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Abstract Aims The aim of this study is to evaluate and compare the impact of the bicaval technique versus the biatrial technique (by Lower and Shumway) in paediatric heart transplant patients. Only a few studies investigate this matter regarding the long‐term outcome after paediatric heart transplantation. We compared the two surgical methods regarding survival, the necessity of pacemaker implantation. Methods and results All 134 patients (aged

IntroductionThe aim of this study was to analyze the results after pediatric heart transplantation (pHTx) at our single center differentiating between ABO-incompatible (ABOi) and -compatible (ABOc) procedures.Methods and patientsWe retrospectively analyzed outcomes of ABO-incompatible HTx procedures performed at our center and compared the data to ABO-compatible HTx of the same era. Eighteen children (

Fusarium head blight (FHB) is a devastating disease of wheat, causing yield losses, reduced grain quality, and mycotoxin contamination. Breeding can mitigate the severity of FHB epidemics, especially with genomics-assisted methods. The mechanisms underlying resistance to FHB in wheat have been extensively studied, including phenological traits and genome-wide markers associated with FHB severity. Here, we aimed to improve genomic prediction for FHB resistance across breeding programs by incorporating FHB-correlated traits and FHB-associated loci as model covariates. We combined phenotypic data on FHB severity, anthesis date, and plant height with genome-wide marker data from five Central European winter wheat breeding programs for genome-wide association studies (GWAS) and genomic prediction. Within all populations, FHB was correlated with anthesis date and/or plant height, and a marker linked to the semi-dwarfing locus Rht-D1 was detected with GWAS for FHB. Including the Rht-D1 marker, anthesis date, and/or plant height as covariates in genomic prediction modeling improved prediction accuracy not only within populations but also in cross-population scenarios.

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students’ t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

The blockade of the CD40/CD40L immune checkpoint is considered essential for cardiac xenotransplantation. However, it is still unclear which single antibody directed against CD40 or CD40L (CD154), or which combination of antibodies, is better at preventing organ rejection. For example, the high doses of antibody administered in previous experiments might not be feasible for the treatment of humans, while thrombotic side effects were described for first-generation anti-CD40L antibodies. To address these issues, we conducted six orthotopic pig-to-baboon cardiac xenotransplantation experiments, combining a chimeric anti-CD40 antibody with an investigational long-acting PASylated anti-CD40L Fab fragment. The combination therapy effectively resulted in animal survival with a rate comparable to a previous study that utilized anti-CD40 monotherapy. Importantly, no incidence of thromboembolic events associated with the administration of the anti-CD40L PAS-Fab was observed. Two experiments failed early because of technical reasons, two were terminated deliberately after 90 days with the baboons in excellent condition and two were extended to 120 and 170 days, respectively. Unexpectedly, and despite the absence of any clinical signs, histopathology revealed fungal infections in all four recipients. This study provides, for the first time, insights into a combination therapy with anti-CD40/anti-CD40L antibodies to block this immune checkpoint.

Abstract Pre‐harvest sprouting (PHS), germination of seeds before harvest, is a major problem in global wheat (Triticum aestivum L.) production, and leads to reduced bread‐making quality in affected grain. Breeding for PHS resistance can prevent losses under adverse conditions. Selecting resistant lines in years lacking pre‐harvest rain, requires challenging of plants in the field or in the laboratory or using genetic markers. Despite the availability of a wheat reference and pan‐genome, linking markers, genes, allelic, and structural variation, a complete understanding of the mechanisms underlying various sources of PHS resistance is still lacking. Therefore, we challenged a population of European wheat varieties and breeding lines with PHS conditions and phenotyped them for PHS traits, grain quality, phenological and agronomic traits to conduct genome‐wide association mapping. Furthermore, we compared these marker‐trait associations to previously reported PHS loci and evaluated their usefulness for breeding. We found markers associated with PHS on all chromosomes, with strong evidence for novel quantitative trait locus/loci (QTL) on chromosome 1A and 5B. The QTL on chromosome 1A lacks pleiotropic effect, for the QTL on 5B we detected pleiotropic effects on phenology and grain quality. Multiple peaks on chromosome 4A co‐located with the major resistance locus Phs‐A1, for which two causal genes, TaPM19 and TaMKK3, have been proposed. Mapping markers and genes to the pan‐genome and chromosomal alignments provide evidence for structural variation around this major PHS‐resistance locus. Although PHS is controlled by many loci distributed across the wheat genome, Phs‐A1 on chromosome 4A seems to be the most effective and widely deployed source of resistance, in European wheat varieties.

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.

