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Background: Allergen-carrying virus-like particles are effective and safe means of allergen immunotherapy (AIT) in rodent models., Objective: To study the development of allergen-blocking immunoglobulin (Ig)G in dogs injected with Der f 2-carrying enveloped plant-based bioparticles (eBPs)., Materials and Methods: Laboratory beagle dogs were injected intradermally (ID) or subcutaneously (SC) with Der f 2-eBP three times at 2-week intervals. A basophil mediator release assay was used to compare the reactivity of Der f 2-eBPs to that of recombinant Der f 2. Allergen-specific IgG serum levels were determined by immunoblotting and ELISA. The allergen-blocking potential of postvaccination IgG was assessed by Pet Allergy Xplorer (PAX) macroarray and basophil mediator release inhibition assays., Results: The amount of Der f 2 eBPs needed to induce basophil activation was 1000-fold higher than that of the soluble natural allergen. In both immunisation groups, eBP injections caused no adverse events and induced Der f 2-specific IgG, first detected on Day (D)14 and peaking on D41. The co-incubation of sera with a Der f 2-IgE-rich canine serum pool resulted in a mean PAX inhibition of 70% (ID) to 80% (SC) on D41. For both groups, the inhibition of basophil mediator release reached 75% on D28 and D41. The percentage inhibition of PAX and mediator release correlated significantly with Der f 2 IgG levels., Conclusion and Clinical Relevance: Intradermal and subcutaneous injections of Der f 2-eBPs were safe and increased Der f 2-specific IgG. The clinical benefit of immunotherapy will be evaluated in future trials enrolling atopic dogs allergic to house dust mites., (© 2024 ESVD and ACVD.)

3D printing, and more recently 4D printing, has emerged as a transformative technology for fabricating structures with complex geometries and responsive properties. However, employing functional colloidal solutions as inks for printing remains unexplored. In this work, we present a novel and versatile 4D printing approach for fabricating functional and complex-shaped objects using polymerizable liquid crystal (LC) emulsion droplets. Leveraging a digital light processing (DLP) 3D printing technique, we achieve rapid production of intricate 3D geometries with high resolution. The printed structures retain the LC ordering from the precursor droplets, imparting the final objects with shape memory properties, including shape fixation and recovery upon heating or light exposure. Light-responsive behavior is introduced post-printing by embedding an azo dye into the 3D structures. Additionally, we explore the potential to create intrinsically porous 3D structures by selectively removing non-reactive components from the printed geometries, adding an extra level of functionality to the printed objects. Furthermore, we incorporate chiral nematic LCs into the emulsion droplets, producing 3D objects with tunable reflective properties. To our knowledge, this is the first example of DLP 3D printing with emulsions, offering an effective and versatile pathway for developing 4D-printed materials with potential applications in optics, robotics, and biomedicine., (© 2024 Wiley‐VCH GmbH.)

Hypertrophic scarring is a common complication in severely burned patients who undergo autologous skin grafting. Meshed skin grafts tend to contract during wound healing, increasing the risk of pathological scarring. Although various technologies have been used to study cellular contraction, current methods for measuring contractile forces at the tissue level are limited and do not replicate the complexity of native tissues. Self-assembled skin substitutes (SASSs) were developed at the "Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX" and are used as permanent full-thickness skin grafts. The autologous skin substitutes are produced using the self-assembly method, allowing the cultured cells to produce their extracellular matrix leading to a tissue-engineered substitute resembling the native skin. The level of contraction of the SASSs during the fabrication process is patient-dependent. Thus, because of its architecture and composition, SASS is an interesting model to study skin contraction in vitro . Unfortunately, standard measurement methods are unsuited for SASS contraction assessment, mainly due to incompatibilities between the SASS manufacturing process and the current contraction force measurement methods. Here, we present an innovative contraction measurement method specifically designed to quantify the contractile behavior of tissue-engineered substitutes, without disrupting the protocol of production. The method uses C-shape anchoring frames that close at different speeds and magnitudes according to the tissue contractile behavior. A finite element analysis model is then used to associate the frame deformation to a contractile force amplitude. This article shows that the method can be used to measure the contraction force of tissues produced with cells displaying different contractile properties, such as primary skin fibroblasts and myofibroblasts. It can also be used to study the effects of cell culture conditions on tissue contraction, such as serum concentration. This protocol can be easily and affordably applied and tuned to many regenerative medicine applications or contraction-related pathological studies. Impact Statement The protocol presented in this article is a new and simple method to quantify contraction forces present in tissue-engineered substitutes. Using finite element analysis, it allows for the measurement of a contraction force rather than a surface reduction as usually provided by other tissue contraction measurement methods. The results shown are in correlation with the current literature relevant to tissue contraction. It can be easily implemented, and hence, this method will open up new avenues to study tissue contraction of living substitutes engineered with various cell types and to optimize culture conditions.

