9,957 research outputs found

    A scoping review of natural language processing of radiology reports in breast cancer

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    Various natural language processing (NLP) algorithms have been applied in the literature to analyze radiology reports pertaining to the diagnosis and subsequent care of cancer patients. Applications of this technology include cohort selection for clinical trials, population of large-scale data registries, and quality improvement in radiology workflows including mammography screening. This scoping review is the first to examine such applications in the specific context of breast cancer. Out of 210 identified articles initially, 44 met our inclusion criteria for this review. Extracted data elements included both clinical and technical details of studies that developed or evaluated NLP algorithms applied to free-text radiology reports of breast cancer. Our review illustrates an emphasis on applications in diagnostic and screening processes over treatment or therapeutic applications and describes growth in deep learning and transfer learning approaches in recent years, although rule-based approaches continue to be useful. Furthermore, we observe increased efforts in code and software sharing but not with data sharing

    OLIG2 neural progenitor cell development and fate in Down syndrome

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    Down syndrome (DS) is caused by triplication of human chromosome 21 (HSA21) and is the most common genetic form of intellectual disability. It is unknown precisely how triplication of HSA21 results in the intellectual disability, but it is thought that the global transcriptional dysregulation caused by trisomy 21 perturbs multiple aspects of neurodevelopment that cumulatively contribute to its etiology. While the characteristics associated with DS can arise from any of the genes triplicated on HSA21, in this work we focus on oligodendrocyte transcription factor 2 (OLIG2). The progeny of neural progenitor cells (NPCs) expressing OLIG2 are likely to be involved in many of the cellular changes underlying the intellectual disability in DS. To explore the fate of OLIG2+ neural progenitors, we took advantage of two distinct models of DS, the Ts65Dn mouse model and induced pluripotent stem cells (iPSCs) derived from individuals with DS. Our results from these two systems identified multiple perturbations in development in the cellular progeny of OLIG2+ NPCs. In Ts65Dn, we identified alterations in neurons and glia derived from the OLIG2 expressing progenitor domain in the ventral spinal cord. There were significant differences in the number of motor neurons and interneurons present in the trisomic lumbar spinal cord depending on age of the animal pointing both to a neurodevelopment and a neurodegeneration phenotype in the Ts65Dn mice. Of particular note, we identified changes in oligodendrocyte (OL) maturation in the trisomic mice that are dependent on spatial location and developmental origin. In the dorsal corticospinal tract, there were significantly fewer mature OLs in the trisomic mice, and in the lateral funiculus we observed the opposite phenotype with more mature OLs being present in the trisomic animals. We then transitioned our studies into iPSCs where we were able to pattern OLIG2+ NPCs to either a spinal cord-like or a brain-like identity and study the OL lineage that differentiated from each progenitor pool. Similar to the region-specific dysregulation found in the Ts65Dn spinal cord, we identified perturbations in trisomic OLs that were dependent on whether the NPCs had been patterned to a brain-like or spinal cord-like fate. In the spinal cord-like NPCs, there was no difference in the proportion of cells expressing either OLIG2 or NKX2.2, the two transcription factors whose co-expression is essential for OL differentiation. Conversely, in the brain-like NPCs, there was a significant increase in OLIG2+ cells in the trisomic culture and a decrease in NKX2.2 mRNA expression. We identified a sonic hedgehog (SHH) signaling based mechanism underlying these changes in OLIG2 and NKX2.2 expression in the brain-like NPCs and normalized the proportion of trisomic cells expressing the transcription factors to euploid levels by modulating the activity of the SHH pathway. Finally, we continued the differentiation of the brain-like and spinal cord-like NPCs to committed OL precursor cells (OPCs) and allowed them to mature. We identified an increase in OPC production in the spinal cord-like trisomic culture which was not present in the brain-like OPCs. Conversely, we identified a maturation deficit in the brain-like trisomic OLs that was not present in the spinal cord-like OPCs. These results underscore the importance of regional patterning in characterizing changes in cell differentiation and fate in DS. Together, the findings presented in this work contribute to the understanding of the cellular and molecular etiology of the intellectual disability in DS and in particular the contribution of cells differentiated from OLIG2+ progenitors

