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Background: Recent research on boredom suggests that it can emerge in situations characterized by over- and under-challenge. In learning contexts, this implies that high boredom may be experienced both by low- and high-achieving students. Aims: This research aimed to explore the existence and prevalence of boredom due to being over- and under-challenged in mathematics, for which empirical evidence is lacking. Sample: We employed a sample of 1.407 students (fifth to ninth graders) from all three secondary school tracks (lower, middle and upper) in Bavaria (Germany). Methods: Boredom was assessed via self-report and achievement via a standardized mathematics test. We used latent profile analysis to identify groups characterized by different levels of boredom and achievement, and we additionally examined gender and school track as group membership predictors. Results: Results revealed four distinct groups, of which two showed considerably high boredom. One was coupled with low achievement on the test (i.e. 'over-challenged group', 13% of the total sample), and one was coupled with high achievement (i.e. 'under-challenged group', 21%). Furthermore, we found a low boredom and high achievement (i.e. 'well-off group', 27%) and a relatively low boredom low achievement group (i.e. 'indifferent group', 39%). Girls were overrepresented in the over-challenged group, and students from the upper school track were underrepresented in the under-challenged group. Conclusion: Our research emphasizes the need to openly discuss and further investigate boredom due to being over- and under-challenged.

Snake venom is an ecologically relevant functional trait directly linked with a snake’s fitness and survival, facilitating predation and defence. Snake venom variation occurs at all taxonomic levels, but the study at the intraspecific level is still in its early stages. The common adder (Vipera berus) exhibits considerable variation in colour phenotypes across its distribution range. Melanistic (fully black) individuals are the subject of myths and fairytales, and in German folklore such ‘hell adders’ are considered more toxic than their normally coloured conspecifics despite any formal investigation. Here, we provide the first comparative analysis of venoms from melanistic and normally coloured common adders. Specifically, we compared the venom profiles by sodium dodecylsulfate polyacrylamide gel electrophoresis and reversed-phase high-performance liquid chromatography and tested the venoms’ protease, phospholipase A2 and cytotoxic activities. Phospholipase A2 activity was similar in both phenotypes, whereas general protease activity was higher in the melanistic venom, which was also more cytotoxic at two concentrations (6.25 and 12.5 µg ml−1). These minor differences between the venoms of melanistic and normally coloured adders are unlikely to be of clinical relevance in the context of human envenomation. In light of our results, the claim that melanistic adders produce more toxic venom than their normally coloured conspecifics appears rooted entirely in folklore.

Introduction In situ simulation (ISS) enables multiprofessional healthcare teams to train for real emergencies in their own working environment and identify latent patient safety threats. This study aimed to determine ISS impact on teamwork, technical skill performance, healthcare staff perception and latent error identification during simulated medical emergencies.Materials and methods Unannounced ISS sessions (n=14, n=75 staff members) using a high-fidelity mannequin were conducted in medical, paediatric and rehabilitation wards at Stepping Hill Hospital (Stockport National Health Service Foundation Trust, UK). Each session encompassed a 15 min simulation followed by a 15 min faculty-led debrief.Results The clinical team score revealed low overall teamwork performances during simulated medical emergencies (mean±SEM: 4.3±0.5). Linear regression analysis revealed that overall communication (r=0.9, p

Hallucinations are a prominent transdiagnostic psychiatric symptom but are also prevalent in individuals who do not require clinical care. Moreover, persistent psychosis-like experience in otherwise healthy individuals may be related to an increased risk to transition to a psychotic disorder. This suggests a common etiology across clinical and non-clinical individuals along a multidimensional psychosis continuum that may be detectable in structural variations of the brain. The current diffusion tensor imaging study assessed 50 healthy individuals (35 females) to identify possible differences in white matter associated with hallucination proneness (HP). This approach circumvents potential confounds related to medication, hospitalization, and disease progression common in clinical individuals. We determined how HP relates to white matter structure in selected association, commissural, and projection fiber pathways putatively linked to psychosis. Increased HP was associated with enhanced fractional anisotropy (FA) in the right uncinate fasciculus, the right anterior and posterior arcuate fasciculus, and the corpus callosum. These findings support the notion of a psychosis continuum, providing first evidence of structural white matter variability associated with HP in healthy individuals. Furthermore, alterations in the targeted pathways likely indicate an association between HP-related structural variations and the putative salience and attention mechanisms that these pathways subserve.

