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In the design of long-term care systems, preferences can serve as an essential indication to better tailor services to the needs, wishes and expectations of its consumers. The aim of this systematic review was to summarize and synthesize available evidence on long-term care preferences that have been elicited by quantitative stated-preference methods. The databases PubMed and Web of Science were searched for the period 2000 to 2020 with an extensive set of search terms. Two independent researchers judged the eligibility of studies. The final number of included studies was 66, conducted in 19 different countries. Studies were systematized according to their content focus as well as the survey method used. Irrespective of the heterogeneity of studies with respect to research focus, study population, sample size and study design, some consistent findings emerged. When presented with a set of long-term care options, the majority of study participants preferred to “age in place” and make use of informal or home-based care. With increasing severity of physical and cognitive impairments, preferences shifted toward the exclusive use of formal care. Next to the severity of care needs, the influence on preferences of a range of other independent variables such as income, family status and education were tested; however, none showed consistent effects across all studies. The inclusion of choice-based elicitation techniques provides an impression of how studies operationalized long-term care and measured preferences. Future research should investigate how preferences might change over time and generations as well as people’s willingness and realistic capabilities of providing care.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is effective in preventing COVID-19 hospitalization and fatal outcome. However, several studies indicated that there is reduced vaccine effectiveness among older individuals, which is correlated with their general health status1,2. How and to what extent age-related immunological defects are responsible for the suboptimal vaccine responses observed in older individuals receiving SARS-CoV-2 messenger RNA vaccine, is unclear and not fully investigated1,3–5. In this observational study, we investigated adaptive immune responses in adults of various ages (22–99 years old) receiving 2 doses of the BNT162b2 mRNA vaccine. Vaccine-induced Spike-specific antibody, and T and memory B cell responses decreased with increasing age. These responses positively correlated with the percentages of peripheral naïve CD4+ and CD8+ T cells and negatively with CD8+ T cells expressing signs of immunosenescence. Older adults displayed a preferred T cell response to the S2 region of the Spike protein, which is relatively conserved and a target for cross-reactive T cells induced by human ‘common cold’ coronaviruses. Memory T cell responses to influenza virus were not affected by age-related changes, nor the SARS-CoV-2-specific response induced by infection. Collectively, we identified signs of immunosenescence correlating with the outcome of vaccination against a new viral antigen to which older adults are immunologically naïve. This knowledge is important for the management of COVID-19 infections in older adults.

In this study, three new mycoviruses were identified co-infecting the apple replant disease (ARD)-associated root endophyte Rugonectria rugulosa. After dsRNA extraction, six viral fragments were visualized. Four fragments belong to a quadrivirus, which has a genome size of 17,166 bp. Each of the fragments of this quadrivirus has a single ORF encoding a protein. Two of these proteins are coat protein subunits, one ORF encodes the RdRp, and one protein has an unknown function. This virus was tentatively named rugonectria rugulosa quadrivirus 1 (RrQV1) as a member of the proposed new species Quadrivirus rugonectria. Another fragment represents the dsRNA intermediate form of a + ssRNA mitovirus with a genome size of 2410 nt. This virus encodes an RdRp and is tentatively called rugonectria rugulosa mitovirus 1 (RrMV1). RrMV1 is suggested as a member of a new species with the proposed name Mitovirus rugonectria. The sixth fragment belongs to the genome of an unclassified dsRNA virus tentatively called rugonectria rugulosa dsRNA virus 1 (RrV1). The monopartite dsRNA genome of RrV1 has a length of 8964 bp and contains two ORFs encoding a structure/gag protein and an RdRp. Full genomic sequences were determined and the genome structure as well as molecular properties are presented. After phylogenetic studies and sequence identity analyses, all three isolates are proposed as new mycoviruses. The results help to improve the understanding of the complexity of the factors involved in ARD and support the interest in mycoviral research. Subsequent analyses need to focus on the impact of mycoviruses on the biology and pathogenicity of ARD-associated fungi. The results of such studies could contribute to the development of mitigation strategies against the disease.

Background Chronic low-grade inflammation is associated with an increased risk of chronic disease and mortality. The objective of the study was to test the effect of a healthy lifestyle intervention on biomarkers of inflammation (among other risk markers). Methods We conducted a non-randomized controlled trial with mostly middle-aged and elderly participants from the general population in rural northwest Germany (intervention: n = 114; control: n = 87). The intervention consisted of a 1-year lifestyle programme focusing on diet (largely plant-based; strongest emphasis), physical activity, stress management, and social support. High-sensitivity C-reactive protein (hs-CRP) was assessed at baseline, 10 weeks, 6 months, and 1 year. Homocysteine (Hcy) was assessed at baseline, 10 weeks, and 1 year. Adiponectin (Apn) was assessed at baseline and 10 weeks. An exploratory analysis of these inflammatory markers assessing the between-group differences with ANCOVA was conducted. Results The 1-year trajectory of hs-CRP was significantly lower in the intervention group compared to control (between-group difference: -0.8 (95% CI -1.2, -0.3) mg/l; p = 0.001; adjusted for baseline). The 1-year trajectory of Hcy was non-significantly higher in the intervention compared to control (between-group difference: 0.2 (95% CI -0.3, 0.7) µmol/l; p = 0.439; adjusted for baseline). From baseline to 10 weeks, Apn decreased significantly more in the intervention group compared to control (between-group difference: -1.6 (95% CI -2.7, -0.5) µg/ml; p = 0.004; adjusted for baseline). Conclusions Our study shows that healthy lifestyle changes can lower hs-CRP and Apn levels and are unlikely to significantly affect Hcy levels within 1 year. Trial registration German Clinical Trials Register (DRKS; reference: DRKS00018775, registered 12 Sept 2019; retrospectively registered; www.drks.de).

Even before the Covid-19 pandemic, beneficial use cases for hygienic, touchless human-machine interaction have been explored. Gaze input, i.e., information input via eye-movements of users, represents a promising method for contact-free interaction in human-machine systems. In this paper, we present the GazeVending interface (GaVe), which lets users control actions on a display with their eyes. The interface works on a regular webcam, available on most of today's laptops, and only requires a one-point calibration before use. GaVe is designed in a hierarchical structure, presenting broad item cluster to users first and subsequently guiding them through another selection round, which allows the presentation of a large number of items. Cluster/item selection in GaVe is based on the dwell time of fixations, i.e., the time duration that users look at a given Cluster/item. A user study (N=22) was conducted to test optimal dwell time thresholds and comfortable human-to-display distances. Users' perception of the system, as well as error rates and task completion time were registered. We found that all participants were able to use the system with a short time training, and showed good performance during system usage, selecting a target item within a group of 12 items in 6.76 seconds on average. Participants were able to quickly understand and know how to interact with the interface. We provide design guidelines for GaVe and discuss the potentials of the system.

An der Leibniz Universität Hannover wurden in enger Kooperation mit dem NIFE und der Medizinischen Hochschule Hannover mobile SARS-CoV-2 Teststationen entwickelt und betrieben. Dank dieses Projekts konnten wichtige Bereiche öffentlicher Institutionen, medizinischer Einrichtungen und kritischer Infrastruktur im südlichen Niedersachsen ihren Betrieb fortführen und Forschungsfragen unter anderem zur Verbreitung des Corona-Virus untersucht werden.

