17 results on '"Santos, Alexandra F"'
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2. Feast for thought: A comprehensive review of food allergy 2021-2023.
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Bartha, Irene, Almulhem, Noorah, and Santos, Alexandra F.
- Abstract
A review of the latest publications in food allergy over the past couple of years confirmed that food allergy is a major public health concern, affecting about 8% of children and 10% of adults in developed countries. The prevalence of food allergy varies around the world, with the increase being driven mainly by environmental factors, possibly together with genetic susceptibility to environmental changes. A precise diagnosis of food allergy is extremely important. Both new tests (eg, the basophil activation test) and improved optimization of information provided by existing tests (eg, the skin prick test and measurement of specific IgE level) can contribute to improving the accuracy and patients' comfort of food allergy diagnosis. Understanding the underlying immune mechanisms is fundamental to designing allergen-specific treatments that can be safe and effective in the long term. New discoveries of the immune response to food allergens, including T-cell and B-cell responses, have emerged. Novel therapeutic approaches are being trialed at various stages of development as attempts to allow for more active intervention to treat food allergy. Prevention is key to reducing the increase in prevalence. Early introduction of allergenic foods seems to be the most effective intervention, but others are being studied, and will, it is hoped, lead to modification of the epidemiologic trajectory of food allergy over time. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Reply.
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Santos, Alexandra F., Evans, Ethan, O'Rourke, Colin, Bahnson, Henry T., and Lack, Gideon
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- 2022
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4. Biomarkers of severity and threshold of allergic reactions during oral peanut challenges.
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Santos, Alexandra F., Du Toit, George, O'Rourke, Colin, Becares, Natalia, Couto-Francisco, Natália, Radulovic, Suzana, Khaleva, Ekaterina, Basting, Monica, Harris, Kristina M., Larson, David, Sayre, Peter, Plaut, Marshall, Roberts, Graham, Bahnson, Henry T., and Lack, Gideon
- Abstract
Oral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity. Our aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut. We assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE, Arachis hypogaea 2–specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC. When a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of Arachis hypogaea 2–specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut in vitro. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients. The BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA. [ABSTRACT FROM AUTHOR]
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- 2020
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5. Defining challenge-proven coexistent nut and sesame seed allergy: A prospective multicenter European study.
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Brough, Helen A., Caubet, Jean-Christoph, Mazon, Angel, Haddad, Diab, Bergmann, Marcel M., Wassenberg, Jacqueline, Panetta, Valentina, Gourgey, Rosalynd, Radulovic, Suzana, Nieto, Maria, Santos, Alexandra F., Nieto, Antonio, Lack, Gideon, and Eigenmann, Philippe A.
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Peanut, tree nut, and sesame allergies are responsible for most life-threatening food-induced allergic reactions. Rates of coexistent allergy between these foods have been from mostly retrospective studies that include only a limited number of tree nuts or were not based on oral food challenges. The Pronuts study is a multicenter European study (London, Geneva, and Valencia) assessing the challenge-proven rate of coexistent peanut, tree nut, and/or sesame seed allergy. Children aged 0 to 16 years with at least 1 confirmed nut or sesame seed allergy underwent sequential diagnostic food challenges to all other nuts and sesame seed. Overall, the rate of coexistent peanut, tree nut, and sesame seed allergy was 60.7% (n = 74/122; 95% CI, 51.4% to 69.4%). Peanut allergy was more common in London, cashew and pistachio nut allergies were more common in Geneva, and walnut and pecan allergies were more common in Valencia. Strong correlations were found between cashew-pistachio, walnut-pecan, and walnut-pecan-hazelnut-macadamia clusters. Age (>36 months) and center (Valencia > Geneva > London) were associated with an increased odds of multiple nut allergies. By pursuing the diagnostic protocol to demonstrate tolerance to other nuts, participants were able to introduce a median of 9 nuts. We found a higher rate of coexistent nut and sesame seed allergies than previously reported. Performing sequential food challenges was labor intensive and could result in severe allergic reactions; however, it reduced dietary restrictions. Age was a significant predictor of multiple nut allergies, and thus the secondary spread of nut allergies occurred in older children. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Reply.
