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Abstract Lupines and faba beans are rising stars among legumes as sources of valuable, vegan plant‐based proteins. To enter new application areas like the production of protein‐rich refreshing beverages, the typical beany aroma impression has to be overcome, and the sensory appearance has to be improved, as it can be accomplished with lactic acid fermentation. An extensive strain screening of 70 lactic acid bacteria from 16 genera was performed to identify suitable strains to transform substrates made from lupines and faba beans into refreshing beverages and to improve their sensory characteristics. By analyzing carbohydrate utilization, production of organic acids and aroma compounds, and sensory appearance, 22 strains for lupine and eight strains for faba bean were preselected. Subsequently, the most suitable strains (five for lupine and three for faba beans) were identified by a trained sensory panel, and finally their growth kinetics were discussed. Generally, the aroma profile varied highly with the utilized strain. However, by selecting suitable strains, the beany impression can be highly reduced and pleasant aroma impressions (e.g., fruity and buttermilk) can be added. Most strikingly, it was proven that using germinated lupines and faba beans instead of raw ones can bypass the usual growth restriction, and the strain selection can be focused exclusively on sensory aspects. This opens the option to use strains usually excluded for the fermentation of legumes due to their lack of utilization of the legume‐typical α‐galactosides.

Abstract Background Clinical practice guidelines are crucial for enhancing healthcare quality and patient outcomes. Yet, their implementation remains inconsistent across various professions and disciplines. Previous findings on the implementation of the German guideline for schizophrenia (2019) revealed low adherence rates among healthcare professionals. Barriers to guideline adherence are multifaceted, influenced by individual, contextual, and guideline-related factors. This study aims to investigate the effectiveness of a digital guideline version compared to print/PDF formats in enhancing guideline adherence. Methods A multicenter, cluster-randomized controlled trial was conducted in South Bavaria, Germany, involving psychologists and physicians. Participants were divided into two groups: implementation of the guideline using a digital online version via the MAGICapp platform and the other using the traditional print/PDF version. The study included a baseline assessment and a post-intervention assessment following a 6-month intervention phase. The primary outcome was guideline knowledge, which was assessed using a guideline knowledge questionnaire. Results The study included 217 participants at baseline and 120 at post-intervention. Both groups showed significant improvements in guideline knowledge; however, no notable difference was found between both study groups regarding guideline knowledge at either time points. At baseline, 43.6% in the control group (CG) and 52.5% of the interventional group (IG) met the criterion. There was no significant difference in the primary outcome between the two groups at either time point (T0: Chi2 (1) = 1.65, p = 0.199, T1: Chi2 (1) = 0.34, p = 0.561). At post-intervention, both groups improved, with 58.2% in the CG and 63.5% in the IG meeting this criterion. Conclusions While the study did not include a control group without any implementation strategy, the overall improvement in guideline knowledge following an implementation strategy, independent of the format, was confirmed. The digital guideline version, while not superior in enhancing knowledge, showed potential benefits in shared decision-making skills. However, familiarity with traditional formats and various barriers to digital application may have influenced these results. The study highlights the importance of tailored implementation strategies, especially for younger healthcare providers. Trial registration https://drks.de/search/de/trial/DRKS00028895

Aim: To provide the first syntaxonomic, plot-based classification of the dry grasslands and thorn-cushion communities in Armenia. Study area: Armenia. Methods: We sampled 111 vegetation plots (10 m2) and recorded environmental and structural parameters. We collected additional 487 relevés from surrounding countries for a broad-scale comparison. We used modified TWINSPAN to derive a syntaxonomic classification system, whose units were then compared among each other regarding species composition, structure, site conditions and distribution. Results: The classification of Armenian vegetation plots resulted in a 12-cluster solution. Unsupervised classification of the broad-scale dataset yielded five main groups, which were used for the high-level syntaxonomic assignments of the Armenian data. We assigned about half of the plots of the Armenian dataset to the Festuco-Brometea, while the remaining represented a potential new class, preliminarily called “Ziziphora tenuior-Stipa arabica grasslands”. Most of the syntaxa below class level are new to science, therefore we provide formal descriptions of three orders (Plantagini atratae-Bromopsietalia variegatae, Onobrychido transcaucasicae-Stipetalia pulcherrimae, Cousinio brachypterae-Stipetalia arabicae), four alliances (Acantholimono caryophyllacei-Stipion holosericeae, Artemision fragrantis, Onobrychido michauxii-Stipion capillatae, Onobrychido transcaucasicae-Stipion pulcherrimae) and six associations. We found significant differences in the topographic, climatic and soil characteristics, and structural parameters, species life forms and distribution range types between the grassland types at different syntaxonomic levels. The mean species richness was 47.3 (vascular plants: 46.8, bryophytes: 0.4, lichens: 0.1). Conclusions: We found remarkable differences of the Armenian dry grasslands from the previously known units and described most of the higher syntaxa and all the associations as new to science. Our study provides arguments for a potential new class of Ziziphora tenuior-Stipa arabica grasslands separate both from the Euro-Siberian Festuco-Brometea and the Anatolian Astragalo-Brometea. Finally, we found plot scale richness of vascular plants clearly above the Palaearctic average of dry grasslands and that of non-vascular plants clearly below, which calls for further biodiversity analyses. Taxonomic reference: Euro+Med (2023) for vascular plants, Hodgetts et al. (2020) for bryophytes, Nimis et al. (2018) for lichens except for Xanthoparmelia camtschadalis (Ach.) Hale. Abbreviations: EDGG = Eurasian Dry Grassland Group; DCA = detrended correspondence analysis; ICPN = International Code of Phytosociological Nomenclature (Theurillat et al. 2021); TWINSPAN = two-way indicator species analysis.

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p

Abstract Background Children of families with a parent with a mental illness have an increased risk of developing social and mental health problems resulting in decreased quality of life. Therefore, children and adolescents living in families with a parent with mental illness are regarded as a target group for preventive interventions. To date, only a few economic evaluation studies for interventions directed at preventing the intergenerational transmission of mental health problems exist. In this investigation we estimated the cost utility of an intervention for the support of children and adolescents with a parent having a mental illness from the perspective of the German health and social care system. Methods We randomly assigned a total of 214 families with 337 children and adolescents to the intervention (INT) group (108/170) or the control (TAU) group (106/167). Families in the intervention group received on average eight intervention sessions (50–90 min) over 6 months. We estimated total cost of illness by means of the Children and Adolescent Mental Health Service Receipt Inventory (CAMHSRI) over 24 months. For the estimation of Quality-Adjusted Live Years (QALYs) we applied the KIDSCREEN-10. For estimating the incremental cost-utility of the intervention compared to treatment as usual we used the net-benefit approach. Results We estimated the annual cost of illness amounting to € 3784.59 (SD € 8581.11) in the TAU group and € 3264.44 (SD € 9431.89) in the INT group. The annual cost difference between INT and TAU was € − 516.14 (SE 1124.95) which was not significant (p ≤ 0.05). We estimated the average QALY to be 0.759 (SD 0.073) in the TAU group and 0.763 (SD 0.072). The QALY difference between INT and TAU was 0.0037 (SE 0.0092) which was not significant (p ≤ 0.05). The incremental cost utility ratio (ICUR) indicated that the gain of one additional year in full health by means of the intervention was associated with the saving of € 139.49. However, the stochastic insecurity of the ICUR did not allow a unique decision about the cost-utility of the intervention. Conclusions More information on the economic value of the intervention for families with a parent with mental illness in comparison to treatment as usual in Germany is needed. Trial registration: ClinicalTrials.gov, identifier NCT02308462; German Clinical Trials Register: DRKS00006806.

