iPSC-derived cells for whole liver bioengineering.

Liver bioengineering stands as a prominent alternative to conventional hepatic transplantation. Through liver decellularization and/or bioprinting, researchers can generate acellular scaffolds to overcome immune rejection, genetic manipulation, and ethical concerns that often accompany traditional transplantation methods, in vivo regeneration, and xenotransplantation. Hepatic cell lines derived from induced pluripotent stem cells (iPSCs) can repopulate decellularized and bioprinted scaffolds, producing an increasingly functional organ potentially suitable for autologous use. In this mini-review, we overview recent advancements in vitro hepatocyte differentiation protocols, shedding light on their pivotal role in liver recellularization and bioprinting, thereby offering a novel source for hepatic transplantation. Finally, we identify future directions for liver bioengineering research that may allow the implementation of these systems for diverse applications, including drug screening and liver disease modeling.

Adaptive infusion of a glucagon-like peptide-1/glucagon receptor co-agonist G3215, in adults with overweight or obesity: Results from a phase 1 randomized clinical trial.

AIMS: To determine whether a continuous infusion of a glucagon-like peptide receptor (GLP-1R)/glucagon receptor (GCGR) co-agonist, G3215 is safe and well tolerated in adults with overweight or obesity. METHODS: A phase 1 randomized, double blind, placebo-controlled trial of G3215 in overweight or obese participants, with or without type 2 diabetes. RESULTS: Twenty-six participants were recruited and randomized with 23 completing a 14-day subcutaneous infusion of G3215 or placebo. The most common adverse events were nausea or vomiting, which were mild in most cases and mitigated by real-time adjustment of drug infusion. There were no cardiovascular concerns with G3215 infusion. The pharmacokinetic characteristics were in keeping with a continuous infusion over 14 days. A least-squares mean body weight loss of 2.39 kg was achieved with a 14-day infusion of G3215, compared with 0.84 kg with placebo infusion (p < .05). A reduction in food consumption was also observed in participants receiving G3215 and there was no deterioration in glycaemia. An improved lipid profile was seen in G3215-treated participants and consistent with GCGR activation, a broad reduction in circulating amino acids was seen during the infusion period. CONCLUSION: An adaptive continuous infusion of the GLP-1/GCGR co-agonist, G3215, is safe and well tolerated offering a unique strategy to control drug exposure. By allowing rapid, response-directed titration, this strategy may allow for mitigation of adverse effects and afford significant weight loss within shorter time horizons than is presently possible with weekly GLP-1R and multi-agonists. These results support ongoing development of G3215 for the treatment of obesity and metabolic disease.

Applied Hepatic Bioengineering: Modeling the Human Liver Using Organoid and Liver-on-a-Chip Technologies.

The liver is the most important metabolic hub of endo and xenobiotic compounds. Pre-clinical studies using rodents to evaluate the toxicity of new drugs and cosmetics may produce inconclusive results for predicting clinical outcomes in humans, moreover being banned in the European Union. Human liver modeling using primary hepatocytes presents low reproducibility due to batch-to-batch variability, while iPSC-derived hepatocytes in monolayer cultures (2D) show reduced cellular functionality. Here we review the current status of the two most robust in vitro approaches in improving hepatocyte phenotype and metabolism while mimicking the hepatic physiological microenvironment: organoids and liver-on-chip. Both technologies are reviewed in design and manufacturing techniques, following cellular composition and functionality. Furthermore, drug screening and liver diseases modeling efficiencies are summarized. Finally, organoid and liver-on-chip technologies are compared regarding advantages and limitations, aiming to guide the selection of appropriate models for translational research and the development of such technologies.

Factorial validity and measurement invariance of the Psychosocial Uncertainty Scale.

This study presents the development of the Psychosocial Uncertainty Scale (PS-US), which articulates the perception of uncertainty in the social context and its psychological experience. It was validated with a sample of 1596 students and active professionals (employed and unemployed). By randomly dividing this sample in three sub-samples, the following analyses were performed: exploratory factor analysis (sample one: N = 827); preliminary confirmatory factor analysis identifying the final version of the scale (sample two: N = 382); confirmatory factor analysis (sample three: N = 387). Multi-group analysis was used to assess measurement invariance, gender, sociocultural level, and group of origin invariance, by using samples two and three. Group differences were explored with the complete sample through Multiple Indicators and Multiple Causes (MIMIC) Models. Associations between this scale and the Uncertainty response Scale were explored through Structural Equation Modelling. Exploratory and confirmatory analyses' results showed good internal consistency and overall good psychometric qualities. The scale reached full metric invariance across groups, gender, SCL level and group of origin. Results highlight the sensitivity of the scale towards social vulnerability, proving the existence of sociocultural levels' effects on experiences of psychosocial uncertainty within working contexts, relationships and community living and self-defeating beliefs; and gender and students versus professionals' effects on psychosocial uncertainty. Furthermore, the scale associated significantly with Uncertainty Response Scale's dimensions, specifically with emotional uncertainty, which can be considered a self-defeating strategy. Results suggest that emotional coping strategies, are explained by psychosocial uncertainty by 57%, and so, may have social origins.

