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1.
Laryngorhinootologie ; 101(8): 660-665, 2022 08.
Artículo en Alemán | MEDLINE | ID: mdl-35373313

RESUMEN

BACKGROUND: Operations on the temporal bone are a special challenge for ENT surgeons. The aim of the BMBF-funded project was to develop a realistic training system for ear operations in the form of a "serious game". METHODS: The presented prototype of the HaptiVisT system functions as a training system for ear surgeries with visual feedback through a glasses-free 3D monitor and feedback by means of a haptic arm simulating the drill. A variety of training options is guaranteed by three available surgical procedures (antrotomy, mastoidectomy, posterior tympanotomy). A weighted point system enables the measurability of the training success. Following the technical development of the prototype, a prospective evaluation was carried out by eight ENT physicians and four students regarding "learning content" and "user experience". A standardized questionnaire was used (ordinal scale: 1=very good to 5=very bad). RESULTS: Regarding the learning content, the aspects "strengthening anatomy (mean=1.58)", "training hand-eye coordination (1.67)", "transferability into practice (1.83)", "usefulness for practice (1.33)" yielded good to very good scores. "User experience" also showed good results for the aspects "realism (2.29)", "interaction of haptics and optics (2.33)" and "immersion in the training system (1.89)". The "motivation factor" was very high for all test subjects (1.2). CONCLUSIONS: The training system for ear surgeries "HaptiVisT" offers the possibility of immersive training. Integration into the daily clinical routine and in particular into the medical training to become an ENT specialist therefore seems to make sense.


Asunto(s)
Procedimientos Quirúrgicos Otológicos , Interfaz Usuario-Computador , Competencia Clínica , Simulación por Computador , Tecnología Háptica , Humanos
2.
Lab Invest ; 99(10): 1527-1534, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31186527

RESUMEN

The co-expression of miRNAs and their target proteins was studied on tissue microarrays from different prostate cancer (PCa) patients. PCa of primary Gleason pattern 4 (GP4), lymph node metastases of GP4, distant metastases, and normal tissue from the transitional and peripheral zones were co-stained by fluorescent miRNA in situ hybridization (miRisH) and protein immunohistofluorescence (IHF). The miRNAs and corresponding target proteins include the pairs miR-145/ERG, miR-143/uPAR, and miR-375/SEC23A. The fluorescence-stained and scanned tissue microarrays (TMAs) were evaluated by experienced uropathologists. The pair miR-145/ERG showed an exclusive staining for miR-145 in the nuclei of stromal cells, both in tumor and normal tissue, and for ERG in the cytoplasm with/without co-expression in the nucleus of tumor cells. The pair miR-143/uPAR revealed a clear distinction between miR-143 in the nuclei of stromal cells and uPAR staining in the cytoplasm of tumor cells. Metastases (lymph node and distant) however, showed tumor cells with cytoplasmic staining for miR-143/uPAR. In normal tissues, beside the nuclei of the stroma cells, gland cells could also express miR-143 and uPAR in the cytoplasm. miR-375 showed particular staining in the nucleoli of GP4 and metastatic samples, suggesting that nucleoli play a special role in sequestering proteins and miRNAs. Combined miRisH/IHF allows for the study of miRNA expression patterns and their target proteins at the single-cell level.


Asunto(s)
Técnica del Anticuerpo Fluorescente/métodos , Hibridación Fluorescente in Situ/métodos , MicroARNs/análisis , Neoplasias de la Próstata/química , Análisis de Matrices Tisulares , Humanos , Masculino , MicroARNs/metabolismo , Neoplasias de la Próstata/metabolismo
3.
Gastrointest Endosc ; 89(3): 576-582.e1, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30342029

