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Context: Recent research on students' experiences with the quality of online learning during the COVID-19 pandemic has increased the challenge to the development of online learning. During the pandemic, anxiety, depression, and fatigue occurred in online studies, which also weakened students' well-being. In this quantitative study, we examined how students thrive in synchronous and asynchronous online implementations. The goal of the research was to support students' well-being in online studies; therefore, the study uses the PERMA well-being theory. Approach: Finnish vocational education and training students (N = 363) participated in the study and answered the questions on positive emotions, engagement, relationships, meaning, and accomplishment from both asynchronous and synchronous online delivery perspectives using a questionnaire. Findings: This study highlighted the importance of the teacher's online learning facilitation skills and task design skills, and the emotions generated in an online course. Based on the results, the respondents were divided into three student profiles: (1) Students thriving in online courses in general; (2) Students thriving, especially in asynchronous online courses; and (3) Students not thriving in online courses in general. Conclusions: According to the findings, students need different options for completing online courses. The role of the teacher in creating a positive and supportive atmosphere, fostering relationships, and creating clear work-related and versatile tasks is of great importance in the generation of emotions, whether it is an asynchronous or synchronous online implementation.

In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland (P = 8.82 × 10-28) and Estonia (P = 1.25 × 10-5). The risk allele of rs570516915 alters a conserved binding site for the transcription factor IRF6 within an enhancer (MCS-9.7) upstream of the IRF6 gene and diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6, suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.

Jing Gao,1,* Tanja Törölä,1,* Chuan-Xing Li,2 Steffen Ohlmeier,3 Tuula Toljamo,4 Pentti Nieminen,5 Noboru Hattori,6 Ville Pulkkinen,1 Hiroshi Iwamoto,6 Witold Mazur1 1Heart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 2Pulmonomics Group, Respiratory Medicine Unit, Department of Medicine & Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; 3Proteomics Core Facility, Biocentre Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; 4Department of Pulmonary Medicine, Lapland Central Hospital, Rovaniemi, Finland; 5Medical Informatics and Statistics Group, University of Oulu, Oulu, Finland; 6Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan*These authors contributed equally to this workCorrespondence: Jing GaoHeart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, FinlandTel +358417071559Email jing.gao@helsinki.fi, HelsinkiIntroduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions.Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed.Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up.Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.Keywords: vitamin D binding protein, VDBP, genotype, COPD, prospective study, sputum

In this conceptual article, we discuss the idea of students' epistemic agency as an overlooked link between assessment, knowledge and society. We transcend the contemporary discourses around assessment that focus on its authenticity and student-centredness and instead investigate assessment from the viewpoints of knowledge and knowing. This approach sees assessment as functioning not only as a promoter of student learning but also as a means to prepare students to be responsible graduates and citizens as epistemic agents. First, we adapt the theory of epistemic agency--that is, students' capability to agentically evaluate, produce, use and transform knowledge--by situating it within the specific context of assessment. Second, we suggest practice-oriented ideas for assessment and feedback design to nurture epistemic agency. Overall, we do not depict epistemic agency as yet another 'soft skill' in higher education but as a necessary focal point for assessment that aims to nurture a transformative relationship between students and knowledge. We suggest epistemic agency as a powerful concept in understanding and nurturing the three-way engagement between assessment, knowledge and society. This concept allows us to understand whether and how assessment shapes students as epistemic agents.

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

BACKGROUND: Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesitys impact on EV secretion from human AT remains limited. METHODS: We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography-mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry. RESULTS: EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation. CONCLUSIONS: We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.

In university mathematics education, students do not simply learn mathematics but are shaped and shape themselves into someone new - mathematicians. In this study, we focus on the becoming of "dis"abled mathematical subjects. We explore the importance of abilities in the processes of being and becoming in university mathematics. Our interest lies in how teaching and assessment practices provide students with ways to understand themselves as both able and "dis"abled, as "dis"abilities are only understood with respect to the norm. We analyse narratives of nine university students diagnosed with learning disabilities or mental health issues to investigate how their subjectivity is constituted in discourse. Our analysis shows how the students are shaped and shape themselves as "dis"abled mathematicians in relation to "speed" in mathematical activities, "disaffection" in mathematics, "individualism" in performing mathematics, and "measurability" of performance. These findings cast light on the ableist underpinnings of the teaching and assessment practices in university mathematics education. We contend that mathematical ableism forms a watershed for belonging in mathematics learning practices, constituting rather narrow, "normal" ways of being "mathematically able". We also discuss how our participants challenge and widen the idea of an "able" mathematics student. We pave the way for more inclusive futures of mathematics education by suggesting that rather than understanding the "dis" in disability negatively, the university mathematics education communities may use dis by disrupting order. Perhaps, we ask, if university mathematics fails to enable accessible learning experiences for students who care about mathematics, these practices should indeed be disrupted.

