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Aegilops tauschii is the diploid progenitor of the wheat D subgenome and a valuable resource for wheat breeding, yet, genetic analysis of resistance against Fusarium head blight (FHB) and the major Fusarium mycotoxin deoxynivalenol (DON) is lacking. We treated a panel of 147 Ae. tauschii accessions with either Fusarium graminearum spores or DON solution and recorded the associated disease spread or toxin-induced bleaching. A k-mer-based association mapping pipeline dissected the genetic basis of resistance and identified candidate genes. After DON infiltration nine accessions revealed severe bleaching symptoms concomitant with lower conversion rates of DON into the non-toxic DON-3-O-glucoside. We identified the gene AET5Gv20385300 on chromosome 5D encoding a uridine diphosphate (UDP)-glucosyltransferase (UGT) as the causal variant and the mutant allele resulting in a truncated protein was only found in the nine susceptible accessions. This UGT is also polymorphic in hexaploid wheat and when expressed in Saccharomyces cerevisiae only the full-length gene conferred resistance against DON. Analysing the D subgenome helped to elucidate the genetic control of FHB resistance and identified a UGT involved in DON detoxification in Ae. tauschii and hexaploid wheat. This resistance mechanism is highly conserved since the UGT is orthologous to the barley UGT HvUGT13248 indicating descent from a common ancestor of wheat and barley.

Estimating the breeding value of individuals using genome-wide marker data (genomic prediction) is currently one of the most important drivers of breeding progress in major crops. Recently, remote sensing technologies and aerial hyperspectral imaging of plant canopies combined with a variety of statistical and machine learning models allow prediction of the breeding value of individuals in the absence of genetic marker data. Hyperspectral measurements in the form of near-infrared spectroscopy have been used since the 80s to predict compositional parameters of harvest products, and some recent studies have also used this tool to predict the important parameter grain yield, suggesting that phenomic prediction can outperform genomic prediction. The genome of an individual can be considered static, however gene expression is tissue specific and differs under environmental influences, leading to a tissue and environment specific phenome. Here, we compare genomic prediction and phenomic prediction from hyperspectral measurements of wheat grains for the prediction of a variety of traits including grain yield. We show that phenomic predictions seem equivalent to genomic predictions for some traits in terms of predictive ability. However, phenomic predictions appear heavily biased towards the information present in the predictor. Future studies on this topic should investigate whether population parameters are conserved in phenomic predictions as they are in genomic predictions. Furthermore, we suggest a method to circumvent this issue, which reveals that unbiased phenomic prediction abilities are considerably lower than previously reported.

Key message Association mapping and phenotypic analysis of a diversity panel of 238 bread wheat accessions highlights differences in resistance against common vs. dwarf bunt and identifies genotypes valuable for bi-parental crosses. Abstract Common bunt caused by Tilletia caries and T. laevis was successfully controlled by seed dressings with systemic fungicides for decades, but has become a renewed threat to wheat yield and quality in organic agriculture where such treatments are forbidden. As the most efficient way to address this problem is the use of resistant cultivars, this study aims to broaden the spectrum of resistance sources available for breeders by identifying resistance loci against common bunt in bread wheat accessions of the USDA National Small Grains Collection. We conducted three years of artificially inoculated field trials to assess common bunt infection levels in a diversity panel comprising 238 wheat accessions for which data on resistance against the closely related pathogen Tilletia controversa causing dwarf bunt was already available. Resistance levels against common bunt were higher compared to dwarf bunt with 99 accessions showing $$\le$$ ≤ 1% incidence. Genome-wide association mapping identified six markers significantly associated with common bunt incidence in regions already known to confer resistance on chromosomes 1A and 1B and novel loci on 2B and 7A. Our results show that resistance against common and dwarf bunt is not necessarily controlled by the same loci but we identified twenty accessions with high resistance against both diseases. These represent valuable new resources for research and breeding programs since several bunt races have already been reported to overcome known resistance genes.

Background COVID-19 causes a wide range of symptoms, with particularly high risk of severe respiratory failure and death in patients with predisposing risk factors such as advanced age or obesity. Recipients of solid organ transplants, and in particular lung transplantation, are more susceptible to viral infection owing to immune suppressive medication. As little is known about the SARS-CoV-2 infection in these patients, this study was undertaken to describe outcomes and potential management strategies in early COVID-19 infection early after lung transplantation. Methods We describe the incidence and outcome of COVID-19 in a cohort of recent lung transplant recipients in Munich. Six of 186 patients who underwent lung transplantation in the period between March 2019 and March 2021 developed COVID-19 within the first year after transplantation. We documented the clinical course and laboratory changes for all patients showing differences in the severity of the infection with COVID-19 and their outcomes. Results Three of 6 SARS-CoV-2 infections were hospital-acquired and the patients were still in inpatient treatment after lung transplantation. All patients suffered from symptoms. One patient did not receive antiviral therapy. Remdesivir was prescribed in 4 patients and the remaining patient received remdesivir, bamlanivimab and convalescent plasma. Conclusions COVID-19 does not appear to cause milder disease in lung transplant recipients compared with the general population. Immunosuppression is potentially responsible for the delayed formation of antibodies and their premature loss. Several comorbidities and a general poor preoperative condition showed an extended hospital stay.

