To study the ways in which compounds can induce adverse effects, toxicologists have been constructing Adverse Outcome Pathways (AOPs). An AOP can be considered as a pragmatic tool to capture and visualize mechanisms underlying different types of toxicity inflicted by any kind of stressor, and describes the interactions between key entities that lead to the adverse outcome on multiple biological levels of organization. The construction or optimization of an AOP is a labor intensive process, which currently depends on the manual search, collection, reviewing and synthesis of available scientific literature. This process could however be largely facilitated using Natural Language Processing (NLP) to extract information contained in scientific literature in a systematic, objective, and rapid manner that would lead to greater accuracy and reproducibility. This would support researchers to invest their expertise in the substantive assessment of the AOPs by replacing the time spent on evidence gathering by a critical review of the data extracted by NLP. As case examples, we selected two frequent adversities observed in the liver: namely, cholestasis and steatosis denoting accumulation of bile and lipid, respectively. We used deep learning language models to recognize entities of interest in text and establish causal relationships between them. We demonstrate how an NLP pipeline combining Named Entity Recognition and a simple rules-based relationship extraction model helps screen compounds related to liver adversities in the literature, but also extract mechanistic information for how such adversities develop, from the molecular to the organismal level. Finally, we provide some perspectives opened by the recent progress in Large Language Models and how these could be used in the future. We propose this work brings two main contributions: 1) a proof-of-concept that NLP can support the extraction of information from text for modern toxicology and 2) a template open-source model for recognition of toxicological entities and extraction of their relationships. All resources are openly accessible via GitHub (https://github.com/ontox-project/en-tox).
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This research article shows that a high intensity exercise program compared to a low intensity exercise program of the same session duration and frequency, increases insulin sensitivity to a larger extend in healthy subjects. It also shows that the short insulin tolerance test can be used to detect differences in insulin sensitivity in intervention studies.
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Detection and identification of body fluids are crucial aspects of forensic investigations, aiding in crime scene reconstructions and providing important leads. Although many methods have been developed for these purposes, no method is currently in use in the forensic field that allows rapid, non-contact detection and identification of vaginal fluids directly at the crime scene. The development of such technique is mainly challenged by the complex chemistry of the constituents, which can differ between donors and exhibits changes based on woman’s menstrual cycle. The use of fluorescence spectroscopy has shown promise in this area for other biological fluids. Therefore, the aim of this study was to identify specific fluorescent signatures of vaginal fluid with fluorescence spectroscopy to allow on-site identification. Additionally, the fluorescent properties were monitored over time to gain insight in the temporal changes of the fluorescent spectra of vaginal fluid. The samples were excited at wavelengths ranging from 200 to 600 nm and the induced fluorescence emission was measured from 220 to 700 nm. Excitation and emission maps (EEMs) were constructed for eight donors at seven time points after donation. Four distinctive fluorescence peaks could be identified in the EEMs, indicating the presence of proteins, fluorescent oxidation products (FOX), and an unidentified component as the dominant contributors to the fluorescence. To further asses the fluorescence characteristics of vaginal fluid, the fluorescent signatures of protein and FOX were used to monitor protein and lipid oxidation reactions over time. The results of this study provide insights into the intrinsic fluorescent properties of vaginal fluid over time which could be used for the development of a detection and identification method for vaginal fluids. Furthermore, the observed changes in fluorescence signatures over time could be utilized to establish an accurate ageing model.
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Understanding taste is key for optimizing the palatability of seaweeds and other non-animal-based foods rich in protein. The lingual papillae in the mouth hold taste buds with taste receptors for the five gustatory taste qualities. Each taste bud contains three distinct cell types, of which Type II cells carry various G protein-coupled receptors that can detect sweet, bitter, or umami tastants, while type III cells detect sour, and likely salty stimuli. Upon ligand binding, receptor-linked intracellular heterotrimeric G proteins initiate a cascade of downstream events which activate the afferent nerve fibers for taste perception in the brain. The taste of amino acids depends on the hydrophobicity, size, charge, isoelectric point, chirality of the alpha carbon, and the functional groups on their side chains. The principal umami ingredient monosodium l-glutamate, broadly known as MSG, loses umami taste upon acetylation, esterification, or methylation, but is able to form flat configurations that bind well to the umami taste receptor. Ribonucleotides such as guanosine monophosphate and inosine monophosphate strongly enhance umami taste when l-glutamate is present. Ribonucleotides bind to the outer section of the venus flytrap domain of the receptor dimer and stabilize the closed conformation. Concentrations of glutamate, aspartate, arginate, and other compounds in food products may enhance saltiness and overall flavor. Umami ingredients may help to reduce the consumption of salts and fats in the general population and increase food consumption in the elderly.
