Forscher” Foundation – with and without computers. (DIPF/Verlag

A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/− nab-paclitaxel in elderly pancreatic cancer patients (GrantPax)

Background: In the group of elderly patients (≥70 years) with metastatic pancreatic ductal adenocarcinoma (mPDAC), it is not known who benefits from intensive 1st line nab-paclitaxel/gemcitabine (nab-p/gem) combination chemotherapy or who would rather suffer from increased toxicity. We aim to determine whether treatment individualization by comprehensive geriatric assessments (CGAs) improves functional outcome of the patients. Methods/Design: GrantPax is a multicenter, open label phase 4 interventional trial. We use a CGA to stratify elderly patients into three parallel treatment groups (n = 45 per arm): 1) GOGO (nab-p/gem), 2) SLOWGO (gem mono) or 3) FRAIL (best supportive care). After the 1st cycle of chemotherapy (or 4 weeks in FRAIL group) another CGA and safety assessment is performed. CGA-stratified patients may not decline in their CGA performance in response to the first cycle of chemotherapy (primary objective), measured as a loss of 5 points or less in Barthels activities of daily living. Based on the second CGA, patients are re-assigned to their definite treatment arm and undergo further CGAs to monitor the course of treatment. Secondary endpoints include CGA scores during the course of therapy (CGA1–4), response rates, safety and survival rates. Discussion: GrantPax is the first trial implementing a CGA-driven treatment to personalize therapy for elderly patients with pancreatic cancer. This may lead to standardization of therapy decisions for elderly patients and may optimize standard of care for this increasing group of patients. Trial registration: NCT02812992 , registered 24.06.2016

No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals

This article is made available through the Brunel Open Access Publishing Fund. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p > 0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10−6 M for Gen and >10−5 M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of genistein and bisphenol A, respectively) would do otherwise.BBSR

Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma

Accurate assessment of neuroblastoma outcome prediction remains challenging. Therefore, this study aims at establishing novel prognostic tumor DNA methylation biomarkers. In total, 396 low- and high-risk primary tumors were analyzed, of which 87 were profiled using methyl-CpG-binding domain (MBD) sequencing for differential methylation analysis between prognostic patient groups. Subsequently, methylation-specific PCR (MSP) assays were developed for 78 top-ranking differentially methylated regions and tested on two independent cohorts of 132 and 177 samples, respectively. Further, a new statistical framework was used to identify a robust set of MSP assays of which the methylation score (i.e. the percentage of methylated assays) allows accurate outcome prediction. Survival analyses were performed on the individual target level, as well as on the combined multimarker signature. As a result of the differential DNA methylation assessment by MBD sequencing, 58 of the 78 MSP assays were designed in regions previously unexplored in neuroblastoma, and 36 are located in non-promoter or non-coding regions. In total, 5 individual MSP assays (located in CCDC177, NXPH1, lnc-MRPL3-2, lnc-TREX1-1 and one on a region from chromosome 8 with no further annotation) predict event-free survival and 4 additional assays (located in SPRED3, TNFAIP2, NPM2 and CYYR1) also predict overall survival. Furthermore, a robust 58-marker methylation signature predicting overall and event-free survival was established. In conclusion, this study encompasses the largest DNA methylation biomarker study in neuroblastoma so far. We identified and independently validated several novel prognostic biomarkers, as well as a prognostic 58-marker methylation signature

SiDroForest: a comprehensive forest inventory of Siberian boreal forest investigations including drone-based point clouds, individually labeled trees, synthetically generated tree crowns, and Sentinel-2 labeled image patches

