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Abstract Glioblastoma (GBM) is the most aggressive glial tumor of the adult brain, associated with invariably fatal outcome, and a deeper understanding of the underlying malignant mechanisms is necessary to address the current therapeutic failure. We previously demonstrated the role of the CXCL12/CXCR4 axis in GBM cell migration and resistance to ionizing radiation. The atypical chemokine receptor ACKR3, responsible for CXCL12 scavenging, was previously suggested as additional important player in the context of GBM. Following validation of the detection tools, we observed that ACKR3 is expressed within GBM patient tumor tissue, distributed in diverse cell types. In contrast to CXCR4, ACKR3 expression in patient-derived stem-like cells (GSCs) remains however low, while ACKR3 gene expression by tumor cells appears to be modulated by the in-vivo environment. Using overexpression models, we also showed that in vitro ACKR3 had no significant direct effect on cell proliferation or invasion. Altogether, these results suggest that in vitro ACKR3 plays a minor role in malignant GBM cell biology and that its expression is possibly regulated by in-vivo influences. The subtle and multifaceted functions ACKR3 could exert in GBM should therefore only be tackled within a comprehensive tumor microenvironment considering tumoral but also non-tumoral cells.

Abstract People cooperate every day in ways that range from largescale contributions that mitigate climate change to simple actions such as leaving another individual with choice – known as social mindfulness. It is not yet clear whether and how these complex and more simple forms of cooperation relate. Prior work has found that countries with individuals who made more socially mindful choices were linked to a higher country environmental performance – a proxy for complex cooperation. Here we replicated this initial finding in 41 samples around the world, demonstrating the robustness of the association between social mindfulness and environmental performance, and substantially built on it to show this relationship extended to a wide range of complex cooperative indices, tied closely to many current societal issues. We found that greater social mindfulness expressed by an individual was related to living in countries with more social capital, more community participation and reduced prejudice towards immigrants. Our findings speak to the symbiotic relationship between simple and more complex forms of cooperation in societies.

Abstract Happiness is a valuable experience, and societies want their citizens to be happy. Although this societal commitment seems laudable, overly emphasizing positivity (versus negativity) may create an unattainable emotion norm that ironically compromises individual well-being. In this multi-national study (40 countries; 7443 participants), we investigate how societal pressure to be happy and not sad predicts emotional, cognitive and clinical indicators of well-being around the world, and examine how these relations differ as a function of countries’ national happiness levels (collected from the World Happiness Report). Although detrimental well-being associations manifest for an average country, the strength of these relations varies across countries. People’s felt societal pressure to be happy and not sad is particularly linked to poor well-being in countries with a higher World Happiness Index. Although the cross-sectional nature of our work prohibits causal conclusions, our findings highlight the correlational link between social emotion valuation and individual well-being, and suggest that high national happiness levels may have downsides for some.

Study design Systematic review. Background and objective The International Ankle Consortium developed a core outcome set for the assessment of impairments in patients with lateral ankle sprain (LAS) without consideration of measurement properties (MP). Therefore, the aim of this study is to investigate MPs of assessments for the evaluation of individuals with a history of LAS. Methods This systematic review of measurement properties follows PRISMA and COSMIN guidelines. Databases Pubmed, CINAHL, Embase, Web of Science, Cochrane Library and SPORTDiscus were searched for eligible studies (last search: July 2022). Studies on MP of specific tests and patient-reported outcome measurements (PROMs) in patients with acute and history of LAS (>4 weeks post injury) were deemed eligible. Results Ten studies of acute LAS and 39 studies of history of LAS patients with a total of 3313 participants met the inclusion criteria. Anterior Drawer Test (ADT) in supine position five days post injury and Reverse Anterolateral Drawer Test are recommended in acute settings in single studies. In the history of LAS patients, Cumberland Ankle Instability Tool (CAIT) (4 studies) as a PROM, Multiple Hop (3 studies) and Star Excursion Balance Tests (SEBT) (3 studies) for dynamic postural balance testing showed good MPs. No studies investigated pain, physical activity level and gait. Only single studies reported on swelling, range of motion, strength, arthrokinematics, and static postural balance. Limited data existed on responsiveness of the tests in both subgroups. Conclusion There was good evidence to support the use of CAIT as PROM, Multiple Hop, and SEBT for dynamic postural balance testing. Insufficient evidence exists in relation to test responsiveness, especially in the acute situation. Future research should assess MPs of assessments of other impairments associated with LAS.

