263 research outputs found
Towards early hemolysis detection: a smartphone based approach
Os especialistas em diagnĂłstico in vitro (IVDs) tĂŞm confiado maioritariamente na inspeção visual (Ăłtica) manual e, em segundo lugar, em sensores Ăłticos ou câmaras embutidas ou dispositivos mĂ©dicos incorporados que suportam o exame da qualidade da amostra na fase prĂ©-analĂtica. Com o aumento dos volumes de amostras para serem processadas e dos respetivos dados complexos gerados por esse processamento, aquelas tĂ©cnicas tornaram-se cada vez mais difĂceis de utilizar, ou os respetivos resultados nĂŁo ficam imediatamente disponĂveis. Para superar as complexidades impostas por tais tĂ©cnicas tradicionais, o aumento do uso de dispositivos mĂłveis e algoritmos de processamento de imagem no setor de saĂşde abriu caminho para a constituição de novos casos de uso baseados em análises mĂłveis de amostras, pois fornecem uma interação simples e intuitiva com objetos gráficos familiares que sĂŁo mostrados no ecrĂŁ dos smartphones. As interfaces gráficas e as tĂ©cnicas de interação suportadas por dispositivos mĂłveis podem pois proporcionar ao especialista em IVD uma sĂ©rie de vantagens e valor agregado devido Ă maior familiaridade com estes dispositivos e Ă grande acessibilidade que evidenciam atualmente, tendo o potencial de facilitar as análises de amostras. No entanto, o uso sistemático de dispositivos mĂłveis no setor da saĂşde encontra-se ainda numa fase muito incipiente, em particular na área de IVD. Nesta tese, propõe-se conceber e discutir a arquitetura, a conceção e a implementação de um protĂłtipo de uma aplicação mĂłvel para smartphone (designada por "HemoDetect") que implementa um conjunto sugerido de algoritmos, interfaces e tĂ©cnicas de interação que foram desenvolvidos com o objetivo de contribuir para a compreensĂŁo de tĂ©cnicas mais eficientes para ajudar a detetar a hemĂłlise, um processo que designa a rotura de glĂłbulos vermelhos (eritrĂłcitos) e libertação do respetivo conteĂşdo (citoplasma) para o fluĂdo circundante (por exemplo, plasma sanguĂneo), complementando-as com estatĂsticas e medições de laboratĂłrio, mostrando a utilização de um protĂłtipo durante experiĂŞncias, permitindo assim chegar-se a um conceito viável que permita apoiar eficazmente a deteção precoce de hemĂłlise.In Vitro Diagnostics (IVDs) specialists have been firstly relying on manual visual (optical) inspection and, secondly, on optical sensors or cameras embedded or built-in medical devices which support the examination of sample quality in pre-analytical phase. With increasing sample processing volumes and their generated complex data, these techniques have become increasingly difficult or results are not readily available. In order to overcome the complexities posed by these traditional techniques, the increased usage of mobile devices and algorithms in the healthcare industry paves the way into shaping new use cases and discovery of mobile analysis of samples, as they provide a user-friendly and familiar interaction with objects displayed on their screens. The interfaces and interaction techniques rendered by mobile devices, bring, to the IVD specialist, a number of advantages and added value due to increased familiarity with the devices or their accessibility, which is made easier. However, they are at the beginning of their journey in the healthcare industry, in particular in the IVD and point-of-care areas. In this thesis, the proposal is to discover and discuss the architecture, design and implementation of a smartphone prototype app (called “HemoDetect”) with its algorithms, interfaces and interaction techniques which was developed to help detect hemolysis which represents the rupture of red blood cells (erythrocytes) and release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma), and complementing it with from-the-lab statistics and measurements showing its utilization during experiments, which ultimately may be a feasible concept that could support early hemolysis detection.Les spĂ©cialistes du diagnostic in vitro (DIV) se sont d'abord appuyĂ©s sur l'inspection visuelle (optique) manuelle et, ensuite, sur des capteurs optiques ou des camĂ©ras intĂ©grĂ©es ou intĂ©grĂ©es Ă des dispositifs mĂ©dicaux qui facilitent l'examen de la qualitĂ© des Ă©chantillons en phase prĂ©-analytique. Avec l'augmentation des volumes de traitement des Ă©chantillons et des donnĂ©es complexes gĂ©nĂ©rĂ©es, ces techniques sont devenues de plus en plus difficiles ou les rĂ©sultats ne sont pas facilement disponibles. Afin de surmonter les complexitĂ©s posĂ©es par ces techniques traditionnelles, l'utilisation croissante des appareils mobiles et des algorithmes dans le secteur de la santĂ© ouvre la voie Ă la dĂ©finition de nouveaux cas d'utilisation et Ă la dĂ©couverte d'analyses d'Ă©chantillons mobiles, car ils fournissent une interaction conviviale et familière. avec des objets affichĂ©s sur leurs Ă©crans. Les interfaces et les techniques d'interaction rendues par les appareils mobiles apportent au spĂ©cialiste des dispositifs de