Novel AI-Based Algorithm for the Automated Measurement of Cervical Sagittal Balance Parameters. A Validation Study on Pre- and Postoperative Radiographs of 129 Patients.

Study Design: Retrospective, mono-centric cohort research study.

Objectives: The analysis of cervical sagittal balance parameters is essential for preoperative planning and dependent on the physician's experience. A fully automated artificial intelligence-based algorithm could contribute to an objective analysis and save time.

Evidence for Enhanced Efficacy of Passive Immunotherapy against Beta-Amyloid in CD33-Negative 5xFAD Mice.

Passive immunotherapy is a very promising approach for the treatment of Alzheimer's disease (AD). Among the different antibodies under development, those targeting post-translationally modified Aβ peptides might combine efficient reduction in beta-amyloid accompanied by lower sequestration in peripheral compartments and thus anticipated and reduced treatment-related side effects. In that regard, we recently demonstrated that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to the attenuation of AD-like amyloid pathology in 5xFAD mice.

Extracellular Vesicles of Mesenchymal Stromal Cells Can be Taken Up by Microglial Cells and Partially Prevent the Stimulation Induced by β-amyloid.

Mesenchymal stromal/stem cells (MSCs) have great capacity for immune regulation. MSCs provide protective paracrine effects, which are partially exerted by extracellular vesicles (EVs). It has been reported that MSCs-derived EVs (MSC-EVs) contain soluble factors, such as cytokines, chemokines, growth factors and even microRNAs, which confer them similar anti-inflammatory and regenerative effects to MSCs.

Visualization and co-registration of correlative microscopy data with the ImageJ plug-in Correlia.

Correlative microscopy experiments require the co-registration of the image data acquired by different micro-analytical techniques. Major challenges are the potentially very different fields-of-view and resolutions as well as the multi-modality of the data. To provide microscopists with an easy-to-use software for two-dimensional image co-registration we have developed Correlia, an open source software based on ImageJ/Fiji, which is fully tailored for the registration of multi-modal microscopy data.

Fractionation platform for target identification using off-line directed two-dimensional chromatography, mass spectrometry and nuclear magnetic resonance.

The unambiguous identification of unknown compounds is of utmost importance in the field of metabolomics. However, current identification workflows often suffer from error-sensitive methodologies, which may lead to incorrect structure annotations of small molecules. Therefore, we have developed a comprehensive identification workflow including two highly complementary techniques, i.

Correlia: an ImageJ plug-in to co-register and visualise multimodal correlative micrographs.

The correlation of different microscopic imaging techniques alongside with microanalytical methods is crucial to better understand biological processes on a subcellular level. For that, micrographs and chemical maps exhibiting both, very different spatial resolution and field-of-view but also a highly multimodal content has to be co-registered. We developed the ImageJ/Fiji plug-in Correlia that provides an environment for handling multimodal correlative microscopy data.

An image dataset related to automated macrophage detection in immunostained lymphoma tissue samples.

Background: We present an image dataset related to automated segmentation and counting of macrophages in diffuse large B-cell lymphoma (DLBCL) tissue sections. For the classification of DLBCL subtypes, as well as for providing a prognosis of the clinical outcome, the analysis of the tumor microenvironment and, particularly, of the different types and functions of tumor-associated macrophages is indispensable. Until now, however, most information about macrophages has been obtained either in a completely indirect way by gene expression profiling or by manual counts in immunohistochemically (IHC) fluorescence-stained tissue samples while automated recognition of single IHC stained macrophages remains a difficult task.

Automated macrophage counting in DLBCL tissue samples: a ROF filter based approach.

Background: For analysis of the tumor microenvironment in diffuse large B-cell lymphoma (DLBCL) tissue samples, it is desirable to obtain information about counts and distribution of different macrophage subtypes. Until now, macrophage counts are mostly inferred from gene expression analysis of whole tissue sections, providing only indirect information. Direct analysis of immunohistochemically (IHC) fluorescence stained tissue samples is confronted with several difficulties, e.

T-Cell Clustering in Neoplastic Follicles of Follicular Lymphoma.

The nonneoplastic microenvironment is abundant in follicular lymphoma. Its composition has been reported to be associated with the course of the disease. Lack of animal models hampers studies of interaction between lymphoma and bystander cells.

Linking stem cell function and growth pattern of intestinal organoids.

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.

Skin regeneration in deep second-degree scald injuries either by infusion pumping or topical application of recombinant human erythropoietin gel.

Large doses of recombinant growth factors formulated in solution form directly injected into the body is usual clinical practice in treating second-degree scald injuries, with promising results, but this approach creates side effects; furthermore, it may not allow appropriate levels of the factor to be sensed by the target injured tissue/organ in the specific time frame, owing to complications arising from regeneration. In this research, two delivery methods (infusion pumping and local topical application) were applied to deliver recombinant human erythropoietin (rHuEPO) for skin regeneration. First, rHuEPO was given in deep second-degree scald injury sites in mice by infusion pump.

Parametric model for the 3D reconstruction of individual fovea shape from OCT data.

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.

Nanostructured self-assembling peptides as a defined extracellular matrix for long-term functional maintenance of primary hepatocytes in a bioartificial liver modular device.

Much effort has been directed towards the optimization of the capture of in vivo hepatocytes from their microenvironment. Some methods of capture include an ex vivo cellular model in a bioreactor based liver module, a micropatterned module, a microfluidic 3D chip, coated plates, and other innovative approaches for the functional maintenance of primary hepatocytes. However, none of the above methods meet US Food and Drug Administration (FDA) guidelines, which recommend and encourage that the duration of a toxicity assay of a drug should be a minimum of 14 days, to a maximum of 90 days for a general toxicity assay.

Quantitative analysis of astrogliosis in drug-dependent humans.

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.

Classifying prostate cancer malignancy by quantitative histomorphometry.

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.

Suitability of infrared microspectroscopic imaging for histopathology of the uterine cervix.

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.

Comparison of different fabrication techniques for human adipose tissue engineering in severe combined immunodeficient mice.

Adipose tissue engineering has been advocated for soft-tissue augmentation and for the treatment of soft tissue defects. The efficacy in terms of persistence of the engineered fat is, however, not yet understood and could depend on the nature of fabrication and application. The high metabolic demand of adipose tissue also points to the problem of vascularization.

Determination of pore size distribution at the cell-hydrogel interface.

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.

Image-processing chain for a three-dimensional reconstruction of basal cell carcinomas.

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.

Local spread of cervical cancer revisited: a clinical and pathological pattern analysis.

Background: Local tumor spread of cervical cancer is currently considered as radial progressive intra- and extracervical permeation. For radical tumor resection or radiation the inclusion of a wide envelope of tumor-free tissue is demanded. However, this concept may lead to considerable treatment-related morbidity and does not prevent local relapse.

Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvic control in patients with cervical cancer: a prospective analysis.

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 (Müllerian) compartment except its distal part. Non-Müllerian paracervical and paravaginal tissues may remain in situ despite their possible close proximity to the tumour.

Identification of metabolites in human hepatic bile using 800 MHz 1H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS.

The first application of high field NMR spectroscopy (800 MHz for (1)H observation) to human hepatic bile (as opposed to gall bladder bile) is reported. The bile sample used for detailed investigation was from a donor liver with mild fat infiltration, collected during organ retrieval prior to transplantation. In addition, to focus on the detection of bile acids in particular, a bile extract was analysed by 800 MHz (1)H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS.

3-D analysis of the invasion front in squamous cell carcinoma of the uterine cervix: histopathologic evidence for collective invasion per continuitatem.

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.