[New treatment strategies for primary lymphoma of the central nervous system]. / Neue Therapiestrategien beim primären Lymphom des Zentralnervensystems.

Primary central nervous system lymphomas (PCNSL) are rare highly aggressive diffuse large B cell non-Hodgkin lymphomas confined to the brain, meninges, the spinal cord and the eyes. Although the implementation of high-dose methotrexate-based chemotherapy has significantly improved the prognosis of PCNSL during the last decades, about one third of patients show refractory disease and about half of the patients eventually relapse after having achieved complete response. This highlights the need for novel treatment strategies. The most promising progress has been made in the field of molecular targeted therapy that interferes with the oncogenic signaling pathways of PCNSL. These include inhibitors of Bruton tyrosine kinase and inhibitors of the PI3K/mTOR signaling pathway. In addition, the thalidomide analogues lenalidomide and pomalidomide, which belong to the class of immunomodulators, show efficacy in the treatment of PCNSL. As immune evasion appears to play a relevant pathogenetic role in PCNSL, immunotherapies in the treatment of PCNSL are the subject of intensive research. Promising initial clinical data are available for both immune checkpoint inhibitors and cellular immunotherapy with chimeric antigen receptor (CAR) T cells. Before the widespread clinical application of these novel therapies, the efficacy needs to be confirmed in larger prospective studies. Despite high response rates, targeted therapies and immunotherapy often fail to achieve lasting tumor control. Therefore, novel approaches are currently being investigated in combination protocols.

Social cognition and occupational reintegration in primary central nervous system lymphoma long-term survivors: a secondary analysis of a combined data set.

OBJECTIVE: Although sociocognitive impairment is linked to failure of occupational reintegration in other clinical populations, less is known on the association of sociocognitive functioning and occupational reintegration in brain tumor patients such as primary central nervous system lymphoma (PCNSL). METHODS: Twenty PCNSL patients with ongoing complete response to therapy for at least one year were evaluated of whom eight resumed work. The association between occupational status, empathy, alexithymia and social problem solving was analyzed. RESULTS: Employed and non-employed patients were significantly different in their ability to provide appropriate solutions for social situations even when accounting for neurocognition. Decreased quality of life was associated with sociocognitive impairment. CONCLUSIONS: Although the results must be replicated in larger, more representative populations, this exploratory analysis tentatively adds facets to the literature on occupational reintegration in brain tumor patients. Forthcoming psychosocial research and clinical practice may target sociocognitive impairment when addressing reintegration after neuro-oncological treatment.

MGMT promoter methylation analysis for allocating combined CCNU/TMZ chemotherapy: Lessons learned from the CeTeG/NOA-09 trial.

The CeTeG/NOA-09 trial showed a survival benefit for combined CCNU/TMZ therapy in MGMT-promoter-methylated glioblastoma patients (quantitative methylation-specific PCR [qMSP] ratio > 2). Here, we report on the prognostic value of the MGMT promoter methylation ratio determined by qMSP and evaluate the concordance of MGMT methylation results obtained by qMSP, pyrosequencing (PSQ) or DNA methylation arrays (MGMT-STP27). A potential association of qMSP ratio with survival was analyzed in the CeTeG/NOA-09 trial population (n = 129; log-rank tests, Cox regression analyses). The concordance of MGMT methylation assays (qMSP, PSQ and MGMT-STP27) was evaluated in 76 screened patients. Patients with tumors of qMSP ratio > 4 showed superior survival compared to those with ratios 2-4 (P = .0251, log-rank test). In multivariate analysis, the qMSP ratio was not prognostic across the study cohort (hazard ratio [HR] = 0.88; 95% CI: 0.72-1.08). With different cutoffs for qMSP ratio (4, 9, 12 or 25), the CCNU/TMZ benefit tended to be larger in subgroups with lower ratios (eg, for cutoff 9: HR 0.32 for lower subgroup, 0.73 for higher subgroup). The concordance rates with qMSP were 94.4% (PSQ) and 90.2% (MGMT-STP27). Discordant results were restricted to tumors with qMSP ratios ≤4 and PSQ mean methylation rate ≤25%. Despite a shorter survival in MGMT-promoter-methylated patients with lower methylation according to qMSP, these patients had a benefit from combined CCNU/TMZ therapy, which even tended to be stronger than in patients with higher methylation rates. With acceptable concordance rates, decisions on CCNU/TMZ therapy may also be based on PSQ or MGMT-STP27.

