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Abstract Avoiding threatening individuals is pivotal for adaptation to our social environment. Yet, it remains unclear whether social threat avoidance is subtended by goal-directed processes, in addition to stimulus-response associations. To test this, we manipulated outcome predictability during spontaneous approach/avoidance decisions from avatars displaying angry facial expressions. Across three virtual reality experiments, we showed that participants avoided more often when they could predict the outcome of their actions, indicating goal-directed processes. However, above-chance avoidance rate when facing unpredictable outcomes suggested that stimulus-response associations also played a role. We identified two latent classes of participants: the “goal-directed class” showed above-chance avoidance only in the predictable condition, while the “stimulus-response class” showed no credible difference between conditions but had a higher overall avoidance rate. The goal-directed class exhibited greater cardiac deceleration in the predictable condition, associated with better value integration in decision-making. Computationally, this class had an increased drift-rate in the predictable condition, reflecting increased value estimation of threat avoidance. In contrast, the stimulus-response class showed higher responsiveness to threat, indicated by increased drift-rate for avoidance and increased muscular activity at response time. These results support the central role of goal-directed processes in social threat avoidance and reveal its physiological and computational correlates.

Abstract ARL13B is a small regulatory GTPase that controls ciliary membrane composition in both motile cilia and non-motile primary cilia. In this study, we investigated the role of ARL13B in the efferent ductules, tubules of the male reproductive tract essential to male fertility in which primary and motile cilia co-exist. We used a genetically engineered mouse model to delete Arl13b in efferent ductule epithelial cells, resulting in compromised primary and motile cilia architecture and functions. This deletion led to disturbances in reabsorptive/secretory processes and triggered an inflammatory response. The observed male reproductive phenotype showed significant variability linked to partial infertility, highlighting the importance of ARL13B in maintaining a proper physiological balance in these small ducts. These results emphasize the dual role of both motile and primary cilia functions in regulating efferent duct homeostasis, offering deeper insights into how cilia related diseases affect the male reproductive system.

Abstract Background Individuals with Autism Spectrum Condition (ASC) are characterized by atypicalities in social interactions, compared to Typically Developing individuals (TD). The social motivation theory posits that these difficulties stem from diminished anticipation, reception, and/or learning from social rewards. Although learning from socioemotional outcomes is core to the theory, studies to date have been sparse and inconsistent. This possibly arises from a combination of theoretical, methodological and sample-related issues. Here, we assessed participants’ ability to develop a spontaneous preference for actions that lead to desirable socioemotional outcomes (approaching/avoiding of happy/angry individuals, respectively), in an ecologically valid social scenario. We expected that learning abilities would be impaired in ASC individuals, particularly in response to affiliative social feedback. Method We ran an online social reinforcement learning task, on two large online cohorts with (n = 274) and without (n = 290) ASC, matched for gender, age and education. Participants had to indicate where they would sit in a waiting room. Each seat was associated with different probabilities of approaching/avoiding emotional individuals. Importantly, the task was implicit, as participants were not instructed to learn, and emotional expressions were never mentioned. We applied both categorical analyses contrasting the ASC and TD groups and dimensional factor analysis on affective questionnaires. Results Contrary to our hypothesis, participants showed spontaneous learning from socioemotional outcomes, regardless of their diagnostic group. Yet, when accounting for dimensional variations in autistic traits, as well as depression and anxiety, two main findings emerged among females who failed to develop explicit learning strategies: (1) autism severity in ASC correlated with reduced learning to approach happy individuals; (2) anxiety-depression severity across both ASC and TD participants correlated with reduced learning to approach/avoid happy/angry individuals, respectively. Conclusions Implicit spontaneous learning from socioemotional outcomes is not generally impaired in autism but may be specifically associated with autism severity in females with ASC, when they do not have an explicit strategy for adapting to their social environment. Clinical diagnosis and intervention ought to take into account individual differences in their full complexity, including the presence of co-morbid anxiety and depression, when dealing with social atypicalities in autism.

Sharing emotions with other individuals is a widespread phenomenon. Previous research proposed that experiencing intense and similar emotions with other individuals reinforces social bonds. However, several aspects of this phenomenon remain unclear, notably whether social bonding requires the convergence and synchronization of emotions in the group, and whether these effects generalize across positively valenced and negatively valenced emotional contexts. To address these questions, we measured subjective emotional experiences, physiological activity (cardiac, respiratory, electrodermal) and social attitudes in dyads of unacquainted individuals who watched videos in the presence of each other. We manipulated the emotional content of the videos and the type of shared attention between participants, to test for the contribution of interpersonal influence. The results revealed that intense emotions indexed by physiological arousal were associated with the emergence of reciprocal prosocial attitudes within dyads, and that this effect depended on joint attention. We did not observe the convergence and synchronization of emotions within dyads, which suggests that experiencing similar emotions was not necessary for social bonding. We discuss implications of this study for research on collective effervescence and the social consequences of shared experiences.