In fermentation processes, changes in yeast cell count and substrate concentration are indicators of yeast performance. Therefore, monitoring the composition of the biological suspension, particularly the dispersed solid phase (i.e., yeast cells) and the continuous liquid phase (i.e., medium), is a prerequisite to ensure favorable process conditions. However, the available monitoring methods are often invasive or restricted by detection limits, sampling requirements, or susceptibility to masking effects from interfering signals. In contrast, ultrasound measurements are non-invasive and provide real-time data. In this study, the suitability to characterize the dispersed and the liquid phase of yeast suspensions with ultrasound was investigated. The ultrasound signals collected from three commercially available Saccharomyces yeast were evaluated and compared. For all three yeasts, the attenuation coefficient and speed of sound increased linearly with increasing yeast concentrations (0.0–1.0 wt%) and cell counts (R2 > 0.95). Further characterization of the dispersed phase revealed that cell diameter and volume density influence the attenuation of the ultrasound signal, whereas changes in the speed of sound were partially attributed to compositional variations in the liquid phase. This demonstrates the ability of ultrasound to monitor industrial fermentations and the feasibility of developing targeted control strategies.

Background and Objectives: Anastomotic insufficiencies (AI) and perforations of the upper gastrointestinal tract (uGIT) result in high morbidity and mortality. Endoscopic stent placement and endoluminal vacuum therapy (EVT) have been established as surgical revision treatment options. The Eso-Sponge® is the only licensed EVT system with limitations in treating small defects (Materials and Methods: Between 01/2018 and 01/2021, the clinical data of patients undergoing FS-EVT or conventional EVT (cEVT; Eso-Sponge®, Braun Melsungen, Melsungen, Germany) due to AI/perforation of the uGIT were recorded. Indication, diameter of leakage, therapeutic success, and complications during the procedure were assessed. FSs were prepared using a nasogastric tube and a porous drainage film (Suprasorb® CNP, Lohmann & Rauscher, Rengsdorf, Germany) sutured to the distal tip. Results: A total of 72 patients were included (20 FS-EVT; 52 cEVT). FS-EVT was performed in 60% suffering from AI (cEVT = 68%) and 40% from perforation (cEVT = 32%; p > 0.05). FS-EVT’s duration was significantly shorter than cEVT (7.6 ± 12.0 d vs. 15.1 ± 14.3 d; p = 0.014). The mean diameter of the defect was 9 mm in the FS-EVT group compared to 24 mm in cEVT (p < 0.001). Therapeutic success was achieved in 90% (FS-EVT) and 91% (cEVT; p > 0.05). Conclusions: EVT comprises an efficient treatment option for transmural defects of the uGIT. In daily clinical practice, fistulas < 10 mm with large abscess formations poses a special challenge since intraluminal cEVT usually is ineffective. In these cases, the concept of extraluminal FS placement is safe and effective.

Introduction: For over two decades, abdominal surgical procedures have been safely performed robotically. After the first patent expiration, alternative robotic systems entered the market. The Dexter Robotic System™ is a small-format, modular, and robotic platform consisting of a surgeon’s console, two patient carts with instrument arms, and one endoscope arm. We report our initial experiences with Dexter since its installation at our visceral surgery department. Methods: The system and surgical setup are described. Demographic and perioperative data of all operated patients as well as the system docking times were analyzed. Results: From 56 procedures performed with Dexter, the most common ones included cholecystectomy (n = 15), inguinal hernia repair (TAPP; unilateral n = 15; bilateral n = 3), and right oncologic hemicolectomy (n = 15). The median docking time was 6 min (2–16 min) and was reduced to 4 min in the last tertile of procedures performed. Conclusions: In our experience, Dexter can be implemented without any major challenges, and visceral surgical procedures of simple to medium complexity can be performed safely. The simplicity and accessibility of the system along with the ease of switching between robotics and laparoscopy could be particularly suitable for beginners in robotic surgery

Summary: The mitochondrial inner membrane plays central roles in bioenergetics and metabolism and contains several established membrane protein complexes. Here, we report the identification of a mega-complex of the inner membrane, termed mitochondrial multifunctional assembly (MIMAS). Its large size of 3 MDa explains why MIMAS has escaped detection in the analysis of mitochondria so far. MIMAS combines proteins of diverse functions from respiratory chain assembly to metabolite transport, dehydrogenases, and lipid biosynthesis but not the large established supercomplexes of the respiratory chain, ATP synthase, or prohibitin scaffold. MIMAS integrity depends on the non-bilayer phospholipid phosphatidylethanolamine, in contrast to respiratory supercomplexes whose stability depends on cardiolipin. Our findings suggest that MIMAS forms a protein-lipid mega-assembly in the mitochondrial inner membrane that integrates respiratory biogenesis and metabolic processes in a multifunctional platform.

Abstract In actively translating 80S ribosomes the ribosomal protein eS7 of the 40S subunit is monoubiquitinated by the E3 ligase Not4 and deubiquitinated by Otu2 upon ribosomal subunit recycling. Despite its importance for translation efficiency the exact role and structural basis for this translational reset is poorly understood. Here, structural analysis by cryo-electron microscopy of native and reconstituted Otu2-bound ribosomal complexes reveals that Otu2 engages 40S subunits mainly between ribosome recycling and initiation stages. Otu2 binds to several sites on the intersubunit surface of the 40S that are not occupied by any other 40S-binding factors. This binding mode explains the discrimination against 80S ribosomes via the largely helical N-terminal domain of Otu2 as well as the specificity for mono-ubiquitinated eS7 on 40S. Collectively, this study reveals mechanistic insights into the Otu2-driven deubiquitination steps for translational reset during ribosome recycling/(re)initiation.

Ribosome collisions serve as proxy for aberrant translation to initiate rescue and quality control pathways. Here, authors elucidate the molecular mechanism of collided ribosome clearance by the ribosome quality control trigger complex.

The mitochondrial ATP synthase produces the bulk of cellular ATP. Here, the authors report a function of the mitochondrial Hsp70 in the formation of the catalytical head and in its assembly with the peripheral stalk to form the mature ATP synthase.

Abstract Techniques for tissue culture have seen significant advances during the last decades and novel 3D cell culture systems have become available. To control their high complexity, experimental techniques and their Digital Twins (modelling and computational tools) are combined to link different variables to process conditions and critical process parameters. This allows a rapid evaluation of the expected product quality. However, the use of mathematical simulation and Digital Twins is critically dependent on the precise description of the problem and correct input parameters. Errors here can lead to dramatically wrong conclusions. The intention of this review is to provide an overview of the state‐of‐the‐art and remaining challenges with respect to generating input values for computational analysis of mass and momentum transport processes within tissue cultures. It gives an overview on relevant aspects of transport processes in tissue cultures as well as modelling and computational tools to tackle these problems. Further focus is on techniques used for the determination of cell‐specific parameters and characterization of culture systems, including sensors for on‐line determination of relevant parameters. In conclusion, tissue culture techniques are well‐established, and modelling tools are technically mature. New sensor technologies are on the way, especially for organ chips. The greatest remaining challenge seems to be the proper addressing and handling of input parameters required for mathematical models. Following Good Modelling Practice approaches when setting up and validating computational models is, therefore, essential to get to better estimations of the interesting complex processes inside organotypic tissue cultures in the future.

Abstract Background Home treatment (HT) is a treatment modality for patients with severe mental illness (SMI) in acute mental crises. It is frequently considered equivalent to psychiatric inpatient treatment in terms of treatment outcome. Peer Support (PS) means that people with lived experience of a mental illness are trained to support others on their way towards recovery. While PS is growing in international importance and despite a growing number of studies supporting its benefits, it is still not comprehensively implemented into routine care. The HoPe (Home Treatment with Peer Support) study investigates a combination of both – HT and PS – to provide further evidence for a recovery-oriented treatment of psychiatric patients. Methods In our randomized controlled trial (RCT), HT with PS is compared with HT without PS within a network of eight psychiatric clinical centers from the North, South and East of Germany. We investigate the effects of a combination of both approaches with respect to the prevention of relapse/recurrence defined as first hospitalization after randomization (primary outcome), disease severity, general functioning, self-efficacy, psychosocial health, stigma resistance, recovery support, and service satisfaction (secondary outcomes). A sample of 286 patients will be assessed at baseline after admission to HT care (data point t0) and randomized into the intervention (HT + PS) and control arm (HT). Follow-Up assessments will be conducted 2, 6 and 12 months after admission (resulting in three further data points, t1 to t3) and will be analyzed via intention-to-treat approach. Discussion This study may determine the positive effects of PS added to HT, prove additional evidence for the efficacy of PS and thereby facilitate its further implementation into psychiatric settings. The aim is to improve quality of mental health care and patients’ recovery as well as to reduce the risk of relapses and hospitalizations for patients with SMI. Trial registration The trial is registered with ClinicalTrials.gov: NCT04336527 , April 7, 2020.

