S1 basic leucine zipper transcription factors shape plant architecture by controlling C/N partitioning to apical and lateral organs.

Plants tightly control growth of their lateral organs, which led to the concept of apical dominance. However, outgrowth of the dormant lateral primordia is sensitive to the plant's nutritional status, resulting in an immense plasticity in plant architecture. While the impact of hormonal regulation on apical dominance is well characterized, the prime importance of sugar signaling to unleash lateral organ formation has just recently emerged. Here, we aimed to identify transcriptional regulators, which control the trade-off between growth of apical versus lateral organs. Making use of locally inducible gain-of-function as well as single and higher-order loss-of-function approaches of the sugar-responsive S1-basic-leucine-zipper (S1-bZIP) transcription factors, we disclosed their largely redundant function in establishing apical growth dominance. Consistently, comprehensive phenotypical and analytical studies of S1-bZIP mutants show a clear shift of sugar and organic nitrogen (N) allocation from apical to lateral organs, coinciding with strong lateral organ outgrowth. Tissue-specific transcriptomics reveal specific clade III SWEET sugar transporters, crucial for long-distance sugar transport to apical sinks and the glutaminase GLUTAMINE AMIDO-TRANSFERASE 1_2.1, involved in N homeostasis, as direct S1-bZIP targets, linking the architectural and metabolic mutant phenotypes to downstream gene regulation. Based on these results, we propose that S1-bZIPs control carbohydrate (C) partitioning from source leaves to apical organs and tune systemic N supply to restrict lateral organ formation by C/N depletion. Knowledge of the underlying mechanisms controlling plant C/N partitioning is of pivotal importance for breeding strategies to generate plants with desired architectural and nutritional characteristics.

Coupling of Ferromagnetic and Antiferromagnetic Spin Dynamics in Mn_{2}Au/NiFe Thin Film Bilayers.

We investigate magnetization dynamics of Mn_{2}Au/Py (Ni_{80}Fe_{20}) thin film bilayers using broadband ferromagnetic resonance (FMR) and Brillouin light scattering spectroscopy. Our bilayers exhibit two resonant modes with zero-field frequencies up to almost 40 GHz, far above the single-layer Py FMR. Our model calculations attribute these modes to the coupling of the Py FMR and the two antiferromagnetic resonance (AFMR) modes of Mn_{2}Au. The coupling strength is in the order of 1.6 T nm at room temperature for nm-thick Py. Our model reveals the dependence of the hybrid modes on the AFMR frequencies and interfacial coupling as well as the evanescent character of the spin waves that extend across the Mn_{2}Au/Py interface.

Does experience change the role of systematic biopsy during MRI-fusion biopsy of the prostate?

PURPOSE: To determine the role of biopsy experience regarding a potential benefit of additional systematic biopsies and fusion failures during MRI-targeted biopsy of the prostate. SUBJECTS/PATIENTS AND METHODS: We retrospectively evaluated 576 men undergoing transrectal (MRI)-targeted biopsy of the prostate by seven residents in urology between November 2019 and March 2022. Benefit of systematic biopsies (detection of ISUP ≥ 2 PCa (clinically significant PCa (csPCa)) solely in systematic biopsies) and fusion failure (detection of csPCa during systematic biopsies in the area of a reported MRI-lesion and no detection of csPCa in targeted biopsy) were compared by growing biopsy experience levels. Multivariable regression analyses were calculated to investigate the association with benefit of systematic biopsies and fusion failure. RESULTS: The overall PCa detection rate was 72% (413/576). A benefit of systematic biopsies was observed in 11% (63/576); of those, fusion failure was seen in 76% (48/63). Benefit of systematic biopsies and fusion failure were more common among residents with very low experience compared to highly experienced residents (18% versus 4%, p = 0.026; 13% versus 3%, p = 0.015, respectively). Increasing biopsy experience was associated with less benefit from systematic biopsies (OR: 0.98, 95% CI 0.97-0.99) and less fusion failure (OR: 0.98, 95% CI 0.97-0.99). CONCLUSIONS: The benefit of systematic biopsies following targeted biopsy decreases with growing biopsy experience. The higher risk of fusion failure among inexperienced residents necessitates systematic biopsies to ensure the detection of csPCa. Further prospective trials are warranted before a targeted only approach can be recommended in routine clinical practice.