Factorial validity and measurement invariance of the Psychosocial Uncertainty Scale

Abstract This study presents the development of the Psychosocial Uncertainty Scale (PS-US), which articulates the perception of uncertainty in the social context and its psychological experience. It was validated with a sample of 1596 students and active professionals (employed and unemployed). By randomly dividing this sample in three subsamples, the following analyses were performed: exploratory factor analysis (sample one: N = 827); preliminary confirmatory factor analysis identifying the final version of the scale (sample two: N = 382); confirmatory factor analysis (sample three: N = 387). Multi-group analysis was used to assess measurement invariance, gender, sociocultural level, and group of origin invariance, by using samples two and three. Group differences were explored with the complete sample through Multiple Indicators and Multiple Causes (MIMIC) Models. Associations between this scale and the Uncertainty response Scale were explored through Structural Equation Modelling. Exploratory and confirmatory analyses' results showed good internal consistency and overall good psychometric qualities. The scale reached full metric invariance across groups, gender, SCL level and group of origin. Results highlight the sensitivity of the scale towards social vulnerability, proving the existence of sociocultural levels' effects on experiences of psychosocial uncertainty within working contexts, relationships and community living and self-defeating beliefs; and gender and students versus professionals' effects on psychosocial uncertainty. Furthermore, the scale associated significantly with Uncertainty Response Scale's dimensions, specifically with emotional uncertainty, which can be considered a self-defeating strategy. Results suggest that emotional coping strategies, are explained by psychosocial uncertainty by 57%, and so, may have social origins.

Factorial validity and measurement invariance of the uncertainty response scale.

This study presents the adaptation of the Uncertainty Response Scale (Greco & Roger, Pers. Individ. Differ, 31:519-534, 2001) to Portuguese. This instrument was administered to a non-clinical community sample composed of 1596 students and professionals, allowing a thorough validity and invariance analysis by randomly dividing participants into three subsamples to perform: an exploratory factor analysis (sample one: N = 512); a preliminary confirmatory factor analysis to identify the final solution for the scale (sample two: N = 543); and the confirmatory factor analysis (sample three: N = 541). Samples two and three were also used for multi-group analysis to assess measurement invariance, invariance across gender, sociocultural levels, and students versus active professionals. Results showed the scale reflects the original factorial structure, as well as good internal consistency and overall good psychometric qualities. Invariance results across groups reached structural invariance which provides a confident invariance measurement for this scale, while invariance across gender and sociocultural levels reached metric invariance. Accordingly, differences between these groups were explored, by comparing means with multi-group analysis to establish the scale's sensitivity toward social vulnerability, by demonstrating the existence of statistically significant differences regarding gender and sociocultural levels on how individuals cope with uncertainty, specifically in terms of emotional strategies, as a self-defeating strategy. Thus, females scored higher on emotional uncertainty, as well as low sociocultural levels, compared with higher ones. Therefore, it is proposed that this scale could be a sound alternative to explore strategies for coping with uncertainty, when considering social, economic, or other environmental circumstances that may affect them.

Factorial validity and measurement invariance of the uncertainty response scale

Abstract This study presents the adaptation of the Uncertainty Response Scale (Greco & Roger, Pers. Individ. Differ, 31:519-534, 2001) to Portuguese. This instrument was administered to a non-clinical community sample composed of 1596 students and professionals, allowing a thorough validity and invariance analysis by randomly dividing participants into three subsamples to perform: an exploratory factor analysis (sample one: N = 512); a preliminary confirmatory factor analysis to identify the final solution for the scale (sample two: N = 543); and the confirmatory factor analysis (sample three: N = 541). Samples two and three were also used for multi-group analysis to assess measurement invariance, invariance across gender, sociocultural levels, and students versus active professionals. Results showed the scale reflects the original factorial structure, as well as good internal consistency and overall good psychometric qualities. Invariance results across groups reached structural invariance which provides a confident invariance measurement for this scale, while invariance across gender and sociocultural levels reached metric invariance. Accordingly, differences between these groups were explored, by comparing means with multi-group analysis to establish the scale's sensitivity toward social vulnerability, by demonstrating the existence of statistically significant differences regarding gender and sociocultural levels on how individuals cope with uncertainty, specifically in terms of emotional strategies, as a self-defeating strategy. Thus, females scored higher on emotional uncertainty, as well as low sociocultural levels, compared with higher ones. Therefore, it is proposed that this scale could be a sound alternative to explore strategies for coping with uncertainty, when considering social, economic, or other environmental circumstances that may affect them.

Is a neutral expression also a neutral stimulus? A study with functional magnetic resonance.

Although neutral faces do not initially convey an explicit emotional message, it has been found that individuals tend to assign them an affective content. Moreover, previous research has shown that affective judgments are mediated by the task they have to perform. Using functional magnetic resonance imaging in 21 healthy participants, we focus this study on the cerebral activity patterns triggered by neutral and emotional faces in two different tasks (social or gender judgments). Results obtained, using conjunction analyses, indicated that viewing both emotional and neutral faces evokes activity in several similar brain areas indicating a common neural substrate. Moreover, neutral faces specifically elicit activation of cerebellum, frontal and temporal areas, while emotional faces involve the cuneus, anterior cingulated gyrus, medial orbitofrontal cortex, posterior superior temporal gyrus, precentral/postcentral gyrus and insula. The task selected was also found to influence brain activity, in that the social task recruited frontal areas while the gender task involved the posterior cingulated, inferior parietal lobule and middle temporal gyrus to a greater extent. Specifically, in the social task viewing neutral faces was associated with longer reaction times and increased activity of left dorsolateral frontal cortex compared with viewing facial expressions of emotions. In contrast, in the same task emotional expressions distinctively activated the left amygdale. The results are discussed taking into consideration the fact that, like other facial expressions, neutral expressions are usually assigned some emotional significance. However, neutral faces evoke a greater activation of circuits probably involved in more elaborate cognitive processing.