RESUMEN

BACKGROUND AND AIMS: Adenoma detection is a highly personalized task that differs markedly among endoscopists. Technical advances are therefore desirable for the improvement of the adenoma detection rate (ADR). An automated computer-driven technology would offer the chance to objectively assess the presence of colorectal polyps during colonoscopy. We present here the application of a real-time automated polyp detection software (APDS) under routine colonoscopy conditions. METHODS: This was a prospective study at a university hospital in Germany. A prototype of a novel APDS ("KoloPol," Fraunhofer IIS, Erlangen, Germany) was used for automated image-based polyp detection. The software functions by highlighting structures of possible polyp lesions in a color-coded manner during real-time colonoscopy procedures. Testing the feasibility of APDS deployment under real-time conditions was the primary goal of the study. APDS polyp detection rates (PDRs) were defined as secondary endpoints provided that endoscopists' detection served as criterion standard. RESULTS: The APDS was applied in 55 routine colonoscopies without the occurrence of any clinically relevant adverse events. Endoscopists' PDRs and ADRs were 56.4% and 30.9%, respectively. The PDRs and ADRs of the APDS were 50.9% and 29.1%, respectively. The APDS detected 55 of 73 polyps (75.3%). Smaller polyp size and flat polyp morphology were correlated with insufficient polyp detection by the APDS. CONCLUSION: Computer-assisted automated low-delay polyp detection is feasible during real-time colonoscopy. Efforts should be undertaken to improve the APDS with respect to smaller and flat shaped polyps. (Clinical trial registration number: NCT02838888.).


Asunto(s)
Pólipos Adenomatosos/diagnóstico , Carcinoma/diagnóstico , Pólipos del Colon/diagnóstico , Neoplasias Colorrectales/diagnóstico , Procesamiento de Imagen Asistido por Computador , Programas Informáticos , Adenoma/diagnóstico , Adenoma/patología , Pólipos Adenomatosos/patología , Anciano , Automatización , Carcinoma/patología , Estudios de Cohortes , Pólipos del Colon/patología , Colonoscopía , Neoplasias Colorrectales/patología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Carga Tumoral
4.
Biochem J ; 475(18): 2955-2967, 2018 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-30120107

RESUMEN

Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts important functions in inflammation, infectious diseases, and cancer. The large GTPase human guanylate-binding protein 1 (GBP-1) is among the most strongly IFN-γ-induced cellular proteins. Previously, it has been shown that GBP-1 mediates manifold cellular responses to IFN-γ including the inhibition of proliferation, spreading, migration, and invasion and through this exerts anti-tumorigenic activity. However, the mechanisms of GBP-1 anti-tumorigenic activities remain poorly understood. Here, we elucidated the molecular mechanism of the human GBP-1-mediated suppression of proliferation by demonstrating for the first time a cross-talk between the anti-tumorigenic IFN-γ and Hippo pathways. The α9-helix of GBP-1 was found to be sufficient to inhibit proliferation. Protein-binding and molecular modeling studies revealed that the α9-helix binds to the DNA-binding domain of the Hippo signaling transcription factor TEA domain protein (TEAD) mediated by the 376VDHLFQK382 sequence at the N-terminus of the GBP-1-α9-helix. Mutation of this sequence resulted in abrogation of both TEAD interaction and suppression of proliferation. Further on, the interaction caused inhibition of TEAD transcriptional activity associated with the down-regulation of TEAD-target genes. In agreement with these results, IFN-γ treatment of the cells also impaired TEAD activity, and this effect was abrogated by siRNA-mediated inhibition of GBP-1 expression. Altogether, this demonstrated that the α9-helix is the proliferation inhibitory domain of GBP-1, which acts independent of the GTPase activity through the inhibition of the Hippo transcription factor TEAD in mediating the anti-proliferative cell response to IFN-γ.


Asunto(s)
Proliferación Celular , Proteínas de Unión al GTP/metabolismo , Interferón gamma/metabolismo , Mutación Missense , Factores de Transcripción/metabolismo , Proteínas de Unión al GTP/genética , Células HeLa , Humanos , Interferón gamma/genética , Dominios Proteicos , Estructura Secundaria de Proteína , Factores de Transcripción/genética
5.
PLoS Pathog ; 12(10): e1005916, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27776189