    ‘Mental fight’ and ‘seeing & writing’ in Virginia Woolf and William Blake

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    This thesis is the first full-length study to assess the writer and publisher Virginia Woolf’s (1882-1941) responses to the radical Romantic poet-painter, and engraver, William Blake (1757-1827). I trace Woolf’s public and private, overt and subtle references to Blake in fiction, essays, notebooks, diaries, letters and drawings. I have examined volumes in Leonard and Virginia Woolf’s library that are pertinent, directly and indirectly, to Woolf’s understanding of Blake. I focus on Woolf’s key phrases about Blake: ‘Mental fight’, and ‘seeing & writing.’ I consider the other phrases Woolf uses to think about Blake in the context of these two categories. Woolf and Blake are both interested in combining visual and verbal aesthetics (‘seeing & writing’). They are both critical of their respective cultures (‘Mental fight’). Woolf mentions ‘seeing & writing’ in connection to Blake in a 1940 notebook. She engages with Blake’s ‘Mental fight’ in ‘Thoughts on Peace in an Air Raid’ (1940). I map late nineteenth and early twentieth-century opinion on Blake and explore Woolf’s engagement with Blake in these wider contexts. I make use of the circumstantial detail of Woolf’s friendship with the great Blake collector and scholar, Geoffrey Keynes (1887-1982), brother of Bloomsbury economist John Maynard Keynes. Woolf was party to the Blake centenary celebrations courtesy of Geoffrey Keynes’s organisation of the centenary exhibition in London in 1927. Chapter One introduces Woolf’s explicit references to Blake and examines the record of Woolf scholarship that unites Woolf and Blake. To see how her predecessors had responded, Chapter Two examines the nineteenth-century interest in Blake and Woolf’s engagement with key nineteenth-century Blakeans. Chapter Three looks at the modernist, early twentieth-century engagement with Blake, to contextualise Woolf’s position on Blake. Chapter Four assesses how Woolf and Blake use ‘Mental fight’ to oppose warmongering and fascist politics. Chapter Five is about what Woolf and Blake write and think about the country and the city. Chapter Six discusses Woolf’s reading of John Milton (1608-1674) in relation to her interest in Blake, drawing on the evidence of Blake’s intense reading of Milton. Chapter Seven examines further miscellaneous continuities between Woolf and Blake. Chapter Eight proposes, in conclusion, that we can only form an impression of Woolf’s Blake. The thesis also has three appendices. First, a chronology of key publications which chart Blake’s reputation as well as Woolf’s allusions to Blake. Second a list all of Blake’s poetry represented in Woolf’s library including contents page. The third lists all the other volumes in Woolf’s library that proved relevant. Although Woolf’s writing is the subject of this thesis, my project necessitates an attempt to recover how Blake was understood and misunderstood by numerous writers in the early twentieth century. The thesis argues Blake is a model radical Romantic who combines the visual and the verbal and that Woolf sees him as a kindred artist

    Um modelo para suporte automatizado ao reconhecimento, extração, personalização e reconstrução de gráficos estáticos