During social interaction, humans prefer to keep a certain distance between themselves and other individuals. This preferred ‘interpersonal distance’ (IPD) is known to be sensitive to social context, and in the present study we aimed to further investigate the extent to which IPD is affected by the specific type of social interaction. In particular, we focused on the contrast between joint actions, where two or more individuals coordinate their actions in space and time to achieve a shared goal, and parallel actions, where individuals act alongside each other but individually. We predicted that joint action would be associated with a smaller preferred IPD compared to parallel action. Additionally, given that this research took place in the midst of the COVID-19 pandemic, we aimed to assess whether IPD preferences are affected by individuals’ concerns about infection in general, as well as COVID-19 in particular. We predicted that higher individual concerns would be associated with greater preferred IPD. To test these hypotheses, we asked participants to imagine different social scenarios (involving either joint or parallel actions alongside a stranger) and indicate, on a visual scale, their preferred IPD. The results of two experiments (n = 211, n = 212) showed that participants preferred a shorter distance when they imagined acting jointly compared to when they imagined acting in parallel. Moreover, participants who reported higher discomfort for potential pathogen contact and who were more aware of the COVID-19 context in which the study took place preferred a larger IPD in general. Our results provide further evidence that different types of social interaction shape IPD preference. We discuss potential reasons for this phenomenon and highlight remaining questions for future research.

So far, it was supposed that the increase of electrical impedance following cochlear implant (CI) insertion was due to technical defects of the electrode, inflammatory and/or formation of scar tissue along the electrode. However, it was recently reported that corrosion of the platinum electrode contacts may be the reason for high impedances. It could be shown that platinum particles were stripped from the electrode surfaces. Its potential cytotoxic effects within the inner ear remains to be examined. In this study in vitro cell culture models of the mouse organ of Corti cell line (HEI-OC1) and the spiral ganglion (SG) cells derived from the cochleae neonatal rats were used to investigate the effects of the polyvinylpyrrolidone coated platinum nanoparticles (Pt-NPPVP, 3 nm) on cell metabolism, neuronal survival and neurite outgrowth. Our data revealed no decrease of the metabolic activity of the HEI-OC1 cells at Pt-NPPVP concentrations between 50–150 μg/ml. Also, staining with Calcein AM/EthD demonstrated prevalent presence of vital cells. As shown by transmission electron microscopy no Pt-NPPVP could be found at the cell surface or in the cytosol of the HEI-OC1 cells. Similarly, the SG cells exposed to 20–100 μg/ml Pt-NPPVP did not show any reduced survival rate and neurite outgrowth following staining of the neurofilament antigen even at the highest Pt-NPPVP concentration. Although the SG cells were exposed to Pt-NPPVP for further 72 h and 96 h immunocytochemical staining of the glial cells and fibroblasts presented normal cell morphology and growth independently of the cultivation period. Our data indicates that the used Pt-NPPVP do not trigger the cellular uptake and, thus, presumable do not initiate apoptotic pathways in cells of the organ of Corti cell line or the auditory nerve. The protection mechanisms to the Pt-NPPVP interactions remain to be clarified.

Räumliches Hören soll verbessert werden. Während die Auditory Prosthetic Group (APG) der HNO-Klinik der Medizinische Hochschule Hannover (MHH) sich auf binaurale Soundcodierungsstrategien für Cochlea-Implantate sowie grundlegende Experimente am Menschen konzentriert, werden Wissenschaftler vom Institut für Informationsverarbeitung (TNT) der Leibniz Universität Hannover (LUH) an Kompressionsalgorithmen zur drahtlosen Übertragung von Audio und elektrischen Signalen für bilaterale Cochlea-Implantate arbeiten.

Die Funktion eines Cochlea-Implantats hängt stark von seiner Position in der Hörschnecke und der Umgebung der Stimulationselektroden ab. Wissenschaftler*innen des Instituts für Grundlagen der Elektrotechnik und Messtechnik (GEM) der LUH sowie der Klinik für Hals-Nasen-Ohrenheilkunde (HNO-Klinik) der MHH forschen daher an einer impedanzspektrometrischen Methode zur Überwachung der Implantatposition.

Künstliche Implantate sind für Patient*innen immer mit Risiken verbunden. Es kann etwa zu einer Abstoßung kommen, außerdem müssen oft dauerhaft Medikamente eingenommen werden. Wissenschaftler*innen der AG Blume am Institut für Technische Chemie (TCI) arbeiten daher an der Entwicklung einer patientenindividuellen Gefäßprothese als Medizinprodukt, welche langfristig als Ersatz erkrankter oder beschädigter Blutgefäße fungieren kann.

Melanoma is responsible for more than half of the deaths related to skin cancer in the last few decades. A dual-modality optical biopsy system with Raman spectroscopy and optical coherence tomography approach was built with the goal of achieving noninvasive skin measurement. To mimic melanoma and evaluate the effect of melanin on skin, models have been created by dissolving synthetic melanin in dimethyl sulfoxide and adding it to fresh skin samples. Compared to the untreated samples, morphological images showed that the imaging depth on melanin-treated skin has been increased from 250 μm to 350 μm due to the optical clearing effect of the DMSO solvent, and Raman analysis revealed that relative spectral intensities of melanin-treated samples were lower in the amide-I and CH2-deformation bands, and higher in the CH2-twist and C–C stretch bands. Using machine learning for skin type classification, an accuracy of 89% is achieved.

Im Rahmen der Exzellenzinitiative des Bundes und der Länder ist an der LUH die „SciKnow – Scientific Knowledge Collider” Clusterinitiative entstanden, die das Ziel hat, Methoden der Künstlichen Intelligenz für die Organisation und Nutzung von Daten, Informationen und Wissen in der Forschung anzuwenden. In diesem Artikel geben wir einen kurzen Überblick über die SciKnow Vision und stellen mit Wissensgraphbasierter personalisierter Medizin einen zentralen Anwendungsfall der Initiative vor.

Herzkreislauferkrankungen sind die Haupttodesursache weltweit. Wissenschaftler*innen vom Institut für Mechatronische Systeme (imes) arbeiten an mechatronisch unterstützten Therapiemöglichkeiten bei Herzinsuffizienz sowie an der Herstellung von Herzmuskeln für in-vitro Tests. Ziel ist, die Leistungsfähigkeit des Herzens nach einem Infarkt wiederherzustellen.

Background Since social distancing during the COVID-19-pandemic had a profound impact on professional life, this study investigated the effect of PCR testing on on-site work. Methods PCR screening, antibody testing, and questionnaires offered to 4,890 working adults in Lower Saxony were accompanied by data collection on demographics, family status, comorbidities, social situation, health-related behavior, and the number of work-related contacts. Relative risks (RR) with 95 % confidence intervals were estimated for the associations between regular PCR testing and other work and health-related variables, respectively, and working on-site. Analyses were stratified by the suitability of work tasks for mobile office. Results Between April 2020 and February 2021, 1,643 employees underwent PCR testing. Whether mobile working was possible strongly influenced the work behavior. Persons whose work was suitable for mobile office (mobile workers) had a lower probability of working on-site than persons whose work was not suitable for mobile office (RR = 0.09 (95 % CI: 0.07 – 0.12)). In mobile workers, regular PCR-testing was slightly associated with working on-site (RR = 1.19 (0.66; 2.14)). In those whose working place was unsuitable for mobile office, the corresponding RR was 0.94 (0.80; 1.09). Compared to persons without chronic diseases, chronically ill persons worked less often on-site if their workplace was suitable for mobile office (RR = 0.73 (0.40; 1.33)), but even more often if their workplace was not suitable for mobile office (RR = 1.17 (1.04; 1.33)). Conclusion If work was suitable for mobile office, regular PCR-testing did not have a strong effect on presence at the work site. Trial registration An ethics vote of the responsible medical association (Lower Saxony, Germany) retrospectively approved the evaluation of the collected subject data in a pseudonymized form in the context of medical studies (No. Bo/30/2020; Bo/31/2020; Bo/32/2020).

