Publications

19 Publications visible to you, out of a total of 19

Abstract (Expand)

A large set of IHC stained DLBCL specimens is provided together with segmentation masks for different cell populations generated by a reference method for automated image analysis, thus featuring considerable reuse potential. Provided image data comprise a) fluorescence microscopy images of 44 multiple immunohistostained DLBCL tumor subregions, captured at four channels corresponding to CD14, CD163, Pax5 and DAPI; b) cartoon-filtered versions of these images, generated by Rudin-Osher-Fatemi (ROF) denoising; c) an automatically generated mask of the evaluation subregion, based on information from the DAPI channel, and d) automatically generated segmentation masks for macrophages, B-cells and the total of cell nuclei, using information from CD14, CD163, Pax5 and DAPI channels, respectively.

Authors: Marcus Wagner, Sarah Reinke, René Hänsel, Wolfram Klapper, Ulf-Dietrich Braumann

Date Published: 12th Mar 2020

Publication Type: Journal article

Human Diseases: diffuse large B-cell lymphoma

Abstract (Expand)

Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture. In this system, manipulation of essential pathways of stem cell maintenance and differentiation results in well-described growth phenotypes. We here provide an individual cell-based model of intestinal organoids that enables a mechanistic explanation of the observed growth phenotypes. In simulation studies of the 3D structure of expanding organoids, we investigate interdependences between Wnt- and Notch-signaling which control the shape of the stem cell niche and, thus, the growth pattern of the organoids. Similar to in vitro experiments, changes of pathway activities alter the cellular composition of the organoids and, thereby, affect their shape. Exogenous Wnt enforces transitions from branched into a cyst-like growth pattern; known to occur spontaneously during long term organoid expansion. Based on our simulation results, we predict that the cyst-like pattern is associated with biomechanical changes of the cells which assign them a growth advantage. The results suggest ongoing stem cell adaptation to in vitro conditions during long term expansion by stabilizing Wnt-activity. Our study exemplifies the potential of individual cell-based modeling in unraveling links between molecular stem cell regulation and 3D growth of tissues. This kind of modeling combines experimental results in the fields of stem cell biology and cell biomechanics constituting a prerequisite for a better understanding of tissue regeneration as well as developmental processes.

Authors: T. Thalheim, M. Quaas, M. Herberg, U. D. Braumann, C. Kerner, M. Loeffler, G. Aust, J. Galle

Date Published: 15th Jan 2018

Publication Type: Not specified

Human Diseases: colonic disease

Abstract (Expand)

As revealed by optical coherence tomography (OCT), the shape of the fovea may vary greatly among individuals. However, none of the hitherto available mathematical descriptions comprehensively reproduces all individual characteristics such as foveal depth, slope, naso-temporal asymmetry, and others. Here, a novel mathematical approach is presented to obtain a very accurate model of the complete 3D foveal surface of an individual, by utilizing recent developments in OCT. For this purpose, a new formula was developed serving as a simple but very flexible way to represent a given fovea. An extensive description of the used model parameters, as well as, of the complete method of reconstructing a foveal surface from OCT data, is presented. Noteworthy, the formula analytically provides characteristic foveal parameters and thus allows for extensive quantification. The present approach was verified on 432 OCT scans and has proved to be able to capture the whole range of asymmetric foveal shapes with high accuracy (i.e. a mean fit error of 1.40 mum).

Authors: P. Scheibe, A. Lazareva, U. D. Braumann, A. Reichenbach, P. Wiedemann, M. Francke, F. G. Rauscher

Date Published: 3rd Dec 2013

Publication Type: Not specified

Human Diseases: eye disease

Abstract (Expand)