Study designSystematic review.Background and objectiveThe International Ankle Consortium developed a core outcome set for the assessment of impairments in patients with lateral ankle sprain (LAS) without consideration of measurement properties (MP). Therefore, the aim of this study is to investigate MPs of assessments for the evaluation of individuals with a history of LAS.MethodsThis systematic review of measurement properties follows PRISMA and COSMIN guidelines. Databases Pubmed, CINAHL, Embase, Web of Science, Cochrane Library and SPORTDiscus were searched for eligible studies (last search: July 2022). Studies on MP of specific tests and patient-reported outcome measurements (PROMs) in patients with acute and history of LAS (>4 weeks post injury) were deemed eligible.ResultsTen studies of acute LAS and 39 studies of history of LAS patients with a total of 3313 participants met the inclusion criteria. Anterior Drawer Test (ADT) in supine position five days post injury and Reverse Anterolateral Drawer Test are recommended in acute settings in single studies. In the history of LAS patients, Cumberland Ankle Instability Tool (CAIT) (4 studies) as a PROM, Multiple Hop (3 studies) and Star Excursion Balance Tests (SEBT) (3 studies) for dynamic postural balance testing showed good MPs. No studies investigated pain, physical activity level and gait. Only single studies reported on swelling, range of motion, strength, arthrokinematics, and static postural balance. Limited data existed on responsiveness of the tests in both subgroups.ConclusionThere was good evidence to support the use of CAIT as PROM, Multiple Hop, and SEBT for dynamic postural balance testing. Insufficient evidence exists in relation to test responsiveness, especially in the acute situation. Future research should assess MPs of assessments of other impairments associated with LAS.

Research questions 1) Do exercise-based rehabilitation programs reduce re-injury following acute ankle sprain?; 2) Is rehabilitation effectiveness moderated by the exercise’s therapeutic quality, content and volume? Methods This systematic review with meta-analysis (PROSPERO: CRD42020210858) included randomized controlled trials in which adults who sustained an acute ankle sprain received exercise-based rehabilitation as an intervention. Databases CINAHL, Web of Science, SPORTDiscus, Cochrane Central Register of Controlled Trials, PEDro and Google Scholar were searched for eligible articles (last search: March 2021). ROB II screening tool by Cochrane was used to assess risk of bias and the i-CONTENT tool was used to assess quality of interventions. Both qualitative analysis and quantitative data synthesis were performed. Results Fourteen randomized controlled trials comprising 2182 participants were included. Five studies were judged overall low risk of bias and i-CONTENT assessment showed poor to moderate therapeutic quality of exercise across all included articles. Pooled data found significant reductions in re-injury prevalence at 12 months, in favour of the exercise-based rehabilitation group vs usual care (OR: 0.60; 95%CI: 0.36 to 0.99). Pooled data for re-injury incidence showed not-significant results (MD: 0.027; 95%CI: -2.14 to 2.19). Meta-regression displayed no statistically significant association between training volume and odds of re-injury (r = -0.00086; SD: 0.00057; 95%CI: -0.00197 to 0.00025). Results from patient-reported outcomes and clinical outcomes were inconclusive at 1 month, 3–6 months and 7–12 months of follow up. Conclusion Exercise-based rehabilitation reduces the risk of recurrent ankle sprain compared to usual care, but there is insufficient data to determine the optimal content of exercise-based interventions. Training volume varied considerably across studies but did not affect the odds of sustaining a re-injury. Effects on patient-reported outcomes and clinical outcomes are equivocal. Future research should compare different exercise contents, training volumes and intensities after ankle sprain.