Complications of intracerebroventricular chemotherapy via subgaleal reservoir in primary central nervous system lymphoma: A single-institution experience on 1247 installations in 94 consecutive patients.

The implantation of a subgaleal reservoir intracerebroventricular (ICV port) in order to apply ICV chemotherapy in patients with leptomeningeal cancer may be complicated by misplacement of the device, pericatheter leucencephalopathy, hemorrhage and iatrogenic ventriculitis/meningitis. Here we analyzed the occurrence of such complications in patients with primary central nervous system lymphoma (PCNSL) treated with systemic and ICV methotrexate- and cytarabine-based chemotherapy. We retrospectively reviewed the medical records of 94 consecutive patients (1247 installations), who had received an ICV port for intraventricular chemotherapy for treatment of histologically confirmed PCNSL at our institution between September 2005 and October 2018. Infectious and noninfectious complications were systematically recorded including clinical, laboratory, and imaging data. In 9/94 patients (9.6%), a misplacement of the ICV port seen on the postoperative computed tomography scan was corrected immediately and chemotherapy was then continued as planned. In 5/94 patients (5.3%), symptomatic noninfectious complications were observed (four patients with symptomatic pericatheter leucencephalopathy and one patient with surgical scar dehiscence with CSF leak). In 8/94 patients (8.5%), asymptomatic white matter lesions around the catheter were visible on cerebral magnetic resonance imaging after completion of therapy. The rate of infectious complications was 6/94 patients (6.4%). No complication was lethal or required intensive care monitoring. This retrospective study shows that complications of ICV treatment have to be expected in a fraction of patients, however, in this series these complications were manageable and did not result in long-term deficits.

Complete response to therapy: why do primary central nervous system lymphoma patients not return to work?

PURPOSE: Although primary central nervous system lymphomas (PCNSL) represent extremely aggressive brain tumours, high-dose methotrexate in combination with other chemotherapeutic agents has resulted in long-term disease control in a substantial fraction of patients. Advances in treatment efficacy with longer survival resulted in a focus on additional outcome measures such as quality of life (QoL) and neurocognition. Despite recent evidence of return to work as an important aspect of patients' QoL, little is known about occupational reintegration in PCNSL long-term survivors. This study aimed to detect specific characteristics of patients who successfully resumed work after complete response to therapy. METHODS: Patients with ongoing complete response to therapy completed a test battery capturing neurocognition, social integration, QoL and psychological burden. Of 25 patients who had been in regular employment before diagnosis only eight returned to work after treatment (32%). RESULTS: Patients who resumed work rated important aspects of their QoL and social integration as higher and suffered less from symptoms affecting QoL than patients who did not resume work. Also, the subjective confidence in their ability to work was higher in patients who resumed work, but independent predictors of return to work were not found in logistic regression analyses. CONCLUSION: Occupational (re)integration is of clinical relevance in PCNSL patients after complete response to therapy. Due to the small size of our cohort the present results should be considered an exploratory first step. Return to work might be a crucial aspect of QoL and (re)integration into society after cure of PCNSL.

Neurocognitive functioning and health-related quality of life in adult medulloblastoma patients: long-term outcomes of the NOA-07 study.