Lipid metabolism is recognised as being central to growth, disease and health. Lipids, therefore, have an important place in current research on globally significant topics such as food security and biodiversity loss. However, answering questions in these important fields of research requires not only identification and measurement of lipids in a wider variety of sample types than ever before, but also hypothesis-driven analysis of the resulting 'big data'. We present a novel pipeline that can collect data from a wide range of biological sample types, taking 1 000 000 lipid measurements per 384 well plate, and analyse the data systemically. We provide evidence of the power of the tool through proof-of-principle studies using edible fish (mackerel, bream, seabass) and colonies of Bombus terrestris . Bee colonies were found to be more like mini-ecosystems and there was evidence for considerable changes in lipid metabolism in bees through key developmental stages. This is the first report of either high throughput LCMS lipidomics or systemic analysis in individuals, colonies and ecosystems. This novel approach provides new opportunities to analyse metabolic systems at different scales at a level of detail not previously feasible, to answer research questions about societally important topics.

Individuals preferentially reciprocate connections with copartisans versus counter-partisans online. However, the mechanisms underlying this partisan bias remain unclear. Do individuals simply prefer viewing politically congenial content, or do they additionally prefer socially connecting with copartisans? Is this driven by preference for in-party ties or distaste for out-party ties? In a Twitter (now called X) field experiment, we created bot accounts varying by partisanship and whether they identified as bots or humans. We randomly assigned Twitter users ( N = 3,013) to be followed by one of these accounts. We found evidence for social motivation-users were much more likely to reciprocate links to copartisan relative to counter-partisan accounts when the accounts identified as humans versus bots. We also found evidence for both in-party preference and out-party dispreference-users were as likely to follow back copartisan accounts as they were unlikely to followback counter-partisan accounts, compared to politically neutral accounts. A follow-up survey experiment ( N = 990) provides further evidence for distinct roles of issue polarization, out-party animosity, and in-party affinity in moderating follow-back decisions online. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Warning labels from professional fact-checkers are one of the most widely used interventions against online misinformation. But are fact-checker warning labels effective for those who distrust fact-checkers? Here, in a first correlational study (N = 1,000), we validate a measure of trust in fact-checkers. Next, we conduct meta-analyses across 21 experiments (total N = 14,133) in which participants evaluated true and false news posts and were randomized to either see no warning labels or to see warning labels on a high proportion of the false posts. Warning labels were on average effective at reducing belief in (27.6% reduction), and sharing of (24.7% reduction), false headlines. While warning effects were smaller for participants with less trust in fact-checkers, warning labels nonetheless significantly reduced belief in (12.9% reduction), and sharing of (16.7% reduction), false news even for those most distrusting of fact-checkers. These results suggest that fact-checker warning labels are a broadly effective tool for combatting misinformation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In the final phases of bacterial cell wall synthesis, penicillin-binding proteins (PBPs) catalyze the cross-linking of peptidoglycan. For many decades, effective and non-toxic β-lactam antibiotics have been successfully used as mimetics of the d-Ala-d-Ala moiety of the natural substrate and employed as irreversible inhibitors of PBPs. In the years following their discovery, the emergence of resistant bacteria led to a decline in their clinical efficacy. Using Staudinger cycloaddition, we synthesized a focused library of novel monocyclic β-lactams in which different substituents were introduced at the C4 position of the β-lactam ring, at the C3 amino position, and at the N1 lactam nitrogen. In biochemical assays, the compounds were evaluated for their inhibitory effect on the model enzyme PBP1b from Streptococcus pneumoniae . Upon investigation of the antibacterial activity of the newly prepared compounds against ESKAPE pathogens, some compounds showed moderate inhibition. We also examined their reactivity and selectivity in a biochemical assay with other enzymes that have a catalytic serine in the active site, such as human cholinesterases, where they also showed no inhibitory activity, highlighting their specificity for bacterial targets. These compounds form the basis for further work on new monocyclic β-lactams with improved antibacterial activity., (© 2024 Katarina Grabrijan et al., published by Sciendo.)

