Data fusion techniques for biomedical informatics and clinical decision support

Data fusion can be used to combine multiple data sources or modalities to facilitate enhanced visualization, analysis, detection, estimation, or classification. Data fusion can be applied at the raw-data, feature-based, and decision-based levels. Data fusion applications of different sorts have been built up in areas such as statistics, computer vision and other machine learning aspects. It has been employed in a variety of realistic scenarios such as medical diagnosis, clinical decision support, and structural health monitoring. This dissertation includes investigation and development of methods to perform data fusion for cervical cancer intraepithelial neoplasia (CIN) and a clinical decision support system. The general framework for these applications includes image processing followed by feature development and classification of the detected region of interest (ROI). Image processing methods such as k-means clustering based on color information, dilation, erosion and centroid locating methods were used for ROI detection. The features extracted include texture, color, nuclei-based and triangle features. Analysis and classification was performed using feature- and decision-level data fusion techniques such as support vector machine, statistical methods such as logistic regression, linear discriminant analysis and voting algorithms --Abstract, page iv

Non-invasive biochemical analysis of cells, tissues and tissue constructs with Raman micro-spectroscopy

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Publications of the space physiology and countermeasures program, regulatory physiology discipline: 1980 - 1990

A 10-year cumulative bibliography of publications resulting from research supported by the Regulatory Physiology discipline of the Space Physiology and Countermeasures Program of NASA's Life Sciences Division is provided. Primary subjects included in this bibliography are circadian rhythms, endocrinology, fluid and electrolyte regulation, hematology, immunology, metabolism and nutrition, temperature regulation, and general regulatory physiology. General physiology references are also included. Principal investigators whose research tasks resulted in publication are identified by asterisk. Publications are identified by a record number corresponding with their entry in the Life Sciences Bibliographic Database, maintained at the George Washington University

Knowledge Management Approaches for predicting Biomarker and Assessing its Impact on Clinical Trials

The recent success of companion diagnostics along with the increasing regulatory pressure for better identification of the target population has created an unprecedented incentive for the drug discovery companies to invest into novel strategies for stratified biomarker discovery. Catching with this trend, trials with stratified biomarker in drug development have quadrupled in the last decade but represent a small part of all Interventional trials reflecting multiple co-developmental challenges of therapeutic compounds and companion diagnostics. To overcome the challenge, varied knowledge management and system biology approaches are adopted in the clinics to analyze/interpret an ever increasing collection of OMICS data. By semi-automatic screening of more than 150,000 trials, we filtered trials with stratified biomarker to analyse their therapeutic focus, major drivers and elucidated the impact of stratified biomarker programs on trial duration and completion. The analysis clearly shows that cancer is the major focus for trials with stratified biomarker. But targeted therapies in cancer require more accurate stratification of patient population. This can be augmented by a fresh approach of selecting a new class of biomolecules i.e. miRNA as candidate stratification biomarker. miRNA plays an important role in tumorgenesis in regulating expression of oncogenes and tumor suppressors; thus affecting cell proliferation, differentiation, apoptosis, invasion, angiogenesis. miRNAs are potential biomarkers in different cancer. However, the relationship between response of cancer patients towards targeted therapy and resulting modifications of the miRNA transcriptome in pathway regulation is poorly understood. With ever-increasing pathways and miRNA-mRNA interaction databases, freely available mRNA and miRNA expression data in multiple cancer therapy have created an unprecedented opportunity to decipher the role of miRNAs in early prediction of therapeutic efficacy in diseases. We present a novel SMARTmiR algorithm to predict the role of miRNA as therapeutic biomarker for an anti-EGFR monoclonal antibody i.e. cetuximab treatment in colorectal cancer. The application of an optimised and fully automated version of the algorithm has the potential to be used as clinical decision support tool. Moreover this research will also provide a comprehensive and valuable knowledge map demonstrating functional bimolecular interactions in colorectal cancer to scientific community. This research also detected seven miRNA i.e. hsa-miR-145, has-miR-27a, has- miR-155, hsa-miR-182, hsa-miR-15a, hsa-miR-96 and hsa-miR-106a as top stratified biomarker candidate for cetuximab therapy in CRC which were not reported previously. Finally a prospective plan on future scenario of biomarker research in cancer drug development has been drawn focusing to reduce the risk of most expensive phase III drug failures

