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1.
Exp Eye Res ; 222: 109172, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35803332

RESUMEN

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most commonly diagnosed human prion disease caused by the abnormal misfolding of the 'cellular' prion protein (PrPC) into the transmissible 'scrapie-type' prion form (PrPSc). Neuropathologic evaluation of brains with sCJD reveals abnormal PrPSc deposits primarily in grey matter structures, often associated with micro-vacuolar spongiform changes in neuropil, neuronal loss, and gliosis. Abnormal PrPSc deposits have also been reported in the retina of patients with sCJD, but few studies have characterized the morphology of these retinal PrPSc deposits or evaluated for any retinal neurodegenerative changes. We performed histopathologic and morphometric analyses of retinal and brain prion deposits in 14 patients with sCJD. Interestingly, we discovered that the morphology of retinal PrPSc deposits generally differs from that of brain PrPSc deposits in terms of size and shape. We found that retinal PrPSc deposits consistently localize to the outer plexiform layer of the retina. Additionally, we observed that the retinal PrPSc deposits are not associated with the spongiform change, neuronal loss, and gliosis often seen in the brain. The stereotypic morphology and location of PrPSc deposits in sCJD retinas may help guide the use of ocular imaging devices in the detection of these deposits for a clinical diagnosis.


Asunto(s)
Síndrome de Creutzfeldt-Jakob , Priones , Enfermedades de la Retina , Encéfalo/patología , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/metabolismo , Síndrome de Creutzfeldt-Jakob/patología , Gliosis/patología , Humanos , Retina/metabolismo , Enfermedades de la Retina/patología
2.
Mol Pharm ; 15(5): 1826-1841, 2018 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-29533634

RESUMEN

Solid dispersions can be a successful way to enhance the bioavailability of poorly soluble drugs. Here 60 solid dispersion formulations were produced using ten chemically diverse, neutral, poorly soluble drugs, three commonly used polymers, and two manufacturing techniques, spray-drying and melt extrusion. Each formulation underwent a six-month stability study at accelerated conditions, 40 °C and 75% relative humidity (RH). Significant differences in times to crystallization (onset of crystallization) were observed between both the different polymers and the two processing methods. Stability from zero days to over one year was observed. The extensive experimental data set obtained from this stability study was used to build multiple linear regression models to correlate physicochemical properties of the active pharmaceutical ingredients (API) with the stability data. The purpose of these models is to indicate which combination of processing method and polymer carrier is most likely to give a stable solid dispersion. Six quantitative mathematical multiple linear regression-based models were produced based on selection of the most influential independent physical and chemical parameters from a set of 33 possible factors, one model for each combination of polymer and processing method, with good predictability of stability. Three general rules are proposed from these models for the formulation development of suitably stable solid dispersions. Namely, increased stability is correlated with increased glass transition temperature ( Tg) of solid dispersions, as well as decreased number of H-bond donors and increased molecular flexibility (such as rotatable bonds and ring count) of the drug molecule.


Asunto(s)
Preparaciones Farmacéuticas/química , Polímeros/química , Disponibilidad Biológica , Química Farmacéutica/métodos , Cristalización/métodos , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Modelos Lineales , Solubilidad/efectos de los fármacos , Temperatura de Transición
3.
Hum Brain Mapp ; 38(11): 5778-5794, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28815863

