A major yellow rust resistance QTL on chromosome 6A shows increased frequency in recent Norwegian spring wheat cultivars and breeding lines.

KEY MESSAGE: A major yellow rust resistance QTL, QYr.nmbu.6A, contributed consistent adult plant resistance in field trials across Europe, China, Kenya and Mexico. Puccinia striiformis f. sp. tritici, causing wheat yellow rust (YR), is one of the most devastating biotrophic pathogens affecting global wheat yields. Owing to the recent epidemic of the PstS10 race group in Europe, yellow rust has become a reoccurring disease in Norway since 2014. As all stage resistances (ASR) (or seedling resistances) are usually easily overcome by pathogen evolution, deployment of durable adult plant resistance (APR) is crucial for yellow rust resistance breeding. In this study, we assessed a Nordic spring wheat association mapping panel (n = 301) for yellow rust field resistance in seventeen field trials from 2015 to 2021, including nine locations in six countries across four different continents. Nine consistent QTL were identified across continents by genome-wide association studies (GWAS). One robust QTL on the long arm of chromosome 6A, QYr.nmbu.6A, was consistently detected in nine out of the seventeen trials. Haplotype analysis of QYr.nmbu.6A confirmed significant QTL effects in all tested environments and the effect was also validated using an independent panel of new Norwegian breeding lines. Increased frequency of the resistant haplotype was found in new varieties and breeding lines in comparison to older varieties and landraces, implying that the resistance might have been selected for due to the recent changes in the yellow rust pathogen population in Europe.

Machine learning identifies pathophysiologically and prognostically informative phenotypes among patients with mitral regurgitation undergoing transcatheter edge-to-edge repair.

AIMS: Patients with mitral regurgitation (MR) present with considerable heterogeneity in cardiac damage depending on underlying aetiology, disease progression, and comorbidities. This study aims to capture their cardiopulmonary complexity by employing a machine-learning (ML)-based phenotyping approach. METHODS AND RESULTS: Data were obtained from 1426 patients undergoing mitral valve transcatheter edge-to-edge repair (MV TEER) for MR. The ML model was developed using 609 patients (derivation cohort) and validated on 817 patients from two external institutions. Phenotyping was based on echocardiographic data, and ML-derived phenotypes were correlated with 5-year outcomes. Unsupervised agglomerative clustering revealed four phenotypes among the derivation cohort: Cluster 1 showed preserved left ventricular ejection fraction (LVEF; 56.5 ± 7.79%) and regular left ventricular end-systolic diameter (LVESD; 35.2 ± 7.52 mm); 5-year survival in Cluster 1, hereinafter serving as a reference, was 60.9%. Cluster 2 presented with preserved LVEF (55.7 ± 7.82%) but showed the largest mitral valve effective regurgitant orifice area (0.623 ± 0.360 cm2) and highest systolic pulmonary artery pressures (68.4 ± 16.2 mmHg); 5-year survival ranged at 43.7% (P-value: 0.032). Cluster 3 was characterized by impaired LVEF (31.0 ± 10.4%) and enlarged LVESD (53.2 ± 10.9 mm); 5-year survival was reduced to 38.3% (P-value: <0.001). The poorest 5-year survival (23.8%; P-value: <0.001) was observed in Cluster 4 with biatrial dilatation (left atrial volume: 312 ± 113 mL; right atrial area: 46.0 ± 8.83 cm2) although LVEF was only slightly reduced (51.5 ± 11.0%). Importantly, the prognostic significance of ML-derived phenotypes was externally confirmed. CONCLUSION: ML-enabled phenotyping captures the complexity of extra-mitral valve cardiac damage, which does not necessarily occur in a sequential fashion. This novel phenotyping approach can refine risk stratification in patients undergoing MV TEER in the future.

Echocardiographic evaluation of left ventricular function using an automated analysis algorithm is feasible for beginners and experts: comparison with invasive and non-invasive methods.

