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Abstract Humans spontaneously take the perspective of others when encoding spatial information in a scene, especially with agentive action cues present. This functional near-infrared spectroscopy (fNIRS) study explored how action observation influences implicit spatial perspective-taking (SPT) by adapting a left–right spatial judgment task to investigate whether transformation strategies underlying altercentric SPT can be predicted on the basis of cortical activation. Strategies associated with two opposing neurocognitive accounts (embodied versus disembodied) and their proposed neural correlates (human mirror neuron system; hMNS versus cognitive control network; CCN) are hypothesized. Exploratory analyses with 117 subjects uncover an interplay between perspective-taking and post-hoc factor, consistency of selection, in regions alluding to involvement of the CCN. Descriptively, inconsistent altercentric SPT elicited greater activation than consistent altercentric SPT and/or inconsistent egocentric SPT in the left inferior frontal gyrus (IFG), left dorsolateral prefrontal cortex (DLPFC) and left motor cortex (MC), but not the inferior parietal lobules (IPL). Despite the presence of grasping cues, spontaneous embodied strategies were not evident during implicit altercentric SPT. Instead, neural trends in the inconsistent subgroups (22 subjects; 13 altercentric; 9 egocentric) suggest that inconsistency in selection modulates the decision-making process and plausibly taps on deliberate and effortful disembodied strategies driven by the CCN. Implications for future research are discussed.

Abstract Various studies have shown that medical professionals are prone to follow the incorrect suggestions offered by algorithms, especially when they have limited inputs to interrogate and interpret such suggestions and when they have an attitude of relying on them. We examine the effect of correct and incorrect algorithmic suggestions on the diagnosis performance of radiologists when (1) they have no, partial, and extensive informational inputs for explaining the suggestions (study 1) and (2) they are primed to hold a positive, negative, ambivalent, or neutral attitude towards AI (study 2). Our analysis of 2760 decisions made by 92 radiologists conducting 15 mammography examinations shows that radiologists’ diagnoses follow both incorrect and correct suggestions, despite variations in the explainability inputs and attitudinal priming interventions. We identify and explain various pathways through which radiologists navigate through the decision process and arrive at correct or incorrect decisions. Overall, the findings of both studies show the limited effect of using explainability inputs and attitudinal priming for overcoming the influence of (incorrect) algorithmic suggestions.

Abstract We aimed to investigate stress-reactive rumination in response to social stress and its association with social anxiety and trait rumination. From previous investigations we know that people with a certain vulnerability to rumination show increased stress-reactive rumination. However, up to date the possible influence of social anxiety on this relationship is still unclear. Therefore, we reanalyzed the data of two of our previous studies assessing healthy low and high trait ruminators and depressed patients performing the Trier Social Stress Test (TSST). We measured cortical oxygenation using functional Near-Infrared Spectroscopy (fNIRS) as well as different behavioral outcome measures (subjective stress levels, negative affect, state rumination). On a behavioral level, we found an influence of both, social anxiety and trait rumination, on state rumination, even when correcting for the other factor, respectively, implying two potentially independent factors of influence. On a neural level, we observed reduced activation in brain regions of the cognitive control network (CCN) for higher social anxiety and trait rumination, which might be a result of reduced cognitive and attentional control. Results indicate a specific role of social anxiety, at least on a behavioral level, and therefore implicate a crucial factor to be considered in the treatment of depression.

Abstract Flavin-binding fluorescent proteins (FPs) are genetically encoded in vivo reporters, which are derived from microbial and plant LOV photoreceptors. In this study, we comparatively analyzed ROS formation and light-driven antimicrobial efficacy of eleven LOV-based FPs. In particular, we determined singlet oxygen (1O2) quantum yields and superoxide photosensitization activities via spectroscopic assays and performed cell toxicity experiments in E. coli. Besides miniSOG and SOPP, which have been engineered to generate 1O2, all of the other tested flavoproteins were able to produce singlet oxygen and/or hydrogen peroxide but exhibited remarkable differences in ROS selectivity and yield. Accordingly, most LOV-FPs are potent photosensitizers, which can be used for light-controlled killing of bacteria. Furthermore, the two variants Pp2FbFP and DsFbFP M49I, exhibiting preferential photosensitization of singlet oxygen or singlet oxygen and superoxide, respectively, were shown to be new tools for studying specific ROS-induced cell signaling processes. The tested LOV-FPs thus further expand the toolbox of optogenetic sensitizers usable for a broad spectrum of microbiological and biomedical applications.