Drug addiction is a chronic, relapsing disease caused by neurochemical and molecular changes in the brain. In this human autopsy study qualitative and quantitative changes of glial fibrillary acidic protein (GFAP)-positive astrocytes in the hippocampus of 26 lethally intoxicated drug addicts and 35 matched controls are described. The morphological characterization of these cells reflected alterations representative for astrogliosis. But, neither quantification of GFAP-positive cells nor the Western blot analysis indicated statistical significant differences between drug fatalities versus controls. However, by semi-quantitative scoring a significant shift towards higher numbers of activated astrocytes in the drug group was detected. To assess morphological changes quantitatively, graph-based representations of astrocyte morphology were obtained from single cell images captured by confocal laser scanning microscopy. Their underlying structures were used to quantify changes in astroglial fibers in an automated fashion. This morphometric analysis yielded significant differences between the investigated groups for four different measures of fiber characteristics (Euclidean distance, graph distance, number of graph elements, fiber skeleton distance), indicating that, e.g., astrocytes in drug addicts on average exhibit significant elongation of fiber structures as well as two-fold increase in GFAP-positive fibers as compared with those in controls. In conclusion, the present data show characteristic differences in morphology of hippocampal astrocytes in drug addicts versus controls and further supports the involvement of astrocytes in human pathophysiology of drug addiction. The automated quantification of astrocyte morphologies provides a novel, testable way to assess the fiber structures in a quantitative manner as opposed to standard, qualitative descriptions.

Authors: M. Weber, N. Scherf, T. Kahl, U. D. Braumann, P. Scheibe, J. P. Kuska, R. Bayer, A. Buttner, H. Franke

Date Published: 15th Mar 2013

Publication Type: Not specified

Human Diseases: heroin dependence

Abstract (Expand)

PURPOSE: Prostate cancer is routinely graded according to the Gleason grading scheme. This scheme is predominantly based on the textural appearance of aberrant glandular structures. Gleason grade is difficult to standardize and often leads to discussion due to interrater and intrarater disagreement. Thus, we investigated whether digital image based automated quantitative histomorphometry could be used to achieve a more standardized, reproducible classification outcome. MATERIALS AND METHODS: In a proof of principle study we developed a method to evaluate digitized histological images of single prostate cancer regions in hematoxylin and eosin stained sections. Preprocessed color images were subjected to color deconvolution, followed by the binarization of obtained hematoxylin related image channels. Highlighted neoplastic epithelial gland related objects were morphometrically assessed by a classifier based on 2 calculated quantitative and objective geometric measures, that is inverse solidity and inverse compactness. The procedure was then applied to the prostate cancer probes of 125 patients. Each probe was independently classified for Gleason grade 3, 4 or 5 by an experienced pathologist blinded to image analysis outcome. RESULTS: Together inverse compactness and inverse solidity were adequate discriminatory features for a powerful classifier that distinguished Gleason grade 3 from grade 4/5 histology. The classifier was robust on sensitivity analysis. CONCLUSIONS: Results suggest that quantitative and interpretable measures can be obtained from image based analysis, permitting algorithmic differentiation of prostate Gleason grades. The method must be validated in a large independent series of specimens.

Authors: M. Loeffler, L. Greulich, P. Scheibe, P. Kahl, Z. Shaikhibrahim, U. D. Braumann, J. P. Kuska, N. Wernert

Date Published: 20th Mar 2012

Publication Type: Not specified

Human Diseases: prostate cancer

Abstract (Expand)

AIMS: Infrared microspectroscopy (IR-MSP) has been proposed for automated histological tissue differentiation of unstained specimens based on chemical analysis of cell and extracellular constituents. This study aimed to determine the accuracy of IR-MSP-based histopathology of cervical carcinoma sections with complex tissue architecture under practically relevant testing conditions. METHODS AND RESULTS: In total, 46 regions of interest, covering an area of almost 50 mm(2) on sections derived from paraffin-embedded tissue of radical hysterectomy specimens, were analysed by IR-MSP (nominal resolution ~4.2 mum). More than 2.8 million pixel spectra that were processed using fuzzy c-means clustering followed by hierarchical cluster analysis permitted image segmentation regarding different biochemical properties. Linear image registration was applied to compare these segmentation results with manual labelling on haematoxylin and eosin-stained references (resolution ~0.7 mum). For recognition of nine tissue types, sensitivities were 42-91% and specificities were 79-100%, mostly being affected by peritumoral inflammatory responses. Algorithmic variation of the outline of dysplasia and carcinoma revealed a spatial preference of false values in tissue transition areas. CONCLUSIONS: This imaging technique has potential as a new method for tissue characterization; however, the recognition accuracy does not justify a pathologist-independent tissue analysis, and the application is only possible in combination with concomitant conventional histopathology.