Liquid crystalline (LC) materials are especially suited for the preparation of active three-dimensional (3D) and 4D microstructures using two-photon laser printing. To achieve the desired actuation, the alignment of the LCs has to be controlled during the printing process. In most cases studied before, the alignment relied on surface modifications and complex alignment patterns and concomitant actuation were not possible. Here, we introduce a strategy for spatially aligning LC domains in three-dimensional space by using 3D-printed polydimethylsiloxane-based microscaffolds as confinement barriers, which induce the desired director field. The director field resulting from the boundary conditions is calculated with Landau de Gennes theory and validated by comparing experimentally measured and theoretically predicted birefringence patterns. We demonstrate our procedures for structures of varying complexity and then employed them to fabricate 4D microstructures that show the desired actuation. Overall, we obtain excellent agreement between theory and experiment. This opens the door for rational design of functional materials for 4D (micro)printing in the future.

Background: Maternally-inherited symbionts can induce pre-mating and/or post-mating reproductive isolation between sympatric host lineages, and speciation, by modifying host reproductive phenotypes. The large parasitoid wasp genus Cotesia (Braconidae) includes a diversity of cryptic species, each specialized in parasitizing one to few related Lepidoptera host species. Here, we characterized the infection status of an assemblage of 21 Cotesia species from 15 countries by several microbial symbionts, as a first step toward investigating whether symbionts may provide a barrier to gene flow between these parasitoid host lineages., Results: The symbiotic microbes Arsenophonus, Cardinium, Microsporidium and Spiroplasma were not detected in the Cotesia wasps. However, the endosymbiotic bacterium Wolbachia was present in at least eight Cotesia species, and hence we concentrated on it upon screening additional DNA extracts and SRAs from NCBI. Some of the closely related Cotesia species carry similar Wolbachia strains, but most Wolbachia strains showed patterns of horizontal transfer between phylogenetically distant host lineages., Conclusions: The lack of co-phylogenetic signal between Wolbachia and Cotesia suggests that the symbiont and hosts have not coevolved to an extent that would drive species divergence between the Cotesia host lineages. However, as the most common facultative symbiont of Cotesia species, Wolbachia may still function as a key-player in the biology of the parasitoid wasps. Its precise role in the evolution of this complex clade of cryptic species remains to be experimentally investigated., (© 2024. The Author(s).)

