Publications by authors named "Thomas Becker"

827 Publications

The Role of ICG in Robot-Assisted Liver Resections.

J Clin Med 2022 Jun 19;11(12). Epub 2022 Jun 19.

Department of General, Abdominal, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, 24105 Kiel, Germany.

Introduction: Robotic-assisted liver surgery (RALS) with its known limitations is gaining more importance. The fluorescent dye, indocyanine green (ICG), is a way to overcome some of these limitations. It accumulates in or around hepatic masses. The integrated near-infrared cameras help to visualize this accumulation. We aimed to compare the influence of ICG staining on the surgical and oncological outcomes in patients undergoing RALS.

Material And Methods: Patients who underwent RALS between 2014 and 2021 at the Department of General Surgery at the University Hospital Schleswig-Holstein, Campus Kiel, were included. In 2019, ICG-supported RALS was introduced.

Results: Fifty-four patients were included, with twenty-eight patients (50.9%) receiving preoperative ICG. Hepatocellular carcinoma (32.1%) was the main entity resected, followed by the metastasis of colorectal cancers (17%) and focal nodular hyperplasia (15.1%). ICG staining worked for different tumor entities, but diffuse staining was noted in patients with liver cirrhosis. However, ICG-supported RALS lasted shorter (142.7 ± 61.8 min vs. 246.4 ± 98.6 min, < 0.001), tumors resected in the ICG cohort were significantly smaller (27.1 ± 25.0 mm vs. 47.6 ± 35.2 mm, = 0.021) and more R0 resections were achieved by ICG-supported RALS (96.3% vs. 80.8%, = 0.075).

Conclusions: ICG-supported RALS achieve surgically and oncologically safe results, while overcoming the limitations of RALS.
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http://dx.doi.org/10.3390/jcm11123527DOI Listing
June 2022

Investigations on Backflush Cleaning of Spent Grain-Contaminated Filter Cloths Using Continuous and Pulsed Jets.

Foods 2022 Jun 15;11(12). Epub 2022 Jun 15.

Chair of Brewing and Beverage Technology, School of Life Sciences, Technical University of Munich, Weihenstephaner Steig 20, 85354 Freising, Germany.

This study investigated the continuous and pulsed backflush cleaning of woven fabrics that act as filter media in the food and beverage industry. Especially in breweries, they are commonly used in mash filters to separate solid spent grains from liquid wort. After filtration, the removal of such cereal residues via self-discharge is necessary. However, this filter cake discharge is typically incomplete, and various spots remain contaminated. In addition to the reduced filter performance of subsequent batches, cross-contamination risk increases significantly. A reproducible contamination method focusing on the use case of a mash filter was developed for this study. Additionally, a residue analysis based on microscopical image processing helped to assess cleaning efficiency. The experimental part compared two backflushing procedures for mash filters and demonstrated fluid dynamical, procedural, and economic differences in cleaning. Specifically, pulsed jets show higher efficiency in reaching cleanliness faster, with fewer cleaning agents and less time. According to the experimental results, the fluid flow conditions depended highly on cloth geometry and mesh sizes. Larger mesh sizes significantly favored the cloth's cleanability as a larger backflush volume can reach contamination. With these results, cloth cleaning can be improved, enabling the realization of demand-oriented cleaning concepts.
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http://dx.doi.org/10.3390/foods11121757DOI Listing
June 2022

[Hepatocellular carcinoma].

Chirurgie (Heidelb) 2022 Jun 17. Epub 2022 Jun 17.

Klinik für Allgemeine Chirurgie, Viszeral‑, Thorax- Transplantations- und Kinderchirurgie, Universitätsklinikum Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Deutschland.

The therapeutic spectrum of hepatocellular carcinoma (HCC) in cirrhosis has expanded over the last decade and consists of surgical, interventional and systemic approaches. The tumor stage and liver function are important for the therapeutic strategy. Curation can be achieved by liver resection or transplantation. Access to transplantation is limited by organ shortage and waiting time. Locoregional therapies can be used as a bridge to transplant or for down-sizing in a neoadjuvant setting as well as palliative therapy. Advanced stages might benefit from systemic or immunotherapy. Modern multimodal therapy planning, timing and reevaluation are part of the tasks of tumor boards specialised in the liver, including the option of liver transplantation. Therapies can be used alone or in combination and according to the experience of the center. A curative strategy should always be pursued at initial presentation.
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http://dx.doi.org/10.1007/s00104-022-01661-4DOI Listing
June 2022

The Cost-Effectiveness Analysis of an Integrated Mental Health Care Programme in Germany.

Int J Environ Res Public Health 2022 Jun 2;19(11). Epub 2022 Jun 2.

Department of Psychiatry II, Ulm University, Bezirkskrankenhaus Günzburg, 89312 Günzburg, Germany.

