Background: Fluorescence-based confocal microscopy (FCM) can be used to create virtual H&E sections in real time. So far, FCM has been used in dermato-, uro-, and gynecopathology. FCM allows the creation of a completely digitized frozen section, which could potentially replace conventional frozen sections in the future.
View Article and Find Full Text PDFBackground: Metabolic dysfunction-associated steatotic liver disease (MASLD), or non-alcoholic fatty liver disease (NAFLD), is a common disease that is diagnosed through manual evaluation of liver biopsies, an assessment that is subject to high interobserver variability (IBV). IBV can be reduced using automated methods.
Objectives: Many existing computer-based methods do not accurately reflect what pathologists evaluate in practice.
Objective: Artificial intelligence (AI) holds the potential to make significant advancements in pathology. However, its actual implementation and certification for practical use are currently limited, often due to challenges related to model transferability. In this context, we investigate the factors influencing transferability and present methods aimed at enhancing the utilization of AI algorithms in pathology.
View Article and Find Full Text PDFBackground: Of all urothelial carcinomas (UCs), 25% are muscle invasive and associated with a 5-year overall survival rate of 50%. Findings regarding the molecular classification of muscle-invasive urothelial carcinomas (MIUCs) have not yet found their way into clinical practice.
Objectives: Prediction of molecular consensus subtypes in MIUCs with artificial intelligence (AI) based on histologic hematoxylin-eosin (HE) sections.
For medicine to fulfill its promise of personalized treatments based on a better understanding of disease biology, computational and statistical tools must exist to analyze the increasing amount of patient data that becomes available. A particular challenge is that several types of data are being measured to cope with the complexity of the underlying systems, enhance predictive modeling and enrich molecular understanding. Here we review a number of recent approaches that specialize in the analysis of multimodal data in the context of predictive biomedicine.
View Article and Find Full Text PDFNodal T-follicular helper cell lymphoma, angioimmunoblastic-type (AITL), is characterized by constitutional symptoms, advanced-stage disease, and generalized lymphadenopathy. A genetic hallmark of this lymphoma is the frequent occurrence of the mutation G17V in neoplastic cells, which is observed in around 60% of patients. Because is involved in both T-cell receptor downstream signalling and cell migration, we hypothesized that the characteristic presentation of AITL could be the result of enhanced tumor cell migration.
View Article and Find Full Text PDFWe aimed to identify hepatocellular carcinoma (HCC) patients who will respond to repetitive transarterial chemoembolization (TACE) to improve the treatment algorithm. Retrospectively, 61 patients (mean age, 65.3 years ± 10.
View Article and Find Full Text PDFBackground: Prostate cancer is a major health concern in aging men. Paralleling an aging society, prostate cancer prevalence increases emphasizing the need for efficient diagnostic algorithms.
Methods: Retrospectively, 106 prostate tissue samples from 48 patients (mean age, [Formula: see text] years) were included in the study.
There is a lot of recent interest in the field of computational pathology, as many algorithms are introduced to detect, for example, cancer lesions or molecular features. However, there is a large gap between artificial intelligence (AI) technology and practice, since only a small fraction of the applications is used in routine diagnostics. The main problems are the transferability of convolutional neural network (CNN) models to data from other sources and the identification of uncertain predictions.
View Article and Find Full Text PDFClassic Hodgkin lymphoma (cHL) is usually characterized by a low tumour cell content, derived from crippled germinal centre B cells. Rare cases have been described in which the tumour cells show clonal T-cell receptor rearrangements. From a clinicopathological perspective, it is unclear if these cases should be classified as cHL or anaplastic large T-cell lymphoma (ALCL).
View Article and Find Full Text PDFIn gastric cancer (GC), there are four molecular subclasses that indicate whether patients respond to chemotherapy or immunotherapy, according to the TCGA. In clinical practice, however, not every patient undergoes molecular testing. Many laboratories have used well-implemented in situ techniques (IHC and EBER-ISH) to determine the subclasses in their cohorts.
