University of Fribourg

β-Carotene (βC), a natural carotenoid, is the most important and effective vitamin A precursor, known also for its antioxidant properties. However, its poor water solubility, chemical instability, and low bioavailability limit its effectiveness as an orally delivered functional nutrient. Nanoparticle encapsulation improves βC's bioaccessibility by enhancing its stability and solubility. This study compares two formulations, i.e. βC-loaded poly(lactic-co-glycolic acid) (PLGA) NPs and liposomes before and after exposure to simulated gastrointestinal fluids using various methods such as Taylor dispersion analysis (TDA), cryo-transmission electron microscopy, dynamic light scattering (DLS), and nanoparticle tracking analysis (NTA). TDA, a microfluidic technique, proved more effective than DLS and NTA in determining nanoparticle size in simulated gastrointestinal fluids. This highlights TDA's potential for assessing nanoparticle colloidal stability in simulated gastro-intestinal fluids, crucial for evaluating encapsulated bioactives' bioavailability. High-performance liquid chromatography (HPLC) revealed that PLGA nanoparticles incorporate and preserve βC more effectively during long-term storage compared to liposomes. Adding ascorbic acid significantly reduced degradation in simulated gastrointestinal fluids. Release studies showed that liposomes released 52% of βC after 36 hours, while PLGA nanoparticles released only 9% over 168 hours. These results provide valuable insights for selecting an appropriate βC nanocarrier for oral delivery based on desired release rates.

Background Tau protein phosphorylation and aggregation are the pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. Multiple phosphorylation sites in Tau protein at serine (S), threonine (T), and tyrosine result in high heterogeneity and enhanced aggregation kinetics. Method Here, we used nanopores coated with a fluid lipid bilayer to characterize native and hyperphosphorylated Tau proteins on a single‐molecule level. Result Single‐molecule level analysis determines the size, shape, net charge, and dipole moment of individual tau protein monomers. The approach makes it possible to differentiate native and hyperphosphorylated Tau proteins based on their net charge. Moreover, single‐particle size analysis revealed the spontaneous formation of low‐n oligomers such as dimer, trimer, tetramer and pentamers; no other molecules were needed to initiate aggregation to these oligomers. Conclusion The nanopore‐based approach enables discrimination of native and hyperphosphorylated Tau proteins based on their net charge. Furthermore, single‐particle size approximation is helpful for detecting early‐stage aggregation of Tau and characterization of various oligomer species.

After a peripheral nerve injury, Schwann cells (SCs), the myelinating glia of the peripheral nervous system, convert into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism depends however on the time needed for axons to regrow. Here, we show that ablation of histone deacetylase 8 (HDAC8) in SCs accelerates the regrowth of sensory axons and sensory function recovery. We found that HDAC8 is specifically expressed in sensory SCs and regulates the E3 ubiquitin ligase TRAF7, which destabilizes hypoxia-inducible factor 1-alpha (HIF1α) and counteracts the phosphorylation and upregulation of c-Jun, a major inducer of the repair SC phenotype. Our study indicates that this phenotype switch is regulated by different mechanisms in sensory and motor SCs and is accelerated by HDAC8 downregulation, which promotes sensory axon regeneration and sensory function recovery.