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    Data charts are widely used in our daily lives, being present in regular media, such as newspapers, magazines, web pages, books, and many others. A well constructed data chart leads to an intuitive understanding of its underlying data and in the same way, when data charts have wrong design choices, a redesign of these representations might be needed. However, in most cases, these charts are shown as a static image, which means that the original data are not usually available. Therefore, automatic methods could be applied to extract the underlying data from the chart images to allow these changes. The task of recognizing charts and extracting data from them is complex, largely due to the variety of chart types and their visual characteristics. Computer Vision techniques for image classification and object detection are widely used for the problem of recognizing charts, but only in images without any disturbance. Other features in real-world images that can make this task difficult are not present in most literature works, like photo distortions, noise, alignment, etc. Two computer vision techniques that can assist this task and have been little explored in this context are perspective detection and correction. These methods transform a distorted and noisy chart in a clear chart, with its type ready for data extraction or other uses. The task of reconstructing data is straightforward, as long the data is available the visualization can be reconstructed, but the scenario of reconstructing it on the same context is complex. Using a Visualization Grammar for this scenario is a key component, as these grammars usually have extensions for interaction, chart layers, and multiple views without requiring extra development effort. This work presents a model for automated support for custom recognition, and reconstruction of charts in images. The model automatically performs the process steps, such as reverse engineering, turning a static chart back into its data table for later reconstruction, while allowing the user to make modifications in case of uncertainties. This work also features a model-based architecture along with prototypes for various use cases. Validation is performed step by step, with methods inspired by the literature. This work features three use cases providing proof of concept and validation of the model. The first use case features usage of chart recognition methods focused on documents in the real-world, the second use case focus on vocalization of charts, using a visualization grammar to reconstruct a chart in audio format, and the third use case presents an Augmented Reality application that recognizes and reconstructs charts in the same context (a piece of paper) overlaying the new chart and interaction widgets. The results showed that with slight changes, chart recognition and reconstruction methods are now ready for real-world charts, when taking time, accuracy and precision into consideration.Os gráficos de dados são amplamente utilizados na nossa vida diária, estando presentes nos meios de comunicação regulares, tais como jornais, revistas, páginas web, livros, e muitos outros. Um gráfico bem construído leva a uma compreensão intuitiva dos seus dados inerentes e da mesma forma, quando os gráficos de dados têm escolhas de conceção erradas, poderá ser necessário um redesenho destas representações. Contudo, na maioria dos casos, estes gráficos são mostrados como uma imagem estática, o que significa que os dados originais não estão normalmente disponíveis. Portanto, poderiam ser aplicados métodos automáticos para extrair os dados inerentes das imagens dos gráficos, a fim de permitir estas alterações. A tarefa de reconhecer os gráficos e extrair dados dos mesmos é complexa, em grande parte devido à variedade de tipos de gráficos e às suas características visuais. As técnicas de Visão Computacional para classificação de imagens e deteção de objetos são amplamente utilizadas para o problema de reconhecimento de gráficos, mas apenas em imagens sem qualquer ruído. Outras características das imagens do mundo real que podem dificultar esta tarefa não estão presentes na maioria das obras literárias, como distorções fotográficas, ruído, alinhamento, etc. Duas técnicas de visão computacional que podem ajudar nesta tarefa e que têm sido pouco exploradas neste contexto são a deteção e correção da perspetiva. Estes métodos transformam um gráfico distorcido e ruidoso em um gráfico limpo, com o seu tipo pronto para extração de dados ou outras utilizações. A tarefa de reconstrução de dados é simples, desde que os dados estejam disponíveis a visualização pode ser reconstruída, mas o cenário de reconstrução no mesmo contexto é complexo. A utilização de uma Gramática de Visualização para este cenário é um componente chave, uma vez que estas gramáticas têm normalmente extensões para interação, camadas de gráficos, e visões múltiplas sem exigir um esforço extra de desenvolvimento. Este trabalho apresenta um modelo de suporte automatizado para o reconhecimento personalizado, e reconstrução de gráficos em imagens estáticas. O modelo executa automaticamente as etapas do processo, tais como engenharia inversa, transformando um gráfico estático novamente na sua tabela de dados para posterior reconstrução, ao mesmo tempo que permite ao utilizador fazer modificações em caso de incertezas. Este trabalho também apresenta uma arquitetura baseada em modelos, juntamente com protótipos para vários casos de utilização. A validação é efetuada passo a passo, com métodos inspirados na literatura. Este trabalho apresenta três casos de uso, fornecendo prova de conceito e validação do modelo. O primeiro caso de uso apresenta a utilização de métodos de reconhecimento de gráficos focando em documentos no mundo real, o segundo caso de uso centra-se na vocalização de gráficos, utilizando uma gramática de visualização para reconstruir um gráfico em formato áudio, e o terceiro caso de uso apresenta uma aplicação de Realidade Aumentada que reconhece e reconstrói gráficos no mesmo contexto (um pedaço de papel) sobrepondo os novos gráficos e widgets de interação. Os resultados mostraram que com pequenas alterações, os métodos de reconhecimento e reconstrução dos gráficos estão agora prontos para os gráficos do mundo real, tendo em consideração o tempo, a acurácia e a precisão.Programa Doutoral em Engenharia Informátic

    Towards a non-equilibrium thermodynamic theory of ecosystem assembly and development

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    Non-equilibrium thermodynamics has had a significant historic influence on the development of theoretical ecology, even informing the very concept of an ecosystem. Much of this influence has manifested as proposed extremal principles. These principles hold that systems will tend to maximise certain thermodynamic quantities, subject to the other constraints they operate under. A particularly notable extremal principle is the maximum entropy production principle (MaxEPP); that systems maximise their rate of entropy production. However, these principles are not robustly based in physical theory, and suffer from treating complex ecosystems in an extremely coarse manner. To address this gap, this thesis derives a limited but physically justified extremal principle, as well as carrying out a detailed investigation of the impact of non-equilibrium thermodynamic constraints on the assembly of microbial communities. The extremal principle we obtain pertains to the switching between states in simple bistable systems, with switching paths that generate more entropy being favoured. Our detailed investigation into microbial communities involved developing a novel thermodynamic microbial community model, using which we found the rate of ecosystem development to be set by the availability of free-energy. Further investigation was carried out using this model, demonstrating the way that trade-offs emerging from fundamental thermodynamic constraints impact the dynamics of assembling microbial communities. Taken together our results demonstrate that theory can be developed from non-equilibrium thermodynamics, that is both ecologically relevant and physically well grounded. We find that broad extremal principles are unlikely to be obtained, absent significant advances in the field of stochastic thermodynamics, limiting their applicability to ecology. However, we find that detailed consideration of the non-equilibrium thermodynamic mechanisms that impact microbial communities can broaden our understanding of their assembly and functioning.Open Acces

