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We report on the design, development, characterization, and a preliminary cellular evaluation of a novel solid material. This material is composed of low-molecular-weight hyaluronic acid (LMWHA) and polyarginine (PArg), which generate aqueous ionic nanocomplexes (INC) that are then freeze-dried to create the final product. Different ratios of LMWHA/PArg were selected to elaborate INC, the size and zeta potential of which ranged from 100 to 200 nm and +25 to −43 mV, respectively. Turbidimetry and nanoparticle concentration analyses demonstrated the high capacity of the INC to interact with increasing concentrations of LMWHA, improving the yield of production of the nanostructures. Interestingly, once the selected formulations of INC were freeze-dried, only those comprising a larger excess of LMWHA could form reproducible sponge formulations, as seen with the naked eye. This optical behavior was consistent with the scanning transmission electron microscopy (STEM) images, which showed a tendency of the particles to agglomerate when an excess of LMWHA was present. Mechanical characterization evidenced low stiffness in the materials, attributed to the low density and high porosity. A preliminary cellular evaluation in a fibroblast cell line (RMF-EG) evidenced the concentration range where swollen formulations did not affect cell proliferation (93−464 µM) at 24, 48, or 72 h. Considering that the reproducible sponge formulations were elaborated following inexpensive and non-contaminant methods and comprised bioactive components, we postulate them with potential for biomedical purposes. Additionally, this systematic study provides important information to design reproducible porous solid materials using ionic nanocomplexes.

The paper explores the literary expression of Slovak-Hungarian cultural and linguistic interactions in 21st-century Hungarian literature in Slovakia. It examines texts or text fragments that approach the issue from a linguistic perspective, or make visible the complexity of the interaction and its implications through the language of the literary text. Authors of Hungarian literature written in Slovakia use various strategies to represent the multicultural environment or to express the complexity of minority identity, which is not homogeneous, is marked by the interaction of cultures/languages/mentalities, and is confronted with the cultural and linguistic patterns of the majority. These textual strategies respond to Slovak-Hungarian contact from a contemporary minority perspective, showing parallels with the strategies of postcolonial literatures that articulate their particularity and peripheral position in relation to the “centre”, or to its codes and patterns. The analysed texts by Lajos Grendel, Péter Hunčík, Zoltán Szalay, Norbert György, and Pál Szász employ diverse strategies, all unified by a shared aim: to express distinct forms of minority identity through the language of literary text.

Adolescence is a stage of significant intrapersonal and interpersonal changes, influenced by cultural and historical shifts. This study aims to analyze the changes in heterosexual behaviors among adolescents in Western countries over the past 50 years approximately. For this purpose, we conducted a systematic review following the PRISMA model, utilizing the online databases EBSCO, WoS, and Scopus, covering the period from 1980 to 2024, across ten European countries. The review focused on studies published in scientific journals with regional or national samples. In addition to the 30 selected studies, three more were included due to their relevance as cited in the selected articles. Despite the considerable methodological heterogeneity, the results showed a relative stabilization of the differences in sexual behaviors of boys and girls throughout time. Those differences were more evident in Southern European countries. Some changes were also noted, such as the delay in the initiation of the first sexual intercourse, a trend observed over the last decade. The findings are discussed in terms of the sexual script theory, highlighting the importance of these mental frameworks in the heteronormative sexual socialization of boys and girls. Future research should emphasize the diversity of heterosexual behaviors, their significance, and the emotional experiences that accompany them.

Abstract The redirection of T lymphocytes against tumor-associated or tumor-specific antigens, using bispecific antibodies or chimeric antigen receptors (CAR), has shown therapeutic success against certain hematological malignancies. However, this strategy has not been effective against solid tumors. Here, we describe the development of CAR T cells targeting p95HER2, a tumor-specific antigen found in HER2-amplified solid tumors. These CAR T cells display robust activity against p95HER2-expressing cell lines but demonstrate limited efficacy against patient-derived xenografts. As p95HER2 is invariably detectable on tumor cells that overexpress HER2, but not those that express HER2 at normal levels, we arm p95HER2-specific CAR T cells with affinity-tuned bispecific antibodies against HER2 and CD3 in order to redirect them only to HER2-amplified cells. The combination of p95HER2.CAR T cells and HER2 x CD3 bispecific antibodies lead to a complete regression in three HER2-positive, patient-derived mouse xenografts tumor models. This combination represents a promising strategy to redirect T cells against a subset of HER2-positive tumors.