RESUMEN

The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4+ T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells. Here, we report that Fascin contributes to HTLV-1 transmission. Using single-cycle replication-dependent HTLV-1 reporter vectors, we found that repression of endogenous Fascin by short hairpin RNAs and by Fascin-specific nanobodies impaired gag p19 release and cell-to-cell transmission in 293T cells. In Jurkat T-cells, Tax-induced Fascin expression enhanced virus release and Fascin-dependently augmented cell-to-cell transmission to Raji/CD4+ B-cells. Repression of Fascin in HTLV-1-infected T-cells diminished virus release and gag p19 transfer to co-cultured T-cells. Spotting the mechanism, flow cytometry and automatic image analysis showed that Tax-induced T-cell conjugate formation occurred Fascin-independently. However, adhesion of HTLV-1-infected MT-2 cells in co-culture with Jurkat T-cells was reduced upon knockdown of Fascin, suggesting that Fascin contributes to dissemination of infected T-cells. Imaging of chronically infected MS-9 T-cells in co-culture with Jurkat T-cells revealed that Fascin's localization at tight cell-cell contacts is accompanied by gag polarization suggesting that Fascin directly affects the distribution of gag to budding sites, and therefore, indirectly viral transmission. In detail, we found gag clusters that are interspersed with Fascin clusters, suggesting that Fascin makes room for gag in viral biofilms. Moreover, we observed short, Fascin-containing membrane extensions surrounding gag clusters and clutching uninfected T-cells. Finally, we detected Fascin and gag in long-distance cellular protrusions. Taken together, we show for the first time that HTLV-1 usurps the host cell factor Fascin to foster virus release and cell-to-cell transmission.


Asunto(s)
Proteínas Portadoras/metabolismo , Productos del Gen tax/metabolismo , Infecciones por HTLV-I/transmisión , Proteínas de Microfilamentos/metabolismo , Liberación del Virus/fisiología , Técnicas de Cocultivo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Técnicas de Silenciamiento del Gen , Células HEK293 , Virus Linfotrópico T Tipo 1 Humano , Humanos , Immunoblotting , Células Jurkat , Microscopía Confocal , Reacción en Cadena de la Polimerasa , Transfección
6.
BMC Bioinformatics ; 18(1): 176, 2017 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-28315633

RESUMEN

BACKGROUND: Manual assessment and evaluation of fluorescent micrograph cell experiments is time-consuming and tedious. Automated segmentation pipelines can ensure efficient and reproducible evaluation and analysis with constant high quality for all images of an experiment. Such cell segmentation approaches are usually validated and rated in comparison to manually annotated micrographs. Nevertheless, manual annotations are prone to errors and display inter- and intra-observer variability which influence the validation results of automated cell segmentation pipelines. RESULTS: We present a new approach to simulate fluorescent cell micrographs that provides an objective ground truth for the validation of cell segmentation methods. The cell simulation was evaluated twofold: (1) An expert observer study shows that the proposed approach generates realistic fluorescent cell micrograph simulations. (2) An automated segmentation pipeline on the simulated fluorescent cell micrographs reproduces segmentation performances of that pipeline on real fluorescent cell micrographs. CONCLUSION: The proposed simulation approach produces realistic fluorescent cell micrographs with corresponding ground truth. The simulated data is suited to evaluate image segmentation pipelines more efficiently and reproducibly than it is possible on manually annotated real micrographs.


Asunto(s)
Algoritmos , Microscopía Fluorescente , Animales , Linfocitos B/citología , Linfocitos B/metabolismo , Forma de la Célula , Procesamiento de Imagen Asistido por Computador , Macrófagos/citología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Protoplastos/citología , Protoplastos/metabolismo
7.
J Surg Oncol ; 115(3): 238-242, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27966220