Implantante sollten individuell angepasst werden und müssen vom Körper angenommen werden. Wissenschaftler*innen vom Institut für Mehrphasenprozesse arbeiten an der Entwicklung, Herstellung und Langzeitlagerung patientenspezifischer Implantate.

Rationale: Although precision medicine is seen by many as one of the most promising advances in the field of medicine, it has also raised critical questions at various levels. Many of these concerns revolve around an observation described by Kimmelman and Tannock as the ‘paradox of precision medicine’: somewhat surprisingly, uncertainty seems to be a key characteristic of precision medicine in practice. Aims and Objective: To better understand this concept and the underlying issues, a scoping review was undertaken to search for factors stated in the literature as contributing to or being aspects of uncertainty in precision medicine. Methods: A systematic search of the literature was conducted in three databases (Pubmed, Web of Science, and Jstor) and complemented with a systematic hand-search. The initial search provided 1.252 items of which 51 articles for selected as eligible for further analysis. These articles were coded with MAXQDA and categorized into four main themes (a–d) of uncertainty. The main results were summarized and discussed with a view to the interrelations between different aspects and implications for precision medicine in practice. Results: The mapping of different aspects and sources of uncertainty leads to the key result that ‘uncertainty’ should be understood as a cluster concept. Uncertainties are identified in many different respects and situated at different levels: Most complexity-related issues (theme a) can best be understood as ontological (‘world-sided’) aspects of the uncertainty paradox. Conceptual (theme b) and evidence-related uncertainties (theme c) are situated on an epistemological or methodological level, addressing foundational and normative challenges related to knowledge production in precision medicine. Finally, theme (d) targets issues on the level of material precision medicine practices. These levels are helpful to understand the different dimensions of the uncertainty paradox. Conclusions: Uncertainty may not merely be a transient effect of the novelty of the precision medicine paradigm. Rather, it should be seen as a consequence of the ontological, epistemological and practical complexity of precision medicine, implying that uncertainty will not necessarily be reduced by more research. This finding encourages further investigations to better understand the interactions among various factors and aspects of uncertainty in precision medicine and the resulting implications for research and medical practice.

The design of implants for tissue transitions remains a major scientific challenge. This is due to gradients in characteristics that need to be restored. The rotator cuff in the shoulder, with its direct osteo-tendinous junction (enthesis), is a prime example of such a transition. Our approach towards an optimized implant for entheses is based on electrospun fiber mats of poly(ε-caprolactone) (PCL) as biodegradable scaffold material, loaded with biologically active factors. Chitosan/tripolyphosphate (CS/TPP) nanoparticles were used to load transforming growth factor-β3 (TGF-β3) with increasing loading concentrations for the regeneration of the cartilage zone within direct entheses. Release experiments were performed, and the concentration of TGF-β3 in the release medium was determined by ELISA. Chondrogenic differentiation of human mesenchymal stromal cells (MSCs) was analyzed in the presence of released TGF-β3. The amount of released TGF-β3 increased with the use of higher loading concentrations. This correlated with larger cell pellets and an increase in chondrogenic marker genes (SOX9, COL2A1, COMP). These data were further supported by an increase in the glycosaminoglycan (GAG)-to-DNA ratio of the cell pellets. The results demonstrate an increase in the total release of TGF-β3 by loading higher concentrations to the implant, which led to the desired biological effect.

Für eine eindeutige Diagnostik nach einer Nierentransplantation sind bisher schmerzhafte Biopsien notwendig. Wissenschaftlerinnen vom Institut für Technische Chemie arbeiten in Kooperation mit Sartorius und der Fassisi GmbH an Schnelltests, die ohne Eingriff in den Körper spezifische und immunologisch bedeutsame Biomarker identifizieren können.

[no abstract available]

The high incidence of aflatoxins (AFs) in chocolates suggests the necessity to create a practical and cost-effective processing strategy for eliminating mycotoxins. The present study aimed to assess the adsorption abilities of activated charcoal (A. charcoal), yeast (Saccharomyces cerevisiae), and the probiotic Lactobacillus rhamnosus as AFs adsorbents in three forms—sole, di- and tri-mix—in phosphate-buffered saline (PBS) through an in vitro approach, simulated to mimic the conditions present in the gastrointestinal tract (GIT) based on pH, time and AFs concentration. In addition, the novel fortification of chocolate with A. charcoal, probiotic, and yeast (tri-mix adsorbents) was evaluated for its effects on the sensory properties. Using HPLC, 60 samples of dark, milk, bitter, couverture, powder, and wafer chocolates were examined for the presence of AFs. Results showed that all the examined samples contained AFs, with maximum concentrations of 2.32, 1.81, and 1.66 µg/kg for powder, milk, and dark chocolates, respectively. The combined treatment demonstrated the highest adsorption efficiency (96.8%) among all tested compounds. Scanning electron microscope (SEM) analysis revealed the tested adsorbents to be effective AF-binding agents. Moreover, the novel combination of tri-mix fortified chocolate had a minor cytotoxicity impact on the adsorptive abilities, with the highest binding at pH 6.8 for 4 h, in addition to inducing an insignificant effect on the sensory attributes of dark chocolate. Tri-mix is thus recommended in the manufacturing of dark chocolate in order to enhance the safety of the newly developed product.

Background Age-related accumulation of highly differentiated CD8+ effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance. In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8+ T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50—70) were randomized to a control (CON) or exercise (EX) group. The EX group completed combined strength and endurance training twice weekly for one hour each time at an intensity of 60% of the one-repetition maximum for strength exercises and a perceived exertion of 15/20 for endurance exercises. The EX group was also randomly subdivided into two groups with or without a concomitant balanced diet intervention in order to examine additional effects besides exercise alone. Before and after the intervention phase, the proportions of CD8+ T-cell subsets and levels of KYN pathway metabolites in peripheral blood were determined. Results The CD8+ EMRA T-cell subsets increased in the CON group but remained almost unchanged in the EX group (p = .02). Plasma levels of kynurenic acid (KA) increased in the EX group and decreased in the CON group (p = .03). Concomitant nutritional intervention resulted in lower levels of quinolinic acid (QA) compared with exercise alone (p = .03). Overall, there was a slight increase in the QA/KA ratio in the CON group, whereas it decreased in the EX group (p > .05). Conclusions Combined strength and endurance training seems to be a suitable approach to attenuate CD8+ T-cell differentiation in the elderly and to redirect the KYN pathway towards KA. The clinical relevance of these effects needs further investigation.

Balance, Sprungkraft und Körpergefühl sind im Sport, aber auch bei der Rehabilitation wichtige Indikatoren. Wissenschaftler*innen am Institut für Mikroelektronische Systeme entwickeln in Kooperation mit externen Partnern aus den Sportwissenschaften und der Industrie ein mobiles Diagnosesystem zur Beurteilung der sensomotorischen Regulationsfähigkeit mithilfe standardisierter Sporttests.

