Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer

Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics methodology while exemplifying each step on the application of prostate cancer recurrence prediction. In particular, we automatically identified tissue-based biomarkers having significant prognostic value for low-and intermediate-risk prostate cancer patients (Gleason scores 6-7b) after radical prostatectomy. We found that promising phenes were related to CD8(+) and CD68(+) cells in the microenvironment of cancerous glands in combination with the local micro-vascularization. Recurrence prediction based on the selected phenes yielded accuracies up to 83% thereby clearly outperforming prediction based on the Gleason score. Moreover, we compared different machine learning algorithms to combine the most relevant phenes resulting in increased accuracies of 88% for tumor progression prediction. These findings will be of potential use for future prognostic tests for prostate cancer patients and provide a proof-of-principle of the Tissue Phenomics approach

Amplifying Signals and avoiding surprises: Potential synergies between ICOS and eLTER at the Water-Climate-Greenhouse Gas nexus

Environmental thresholds. tipping points and subsequent regime shifts associated with the water/climate/greenhouse gas nexus pose a genuine threat to sustainability. Both the ongoing forest dieback in Central Europe caused by the extreme droughts of the last years and the effect of global warming on ecosystem functioning have the potential to cause ecological surprise (sensu Lindenmayer et al. 2010) where ecosystems are pushed into new, unexpected and usually undesirable states. Formulating appropriate scientific and societal responses to such regime shifts requires breadth, depth, intensity and duration of environmental, ecological and socio-ecological monitoring. Broad geographic coverage to encompass relevant biophysical and societal gradients, consideration of all appropriate parameters, adequate measurement frequency and long-term, standardized observations are all needed to provide reliable early warnings of severe environmental change, test ecosystem models, avoid double counting in carbon accounting and to reduce the likelihood of undesirable ecological outcomes. This is especially true of events driven by simultaneous changes in climate, the water cycle and human activities. Well-supported, site-based research infrastructures (RIs; e.g., eLTER and ICOS) are essential tools with the necessary breadth, depth, intensity and duration for early detection and attribution of environmental change. Individually, the eLTER and ICOS RIs generate a wealth of data supporting the ecosystem and carbon research communities. Achieving synergies between the two RIs can add value to both communities and potentially offer meaningful insight into the European water-climate-greenhouse gas nexus. The unique insights into processes and mechanisms of ecosystem dynamics and functioning obtained from high intensity monitoring conducted by the ICOS RI greatly increase the likelihood of detecting signals of environmental change. These signals must be placed into the context of their long-term trajectory and potential societal and environmental drivers. The spatially extensive, long-term, multi-disciplinary monitoring conducted at LTER sites and LTSER platforms under the umbrella of the eLTER programme can provide this context. Here, we outline one potential roadmap for achieving synergies between the ICOS and eLTER RIs focussing on the value of co-location for improved understanding of the water/climate/greenhouse gas nexus. Based on data and experiences from intensively studied research sites, we highlight some of the possibilities for reducing the likelihood of ecological surprise that could result from such synergies.Peer reviewe

Semi-automatic identification of punching areas for tissue microarray building: the tubular breast cancer pilot study

Background: Tissue MicroArray technology aims to perform immunohistochemical staining on hundreds of different tissue samples simultaneously. It allows faster analysis, considerably reducing costs incurred in staining. A time consuming phase of the methodology is the selection of tissue areas within paraffin blocks: no utilities have been developed for the identification of areas to be punched from the donor block and assembled in the recipient block.Results: The presented work supports, in the specific case of a primary subtype of breast cancer (tubular breast cancer), the semi-automatic discrimination and localization between normal and pathological regions within the tissues. The diagnosis is performed by analysing specific morphological features of the sample such as the absence of a double layer of cells around the lumen and the decay of a regular glands-and-lobules structure. These features are analysed using an algorithm which performs the extraction of morphological parameters from images and compares them to experimentally validated threshold values. Results are satisfactory since in most of the cases the automatic diagnosis matches the response of the pathologists. In particular, on a total of 1296 sub-images showing normal and pathological areas of breast specimens, algorithm accuracy, sensitivity and specificity are respectively 89%, 84% and 94%.Conclusions: The proposed work is a first attempt to demonstrate that automation in the Tissue MicroArray field is feasible and it can represent an important tool for scientists to cope with this high-throughput technique