Mitochondrial biogenesis requires the import of >1,000 mitochondrial preproteins from the cytosol. Most studies on mitochondrial protein import are focused on the core import machinery. Whether and how the biophysical properties of substrate preproteins affect overall import efficiency is underexplored. Here, we show that protein traffic into mitochondria can be disrupted by amino acid substitutions in a single substrate preprotein. Pathogenic missense mutations in ADP/ATP translocase 1 (ANT1), and its yeast homolog ADP/ATP carrier 2 (Aac2), cause the protein to accumulate along the protein import pathway, thereby obstructing general protein translocation into mitochondria. This impairs mitochondrial respiration, cytosolic proteostasis, and cell viability independent of ANT1’s nucleotide transport activity. The mutations act synergistically, as double mutant Aac2/ANT1 causes severe clogging primarily at the translocase of the outer membrane (TOM) complex. This confers extreme toxicity in yeast. In mice, expression of a super-clogger ANT1 variant led to neurodegeneration and an age-dependent dominant myopathy that phenocopy ANT1-induced human disease, suggesting clogging as a mechanism of disease. More broadly, this work implies the existence of uncharacterized amino acid requirements for mitochondrial carrier proteins to avoid clogging and subsequent disease.

A variety of yeast applications in the food and beverage industry require individual and reproducible yeast propagation at high yields and consistent quality. One quality-determining parameter for yeast propagation is effective aeration to avoid oxygen depletion. Therefore, this work investigated three important aeration parameters: airflow, pulse time, and oxygen concentration, for their influence on yeast propagation. The aeration of a propagator involves phase transitions which are gradient-driven processes and can be accelerated with higher gradients between the liquid medium and the gas bubbles. In this study, oxygen-enriched air generated with membrane filters was used to aerate the system in an easy and cost-efficient way without the need for expensive technical gas usage. Propagation experiments were carried out in a pilot-scale reactor equipped with a membrane filter system for enhanced oxygen concentrations in ingas and online sensors for representative monitoring of the process. The membrane filter system is based on the separation of nitrogen in compressed air, leading to oxygen enrichment. Using oxygen-enriched air for propagation aeration showed higher oxygen transfer into the medium and the anaerobic process time caused by oxygen depletion due to high cell numbers was reduced by an average of 7.4% for pulsed aeration. Additionally, we conducted experiments with controlled measures of dissolved oxygen using different oxygen concentrations for aeration. The main objective of this study is to present a new and affordable optimization of propagation aeration using membrane filtration to enrich process air. The results showed increased cell counts for higher ingas oxygen concentrations and no negative impact on cell vitality was observed. Hence, our investigations showed that using oxygen-enriched air reduced the frequency of pulsed aeration, thus hindering foam formation, a limiting factor of the yeast propagation process.

From the nature and rationale of universal jurisdiction trials it follows that the right to information in the form of interpretation and translation is an essential factor in strengthening the nexus between the trial and the victims and affected communities. This normative standard is enshrined in legal rights in the international, EU and ECHR dimension, which applies to victims in particular but to affected communities as well. Although Germany is a frontrunner in investigating and prosecuting international core crimes committed in Syria it leaves a gap with this normative standard. A lack of information and outreach to victims and affected communities poses a risk of their rights becoming lost in translation. It follows from the cases of Anwar Raslan & Eyad Al-Gharib, Taha al-Jumailly and Alaa M that the most pressing problems include a lack of documentation, simultaneous interpretation, Arabic interpretation, and information available to the public. To close the information gap and facilitate ‘ownership of the proceedings’ to those affected by heinous crimes, a shift in policy of the domestic prosecutor is required: towards a service-oriented and victim centred approach. This conclusion leads to some practical recommendations that could be adopted across many European jurisdiction.

Cotranslational modification of the nascent polypeptide chain is one of the first events during the birth of a new protein. In eukaryotes, methionine aminopeptidases (MetAPs) cleave off the starter methionine, whereas N-acetyl-transferases (NATs) catalyze N-terminal acetylation. MetAPs and NATs compete with other cotranslationally acting chaperones, such as ribosome-associated complex (RAC), protein targeting and translocation factors (SRP and Sec61) for binding sites at the ribosomal tunnel exit. Yet, whereas well-resolved structures for ribosome-bound RAC, SRP and Sec61, are available, structural information on the mode of ribosome interaction of eukaryotic MetAPs or of the five cotranslationally active NATs is only available for NatA. Here, we present cryo-EM structures of yeast Map1 and NatB bound to ribosome-nascent chain complexes. Map1 is mainly associated with the dynamic rRNA expansion segment ES27a, thereby kept at an ideal position below the tunnel exit to act on the emerging substrate nascent chain. For NatB, we observe two copies of the NatB complex. NatB-1 binds directly below the tunnel exit, again involving ES27a, and NatB-2 is located below the second universal adapter site (eL31 and uL22). The binding mode of the two NatB complexes on the ribosome differs but overlaps with that of NatA and Map1, implying that NatB binds exclusively to the tunnel exit. We further observe that ES27a adopts distinct conformations when bound to NatA, NatB, or Map1, together suggesting a contribution to the coordination of a sequential activity of these factors on the emerging nascent chain at the ribosomal exit tunnel.

Brewer’s spent grain (BSG) is the most abundant residual in the brewing process. Non-starch polysaccharides such as 1,3-1,4-β-D-glucan (β-glucan) and arabinoxylan (AX) with proven beneficial effects on human health remain in this by-product in high amounts. Incorporating the valuable dietary fiber into the food industry could contribute to a healthy diet. However, a major challenge is extracting these dietary fibers (i.e., β-glucan and AX) from the solid residue. In this study, hydrothermal treatment (HT) was applied to dissolve the remaining water-insoluble carbohydrates from BSG with the aim to extract high amounts of β-glucan and AX. Particular focus was placed on the molecular weight (MW) range above 50 kDa and 20 kDa, respectively, as these are considered to have health-promoting effects. Different treatment temperatures, reaction times, and internal reactor pressures were tested to determine the best process settings to achieve high yields of β-glucan and AX and to examine the influence on their molecular weight distribution (MWD). Overall, 85.1% β-glucan and 77.3% AX were extracted corresponding to 6.3 g per kg BSG at 160 °C and 178.3 g kg−1 at 170 °C, respectively. However, less than 20% of both fiber substances were in the desirable MW range above 50 kDa and 20 kDa, respectively. When lower temperatures of 140 and 150 °C were applied, yields of only 3.0 g kg−1 β-glucan and 128.8 g kg−1 AX were obtained, whereby the proportion of desirable fiber fractions increased up to 45%. Further investigations focused on the heat-induced degradation of monosaccharides and the formation of undesirable by-products (i.e., HMF and furfural) that might pose a health risk.

Abstract Migration rates increase globally and require an adaption of national mental health services to the needs of persons with migration background. Therefore, we aimed to identify differences between persons with and without migratory background regarding (1) treatment satisfaction, (2) needed and received mental healthcare and (3) utilization of mental healthcare. In the context of a cross-sectional multicenter study, inpatients and day hospital patients of psychiatric settings in Southern Germany with severe affective and non-affective psychoses were included. Patients’ satisfaction with and their use of mental healthcare services were assessed by VSSS-54 and CSSRI-EU; patients’ needs were measured via CAN-EU. In total, 387 participants (migratory background: n = 72; 19%) provided sufficient responses for analyses. Migrant patients were more satisfied with the overall treatment in the past year compared to non-migrant patients. No differences between both groups were identified in met and unmet treatment needs and use of supply services (psychiatric, psychotherapeutic, and psychosocial treatment). Despite a comparable degree of met and unmet treatment needs and mental health service use among migrants and non-migrants, patients with migration background showed higher overall treatment satisfaction compared to non-migrants. The role of sociocultural and migrant-related factors may explain our findings.

