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Background and Aims: Histological disease activity in inflammatory bowel disease [IBD] is associated with clinical outcomes and is an important endpoint in drug development. We developed deep learning models for automating histological assessments in IBD., Methods: Histology images of intestinal mucosa from phase 2 and phase 3 clinical trials in Crohn's disease [CD] and ulcerative colitis [UC] were used to train artificial intelligence [AI] models to predict the Global Histology Activity Score [GHAS] for CD and Geboes histopathology score for UC. Three AI methods were compared. AI models were evaluated on held-back testing sets, and model predictions were compared against an expert central reader and five independent pathologists., Results: The model based on multiple instance learning and the attention mechanism [SA-AbMILP] demonstrated the best performance among competing models. AI-modelled GHAS and Geboes subgrades matched central readings with moderate to substantial agreement, with accuracies ranging from 65% to 89%. Furthermore, the model was able to distinguish the presence and absence of pathology across four selected histological features, with accuracies for colon in both CD and UC ranging from 87% to 94% and for CD ileum ranging from 76% to 83%. For both CD and UC and across anatomical compartments [ileum and colon] in CD, comparable accuracies against central readings were found between the model-assigned scores and scores by an independent set of pathologists., Conclusions: Deep learning models based upon GHAS and Geboes scoring systems were effective at distinguishing between the presence and absence of IBD microscopic disease activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Biomedical imaging techniques such as high content screening (HCS) are valuable for drug discovery, but high costs limit their use to pharmaceutical companies. To address this issue, The JUMP-CP consortium released a massive open image dataset of chemical and genetic perturbations, providing a valuable resource for deep learning research. In this work, we aim to utilize the JUMP-CP dataset to develop a universal representation model for HCS data, mainly data generated using U2OS cells and CellPainting protocol, using supervised and self-supervised learning approaches. We propose an evaluation protocol that assesses their performance on mode of action and property prediction tasks using a popular phenotypic screening dataset. Results show that the self-supervised approach that uses data from multiple consortium partners provides representation that is more robust to batch effects whilst simultaneously achieving performance on par with standard approaches. Together with other conclusions, it provides recommendations on the training strategy of a representation model for HCS images., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jacek Tabor reports financial support was provided by National Science Centre Poland. Dawid Rymarczyk reports financial support was provided by National Science Centre Poland. Lukasz Struski reports financial support was provided by National Science Centre Poland. Bartosz Zielinski reports financial support was provided by National Science Centre Poland. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The work primarily concerns development of activated carbon dedicated for adsorption of pesticides from water prior directing it to the distribution system. We provide an information on research on important practical aspects related to research carried out to develop and to manufacture activated carbons. The paper concerns preliminary works on selection raw materials, a binder used for producing granulated adsorbent, activating gases, conditions of the production process, and others. The key attention in this research was paid to its target, i.e., industrial process to produce activated carbon revealing fulfilling required properties including satisfying adsorption of selected pesticides and meeting the requirements of companies dealing with a large-scale production of drinking water. Therefore, among others, the work includes considerations concerning such aspects like pore structure and specific surface area of the activated carbon, formation of granules that are the most demanded and thus preferred in an industrial practice form of activated carbons, and other aspects important from practical point of view. Using the results of our preliminary work, a batch of granular activated carbon was produced in industrial conditions. The obtained material was tested in terms of removing several pesticides at a water treatment plant operating on an industrial scale. During tests the concentration of acetochlor ESA was decreased from ca. 0.4 µg/l in raw water to below 0.1 µg/l. During 11 months of AC use specific surface area of adsorbent lowered significantly by 164 m 2 /g, and total pore volume declined from initial 0.56 cm 3 /g to 0.455 cm 3 /g. We discuss both a performance of the obtained activated carbon in a long-term removal of acetochlor and its derivatives from water and an effect of exploitation time on the removal efficiency. The explanations for the reduction in pesticide removal efficiency are also proposed and discussed., (© 2022. The Author(s).)

