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Abstract Vision and magnetoreception in navigating songbirds are strongly connected as recent findings link a light dependent radical-pair mechanism in cryptochrome proteins to signalling pathways in cone photoreceptor cells. A previous yeast-two-hybrid screening approach identified six putative candidate proteins showing binding to cryptochrome type 4a. So far, only the interaction of the cone specific G-protein transducin α-subunit was investigated in more detail. In the present study, we compare the binding features of the G-protein α-subunit with those of another candidate from the yeast-two-hybrid screen, cellular retinol binding protein. Purified recombinant European robin retinol binding protein bound retinol with high affinity, displaying an EC50 of less than 5 nM, thereby demonstrating its functional state. We applied surface plasmon resonance and a Förster resonance transfer analysis to test for interactions between retinol binding protein and cryptochrome 4a. In the absence of retinol, we observed no robust binding events, which contrasts the strong interaction we observed between cryptochrome 4a and the G-protein α-subunit. We conclude that retinol binding protein is unlikely to be involved in the primary magnetosensory signalling cascade.

Abstract Stiffness-related eye diseases such as keratoconus require comprehensive visualization of the complex morphological matrix changes. The aim of this study was to use three-dimensional (3D) light sheet fluorescence microscopy (LSFM) to analyze unlabeled corneal tissue samples, qualitatively visualizing changes in corneal stiffness. Isolated porcine corneal tissue samples were treated with either NaCl or 0.1% glutaraldehyde (GTA) prior to clearing with benzyl alcohol/benzyl benzoate (BABB) and subsequently scanned with LSFM. After analysis of the LSFM data sets, the samples were embedded in paraffin to validate the results by conventional planar microscopy. In the unlabeled corneal tissue samples the 2D/3D morphology of the entire tissue volume was identified by specific autofluorescence signals. An enhancement of collagen crosslinking was induced by applying GTA to the corneal tissue. Subsequent LSFM scans showed specific morphological changes due to altered autofluorescence signals of the corneal stroma, which were confirmed by conventional histology. Therefore, LSFM analysis of corneal tissue samples allowed label-free 3D autofluorescence assessment of the corneal morphology in its anatomical context. It provides the technical basis for the examination of the pathologically altered cornea and facilitates ophthalmologic examinations of corneal diseases based on the altered tissue stiffness.

Abstract Community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) often result in sudden and persistent reduction in health-related quality of life (HRQoL), which may be alleviated with palliative care. Among individuals with COPD, we aimed to investigate potential associations between HRQoL at admission with CAP and the risk of re-hospitalization and mortality and potential associations between specific HRQoL domains and CAP treatment outcomes. HRQoL was assessed at admission and the participants were grouped into tertiles based on the HRQoL utility index and specific domains. The results revealed that participants in the middle and highest tertiles of HRQoL had a lower 90-day re-hospitalization risk compared to those in the lowest tertile, whereas no differences in re-hospitalization risk were observed 30 and 180 days after discharge. Almost one in four had severe pain or discomfort at admission and the domain pain or discomfort emerged as a predictor of re-hospitalization. In addition, participants in the middle and highest tertiles had lower risk of 180-day mortality compared to those in the lowest, while no differences were observed in 30-day or 90-day mortality risk. An increased focus on in-hospital palliative care could alleviate the pain and discomfort reported by many participants with potential to reduce re-hospitalization rates.

Abstract In Wuerzburg, Germany, a terrorist attack and a killing rampage occurred five years apart (2016 and 2021). Following a structured evaluation of the rescue mission in 2016, a bundle of quality indicators and ten “lessons learned” were defined. Aim of the presented study was to compare the two rescue missions and to critically review the lessons learned from 2016 for their implementation and feasibility. An interdisciplinary and inter-professional group of experts analyzed the data using predefined quality indicators. All lessons defined in 2016 were critically reviewed and qualified as either lessons learned or lessons identified. While seven out of ten lessons were successfully implemented after 2016 (lessons learned), three lessons didn´t work and were recategorized as lessons identified (communication, zoning and the mutual exchange of different tactical approaches). Our results demonstrate that the conclusions drawn in 2016 have helped to improve the performance of the rescue forces in 2021. In addition, the identified lessons are now the basis for further improving emergency and disaster preparedness. It is important to understand, that the process of preparedness improvement is not completed with the definition of lessons identified. These must first be integrated into response plans and then trained intensively. A lesson identified only becomes a lesson learned once it has been successfully applied.