[Costs of potentially outpatient endoscopic procedures in cases with a 1-day hospital stay versus a longer stay]. / Kosten potenziell ambulant erbringbarer endoskopischer Leistungen in Fällen mit 1-Tages-Verweildauer gegenüber einer längeren Verweildauer.

INTRODUCTION: The transfer of patient care and medical interventions that was previously provided on an inpatient basis to outpatient settings is a stated goal of health politics. It is unclear to what extent costs of an endoscopic procedure and the disease severity depend on the duration of inpatient treatment. We therefore examined whether endoscopic services for cases with a one-day length of stay (VWD) are comparably expensive to cases with a longer VWD. METHODS: Outpatient services were selected from the DGVS service catalog. Day cases with exactly one such gastroenterological endoscopic (GAEN) service were compared with cases with VWD>1 day regarding their patient clinical complexity levels (PCCL) and mean costs. Data from the DGVS-DRG project with §21-KHEntgG cost data from a total of 57 hospitals from 2018 and 2019 served as the basis. Endoscopic costs were taken from cost center group 8 of the InEK cost matrix and plausibility checked. RESULTS: A total of 122,514 cases with exactly one GAEN service were identified. Statistically equal costs were shown in 30 of 47 service groups. In 10 groups, the cost difference was not relevant (<10%). Cost differences >10% existed only for EGD with variceal therapy, insertion of a self-expanding prosthesis, dilatation/bougienage/exchange with PTC/PTCD in place, non-extensive ERCP, endoscopic ultrasound in the upper gastrointestinal tract, and colonoscopy with submucosal or full thickness resection, or foreign object removal. PCCL differed in all but one group. CONCLUSION: Gastroenterology endoscopy services provided as part of inpatient care but potentially performable on an outpatient basis are predominantly equally expensive for day cases as for patients with a length of stay greater than one day. The disease severity is lower. Calculated §21-KHEntgG cost data thus form a reliable basis for the calculation of appropriate reimbursement for hospital services to be provided as outpatient services under the AOP in the future.

Structure-Based Design, Docking and Binding Free Energy Calculations of A366 Derivatives as Spindlin1 Inhibitors.

The chromatin reader protein Spindlin1 plays an important role in epigenetic regulation, through which it has been linked to several types of malignant tumors. In the current work, we report on the development of novel analogs of the previously published lead inhibitor A366. In an effort to improve the activity and explore the structure-activity relationship (SAR), a series of 21 derivatives was synthesized, tested in vitro, and investigated by means of molecular modeling tools. Docking studies and molecular dynamics (MD) simulations were performed to analyze and rationalize the structural differences responsible for the Spindlin1 activity. The analysis of MD simulations shed light on the important interactions. Our study highlighted the main structural features that are required for Spindlin1 inhibitory activity, which include a positively charged pyrrolidine moiety embedded into the aromatic cage connected via a propyloxy linker to the 2-aminoindole core. Of the latter, the amidine group anchor the compounds into the pocket through salt bridge interactions with Asp184. Different protocols were tested to identify a fast in silico method that could help to discriminate between active and inactive compounds within the A366 series. Rescoring the docking poses with MM-GBSA calculations was successful in this regard. Because A366 is known to be a G9a inhibitor, the most active developed Spindlin1 inhibitors were also tested over G9a and GLP to verify the selectivity profile of the A366 analogs. This resulted in the discovery of diverse selective compounds, among which 1s and 1t showed Spindlin1 activity in the nanomolar range and selectivity over G9a and GLP. Finally, future design hypotheses were suggested based on our findings.

Application of the SCAI classification in a cohort of patients with cardiogenic shock.

BACKGROUND: The Society of Cardiovascular Angiography and Interventions (SCAI) have recently proposed a new classification of cardiogenic shock (CS) dividing patients into five subgroups. OBJECTIVE: Aim of this study was to apply the SCAI classification to a cohort of patients presenting with CS and to evaluate its ability to predict 30-day survival. METHODS: SCAI CS subgroups were interpreted based on the recent consensus statement and then applied to N = 1,007 consecutive patients presenting with CS or large myocardial infarction (MI) between October 2009 and October 2017. The association between SCAI classification and 30-day all-cause mortality was assessed by logistic regression analysis. RESULTS: Mean age in the study cohort was 67 (±15) years, 72% were male. Mean lactate at baseline was 6.05 (±5.13) mmol/l and 51% of the patients had prior cardiac arrest. Overall survival probability was 50.6% (95% confidence interval [CI] 47.5-54.0%). In view of the SCAI classification, the survival probability was 96.4% (95% CI 93.7-99.0%) in class A, 66.1% (95% CI 50.2-87.1%) in class B, 46.1% (95% CI 40.6-52.4%) in class C, 33.1% (95% CI 26.6-41.1%) in class D, and 22.6% (95% CI 17.1-30.0%) in class E. Higher SCAI classification was significantly associated with lower 30-day survival (p < .01). CONCLUSION: In this large clinical cohort, the SCAI classification was significantly associated with 30-day survival. This finding supports the rationale of the SCAI CS classification and calls for a validation in a prospective trial.