Papers on Anthropology XX

-M. Toomsalu, A. Arend. Medical Collections in Tartu Old Anatomical Theatre – from August Rauber’s anatomy museum to a multifunctional research and edutainment centre -H. Kaarma. A short overview of the work of anthropologists of the Old Anatomical Theatre -M. Viikmaa. Leiu Heapost – 75 -R. Allmäe. Human bones in Salme I boat-grave, the Island of Saaremaa; Estonia -N. Balciuniene, D. graf von Keyserlingk, A. Valanciute, I. Balnyte,A. Macas, A. Tamasauskas. Changes of the chicken chorioallantoic membrane and the behaviour of the transplanted glioblastoma -A. Barzdina, M. Pilmane, A. Petersons. Grap and NF expression in brain tissue in children and adults after fatal traumatic brain injury -D. Batulevicius, G. Skripkiene, V. Batuleviciene, V. Skripka, A. Dabuzinskiene, D. H. Pauza. Complexity of the frog intracardiac neurons. Intracellular injection study -A. Dabuzinskiene, A. Ratkevicius, D. Batulevicius, G. Skripkiene, V. Skripka, G. Liutkiene, U. A. Bagdonas, S. Razbadauskiene. Gender differences in the human cervicothoracic ganglia -C. Dogan, C. Raschka. Anthropometrical and sport constitutional comparison of German male soccer players and male students of sport sciences -D. Gudiene, I. Balnyte, J. Palubinskiene, A. Valanciute. Age related structural changes in human basilar artery -L. Heapost. Taste sensitivity to PTC and colour blindness in Estonians -P. Hussar, I. Tokin, G. Filimonova, I. Tokin, Ü. Hussar. Dexamethazone-induced T-lymphocyte apoptosis in different lymphoid organs -L. Kalichman, E. Kobyliansky. Hand osteoarthritis and aging: the results of large-scale cross-sectional study -S. Kana, T. Viik. Annual report of the Estonian Naturalists’ Society 2010 -B. Karmakar, E. Kobyliansky. Finger and palmar dermatoglyphics in Muzeina Bedouins from South Sinai: a qualitative traits -D. Kažoka, J. Vētra. Variations in some anthropometrical parameters of the women with the different iris colour in Latvia -J. Kasmel, T. Kasmel. Seventy years of the Anthropology Section of the Estonian Naturalists’ Society (Part III) -R. Kisenauskaite, D. Paskeviciene. The research of physical condition, physical activity and nutrition of teacher education students -R. Kleina, I. Franckevica, M. Sperga, D. Lutinska. The analysis of undiagnosed malignancies -G. Kolesova, J. Vētra. Sexual dimorphism of pelvic morphology variation in live humans -V. Kulvietis, V. Žalgeviečienė, J. Didžiapetriene,D. Bulotienė, R. Rotomskis. Distribution of nanoparticles in the pregnant rat:the morphologic and spectroscopic study -A. Kuzminienė, S. Šalomskaitė-Davalgienė, I. Balnyte, J. Palubinskienė, A. Valančiūte, V. Ulozas. Evaluation of the chicken embryo choriaollantoic membrane model for laryngeal tumor transplantation -J. Limbo. The tooth size in the end of the Estonian iron age -M. Lintsi, H. Kaarma, M. Aunapuu, A. Arend, R. Aule. Correlation between anthropometrical variables and body surface area -M. Matyk, C. Raschka. Body composition and somatotype of European top roller speed skaters -A. Miskova, M. Pilmane, D. Rezeberga. Immunochistochemical distribution of IGF-1, bFGF and their receptors in decidual embryonic and tubal human pregnancy tissue -E. Mozeika, M. Pilmane, J. Kisis. Distribution of human B-defensin 2,TNF-alpha, IL-1alpha, IL-6 and IL-8 in psoriatic skin -P. Männik, R. T. Kibur, A. Arend, M. Aunapuu. Trophinin and integrin β3 expression in the human endometrium. A pilot study -A. Namm, A. Arend, M. Aunapuu. Bone morphogenetic proteins as regulators of neural tube development -E. Pētersone-Gordina, G. Geshards. Dental disease in a 17th–18th century German community in Jelgava, Latvia -L. Pļaviņa. Assessment of the physical activity level for the staff military personnel -V. Russeva. Alternations of cervical vertebrae in two individuals from the Late Antiquty Necropolis from the “Big Mound” near Cabyle, Bulgaria -S. Skuja, V. Groma, R. Kleina. Chronic alcohol abuse is implicated in the oxidative stress and the changes in the neurotrophic factor receptor expression in the human CNS -R. Stamm, M. Stamm, N. Sorgina, S. Koskel. Training programme to develop young volleyballers’ jumping ability -G. Sumeraga, M. Pilmane. Distribution of neuropeptides in nasal and nasopharyngeal mucosa in patients with the post nasal drip syndrome -N. Szoldatits, B. L. Buda, G. A. Tóth. Body proportion changes of nursing home oligophrenics in western Hungary (1991–2011) -A. Valdovska, M. Pilmane. Relation between serum enzymes and liver histopathology in mink with hepatitis -G. Veldre, T. Kums, E. Salum, J. Eha. Relationship between soldiers’ body height-weight category and changes in their spinal column kyphotic curvature during a long-term military missio