Authors: J. Einenkel, U. D. Braumann, W. Steller, H. Binder, L. C. Horn

Date Published: 1st Mar 2012

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

BACKGROUND: Analyses of the pore size distribution in 3D matrices such as the cell-hydrogel interface are very useful when studying changes and modifications produced as a result of cellular growth and proliferation within the matrix, as pore size distribution plays an important role in the signaling and microenvironment stimuli imparted to the cells. However, the majority of the methods for the assessment of the porosity in biomaterials are not suitable to give quantitative information about the textural properties of these nano-interfaces. FINDINGS: Here, we report a methodology for determining pore size distribution at the cell-hydrogel interface, and the depth of the matrix modified by cell growth by entrapped HepG(2) cells in microcapsules made of 0.8% and 1.4% w/v alginate. The method is based on the estimation of the shortest distance between two points of the fibril-like network hydrogel structures using image analysis of TEM pictures. Values of pore size distribution determined using the presented method and those obtained by nitrogen physisorption measurements were compared, showing good agreement. A combination of these methodologies and a study of the cell-hydrogel interface at various cell culture times showed that after three days of culture, HepG(2) cells growing in hydrogels composed of 0.8% w/v alginate had more coarse of pores at depths up to 40 nm inwards (a phenomenon most notable in the first 20 nm from the interface). This coarsening phenomenon was weakly observed in the case of cells cultured in hydrogels composed of 1.4% w/v alginate. CONCLUSIONS: The method purposed in this paper allows us to obtain information about the radial deformation of the hydrogel matrix due to cell growth, and the consequent modification of the pore size distribution pattern surrounding the cells, which are extremely important for a wide spectrum of biotechnological, pharmaceutical and biomedical applications.

Authors: A. Leal-Egana, U. D. Braumann, A. Diaz-Cuenca, M. Nowicki, A. Bader

Date Published: 27th May 2011

Publication Type: Not specified

Abstract (Expand)

Basal cell carcinoma (BCC) is the most common malignant skin cancer. For a deeper insight into the specific growth patterns of the tumorous tissue in BCC, we have focused on the development of a novel automated image-processing chain for 3D reconstruction of BCC using histopathological serial sections. For fully automatic delineation of the tumor within the tissue, we apply a fuzzy c-means segmentation method. We used a novel multi-grid form of the non-linear registration introduced by Braumann and Kuska in 2005 effectively suppressing registration runs into local minima (possibly caused by diffuse nature of the tumor). Our method was successfully applied in a proof-of-principle study for automated reconstruction.

Authors: P. Scheibe, U. D. Braumann, J. P. Kuska, M. Loffler, J. C. Simon, U. Paasch, T. Wetzig

Date Published: 1st Jul 2010

Publication Type: Not specified

Human Diseases: basal cell carcinoma

Abstract (Expand)

BACKGROUND: Radical hysterectomy based on empirical surgical anatomy to achieve a wide tumour resection is currently applied to treat early cervical cancer. Total mesometrial resection (TMMR) removes the embryologically defined uterovaginal (Mullerian) compartment except its distal part. Non-Mullerian paracervical and paravaginal tissues may remain in situ despite their possible close proximity to the tumour. We propose that in patients with early cervical cancer, the resection of the Mullerian compartment will lead to maximum local tumour control with low morbidity. We also propose that the relatively high rate of pelvic failure after conventional radical hysterectomy, despite adjuvant radiation, might be a consequence of the incomplete removal of the Mullerian compartment. The aim of our study was to test these hypotheses. METHODS: We did a prospective trial to assess the effectiveness of TMMR without adjuvant radiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB, IIA, and selected IIB cervical cancer. We also generated MRI-based pelvic relapse landscapes from patients who had experienced pelvic failure after conventional radical hysterectomy. FINDINGS: 212 consecutive patients underwent TMMR without adjuvant radiation. 134 patients (63%) had high-risk histopathological factors. At a median follow-up of 41 months (5-110), three patients developed pelvic recurrences, two patients developed pelvic and distant recurrences, and five patients developed distant recurrences. Recurrence-free and overall 5-year survival probabilities were 94% (95% CI 91-98) and 96% (93-99), respectively. Treatment-related grade 2 morbidity was detected in 20 (9%) patients, the most common being vascular complications. Resection of the Mullerian compartment resulted in local tumour control irrespective of the metric extension of the resection margins. The pelvic topography of the peak relapse probability after conventional radical hysterectomy indicates an incomplete resection of the posterior subperitoneal and retroperitoneal extension of the Mullerian compartment. INTERPRETATION: Resection of the embryologically defined uterovaginal compartment seems to be pivotal for pelvic control in patients with cervical cancer. TMMR without adjuvant radiation has great potential to improve the effectiveness of surgical treatment of early-stage cervical cancer. FUNDING: University of Leipzig, Leipzig, Germany.

