The Process of Digital Pathology and its Application in a Study

Digital pathology saw its advent in the 60’s with the introduction of telepathology and was brought into a brighter spotlight in the late 90’s through the technological breakthrough in histopathological imaging, called whole slide imaging (WSI). With steady growth in interest among experts, the latest breakthrough in WSI happened in 2017, when both the US Food and Drug Administration and the European Union approved the use of WSI systems in primary diagnostics. So far, the adoption of digital pathology has been slower than many expected, but many laboratories around the world are looking to switch into a digital workflow. In this text, I aim to describe the history and the technical basics of digital pathology and WSI, as well as discuss some of its most widely used and promising applications in education, research, telepathology, clinical work, and image analysis. To better illuminate the digital workflow, I describe the use of digital pathology in a study by Anttinen M et al., in which the author of this text participated in the form of digitizing the whole slide images used in the study. With the advancements in digital pathology in the past two decades and with the regulation catching up, wider adoption WSI systems is to be expected. Many advantages can be associated with digital pathology e.g., better results in learning for students, cost reductions in clinical work, and the reduction in pathologists’ workload due to automated image analysis methods

Atlas of the forest sector in Ukraine with the focus on wood fuels

Layout: Anne Siika, MetlaThis is a review of the current situation of the forest sector in Ukraine by considering a collection of maps. The cartographic information is grouped in the following way: forest resources, silviculture, wood harvesting, production and the most important producers of wood-based products, forest education and research and the potential of wood energy. This review serves the information needs ofdifferent stakeholders and of those interested in the forest sector in Ukraine

Targeting beta 1-integrin inhibits vascular leakage in endotoxemia

Loss of endothelial integrity promotes capillary leakage in numerous diseases, including sepsis, but there are no effective therapies for preserving endothelial barrier function. Angiopoietin-2 (ANGPT2) is a context-dependent regulator of vascular leakage that signals via both endothelial TEK receptor tyrosine kinase (TIE2) and integrins. Here, we show that antibodies against beta 1-integrin decrease LPS-induced vascular leakage in murine endotoxemia, as either a preventative or an intervention therapy. beta 1-integrin inhibiting antibodies bound to the vascular endotheliumin vivo improved the integrity of endothelial cell-cell junctions and protected mice from endotoxemia-associated cardiac failure, without affecting endothelial inflammation, serum proinflammatory cytokine levels, or TIE receptor signaling. Moreover, conditional deletion of a single allele of endothelial beta 1-integrin protected mice from LPS-induced vascular leakage. In endothelial mono-layers, the inflammatory agents thrombin, lipopolysaccharide (LPS), and IL-1 beta decreased junctional vascular endothelial (VE)-cadherin and induced actin stress fibers via beta 1- and alpha 5-integrins and ANGPT2. Additionally, beta 1-integrin inhibiting antibodies prevented inflammation-induced endothelial cell contractility and monolayer permeability. Mechanistically, the inflammatory agents stimulated ANGPT2-dependent translocation of alpha 5 beta 1-integrin into tensin-1-positive fibrillar adhesions, which destabilized the endothelial monolayer. Thus, beta 1-integrin promotes endothelial barrier disruption during inflammation, and targeting beta 1-integrin signaling could serve as a novel means of blocking pathological vascular leak.Peer reviewe

Enhancing Transcranial Blood Flow Visualization with Dynamic Light Scattering Technologies: Advances in Quantitative Analysis