The most widely used method for shaping technical blades is grinding with abrasive tools made of cubic boron nitride (cBN) grains and vitrified bond. The goal of this work was to determine the effect of grinding wheel grain size (cBN grain number according to FEPA standards: B126, B181 and B251), kinematics (grinding with the circumference, face and conical surface of the wheel) and feed rate ( v f = 100; 150; 200 mm/min) on the effects of the grinding process evaluated by the cutting force of the blade after machining F , blade surface texture parameters ( Sa , St , Smvr , Str , Sdq , Sdr and Sbi ) as well as blade surface morphology. An analysis of output quantities showed that grinding wheels made of B181 cBN grains are most favorable for shaping planar technical blades of X39Cr13 steel in the grinding process.

This work presents the results of an experimental study of the sharpening of planar technical blades used in the fish processing industry. Sharpening was carried out in the grinding process using several environmentally friendly methods of cooling and lubricating the machining zone (MQL method, CAG nozzle, hybrid method that is a combination of MQL and CAG methods, as well as WET flooding method as reference). The purpose of the research was to determine the possibility of reducing the negative environmental impact of the sharpening process of technical blades by minimizing the expenditure of coolant. The application of the MQL method and the hybrid MQL + CAG method provided a very good realization of the lubricating function so that the share of friction of dulled cutting vertices against the workpiece surface is reduced, which manifests itself in the reduction of the grinding force and the correlated grinding power. In the case of grinding under cooled compressed air delivery conditions, the average cutting force was as much as 91.6% higher ( F = 22.63 N) compared to the result obtained for the most favorable flooding method, demonstrating the insufficient quality of the blade shaped under such conditions. A comprehensive comparison of test results on grinding power gain, cutting force and surface texture suggests that the most favorable sharpening results were obtained using the environmentally friendly MQL method of cooling and lubricating the grinding zone.

Lamiaceae species are rich sources of biologically active compounds which have been applied in medicine since ancient times. Especially their antineoplastic properties have been thoroughly studied with respect to their putative application in chemoprevention and adjuvant therapy of cancer. However, the most known biological effects of Lamiaceae have been ascribed to their essential oil fractions, whereas their (poly)phenolic metabolites being also abundant in these plants, are much less recognized, nevertheless contributing to their beneficial properties, such as anti-cancer actions. The aim of this study was to evaluate the impact of dried aqueous extracts from common thyme ( Thymus vulgaris L.) (ExTv), wild thyme ( Thymus serpyllum L.) (ExTs), sweet marjoram ( Origanum majorana L.) (ExOm), and peppermint ( Mentha × piperita L.) (ExMp), as well as (poly)phenolic compounds: caffeic acid (CA), rosmarinic acid (RA), lithospermic acid (LA), luteolin-7-O-β-glucuronide (Lgr), luteolin-7-O-rutinoside (Lr), eriodictyol-7-O-rutinoside (Er), and arbutin (Ab), on unstimulated Jurkat cells, in comparison with their effect on staurosporine-stimulated Jurkat cells. Jurkat T cells were incubated with different concentrations of ExTv, ExTs, ExOm, ExMp, Lgr, LA, Er, Lr, RA, CA, or Ab. Subsequently, staurosporine was added to half of the samples and flow cytometry combined with fluorescence-activated cell sorting analysis was conducted, which allowed for the selection of early and late apoptotic cells. Both ExTs and ExOm stimulated apoptosis of Jurkat cells and enhanced the proapoptotic effect of staurosporine. Conversely, ExTv and ExMp demonstrated no clear effect on apoptosis. CA and RA raised the staurosporine-induced apoptotic effect. The impact of Er and Lgr on Jurkat cells showed fluctuations depending on the compound concentration. Neither Er nor Ab altered staurosporine-induced apoptosis in Jurkat cells, whereas Lgr seemed to weaken the proapoptotic action of staurosporine. The most evident observation in this study was the pro-apoptotic action of ExTs and ExOm observed both in staurosporine-unstimulated and stimulated Jurkat cells. Additionally, an enhancement of staurosporine-induced apoptosis by caffeic and rosmarinic acids was reported. Therefore, it might be concluded that these are the mixtures of biologically active polyphenols which often exert more pronounced beneficial effects than purified molecules., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Berdowska, Zieliński, Matusiewicz and Fecka.)