Background Transcatheter Aortic Valve Implantation (TAVI) procedures are rapidly expanding, necessitating a more extensive stratification of patients with aortic stenosis. Especially in the high-risk group, some patients fail to derive optimal or any benefits from TAVI, leading to the risk of futile interventions. Despite consensus among several experts regarding the importance of recognizing and anticipating such interventions, the definition, and predictive criteria for futility in TAVI remain ambiguous. Aim The purpose of this study is to explore the literature addressing the definition, predictive criteria, and medical predictive models for futility in cases of TAVI. Design A scoping review was conducted by two researchers and reported in accordance with the PRISMA-ScR guidelines. Eligibility criteria Studies addressing futility in TAVI, including definitions, predictive variables, and models, were included without restrictions on study design but were excluded study only on surgical valve replacement, valve in valve or aortic stenosis causes by other pathology than calcification. Information sources We identified 129 studies from five key sources: CINAHL, PUBMED, the Cochrane Library, ClinicalTrials.gov, and EMBASE. The literature search was conducted in two rounds—first in February 2024 and again in October 2024—using no restrictions on the year of publication or the language of the studies. Additional references were included through cross-referencing. Results The definition of futility is not unanimous, although most researchers agreed on 1-year survival as a cutoff. The majority of studies focused on single variables that can predict 1-year survival, employing either prospective or retrospective designs. Frailty was the major concept studied. Numerous predictive models have been identified, but no consensus was found. Conclusion Futility concepts generate interest in the TAVI procedure. In this review, numerous articles state that 1-year mortality serves as a cutoff to define futile procedures. Some variables, cardiac or otherwise, are independent predictors of 1-year mortality. Medical predictive models showed moderate sensitivity and specificity, except for machine learning, which shows promise for the future. However, few articles delve deeply into non-quantifiable parameters such as patient goals and objectives or ethical questions. More studies should focus on these parameters.

Difficulties regulating emotions have been coined as inherent to autism, possibly even presenting a core difficulty of autism. While several models of emotion regulation have been proposed in the past, in this targeted review article, we aim to map emotion regulation difficulties in autistic individuals within the framework of the extended process model of emotion regulation. This model can be considered the most comprehensive one currently incorporating not only different emotion regulation strategy groups but also different stages and processes involved in successful self-focused emotion regulation. Within this model, we will identify areas and domains as specifically impacted by autistic individuals. We will also outline gaps in the literature and provide suggestions for future research that can help deepen our understanding of the emotion regulation processes of autistic individuals. The ultimate goal is to develop specific support programs that address specific emotion regulation mechanisms, providing a much more individualized support approach. Lay abstract What do we already know about emotion regulation in autism? We know that many autistic children, youth, and adults experience difficulties regulating emotions. Existing research has focused mainly on the differences in emotion regulation capabilities between autistic and non-autistic individuals, the relationships between autistic traits and emotion regulation, and how emotion regulation relates to other outcomes, such as social skills and mental health. What does this paper add? We want to take a new approach to review the existing emotion regulation research through the lens of a specific theoretical model: the extended process model of emotion regulation. Professor James Gross developed this model. It consists of four emotion regulation phases: identification, selection, implementation, and monitoring. Our review revealed specific areas within these emotion regulation phases that could significantly impact the emotion regulation experiences of autistic individuals. We also outline the gaps in the research and propose avenues for future investigation. Implications for practice By deepening our understanding of emotion regulation in autistic individuals through the proposed future research, researchers and clinicians can pave the way for the development of tailored support programs. These programs will directly target specific emotion regulation mechanisms, offering a much-needed individualized support approach.

Background Good communication between health authorities and citizens is crucial for adherence to preventive measures during a pandemic. Crisis communication often appeals to worries about negative consequences for oneself or others. While worry can motivate protective behavior, it can also be overwhelming and lead to irrational choices or become a mental health problem. Also, the levels and consequences of worry can differ between different groups of citizens. Little is known about the evolution of worries during the pandemic and adherence to measures in distinct groups. Objective This study aimed to evaluate worries in the Swiss population as well as associations between worry levels and citizens’ adherence to government restrictions during different phases of the COVID-19 pandemic. Methods We carried out an observational study with 4 cross-sectional online surveys of adults in the Canton of Vaud, Switzerland. Questionnaires were distributed through social media and websites during 4 periods: survey 1: April 17 to May 14, 2020; survey 2: May 15 to June 22, 2020; survey 3: October 30 to December 12, 2020; and survey 4: June 18 to December 30, 2021. On visual analog scales from 0 to 100, participants reported worry, self-adherence to pandemic restrictions, and their perceived adherence to others. We used multivariable linear regression, adjusting for age, gender, health literacy, and education to assess associations between self-reported worry, adherence, and study periods. Results We collected 7106 responses. After excluding 2377 questionnaires (incomplete, age <18 years, residence outside Vaud), 4729 (66.55%) were analyzed (mean age 47, SD 15.6 years, 63.96% women). Mean worry across the 4 periods was 42/100, significantly higher in women (44.25/100, vs 37.98/100; P<.001) and young people (43.77/100 in those aged 18-39 years, vs 41.69/100; P=.005; in those aged 40-64 years and 39.16/100; P=.002; in those aged >64 years). Worries were higher during survey 1 and survey 3 (52.41/100 and 56.32/100 vs 38.93/100, P<.001; and 35.71/100, P<.001) than during survey 2 and survey 4, respectively. This corresponds to pandemic peaks during which federal restrictions were better followed with self-reported adherence of 84.80/100 and 89.59/100 in survey 1 and survey 3 versus 78.69/100 (P<.001) and 78.64/100 (P<.001) in survey 2 and survey 4. A 2.9-point increase in worry score, adjusted for the pandemic period, gender, age, education, and health literacy, was associated with a 10-point increase in personal adherence score (95% CI 2.5-3.2; P<.001). Conclusions Worries were higher in women, young people, and during the peak of the COVID-19 pandemic. Higher worry levels were associated with increased self-reported adherence to federal restrictions. Authorities should consider population worry levels and population subgroups in the planning and design of pandemic communication.