Research questions1) Do exercise-based rehabilitation programs reduce re-injury following acute ankle sprain?; 2) Is rehabilitation effectiveness moderated by the exercise's therapeutic quality, content and volume?MethodsThis systematic review with meta-analysis (PROSPERO: CRD42020210858) included randomized controlled trials in which adults who sustained an acute ankle sprain received exercise-based rehabilitation as an intervention. Databases CINAHL, Web of Science, SPORTDiscus, Cochrane Central Register of Controlled Trials, PEDro and Google Scholar were searched for eligible articles (last search: March 2021). ROB II screening tool by Cochrane was used to assess risk of bias and the i-CONTENT tool was used to assess quality of interventions. Both qualitative analysis and quantitative data synthesis were performed.ResultsFourteen randomized controlled trials comprising 2182 participants were included. Five studies were judged overall low risk of bias and i-CONTENT assessment showed poor to moderate therapeutic quality of exercise across all included articles. Pooled data found significant reductions in re-injury prevalence at 12 months, in favour of the exercise-based rehabilitation group vs usual care (OR: 0.60; 95%CI: 0.36 to 0.99). Pooled data for re-injury incidence showed not-significant results (MD: 0.027; 95%CI: -2.14 to 2.19). Meta-regression displayed no statistically significant association between training volume and odds of re-injury (r = -0.00086; SD: 0.00057; 95%CI: -0.00197 to 0.00025). Results from patient-reported outcomes and clinical outcomes were inconclusive at 1 month, 3-6 months and 7-12 months of follow up.ConclusionExercise-based rehabilitation reduces the risk of recurrent ankle sprain compared to usual care, but there is insufficient data to determine the optimal content of exercise-based interventions. Training volume varied considerably across studies but did not affect the odds of sustaining a re-injury. Effects on patient-reported outcomes and clinical outcomes are equivocal. Future research should compare different exercise contents, training volumes and intensities after ankle sprain.

INTRODUCTION:Substance use disorders (SUD) in physicians often remain concealed for a long time. Peer monitoring and open discussions with colleagues are essential for identifying SUD. However, physicians often feel uncomfortable discussing substance use with a colleague. We explored physicians' attitudes and norms about substance use (disorders) and their (intended) approach upon a presumption of substance use in a colleague. MATERIALS AND METHODS:An online cross-sectional survey concerning "Addiction in physicians" was administered by the Royal Dutch Medical Association physician panel. Overall, 1685 physicians (47%) responded. Data were analyzed by logistic regression to explore factors associated with taking action upon a substance use presumption. RESULTS:Most physicians agreed that SUD can happen to anyone (67%), is not a sign of weakness (78%) and that it is a disease that can be treated (83%). Substance use in a working context was perceived as unacceptable (alcohol at work: 99%, alcohol during a standby duty: 91%, alcohol in the eight hours before work: 77%, and illicit drugs in the eight hours before work: 97%). Almost all respondents (97%) intend to act upon a substance use presumption in a colleague. Of the 29% who ever had this presumption, 65% took actual action. Actual action was associated with male gender and older age (OR = 1.81; 95% CI = 1.20-2.74 and OR = 1.03; 95% CI = 1.01-1.05, respectively). CONCLUSIONS:About one-third of physicians reported experience with a presumption of substance use in a colleague. Whilst most physicians intend to take action upon such a presumption, two-thirds actually do act upon a presumption. To bridge this intention-behavior gap continued medical education on signs and symptoms of SUD and instructions on how to enter a supportive dialogue with a colleague about personal issues, may enhance physicians' knowledge, confidence, and ethical responsibility to act upon a presumption of substance use or other concerns in a colleague.