The purpose of this study is to investigate how teachers use different types of discourse to support dialogic argumentation. Dialogic argumentation is a collaborative process in which students construct arguments together and examine arguments presented by their peers. Science teachers can use argumentation as a vehicle to help students gain a working understanding of science content and the nature of science and its practices. Whole-class closing discussions from video-recorded lessons are analyzed to study the discourse used to support argumentation by two physics teachers in lower secondary schools. Analysis of discourse includes coding of communicative approach at the episode level and coding of teacher roles of questioning at the level of speaking turns. Student argumentation is also assessed on the basis of dialogicity and complexity of arguments. Findings characterize different ways of orchestrating argumentative discussions. Authoritative episodes were characterized by the presence of the dispenser role, with teachers retaining ownership over ideas and classroom activities to emphasize the correctness of a justification. Dialogic episodes of classroom interaction showed openness to student perspectives, but teachers' use of questioning roles revealed different ways of orchestrating argumentative discussions. The moderator role granted ownership of ideas to students to either pursue a single student's argument in more depth or to directly contrast opposing justifications. Less commonly used were the roles of coach and participant, which teachers used to elicit student justifications in more depth or support students in examining the arguments of their peers. Examination of discourse using multiple frameworks revealed differences in teachers' values and the impact of the use of teacher questioning roles on student contributions to argumentative discussions.

Abstract In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10−34, OR = 8.65, 95% CI 6.11–12.25), but not with CL/P (P = 7.2 × 10−5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland (P = 8.82 × 10−28) and Estonia (P = 1.25 × 10−5). The risk allele of rs570516915 alters a conserved binding site for the transcription factor IRF6 within an enhancer (MCS-9.7) upstream of the IRF6 gene and diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6, suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.

Abstract High mitochondrial DNA (mtDNA) amount has been reported to be beneficial for resistance and recovery of metabolic stress, while increased mtDNA synthesis activity can drive aging signs. The intriguing contrast of these two mtDNA boosting outcomes prompted us to jointly elevate mtDNA amount and frequency of replication in mice. We report that high activity of mtDNA synthesis inhibits perinatal metabolic maturation of the heart. The offspring of the asymptomatic parental lines are born healthy but manifest dilated cardiomyopathy and cardiac collapse during the first days of life. The pathogenesis, further enhanced by mtDNA mutagenesis, involves prenatal upregulation of mitochondrial integrated stress response and the ferroptosis-inducer MESH1, leading to cardiac fibrosis and cardiomyocyte death after birth. Our evidence indicates that the tight control of mtDNA replication is critical for early cardiac homeostasis. Importantly, ferroptosis sensitivity is a potential targetable mechanism for infantile-onset cardiomyopathy, a common manifestation of mitochondrial diseases.

This article focuses on the history of Finnish academic women and examines the discussions about women's academic education and women scholars that took place in two Finnish magazines of the women's movement between 1890 and 1939. The article examines how the two magazines addressed the topics and represented academic women and women scholars. The results indicate that at first, access to higher education and the complex status of female students at the university were the centre of attention in the discussions. The discussions were supplemented by new tones, strengthening the support for educational equality in relation to human rights with utilitarian perspectives. The emphasis of the topics shifted during the first decade of the twentieth century, when the magazines raised public awareness of the career paths for women scholars. The representations of academic women and women scholars also highlighted the efforts of the women's movement to promote the scholarly work of women pioneering in academic circles.

Students' emotions have been increasingly examined in feedback research. Socioculturally positioned research has particularly noted that emotions do not exist in a vacuum but are contextually situated, which also holds true for feedback encounters. In this scoping review, we provide a synthesis of earlier studies on emotions in feedback in higher education (2003-2023, 46 studies). First, we outline the research designs and methods. Second, we analyse the contextual influences on students' emotions in feedback. We used Bronfenbrenner's ecological theory as our guiding framework. The findings reveal that self-report methods have been widely utilized. Most studies have investigated emotions either on an individualistic or at the microsystem level, while only a few have considered the wider influence of the macrosystem and chronosystem levels. Future research must consider the macrosystem since emotions are historically, culturally and politically embedded in social interactions. Scholars must take into account the chronosystem level since emotions are dynamic, evolve over time and reflect wider societal changes.