Lymphatic vessels are essential for preventing the accumulation of harmful components within peripheral tissues, including the artery wall. Various endogenous mechanisms maintain adequate lymphatic function throughout life, with platelets being essential for preserving lymphatic vessel integrity. However, since lymph lacks platelets, their impact on the lymphatic system has long been viewed as restricted to areas where lymphatics intersect with blood vessels. Nevertheless, platelets can also exert long range effects through the release of extracellular vesicles (EVs) upon activation. We observed that platelet EVs (PEVs) are present in lymph, a compartment to which they could transfer regulatory effects of platelets. Here, we report that PEVs in lymph exhibit a distinct signature enabling them to interact with lymphatic endothelial cells (LECs). In vitro experiments show that the internalization of PEVs by LECs maintains their functional integrity. Treatment with PEVs improves lymphatic contraction capacity in atherosclerosis-prone mice. We suggest that boosting lymphatic pumping with exogenous PEVs offers a novel therapeutic approach for chronic inflammatory diseases characterized by defective lymphatics., (© 2024. The Author(s).)

Multi-photon 3D laser printing has gathered much attention in recent years as a means of manufacturing biocompatible scaffolds that can modify and guide cellular behavior in vitro. However, in vivo tissue engineering efforts have been limited so far to the implantation of beforehand 3D printed biocompatible scaffolds and in vivo bioprinting of tissue constructs from bioinks containing cells, biomolecules, and printable hydrogel formulations. Thus, a comprehensive 3D laser printing platform for in vivo and in situ manufacturing of microimplants raised from synthetic polymer-based inks is currently missing. Here, a platform for minimal-invasive manufacturing of microimplants directly in the organism is presented by one-photon photopolymerization and multi-photon 3D laser printing. Employing a commercially available elastomeric ink giving rise to biocompatible synthetic polymer-based microimplants, first applicational examples of biological responses to in situ printed microimplants are demonstrated in the teleost fish Oryzias latipes and in embryos of the fruit fly Drosophila melanogaster. This provides a framework for future studies addressing the suitability of inks for in vivo 3D manufacturing. The platform bears great potential for the direct engineering of the intricate microarchitectures in a variety of tissues in model organisms and beyond., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Microalgae have emerged as sustainable feedstocks due to their ability to fix CO 2 during cultivation, rapid growth rates, and capability to produce a wide variety of metabolites. Several microalgae accumulate lipids in high concentrations, especially triglycerides, along with lipid-soluble, photoactive pigments such as chlorophylls and derivatives. Microalgae-derived triglycerides contain longer fatty acid chains with more double bonds on average than vegetable oils, allowing a higher degree of post-functionalization. Consequently, they are especially suitable as precursors for materials that can be used in 3D printing with light. This work presents the use of microalgae as "biofactories" to generate materials that can be further 3D printed in high resolution. Two taxonomically different strains -Odontella aurita (O. aurita, BEA0921B) and Tetraselmis striata (T. striata, BEA1102B)- are identified as suitable microalgae for this purpose. The extracts obtained from the microalgae (mainly triglycerides with chlorophyll derivatives) are functionalized with photopolymerizable groups and used directly as printable materials (inks) without the need for additional photoinitiators. The fabrication of complex 3D microstructures with sub-micron resolution is demonstrated. Notably, the 3D printed materials show biocompatibility. These findings open new possibilities for the next generation of sustainable, biobased, and biocompatible materials with great potential in life science applications., (© 2024 Wiley‐VCH GmbH.)