RESUMEN

OBJECTIVE: Three-dimensional (3D) printing has become widely available, and a few cases of its use in clinical practice have been described. The aim of this study was to explore facilities for the semi-automated delineation of breast cancer tumors and to assess the feasibility of 3D printing of breast cancer tumors. METHODS: In a case series of five patients, different 3D imaging methods-magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and 3D ultrasound-were used to capture 3D data for breast cancer tumors. The volumes of the breast tumors were calculated to assess the comparability of the breast tumor models, and the MRI information was used to render models on a commercially available 3D printer to materialize the tumors. RESULTS: The tumor volumes calculated from the different 3D methods appeared to be comparable. Tumor models with volumes between 325 mm3 and 7,770 mm3 were printed and compared with the models rendered from MRI. The materialization of the tumors reflected the computer models of them. CONCLUSION: 3D printing (rapid prototyping) appears to be feasible. Scenarios for the clinical use of the technology might include presenting the model to the surgeon to provide a better understanding of the tumor's spatial characteristics in the breast, in order to improve decision-making in relation to neoadjuvant chemotherapy or surgical approaches. J. Surg. Oncol. 2017;115:238-242. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Modelos Anatómicos , Impresión Tridimensional , Anciano , Automatización , Neoplasias de la Mama/patología , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Mamografía/métodos , Persona de Mediana Edad , Intensificación de Imagen Radiográfica/métodos , Ultrasonografía/métodos
8.
Sci Data ; 11(1): 680, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38914545

RESUMEN

The Me 163 was a Second World War fighter airplane and is currently displayed in the Deutsches Museum in Munich, Germany. A complete computed tomography (CT) scan was obtained using a large scale industrial CT scanner to gain insights into its history, design, and state of preservation. The CT data enables visual examination of the airplane's structural details across multiple scales, from the entire fuselage to individual sprockets and rivets. However, further processing requires instance segmentation of the CT data-set. Currently, there are no adequate computer-assisted tools for automated or semi-automated segmentation of such large scale CT airplane data. As a first step, an interactive data annotation process has been established. So far, seven 512 × 512 × 512 voxel sub-volumes of the Me 163 airplane have been annotated, which can potentially be used for various applications in digital heritage, non-destructive testing, or machine learning. This work describes the data acquisition process, outlines the interactive segmentation and post-processing, and discusses the challenges associated with interpreting and handling the annotated data.

9.
Cytometry A ; 83(4): 409-18, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23307590

RESUMEN

To evaluate macrophage spreading in immunofluorescence images of macrophages for surface protein CD11b and nuclear counterstaining with DAPI, it is necessary to measure the size of the macrophages at different time points after stimulation. Manual evaluation of fluorescent micrographs is usually a time-consuming and error-prone task, with poor reproducibility. Automatic image analysis methods can be used to improve the results. The quality of the analysis with these methods mainly depends on the quality of the image segmentation. A segmentation and quantification scheme based on shading correction, k-means clustering, and fast marching level sets has been developed for the purpose. An initial application of this approach showed that separating touching and overlapping cells in particular suffers severely in the inevitably blurred conditions, leading to partly erroneous measurements of macrophage spreading. An alternative method of segmentation in fluorescent micrographs was therefore investigated and evaluated in this study. The proposed approach uses a methodology that separates foreground objects from background objects on the basis of Boykov's graph cuts. In this process, a rough estimation of background pixels is used for background seeds. To identify foreground seeds, a difference of Gaussian band pass filter based workflow is developed. Information on foreground and background seeds is then used for a gradient magnitude based graph cut resulting in a robust figure-ground separation method. In addition, a fast marching level set approach is used in the post-processing step, which makes it possible to split touching cells by incorporating information about the cell nuclei. An evaluation based on a total of 553 manually labeled macrophages depicted in 21 micrographs showed that the proposed method significantly improves segmentation and splitting performance for fluorescent micrographs of LPS-stimulated macrophages and reduces the rate of error in automated analysis of macrophage spreading in comparison with alternative methods.


Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Aumento de la Imagen/métodos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Algoritmos , Animales , Biomarcadores/análisis , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/ultraestructura , Antígeno CD11b/análisis , Núcleo Celular/ultraestructura , Tamaño de la Célula , Humanos , Indoles/análisis , Activación de Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/ultraestructura , Ratones , Microscopía Fluorescente , Reconocimiento de Normas Patrones Automatizadas , Reproducibilidad de los Resultados , Relación Señal-Ruido , Análisis de la Célula Individual/métodos
10.
Front Plant Sci ; 14: 1269005, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38239230

RESUMEN

Introduction: In the past years, it has been observed that the breeding of plants has become more challenging, as the visible difference in phenotypic data is much smaller than decades ago. With the ongoing climate change, it is necessary to breed crops that can cope with shifting climatic conditions. To select good breeding candidates for the future, phenotypic experiments can be conducted under climate-controlled conditions. Above-ground traits can be assessed with different optical sensors, but for the root growth, access to non-destructively measured traits is much more challenging. Even though MRI or CT imaging techniques have been established in the past years, they rely on an adequate infrastructure for the automatic handling of the pots as well as the controlled climate. Methods: To address both challenges simultaneously, the non-destructive imaging of plant roots combined with a highly automated and standardized mid-throughput approach, we developed a workflow and an integrated scanning facility to study root growth. Our "chamber #8" contains a climate chamber, a material flow control, an irrigation system, an X-ray system, a database for automatic data collection, and post-processing. The goals of this approach are to reduce the human interaction with the various components of the facility to a minimum on one hand, and to automate and standardize the complete process from plant care via measurements to root trait calculation on the other. The user receives standardized phenotypic traits and properties that were collected objectively. Results: The proposed holistic approach allows us to study root growth of plants in a field-like substrate non-destructively over a defined period and to calculate phenotypic traits of root architecture. For different crops, genotypic differences can be observed in response to climatic conditions which have already been applied to a wide variety of root structures, such as potatoes, cassava, or corn. Discussion: It enables breeders and scientists non-destructive access to root traits. Additionally, due to the non-destructive nature of X-ray computed tomography, the analysis of time series for root growing experiments is possible and enables the observation of kinetic traits. Furthermore, using this automation scheme for simultaneously controlled plant breeding and non-destructive testing reduces the involvement of human resources.

11.
Head Face Med ; 19(1): 46, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37891625

RESUMEN

Current 3D scanning and printing technologies offer not only state-of-the-art developments in the field of medical imaging and bio-engineering, but also cost and time effective solutions for surgical reconstruction procedures. Besides tissue engineering, where living cells are used, bio-compatible polymers or synthetic resin can be applied. The combination of 3D handheld scanning devices or volumetric imaging, (open-source) image processing packages, and 3D printers form a complete workflow chain that is capable of effective rapid prototyping of outer ear replicas. This paper reviews current possibilities and latest use cases for 3D-scanning, data processing and printing of outer ear replicas with a focus on low-cost solutions for rehabilitation engineering.


Asunto(s)
Procedimientos de Cirugía Plástica , Impresión Tridimensional , Humanos , Análisis Costo-Beneficio , Oído Externo , Ingeniería de Tejidos
12.
Front Plant Sci ; 14: 1120189, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37082341

RESUMEN

Background: The non-invasive 3D-imaging and successive 3D-segmentation of plant root systems has gained interest within fundamental plant research and selectively breeding resilient crops. Currently the state of the art consists of computed tomography (CT) scans and reconstruction followed by an adequate 3D-segmentation process. Challenge: Generating an exact 3D-segmentation of the roots becomes challenging due to inhomogeneous soil composition, as well as high scale variance in the root structures themselves. Approach: (1) We address the challenge by combining deep convolutional neural networks (DCNNs) with a weakly supervised learning paradigm. Furthermore, (2) we apply a spatial pyramid pooling (SPP) layer to cope with the scale variance of roots. (3) We generate a fine-tuned training data set with a specialized sub-labeling technique. (4) Finally, to yield fast and high-quality segmentations, we propose a specialized iterative inference algorithm, which locally adapts the field of view (FoV) for the network. Experiments: We compare our segmentation results against an analytical reference algorithm for root segmentation (RootForce) on a set of roots from Cassava plants and show qualitatively that an increased amount of root voxels and root branches can be segmented. Results: Our findings show that with the proposed DCNN approach combined with the dynamic inference, much more, and especially fine, root structures can be detected than with a classical analytical reference method. Conclusion: We show that the application of the proposed DCNN approach leads to better and more robust root segmentation, especially for very small and thin roots.