Abstract Background Unhealthy lifestyle constitutes a cause of increased morbidity and mortality in people with severe mental illness. The aim of this mixed-method pilot study was to investigate the feasibility and preliminary effectiveness of an intervention to promote a health-conscious lifestyle in comparison to care as usual among people with severe mental illness receiving accommodational support in community settings. Methods This was a prospective, quasi-experimental, controlled study over four six-month assessment points (t0, + 6 months, + 12 months, + 18 months) with 70 persons with severe mental illness receiving community based accommodational support. Mental health staff members of the housing facilities were trained in Motivational Interviewing and conducted a six-week health course with the intervention group participants in addition to care as usual. Next to the primary outcome - self-rated physical well-being (FEW 16) - anthropometric parameters and unhealthy behaviours (diet, physical activity, alcohol and tobacco consumption, and oral hygiene) were examined. Effectiveness analysis was conducted using mixed-effects regression models with propensity score adjustment to control for selection bias. One year after the end of the intervention, semi-standardized expert interviews were conducted with 12 of these employees and evaluated by content analysis. Results The qualitative interviews with mental health staff underline the intervention’s feasibility in people with severe mental illness in sheltered housing, and the acceptability of and satisfaction with the intervention among mental health workers. But in this pilot study no superiority of the HELPS intervention compared to routine care could be demonstrated in terms of the investigated outcomes. Conclusions The findings of this pilot study underscore the feasibility and acceptability of health promotion programmes based on Motivational Interviewing and highlight the need to further develop multi-modal programs according to the needs of the target group. Long-term and sustainable support for healthy lifestyles of people with severe mental illness receiving community mental health care requires multi-modal concepts and organisational change. Trial registration DRKS00011659 , date of registration was 2017/02/15; retrospectively registered as date of first enrolment was 2017/01/24.

Abstract The use of corrosion inhibitors is a cost-effective corrosion mitigation strategy for carbon steel. There is an increased focus on developing and using low-cost, biodegradable and environmentally friendly inhibitor formulations. Plant-based extracts have been evaluated in many studies using a multitude of electrochemical methods and characterisation techniques. Although plant extracts appear as promising alternatives for commercially synthesised inhibitor formulations, a significant amount of optimisation is required. The majority of the research on plant extracts does not elucidate the effect of other synergistic combinations in commercial inhibitor formulations. Therefore, further development of plant extracts as corrosion inhibitors is of significant interest.

German abstract Hintergrund Berufliche Beschäftigung ist von großer Bedeutung für den Einzelnen, da sie mit verschiedenen positiven Effekten verbunden ist. Menschen mit schweren psychischen Erkrankungen sind oft vom allgemeinen Arbeitsmarkt ausgeschlossen. Aktuelle Daten zur Beschäftigung von Menschen mit psychischen Erkrankungen liegen kaum vor und die Einflussfaktoren sind bisher wenig erforscht. Die vorliegende Studie untersucht mögliche Prädiktoren für eine wettbewerbsfähige Beschäftigung bei Menschen mit schweren psychischen Erkrankungen. Methoden Berichtet werden Ergebnisse einer multizentrischen Querschnittsstudie mit 300 Menschen mit schweren psychischen Erkrankungen im Alter von 18 bis 65 Jahren. Die folgenden Einschlusskriterien wurden verwendet: (I) Diagnose einer Schizophrenie, schizotypen oder wahnhaften Störung (ICD-10 F2x) oder affektiven Störung (ICD-10 F3x), (II) Dauer der psychiatrischen Erkrankung ≥ 2 Jahre und (III) erhebliche Auswirkungen der Erkrankung auf das soziale Funktionsniveau. Die Teilnehmenden wurden von geschultem Personal mit standardisierten Instrumenten befragt. Der Zusammenhang zwischen möglichen Prädiktoren (Alter, Geschlecht, Bildung, Familienstand, Wohnsituation, Migrationshintergrund, psychosoziale Funktionsfähigkeit, Alter bei ersten psychischen Problemen, körperliche Erkrankung, Arbeitsfähigkeit) und der Beschäftigung wurde mittels eines hierarchischen binären logistischen Regressionsmodells analysiert. Ergebnisse Nur ein Drittel (34 %) der Teilnehmenden war kompetitiv beschäftigt. Fast ein Drittel der Teilnehmenden war arbeitslos (30 %), und 28 % berichteten über eine Frühverrentung aufgrund der psychischen Erkrankung. Die psychosoziale Funktionsfähigkeit war positiv mit kompetitiver Beschäftigung assoziiert (OR = 1,09, 95% CI: 1,05 - 1,13, p < 0,001); gleichzeitige chronische körperliche Erkrankungen waren negativ mit kompetitiver Beschäftigung assoziiert (OR = 0,38, 95% CI: 0,21 - 0,71, p = 0,002). Schlussfolgerungen Die Ergebnisse bestätigen ein hohes Risiko des Ausschlusses von kompetitiver Beschäftigung bei Menschen mit schwerer psychischer Erkrankung. Gleichwohl ist ein beträchtlicher Anteil beschäftigt. Die Bemühungen, die Erwerbsbeteiligung der Betroffenen zu erhalten bzw. zu erweitern, müssen intensiviert werden. Ein besonderer Fokus sollte dabei auf die körperliche Gesundheit sowie die Stärkung der psychosozialen Funktionen gelegt werden.

During the baking process, the functionality of the heterogeneous dough matrix changes as the composing polymers experience conformational transition processes. The thermally induced structural changes affect the involvement and functionality of the polymers in the dough matrix. With the main hypothesis being that different types and magnitudes of strain exerted during the measurement would provide information on different structural levels and interactions, SAOS rheology in multiwave mode and large deformation extensional rheometry were applied to two microstructurally different systems. The functionality of the two systems, a highly connected standard wheat dough (φ ≈ 1.1) and an aerated, yeasted wheat dough (φ ≈ 2.3), depicting limited connectivity and strength of interactions, was accessed under different deformations and types of strains. Applying SAOS rheology, starch functionality prevailed on the behavior of the dough matrix. In contrast, gluten functionality prevailed the large deformation behavior. Using an inline fermentation and baking LSF technique, the heat-induced gluten polymerization was shown to increase strain hardening behavior above 70°C. In the aerated system, the strain hardening effect became already evident under small deformation testing, as the expansion of gas cells caused a pre-expansion of the gluten strands. The expanded dough matrix of yeasted dough was further shown to be substantially subjected to degradation once the network reached beyond its maximal gas holding capacity. Using this approach, the combined impact of yeast fermentation and thermal treatment on the strain hardening behavior of wheat dough was revealed for the first time by LSF. Furthermore, the rheological properties were successfully linked to oven rise behavior: a decreasing connectivity combined with the initiation of strain hardening by fast extension processes occurring in the yeasted dough matrix during the final baking phase was linked to limited oven rise functionality prematurely around 60°C.

