3714 research outputs found
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Augmenting care in hepatocellular carcinoma with artificial intelligence
No full textHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and prognosis remains poor. The recent paradigm shifts in management algorithms of such patients have resulted in unique challenges in the early identification of HCC, prognosis, surgical outcomes, prioritization of potential transplant recipients, donor-recipient matching, and so on. In recent years, advancements in artificial intelligence (AI) capabilities have shown potential in HCC treatment. In this narrative review, we outline first the different types of AI models that are applied in clinical practice and then focus on the frontiers of AI research in the diagnosis, prognostication, and treatment of HCC, particularly in classification of indeterminate liver lesions, tumor staging, survival prediction, improving equity in transplant recipient selection, prediction of treatment response and prognosis. We show that US coupled with AI-driven predictive models can provide accurate noninvasive screening tools for early disease. While AI models applied to contrast-enhanced CT, MRI and PET studies may appear to have limited clinical utility in disease diagnosis and differentials, owing to their accuracy, we highlighted the importance of such models in predicting pathological findings preoperatively. Despite the availability of many accurate, sensitive, and specific AI algorithms that outperform traditional scoring systems, they have not been widely used in clinical practice. The challenges in AI application, including distributional shift and imbalanced data, lack of standardization, and the ‘black box’ phenomenon, are addressed here. The importance of AI in the future of HCC makes it important for clinicians to have a good understanding of different AI techniques, their benefits, and potential pitfalls
The role of social institutions in community resilience following extreme natural hazard events
No full textSocial institutions such as hospitals and schools are among the main pillars of community stability. A drop in the functionality of hospitals and schools is likely to have short-term and long-term effects on a community, including a reduction in medical interventions, an increase in unschooled children, and population outmigration in search of essential social services. However, comprehensive community resilience models that consider the role played by social institutions in community stability following natural disasters are scarce at the present time. This paper provides a literature review and critical appraisal of previous studies on the resilience of hospital and school systems and their impact on community well-being. The review encompasses existing resilience models for single hospitals and schools, their role when connected with other hospitals and schools in a network, their reliance on each other as interdependent systems, and their role in community resilience and stability. Different mitigation strategies and policies to enhance hospital and school systems’ resilience after extreme natural hazards are also summarized. The paper concludes with a series of recommendations to improve current models for social institutions, enhance the connection between existing hospital and school resilience models and community resilience frameworks, and develop social stability indices that policymakers can use in preparing and mitigating future extreme events
Immune cell-derived serine protease as pathogenic drivers of vascular remodeling in pulmonary arterial hypertension
No full textIn recent years, accumulating evidence has shown that pulmonary arterial hypertension (PAH) has a strong underlying inflammatory component. Vascular remodeling, a common pathology observed in all forms of pulmonary hypertension (PH), is accompanied by a pronounced accumulation of leukocytes around and within the vessels. Proteolytic products of immune cells, particularly neutrophil and mast cell serine proteases, have been shown to play a central pathogenic role in vascular remodeling and PAH development. Serine proteases are involved in many aspects of the inflammatory response, such as extracellular matrix degradation, regulation of bioavailability of cytokines, chemokines, and growth factors, and dysregulation of their activity can have devastating consequences. In this review, we will focus on immune dysregulation in PAH and shed light on the pro-inflammatory role of serine proteases in vascular pathology observed in the context of this disease
Neutrophil serine proteases
No full textThe identification and characterization of the four active neutrophil serine proteases (NSPs) have provided a better understanding of their roles in various physiological and pathological processes. The availability of appropriate tools such as substrates, inhibitors, and activity-based probes (ABPs) for studying their activity and functions in cells has become increasingly important. In this paper, the authors provide a comprehensive overview of the current knowledge on the tools available for studying NSPs. The substrates, inhibitors, and ABPs developed to date are described, including their strengths and limitations. The authors also discuss the potential implications of these tools for future research on NSPs, including their potential use in the development of new therapeutics for various diseases. Overall, this paper highlights the importance of understanding the activity and functions of NSPs and provides valuable information on the tools available for studying these proteases
Thermodynamic modeling of the Fe-Sn system including an experimental re-assessment of the liquid miscibility gap