Self-supervised methods gain more and more attention, especially in the medical domain, where the number of labeled data is limited. They provide results on par or superior to their fully supervised competitors, yet the difference between information coded by both methods is unclear. This work introduces a novel comparison framework for explaining differences between supervised and self-supervised models using visual characteristics important to the human perceptual system. We apply this framework to models trained for Gleason score and conclude that self-supervised methods are more biased toward contrast and texture transformation than their supervised counterparts. At the same time, supervised methods code more information about the shape.

In the food industry, there are many varieties of technical blades with different contours as well as different cutting edge geometries. The evaluation of the ability of technical blades to separate (cut) animal tissues is not a simple task and is usually based on the evaluation of the cutting effects in a technological process. This paper presents a methodology for evaluating the cutting force of technical blades used in food processing. A specially made test stand with numerical control was used in the study. Its application enabled a comparison of cutting force values for four different cutting edge geometries of planar knives used in the skinning operation of flat fishes. A unique feature of the conducted research was the use of a relatively high cutting speed value of v f = 214 mm/s, which corresponded to the real conditions of this process carried out in the industry. Obtained test results allow unambiguously choosing the most advantageous variant of knife geometry from among four different variants used for the tests. The results showed a clear relationship between the cutting force value and the value of the tip angle of the blades tested: for blades with the lowest tip angle, the lowest cutting force values were obtained.

In the modern fish processing industry, flat fishes play an important role. They are processed into a final product in the form of a fillet during the skinning operation, which is carried out on machines operating in automated production lines. These machines are usually equipped with a single planar cutting blade or a few of such blades. The high-efficiency skinning and industrial conditions cause rapid wear of the cutting edge of the blade, which is detrimental to the quality of the final product. One of the forms of renewing the cutting ability of these types of tools is the regeneration carried out with the use of precise traverse surface grinding. The results of this process must be carefully verified for determining its correctness and possible optimization of its parameters. The main goal of this article was to characterize the usefulness of a number of observational and measuring methods to evaluate the results of the technical blade regeneration process. In this work, a number of contemporary observation-measurement methods such as optical microscopy (OM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), optical profilometry (OP), and angle-resolved scattering (ARS), supported by image processing and analysis techniques, were analyzed. The authors focused on presenting the role of the abovementioned methods in the surface characterization of planar cutting blades made of X39Cr13 chromium martensitic stainless steel before and after the technological operation of flat-fish skinning. Additionally, the surface condition after the regeneration process carried out using the five-axis CNC (computerized numerical control) grinding machine was also assessed. Numerous results of surface observations, elemental composition microanalysis, high-accuracy surface microgeometry measurements, and quantitative and qualitative analysis confirming the possibility of using the proposed methods in the presented applications are presented.