Estudio del armazón arquitectónico y del sistema vascular de los tumores neuroblásticos

Los pacientes con tumores neuroblásticos presentan una evolución clínica heterogénea, desde la regresión espontánea hasta una alta propensión para la diseminación metastática generalizada. Aunque la aplicación de una clasificación de riesgo pre-tratamiento bien definida tiene un papel central en la mejora de la supervivencia durante los últimos años, han de llevarse a cabo más avances para mejorar la superviencia de los pacientes en general y específicamente el subgrupo de pacientes de alto riesgo. El estudio morfológico del tejido tumoral está contribuyendo a dicha mejora. La categoría histológica o el porcentaje de estroma tumoral, así como el grado de diferenciación de las células neuroblásticas, determinadas por el patólogo con el microscopio óptico, son factores con un papel importante en el diagnóstico y el pronóstico de los pacientes. Actualmente, dada la relevancia de la matriz extracelular tumoral en la biotensegridad y la mecanotransducción, su arquitectura y la topología de sus elementos, así como su interacción están siendo cada vez más considerados. Su cuantificación y caracterización con técnicas de imagen microscópicas empiezan a ser utilizadas. Nuestra hipótesis es que el destino de una célula tumoral neuroblástica es complejo y entre otros factores, está determinado por las características de un grupo de elementos estructurales no celulares de la matriz extracelular. Además pensamos que aplicando los patrones derivados del análisis morfométrico de estos elementos y asociandolos al impacto de los factores pronósticos conocidos, se mejorará la supervivencia de los pacientes. Nuestro objetivo es el desarrollo de técnicas morfométricas para caracterizar distintos elementos del andamiaje de la matriz extracelular y de la vascularización con el fin de encontrar usos potenciales como nuevos marcadores con valor pronóstico para mejorar la estratificación de los pacientes, o como dianas terapéuticas para ser capaces de remodelar los elementos aberrantes del andamiaje tisular, incluyendo la microvascularización. Hemos construido 19 micromatrices de tejido incluyendo más de 500 neuroblastomas, que fueron teñidos con alzul alcián a pH 2,5, Gomori, tricrómico de Masson, orceína y anti-CD31 para glicosaminoglicanos, fibras de reticulina, fibras de colágeno tipo I, fibras elásticas y vasos sanguíneos, respectivamente. Las laminillas fueron digitalizadas con un escáner de preparaciones y distintos algoritmos de análisis de imagen fueron diseñados o personalizados para detectar y caracterizar la cantidad, el tamaño y la forma de los distintos elementos estudiados de la matriz extracelular. Estos parámetros se relacionaron con los distintos subgrupos de neuroblastoma, teniendo en cuenta varias características clínicas, histopatológicas y genéticas. Los resultados obtenidos mostraron que las fibras de reticulina eran los componentes mayoritarios del andamiaje fibroso y que la abundancia y arquitectura de la microvascularización era relevante para el pronóstico de los niños con neuroblastoma. Una matriz extracelular rígida y poco porosa con vasos sanguíneos con luces irregulares se detectó principalmente en tumores pertenecientes a pacientes con pronóstico desfavorable. Un subgrupo de la cohorte de alto riesgo con muy mala supervivencia pudo ser definido por variables morfométricas de las fibras de reticulina y de los vasos sanguíneos. Concretamente, las muestras con un mayores áreas ocupadas tanto por fibras de reticulina formando grandes redes entrecruzadas, ramificadas y de organización compleja, como por vasos sanguíneos, junto con capilares y vasos tipo sinusoide de forma irregular y vénulas y arteriolas dilatas, estaban asociadas a un pronóstico muy desfavorable. En esta cohorte, las células con amplificación del gen MYCN conllevaron cambios topológicos detectables en relación a las fibras de reticulina y los vasos sanguíneos. Podemos concluir que es possible y conveniente cuantificar la sustancia fundamental, caracterizar el andamiaje fibroso y el sistema vascular de los tumors neuroblásticos gracias al análisis morfométrico de imágenes microscópicas. Algunas de las características morfométricas relaciondas con los distintos elementos de la matriz extracelular estudiados podrían ser usadas como ayuda diagnóstica del grupo de pacientes con riesgo ultra alto, tras estudiar una mayor cohorte. Los resultados obtenidos sugieren la necesidad de realizar trabajos multidisciplinarios para integrar de estos estudios a nivel internacional y que la información morfométrica de los elementos de la matriz extracelular, incluyendo el sistema vascular, pueda ser utilizada para una terapia basada en la mecanotransducción.Neuroblastic tumor patients present an heterogeneous clinical evolution, from spontaneous regression to a high propensity for widespread metastatic dissemination. Although the application of a well-defined pre-treatment risk classification plays a central role in the improvement of survival during the last