Moral vitalism refers to a tendency to view good and evil as actual forces that can influence people and events. The Moral Vitalism Scale had been designed to assess moral vitalism in a brief survey form. Previous studies established the reliability and validity of the scale in US-American and Australian samples. In this study, the cross-cultural comparability of the scale was tested across 28 different cultural groups worldwide through measurement invariance tests. A series of exact invariance tests marginally supported partial metric invariance, however, an approximate invariance approach provided evidence of partial scalar invariance for a 5-item measure. The established level of measurement invariance allows for comparisons of latent means across cultures. We conclude that the brief measure of moral vitalism is invariant across 28 cultures and can be used to estimate levels of moral vitalism with the same precision across very different cultural settings.

The extent to which people are aware of their emotional experiences, label them and communicate them to the outside world are considered to impact emotional experience itself and potentially people's depressive symptom levels. All of these aspects are important elements of one of the most common methods to study and measure emotions in the context of daily life, the so-called experience sampling method (ESM). A straightforward question that arises when using this method is whether participating in ESM may bring about changes in the momentary emotional self-reports of the people engaging in it, thereby effectively influencing that what it intends to measure; emotional experience over time, and whether this would relate to average levels of depressive symptoms. To examine these questions, we conducted a 7-day ESM study in which 90 participants were randomly assigned to repeatedly report either positive emotions only, negative emotions only or non-emotional internal states only, course using smartphones. Participants also completed pre-, post- and follow-up measurements of levels of depressive symptoms. Results showed no significant impact on self-reported momentary emotions, respective to their condition, over time nor on average levels of depressive symptoms across groups. These findings suggest that the repeated assessment of emotions in daily life, over the course of seven days, does not impact their emotional experience over time nor levels of depressive symptoms.

This study examines two contrasting explanations for early tendencies to fight and flee. According to a stimulus-driven explanation, goal-incompatible stimuli that are easy/difficult to control lead to the tendency to fight/flee. According to a goal-directed explanation, on the other hand, the tendency to fight/flee occurs when the expected utility of fighting/fleeing is the highest. Participants did a computer task in which they were confronted with goal-incompatible stimuli that were (a) easy to control and fighting had the highest expected utility, (b) easy to control and fleeing had the highest expected utility, and (c) difficult to control and fleeing and fighting had zero expected utility. After participants were trained to use one hand to fight and another hand to flee, they either had to choose a response or merely observe the stimuli. During the observation trials, single-pulse Transcranial Magnetic Stimulation (TMS) was applied to the primary motor cortex 450 ms post-stimulus onset and motor-evoked potentials (MEPs) were measured from the hand muscles. Results showed that participants chose to fight/flee when the expected utility of fighting/fleeing was the highest, and that they responded late when the expected utility of both responses was low. They also showed larger MEPs for the right/left hand when the expected utility of fighting/fleeing was the highest. This result can be interpreted as support for the goal-directed account, but only if it is assumed that we were unable to override the presumed natural mapping between hand (right/left) and response (fight/flight).

In everyday life, people often combine strategies to regulate their emotions. However, to date, most research has investigated emotion regulation strategies as if they occur independently from one another. The current study aims to better understand the sequential interplay between strategies by investigating how reappraisal and rumination interact to affect anger experience. After participants (N = 156) recalled a recent anger-provoking event, they were instructed to either a) reappraise the event twice, b) reappraise the event, and then ruminate about the event, c) ruminate about the event, and then reappraise the event, or d) ruminate twice about the event. The effects of the first strategy used replicated a large body of research: reappraisal was associated with a decrease in anger, but rumination was associated with no change in anger. There was a small interactive effect of the combination of the two strategies, such that those who ruminated and then reappraised showed a larger decrease in anger than those who reappraised and then ruminated. There were no other differences between groups. This suggests that the second strategy does have an effect over and beyond the first strategy, but this effect is small in size, highlighting the importance of the initial emotion regulation strategy used.