The network for mental health (NWpG = Netzwerk psychische Gesundheit) is an umbrella association for non-medical community mental health care facilities across Germany which are enabled to provide multi-professional mental health care packages including medical and psychosocial services reimbursed by German statutory health insurances since 2009. The aim of this study is to analyse the cost-effectiveness of providing NWpG mental health care packages plus treatment as usual (NWpG) to treatment as usual alone (TAU) in Germany. In a prospective, multicenter, controlled trial over 18 months, a total of 511 patients (NWpG = 251; TAU = 260) were observed in five regions, four times at six-month intervals. The EQ-5D-3L and the Client Sociodemographic and Service Receipt Inventory (CSSRI) were used to estimate quality-adjusted life-years and total costs of illness. Propensity score-adjusted cost-utility analysis was applied using the net benefit approach. No significant differences in costs and QALYs between NWpG and TAU groups were identified. The probability of NWpG being cost-effective compared to TAU was estimated below 75% for maximum willingness to pay (MWTP) values between 0 and 125,000 EUR. The additional provision of the NWpG package is not cost-effective compared to TAU alone.
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http://dx.doi.org/10.3390/ijerph19116814DOI Listing
June 2022

Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of Differences Between Alcohol-Related and Non-Alcohol-Related Cirrhosis Candidates.

Ann Transplant 2022 Jun 7;27:e936293. Epub 2022 Jun 7.

Department of Psychiatry and Psychotherapy, University of Basel, Basel, Switzerland.

BACKGROUND Monitoring sobriety is mandatory for liver transplant (LT) candidates with alcohol-related cirrhosis in Germany. Prior to listing, abstinence of 6 months is required. However, little is known about biomarker performance in alcohol-related cirrhosis. Routine testing of ethyl glucuronide in urine (uEtG) or hair (hEtG) is prone to manipulation or is unfeasible in anuria. Phosphatidylethanol (PEth) in dried-blood spots is a promising alternative. We compared PEth with routine parameters and self-reports in alcohol-related and non-alcohol-related cirrhosis at our transplant center. MATERIAL AND METHODS All patients received self-report questionnaires (AUDIT & TLFB). Blood, urine and hair samples, as well as PEth dried-blood spots were drawn at baseline. In addition, survival analyses were conducted. RESULTS Out of 66 patients, 53 were listed for LT and 13 were candidates not listed so far. An alcohol-use disorder was found in 25 patients. Positive results for uEtG, hEtG, and PEth were found in 5/65, 9/65, and 34/66 cases, respectively. PEth positivity was found in 52% of patients with alcohol-related cirrhosis, while 53% of patients with other liver diseases were positive. While uEtG, hEtG, and TLFB correlated with higher PEth values, active waiting list status was significantly correlated with negative PEth values. During the mean follow-up of 41.15 months, 23 patients were transplanted (34.9%). None of the biomarkers significantly predicted survival. CONCLUSIONS PEth can importantly assist abstinence monitoring in LT candidates due to its high validity and objectivity. The high percentage of patients with alcohol consumption in the non-alcoholic liver disease cohort underscores the importance of testing all transplant candidates.
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http://dx.doi.org/10.12659/AOT.936293DOI Listing
June 2022

Identification of potential odorant markers to monitor the aroma formation in kilned specialty malts.

Food Chem 2022 Oct 18;392:133251. Epub 2022 May 18.

Chair of Brewing and Beverage Technology, Technical University of Munich, Weihenstephaner Steig 20, 85354 Freising, Germany.

Specialty malts are strategic ingredients regarding their contribution to colour and flavour of beer. Malts with the same colour may present distinct flavour characteristics and intensities. Contradictorily, colour is the benchmark in practical quality control. To investigate the correlation between colour and flavour of kilned barley specialty malts, odorants of commercial products of pale ale (5-9 EBC), Vienna (6-10 EBC), Munich (11-35 EBC) and melanoidin malts (80-90 EBC) were screened via solvent-assisted flavour evaporation (SAFE) and compared via comparative aroma extract dilution analysis (cAEDA). Subsequently, selected odorants were quantified using solid-phase microextraction (SPME). A total of 34 odorants were detected, of which 12 exhibited a concentration increase as the coloration increased, whereas 4 suggested the influence of temperature and modification degree on aroma formation. Such odorants are thus elected as potential markers for monitoring the influence of process variations on the formation of aroma in commercial kilned specialty malts.
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http://dx.doi.org/10.1016/j.foodchem.2022.133251DOI Listing
October 2022

Paracrine Interaction of Cholangiocellular Carcinoma with Cancer-Associated Fibroblasts and Schwann Cells Impact Cell Migration.

J Clin Med 2022 May 15;11(10). Epub 2022 May 15.

Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, Arnold-Heller-Str. 3, Building C, 24105 Kiel, Germany.

Although the Mitogen-activated protein kinase (MAPK) pathway is enriched in cholangiocarcinoma (CCA), treatment with the multityrosine kinase-inhibitor Sorafenib is disappointing. While cancer-associated fibroblasts (CAF) are known to contribute to treatment resistance in CCA, knowledge is lacking for Schwann cells (SC). We investigated the impact of stromal cells on CCA cells and whether this is affected by Sorafenib. Immunohistochemistry revealed elevated expression of CAF and SC markers significantly correlating with reduced tumor-free survival. In co-culture with CAF, CCA cells mostly migrated, which could be diminished by Sorafenib, while in SC co-cultures, SC predominantly migrated towards CCA cells, unaffected by Sorafenib. Moreover, increased secretion of pro-inflammatory cytokines MCP-1, CXCL-1, IL-6 and IL-8 was determined in CAF mono- and co-cultures, which could be reduced by Sorafenib. Corresponding to migration results, an increased expression of phospho-AKT was measured in CAF co-cultured HuCCT-1 cells, although was unaffected by Sorafenib. Intriguingly, CAF co-cultured TFK-1 cells showed increased activation of STAT3, JNK, ERK and AKT pathways, which was partly reduced by Sorafenib. This study indicates that CAF and SC differentially impact CCA cells and Sorafenib partially reverts these stroma-mediated effects. These findings contribute to a better understanding of the paracrine interplay of CAF and SC with CCA cells.
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http://dx.doi.org/10.3390/jcm11102785DOI Listing
May 2022

Combined Longitudinal and Surface Acoustic Wave Analysis for Determining Small Filling Levels in Curved Steel Containers.