Humans are capable to skillfully perform a huge variety of complex movements seemingly effortless and to flexibly adjust movement execution to ever-changing environmental conditions, often without apparent differences in the movement outcome. This impressive ability has sparked scientific interest in the mechanisms underlying movement execution for decades. In this perspective article, we argue that investigating the processes and mechanisms leading to failure of motor functions is a fruitful approach to advance the field of human motor neuroscience and beyond. The study of failure of motor function in specific populations (patient groups, skilled experts) has already provided tremendous insight in the systemic characteristics and multi-level functional dependencies of movement execution. However, particularly the transient failure of function in everyday motor actions remains a blind spot. Coming from the perspective of Developmental Embodiment Research, we argue that the integration of a developmental embodiment and lifespan perspective with existing systemic and multi-level methodological approaches of failure of function analyses provides an integrative, interdisciplinary framework, which will allow us to overcome this shortcoming. We further suggest that stress-induced failure of motor function situations might represent a promising starting point for this endeavor. Identifying the involved cross-level functional dependencies of acute and chronic stress on transient and persistent motor functioning would further advance our knowledge on the mechanisms underlying movement execution, and would allow to identify targets for intervention and prevention across the whole spectrum of motor function and failure.

Eine Stichkanalbohrung durch den Mastoid gewährt einen minimalinvasiven Zugang zur Cochlea, verläuft jedoch nahe wichtiger Nervenbahnen im menschlichen Schädel. Gegenüber dem konventionellen Auffräsen von Hand geht dem Chirurgen dabei die unmittelbare Sicht auf Risikostrukturen im Operationsgebiet verloren - der Verlauf der Bohrtrajektorie ist für ihn nicht zu erkennen. Die wichtigen Geschmacks- und Gesichtsnerven werden daher einem erhöhten Verletzungsrisiko ausgesetzt und das Vertrauen von Chirurgen und Patienten in den Eingriff kann beeinträchtigt werden. Eine intraoperative Kontrolle der Bohrtrajektorie ist deshalb wichtig, um einen sicheren Eingriff zu ermöglichen und Vertrauen zu bewahren. Bekannte Methoden zur intraoperativen Lageprüfung, die auf teuren, gesundheitsschädlichen oder im Operationssaal standardmäßig nicht vorhandenen technischen Einrichtungen basieren, werden in dieser Arbeit durch einen endoskopischen Ansatz ersetzt. Die schwammartige Mastoidknochenstruktur, die ein dreidimensionales Muster bietet, wird als Feld aus Merkmalen für eine Registrierung verwendet. Dafür werden in der minimalinvasiven Bohrung intraoperativ 2D-Endoskopaufnahmen erstellt, die mit präoperativen 3D-CT-Daten verglichen werden. Konkret handelt es sich um eine 2D-3D Bild-zu-Patient-Registrierung durch 2D-2D Bild-zu-Bild-Vergleiche. Einzelne Endoskopaufnahmen werden dazu zu einem Panoramabild zusammengefügt. Vergleichbare 2D-Bilder werden aus den 3D-CT-Daten in vielen verschiedenen Bohrkanallagen extrahiert. Je nach Lage unterscheidet sich die Struktur in den CT-Bildern, sodass über den Vergleich des Musters im Endoskopbild (realer Bohrkanal) zu den CT-Bildern (simulierter Bohrkanal) die größte Übereinstimmung und damit die Lage des Bohrkanals bestimmt werden kann. Für eine Vielfalt an sichtbaren Merkmalen ist ein Großteil der Bohrkanaloberfläche aufzuzeichnen. Verschiedene Endoskoptypen führen, in Kombination mit Stitching-Techniken, zu Panoramaaufnahmen der Mastoidstruktur an der Bohrkanaloberfläche. Kommerzielle Optiken werden auf ihre Eignung hin untersucht und eine miniaturisierte Rundblickoptik entwickelt. Die Stitching-Methoden werden speziell an die endoskopischen Bilddaten der verschiedenen Optiken angepasst. Das Vorgehen zur Registrierung wird sowohl simulativ als auch in aufeinander aufbauenden Mastoidphantomen untersucht. Erreichbare Genauigkeiten werden ausgewertet, während die beteiligten Parameter Suchraumdichte, Bohrkanaldurchmesser, Größe des endoskopierten Bereichs und die Auflösung der CT-Daten variiert werden, um deren Einflüsse zu ermitteln. Endoskopische Aufnahmen in Humanpräparaten zeigen den Transfer in die Praxis und die Integration in den Verlauf einer minimalinvasiven Cochleaimplantation. Eine Registrierung ermöglicht sowohl die Kontrolle der Bohrkanallage als auch eine intraoperative Korrektur und kann so eine vom gewünschten Pfad abweichende Bohrung berichtigen., A branch canal drilling through the mastoid provides a minimally invasive access to the cochlea, but passes nearby important nerve tracts in the human skull. Compared to conventional milling by hand, the surgeon loses the immediate view of high-risk structures in the operating area - the course of the drilling trajectory is not visible to him. The important taste and facial nerves are therefore exposed to an increased risk of injury and the confidence of surgeons and patients in the surgical intervention may be impaired. Intraoperative control of the drilling trajectory is therefore important to enable a safe intervention and to maintain confidence. Known methods for intraoperative pose verification, which are based on expensive, harmful or by default non-existent technical equipment in the operating room, are replaced by an endoscopic approach in this thesis. The sponge-like mastoid bone structure, providing a three-dimensional pattern, is used as a field of features for registration. For this purpose, 2D endoscopic images are recorded intraoperatively in the minimally invasive drill hole and compared to preoperative 3D CT data. In concrete terms, this is an 2D-3D image-to-patient registration using 2D-2D image-to-image comparisons. Individual endoscopic images are combined to form a panoramic image. Comparable 2D images are extracted from the 3D CT data in many different drill hole poses. Depending on the pose, the pattern in the CT images differs, so that by comparing the pattern in the endoscope image (real drill hole) to the CT images (simulated drill hole), the best match and thus the position of the drill hole can be determined. For a variety of visible features, a large portion of the drill hole surface must be recorded. Different types of endoscopes in combination with stitching techniques lead to panoramic images of the mastoid structure at the drill hole surface. Commercial optics are investigated for their suitability and a miniaturized panoramic optics is developed. The stitching methods are specially tailored to the endoscopic image data of the different optics. The procedure for the registration is evaluated in simulations as well as in mastoid phantoms that build on one another. Achievable accuracies are evaluated while the parameters involved -- search space density, drill hole diameter, size of the area recorded via endoscope and the resolution of the CT data -- are varied to determine their influences. Endoscopic recordings in human specimens show the transfer into practice and the integration into the procedure of a minimally invasive cochlear implantation. A registration allows for both, the verification of the drill hole pose as well as an intraoperative correction, and can thus correct a drill hole that deviates from the desired path

Bei der Behandlung verengter oder verstopfter Gefäße müssen diese häufig ersetzt werden. Bisher eingesetzte Implantate beinhalten eine Reihe von Risiken für die Patient*innen. Daher forschen Wissenschaftler am Institut für Mikroelektronische Systeme (IMS) an Systemen zur Kultivierung bioartifizieller Gefäßprothesen, die aus Gefäßzellen in vitro gezüchtet werden sollen.

Widespread vaccination in pursuit of herd immunity has been recognized as the most promising approach to ending the global pandemic of coronavirus disease 19 (COVID-19). The vaccination of children and adolescents has been extensively debated and the first COVID-19 vaccine is now approved in European countries for children aged > 12 years of age. Our study investigates vaccination hesitancy in a cohort of German secondary school students. We assessed 903 students between age 9 and 20 in the period between 17 May 2021 and 30 June 2021. 68.3% (n = 617) reported intention to undergo COVID-19 vaccination, while 7% (n = 62) did not want to receive the vaccine and 15% (n = 135) were not yet certain. Age and parental level of education influenced COVID-19 vaccine hesitancy. Children under the age of 16 as well as students whose parents had lower education levels showed significantly higher vaccine hesitancy. Conclusion: Identifying subsets with higher vaccination hesitancy is important for targeting public information campaigns in support of immunization. What is Known:• The willingness to receive COVID-19 vaccination among adults in Europe is about 70%, but data for children and adolescents is lacking.• The lack of immunization in younger cohorts represents a significant barrier to achieving herd immunity, and also leaves children and adolescents vulnerable to acute and long-term morbidity from natural COVID-19 infections. What is New:• Intention-to-vaccinate among children and adolescents is high (~ 70%); conversely, vaccination hesitancy is low.• Age and parental level of education influenced COVID-19 vaccine hesitancy among children and adolescents.