Introduction: This study aims to investigate the validity and psychometric properties of the Hungarian version of the Coparenting Relationship Scale (CRS-HU), a measurement designed to assess different dimensions of coparenting. Only a few validation studies can be found, even though CRS is a widely used measurement. Methods: Currently, no assessment instruments exist in Hungarian that measure coparenting relationships and practices; therefore, we adapted CRS and designed a validation study to investigate mothers’ coparenting characteristics (N = 381). We checked the construct validity using confirmatory factor analysis (CFA), then to assess convergent and discriminant validity, we examined correlations between the coparenting questionnaire factors and other similar constructs. We also examined the relationship between CRS-HU and different background variables using Kruskal-Wallis and Mann-Whitney tests. Results: Our main results showed that the internal consistency in the Hungarian version of CRS and its subscales is good or excellent (Cronbach’s apha = .75–.89). The seven-factor structure had a poor model fit in CFA, however, the brief version of the CRS-HU (RMSEA = .057; CFI = .962) and six subscales separately (RMSEA = .031–.066; CFI = .978–.999) demonstrated a good model fit. Conclusions: The brief version of Hungarian CRS and the different subscales are valid and feasible measures for assessing coparenting and its dimensions. Thus, CRS can be effectively used at last in our culture, as well.

IntroductionSepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood. This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis.MethodsA prospective case-control study was conducted to compare DNA methylation profiles between patients with community-acquired sepsis and matched controls who had similar infections but did not develop sepsis. Whole blood samples from these patients were analyzed using the Infinium MethylationEPIC v2.0 kit, enabling genome-wide methylation analysis. Selected genes with differential methylation were validated by pyrosequencing.ResultsSignificant differential DNA methylation patterns were identified between septic and non-septic individuals uising. Our results suggest that DNA methylation changes are closely linked to the pathophysiological processes of sepsis, influencing immune cell activation, inflammation, and organ dysfunction. The most prominent findings include the hypomethylation of immune-related genes (SERPINA1, AZU1, MPO, and SLX4), which were strongly correlated with clinical severity and inflammatory markers such as SOFA scores and PCT levels. Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and PCT levels. Notably, SLX4 hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while SERPINA1 hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858).DiscussionOur results underscore the potential of DNA methylation changes, particularly in immune-related genes, to enhance the early detection of sepsis and to stratify patients based on severity. Future research should explore the therapeutic implications of these epigenetic alterations in sepsis care.

Abstract Background Several studies have shown that the knowledge about coeliac disease (CD) is not satisfactory among healthcare professionals (HCP). The aim of our study was to assess the knowledge of HCPs about CD in the Danube region. Methods HCPs from 8 countries in the Danube region were asked to complete the web-based questionnaire about CD. Scores of HCPs were compared according to their speciality, work experience and country of residence. The results were compared with the results of a similar study conducted in Central Europe within the Focus IN CD project in 2016. Results Questionnaire was completed by 799 HCPs from Austria, Croatia, Czech Republic, Hungary, Moldova, Romania, Serbia, and Slovenia. Mean score achieved by HCPs was 52.2%. Paediatric gastroenterologists scored the highest (75.3%). Comparing the data with the study conducted in Central Europe in 2016, we found a significant rise (p

Acquiring the relative order of function and content words is a fundamental aspect of language development, and previous studies show that infants develop prelexical representations of this word order. As functors are more frequent than content words, they serve as anchors with respect to which the positions of other words can readily be encoded. This frequency-based bootstrapping strategy has been shown to be used both by infants and adults. However, only a handful of languages, mainly spoken in Western countries, have been tested so far. One hurdle to more inclusive testing is the lack of laboratory facilities in some geographical areas of the world. Online testing is a useful tool to overcome this difficulty. The current study, therefore, implements and validates an online version of an artificial grammar learning paradigm originally developed for laboratory use to test the frequency-based anchoring effect on adults in typologically different languages, Italian and Turkish. Italian has functor-initial word order, while Turkish is functor-final. Our study thus has two related goals. We test whether previous lab-based results by Gervain et al. (2013) with Italian adults are replicable using online testing. Additionally, we leverage online testing to assess a hitherto understudied language, Turkish, which has opposite word order properties compared to Italian. Our findings indicate that online testing can efficiently reproduce laboratory-based results: Italian adults in our online study show similar word order preferences to those tested in the laboratory earlier. Further, we found that Turkish participants have opposite word order preferences, as we predicted. These findings pave the way for testing the frequency-based bootstrapping hypothesis on a more inclusive and diverse sample of languages than previously available.