13.
Med Image Anal ; 84: 102699, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36463832

RESUMEN

The density of mitotic figures (MF) within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of MF by pathologists is subject to a strong inter-rater bias, limiting its prognostic value. State-of-the-art deep learning methods can support experts but have been observed to strongly deteriorate when applied in a different clinical environment. The variability caused by using different whole slide scanners has been identified as one decisive component in the underlying domain shift. The goal of the MICCAI MIDOG 2021 challenge was the creation of scanner-agnostic MF detection algorithms. The challenge used a training set of 200 cases, split across four scanning systems. As test set, an additional 100 cases split across four scanning systems, including two previously unseen scanners, were provided. In this paper, we evaluate and compare the approaches that were submitted to the challenge and identify methodological factors contributing to better performance. The winning algorithm yielded an F1 score of 0.748 (CI95: 0.704-0.781), exceeding the performance of six experts on the same task.


Asunto(s)
Algoritmos , Mitosis , Humanos , Clasificación del Tumor , Pronóstico
14.
Breast Cancer Res ; 14(2): R59, 2012 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-22490545

RESUMEN

INTRODUCTION: Although mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design. METHODS: A case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model. RESULTS: Of the 470 image-analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model. CONCLUSIONS: Using texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Mamografía/métodos , Anciano , Área Bajo la Curva , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo
15.
Int J Cancer ; 131(11): 2643-9, 2012 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-22392346

RESUMEN

For many breast cancer (BC) risk factors, there is growing evidence concerning molecular subtypes for which the risk factor is specific. With regard to mammographic density (MD), there are inconsistent data concerning its association with estrogen receptor (ER) and progesterone receptor (PR) expression. The aim of our study was to analyze the association between ER and PR expression and MD. In our case-only study, data on BC risk factors, hormone receptor expression and MD were available for 2,410 patients with incident BC. MD was assessed as percent MD (PMD) using a semiautomated method by two readers for every patient. The association of ER/PR and PMD was studied with multifactorial analyses of covariance with PMD as the target variable and including well-known factors that are also associated with MD, such as age, parity, use of hormone replacement therapy, and body mass index (BMI). In addition to the commonly known associations between PMD and age, parity, BMI and hormone replacement therapy, a significant inverse association was found between PMD and ER expression levels. Patients with ER-negative tumors had an average PMD of 38%, whereas patients with high ER expression had a PMD of 35%. A statistical trend toward a positive association between PMD and PR expression was also seen. PMD appears to be inversely associated with ER expression and may correlate positively with PR expression. These effects were independent of other risk factors such as age, BMI, parity, and hormone replacement therapy, possibly suggesting other pathways that mediate this effect.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Receptores de Estrógenos/biosíntesis , Receptores de Progesterona/biosíntesis , Anciano , Índice de Masa Corporal , Densidad de la Mama , Neoplasias de la Mama/genética , Femenino , Terapia de Reemplazo de Hormonas/métodos , Humanos , Glándulas Mamarias Humanas/anomalías , Glándulas Mamarias Humanas/metabolismo , Glándulas Mamarias Humanas/patología , Persona de Mediana Edad , Paridad , Factores de Riesgo
16.
J Gen Virol ; 93(Pt 8): 1756-1768, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22552943

RESUMEN

The multifunctional protein kinase pUL97 of human cytomegalovirus (HCMV) strongly determines the efficiency of virus replication. Previously, the existence of two pUL97 isoforms that arise from alternative translational initiation and show a predominant nuclear localization was described. Two bipartite nuclear localization sequences, NLS1 and NLS2, were identified in the N terminus of the large isoform, whilst the small isoform exclusively contained NLS2. The current study found the following: (i) pUL97 nuclear localization in HCMV-infected primary fibroblasts showed accumulations in virus replication centres and other nuclear sections; (ii) in a quantitative evaluation system for NLS activity, the large isoform showed higher efficiency of nuclear translocation than the small isoform; (iii) NLS1 was mapped to aa 6-35 and NLS2 to aa 190-213; (iv) using surface plasmon resonance spectroscopy, the binding of both NLS1 and NLS2 to human importin-α was demonstrated, stressing the importance of individual arginine residues in the bipartite consensus motifs; (v) nuclear magnetic resonance spectroscopy of pUL97 peptides confirmed an earlier statement about the functional requirement of NLS1 embedding into an intact α-helical structure; and (vi) a bioinformatics investigation of the solvent-accessible surface suggested a high accessibility of NLS1 and an isoform-specific, variable accessibility of NLS2 for interaction with importin-α. Thus, the nucleocytoplasmic transport mechanism of the isoforms appeared to be differentially regulated, and this may have consequences for isoform-dependent functions of pUL97 during virus replication.