Abstract As early detection of symptoms in the subclinical to clinical psychosis spectrum may improve health outcomes, knowing the probabilistic susceptibility of developing a disorder could guide mitigation measures and clinical intervention. In this context, polygenic risk scores (PRSs) quantifying the additive effects of multiple common genetic variants hold the potential to predict complex diseases and index severity gradients. PRSs for schizophrenia (SZ) and bipolar disorder (BD) were computed using Bayesian regression and continuous shrinkage priors based on the latest SZ and BD genome-wide association studies (Psychiatric Genomics Consortium, third release). Eight well-phenotyped groups (n = 1580; 56% males) were assessed: control (n = 305), lower (n = 117) and higher (n = 113) schizotypy (both groups of healthy individuals), at-risk for psychosis (n = 120), BD type-I (n = 359), BD type-II (n = 96), schizoaffective disorder (n = 86), and SZ groups (n = 384). PRS differences were investigated for binary traits and the quantitative Positive and Negative Syndrome Scale. Both BD-PRS and SZ-PRS significantly differentiated controls from at-risk and clinical groups (Nagelkerke’s pseudo-R 2: 1.3–7.7%), except for BD type-II for SZ-PRS. Out of 28 pairwise comparisons for SZ-PRS and BD-PRS, 9 and 12, respectively, reached the Bonferroni-corrected significance. BD-PRS differed between control and at-risk groups, but not between at-risk and BD type-I groups. There was no difference between controls and schizotypy. SZ-PRSs, but not BD-PRSs, were positively associated with transdiagnostic symptomology. Overall, PRSs support the continuum model across the psychosis spectrum at the genomic level with possible irregularities for schizotypy. The at-risk state demands heightened clinical attention and research addressing symptom course specifiers. Continued efforts are needed to refine the diagnostic and prognostic accuracy of PRSs in mental healthcare.

Abstract Climate change, pollution, and deforestation have a negative impact on global mental health. There is an environmental justice dimension to this challenge as wealthy people and high‐income countries are major contributors to climate change and pollution, while poor people and low‐income countries are heavily affected by the consequences. Using state‐of‐the art data mining, we analyzed and visualized the global research landscape on mental health, climate change, pollution and deforestation over a 15‐year period. Metadata of papers were exported from PubMed®, and both relevance and relatedness of terms in different time frames were computed using VOSviewer. Co‐occurrence graphs were used to visualize results. The development of exemplary terms over time was plotted separately. The number of research papers on mental health and environmental challenges is growing in a linear fashion. Major topics are climate change, chemical pollution, including psychiatric medication in wastewater, and neurobiological effects. Research on specific psychiatric syndromes and diseases, particularly on their ethical and social aspects is less prominent. There is a growing body of research literature on links between mental health, climate change, pollution, and deforestation. This research provides a graphic overview to mental healthcare professionals and political stakeholders. Social and ethical aspects of the climate change‐mental health link have been neglected, and more research is needed.

When confronted with environmental stress, yeast cell reacts, among others, by modifying the expression of specific genes. In this study, gene expression was analyzed via RT-qPCR to quantify the oxidative stress of Saccharomyces pastorianus during yeast propagation as a reaction to different aeration levels. Target genes were identified, and a reference gene system was developed. Fermentation experiments were conducted in shaking flasks, applying different shaking speeds to generate various aeration efficiencies. The cells were sampled at different propagation stages and, additionally to the expression study, analyzed by flow cytometry after staining with dihydroethidium (DHE) to quantify reactive oxygen species (ROS) inside the cells. The results indicate that high oxygen fermentation conditions led to an increased expression of the catalase-A gene CTA1 during propagation. Furthermore, the determination of cell internal ROS shows increasing oxidative stress over the process in accordance with the RT-qPCR measurements.

BackgroundLiver transplantation (LT) is considered a therapeutic option for unresectable perihilar cholangiocarcinoma (PHC) within defined criteria. It remains uncertain whether patients can safely receive adjuvant chemotherapy after LT.MethodsWe performed a prospective, multi-center, randomized, non-blinded two-arm trial (pro-duct001). Patients after LT for unresectable PHC within defined criteria were randomized to adjuvant gemcitabine (LT-Gem group) and LT alone (LT alone group). The primary objective was to investigate if adjuvant chemotherapy is feasible in ≥ 85% of patients after LT. The primary endpoint was the percentage of patients completing the 24 weeks course of adjuvant chemotherapy. Secondary endpoints included overall survival (OS) and disease-free (DFS), and complication rates.ResultsTwelve patients underwent LT for PHC, of which six (50%) were eligible for randomization (LT-Gem: three patients, LT alone: three patients). Two out of three patients discontinued adjuvant chemotherapy after LT due to intolerance. The study was prematurely terminated due to slow enrollment. One patient with PHC had underlying primary sclerosing cholangitis (PSC). Tumor-free margins could be achieved in all patients. In both the LT-Gem and the LT alone group, the cumulative 1-, 3-, and 5-year OS and DFS rates were 100%, 100%, 67%, and 100%, 67% and 67%, respectively.ConclusionsThis prospective, multi-center study was prematurely terminated due to slow enrollment and a statement on the defined endpoints cannot be made. Nevertheless, long-term survival data are consistent with available retrospective data and confirm defined criteria for LT. Since more evidence of LT per se in unresectable PHC is urgently needed, a prospective, non-randomized follow-up study (pro-duct002) has since been launched.

During the germination of legumes, raffinose family oligosaccharides (RFOs) are decomposed into mono- and disaccharides. As legumes are a traditional part of the human nutrition, storage carbohydrates are generally incorporated in the daily meals and can cause flatulence or even abdominal pain. However, their decomposition products can be metabolized without any difficulty. To date, no validated method is available to quantify the main decomposition products, glucose, and galactose simultaneously with the RFOs and the starch decomposition product maltose in a single measurement without derivatization. To provide a suitable method and fill the existing knowledge gap, a highly sensitive ion chromatography method was established. By using an optimized gradient, the separation of the RFOs, namely raffinose, stachyose, and verbascose, from their decomposition products, including glucose, galactose, fructose, and saccharose was accomplished. An advanced repeatability study proved that the method could be used for up to 4 days until the sample or eluent degradation made further measurement unfeasible. To improve the repeatability while avoiding to overload the chromatogram with several internal standards, a mathematical approach was presented to cope with different decomposition characteristics of the analytes and the internal standard. This study presents a modified and validated method allowing the measurement of all relevant carbohydrates in the germination of legumes. By using only a single method, a high number of samples can be processed. Therefore, a deeper and more detailed insight into the changes in the carbohydrate spectrum during the germination of legumes becomes feasible.

Abstract Obesity is associated with a “natriuretic handicap” indicated by reduced N-terminal fragment of proBNP (NT-proBNP) concentration. While gastric bypass surgery improves the natriuretic handicap, it is presently unclear if sleeve gastrectomy exhibits similar effects. We examined NT-proBNP serum concentration in n = 72 obese participants without heart failure before and 6 months after sleeve gastrectomy (n = 28), gastric bypass surgery (n = 19), and 3-month 800 kcal/day very-low calorie diet (n = 25). A significant weight loss was observed in all intervention groups. Within 6 months, NT-proBNP concentration tended to increase by a median of 44.3 pg/mL in the sleeve gastrectomy group (p = 0.07), while it remained unchanged in the other groups (all p ≥ 0.50). To gain insights into potential effectors, we additionally analyzed NT-proBNP serum concentration in n = 387 individuals with different metabolic phenotypes. Here, higher NT-proBNP levels were associated with lower nutritional fat and protein but not with carbohydrate intake. Of interest, NT-proBNP serum concentrations were inversely correlated with fasting glucose concentration in euglycemic individuals but not in individuals with prediabetes or type 2 diabetes. In conclusion, sleeve gastrectomy tended to increase NT-proBNP levels in obese individuals and might improve the obesity-associated “natriuretic handicap”. Thereby, nutritional fat and protein intake and the individual glucose homeostasis might be metabolic determinants of NT-proBNP serum concentration.

