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Abstract To gain a deeper understanding of skeletal muscle function in younger age and aging in elderly, identification of molecular signatures regulating these functions under physiological conditions is needed. Although molecular studies of healthy muscle have been conducted on adults and older subjects, there is a lack of research on infant muscle in terms of combined morphological, transcriptomic and proteomic profiles. To address this gap of knowledge, we performed RNA sequencing (RNA-seq), tandem mass spectrometry (LC–MS/MS), morphometric analysis and assays for mitochondrial maintenance in skeletal muscle biopsies from both, infants aged 4–28 months and adults aged 19–65 years. We identified differently expressed genes (DEGs) and differentially expressed proteins (DEPs) in adults compared to infants. The down-regulated genes in adults were associated with functional terms primarily related to sarcomeres, cellular maintenance, and metabolic, immunological and developmental processes. Thus, our study indicates age-related differences in the molecular signatures and associated functions of healthy skeletal muscle. Moreover, the findings assert that processes previously associated solely with aging are indeed part of development and healthy aging. Hence, combined findings of this study also indicate that age-dependent controls are crucial in muscle disease studies, as otherwise the comparative results may not be reliable.

Abstract Multimodal therapy for peritoneal metastasis (PM) including cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provides long-term survival in highly selected colorectal cancer patients. Mechanisms behind HIPEC are unknown and may include induction of adaptive immunity. We therefore analyzed human PM samples and explored the impact of HIPEC in experimental models. Human samples from colorectal primary tumors (n = 19) and PM lesions (n = 37) were examined for the presence of CD8 + T-cells and their association with disease free (DFS) and overall survival (OS). CD8 + T cell response after HIPEC was assessed using an in-vivo PM mouse model, tumor cell lines and patient-derived tumor organoids. Patients with high intraepithelial CD8 + T cell counts showed longer DFS and OS. In the mouse model, HIPEC controlled growth of PM and increased numbers of functional granzyme positive CD8 + T cells within tumors. Cell lines and human organoids that were treated with heated chemotherapies showed immunogenic changes, reflected by significantly higher levels of MHC-class I molecules and expression of Cancer Testis Antigens Cyclin A1 and SSX-4. Using in-vitro co-culture assays, we noticed that cancer cells treated with heated chemotherapy primed dendritic cells, which subsequently enhanced effector functions of CD8 + T cells. The presence of CD8 + T-cells within PM lesions is associated with prolonged survival of patients with PM. Data from PM mouse model and in-vitro assay show that heated chemotherapies induce immunogenic changes on cancer cells leading to induction of CD8 + T-cells mediated immunity, which seems to control growth of PM lesions in mice after HIPEC.

Abstract Musculoskeletal disorders challenge significantly the performance of many daily life activities, thus impacting the quality of life. The efficiency of the traditional physical therapy programs is limited by ecological parameters such as intervention duration and frequency, number of caregivers, geographic accessibility, as well as by subjective factors such as patient’s motivation and perseverance in training. The implementation of VR rehabilitation systems may address these limitations, but the technology still needs to be improved and clinically validated. Furthermore, current applications generally lack flexibility and personalization. A VR rehabilitation game simulation is developed, which focuses on the upper-limb movement of reaching, an essential movement involved in numerous daily life activities. Its novelty consists in the integration of a machine learning algorithm, enabling highly adaptive and patient-customized therapeutic intervention. An immersive VR system for the rehabilitation of reaching movement using a bubble popping game is proposed. In the virtual space, the patient is presented with bubbles appearing at different locations and is asked to reach the bubble with the injured limb and pop it. The implementation of a Q-learning algorithm enables the game to adjust the location of the next bubble according to the performance of the patient, represented by his kinematic characteristics. Two test cases simulate the performance of the patient during a training program of 10 days/sessions, in order to validate the effectiveness of the algorithm, demonstrated by the spatial and temporal distribution of the bubbles in each evolving scenario. The results show that the algorithm learns the patient’s capabilities and successfully adapts to them, following the reward policy dictated by the therapist; moreover, the algorithm is highly responsive to kinematic features’ variation, while demanding a reasonable number of iterations. A novel approach for upper limb rehabilitation is presented, making use of immersive VR and reinforcement learning. The simulation suggests that the algorithm offers adaptive capabilities and high flexibility, needed in the comprehensive personalization of a rehabilitation process. Future work will demonstrate the concept in clinical trials.