We analyzed the early and long-term survival after ABO-compatible heart transplantation in children under 3 years of age from 1991 to 2021 at our center. This retrospective and descriptive study aimed to identify serious adverse events associated with mortality after pediatric heart transplantation.46 patients with congenital heart failure (37%) in end-stage heart failure have undergone a pediatric heart transplantation. Primary outcome of interest was survival at follow-up time.Median (IQR) follow-up time (y), age (y), body-weight (kg) and BMI (kg/cmPediatric heart transplantation has acceptable long-term results and is still the best therapeutic option in children with end-stage cardiac failure. Underlying anomalies and single ventricle physiology, age below 3 months had a significant impact on survival.

Key message A novel genomic selection strategy offers the unique opportunity to develop qualitative race-specific resistant varieties that possess high levels of the more durable quantitative race-nonspecific resistance in their genetic background. Abstract Race-specific qualitative resistance genes (R-genes) are conferring complete resistance in many pathosystems, but are frequently overcome by new virulent pathogen races. Once the deployed R-genes are overcome, a wide variation of quantitative disease resistance (QDR) can be observed in a set of previously race-specific, i.e., completely resistant genotypes—a phenomenon known as “vertifolia effect.” This race-nonspecific QDR is considered to be more durable in the long term, but provides merely a partial protection against pathogens. This simulation study aimed to detangle race-specific R-gene-mediated resistance of pending selection candidates and the QDR in their genetic background by employing different genomic selection strategies. True breeding values that reflected performance data for rust resistance in wheat were simulated, and used in a recurrent genomic selection based on several prediction models and training population designs. Using training populations that were devoid of race-specific R-genes was thereby pivotal for an efficient improvement of QDR in the long term. Marker-assisted preselection for the presence of R-genes followed by a genomic prediction for accumulating the many small to medium effect loci underlying QDR in the genetic background of race-specific resistant genotypes appeared furthermore to be a promising approach to select simultaneously for both types of resistance. The practical application of such a knowledge-driven genomic breeding strategy offers the opportunity to develop varieties with multiple layers of resistance, which have the potential to prevent intolerable crop losses under epidemic situations by displaying a high level of QDR even when race-specific R-genes have been overcome by evolving pathogen populations.

Previous studies suggested that microbial communities harbor keystone species whose removal can cause a dramatic shift in microbiome structure and functioning. Yet, an efficient method to systematically identify keystone species in microbial communities is still lacking. This is mainly due to our limited knowledge of microbial dynamics and the experimental and ethical difficulties of manipulating microbial communities. Here, we propose a Data-driven Keystone species Identification (DKI) framework based on deep learning to resolve this challenge. Our key idea is to implicitly learn the assembly rules of microbial communities from a particular habitat by training a deep learning model using microbiome samples collected from this habitat. The well-trained deep learning model enables us to quantify the community-specific keystoneness of each species in any microbiome sample from this habitat by conducting a thought experiment on species removal. We systematically validated this DKI framework using synthetic data generated from a classical population dynamics model in community ecology. We then applied DKI to analyze human gut, oral microbiome, soil, and coral microbiome data. We found that those taxa with high median keystoneness across different communities display strong community specificity, and many of them have been reported as keystone taxa in literature. The presented DKI framework demonstrates the power of machine learning in tackling a fundamental problem in community ecology, paving the way for the data-driven management of complex microbial communities.

