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Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded with micro-solar cells, seeded with cardiomyocytes to form light-stimulable tissues. This enables untethered, noninvasive, and damage-free optoelectronic stimulation–induced modulation of cardiac beating behaviors without needing wires or genetic modifications to the tissue solely with light. Pulsed light stimulation of human cardiomyocytes showed that the optoelectronically active scaffold could increase their beating rates (>40%), maintain high cell viability under light stimulation (>96%), and negligibly affect the electrocardiogram morphology. The seeded scaffolds, termed optoelectronically active tissues, were able to successfully accelerate heart beating in vivo in rats. Our work demonstrates a viable wireless, printable, and optically controllable tissue, suggesting a transformative step in future therapy of electrically active tissues/organs. 

Abstract BackgroundDue to intrinsic differences in data formatting, data structure, and underlying semantic information, the integration of imaging data with clinical data can be non‐trivial. Optimal integration requires robust data fusion, that is, the process of integrating multiple data sources to produce more useful information than captured by individual data sources. Here, we introduce the concept offusion qualityfor deep learning problems involving imaging and clinical data. We first provide a general theoretical framework and numerical validation of our technique. To demonstrate real‐world applicability, we then apply our technique to optimize the fusion of CT imaging and hepatic blood markers to estimate portal venous hypertension, which is linked to prognosis in patients with cirrhosis of the liver. PurposeTo develop a measurement method of optimal data fusion quality deep learning problems utilizing both imaging data and clinical data. MethodsOur approach is based on modeling the fully connected layer (FCL) of a convolutional neural network (CNN) as a potential function, whose distribution takes the form of the classical Gibbs measure. The features of the FCL are then modeled as random variables governed by state functions, which are interpreted as the different data sources to be fused. The probability density of each source, relative to the probability density of the FCL, represents a quantitative measure of source‐bias. To minimize this source‐bias and optimize CNN performance, we implement a vector‐growing encoding scheme called positional encoding, where low‐dimensional clinical data are transcribed into a rich feature space that complements high‐dimensional imaging features. We first provide a numerical validation of our approach based on simulated Gaussian processes. We then applied our approach to patient data, where we optimized the fusion of CT images with blood markers to predict portal venous hypertension in patients with cirrhosis of the liver. This patient study was based on a modified ResNet‐152 model that incorporates both images and blood markers as input. These two data sources were processed in parallel, fused into a single FCL, and optimized based on our fusion quality framework. ResultsNumerical validation of our approach confirmed that the probability density function of a fused feature space converges to a source‐specific probability density function when source data are improperly fused. Our numerical results demonstrate that this phenomenon can be quantified as a measure of fusion quality. On patient data, the fused model consisting of both imaging data and positionally encoded blood markers at the theoretically optimal fusion quality metric achieved an AUC of 0.74 and an accuracy of 0.71. This model was statistically better than the imaging‐only model (AUC = 0.60; accuracy = 0.62), the blood marker‐only model (AUC = 0.58; accuracy = 0.60), and a variety of purposely sub‐optimized fusion models (AUC = 0.61–0.70; accuracy = 0.58–0.69). ConclusionsWe introduced the concept of data fusion quality for multi‐source deep learning problems involving both imaging and clinical data. We provided a theoretical framework, numerical validation, and real‐world application in abdominal radiology. Our data suggests that CT imaging and hepatic blood markers provide complementary diagnostic information when appropriately fused. 

Abstract The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this publication we describe enhancements made to our data processing pipeline and to our website to adapt to an ever-increasing information content. The number of sequences in UniProtKB has risen to over 227 million and we are working towards including a reference proteome for each taxonomic group. We continue to extract detailed annotations from the literature to update or create reviewed entries, while unreviewed entries are supplemented with annotations provided by automated systems using a variety of machine-learning techniques. In addition, the scientific community continues their contributions of publications and annotations to UniProt entries of their interest. Finally, we describe our new website (https://www.uniprot.org/), designed to enhance our users’ experience and make our data easily accessible to the research community. This interface includes access to AlphaFold structures for more than 85% of all entries as well as improved visualisations for subcellular localisation of proteins. 

Abstract The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.