RESUMEN

Most functional MRI (fMRI) studies map task-driven brain activity using a block or event-related paradigm. Sparse paradigm free mapping (SPFM) can detect the onset and spatial distribution of BOLD events in the brain without prior timing information, but relating the detected events to brain function remains a challenge. In this study, we developed a decoding method for SPFM using a coordinate-based meta-analysis method of activation likelihood estimation (ALE). We defined meta-maps of statistically significant ALE values that correspond to types of events and calculated a summation overlap between the normalized meta-maps and SPFM maps. As a proof of concept, this framework was applied to relate SPFM-detected events in the sensorimotor network (SMN) to six motor functions (left/right fingers, left/right toes, swallowing, and eye blinks). We validated the framework using simultaneous electromyography (EMG)-fMRI experiments and motor tasks with short and long duration, and random interstimulus interval. The decoding scores were considerably lower for eye movements relative to other movement types tested. The average successful rate for short and long motor events were 77 ± 13% and 74 ± 16%, respectively, excluding eye movements. We found good agreement between the decoding results and EMG for most events and subjects, with a range in sensitivity between 55% and 100%, excluding eye movements. The proposed method was then used to classify the movement types of spontaneous single-trial events in the SMN during resting state, which produced an average successful rate of 22 ± 12%. Finally, this article discusses methodological implications and improvements to increase the decoding performance. Hum Brain Mapp 38:5778-5794, 2017. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Imagen por Resonancia Magnética/métodos , Actividad Motora/fisiología , Parpadeo/fisiología , Deglución/fisiología , Electromiografía , Movimientos Oculares/fisiología , Dedos/fisiología , Lateralidad Funcional , Humanos , Funciones de Verosimilitud , Boca/fisiología , Músculo Esquelético/fisiología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Prueba de Estudio Conceptual , Descanso , Dedos del Pie/fisiología
5.
J Exp Bot ; 68(17): 4969-4981, 2017 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-29048563

RESUMEN

Root architecture impacts water and nutrient uptake efficiency. Identifying exactly which root architectural properties influence these agronomic traits can prove challenging. In this paper, approximately 300 wheat (Triticum aestivum) plants were divided into four groups using two binary classifications, high versus low nitrogen uptake efficiency (NUpE), and high versus low nitrate in the growth medium. The root system architecture for each wheat plant was captured using 16 quantitative variables. The multivariate analysis tool, linear discriminant analysis, was used to construct composite variables, each a linear combination of the original variables, such that the score of the plants on the new variables showed the maximum between-group variability. The results show that the distribution of root-system architecture traits differs between low- and high-NUpE plants and, less strongly, between low-NUpE plants grown on low versus high nitrate media.


Asunto(s)
Nitrógeno/metabolismo , Raíces de Plantas/anatomía & histología , Triticum/anatomía & histología , Análisis Discriminante , Nitratos/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Plantones/anatomía & histología , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Triticum/crecimiento & desarrollo , Triticum/metabolismo
6.
Mol Pharm ; 12(9): 3389-98, 2015 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-26236939

RESUMEN

The purpose of this study was to develop a predictive model of the amorphous stability of drugs with particular relevance for poorly water-soluble compounds. Twenty-five representative neutral poorly soluble compounds with a diverse range of physicochemical properties and chemical structures were systematically selected from an extensive library of marketed drug products. The physical stability of the amorphous form, measured over a 6 month period by the onset of crystallization of amorphous films prepared by melting and quench-cooling, was assessed using polarized light microscopy. The data were used as a response variable in a statistical model with calculated/predicted or measured molecular, thermodynamic, and kinetic parameters as explanatory variables. Several multiple linear regression models were derived, with varying balance between calculated/predicted and measured parameters. It was shown that inclusion of measured parameters significantly improves the predictive ability of the model. The best model demonstrated a prediction accuracy of 82% and included the following as parameters: melting and glass transition temperatures, enthalpy of fusion, configurational free energy, relaxation time, number of hydrogen bond donors, lipophilicity, and the ratio of carbon to heteroatoms. Good predictions were also obtained with a simpler model, which was comprised of easily acquired quantities: molecular weight and enthalpy of fusion. Statistical models are proposed to predict long-term amorphous drug stability. The models include readily accessible parameters, which are potentially the key factors influencing amorphous stability. The derived models can support faster decision making in drug formulation development.