Infants are exposed to a myriad of sounds early in life, including caregivers' speech, songs, human-made and natural (non-anthropogenic) environmental sounds. While decades of research have established that infants have sophisticated perceptual abilities to process speech, less is known about how they perceive natural environmental sounds. This review synthesizes current findings about the perception of natural environmental sounds in the first years of life, emphasizing their role in auditory development and describing how these studies contribute to the emerging field of human auditory ecology. Some of the existing studies explore infants' responses to animal vocalizations and water sounds. Infants demonstrate an initial broad sensitivity to primate vocalizations, which narrows to human speech through experience. They also show early recognition of water sounds, with preferences for natural over artificial water sounds already at birth, indicating an evolutionary ancient sensitivity. However, this ability undergoes refinement with age and experience. The few studies available suggest that infants' auditory processing of natural sounds is complex and influenced by both genetic predispositions and exposure. Building on these existing results, this review highlights the need for ecologically valid experimental paradigms that better represent the natural auditory environments humans evolved in. Understanding how children process natural soundscapes not only deepens our understanding of auditory development but also offers practical insights for advancing environmental awareness, improving auditory interventions for children with hearing loss, and promoting wellbeing through exposure to natural sounds.

The study aimed to assess respondents’ opinions on healthiness of various types of meat derived from different animal species across multiple countries. A total of 1116 questionnaires from Spain, Italy, Poland, Hungary and China were analysed. According to the perception of all respondents, the ranking on the healthiness of different types of meat is as follows: fish (39.9%), rabbit (20.8%), chicken (15.1%), beef (13.4%), pork (4.9%), lamb (4.3%) and horse meat (1.6%). In specific countries, variations in rankings were observed. In Italy, Poland and Hungary fish claimed the top position, while in Spain rabbit meat was ranked the highest. Conversely, in China, fish and beef were considered the healthiest options. Gender exhibited only a marginal effect. Fish was considered the healthiest for all ages. With the exception of China, where beef overtook the second place, rabbit meat was in the second position. Regarding household income, a difference emerged only in the case of fish; the 'Live well' and 'Live very well' groups considered it healthier than those with lower incomes. The findings suggest that respondents’ opinions on the healthiness of different meat types could be leveraged for the development of marketing strategies with the meat industry.

Archivo histórico de Kipus: Revista Andina de Letras y Estudios Culturales, 1994.

TerraSAR-X (TSX), TanDEM-X (TDX), and PAZ Synthetic Aperture Radar data have been used at over 120 volcanoes to assess surface characteristics and change over time. We examine previous work, adding additional examples to understand where and when these data are most useful for volcanology. We focus on volcanoes as part of the Committee on Earth Observation Satellites (CEOS) Volcano Demonstrator Project. TSX/TDX/PAZ data provide a valuable means of detecting small surface changes from amplitude images and topographic changes from bistatic TSX/TDX data. For short temporal and perpendicular baselines, TDX/TSX/PAZ can also provide useful deformation data, even in presence of vegetation. No global background mission currently acquires TSX/TDX/PAZ data at volcanoes: 70 % high spatial resolution data, limiting their suitability for studying pre-eruptive unrest. Coordinated targeting by SAR constellations of priority volcanoes would provide data and insights valuable for forecasting eruptions and associated hazards.

Abstract Aquatic macrophytes form a three dimensional complex structure in the littoral zones of lakes, with many physical, chemical and biological gradients and interactions. This special habitat harbours a unique microalgal assemblage called metaphyton, that differs both from the phytoplankton of the pelagial and from the benthic assemblages whose elements are tightly attached to the substrates. Since metaphytic assemblages significantly contribute to the diversity of lakes’ phytoplankton, it is crucial to understand and disentangle those mechanisms that ensure their development. Therefore, we focused on the question of how a single solid physical structure contribute to maintaining metaphytic assemblages. Using a laboratory experiment we studied the floristic and functional differences of microalgal assemblages in microcosms that simulated the conditions that an open water, a complex natural macrophyte stand (Utricularia vulgaris L.), or an artificial substrate (cotton wool) provide for them. We inoculated the systems with a species rich (> 326 species) microalgal assemblage collected from a eutrophic oxbow lake, and studied the diversity, trait and functional group composition of the assemblages in a 24 day long experimental period. We found that both natural and artificial substrates ensured higher species richness than the open water environment. Functional richness in the open water environment was lower than in the aquaria containing natural macrophyte stand but higher than in which cotton wool was placed. This means that the artificial physical structure enhanced functional redundancy of the resident functional groups. Elongation measures of microalgal assemblages showed the highest variation in the microcosms that simulated the open water environment. Our results suggest that assembly of metaphytic algal communities is not a random process, instead a deterministic one driven by the niche characteristics of the complex three dimensional structure created by the stands of aquatic macrophytes.