Background More than 10 million Syrians have left their homes and sought refuge in neighboring countries, including Europe, since the beginning of the Syrian conflict in March 2011, and immigration continues to this day. This cross-sectional study included Syrian refugees residing in and around Hannover, Germany. We investigated whether general socioeconomic factors (e.g. age, sex, housing, asylum duration) were predictive factors for the quality of life (QOL) of Syrian refugees in Germany. Methods The QOL of Syrian refugees was assessed using the WHOQOL-BREF tool, a questionnaire assessing the QOL in four domains: Physical health, psychological, social relationships and environment. A total of 114 Syrian refugees, aged between 18 and 45 years, who obtained one of the following statuses, asylum, refugee protection or subsidiary protection, were included. The QOL domain and total scores of Syrian refugees in Germany were compared with a Western norm and Sub-Saharan population. Data were analyzed with the Spearman Rho correlation coefficient, Kruskal–Wallis and Mann–Whitney U test and multivariate linear regression. Results More than 65% of the participants (62.3% male, 37.7% female) were between 18 and 29 years old, and 45% had lived in Germany for less than four years. The lowest QOL score was reported in the social relationship’s domain (60.5%), while the psychological score was lowest in participants aged 40–45 years (P = 0.011). The age was significantly negatively associated with physical health (P = 0.010), psychological (P P = 0.005). Asylum duration was associated with the environment domain (P = 0.040), the short-time refugees were less satisfied than the longtime refugees, and with aspects of the psychological domain in Enjoying life and Concentration ability (P P = 0.033, respectively), yet was not associated with total QOL or total domain scores. There were significant associations between housing and the psychological domain (P = 0.032) and housing and the social relationship domain (P P = 0.032 and P = 0.035, respectively). Conclusions The Syrian refugees participating in this study showed a low QOL score in the assessment of all domains compared to the normal population, especially regarding social relations and psychological; it was associated with socioeconomic factors, such as housing, asylum duration and marital status. This calls for urgent societal and political efforts to strengthen the social living conditions of Syrian refugees in Germany.

Background: World-wide the prevalence of obesity is high, and promoting a shift toward more healthful and more plant-based dietary patterns appears to be one promising strategy to address this issue. A dietary score to assess adherence to a healthy plant-based diet is the healthful plant-based diet index. While there is evidence from cohort studies that an increased healthful plant-based diet index is associated with improved risk markers, evidence from intervention studies is still lacking. Methods: A lifestyle intervention was conducted with mostly middle-aged and elderly participants from the general population (n = 115). The intervention consisted of a 16-month lifestyle program focusing on a healthy plant-based diet, physical activity, stress management, and community support. Results: After 10 weeks, significant improvements were seen in dietary quality, body weight, body mass index, waist circumference, total cholesterol, measured and calculated low-density lipoprotein (LDL) cholesterol, oxidized LDL particles, non-high-density lipoprotein cholesterol, remnant cholesterol, glucose, insulin, blood pressure, and pulse pressure. After 16 months, significant decreases were seen in body weight (−1.8 kg), body mass index (−0.6 kg/m2), and measured LDL cholesterol (−12 mg/dl). Increases in the healthful plant-based diet index were associated with risk marker improvements. Conclusions: The recommendation of moving toward a plant-based diet appears acceptable and actionable and may improve body weight. The healthful plant-based diet index can be a useful parameter for intervention studies.

In this review, we focus on the holistic continuous enzymatic production and put special emphasis on process intensification by up- and downstream processing in continuous flow biocatalysis. After a brief introduction, we provide an overview of current examples of enzyme immobilization as an upstream process for flow biocatalysis. Thereafter, we provide an overview of unit operations as downstream processing strategies, namely continuous (i) liquid–liquid extraction, (ii) adsorptive downstream processing, and (iii) crystallization and precipitation. Eventually, we present our perspectives on future trends in this research field.

Objective: Residual hearing preservation during cochlear implant (CI) surgery is closely linked to the magnitude of intracochlear forces acting during the insertion process. So far, these forces have only been measured in vitro. Therefore, the range of insertion forces and the magnitude of damage-inducing thresholds in the human cochlea in vivo remain unknown. We aimed to develop a method to intraoperatively measure insertion forces without negatively affecting the established surgical workflow. Initial experiments showed that this requires the compensation of orientation-dependent gravitational forces. Methods: We devised design requirements for a force-sensing manual insertion tool. Experienced CI surgeons evaluated the proposed design for surgical safety and handling quality. Measured forces from automated and manual insertions into an artificial cochlea model were evaluated against data from a static external force sensor representing the gold standard. Results: The finalized manual insertion tool uses an embedded force sensor and inertial measurement unit to measure insertion forces. The evaluation of the proposed design shows the feasibility of orientation-independent insertion force measurements. Recorded forces correspond well to externally recorded reference forces after reliable removal of gravitational disturbances. CI surgeons successfully used the tool to insert electrode arrays into human cadaver cochleae. Conclusion: The presented positive evaluation poses the first step towards intraoperative use of the proposed tool. Further in vitro experiments with human specimens will ensure reliable in vivo measurements. Significance: Intraoperative insertion force measurements enabled by this tool will provide insights on the relationship between forces and hearing outcomes in cochlear implant surgery.

Purpose Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery. Methods Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time. Results 27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI − 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference − 114.34 [− 122.97; − 105.71]) and RH (mean difference − 287.14 [− 392.99; − 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference − 3.06 [− 3.28; − 2.83]) and RH (mean difference − 3.77 [− 5.10; − 2.44]) compared to AH. Conclusion Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials.

In recent years, stem cell-derived organoids have become a cell culture standard that is widely used for studying various scientific issues that were previously investigated through animal experiments and using common tumor cell lines. After their initial hype, concerns regarding their standardization have been raised. Here, we aim to provide some insights into our experience in standardizing murine colonic epithelial organoids, which we use as a replacement method for research on inflammatory bowel disease. Considering good scientific practice, we examined various factors that might challenge the design and outcome of experiments using these organoids. First, to analyze the impact of antibiotics/antimycotics, we performed kinetic experiments using ZellShield® and measured the gene expression levels of the tight junction markers Ocln, Zo-1, and Cldn4, the proliferation marker Ki67, and the proinflammatory cytokine Tnfα. Because we found no differences between cultivations with and without ZellShield®, we then performed infection experiments using the probiotic Escherichia coli Nissle 1917 as an already established model setup to analyze the impact of technical, interexperimental, and biologic replicates. We demonstrate that interexperimental differences pose the greatest challenge for reproducibility and explain our strategies for addressing these differences. Additionally, we conducted infection experiments using freshly isolated and cryopreserved/thawed organoids and found that cryopreservation influenced the experimental outcome during early passages. Formerly cryopreserved colonoids exhibited a premature appearance and a higher proinflammatory response to bacterial stimulation. Therefore, we recommend analyzing the growth characteristics and reliability of cryopreserved organoids before to their use in experiments together with conducting several independent experiments under standardized conditions. Taken together, our findings demonstrate that organoid culture, if standardized, constitutes a good tool for reducing the need for animal experiments and might further improve our understanding of, for example, the role of epithelial cells in inflammatory bowel disease development.