May–Thurner syndrome is a venous compression syndrome of the pelvic vessels that represents a relevant risk factor for thrombus formation. The standard procedure to secure a diagnosis is venography, followed by endovascular therapy as the preferred treatment choice if the patient is symptomatic. In our case series, there are three related patients with May–Thurner syndrome. A 16-year-old female was admitted with pulmonary embolism, dyspnoea and hip pain. The compression syndrome was diagnosed with interventional venography, and the patient received venous stent implantation. Due to her family history, we also suspected her mother to be affected by the syndrome and elucidated the diagnosis shortly afterwards by invasive venography. Subsequently, we examined the patient’s 19-year-old brother, and magnetic resonance imaging confirmed May–Thurner syndrome. A similar case series has not been published before. In this case, the family relation indicates a possible hereditary aspect of May–Thurner syndrome. This hypothesis should be the subject of further research. In conclusion, it is essential to assess family history thoroughly when treating patients with May–Thurner syndrome.

Prolonged mechanical ventilation (PMV) after lung transplantation poses several risks, including higher tracheostomy rates and increased in-hospital mortality. Mechanical power (MP) of artificial ventilation unifies the ventilatory variables that determine gas exchange and may be related to allograft function following transplant, affecting ventilator weaning. We retrospectively analyzed consecutive double lung transplant recipients at a national transplant center, ventilated through endotracheal tubes upon ICU admission, excluding those receiving extracorporeal support. MP and derived indexes assessed up to 36 h after transplant were correlated with invasive ventilation duration using Spearman’s coefficient, and we conducted receiver operating characteristic (ROC) curve analysis to evaluate the accuracy in predicting PMV (>72 h), expressed as area under the ROC curve (AUROC). PMV occurred in 82 (35%) out of 237 cases. MP was significantly correlated with invasive ventilation duration (Spearman’s ρ = 0.252 [95% CI 0.129–0.369], p < 0.01), with power density (MP normalized to lung-thorax compliance) demonstrating the strongest correlation (ρ = 0.452 [0.345–0.548], p < 0.01) and enhancing PMV prediction (AUROC 0.78 [95% CI 0.72–0.83], p < 0.01) compared to MP (AUROC 0.66 [0.60–0.72], p < 0.01). Mechanical power density may help identify patients at risk for PMV after double lung transplantation.

We report the long-term effect after successfully implanting an 8 mm Atrial-flow-regulator (AFR) device in a 7-year-old girl with idiopathic pulmonary hypertension with persistent syncope under triple therapy with significant improvement after implantation and absence of any further syncope. Early Implantation of the AFR device (Occlutech, Germany) can be efficient and safe interventional therapy option for pulmonary arterial hypertension with a history of syncope.

Abstract Microbes can form complex communities that perform critical functions in maintaining the integrity of their environment or their hosts' wellbeing. Rationally managing these microbial communities requires improving our ability to predict how different species assemblages affect the final species composition of the community. However, making such a prediction remains challenging because of our limited knowledge of the diverse physical, biochemical, and ecological processes governing microbial dynamics. To overcome this challenge, we present a deep learning framework that automatically learns the map between species assemblages and community compositions from training data only, without knowing any of the above processes. First, we systematically validate our framework using synthetic data generated by classical population dynamics models. Then, we apply our framework to data from in vitro and in vivo microbial communities, including ocean and soil microbiota, Drosophila melanogaster gut microbiota, and human gut and oral microbiota. We find that our framework learns to perform accurate out‐of‐sample predictions of complex community compositions from a small number of training samples. Our results demonstrate how deep learning can enable us to understand better and potentially manage complex microbial communities.

Legume grains such as field peas and field beans can be produced on a local level, and may be reliable sources of dietary protein and energy apart from common soybean and rapeseed meals. In ruminants, protein, starch, and carbohydrates from peas and field beans are fermented in large part before reaching the small intestine. The objective of this study was to evaluate the effects of a combination of ensiling and hydro-thermic treatment (i.e., toasting at 160 °C for 30 min) of grains of peas and field beans on the concentrations of post-ruminal crude protein (PRCP) and rumen-undegraded protein (RUP). Moreover, 24-h gas production and methane production were measured. For this, an in vitro batch culture system with ruminal fluid from sheep was used. Rumen-undegraded protein was determined using the Streptomyces griseus protease test. Scanning electron micrographs were used to visualize morphological changes of starch granules and their joint matrices in peas and field beans after ensiling, toasting, or a combination of both. Native pea grains contained crude protein (CP) at 199 g/kg DM, PRCP at 155 g/kg DM at a ruminal passage rate of 0.08/h (Kp8), RUP at 33 g/kg DM at Kp8, and starch at 530 g/kg DM. Native field beans contained CP at 296 g/kg DM, PRCP at 212 g/kg DM at Kp8, RUP at 54 g of/kg DM at Kp8, and starch at 450 g/kg DM. The PRCP did not considerably differ among native and treated peas or field beans. Especially in the peas, RUP at Kp8 increased after ensiling by 10 g/kg DM (i.e., 30%; P