Drug-induced liver injury (DILI) represents a major issue for pharmaceutical companies, being a potential cause of black-box warnings on marketed pharmaceuticals, or drug withdrawal from the market. Lipid accumulation in the liver also referred to as steatosis, may be secondary to impaired mitochondrial fatty acid oxidation (mtFAO). However, an overall causal relationship between drug-induced mtFAO inhibition and the occurrence of steatosis in patients has not yet been established with a high number of pharmaceuticals. Hence, 32 steatogenic and 13 nonsteatogenic drugs were tested for their ability to inhibit mtFAO in isolated mouse liver mitochondria. To this end, mitochondrial respiration was measured with palmitoyl-l-carnitine, palmitoyl-CoA + l-carnitine, or octanoyl- l-carnitine. This mtFAO tri-parametric assay was able to predict the occurrence of steatosis in patients with a sensitivity and positive predictive value above 88%. To get further information regarding the mechanism of drug-induced mtFAO impairment, mitochondrial respiration was also measured with malate/glutamate or succinate. Drugs such as diclofenac, methotrexate, and troglitazone could inhibit mtFAO secondary to an impairment of the mitochondrial respiratory chain, whereas dexamethasone, olanzapine, and zidovudine appeared to impair mtFAO directly. Mitochondrial swelling, transmembrane potential, and production of reactive oxygen species were also assessed for all compounds. Only the steatogenic drugs amiodarone, ketoconazole, lovastatin, and toremifene altered all these 3 mitochondrial parameters. In conclusion, our tri-parametric mtFAO assay could be useful in predicting the occurrence of steatosis in patients. The combination of this assay with other mitochondrial parameters could also help to better understand the mechanism of drug-induced mtFAO inhibition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Digital light processing (DLP) is a 3D printing technology offering high resolution and speed. Printable materials are commonly based on multifunctional monomers, resulting in the formation of thermosets that usually cannot be reprocessed or recycled. Some efforts are made in DLP 3D printing of thermoplastic materials. However, these materials exhibit limited and poor mechanical properties. Here, a new strategy is presented for DLP 3D printing of thermoplastics based on a sequential construction of two linear polymers with contrasting (stiff and flexible) mechanical properties. The inks consist of two vinyl monomers, which lead to the stiff linear polymer, and α-lipoic acid, which forms the flexible linear polymer via thermal ring-opening polymerization in a second step. By varying the ratio of stiff and flexible linear polymers, the mechanical properties can be tuned with Young's modulus ranging from 1.1 GPa to 0.7 MPa, while the strain at break increased from 4% to 574%. Furthermore, these printed thermoplastics allow for a variety of reprocessability pathways including self-healing, solvent casting, reprinting, and closed-loop recycling of the flexible polymer, contributing to the development of a sustainable materials economy. Last, the potential of the new material in applications ranging from soft robotics to electronics is demonstrated., (© 2024 Wiley‐VCH GmbH.)

Despite the major roles of choroid plexus epithelial cells (CPECs) in brain homeostasis and repair, their developmental lineage and diversity remain undefined. In simplified differentiations from human pluripotent stem cells, derived CPECs (dCPECs) displayed canonical properties and dynamic multiciliated phenotypes that interacted with Aβ uptake. Single dCPEC transcriptomes over time correlated well with human organoid and fetal CPECs, while pseudotemporal and cell cycle analyses highlighted the direct CPEC origin from neuroepithelial cells. In addition, time series analyses defined metabolic (type 1) and ciliogenic dCPECs (type 2) at early timepoints, followed by type 1 diversification into anabolic-secretory (type 1a) and catabolic-absorptive subtypes (type 1b) as type 2 cells contracted. These temporal patterns were then confirmed in independent derivations and mapped to prenatal stages using human tissues. In addition to defining the prenatal lineage of human CPECs, these findings suggest new dynamic models of ChP support for the developing human brain.