Asunto(s)
Química Farmacéutica , Estabilidad de Medicamentos , Modelos Estadísticos , Preparaciones Farmacéuticas/química , Rastreo Diferencial de Calorimetría , Enlace de Hidrógeno , Cinética , Solubilidad , Temperatura , Termodinámica , Temperatura de Transición , Difracción de Rayos X
8.
Biom J ; 56(5): 758-60, 2014 09.
Artículo en Inglés | MEDLINE | ID: mdl-24740922

RESUMEN

This is a discussion of the paper: 'Overview of object oriented data analysis' by J. Steve Marron and Andrés M. Alonso.


Asunto(s)
Análisis de Datos
9.
Hum Brain Mapp ; 34(6): 1319-29, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22331588

RESUMEN

fMRI studies of brain activity at rest study slow (<0.1 Hz) intrinsic fluctuations in the blood-oxygenation-level-dependent (BOLD) signal that are observed in a temporal scale of several minutes. The origin of these fluctuations is not clear but has previously been associated with slow changes in rhythmic neuronal activity resulting from changes in cortical excitability or neuronal synchronization. In this work, we show that individual spontaneous BOLD events occur during rest, in addition to slow fluctuations. Individual spontaneous BOLD events were identified by deconvolving the hemodynamic impulse response function for each time point in the fMRI time series, thus requiring no information on timing or a-priori spatial information of events. The patterns of activation detected were related to the motor, visual, default-mode, and dorsal attention networks. The correspondence between spontaneous events and slow fluctuations in these networks was assessed using a sliding window, seed-correlation analysis, where seed regions were selected based on the individual spontaneous event BOLD activity maps. We showed that the correlation varied considerably over time, peaking at the time of spontaneous events in these networks. By regressing spontaneous events out of the fMRI signal, we showed that both the correlation strength and the power in spectral frequencies <0.1 Hz decreased, indicating that spontaneous activation events contribute to low-frequency fluctuations observed in resting state networks with fMRI. This work provides new insights into the origin of signals detected in fMRI studies of functional connectivity.


Asunto(s)
Mapeo Encefálico , Encéfalo/fisiología , Descanso/fisiología , Adulto , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Adulto Joven
10.
Hum Brain Mapp ; 34(3): 501-18, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22121048

RESUMEN

The ability to detect single trial responses in functional magnetic resonance imaging (fMRI) studies is essential, particularly if investigating learning or adaptation processes or unpredictable events. We recently introduced paradigm free mapping (PFM), an analysis method that detects single trial blood oxygenation level dependent (BOLD) responses without specifying prior information on the timing of the events. PFM is based on the deconvolution of the fMRI signal using a linear hemodynamic convolution model. Our previous PFM method (Caballero-Gaudes et al., 2011: Hum Brain Mapp) used the ridge regression estimator for signal deconvolution and required a baseline signal period for statistical inference. In this work, we investigate the application of sparse regression techniques in PFM. In particular, a novel PFM approach is developed using the Dantzig selector estimator, solved via an efficient homotopy procedure, along with statistical model selection criteria. Simulation results demonstrated that, using the Bayesian information criterion to select the regularization parameter, this method obtains high detection rates of the BOLD responses, comparable with a model-based analysis, but requiring no information on the timing of the events and being robust against hemodynamic response function variability. The practical operation of this sparse PFM method was assessed with single-trial fMRI data acquired at 7T, where it automatically detected all task-related events, and was an improvement on our previous PFM method, as it does not require the definition of a baseline state and amplitude thresholding and does not compromise on specificity and sensitivity.