Preliminary diagnosis of fungal infections can rely on microscopic examination. However, in many cases, it does not allow unambiguous identification of the species due to their visual similarity. Therefore, it is usually necessary to use additional biochemical tests. That involves additional costs and extends the identification process up to 10 days. Such a delay in the implementation of targeted therapy may be grave in consequence as the mortality rate for immunosuppressed patients is high. In this paper, we apply a machine learning approach based on deep neural networks and bag-of-words to classify microscopic images of various fungi species. Our approach makes the last stage of biochemical identification redundant, shortening the identification process by 2-3 days, and reducing the cost of the diagnosis., Competing Interests: Two of the authors, Bartosz Zieliński (BZ) and Dawid Rymarczyk (DR), are employed by a commercial company Ardigen. Ardigen provided support in the form of salaries for authors BZ and DR. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Terrestrial isopods have evolved pleopodal lungs that provide access to the rich aerial supply of oxygen. However, isopods occupy conditions with wide and unpredictable thermal and oxygen gradients, suggesting that they might have evolved adaptive developmental plasticity in their respiratory organs to help meet metabolic demand over a wide range of oxygen conditions. To explore this plasticity, we conducted an experiment in which we reared common rough woodlice (Porcellio scaber) from eggs to maturation at different temperatures (15 and 22 °C) combined with different oxygen levels (10% and 22% O 2 ). We sampled animals during development (only females) and then examined mature adults (both sexes). We compared woodlice between treatments with respect to the area of their pleopod exopodites (our proxy of lung size) and the shape of Bertalanffy's equations (our proxy of individual growth curves). Generally, males exhibited larger lungs than females relative to body size. Woodlice also grew relatively fast but achieved a decreased asymptotic body mass in response to warm conditions; the oxygen did not affect growth. Under hypoxia, growing females developed larger lungs compared to under normoxia, but only in the late stage of development. Among mature animals, this effect was present only in males. Woodlice reared under warm conditions had relatively small lungs, in both developing females (the effect was increased in relatively large females) and among mature males and females. Our results demonstrated that woodlice exhibit phenotypic plasticity in their lung size. We suggest that this plasticity helps woodlice equilibrate their gas exchange capacity to differences in the oxygen supply and metabolic demand along environmental temperature and oxygen gradients. The complex pattern of plasticity might indicate the effects of a balance between water conservation and oxygen uptake, which would be especially pronounced in mature females that need to generate an aqueous environment inside their brood pouch., Competing Interests: Declaration of competing interest The authors declare no conflicting interests., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Paraoxonase 1 (PON1) is an enzyme with the capability to protect against lipid oxidation and atherosclerotic lesions formation. Impaired antioxidative capacity and enhanced lipid peroxidation (reflected by malondialdehyde rise) accompany dementias., Objectives: The aim of this study was to discern the possible differences in the activity and phenotype distribution of PON1, and lipid peroxidation level in dementias of neurodegenerative and vascular pathology, to assess whether they reflect structural changes in the brain, and to evaluate their potential as dementia markers., Material and Methods: Paraoxonase 1 arylesterase activity and polymorphisms (dual-substrate method), and malondialdehyde/thiobarbituric acid reactive substances (MDA/TBARS) levels were determined spectrophotometrically in 257 serum samples derived from 136 dementive patients (with Alzheimer's disease (AD; n = 63), vascular dementia (VaD; n = 40) and mixed-type dementia (MD; n = 33), as well as from 121 non-dementive individuals. The results were analyzed with reference to dementia type and severity (assessed with Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scales), structural brain changes (estimated with magnetic resonance imaging (MRI) - Global Cortical Atrophy (GCA), Medial Temporal lobe Atrophy (MTA) and Fazekas scales)) and brain ischemia (Hachinski Ischemic Scale (HIS) index), and evaluated using receiver operating characteristic (ROC) analysis., Results: Malondialdehyde/thiobarbituric acid reactive substances were increased in dementia (more in VaD than AD). In patients with vascular involvement, MDA/TBARS elevation reflected a degree of global cortical atrophy. Paraoxonase 1 activity was decreased in patients with dementia, especially in patients with severe cognitive deficits. In VaD, a drop in PON1 reflected a degree of MTA and brain ischemia. MDA/TBARS displayed 75% accuracy as a general dementia marker, but, similarly to PON1, were a poor differential marker., Conclusions: Both indices were more associated with vascular involvement and the severity of brain atrophy or ischemia rather than with degree of cognitive decline.

Hepcidin is a peptide hormone regulating iron metabolism, the dyshomeostasis of which has been implicated in dementia. Yet, data on hepcidin status in dementia are scanty, limited to Alzheimer's disease (AD) and inconsistent due to methodological problems with its determination using immunoassays and/or lack of homogeneity of evaluated groups. Hepcidin association with vascular dementia (VaD) remains unknown. We proposed a mass spectrometry method of hepcidin quantification in sera and aimed at determining hepcidin systemic status in patients with dementia of AD, VaD, or mixed (MD) pathology, with reference to the degree of cognitive loss and structural changes in the brain as well as at evaluating the diagnostic potential of hepcidin as a biomarker. We found that hepcidin concentrations were significantly elevated in VaD and insignificantly so in AD or MD and that they positively correlated with the Clinical Dementia Rating and inversely with the Mini Mental State Examination. Hepcidin tended to be more pronouncedly elevated in patients with advanced cortical atrophy and white matter lesions. It displayed a biphasic relationship with the Hachinski Ischemic Scale and a good accuracy as dementia but not differential marker. Taken together, our results demonstrated that dementia of vascular and not neurodegenerative pathology is associated with significant elevation of systemic hepcidin. Hepcidin elevation reflects the degree of cognitive loss as well as the severity of structural changes in the brain. If confirmed in a prospective study, hepcidin quantification may hold promise as a diagnostic marker; its accuracy as a differential marker of VaD is insufficient., (Copyright © 2019 Elsevier Inc. All rights reserved.)