DIV un certain nombre d'avantages et de valeur ajoutĂ©e en raison d'une familiarisation accrue avec les appareils ou de leur accessibilitĂ©, ce qui est facilitĂ©. Cependant, ils sont au dĂ©but de leur parcours dans le secteur de la santĂ©, en particulier dans le domains des DIV et point-of-care. Dans cette thèse, la proposition est de dĂ©couvrir et de discuter de l’architecture, de la conception et de la mise en oeuvre d’une application pour smartphone (appelĂ©e «HemoDetect») avec ses algorithmes, interfaces et techniques d’interaction, qui a Ă©tĂ© dĂ©veloppĂ©e pour aider Ă dĂ©tecter l’hĂ©molyse qui reprĂ©sente une rupture des globules rouges (Ă©rythrocytes) et la libĂ©ration de leur contenu (cytoplasme) dans le liquide environnant (par exemple, le plasma sanguin), en le complĂ©tant par des statistiques de laboratoire et des mesures montrant son utilisation au cours des expĂ©riences, ce qui pourrait finalement ĂŞtre un concept rĂ©alisable qui pourrait permettre une dĂ©tection prĂ©coce de l'hĂ©molyse
Modeling and Simulation of Lipid Membranes
Cell membranes are complex structures able to contain the main elements of the cell and to protect them from the external surroundings, becoming the most fundamental interface in Biology. The main subject of this book is the study of the structure and characteristics of lipid membranes in a wide variety of environments, ranging from simple phospholipid membranes to complex systems including proteins, peptides, or oncogenes as well as the analysis of the interactions of the membrane components with small molecules and drugs. The scope of this book is to provide recent developments on membrane structure, composition and function by means of theoretical and experimental techniques, some of them combining computer simulations with available data obtained at the laboratory.This Special Issue aims to report brand new key contributions to the field and also to give an overview about the connection between experiments and computer simulations, addressing fundamental aspects and applied research in biological membranes, with particular attention paid to the applications of computer modeling and simulation to medicine
A Changing Perspective for Treatment of Chronic Kidney Disease
Chronic kidney disease (CKD) has become an enormous worldwide health problem, both in developed and less developed countries. The incidence and prevalence of CKD is high, and is associated with increased mortality and morbidity. Of note, CKD is the 12th most common primary cause of death, accounting for about 1 million deaths per year worldwide. CKD and end-stage renal disease are characterized by the progressive development of a series of complications, such as anemia, hyperkalemia, hypervolemia, mineral and bone disorders (CKD-MBD), metabolic acidosis, hyperuricemia and wasting; all of these complications have been shown to be associated with adverse outcomes, and can contribute either individually or in association to the cardiovascular morbidity and mortality observed in CKD. While at this time CKD progression is not treated with high efficacy, new biomarkers of kidney fibrosis have become available in recent years and new treatments for kidney fibrosis and cell loss could become soon available. In addition recent progress in our understanding of CKD pathophysiology together with the development of novel therapeutic agents has led to a renewed attention on the treatment of CKD–associated metabolic complications which are now are amenable to therapeutic interventions. All these important issues are addressed in this volume
Vitamin C: Current Concepts in Human Physiology
ca. 200 words; this text will present the book in all promotional forms (e.g. flyers). Please describe the book in straightforward and consumer-friendly terms. [Vitamin C is synthesized by almost all animals. However, for humans, it is a vitamin that needs constant replenishment in the diet. While its role as an anti-oxidant and for preventing scurvy have been known for a long time, novel functions and unrecognized associations continue to be identified for this enigmatic molecule. In the past decade, new details have emerged regarding differences in its uptake by oral and intravenous modes. While vitamin C deficiency remains largely unknown and poorly addressed in many segments of the population, novel pharmacological roles for high-dose, intravenous vitamin C in many disease states have now been postulated and investigated. This has shifted its role in health and disease from the long-perceived notion as merely a vitamin and an anti-oxidant to a pleiotropic molecule with a broad anti-inflammatory, epigenetic, and anti-cancer profile. This Special Issue comprises original research papers and reviews on vitamin C metabolism and function that relate to the following topics: understanding its role in the modulation of inflammation and immunity, therapeutic applications and safety of pharmacological ascorbate in disease, and the emerging role of vitamin C as a pleiotropic modulator of critical care illness and cancer.