Abstract The effects of prolonged infrasound (IS) exposure on brain function and behavior are largely unknown, with only one prior study investigating functional connectivity (FC) changes. In a long-term randomized-controlled trial, 38 participants were exposed to inaudible airborne IS (6 Hz, 80–90 dB) or sham devices for four weeks (8 h/night). We assessed FC changes in resting-state networks (auditory, default mode (DMN), sensorimotor (SMN), and executive control (ECN)), and explored IS ‘sensitivity’ as a predictor of identified significant FC changes. We also examined correlations between somatic symptoms and FC. IS exposure led to decreased FC in the right precuneus (DMN) and increased FC in the Vermis IV and V (SMN). In the ECN, we observed increased FC in the right frontal middle gyrus (BA8) and the right inferior parietal lobe, and decreased FC in another region of the right frontal middle gyrus. Changes in the ECN (right inferior parietal lobe) were negatively associated with self-reported annoyance from IS/low-frequency noise. A significant negative association was found between FC changes in the DMN (right precuneus) and somatic symptoms. Our study is the first to investigate prolonged IS exposure effects on brain FC, revealing changes in the vDMN, SMN, and ECN, but not in the auditory network. Future studies should assess annoyance and sensitivity markers, fine-grained measures of somatic symptoms, and stratify samples by sensitivity to uncover individual differences in response to IS.

Abstract This paper analyzes effects of the mutual presentation of weak and strong arguments. Departing from the prevalent “the-more-the-better” heuristic, our research scrutinizes whether the inclusion of weak arguments enhances or diminishes the persuasive impact of strong arguments. Leveraging insights from judgment formation literature, we conducted four experimental studies on political and health-related topics to unravel whether the presenting weak arguments strengthens the persuasive effect of a strong argument (adding) or actually weakens this persuasive effect (averaging). The results show that providing supporting arguments of moderate strength along with a strong argument increases persuasion, representing an additive pattern. However, presenting weak supporting arguments along with a strong argument reduces the persuasive effect of the strong argument, representing an averaging pattern. Exposure to weak arguments diminishes the strength of strong ones, suggesting the omission of weak arguments. These findings underscore the vital role of strategically selecting arguments to optimize persuasion across disciplines.

Abstract Smart textiles that promise to become sensors and actuators for multiple applications are an active area of research. Conductive textiles formed by coating a fabric with a conductive film will play a key role in such applications. Here we present contactless mapping of the terahertz (THz) conductivity of thin conductive films deposited on textiles. These conductivity maps enable non-destructive assessment of the conductivity of such layers and therefore the identification and localization of non-uniformities in local conductivity. The THz measurements are quantitatively consistent with four-point probe measurements of the same areas.

Abstract Cognitive deficits are prevalent in individuals with psychosis and are associated with neurobiological changes, potentially serving as an endophenotype for psychosis. Using the HCP-Early-Psychosis-dataset (n = 226), we aimed to investigate cognitive subtypes (deficit/intermediate/spared) through data-driven clustering in affective (AP) and non-affective psychosis patients (NAP) and controls (HC). We explored differences between three clusters in symptoms, cognition, medication, and grey matter volume. Applying principal component analysis, we selected features for clustering. Features that explained most variance were scores for intelligence, verbal recognition and comprehension, auditory attention, working memory, reasoning and executive functioning. Fuzzy K-Means clustering on those features revealed that the subgroups significantly varied in cognitive impairment, clinical symptoms, and, importantly, also in medication and grey matter volume in fronto-parietal and subcortical networks. The spared cluster (86%HC, 37%AP, 17%NAP) exhibited unimpaired cognition, lowest symptoms/medication, and grey matter comparable to controls. The deficit cluster (4%HC, 10%AP, 47%NAP) had impairments across all domains, highest symptoms scores/medication dosage, and pronounced grey matter alterations. The intermediate deficit cluster (11%HC, 54%AP, 36%NAP) showed fewer deficits than the second cluster, but similar symptoms/medication/grey matter to the spared cluster. Controlling for medication, cognitive scores correlated with grey matter changes and negative symptoms across all patients. Our findings generally emphasize the interplay between cognition, brain structure, symptoms, and medication in AP and NAP, and specifically suggest a possible mediating role of cognition, highlighting the potential of screening cognitive changes to aid tailoring treatments and interventions.