Endothelial cells (ECs) respond to concurrent stimulation by biochemical factors and wall shear stress (SS) exerted by blood flow. Disruptions in flow-induced responses can result in remodeling issues and cardiovascular diseases, but the detailed mechanisms linking flow-mechanical cues and biochemical signaling remain unclear. Activin receptor-like kinase 1 (ALK1) integrates SS and ALK1-ligand cues in ECs; ALK1 mutations cause hereditary hemorrhagic telangiectasia (HHT), marked by arteriovenous malformation (AVM) development. However, the mechanistic underpinnings of ALK1 signaling modulation by fluid flow and the link to AVMs remain uncertain. We recorded EC responses under varying SS magnitudes and ALK1 ligand concentrations by assaying pSMAD1/5/9 nuclear localization using a custom multi-SS microfluidic device and a custom image analysis pipeline. We extended the previously reported synergy between SS and BMP9 to include BMP10 and BMP9/10. Moreover, we demonstrated that this synergy is effective even at extremely low SS magnitudes (0.4 dyn/cm2) and ALK1 ligand range (femtogram/mL). The synergistic response to ALK1 ligands and SS requires the kinase activity of ALK1. Moreover, ALK1’s basal activity and response to minimal ligand levels depend on endocytosis, distinct from cell–cell junctions, cytoskeleton-mediated mechanosensing, or cholesterol-enriched microdomains. However, an in-depth analysis of ALK1 receptor trafficking’s molecular mechanisms requires further investigation.

Background: Chronic tinnitus can have an immense impact on quality of life. Despite recent treatment advances, many tinnitus patients remain refractory to them. Preclinical and clinical evidence suggests that deep brain stimulation (DBS) is a promising treatment to suppress tinnitus. In rats, it has been shown in multiple regions of the auditory pathway that DBS can have an alleviating effect on tinnitus. The thalamic medial geniculate body (MGB) takes a key position in the tinnitus network, shows pathophysiological hallmarks of tinnitus, and is readily accessible using stereotaxy. Here, a protocol is described to evaluate the safety and test the therapeutic effects of DBS in the MGB in severe tinnitus sufferers. Methods: Bilateral DBS of the MGB will be applied in a future study in six patients with severe and refractory tinnitus. A double-blinded, randomized 2 × 2 crossover design (stimulation ON and OFF) will be applied, followed by a period of six months of open-label follow-up. The primary focus is to assess safety and feasibility (acceptability). Secondary outcomes assess a potential treatment effect and include tinnitus severity measured by the Tinnitus Functional Index (TFI), tinnitus loudness and distress, hearing, cognitive and psychological functions, quality of life, and neurophysiological characteristics. Discussion: This protocol carefully balances risks and benefits and takes ethical considerations into account. This study will explore the safety and feasibility of DBS in severe refractory tinnitus, through extensive assessment of clinical and neurophysiological outcome measures. Additionally, important insights into the underlying mechanism of tinnitus and hearing function might be revealed. Trial registration: ClinicalTrials.gov NCT03976908 (6 June 2019).

Measurement(s) vegetation-plot resurvey data of vascular plant species Technology Type(s) vegetation-plot records Factor Type(s) Cover of species in plots Sample Characteristic - Organism Vascular plant species Sample Characteristic - Environment Terrestrial habitats Sample Characteristic - Location Germany