Purpose The aim of the study was to evaluate whether the quantification of B-lines via lung ultrasound after lung transplantation is feasible and correlates with the diagnosis of primary graft dysfunction. Methods Following lung transplantation, patients underwent daily lung ultrasound on postoperative days 1–3. B-lines were quantified by an ultrasound score based on the number of single and confluent B-lines per intercostal space, using a four-region protocol. The ultrasound score was correlated with the diagnosis of primary graft dysfunction. Furthermore, correlation analyses and receiver operating characteristics analyses taking into account ultrasound score, chest radiographs, and PaO2/FiO2 ratio were performed. Results A total of 32 patients (91 ultrasound measurements) were included, whereby 10 were diagnosed with primary graft dysfunction. The median B-line score was 5 [IQR: 4, 8]. There was a significant correlation between B-line score and the diagnosis of primary graft dysfunction (r = 0.59, p < 0.001). A significant correlation could also be seen between chest X-rays and primary graft dysfunction (r = 0.34, p = 0.008), but the B-line score showed superiority over chest X-rays with respect to diagnosing primary graft dysfunction in the receiver operating characteristics curves with an area under the curve value of 0.921 versus 0.708. There was a significant negative correlation between B-line score and PaO2/FiO2 ratio (r = –0.41, p < 0.001), but not between chest X-rays and PaO2/FiO2 ratio (r = –0.14, p = 0.279). Conclusion The appearance of B-lines correlated well with primary graft dysfunction and outperformed chest radiographs.

An experimental analysis regarding the distribution of the cutting fluid is very difficult due to the inaccessibility of the contact zone within the bore hole. Therefore, suitable simulation models are necessary to evaluate new tool designs and optimize drilling processes. In this paper the coolant distribution during helical deep hole drilling is analyzed with high-speed microscopy. Micro particles are added to the cutting fluid circuit by a developed high-pressure mixing vessel. After the evaluation of suitable particle size, particle concentration and coolant pressure, a computational fluid dynamics (CFD) simulation is validated with the experimental results. The comparison shows a very good model quality with a marginal difference for the flow velocity of 1.57% between simulation and experiment. The simulation considers the kinematic viscosity of the fluid. The results show that the fluid velocity in the chip flutes is low compared to the fluid velocity at the exit of the coolant channels of the tool and drops even further between the guide chamfers. The flow velocity and the flow pressure directly at the cutting edge decrease to such an extent that the fluid cannot generate a sufficient cooling or lubrication. With the CFD simulation a deeper understanding of the behavior and interactions of the cutting fluid is achieved. Based on these results further research activities to improve the coolant supply can be carried out with great potential to evaluate new tool geometries and optimize the machining process., Advances in manufacturing;Vol.10. 2022, issue 2, pp 235-249

Background: Long-term outcome of lung transplantation (LTx) recipients is limited by chronic lung allograft dysfunction (CLAD). In this setting of new onset respiratory failure, the amount of oxygenated hemoglobin (OxyHem; hemoglobin (Hb) concentration × fractional oxygen saturation) may provide valuable information. Objective: We hypothesized that OxyHem predicts survival of LTx recipients at the onset of CLAD. Methods: Data from 292 LTx recipients with CLAD were analyzed. After excluding patients with missing data or supplemental oxygen, the final population comprised 218 patients. The relationship between survival upon CLAD and OxyHem was analyzed by Cox regression analyses and ROC curves. Results: Among the 218 patients (102 males, 116 females), 128 (58.7%) died, median survival time after CLAD onset being 1,156 days. Survival was significantly associated with type of transplantation, time to CLAD, CLAD stage at onset, and OxyHem, which was superior to Hb or oxygen saturation. The risk for death after CLAD increased by 14% per reduction of OxyHem by 1 g/dL, and values below 11 g/dL corresponded to an 80% increase in mortality risk. Conclusion: Thus, OxyHem was identified as an independent predictor of mortality after CLAD onset. Whether it is useful in supporting therapeutic decisions and potentially home monitoring in the surveillance of lung transplant recipients has to be studied further.

Die Verfahrenskombination aus Laserpilotieren und Einlippentiefbohren ist ein vielversprechender Ansatz, die Flexibilität bei Tiefbohrbearbeitungen signifikant zu steigern. Mithilfe des Lasersystems ist es dabei möglich, verschleißfrei Pilotbohrungen auf schrägen, gekrümmten oder sogar randschichtgehärteten Bauteilen zu erzeugen.

The increasingly cost-efficient availability of ‘omics’ data has led to the development of a rich framework for predicting the performance of non-phenotyped selection candidates in recent years. The improvement of phenotypic analyses by using pedigree and/or genomic relationship data has however received much less attention, albeit it has shown large potential for increasing the efficiency of early generation yield trials in some breeding programs. The aim of this study was accordingly to assess the possibility to enhance phenotypic analyses of multi-location field trials with complete relationship information as well as when merely incomplete pedigree and/or genomic relationship information is available for a set of selection candidates. For his purpose, four winter bread wheat trial series conducted in Eastern and Western Europe were used to determine the experimental efficiency and accuracy of different resource allocations with a varying degree of relationship information. The results showed that modelling relationship between the selection candidates in the analyses of multi-location trial series was up to 20% more efficient than employing routine analyses, where genotypes are assumed to be unrelated. The observed decrease in efficiency and accuracy when reducing the testing capacities was furthermore less pronounced when modelling relationship information, even in cases when merely partial pedigree and/or genomic information was available for the phenotypic analyses. Exploiting complete and incomplete relationship information in both preliminary yield trials and multi-location trial series has thus large potential to optimize resource allocations and increase the selection gain in programs that make use of various predictive breeding methods.

Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation.We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19).The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p .0001) and having cystic fibrosis (CF) (OP = 10.1, p .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES.Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log10 ) after a median of 17 [14-27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.

Key message We combined quantitative and population genetic methods to identify loci under selection for adult plant resistance to stripe rust in an Austrian winter wheat breeding population from 2008 to 2018. Abstract Resistance to stripe rust, a foliar disease caused by the fungus P. striiformis f. sp. tritici, in wheat (Triticum aestivum L.) is both qualitatively and quantitatively controlled. Resistance genes confer complete, race-specific resistance but are easily overcome by evolving pathogen populations, while quantitative resistance is controlled by many small- to medium-effect loci that provide incomplete yet more durable protection. Data on resistance loci can be applied in marker-assisted selection and genomic prediction frameworks. We employed genome-wide association to detect loci associated with stripe rust and selection testing to identify regions of the genome that underwent selection for stripe rust resistance in an Austrian winter wheat breeding program from 2008 to 2018. Genome-wide association mapping identified 150 resistance loci, 62 of which showed significant evidence of selection over time. The breeding population also demonstrated selection for resistance at the genome-wide level.

BackgroundThe published experience of lung transplantation in acute respiratory distress syndrome (ARDS) is limited. The aim of this study was to investigate the contemporary results of lung transplantation attempts in ARDS in major European centres.MethodsWe conducted a retrospective multicentre cohort study of all patients listed for lung transplantation between 2011 and 2019. We surveyed 68 centres in 22 European countries. All patients admitted to the waitlist for lung transplantation with a diagnosis of “ARDS/pneumonia” were included. Patients without extracorporeal membrane oxygenation (ECMO) or mechanical ventilation were excluded. Patients were followed until 1 October 2020 or death. Multivariable analysis for 1-year survival after listing and lung transplantation was performed.Results55 centres (81%) with a total transplant activity of 12 438 lung transplants during the 9-year period gave feedback. 40 patients with a median age of 35 years were identified. Patients were listed for lung transplantation in 18 different centres in 10 countries. 31 patients underwent lung transplantation (0.25% of all indications) and nine patients died on the waitlist. 90% of transplanted patients were on ECMO in combination with mechanical ventilation before lung transplantation. On multivariable analysis, transplantation during 2015–2019 was independently associated with better 1-year survival after lung transplantation (OR 10.493, 95% CI 1.977–55.705; p=0.006). 16 survivors out of 23 patients with known status (70%) returned to work after lung transplantation.ConclusionsLung transplantation in highly selected ARDS patients is feasible and outcome has improved in the modern era. The selection process remains ethically and technically challenging.

Key message Genomic relationship matrices based on mid-parent and family bulk genotypes represent cost-efficient alternatives to full genomic prediction approaches with individually genotyped early generation selection candidates. Abstract The routine usage of genomic selection for improving line varieties has gained an increasing popularity in recent years. Harnessing the benefits of this approach can, however, be too costly for many small-scale breeding programs, as in most genomic breeding strategies several hundred or even thousands of lines have to be genotyped each year. The aim of this study was thus to compare a full genomic prediction strategy using individually genotyped selection candidates with genomic predictions based on genotypes obtained from pooled DNA of progeny families as well as genotypes inferred from crossing parents. A population of 722 wheat lines representing 63 families tested in more than 100 multi-environment trials during 2010–2019 was for this purpose employed to conduct an empirical study, which was supplemented by a simulation with genotypic data from further 3855 lines. A similar or higher prediction ability was achieved for grain yield, protein yield, and the protein content when using mid-parent or family bulk genotypes in comparison with pedigree selection in the empirical across family prediction scenario. The difference of these methods with a full genomic prediction strategy became furthermore marginal if pre-existing phenotypic data of the selection candidates was already available. Similar observations were made in the simulation, where the usage of individually genotyped lines or family bulks was generally preferable with smaller family sizes. The proposed methods can thus be regarded as alternatives to full genomic or pedigree selection strategies, especially when pedigree information is limited like in the exchange of germplasm between breeding programs.