The effect of the reset-pulse parameters of a phase-change memory line cell on the electrical cell properties is examined. The effect of the reset-pulse parameters on the transient characteristics of the rest switching is studied by using a simulation that has shown how they affect physical parameters like the temporal and spatial distribution of the temperature during switching, the maximum temperature reached and the time-under-melt parameter.

The studies of the endurance properties of an integrated phase-change line cell are presented. The results obtained revealed that the endurance lifetime could be extended by timely adjustment of the reset-pulse polarity by using short reset pulses.

An attempt was made to report the electrical and reliability properties of integrated 3-D FeCAPs and detailed work on densely scaled Ferroelectric random access memories (FeRAMs) having properties such as low voltage operation, fast write and nonvolatility was provided. It was demonstrated that the negative signal-scaling trend could be halted using 3-D FeCAPs.

Glutaric aciduria type 1 (GA1) is a rare inherited metabolic disorder caused by a deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), with accumulation of neurotoxic metabolites, resulting in a complex movement disorder, irreversible brain damage, and premature death in untreated individuals. While early diagnosis and a lysine restricted diet can extend survival, they do not prevent neurological damage in approximately one-third of treated patients, and more effective therapies are required. Here we report the efficacy of adeno-associated virus 9 (AAV9)-mediated systemic delivery of human GCDH at preventing a high lysine diet (HLD)-induced phenotype in Gcdh−/− mice. Neonatal treatment with AAV-GCDH restores GCDH expression and enzyme activity in liver and striatum. This treatment protects the mice from HLD-aggressive phenotype with all mice surviving this exposure; in stark contrast, a lack of treatment on an HLD triggers very high accumulation of glutaric acid, 3-hydroxyglutaric acid, and glutarylcarnitine in tissues, with about 60% death due to brain accumulation of toxic lysine metabolites. AAV-GCDH significantly ameliorates the striatal neuropathology, minimizing neuronal dysfunction, gliosis, and alterations in myelination. Magnetic resonance imaging findings show protection against striatal injury. Altogether, these results provide preclinical evidence to support AAV-GCDH gene therapy for GA1.

Introduction: The Hungarian version of the 36-item self-report Experiences in Close Relationships – Revised (ECR-R-HU) questionnaire assessing adult romantic attachment has been published recently. Short versions provide a useful tool for large-scale research and in the clinical field as well. Aims: The present study reports developing and validating the short form of the Hungarian version of the ECR-R (ECR-R-HU-SF). Methods: The development of the short form, data reduction, and item selection were performed in a nationally representative adult (18+) community sample (N = 958; Study 1). The newly developed ECR-R-HU-SF was then tested and validated in a different national study representative of children aged 3–36 months, using data from respondent mothers with diverse sociodemographic backgrounds (N = 980; Study 2). Results: In Study 1, using randomly split subsamples, the ECR-R-HU-SF retained 8 items and confirmed the original two-factor structure of the measure. The subscales showed very good reliability and correlated highly with their corresponding original long versions. Psychometric properties, construct (convergent) validity, sociodemographic associations, and mean population scores for the short-version subscales (Avoidance, Anxiety) were compared with those of the long version. In Study 2, subscales were highly reliable, and scores correlated in the expected directions with related constructs (depressive mood, perceived stress). Conclusions: In summary, the ECR-R-HU-SF is a valid instrument that can be used as an effective screening tool for measuring adult romantic attachment.

Abstract RBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the contribution of rbfox1 to behaviour, we used rbfox1 sa15940 , a zebrafish mutant line with TL background. We found that rbfox1 sa15940 mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a second rbfox1 mutant line with a different genetic background (TU), rbfox1 del19 , and found that rbfox1 deficiency affects behaviour similarly in this line, although there were some differences. rbfox1 del19 mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity than rbfox1 sa15940 fish. Taken together, these results suggest that mutations in rbfox1 lead to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present in Rbfox1-deficient mice and in patients with different psychiatric conditions. Our study, thus, highlights the evolutionary conservation of rbfox1 function in behaviour and paves the way to further investigate the mechanisms underlying rbfox1 pleiotropy on the onset of neurodevelopmental and psychiatric disorders.