COSMOS-Europe: a European network of cosmic-ray neutron soil moisture sensors

[EN] Climate change increases the occurrence and severity of droughts due to increasing temperatures, altered circulation patterns, and reduced snow occurrence. While Europe has suffered from drought events in the last decade unlike ever seen since the beginning of weather recordings, harmonized long-term datasets across the continent are needed to monitor change and support predictions. Here we present soil moisture data from 66 cosmic-ray neutron sensors (CRNSs) in Europe (COSMOS-Europe for short) covering recent drought events. The CRNS sites are distributed across Europe and cover all major land use types and climate zones in Europe. The raw neutron count data from the CRNS stations were provided by 24 research institutions and processed using state-of-the-art methods. The harmonized processing included correction of the raw neutron counts and a harmonized methodology for the conversion into soil moisture based on available in situ information. In addition, the uncertainty estimate is provided with the dataset, information that is particularly useful for remote sensing and modeling applications. This paper presents the current spatiotemporal coverage of CRNS stations in Europe and describes the protocols for data processing from raw measurements to consistent soil moisture products. The data of the presented COSMOS-Europe network open up a manifold of potential applications for environmental research, such as remote sensing data validation, trend analysis, or model assimilation The dataset could be of particular importance for the analysis of extreme climatic events at the continental scale. Due its timely relevance in the scope of climate change in the recent years, we demonstrate this potential application with a brief analysis on the spatiotemporal soil moisture variability. The dataset, entitled "Dataset of COSMOS-Europe: A European network of Cosmic-Ray Neutron Soil Moisture Sensors", is shared via Forschungszentrum Julich: https://doi.org/10.34731/x9s3-kr48 (Bogena and Ney, 2021).We thank TERENO (Terrestrial Environmental Observatories), funded by the Helmholtz-Gemeinschaft for the financing and maintenance of CRNS stations. We acknowledge financial support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) of the research unit FOR 2694 Cosmic Sense (grant no. 357874777) and by the German Federal Ministry of Education of the Research BiookonomieREVIER, Digitales Geosystem -Rheinisches Revier project (grant no. 031B0918A). COSMOS-UK has been supported financially by the UK's Natural Environment Research Council (grant no. NE/R016429/1). The Olocau experimental watershed is partially supported by the Spanish Ministry of Science and Innovation through the research project TETISCHANGE (grant no. RTI2018-093717-BI00). The Calderona experimental site is partially supported by the Spanish Ministry of Science and Innovation through the research projects CEHYRFO-MED (grant no. CGL2017-86839C3-2-R) and SILVADAPT.NET (grant no. RED2018-102719-T) and the LIFE project RESILIENT FORESTS (grant no. LIFE17 CCA/ES/000063). The University of Bristol's Sheepdrove sites have been supported by the UK's Natural Environment Research Council through a number of projects (grant nos. NE/M003086/1, NE/R004897/1, and NE/T005645/1) and by the International Atomic Energy Agency of the United Nations (grant no. CRP D12014).Bogena, HR.; Schrön, M.; Jakobi, J.; Ney, P.; Zacharias, S.; Andreasen, M.; Baatz, R.... (2022). COSMOS-Europe: a European network of cosmic-ray neutron soil moisture sensors. Earth System Science Data. 14(3):1125-1151. https://doi.org/10.5194/essd-14-1125-20221125115114

Beneficial actions of oleanolic acid in an experimental model of multiple sclerosis: A potential therapeutic role

11 páginas, 8 figuras.Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease for which there exist no therapies without undesired side effects. Thus, the establishment of less toxic treatments is an ongoing challenge. Nowadays, research on medicinal plants has been attracting much attention, since screening of its active principles could prove useful in identification of safe and innovative pharmaceutical molecules. In this study we investigated the therapeutic effect of oleanolic acid (OA) a plant-derived triterpene with potent anti-inflammatory and immunomodulatory activities, whose actions on CNS diseases remain far from completely characterized. We focussed on the potential therapeutic effect of oleanolic acid (OA) on an accepted experimental model of MS, the experimental autoimmune encephalomyelitis (EAE). We have found that OA treatment, before or at the early onset of EAE, ameliorates neurological signs of EAE-mice. These beneficial effects of OA seem to be associated with a reduction of blood–brain barrier leakage and lower infiltration of inflammatory cells within the CNS, as well as with its modulatory role in Th1/Th2 polarization: inhibition of proinflammatory cytokines and chemokines, and stimulation of anti-inflammatory ones. Moreover, EAE-animals that were treated with OA had lower levels of anti-MOG antibodies than untreated EAE-mice. Our findings show that the administration of the natural triterpenoid OA reduces and limits the severity and development of EAE. Therefore, OA therapy might be of clinical interest for human MS and other Th1 cell-mediated inflammatory diseases.This work was supported by the Ramon y Cajal Program (to M.H.), F.P.I. Program from the Autonomous Government of Castilla y Leon (to R.M.) both co-funded by F.S.E., Grants SAF2005-01242 and SAF2008-00245 from the Spanish Ministry of Science and Technology, and Grant CSI11A08 from the Autonomous Government of Castilla y Leon.Peer reviewe

Remote sensing of geomorphodiversity linked to biodiversity — part III: traits, processes and remote sensing characteristics