Abstract Poaching is again driving rhinos to the brink of extinction due to the demand for rhino horn products consumed for cultural, medicinal, and social purposes. Paradoxically, the same horn for which rhinos are killed may contain valuable clues about the species’ health. Analyses of horn composition could reveal such useful bioindicators while elucidating what people actually ingest when they consume horn derivatives. Our goals were to quantify minerals (including metals) in rhino horn and investigate sampling factors potentially impacting results. Horns (n = 22) obtained during necropsies of white (n = 3) and black (n = 13) zoo rhinos were sampled in several locations yielding 182 specimens for analysis. Initial data exposed environmental (soil) contamination in the horn’s exterior layer, but also confirmed that deep (≥ 1 cm), contaminant-free samples contained measurable concentrations of numerous minerals (n = 18). Of the factors examined in deep samples, color-associated mineral differences were the most profound with dark samples higher in zinc, copper, lead, and barium (p

Abstract Primate faces provide information about a range of variant and invariant traits, including some that are relevant for mate choice. For example, faces of males may convey information about their health or genetic quality through symmetry or facial masculinity. Because perceiving and processing such information may have bearing on the reproductive success of an individual, cognitive systems are expected to be sensitive to facial cues of mate quality. However, few studies have investigated this topic in non-human primate species. Orang-utans are an interesting species to test mate-relevant cognitive biases, because they are characterised by male bimaturism: some adult males are fully developed and bear conspicuous flanges on the side of their face, while other males look relatively similar to females. Here, we describe two non-invasive computerised experiments with Bornean orang-utans (Pongo pygmaeus), testing (i) immediate attention towards large flanges and symmetrical faces using a dot-probe task (N = 3 individuals; 2F) and (ii) choice bias for pictures of flanged males over unflanged males using a preference test (N = 6 individuals; 4F). In contrast with our expectations, we found no immediate attentional bias towards either large flanges or symmetrical faces. In addition, individuals did not show a choice bias for stimuli of flanged males. We did find exploratory evidence for a colour bias and energy efficiency trade-offs in the preference task. We discuss our null results and exploratory results in the context of the evolutionary history of Bornean orang-utans, and provide suggestions for a more biocentric approach to the study of orang-utan cognition.

Abstract There is an ongoing debate about anxiety deficits in psychopathy and their possible impact on individual behavior. Data on actual anxiety- and threat-related behavior associated with psychopathy is still limited. We performed a mixed reality study using the elevated plus-maze (EPM) in a non-clinical sample (N = 160) to test anxiety-related behavior in relation to psychopathic personality traits measured through the Brief Questionnaire of Psychopathic Personality Traits (FPP). The psychopathy sum score correlated significantly with all measures of anxiety-related behavior on the EPM. Sensation seeking, but not general levels of acrophobia was moreover associated with psychopathic traits. Multivariate analyses revealed that the subscales Fearlessness and Lack of Empathy of the FPP predicted anxious behavior. Our findings are the first to demonstrate the relationship between psychopathic traits and actual behavior in an anxiety-inducing environment. This supports the low-anxiety hypothesis in psychopathy research. Implications for potentially harmful or risky behavior are discussed.