    Development of in-vitro in-silico technologies for modelling and analysis of haematological malignancies

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    Worldwide, haematological malignancies are responsible for roughly 6% of all the cancer-related deaths. Leukaemias are one of the most severe types of cancer, as only about 40% of the patients have an overall survival of 10 years or more. Myelodysplastic Syndrome (MDS), a pre-leukaemic condition, is a blood disorder characterized by the presence of dysplastic, irregular, immature cells, or blasts, in the peripheral blood (PB) and in the bone marrow (BM), as well as multi-lineage cytopenias. We have created a detailed, lineage-specific, high-fidelity in-silico erythroid model that incorporates known biological stimuli (cytokines and hormones) and a competing diseased haematopoietic population, correctly capturing crucial biological checkpoints (EPO-dependent CFU-E differentiation) and replicating the in-vivo erythroid differentiation dynamics. In parallel, we have also proposed a long-term, cytokine-free 3D cell culture system for primary MDS cells, which was firstly optimized using easily-accessible healthy controls. This system enabled long-term (24-day) maintenance in culture with high (>75%) cell viability, promoting spontaneous expansion of erythroid phenotypes (CD71+/CD235a+) without the addition of any exogenous cytokines. Lastly, we have proposed a novel in-vitro in-silico framework using GC-MS metabolomics for the metabolic profiling of BM and PB plasma, aiming not only to discretize between haematological conditions but also to sub-classify MDS patients, potentially based on candidate biomarkers. Unsupervised multivariate statistical analysis showed clear intra- and inter-disease separation of samples of 5 distinct haematological malignancies, demonstrating the potential of this approach for disease characterization. The work herein presented paves the way for the development of in-vitro in-silico technologies to better, characterize, diagnose, model and target haematological malignancies such as MDS and AML.Open Acces

    The Role of Transient Vibration of the Skull on Concussion

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    Concussion is a traumatic brain injury usually caused by a direct or indirect blow to the head that affects brain function. The maximum mechanical impedance of the brain tissue occurs at 450±50 Hz and may be affected by the skull resonant frequencies. After an impact to the head, vibration resonance of the skull damages the underlying cortex. The skull deforms and vibrates, like a bell for 3 to 5 milliseconds, bruising the cortex. Furthermore, the deceleration forces the frontal and temporal cortex against the skull, eliminating a layer of cerebrospinal fluid. When the skull vibrates, the force spreads directly to the cortex, with no layer of cerebrospinal fluid to reflect the wave or cushion its force. To date, there is few researches investigating the effect of transient vibration of the skull. Therefore, the overall goal of the proposed research is to gain better understanding of the role of transient vibration of the skull on concussion. This goal will be achieved by addressing three research objectives. First, a MRI skull and brain segmentation automatic technique is developed. Due to bones’ weak magnetic resonance signal, MRI scans struggle with differentiating bone tissue from other structures. One of the most important components for a successful segmentation is high-quality ground truth labels. Therefore, we introduce a deep learning framework for skull segmentation purpose where the ground truth labels are created from CT imaging using the standard tessellation language (STL). Furthermore, the brain region will be important for a future work, thus, we explore a new initialization concept of the convolutional neural network (CNN) by orthogonal moments to improve brain segmentation in MRI. Second, the creation of a novel 2D and 3D Automatic Method to Align the Facial Skeleton is introduced. An important aspect for further impact analysis is the ability to precisely simulate the same point of impact on multiple bone models. To perform this task, the skull must be precisely aligned in all anatomical planes. Therefore, we introduce a 2D/3D technique to align the facial skeleton that was initially developed for automatically calculating the craniofacial symmetry midline. In the 2D version, the entire concept of using cephalometric landmarks and manual image grid alignment to construct the training dataset was introduced. Then, this concept was extended to a 3D version where coronal and transverse planes are aligned using CNN approach. As the alignment in the sagittal plane is still undefined, a new alignment based on these techniques will be created to align the sagittal plane using Frankfort plane as a framework. Finally, the resonant frequencies of multiple skulls are assessed to determine how the skull resonant frequency vibrations propagate into the brain tissue. After applying material properties and mesh to the skull, modal analysis is performed to assess the skull natural frequencies. Finally, theories will be raised regarding the relation between the skull geometry, such as shape and thickness, and vibration with brain tissue injury, which may result in concussive injury

