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Incidence, molecular presentation and outcome of acute myeloid leukaemia (AML) are influenced by sex, but little attention has been directed at untangling sex-related molecular and phenotypic differences between female and male patients. While increased incidence and poor risk are generally associated with a male phenotype, the poor prognostic FLT3 internal tandem duplication (FLT3-ITD) mutation and co-mutations with NPM1 and DNMT3A are overrepresented in female AML. Here, we have investigated the relationship between sex and FLT3-ITD mutation status by comparing clinical data, mutational profiles, gene expression and ex vivo drug sensitivity in four cohorts: Beat AML, LAML-TCGA and two independent HOVON/SAKK cohorts, comprising 1755 AML patients in total. We found prevalent sex-associated molecular differences. Co-occurrence of FLT3-ITD, NPM1 and DNMT3A mutations was overrepresented in females, while males with FLT3-ITDs were characterized by additional mutations in RNA splicing and epigenetic modifier genes. We observed diverging expression of multiple leukaemia-associated genes as well as discrepant ex vivo drug responses, suggestive of discrete functional properties. Importantly, significant prognostication was observed only in female FLT3-ITD-mutated AML. Thus, we suggest optimization of FLT3-ITD mutation status as a clinical tool in a sex-adjusted manner and hypothesize that prognostication, prediction and development of therapeutic strategies in AML could be improved by including sex-specific considerations.

Changes in plant communities can have large effects on ecosystem carbon (C) dynamics and long-term C stocks. However, how these effects are mediated by environmental context or vary among ecosystems is not well understood. To study this, we used a long-term plant removal experiment set up across 30 forested lake islands in northern Sweden that collectively represent a strong gradient of soil fertility and ecosystem productivity. We measured forest floor CO2 exchange and aboveground and belowground C stocks for a 22-yr experiment involving factorial removal of the two dominant functional groups of the boreal forest understory, namely ericaceous dwarf shrubs and feather mosses, on each of the 30 islands. We found that long-term shrub and moss removal increased forest floor net CO2 loss and decreased belowground C stocks consistently across the islands irrespective of their productivity or soil fertility. However, we did see context-dependent responses of respiration to shrub removals because removals only increased respiration on islands of intermediate productivity. Both CO2 exchange and C stocks responded more strongly to shrub removal than to moss removal. Shrub removal reduced gross primary productivity of the forest floor consistently across the island gradient, but it had no effect on respiration, which suggests that loss of belowground C caused by the removals was driven by reduced litter inputs. Across the island gradient, shrub removal consistently depleted C stocks in the soil organic horizon by 0.8 kg C/m2 . Our results show that the effect of plant functional group diversity on C dynamics can be relatively consistent across contrasting ecosystems that vary greatly in productivity and soil fertility. These findings underline the key role of understory vegetation in forest C cycling, and suggest that global change leading to changes in the relative abundance of both shrubs and mosses could impact on the capacity of boreal forests to store C.

Goldberg, the author of the \"novelty-routinization\" framework, suggested a new pair of cognitive styles for agent-centered decision-making (DM), context-dependency/independency (CD/CI), quantified by the Cognitive Bias Task (CBT) and supposedly reflecting functional brain hemispheric specialization. To date, there are only three lesion and activation neuroimaging studies on the CBT with the largest sample of 12 participants. The present study is the first to analyze whole-brain functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC), involved in contextual agent-centered DM.
We compared whole-brain resting-state FC of the DLPFC between CD (n = 24) and CI (n = 22) healthy participants. Additionally, we investigated associations between CD/CI and different aspects of executive functions.
CD participants had stronger positive FC of the DLPFC with motor and visual regions; FC of the left DLPFC was more extensive. CI participants had stronger positive FC of the left DLPFC with right prefrontal and parietal-occipital areas and of the left and right DLPFC with ipsilateral cerebellar hemispheres. No sex differences were found. CD/CI had nonlinear associations with working memory.
The findings suggest that CD and CI are associated with different patterns of DLPFC FC. While CD is associated with FC between DLPFC and areas presumably involved in storing representations of current situation, CI is more likely to be associated with FC between DLPFC and right-lateralized associative regions, probably involved in the inhibition of the CD response and switching from processing of incoming perceptual information to creation of original response strategies.

Studying neuroendocrine behavioral regulatory mechanisms in a variety of species across vertebrate groups is critical for determining how they work in natural contexts, how they evolved, and ultimately what can be generalized from them, potentially even to humans. All of the above are difficult, at best, if work within our field is exclusively done in traditional laboratory organisms. The importance of comparative approaches for understanding the relationships between hormones and behavior has been recognized and advocated for since our field\'s inception through a series of papers centered upon a poetic metaphor of Snarks and Boojums, all of which have articulated the benefits that come from studying a diverse range of species and the risks associated with a narrow focus on \"model organisms.\" This mini-review follows in the footsteps of those powerful arguments, highlighting some of the comparative work since the latest interactions of the metaphor that has shaped how we think about three major conceptual frameworks within our field, two of them formalized - the Organization/Activation Model of sexual differentiation and the Social Brain Network - and one, context-dependency, that is generally associated with virtually all modern understandings of how hormones affect behavior. Comparative approaches are broadly defined as those in which the study of mechanism is placed within natural and/or evolutionary contexts, whether they directly compare different species or not. Studies are discussed in relation to how they have either extended or challenged generalities associated with the frameworks, how they have shaped subsequent work in model organisms to further elucidate neuroendocrine behavioral regulatory mechanisms, and how they have stimulated work to determine if and when similar mechanisms influence behavior in our own species.