Authors: M. Hockel, L. C. Horn, N. Manthey, U. D. Braumann, U. Wolf, G. Teichmann, K. Frauenschlager, N. Dornhofer, J. Einenkel

Date Published: 2nd Jun 2009

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract

Not specified

Authors: L. C. Horn, B. Hentschel, U. D. Braumann

Date Published: 30th Aug 2008

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

OBJECTIVE: To investigate spatial tumor invasion using ex vivo specimens and pursue a new morphometric approach for a quantitative assessment of the invasion front. STUDY DESIGN: Based on histologic serial sections with up to 500 slices stained with hematoxylin-eosin, volumes of interest of the tumor invasion front were 3-D reconstructed for 13 specimens from patients with squamous cell carcinoma (SCC) of the uterine cervix. Starting from very sensitive automatic tumor segmentation, 404 presumptive loci of isolated tumor islets were detected within the reconstructed volume data sets. These loci were microscopically inspected on the slides utilizing the volume date set's coordinates. RESULTS: A single detached tumor cell cluster within the stroma could be verified and, additionally, 4 tumor emboli within lymph vessels. The main cause of all other suspect islets (false positive segmentations) was peritumoral inflammatory response. Spatial invasion front quantification was done using discrete compactness (3-D C(D)). A comparison with 2-D C(D) values from single slides yielded strong correlation (correlation coefficient: r = 0.94; p < 0.001). CONCLUSION: Collective migration in SCC of the cervix mainly occurs per continuitatem. 2-D C(D) appears adequate and applicable for the morphometry of tumor invasion front phenotypes.

Authors: J. Einenkel, U. D. Braumann, L. C. Horn, J. P. Kuska, M. Hockel

Date Published: 9th Nov 2007

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

OBJECTIVES: A proof of principle study was conducted for microscopic tissue volume reconstructions using a new image processing chain operating on alternately stained large histological serial sections. METHODS: Digital histological images were obtained from conventional brightfield transmitted light microscopy. A powerful nonparametric nonlinear optical flow-based registration approach was used. In order to apply a simple but computationally feasible sum-of-squared-differences similarity measure even in case of differing histological stainings, a new consistent tissue segmentation procedure was placed upstream. RESULTS: Two reconstructions from uterine cervix carcinoma specimen were accomplished, one alternately stained with p16(INK4a) (surrogate tumor marker) and H&E (routine reference), and another with three different alternate stainings, H&E, p16(INK4a), and CD3 (a T-lymphocyte marker). For both cases, due to our segmentation-based reference-free nonlinear registration procedure, resulting tissue reconstructions exhibit utmost smooth image-to-image transitions without impairing warpings. CONCLUSIONS: Our combination of modern nonparametric nonlinear registration and consistent tissue segmentation has turned out to provide a superior tissue reconstruction quality.

