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Abstract Ectothermic animals that live in seasonally cold regions must adapt to seasonal variation and specific environmental conditions. During the winter, some amphibians hibernate on land and encounter limited environmental water, deficient oxygen, and extremely low temperatures that can cause the whole body freezing. These stresses trigger physiological and biochemical adaptations in amphibians that allow them to survive. Rana sylvatica, commonly known as the wood frog, shows excellent freeze tolerance. They can slow their metabolic activity to a near halt and endure freezing of 65–70% of their total body water as extracellular ice during hibernation, returning to normal when the temperatures rise again. To investigate the molecular adaptations of freeze-tolerant wood frogs, a comprehensive proteomic analysis was performed on frog liver tissue after anoxia, dehydration, or freezing exposures using a label-free LC–MS/MS proteomic approach. Quantitative proteomic analysis revealed that 87, 118, and 86 proteins were significantly upregulated in dehydrated, anoxic, and frozen groups, suggesting potential protective functions. The presence of three upregulated enzymes, glutathione S-transferase (GST), aldolase (ALDOA), and sorbitol dehydrogenase (SORD), was also validated. For all enzymes, the specific enzymatic activity was significantly higher in the livers of frozen and anoxic groups than in the controls. This study reveals that GST, ALDOA, and SORD might participate in the freeze tolerance mechanism by contributing to regulating cellular detoxification and energy metabolism.

In recent years, optoretinography has become an important functional imaging method for the retina, as light-evoked changes in the photoreceptors have been demonstrated for a large number of different OCT systems. Full-field swept-source optical coherence tomography (FF-SS-OCT) is particularly phase-stable, and it is currently the only technique sensitive enough to detect the smaller functional changes in the inner plexiform layer (IPL). However, the resolution of state-of-the art FF-SS-OCT systems is not high enough to distinguish individual photoreceptors. This makes it difficult to separate rods from cones. In this work, we circumvent this problem by separating the functional changes in rods and cones by their different temporal dynamics to the same light stimulus. For this purpose, a mathematical model was developed that represents the measured signals as a superposition of two impulse responses. The developed model describes the measured data under different imaging conditions very well and is able to analyze the sensitivity and temporal dynamics of the two photoreceptor types separately.

Abstract Convolutional neural networks (CNNs) may improve response prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to investigate the feasibility of a CNN using maximum intensity projection (MIP) images from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) baseline scans to predict the probability of time-to-progression (TTP) within 2 years and compare it with the International Prognostic Index (IPI), i.e. a clinically used score. 296 DLBCL 18F-FDG PET/CT baseline scans collected from a prospective clinical trial (HOVON-84) were analysed. Cross-validation was performed using coronal and sagittal MIPs. An external dataset (340 DLBCL patients) was used to validate the model. Association between the probabilities, metabolic tumour volume and Dmaxbulk was assessed. Probabilities for PET scans with synthetically removed tumors were also assessed. The CNN provided a 2-year TTP prediction with an area under the curve (AUC) of 0.74, outperforming the IPI-based model (AUC = 0.68). Furthermore, high probabilities (> 0.6) of the original MIPs were considerably decreased after removing the tumours (

The spread of COVID-19 has affected billions of people across the globe, and the diagnosis of viral infection still needs improvement. Because of high immunogenicity and abundant expression during viral infection, SARS-CoV-2 nucleocapsid (N) protein could be an important diagnostic marker. This study aimed to develop a label-free optical aptasensor fabricated with a novel single-stranded DNA aptamer to detect the N protein. The N-binding aptamers selected using asymmetric-emulsion PCR-SELEX and their binding affinity and cross-reactivity were characterized by biolayer interferometry. The tNSP3 aptamer (44 nt) was identified to bind the N protein of wild type and Delta and Omicron variants with high affinity (KD in the range of 0.6–3.5 nM). Utilizing tNSP3 to detect the N protein spiked in human saliva evinced the potential of this aptamer with a limit of detection of 4.5 nM. Mass spectrometry analysis was performed along with molecular dynamics simulation to obtain an insight into how tNSP3 binds to the N protein. The identified epitope peptides are localized within the RNA-binding domain and C terminus of the N protein. Hence, we confirmed the performance of this aptamer as an analytical tool for COVID-19 diagnosis.

Breast cancer (BC) is the second most frequently diagnosed cancer and accounts for approximately 25% of new cancer cases in Canadian women. Using biomarkers as a less-invasive BC diagnostic method is currently under investigation but is not ready for practical application in clinical settings. During the last decade, extracellular vesicles (EVs) have emerged as a promising source of biomarkers because they contain cancer-derived proteins, RNAs, and metabolites. In this study, EV proteins from small EVs (sEVs) and medium EVs (mEVs) were isolated from BC MDA-MB-231 and MCF7 and non-cancerous breast epithelial MCF10A cell lines and then analyzed by two approaches: global proteomic analysis and enrichment of EV surface proteins by Sulfo-NHS-SS-Biotin labeling. From the first approach, proteomic profiling identified 2459 proteins, which were subjected to comparative analysis and correlation network analysis. Twelve potential biomarker proteins were identified based on cell line-specific expression and filtered by their predicted co-localization with known EV marker proteins, CD63, CD9, and CD81. This approach resulted in the identification of 11 proteins, four of which were further investigated by Western blot analysis. The presence of transmembrane serine protease matriptase (ST14), claudin-3 (CLDN3), and integrin alpha-7 (ITGA7) in each cell line was validated by Western blot, revealing that ST14 and CLDN3 may be further explored as potential EV biomarkers for BC. The surface labeling approach enriched proteins that were not identified using the first approach. Ten potential BC biomarkers (Glutathione S-transferase P1 (GSTP1), Elongation factor 2 (EEF2), DEAD/H box RNA helicase (DDX10), progesterone receptor (PGR), Ras-related C3 botulinum toxin substrate 2 (RAC2), Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), Aconitase 2 (ACO2), UTP20 small subunit processome component (UTP20), NEDD4 binding protein 2 (N4BP2), Programmed cell death 6 (PDCD6)) were selected from surface proteins commonly identified from MDA-MB-231 and MCF7, but not identified in MCF10A EVs. In total, 846 surface proteins were identified from the second approach, of which 11 were already known as BC markers. This study supports the proposition that Evs are a rich source of known and novel biomarkers that may be used for non-invasive detection of BC. Furthermore, the presented datasets could be further explored for the identification of potential biomarkers in BC.