Two decades ago, the introduction of the Implicit Association Test (IAT) sparked enthusiastic reactions. With implicit measures like the IAT, researchers hoped to finally be able to bridge the gap between self-reported attitudes on one hand and behavior on the other. Twenty years of research and several meta-analyses later, however, we have to conclude that neither the IAT nor its derivatives have fulfilled these expectations. Their predictive value for behavioral criteria is weak and their incremental validity over and above self-report measures is negligible. In our review, we present an overview of explanations for these unsatisfactory findings and delineate promising ways forward. Over the years, several reasons for the IAT\'s weak predictive validity have been proposed. They point to four potentially problematic features: First, the IAT is by no means a pure measure of individual differences in associations but suffers from extraneous influences like recoding. Hence, the predictive validity of IAT-scores should not be confused with the predictive validity of associations. Second, with the IAT, we usually aim to measure evaluation (\"liking\") instead of motivation (\"wanting\"). Yet, behavior might be determined much more often by the latter than the former. Third, the IAT focuses on measuring associations instead of propositional beliefs and thus taps into a construct that might be too unspecific to account for behavior. Finally, studies on predictive validity are often characterized by a mismatch between predictor and criterion (e.g., while behavior is highly context-specific, the IAT usually takes into account neither the situation nor the domain). Recent research, however, also revealed advances addressing each of these problems, namely (1) procedural and analytical advances to control for recoding in the IAT, (2) measurement procedures to assess implicit wanting, (3) measurement procedures to assess implicit beliefs, and (4) approaches to increase the fit between implicit measures and behavioral criteria (e.g., by incorporating contextual information). Implicit measures like the IAT hold an enormous potential. In order to allow them to fulfill this potential, however, we have to refine our understanding of these measures, and we should incorporate recent conceptual and methodological advancements. This review provides specific recommendations on how to do so.

Social anxiety (SA) means fear of scrutiny and of others\' negative evaluation, thus indicating that hypermentalizing (HMZ) (i.e., the over-attribution of intentions and thoughts to others) might be the most common error of social cognition in SA. However, evidence for this is weak. One explanation is that HMZ is not stable in SA, but rather context-dependent. The first aim of the current study was testing this hypothesis. The second aim was analyzing whether the association between SA and HMZ is moderated by a negative self-image. One-hundred and thirteen young adults (85.8% females; M = 21.1 years old; SD = 2.7) were assessed on measures of SA, HMZ, and self-image. Given the over-representation of females, conclusions may not be safely extrapolated to males. Results revealed that HMZ is associated with SA only in the self-referential social situation [B = 2.68 (95% CI: 0.72-4.65), p = 0.007]. This supports that HMZ is not global in SA (i.e., a stable cognitive style), but rather is active only in some contexts. Implications for the conceptualization and treatment of SA are discussed. Contrary to predictions, neither self-esteem, nor positive or negative self-schema moderated the association between SA and self-referential HMZ. This contradicts findings in the field of paranoid delusion and requires replication, including measures of implicit self-esteem.

Oxytocin is both a hormone and a neurotransmitter and has been originally recognized for its role in childbirth and lactation. Later, it became widely known as a \"cuddle hormone\" that induces trusting behavior towards strangers and reduces social stress and anxiety. Several studies showed that oxytocin influences empathic behavior and has prosocial effects. The anterior cingulate cortex and the anterior insula are brain regions that are active when humans observe fear in others. Therefore, the aim of this study was to investigate whether oxytocin administration affects activity in these regions depending on whether a threat is directed at another person (empathy) compared to when the threat is directed at the subject itself (fear). Our findings demonstrate increased anterior cingulate cortex activation after oxytocin administration in the fear, but not in the empathy condition. Furthermore, oxytocin administration was associated with deceased anterior insula activity in the empathy condition. However, our findings do not support the idea that oxytocin generally augments activity in brain regions associated with empathy. Thereby this study supports current research questioning that oxytocin has exclusively prosocial effects on human behavior. Rather, the effect of oxytocin depends on various contextual (e.g. presence of a familiar person) and interindividual (e.g. sex, mental disorder) factors. Therefore, to consider oxytocin an empathy inducing hormone is an oversimplification and future research should focus on factors moderating oxytocin effects.

Some studies in experimental pragmatics have concluded that scalar inferences (e.g., \'some X are Y\' implicates \'not all X are Y\') are context-dependent pragmatic computations delayed relative to semantic computations. However, it remains unclear whether strong contextual support is necessary to trigger such inferences. Here we tested if the scalar inference \'not all\' triggered by some can be evoked in a maximally neutral context. We investigated event-related potential (ERP) amplitude modulations elicited by Stroop-like conflicts in participants instructed to indicate whether strings of letters were printed with all their letters in upper case or otherwise. In a randomized stream of non-words and distractor words, the words all, some and case were either presented in capitals or they featured at least one lower case letter. As expected, we found a significant conflict-related N450 modulation when comparing e.g., \'aLl\' with \'ALL\'. Surprisingly, despite the fact that most responses from the same participants in a sentence-picture verification task were literal, we also found a similar modulation when comparing \'SOME\' with e.g., \'SoMe\', even though SOME could only elicit such a Stroop conflict when construed pragmatically. No such modulation was found for e.g., \'CasE\' vs. \'CASE\' (neutral contrast). These results suggest that some can appear incongruent with the concept of \'all\' even when contextual support is minimal. Furthermore, there was no significant correlation between N450 effect magnitude (\'SOME\' minus e.g., \'sOMe\') and pragmatic response rate recorded in the sentence-picture verification task. Overall, this study shows for the first time that the pragmatic meaning of some can be accessed in a maximally neutral context, and thus, that the scalar inference \'not all\' triggered by some should be construed as context-sensitive rather than context-dependent, that is, more or less salient and relevant depending on the context rather than entirely contingent upon it.