AIMS: Echocardiographic measurement of left ventricular function using a user-friendly automated three-dimensional algorithm is highly attractive as it promises quick and accurate diagnosis, circumventing limitations associated with visual estimation or manual biplane measurements. We sought to assess the feasibility and correlation of such automated analysis with clinically established methods. METHODS: A total of 198 patients undergoing transthoracic echocardiography (TTE) with assessment of left ventricular parameters by automated software algorithm (Philips 3D-Heartmodel; 3D-HM) which additionally had either left ventricular angiography (LVA) or cardiac magnetic resonance (CMR) within 24 h of the TTE examination were analyzed. Left ventricular parameters (left ventricular end-diastolic volume, LVEDV, left ventricular end-systolic volume, LVESV as well as left ventricular ejection fraction, LVEF) were compared between 3D-HM, CMR and LVA. RESULTS: Correlation of left ventricular measurements was overall good to excellent and stronger for CMR (EF r = 0.824) than for LVA (EF r = 0.746). Unexperienced and expert clinicians yielded comparable good results. For CMR, highest correlation was detected in patients with BMI < 25 and excellent image quality. High agreement was seen between 3D-HM and CMR or LVA when stratifying patients according to heart failure categories. CONCLUSIONS: Echocardiographic quantification of left ventricular parameters using a software-based algorithm correlated well with established invasive and non-invasive modalities in the clinical setting, even for unexperienced clinicians. Such automated approaches are promising as they allow a reliable, more observer-independent as well as reproducible assessment of left ventricular function.

The impact of extra-valvular cardiac damage on mid-term clinical outcome following transcatheter aortic valve replacement in patients with severe aortic stenosis.

Aims: To quantify extra-valvular cardiac damage associated with severe aortic valve stenosis (AS), a novel staging model was proposed. This study aimed to validate this model in patients undergoing transcatheter aortic valve replacement (TAVR) as well as to assess its prognostic impact. Methods and results: Based on echocardiographic findings, the following stages were applied: isolated AS (stage 0), left ventricular (LV) damage (stage 1), left atrial or mitral valve damage (stage 2), pulmonary hypertension or tricuspid regurgitation (stage 3), or right ventricular dysfunction (stage 4). The primary endpoint was 2-year all-cause mortality. The distribution across stages was 0.8% at stage 0, 7.5% at stage 1, 63.3% at stage 2, 18.3% at stage 3, and 10.1% at stage 4. All-cause mortality increased at all stages 1-4 (12.1%, 18.2%, 26.6%, and 28.2%; p = 0.023). In the multivariate model, the stage of cardiac damage, age, New York Heart Association (NYHA) class III/IV, peripheral artery disease, and previous pacemaker were independent predictors of the primary endpoint. Conclusions: Patients treated for severe AS show a high prevalence of extra-valvular cardiac damage. An increase in stage is associated with higher 2-year all-cause mortality. The application of this staging model may add value to current treatment algorithms.

Genome-wide association study and genomic prediction of resistance to stripe rust in current Central and Northern European winter wheat germplasm.

KEY MESSAGE: We found two loci on chromosomes 2BS and 6AL that significantly contribute to stripe rust resistance in current European winter wheat germplasm. Stripe or yellow rust, caused by the fungus Puccinia striiformis Westend f. sp. tritici, is one of the most destructive wheat diseases. Sustainable management of wheat stripe rust can be achieved through the deployment of rust resistant cultivars. To detect effective resistance loci for use in breeding programs, an association mapping panel of 230 winter wheat cultivars and breeding lines from Northern and Central Europe was employed. Genotyping with the Illumina® iSelect® 25 K Infinium® single nucleotide polymorphism (SNP) genotyping array yielded 8812 polymorphic markers. Structure analysis revealed two subpopulations with 92 Austrian breeding lines and cultivars, which were separated from the other 138 genotypes from Germany, Norway, Sweden, Denmark, Poland, and Switzerland. Genome-wide association study for adult plant stripe rust resistance identified 12 SNP markers on six wheat chromosomes which showed consistent effects over several testing environments. Among these, two marker loci on chromosomes 2BS (RAC875_c1226_652) and 6AL (Tdurum_contig29607_413) were highly predictive in three independent validation populations of 1065, 1001, and 175 breeding lines. Lines with the resistant haplotype at both loci were nearly free of stipe rust symptoms. By using mixed linear models with those markers as fixed effects, we could increase predictive ability in the three populations by 0.13-0.46 compared to a standard genomic best linear unbiased prediction approach. The obtained results facilitate an efficient selection for stripe rust resistance against the current pathogen population in the Northern and Central European winter wheat gene pool.