Abstract Randomized controlled trials have established that seasonal malaria chemoprevention (SMC) in children is a promising strategy to reduce malaria transmission in Sahelian West Africa. This strategy was recently introduced in a dozen countries, and about 12 million children received SMC in 2016. However, evidence on SMC effectiveness under routine programme conditions is sparse. We aim to measure the effects of the nationwide SMC programme in Mali on the prevalence of malaria and anemia in children 6–59 months. We used data from the 2015 nationally representative malaria indicator survey. A post-test only with non-randomized control group study was designed. We fitted a generalized structural equation model that controlled for potential bias on observed and non-observed variables (endogenous treatment effect model). Having received SMC reduced by 44% (95% CI [0.39–0.49]) the risk of having a positive rapid diagnostic test for malaria. In addition, the programme indirectly reduced by 18% the risk of moderate-to-severe anemia (95% CI [0.15–0.21]). SMC in Mali has substantial protective effects under routine nationwide programme conditions. Endogenous treatment effects analyses can contribute to rigorously measuring the effectiveness of health programmes and to bridging a widening gap in evaluation methods to measure progress towards achieving malaria elimination.

There are currently no therapeutics to treat infection with the alphavirus Venezuelan equine encephalitis virus (VEEV), which causes flu-like symptoms leading to neurological symptoms in up to 14% of cases. Large outbreaks of VEEV can result in 10,000 s of human cases and mass equine death. We previously showed that mifepristone (RU486) has anti-VEEV activity (EC 50  = 20 μM) and only limited cytotoxicity (CC 50  > 100 μM), but a limitation in its use is its abortifacient activity resulting from its ability to antagonize the progesterone receptor (PR). Here we generate a suite of new mifepristone analogues with enhanced antiviral properties, succeeding in achieving >11-fold improvement in anti-VEEV activity with no detectable increase in toxicity. Importantly, we were able to derive a lead compound with an EC 50 of 7.2 µM and no detectable PR antagonism activity. Finally, based on our SAR analysis we propose avenues for the further development of these analogues as safe and effective anti-VEEV agents.

Hendra virus (HeV) is a paramyxovirus that causes lethal disease in humans, for which no vaccine or antiviral agent is available. HeV V protein is central to pathogenesis through its ability to interact with cytoplasmic host proteins, playing key antiviral roles. Here we use immunoprecipitation, siRNA knockdown and confocal laser scanning microscopy to show that HeV V shuttles to and from the nucleus through specific host nuclear transporters. Spectroscopic and small angle X-ray scattering studies reveal HeV V undergoes a disorder-to-order transition upon binding to either importin α/β1 or exportin-1/Ran-GTP, dependent on the V N-terminus. Importantly, we show that specific inhibitors of nuclear transport prevent interaction with host transporters, and reduce HeV infection. These findings emphasize the critical role of host-virus interactions in HeV infection, and potential use of compounds targeting nuclear transport, such as the FDA-approved agent ivermectin, as anti-HeV agents.

Therapeutics are currently unavailable for Venezuelan equine encephalitis virus (VEEV), which elicits flu-like symptoms and encephalitis in humans, with an estimated 14% of cases resulting in neurological disease. Here we identify anti-VEEV agents using in silico structure-based-drug-design (SBDD) for the first time, characterising inhibitors that block recognition of VEEV capsid protein (C) by the host importin (IMP) α/β1 nuclear transport proteins. From an initial screen of 1.5 million compounds, followed by in silico refinement and screening for biological activity in vitro, we identified 21 hit compounds which inhibited IMPα/β1:C binding with IC 50 s as low as 5 µM. Four compounds were found to inhibit nuclear import of C in transfected cells, with one able to reduce VEEV replication at µM concentration, concomitant with reduced C nuclear accumulation in infected cells. Further, this compound was inactive against a mutant VEEV that lacks high affinity IMPα/β1:C interaction, supporting the mode of its antiviral action to be through inhibiting C nuclear localization. This successful application of SBDD paves the way for lead optimization for VEEV antivirals, and is an exciting prospect to identify inhibitors for the many other viral pathogens of significance that require IMPα/β1 in their infectious cycle.