Inflammation mediators enhance the activity of connexin (Cx) hemichannels especially in the epithelial and endothelial tissues. As potential release route for injury signals like (oligo)nucleotides, Cx hemichannels may contribute to long lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells using the dye uptake as functional assay. Moreover, possible impact of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (> 5 µM) and Cx46 (> 20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversible inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to stimulation of adenosine signaling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversible block Cx hemichannels. Deciphering the interaction mechanisms with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for a better and safer use in treatment of pathologies that involve Cx hemichannels.

In classical representation-oriented approaches of social cognition, agents are thought to interact with conspecifics based on their capacity to develop a “theory-of-mind”, i.e., to generate complex models of the intentions, beliefs, and personalities of their interaction partners. In this framework, the primary mode of interaction with the social environment is that of a detached observer who theorizes and produces inferences about other participants. In contrast, this Research Topic seeks to turn the spotlight on the grounding of social cognition in dynamic sensorimotor and informational coupling of agents, in human-human as well as human-robot interaction settings. According to this view, interaction dynamics hold substantial clues to the mechanism of social understanding and its disturbances (as for example observed in autism spectrum disorders). The argument is that high-level social deficits may be rooted in the impaired capacity for entraining and sustaining sensorimotor and informational coupling. Beyond novel insights into the mechanisms of functional and dysfunctional social behavior, the investigation of basic sensorimotor interaction patterns may help the development of socially competent robot technology. Tapping into the same logic, robotic agents sensitive to interpersonal sensorimotor contingencies should have an advantage over technology that does not consider this key aspect of human interaction. This Research Topic provides an interdisciplinary overview of trends and recent developments in conceptual, methodological and basic research, as well as applications of sensorimotor approaches in social cognitive science, neuroscience, and robotic research. One of the key questions is how concepts and methods from social cognitive and neuroscience transfer to human-robot interaction. The authors acknowledge support by the EU through project socSMCs (H2020-641321).

Background In times of exponential data growth in the life sciences, machine-supported approaches are becoming increasingly important and with them the need for FAIR (Findable, Accessible, Interoperable, Reusable) and eScience-compliant data and metadata standards. Ontologies, with their queryable knowledge resources, play an essential role in providing these standards. Unfortunately, biomedical ontologies only provide ontological definitions that answer What is it? questions, but no method-dependent empirical recognition criteria that answer How does it look? questions. Consequently, biomedical ontologies contain knowledge of the underlying ontological nature of structural kinds, but often lack sufficient diagnostic knowledge to unambiguously determine the reference of a term. Results We argue that this is because ontology terms are usually textually defined and conceived as essentialistic classes, while recognition criteria often require perception-based definitions because perception-based contents more efficiently document and communicate spatial and temporal information—a picture is worth a thousand words. Therefore, diagnostic knowledge often must be conceived as cluster classes or fuzzy sets. Using several examples from anatomy, we point out the importance of diagnostic knowledge in anatomical research and discuss the role of cluster classes and fuzzy sets as concepts of grouping needed in anatomy ontologies in addition to essentialistic classes. In this context, we evaluate the role of the biological type concept and discuss its function as a general container concept for groupings not covered by the essentialistic class concept. Conclusions We conclude that many recognition criteria can be conceptualized as text-based cluster classes that use terms that are in turn based on perception-based fuzzy set concepts. Finally, we point out that only if biomedical ontologies model also relevant diagnostic knowledge in addition to ontological knowledge, they will fully realize their potential and contribute even more substantially to the establishment of FAIR and eScience-compliant data and metadata standards in the life sciences.

Dermoscopy is the main tool for early detection of skin cancer. Non-contact dermoscopes often suffer from a small depth of field leading to images of skin topographies with regions that are not in focus. We aim to provide an easy-to-implement focus stacking-based approach to ensure all-in-focus images from a non-contact dermoscope. Further, we aim to extract additional information about the skin topography from the image stacks. The focus stacking procedure itself is implemented in a non-contact dermoscope with an electrically adjustable focus realized by using a tunable liquid lens. We show that all-in-focus imaging is possible for non-contact dermoscopy and deliver a method to extract topographical information for dermatologists from the acquired image stacks. Our finding indicate that the approach can be valuable for non-contact dermoscopic examination as well as for the early detection of skin diseases such as cancer as it possible to derive hyperfocus images and information on the skin topography. With this, we were able to develop a software for the acquisition of the raw image data and its processing into a high resolution hyperresolution dermoscopic image. In the next steps, we plan to apply the approach in the clinical environment for skin cancer diagnostics or imaging of inflammatory skin diseases.

Water soaking is a common disorder of field-grown strawberries (Fragaria × ananassa Duch.). It develops when ripe fruit is exposed to rain. Here we investigate the effects of Ca on water soaking. Fruit was incubated in solutions of various Ca salts and the extent of water soaking quantified using a simple rating scheme. Exposure to CaCl2 (10 mM) decreased water soaking and anthocyanin leakage but had no effect on water uptake. The decrease in water soaking due to CaCl2 was not limited to a single cultivar but occurred in all cultivars examined. Incubating fruit in a chelating agent (EGTA) increased water soaking compared to the water control. Calcium salts of different acids varied in their effects on water soaking. Only CaCl2 reduced water soaking significantly. The chlorides of different cations, also varied in their effects on water soaking. Those of the monovalent cations had no effects on water soaking, while those of the divalent cations (CaCl2, BaCl2 and SrCl2) and of the trivalent cations (FeCl3 and AlCl3) were all effective in decreasing water soaking. Overall, CaCl2 decreased microcracking of the strawberry cuticle as compared to deionized water. Furthermore, CaCl2 also reduced the leakage of anthocyanins from flesh discs, irrespective of the osmotic potential of the incubation solution. Our results indicate that CaCl2 reduced water soaking by decreasing cuticular microcracking, by decreasing leakage of plasma membranes and, possibly, by increasing the crosslinking of cell wall constituents.

All optical approaches to control and read out the electrical activity in a cardiac syncytium can improve our understanding of cardiac electrophysiology. Here, we demonstrate optogenetic stimulation of cardiomyocytes with high spatial precision using light foci generated with a ferroelectric spatial light modulator. Computer generated holograms binarized by bidirectional error diffusion create multiple foci with more even intensity distribution compared with thresholding approach. We evoke the electrical activity of cardiac HL1 cells expressing the channelrhodopsin-2 variant, ChR2(H134R) using single and multiple light foci and at the same time visualize the action potential using a calcium sensitive indicator called Cal-630. We show that localized regions in the cardiac monolayer can be stimulated enabling us to initiate signal propagation from a precise location. Furthermore, we demonstrate that probing the cardiac cells with multiple light foci enhances the excitability of the cardiac network. This approach opens new applications in manipulating and visualizing the electrical activity in a cardiac syncytium.

Working with the dead is a very specific kind of work. Although a dignified handling of the corpses is demanded by the legislator and by the general public, neither the legal status of the corpse is undisputed nor is it obvious what a dignified handling of the deceased should consist of. In our hypothesis generating pilot study, we asked which concrete considerations are involved in daily practice of forensic specialists. We used an online questionnaire (invitations via e-mail) consisting of questions with single choice, multiple choice, and free text entries. The answers to single or multiple choice questions were displayed in pivot tables. The data was thus summarized, viewed, descriptively analyzed, and displayed together with the free text answers. 84.54% of the physicians and 100% of the autopsy assistants stated that considerations concerning the dignity of the deceased should play a role in daily autopsy practice. 45.87% stated that the conditions surrounding the autopsy need improvement to be ethically suitable. The analysis of the survey’s results was based on Robert Audi’s ethics, according to which three aspects need to be lightened in order to evaluate the conduct of a person morally: the actions, the motivation, and the way in which the actions are carried out. This systematization helps to identify the need for improvement and to make the vague demands for a dignified handling of corpses more concrete.