Authors: U. D. Braumann, N. Scherf, J. Einenkel, L. C. Horn, N. Wentzensen, M. Loeffler, J. P. Kuska

Date Published: 17th Oct 2007

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

The invasion front pattern of squamous cell carcinoma (SCC) is a conspicuous histological phenomenon, which is assessed without precise criteria. The current study was performed to introduce the classical (C(C)) and discrete compactness (C(D)) as new morphometric parameters for quantification of this pattern. A retrospective analysis of 76 surgically treated patients with cervical carcinoma was conducted and the pattern of invasion was qualitatively classified as closed, finger-like or diffuse, respectively, by two pathologists. After digitization of the histological slides with a field of view of 10.4 mm x 8.3mm, tumor areas were labeled and C(C) and C(D) were computed based on the drawings (binary images). Additionally, intraindividual variation of compactness was evaluated for 12 selected tumors. The qualitative pattern assessment by the pathologists was moderately reproducible with an interobserver agreement of 72% and a kappa coefficient of 0.44. The values of C(C) and C(D) referring to the invasion front patterns assigned by both pathologists were significantly different between the three classified groups (p< or =0.01 and p< or =0.0001), so that, both theoretically and in practice, compactness regards the same morphological feature. In due consideration of the analysis of the area under the ROC (receiver operating characteristic) curves and the variation coefficient of different tumor regions, C(D) is more suitable for practical use than C(C). Tumors with a microscopic invasion into the parametria and with lymph-vascular space invasion were found to have a lower value of C(D), which indicates a more diffuse pattern of invasion (p=0.028 and p=0.033). We conclude that the discrete compactness C(D) is a new and reproducible parameter for a computer assisted quantification of the invasion front pattern and, thus, defines a further phenotypic feature of SCC of the uterine cervix.

Authors: J. Einenkel, U. D. Braumann, L. C. Horn, N. Pannicke, J. P. Kuska, A. Schutz, B. Hentschel, M. Hockel

Date Published: 25th May 2007

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

BACKGROUND: Malignant growth and invasiveness of cancers is a function of both intratumoral and stromal factors. The accessibility to nutrients, oxygen and growth factors, the stromal composition, and the interference with the immune system all shape the tumor invasion front. A recent study has shown a prognostic difference with respect to different invasion patterns analyzed on histological specimens of cervical cancers. The present study analyzes the spatial organization of a cervical cancer and the relation of the tumor invasion front and the infiltration with CD3(+) T-cells. METHODS: From a cervical squamous cell carcinoma specimen, 84 serial sections were performed and three interleaving series were stained with hematoxylin/eosin and immunohistochemistry directed against the cervical carcinoma biomarker p16(INK4a) and the T-cell marker CD3. Sections were passed through an image processing chain to obtain a reconstructed and segmented tissue volume. For local tumor invasion front analysis the mean curvature was used, which in turn was related to the respective local minimum tumor to T-cell distance as well to a T-cell originated diffusing substance's concentration at the tumor surface. RESULTS: Spatial models of the tumor tissue and the infiltrating T-cells were computed. The overall discrete compactness of the tumor invasion front was 0.89, corresponding to a pathological assessment of diffuse infiltration. The comparison of the tumor invasion front with the density of T-cell infiltration revealed an increased smoothening in regions with high T-cell infiltration. CONCLUSIONS: We could demonstrate the spatial organization of a cervical cancer and model the interaction between infiltrating T-cells with the tumor invasion front shape. Increased smoothening in regions with high T-cell infiltration suggests that T-cells may have an influence on the shaping of the tumor invasion front, e.g., by attacking tumor cells displaying specific antigens. The applied technique allows visualization of the spatial organization of tissues and could be extended to analyze multiple stains on alternating sections.

Authors: N. Wentzensen, U. D. Braumann, J. Einenkel, L. C. Horn, M. von Knebel Doeberitz, M. Loffler, J. P. Kuska

Date Published: 7th Feb 2007

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract

Not specified

Authors: J. Einenkel, W. Steller, U. D. Braumann, L. C. Horn, C. Krafft

Date Published: 11th Jan 2007

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract

Not specified

Authors: J. Einenkel, J. P. Kuska, L. C. Horn, N. Wentzensen, M. Hockel, U. D. Braumann

