Biomax Informatics (Germany)

Increasingly Findable, Accessible, Reusable and Interoperable (FAIR) nanomaterials environmental health and safety (nanoEHS) data and demoncratised access to nanoinformatics models will directly support 12 SDGs and indireclty benefit the other 5 SDGs.

Nanoscience as a key enabling technology will be fundamental to address several of the current global challenges. Developing safe and sustainable solutions requires high quality data and appropriate analysis approaches. Therefore, implementation of the Findability, Accessibility, Interoperability and Reusability (FAIR) principles within the nanosafety community is key to achieve this and the main goal of the AdvancedNano GO FAIR Implementation Network. Here we highlight the activities of the network to support the nanosafety community in achieving this goal under the overarching aim of maximizing both safe and sustainable application of nano- and advanced materials.

Abstract BackgroundDepending on disease progression, differentiation of patients with mild cognitive impairments from those with Alzheimer disease from structural MRI is often difficult as grey matter (GM) loss is not yet present in MCI patients. Therefore, we re‐assessed WM densities at the initial and changes between two measurements in 22 randomly chosen MCI patients from the ADNI3 cohort [Weiner MW et al. 2017] and compared them to 25 matched controls.MethodWe computed full brain probabilistic tractography by MrTrix3 [Tournier et al. 2019]. ROI to ROI connectivity (HCP MMP 1.0 brain atlas) was compared between groups for Superior Longitudinal Fasciculus (SLF) and Occipital Cortex networks in two longitudinal DTI scans with one year interval by the help of NICARA (www.nicara.eu) [Kopetzky, Butz‐Ostendorf, 2018].ResultSurprisingly, MCI patients showed an increase in brain connectivity of the SLF that was associated with an increased brain rewiring, which we did not observe in matched controls. By contrast, we did not find a similar pattern in WM connections of the visual cortex. This observation was seen in about 40% of MCI patients and did not correlate with age, nor with disease onset. Patients with increased connectivity did not show a decrease in MMSE scores over time whereas patients with a loss in connectivity were more likely to decrease in MMSE score.ConclusionThis study is the first that reports a pronounced brain [Van Ooyen, Butz‐Ostendorf 2017 (eds)] rewiring in association with WM hyperconnectivity [Delli Puzzi et al. 2019] in MCI patients. Phases of pronounced brain rewiring could be an expression of a compensatory response aiming at functional reorganization of brain networks. Our findings point to the urgent need for including longitudinal DTI tractographies in routine brain scans and clinical trials.

PURPOSETrastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2–positive (HER2+) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC.METHODSPatients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, HER2 gene expression was assessed using qPCR.RESULTSFive hundred forty-eight patients were enrolled, and 77 had HER2+ mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER2+ mGC (central HER2+/local HER2+) lived significantly longer as compared with patients who received trastuzumab for local HER2+ but central HER2− mGC (20.5 months, n = 60 v 10.9 months, n = 65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; P < .001). In the centrally confirmed cohort, significantly more tumor cells stained HER2+ than in the unconfirmed cohort, and the HER2 amplification ratio was significantly higher. A minimum of 40% HER2+ tumor cells and a HER2 amplification ratio of ≥ 3.0 were calculated as optimized thresholds for predicting benefit from trastuzumab.CONCLUSIONSignificant discrepancies in HER2 assessment of mGC were found in tumor specimens with intermediate HER2 expression. Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC. HER2 thresholds should be reconsidered. Detailed reports with quantification of HER2 expression and amplification levels may improve selection of patients for HER2-directed treatment.

Seabirds have increasingly encountered offshore wind farms (OWFs) in European waters in the past 10 years, resulting in potential conflicts with offshore foraging areas. During the breeding season, seabirds are restricted in their choice of foraging habitat and are under increased pressure to find enough prey to raise their offspring. However, information on the individual reactions of seabirds towards OWFs during the breeding season is lacking. Three OWFs located 23–35 km north of the island of Helgoland have operated since October 2015. We studied their possible effects on locally breeding common guillemots (Uria aalge) using GPS tracking. GPS tags were deployed on 12 breeding guillemots from Helgoland for 8–26 days during 2016–2017. Most individuals avoided the OWFs, but one individual in each year briefly entered the OWFs on two or three occasions. Using a point process model, we revealed a 63% reduction in the resource selection of the OWF areas compared with the surroundings (lower confidence interval (CI) = 79% reduction, upper CI = 36% reduction). Furthermore, OWF avoidance was increased to 75% when the turbine blades were rotating (lower CI = 93% reduction, upper CI = 11% reduction). Guillemots mainly approached the OWFs from their eastern edge when resting or diving, and rarely approached the areas when commuting. These results provide a detailed description of guillemot reactions to OWFs during the breeding season, and the first comprehensive analysis of OWF effects on this species based on telemetry data. The strong avoidance effect for guillemots during the breeding season indicates the need to consider the presence of OWFs when interpreting future trends in the abundance and breeding success of this species.