The SiDroForest (Siberian drone-mapped forest inventory) data collection is an attempt to remedy the scarcity of forest structure data in the circumboreal region by providing adjusted and labeled tree-level and vegetation plot-level data for machine learning and upscaling purposes. We present datasets of vegetation composition and tree and plot level forest structure for two important vegetation transition zones in Siberia, Russia; the summergreen–evergreen transition zone in Central Yakutia and the tundra–taiga transition zone in Chukotka (NE Siberia). The SiDroForest data collection consists of four datasets that contain different complementary data types that together support in-depth analyses from different perspectives of Siberian Forest plot data for multi-purpose applications. i. Dataset 1 provides unmanned aerial vehicle (UAV)-borne data products covering the vegetation plots surveyed during fieldwork (Kruse et al., 2021, https://doi.org/10.1594/PANGAEA.933263). The dataset includes structure-from-motion (SfM) point clouds and red–green–blue (RGB) and red–green–near-infrared (RGN) orthomosaics. From the orthomosaics, point-cloud products were created such as the digital elevation model (DEM), canopy height model (CHM), digital surface model (DSM) and the digital terrain model (DTM). The point-cloud products provide information on the three-dimensional (3D) structure of the forest at each plot.ii. Dataset 2 contains spatial data in the form of point and polygon shapefiles of 872 individually labeled trees and shrubs that were recorded during fieldwork at the same vegetation plots (van Geffen et al., 2021c, https://doi.org/10.1594/PANGAEA.932821). The dataset contains information on tree height, crown diameter, and species type. These tree and shrub individually labeled point and polygon shapefiles were generated on top of the RGB UVA orthoimages. The individual tree information collected during the expedition such as tree height, crown diameter, and vitality are provided in table format. This dataset can be used to link individual information on trees to the location of the specific tree in the SfM point clouds, providing for example, opportunity to validate the extracted tree height from the first dataset. The dataset provides unique insights into the current state of individual trees and shrubs and allows for monitoring the effects of climate change on these individuals in the future.iii. Dataset 3 contains a synthesis of 10 000 generated images and masks that have the tree crowns of two species of larch (Larix gmelinii and Larix cajanderi) automatically extracted from the RGB UAV images in the common objects in context (COCO) format (van Geffen et al., 2021a, https://doi.org/10.1594/PANGAEA.932795). As machine-learning algorithms need a large dataset to train on, the synthetic dataset was specifically created to be used for machine-learning algorithms to detect Siberian larch species.iv. Dataset 4 contains Sentinel-2 (S-2) Level-2 bottom-of-atmosphere processed labeled image patches with seasonal information and annotated vegetation categories covering the vegetation plots (van Geffen et al., 2021b, https://doi.org/10.1594/PANGAEA.933268). The dataset is created with the aim of providing a small ready-to-use validation and training dataset to be used in various vegetation-related machine-learning tasks. It enhances the data collection as it allows classification of a larger area with the provided vegetation classes. The SiDroForest data collection serves a variety of user communities. The detailed vegetation cover and structure information in the first two datasets are of use for ecological applications, on one hand for summergreen and evergreen needle-leaf forests and also for tundra–taiga ecotones. Datasets 1 and 2 further support the generation and validation of land cover remote-sensing products in radar and optical remote sensing. In addition to providing information on forest structure and vegetation composition of the vegetation plots, the third and fourth datasets are prepared as training and validation data for machine-learning purposes. For example, the synthetic tree-crown dataset is generated from the raw UAV images and optimized to be used in neural networks. Furthermore, the fourth SiDroForest dataset contains S-2 labeled image patches processed to a high standard that provide training data on vegetation class categories for machine-learning classification with JavaScript Object Notation (JSON) labels provided. The SiDroForest data collection adds unique insights into remote hard-to-reach circumboreal forest regions.</p

Focal DNA copy number changes in neuroblastoma target MYCN regulated genes

Neuroblastoma is an embryonic tumor arising from immature sympathetic nervous system cells. Recurrent genomic alterations include MYCN and ALK amplification as well as recurrent patterns of gains and losses of whole or large partial chromosome segments. A recent whole genome sequencing effort yielded no frequently recurring mutations in genes other than those affecting ALK. However, the study further stresses the importance of DNA copy number alterations in this disease, in particular for genes implicated in neuritogenesis. Here we provide additional evidence for the importance of focal DNA copy number gains and losses, which are predominantly observed in MYCN amplified tumors. A focal 5 kb gain encompassing the MYCN regulated miR-17,92 cluster as sole gene was detected in a neuroblastoma cell line and further analyses of the array CGH data set demonstrated enrichment for other MYCN target genes in focal gains and amplifications. Next we applied an integrated genomics analysis to prioritize MYCN down regulated genes mediated by MYCN driven miRNAs within regions of focal heterozygous or homozygous deletion. We identified RGS5, a negative regulator of G-protein signaling implicated in vascular normalization, invasion and metastasis, targeted by a focal homozygous deletion, as a new MYCN target gene, down regulated through MYCN activated miRNAs. In addition, we expand the miR-17,92 regulatory network controlling TGFß signaling in neuroblastoma with the ring finger protein 11 encoding gene RNF11, which was previously shown to be targeted by the miR-17,92 member miR-19b. Taken together, our data indicate that focal DNA copy number imbalances in neuroblastoma (1) target genes that are implicated in MYCN signaling, possibly selected to reinforce MYCN oncogene addiction and (2) serve as a resource for identifying new molecular targets for treatment