Land-use change is one the greatest threats to biodiversity and is projected to increase in magnitude in the coming years, stressing the importance of better understanding how land-use change may affect vital ecosystem services, such as pollination. Past studies on the impact of land-use change have largely focused on only one aspect of the pollination process (e.g., pollinator composition, pollinator visitation, and pollen transfer), potentially misrepresenting the full complexity of land-use effects on pollination services. Evaluating the impacts across multiple components of the pollination process can also help pinpoint the underlying mechanisms driving land-use change effects. This study evaluates how land-use change affects multiple aspects of the pollination process in common milkweed populations, including pollinator community composition, pollinator visitation rate, pollen removal, and pollen deposition. Overall, land-use change altered floral visitor composition, with small bees having a larger presence in developed areas. Insect visitation rate and pollen removal were also higher in more developed areas, perhaps suggesting a positive impact of land-use change. However, pollen deposition did not differ between developed and undeveloped sites. Our findings highlight the complexity evaluating land-use change effects on pollination, as these likely depend on the specific aspect of pollination evaluated and on the of the intensity of disturbance. Our study stresses the importance of evaluating multiple components of the pollination process in order to fully understand overall effects and mechanisms underlying land-use change effects on this vital ecosystem service., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Objective: We decided to conduct a study based on these multidisciplinary team (MDT) in order to investigate their impact at the University Hospitals of Strasbourg and look for ways to improve this MDT., Methods: This is a retrospective study of the 682 patients presented to endometriosis MDT from its inception in March 2017 to December 2020., Results: The MDT decision was different from that initially proposed by the patient's referent for 406 patients (60%). Surgery was chosen for 417 patients (61%) and assisted reproduction for 261 patients (38%). A review of the MRI by a referring radiologist was carried out for 348 cases (51%), with a modification of the results for 255 patients (73%). Initial underestimation of lesions was noted in 198 cases., Conclusion: Our study has shown the importance of MDT in endometriosis since the therapeutic proposal was modified in 60% of cases. In addition, we supported the importance of radiologists specializing in this field since they made a modification in two-thirds of the MRIs reread. These results show the importance of collegial discussions, which can modify the decisions of medical teams. This underlines the importance of setting up endometriosis networks., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

There is strong political assortment of Americans on social media networks. This is typically attributed to preferential tie formation (i.e. homophily) among those with shared partisanship. Here, we demonstrate an additional factor beyond homophily driving assorted networks: preferential prevention of social ties. In two field experiments on Twitter, we created human-looking bot accounts that identified as Democrats or Republicans, and then randomly assigned users to be followed by one of these accounts. In addition to preferentially following-back copartisans, we found that users were 12 times more likely to block counter-partisan accounts compared to copartisan accounts in the first experiment, and 4 times more likely to block counter-partisan accounts relative to a neutral account or a copartisan account in the second experiment. We then replicated these findings in a survey experiment and found evidence of a key motivation for blocking: wanting to avoid seeing any content posted by the blocked user. Additionally, we found that Democrats preferentially blocked counter-partisans more than Republicans, and that this asymmetry was likely due to blocking accounts who post low-quality or politically slanted content (rather than an asymmetry in identity-based blocking). Our results demonstrate that preferential blocking of counter-partisans is an important phenomenon driving political assortment on social media., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Infection by certain pathogens is associated with cancer development. We conducted a case-cohort study of ~2500 incident cases of esophageal, gastric and duodenal cancer, and gastric and duodenal ulcer and a randomly selected subcohort of ~2000 individuals within the China Kadoorie Biobank study of >0.5 million adults. We used a bead-based multiplex serology assay to measure antibodies against 19 pathogens (total 43 antigens) in baseline plasma samples. Associations between pathogens and antigen-specific antibodies with risks of site-specific cancers and ulcers were assessed using Cox regression fitted using the Prentice pseudo-partial likelihood. Seroprevalence varied for different pathogens, from 0.7% for Hepatitis C virus (HCV) to 99.8% for Epstein-Barr virus (EBV) in the subcohort. Compared to participants seronegative for the corresponding pathogen, Helicobacter pylori seropositivity was associated with a higher risk of non-cardia (adjusted hazard ratio [HR] 2.73 [95% CI: 2.09-3.58]) and cardia (1.67 [1.18-2.38]) gastric cancer and duodenal ulcer (2.71 [1.79-4.08]). HCV was associated with a higher risk of duodenal cancer (6.23 [1.52-25.62]) and Hepatitis B virus was associated with higher risk of duodenal ulcer (1.46 [1.04-2.05]). There were some associations of antibodies again some herpesviruses and human papillomaviruses with risks of gastrointestinal cancers and ulcers but these should be interpreted with caution. This first study of multiple pathogens with risk of gastrointestinal cancers and ulcers demonstrated that several pathogens are associated with risks of gastrointestinal cancers and ulcers. This will inform future investigations into the role of infection in the etiology of these diseases., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The spread of misinformation is a pressing societal challenge. Prior work shows that shifting attention to accuracy increases the quality of people's news-sharing decisions. However, researchers disagree on whether accuracy-prompt interventions work for U.S. Republicans/conservatives and whether partisanship moderates the effect. In this preregistered adversarial collaboration, we tested this question using a multiverse meta-analysis ( k = 21; N = 27,828). In all 70 models, accuracy prompts improved sharing discernment among Republicans/conservatives. We observed significant partisan moderation for single-headline "evaluation" treatments (a critical test for one research team) such that the effect was stronger among Democrats than Republicans. However, this moderation was not consistently robust across different operationalizations of ideology/partisanship, exclusion criteria, or treatment type. Overall, we observed significant partisan moderation in 50% of specifications (all of which were considered critical for the other team). We discuss the conditions under which moderation is observed and offer interpretations.