Abstract Genomic selection has become a valuable tool for selecting cultivar candidates in many plant breeding programs. Genomic selection of elite parents and crossing combinations with germplasm developed outside a breeding program has, however, hardly been explored until now. The aim of this study was to assess the potential of this method for commonly ranking and selecting elite germplasm developed within and beyond a given breeding program. A winter wheat (Triticum aestivum L.) population consisting of 611 in‐house and 87 externally developed lines was used to compare training population compositions and statistical models for genomically predicting baking quality in this framework. Augmenting training populations with lines from other breeding programs had a larger influence on the prediction ability than adding in‐house generated lines when aiming to commonly rank both germplasm sets. Exploiting preexisting information of secondary correlated traits resulted likewise in more accurate predictions both in empirical analyses and simulations. Genotyping germplasm developed beyond a given breeding program is moreover a convenient way to clarify its relationships with a breeder's own germplasm because pedigree information is oftentimes not available for this purpose. Genomic predictions can thus support a more informed diversity management, especially when integrating simply to phenotype correlated traits to partly circumvent resource reallocations for a costly phenotyping of germplasm from other programs.

Tobacco use after lung transplantation is associated with adverse outcome. Therefore, active smoking is regarded as a contraindication for lung transplantation and should be excluded prior to placement on the waiting list. The aim of the study was to compare self-reporting with a systematic cotinine based screening approach to identify patients with active nicotine abuse. Nicotine use was systematically assessed by interviews and cotinine test in all lung transplant candidates at every visit in our center. Patients were classified according to the stage prior to transplantation and cotinine test results were compared to self-reports and retrospectively analyzed until June 2019. Of 620 lung transplant candidates, 92 patients (14.8%) had at least one positive cotinine test. COPD as underlying disease (OR 2.102, CI 1.110-3.981; p = 0.023), number of pack years (OR 1.014, CI 1.000-1.028; p = 0.047) and a time of cessation less than one year (OR 2.413, CI 1.410-4.128; p = 0.001) were associated with a positive cotinine test in multivariable regression analysis. The majority of non-COPD patients (n = 13, 72.2%) with a positive test had a cessation time of less than one year. 78 patients (84.7%) falsely declared not consuming any nicotine-based products prior to the test. Finally, all never smokers were test negative. In conclusion, our data demonstrate that active nicotine use is prevalent in transplant candidates with a high prevalence of falsely declaring nicotine abstinence. COPD was the main diagnosis in affected patients. Short cessation time and a high number of pack years are risk factors for continued nicotine abuse.

Winter hardiness is a major constraint for autumn sown crops in temperate regions, and thus an important breeding goal in the development of new winter wheat varieties. Winter hardiness is though influenced by many environmental factors rendering phenotypic selection under field conditions a difficult task due to irregular occurrence or absence of winter damage in field trials. Controlled frost tolerance tests in growth chamber experiments are, on the other hand, even with few genotypes, often costly and laborious, which makes a genomic breeding strategy for early generation selection an attractive alternative. The aims of this study were thus to compare the merit of marker-assisted selection using the major frost tolerance QTL Fr-A2 with genomic prediction for winter hardiness and frost tolerance, and to assess the potential of combining both measures with a genomic selection index using a high density marker map or a reduced set of pre-selected markers. Cross-validation within two training populations phenotyped for frost tolerance and winter hardiness underpinned the importance of Fr-A2 for frost tolerance especially when upweighting its effect in genomic prediction models, while a combined genomic selection index increased the prediction accuracy for an independent validation population in comparison to training with winter hardiness data alone. The prediction accuracy could moreover be maintained with pre-selected marker sets, which is highly relevant when employing cost reducing fingerprinting techniques such as targeted genotyping-by-sequencing. Genomic selection showed thus large potential to improve or maintain the performance of winter wheat for these difficult, costly, and laborious to phenotype traits.

