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SGIP1 encodes a protein Src homology 3-domain growth factor receptor-bound 2-like endophilin interacting protein 1. It is involved in the regulation of clathrin-mediated endocytosis along with having a role in energy homeostasis in neuronal systems. We generated an isogenic human induced pluripotent stem cell (iPSC) line with a biallelic frameshift variant in SGIP1. This exon has been shown to be subject to alternative splicing, leading to an isoform lacking 24 amino acids that are present in the longest SGIP isoform. The newly generated iPSC line will be helpful to dissect the differential properties of the two SGIP isoforms.

Abstract Bayesian networks are commonly used for learning with uncertainty and incorporating expert knowledge. However, they are hard to interpret, especially when the network structure is complex. Methods used to explain Bayesian networks operate under certain assumptions about what constitutes the best explanation, without actually verifying these assumptions. One such common assumption is that a shorter length of the causal chain of one variable to another enhances its explanatory strength. Counterfactual explanations gained popularity in artificial intelligence over the last years. It is well-known that it is possible to generate counterfactuals from causal Bayesian networks, but there is no indication which of them are useful for explanatory purposes. In this paper, we examine how to apply findings from psychology to search for counterfactuals that are perceived as more useful explanations for the end user. For this purpose, we have conducted a questionnaire to test whether counterfactuals that change an actionable cause are considered more useful than counterfactuals that change a direct cause. The results of the questionnaire indicate that actionable counterfactuals are preferred regardless of being the direct cause or having a longer causal chain.

Intellectual disability (ID) is a diverse neurodevelopmental condition and almost half of the cases have a genetic etiology. SGIP1 acts as an endocytic protein that influences the signaling of receptors in neuronal systems related to energy homeostasis through its interaction with endophilins. This study focuses on the generation and characterization of induced pluripotent stem cells (iPSC) from two unrelated patients due to a frameshift variant (c.764dupA, NM_032291.4) and a splice donor site variant (c.74 + 1G > A, NM_032291.4) in the SGIP1 gene.

The Wadden Sea is a highly dynamic tidal system and an important area for a variety of species, including wild and cultivated mussels. Increased suspended sediment concentrations may negatively affect ecosystem functioning across trophic levels; hence, insight into the effects of anthropogenic activities is of importance. The aim of this study was to investigate the scale of sediment resuspension associated with commercial mussel cultivation activities. Turbidity prior to and during fisheries and harvest was investigated by in situ measurements with towed and fixed sensors. Four case studies were selected to represent maximum disturbance. For one case study, sediment resuspension was further investigated by analysis of satellite images. The in situ measurements showed that turbidity is enhanced by mussel fisheries and harvest but that effects are limited in time and space. Turbidity enhancement during fisheries was several-fold higher than that during harvest, whereas the spatial scale of both activities was limited to their direct vicinity. In contrast to the in situ study, the satellite image analysis identified a spatial magnitude that extended over a somewhat larger spatial scale, in the form of a dark water plume, and further revealed that this plume consisted of high concentrations of coloured dissolved organic matter (CDOM), rather than suspended particles. Along with turbidity, CDOM thus seems an important consideration for determining light attenuation in a water body affected by anthropogenic seafloor disturbance. As we presented case studies that were expected to represent maximum impact, we conclude that there is no specific need for further in-depth studies that allow upscaling to ecosystem-wide effects.