We propose that deviancy aversion-people's domain-general discomfort toward the distortion of patterns (repeated forms or models)-contributes to the strength and prevalence of social norms in society. Five studies ( N = 2,390) supported this hypothesis. In Study 1, individuals' deviancy aversion, for instance, their aversion toward broken patterns of simple geometric shapes, predicted negative affect toward norm violations (affect), greater self-reported norm following (behavior), and judging norms as more valuable (belief). Supporting generalizability, deviancy aversion additionally predicted greater conformity on accuracy-orientated estimation tasks (Study 2), adherence to physical distancing norms during COVID-19 (Study 3), and increased following of fairness norms (Study 4). Finally, experimentally heightening deviancy aversion increased participants' negative affect toward norm violations and self-reported norm behavior, but did not convincingly heighten belief-based norm judgments (Study 5). We conclude that a human sensitivity to pattern distortion functions as a low-level affective process that promotes and maintains social norms in society., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lean patients with NAFLD may develop cardiac complications independently of pre-existent metabolic disruptions and comorbidities. To address the underlying mechanisms independent of the development of obesity, we used a murine model of hepatic mitochondrial deficiency. The liver-heart axis was studied as these mice develop microvesicular steatosis without obesity. Our results unveil a sex-dependent phenotypic remodeling beyond liver damage. Males, more than females, show fasting hypoglycemia and increased insulin sensitivity. They exhibit diastolic dysfunction, remodeling of the circulating lipoproteins and cardiac lipidome. Conversely, females do not manifest cardiac dysfunction but exhibit cardiometabolic impairments supported by impaired mitochondrial integrity and β-oxidation, remodeling of circulating lipoproteins and intracardiac accumulation of deleterious triglycerides. This study underscores metabolic defects in the liver resulting in significant sex-dependent cardiac abnormalities independent of obesity. This experimental model may prove useful to better understand the sex-related variability, notably in the heart, involved in the progression of lean-NAFLD., (© 2024. The Author(s).)

Identifying successful approaches for reducing the belief and spread of online misinformation is of great importance. Social media companies currently rely largely on professional fact-checking as their primary mechanism for identifying falsehoods. However, professional fact-checking has notable limitations regarding coverage and speed. In this article, we summarize research suggesting that the "wisdom of crowds" can be harnessed successfully to help identify misinformation at scale. Despite potential concerns about the abilities of laypeople to assess information quality, recent evidence demonstrates that aggregating judgments of groups of laypeople, or crowds, can effectively identify low-quality news sources and inaccurate news posts: Crowd ratings are strongly correlated with fact-checker ratings across a variety of studies using different designs, stimulus sets, and subject pools. We connect these experimental findings with recent attempts to deploy crowdsourced fact-checking in the field, and we close with recommendations and future directions for translating crowdsourced ratings into effective interventions.

