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Objectives SARS-CoV-2 rapid antigen tests (RAT) provide fast identification of infectious patients when RT-PCR results are not immediately available. We aimed to develop a prediction model for identification of false negative (FN) RAT results. Methods In this multicenter trial, patients with documented paired results of RAT and RT-PCR between October 1st 2020 and January 31st 2021 were retrospectively analyzed regarding clinical findings. Variables included demographics, laboratory values and specific symptoms. Three different models were evaluated using Bayesian logistic regression. Results The initial dataset contained 4,076 patients. Overall sensitivity and specificity of RAT was 62.3% and 97.6%. 2,997 cases with negative RAT results (FN: 120; true negative: 2,877; reference: RT-PCR) underwent further evaluation after removal of cases with missing data. The best-performing model for predicting FN RAT results containing 10 variables yielded an area under the curve of 0.971. Sensitivity, specificity, PPV and NPV for 0.09 as cut-off value (probability for FN RAT) were 0.85, 0.99, 0.7 and 0.99. Conclusion FN RAT results can be accurately identified through ten routinely available variables. Implementation of a prediction model in addition to RAT testing in clinical care can provide a decision guidance for initiating appropriate hygiene measures and therefore helps avoiding nosocomial infections., Graphical abstract Image, graphical abstract

Graphical abstract, Highlights • Patients with cerebellar stroke have deficits in emotional prosody recognition. • Patients with right-hemispheric lesions make more misattributions. • Emotion deficits correlate with lesions in right Lobules VIIb–VIII and Crus I–II. • Acoustic features explain a significant proportion of the variance. • The posterior cerebellar lobe is involved in both sensory and emotional processes., In recent years, there has been increasing evidence of cerebellar involvement in emotion processing. Difficulties in the recognition of emotion from voices (i.e., emotional prosody) have been observed following cerebellar stroke. However, the interplay between sensory and higher-order cognitive dysfunction in these deficits, as well as possible hemispheric specialization for emotional prosody processing, has yet to be elucidated. We investigated the emotional prosody recognition performances of patients with right versus left cerebellar lesions, as well as of matched controls, entering the acoustic features of the stimuli in our statistical model. We also explored the cerebellar lesion-behavior relationship, using voxel-based lesion-symptom mapping. Results revealed impairment of vocal emotion recognition in both patient subgroups, particularly for neutral or negative prosody, with a higher number of misattributions in patients with right-hemispheric stroke. Voxel-based lesion-symptom mapping showed that some emotional misattributions correlated with lesions in the right Lobules VIIb and VIII and right Crus I and II. Furthermore, a significant proportion of the variance in this misattribution was explained by acoustic features such as pitch, loudness, and spectral aspects. These results point to bilateral posterior cerebellar involvement in both the sensory and cognitive processing of emotions.

Epidemiologic studies recognize that trauma and posttraumatic stress are associated with heightened suicidal behavior severity, yet examination of these associations from a genetic perspective is limited. We performed a multivariate gene-by-environment genome-wide interaction study (GEWIS) of suicidality in 123,633 individuals using a covariance matrix based on 26 environments related to traumatic experiences, posttraumatic stress, social support, and socioeconomic status. We discovered five suicidality risk loci, including the male-associated rs2367967 (CWC22), which replicated in an independent cohort. All GEWIS-significant loci exhibited interaction effects where at least 5% of the sample had environmental profiles conferring opposite SNP effects from the majority. We identified PTSD as a primary driving environment for GxE at suicidality risk loci. The male suicidality GEWIS was enriched for three middle-temporal-gyrus inhibitory neuron transcriptomic profiles: SCUBE- and PVALB-expressing cells (β = 0.028, p = 3.74 × 10−4), OPRM1-expressing cells (β = 0.030, p = 0.001), and SPAG17-expressing cells (β = 0.029, p = 9.80 × 10−4). Combined with gene-based analyses (CNTN5 passociation = 2.38 × 10−9, pinteraction = 1.51 × 10−3; PSMD14 passociation = 2.04 × 10−7, pinteraction = 7.76 × 10−6; HEPACAM passociation = 2.43 × 10−6, pinteraction = 3.82 × 10−7) including information about brain chromatin interaction profiles (UBE2E3 in male neuron p = 1.07 × 10−5), our GEWIS points to extracellular matrix biology and synaptic plasticity as biological interactors with the effects of potentially modifiable lifetime traumatic experiences on genetic risk for suicidality. Characterization of molecular basis for the effects of traumatic experience and posttraumatic stress on risk of suicidal behaviors may help to identify novel targets for which more effective treatments can be developed for use in high-risk populations., Highlights • Investigate interaction of traumatic events, posttraumatic stress, and suicidality. • Male suicidality risk loci interact with physically violent trauma. • Female suicidality risk locus interacts with posttraumatic stress. • Functional annotation highlights brain cell types and extracellular matrix biology. • Modifiable suicidality risk environments may mitigate suicidality genetic risk.

Is motor response inhibition supported by a specialised neuronal inhibitory control mechanism, or by a more general system of action updating? This pre-registered study employed a context-cueing paradigm requiring both inhibitory and non-inhibitory action updating in combination with functional magnetic resonance imaging to test the specificity of responses under different updating conditions, including the cancellation of actions. Cortical regions of activity were found to be common to multiple forms of action updating. However, functional specificity during response inhibition was observed in the anterior right inferior frontal gyrus. In addition, fronto-subcortical activity was explored using a novel contrast method. These exploratory results indicate that the specificity for response inhibition observed in right prefrontal cortex continued downstream and was observed in right hemisphere subcortical activity, while left hemisphere activity was associated with right-hand response execution. Overall, our findings reveal both common and distinct correlates of response inhibition in prefrontal cortex, with exploratory analyses supporting putative models of subcortical pathways and extending them through the demonstration of lateralisation., Highlights • Anterior specificity in cortical activity to response inhibition was identified. • Methodological development of a compound contrast methodology optimising data usage. • Exploratory demonstration of lateralised subcortical action control pathways.

Parkinson's disease is a common and debilitating condition, caused by aberrant activity in a complex basal ganglia–thalamocortical circuit. Therapeutic advances rely on characterising interactions in this circuit. However, recording electrophysiological responses over the entire circuit is impractical. Dynamic causal modelling offers large-scale models of predictive value based on a limited or partial sampling of complex networks. Using dynamic causal modelling, we determined the network changes underlying the pathological excess of beta oscillations that characterise the Parkinsonian state. We modelled data from five patients undergoing surgery for deep brain stimulation of more than one target. We found that connections to and from the subthalamic nucleus were strengthened and promoted beta synchrony, in the untreated compared to the treated Parkinsonian state. Dynamic causal modelling was able to replicate the effects of lesioning this nucleus and may provide a new means of directing the search for therapeutic targets., Highlights ► Novel model of basal ganglia-cortical system based on data from Parkinson’s patients. ► Model exposes criticality of connections to and from subthalamic nucleus in PD. ► Model able to replicate the effects of known surgical interventions in PD. ► Allows in silico tests of candidate therapeutic interventions in circuit disorders.