years, more efforts must be done to improve patient’s survival in general and specifically in the subgroup of high risk patients. The morphological study of the tumoral tissue is contributing to such improvement. The histological category or the percentage of tumoral stroma, as well as the degree of differentiation of neuroblastic cells, evaluated by the pathologist with light microscopy, are factors that play a role in the diagnosis and prognosis of the patients. Given the role of tumoral extracellular matrix in biotensegrity and mechanotransduction, its architecture and the topology of its elements, as well as their interaction are being increasingly considered. Its quantification and characterization with microscopic image techniques start to be used. We hypothesize that the destiny of a neuroblastic tumor cell is complex and, is in part directed by characteristics of a set of non-cellular extracellular matrix structural elements. Additionally, we think that the application of the patterns derived from the morphometric analysis of such elements and their association with the impact of the known prognostic factors, patient’s survival will be improved. We aim to develop morphometric techniques to characterize different extracellular matrix scaffolding and vascular elements to find out potential uses as new prognostic markers for a better pre-treatment stratification of the patients or as therapeutic targets to be able to remodel the aberrant elements of the tissue scaffolding, including microvascularization. We constructed 19 tissue microarrays including more than 500 neuroblastomas which were stained with alcian blue pH 2.5, Gomori, Masson’s trichrome, orcein and anti-CD31 for glycosaminoglycans, reticulin fibers, collagen type I fibers, elastic fibers and blood vessels, respectively. The slides were digitized with a whole-slide scanner and different image-analysis algorithms were designed or customized to specifically detect and characterize the amount, the size and the shape of the different extracellular matrix elements studied. These parameters were related to different neuroblastoma subgroups, taking into account several clinical, histopathological and genetic features. The results obtained showed that reticulin fibers were the main components of the fibrous scaffolding and that microvasculature amount and architecture were relevant in the prognosis of neuroblastoma patients. A stiff and poorly porous extracellular matrix with irregularly-shaped vascular lumens was mainly detected in tumors belonging to patients with unfavorable prognosis. A subgroup of the high risk cohort with very poor survival could be defined by morphometric variables of reticulin fibers and blood vessels. Specificallly, those samples with high stained areas occupied by reticulin fibers forming large, crosslinking, branching and disorganized networks and by blood vessels, as well as with irregularly-shaped capillaries and sinusoid-like vessels and dilated venules, presented a very unfavorable survival. In this cohort, cells with MYCN gene amplification led to detectable topological changes regarding reticulin fibers and bood vessels. We can conclude that it is possible and convenient to quantify the fundamental substance and characterize the architecture of the fibrous scaffolding and the vascular system of neuroblastic tumors by means of the morphometric analysis of microscopic images. Some of the morphometric features related to the different extracellular matrix elements studied could be used as a diagnostic support for the ultra-high risk group of patients, after studying a larger cohort. The obtained results suggest the need of developing multidisciplinary efforts for an international integration of these studies, and that the morphometric information of the elements of the extracellular matrix, including the vascular system, could be used for a therapy based on mechanotransduction

Molecular Science for Drug Development and Biomedicine

With the avalanche of biological sequences generated in the postgenomic age, molecular science is facing an unprecedented challenge, i.e., how to timely utilize the huge amount of data to benefit human beings. Stimulated by such a challenge, a rapid development has taken place in molecular science, particularly in the areas associated with drug development and biomedicine, both experimental and theoretical. The current thematic issue was launched with the focus on the topic of “Molecular Science for Drug Development and Biomedicine”, in hopes to further stimulate more useful techniques and findings from various approaches of molecular science for drug development and biomedicine

2016 IMSAloquium, Student Investigation Showcase

Welcome to the twenty-eighth year of the Student Inquiry and Research Program (SIR)! This is a program that is as old as IMSA. The SIR program represents our unending dedication to enabling our students to learn what it is to be an innovator and to make contributions to what is known on Earth.https://digitalcommons.imsa.edu/archives_sir/1026/thumbnail.jp