Asunto(s)
Mapeo Encefálico , Encéfalo/irrigación sanguínea , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Oxígeno/sangre , Simulación por Computador , Bases de Datos Factuales , Humanos , Modelos Estadísticos , Sensibilidad y Especificidad
11.
Environ Sci Pollut Res Int ; 30(50): 109283-109298, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37770738

RESUMEN

Morbidities generally show patterns of concentration that vary by space and time. Disease mapping models are useful in estimating the spatiotemporal patterns of disease risks and are therefore pivotal for effective disease surveillance, resource allocation, and the development of prevention strategies. This study considers six spatiotemporal Bayesian hierarchical models based on two spatial conditional autoregressive priors. It could serve as a guideline on the development and application of Bayesian hierarchical models to assess the emerging risk trends, risk clustering, and spatial inequality trends, with estimation of covariables' effects on the interested disease risk. The method is applied to the Florida Birth Record data between 2006 and 2015 to study two cardiovascular risk factors: preeclampsia and gestational diabetes. High-risk clusters were detected in North Central Florida for preeclampsia and in Central Florida for gestational diabetes. While the adjusted disease trend was stable, spatial inequality peaked in 2011-2012 for both diseases. Exposure to PM2.5 at first or/and second trimester increased the risk of preeclampsia and gestational diabetes, but the magnitude is less severe compared to previous studies. In conclusion, this study underscores the significance of selecting appropriate disease mapping models in estimating the intricate spatiotemporal patterns of disease risk and suggests the importance of localized interventions to reduce health disparities. The result also identified an opportunity to study potential risk factors of preeclampsia, as the spike of risk in North Central Florida cannot be explained by current covariables.


Asunto(s)
Diabetes Gestacional , Preeclampsia , Embarazo , Femenino , Estados Unidos , Humanos , Diabetes Gestacional/epidemiología , Florida/epidemiología , Preeclampsia/epidemiología , Teorema de Bayes , Factores de Riesgo
12.
Ocul Oncol Pathol ; 8(2): 133-140, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35959159

RESUMEN

Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and despite treatment of the primary tumor, approximately 15%-50% of patients will develop metastatic disease. Based on gene expression profiling (GEPs), UM can be categorized as Class 1A (low metastatic risk), Class 1B (intermediate metastatic risk), or Class 2 (high metastatic risk). PReferentially expressed Antigen in MElanoma (PRAME) status is an independent prognostic UM biomarker and a potential target for immunotherapy in metastatic UM. PRAME expression status can be detected in tumors using reverse-transcription polymerase chain reaction (RT-PCR). More recently, immunohistochemistry (IHC) has been developed to detect PRAME protein expression. Here, we employed both techniques to evaluate PRAME expression in 18 UM enucleations. Methods: Tumor material from the 18 UM patients who underwent enucleation was collected by fine-needle aspiration before or during enucleation and sent for GEP and PRAME analysis by RT-PCR. Histologic sections from these patients were stained with an anti-PRAME monoclonal antibody. We collected patient demographics and tumor characteristics and included this with our analysis of GEP class, PRAME status by RT-PCR, and PRAME status by IHC. PRAME IHC and RT-PCR results were compared. Results: Twelve males (12/18) and 6 females (6/18) with an average age of 60.6 years underwent enucleation for UM. TNM staging of the UM diagnosed Stage I in 2 patients (2/18), Stage II in 7 patients (7/18), Stage III in 8 patients (8/18), and Stage IV in 1 (1/18). GEP was Class 1A in 6 tumors (6/18), Class 1B in 6 tumors (6/18), and Class 2 in 6 tumors (6/18). PRAME IHC showed diffusely positive labeling of all UM cells in 2/18 enucleations; negative IHC labeling of UM cells in 9/18 enucleations; and IHC labeling of subsets of UM cells in 7/18 enucleations. Eleven of the 17 UMs tested for PRAME by both RT-PCR and IHC had consistent PRAME results. In the remaining 6/17 cases tested by both modalities, PRAME results were discordant between RT-PCR and IHC. Conclusions: We find that PRAME IHC distinguishes PRAME-positive and PRAME-negative UM tumor cells. Interestingly, IHC reveals focal PRAME expression in subsets of tumor cells consistent with tumor heterogeneity. PRAME RT-PCR and IHC provide concordant results in most of our cases. We suggest that discordance in PRAME results could arise from spatial or temporal variation in PRAME expression between tumor cells. Further studies are required to determine the prognostic implications of PRAME IHC in UM.