Sensors (Basel) 2022 May 3;22(9). Epub 2022 May 3.

Institute of Brewing and Beverage Technology, Technical University of Munich, 85354 Freising, Germany.

Measurement of the small filling levels in closed steel container systems is still a challenge. Ultrasound, however, is a sensitive and non-invasive technique and is suitable for online monitoring. This study describes a new ultrasonic sensor system for sensing small filling levels using longitudinal and surface acoustic wave analysis. The sensor system consists of one transducer for the longitudinal wave analysis and two transducers for the longitudinal and surface acoustic wave analysis. All transducers were mounted to the outer wall of the steel container, ensuring non-invasiveness, and a filling level ranging from 0 to 5 cm was investigated. Combining both approaches, a consistent determination of small filling levels was achieved for the entire measuring range (R = 0.99).
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http://dx.doi.org/10.3390/s22093476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102324PMC
May 2022

Relation between polymer transitions and the extensional viscosity of dough systems during thermal stabilization assessed by lubricated squeezing flow.

Food Chem 2022 Sep 22;389:133048. Epub 2022 Apr 22.

Research Group Cereal Technology and Process Engineering, Chair of Brewing and Beverage Technology, Technical University of Munich, 85354 Freising, Germany.

Polymer transitions occurring during the thermal processing of dough are defining the rheological behaviour of solidifying dough. Yeast, an essential ingredient in breadmaking, plays an important role in this transformation process, but its impact on the transitional behavior of the polymers remains unknown. Therefore, the aim of this study was to elucidate the impact of hydrothermally induced polymer transitions on the elongational rheological behavior of dough under process-relevant strain-strain-rate combinations transitions in dependence of the presence of yeast. Using elongational rheology together with DSC, TD-NMR and microscopy, yeast-induced degradation on the microstructural level (average decrease of protein strand length of 46%) and microstructural level were shown to affect the course of the starch gelatinization process and the functionality of gluten while baking. These findings can be used to relate oven rise performance to fundamental rheological behavior based on occurring phase transitions, leading to a more comprehensive process understanding.
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http://dx.doi.org/10.1016/j.foodchem.2022.133048DOI Listing
September 2022

Crosstalk between Mitochondrial Protein Import and Lipids.

Int J Mol Sci 2022 May 9;23(9). Epub 2022 May 9.

Institute for Biochemistry and Molecular Biology, Faculty of Medicine, University of Bonn, 53115 Bonn, Germany.

Mitochondria import about 1000 precursor proteins from the cytosol. The translocase of the outer membrane (TOM complex) forms the major entry site for precursor proteins. Subsequently, membrane-bound protein translocases sort the precursor proteins into the outer and inner membrane, the intermembrane space, and the matrix. The phospholipid composition of mitochondrial membranes is critical for protein import. Structural and biochemical data revealed that phospholipids affect the stability and activity of mitochondrial protein translocases. Integration of proteins into the target membrane involves rearrangement of phospholipids and distortion of the lipid bilayer. Phospholipids are present in the interface between subunits of protein translocases and affect the dynamic coupling of partner proteins. Phospholipids are required for full activity of the respiratory chain to generate membrane potential, which in turn drives protein import across and into the inner membrane. Finally, outer membrane protein translocases are closely linked to organellar contact sites that mediate lipid trafficking. Altogether, intensive crosstalk between mitochondrial protein import and lipid biogenesis controls mitochondrial biogenesis.
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http://dx.doi.org/10.3390/ijms23095274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101885PMC
May 2022

Regenerative neurogenesis: the integration of developmental, physiological and immune signals.

Development 2022 Apr 3;149(8). Epub 2022 May 3.

Center for Regenerative Therapies at the TU Dresden, Technische Universität Dresden, 01307 Dresden, Germany.

In fishes and salamanders, but not mammals, neural stem cells switch back to neurogenesis after injury. The signalling environment of neural stem cells is strongly altered by the presence of damaged cells and an influx of immune, as well as other, cells. Here, we summarise our recently expanded knowledge of developmental, physiological and immune signals that act on neural stem cells in the zebrafish central nervous system to directly, or indirectly, influence their neurogenic state. These signals act on several intracellular pathways, which leads to changes in chromatin accessibility and gene expression, ultimately resulting in regenerative neurogenesis. Translational approaches in non-regenerating mammals indicate that central nervous system stem cells can be reprogrammed for neurogenesis. Understanding signalling mechanisms in naturally regenerating species show the path to experimentally promoting neurogenesis in mammals.
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http://dx.doi.org/10.1242/dev.199907DOI Listing
April 2022

Robotic-assisted minimally invasive Ivor Lewis esophagectomy within the prospective multicenter German da Vinci Xi registry trial.

