Upon first exposure to cetuximab, hypersensitivity reactions can occur. We aimed to assess the utility of the basophil activation test (BAT) to alpha-gal and cetuximab for predicting severe ...reactions. We prospectively recruited 38 patients and evaluated sIgE to alpha-gal in all patients before the first application of cetuximab. In all alpha-gal-sensitized patients, we evaluated skin tests to meat extracts, gelatine, and cetuximab and performed BAT with alpha-gal and cetuximab. In 24% (9/38) of patients, sIgE to alpha-gal was >0.10 kUA/L, and 8/9 reacted to the cetuximab. Basophil activation tests with alpha-gal were positive in all sensitized patients and were higher in those with severe reactions (18.3% in grade 4 n = 4 vs. 1.8% in grade 2 n = 3 or no reaction n = 1 at 3.3 ng/mL of alpha-gal; p = 0.03). All patients with severe grade 4 reactions had a positive CD63 BAT response to cetuximab compared to patients with moderate or no reaction, who all had negative BAT (57.7% vs. 0.9% at 500 µg/mL, 63.2% vs. 4.1% at 100 µg/mL, 58.2% vs. 2.7% at 10 µg/mL, and 32.1% vs. 3.3% at 1 µg/mL of cetuximab, respectively; p ≤ 0.001). In summary, before initiating cetuximab treatment, sIgE to alpha-gal should be assessed in all patients. To predict the severity of the reaction and to assess the risk of cetuximab-induced anaphylaxis, we should perform BATs with alpha-gal or more discriminative BATs with cetuximab.
The environment in swimming pools, which contain chlorine, might interact with the airway epithelium, resulting in oxidative stress and/or inflammation during high intensity training periods.
We ...evaluated pulmonary functional (metacholine challenge test, FEV1 and VC), cellular (eosinophils and neutrophils), inflammatory (FeNo, IL-5, IL-6, IL-8 and TNF-α), oxidative (8-isoprostanes) and angiogenesis factors (VEGF) in induced sputum and peripheral blood of 41 healthy non-asthmatic elite swimmers (median 16 years) during the period of high intensity training before a national championship. The second paired sampling was performed seven months later after training had been stopped for one month.
There was a ten-fold increase (median 82–924 pg/ml; P < 0.001) in 8-isoprostanes in induced sputum and five-fold increase (median 82–924 pg/ml; P < 0.001) in sera during training in comparison to the period of rest. However, there was no difference in FEV1 (113 vs 116%), VC (119 vs 118%), FeNo (median 34 vs 38 ppb), eosinophils (2.7 vs 2.9% in sputum; 180 vs 165 cells/μl in blood), neutrophils, different cytokines or VEGF in induced sputum or sera. The only exception was TNF-α, which was moderately increased in sera (median 23 vs 40 pg/ml; P = 0.02) during the peak training period. Almost half (18 of 41) of swimmers showed bronchial hyperresponsiveness during the peak training period (PC20 cutoff was 4 mg/ml). There was no correlation between hyperresponsiveness and the markers of oxidative stress or inflammation.
High intensity training in healthy, non-asthmatic competitive swimmers results in marked oxidative stress at the airway and systemic levels, but does not lead to airway inflammation. However, we could not confirm that oxidative stress is associated with bronchial hyperresponsiveness (AHR), which is often observed during the peak exercise training period.
•Competitive swimmers have marked oxidative stress at the airway and systemic levels but without concomitant inflammation.•Almost half of healthy non-asthmatic competitive swimmers have bronchial hyperresponsiveness in the peak training season.•However, we could not confirm that oxidative stress is associated with bronchial hyperresponsiveness (AHR).