Abstract Sociopositive interactions with conspecifics are essential for equine welfare and quality of life. This study aimed to validate the use of wearable ultra-wideband (UWB) technology to quantify the spatial relationships and dynamics of social behaviour in horses by continuous (1/s) measurement of interindividual distances. After testing the UWB devices’ spatiotemporal accuracy in a static environment, the UWB measurement validity, feasibility and utility under dynamic field conditions was assessed in a group of 8 horses. Comparison of the proximity measurements with video surveillance data established the measurement accuracy and validity (r = 0.83, p

Abstract Despite increasing efforts across various disciplines, the fate, transport, and impact of synthetic plastics on the environment and public health remain poorly understood. To better elucidate the microbial ecology of plastic waste and its potential for biotransformation, we conducted a large-scale analysis of all publicly available meta-omic studies investigating plastics (n = 27) in the environment. Notably, we observed low prevalence of known plastic degraders throughout most environments, except for substantial enrichment in riverine systems. This indicates rivers may be a highly promising environment for discovery of novel plastic bioremediation products. Ocean samples associated with degrading plastics showed clear differentiation from non-degrading polymers, showing enrichment of novel putative biodegrading taxa in the degraded samples. Regarding plastisphere pathogenicity, we observed significant enrichment of antimicrobial resistance genes on plastics but not of virulence factors. Additionally, we report a co-occurrence network analysis of 10 + million proteins associated with the plastisphere. This analysis revealed a localized sub-region enriched with known and putative plastizymes—these may be useful for deeper investigation of nature’s ability to biodegrade man-made plastics. Finally, the combined data from our meta-analysis was used to construct a publicly available database, the Plastics Meta-omic Database (PMDB)—accessible at plasticmdb.org. These data should aid in the integrated exploration of the microbial plastisphere and facilitate research efforts investigating the fate and bioremediation potential of environmental plastic waste.

Abstract The assessment of prediction variance or uncertainty contributes to the evaluation of machine learning models. In molecular machine learning, uncertainty quantification is an evolving area of research where currently no standard approaches or general guidelines are available. We have carried out a detailed analysis of deep neural network variants and simple control models for compound potency prediction to study relationships between prediction accuracy and uncertainty. For comparably accurate predictions obtained with models of different complexity, highly variable prediction uncertainties were detected using different metrics. Furthermore, a strong dependence of prediction characteristics and uncertainties on potency levels of test compounds was observed, often leading to over- or under-confident model decisions with respect to the expected variance of predictions. Moreover, neural network models responded very differently to training set modifications. Taken together, our findings indicate that there is only little, if any correlation between compound potency prediction accuracy and uncertainty, especially for deep neural network models, when predictions are assessed on the basis of currently used metrics for uncertainty quantification.

Abstract With the advent of the first laser sources and suitable detectors, optical sensor applications immediately also came into focus. During the last decades, a huge variety of optical sensor concepts were developed, yet the forecast for the future application potential appears even larger. In this context, the development of new sensor probes at different scales down to the atomic or molecular level open new avenues for research and development. We investigated an iron based triazole molecular spin-crossover complex changing its absorption characteristics significantly by varying environmental parameters such as humidity, temperature, magnetic or electric field, respectively, with respect to its suitability for a new class of versatile molecular sensor probes. Hereby, besides the investigation of synthesized pure bulk material using different analyzing methods, we also studied amorphous micro particles which were applied in or onto optical waveguide structures. We found that significant changes of the reflection spectra can also be obtained after combining the particles with different types of optical waveguides.The obtained results demonstrate the suitability of the material complex for a broad field of future sensor applications.

Abstract The accurate determination of the size and depth of infiltration is critical to the treatment and excision of melanoma and other skin cancers. However, current techniques, such as skin biopsy and histological examination, pose invasiveness, time-consumption, and have limitations in measuring at the deepest level. Non-invasive imaging techniques like dermoscopy and confocal microscopy also present limitations in accurately capturing contrast and depth information for various skin types and lesion locations. Thus, there is a pressing need for non-invasive devices capable of obtaining high-resolution 3D images of skin lesions. In this study, we introduce a novel device that combines 18 MHz ultrasound and photoacoustic tomography into a single unit, enabling the acquisition of colocalized 3D images of skin lesions. We performed in vivo measurements on 25 suspicious human skin nevi that were promptly excised following measurements. The combined ultrasound/photoacoustic tomography imaging technique exhibited a strong correlation with histological Breslow thickness between 0.2 and 3 mm, achieving a coefficient of determination (R $$^2$$ 2 ) of 0.93, which is superior to the coefficients from the individual modalities. The results procured in our study underscore the potential of combined ultrasound and photoacoustic tomography as a promising non-invasive 3D imaging approach for evaluating human nevi and other skin lesions. Furthermore, the system allows for integration of other optical modalities such as optical coherence tomography, microscopy, or Raman spectroscopy in future applications.