Langenbecks Arch Surg 2022 May 2. Epub 2022 May 2.

Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany.

Purpose: Robotic-assisted minimally invasive esophagectomy (RAMIE) has become one standard approach for the operative treatment of esophageal tumors at specialized centers. Here, we report the results of a prospective multicenter registry for standardized RAMIE.

Methods: The German da Vinci Xi registry trial included all consecutive patients who underwent RAMIE at five tertiary university centers between Oct 17, 2017, and Jun 5, 2020. RAMIE was performed according to a standard technique using an intrathoracic circular stapled esophagogastrostomy.

Results: A total of 220 patients were included. The median age was 64 years. Total minimally invasive RAMIE was accomplished in 85.9%; hybrid resection with robotic-assisted thoracic approach was accomplished in an additional 11.4%. A circular stapler size of ≥28 mm was used in 84%, and the median blood loss and operative time were 200 (IQR: 80-400) ml and 425 (IQR: 335-527) min, respectively. The rate of anastomotic leakage was 13.2% (n=29), whereas the two centers with >70 cases each had rates of 7.0% and 12.0%. Pneumonia occurred in 19.5% of patients, and the 90-day mortality was 3.6%. Cumulative sum analysis of the operative time indicated the end of the learning curve after 22 cases.

Conclusions: High-quality multicenter registry data confirm that RAMIE is a safe procedure and can be reproduced with acceptable leak rates in a multicenter setting. The learning curve is comparably low for experienced robotic surgeons.
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http://dx.doi.org/10.1007/s00423-022-02520-wDOI Listing
May 2022

Recombinant protein linker production as a basis for non-invasive determination of single-cell yeast age in heterogeneous yeast populations.

RSC Adv 2021 Sep 28;11(51):31923-31932. Epub 2021 Sep 28.

Technical University of Munich, Chair of Brewing and Beverage Technology, Research Group Beverage and Cereal Biotechnology Weihenstephaner Steig 20 85354 Freising Germany

The physiological and metabolic diversity of a yeast culture is the sum of individual cell phenotypes. As well as environmental conditions, genetics, and numbers of cell divisions, a major factor influencing cell characteristics is cell age. A postcytokinesis bud scar on the mother cell, a benchmark in the replicative life span, is a quantifiable indicator of cell age, characterized by significant amounts of chitin. We developed a binding process for visualizing the bud scars of var. using a protein linker containing a polyhistidine tag, a superfolder green fluorescent protein (sfGFP), and a chitin-binding domain (His6-SUMO-sfGFP-ChBD). The binding did not affect yeast viability; thus, our method provides the basis for non-invasive cell age determination using flow cytometry. The His6-SUMO-sfGFP-ChBD protein was synthesized in , purified using two-stage chromatography, and checked for monodispersity and purity. Linker-cell binding and the characteristics of the bound complex were determined using flow cytometry and confocal laser scanning microscopy (CLSM). Flow cytometry showed that protein binding increased to 60 455 ± 2706 fluorescence units per cell. The specific coupling of the linker to yeast cells was additionally verified by CLSM and adsorption isotherms using yeast cells, cells, and chitin resin. We found a relationship between the median bud scar number, the median of the fluorescence units, and the chitin content of yeast cells. A fast measurement of yeast population dynamics by flow cytometry is possible, using this protein binding technique. Rapid qualitative determination of yeast cell age distribution can therefore be performed.
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http://dx.doi.org/10.1039/d1ra05276dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041608PMC
September 2021

Screening of Mycotoxigenic Fungi in Barley and Barley Malt ( L.) Using Real-Time PCR-A Comparison between Molecular Diagnostic and Culture Technique.

Foods 2022 Apr 15;11(8). Epub 2022 Apr 15.

Chair of Brewing and Beverage Technology, TUM School of Life Sciences, Technical University of Munich, 85354 Freising, Germany.

Filamentous fungi have a crucial impact on the food safety and technological quality of malting barley. Commonly used techniques for the detection of seed-borne fungi are based on cultivation and identification by morphological criteria. In contrast, this study established a quantitative real-time polymerase chain reaction (PCR) assay based on SYBR green technology for the detection and quantification of black fungal species ( spp., , , and ) on brewing barley and compares it with the traditional cultivation technique and visual assessment. To screen the fungal spectrum over different barley varieties and harvest years, naturally infected samples of malting barley and corresponding malts ( L.) were analyzed over four consecutive years (2018-2021), grown under different climatic conditions in Germany. and spp. DNA were present in all examined barley samples, even without visible contamination. In contrast, detection via culture-based methods does not reliably cover all species. Molecular analysis showed that there was less fungal biomass after malting, by 58.57% in the case of , by 28.27% for spp. and by 12.79% for . Correlation analysis showed no causal relationship between fungal DNA and the number of black kernels. The qPCR provides a highly sensitive and time-saving screening method for detecting latent fungal infections in brewing grains to identify batches that are potentially highly contaminated with toxigenic fungi.
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http://dx.doi.org/10.3390/foods11081149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030328PMC
April 2022

Eso-Sponge® for anastomotic leakage after oesophageal resection or perforation: outcomes from a national, prospective multicentre registry.

BJS Open 2022 03;6(2)

Department of General Surgery, University Hospital Rostock, Rostock, Germany.

