1,967 research outputs found
Automated quantitative assay of fibrosis characteristics in tuberculosis granulomas
IntroductionGranulomas, the pathological hallmark of Mycobacterium tuberculosis (Mtb) infection, are formed by different cell populations. Across various stages of tuberculosis conditions, most granulomas are classical caseous granulomas. They are composed of a necrotic center surrounded by multilayers of histocytes, with the outermost layer encircled by fibrosis. Although fibrosis characterizes the architecture of granulomas, little is known about the detailed parameters of fibrosis during this process.MethodsIn this study, samples were collected from patients with tuberculosis (spanning 16 organ types), and Mtb-infected marmosets and fibrotic collagen were characterized by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy using a stain-free, fully automated analysis program.ResultsHistopathological examination revealed that most granulomas share common features, including necrosis, solitary and compact structure, and especially the presence of multinuclear giant cells. Masson’s trichrome staining showed that different granuloma types have varying degrees of fibrosis. SHG imaging uncovered a higher proportion (4%~13%) of aggregated collagens than of disseminated type collagens (2%~5%) in granulomas from matched tissues. Furthermore, most of the aggregated collagen presented as short and thick clusters (200~620 µm), unlike the long and thick (200~300 µm) disseminated collagens within the matched tissues. Matrix metalloproteinase-9, which is involved in fibrosis and granuloma formation, was strongly expressed in the granulomas in different tissues.DiscussionOur data illustrated that different tuberculosis granulomas have some degree of fibrosis in which collagen strings are short and thick. Moreover, this study revealed that the SHG imaging program could contribute to uncovering the fibrosis characteristics of tuberculosis granulomas
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Cancer Care in Pandemic Times: Building Inclusive Local Health Security in Africa and India
This is a book about improving cancer care in Africa and India that is a child of its pandemic times. It has been collaboratively researched and written by colleagues in Kenya, Tanzania, India and the UK, working within a cross-country, multidisciplinary research project, Innovation for Cancer Care in Africa (ICCA). Since this was a health-focused research project, ICCA researchers during the pandemic not only continued to work on the cancer research project but were also called upon by their governments to respond to immediate pandemic needs. In combining these two concerns, for improving cancer care and responding to pandemic needs, our original project aims have been challenged, deepened and reworked. ICCA’s initial collaborative research focus included—against the grain of most global health literature—the potential role of enhanced local production of essential healthcare supplies for improving cancer care in African countries. The pandemic experience has strikingly validated these earlier findings on the importance of industrial development for health care. The pandemic crystallised for researchers and policymakers an often overlooked phenomenon: global health security is built on the foundations of strong local health security. We argue in this book that new analytical thinking from social scientists and others is required on how to build local health security. We use the “lens” of original research on cancer care in East Africa and India to build up an understanding of the scope for the development of stronger synergies between local health industries and health care, in order to strengthen local health security and develop tools for policy making. The rethinking and reimagining presented here is required for different African countries, for India and the wider world, and this research on cancer care has taught us that this imperative goes much wider than infectious diseases
Design of new algorithms for gene network reconstruction applied to in silico modeling of biomedical data
Programa de Doctorado en BiotecnologĂa, IngenierĂa y TecnologĂa QuĂmicaLĂnea de InvestigaciĂłn: IngenierĂa, Ciencia de Datos y BioinformáticaClave Programa: DBICĂłdigo LĂnea: 111The root causes of disease are still poorly understood. The success of current therapies is limited because persistent diseases are frequently treated based on their symptoms rather than the underlying cause of the disease. Therefore, biomedical research is experiencing a technology-driven shift to data-driven holistic approaches to better characterize the molecular mechanisms causing disease. Using omics data as an input, emerging disciplines like network biology attempt to model the relationships between biomolecules. To this effect, gene co- expression networks arise as a promising tool for deciphering the relationships between genes in large transcriptomic datasets. However, because of their low specificity and high false positive rate, they demonstrate a limited capacity to retrieve the disrupted mechanisms that lead to disease onset, progression, and maintenance. Within the context of statistical modeling, we dove deeper into the reconstruction of gene co-expression networks with the specific goal of discovering disease-specific features directly from expression data. Using ensemble techniques, which combine the results of various metrics, we were able to more precisely capture biologically significant relationships between genes. We were able to find de novo potential disease-specific features with the help of prior biological knowledge and the development of new network inference techniques.
Through our different approaches, we analyzed large gene sets across multiple samples and used gene expression as a surrogate marker for the inherent biological processes, reconstructing robust gene co-expression networks that are simple to explore. By mining disease-specific gene co-expression networks we come up with a useful framework for identifying new omics-phenotype associations from conditional expression datasets.In this sense, understanding diseases from the perspective of biological network perturbations will improve personalized medicine, impacting rational biomarker discovery, patient stratification and drug design, and ultimately leading to more targeted therapies.Universidad Pablo de Olavide de Sevilla. Departamento de Deporte e Informátic
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