Der vorliegende Artikel befasst sich mit dem Zusammenspiel von digitalen Medien, Bildung und Teilhabe mit einer Fokussierung auf das Thema Flucht. Das durch das BMBF geförderte ethnografische Forschungsvorhaben Bildungsteilhabe Geflüchteter in digitalisierten Bildungsarrangements (BIGEDIB) (Laufzeit 2019-2022) widmet sich in praxistheoretischer Perspektive der Frage nach (Bildungs-)Teilhabe in unterschiedlichen medial durchdrungenen Bildungs- und Alltagskontexten junger Geflüchteter mittels Feldprotokolle teilnehmender Beobachtungen. Der Artikel zeigt anhand beispielhafter Sequenzanalysen zentrale Forschungserkenntnisse im Hinblick auf Bedingungen für die Ermöglichung von (Bildungs-) Teilhabe im Kontext digitalisierter Bildungsarrangements. Ein zentrales Analyseergebnis ist die Notwendigkeit der Herstellung von Passung zwischen fachlich-personalen Anforderungen, subjektiven Voraussetzungen junger Geflüchteter und Charakteristika digitaler Artefakte unter der Rahmung der institutionellen Bedingungen im Bildungsarrangement.

Hemojuvelin (HJV), a BMP co-receptor promoting hepcidin expression in the liver, has a hepatoprotective function and its deficiency in mice triggers mitochondrial dysfunction and hepatocarcinogenesis.

Abstract Background Interim [18F]fluoro-deoxyglucose-positron emission tomography predicts outcome in peripheral T-cell lymphoma (PTCL). We compared two quantitative evaluation methods. Methods Interim scans from 43 patients with anaplastic lymphoma kinase-negative PTCL from the ‘Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas’ trial were re-analyzed by qPET (relating residual lymphoma-related uptake to liver uptake) and ∆SUVmax (relating interim scan to baseline scan). The endpoint was progression-free survival. Results qPET and ∆SUVmax were closely correlated (Pearson’s r = 0.627). Up to the 60th percentile of values ranked by increasing residual activity, the positive predictive value for progression or death increased from 60 to 95%, with stable negative predictive values (NPV) of 60%. Beyond the 60th percentile, the NPV decreased to 40%. qPET ≥ 2 and ∆SUVmax

In endovascular aneurysm repair (EVAR) procedures, the stent graft navigation and implantation is currently performed under a two-dimensional (2D) imaging based guidance requiring X-rays and contrast agent. In this work, a novel 3D stent graft guidance approach based on tracking systems is introduced. A calibration method and the visualization of the stent graft guidance are described. The tracking based stent graft guidance is evaluated by conducting an EVAR procedure on a torso phantom using a stent graft system equipped with an optical fiber and three EM sensors. The physicians were able to navigate the stent graft to the landing zone, and to place and implant it as intended using the introduced guidance. This showed that the application of the stent graft guidance is feasible in a clinical environment and promising for the reduction of radiation and contrast agent.

Hypothesis: Otitis media (OM) can be successfully visualized and diagnosed by dynamic microscopic optical coherence tomography (dmOCT). Background: OM is one of the most common infectious diseases and, according to the WHO, one of the leading health problems with high mortality in developing countries. Despite intensive research, the only definitive treatment of therapy-refractory OM for decades has been the surgical removal of inflamed tissue. Thereby, the intra-operative diagnosis is limited to the surgeon’s visual impression. Supportive imaging modalities have been little explored and have not found their way into clinical application. Finding imaging techniques capable of identifying inflamed tissue intraoperatively, therefore, is of significant clinical relevance. Methods: This work investigated a modified version of optical coherence tomography with a microscopic resolution (mOCT) regarding its ability to differentiate between healthy and inflamed tissue. Despite its high resolution, the differentiation of single cells with mOCT is often impossible. A new form of mOCT termed dynamic mOCT (dmOCT) achieves cellular contrast using micro-movements within cells based on their metabolism. It was used in this study to establish correlative measurements with histology. Results: Using dmOCT, images with microscopic resolution were acquired on ex vivo tissue samples of chronic otitis media and cholesteatoma. Imaging with dmOCT allowed the visualization of specific and characteristic cellular and subcellular structures in the cross-sectional images, which can be identified only to a limited extent in native mOCT. Conclusion: We demonstrated for the first time a new marker-free visualization in otitis media based on intracellular motion using dmOCT.