Abstract The demand for automated systems monitoring and supporting patients in their home-based recovery programs is substantial. While emerging technologies have been proposed as potential solutions to enhance at-home patient care, limited systems are in place due to their challenges in offering real-time monitoring and corrective feedback. Most proposed methodologies provide an overall measure or score for the executed movement. The proposed work involves the adaptation of an existing published dataset to cater to the needs of a system capable of remotely assisting patients, effectively acting as a virtual physical therapist able to provide corrective feedback. A dataset containing a set of three simple exercises for shoulder rehabilitation was processed. Each movement was meticulously annotated for temporal and categorical motion domains to monitor exercise execution in terms of the range of motion completeness and to evaluate compensatory movement patterns. This work carries substantial significance by offering a standardized and easily accessible model for human movement data, thus fostering the advancement of digital assistive systems designed to support home-based rehabilitation programs.

Abstract Centrosomes and cilia are microtubule-based superstructures vital for cell division, signaling, and motility. The once thought hollow lumen of their microtubule core structures was recently found to hold a rich meshwork of microtubule inner proteins (MIPs). To address the outstanding question of how distinct MIPs evolved to recognize microtubule inner surfaces, we applied computational sequence analyses, structure predictions, and experimental validation to uncover evolutionarily conserved microtubule- and MIP-binding modules named NWE, SNYG, and ELLEn, and PYG and GFG-repeat by their signature motifs. These modules intermix with MT-binding DM10-modules and Mn-repeats in 24 Chlamydomonas and 33 human proteins. The modules molecular characteristics provided keys to identify elusive cross-species homologs, hitherto unknown human MIP candidates, and functional properties for seven protein subfamilies, including the microtubule seam-binding NWE and ELLEn families. Our work defines structural innovations that underpin centriole and axoneme assembly and demonstrates that MIPs co-evolved with centrosomes and cilia.

Systemic sclerosis (SSc) is a rare autoimmune disease whose molecular mechanisms are not yet fully understood. There is no definitive cure, and the main causes of death are pulmonary fibrosis and pulmonary arterial hypertension. Here, we focus on the interferon regulators factor 8 (IRF8), a factor involved in the type I interferon (IFN-I) signature, which is present in about half of SSc patients. Variants of this factor may play a role in autoimmunity, but little is known regarding the role of IRF8 in SSc pathogenesis. We carried out a literature search to address the association between the IRF8 factor and SSc susceptibility and clinical manifestations. The current studies appear to confirm a possible association between the alteration of the gene for IRF8 and SSc susceptibility. A link between IRF8 mutations and expression of a pro-fibrotic phenotype at the cellular level also emerges. Additional investigations are needed to confirm the role of IRF8 in SSc. However, IRF8 is worth consideration as a possible new disease marker of fibrosis in SSc patients.

Abstract Background Globally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls. Methods Chorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses. Results A total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR

Summary: Emotional signals, notably those signaling threat, benefit from prioritized processing in the human brain. Yet, it remains unclear whether perceptual decisions about the emotional, threat-related aspects of stimuli involve specific or similar neural computations compared to decisions about their non-threatening/non-emotional components. We developed a novel behavioral paradigm in which participants performed two different detection tasks (emotion vs. color) on the same, two-dimensional visual stimuli. First, electroencephalographic (EEG) activity in a cluster of central electrodes reflected the amount of perceptual evidence around 100 ms following stimulus onset, when the decision concerned emotion, not color. Second, participants’ choice could be predicted earlier for emotion (240 ms) than for color (380 ms) by the mu (10 Hz) rhythm, which reflects motor preparation. Taken together, these findings indicate that perceptual decisions about threat-signaling dimensions of facial displays are associated with prioritized neural coding in action-related brain regions, supporting the motivational value of socially relevant signals.