Unlocking big data doubled the accuracy in predicting the grain yield in hybrid wheat.

The potential of big data to support businesses has been demonstrated in financial services, manufacturing, and telecommunications. Here, we report on efforts to enter a new data era in plant breeding by collecting genomic and phenotypic information from 12,858 wheat genotypes representing 6575 single-cross hybrids and 6283 inbred lines that were evaluated in six experimental series for yield in field trials encompassing ~125,000 plots. Integrating data resulted in twofold higher prediction ability compared with cases in which hybrid performance was predicted across individual experimental series. Our results suggest that combining data across breeding programs is a particularly appropriate strategy to exploit the potential of big data for predictive plant breeding. This paradigm shift can contribute to increasing yield and resilience, which is needed to feed the growing world population.

Negative dominance and dominance-by-dominance epistatic effects reduce grain-yield heterosis in wide crosses in wheat.

The genetics underlying heterosis, the difference in performance of crosses compared with midparents, is hypothesized to vary with relatedness between parents. We established a unique germplasm comprising three hybrid wheat sets differing in the degree of divergence between parents and devised a genetic distance measure giving weight to heterotic loci. Heterosis increased steadily with heterotic genetic distance for all 1903 hybrids. Midparent heterosis, however, was significantly lower in the hybrids including crosses between elite and exotic lines than in crosses among elite lines. The analysis of the genetic architecture of heterosis revealed this to be caused by a higher portion of negative dominance and dominance-by-dominance epistatic effects. Collectively, these results expand our understanding of heterosis in crops, an important pillar toward global food security.

Ultrasound-guided thrombin injection for treatment of femoral artery pseudoaneurysm with concomitant AV-fistula - a retrospective single centre experience.

BACKGROUND: Increasing volume of complex percutaneous endovascular procedures in highly anticoagulated patients generate a not negligible percentage of femoral pseudoaneurysms (PSA) with concomitant arteriovenous fistulas (AVF). While ultrasound-guided thrombin injection (UGTI) is the therapy of choice for PSA, concomitant AVF is regarded as a contraindication for UGTI, as venous thromboembolism is feared. In this retrospective, register-based cohort study, we report on and evaluate the use of UGTI for the treatment of PSA with AFV. PATIENTS AND METHODS: All patients (n = 523), who underwent UGTI for femoral PSA at the German Heart Centre Munich from January 2011 until January 2018, were retrospectively reviewed for the presence of a concomitant AVF and outcomes were recorded. RESULTS: Forty femoral PSA/AVFs treated by UGTI were identified. The mean enddiastolic arterial-flow-velocity above the AVF, an estimate of the AVF size, was 14.61 ± 1.7 cm/sec. The Majority of patients exhibited flow-velocities < 25 cm/sec (n = 31; 77.5 %) and were on either uninterrupted oral anticoagulation (n = 32; 80 %) or dual antiplatelet therapy (n = 8). Twenty-eight (70 %) PSA/AVFs could be successfully closed by UGTI. In eight multicompartmental PSAs, partial obliteration necessitated combined treatment with manual compression, while one partial occlusion was treated by observation. There were three failures, of which two underwent covered-stent-graft-implantation and one surgical repair. One DVT (2.5 %) occurred two days after UGTI in the by far largest AVF (60 cm/sec) included in the study. Besides two late PSA recurrences treated by surgery, no other complications were observed. AVF persisted in 65 %, all of them asymptomatic. The mean follow-up was 6 ± 15.5 months. CONCLUSIONS: UGTI appears to be a treatment option in femoral PSA/AVF, at least under oral anticoagulation in small fistulas with enddiastolic arterial-flow-velocities ≤ 25 cm/sec. However, caution is necessary in larger AVFs, which should remain a contraindication for UGTI.