Language modelling for clinical natural language understanding and generation
One of the long-standing objectives of Artificial Intelligence (AI) is to design and develop algorithms for social good including tackling public health challenges. In the era of digitisation, with an unprecedented amount of healthcare data being captured in digital form, the analysis of the healthcare data at scale can lead to better research of diseases, better monitoring patient conditions and more importantly improving patient outcomes. However, many AI-based analytic algorithms rely solely on structured healthcare data such as bedside measurements and test results which only account for 20% of all healthcare data, whereas the remaining 80% of healthcare data is unstructured including textual data such as clinical notes and discharge summaries which is still underexplored.
Conventional Natural Language Processing (NLP) algorithms that are designed for clinical applications rely on the shallow matching, templates and non-contextualised word embeddings which lead to limited understanding of contextual semantics. Though recent advances in NLP algorithms have demonstrated promising performance on a variety of NLP tasks in the general domain with contextualised language models, most of these generic NLP algorithms struggle at specific clinical NLP tasks which require biomedical knowledge and reasoning. Besides, there is limited research to study generative NLP algorithms to generate clinical reports and summaries automatically by considering salient clinical information.
This thesis aims to design and develop novel NLP algorithms especially clinical-driven contextualised language models to understand textual healthcare data and generate clinical narratives which can potentially support clinicians, medical scientists and patients. The first contribution of this thesis focuses on capturing phenotypic information of patients from clinical notes which is important to profile patient situation and improve patient outcomes. The thesis proposes a novel self-supervised language model, named Phenotypic Intelligence Extraction (PIE), to annotate phenotypes from clinical notes with the detection of contextual synonyms and the enhancement to reason with numerical values. The second contribution is to demonstrate the utility and benefits of using phenotypic features of patients in clinical use cases by predicting patient outcomes in Intensive Care Units (ICU) and identifying patients at risk of specific diseases with better accuracy and model interpretability. The third contribution is to propose generative models to generate clinical narratives to automate and accelerate the process of report writing and summarisation by clinicians. This thesis first proposes a novel summarisation language model named PEGASUS which surpasses or is on par with the state-of-the-art performance on 12 downstream datasets including biomedical literature from PubMed. PEGASUS is further extended to generate medical scientific documents from input tabular data.Open Acces
Anthocyanins
This book contains 20 articles published in Molecules that concern the color quality of food and wine, anthocyanin biosynthesis and regulation, anthocyanin composition and the biological properties of anthocyanin pigments
Développement de tensioactifs à base d’acides biliaires pegylés pour des applications pharmaceutiques
Les acides biliaires sont reconnus comme des tensioactifs d’origine biologique
potentiellement applicables dans le domaine pharmaceutique. Leurs structures en font
une plateforme idéale pour l’obtention de nouvelles architectures polymères. Des
composés synthétisés par polymérisation anionique de dérivés d’oxirane comme
l’oxyde d’éthylène, offre des dérivés amphiphiles pegylés démontrant des propriétés
d’agrégation intéressantes en vue d’une amélioration de la biocompatibilité et de la
capacité d’encapsulation médicamenteuse. Une large gamme d’acides biliaires
pegylés (BA(EGn)x) a été préparée avec comme objectif premier leurs applications
dans la formulation de principes actifs problématiques. Pour cela, une caractérisation
rigoureuse du comportement de ces dérivés (modulation de la longueur (2 < n < 19)
et du nombre de bras (2 < x < 4) de PEG) en solution a été réalisée. Dans le but
d’améliorer la biodisponibilité de principes actifs lipophiles (cas de l’itraconazole),
des nanoémulsions spontanées, composées de BA(EGn)x et d’acide oléique, ont été
développées. L’évaluation in vitro, de la toxicité (cellulaire), et de la capacité de
solubilisation des systèmes BA(EGn)x, ainsi que les paramètres pharmacocinétiques in
vivo (chez le rat), suggèrent une livraison contrôlée par nos systèmes auto-assemblés
lors de l’administration orale et intraveineuse.
Aussi, la synthèse de copolymères en blocs en étoile à base d’acide cholique
pegylés a été effectuée par polymérisation anionique par addition d’un second bloc au
caractère hydrophobe de poly(éther d’allyle et de glycidyle) (CA(EGn-b-AGEm)4).