Stroke, resulting in hypoxia and glucose deprivation, is a leading cause of death and disability worldwide. Presently, there are no treatments that reduce neuronal damage and preserve function aside from tissue plasminogen activator administration and rehabilitation therapy. Interestingly, Drosophila melanogaster, the common fruit fly, demonstrates robust hypoxic tolerance, characterized by minimal effects on survival and motor function following systemic hypoxia. Due to its organized brain, conserved neurotransmitter systems, and genetic similarity to humans and other mammals, uncovering the mechanisms of Drosophila’s tolerance could be a promising approach for the development of new therapeutics. Interestingly, a key facet of hypoxic tolerance in Drosophila is organism-wide metabolic suppression, a response involving multiple genes and pathways. Specifically, studies have demonstrated that pathways associated with oxidative stress, insulin, hypoxia-inducible factors, NFκB, Wnt, Hippo, and Notch, all potentially contribute to Drosophila hypoxic tolerance. While manipulating the oxidative stress response and insulin signaling pathway has similar outcomes in Drosophila hypoxia and the mammalian middle cerebral artery occlusion (MCAO) model of ischemia, effects of Notch pathway manipulation differ between Drosophila and mammals. Additional research is warranted to further explore how other pathways implicated in hypoxic tolerance in Drosophila, such as NFκB, and Hippo, may be utilized to benefit mammalian response to ischemia. Together, these studies demonstrate that exploration of the hypoxic response in Drosophila may lead to new avenues of research for stroke treatment in humans.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular and immunity alterations and skin/internal organ fibrosis. Aberrant levels of plasma CXCL4, CXCL4–RNA/DNA complexes, type I IFN (IFN-I) and anti-CXCL4 antibodies characterize SSc. These parameters influence each other: CXCL4–self-DNA/RNA complexes are triggers of IFN-I in plasmacytoid dendritic cells (pDCs), and anti-CXCL4 autoantibodies amplify this effect. Here, we assess the modulation over time of plasma CXCL4 and the related parameters of CXCL4–DNA/RNA complexes, anti-CXCL4 antibodies, IFN-α and TNF-α in an SSc cohort under the synthetic analogue of prostacyclin PGI2 (iloprost) treatment to address contribution of these parameters to pathogenesis and their role as biomarkers. Methods: We analyzed immunological parameters at baseline (T0) and after 3 (T3) and 6 (T6) months in 30 SSc patients. Responders were the patients that lowered their disease activity parameters after six months of treatment. Results: Anti-CXCL4 autoantibodies correlated with both IFN-α and TNF-α levels in SSc plasma. Responders significantly down-regulated serum IFN-α. In seven patients with a shorter disease duration, improvement coincides with a decrease in plasma IFN-α, CXCL4 and TNF-α. Iloprost efficiently blocks pDCs IFN-α production induced by CXCL4–DNA/RNA complexes in vitro. Conclusions: The data suggest a possible role of iloprost as a disease-modifying drug, mainly accompanied by down-regulation of plasma IFN-I levels. Since CXCL4, IFN-I and TNF-α down-modulation was evident and significant in improving SSc patients with a shorter disease duration, these results warrant future investigations on the early use of iloprost to slow SSc progression.

Over the past decade, there has been a notable surge in AI-driven research, specifically geared toward enhancing crucial clinical processes and outcomes. The potential of AI-powered decision support systems to streamline clinical workflows, assist in diagnostics, and enable personalized treatment is increasingly evident. Nevertheless, the introduction of these cutting-edge solutions poses substantial challenges in clinical and care environments, necessitating a thorough exploration of ethical, legal, and regulatory considerations.A robust governance framework is imperative to foster the acceptance and successful implementation of AI in healthcare. This article delves deep into the critical ethical and regulatory concerns entangled with the deployment of AI systems in clinical practice. It not only provides a comprehensive overview of the role of AI technologies but also offers an insightful perspective on the ethical and regulatory challenges, making a pioneering contribution to the field.This research aims to address the current challenges in digital healthcare by presenting valuable recommendations for all stakeholders eager to advance the development and implementation of innovative AI systems.

Summary: R2TP is a chaperone complex consisting of the AAA+ ATPases RUVBL1 and RUVBL2, as well as RPAP3 and PIH1D1 proteins. R2TP is responsible for the assembly of macromolecular complexes mainly acting through different adaptors. Using proximity-labeling mass spectrometry, we identified deleted in primary ciliary dyskinesia (DPCD) as an adaptor of R2TP. Here, we demonstrate that R2TP-DPCD influences ciliogenesis initiation through a unique mechanism by interaction with Akt kinase to regulate its phosphorylation levels rather than its stability. We further show that DPCD is a heart-shaped monomeric protein with two domains. A highly conserved region in the cysteine- and histidine-rich domains-containing proteins and SGT1 (CS) domain of DPCD interacts with the RUVBL2 DII domain with high affinity to form a stable R2TP-DPCD complex both in cellulo and in vitro. Considering that DPCD is one among several CS-domain-containing proteins found to associate with RUVBL1/2, we propose that RUVBL1/2 are CS-domain-binding proteins that regulate complex assembly and downstream signaling.