Abstract The pathogenesis of appendicitis is not understood fully, and the diagnosis can be challenging. Previous research has suggested an association between a T helper (Th) 1-dependent immune response and complicated appendicitis. This prospective cohort study aimed to evaluate the association between serum concentrations of the Th1-associated cytokines interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-10, IL-17A and tumor necrosis factor beta (TNF-β) and the risk of complicated appendicitis in children. Appendicitis severity was determined through histopathological examination. A total of 137 children

Abstract Asthma control and health related quality of life are an important goal of asthma management, but their association with sputum eosinophilic inflammation has been less firmly established. To investigate the relationship of asthma control and quality of life with sputum eosinophils in clinical practice. Cross-sectional study with a convenience sample, including patients with asthma, aged between 18 and 65 years, attending to outpatient clinic. Patients underwent sputum induction, pulmonary function tests, Juniper’s Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT), Global Initiative for Asthma (GINA) criteria for evaluation of asthma control and severity of the disease, blood count analysis, serum IgE and cutaneous prick test. Sputum sample was considered as eosinophilic if the percentage of eosinophils was ≥ 3%. A total of 45 individuals were enrolled, 15 with eosinophilic sputum (≥ 3% eosinophil cells) and 30 with non-eosinophilic sputum ( 0.05). This study suggested that the finding of sputum eosinophilia was not related to asthma control neither with health-related quality of life in patients with severe asthma.

Our senses provide us with a rich experience of a detailed visual world, yet the empirical results seem to suggest severe limitations on our ability to perceive and remember. In recent attempts to reconcile the contradiction between what is experienced and what can be reported, it has been argued that the visual world is condensed to a set of summary statistics, explaining both the rich experience and the sparse reports. Here, we show that explicit reports of summary statistics underestimate the richness of ensemble perception. Our observers searched for an odd-one-out target among heterogeneous distractors and their representation of distractor characteristics was tested explicitly or implicitly. Observers could explicitly distinguish distractor sets with different mean and variance, but not differently-shaped probability distributions. In contrast, the implicit assessment revealed that the visual system encodes the mean, the variance, and even the shape of feature distributions. Furthermore, explicit measures had common noise sources that distinguished them from implicit measures. This suggests that explicit judgments of stimulus ensembles underestimate the richness of visual representations. We conclude that feature distributions are encoded in rich detail and can guide behavior implicitly, even when the information available for explicit summary judgments is coarse and limited.

The salamander chytrid fungus (Batrachochytrium salamandrivorans [Bsal]) is causing massive mortality of salamanders in Europe. The potential for spread via international trade into North America and the high diversity of salamanders has catalyzed concern about Bsal in the U.S. Surveillance programs for invading pathogens must initially meet challenges that include low rates of occurrence on the landscape, low prevalence at a site, and imperfect detection of the diagnostic tests. We implemented a large-scale survey to determine if Bsal was present in North America designed to target taxa and localities where Bsal was determined highest risk to be present based on species susceptibility and geography. Our analysis included a Bayesian model to estimate the probability of occurrence of Bsal given our prior knowledge of the occurrence and prevalence of the pathogen. We failed to detect Bsal in any of 11,189 samples from 594 sites in 223 counties within 35 U.S. states and one site in Mexico. Our modeling indicates that Bsal is highly unlikely to occur within wild amphibians in the U.S. and suggests that the best proactive response is to continue mitigation efforts against the introduction and establishment of the disease and to develop plans to reduce impacts should Bsal establish.