Background: Anastomotic leakage (AL) after oesophagectomy and oesophageal perforations are associated with significant morbidity and mortality. Minimally invasive endoscopy is often used as first-line treatment, particularly endoluminal vacuum therapy (EVT). The aim was to assess the performance of the first commercially available endoluminal vacuum device (Eso-Sponge®) in the management of AL and perforation of the upper gastrointestinal tract (GIT).

Methods: The Eso-Sponge® registry was designed in 2014 as a prospective, observational, national, multicentre registry. Patients were recruited with either AL or perforation within the upper GIT. Data were collected with a standardized form and transferred into a web-based platform. Twenty hospitals were enrolled at the beginning of the study (registration number NCT02662777; http://www.clinicaltrials.gov). The primary endpoint was successful closure of the oesophageal defect.

Results: Eleven out of 20 centres recruited patients. A total of 102 patients were included in this interim analysis; 69 patients with AL and 33 with a perforation were treated by EVT. In the AL group, a closure of 91 per cent was observed and 76 per cent was observed in the perforation group. The occurrence of mediastinitis (P = 0.002) and the location of the defect (P = 0.008) were identified as significant predictors of defect closure.

Conclusions: The Eso-Sponge® registry offers the opportunity to collate data on EVT with a uniform, commercially available product to improve standardization. Our data show that EVT with the Eso-Sponge® is an option for the management of AL and perforation within the upper GIT.
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http://dx.doi.org/10.1093/bjsopen/zrac030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023777PMC
March 2022

Coupling to Pam16 differentially controls the dual role of Pam18 in protein import and respiratory chain formation.

Cell Rep 2022 04;39(1):110619

Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Bonn, 53115 Bonn, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.celrep.2022.110619DOI Listing
April 2022

Ensemble-based adaptive soft sensor for fault-tolerant biomass monitoring.

Eng Life Sci 2022 Mar 8;22(3-4):229-241. Epub 2022 Jan 8.

Chair of Brewing and Beverage Technology Technical University of Munich Freising Germany.

The accuracy and precision of soft sensors depend strongly on the reliability of underlying model inputs. These inputs (particularly readings of hardware sensors) are frequently subject to faults. This study aims to develop an adaptive soft sensor capable of reliable and robust biomass concentration predictions in the presence of faulty model inputs for a bioprocess. Hence, three soft sensor submodels were developed based on three independent model inputs (base addition, CO production, and mid-infrared spectrum). An ensemble-based algorithm combined the submodels to form an ensemble model, that is, an adaptive soft sensor, to achieve fault-tolerant prediction. The algorithm's basic steps are as follows: the initial determination of submodel reliability is followed by selecting appropriate submodels to generate a reliable prediction via variance-based weighting of the submodels. The adaptive soft sensor demonstrated high robustness and accuracy in biomass prediction in the presence of multiple simulated sensor faults (RMSE = 0.43 g L) and multiple real sensor faults (RMSE = 0.70 g L).
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http://dx.doi.org/10.1002/elsc.202100091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961066PMC
March 2022

Fidelity of organellar protein targeting.

Curr Opin Cell Biol 2022 Apr 17;75:102071. Epub 2022 Mar 17.

Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Bonn, 53115 Bonn, Germany. Electronic address:

The majority of cellular proteins are targeted to organelles. Cytosolic ribosomes produce these proteins as precursors with cleavable or non-cleavable targeting sequences that direct them to receptor proteins on the organelle surface. Multiple targeting factors ensure cellular sorting of the precursor proteins. In co-translational protein import, the ribosome-nascent chain complex is transported to the organellar protein translocase to couple protein synthesis and protein import. In post-translational mode, targeting factors like molecular chaperones guide the precursor proteins from ribosomes to the cell organelle. Defects in protein targeting and import cause mistargeting of proteins to different cellular compartments and challenge the balance of cellular proteostasis. Specific dislocases and degradation machineries remove such mislocalized proteins from the membrane to allow retargeting or their proteasomal turnover. In this review, we discuss targeting and quality control factors that ensure fidelity of protein targeting to mitochondria.
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http://dx.doi.org/10.1016/j.ceb.2022.02.005DOI Listing
April 2022

Gluten-starch interface characteristics and wheat dough rheology-Insights from hybrid artificial systems.

J Food Sci 2022 Apr 15;87(4):1375-1385. Epub 2022 Mar 15.

Research Group Cereal Process Engineering and Technology, Institute of Brewing and Beverage Technology, Technical University of Munich, Freising, Germany.

Referring to the total surface existing in wheat dough, gluten-starch interfaces are a major component. However, their impact on dough rheology is largely unclear. Common viewpoints, based on starch surface modifications or reconstitution experiments, failed to show unambiguous relations of interface characteristics and dough rheology. Observing hybrid artificial dough systems with defined particle surface functionalization gives a new perspective. Since surface functionalization standardizes particle-polymer interfaces, the impact on rheology becomes clearly transferable and thus, contributes to a better understanding of gluten-starch interfaces. Based on this perspective, the effect of particle/starch surface functionality is discussed in relation to the rheological properties of natural wheat dough and modified gluten-starch systems. A competitive relation of starch and gluten for intermolecular interactions with the network-forming polymer becomes apparent during network development by adsorption phenomena. This gluten-starch adhesiveness delays the beginning of non-linearity under large deformations, thus contributing to a high deformability of dough. Consequently, starch surface functionality affects the mechanical properties, starting from network formation and ending with the thermal fixation of structure.
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http://dx.doi.org/10.1111/1750-3841.16115DOI Listing
April 2022

Parenchyma Sparing ALPPS - Ultrasound Guided Partition Through Segment 4 to Maximize Resectability (with video).