    An Overview of the Mechanisms Involved in Coffee-Hemileia vastatrix Interactions: Plant and Pathogen Perspectives

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    Coffee is one of the most consumed beverages in the world. It is also one of the most globally traded commodities. Coffee leaf rust (CLR), caused by the biotrophic fungus Hemileia vastatrix, is the most important disease affecting Arabica coffee growing worldwide, leading to significant yield losses if no control measures are applied. A deep understanding of the complex mechanisms involved in coffee-H. vastatrix interactions, such as the pathogen variability and the mechanisms governing plant resistance and susceptibility, is required to breed efficiently for durable resistance and design new approaches for crop protection. Here we summarize our current understanding across multiple areas related to pathogen infection, variability and candidate effectors, breeding for disease resistance, and the various components of the coffee immune system, by reviewing a comprehensive body of research on CLR and the advances recently made. We also update information about the defense responses activated by the application of plant resistance inducers, a promising alternative to fungicides in the control of CLR. Moreover, we identify and discuss future directions for further researchinfo:eu-repo/semantics/publishedVersio

    Optimizing transcriptomics to study the evolutionary effect of FOXP2

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    The field of genomics was established with the sequencing of the human genome, a pivotal achievement that has allowed us to address various questions in biology from a unique perspective. One question in particular, that of the evolution of human speech, has gripped philosophers, evolutionary biologists, and now genomicists. However, little is known of the genetic basis that allowed humans to evolve the ability to speak. Of the few genes implicated in human speech, one of the most studied is FOXP2, which encodes for the transcription factor Forkhead box protein P2 (FOXP2). FOXP2 is essential for proper speech development and two mutations in the human lineage are believed to have contributed to the evolution of human speech. To address the effect of FOXP2 and investigate its evolutionary contribution to human speech, one can utilize the power of genomics, more specifically gene expression analysis via ribonucleic acid sequencing (RNA-seq). To this end, I first contributed in developing mcSCRB-seq, a highly sensitive, powerful, and efficient single cell RNA-seq (scRNA-seq) protocol. Previously having emerged as a central method for studying cellular heterogeneity and identifying cellular processes, scRNA-seq was a powerful genomic tool but lacked the sensitivity and cost-efficiency of more established protocols. By systematically evaluating each step of the process, I helped find that the addition of polyethylene glycol increased sensitivity by enhancing the cDNA synthesis reaction. This, along with other optimizations resulted in developing a sensitive and flexible protocol that is cost-efficient and ideal in many research settings. A primary motivation driving the extensive optimizations surrounding single cell transcriptomics has been the generation of cellular atlases, which aim to identify and characterize all of the cells in an organism. As such efforts are carried out in a variety of research groups using a number of different RNA-seq protocols, I contributed in an effort to benchmark and standardize scRNA-seq methods. This not only identified methods which may be ideal for the purpose of cell atlas creation, but also highlighted optimizations that could be integrated into existing protocols. Using mcSCRB-seq as a foundation as well as the findings from the scRNA-seq benchmarking, I helped develop prime-seq, a sensitive, robust, and most importantly, affordable bulk RNA-seq protocol. Bulk RNA-seq was frequently overlooked during the efforts to optimize and establish single-cell techniques, even though the method is still extensively used in analyzing gene expression. Introducing early barcoding and reducing library generation costs kept prime-seq cost-efficient, but basing it off of single-cell methods ensured that it would be a sensitive and powerful technique. I helped verify this by benchmarking it against TruSeq generated data and then helped test the robustness by generating prime-seq libraries from over seventeen species. These optimizations resulted in a final protocol that is well suited for investigating gene expression in comprehensive and high-throughput studies. Finally, I utilized prime-seq in order to develop a comprehensive gene expression atlas to study the function of FOXP2 and its role in speech evolution. I used previously generated mouse models: a knockout model containing one non-functional Foxp2 allele and a humanized model, which has a variant Foxp2 allele with two human-specific mutations. To study the effect globally across the mouse, I helped harvest eighteen tissues which were previously identified to express FOXP2. By then comparing the mouse models to wild-type mice, I helped highlight the importance of FOXP2 within lung development and the importance of the human variant allele in the brain. Both mcSCRB-seq and prime-seq have already been used and published in numerous studies to address a variety of biological and biomedical questions. Additionally, my work on FOXP2 not only provides a thorough expression atlas, but also provides a detailed and cost-efficient plan for undertaking a similar study on other genes of interest. Lastly, the studies on FOXP2 done within this work, lay the foundation for future studies investigating the role of FOXP2 in modulating learning behavior, and thereby affecting human speech

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms
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