Abstract With the growing interest in establishing brain-based biomarkers for precision medicine, there is a need for noninvasive, scalable neuroimaging devices that yield valid and reliable metrics. Kernel’s second-generation Flow2 Time-Domain Functional Near-Infrared Spectroscopy (TD-fNIRS) system meets the requirements of noninvasive and scalable neuroimaging, and uses a validated modality to measure brain function. In this work, we investigate the test-retest reliability (TRR) of a set of metrics derived from the Flow2 recordings. We adopted a repeated-measures design with 49 healthy participants, and quantified TRR over multiple time points and different headsets—in different experimental conditions including a resting state, a sensory, and a cognitive task. Results demonstrated high reliability in resting state features including hemoglobin concentrations, head tissue light attenuation, amplitude of low frequency fluctuations, and functional connectivity. Additionally, passive auditory and Go/No-Go inhibitory control tasks each exhibited similar activation patterns across days. Notably, areas with the highest reliability were in auditory regions during the auditory task, and right prefrontal regions during the Go/No-Go task, consistent with prior literature. This study underscores the reliability of Flow2-derived metrics, supporting its potential to actualize the vision of using brain-based biomarkers for diagnosis, treatment selection and treatment monitoring of neuropsychiatric and neurocognitive disorders.

Abstract This study was aimed to investigate the frequency of PiCV recombination, the kinetics of PiCV viremia and shedding and the correlation between viral replication and host immune response in young pigeons subclinically infected with various PiCV variants and kept under conditions mimicking the OLR system. Fifteen racing pigeons originating from five breeding facilities were housed together for six weeks. Blood and cloacal swab samples were collected from birds every seven days to recover complete PiCV genomes and determine PiCV genetic diversity and recombination dynamics, as well as to assess virus shedding rate, level of viremia, expression of selected genes and level of anti-PiCV antibodies. Three hundred and eighty-eight complete PiCV genomes were obtained and thirteen genotypes were distinguished. Twenty-five recombination events were detected. Recombinants emerged during the first three weeks of the experiment which was consistent with the peak level of viremia and viral shedding. A further decrease in viremia and shedding partially corresponded with IFN-γ and MX1 gene expression and antibody dynamics. Considering the role of OLR pigeon rearing system in spreading infectious agents and allowing their recombination, it would be reasonable to reflect on the relevance of pigeon racing from both an animal welfare and epidemiological perspective.

Abstract Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is considered a growing health concern. The majority of NTM-PD cases in Europe are caused by slow-growing mycobacteria (SGM). However, distinct radiological features of different SGM remain largely uninvestigated. We applied a previously described radiological score to a patient cohort consisting of individuals with isolation of different SGM. Correlations between clinical data, species and computed tomography (CT) features were examined by logistic and linear regression analyses, as well as over the course of time. Overall, 135 pulmonary CT scans from 84 patients were included. The isolated NTM-species were mainly Mycobacterium avium complex (MAC, n = 49), as well as 35 patients with non-MAC-species. Patients with isolation of M. intracellulare had more extensive CT findings compared to all other SGM species (coefficient 3.53, 95% Cl − 0.37 to 7.52, p = 0.075) while patients meeting the ATS criteria and not undergoing therapy exhibited an increase in CT scores over time. This study provides insights into differential radiological features of slow-growing NTM. While M. intracellulare exhibited a tendency towards higher overall CT scores, the radiological features were similar across different SGM. The applied CT score might be a useful instrument for monitoring patients and could help to guide antimycobacterial therapy.

Abstract Health-related quality of life (HRQoL) has recently gained importance as treatment options for tumors of the upper GI tract lead to improved long-term survival. HRQoL is often estimated by physicians even though their reliability and the impact of outside factors such as contact time and level of medical education is unclear. Therefore, in this study we investigated the correlation between physicians’, students’, and patients’ assessment of HRQoL. 54 patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaires EORTC QLQ-C30 and QLQ-OG25. Attending physicians and medical students filled out the same questionnaires through estimation of patients’ HRQoL. Correlation was assessed through Pearson’s and Kendall’s τb coefficients. Physicians’ and patients’ assessments correlated for one out of six of the functional and a third of the symptom scores. Students’ and patients’ assessments correlated for one third of the functional and two thirds of the symptom scores. Students tended to underestimate patients’ symptom burden while physicians tended to overestimate it. Physicians failed to correctly assess several pathognomonic symptoms in this study. Students showed higher correlation with patients’ symptoms than physicians. Even so, this adds to mounting evidence that shows the benefit of using patient-reported outcomes as a gold standard regarding HRQoL.