Selon le ratio de blocs hydrophiles-hydrophobes CA(EGn-b-AGEm)4, des réponses
thermiques en solution (LCST) ont été observées par un point de trouble (Cp) entre 8
oC et 37 oC. Un mécanisme de formation d’agrégats en plusieurs étapes est suggéré.
La thiolation des allyles des PAGE permet une fonctionnalisation terminale Ă haute
densité, comparable aux dendrimères. Les caractérisations physico-chimiques des
CA(EGn-b-AGEm-NH2)4 et CA(EGn-b-AGEm-COOH)4 indiquent la formation de
structures auto-assemblées en solution, sensibles à la température ou au pH. Cette
fonctionnalisation élargie le domaine d’application des dérivés d’acides biliaires
pegylés en étoile vers la transfection d’ADN, la livraison de siRNA thérapeutiques ou
encore à une sélectivité de livraison médicamenteux (ex. sensibilité au pH, greffage
ligands).Bile acids are natural compounds and may have potential for pharmaceutical applications. Their structures provide an interesting platform for polymerization to obtain well-defined architectures. The anionic polymerization of oxirane derivatives, mainly PEG derivatives, endowed new aggregation properties and improvement of biocompatibility of the new amphiphilic polymers based on bile acids.
A library of pegylated bile acids (BA(EGn)x) was prepared for the formulation of lipophilic drugs. The aqueous physicochemical behaviors of these derivatives (modulation of the length (2 < n < 19) and the number (2 < x < 4) of PEG arm) were investigated.
In order to improve the bioavailability of insoluble active compounds (itraconazole, an antifungal drug), a binary system based on the association of BA(EGn)x and oleic acid, formed self-emulsifying drug delivery systems. The in vitro evaluation of cell toxicity and solubilization capacities of the BA(EGn)x systems followed by the in vivo evaluation in rats of the pharmacokinetic parameters demonstrated the advantages of our self-assembled system for controlled drug delivery for both oral and intravenous administration.
Star-shaped block copolymers of pegylated cholic acid (CA(EGn-b-AGEm)4) were prepared by the introduction of a second hydrophobic block of PAGE poly(allyl glycidyl ether). They demonstrated thermosensitivity (8 oC < LCST < 37 oC) in aqueous solution, suggesting a mechanism based on the formation of aggregates in two steps. The PAGE block with pendant groups may facilitate futher functionalization. The thiolation of allyl yields a new class of charged PEGylated star polymers (with multiple amines or carboxylic groups). CA(EGn-b-AGEm-NH2)4 and CA(EGn-b-AGEm-COOH)4 derivatives showed self-assembled structures in solution with temperature and pH responsiveness, respectively. This functionalization may lead to broader application of pegylated star derivatives in DNA transfection systems, siRNA delivery systems or as selective delivery system (pH-dependent)
Aerococcus Urinae: Establishing the Pathogenesis of an Emerging Uropathogen
Urinary tract infection (UTI) is the world\u27s most common bacterial infection. Much is known about the infectious process (pathogenesis) of a few of the bacteria that cause these infections, especially E. coli. Unfortunately, the pathogenesis of E. coli and other uropathogenic bacteria was explored almost exclusively in the belief that the bladder is supposed to be sterile. Our recent evidence, however, debunks this dogma. We used modern methods to reveal diverse bacterial communities in the bladders of adult women. These communities differ in women with and without lower urinary tract symptoms (LUTS), including UTI and urinary incontinence (UI). Many bacteria that we have detected in women with LUTS are understudied precisely because they were previously undetected or overlooked. Thus, very little is known about their pathogenesis. Aerococcus urinae is one of those understudied uropathogenic bacteria. It is associated with both UTI and UI. It is highly resistant to many antibiotics and, when undiagnosed, can cause invasive and life-threatening sepsis. Thus, I have begun a study of A. urinae\u27s pathogenesis. For well-studied uropathogens, the earliest stages of pathogenesis involve attachment to the cells that line the bladder wall (urothelium) and subsequent disruption of the host\u27s bladder immune system. I hypothesized that A. urinae also attaches to the urothelium and alters signaling to the host\u27s bladder immune system. To test my hypothesis, I first studied in vitro phenotypes of A. urinae related to attachment and colonization of the urothelium. Then, I studied the interaction between human urothelium and A. urinae strains isolated from womenwith LUTS. Results from this dissertation could be used to develop therapies that specifically target A. urinae
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