Background: We were able to demonstrate the feasibility of a new robotic system (Versius, CMR Surgical, Cambridge, UK) for procedures in small inanimate cavities. The aim of this consecutive study was to test the Versius® system for its feasibility, performance, and safety of robotic abdominal and thoracic surgery in piglets simulating infants with a body weight lower than 10 kg. Methods: A total of 24 procedures (from explorative laparoscopy to thoracoscopic esophageal repair) were performed in 4 piglets with a mean age of 12 days and a mean body weight of 6.4 (7–7.5) kg. Additional urological procedures were performed after euthanasia of the piglet. The Versius® robotic system was used with 5 mm wristed instruments and a 10 mm 3D 0° or 30° camera. The setup consisted of the master console and three to four separate arms. The performance of the procedure, the size, position, and the distance between the ports, the external and internal collisions, and complications of the procedures were recorded and analyzed. Results: We were able to perform all surgical procedures as planned. We encountered neither surgical nor robot-associated complications in the live model. Whereas all abdominal procedures could be performed successfully under general anesthesia, one piglet was euthanized early before the thoracic interventions, likely due to pulmonary inflammatory response. Technical limitations were based on the size of the camera (10 mm) being too large and the minimal insertion depth of the instruments for calibration of the fulcrum point. Conclusions: Robotic surgery on newborns and infants appears technically feasible with the Versius® system. Software adjustments for fulcrum point calibration need to be implemented by the manufacturer as a result of our study. To further evaluate the Versius® system, prospective trials are needed, comparing it to open and laparoscopic surgery as well as to other robotic systems.

An ultrasonic wave mode-based method for density measurement in highly foamed batters was developed. Therefore, a non-contact ultrasonic sensor system was designed to generate signals for batch-wise processes. An ultrasonic sensor, containing a piezoelectric ceramic at the fundamental longitudinal frequency of 2 MHz, was used to take impedance measurements in pulse-echo mode. The ultrasonic signals were processed and analysed wave-mode wise, using a feature-driven approach. The measurements were carried out for different mixing times within a container, with the attached ultrasonic sensor. Within the biscuit batter, the change to the ultrasonic signals caused by density changes during the batter-mixing process was monitored (R2 = 0.96). The density range detected by the sensor ranges between 500 g/L and 1000 g/L. The ultrasonic sensor system developed also shows a reasonable level of accuracy for the measurements of biscuit batter variations (R2 > 0.94). The main benefit of this novel technique, which comprises multiple wave modes for signal features and combines these features with the relevant process parameters, leads to a more robust system as regards to multiple interference factors.

Abstract Ancient Indian iron artefacts have always fascinated researchers due to their excellent corrosion resistance, but the scientific explanation of this feature remains to be elucidated. We have investigated corrosion resistance of iron manufactured according to traditional metallurgical processes by the Indian tribes called ‘Agaria’. Iron samples were recovered from central India (Aamadandh, Korba district, Chhattisgarh). Iron artefacts are investigated using a range of correlative microscopic, spectroscopic, diffraction and tomographic techniques to postulate the hidden mechanisms of superlative corrosion resistance. The importance of manufacturing steps, ingredients involved in Agaria’s iron making process, and post-metal treatment using metal-working operation called hot hammering (forging) is highlighted. This study also hypothesizes the probable protective mechanisms of corrosion resistance of iron. Findings are expected to have a broad impact across multiple disciplines such as archaeology, metallurgy and materials science.

Summary: The presequence translocase (TIM23 complex) imports precursor proteins into the mitochondrial inner membrane and matrix. The presequence translocase-associated motor (PAM) provides a driving force for transport into the matrix. The J-protein Pam18 stimulates the ATPase activity of the mitochondrial Hsp70 (mtHsp70). Pam16 recruits Pam18 to the TIM23 complex to ensure protein import. The Pam16-Pam18 module also associates with components of the respiratory chain, but the function of the dual localization of Pam16-Pam18 is largely unknown. Here, we show that disruption of the Pam16-Pam18 heterodimer causes redistribution of Pam18 to the respiratory chain supercomplexes, where it forms a homodimer. Redistribution of Pam18 decreases protein import into mitochondria but stimulates mtHsp70-dependent assembly of respiratory chain complexes. We conclude that coupling to Pam16 differentially controls the dual function of Pam18. It recruits Pam18 to the TIM23 complex to promote protein import but attenuates the Pam18 function in the assembly of respiratory chain complexes.

Abstract Background The underestimation of depression among men may result from atypical depression symptoms and male help-seeking behaviour. However, higher suicide rates among men than among women indicate a need for gender-specific services for men with depression. In order to develop gender-specific services, it is essential to examine professionals’ attitudes towards men’s depressive symptoms and treatment needs as well as barriers to and facilitators of treatment. This study examined gender-specific treatment needs in male patients and treatment approaches to male patients from a professional perspective. Methods Semi-structured face-to-face interviews were conducted with 33 mental health professionals (MHPs) from five German psychiatric institutions. The study assessed the characteristics and attributes of male patients with depression risk factors for the development of depression among men, their condition at the beginning of treatment, male patients’ depressive symptoms, the needs and expectations of male patients, the importance of social networks in a mental health context, and MHPs’ treatment aims and treatment methods. Transcripts were analysed using qualitative content analysis. Results The professionals’ reference group of male patients were men who were characterised in accordance with traditional masculinity. Attributes reported as in line with this type of men were late initiations of inpatient treatment after crisis, suicidal ideation or attempted suicide, and high expectations towards treatment duration, success rate in recovery and therapeutic sessions. In contrast, male patients who deviate from these patterns were partially described with reference to female stereotypes. Professionals referred to psychosocial models in their explanations of the causes of depression and provided sociological explanations for the development of masculine ideals among men. The consequences of these for treatment were discussed against the background of normative expectations regarding the male gender. From the professionals’ point of view, psychoeducation and the acceptance of depression (as a widespread mental illness) were the most important goals in mental health treatment. Conclusions In order to improve mental health among men, gender-specific services should be offered. Awareness of the role of gender and its implications on mental health treatment should be an integral part of MHPs’ education and their daily implementation of mental health treatment practices.

Abstract Background The community-based mental health care programme GBV is based on the British Community Mental Health Teams and the Dutch Flexible Assertive Community Treatment model. In addition, the programme offers crisis-intervention services. A special feature of this integrated care programme is the initial standardised assessment process regarding empowerment, unmet care needs, and psychosocial functioning, used to verify the need for such a comprehensive form of care. The project evaluates the assessment process and analyses the effectiveness and cost-effectiveness of GBV compared to treatment as usual. Methods This randomised, controlled study includes five assessments over 2 years. In twelve regions in Germany, 1000 patients with severely impaired psychosocial functioning and unmet care needs will be recruited. Study eligibility relies on an indication for GBV based on the results of the initial assessment. The primary outcome is improved self-reported empowerment. Further outcomes include improved treatment satisfaction and subjective quality of life, reductions in patients’ unmet needs and illness-related clinical and social impairment, and an improved cost-effectiveness ratio of the resources used (from the perspectives of both statutory health insurance and the national economy). In addition, the GBV’s effects on the burden and quality of life of informal caregivers of patients will be investigated. Discussion The study’s results are expected to provide information on whether the community-based mental health care programme GBV contributes to improving mental health care provision in Germany. In addition, the study will show whether the GBV successfully overcomes the weaknesses that former research has identified regarding a German integrated care programme. Such improvement is particularly expected with respect to the semi-structured assessment within GBV. Trial registration German Clinical Trial Register, DRKS00019086 . Registered on 3 January 2020.

Abstract Background The German guideline on psychosocial interventions for people with severe mental disorders recommends a broad spectrum of evidence-based treatments. Structured implementation of the associated patient version of the guideline is missing to date. The study aims to assess whether structured implementation of a patient guideline improves the empowerment of patients with severe mental disorders, as well as knowledge, attitudes and experiences regarding psychosocial interventions, service use, treatment satisfaction, treatment needs, quality of life and burden of care. Methods The study is a multicentre, cluster-randomised, controlled study with two parallel groups. Inpatients and day hospital patients (all sexes; 18–65 years) with severe mental disorders will be included. Additionally, relatives of patients with mental disorders (all sexes; ≥ 18 years) will be included. In the experimental group, the patient guideline will be implemented using a multimodal strategy. Participants in the control group will receive treatment as usual but will be made aware of the patient guideline. The primary outcome is the change of empowerment, assessed by using the ‘empowerment in the process of psychiatric treatment of patients with affective and schizophrenia disorders’ (EPAS) scale. In addition, knowledge, attitudes and experiences regarding psychosocial interventions will be assessed as secondary outcomes, as well as service use, satisfaction with care, patient need and quality of life and participation and social inclusion. For relatives, the perceived burden of care also will be recorded. Results will be analysed using hierarchical linear models. For the health economic evaluation, the incremental cost-utility ratios will be computed using the differences in total costs of illness and the differences in quality-adjusted life years (QALY) between study groups. Discussion The study will be the first to assess the effects of a structured implementation of the patient version of a psychiatric treatment guideline. The study has some limitations regarding the transferability of the results to other patients and other regions. Furthermore, problems with the recruitment of patients and relatives and with the implementation of intervention could occur during the study. Trial registration The study is registered in the German Clinical Trials Register (DRKS) and the WHO International Clinical Trials Registry Platform (ICTRP) under registration number DRKS00017577 (Date of registration: 23 October 2019.