Abstract Studying the oculomotor system provides a unique window to assess brain health and function in various clinical populations. Although the use of detailed oculomotor parameters in clinical research has been limited due to the scalability of the required equipment, the development of novel tablet-based technologies has created opportunities for fast, easy, cost-effective, and reliable eye tracking. Oculomotor measures captured via a mobile tablet-based technology have previously been shown to reliably discriminate between Parkinson’s Disease (PD) patients and healthy controls. Here we further investigate the use of oculomotor measures from tablet-based eye-tracking to inform on various cognitive abilities and disease severity in PD patients. When combined using partial least square regression, the extracted oculomotor parameters can explain up to 71% of the variance in cognitive test scores (e.g. Trail Making Test). Moreover, using a receiver operating characteristics (ROC) analysis we show that eye-tracking parameters can be used in a support vector classifier to discriminate between individuals with mild PD from those with moderate PD (based on UPDRS cut-off scores) with an accuracy of 90%. Taken together, our findings highlight the potential usefulness of mobile tablet-based technology to rapidly scale eye-tracking use and usefulness in both research and clinical settings by informing on disease stage and cognitive outcomes.

Abstract Investigating acute stress responses is crucial to understanding the underlying mechanisms of stress. Current stress assessment methods include self-reports that can be biased and biomarkers that are often based on complex laboratory procedures. A promising additional modality for stress assessment might be the observation of body movements, which are affected by negative emotions and threatening situations. In this paper, we investigated the relationship between acute psychosocial stress induction and body posture and movements. We collected motion data from N = 59 individuals over two studies (Pilot Study: N = 20, Main Study: N = 39) using inertial measurement unit (IMU)-based motion capture suits. In both studies, individuals underwent the Trier Social Stress Test (TSST) and a stress-free control condition (friendly-TSST; f-TSST) in randomized order. Our results show that acute stress induction leads to a reproducible freezing behavior, characterized by less overall motion as well as more and longer periods of no movement. Based on these data, we trained machine learning pipelines to detect acute stress solely from movement information, achieving an accuracy of $${75.0 \pm 17.7}{\%}$$ 75.0 ± 17.7 % (Pilot Study) and $${73.4 \pm 7.7}{\%}$$ 73.4 ± 7.7 % (Main Study). This, for the first time, suggests that body posture and movements can be used to detect whether individuals are exposed to acute psychosocial stress. While more studies are needed to further validate our approach, we are convinced that motion information can be a valuable extension to the existing biomarkers and can help to obtain a more holistic picture of the human stress response. Our work is the first to systematically explore the use of full-body body posture and movement to gain novel insights into the human stress response and its effects on the body and mind.

Abstract Large population-based cohort studies utilizing device-based measures of physical activity are crucial to close important research gaps regarding the potential protective effects of physical activity on chronic diseases. The present study details the quality control processes and the derivation of physical activity metrics from 100 Hz accelerometer data collected in the German National Cohort (NAKO). During the 2014 to 2019 baseline assessment, a subsample of NAKO participants wore a triaxial ActiGraph accelerometer on their right hip for seven consecutive days. Auto-calibration, signal feature calculations including Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD), identification of non-wear time, and imputation, were conducted using the R package GGIR version 2.10-3. A total of 73,334 participants contributed data for accelerometry analysis, of whom 63,236 provided valid data. The average ENMO was 11.7 ± 3.7 mg (milli gravitational acceleration) and the average MAD was 19.9 ± 6.1 mg. Notably, acceleration summary metrics were higher in men than women and diminished with increasing age. Work generated in the present study will facilitate harmonized analysis, reproducibility, and utilization of NAKO accelerometry data. The NAKO accelerometry dataset represents a valuable asset for physical activity research and will be accessible through a specified application process.

Abstract The inhibition of action is a fundamental executive mechanism of human behaviour that involve a complex neural network. In spite of the progresses made so far, many questions regarding the brain dynamics occurring during action inhibition are still unsolved. Here, we used a novel approach optimized to investigate real-time effective brain dynamics, which combines transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recordings. 22 healthy volunteers performed a motor Go/NoGo task during TMS of the hand-hotspot of the primary motor cortex (M1) and whole-scalp EEG recordings. We reconstructed source-based real-time spatiotemporal dynamics of cortical activity and cortico-cortical connectivity throughout the task. Our results showed a task-dependent bi-directional change in theta/gamma supplementary motor cortex (SMA) and M1 connectivity that, when participants were instructed to inhibit their response, resulted in an increase of a specific TMS-evoked EEG potential (N100), likely due to a GABA-mediated inhibition. Interestingly, these changes were linearly related to reaction times, when participants were asked to produce a motor response. In addition, TMS perturbation revealed a task-dependent long-lasting modulation of SMA–M1 natural frequencies, i.e. alpha/beta activity. Some of these results are shared by animal models and shed new light on the physiological mechanisms of motor inhibition in humans.