When sensory input conveys rhythmic regularity, we can form predictions about the timing of upcoming events. Although rhythm processing capacities differ considerably between individuals, these differences are often obscured by participant- and trial-level data averaging procedures in M/EEG research. Here, we systematically assessed neurophysiological variability displayed by individuals listening to isochronous (1.54 Hz) equitone sequences interspersed with unexpected (amplitude-attenuated) deviant tones. Our approach aimed at revealing time-varying adaptive neural mechanisms for sampling the acoustic environment at multiple timescales. Rhythm tracking analyses confirmed that individuals encode temporal regularities and form temporal expectations, as indicated in delta-band (1.54 Hz) power and its anticipatory phase alignment to expected tone onsets. Zooming into tone- and participant-level data, we further characterized intra- and inter-individual variabilities in phase-alignment across auditory sequences. Further, individual modeling of beta-band tone-locked responses showed that a subset of auditory sequences was sampled rhythmically by superimposing binary (strong-weak; S-w), ternary (S-w-w) and mixed accentuation patterns. In these sequences, neural responses to standard and deviant tones were modulated by a binary accentuation pattern, thus pointing towards a mechanism of dynamic attending. Altogether, the current results point toward complementary roles of delta- and beta-band activity in rhythm processing and further highlight diverse and adaptive mechanisms to track and sample the acoustic environment at multiple timescales, even in the absence of task-specific instructions.

Digital literacy and technology education has gained much relevance in humanities and heritage related disciplines during the recent decades. Against this background, the purpose of this article is to examine the current state of educational programs in digital cultural heritage and related disciplines primarily in Europe with supplemental information from the US. A further aim is to highlight core topics, challenges, and demands, and to show innovative formats and prospects.

Voices are a complex and rich acoustic signal processed in an extensive cortical brain network. Specialized regions within this network support voice perception and production and may be differentially affected in pathological voice processing. For example, the experience of hallucinating voices has been linked to hyperactivity in temporal and extra-temporal voice areas, possibly extending into regions associated with vocalization. Predominant self-monitoring hypotheses ascribe a primary role of voice production regions to auditory verbal hallucinations (AVH). Alternative postulations view a generalized perceptual salience bias as causal to AVH. These theories are not mutually exclusive as both ascribe the emergence and phenomenology of AVH to unbalanced top-down and bottom-up signal processing. The focus of the current study was to investigate the neurocognitive mechanisms underlying predisposition brain states for emergent hallucinations, detached from the effects of inner speech. Using the temporal voice area (TVA) localizer task, we explored putative hypersalient responses to passively presented sounds in relation to hallucination proneness (HP). Furthermore, to avoid confounds commonly found in in clinical samples, we employed the Launay-Slade Hallucination Scale (LSHS) for the quantification of HP levels in healthy people across an experiential continuum spanning the general population. We report increased activation in the right posterior superior temporal gyrus (pSTG) during the perception of voice features that positively correlates with increased HP scores. In line with prior results, we propose that this right-lateralized pSTG activation might indicate early hypersensitivity to acoustic features coding speaker identity that extends beyond own voice production to perception in healthy participants prone to experience AVH.

In the absence of sensory stimulation, the brain transits between distinct functional networks. Network dynamics such as transition patterns and the time the brain stays in each network link to cognition and behavior and are subject to much investigation. Auditory verbal hallucinations (AVH), the temporally fluctuating unprovoked experience of hearing voices, are associated with aberrant resting state network activity. However, we lack a clear understanding of how different networks contribute to aberrant activity over time. An accurate characterization of latent network dynamics and their relation to neurocognitive changes necessitates methods that capture the sub-second temporal fluctuations of the networks’ functional connectivity signatures. Here, we critically evaluate the assumptions and sensitivity of several approaches commonly used to assess temporal dynamics of brain connectivity states in M/EEG and fMRI research, highlighting methodological constraints and their clinical relevance to AVH. Identifying altered brain connectivity states linked to AVH can facilitate the detection of predictive disease markers and ultimately be valuable for generating individual risk profiles, differential diagnosis, targeted intervention, and treatment strategies.