Electro-hydraulic compact drives (ECDs) are an emerging technology for linear actuation in a wide range of applications. Especially within the low power range of 5–10 kW, the plug-and-play capability, good energy efficiency and small space requirements of ECDs render this technology a promising alternative to replace conventional valve-controlled linear drive solutions. In this power range, ECDs generally rely on passive cooling to keep oil and system temperatures within the tolerated range. When expanding the application range to larger power classes, passive cooling may not be sufficient. Research investigating the thermal behaviour of ECDs is limited but indeed required for a successful expansion of the application range. In order to obtain valuable insights into the thermal behaviour of ECDs, thermo-hydraulic simulation is an important tool. This may enable system design engineers to simulate thermal behaviour and thus develop proper thermal designs during the early design phase, especially if such models contain few parameters that can be determined with limited information available. Our paper presents a lumped thermo-hydraulic model derived from the conservation of mass and energy. The derived model was experimentally validated based on experimental data from an ECD prototype. Results show good accuracy between measured and simulated temperatures. Even a simple thermal model containing only a few thermal resistances may be sufficient to predict steady-state and transient temperatures with reasonable accuracy. The presented model may be used for further investigations into the thermal behaviour of ECDs and thus toward proper thermal designs required to expand the application range.

Dietary fibers may have positive impact on health and wellbeing of pigs. The study examined physicochemical properties of two lignocelluloses (including and excluding bark), powdered cellulose, Aspergillus niger mycelium, lucerne chaff, soybean shells, wheat bran, and sugar beet pulp in relation to fermentability and digestibility using in vitro batch-culture incubation. Maize starch and a purified cellulose were used as standardized substrates for classification of the test substrates. The substrates covered a wide range regarding their physicochemical properties. Swelling capacity (SC) was 9–411%, water binding capacity (WBC) was 4.4–14.3 g/g dry matter (DM), and water holding capacity (WHC) was 4.1–10.6 g/g DM. Gas production and other fermentation parameters—namely post-incubation pH, CH4, NH3, and short chain fatty acids (SCFA) concentrations—revealed a significant fermentation of sugar beet pulp, soybean shells, lucerne chaff, wheat bran, A. niger mycelium, and powdered cellulose, whereas the lignocelluloses were not fermented. Significant correlations were found between the physicochemical properties and the fermentation parameters (p < 0.05). Enzymatic pre-digestion mostly reduced gas, NH3, and SCFA production. In vitro digestibility of DM (IVDMD) and organic matter (IVOMD) was mostly negligible after enzymatic pre-digestion. Fermentation alone led to only 0.10–0.15 IVDMD and 0.14–0.15 IVOMD in lignocelluloses and powdered cellulose, respectively, but 0.44–0.37 IVDMD and 0.46–0.38 IVOMD in the remainder of substrates (p < 0.05). In vitro digestibility was again correlated with the physicochemical properties of the substrates and the fermentation parameters (p < 0.05). The fiber preparations and fiber-rich byproducts were fermented to a relevant extent. In contrast, lignocelluloses were not fermented and can be used rather as bulk material.

Environmental factors like temperature and humidity are presumed to greatly influence Fusarium head blight FHB infections in wheat. Anther retention AR, on the other hand, is a morphologically neutral trait that shares a common genetic basis with FHB resistance. In this study, our aims were to: (i) Evaluate two types of corrections of FHB severity scores, namely method-1 via linear regression on flowering time (FT), and method-2 via a best-subset multiple linear regression analysis comprising FT plus accumulated thermal time variables; and (ii) assess the performance of multi-trait genomic selection (MT.GS) models for FHB severity assisted by AR. The forward prediction scenarios where GS models were trained with data from the previous years revealed average prediction accuracies (PA) of 0.28, 0.33, and 0.36 for FHB severity scores that were uncorrected or corrected by method-1 and method-2, respectively. FHB severity scores free from the influences of both environment and phenology seemed to be the most efficient trait to be predicted across different seasons. Average PA increments up to 1.9-fold were furthermore obtained for the MT.GS models, evidencing the feasibility of using AR as an assisting trait to improve the genomic selection of FHB resistance breeding lines.

The availability of cost-efficient genotyping technologies has facilitated the implementation of genomic selection into numerous breeding programs. However, some studies reported a superiority of pedigree over genomic selection in line breeding, and as, aside from systematic record keeping, no additional costs are incurring in pedigree-based prediction, the question about the actual benefit of fingerprinting several hundred lines each year might suggest itself. This study aimed thus on shedding some light on this question by comparing pedigree, genomic, and single-step prediction models using phenotypic and genotypic data that has been collected during a time period of ten years in an applied wheat breeding program. The mentioned models were for this purpose empirically tested in a multi-year forward prediction as well as a supporting simulation study. Given the availability of deep pedigree records, pedigree prediction performed similar to genomic prediction for some of the investigated traits if preexisting information of the selection candidates was available. Notwithstanding, blending both information sources increased the prediction accuracy and thus the selection gain substantially, especially for low heritable traits. Nevertheless, the largest advantage of genomic predictions can be seen for breeding scenarios where such preexisting information is not systemically available or difficult and costly to obtain.