Objective: Food processing greatly contributed to increased food safety, diversity, and accessibility. However, the prevalence of highly palatable and highly processed food in our modern diet has exacerbated obesity rates and contributed to a global health crisis. While accumulating evidence suggests that chronic consumption of such foods is detrimental to sensory and neural physiology, it is unclear whether its short-term intake has adverse effects. Here, we assessed how short-term consumption (

Oleoylethanolamide (OEA) is a safe bioactive lipid that demonstrated strong anorexigenic properties in preclinical and clinical models. In order to evaluate the importance of OEA delivery kinetic on its anorectic properties, we developed OEA-containing dairy snacks with either a liquid or a semi-solid form. The OEA+ liquid snack, but not the semi-solid one, reduced by 14 and 18 % the amount of feed eaten by normal-weight and obese minipigs, respectively, in an eating behavior test performed 4 h after snack ingestion. In vitro digestion experiments revealed that OEA release in intestinal digesta was greatly enhanced when the snack was liquid compared to the semi-solid structure. Kinetic investigations of several plasma parameters after liquid snack ingestion points towards different potential mechanism depending upon the minipig weight status, with an effect of the OEA+ liquid snack likely on endocannabinoid and other related N-acylethanolamine metabolism in normal-weight minipigs and on ketogenesis in obese ones.

In tomatoes, grafting onto resistant rootstocks represents an effective strategy to control several soil-borne diseases that reduce crop profitability, especially for landraces with little or no resistance to multiple pathogens/pests. In this study, the high-value ‘Corbarino’ tomato landrace was grafted onto seven commercial Solanum interspecific rootstocks to evaluate graft compatibility, yield performance, and qualitative characteristics under greenhouse healthy conditions. Three rootstocks were the most effective in improving fruit yield without negatively affecting the carpometric, technological, and health-related traits of the traditional tomato. ‘Dinafort’ rootstock increased fresh and dry yield, harvest index, and fruit/clusters, while mean fruit weight, shape index, total and soluble solid content, simple sugars, organic acids, flavonoids, ascorbic acid, and trans-lycopene content did not differ with respect to the ungrafted ‘Corbarino’. ‘Interpro’ rootstock also showed promising results for the overall yield and quality traits, although it reduced the trans-lycopene content in the fruit. ‘Silex’ rootstock showed the highest harvest index as result of decreased vigour. The fruit quality induced by ‘Silex’ was satisfactory and high levels of simple sugars, flavonoids, ascorbic acid, and trans-lycopene were also observed. However, graft success, especially for ‘Dinafort’ and ‘Silex’, needs to be improved by investigating more suitable methods for seedling production, grafting, acclimatization, etc.

Autoantibodies represent a primary characteristic of many systemic autoimmune diseases [...]

Artificial intelligence technologies are considered crucial in supporting a decentralized model of care in which therapeutic interventions are provided from a distance. In the last years, various approaches have been proposed to support remote monitoring and smart assistance in rehabilitation services. Comprehensive state-of-the-art of machine learning methods and applications is presented in this review. Following PRISMA guidelines, a systematic literature search strategy was led in PubMed, Scopus, and IEEE Xplore databases. The search yielded 519 records, resulting in 35 articles included in this study. Supervised and unsupervised machine learning algorithms were identified. Unobtrusive capture motion technologies have been identified as strategic applications to support remote and smart monitoring. The main tasks addressed by algorithms were activity recognition, movement classification, and clinical status prediction. Some authors evidenced drawbacks concerning the low generalizability of the results retrieved. Artificial intelligence-based applications are likely to impact the delivery of decentralized rehabilitation services by providing broad access to sustained and high-quality therapy. Future efforts are needed to validate artificial intelligence technologies in specific clinical populations and evaluate results reliability in remote conditions and home-based settings.

Abstract Adaptation to our social environment requires learning how to avoid potentially harmful situations, such as encounters with aggressive individuals. Threatening facial expressions can evoke automatic stimulus-driven reactions, but whether their aversive motivational value suffices to drive instrumental active avoidance remains unclear. When asked to freely choose between different action alternatives, participants spontaneously—without instruction or monetary reward—developed a preference for choices that maximized the probability of avoiding angry individuals (sitting away from them in a waiting room). Most participants showed clear behavioral signs of instrumental learning, even in the absence of an explicit avoidance strategy. Inter-individual variability in learning depended on participants’ subjective evaluations and sensitivity to threat approach feedback. Counterfactual learning best accounted for avoidance behaviors, especially in participants who developed an explicit avoidance strategy. Our results demonstrate that implicit defensive behaviors in social contexts are likely the product of several learning processes, including instrumental learning.

The Q&U Bolometric Interferometer for Cosmology (QL’BIC) is the first bolometric interferometer designed to measure the primordial B-mode polarization of the Cosmic Microwave Background (CMB). Bolometric interferometry is a novel technique that combines the sensitivity of bolometric detectors with the control of systematic effects that is typical of interferometry, both key features in the quest for the faint signal of the primordial B-modes. A unique feature is the so-called “spectral imaging”, i.e., the ability to recover the sky signal in several sub-bands within the physical band during data analysis. This feature provides an in-band spectral resolution of ∆v/v ~ 0.04 that is unattainable by a traditional imager. This is a key tool for controlling the Galactic foregrounds contamination. In this paper, we describe the principles of bolometric interferometry, the current status of the QU BIC experiment and future prospects.