Bei BTA-Tiefbohrprozessen kommt es aufgrund der großen Werkzeuglängen häufig zu Torsionsschwingungen des Werkzeugsystems aus Bohrkopf und Bohrrohr. Im Vergleich zu konventionellen Stahl-Bohrrohren reduzieren Bohrrohre aus faserverstärktem Kunststoff diese Schwingungen durch ihr materialspezifisches Dämpfungspotenzial und erhöhen damit die Prozesssicherheit und verringern den Werkzeugverschleiß. Die Einbindung von Sensorfasern direkt in das Laminat erlaubt zudem eine Prozessüberwachung. In BTA deep hole drilling, torsional vibrations of the tool system consisting of a drill head and a drill tube often occur due to the long tool lengths. Compared to conventional steel drill tubes, drill tubes made of fiber-reinforced plastic reduce these vibrations through their material-specific damping behavior and thus increase the process reliability and reduce the tool wear. The integration of sensor fibers directly into the laminate also allows a monitoring of the drilling process.

Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) recipients is challenging. The aim of this study was to assess the diagnostic and prognostic value of longitudinal lung function tests in SLTX recipients with CLAD.A total of 295 SLTX recipients were analyzed and stratified according to native lung physiology. In addition to spirometry, measurements of static lung volumes and lung capacities were used to phenotype patients and to assess their prognostic value. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n = 71).Of 224 lung transplant recipients, 105 (46.9%) developed CLAD. Time to CLAD onset (hazard ratio [HR]: 0.82, 95% CI: 0.74-0.90; p0.001), severity of CLAD at onset (HR: 0.97, 95% CI: 0.94-0.99; p = 0.009), and progression after onset of CLAD (HR: 1.03, 95% CI: 1.00-1.05; p = 0.023) were associated with outcome. Phenotypes at onset were bronchiolitis obliterans syndrome (BOS) (59.1%), restrictive allograft syndrome (RAS) (12.4%), mixed phenotype (6.7%), and undefined phenotype (21.9%). Survival estimates differed significantly between phenotypes (p = 0.004), with RAS and mixed phenotype being associated with the worst survival, followed by BOS and undefined phenotype. Finally, a higher hazard for mortality was noticed for RAS (HR: 2.34, 95% CI: 0.99-5.52; p = 0.054) and mixed phenotype (HR: 3.30, 95% CI: 1.20-9.11; p = 0.021) while controlling for time to CLAD onset and severity of CLAD at onset.Phenotyping CLAD in SLTX remains challenging with a high number of patients with an undefined phenotype despite comprehensive lung function testing. However, phenotyping is of prognostic value. Furthermore, early, severe, and progressive CLADs are associated with worse survival.

Tricuspid annular plane systolic excursion (TAPSE) is important in the noninvasive echocardiographic assessment of right heart function. This retrospective observational study shows correlations of TAPSE with invasive right heart catheterization parameters after pediatric heart transplantation (HTx). The study included patients after pediatric HTx with cardiac catheterizations in 2018/2019 and measurement of TAPSE (n = 52 patients with 57 examinations; 50.9% adults, 52.6% female, median age: 18.54 years). TAPSE was compared with normal values. Stepwise, linear and multiple regression were used to show influencing variables on TAPSE. Mean TAPSE z-score was -3.48 (SD: 2.25) and 68.4% of HTx-recipients showed abnormally reduced TAPSE (z-score ←2) compared to normal values. Multiple regression (p-value0.001; corrected R

Research needs a balance of risk-taking in "breakthrough projects" and gradual progress. For building a sustainable knowledge base, it is indispensable to provide support for both.

Key messageResistance QTL on chromosomes 1AL and 7AL are effective against common and dwarf bunt, QTL on 1BS affects common bunt and QTL on 7DS affects dwarf bunt in bread wheat.AbstractCommon bunt, caused byTilletia cariesandT. laevis, and dwarf bunt, caused byT. controversa, negatively affect grain yield and quality of wheat and are particularly destructive in low-input and organic production systems. Two recombinant inbred line (RIL) populations derived by crossing the highly and durably resistant cultivars ‘Blizzard’ and ‘Bonneville’ to the susceptible cultivar ‘Rainer’ were evaluated for their resistance to common and dwarf bunt in artificially inoculated field and greenhouse trials over two growing seasons and genotyped with a 15 K SNP array. Bunt resistance QTL were mapped to chromosomes 1AL, 1BS, 7AL and 7DS. Common bunt resistance was regulated by the major QTLQBt.ifa-1BSandQBt.ifa-1ALtogether with the moderate effect QTLQBt.ifa-7AL. Dwarf bunt resistance was on the other hand regulated by the QTLQBt.ifa-1AL,QBt.ifa-7ALandQBt.ifa-7DS.Common bunt resistance QTL exhibited pronounced epistatic effects, while epistatic effects were of smaller magnitude for dwarf bunt QTL. Kompetitive Allele-Specific PCR (KASP) markers were developed from SNPs associated with bunt resistance QTL and successfully used for QTL validation in an independent set of RILs. These KASP markers have the potential to support targeted introgression of QTL into elite wheat germplasm and accelerate breeding for enhanced bunt resistance. Durable protection against both common and dwarf bunt can be achieved by combining multiple resistance genes in the same genetic background.