Chirurgia (Bucur) 2022 02;117(1):81-93

Associating liver partition and portal vein ligation (ALPPS) has evolved as a treatment strategy for patients with liver tumors who are not amenable for upfront hepatectomy because of an insufficient future liver remnant (FLR). Aim of this study was to test the applicability of ultrasound guided parenchyma sparing surgery to ALPPS concept, by non-anatomically shifting the plane of transection in favor of FLR, resulting in a new technical variant of ALPPS, entitled parenchyma sparing ALPPS (psALPPS). Patients who could not safely undergo right trisectionectomy ALPPS because of insufficient FLR were considered eligible for psALPPS, consisting in liver partition through segment 4 using ultrasound guidance. Between April 2017 and April 2021, five patients with median age of 68 years (range: 66-78), four male and one female, underwent psALPPS for colorectal liver metastases (N=2), intrahepatic cholangiocarcinoma (N=2), and hepatocellular carcinoma (N=1). Standardized FLR (sFLR) for segments 2-3 before stage 1 surgery would have been a median of 11.6%. PsALPPS could double the sFLR at stage 1 resulting in an increase of ps-sFLR from a median of 22.7% (at stage 1) to 34.0% (at stage 2) after a median interstage interval of 15 days. All patients tolerated surgery well and no major complications were recorded. Applying the principles of parenchyma sparing surgery to ALPPS offers the advantage to maximize FLR and simultaneously reduce ischemic injury of segment 4 compared to conventional ALPPS. In this way, psALPPS may markedly increase resectability while reducing morbidity. Video version: https://www.revistachirurgia.ro/pdfs/?EntryID=922974&art=2021-parenchyma-sparing-ALPPS-ultrasound-guided-partition.pdf
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http://dx.doi.org/10.21614/chirurgia.2652DOI Listing
February 2022

Detection of Circulating and Disseminated Tumor Cells and Their Prognostic Value under the Influence of Neoadjuvant Therapy in Esophageal Cancer Patients.

Cancers (Basel) 2022 Mar 1;14(5). Epub 2022 Mar 1.

Institute for Experimental Cancer Research, Kiel University (CAU) and University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, 24105 Kiel, Germany.

Detection of circulating (CTC) or disseminated tumor cells (DTC) are correlated with negative prognosis in esophageal cancer (EC) patients. In this study, DTC- and CTC-associated markers CK20 and DEFA5 were determined by RT-PCR in EC patients and correlated with clinical parameters to determine their prognostic impact. The blood and bone marrow (BM) of 216 EC patients after tumor resection with or without neoadjuvant therapy and as control blood samples from 38 healthy donors and BM from 24 patients with non-malignant diseases were analyzed. Both markers were detected in blood and BM of EC patients and the control cohort. A cut-off value was determined to define marker positivity for correlation with clinical data. CK20 expression was detected in 47/206 blood samples and in 49/147 BM samples of EC patients. DEFA5 positivity was determined in 96/206 blood samples and 98/147 BM samples, not correlating with overall survival (OS). However, CK20 positivity in BM and DEFA5 negativity in blood were associated with reduced OS in EC patients without neoadjuvant therapy, while in patients with neoadjuvant therapy DEFA5 positivity in BM was associated with improved OS. Overall, our study suggests DEFA5 as a prognostic biomarker in liquid biopsies of EC patients which requires further validation.
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http://dx.doi.org/10.3390/cancers14051279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909540PMC
March 2022

Patients Benefit from Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria without Harming the Health Care System.

Cancers (Basel) 2022 Feb 23;14(5). Epub 2022 Feb 23.

Department of General, Visceral-, Thoracic-, Transplantation- and Pediatric Surgery, UKSH Campus Kiel, Arnold-Heller-Str. 3, 24105 Kiel, Germany.

Liver transplantation (LT) is the only definitive treatment to cure hepatocellular carcinoma (HCC) in cirrhosis. Waiting-list candidates are selected by the model for end-stage liver disease (MELD). However, many indications are not sufficiently represented by labMELD. For HCC, patients are selected by Milan-criteria: Milan-in qualifies for standard exception (SE) and better organ access on the waiting list; while Milan-out patients are restricted to labMELD and might benefit from extended criteria donor (ECD)-grafts. We analyzed a cohort of 102 patients (2011-2020). Patients with labMELD (no SE, Milan-out, = 56) and matchMELD (SE-HCC, Milan-in, = 46) were compared. The median overall survival was not significantly different ( = 0.759). No difference was found in time on the waiting list ( = 0.881), donor risk index ( = 0.697) or median costs ( = 0.204, EUR 43,500 (EUR 17,800-185,000) for labMELD and EUR 30,300 (EUR 17,200-395,900) for matchMELD). Costs were triggered by a cut-off labMELD of 12 points. Overall, the deficit increased by EUR 580 per labMELD point. Cost drivers were re-operation ( < 0.001), infection with multiresistant germs ( = 0.020), dialysis ( = 0.017), operation time ( = 0.012) and transfusions ( < 0.001). In conclusion, this study demonstrates that LT for HCC is successful and cost-effective in low labMELD patients independent of Milan-criteria. Therefore, ECD-grafts are favorized in Milan-out HCC patients with low labMELD.
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http://dx.doi.org/10.3390/cancers14051136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909584PMC
February 2022

Micro-Scale Shear Kneading-Gluten Network Development under Multiple Stress-Relaxation Steps and Evaluation via Multiwave Rheology.