Abstract Background Liquid biopsies of blood plasma cell free DNA can be used to monitor treatment response and potentially detect mutations that are present in resistant clones in metastatic cancer patients. Case presentation In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3 cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle, CT imaging, CEA and CA19–9 markers validated the cfDNA findings of treatment response. However, 5 weeks later, the tumour had rapidly progressed. Conclusion As FOLFIRI+Bevacizumab has recently also been associated with sustained complete remission in a APC/TP53/KRAS triple-mutated patient, these driver genes should be tested and monitored in a more in-depth manner in future patients. Patients with metastatic disease should be monitored more closely during and after chemotherapy, ideally using cfDNA.

Purpose Beyond its direct effects on physical health the COVID-19 pandemic has been shown to have negative effects on the living situation of people with severe mental illness (SMI). To date, there has been little research on resilience factors preventing people with SMI from experiencing negative effects of the COVID-19 pandemic. The objective of this study was to investigate the role of perceived empowerment (PE) as a resilience factor, preventing people with SMI from experiencing negative effects of the COVID-19 pandemic on daily living. Methods We investigated negative effects of the COVID-19 pandemic on daily living in 931 persons with SMI at two times within six month between June 2020 and Mai 2021. To take into account the longitudinal structure of the data we applied mixed effects regression analyses and longitudinal path models. Results A majority of participants experienced negative effects of the COVID-19 pandemic on several dimensions of daily living. Negative effects increased with rising levels of illness-related impairment but decreased as the level of PE rose. While negative effects of the COVID-19 pandemic at follow-up were negatively associated with overall subjective quality of life baseline, PE was negatively associated with the negative impact of the pandemic and positively with quality of life. Conclusion Patients with SMI need support to reduce negative effects of the COVID-19 pandemic on their quality of life. The promotion of PE could help strengthen resilience in this target group. Trial registration German Clinical Trial Register, DRKS00019086, registered on 3 January 2020. (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00019086).

Summary: Invaginations of the mitochondrial inner membrane, termed cristae, are hubs for oxidative phosphorylation. The mitochondrial contact site and cristae organizing system (MICOS) and the dimeric F1Fo-ATP synthase play important roles in controlling cristae architecture. A fraction of the MICOS core subunit Mic10 is found in association with the ATP synthase, yet it is unknown whether this interaction is of relevance for mitochondrial or cellular functions. Here, we established conditions to selectively study the role of Mic10 at the ATP synthase. Mic10 variants impaired in MICOS functions stimulate ATP synthase oligomerization like wild-type Mic10 and promote efficient inner membrane energization, adaptation to non-fermentable carbon sources, and respiratory growth. Mic10's functions in respiratory growth largely depend on Mic10ATPsynthase, not on Mic10MICOS. We conclude that Mic10 plays a dual role as core subunit of MICOS and as partner of the F1Fo-ATP synthase, serving distinct functions in cristae shaping and respiratory adaptation and growth.

A soft sensor concept is typically developed and calibrated for individual bioprocesses in a time-consuming manual procedure. Following that, the prediction performance of these soft sensors degrades over time, due to changes in raw materials, biological variability, and modified process strategies. Through automatic adaptation and recalibration, adaptive soft sensor concepts have the potential to generalize soft sensor principles and make them applicable across bioprocesses. In this study, a new generalized adaptation algorithm for soft sensors is developed to provide phase-dependent recalibration of soft sensors based on multiway principal component analysis, a similarity analysis, and robust, generalist phase detection in multiphase bioprocesses. This generalist soft sensor concept was evaluated in two multiphase bioprocesses with various target values, media, and microorganisms. Consequently, the soft sensor concept was tested for biomass prediction in a Pichia pastoris process, and biomass and protein prediction in a Bacillus subtilis process, where the process characteristics (cultivation media and cultivation strategy) were varied. High prediction performance was demonstrated for P. pastoris processes (relative error = 6.9%) as well as B. subtilis processes in two different media during batch and fed-batch phases (relative errors in optimized high-performance medium: biomass prediction = 12.2%, protein prediction = 7.2%; relative errors in standard medium: biomass prediction = 12.8%, protein prediction = 8.8%).

Mitochondria contain two membranes, the outer and inner membrane. The outer membrane fulfills crucial functions for the communication of mitochondria with the cellular environment like exchange of lipids via organelle contact sites, the transport of metabolites and the formation of a signaling platform in apoptosis and innate immunity. The translocase of the outer membrane (TOM complex) forms the entry gate for the vast majority of precursor proteins that are produced on cytosolic ribosomes. Surveillance of the functionality of outer membrane proteins is critical for mitochondrial functions and biogenesis. Quality control mechanisms remove defective and mistargeted proteins from the outer membrane as well as precursor proteins that clog the TOM complex. Selective degradation of single proteins is also an important mode to regulate mitochondrial dynamics and initiation of mitophagy pathways. Whereas inner mitochondrial compartments are equipped with specific proteases, the ubiquitin-proteasome system is a central player in protein surveillance on the mitochondrial surface. In this review, we summarize our current knowledge about the molecular mechanisms that govern quality control of proteins at the outer mitochondrial membrane.

Among the greatest challenges in soft sensor development for bioprocesses are variable process lengths, multiple process phases, and erroneous model inputs due to sensor faults. This review article describes these three challenges and critically discusses the corresponding solution approaches from a data scientist’s perspective. This main part of the article is preceded by an overview of the status quo in the development and application of soft sensors. The scope of this article is mainly the upstream part of bioprocesses, although the solution approaches are in most cases also applicable to the downstream part. Variable process lengths are accounted for by data synchronization techniques such as indicator variables, curve registration, and dynamic time warping. Multiple process phases are partitioned by trajectory or correlation-based phase detection, enabling phase-adaptive modeling. Sensor faults are detected by symptom signals, pattern recognition, or by changing contributions of the corresponding sensor to a process model. According to the current state of the literature, tolerance to sensor faults remains the greatest challenge in soft sensor development, especially in the presence of variable process lengths and multiple process phases.

Abstract Background Aspergillus fumigatus infections frequently occur after solid organ transplantation. Yet, a fungal thrombosis after liver transplantation is an exceptional finding. Case presentation We report on a 44-year-old female with an aspergillosis after liver transplantation for autoimmune hepatitis. On postoperative day (pod) 7, seizures occurred and imaging diagnostics revealed an intracranial lesion. Anidulafungin was initiated in suspicion of mycosis and switched to voriconazole on suspicion of an Aspergillus spp. infection. Progression of the cerebral lesion prompted craniotomy (pod 48) and the aspergillosis was verified. The patient was discharged with oral voriconazole therapy. Re-admission was necessary with acute-on-chronic renal failure after a tacrolimus overdose on pod 130. The patient received a pelvic angiography due to a temperature difference in the legs. It showed a complete iliac artery thrombosis which was subsecutively surgically removed. The histopathological examination revealed an Aspergillus fumigatus conglomerate. The patient died on pod 210 due to systemic aspergillosis. Conclusion The acute development of focal neurologic deficits is common in patients with an aspergillosis of the brain. Nevertheless, arterial thrombosis after Aspergillus fumigatus is less frequent and, to the best of our knowledge, its occurrence after liver transplantation has not yet been reported so far. Due to its rarity, we added a review of the literature to this manuscript.