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Brough, Helen A., Caubet, Jean-Christoph, Mazon, Angel, Haddad, Diab, Bergmann, Marcel M., Wassenberg, Jacqueline, Panetta, Valentina, Gourgey, Rosalynd, Radulovic, Suzana, Nieto, Maria, Santos, Alexandra F., Nieto, Antonio, Lack, Gideon, and Eigenmann, Philippe A.
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- 2020
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7. IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens.
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Santos, Alexandra F., James, Louisa K., Bahnson, Henry T., Shamji, Mohammed H., Couto-Francisco, Natália C., Islam, Sabita, Houghton, Sally, Clark, Andrew T., Stephens, Alick, Turcanu, Victor, Durham, Stephen R., Gould, Hannah J., and Lack, Gideon
- Abstract
Background Most children with detectable peanut-specific IgE (P-sIgE) are not allergic to peanut. We addressed 2 non–mutually exclusive hypotheses for the discrepancy between allergy and sensitization: (1) differences in P-sIgE levels between children with peanut allergy (PA) and peanut-sensitized but tolerant (PS) children and (2) the presence of an IgE inhibitor, such as peanut-specific IgG 4 (P-sIgG 4 ), in PS patients. Methods Two hundred twenty-eight children (108 patients with PA, 77 PS patients, and 43 nonsensitized nonallergic subjects) were studied. Levels of specific IgE and IgG 4 to peanut and its components were determined. IgE-stripped basophils or a mast cell line were used in passive sensitization activation and inhibition assays. Plasma of PS subjects and patients submitted to peanut oral immunotherapy (POIT) were depleted of IgG 4 and retested in inhibition assays. Results Basophils and mast cells sensitized with plasma from patients with PA but not PS patients showed dose-dependent activation in response to peanut. Levels of sIgE to peanut and its components could only partially explain differences in clinical reactivity between patients with PA and PS patients. P-sIgG 4 levels ( P = .023) and P-sIgG 4 /P-sIgE ( P < .001), Ara h 1–sIgG 4 /Ara h 1–sIgE ( P = .050), Ara h 2–sIgG 4 /Ara h 2–sIgE ( P = .004), and Ara h 3–sIgG 4 /Ara h 3–sIgE ( P = .016) ratios were greater in PS children compared with those in children with PA. Peanut-induced activation was inhibited in the presence of plasma from PS children with detectable P-sIgG 4 levels and POIT but not from nonsensitized nonallergic children. Depletion of IgG 4 from plasma of children with PS (and POIT) sensitized to Ara h 1 to Ara h 3 partially restored peanut-induced mast cell activation ( P = .007). Conclusions Differences in sIgE levels and allergen specificity could not justify the clinical phenotype in all children with PA and PS children. Blocking IgG 4 antibodies provide an additional explanation for the absence of clinical reactivity in PS patients sensitized to major peanut allergens. [ABSTRACT FROM AUTHOR]
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- 2015
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8. Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children.
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Santos, Alexandra F., Douiri, Abdel, Bécares, Natalia, Wu, Shih-Ying, Stephens, Alick, Radulovic, Suzana, Chan, Susan M.H., Fox, Adam T., Du Toit, George, Turcanu, Victor, and Lack, Gideon
- Abstract
Background Most of the peanut-sensitized children do not have clinical peanut allergy. In equivocal cases, oral food challenges (OFCs) are required. However, OFCs are laborious and not without risk; thus, a test that could accurately diagnose peanut allergy and reduce the need for OFCs is desirable. Objective To assess the performance of basophil activation test (BAT) as a diagnostic marker for peanut allergy. Methods Peanut-allergic (n = 43), peanut-sensitized but tolerant (n = 36) and non–peanut-sensitized nonallergic (n = 25) children underwent skin prick test (SPT) and specific IgE (sIgE) to peanut and its components. BAT was performed using flow cytometry, and its diagnostic performance was evaluated in relation to allergy versus tolerance to peanut and validated in an independent population (n = 65). Results BAT in peanut-allergic children showed a peanut dose-dependent upregulation of CD63 and CD203c while there was no significant response to peanut in peanut-sensitized but tolerant ( P < .001) and non–peanut-sensitized nonallergic children ( P < .001). BAT optimal diagnostic cutoffs showed 97% accuracy, 95% positive predictive value, and 98% negative predictive value. BAT allowed reducing the number of required OFCs by two-thirds. BAT proved particularly useful in cases in which specialists could not accurately diagnose peanut allergy with SPT and sIgE to peanut and to Arah2. Using a 2-step diagnostic approach in which BAT was performed only after equivocal SPT or Arah2-sIgE, BAT had a major effect (97% reduction) on the number of OFCs required. Conclusions BAT proved to be superior to other diagnostic tests in discriminating between peanut allergy and tolerance, particularly in difficult cases, and reduced the need for OFCs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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9. Peanut protein in household dust is related to household peanut consumption and is biologically active.