Social insects form complex societies with division of labour between different female castes. In most species, a single queen heads the colony; in others, several queens share the task of reproduction. These different social organisations are often associated with distinct queen morphologies and life‐history strategies and occur in different environments. In the ant Temnothorax rugatulus , queens are dimorphic. Macrogynes and microgynes reside in mono‐ and polygynous colonies and at lower and higher elevations, respectively. We analysed plastic changes in brain transcriptomes in response to the social environment in these queen morphs and their workers. We manipulated the number of queens over 4 months to investigate whether transcriptional activity is influenced by queen morph, social environment or their interaction. Changes in gene expression in the queens' brains in response to our manipulations were largely influenced by the interaction between social environment and queen morph, rather than independently by these factors. Macrogynes and microgynes thus adjust differently to their social environment. Similarly, worker transcriptomes were influenced by an interaction between behavioural type, that is, nurses or foragers, and queen morph. Nurses differentially regulated genes related to nutrition depending on queen morph, suggesting a link between social environment and metabolic dynamics in ant colonies. Overall, our study sheds light on how the social environment influences the molecular physiology of social insects. Furthermore, we demonstrate that in this ant with two queen morphs, worker physiology depends on queen morph and their role in the colony.

Host manipulation is a common strategy of parasites with complex life cycles. It directly affects predator–prey dynamics in trophically transmitted parasites. Theoretical studies suggest that predation‐enhancing manipulation often decimates the prey population, making parasites prone to extinction. Host manipulation, however, can also reduce predation due to conflicting interests when multiple parasites infect a host, which is often neglected in theoretical studies. Misaligned interests of coinfecting parasites can occur due to limited carrying capacity or parasitoid developmental stage. Including this realistic complexity in a mathematical model, the results depart from previous studies substantially. We show that coinfecting multi‐trophic parasites can preserve the predator–prey system and themselves through manipulation and reproduction parameters. Our study highlights the necessity of and provides the means for incorporating the reality of multiple parasites and their multi‐trophic life cycles into the theory of parasite ecology.

This paper investigates how different lexical factors influence inter-annotator agreement in a semantic annotation task, with the level of agreement serving as an indicator of task complexity. The study uses a dataset of approximately 5000 corpus instances of French nouns, each double annotated with supersenses representing broad semantic classes such as Person, Object and Event. Through statistical analysis, the study evaluates the individual impact of word ambiguity, frequency, concreteness and meaning hybridity on semantic classification. The results show that the four lexical factors under study are correlated with inter-annotator agreement and that they jointly predict a significant portion of the agreement data. More importantly, they contribute to a better understanding of how speakers categorise words semantically, while allowing for a comparison of manual and automated semantic classification based on lexical properties.