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

The large tool length in BTA deep hole drilling often leads to strong torsional vibrations of the tool system, leading to a reduced bore hole quality failures. When substituting steel drill tubes with tubes from composite material, the laminate structure dampens these vibrations. Secondly, the integration of sensors allow to monitor process vibrations. This contribution introduces a new sensor platform to measure process vibrations, feed force and drilling torque using Fibre-Bragg Grating Sensors. The presented experimental results focus on characteristic frequency spectra with natural torsional and compression frequencies of the CFRP drill tube, which show variations due to changed feed.

Key message This study identified a significant number of QTL that are associated with FHB disease resistance in NMBU spring wheat panel by conducting genome-wide association study. Abstract Fusarium head blight (FHB) is a widely known devastating disease of wheat caused by Fusarium graminearum and other Fusarium species. FHB resistance is quantitative, highly complex and divided into several resistance types. Quantitative trait loci (QTL) that are effective against several of the resistance types give valuable contributions to resistance breeding. A spring wheat panel of 300 cultivars and breeding lines of Nordic and exotic origins was tested in artificially inoculated field trials and subjected to visual FHB assessment in the years 2013–2015, 2019 and 2020. Deoxynivalenol (DON) content was measured on harvested grain samples, and anther extrusion (AE) was assessed in separate trials. Principal component analysis based on 35 and 25 K SNP arrays revealed the existence of two subgroups, dividing the panel into European and exotic lines. We employed a genome-wide association study to detect QTL associated with FHB traits and identify marker–trait associations that consistently influenced FHB resistance. A total of thirteen QTL were identified showing consistent effects across FHB resistance traits and environments. Haplotype analysis revealed a highly significant QTL on 7A, Qfhb.nmbu.7A.2, which was further validated on an independent set of breeding lines. Breeder-friendly KASP markers were developed for this QTL that can be used in marker-assisted selection. The lines in the wheat panel harbored from zero to five resistance alleles, and allele stacking showed that resistance can be significantly increased by combining several of these resistance alleles. This information enhances breeders´ possibilities for genomic prediction and to breed cultivars with improved FHB resistance.

After orthotopic cardiac xenotransplantation, the combination of both the inflammatory responses to the exposure of a recipient to the xenogeneic organ and the use of cardiopulmonary bypass has been assumed to cause detrimental side effects. These have been described not only to affect the transplanted organ (heart) itself, but also the recipient's lungs. In this article, we summarize how these possible detrimental processes can be minimized or even avoided.Data from eight pig-to-baboon orthotopic cardiac xenotransplantation experiments were analyzed with a special focus on early (within the first week) postoperative organ dysfunction and systemic inflammatory responses. Non-ischemic heart preservation and the careful management of the heart-lung machine were deemed essential to guarantee not only the immediate function of the transplanted xenogeneic organ but also the prompt recovery of the recipient.After weaning from cardiopulmonary bypass, very low catecholamine amounts were needed to ensure an adequate pump function and cardiac output. Central venous oxygen saturation and serum lactate levels remained within normal ranges. All animals were successfully weaned from ventilation within the first postoperative hours. Serum parameters of the transplants and native kidneys and livers were initially slightly elevated or always normal, as were hemoglobin, LDH, and platelet measurements. Markers of systemic inflammation, C-reactive protein, and IL-6 were slightly elevated, but the reactions caused no lasting damage.Consistent short-term and long-term results were achieved after orthotopic cardiac pig-to-baboon transplantation without detrimental inflammatory responses or signs of multiorgan failure. In comparison to allogeneic procedures, non-ischemic heart preservation was important for successful immediate organ function, as was the management of the heart-lung machine. Thus, we believe that genetically modified porcine hearts are ready for use in the clinical setting.

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.