Timing is an essential part of human cognition and of everyday life activities, such as walking or holding a conversation. Previous studies showed that traumatic brain injury (TBI) often affects cognitive functions such as processing speed and time-sensitive abilities, causing long-term sequelae as well as daily impairments. However, the existing evidence on timing capacities in TBI is mostly limited to perception and the processing of isolated intervals. It is therefore open whether the observed deficits extend to motor timing and to continuous dynamic tasks that more closely match daily life activities. The current study set out to answer these questions by assessing audio motor timing abilities and their relationship with cognitive functioning in a group of TBI patients (n = 15) and healthy matched controls. We employed a comprehensive set of tasks aiming at testing timing abilities across perception and production and from single intervals to continuous auditory sequences. In line with previous research, we report functional impairments in TBI patients concerning cognitive processing speed and perceptual timing. Critically, these deficits extended to motor timing: The ability to adjust to tempo changes in an auditory pacing sequence was impaired in TBI patients, and this motor timing deficit covaried with measures of processing speed. These findings confirm previous evidence on perceptual and cognitive timing deficits resulting from TBI and provide first evidence for comparable deficits in motor behavior. This suggests basic co-occurring perceptual and motor timing impairments that may factor into a wide range of daily activities. Our results thus place TBI into the wider range of pathologies with well-documented timing deficits (such as Parkinson’s disease) and encourage the search for novel timing-based therapeutic interventions (e.g., employing dynamic and/or musical stimuli) with high transfer potential to everyday life activities.

The flexible and efficient adaptation to dynamic, rapid changes in the auditory environment likely involves generating and updating of internal models. Such models arguably exploit connections between the neocortex and the cerebellum, supporting proactive adaptation. Here, we tested whether temporo-cerebellar disconnection is associated with the processing of sound at short timescales. First, we identify lesion-specific deficits for the encoding of short timescale spectro-temporal non-speech and speech properties in patients with left posterior temporal cortex stroke. Second, using lesion-guided probabilistic tractography in healthy participants, we revealed bidirectional temporo-cerebellar connectivity with cerebellar dentate nuclei and crura I/II. These findings support the view that the encoding and modeling of rapidly modulated auditory spectro-temporal properties can rely on a temporo-cerebellar interface. We discuss these findings in view of the conjecture that proactive adaptation to a dynamic environment via internal models is a generalizable principle.

Abstract Auditory verbal hallucinations (AVH) are a cardinal symptom of psychosis but also occur in 6–13% of the general population. Voice perception is thought to engage an internal forward model that generates predictions, preparing the auditory cortex for upcoming sensory feedback. Impaired processing of sensory feedback in vocalization seems to underlie the experience of AVH in psychosis, but whether this is the case in nonclinical voice hearers remains unclear. The current study used electroencephalography (EEG) to investigate whether and how hallucination predisposition (HP) modulates the internal forward model in response to self-initiated tones and self-voices. Participants varying in HP (based on the Launay-Slade Hallucination Scale) listened to self-generated and externally generated tones or self-voices. HP did not affect responses to self vs. externally generated tones. However, HP altered the processing of the self-generated voice: increased HP was associated with increased pre-stimulus alpha power and increased N1 response to the self-generated voice. HP did not affect the P2 response to voices. These findings confirm that both prediction and comparison of predicted and perceived feedback to a self-generated voice are altered in individuals with AVH predisposition. Specific alterations in the processing of self-generated vocalizations may establish a core feature of the psychosis continuum.

Das Thüringer Kompetenznetzwerk Forschungsdatenmanagement stellt seinen kampagnenbasierten Ansatz zur Kommunikation des Themas Forschungsdatenmanagement und der landesweiten FDM-Aktivitäten vor. Die Strategie zielt auf eine regelmäßige Kommunikation mit allen Adressaten des Netzwerks ab, die in Inhalt und Frequenz den jeweiligen Zielgruppen angepasst ist. Dem Gedanken der Nachhaltigkeit folgend, werden ausschließlich Materialien, die noch nicht anderweitig in ähnlicher Form bestehen, selbst gestaltet und zur Nachnutzung zur Verfügung gestellt. Wo angemessen, wird auf bestehende Angebote der FDM-Community aufgebaut.

Summary: TMEM18 is the strongest candidate for childhood obesity identified from GWASs, yet as for most GWAS-derived obesity-susceptibility genes, the functional mechanism remains elusive. We here investigate the relevance of TMEM18 for adipose tissue development and obesity. We demonstrate that adipocyte TMEM18 expression is downregulated in children with obesity. Functionally, downregulation of TMEM18 impairs adipocyte formation in zebrafish and in human preadipocytes, indicating that TMEM18 is important for adipocyte differentiation in vivo and in vitro. On the molecular level, TMEM18 activates PPARG, particularly upregulating PPARG1 promoter activity, and this activation is repressed by inflammatory stimuli. The relationship between TMEM18 and PPARG1 is also evident in adipocytes of children and is clinically associated with obesity and adipocyte hypertrophy, inflammation, and insulin resistance. Our findings indicate a role of TMEM18 as an upstream regulator of PPARG signaling driving healthy adipogenesis, which is dysregulated with adipose tissue dysfunction and obesity.