Asunto(s)
Citomegalovirus/metabolismo , Regulación Viral de la Expresión Génica/fisiología , Señales de Localización Nuclear , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , alfa Carioferinas/metabolismo , Secuencia de Aminoácidos , Células Cultivadas , Simulación por Computador , Citomegalovirus/genética , Fibroblastos/metabolismo , Humanos , Modelos Moleculares , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Unión Proteica , Conformación Proteica , Isoformas de Proteínas , alfa Carioferinas/genética
17.
Breast Cancer Res Treat ; 135(3): 885-92, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22936391

RESUMEN

There is growing evidence that certain breast cancer (BC) risk factors specifically increase the risk for specific molecular tumor subtypes. Different molecular subtypes of BC can partly be described by analyzing proliferation in tumors. Very few data are available regarding the association of mammographic density (MD), as a BC risk factor, with proliferation. The aim of this study was to analyze the association between Ki-67 expression in BCs and MD. In this case-only study, data on BC risk factors, hormone receptor expression, and MD were available for 1,975 patients with incident BC. MD was assessed as percentage mammographic density (PMD) using a semiautomated method by two readers for every patient. The association of the Ki-67 proliferation index and PMD was studied using multifactorial analyses of covariance (ANCOVA), with PMD as the target variable and including well-known factors that are also associated with MD such as age, parity, use of hormone replacement therapy (HRT), and body mass index (BMI). There were no significant differences in PMD between women with BC who had low and high Ki-67 values (P = 0.31). However, there were relevant differences in women with low BMI (P = 0.07), and in women using postmenopausal HRT (P = 0.06) as well as in women with low PR values (P = 0.07). In these subgroups, the Ki-67 expression index increased with decreasing PMD. Likewise PMD is correlated with BMI, parity status, and menopausal status stronger in patients with low proliferating tumors, and with progesterone receptor expression in patients with high proliferating tumors. MD correlates inversely with Ki-67 proliferation in BC tumors only in some subgroups of BC patients, defined by commonly known BC risk factors that are usually associated with MD as well.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Antígeno Ki-67/análisis , Mamografía , Anciano , Biomarcadores de Tumor/análisis , Índice de Masa Corporal , Neoplasias de la Mama/metabolismo , Terapia de Reemplazo de Estrógeno , Femenino , Humanos , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo
18.
Arch Gynecol Obstet ; 285(6): 1663-9, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22262493

RESUMEN

PURPOSE: To compare diagnostic performance and interobserver variability in a group of 36 examiners, with four different levels of experience. METHODS: Nine junior trainees, eight level I senior trainees, 11 level II senior gynecologists, and eight level III expert sonologists classified 105 ultrasound images of adnexal masses into three subgroups of ovarian lesions (malignancies, functional cysts, and dermoid cysts). RESULTS: The level III sonologists obtained the best diagnostic results together with the lowest interobserver variability (κ = 0.70, SD = 0.04). They achieved significantly better results in comparison with the junior trainees and also the senior trainees (κ = 0.51, SD = 0.12, p < 0.001; and κ = 0.51, SD = 0.09, p < 0.001). Differences between level III sonologists and the group of level II observers did not reach statistical significance (κ = 0.65, SD = 0.09, p = 0.70). There were no significant differences between senior and junior trainees (p = 1.0) and both groups achieved a significantly poorer diagnostic performance in comparison with the level II observers (p < 0.01 and p < 0.01). For all observers, the largest differences were seen for classifying malignancies, the best results for classifying functional cysts, and the poorest for evaluating dermoid cysts. CONCLUSIONS: Diagnostic performance of pattern recognition significantly improves with an increasing level of experience, emphasizing the importance of standardized ultrasound training programs with supervision by experts.