Pneumonia is one of the most common infections in intensive care patients, and it is often treated with beta-lactam antibiotics. Even if therapeutic drug monitoring in blood is available, it is unclear whether sufficient concentrations are reached at the target site: the lung. The present study was initiated to fill this knowledge gap. Various compartments from 10 patients' explanted lungs were subjected to laboratory analysis. Meropenem was quantified in serum, bronchoalveolar lavage (BAL) fluid, microdialysate, and homogenized lung tissue with isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS). BAL fluid represents diluted epithelial lining fluid (ELF), and microdialysate represents interstitial fluid (IF). Differences between target site and blood concentrations were investigated. The median meropenem concentration in blood, ELF, IF, and tissue were 26.8, 18.0, 12.1, and 9.1 mg/liter, respectively. A total of 37.5% of the target site ELF and IF meropenem concentrations were below the clinical EUCAST breakpoint of 8 mg/liter. The median ELF/serum quotient was 61.8% (interquartile range [IQR], 24.8% to 87.6%), the median IF/serum quotient was 35.4% (IQR, 23.8% to 54.3%), and the median tissue/serum quotient was 34.2% (IQR, 28.3% to 38.2%). We observed a substantial interindividual variability between the blood and the compartments (ELF and IF), whereas the intraindividual variability was relatively low. Target site measurement in different lung compartments was feasible and successfully applied in a clinical setting. A relevant amount of 37.5% of the target site concentrations were below the clinical EUCAST breakpoint, indicating subtherapeutic dosing in high-risk patients receiving perioperative antibiotic prophylaxis in lung transplantation. (This study has been registered at ClinicalTrials.gov under identifier NCT03970265.).

INTRODUCTION Chronic kidney disease (CKD) is associated with significant morbidity and mortality after lung transplantation (LTX). Calcineurin inhibitor (CNI) nephrotoxicity is the leading cause of CKD. After kidney transplantation, polyomavirus-associated nephropathy (PyVAN) is a well-recognized problem. This study aims to evaluate the role of polyomavirus in patients after LTX. METHODS From January 2017 to January 2020, all lung transplant recipients who performed follow-up visits in our center were included in the study and retrospectively assessed. We measured renal function (creatinine levels before and after transplantation), JCPyV, and BKPyV load by polymerase chain reaction (PCR) in serum and urine samples after transplantation. RESULTS In total, 104 consecutive patients (59 males, 56.7%) with a mean age of 49.6 ± 11.1 years were identified. JCPyV was found in urine of 36 patients (34.6%) and serum of 3 patients (2.9%). BKPyV was found in urine of 40 patients (38.5%) and serum of 4 patients (3.8%), respectively. Urine evidence for JCPyV (p

Microbes can form complex communities that perform critical functions in maintaining the integrity of their environment or their hosts’ well-being. 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, here we present a deep learning framework that automatically learns the map between species assemblages and community compositions from training data only, without knowledge of any of the above processes. First, we systematically validate our framework using synthetic data generated by classical population dynamics models. Then, we apply it to experimental data of both in vitro and in vivo communities, including ocean and soil microbial communities, Drosophila melanogaster gut microbiota, and human gut and oral microbiota. In particular, we show how 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.

OBJECTIVES We evaluated the outcome of patients in cardiogenic shock receiving a paracorporeal pulsatile biventricular assist device as a bridge to transplantation. METHODS We performed a retrospective single-centre analysis of all patients who received a Berlin Heart Excor® at our institution between 2004 and 2019. RESULTS A total of 97 patients (90 adults, 7 paediatric) were analysed. Eighty-four patients were in Interagency Registry for Mechanically Assisted Circulatory Support level 1 (80 adults, 4 paediatric). Diagnoses were dilated cardiomyopathy (n = 41), ischaemic cardiomyopathy (n = 17) or myocardial infarction (n = 4), myocarditis (n = 15), restrictive cardiomyopathy (n = 2), graft failure after heart transplant (n = 7), postcardiotomy heart failure (n = 5), postpartum cardiomyopathy (n = 3), congenital heart disease (n = 1), valvular cardiomyopathy (n = 1) and toxic cardiomyopathy (n = 1). All patients were in biventricular heart failure and had secondary organ dysfunction. The mean duration of support was 63 days (0–487 days). There was a significant decrease in creatinine values after assist device implantation (from 1.83 ± 0.79 to 1.12 ± 0.67 mg/dl, P = 0.001) as well as a decrease in bilirubin values (from 3.94 ± 4.58 to 2.65 ± 3.61 mg/dl, P = 0.084). Cerebral stroke occurred in 16 patients, bleeding in 15 and infection in 13 patients. Forty-eight patients died on support, while 49 patients could be successfully bridged to transplantation. Thirty-day survival and 1-year survival were 70.1% and 41.2%, respectively. CONCLUSIONS A pulsatile biventricular assist device is a reasonable therapeutic option in cardiogenic shock, when immediate high cardiac output is necessary to rescue the already impaired kidney and liver function of the patient.