The Entomophthoromycotina, a subphylum close to the root of terrestrial fungi with a bias toward insects as their primary hosts, has been notoriously difficult to categorize taxonomically for decades. Here, we reassess the phylogeny of this group based on conserved genes encoding ribosomal RNA and RNA polymerase II subunits, confirming their general monophyly, but challenging previously assumed taxonomic relationships within and between particular clades. Furthermore, for the prominent, partially human-pathogenic taxon Conidiobolus, a new type species C. coronatus is proposed in order to compensate for the unclear, presumably lost previous type species C. utriculosus Brefeld 1884. We also performed an exhaustive survey of the broad host spectrum of the Entomophthoromycotina, which is not restricted to insects alone, and investigated potential patterns of co-evolution across their megadiverse host range. Our results suggest multiple independent origins of parasitism within this subphylum and no apparent co-evolutionary events with any particular host lineage. However, Pterygota (i.e., winged insects) clearly constitute the most dominantly parasitized superordinate host group. This appears to be in accordance with an increased dispersal capacity mediated by the radiation of the Pterygota during insect evolution, which has likely greatly facilitated the spread, infection opportunities, and evolutionary divergence of the Entomophthoromycotina as well.

Existing research shows that high achievement boredom is correlated with a range of undesirable behavioral and personality variables and that the main antecedents of boredom are being over- or under-challenged. However, merely knowing that students are highly bored, without taking their achievement level into account, might be insufficient for drawing conclusions about students' behavior and personality. We, therefore, investigated if low- vs. high-achieving students who experience strong mathematics boredom show different behaviors and personality traits. The sample consisted of 1,404 German secondary school students (fifth to 10th grade, mean age 12.83 years, 52% female). We used self-report instruments to assess boredom in mathematics, behavioral (social and emotional problems, positive/negative affect, cognitive reappraisal, and expressive suppression), and personality variables (neuroticism and conscientiousness). In comparing highly bored students (more than one SD above M, n = 258) who were low vs. high achievers (as indicated by the math grade, n = 125 / n = 119), results showed that there were no mean level differences across those groups for all variables. In conclusion, our results suggest that high boredom can occur in both low- and high-achieving students and that bored low- and high-achievers show similar behaviors and personality profiles.

With the advances in sensor technology, big data, and artificial intelligence, unobtrusive in-home health monitoring has been a research focus for decades. Following up our research on smart vehicles, within the framework of unobtrusive health monitoring in private spaces, this work attempts to provide a guide to current sensor technology for unobtrusive in-home monitoring by a literature review of the state of the art and to answer, in particular, the questions: (1) What types of sensors can be used for unobtrusive in-home health data acquisition? (2) Where should the sensors be placed? (3) What data can be monitored in a smart home? (4) How can the obtained data support the monitoring functions? We conducted a retrospective literature review and summarized the state-of-the-art research on leveraging sensor technology for unobtrusive in-home health monitoring. For structured analysis, we developed a four-category terminology (location, unobtrusive sensor, data, and monitoring functions). We acquired 912 unique articles from four relevant databases (ACM Digital Lib, IEEE Xplore, PubMed, and Scopus) and screened them for relevance, resulting in n=55 papers analyzed in a structured manner using the terminology. The results delivered 25 types of sensors (motion sensor, contact sensor, pressure sensor, electrical current sensor, etc.) that can be deployed within rooms, static facilities, or electric appliances in an ambient way. While behavioral data (e.g., presence (n=38), time spent on activities (n=18)) can be acquired effortlessly, physiological parameters (e.g., heart rate, respiratory rate) are measurable on a limited scale (n=5). Behavioral data contribute to functional monitoring. Emergency monitoring can be built up on behavioral and environmental data. Acquired physiological parameters allow reasonable monitoring of physiological functions to a limited extent. Environmental data and behavioral data also detect safety and security abnormalities. Social interaction monitoring relies mainly on direct monitoring of tools of communication (smartphone; computer). In summary, convincing proof of a clear effect of these monitoring functions on clinical outcome with a large sample size and long-term monitoring is still lacking.