This article focuses on the occupational emancipation of women in Finland and examines the professional careers of women who graduated with a matriculation examination from three upper secondary girls' schools during the period of the 1890s to the 1910s. One of the schools was for Finnish-speaking girls, and two of the schools were for Swedish-speaking girls. This article asks what kinds of educational paths and professional careers these upper secondary girls' school graduates had during their lives after graduation. Attention is paid to both the typical professional careers and to those careers that could be characterised as exceptional and atypical. The source material consists of student registers that offered an opportunity to create a prosopography (i.e. set biography). In this article, the prosopography and individual biographies of women with exceptional careers shed light on the horizon of possibilities for Finnish women at the end of the nineteenth century and in the early twentieth century, specifically, their horizon of possibilities to gain education and degrees, as well as posts in the labour market.

How could assessment inclusively consider the diversity of students? In higher education, the most common answer is: through individual assessment accommodations. Inclusive assessment design has also been promoted to foster accessibility for all students. However, both of these approaches have largely drawn on the procedural understanding of 'inclusion' as 'enhanced academic outcomes'. In this conceptual study, a critical, socio-political approach to inclusive assessment is taken instead, considering assessment in its wider context of academic ableism. The rationale for Assessment for Inclusion (AfI) is formulated to harness assessment to promote the inclusion of marginalised students as fully accepted, agentic members of academic communities. Five practical principles for promoting AfI are introduced: rethinking accommodations, anti-ableist work, celebration of human diversity, student partnership, and interdependence. This study suggests that if mass higher education truly wishes to include students from increasingly diverse backgrounds, assessment needs to be rethought from the viewpoint of inclusion.

Assessment is often used to promote learning, but the mechanisms of how assessment relates to epistemology -- knowledge and knowing -- have been scarcely studied and theorised. In this study, we examine students' epistemic resources in relation assessment in the context of university mathematics education. We draw on the theoretical framework of epistemic injustice in order to understand how assessment produces knowledge and knowers. Using reflexive thematic analysis, we analyse 77 students' essays about their experiences and ideals of assessment practices. We discuss how the students contributed to co-constructing the dominant status of exams in mathematics -- exams were deemed fit to assess mathematical knowledge. At the same time, experiences of alternative assessment practices enabled students to re-define what constitutes valid knowledge and how such knowledge can be demonstrated and assessed. We conclude by noting that developing student-centred assessment practices not only fosters students' learning but also promotes their epistemic resources.

When students enter higher education, they not only start learning and studying but begin a journey of becoming someone new in relation to themselves and to society. Scholarly research has increasingly emphasised this transformative element of higher education yet, to date, the role of assessment has received little attention in the processes of being and becoming. This is a crucial limitation given how profoundly assessment - exams, self- and peer-assessment, grades, rankings, metrics - characterises contemporary higher education. In this conceptual study, we propose a novel way of rethinking assessment as a matter of being and becoming. We bring together the separate fields of research on assessment and the philosophy of higher education by theorising other-formation and self-formation in and through assessment encounters. First, we discuss how assessment shapes students in 'the measured university' ("other-formation"). We then reconceptualise assessment from the viewpoint of how it promotes student agency and self-reflexivity ("self-formation"). Finally, we discuss some frequently used assessment practices in light of student self/other-formation. Our study sets the agenda of understanding student formation in and through assessment by laying the philosophical foundation for future studies.

Using two heliospheric vantage points, we study 22 solar energetic particle (SEP) events, 14 of which were detected at both locations. SEP proton events were detected during the declining phase of solar cycle 23 (November 2003–December 2006) by means of two nearly identical Standard Radiation Environment Monitor (SREM) units in energies ranging between 12.6 MeV and 166.3 MeV. In this work we combine SREM data with diverse solar and interplanetary measurements, aiming to backtrace solar eruptions from their impact in geospace (i.e., from L1 Lagrangian point to Earth’s magnetosphere) to their parent eruptions at the Sun’s low atmosphere. Our SREM SEP data support and complement a consistent inner-heliospheric description of solar eruptions (solar flares and coronal mass ejections [CMEs]) and their magnetospheric impact. In addition, they provide useful information on the understanding of the origin, acceleration, and propagation of SEP events at multi-spacecraft settings. All SEP events in our sample originate from major eruptions consisting of major (>M-class) solar flares and fast (>1800 km/s, on average), overwhelmingly (>78%) halo, CMEs. All but one SEP event studied are unambiguously associated with shock-fronted CMEs, suggesting a CME-driven shock acceleration mechanism. Moreover, a significant correlation is found between the SEP event peak and the onset of the storm sudden commencement, that might help improve prediction of magnetospheric disturbances. In general, SEP events correlate better with interplanetary (i.e., in-situ; L1-based) than with solar eruption features. Our findings support (a) the routine use of cost-effective SREM units, or future improvements thereof, for the detection of SEP events and (b) their implementation in multi-spacecraft settings as a means to improve both the physical understanding of SEP events and their forecasting.

