Abstract
Determining protein levels in each tissue and how they compare with RNA levels is important for understanding human biology and disease as well as regulatory processes that control protein levels. We quantified the relative protein levels from over 12,000 genes across 32 normal human tissues. Tissue-specific or tissue-enriched proteins were identified and compared to transcriptome data. Many ubiquitous transcripts are found to encode tissue-specific proteins. Discordance of RNA and protein enrichment revealed potential sites of synthesis and action of secreted proteins. The tissue-specific distribution of proteins also provides an in-depth view of complex biological events that require the interplay of multiple tissues. Most importantly, our study demonstrated that protein tissue-enrichment information can explain phenotypes of genetic diseases, which cannot be obtained by transcript information alone. Overall, our results demonstrate how understanding protein levels can provide insights into regulation, secretome, metabolism, and human diseases.

Abstract
Diabetic retinopathy (DR) grading is crucial in determining the adequate treatment and follow up of patient, but the screening process can be tiresome and prone to errors. Deep learning approaches have shown promising performance as computer-aided diagnosis (CAD) systems, but their black-box behaviour hinders clinical application. We propose DR vertical bar GRADUATE, a novel deep learning-based DR grading CAD system that supports its decision by providing a medically interpretable explanation and an estimation of how uncertain that prediction is, allowing the ophthalmologist to measure how much that decision should be trusted. We designed DR vertical bar GRADUATE taking into account the ordinal nature of the DR grading problem. A novel Gaussian-sampling approach built upon a Multiple Instance Learning framework allow DR vertical bar GRADUATE to infer an image grade associated with an explanation map and a prediction uncertainty while being trained only with image-wise labels. DR vertical bar GRADUATE was trained on the Kaggle DR detection training set and evaluated across multiple datasets. In DR grading, a quadratic-weighted Cohen's kappa (kappa) between 0.71 and 0.84 was achieved in five different datasets. We show that high kappa values occur for images with low prediction uncertainty, thus indicating that this uncertainty is a valid measure of the predictions' quality. Further, bad quality images are generally associated with higher uncertainties, showing that images not suitable for diagnosis indeed lead to less trustworthy predictions. Additionally, tests on unfamiliar medical image data types suggest that DR vertical bar GRADUATE allows outlier detection. The attention maps generally highlight regions of interest for diagnosis. These results show the great potential of DR vertical bar GRADUATE as a second-opinion system in DR severity grading.

Abstract
Background Self-reported client assessments during online treatments enable the development of statistical models for the prediction of client improvement and symptom development. Evaluation of these models is mandatory to ensure their validity. Methods For this purpose, we suggest besides a model evaluation based on study data the use of a simulation analysis. The simulation analysis provides insight into the model performance and enables to analyse reasons for a low predictive accuracy. In this study, we evaluate a temporal causal model (TCM) and show that it does not provide reliable predictions of clients' future mood levels. Results Based on the simulation analysis we investigate the potential reasons for the low predictive performance, for example, noisy measurements and sampling frequency. We conclude that the analysed TCM in its current form is not sufficient to describe the underlying psychological processes. Conclusions The results demonstrate the importance of model evaluation and the benefit of a simulation analysis. The current manuscript provides practical guidance for conducting model evaluation including simulation analysis.

Abstract
EGFR and KRAS are the most frequently mutated genes in lung cancer, being active research topics in targeted therapy. The biopsy is the traditional method to genetically characterise a tumour. However, it is a risky procedure, painful for the patient, and, occasionally, the tumour might be inaccessible. This work aims to study and debate the nature of the relationships between imaging phenotypes and lung cancer-related mutation status. Until now, the literature has failed to point to new research directions, mainly consisting of results-oriented works in a field where there is still not enough available data to train clinically viable models. We intend to open a discussion about critical points and to present new possibilities for future radiogenomics studies. We conducted high-dimensional data visualisation and developed classifiers, which allowed us to analyse the results for EGFR and KRAS biological markers according to different combinations of input features. We show that EGFR mutation status might be correlated to CT scans imaging phenotypes; however, the same does not seem to hold for KRAS mutation status. Also, the experiments suggest that the best way to approach this problem is by combining nodule-related features with features from other lung structures.

Abstract
Diabetic Retinopathy (DR) is the most common cause of avoidable vision loss, predominantly affecting the working-age population across the globe. Screening for DR, coupled with timely consultation and treatment, is a globally trusted policy to avoid vision loss. However, implementation of DR screening programs is challenging due to the scarcity of medical professionals able to screen a growing global diabetic population at risk for DR. Computer-aided disease diagnosis in retinal image analysis could provide a sustainable approach for such large-scale screening effort. The recent scientific advances in computing capacity and machine learning approaches provide an avenue for biomedical scientists to reach this goal. Aiming to advance the state-of-the-art in automatic DR diagnosis, a grand challenge on "Diabetic Retinopathy - Segmentation and Grading" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI-2018). In this paper, we report the set-up and results of this challenge that is primarily based on Indian Diabetic Retinopathy Image Dataset (IDRiD). There were three principal subchallenges: lesion segmentation, disease severity grading, and localization of retinal landmarks and segmentation. These multiple tasks in this challenge allow to test the generalizability of algorithms, and this is what makes it different from existing ones. It received a positive response from the scientific community with 148 submissions from 495 registrations effectively entered in this challenge. This paper outlines the challenge, its organization, the dataset used, evaluation methods and results of top-performing participating solutions. The top-performing approaches utilized a blend of clinical information, data augmentation, and an ensemble of models. These findings have the potential to enable new developments in retinal image analysis and image-based DR screening in particular.

Abstract
Deep brain stimulation (DBS) surgery is the gold standard therapeutic intervention in Parkinson's disease (PD) with motor complications, notwithstanding drug therapy. In the intraoperative evaluation of DBS's efficacy, neurologists impose a passive wrist flexion movement and qualitatively describe the perceived decrease in rigidity under different stimulation parameters and electrode positions. To tackle this subjectivity, we designed a wearable device to quantitatively evaluate the wrist rigidity changes during the neurosurgery procedure, supporting physicians in decision-making when setting the stimulation parameters and reducing surgery time. This system comprises a gyroscope sensor embedded in a textile band for patient's hand, communicating to a smartphone via Bluetooth and has been evaluated on three datasets, showing an average accuracy of 80%. In this work, we present a system that has seen four iterations since 2015, improving on accuracy, usability and reliability. We aim to review the work done so far, outlining the iHandU system evolution, as well as the main challenges, lessons learned, and future steps to improve it. We also introduce the last version (iHandU 4.0), currently used in DBS surgeries at SAo JoAo Hospital in Portugal.