IntroductionTo understand the puberty-related sex shift in the prevalence of asthma and rhinitis as single entities and as respiratory multimorbidities, we investigated if there is also a sex-specific and puberty-related pattern of their incidences.MethodsWe used harmonised questionnaire data from 18 451 participants in five prospective observational European birth cohorts within the collaborative MeDALL (Mechanisms of the Development of Allergy) project. Outcome definitions for IgE-associated and non-IgE-associated asthma, rhinitis and respiratory multimorbidity (first occurrence of coexisting asthma and rhinitis) were based on questionnaires and the presence of specific antibodies (IgE) against common allergens in serum. For each outcome, we used proportional hazard models with sex–puberty interaction terms and conducted a one-stage individual participant data meta-analysis.ResultsGirls had a lower risk of incident asthma (adjusted HR 0.67, 95% CI 0.61 to 0.74), rhinitis (0.73, 0.69 to 0.78) and respiratory multimorbidity (0.58, 0.51 to 0.66) before puberty compared with boys. After puberty onset, these incidences became more balanced across the sexes (asthma 0.84, 0.64 to 1.10; rhinitis 0.90, 0.80 to 1.02; respiratory multimorbidity 0.84, 0.63 to 1.13). The incidence sex shift was slightly more distinct for non-IgE-associated respiratory diseases (asthma 0.74, 0.63 to 0.87 before vs 1.23, 0.75 to 2.00 after puberty onset; rhinitis 0.88, 0.79 to 0.98 vs 1.20, 0.98 to 1.47; respiratory multimorbidity 0.66, 0.49 to 0.88 vs 0.96, 0.54 to 1.71) than for IgE-associated respiratory diseases.DiscussionWe found an incidence ‘sex shift’ in chronic respiratory diseases from a male predominance before puberty to a more sex-balanced incidence after puberty onset, which may partly explain the previously reported sex shift in prevalence. These differences need to be considered in public health to enable effective diagnoses and timely treatment in adolescent girls.

To fulfill the promises of Augmented Reality (AR) in the manufacturing and maintenance industry, the development of AR application has to become faster, simpler and cheaper. Since typical AR applications make use of basic functionality like reading markers and displaying simple overlays, a clever combination of such basic building blocks would ease the development of complex AR applications.In this paper, we present a distributed architecture for creating and managing basic AR services, e.g. for information management, user interaction, and documentation. This way, complex AR processes can be orchestrated from those services for being used in different application domains.

Abstract Targeted cancer therapies are powerful alternatives to chemotherapies or can be used complementary to these. Yet, the response to targeted treatments depends on a variety of factors, including mutations and expression levels, and therefore their outcome is difficult to predict. Here, we develop a mechanistic model of gastric cancer to study response and resistance factors for cetuximab treatment. The model captures the EGFR, ERK and AKT signaling pathways in two gastric cancer cell lines with different mutation patterns. We train the model using a comprehensive selection of time and dose response measurements, and provide an assessment of parameter and prediction uncertainties. We demonstrate that the proposed model facilitates the identification of causal differences between the cell lines. Furthermore, our study shows that the model provides accurate predictions for the responses to different perturbations, such as knockdown and knockout experiments. Among other results, the model predicted the effect of MET mutations on cetuximab sensitivity. These predictive capabilities render the model a powerful basis for the assessment of gastric cancer signaling and for the development and discovery of predictive biomarkers.Author SummaryUnraveling the causal differences between drug responders and non-responders is an important challenge. The information can help to understand molecular mechanisms and to guide the selection and design of targeted therapies. Here, we approach this problem for cetuximab treatment for gastric cancer using mechanistic mathematical modeling. The proposed model describes multiple gastric cancer cell lines and can accurately predict the response in several validation experiments. Our analysis provides a differentiated view on mutations and explains, for instance, the relevance of MET mutations and the insignificance of PIK3CA mutation in the considered cell lines. The model might provide the basis for understanding the recent failure of several clinical studies.

The article addresses the strategic role of workforce preparation in the process of adoption of Systems Medicine as a driver of biomedical research in the new health paradigm. It reports on relevant initiatives, like CASyM, fostering Systems Medicine at EU level. The chapter focuses on the BioHealth Computing Program as a reference for multidisciplinary training of future systems-oriented researchers describing the productive interactions with the Synergy-COPD project.