SUMOylation regulates the intracellular fate of ZO-2.

The zonula occludens (ZO)-2 protein links tight junctional transmembrane proteins to the actin cytoskeleton and associates with splicing and transcription factors in the nucleus. Multiple posttranslational modifications control the intracellular distribution of ZO-2. Here, we report that ZO-2 is a target of the SUMOylation machinery and provide evidence on how this modification may affect its cellular distribution and function. We show that ZO-2 associates with the E2 SUMO-conjugating enzyme Ubc9 and with SUMO-deconjugating proteases SENP1 and SENP3. In line with this, modification of ZO-2 by endogenous SUMO1 was detectable. Ubc9 fusion-directed SUMOylation confirmed SUMOylation of ZO-2 and was inhibited in the presence of SENP1 but not by an enzymatic-dead SENP1 protein. Moreover, lysine 730 in human ZO-2 was identified as a potential modification site. Mutation of this site to arginine resulted in prolonged nuclear localization of ZO-2 in nuclear recruitment assays. In contrast, a construct mimicking constitutive SUMOylation of ZO-2 (SUMO1ΔGG-ZO-2) was preferentially localized in the cytoplasm. Based on previous findings the differential localization of these ZO-2 constructs may affect glycogen-synthase-kinase-3ß (GSK3ß) activity and ß-catenin/TCF-4-mediated transcription. In this context we observed that ZO-2 directly binds to GSK3ß and SUMO1ΔGG-ZO-2 modulates its kinase activity. Moreover, we show that ZO-2 forms a complex with ß-catenin. Wild-type ZO-2 and ZO-2-K730R inhibited transcriptional activity in reporter gene assays, whereas the cytosolic SUMO1ΔGG-ZO-2 did not. From these data we conclude that SUMOylation affects the intracellular localization of ZO-2 and its regulatory role on GSK3ß and ß-catenin signaling activity.

Identification of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening platform.

Epigenetic modifications of histone tails play an essential role in the regulation of eukaryotic transcription. Writer and eraser enzymes establish and maintain the epigenetic code by creating or removing posttranslational marks. Specific binding proteins, called readers, recognize the modifications and mediate epigenetic signalling. Here, we present a versatile assay platform for the investigation of the interaction between methyl lysine readers and their ligands. This can be utilized for the screening of small-molecule inhibitors of such protein-protein interactions and the detailed characterization of the inhibition. Our platform is constructed in a modular way consisting of orthogonal in vitro binding assays for ligand screening and verification of initial hits and biophysical, label-free techniques for further kinetic characterization of confirmed ligands. A stability assay for the investigation of target engagement in a cellular context complements the platform. We applied the complete evaluation chain to the Tudor domain containing protein Spindlin1 and established the in vitro test systems for the double Tudor domain of the histone demethylase JMJD2C. We finally conducted an exploratory screen for inhibitors of the interaction between Spindlin1 and H3K4me3 and identified A366 as the first nanomolar small-molecule ligand of a Tudor domain containing methyl lysine reader.

Fear of cancer progression in patients with stage IA malignant melanoma.

We aimed to determine the prevalence and importance of fear of cancer progression (FoP) in melanoma patients with stage IA tumours to assess psychosocial and demographic factors associated with severity of FoP and to determine the relationship of FoP and quality of life (QoL). One hundred and thirty-six patients with stage IA melanoma completed the short version of the Fear of Progression Questionnaire (FoP-Q-SF), the Hospital Anxiety and Depression Scale (HADS) and the EORTC-QLQ-C30. We found a mean FoP-Q-SF sum score of 30.2 points (±8.4 points SD). In this study, 33% of patients reported high FoP at or above the cutoff-value of 34 points. Higher FoP was found in women (p < 0.01), young (p = 0.03) and employed (p = 0.02) patients. Being confronted with a cancer diagnosis in closely related persons predicted higher FoP (p < 0.01). FoP correlated positively with the HADS anxiety (r = 0.50, p < 0.01) and depression scales (r = 0.26, p < 0.01) and negatively with the EORTC-QLQ-C30 global health state (r = -0.32, p < 0.01). FoP is considerably prevalent in low-risk melanoma patients and associated with reduced QoL, cancer in related persons, women sex and participation in working life. Considerably high levels of FoP, even in patients with low-risk malignancies, underline the need for psychosocial support and psychotherapeutic interventions for melanoma patients.