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Boven titel staat vermeld: De symbiose van biologie en technologie. Zowel vanuit het Applied Science onderwijs als vanuit het werkveld kwam er meer vraag om biologische expertise toe te voegen aan het bestaande lectoraat Thin Films & Functional Materials.
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Implementation of reliable methodologies allowing Reduction, Refinement, and Replacement (3Rs) of animal testing is a process that takes several decades and is still not complete. Reliable methods are essential for regulatory hazard assessment of chemicals where differences in test protocol can influence the test outcomes and thus affect the confidence in the predictive value of the organisms used as an alternative for mammals. Although test guidelines are common for mammalian studies, they are scarce for non-vertebrate organisms that would allow for the 3Rs of animal testing. Here, we present a set of 30 reporting criteria as the basis for such a guideline for Developmental and Reproductive Toxicology (DART) testing in the nematode Caenorhabditis elegans. Small organisms like C. elegans are upcoming in new approach methodologies for hazard assessment; thus, reliable and robust test protocols are urgently needed. A literature assessment of the fulfilment of the reporting criteria demonstrates that although studies describe methodological details, essential information such as compound purity and lot/batch number or type of container is often not reported. The formulated set of reporting criteria for C. elegans testing can be used by (i) researchers to describe essential experimental details (ii) data scientists that aggregate information to assess data quality and include data in aggregated databases (iii) regulators to assess study data for inclusion in regulatory hazard assessment of chemicals.
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Er lijkt een duidelijke mate van evidentie te bestaan betreffende de relatie fysieke activiteit, respectievelijk fitheid en gezondheid in de algemene populatie en bij bepaalde pathologieën. Er is evenwel nog behoefte aan verder wetenschappelijk onderzoek naar mogelijke determinanten en onderliggende mechanismen, als ook naar evidentie bij bepaalde, specifieke aandoeningen. Tevens mag duidelijk zijn dat ondanks de bestaande evidentie fysieke activiteit/oefening te weinig toegepast wordt in de gezondheidszorg. Het onderzoek naar de effectiviteit van gezondheidskundige interventies is dan ook uitermate belangrijk. Dit lectoraat hoopt dan ook een bescheiden bijdrage hieraan te kunnen leveren. Hiervoor heeft zij reeds afspraken tot samenwerking met de academische en medische wereld (in Utrecht, Amsterdam, Maastricht en Leuven), met de gezondheidszorg (RIVM Bilthoven en GG&GD Utrecht) en met de beroepen- of bedrijfswereld (Politie regio Utrecht; Enraf Nonius, Delft). De beoogde doelstellingen zullen echter naar alle waarschijnlijkheid beduidend meer tijd in beslag nemen dan de periode van 4 jaar die de Stichting Kennis Ontwikkeling voorzien heeft met betrekking tot het oprichten en financieren van de lectoraten.
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Introduction: Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer. However, knowledge regarding the effects of exercise on immune markers in patients undergoing chemo- or radiotherapy is limited. The aim of this study is to systematically review the effects of moderate- and high-intensity exercise interventions in patients with cancer during chemotherapy or radiotherapy on immune markers. Methods: For this review, a search was performed in PubMed and EMBASE, until March 2023. Methodological quality was assessed with the PEDro tool and best-evidence syntheses were performed both per immune marker and for the inflammatory profile. Results: Methodological quality of the 15 included articles was rated fair to good. The majority of markers were unaltered, but observed effects included a suppressive effect of exercise during radiotherapy on some proinflammatory markers, a preserving effect of exercise during chemotherapy on NK cell degranulation and cytotoxicity, a protective effect on the decrease in thrombocytes during chemotherapy, and a positive effect of exercise during chemotherapy on IgA. Conclusion: Although exercise only influenced a few markers, the results are promising. Exercise did not negatively influence immune markers, and some were positively affected since suppressed inflammation might have positive clinical implications. For future research, consensus is needed regarding a set of markers that are most responsive to exercise. Next, differential effects of training types and intensities on these markers should be further investigated, as well as their clinical implications.