We conducted a survey about the 2014 FIFA World Cup that measured attitudes about FIFA, players, and officials in 18 languages with 4600 respondents from 29 countries. Sixty percent of respondents perceived FIFA officials as being dishonest, and people from countries with less institutional corruption and stronger rule of law perceived FIFA officials as being more corrupt and less competent running the tournament than people from countries with more corruption and weaker rule of law. In contrast, respondents evaluated players as skilled and honest and match officials as competent and honest. We discuss the implications of our findings for perceptions of corruption in general.

Negative emotionality (NE) and positive emotionality (PE) have repeatedly shown to act as vulnerability factors for youth depression. Less research examined the mechanisms through which these reactive temperament traits may differently confer vulnerability to depression. Based on recent integrated models of depression proposing emotion regulation as a key underlying mechanism, the current study aimed to clarify the general and day-to-day relations among temperament, emotion regulation strategies, and depressive symptoms in Dutch-speaking youth (35% boys; Mage = 13.27 years, SD = 1.98) using a cross-sectional (n = 495) and a 7-day daily diary design (n = 469). Self-reported temperament, trait rumination, trait positive refocusing, and depressive symptoms were measured at baseline. State rumination, state positive refocusing, and depressive symptoms were further assessed daily. Whereas results revealed that NE and PE interacted in predicting baseline and daily depressive symptoms, the cross-sectional analyses provide preliminary evidence for the hypothesis that NE and PE each provide unique pathways for understanding vulnerability to depression. Additional analyses in the daily diary study showed NE to be significantly related to trajectories of state rumination. Results contribute to a more nuanced understanding of the associations between temperament, emotion regulation strategies, and depressive symptoms in youth.

Emotions unfold over time with episodes differing in explosiveness (i.e., profiles having a steep vs. a gentle start) and accumulation (i.e., profiles increasing over time vs. going back to baseline). In the present fMRI study, we wanted to replicate and extend previous findings on the psychological and neural mechanisms underlying emotion explosiveness and accumulation. Specifically, we aimed to: (a) replicate the finding that different neural mechanisms are associated with emotion explosiveness and accumulation, (b) replicate the finding that adopting a self-distanced (vs. self-immersed) perspective decreases emotion explosiveness and accumulation at the level of self-report, and (c) examine whether adopting a self-distanced (vs. self-immersed) perspective similarly modulates activity in the brain regions associated with emotion explosiveness and accumulation. Participants in an fMRI scanner were asked to adopt a self-immersed or self-distanced perspective while reading and thinking about negative social feedback, and to report on felt changes in negative affect during that period using an emotion intensity profile tracking approach. We replicated previous findings showing that emotion explosiveness and accumulation were related to activity in regions involved in self-referential processing (such as the medial prefrontal cortex) and sustained visceral arousal (such as the posterior insula), respectively. The finding that adopting a self-distanced (vs. self-immersed) perspective lowers emotion explosiveness and accumulation was also replicated at a self-report level. However, perspective taking did not impact activity in the neural correlates of emotion explosiveness and accumulation.

Birth preparedness and complication readiness aims to reduce delays in care seeking, promote skilled birth attendance, and facility deliveries. Little is known about birth preparedness practices among populations living in hard-to-reach areas in Bangladesh.To describe levels of birth preparedness and complication readiness among recently delivered women, identify determinants of being better prepared for birth, and assess the impact of greater birth preparedness on maternal and neonatal health practices.A cross-sectional survey with 2,897 recently delivered women was undertaken in 2012 as part of an evaluation trial done in five hard-to-reach districts in rural Bangladesh. Mothers were considered well prepared for birth if they adopted two or more of the four birth preparedness components. Descriptive statistics and multivariable logistic regression were used for analysis.Less than a quarter (24.5%) of women were considered well prepared for birth. Predictors of being well-prepared included: husband's education (OR = 1.3; CI: 1.1-1.7), district of residence, exposure to media in the form of reading a newspaper (OR = 2.2; CI: 1.2-3.9), receiving home visit by a health worker during pregnancy (OR = 1.5; CI: 1.2-1.8), and receiving at least 3 antenatal care visits from a qualified provider (OR = 1.4; CI: 1.0-1.9). Well-prepared women were more likely to deliver at a health facility (OR = 2.4; CI: 1.9-3.1), use a skilled birth attendant (OR = 2.4, CI: 1.9-3.1), practice clean cord care (OR = 1.3, CI: 1.0-1.5), receive post-natal care from a trained provider within two days of birth for themselves (OR = 2.6, CI: 2.0-3.2) or their newborn (OR = 2.6, CI: 2.1-3.3), and seek care for delivery complications (OR = 1.8, CI: 1.3-2.6).Greater emphasis on BPCR interventions tailored for hard to reach areas is needed to improve skilled birth attendance, care seeking for complications and essential newborn care and facilitate reductions in maternal and neonatal mortality in low performing districts in Bangladesh.