This paper introduces the “NEBULA101 - Neuro-behavioural Understanding of Language Aptitude” dataset, which comprises behavioural and brain imaging data from 101 healthy adults to examine individual differences in language and cognition. Human language, a multifaceted behaviour, varies significantly among individuals, at different processing levels. Recent advances in cognitive science have embraced an integrated approach, combining behavioural and brain studies to explore these differences comprehensively. The NEBULA101 dataset offers brain structural, diffusion-weighted, task-based and resting-state MRI data, alongside extensive linguistic and non-linguistic behavioural measures to explore the complex interaction of language and cognition in a highly multilingual sample. By sharing this multimodal dataset, we hope to promote research on the neuroscience of language, cognition and multilingualism, enabling the field to deepen its understanding of the multivariate panorama of individual differences and ultimately contributing to open science.

A metric measure space is said to be Carnot‐rectifiable if it can be covered up to a null set by countably many bi‐Lipschitz images of compact sets of a fixed Carnot group. In this paper, we give several characterisations of such notion of rectifiability both in terms of Alberti representations of the measure and in terms of differentiability of Lipschitz maps with values in Carnot groups. In order to obtain this characterisation, we develop and study the analogue of the notion of Lipschitz differentiability space by Cheeger, using Carnot groups and Pansu derivatives as models. We call such metric measure spaces Pansu differentiability spaces .

Introduction The impact of sex on coronary artery disease prognosis is debated. It has been postulated that women receive less prompt treatment compared with men, potentially adversely affecting their prognosis by significantly increasing the risk of morbidity and mortality. We aim to investigate the influence of sex on the timing and clinical outcomes of ST-segment elevation myocardial infarction (STEMI) patients using a controlled Swiss registry. Methods and results Based on the Fribourg STEMI Fast Track Registry, 1177 patients (288 women, 889 men) with >12 months clinical follow-up were selected. Women had longer first medical contact to reperfusion times (1.31 (1.14–2.00) vs 1.27 (1.09–1.54) hours, p=0.035) but similar total ischaemic times (3.04 (2.15–4.50) vs 2.56 (2.07–4.38) hours, p=0.064). Men had higher rates of diabetes, smoking and dyslipidaemia, while women had higher hypertension and renal insufficiency rates. No significant sex differences in clinical outcomes were observed at 1-year and 5-year follow-ups. Discussion The study found sex differences in patient profiles and minor treatment delays for women, which did not significantly affect outcomes. Efforts to improve sex equity in STEMI care are effective, as no significant outcome differences were observed. Disparities are more related to patient characteristics than sex. Conclusion Despite slight delays and different risk profiles for women with STEMI, clinical outcomes are similar between sexes. Ongoing efforts are needed to ensure sex equity in acute coronary syndrome management. Trial registration number NCT04185285 .

We aimed to identify and validate factors related to uncontrolled hypertension. Participants treated with at least one antihypertensive drug from the prospective contemporaneous CoLaus|PsyCoLaus study were enrolled. We investigated the association between hypertension status (uncontrolled, defined as systolic blood pressure [SBP] ≥ 140 mm Hg and/or diastolic blood pressure [DBP] ≥ 90 mm Hg, versus controlled hypertension [SBP/DBP < 140/90 mm Hg]) and potential risk factors. Additionally, the prospective association of uncontrolled hypertension with cardiovascular disease and all-cause mortality was evaluated. 1040 participants recruited between 2003 and 2006 with a mean follow-up of 12.3 years (SD ± 3.4) were included in the analyses. Heavy alcohol consumption, increased BMI, increased ferritin and albuminuria were positively associated with uncontrolled hypertension. Factors inversely associated with uncontrolled hypertension were university degree, current smoker, and high potassium urinary excretion. Uncontrolled hypertension status was not associated with incident ASCVD nor all-cause mortality in our study. In conclusion, uncontrolled hypertension was associated with modifiable factors, such as heavy drinking, obesity and level of education. Further studies should investigate whether including biological markers in clinical practice, such as potassium excretion, ferritin levels, or albuminuria, would help identify individuals who may develop uncontrolled hypertension.