Sequence errors in foamy virus sequences in the GenBank database: resequencing of the prototypic foamy virus proviral plasmids.

Nucleotide sequences are the fundamental basis for work on molecular mechanisms and for phylogenetic analysis. Recently, we identified sequence errors in all of the LTR sequences of the prototypic foamy virus stored in the GenBank database. Here, we report the resequencing of the proviral plasmids pHSRV13 and pHSRV2. Sequence comparisons revealed an error rate for the foamy virus sequences stored in the database of up to 10 errors per 1000 bp. Even the newest sequences of the codon-optimized foamy virus synthetic Gag, Pol, and Env amino acid sequences showed exchanges compared to the new proviral pHSRV13n sequence. Our results provide evidence that some prototypic foamy virus sequences contain errors and should be revised.

Histone deacetylase 2 controls p53 and is a critical factor in tumorigenesis.

Histone deacetylase 2 (HDAC2) regulates biological processes by deacetylation of histones and non-histone proteins. HDAC2 is overexpressed in numerous cancer types, suggesting general cancer-relevant functions of HDAC2. In human tumors the TP53 gene encoding p53 is frequently mutated and wild-type p53 is often disarmed. Molecular pathways inactivating wild-type p53 often remain to be defined and understood. Remarkably, current data link HDAC2 to the regulation of the tumor suppressor p53 by deacetylation and to the maintenance of genomic stability. Here, we summarize recent findings on HDAC2 overexpression in solid and hematopoietic cancers with a focus on mechanisms connecting HDAC2 and p53 in vitro and in vivo. In addition, we present an evidence-based model that integrates molecular pathways and feedback loops by which p53 and further transcription factors govern the expression and the ubiquitin-dependent proteasomal degradation of HDAC2 and of p53 itself. Understanding the interactions between p53 and HDAC2 might aid in the development of new therapeutic approaches against cancer.

R2 Indicator-Based Multiobjective Search.

In multiobjective optimization, set-based performance indicators are commonly used to assess the quality of a Pareto front approximation. Based on the scalarization obtained by these indicators, a performance comparison of multiobjective optimization algorithms becomes possible. The R2 and the hypervolume (HV) indicator represent two recommended approaches which have shown a correlated behavior in recent empirical studies. Whereas the HV indicator has been comprehensively analyzed in the last years, almost no studies on the R2 indicator exist. In this extended version of our previous conference paper, we thus perform a comprehensive investigation of the properties of the R2 indicator in a theoretical and empirical way. The influence of the number and distribution of the weight vectors on the optimal distribution of µ solutions is analyzed. Based on a comparative analysis, specific characteristics and differences of the R2 and HV indicator are presented. Furthermore, the R2 indicator is integrated into an indicator-based steady-state evolutionary multiobjective optimization algorithm (EMOA). It is shown that the so-called R2-EMOA can accurately approximate the optimal distribution of µ solutions regarding R2.

Structures of KcsA in complex with symmetrical quaternary ammonium compounds reveal a hydrophobic binding site.

Potassium channels allow for the passive movement of potassium ions across the cell membrane and are instrumental in controlling the membrane potential in all cell types. Quaternary ammonium (QA) compounds block potassium channels and have long been used to study the functional and structural properties of these channels. Here we describe the interaction between three symmetrical hydrophobic QAs and the prokaryotic potassium channel KcsA. The structures demonstrate the presence of a hydrophobic pocket between the inner helices of KcsA and provide insight into the binding site and blocking mechanism of hydrophobic QAs. The structures also reveal a structurally hidden pathway between the central cavity and the outside membrane environment reminiscent of the lateral fenestration observed in sodium channels that can be accessed through small conformational changes in the pore wall. We propose that the hydrophobic binding pocket stabilizes the alkyl chains of long-chain QA molecules and may play a key role in hydrophobic drug binding in general.