To harness the full potential of human pluripotent stem cells (hPSCs) we combined instrumented stirred tank bioreactor (STBR) technology with the power of in silico process modeling to overcome substantial, hPSC‐specific hurdles toward their mass production. Perfused suspension culture (3D) of matrix‐free hPSC aggregates in STBRs was applied to identify and control process‐limiting parameters including pH, dissolved oxygen, glucose and lactate levels, and the obviation of osmolality peaks provoked by high density culture. Media supplements promoted single cell‐based process inoculation and hydrodynamic aggregate size control. Wet lab‐derived process characteristics enabled predictive in silico modeling as a new rational for hPSC cultivation. Consequently, hPSC line‐independent maintenance of exponential cell proliferation was achieved. The strategy yielded 70‐fold cell expansion in 7 days achieving an unmatched density of 35 × 106 cells/mL equivalent to 5.25 billion hPSC in 150 mL scale while pluripotency, differentiation potential, and karyotype stability was maintained. In parallel, media requirements were reduced by 75% demonstrating the outstanding increase in efficiency. Minimal input to our in silico model accurately predicts all main process parameters; combined with calculation‐controlled hPSC aggregation kinetics, linear process upscaling is also enabled and demonstrated for up to 500 mL scale in an independent bioreactor system. Thus, by merging applied stem cell research with recent knowhow from industrial cell fermentation, a new level of hPSC bioprocessing is revealed fueling their automated production for industrial and therapeutic applications., Wet lab‐derived process characteristics enabled predictive in silico modeling as a rational for suspension‐based human pluripotent stem cells (hPSC) cultivation in stirred bioreactors. Consequently, this hPSC line‐independent strategy yielded 70‐fold cell expansion in 7 days achieving a density of 35 × 106 cells/mL equivalent to 5.25 billion hPSC in 150 mL scale while maintaining a pluripotent phenotype and simultaneously reducing media requirements by 75%.

Summary Members of the genus Pseudomonas inhabit diverse environments, such as soil, water, plants and humans. The variability of habitats is reflected in the diversity of the structure and composition of their genomes. This cosmopolitan bacterial genus includes species of biotechnological, medical and environmental importance. In this study, we report on the most relevant genomic characteristics of Pseudomonas sp. strain ABC1, a siderophore‐producing fluorescent strain recently isolated from soil. Phylogenomic analyses revealed that this strain corresponds to a novel species forming a sister clade of the recently proposed Pseudomonas kirkiae. The genomic information reveals an overrepresented repertoire of mechanisms to hoard iron when compared to related strains, including a high representation of fecI‐fecR family genes related to iron regulation and acquisition. The genome of the Pseudomonas sp. ABC1 contains the genes for non‐ribosomal peptide synthetases (NRPSs) of a novel putative Azotobacter‐related pyoverdine‐type siderophore, a yersiniabactin‐type siderophore and an antimicrobial betalactone; the last two are found only in a limited number of Pseudomonas genomes. Strain ABC1 can produce siderophores in a low‐cost medium, and the supernatants from cultures of this strain promote plant growth, highlighting their biotechnological potential as a sustainable industrial microorganism., ‘Pseudomonas chilensis’ strain ABC1 was fully sequenced. About 5% of the ABC1 genome is devoted to iron acquisition, including 37 ECF sigma factors. Strain ABC1 produces pyoverdine and has the genes for the production of yersiniabactin.

Recent research in economics emphasizes the role of in utero conditions for the health endowment at birth and in early childhood and for social as well as economic outcomes in later life. This paper analyzes the relation between maternal mental health during pregnancy and birth outcomes of the child. In particular, we analyze the relationship between maternal mental health during pregnancy and the probability of giving birth preterm (PT), having a newborn at low birth weight (LBW) or being small for gestational age (SGA). Based on large population-representative data from the German Socio-Economic Panel (SOEP) and cohort data from the National Educational Panel Study (NEPS), we present extensive descriptive evidence on the relationship between maternal mental health and preterm birth by carrying out OLS estimates controlling for a wide range of socioeconomic characteristics. In addition, we apply matching estimators and mother fixed effects models, which bring us closer toward a causal interpretation of estimates. In summary, the results uniformly provide evidence that poor maternal mental health is a risk factor for preterm birth and low birth weight in offspring. In contrast, we find no evidence for an relationship between maternal mental health and small for gestational age at birth.

Despite great efforts, transoral robotic laser surgery has not been established clinically. Patient benefits are yet to be proven to accept shortcomings of robotic systems. In particular, laryngeal reachability and transition from microscope to accurate endoscopic laser ablation have not been achieved. We have addressed those challenges with a highly integrated robotic endoscope for non-contact endolaryngeal laser surgery. The current performance status has been assessed in multi-level user studies. In addition, the system was deployed to an ex vivo porcine larynx. The robotic design comprises an extensible continuum manipulator with multifunctional tip. The latter features laser optics, stereo vision, and illumination. Vision-based performance assessment is derived from depth estimation and scene tracking. Novices and experts (n = 20) conducted teleoperated delineation tasks to mimic laser ablation of delicate anatomy. Delineation with motion-compensated and raw endoscopic visualisation was carried out on planar and non-planar nominal patterns. Root mean square tracing errors of less than 0.75 mm were feasible with task completion times below 45 s. Relevant anatomy in the porcine larynx was exposed successfully. Accuracy and usability of the integrated platform bear potential for dexterous laser manipulation in clinical settings. Cadaver and in vivo animal studies may translate ex vivo findings. Electronic supplementary material The online version of this article (10.1007/s10439-020-02577-y) contains supplementary material, which is available to authorized users.

Background 4D flow magnetic resonance imaging (MRI) of CSF can make an important contribution to the understanding of hydrodynamic changes in various neurological diseases but remains limited in clinical application due to long acquisition times. The aim of this study was to evaluate the accuracy of compressed SENSE accelerated MRI measurements of the spinal CSF flow. Methods In 20 healthy subjects 4D flow MRI of the CSF in the cervical spine was acquired using compressed sensitivity encoding [CSE, a combination of compressed sensing and parallel imaging (SENSE) provided by the manufacturer] with acceleration factors between 4 and 10. A conventional scan using SENSE was used as reference. Extracted parameters were peak velocity, absolute net flow, forward flow and backward flow. Bland–Altman analysis was performed to determine the scan-rescan reproducibility and the agreement between SENSE and compressed SENSE. Additionally, a time accumulated flow error was calculated. In one additional subject flow of the spinal canal at the level of the entire spinal cord was assessed. Results Averaged acquisition times were 10:21 min (SENSE), 9:31 min (CSE4), 6:25 min (CSE6), 4:53 min (CSE8) and 3:51 min (CSE10). Acquisition of the CSF flow surrounding the entire spinal cord took 14:40 min. Bland–Altman analysis showed good agreement for peak velocity, but slight overestimations for absolute net flow, forward flow and backward flow ( Conclusion A quantitative analysis of acceleration factors CSE4–10 showed that CSE with an acceleration factor up to 6 is feasible. This allows a scan time reduction of 40% and enables the acquisition and analysis of the CSF flow dynamics surrounding the entire spinal cord within a clinically acceptable scan time.