Purpose: Pulmonary rehabilitation programs (PR) are an important part of the comprehensive treatment of patients with chronic pulmonary diseases. Patients respond individually to PR. The aim of this ...study is to identify potential predictors of success of PR to recognise patients who benefit most and to uncover possible reasons for poor response to PR. Patients and Methods: We included 121 patients with chronic obstructive pulmonary disease (COPD) who completed our 4-week inpatient PR without any exacerbations of disease during PR that could potentially affect PR outcomes. Improvement in distance of greater than or equal to 30 m on the 6-minute walk test (6MWT) after PR was chosen as a primary marker of physical success. Ninety-one patients achieved improvement of greater than or equal to 30 m on the 6MWT and were thus considered good responders, and 30 patients were poor responders with improvement in the distance of <30 m on the 6MWT. Results: We compared baseline clinical characteristics, medication, lung function, physical capacity, body composition, and laboratory blood tests between groups of good and poor responders. The most prominent differences between groups were associated with differences in baseline body composition and erythrocyte-related parameters. Good responders had significantly lower body water content (p = 0.042) and higher body weight (p = 0.036), body fat content (p = 0.049), dry lean mass (p = 0.021), haemoglobin levels (p = 0.040), erythrocyte count (p = 0.017), haematocrit (p = 0.030) and iron level (p = 0.028). Conclusion: A more muscular body composition and a higher ability to transport oxygen from the blood to the muscles could be beneficial for the outcome of PR. Plain Language Summary: Pulmonary rehabilitation programs (PR) are important part of management of patients with chronic obstructive pulmonary diseases and other chronic pulmonary diseases. Nevertheless, PR are sparsely available to patients, and patients respond to PR individually. Our study will help identify patients who benefit most from PR and find possible reasons why the physical condition of some patients does not improve with PR. Only patients with chronic obstructive pulmonary disease who completed inpatient pulmonary rehabilitation program without any exacerbations of disease that could potentially affect PR outcomes were included in this study to determine what baseline patient characteristics could predict good and poor responders to PR. The results of our study suggest that a more muscular body composition and a higher ability to transport oxygen from the blood to the muscles could be beneficial to the outcome of PR. We suggest that before sarcopenic or anaemic patients are referred for PR, special care should first be taken to address and remedy their condition to maximise their physical gain in PR. Keywords: pulmonary rehabilitation, COPD, predictors, responders
In this paper, we propose an extension of a recently proposed Deep Statistical Comparison (DSC) approach, called practical Deep Statistical Comparison (pDSC), which takes into account practical ...significance when making a statistical comparison of meta-heuristic stochastic optimization algorithms for single-objective optimization. For achieving practical significance, two variants of the standard DSC ranking scheme are proposed. The first is called sequential pDSC, and takes into account practical significance by preprocessing of the independent optimization runs in a sequential order. The second is called Monte Carlo pDSC, and avoids any dependency of practical significance with regard to the ordering of optimization runs. The analysis of identifying practical significance on benchmark tests for single-objective problems, shows that for some cases, both variants of pDSC compared to the Chess Rating System for Evolutionary Algorithms (CRS4EAs) approach give different conclusions. Preprocessing for practical significance is carried out in a similar way, but there are cases when the conclusion for practical significance differ, which comes from the different statistical concepts used to identify practical significance.
•A statistical methodology for identifying practical significance.•Two ranking schemes working/dealing with practical significance.•The proposed methodology outperforming state-of-the-art approaches.
Evolutionary computation has been widely used in computer science for decades. Even though it started as far back as the 1960s with simulated evolution, the subject is still evolving. During this ...time, new metaheuristic optimization approaches, like evolutionary algorithms, genetic algorithms, swarm intelligence, etc., were being developed and new fields of usage in artificial intelligence, machine learning, combinatorial and numerical optimization, etc., were being explored. However, even with so much work done, novel research into new techniques and new areas of usage is far from over. This book presents some new theoretical as well as practical aspects of evolutionary computation. This book will be of great value to undergraduates, graduate students, researchers in computer science, and anyone else with an interest in learning about the latest developments in evolutionary computation.
Besides the numerous studies in the last decade involving food and nutrition data, this domain remains low resourced. Annotated corpuses are very useful tools for researchers and experts of the ...domain in question, as well as for data scientists for analysis. In this paper, we present the annotation process of food consumption data (recipes) with semantic tags from different semantic resources—Hansard taxonomy, FoodOn ontology, SNOMED CT terminology and the FoodEx2 classification system. FoodBase is an annotated corpus of food entities—recipes—which includes a curated version of 1000 instances, considered a gold standard. In this study, we use the curated version of FoodBase and two different approaches for annotating—the NCBO annotator (for the FoodOn and SNOMED CT annotations) and the semi-automatic StandFood method (for the FoodEx2 annotations). The end result is a new version of the golden standard of the FoodBase corpus, called the CafeteriaFCD (Cafeteria Food Consumption Data) corpus. This corpus contains food consumption data—recipes—annotated with semantic tags from the aforementioned four different external semantic resources. With these annotations, data interoperability is achieved between five semantic resources from different domains. This resource can be further utilized for developing and training different information extraction pipelines using state-of-the-art NLP approaches for tracing knowledge about food safety applications.
The association between Hymenoptera venom‐triggered anaphylaxis (HVA) and clonal mast cell‐related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood ...screening for KIT p.D816V missense variant have revealed the true extent of this clinical association whilst adding to our understanding of the underlying aetiology. Thus, recent large studies highlighted the presence of KIT p.D816V among 18.2% and 23% of patients with severe Hymenoptera venom‐triggered anaphylaxis. A significant proportion of those patients have normal serum basal tryptase (BST) levels, with no cutaneous findings such as urticaria pigmentosa or other systemic findings such as organomegaly that would have suggested the presence of cMCD. These findings of an increased prevalence suggest that the impact of cMCD on anaphylaxis could be clinically underestimated and that the leading question for clinicians could be changed from ‘how many patients with cMCD have anaphylaxis?’ to ‘how many patients with anaphylaxis have cMCD?’. The discovery of hereditary α‐tryptasemia (HαT)—a genetic trait caused by an increased copy number of the Tryptase Alpha/Beta 1 (TPSAB1) gene‐, first described in 2016, is now known to underlie the majority of cases of elevated BST outside of cMCD and chronic kidney disease. HαT is the first common heritable genetic modifier of anaphylaxis described, and it is associated with increased risk for severe HVA (relative risk = 2.0), idiopathic anaphylaxis, and an increased prevalence of anaphylaxis in patients with cMCD, possibly due to the unique activity profile of α/β ‐tryptase heterotetramers that may potentiate immediate hypersensitivity reaction severity. Our narrative review aims to highlight recent research to have increased our understanding of cMCD and HαT, through recent lessons learned from studying their association with HVA. Additionally, we examined the studies of mast cell‐related disorders in food and drug allergy in an effort to determine whether one should also consider cMCD and/or HαT in cases of severe anaphylaxis triggered by food or drugs.