Enhancer-promoter specificity in gene transcription: molecular mechanisms and disease associations.

Although often located at a distance from their target gene promoters, enhancers are the primary genomic determinants of temporal and spatial transcriptional specificity in metazoans. Since the discovery of the first enhancer element in simian virus 40, there has been substantial interest in unraveling the mechanism(s) by which enhancers communicate with their partner promoters to ensure proper gene expression. These research efforts have benefited considerably from the application of increasingly sophisticated sequencing- and imaging-based approaches in conjunction with innovative (epi)genome-editing technologies; however, despite various proposed models, the principles of enhancer-promoter interaction have still not been fully elucidated. In this review, we provide an overview of recent progress in the eukaryotic gene transcription field pertaining to enhancer-promoter specificity. A better understanding of the mechanistic basis of lineage- and context-dependent enhancer-promoter engagement, along with the continued identification of functional enhancers, will provide key insights into the spatiotemporal control of gene expression that can reveal therapeutic opportunities for a range of enhancer-related diseases.

Mn-promoted MoS2 catalysts for CO2 hydrogenation: enhanced methanol selectivity due to MoS2/MnOx interfaces.

Considering the alarming scenario of climate change, CO2 hydrogenation to methanol is considered a key process for phasing out fossil fuels by means of CO2 utilization. In this context, MoS2 catalysts have recently shown to be promising catalysts for this reaction, especially in the presence of abundant basal-plane sulfur vacancies and due to synergistic mechanisms with other phases. In this work, Mn-promoted MoS2 prepared by a hydrothermal method presents considerable selectivity for CO2 hydrogenation to methanol in comparison with pure MoS2 and other promoters such as K and Co. Interestingly, if CO is used as a carbon source for the reaction, methanol production is remarkably lower, which suggests the absence of a CO intermediate during CO2 hydrogenation to methanol. After optimization of synthesis parameters, a methanol selectivity of 64% is achieved at a CO2 conversion of 2.8% under 180 °C. According to material characterization by X-ray Diffraction and X-ray Absorption, the Mn promoter is present mainly in the form of MnO and MnCO3 phases, with the latter undergoing convertion to MnO upon H2 pretreatment. However, following exposure to reaction conditions, X-ray photoelectron spectroscopy suggests that higher oxidation states of Mn may be present at the surface, suggesting that the improved catalytic activity for CO2 hydrogenation to methanol arises from a synergy between MoS2 and MnOx at the catalyst surface.

Recruitment of CTCF to the SIRT1 promoter after Oxidative Stress mediates Cardioprotective Transcription.

Because most DNA-binding transcription factors (dbTFs), including the architectural regulator CTCF, bind RNA and exhibit di-/multimerization, a central conundrum is whether these distinct properties are regulated post-transcriptionally to modulate transcriptional programs. Here, investigating stress-dependent activation of SIRT1, encoding an evolutionarily-conserved protein deacetylase, we show that induced phosphorylation of CTCF acts as a rheostat to permit CTCF occupancy of low-affinity promoter DNA sites to precisely the levels necessary. This CTCF recruitment to the SIRT1 promoter is eliciting a cardioprotective cardiomyocyte transcriptional activation program and provides resilience against the stress of the beating heart in vivo . Mice harboring a mutation in the conserved low-affinity CTCF promoter binding site exhibit an altered, cardiomyocyte-specific transcriptional program and a systolic heart failure phenotype. This transcriptional role for CTCF reveals that a covalent dbTF modification regulating signal-dependent transcription serves as a previously unsuspected component of the oxidative stress response.

Uncertainty estimation for deep learning-based pectoral muscle segmentation via Monte Carlo dropout.