Polymers (Basel) 2022 Feb 21;14(4). Epub 2022 Feb 21.

Research Group Cereal Technology and Process Engineering, Institute of Brewing and Beverage Technology, Technical University of Munich, 85354 Freising, Germany.

To evaluate the kneading process of wheat flour dough, the state of the art is a subsequent and static measuring step on kneaded dough samples. In this study, an in-line measurement setup was set up in a rheometer based on previously validated shear kneading processes. With this approach, the challenge of sample transfer between the kneader and a measurement device was overcome. With the developed approach, an analysis of the dynamic development of the dough is possible. Through consecutive stress-relaxation steps with increasing deformation, a kneading setup in a conventional rheometer is implemented. Fitting of the shear stress curve with a linearization approach, as well as fitting of the relaxation modulus after each kneading step, is a new way to evaluate the matrix development. Subsequently, multiwave rheology is used to validate the kneading process in-line. The shear kneading setup was capable of producing an optimally developed dough matrix close to the reference kneading time of 150 ± 7.9 s (n = 3). The linearization approach as well as the power-law fit of the relaxation modulus revealed gluten network development comparable to the reference dough. With this approach, a deeper insight into gluten network development and crosslinking processes during wheat flour dough kneading is given.
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http://dx.doi.org/10.3390/polym14040846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8963076PMC
February 2022

The role of migration in mental healthcare: treatment satisfaction and utilization.

BMC Psychiatry 2022 02 15;22(1):116. Epub 2022 Feb 15.

Department of Psychiatry, Psychotherapy and Psychosomatic, University of Augsburg, Medical Faculty, BKH Augsburg, Augsburg, Germany.

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.
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http://dx.doi.org/10.1186/s12888-022-03722-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845273PMC
February 2022

Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth.

Cell Rep 2022 01;38(4):110290

Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. Electronic address:

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 FF-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 Mic10, not on Mic10. We conclude that Mic10 plays a dual role as core subunit of MICOS and as partner of the FF-ATP synthase, serving distinct functions in cristae shaping and respiratory adaptation and growth.
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http://dx.doi.org/10.1016/j.celrep.2021.110290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810396PMC
January 2022

Predictors of competitive employment in individuals with severe mental illness: results from an observational, cross-sectional study in Germany.

J Occup Med Toxicol 2022 Jan 18;17(1). Epub 2022 Jan 18.

Institute of Social Medicine, Occupational Health and Public Health (ISAP), Medical Faculty, University of Leipzig, Philipp-Rosenthal-Straße 55, 04103, Leipzig, Germany.

Background: Employment is of great importance as it is associated with various positive effects. Individuals with severe mental illness (SMI) are often excluded from competitive employment. Current data on employment of individuals with mental illness are rare, and influencing factors are under-researched. The present study examines possible predictors of competitive employment among individuals with SMI.

Methods: This was a cross-sectional and multicentered study of 300 individuals with SMI aged 18 to 65 years. The following inclusion criteria were used: (I) diagnosis of schizophrenia, schizotypal and delusional disorders (ICD-10 F2x), or affective disorders (ICD-10 F3x), (II) duration of psychiatric illness ≥ 2 years, and (III) substantial impact of illness on social functioning. Participants were interviewed by trained staff using standardised instruments. The relationship between potential predictors (age, sex, education, marital status, living situation, migration background, psychosocial functioning, age at first mental problem, physical illness, work ability) and employment was analysed using a hierarchic binary logistic regression model.

Results: Only one-third (34%) of participants were competitively employed. Almost one-third were unemployed (30%), and 28% reported early retirement due to mental illness. Psychosocial functioning was positively associated with competitive employment (OR = 1.09, 95% CI: 1.05 - 1.13, p < 0.001); concurrent chronic physical illness was negatively associated with competitive employment (OR = 0.38, 95% CI: 0.21 - 0.71, p = 0.002).

Conclusions: Findings confirm a high risk of exclusion from competitive employment among individuals with SMI. Nonetheless, a substantial proportion of individuals are employed. Findings call for efforts to maintain or enhance workforce participation among individuals with SMI. A special focus should be placed on improving physical health and strengthening psychosocial functioning.

Trial Registration: The study was registered in the German Clinical Trials Register (DRKS) under the registration number DRKS00015801 before the start of recruitment (Registration date: 21.02.2019).
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http://dx.doi.org/10.1186/s12995-022-00345-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767732PMC
January 2022

Mitochondria shed their outer membrane in response to infection-induced stress.

Science 2022 Jan 14;375(6577):eabi4343. Epub 2022 Jan 14.

Max Planck Institute for Biology of Ageing, Cologne, Germany.