13.
Hum Brain Mapp ; 32(9): 1400-18, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20963818

RESUMEN

This work presents a novel method of mapping the brain's response to single stimuli in space and time without prior knowledge of the paradigm timing: paradigm free mapping (PFM). This method is based on deconvolution of the hemodynamic response from the voxel time series assuming a linear response and using a ridge-regression algorithm. Statistical inference is performed by defining a spatio-temporal t-statistic and by controlling for multiple comparisons using the false discovery rate procedure. The methodology was validated on five subjects who performed self-paced and visually cued finger tapping at 7 Tesla, with moderate (TR = 2 s) and high (TR = 0.4 s) temporal resolution. The results demonstrate that detection of single-trial BOLD events is feasible without a priori information on the stimulus paradigm. The proposed method opens up the possibility of designing temporally unconstrained paradigms to study the cortical response to unpredictable mental events.


Asunto(s)
Mapeo Encefálico , Encéfalo/irrigación sanguínea , Encéfalo/fisiología , Imagen por Resonancia Magnética , Adulto , Algoritmos , Señales (Psicología) , Electromiografía , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Pruebas Neuropsicológicas , Análisis de Componente Principal , Desempeño Psicomotor , Estadísticas no Paramétricas , Factores de Tiempo , Adulto Joven
14.
Biostatistics ; 11(4): 609-30, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20350956

RESUMEN

Some methods for the statistical analysis of surface shapes and asymmetry are introduced. We focus on a case study where magnetic resonance images of the brain are available from groups of 30 schizophrenia patients and 38 controls, and we investigate large-scale brain surface shape differences. Key aspects of shape analysis are to remove nuisance transformations by registration and to identify which parts of one object correspond with the parts of another object. We introduce maximum likelihood and Bayesian methods for registering brain images and providing large-scale correspondences of the brain surfaces. Brain surface size-and-shape analysis is considered using random field theory, and also dimension reduction is carried out using principal and independent components analysis. Some small but significant differences are observed between the the patient and control groups. We then investigate a particular type of asymmetry called torque. Differences in asymmetry are observed between the control and patient groups, which add strength to other observations in the literature. Further investigations of the midline plane location in the 2 groups and the fitting of nonplanar curved midlines are also considered.


Asunto(s)
Bioestadística/métodos , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Esquizofrenia/patología , Adulto , Algoritmos , Teorema de Bayes , Encéfalo/anatomía & histología , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Cadenas de Markov , Modelos Estadísticos , Método de Montecarlo , Análisis de Componente Principal , Distribuciones Estadísticas , Propiedades de Superficie
15.
J Chem Theory Comput ; 17(12): 7930-7937, 2021 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-34852200

RESUMEN

We describe a general approach to transforming molecular models between different levels of resolution, based on machine learning methods. The approach uses a matched set of models at both levels of resolution for training, but requires only the coordinates of their particles and no side information (e.g., templates for substructures, defined mappings, or molecular mechanics force fields). Once trained, the approach can transform further molecular models of the system between the two levels of resolution in either direction with equal facility.