Objective. Deep Learning models are often susceptible to failures after deployment. Knowing when your model is producing inadequate predictions is crucial. In this work, we investigate the utility of Monte Carlo (MC) dropout and the efficacy of the proposed uncertainty metric (UM) for flagging of unacceptable pectoral muscle segmentations in mammograms.Approach. Segmentation of pectoral muscle was performed with modified ResNet18 convolutional neural network. MC dropout layers were kept unlocked at inference time. For each mammogram, 50 pectoral muscle segmentations were generated. The mean was used to produce the final segmentation and the standard deviation was applied for the estimation of uncertainty. From each pectoral muscle uncertainty map, the overall UM was calculated. To validate the UM, a correlation between the dice similarity coefficient (DSC) and UM was used. The UM was first validated in a training set (200 mammograms) and finally tested in an independent dataset (300 mammograms). ROC-AUC analysis was performed to test the discriminatory power of the proposed UM for flagging unacceptable segmentations.Main results. The introduction of dropout layers in the model improved segmentation performance (DSC = 0.95 ± 0.07 versus DSC = 0.93 ± 0.10). Strong anti-correlation (r= -0.76,p< 0.001) between the proposed UM and DSC was observed. A high AUC of 0.98 (97% specificity at 100% sensitivity) was obtained for the discrimination of unacceptable segmentations. Qualitative inspection by the radiologist revealed that images with high UM are difficult to segment.Significance. The use of MC dropout at inference time in combination with the proposed UM enables flagging of unacceptable pectoral muscle segmentations from mammograms with excellent discriminatory power.

Medial temporal theta/alpha power enhancement precedes successful memory encoding: evidence based on intracranial EEG.

Not only poststimulus, but also prestimulus neural activity has been shown to be predictive for later successful memory encoding. However, it is still not clear which medial temporal lobe processes precede effective memory formation. Here, our aim was to investigate whether such prestimulus markers for successful memory encoding can be specified based on intracranial recordings directly from the hippocampus and rhinal cortex. For this purpose, we analyzed subsequent memory effects during a continuous word recognition paradigm in 31 presurgical epilepsy patients. We found that rhinal and hippocampal theta and successive alpha power enhancement before word presentation predicted successful memory encoding. Previous studies suggest that stimulus-triggered hippocampal theta activity is particularly related to memory retrieval and activation of a mnemonic context, whereas the alpha rhythm reflects inhibitory top-down control of task processing and executive functioning. In line with these suggestions, we propose that the observed medial temporal theta and alpha power increases before stimulus presentation reflect activation of contextual information and inhibitory top-down control processes preparing for stimulus-triggered memory processing.

On the effect of response transformations in sequential parameter optimization.

Parameter tuning of evolutionary algorithms (EAs) is attracting more and more interest. In particular, the sequential parameter optimization (SPO) framework for the model-assisted tuning of stochastic optimizers has resulted in established parameter tuning algorithms. In this paper, we enhance the SPO framework by introducing transformation steps before the response aggregation and before the actual modeling. Based on design-of-experiments techniques, we empirically analyze the effect of integrating different transformations. We show that in particular, a rank transformation of the responses provides significant improvements. A deeper analysis of the resulting models and additional experiments with adaptive procedures indicates that the rank and the Box-Cox transformation are able to improve the properties of the resultant distributions with respect to symmetry and normality of the residuals. Moreover, model-based effect plots document a higher discriminatory power obtained by the rank transformation.

Impact of diastolic pulmonary gradient and pulmonary artery pulse index on outcomes in heart transplant patients-Results from the Eurotransplant database.

Background: Predicting complications associated with pulmonary hypertension (PH) after cardiac transplantation is an important factor when considering cardiac transplantation. The transpulmonary gradient (TPG) is recommended to quantify PH in transplant candidates. Nonetheless, PH remains a common driver of mortality. The diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) can differentiate post- from combined pre- and post-capillary PH and may improve estimation of PH-associated risks. We used a large European cohort of transplant candidates to assess whether the pulmonary pulsatility index (PAPi), improves prediction of graft failure and mortality compared to DPG and PVR. Methods: Out of all patients undergoing heart transplantation between 2009 and 2019 in Eurotransplant member states (n = 10,465), we analyzed the impact of PH (mPAP > 25 mmHg) and right heart catheter hemodynamic data on graft failure and mortality within 1-5 years. Results: In 1,407 heart transplant patients with PH (79% male, median age 54 years, IQR 39-69 years), the median PVR was 2.5 WU (IQR 1.6 WU) with a median mPAP (pulmonary arterial pressure) of 32 mmHg (IQR 9 mmHg). Patients with low (< 3 mmHg) DPG had a better 5 year survival than those with higher DPG (log rank p = 0.023). TPG, mPAP, PAPi, and PVR did not improve prediction of survival. Low PAPi (OR = 2.24, p < 0.001) and high PVR (OR = 2.12, p = 0.005) were associated with graft failure. Conclusion: PAPI and PVR are associated with graft failure in patients with PH undergoing cardiac transplantation. DPG is associated with survival in this cohort.