Asunto(s)
Enfermedades del Ovario/patología , Ovario/patología , Reconocimiento Visual de Modelos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Tamaño de los Órganos , Enfermedades del Ovario/diagnóstico por imagen , Ovario/diagnóstico por imagen , Ultrasonografía , Adulto Joven
19.
Acta Cytol ; 56(5): 554-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23075899

RESUMEN

PURPOSE: Diagnosis of cervical intraepithelial neoplasia (CIN) is currently based on the histological result of an aiming biopsy. This preliminary study investigated whether diagnostics for CIN can potentially be improved using semiautomatic colposcopic image analysis. METHODS: 198 women with unremarkable or abnormal smears underwent colposcopy examinations. 375 regions of interest (ROIs) were manually marked on digital screen shots of the streaming documentation, which we provided during our colposcopic examinations (39 normal findings, 41 CIN I, and 118 CIN II-III). These ROIs were classified into two groups (211 regions with normal findings and CIN I, and 164 regions with CIN II-III). We developed a prototypical computer-assisted diagnostic (CAD) device based on image-processing methods to automatically characterize the color, texture, and granulation of the ROIs. RESULTS: Using n-fold cross-validation, the CAD system achieved a maximum diagnostic accuracy of 80% (sensitivity 85% and specificity 75%) corresponding to a correct assignment of abnormal or unremarkable findings. CONCLUSIONS: The CAD system may be able to play a supportive role in the further diagnosis of CIN, potentially paving the way for new and enhanced developments in colposcopy-based diagnosis.


Asunto(s)
Colposcopía/métodos , Diagnóstico por Computador/métodos , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , Cuello del Útero/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Frotis Vaginal
20.
Int J Comput Assist Radiol Surg ; 17(12): 2269-2280, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36087229

RESUMEN

BACKGROUND: Colorectal anastomoses are among the most commonly performed interventions in abdominal surgery, while associated patient trauma is still high. Most recent trends of endoscopic anastomosis devices integrate magnetic components to overcome the challenges of minimally invasive surgery. However, the mutual attraction between magnetic implant halves may increase the risk of inadvertently pinching healthy structures. Thus, we present a novel anastomosis device to improve system controllability and flexibility. METHODS: A magnetic implant and an applicator with electromagnetic control units were developed. The interaction of magnetic implants with the electromagnets bears particular challenges with respect to the force-related dimensioning. Here, attraction forces must be overcome by the electromagnet actuation to detach the implant, while the attraction force between the implant halves must be sufficient to ensure a stable connection. Thus, respective forces were measured and the detachment process was reproducibly investigated. Patient hazards, associated with resistance-related heating of the coils were investigated. RESULTS: Anastomosis formation was reproducibly successful for an implant, with an attraction force of 1.53 [Formula: see text], resulting in a compression pressure of [Formula: see text]. The implant was reproducibly detachable from the applicator at the anastomosis site. Coils heated up to a maximum temperature of [Formula: see text]. Furthermore, we were able to establish a neat reconnection of intestinal bowel endings using our implant. DISCUSSION: As we achieved nearly equal compression forces with our implant as other magnetic anastomosis systems did (Magnamosis™: 1.48 N), we concluded that our approach provides sufficient holding strength to counteract the forces acting immediately postoperatively, which would eventually lead to an undesired slipping of the implant halves during the healing phase. Based on heat transfer investigations, preventive design specifications were derived, revealing that the wall thickness of a polymeric isolation is determined rather by stability considerations, than by heat shielding requirements.


Asunto(s)
Fenómenos Electromagnéticos , Recto , Humanos , Estudios de Factibilidad , Anastomosis Quirúrgica/métodos , Recto/cirugía , Colon/cirugía
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