[This corrects the article DOI: 10.1371/journal.pgen.1004496.].

Introduction: Interprofessional collaboration is crucial to the optimization of patient care.Aim: This paper aims to provide recommendations for implementing an innovative constructivist educational concept with the core element of video-based self-assessment.Methodology: A course for students in medicine, physiotherapy, and nursing was developed through interprofessional, cross-institutional collaboration. The course consisted of We evaluated the preparation and implementation of the three courses conducted thus far. Concrete recommendations for implementation were made based on evaluation sheets (students), open discussions (tutors, instructors, institutions) and recorded meeting minutes (project managers, project participants).Results: Basic recommendations for implementation include: selecting appropriate criteria for self-assessment and a simulated situation that offers members of each professional group an equal opportunity to act in the role play. In terms of administrative implementation we recommend early coordination among the professions and educational institutions regarding the target groups, scheduling and attendance policy to ensure participant recruitment across all professions. Procedural planning should include developing teaching materials, such as the case vignette and treatment scenario, and providing technical equipment that can be operated intuitively in order to ensure efficient recording.Conclusion: These recommendations serve as an aid for implementing an innovative constructivist educational concept with video-based self-assessment at its core.

QGIS releases equal to or newer than 0.7 can easily connected to GRASS GIS by means of a toolbox that provides a wide range of standard GRASS modules you can launch – albeit only on data coming from GRASS. This QGIS plugin is expandable through XML configurations describing the assignment of options and inputs for a certain module. But how about embedding a precise workflow where the several processes don’t consist of a single GRASS module by force? Especially for a sequence of dependent tasks it makes sense to merge relevant GRASS functionality into an own and encapsulated QGIS extension. Its architecture and development is tested and combined with the Web Processing Service (WPS) for remote execution using the concept of hydrological response units (HRUs) as an example. The results of this assay may be suitable for discussing and planning other wizard-like geoprocessing plugins in QGIS that also should make use of an additional GRASS server.

Lichtheimia species are the second most important cause of mucormycosis in Europe. To provide broader insights into the molecular basis of the pathogenicity-associated traits of the basal Mucorales, we report the full genome sequence of L. corymbifera and compared it to the genome of Rhizopus oryzae, the most common cause of mucormycosis worldwide. The genome assembly encompasses 33.6 MB and 12,379 protein-coding genes. This study reveals four major differences of the L. corymbifera genome to R. oryzae: (i) the presence of an highly elevated number of gene duplications which are unlike R. oryzae not due to whole genome duplication (WGD), (ii) despite the relatively high incidence of introns, alternative splicing (AS) is not frequently observed for the generation of paralogs and in response to stress, (iii) the content of repetitive elements is strikingly low (

Although the number of mucormycosis cases has increased during the last decades, little is known about the pathogenic potential of most mucoralean fungi. Lichtheimia species represent the second and third most common cause of mucormycosis in Europe and worldwide, respectively. To date only three of the five species of the genus have been found to be involved in mucormycosis, namely L. corymbifera, L. ramosa and L. ornata. However, it is not clear whether the clinical situation reflects differences in virulence between the species of Lichtheimia or whether other factors are responsible. In this study the virulence of 46 strains of all five species of Lichtheimia was investigated in chicken embryos. Additionally, strains of the closest-related genus Dichotomocladium were tested. Full virulence was restricted to the clinically relevant species while all strains of L. hyalospora, L. sphaerocystis and Dichotomocladium species were attenuated. Although virulence differences were present in the clinically relevant species, no connection between origin (environmental vs clinical) or phylogenetic position within the species was observed. Physiological studies revealed no clear connection of stress resistance and carbon source utilization with the virulence of the strains. Slower growth at 37°C might explain low virulence of L. hyalospora, L. spaherocystis and Dichotomocladium; however, similarly slow growing strains of L. ornata were fully virulent. Thus, additional factors or a complex interplay of factors determines the virulence of strains. Our data suggest that the clinical situation in fact reflects different virulence potentials in the Lichtheimiaceae.