Date Published: 5th Aug 2006

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

Infrared (IR) spectroscopic imaging coupled with microscopy has been used to investigate thin sections of cervix uteri encompassing normal tissue, precancerous structures, and squamous cell carcinoma. Methods for unsupervised distinction of tissue types based on IR spectroscopy were developed. One-hundred and twenty-two images of cervical tissue were recorded by an FTIR spectrometer with a 64x64 focal plane array detector. The 499,712 IR spectra obtained were grouped by an approach which used fuzzy C-means clustering followed by hierarchical cluster analysis. The resulting false color maps were correlated with the morphological characteristics of an adjacent section of hematoxylin and eosin-stained tissue. In the first step, cervical stroma, epithelium, inflammation, blood vessels, and mucus could be distinguished in IR images by analysis of the spectral fingerprint region (950-1480 cm(-1)). In the second step, analysis in the spectral window 1420-1480 cm(-1) enables, for the first time, IR spectroscopic distinction between the basal layer, dysplastic lesions and squamous cell carcinoma within a particular sample. The joint application of IR microspectroscopic imaging and multivariate spectral processing combines diffraction-limited lateral optical resolution on the single cell level with highly specific and sensitive spectral classification on the molecular level. Compared with previous reports our approach constitutes a significant progress in the development of optical molecular spectroscopic techniques toward an additional diagnostic tool for the early histopathological characterization of cervical cancer.

Authors: W. Steller, J. Einenkel, L. C. Horn, U. D. Braumann, H. Binder, R. Salzer, C. Krafft

Date Published: 6th Dec 2005

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

AIM: Achieving a high quality gynaecological ultrasound examination requires thorough knowledge of topographic anatomy. To date, there are no guidelines for a standardised course of the examination. The goal of the study was to define exact planes by means of cross-sectional anatomy and then to standardise the gynaecological ultrasound examination with the transabdominal, introital and transvaginal technique. METHOD: We developed a software tool based on IDL (Interactive Data Language) for the female data set of the Visible Human Project which generates free determinable planes in the volume. The organs of the female pelvis were divided into landmark- and target structures according to the ultrasonic visibility and the variability of the position, shape and structure. From this, a course for the gynaecological ultrasound examination was created and verified on 65 patients each with an inconspicuous ultrasound finding. In addition, the average duration of the examination was determined. RESULTS: The landmark structures could be demonstrated in all patients. Five planes were defined for each technique, and the course of the whole examination with 15 exact planes was described. The average duration of the examination was 4.5 minutes. CONCLUSION: As of now, the digitally reconstructed anatomical illustrations have achieved the best image resolution and quality regardless of the position of the plane in the examination volume. The standardised course of the gynaecological ultrasound examination can serve as a basis for the improvement of training quality and the evaluation of a general gynaecological ultrasound screening.

Authors: J. Einenkel, U. D. Braumann, D. Baier, J. P. Kuska, L. C. Horn, M. Hockel

Date Published: 22nd Oct 2005

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

The analysis of the three-dimensional (3-D) structure of tumoral invasion fronts of carcinoma of the uterine cervix is the prerequisite for understanding their architectural-functional relationship. The variation range of the invasion patterns known so far reaches from a smooth tumor-host boundary surface to more diffusely spreading patterns, which all are supposed to have a different prognostic relevance. As a very decisive limitation of previous studies, all morphological assessments just could be done verbally referring to single histological sections. Therefore, the intention of this paper is to get an objective quantification of tumor invasion based on 3-D reconstructed tumoral tissue data. The image processing chain introduced here is capable to reconstruct selected parts of tumor invasion fronts from histological serial sections of remarkable extent (90-500 slices). While potentially gaining good accuracy and reasonably high resolution, microtome cutting of large serial sections especially may induce severe artifacts like distortions, folds, fissures or gaps. Starting from stacks of digitized transmitted light color images, an overall of three registration steps are the main parts of the presented algorithm. By this, we achieved the most detailed 3-D reconstruction of the invasion of solid tumors so far. Once reconstructed, the invasion front of the segmented tumor is quantified using discrete compactness.

Authors: U. D. Braumann, J. P. Kuska, J. Einenkel, L. C. Horn, M. Loffler, M. Hockel

Date Published: 19th Oct 2005

Publication Type: Not specified

Human Diseases: cervical cancer

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