Abstract Studies have repeatedly shown sex differences in some areas of language development, typically with an advantage for female over male children. However, the tested samples are typically small and the effects do not always replicate. Here, we used a meta-analytic approach to address this issue in a larger sample, combining seven fNIRS studies on the neural correlates of repetition- and non-repetition-based rule learning in newborns and 6-month-old infants. The ability to extract structural regularities from the speech input is fundamental for language development, it is therefore highly relevant to understand whether this ability shows sex differences. The meta-analysis tested the effect of Sex, as well as of other moderators on infants’ hemodynamic responses to repetition-based (e.g. ABB: “mubaba”) and non-repetition-based (e.g. ABC: “mubage”) sequences in both anatomically and functionally defined regions of interests. Our analyses did not reveal any sex differences at birth or at 6 months, suggesting that the ability to encode these regularities is robust across sexes. Interestingly, the meta-analysis revealed other moderator effects. Thus in newborns, we found a greater involvement of the bilateral temporal areas compared to the frontal areas for both repetition and non-repetition sequences. Further, non-repetition sequences elicited greater responses in 6-month-olds than in newborns, especially in the bilateral frontal areas. When analyzing functional clusters of HbR timetraces, we found that a larger right-left asymmetry for newborn boys in brain responses compared to girls, which may be interpreted in terms of a larger right-left asymmetry in cerebral blood flow in boys than in girls early in life. We conclude that extracting repetition-based regularities from speech is a robust ability with a well-defined neural substrate present from birth and it does not exhibit sex differences.

Tick-borne diseases have emerged as a major global public health problem in recent decades. The increasing incidence and geographical dissemination of these diseases requires the implementation of robust surveillance systems to monitor their prevalence, distribution, and public health impact. It is therefore not unexpected that tick-borne pathogens coexist in the same vectors, but the interactions of these agents between vectors and vertebrate hosts, including humans, remain poorly understood. The impact of infection in humans extends to the diagnostic challenges that arise when the same symptomatology can be associated with any tick-borne pathogen, and therapeutic recommendations only focus on the major or best-known tick-borne diseases, ignoring other lesser-known or less prevalent infections. Both surveillance systems and the holistic diagnosis of tick-borne pathogens are necessary tools to address the emergence of vector-borne diseases. In this study, we will focus on the main tick-borne viral, bacterial, and parasitic diseases in Spain to reflect the need to establish syndromic diagnostics in samples from patients with a history of tick bites and symptomatology compatible with them. On the other hand, and highlighting this need, innovations in molecular techniques, syndromic surveillance, and surveillance programs for ticks and tick-borne pathogens with public health implications are expected to be developed.

In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia’s NBS program has effectively reduced morbidity and improved affected children’s quality of life.

This paper was set to address to what extent intellectual property law is prepared for keeping pace with the rapid development of artificial intelligence and digitalization? We examined, by way of using empirical methods, the relationship between artificial intelligence, its regulation and the current trends in intellectual works. The overall conclusion of our research findings demonstrates that current legislation is well suited to support the requirements of technological progress. Nevertheless, there are some new dimensions in terms of worthy proposals that may also be considered. This paper stresses that given AI is capable of bringing significant transformations in our daily lives about, a major paradigm shift in legislation may soon be inevitably required.

When volcanic unrest occurs, the scientific community can advance fundamental understanding of volcanic systems, but only with coordination before, during, and after the event across academic and governmental agencies. To develop a coordinated response plan, the Community Network for Volcanic Eruption Response (CONVERSE) orchestrated a scenario exercise centered around a hypothetical volcanic crisis in Arizona’s San Francisco Volcanic Field (SFVF). The exercise ran virtually from February 4 to March 4, 2022. Over 60 scientists from both academic and governmental spheres participated. The scenario exercise was assessed for its effectiveness in supporting collaborative production of knowledge, catalyzing transdisciplinary collaboration, supporting researcher confidence, and fostering a culture of inclusion within the volcanology community. This identified a need to support early career researchers through community and allyship. Overall, the 2022 CONVERSE exercise demonstrated how a fully remote, extended scenario can be authentically implemented and help broaden participation within the volcano science community.

Abstract Sensitisation to the lipid transfer protein Pru p 3 is associated with severe allergic reactions to peach, the proteins stability being thought to play a role in its allergenicity. Lipid binding increases susceptibility of Pru p 3 to digestion and so the impact of bile salts on the in vitro gastrointestinal digestibility of Pru p 3 was investigated and digestion products mapped by SDS-PAGE and mass spectrometry. Bile salts enhanced the digestibility of Pru p 3 resulting in an ensemble of around 100 peptides spanning the protein’s sequence which were linked by disulphide bonds into structures of ~ 5–6 kDa. IgE binding studies with a serum panel from peach allergic subjects showed digestion reduced, but did not abolish, the IgE reactivity of Pru p 3. These data show the importance of including bile salts in vitro digestion systems and emphasise the need to profile of digestion in a manner that allows identification of immunologically relevant disulphide-linked peptide aggregates.