16.
Biomaterials ; 271: 120740, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33714019

RESUMEN

Human mesenchymal stem cells (hMSCs) are widely represented in regenerative medicine clinical strategies due to their compatibility with autologous implantation. Effective bone regeneration involves crosstalk between macrophages and hMSCs, with macrophages playing a key role in the recruitment and differentiation of hMSCs. However, engineered biomaterials able to simultaneously direct hMSC fate and modulate macrophage phenotype have not yet been identified. A novel combinatorial chemistry-topography screening platform, the ChemoTopoChip, is used here to identify materials suitable for bone regeneration by screening 1008 combinations in each experiment for human immortalized mesenchymal stem cell (hiMSCs) and human macrophage response. The osteoinduction achieved in hiMSCs cultured on the "hit" materials in basal media is comparable to that seen when cells are cultured in osteogenic media, illustrating that these materials offer a materials-induced alternative to osteo-inductive supplements in bone-regeneration. Some of these same chemistry-microtopography combinations also exhibit immunomodulatory stimuli, polarizing macrophages towards a pro-healing phenotype. Maximum control of cell response is achieved when both chemistry and topography are recruited to instruct the required cell phenotype, combining synergistically. The large combinatorial library allows us for the first time to probe the relative cell-instructive roles of microtopography and material chemistry which we find to provide similar ranges of cell modulation for both cues. Machine learning is used to generate structure-activity relationships that identify key chemical and topographical features enhancing the response of both cell types, providing a basis for a better understanding of cell response to micro topographically patterned polymers.


Asunto(s)
Materiales Biocompatibles , Células Madre Mesenquimatosas , Materiales Biocompatibles/farmacología , Regeneración Ósea , Diferenciación Celular , Humanos , Osteogénesis
17.
Sci Transl Med ; 13(584)2021 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-33692134

RESUMEN

Current treatments for chronic pain rely largely on opioids despite their substantial side effects and risk of addiction. Genetic studies have identified in humans key targets pivotal to nociceptive processing. In particular, a hereditary loss-of-function mutation in NaV1.7, a sodium channel protein associated with signaling in nociceptive sensory afferents, leads to insensitivity to pain without other neurodevelopmental alterations. However, the high sequence and structural similarity between NaV subtypes has frustrated efforts to develop selective inhibitors. Here, we investigated targeted epigenetic repression of NaV1.7 in primary afferents via epigenome engineering approaches based on clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9 and zinc finger proteins at the spinal level as a potential treatment for chronic pain. Toward this end, we first optimized the efficiency of NaV1.7 repression in vitro in Neuro2A cells and then, by the lumbar intrathecal route, delivered both epigenome engineering platforms via adeno-associated viruses (AAVs) to assess their effects in three mouse models of pain: carrageenan-induced inflammatory pain, paclitaxel-induced neuropathic pain, and BzATP-induced pain. Our results show effective repression of NaV1.7 in lumbar dorsal root ganglia, reduced thermal hyperalgesia in the inflammatory state, decreased tactile allodynia in the neuropathic state, and no changes in normal motor function in mice. We anticipate that this long-lasting analgesia via targeted in vivo epigenetic repression of NaV1.7 methodology we dub pain LATER, might have therapeutic potential in management of persistent pain states.


Asunto(s)
Analgesia , Dolor Crónico , Neuralgia , Animales , Ganglios Espinales , Hiperalgesia , Ratones
18.
Int J Numer Method Biomed Eng ; 36(2): e3252, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31444852

RESUMEN

In a previous contribution, a new Riemannian shape space, named TPS space, was introduced to perform statistics on shape data. This space was endowed with a Riemannian metric and a flat connection, with torsion, compatible with the given metric. This connection allows the definition of a Parallel Transport of the deformation compatible with the three-fold decomposition in spherical, deviatoric, and non-affine components. Such a parallel transport also conserves the Γ-energy, strictly related to the total elastic strain energy stored by the body in the original deformation. A new approach is here presented in order to calculate the bending energy on the body alone (body bending energy) and to restrict it exclusively within physical boundaries of objects involved in the deformation analysis. The novelty of this new procedure resides in the fact that we propose a new metric to be preserved during the TPS direct transport. This allows transporting the shape change more coherently with the mechanical meaning of the deformation. The geometry of the TPS space is then further discussed in order to better represent the relationship between the Γ-energy, the strain energy, and the so-called bending energy densities.