An application of FTIR spectroscopic imaging for the identification and visualization of early micrometastasis from breast cancer to lungs in a murine model is shown. Spectroscopic and histological examination is focused on lung cross-sections derived from animals at the early phase of metastasis (early micrometastasis, EM) as compared to healthy control (HC) and late phase of metastasis (advanced macrometastasis, AM) using murine model of metastatic breast cancer with 4T1 cells orthotopically inoculated. FTIR imaging allows for a detailed, objective and label-free differentiation and visualization of EM foci including large and small micrometastases as well as single cancer cells grouped in clusters. An effect of the EM phase on the entire lung tissue matrix as well as characteristic biochemical profiles for HC and advanced macrometastasis were determined from morphological and spectroscopic points of view. The extraordinary sensitivity of FTIR imaging toward EM detection and discrimination of AM borders confirms its applicability as a complementary tool for the histopathological assessment of the metastatic cancer progression., (Copyright © 2018. Published by Elsevier B.V.)

In microbiology it is diagnostically useful to recognize various genera and species of bacteria. It can be achieved using computer-aided methods, which make the recognition processes more automatic and thus significantly reduce the time necessary for the classification. Moreover, in case of diagnostic uncertainty (the misleading similarity in shape or structure of bacterial cells), such methods can minimize the risk of incorrect recognition. In this article, we apply the state of the art method for texture analysis to classify genera and species of bacteria. This method uses deep Convolutional Neural Networks to obtain image descriptors, which are then encoded and classified with Support Vector Machine or Random Forest. To evaluate this approach and to make it comparable with other approaches, we provide a new dataset of images. DIBaS dataset (Digital Image of Bacterial Species) contains 660 images with 33 different genera and species of bacteria.

The aim of this study was to evaluate the cytotoxicity of dried aqueous extracts from Thymus serpyllum (ExTs), Thymus vulgaris (ExTv), Majorana hortensis (ExMh), and Mentha piperita (ExMp), and the phenolic compounds caffeic acid (CA), rosmarinic acid (RA), lithospermic acid (LA), luteolin-7-O-glucuronide (Lgr), luteolin-7-O-rutinoside (Lr), eriodictiol-7-O-rutinoside (Er), and arbutin (Ab), on two human breast cancer cell lines: Adriamycin-resistant MCF-7/Adr and wild-type MCF-7/wt. In the MTT assay, ExMh showed the highest cytotoxicity, especially against MCF-7/Adr, whereas ExMp was the least toxic; particularly against MCF-7/wt cells. RA and LA exhibited the strongest cytotoxicity against both MCF-7 cell lines, over 2-fold greater than CA and Lgr, around 3-fold greater than Er, and around 4- to 7-fold in comparison with Lr and Ab. Except for Lr and Ab, all other phytochemicals were more toxic against MCF-7/wt, and all extracts exhibited higher toxicity against MCF-7/Adr. It might be concluded that the tested phenolics exhibited more beneficial properties when they were applied in the form of extracts comprising their mixtures., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Photofrin-mediated PDT was applied to malignant (A549 and MCF-7) and normal (HUV-EC-C) cells. The cells were incubated for different lengths of time after PDT. The cell responses to the therapy were examined by changes in SOD activity, phototoxicity, and mode of the cell death. PDT induced dynamic changes in SOD activity. Initially, an increase in SOD activity was observed, and after 6 hours of culture it decreased to the control level. Results obtained from MTT and the comet assay indicate that PDT caused immediate cell death via apoptosis in the A549, MCF-7, and HUV-EC-C cell lines. Our studies confirm that SOD is involved in the response of both cancer and normal cells to PDT.