Abstract Background Physical activity (PA) is known to be beneficial for health, but adherence to international PA guidelines is low across different subpopulations. Interventions have been designed to stimulate PA of different target groups by influencing relevant psycho-social determinants, essentially based on a combination of the Integrated Model for Change, the Theory of Planned Behaviour, its successor the Reasoned Action Approach and the self-determination theory. The current study investigates the pathways through which interventions influence PA. Further, gender differences in pathways of change are studied. Methods An integrated dataset of five different randomised controlled trial intervention studies is analysed by estimating a Bayesian network. The data include measurements, at baseline and at 3, 6 (short-term), and 12 (long-term) months after the baseline, of important socio-cognitive determinants of PA, demographic factors, and PA outcomes. A fragment is extracted from the Bayesian network consisting of paths between the intervention variable, determinants, and short- and long-term PA outcomes. For each relationship between variables, a stability indicator and its mutual information are computed. Such a model is estimated for the full dataset, and in addition such a model is estimated based only on male and female participants’ data to investigate gender differences. Results The general model (for the full dataset) shows complex paths, indicating that the intervention affects short-term PA via the direct determinants of intention and habit and that self-efficacy, attitude, intrinsic motivation, social influence concepts, planning and commitment have an indirect influence. The model also shows how effects are maintained in the long-term and that previous PA behaviour, intention and attitude pros are direct determinants of long-term PA. The gender-specific models show similarities as well as important differences between the structures of paths for the male- and female subpopulations. For both subpopulations, intention and habit play an important role for short-term effects and maintenance of effects in the long-term. Differences are found in the role of self-efficacy in paths of behaviour change and in the fact that attitude is relevant for males, whereas planning plays a crucial role for females. The average of these differences in subpopulation mechanisms appears to be presented in the general model. Conclusions While previous research provided limited insight into how interventions influence PA through relevant determinants, the Bayesian network analyses show the relevance of determinants mentioned by the theoretical framework. The model clarifies the role that different determinants play, especially in interaction with each other. The Bayesian network provides new knowledge about the complex working mechanism of interventions to change PA by giving an insightful overview of influencing paths. Furthermore, by presenting subpopulation-specific networks, the difference between the influence structure of males and females is illustrated. These new insights can be used to improve interventions in order to enhance their effects. To accomplish this, we have developed a new methodology based on a Bayesian network analysis which may be applicable in various other studies.

BackgroundDuring the COVID-19 pandemic, there was limited adoption of contact-tracing apps (CTAs). Adoption was particularly low among vulnerable people (eg, people with a low socioeconomic position or of older age), while this part of the population tends to have lesser access to information and communication technology and is more vulnerable to the COVID-19 virus. ObjectiveThis study aims to understand the cause of this lagged adoption of CTAs in order to facilitate adoption and find indications to make public health apps more accessible and reduce health disparities. MethodsBecause several psychosocial variables were found to be predictive of CTA adoption, data from the Dutch CTA CoronaMelder (CM) were analyzed using cluster analysis. We examined whether subgroups could be formed based on 6 psychosocial perceptions (ie, trust in the government, beliefs about personal data, social norms, perceived personal and societal benefits, risk perceptions, and self-efficacy) of (non)users concerning CM in order to examine how these clusters differ from each other and what factors are predictive of the intention to use a CTA and the adoption of a CTA. The intention to use and the adoption of CM were examined based on longitudinal data consisting of 2 time frames in October/November 2020 (N=1900) and December 2020 (N=1594). The clusters were described by demographics, intention, and adoption accordingly. Moreover, we examined whether the clusters and the variables that were found to influence the adoption of CTAs, such as health literacy, were predictive of the intention to use and the adoption of the CM app. ResultsThe final 5-cluster solution based on the data of wave 1 contained significantly different clusters. In wave 1, respondents in the clusters with positive perceptions (ie, beneficial psychosocial variables for adoption of a CTA) about the CM app were older (P

CACNA1A encodes a P/Q-type voltage-gated calcium channel. Heterozygous loss-of-function variants in this gene have been associated with episodic ataxia type 2. In this study, we used CRISPR/Cas9 to generate isogenic human induced pluripotent stem cell lines with a gene-dosage dependent deficiency of CACNA1A. We obtained one clone with monoallelic (UCSFi001-A-60) and two clones with biallelic (UCSFi001-A-61; UCSFi001-A-62) frameshift variants in CACNA1A. All three lines showed expression of pluripotency markers and a normal karyotype.