The outer mitochondrial membrane (OMM) is essential for cellular homeostasis. Yet little is known of the mechanisms that remodel it during natural stresses. We found that large “SPOTs” (structures positive for OMM) emerge during infection in mammalian cells. SPOTs mediated the depletion of the OMM proteins mitofusin 1 and 2, which restrict parasite growth. The formation of SPOTs depended on the parasite effector TgMAF1 and the host mitochondrial import receptor TOM70, which is required for optimal parasite proliferation. TOM70 enabled TgMAF1 to interact with the host OMM translocase SAM50. The ablation of SAM50 or the overexpression of an OMM-targeted protein promoted OMM remodeling independently of infection. Thus, hijacks the formation of SPOTs, a cellular response to OMM stress, to promote its growth.
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http://dx.doi.org/10.1126/science.abi4343DOI Listing
January 2022

Effectiveness of a WHO self-help psychological intervention for preventing mental disorders among Syrian refugees in Turkey: a randomized controlled trial.

World Psychiatry 2022 Feb;21(1):88-95

WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.

Refugees are at high risk of developing mental disorders. There is no evidence from randomized controlled trials (RCTs) that psychological interventions can prevent the onset of mental disorders in this group. We assessed the effectiveness of a self-help psychological intervention developed by the World Health Organization, called Self-Help Plus, in preventing the development of mental disorders among Syrian refugees experiencing psychological distress in Turkey. A two-arm, assessor-masked RCT was conducted in two Turkish areas. Eligible participants were adult Syrian refugees experiencing psychological distress (General Health Questionnaire ≥3), but without a diagnosis of mental disorder. They were randomly assigned either to the Self-Help Plus arm (consisting of Self-Help Plus combined with Enhanced Care as Usual, ECAU) or to ECAU only in a 1:1 ratio. Self-Help Plus was delivered in a group format by two facilitators over five sessions. The primary outcome measure was the presence of any mental disorder assessed by the Mini International Neuropsychiatric Interview at six-month follow-up. Secondary outcome measures were the presence of mental disorders at post-intervention, and psychological distress, symptoms of post-traumatic stress disorder and depression, personally identified psychological outcomes, functional impairment, subjective well-being, and quality of life at post-intervention and six-month follow-up. Between October 1, 2018 and November 30, 2019, 1,186 refugees were assessed for inclusion. Five hundred forty-four people were ineligible, and 642 participants were enrolled and randomly assigned to either Self-Help Plus (N=322) or ECAU (N=320). Self-Help Plus participants were significantly less likely to have any mental disorders at six-month follow-up compared to the ECAU group (21.69% vs. 40.73%; Cramer's V = 0.205, p<0.001, risk ratio: 0.533, 95% CI: 0.408-0.696). Analysis of secondary outcomes suggested that Self-Help Plus was not effective immediately post-intervention, but was associated with beneficial effects at six-month follow-up in terms of symptoms of depression, personally identified psychological outcomes, and quality of life. This is the first prevention RCT ever conducted among refugees experiencing psychological distress but without a mental disorder. Self-Help Plus was found to be an effective strategy for preventing the onset of mental disorders. Based on these findings, this low-intensity self-help psychological intervention could be scaled up as a public health strategy to prevent mental disorders in refugee populations exposed to ongoing adversities.
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http://dx.doi.org/10.1002/wps.20939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751562PMC
February 2022

Detection of Marker Associated with CTC in Colorectal Cancer in Mononuclear Cells of Patients with Benign Inflammatory Intestinal Diseases.

Cancers (Basel) 2021 Dec 23;14(1). Epub 2021 Dec 23.

Institute for Experimental Cancer Research, Kiel University and University Hospital Schleswig-Holstein Campus Kiel, Arnold-Heller-Str. 3, Building U30 Entrance 1, 24105 Kiel, Germany.

Colorectal carcinoma (CRC) belongs to the most common tumor entities in western countries. Circulating tumor cells (CTC) in blood of CRC patients are a powerful prognostic and predictive biomarker. However, whether CTC-associated markers can also be used for early CRC detection and discrimination from benign diseases is not known. This study investigated the presence of CTC-associated markers CK20, PLS3, LAD1, and DEFA5 in blood of patients with benign inflammatory intestinal disease (IID) and their correlation with malignancy. The detection rate of CK20 and DEFA5 significantly differed between diseased patients and healthy controls. LAD1 and PLS3 were detected in all samples with clear differences in gene expression. DEFA5 expression was higher in CRC and IID patients compared to healthy donors, while CK20 and PLS3 were lower in CRC compared to IID patients or healthy controls. Overall, all CTC-associated markers were detectable in blood of IID patients, but not correlating with inflammation severity. Finally, PLS3 emerged as a suitable marker for differentiation between malignant and non-malignant intestinal diseases or healthy controls, however its suitability for early CRC detection needs to be further validated.
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http://dx.doi.org/10.3390/cancers14010047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8750406PMC
December 2021

The evaluation of a physical health promotion intervention for people with severe mental illness receiving community based accommodational support: a mixed-method pilot study.

BMC Psychiatry 2022 01 4;22(1). Epub 2022 Jan 4.

Department of Psychiatry II, University of Ulm, Lindenallee 2, 89312, Günzburg, Germany.

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.
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http://dx.doi.org/10.1186/s12888-021-03640-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728992PMC
January 2022
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