Previous research has shown that being affectively unstable is an indicator of several forms of psychological maladjustment. However, little is known about the mechanisms underlying affective instability. Our research aims to examine the possibility that being prone to extreme fluctuations in one's feelings is related to maladaptive emotion regulation. We investigated this hypothesis by relating affective instability, assessed in daily life using the experience sampling method, to self-reported emotion regulation strategies and to parasympathetically mediated heart rate variability (HRV), a physiological indicator of emotion regulation capacity. Results showed that HRV was negatively related to instability of positive affect (as measured by mean square successive differences), indicating that individuals with lower parasympathetic tone are emotionally less stable, particularly for positive affect.

The ability to regulate emotions is a critical component of healthy emotional functioning. Therefore, it is important to determine factors that contribute to the efficacy of emotion regulation. The present article examined whether the ability to update emotional information in working memory is a predictor of the efficacy of rumination and reappraisal on affective experience both at the trait level (Study 1) and in daily life (Study 2). In both studies, results revealed that the relationship between use of reappraisal and high arousal negative emotions was moderated by updating ability. Specifically, use of reappraisal was associated with decreased high arousal negative emotions for participants with high updating ability, while no significant relationship was found for those with low updating ability. In addition, both studies also revealed that the relationship between rumination and high arousal negative emotions was moderated by updating ability. In general, use of rumination was associated with elevated high arousal negative emotions. However, this relationship was blunted for participants with high updating ability. That is, use of rumination was associated with less elevated high arousal negative emotions for participants with high updating ability. These results identify the ability to update emotional information in working memory as a crucial process modulating the efficacy of emotion regulation efforts.

In the network approach to psychopathology, disorders are conceptualized as networks of mutually interacting symptoms (e.g., depressed mood) and transdiagnostic factors (e.g., rumination). This suggests that it is necessary to study how symptoms dynamically interact over time in a network architecture. In the present paper, we show how such an architecture can be constructed on the basis of time-series data obtained through Experience Sampling Methodology (ESM). The proposed methodology determines the parameters for the interaction between nodes in the network by estimating a multilevel vector autoregression (VAR) model on the data. The methodology allows combining between-subject and within-subject information in a multilevel framework. The resulting network architecture can subsequently be analyzed through network analysis techniques. In the present study, we apply the method to a set of items that assess mood-related factors. We show that the analysis generates a plausible and replicable network architecture, the structure of which is related to variables such as neuroticism; that is, for subjects who score high on neuroticism, worrying plays a more central role in the network. Implications and extensions of the methodology are discussed.

This study examines the role of teachers' expectations in the association between children's socio-economic background and achievement outcomes. Furthermore, the role of children's ethnicity in moderating this mediated relation is investigated. In the present study, 3,948 children from kindergarten are examined. Data are analysed by means of structural equation modeling. First, results show that teachers' expectations mediate the relation between children's SES and their later language and math achievement, after controlling for children's ethnicity, prior achievement and gender. This result indicates that teachers may exacerbate individual differences between children. Second, children's ethnicity moderates the mediation effect of teachers' expectations with respect to math outcomes. The role of teachers' expectations in mediating the relation between SES and math outcomes is stronger for majority children than for minority children.