View Article and Find Full Text PDFProfound knowledge exists about the clinical, morphologic, genomic, and transcriptomic characteristics of most lymphoma entities. However, information is currently lacking on the dynamic behavior of malignant lymphomas. This pilot study aimed to gain insight into the motility of malignant lymphomas and bystander cells in 20 human lymph nodes.
View Article and Find Full Text PDFThe insertion of organellar membrane proteins with the correct topology requires the following: First, the proteins must contain topogenic signals for translocation across and insertion into the membrane. Second, proteinaceous complexes in the cytoplasm, membrane, and lumen of organelles are required to drive this process. Many complexes required for the intracellular distribution of membrane proteins have been described, but the signals and components required for the insertion of plastidic β-barrel-type proteins into the outer membrane are largely unknown.
View Article and Find Full Text PDFRising interest in three-dimensional volume imaging of biological tissues for diagnostic and research purposes, calls for appropriate optical clearing methods as an indispensable requirement for high-resolution imaging on a cellular level. In recent years, many clearing protocols have emerged, though most of them focus on murine central nervous tissue. Peripheral organs or tissues of human origin have only been investigated sparsely.
View Article and Find Full Text PDFT follicular helper (Tfh) cells play a very important role in mounting a humoral response. Studies conducted in mouse models have revealed with good kinetic and spatial resolution the dynamics of these cells in germinal centers (GC) and their cross-talk with B cells upon an immune response. However, whether a similar migratory behavior is performed by human Tfh cells is unclear, as technology to track them in situ has been lacking.
View Article and Find Full Text PDFAnaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (cHL) are lymphomas that contain CD30-expressing tumor cells and have numerous pathological similarities. Whereas ALCL is usually diagnosed at an advanced stage, cHL more frequently presents with localized disease. The aim of the present study was to elucidate the mechanisms underlying the different clinical presentation of ALCL and cHL.
View Article and Find Full Text PDFGlycerolipid synthesis in plants is coordinated between plastids and the endoplasmic reticulum (ER). A central step within the glycerolipid synthesis is the transport of phosphatidic acid from ER to chloroplasts. The chloroplast outer envelope protein TGD4 belongs to the LptD family conserved in bacteria and plants and selectively binds and may transport phosphatidic acid.
View Article and Find Full Text PDFThe endoplasmic reticulum-mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level.
View Article and Find Full Text PDFMitochondrial β-barrel proteins are synthesized on cytosolic ribosomes and must be specifically targeted to the organelle before their integration into the mitochondrial outer membrane. The signal that assures such precise targeting and its recognition by the organelle remained obscure. In the present study we show that a specialized β-hairpin motif is this long searched for signal.
View Article and Find Full Text PDFApicomplexa are unicellular parasites causing important human and animal diseases, including malaria and toxoplasmosis. Most of these pathogens possess a relict but essential plastid, the apicoplast. The apicoplast was acquired by secondary endosymbiosis between a red alga and a flagellated eukaryotic protist.
View Article and Find Full Text PDFMembranes are central for cells as borders to the environment or intracellular organelle definition. They are composed of and harbor different molecules like various lipid species and sterols, and they are generally crowded with proteins. The membrane system is very dynamic and components show lateral, rotational and translational diffusion.
View Article and Find Full Text PDFUnlabelled: Filamentous, heterocyst-forming cyanobacteria exchange nutrients and regulators between cells for diazotrophic growth. Two alternative modes of exchange have been discussed involving transport either through the periplasm or through septal junctions linking adjacent cells. Septal junctions and channels in the septal peptidoglycan are likely filled with septal junction complexes.
View Article and Find Full Text PDFProteins of the Omp85 family chaperone the membrane insertion of β-barrel-shaped outer membrane proteins in bacteria, mitochondria, and probably chloroplasts and facilitate the transfer of nuclear-encoded cytosolically synthesized preproteins across the outer envelope of chloroplasts. This protein family is characterized by N-terminal polypeptide transport-associated (POTRA) domains and a C-terminal membrane-embedded β-barrel. We have investigated a recently identified Omp85 family member of Arabidopsis thaliana annotated as P39.
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