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Brough, Helen A., Santos, Alexandra F., Makinson, Kerry, Penagos, Martin, Stephens, Alick C., Douiri, Abdel, Fox, Adam T., Du Toit, George, Turcanu, Victor, and Lack, Gideon
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Background: Peanut allergy is an important public health concern. To understand the pathogenesis of peanut allergy, we need to determine the route by which children become sensitized. A dose-response between household peanut consumption (HPC; used as an indirect marker of environmental peanut exposure) and the development of peanut allergy has been observed; however, environmental peanut exposure was not directly quantified. Objective: We sought to explore the relationship between reported HPC and peanut protein levels in an infant’s home environment and to determine the biological activity of environmental peanut. Methods: Peanut protein was quantified in wipe and dust samples collected from 45 homes with infants by using a polyclonal peanut ELISA. Environmental peanut protein levels were compared with peanut consumption assessed by using a validated peanut food frequency questionnaire and other clinical and household factors. Biological activity of peanut protein in dust was assessed with a basophil activation assay. Results: There was a positive correlation between peanut protein levels in the infant’s bed, crib rail, and play area and reported HPC over 1 and 6 months. On multivariate regression analysis, HPC was the most important variable associated with peanut protein levels in the infant’s bed sheet and play area. Dust samples containing high peanut protein levels induced dose-dependent activation of basophils in children with peanut allergy. Conclusions: We have shown that an infant’s environmental exposure to peanut is most likely to be due to HPC. Peanut protein in dust is biologically active and should be assessed as a route of possible early peanut sensitization in infants. [Copyright &y& Elsevier]
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- 2013
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10. Peanut diversity and specific activity are the dominant IgE characteristics for effector cell activation in children.
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Hemmings, Oliver, Niazi, Umar, Kwok, Matthew, James, Louisa K., Lack, Gideon, and Santos, Alexandra F.
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IgE mediates allergic reactions to peanut; however, peanut-specific IgE (sIgE) levels do not always equate to clinical peanut allergy. Qualitative differences between sIgE of peanut-sensitized but tolerant (PS) and peanut-allergic (PA) individuals may be important. We sought to assess the influence of IgE characteristics on effector cell activation in peanut allergy. A cohort of 100 children was studied. The levels of IgE to peanut and peanut components were measured. Specific activity (SA) was estimated as the ratio of allergen-sIgE to total IgE. Avidity was measured by ImmunoCAP with sodium thiocyanate. IgE diversity was calculated on the basis of ImmunoCAP-Immuno Solid-phase Allergen Chip assays for 112 allergens or for 6 peanut allergens. Whole-blood basophils and mast cell line Laboratory of Allergic Diseases 2 sensitized with patients' plasma were stimulated with peanut or controls and assessed by flow cytometry. SA to peanut (P <.001), Ara h 1 (P =.004), Ara h 2 (P <.001), Ara h 3 (P =.02), and Ara h 6 (P <.001) and the avidity of peanut-sIgE (P <.001) were higher in PA than in PS individuals. Diversity for peanut allergens was greater in PA individuals (P <.001). All IgE characteristics were correlated with basophil and mast cell activation. Peanut SA (R = 0.447) and peanut diversity (R = 0.440) had the highest standardized β -coefficients in combined multivariable regression models (0.447 and 0.440, respectively). IgE specificity, SA, avidity, and peanut diversity were greater in PA than in PS individuals. IgE peanut SA and peanut diversity had the greatest influence on effector cell activation and could be used clinically. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2021
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11. Ara h 2 is the dominant peanut allergen despite similarities with Ara h 6.
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Hemmings, Oliver, Du Toit, George, Radulovic, Suzana, Lack, Gideon, and Santos, Alexandra F.