Abstract Stress-related overeating can lead to excessive weight gain, increasing the risk of metabolic and cardiovascular disease. Mindfulness meditation has been demonstrated to reduce stress and increase interoceptive awareness and could, therefore, be an effective intervention for stress-related overeating behavior. To investigate the effects of mindfulness meditation on stress-eating behavior, meditation-naïve individuals with a tendency to stress-eat (N = 66) participated in either a 31-day, web-based mindfulness meditation training or a health training condition. Behavioral and resting-state fMRI data were acquired before and after the intervention. Mindfulness meditation training, in comparison to health training, was found to significantly increase mindfulness while simultaneously reducing stress- and emotional-eating tendencies as well as food cravings. These behavioral results were accompanied by functional connectivity changes between the hypothalamus, reward regions, and several areas of the default mode network in addition to changes observed between the insula and somatosensory areas. Additional changes between seed regions (i.e., hypothalamus and insula) and brain areas attributed to emotion regulation, awareness, attention, and sensory integration were observed. Notably, these changes in functional connectivity correlated with behavioral changes, thereby providing insight into the underlying neural mechanisms of the effects of mindfulness on stress-eating. Clinical trial on the ISRCTN registry: trial ID ISRCTN12901054

Abstract Stroke may affect physical functioning, cognition, and mental and social aspects of one’s life. Health literacy and self-efficacy are associated with positive health outcomes and are important factors for managing the diverse consequences of a stroke. However, there is very little literature on the association between health literacy and self-efficacy. This study aimed to investigate the association between health literacy and self-efficacy among stroke survivors 1 year after discharge from hospital. Participants in this cross-sectional study were patients diagnosed with a stroke, mainly a mild stroke, who were referred to rehabilitation in primary care after discharge from hospital in Sweden. Data was collected using questionnaires, performance-based tests, and medical records. Ordinal logistic regression was used to analyze the association between general self-efficacy and health literacy in adjusted models. The analysis revealed that higher levels of general self-efficacy and higher levels of performing activities of daily living were associated with higher levels of health literacy. Stroke survivors with higher general self-efficacy also report higher health literacy 1-year post-discharge from hospital. Future studies should focus on the pathways by which health literacy and general self-efficacy work among stroke survivors and in populations with low health literacy, severe stroke or significant cognitive impairments.

Abstract Terahertz imaging is unlocking unique capabilities for the analysis of cultural heritage artifacts. This paper uses terahertz time-domain imaging for the study of a gilded wooden artifact, providing a means to perform stratigraphic analysis, yielding information about the composition of the artifact, presence of certain materials identifiable through their THz spectral fingerprint, as well as alterations that have been performed over time. Due to the limited information that is available for many historic artifacts, the data that can be obtained through the presented technique can guide proper stewardship of the artifact, informing its long-term preservation.

Abstract Globally, food production for an ever-growing population is a well-known threat to the environment due to losses of excess reactive nitrogen (N) from agriculture. Since the 1980s, many countries of the Global North, such as Denmark, have successfully combatted N pollution in the aquatic environment by regulation and introduction of national agricultural one-size-fits-all mitigation measures. Despite this success, further reduction of the N load is required to meet the EU water directives demands, and implementation of additional targeted N regulation of agriculture has scientifically and politically been found to be a way forward. In this paper, we present a comprehensive concept to make future targeted N regulation successful environmentally and economically. The concept focus is on how and where to establish detailed maps of the groundwater denitrification potential (N retention) in areas, such as Denmark, covered by Quaternary deposits. Quaternary deposits are abundant in many parts of the world, and often feature very complex geological and geochemical architectures. We show that this subsurface complexity results in large local differences in groundwater N retention. Prioritization of the most complex areas for implementation of the new concept can be a cost-efficient way to achieve lower N impact on the aquatic environment.

Abstract Avian A(H5N1) influenza virus poses an elevated zoonotic threat to humans, and no pharmacological products are currently registered for fast-acting pre-exposure protection in case of spillover leading to a pandemic. Here, we show that an epitope on the stem domain of H5 hemagglutinin is highly conserved and that the human monoclonal antibody CR9114, targeting that epitope, potently neutralizes all pseudotyped H5 viruses tested, even in the rare case of substitutions in its epitope. Further, intranasal administration of CR9114 fully protects mice against A(H5N1) infection at low dosages, irrespective of pre-existing immunity conferred by the quadrivalent seasonal influenza vaccine. These data provide a proof-of-concept for broad, pre-exposure protection against a potential future pandemic using the intranasal administration route. Studies in humans should assess if autonomous administration of a broadly-neutralizing monoclonal antibody is safe and effective and can thus contribute to pandemic preparedness.