No full textThe usage of low-grade ferrous scrap has increased over decades to decrease CO2 emissions and to produce steel products at a low cost. A serious problem in melting post-consumer scrap material is the accumulation of tramp elements, e.g., Cu and Sn, in the liquid steel. These tramp elements are difficult to remove during conventional steelmaking processes. Sn is considered as one of the most harmful tramp elements because, together with Cu, it sometimes induces the liquid metal embrittlement in high-temperature ferrous processing, e.g., continuous casting and hot rolling. Furthermore, the chemical interaction between Fe and Sn plays an important role in the Sn smelting process. The raw material used in the Sn smelting process is SnO2 (cassiterite), in which Fe3O4 is a gangue in the Sn ore. In the process, the reduction of Fe3O4 is unavoidable, which results in forming a Fe-Sn alloy (hardhead). The recirculation of the hardhead decreases the furnace capacity and increases the energy consumption in the smelting. The need to efficiently recover Sn from secondary resources is therefore inevitable. The CALculation of PHAse Diagrams (CALPHAD) approach helps to predict the equilibrium state of the multicomponent system. Previously reported studies of the Fe-Sn system show inconsistencies in the calculations and the experimental results. Mainly the miscibility gap in the liquid phase was under debate, as experimental data of the phase boundary are scattered. Experimental study and re-optimization of model parameters were carried out with emphasis on the correct shape of the miscibility gap. Three different experimental techniques were employed: differential scanning calorimetry, electromagnetic levitation, and contact angle measurement. The present thermodynamic model has higher accuracy in predicting the solubility of Sn in the body-centered cubic (bcc), compared to previous assessments. This is achieved by re-evaluating the Gibbs energies of the FeSn and FeSn2 compounds and the peritectic reaction related to Fe5Sn3. Also, the inconsistencies related to the miscibility gap around XSn = 0.31-0.81 were resolved. The database developed in the present study can contribute to the development of a large CALPHAD database containing tramp elements
Dry mineral processing: the new topic of XXXII international mineral processing congress
No full textGraphene oxide modified electrode enhances electricity generation and heavy metal removal in photosynthetic microalgae microbial fuel cells
No full textImproving the power generation performance and pollutant removal of photosynthetic microalgae microbial fuel cells (PMMFCs) is the key to their large-scale application. In this work, microalgae (Chlorella sp. QB-102) were used as a biocatalyst in the cathode, and foam nickel modified by graphene oxide with two degrees of oxidation was used as the electrode. The results showed that the maximum power density of PMMFCs with high oxidation degree graphene oxide modified electrode (NF-GO-H) reached 209.07 mW·m-2, which was 6 times that of PMMFCs with low oxidation degree graphene oxide modified electrode (NF-GO-L), indicating that the use of the NF-GO-H electrode can effectively improve the electrical properties of PMMFCs. Simultaneously, the NF-GO-H electrode can effectively remove Cd(II), with a capacity of 6.039 g·m-2, which is twice that of the NF-GO-L electrode. Moreover, through the synergistic electrochemical action of Chlorella sp. QB-102, a large number of hydroxyl groups can be generated to convert the adsorbed Cd(II) into a more stable Cd(OH)2 precipitate. The results of this work will further expand the application of PMMFCs in power generation and heavy metal removal
Targeting hormone-resistant breast cancer cells with docetaxel: a look inside the resistance
No full textAim: The study aims to analyze the effect of long-term incubation of ERα-positive MCF7 breast cancer cells with 4-hydroxytamoxifen (HT) on their sensitivity to tubulin polymerization inhibitor docetaxel.Methods: The analysis of cell viability was performed by the MTT method. The expression of signaling proteins was analyzed by immunoblotting and flow cytometry. ERα activity was evaluated by gene reporter assay. To establish hormone-resistant subline MCF7, breast cancer cells were treated with 4-hydroxytamoxifen for 12 months.Results: The developed MCF7/HT subline has lost sensitivity to 4-hydroxytamoxifen, and the resistance index was 2. Increased Akt activity (2.2-fold) and decreased ERα expression (1.5-fold) were revealed in MCF7/HT cells. The activity of the estrogen receptor α was reduced (1.5-fold) in MCF7/HT. Evaluation of class III β-tubulin expression (TUBB3), a marker associated with metastasis, revealed the following trends: higher expression of TUBB3 was detected in triple-negative breast cancer MDA-MB-231 cells compared to hormone-responsive MCF7 cells (P < 0.05). The lowest expression of TUBB3 was found in hormone-resistant MCF7/HT cells (MCF7/HT < MCF7 < MDA-MB-231, approximately 1:2:4). High TUBB3 expression strongly correlated with docetaxel resistance: IC50 value of docetaxel for MDA-MB-231 cells was greater than that for MCF7 cells, whereas resistant MCF7/HT cells were the most sensitive to the drug. The accumulation of cleaved PARP (a 1.6-fold increase) and Bcl-2 downregulation (1.8-fold) were more pronounced in docetaxel-treated resistant cells (P < 0.05). The expression of cyclin D1 decreased (2.8-fold) only in resistant cells after 4 nM docetaxel treatment, while this marker was unchanged in parental MCF7 breast cancer cells.Conclusion: Further development of taxane-based chemotherapy for hormone-resistant cancer looks highly promising, especially for cancers with low TUBB3 expression
Epigenetic effects of high-fat diet on intestinal tumorigenesis in C57BL/6J-ApcMin/+ mice
No full textAim: Obesity and obesogenic diets might partly accelerate cancer development through epigenetic mechanisms. To determine these early effects, we investigated the impact of three days of a high-fat diet on epigenomic and transcriptomic changes in ApcMin/+ murine intestinal epithelia.Method: ChIP-Seq and RNA-Seq were performed on small intestinal epithelia of WT and ApcMin/+ male mice fed high-fat diet (HFD) or low-fat diet (LFD) for three days to identify genomic regions associated with differential H3K27ac levels as a marker of variant enhancer loci (VELs) as well as differentially expressed genes (DEGs).Results: Regarding epigenetic and transcriptomic changes, diet type (LFD vs. HFD) showed a significant impact, and genotype (WT vs. ApcMin/+) showed a small impact. Compared to LFD, HFD resulted in 1306 gained VELs, 230 lost VELs, 133 upregulated genes, and 127 downregulated genes in WT mice, with 1056 gained VELs, 371 lost VELs, 222 upregulated genes, and 182 downregulated genes in ApcMin/+ mice. Compared to the WT genotype, theApcMin/+ genotype resulted in zero changed VELs for either diet type group, 21 DEGs for LFD, and 48 DEGs for HFD. Most gained VELs, and upregulated genes were associated with lipid metabolic processes. Gained VELs were also associated with Wnt signaling. Downregulated genes were associated with antigen presentation and processing.Conclusion: Three days of HFD-induced epigenomic and transcriptomic changes involving metabolic and immunologic pathways that may promote tumor growth in the genetically predisposed murine intestine without affecting key cancer signaling pathways
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