A comparative application of major dynamic light scattering (DLS)-based image methodologies applied to transcranial cerebral blood flow imaging is presented. In particular, the study delves into assessing capability of Laser Doppler Flowmetry (LDF), Laser Speckle Contrast Imaging (LSCI), and Diffuse Correlation Spectroscopy (DCS) in enhancing the spatial and temporal resolution of transcranial blood flow imaging. An integral part of the study is focused on the modulation of blood flow through the administration of the vasodilator drug, Sodium Nitroprusside (SNP). This pharmacological intervention facilitated a direct observation of cerebral vasculature's responsiveness to external stimuli, illuminating the physiological adaptations within the brain's microvascular architecture. Advanced LSCI processing techniques are incorporated, notably entropy and principal component analysis (PCA). Entropy is providing a quantifiable measure of the randomness and complexity within the speckle patterns of transcranial blood flow images, revealing remarkably similar outcomes with DSC approach in terms of blood flow dynamics and its quantitative evaluation. The application of PCA approach is provided a more nuanced understanding of blood flow dynamics, facilitating the identification of subtle changes induced by drug administration. This method proved instrumental in enhancing the visualization and detection of nuanced blood flow dynamics, thereby allowing for a more detailed examination of cerebral circulation alterations induced by SNP administration. The study seeks to offer a wider-ranging insight into comprehending the translating further the concept of DLS into transcrainial blood flow vizualization and explore its practical applications, considering hardware, advanced quantitative image processing, and data acquisition

Functional human cell-based vascularised cardiac tissue model for biomedical research and testing

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) are widely used in in vitro biomedical research and testing. However, fully matured, adult cardiomyocyte characteristics have not been achieved. To improve the maturity and physiological relevance of hiPSC-derived cardiomyocytes, we co-cultured them with preconstructed vascular-like networks to form a functional, human cell-based cardiac tissue model. The morphology and gene expression profiles indicated advanced maturation in the cardiac tissue model compared to those of a cardiomyocyte monoculture. The cardiac tissue model’s functionality was confirmed by measuring the effects of 32 compounds with multielectrode array and comparing results to human data. Our model predicted the cardiac effects with a predictive accuracy of 91%, sensitivity of 90% and specificity of 100%. The correlation between the effective concentration (EC50) and the reported clinical plasma concentrations was 0.952 (R2 = 0.905). The developed advanced human cell-based cardiac tissue model showed characteristics and functionality of human cardiac tissue enabling accurate transferability of gained in vitro data to human settings. The model is standardized and thus, it would be highly useful in biomedical research and cardiotoxicity testing.publishedVersionPeer reviewe

Endothelial destabilization by angiopoietin-2 via integrin beta 1 activation

Peer reviewe

Histopathological evaluation of prostate specimens after thermal ablation may be confounded by the presence of thermally-fixed cells

Purpose: Prostate cancer can be eradicated with heat exposure. However, high and rapid temperature elevations may cause thermofixation giving the appearance of viable tissue. The purpose was to characterize the immunoprofile and evaluate the viability of prostate regions with suspected thermofixation. Methods and materials: A prospective, ethics-approved and registered study (NCT03350529) enrolled six patients with MRI-visible, biopsy-concordant prostate cancer to undergo lesion-targeted MRI-guided transurethral ultrasound ablation (TULSA) followed by radical prostatectomy at 3 weeks, to evaluate the accuracy and efficacy of TULSA with whole-mount histology as a reference standard. If ambiguity about complete necrosis within the ablated region remained after hematoxylin-eosin staining, viability was assessed by immunohistochemistry. Treatment day MRI-thermometry and 3-week contrast-enhanced MRI post-TULSA were examined to assess ablation success and correlation with histopathology. Results: One patient presented with an apparently viable subregion inside the ablated area, surrounded by necrosis on H&E staining, located where temperature was highest on MRI-thermometry and tissues completely devascularized on MRI. Immunoprofile of the apparently viable tissue revealed changes in staining patterns suggesting thermofixation; the most significant evidence was the negative cytokeratin 8 staining detected with Cam5.2 antibody. A comprehensive literature review supports these observations of thermofixation with similar findings in prostate and other tissues. Conclusion: Thermally-fixed cells can sustain morphology on H&E staining. Misinterpretation of treatment failure may occur, if this phenomenon is not recognized and immunohistochemistry performed. Based on the previous literature and the current study, Cam5.2 staining for cytokeratin 8 appears to be a practical and reliable tool for distinguishing thermally-fixed from viable cells.</p

VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart

Peer reviewe