Glyceraldehyde-3-phosphate dehydrogenase is a glycolytic enzyme that catalyses conversion of glyceraldehyde-3-phosphate to 1,3-diphosphoglycerate. ATP has been found to have an inhibitory effect on this enzyme. To establish the interaction between the enzyme and ATP, a fluorescence technique was used. Fluorescence quenching in the presence of ATP suggests cooperative binding of ATP to the enzyme (the Hill obtained coefficient equals 2.78). The interaction between glyceraldehyde-3-phosphate dehydrogenase and ATP may control not only glycolysis but other activities of this enzyme, such as binding to the cytoskeleton.

Two subtypes of angiotensin II receptors have been characterised so far: AT1 and AT2. In PC12W pheochromocytoma cells, only AT2 receptors have been found (acting probably through G1 proteins or via G protein-independent mechanism). Here, dynamic changes in phosphorylation pattern in PC12W cells upon induction of angiotensin II and under influence of redox agents were investigated. PC12W pheochromocytoma cell line was preincubated with angiotensin II, then incubated with redox agents. After lysis the cells were subjected to Western-Blotting technique with antiphosphotyrosine and anti-ERK2 antibodies, as well as phosphotyrosine phosphatases and kinases activity was measured. Angiotensin II through its AT2 receptor induced dephosphorylation of tyrosines of the proteins in the range of 60 to 150 kD in PC12W cells. The obtained phosphorylation pattern suggests that AT2 receptors may act comparably to leukocyte CD45 receptor pathway. Treatment of PC12W cells with H2O2 resulted in significant decrease in phosphotyrosine phosphatases activity. It could be assumed that signal transduction based on protein phosphorylation might be controlled by cellular redox mechanisms.

We have previously documented amelioration of rat autologous anti-GBM nephritis with the antiproteolytic drugs epsilon-aminocaproic acid (EACA) and aprotinin, given from the day of induction or later in the course of disease. In the present study we investigated potential mechanisms of this effect by assessing interactions of the drugs with proteinase-dependent generation of superoxide anion in glomeruli, and their influence on both GBM degradation in vitro and activity of glomerular proteolytic enzymes. Release of O2- by enzymatically disrupted glomeruli, isolated from nephritic control or EACA/aprotinin-treated rats, was measured with the ferricytochrome reduction method and its activity was correlated with proteinuria and glomerular cellularity at the early phase of the disease. The hydroxyproline release assay was used to quantitate degradation of rat GBM in vitro by leukocyte proteinases stimulated by phorbol myristate acetate (PMA), in the presence or absence of EACA and aprotinin. Finally, the activities of elastase, cathepsins B and L, and plasmin, together with collagenase-like activity, were assessed fluorimetrically in homogenates of glomeruli isolated from control and antiproteolytic-drug-treated nephritic rats. EACA and aprotinin notably inhibited production of superoxide by nephritic glomeruli (by 47% and 66%, respectively), and this effect was not significantly correlated with proteinuria or glomerular hypercellularity at the early stage of disease. On the other hand, generation of O2- by glomeruli of untreated nephritic rats was notably correlated with total glomerular cell counts and numbers of macrophages infiltrating glomeruli. PMA-stimulated neutrophils and macrophages caused degradation of isolated rat GBM in vitro, markedly attenuated in the presence of EACA (P<0.0005) and, to a lesser extent, by addition of aprotinin (P<0.01). The activity of elastase was significantly reduced in glomeruli of nephritic rats treated with EACA or aprotinin (both P<0.001), while activities of remaining proteinases were not appreciably affected. The beneficial influence of proteinase inhibitors on rat anti-GBM disease may be due, at least in part, to abrogation of superoxide generation in nephritic glomeruli. EACA and aprotinin also have potential to interfere with digestion of GBM, and both these effects may be related to suppression of glomerular elastase.