Remote sensing (RS) enables a cost-effective, extensive, continuous and standardized monitoring of traits and trait variations of geomorphology and its processes, from the local to the continental scale. To implement and better understand RS techniques and the spectral indicators derived from them in the monitoring of geomorphology, this paper presents a new perspective for the definition and recording of five characteristics of geomorphodiversity with RS, namely: geomorphic genesis diversity, geomorphic trait diversity, geomorphic structural diversity, geomorphic taxonomic diversity, and geomorphic functional diversity. In this respect, geomorphic trait diversity is the cornerstone and is essential for recording the other four characteristics using RS technologies. All five characteristics are discussed in detail in this paper and reinforced with numerous examples from various RS technologies. Methods for classifying the five characteristics of geomorphodiversity using RS, as well as the constraints of monitoring the diversity of geomorphology using RS, are discussed. RS-aided techniques that can be used for monitoring geomorphodiversity in regimes with changing land-use intensity are presented. Further, new approaches of geomorphic traits that enable the monitoring of geomorphodiversity through the valorisation of RS data from multiple missions are discussed as well as the ecosystem integrity approach. Likewise, the approach of monitoring the five characteristics of geomorphodiversity recording with RS is discussed, as are existing approaches for recording spectral geomorhic traits/ trait variation approach and indicators, along with approaches for assessing geomorphodiversity. It is shown that there is no comparable approach with which to define and record the five characteristics of geomorphodiversity using only RS data in the literature. Finally, the importance of the digitization process and the use of data science for research in the field of geomorphology in the 21st century is elucidated and discussed

Using mixed objects in the training of object-based image classifications

Image classification for thematic mapping is a very common application in remote sensing, which is sometimes realized through object-based image analysis. In these analyses, it is common for some of the objects to be mixed in their class composition and thus violate the commonly made assumption of object purity that is implicit in a conventional object-based image analysis. Mixed objects can be a problem throughout a classification analysis, but are particularly challenging in the training stage as they can result in degraded training statistics and act to reduce mapping accuracy. In this paper the potential of using mixed objects in training object-based image classifications is evaluated. Remotely sensed data were submitted to a series of segmentation analyses from which a range of under- to over-segmented outputs were intentionally produced. Training objects were then selected from the segmentation outputs, resulting in training data sets that varied in terms of size (i.e. number of objects) and proportion of mixed objects. These training data sets were then used with an artificial neural network and a generalized linear model, which can accommodate objects of mixed composition, to produce a series of land cover maps. The use of training statistics estimated based on both pure and mixed objects often increased classification accuracy by around 25% when compared with accuracies obtained from the use of only pure objects in training. So rather than the mixed objects being a problem, they can be an asset in classification and facilitate land cover mapping from remote sensing. It is, therefore, desirable to recognize the nature of the objects and possibly accommodate mixed objects directly in training. The results obtained here may also have implications for the common practice of seeking an optimal segmentation output, and also act to challenge the widespread view that object-based classification is superior to pixel-based classification

COSMOS-Europe : a European network of cosmic-ray neutron soil moisture sensors

We thank TERENO (Terrestrial Environmental Observatories), funded by the Helmholtz-Gemeinschaft for the financing and maintenance of CRNS stations. We acknowledge financial support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) of the research unit FOR 2694 Cosmic Sense (grant no. 357874777) and by the German Federal Ministry of Education of the Research BioökonomieREVIER, Digitales Geosystem – Rheinisches Revier project (grant no. 031B0918A). COSMOS-UK has been supported financially by the UK’s Natural Environment Research Council (grant no. NE/R016429/1). The Olocau experimental watershed is partially supported by the Spanish Ministry of Science and Innovation through the research project TETISCHANGE (grant no. RTI2018-093717-BI00). The Calderona experimental site is partially supported by the Spanish Ministry of Science and Innovation through the research projects CEHYRFO-MED (grant no. CGL2017-86839- C3-2-R) and SILVADAPT.NET (grant no. RED2018-102719-T) and the LIFE project RESILIENT FORESTS (grant no. LIFE17 CCA/ES/000063). The University of Bristol’s Sheepdrove sites have been supported by the UK’s Natural Environment Research Council through a number of projects (grant nos. NE/M003086/1, NE/R004897/1, and NE/T005645/1) and by the International Atomic Energy Agency of the United Nations (grant no. CRP D12014). Acknowledgements. We thank Peter Strauss and Gerhab Rab from the Institute for Land and Water Management Research, Federal Agency for Water Management Austria, Petzenkirchen, Austria. We thank Trenton Franz from the School of Natural Resources, University of Nebraska–Lincoln, Lincoln, NE, United States. We also thank Carmen Zengerle, Mandy Kasner, Felix Pohl, and Solveig Landmark, UFZ Leipzig, for supporting field calibration, lab analysis, and data processing. We furthermore thank Daniel Dolfus, Marius Schmidt, Ansgar Weuthen, and Bernd Schilling, Forschungszentrum Jülich, Germany. The COSMOS-UK project team is thanked for making its data available to COSMOS-Europe. Luca Stevanato is thanked for the technical details about the Finapp sensor. The stations at Cunnersdorf, Lindenberg, and Harzgerode have been supported by Falk Böttcher, Frank Beyrich, and Petra Fude, German Weather Service (DWD). The Zerbst site has been supported by Getec Green Energy GmbH and Jörg Kachelmann (Meteologix AG). The CESBIO sites have been supported by the CNES TOSCA program. The ERA5-Land data are provided by ECMWF (Muñoz Sabater, 2021). The Jena dataset was retrieved at the site of The Jena Experiment, operated by DFG research unit FOR 1451.Peer reviewedPublisher PD