Purpose Treatments for patients with metastatic castration-resistant prostate cancer (mCRPC) have expanded rapidly. They include the chemotherapies docetaxel and cabazitaxel, hormonal drugs abiraterone and enzalutamide, and best supportive care (BSC). Cabazitaxel has proven to be the last life-prolonging option, associated with a significant risk of serious adverse events. Given the lack of real-world evidence, we aimed to compare healthcare resource utilization (HRU) and costs in patients with mCRPC treated with cabazitaxel, docetaxel, abiraterone, enzalutamide, and BSC. Methods We used 2014–2017 claims data from a large German statutory health insurance fund, the Techniker Krankenkasse, to identify patients with mCRPC. Patient allocation to individual therapy regimens was based on clinical knowledge and included therapy cycles, duration of therapy, and continuous treatment. The study period lasted from the first claim until death, the end of data availability, a drug switch, or discontinuation of therapy, whichever came first. Multivariate regression models were used to compare monthly all-cause and mCRPC-related HRU and costs across cohorts by adjusting for baseline covariates (including age and comorbidities). Results The 3944 identified patients with mCRPC initiated treatment with cabazitaxel (n = 240), docetaxel (n = 539), abiraterone (n = 486), enzalutamide (n = 351), or BSC (n = 2328). In most domains, HRU was highest in the cabazitaxel cohort and lowest in the BSC group. Accordingly, the highest all-cause and mCRPC-related costs per month, respectively, were observed in patients receiving cabazitaxel (€7631/€6343), followed by abiraterone (€5226/€4579), enzalutamide (€5079/€4416), docetaxel (€2392/€1580), and BSC (€959/€438). Cost variations were mostly attributable to drugs, inpatient treatment, and sick leave payments. Conclusion mCRPC treatment imposes a high economic burden on statutory health insurance. Cabazitaxel is associated with substantially higher expenses, resulting from higher drug costs and a greater need for inpatient treatment. As mCRPC continues to be incurable, decision makers and clinician leaders should carefully evaluate public access to innovative agents and optimal treatment strategies. Electronic supplementary material The online version of this article (10.1007/s41669-020-00219-6) contains supplementary material, which is available to authorized users.

Purpose of Review This article provides an overview of current findings on Theory of Mind (ToM) in human children and adults and highlights the relationship between task specifications and their outcome in socio-cognitive research. Recent Findings ToM, the capacity to reason about and infer others’ mental states, develops progressively throughout childhood—the exact time course is still a matter of debate. Neuroimaging studies indicate the involvement of a widespread neuronal network during mentalizing, suggesting that ToM is a multifaceted process. Accordingly, the tasks and trainings that currently exist to investigate and enhance ToM are heterogeneous, and the outcomes largely depend on the paradigm that was used. Summary We argue for the implementation of multiple-task batteries in the assessment of socio-cognitive abilities. Decisions for a particular paradigm need to be carefully considered and justified. We want to emphasize the importance of targeted research on the relationship between task specifications and outcomes.

Cd14 and Alpk1 both encode pathogen recognition receptors and are known candidate genes for affecting severity in inflammatory bowel diseases. CD14 acts as a coreceptor for bacterial lipopolysaccharide (LPS), while ALPK1 senses ADP-D-glycero-beta-D-manno-heptose, a metabolic intermediate of LPS biosynthesis. Intestinal barrier integrity can be influenced by CD14, whereas to date, the role of ALPK1 in maintaining barrier function remains unknown. We used colon-derived 3D organoids, first characterised for growth, proliferation, stem cell markers, and expression of tight junction (TJ) components using qPCR and immunohistochemistry. They showed characteristic crypt stem cells, apical shedding of dead cells, and TJ formation. Afterwards, organoids of different genotypes (WT, Il10-/-, Cd14-/-, and Alpk1-/-) were then stimulated with either LPS or Escherichia coli Nissle 1917 (EcN). Gene expression and protein levels of cytokines and TJ components were analysed. WT organoids increased expression of Tnfα and tight junction components. Cd14-/- organoids expressed significantly less Tnfα and Ocln after LPS stimulation than WT organoids but reacted similarly to WT organoids after EcN stimulation. In contrast, compared to WT, Alpk1-/- organoids showed decreased expression of different TJ and cytokine genes in response to EcN but not LPS. However, Western blotting revealed an effect of ALPK1 on TJ protein levels. These findings demonstrate that Cd14, but not Alpk1, alters the response to LPS stimulation in colonic epithelial cells, whereas Alpk1 is involved in the response upon bacterial challenge.

T cell activation initiates protective adaptive immunity, but counterbalancing mechanisms are critical to prevent overshooting responses and to maintain immune homeostasis. The CARD11-BCL10-MALT1 (CBM) complex bridges T cell receptor engagement to NF-κB signaling and MALT1 protease activation. Here, we show that ABIN-1 is modulating the suppressive function of A20 in T cells. Using quantitative mass spectrometry, we identified ABIN-1 as an interactor of the CBM signalosome in activated T cells. A20 and ABIN-1 counteract inducible activation of human primary CD4 and Jurkat T cells. While A20 overexpression is able to silence CBM complex-triggered NF-κB and MALT1 protease activation independent of ABIN-1, the negative regulatory function of ABIN-1 depends on A20. The suppressive function of A20 in T cells relies on ubiquitin binding through the C-terminal zinc finger (ZnF)4/7 motifs, but does not involve the deubiquitinating activity of the OTU domain. Our mechanistic studies reveal that the A20/ABIN-1 module is recruited to the CBM complex via A20 ZnF4/7 and that proteasomal degradation of A20 and ABIN-1 releases the CBM complex from the negative impact of both regulators. Ubiquitin binding to A20 ZnF4/7 promotes destructive K48-polyubiquitination to itself and to ABIN-1. Further, after prolonged T cell stimulation, ABIN-1 antagonizes MALT1-catalyzed cleavage of re-synthesized A20 and thereby diminishes sustained CBM complex signaling. Taken together, interdependent post-translational mechanisms are tightly controlling expression and activity of the A20/ABIN-1 silencing module and the cooperative action of both negative regulators is critical to balance CBM complex signaling and T cell activation. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-022-04154-z.

Since the COronaVIrus Disease 2019 (COVID-19) outbreak, developing a digital diagnostic tool to detect COVID-19 from respiratory sounds with computer audition has become an essential topic due to its advantages of being swift, low-cost, and eco-friendly. However, prior studies mainly focused on small-scale COVID-19 datasets. To build a robust model, the large-scale multi-sound FluSense dataset is utilised to help detect COVID-19 from cough sounds in this study. Due to the gap between FluSense and the COVID-19-related datasets consisting of cough only, the transfer learning framework (namely CovNet) is proposed and applied rather than simply augmenting the training data with FluSense. The CovNet contains (i) a parameter transferring strategy and (ii) an embedding incorporation strategy. Specifically, to validate the CovNet's effectiveness, it is used to transfer knowledge from FluSense to COUGHVID, a large-scale cough sound database of COVID-19 negative and COVID-19 positive individuals. The trained model on FluSense and COUGHVID is further applied under the CovNet to another two small-scale cough datasets for COVID-19 detection, the COVID-19 cough sub-challenge (CCS) database in the INTERSPEECH Computational Paralinguistics challengE (ComParE) challenge and the DiCOVA Track-1 database. By training four simple convolutional neural networks (CNNs) in the transfer learning framework, our approach achieves an absolute improvement of 3.57% over the baseline of DiCOVA Track-1 validation of the area under the receiver operating characteristic curve (ROC AUC) and an absolute improvement of 1.73% over the baseline of ComParE CCS test unweighted average recall (UAR). Copyright © 2022 Chang, Jing, Ren and Schuller.