Abstract Background Surgical robots are increasingly being used in bariatric surgery. While several studies describe the safety of using barbed sutures in laparoscopic gastric bypass surgery, no reports are available for robotic bariatric procedures. The aim of our article is to determine whether barbed sutures can be used safely in robotic Roux-en-Y bypass (RYGB) surgery. Methods This was a single-center, single-surgeon case series of RYGB procedures using the da Vinci® Xi Surgical System (Intuitive Surgery, Sunnyvale, CA, USA) in combination with the use of barbed sutures (Stratafix, Ethicon, Johnson & Johnson, Cincinnati, OH, USA). Results Fifty robotic proximal and distal RYGB surgeries were performed. A linear stapled, side-to-side gastrojejunostomy was carried out, whereby the enterotomy was completed with a running resorbable unidirectional barbed suture, Stratafix 2–0. In one case after robotic proximal RYGB, revision surgery was required due to omentum necrosis. Another patient was readmitted due to gastrointestinal bleeding from anastomosis. No anastomotic insufficiencies, no stenoses, or higher-grade complications according to Clavien-Dindo 4a-5 were found. Conclusions We found that the use of self-fixing barbed sutures in robotic RYGB is safe. The self-fixing suture enables the robotic surgeon to perform a simple continuous suture without the need for recurrent retraction. Although we are the first to report this procedure, we had a low number of cases and no control group; thus, further studies with a higher level of evidence are required.

Consumer health concerns and regulatory policies lead to a growing demand for sugar-sweetened beverage alternatives. A reduced energy content can be achieved using artificial sweeteners, which often also convey a metallic or bitter off-flavor. Therefore, the alteration of sweetness perception and masking of potential off-flavors are paramount for improving sweet beverages. Trigeminal stimuli, such as capsaicin (spicy) or menthol (cooling), have been used to influence taste perception in food items, although their use in beverages has not yet been systematically investigated. Here, the influence of menthol on sweetness perception in an aqueous solution is examined both on the sensory and psychophysiological level. The addition of menthol had no sensory effect on sweetness perception; however, psychophysiological measurements suggest a boost in the physiological response to cold perception through the addition of sugar. Moreover, menthol addition shifted the recognition threshold of unpleasant bitterness of the sweetener acesulfame-K from 21.35 to 36.93 mg/L, masking the off-flavor. These findings illuminate the complexity of trigeminal perception influences on taste. Further investigation of these effects can render trigeminal stimuli an effective tool to enhance beverage aroma and flavor.

In yeast, aging is widely understood as the decline of physiological function and the decreasing ability to adapt to environmental changes. Saccharomyces cerevisiae has become an important model organism for the investigation of these processes. Yeast is used in industrial processes (beer and wine production), and several stress conditions can influence its intracellular aging processes. The aim of this review is to summarize the current knowledge on applied stress conditions, such as osmotic pressure, primary metabolites (e.g., ethanol), low pH, oxidative stress, heat on aging indicators, age-related physiological changes, and yeast longevity. There is clear evidence that yeast cells are exposed to many stressors influencing viability and vitality, leading to an age-related shift in age distribution. Currently, there is a lack of rapid, non-invasive methods allowing the investigation of aspects of yeast aging in real time on a single-cell basis using the high-throughput approach. Methods such as micromanipulation, centrifugal elutriator, or biotinylation do not provide real-time information on age distributions in industrial processes. In contrast, innovative approaches, such as non-invasive fluorescence coupled flow cytometry intended for high-throughput measurements, could be promising for determining the replicative age of yeast cells in fermentation and its impact on industrial stress conditions.

IntroductionLiquid biopsies allowing for individualized risk stratification of cancer patients have become of high significance in individualized cancer diagnostics and treatment. The detection of circulating tumor cells (CTC) has proven to be highly relevant in risk prediction, e.g., in colorectal cancer (CRC) patients. In this study, we investigate the clinical relevance of longitudinal CTC detection over a course of follow-up after surgical resection of the tumor and correlate these findings with clinico-pathological characteristics.MethodsIn total, 49 patients with histologically proven colorectal carcinoma were recruited for this prospective study. Blood samples were analyzed for CTC presence by two methods: first by marker-dependent immunofluorescence staining combined with automated microscopy with the NYONE® cell imager and additionally, indirectly, by semi-quantitative Cytokeratin-20 (CK20) RT-qPCR. CTC quantification data were compared and correlated with the clinico-pathological parameters.ResultsDetection of CTC over a post-operative time course was feasible with both applied methods. In patients who were pre-operatively negative for CTCs with the NYONE® method or below the cut-off for relative CK20 mRNA expression after analysis by PCR, a statistically significant rise in the immediate post-operative CTC detection could be demonstrated. Further, in the cohort analyzed by PCR, we detected a lower CTC load in patients who were adjuvantly treated with chemotherapy compared to patients in the follow-up subgroup. This finding was contrary to the same patient subset analyzed with the NYONE® for CTC detection.ConclusionOur study investigates the occurrence of CTC in CRC patients after surgical resection of the primary tumor and during postoperative follow-up. The resection of the tumor has an impact on the CTC quantity and the longitudinal CTC analysis supports the significance of CTC as a prognostic biomarker. Future investigations with an even more extended follow-up period and larger patient cohorts will have to validate our results and may help to define an optimal longitudinal sampling scheme for liquid biopsies in the post-operative monitoring of cancer patients to enable tailored therapy concepts for precision medicine.

Zebrafish exhibit robust regeneration following spinal cord injury, promoted by macrophages that control post-injury inflammation. However, the mechanistic basis of how macrophages regulate regeneration is poorly understood. To address this gap in understanding, we conducted a rapid in vivo phenotypic screen for macrophage-related genes that promote regeneration after spinal injury. We used acute injection of synthetic RNA Oligo CRISPR guide RNAs (sCrRNAs) that were pre-screened for high activity in vivo. Pre-screening of over 350 sCrRNAs allowed us to rapidly identify highly active sCrRNAs (up to half, abbreviated as haCRs) and to effectively target 30 potentially macrophage-related genes. Disruption of 10 of these genes impaired axonal regeneration following spinal cord injury. We selected 5 genes for further analysis and generated stable mutants using haCRs. Four of these mutants (tgfb1a, tgfb3, tnfa, sparc) retained the acute haCR phenotype, validating the approach. Mechanistically, tgfb1a haCR-injected and stable mutant zebrafish fail to resolve post-injury inflammation, indicated by prolonged presence of neutrophils and increased levels of il1b expression. Inhibition of Il-1β rescues the impaired axon regeneration in the tgfb1a mutant. Hence, our rapid and scalable screening approach has identified functional regulators of spinal cord regeneration, but can be applied to any biological function of interest.

Background: Human rights violations such as torture are associated with a high risk of post-traumatic stress disorder (PTSD). The judgements of the European Court of Human Rights (ECtHR) include a normative perspective on PTSD and address central ethical questions. Objective: To help bridge the gap between the psycho-medical and the legal discourse on human rights violations and to illustrate their medico-ethical implications by systematically assessing and categorizing all judgements by the ECtHR dealing with PTSD. Method: The ECtHR database was searched for ‘post-traumatic stress disorder’. A descriptive statistic was performed on the Articles of the European Convention on Human Rights involved and violations to these articles. In a qualitative analysis, the judgements were thematically grouped. Results: The search yielded n = 103 judgements, of which n = 90 were included. There were mostly violations of Article 3 (prohibition of torture), Article 8 (Right to respect for private and family life) and Article 6 (Right to a fair trial). PTSD in these judgements is normatively discussed with regards to ethical, social and political themes such as inadequate access to healthcare, especially in prison, matters of asylum, expulsion and extradition, protection of minorities and minors, as well as rights and duties of traumatized witnesses. Conclusion: PTSD plays a central role in a large number of ECtHR judgements. Our results show that PTSD as a medical diagnosis also encompasses legal, ethical, social, and political dimensions. This knowledge is essential for healthcare professionals working with traumatized persons, but can also be relevant for political decision-makers.