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Introduction: Strenuous physical stress induces a range of physiological responses, the extent depending, among others, on the nature and severity of the exercise, a person’s training level and overall physical resilience. This principle can also be used in an experimental set-up by measuring time-dependent changes in biomarkers for physiological processes. In a previous report, we described the effects of workload delivered on a bicycle ergometer on intestinal functionality. As a follow-up, we here describe an analysis of the kinetics of various other biomarkers. Aim: To analyse the time-dependent changes of 34 markers for different metabolic and immunological processes, comparing four different exercise protocols and a rest protocol. Methods: After determining individual maximum workloads, 15 healthy male participants (20–35 years) started with a rest protocol and subsequently performed (in a cross-over design with 1-week wash-out) four exercise protocols of 1-h duration at different intensities: 70% Wmax in a hydrated and a mildly dehydrated state, 50% Wmax and intermittent 85/55% Wmax in blocks of 2 min. Perceived exertion was monitored using the Borg’ Rating of Perceived Exertion scale. Blood samples were collected both before and during exercise, and at various timepoints up to 24 h afterward. Data was analyzed using a multilevel mixed linear model with multiple test correction. Results: Kinetic changes of various biomarkers were exercise-intensity-dependent. Biomarkers included parameters indicative of metabolic activity (e.g., creatinine, bicarbonate), immunological and hematological functionality (e.g., leukocytes, hemoglobin) and intestinal physiology (citrulline, intestinal fatty acid-binding protein, and zonulin). In general, responses to high intensity exercise of 70% Wmax and intermittent exercise i.e., 55/85% Wmax were more pronounced compared to exercise at 50% Wmax. Conclusion: High (70 and 55/85% Wmax) and moderate (50% Wmax) intensity exercise in a bicycle ergometer test produce different time-dependent changes in a broad range of parameters indicative of metabolic activity, immunological and hematological functionality and intestinal physiology. These parameters may be considered biomarkers of homeostatic resilience. Mild dehydration intensifies these time-related changes. Moderate intensity exercise of 50% Wmax shows sufficient physiological and immunological responses and can be employed to test the health condition of less fit individuals.
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Bitterness has been suggested to be the main reason for the limited palatability of several vegetables. Vegetable acceptance has been associated with preparation method. However, the taste intensity of a variety of vegetables prepared by differentmethods has not been studied yet. The objective of this study is to assess the intensity of the five basic tastes and fattiness of ten vegetables commonly consumed in the Netherlands prepared by different methods using the modified Spectrum method. Intensities of sweetness, sourness, bitterness, umami, saltiness and fattiness were assessed for ten vegetables (cauliflower, broccoli, leek, carrot, onion, red bell pepper, French beans, tomato, cucumber and iceberg lettuce) by a panel (n = 9) trained in a modified Spectrum method. Each vegetable was assessed prepared by different methods (raw, cooked, mashed and as a cold pressed juice). Spectrum based reference solutions were available with fixed reference points at 13.3 mm (R1), 33.3mm(R2) and 66.7mm(R3) for each tastemodality on a 100mmline scale. For saltiness, R1 and R3 differed (16.7 mm and 56.7 mm). Mean intensities of all taste modalities and fattiness for all vegetables were mostly below R1 (13.3 mm). Significant differences (p b 0.05) within vegetables between preparation methods were found. Sweetness was the most intensive taste, followed by sourness, bitterness, fattiness, umami and saltiness.In conclusion, all ten vegetables prepared by different methods showed low mean intensities of all taste modalities and fattiness. Preparation method affected taste and fattiness intensity and the effect differed by vegetable type.
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