Non‐clonal mast cell disease, hereditary alpha‐tryptasemia, and anaphylaxis. Hereditary alpha‐tryptasemia (HαT) is strongly associated with clonal mast cell disease (cMCD). Either of those conditions alone is a predisposing factor for severe IgE‐dependent and IgE‐independent anaphylaxis however, the presence of HαT in patients with cMCD serves to further increase the severity of anaphylactic reactions.
Previous reports suggest the usefulness of basophil activation testing (BAT) in Hymenoptera-allergic patients with negative venom-specific IgE antibodies. We sought to evaluate the diagnostic utility ...of this testing in a routine clinical laboratory setting.
Twenty-one patients with anaphylactic reactions to Hymenoptera sting (median grade III) and negative venom-specific IgE were routinely and prospectively tested with BAT.
We were able to diagnose 81% (17 of 21) of patients with BAT and 57% (12 of 21) with intradermal skin testing. Three wasp venom-allergic patients showed IgE positivity to rVes v 5. Four patients (19%) were negative for all tests. In the case of double-positive BAT, the culprit insect correlated with the venom that induced a significantly higher basophil response.
BAT allows the identification of severe Hymenoptera-allergic patients with negative specific IgE and skin tests. The routine use of this cellular test should facilitate prescription of venom immunotherapy in complex cases with inconclusive diagnostic results.
This paper identifies the requirements for computer-supported food matching, in order to address not only national and European but also international current related needs and represents an ...integrated research contribution of the FP7 EuroDISH project. The available classification and coding systems and the specific problems of food matching are summarized and a new concept for food matching based on optimization methods and machine-based learning is proposed. To illustrate and test this concept, a study has been conducted in four European countries (i.e., Germany, The Netherlands, Italy and the UK) using different classification and coding systems. This real case study enabled us to evaluate the new food matching concept and provide further recommendations for future work. In the first stage of the study, we prepared subsets of food consumption data described and classified using different systems, that had already been manually matched with national food composition data. Once the food matching algorithm was trained using this data, testing was performed on another subset of food consumption data. Experts from different countries validated food matching between consumption and composition data by selecting best matches from the options given by the matching algorithm without seeing the result of the previously made manual match. The evaluation of study results stressed the importance of the role and quality of the food composition database as compared to the selected classification and/or coding systems and the need to continue compiling national food composition data as eating habits and national dishes still vary between countries. Although some countries managed to collect extensive sets of food consumption data, these cannot be easily matched with food composition data if either food consumption or food composition data are not properly classified and described using any classification and coding systems. The study also showed that the level of human expertise played an important role, at least in the training stage. Both sets of data require continuous development to improve their quality in dietary assessment.
Uroplakins, cytokeratins and the apical plasma membrane were studied in the epithelia of mouse urinary tract. In the simple epithelium covering the inner medulla of the renal pelvis, no uroplakins or ...cytokeratin 20 were detected and cells had microvilli on their apical surface. The epithelium covering the inner band of the outer medulla became pseudostratified, with the upper layer consisting of large cells with stalks connecting them to the basal lamina. Uroplakins and cytokeratin 20 were not expressed in these cells. However, some superficial cells appeared without connections to the basal lamina; these cells expressed uroplakins Ia, Ib, II and III and cytokeratin 20, they contained sparse small uroplakin-positive cytoplasmic vesicles and their apical surface showed both microvilli and ridges. Cytokeratin 20 was seen as dots in the cytoplasm. This epithelium therefore showed partial urothelial differentiation. The epithelium covering the outer band of the outer medulla gradually changed from a two-layered to a three-layered urothelium with typical umbrella cells that contained all four uroplakins. Cytokeratin 20 was organized into a complex network. The epithelium possessed an asymmetric unit membrane at the apical cell surface and fusiform vesicles. Umbrella cells were also observed in the ureter and urinary bladder. In males and females, the urothelium ended in the bladder neck and was continued by a non-keratinized stratified epithelium in the urethra in which no urothelial cell differentiation markers were detected. We thus show here the expression, distribution and organization of specific proteins associated with the various cell types in the urinary tract epithelium.
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