Overdose of acetaminophen (APAP) produces fulminant hepatic necrosis. The underlying mechanism of APAP hepatotoxicity involves mitochondrial dysfunction, including mitochondrial oxidant stress and the onset of mitochondrial permeability transition (MPT). Reactive oxygen species (ROS) play an important role in APAP-induced hepatotoxicity, and iron is a critical catalyst for ROS formation. This review summarizes the role of mitochondrial ROS formation in APAP hepatotoxicity and further focuses on the role of iron. Normally, hepatocytes take up Fe3+-transferrin bound to transferrin receptors via endocytosis. Concentrated into lysosomes, the controlled release of iron is required for the mitochondrial biosynthesis of heme and non-heme iron-sulfur clusters. After APAP overdose, the toxic metabolite, NAPQI, damages lysosomes, causing excess iron release and the mitochondrial uptake of Fe2+ by the mitochondrial calcium uniporter (MCU). NAPQI also inhibits mitochondrial respiration to promote ROS formation, including H2O2, with which Fe2+ reacts to form highly reactive •OH through the Fenton reaction. •OH, in turn, causes lipid peroxidation, the formation of toxic aldehydes, induction of the MPT, and ultimately, cell death. Fe2+ also facilitates protein nitration. Targeting pathways of mitochondrial iron movement and consequent iron-dependent mitochondrial ROS formation is a promising strategy to intervene against APAP hepatotoxicity in a clinical setting.

Abstract Background Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity’s impact on EV secretion from human AT remains limited. Methods We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography–mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry. Results EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation. Conclusions We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.

Abstract Background Equine asthma (EA) is a chronic lower airway inflammation that leads to structural and functional changes. Hyaluronic acid (HA) has crucial functions in the extracellular matrix homeostasis and inflammatory mediator activity. HA concentration in the lungs increases in several human airway diseases. However, its associations with naturally occurring EA and airway remodelling have not been previously studied. Our aim was to investigate the association of equine neutrophilic airway inflammation (NAI) severity, airway remodelling, and HA concentration in horses with naturally occurring EA. We hypothesised that HA concentration and airway remodelling would increase with the severity of NAI. HA concentrations of bronchoalveolar lavage fluid supernatant (SUP) and plasma of 27 neutrophilic EA horses, and 28 control horses were measured. Additionally, remodelling and HA staining intensity were assessed from endobronchial biopsies from 10 moderate NAI horses, 5 severe NAI horses, and 15 control horses. Results The HA concentration in SUP was higher in EA horses compared to controls (p = 0.007). Plasma HA concentrations were not different between the groups. In the endobronchial biopsies, moderate NAI horses showed epithelial hyperplasia and inflammatory cell infiltrate, while severe NAI horses also showed fibrosis and desquamation of the epithelium. The degree of remodelling was higher in severe NAI compared to moderate NAI (p = 0.048) and controls (p = 0.016). Intense HA staining was observed in bronchial cell membranes, basement membranes, and connective tissue without significant differences between the groups. Conclusion The release of HA to the airway lumen increases in naturally occurring neutrophilic EA without clear changes in its tissue distribution, and significant airway remodelling only develops in severe NAI.

Abstract Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0–50 μg/g; n = 602), moderate (> 50–100 μg/g; n = 64) and high (> 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.

Disabilities and neurodiversity are dominantly understood as something that challenges higher education rather than something that enriches it: ableist underpinnings characterize higher education despite policies of widened access. While earlier research has explored ideas such as 'inclusive pedagogies' and 'pedagogies of belonging', these important contributions have downplayed the marginalizing nature of pedagogy itself. In this conceptual study, we argue that non-ableist approaches to teaching are not sufficient in itself. We suggest a conceptual model for anti-ableist pedagogies to promote belonging and to challenge the exclusion and marginalization of disabled students. We have drawn on the ecological systems model by Bronfenbrenner to examine anti-ableist pedagogies as understood through the theory of systemic change. We provide a theory synthesis by drawing on earlier work on disability studies and anti-racist pedagogies: without systematic approaches to unpack and challenge the idea of a 'normal, able student' in pedagogical design and policies, 'pedagogies of belonging' fail to foster 'belonging' in a system that builds on exclusion. Our study will benefit both practitioners striving for more inclusive higher education as well as researchers aiming to better conceptualize the questions of belonging in the exclusive systems of higher education.