BACKGROUND Posaconazole and itraconazole are commonly used for systemic antifungal prophylaxis after lung transplantation. The aim of this study on critically ill lung transplant recipients was to assess the rate of adequate plasma concentrations and the frequency of fungal-induced transitions from antifungal prophylaxis to therapy after the administration of either posaconazole or itraconazole for systemic prophylaxis. METHODS Critically ill lung transplant recipients with postoperative posaconazole or itraconazole prophylaxis and therapeutic drug monitoring from February 2016 to November 2019 were retrospectively included in the study. Positive fungal cultures or Aspergillus antigen tests resulting in a transition from antifungal prophylaxis to therapy were analyzed from the first day of prophylaxis until 7 days after the last sample for each patient. Adequate plasma concentrations were defined as ≥500 µg/L for itraconazole and ≥700 µg/L for posaconazole. RESULTS Two hundred seventy-five samples from 73 patients were included in the analysis. Overall, 60% of the posaconazole and 55% of the itraconazole concentrations were subtherapeutic. Administration of posaconazole suspension resulted significantly (P

The current COVID-19 pandemia affects health care systems worldwide, however, to a variable extent depending on the caseload in each country. We aimed to provide a cross-sectional overview of current limitations or adaptions in lung transplant programs in Germany in from January to May 2020 due to the COVID-19 pandemia caused by severe acute respiratory syndrome coronavirus 2. A cross-sectional survey assessing various aspects of lung transplant activity was sent to all active lung transplant programs (n = 12) in Germany. Eight centers (66%) responded to the survey within the requested time frame. Four centers (50%) reported their activity is not restricted at all and four centers (50%) reported on moderate general limitations. The overall lung transplant activity in Germany from January to May 2020 contains 128 bilateral and 11 single lung transplantations, which is similar to the same period in the year 2019 (126 bilateral transplantations and 12 single lung transplantations). The results suggest that the influence of the COVID-19 pandemia on lung transplantation activity in Germany has been moderate so far. Nevertheless, adaptions such as extensive testing of donors and recipients were introduced to reduce the likelihood of infections and increase patient safety. Alertness to changes in COVID-19 reproduction rates might be required until effective antiviral therapy or vaccination is available.

We present COMPETE , a novel approach that models and computes dominance over user-provided input entities, given a database of top-k rankings. The resulting entities are found superior or inferior with tunable degree of dominance over the input set—a very intuitive, yet insightful way to explore pros and cons of entities of interest. Several notions of dominance are defined which differ in computational complexity and strictness of the dominance concept—yet, interdependent through containment relations. COMPETE is able to pick the most promising approach to satisfy a user request at minimal runtime latency, using a probabilistic model that is estimating the result sizes. The individual flavors of dominance are cast into a stack of algorithms over inverted indices and auxiliary structures. The extensive experimental evaluation over real-world and synthetically generated data and workloads demonstrates the diversity of the problem in terms of number of valid results and need for result ordering and, in particular, emphasizes the immense effect of the pruning strategies with performance gains up to an order of magnitude over baseline approaches.

Pirfenidone demonstrated pleiotropic antiinflammatory effects in various experimental and clinical settings. The aim of this study was to assess the impact of previous treatment with pirfenidone on short-term outcomes after single lung transplantation (SLTx). Therefore, patients with idiopathic pulmonary fibrosis (IPF) who were undergoing SLTx were screened retrospectively for previous use of pirfenidone and compared to respective controls. Baseline parameters and short-term outcomes were recorded and analyzed. In total, 17 patients with pirfenidone were compared with 26 patients without antifibrotic treatment. Baseline characteristics and severity of disease did not differ between groups. Use of pirfenidone did not increase blood loss, wound-healing, or anastomotic complications. Severity of primary graft dysfunction at 72 hours was less (0.3 ± 0.6 vs 1.4 ± 1.3, P = .002), and length of mechanical ventilation (37.5 ± 34.8 vs 118.5 ± 151.0 hours, P = .016) and intensive care unit (ICU) stay (6.6 ± 7.1 vs 15.6 ± 20.3, P = .089) were shorter in patients with pirfenidone treatment. An independent beneficial effect of pirfenidone was confirmed by regression analysis while controlling for confounding variables (P = .016). Finally, incidence of acute cellular rejections within the first 30 days after SLTx was lower in patients with previous pirfenidone treatment (0.0% vs 19.2%; P = .040). Our data suggest a beneficial role of previous use of pirfenidone in patients with IPF who were undergoing SLTx.