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Arachis hypogaea 2 (Ara h 2)-specific IgE is to date the best serologic marker to diagnose peanut allergy. Ara h 6 shares approximately 60% sequence identity and multiple epitopes with Ara h 2. Our aim was to assess the diagnostic utility and relative importance of Ara h 2 and Ara h 6 in peanut allergy. A cohort 100 of children was studied. The cohort included chidren who had peanut allergy, children who were sensitized to but tolerant of peanut, and children who were neither sensitized nor allergic to peanut. Levels of specific IgE to peanut and individual allergens were quantified by using ImmunoCAP. ImmunoCAP inhibition experiments and mast cell activation tests in response to both Ara h 2 and Ara h 6 were performed. Statistical analyses were done using SPSS version 14 and Prism version 7 software. Ara h 2–specific IgE and Ara h 6–specific IgE showed the greatest diagnostic accuracy for peanut allergy when compared with specific IgE to peanut and other peanut allergens. Most patients with peanut allergy were sensitized to both Ara h 2 and Ara h 6. Ara h 2 reduced Ara h 2–specific IgE binding more than Ara h 6 did (P <.001), whereas Ara h 6–specific IgE binding was inhibited to a similar degree by Ara h 2 and Ara h 6 (P =.432). In the mast cell activation test, Ara h 2 induced significantly greater maximal reactivity (P =.001) and a lower half maximal effective concentration (P =.002) than did Ara h 6 when testing cosensitized individuals. Ara h 2–specific IgE and Ara h 6–specific IgE provide the greatest accuracy to diagnose peanut allergy. Ara h 2 is the dominant conglutin in peanut allergy in the United Kingdom, despite a degree of cross-reactivity with Ara h 6. [ABSTRACT FROM AUTHOR]
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- 2020
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12. Peanut oral immunotherapy induces blocking antibodies but does not change the functional characteristics of peanut-specific IgE.
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Santos, Alexandra F., James, Louisa K., Kwok, Matthew, McKendry, Richard T., Anagnostou, Katherine, Clark, Andrew T., and Lack, Gideon
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- 2020
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13. A novel human mast cell activation test for peanut allergy.
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Santos, Alexandra F., Couto-Francisco, Natália, Bécares, Natalia, Kwok, Matthew, Bahnson, Henry T., and Lack, Gideon
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- 2018
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14. “Auto-anti-IgE”: Naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation.
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Chan, Yih-Chih, Ramadani, Faruk, Santos, Alexandra F., Pillai, Prathap, Ohm-Laursen, Line, Harper, Clare E., Fang, Cailong, Dodev, Tihomir S., Wu, Shih-Ying, Ying, Sun, Corrigan, Christopher J., and Gould, Hannah J.
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Background Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood. Objective Address the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation. Methods IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FcεRI. Results IgG autoantibodies binding to both free and FcεRI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen. Conclusion Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma. [ABSTRACT FROM AUTHOR]
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- 2014
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15. Epitope Mapping The Peanut Panallergen Ara h 8.
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Hurlburt, Barry K., Cheng, Hsiaopo, Offermann, Lesa, Chruszcz, Maksymilian, Santos, Alexandra F., Lack, Gideon, and Maleki, Soheila J.
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- 2014
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16. Basophil Activation Test Discriminates Between Allergy and Tolerance Among Peanut Sensitized Children.
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Santos, Alexandra F., Bécares, Natalia, Wu, Shih-Ying, Radulovic, Suzana, Stephens, Alick, Turcanu, Victor, Du Toit, George, and Lack, Gideon
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- 2013
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17. Immune mechanisms of food allergy and its prevention by early intervention.
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Turcanu, Victor, Brough, Helen A, Du Toit, George, Foong, Ru-Xin, Marrs, Tom, Santos, Alexandra F, and Lack, Gideon
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FOOD allergy prevention , *IMMUNE response , *ANTIBODY formation , *IMMUNOGLOBULIN E , *IMMUNOGLOBULIN G - Abstract
The environmental factors driving the increase in food allergies are unclear and possibly involve dual exposure to allergens, microbiome-driven effects or other mechanisms. Until they can be better understood, early intervention aiming at establishing oral tolerance provides an effective way to decrease the window-of-risk when children may develop allergic sensitisation to foods due to the absence of a protective immune response. Thus, the recent LEAP (Learning Early About Peanut allergy) and LEAP-On studies achieved a high level of peanut allergy prevention by early introduction of peanuts in the infants diet and conveyed more information regarding the evolution of IgE and IgG4 antibody responses to food antigens over time. [ABSTRACT FROM AUTHOR]
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- 2017
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