Asunto(s)
Diagnóstico por Imagen/métodos , Algoritmos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos
19.
Med Image Anal ; 46: 35-56, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29502032

RESUMEN

In landmarks-based Shape Analysis size is measured, in most cases, with Centroid Size. Changes in shape are decomposed in affine and non affine components. Furthermore the non affine component can be in turn decomposed in a series of local deformations (partial warps). If the extent of deformation between two shapes is small, the difference between Centroid Size and m-Volume increment is barely appreciable. In medical imaging applied to soft tissues bodies can undergo very large deformations, involving large changes in size. The cardiac example, analyzed in the present paper, shows changes in m-Volume that can reach the 60%. We show here that standard Geometric Morphometrics tools (landmarks, Thin Plate Spline, and related decomposition of the deformation) can be generalized to better describe the very large deformations of biological tissues, without losing a synthetic description. In particular, the classical decomposition of the space tangent to the shape space in affine and non affine components is enriched to include also the change in size, in order to give a complete description of the tangent space to the size-and-shape space. The proposed generalization is formulated by means of a new Riemannian metric describing the change in size as change in m-Volume rather than change in Centroid Size. This leads to a redefinition of some aspects of the Kendall's size-and-shape space without losing Kendall's original formulation. This new formulation is discussed by means of simulated examples using 2D and 3D platonic shapes as well as a real example from clinical 3D echocardiographic data. We demonstrate that our decomposition based approaches discriminate very effectively healthy subjects from patients affected by Hypertrophic Cardiomyopathy.


Asunto(s)
Cardiomiopatía Hipertrófica/diagnóstico por imagen , Ecocardiografía Tridimensional , Interpretación de Imagen Asistida por Computador/métodos , Pericardio/diagnóstico por imagen , Algoritmos , Cardiomiopatía Hipertrófica/patología , Estudios de Casos y Controles , Humanos , Aumento de la Imagen/métodos , Pericardio/patología
20.
J Clin Oncol ; 23(22): 5088-93, 2005 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-16051955

RESUMEN

PURPOSE: Currently known serum biomarkers do not predict clinical outcome in melanoma. S100-beta is widely established as a reliable prognostic indicator in patients with advanced metastatic disease but is of limited predictive value in tumor-free patients. This study was aimed to determine whether molecular profiling of the serum proteome could discriminate between early- and late-stage melanoma and predict disease progression. PATIENTS AND METHODS: Two hundred five serum samples from 101 early-stage (American Joint Committee on Cancer [AJCC] stage I) and 104 advanced stage (AJCC stage IV) melanoma patients were analyzed by matrix-assisted laser desorption/ionisation (MALDI) time-of-flight (ToF; MALDI-ToF) mass spectrometry utilizing protein chip technology and artificial neural networks (ANN). Serum samples from 55 additional patients after complete dissection of regional lymph node metastases (AJCC stage III), with 28 of 55 patients relapsing within the first year of follow-up, were analyzed in an attempt to predict disease recurrence. Serum S100-beta was measured using a sandwich immunoluminometric assay. RESULTS: Analysis of 205 stage I/IV serum samples, utilizing a training set of 94 of 205 and a test set of 15 of 205 samples for 32 different ANN models, revealed correct stage assignment in 84 (88%) of 96 of a blind set of 96 of 205 serum samples. Forty-four (80%) of 55 stage III serum samples could be correctly assigned as progressors or nonprogressors using random sample cross-validation statistical methodologies. Twenty-three (82%) of 28 stage III progressors were correctly identified by MALDI-ToF combined with ANN, whereas only six (21%) of 28 could be detected by S100-beta. CONCLUSION: Validation of these findings may enable proteomic profiling to become a valuable tool for identifying high-risk melanoma patients eligible for adjuvant therapeutic interventions.


Asunto(s)
Melanoma/patología , Recurrencia Local de Neoplasia , Análisis por Matrices de Proteínas , Neoplasias Cutáneas/patología , Progresión de la Enfermedad , Humanos , Espectrometría de Masas , Redes Neurales de la Computación , Valor Predictivo de las Pruebas , Pronóstico , Proteómica , Factores de Riesgo , Sensibilidad y Especificidad
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