Background: Angiopoietin-like 2 (ANGPTL2) is a pro-inflammatory and pro-oxidant circulating protein that predicts and promotes chronic inflammatory diseases such as atherosclerosis in humans. Transgenic murine models demonstrated the deleterious role of ANGPTL2 in vascular diseases, while deletion of ANGPTL2 was protective. The nature of its role in cardiac tissues is, however, less clear. Indeed, in adult mice knocked down (KD) for ANGPTL2, we recently reported a mild left ventricular (LV) dysfunction originating from a congenital aortic valve stenosis, demonstrating that ANGPTL2 is essential to cardiac development and function. Hypothesis: Because we originally demonstrated that the KD of ANGPTL2 protected vascular endothelial function via an upregulation of arterial NOX4, promoting the beneficial production of dilatory H 2 O 2 , we tested the hypothesis that increased cardiac NOX4 could negatively affect cardiac redox and remodeling and contribute to LV dysfunction observed in adult Angptl2 -KD mice. Methods and results: Cardiac expression and activity of NOX4 were higher in KD mice, promoting higher levels of cardiac H 2 O 2 when compared to wild-type (WT) mice. Immunofluorescence showed that ANGPTL2 and NOX4 were co-expressed in cardiac cells from WT mice and both proteins co-immunoprecipitated in HEK293 cells, suggesting that ANGPTL2 and NOX4 physically interact. Pressure overload induced by transverse aortic constriction surgery (TAC) promoted LV systolic dysfunction in WT mice but did not further exacerbate the dysfunction in KD mice. Importantly, the severity of LV systolic dysfunction in KD mice (TAC and control SHAM) correlated with cardiac Nox4 expression. Injection of an adeno-associated virus (AAV9) delivering shRNA targeting cardiac Nox4 expression fully reversed LV systolic dysfunction in KD-SHAM mice, demonstrating the causal role of NOX4 in cardiac dysfunction in KD mice. Targeting cardiac Nox4 expression in KD mice also induced an antioxidant response characterized by increased expression of NRF2/KEAP1 and catalase. Conclusion: Together, these data reveal that the absence of ANGPTL2 induces an upregulation of cardiac NOX4 that contributes to oxidative stress and LV dysfunction. By interacting and repressing cardiac NOX4, ANGPTL2 could play a new beneficial role in the maintenance of cardiac redox homeostasis and function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Labbé, Martel, Shi, Montezano, He, Gillis, Higgins, Villeneuve, Touyz, Tardif, Thorin-Trescases and Thorin.)

We present adult normalized data for MindPulse (MP), a new tool evaluating attentional and executive functioning (AEF) in decision-making. We recruited 722 neurotypical participants (18-80 years), with 149 retested. The MP test includes three tasks: Simple Reaction Time (SRT), Go/No-go, and complex Go/No-go, involving perceptual components, motor responses, and measurements of reaction time (RT) and correctness. We compare responses, evaluating 14 cognitive indices (including new composite indices to describe AEF: Executive Speed and Reaction to Difficulty). We adjust for age/sex effects, introduce a difficulty scale, and consider standard deviations, aberrant times, and Spearman Correlation for speed-accuracy balance. Wilcoxon unpaired rank test is used to assess sex effects, and linear regression is employed to assess the age linear dependency model on the normalized database. The study demonstrated age and sex effects on RTs, in all three subtests, and the ability to correct it for individual results. The test showed excellent validity (Cronbach Alpha for the three subtasks is 92, 87, 95%) and high internal consistency ( p  < 0.001 for each subtask significantly faster than the more complex subtask) of the MP across the wide age range. Results showed correlation within the three RT parts of the test ( p  < .001 for each) and the independence of SRT, RD, and ES indices. The Retest effect was lower than intersubject variance, showing consistency over time. This study highlights the MP test's strong validity on a homogeneous, large adult sample. It emphasizes assessing AEF and Reaction to Difficulty dynamically with high sensitivity.