BACKGROUND: Combined radiochemotherapy followed by maintenance chemotherapy with cisplatin, lomustine and vincristine within the NOA-07 study resulted in considerable short-term toxicity in adult medulloblastoma patients. Here we investigated the long-term impact of this treatment, focusing on neurocognitive functioning and health-related quality of life (HRQoL). METHODS: Neurocognitive functioning and HRQoL scores over time were determined, and differences between the post-treatment and follow-up assessments were calculated up to 18 months for neurocognition and 60 months for HRQoL. RESULTS: 28/30 patients were analyzed. The three preselected HRQoL scales (role, social and cognitive functioning) showed improved scores, to a clinically relevant extent (≥ 10 points), compared to post-treatment levels up to 30 months, but decreased afterwards. Z-scores for verbal working memory were worse during follow-up compared to post-treatment scores and remained impaired during 18 months follow-up (i.e. z-score below - 1 standard deviation). Attention was impaired post-treatment, and remained impaired to a clinically relevant extent during follow-up. Coordination/processing speed and lexical verbal fluency improved compared to post-treatment scores, and remained within the normal range thereafter. Other tests of verbal fluency were stable over time, with z-scores within the normal range. CONCLUSIONS: This long-term follow-up study showed that the NOA-07 treatment regimen was not associated with a deterioration in HRQoL in the post-treatment period. Verbal working memory deteriorated, while other neurocognitive domains did not seem to be impacted negatively by the treatment.

Deep Learning for Non-Invasive Diagnosis of Nutrient Deficiencies in Sugar Beet Using RGB Images.

In order to enable timely actions to prevent major losses of crops caused by lack of nutrients and, hence, increase the potential yield throughout the growing season while at the same time prevent excess fertilization with detrimental environmental consequences, early, non-invasive, and on-site detection of nutrient deficiency is required. Current non-invasive methods for assessing the nutrient status of crops deal in most cases with nitrogen (N) deficiency only and optical sensors to diagnose N deficiency, such as chlorophyll meters or canopy reflectance sensors, do not monitor N, but instead measure changes in leaf spectral properties that may or may not be caused by N deficiency. In this work, we study how well nutrient deficiency symptoms can be recognized in RGB images of sugar beets. To this end, we collected the Deep Nutrient Deficiency for Sugar Beet (DND-SB) dataset, which contains 5648 images of sugar beets growing on a long-term fertilizer experiment with nutrient deficiency plots comprising N, phosphorous (P), and potassium (K) deficiency, as well as the omission of liming (Ca), full fertilization, and no fertilization at all. We use the dataset to analyse the performance of five convolutional neural networks for recognizing nutrient deficiency symptoms and discuss their limitations.

Osteopontin in cerebrospinal fluid as diagnostic biomarker for central nervous system lymphoma.

Central nervous system lymphoma (CNSL) is diagnostically challenging. The identification of reliable and easy to measure biomarkers is desirable to facilitate diagnosis. Here, we evaluated the value of cerebrospinal fluid (CSF) osteopontin (OPN) as a diagnostic biomarker for CNSL. OPN concentrations in CSF from 37 patients with CNSL (29 with primary CNSL and 8 with secondary CNS involvement of systemic lymphoma) and 36 controls [6 patients with inflammatory CNS disease other than multiple sclerosis (MS), 8 with MS, 9 with glioblastoma (GBM) and 13 healthy controls] were determined using an enzyme-linked immunosorbent assay. Non-parametric tests and receiver operating characteristic (ROC) curves were performed for determination of diagnostic accuracy. Median CSF OPN level in all CNSL patients was 620 ng/mL and higher than in patients with inflammatory CNS disease (356 ng/mL); P < .05, MS (163 ng/mL); P < .01, GBM (41 ng/mL); P < .01, or healthy controls (319 ng/mL); P < .01. The area under the ROC curve was 0.865 [95 % confidence interval (CI) 0.745-0.985] for differentiating CNSL and patients with inflammatory CNS disease; 0.956 (95 % CI 0.898-1.000) for CNSL and MS patients; 0.988 (95 % CI 0.964-1.000) for CNSL and GBM patients, and 0.915 (95 % CI 0.834-0.996) for CNSL patients and healthy controls. In multivariate analysis, high CSF OPN level was associated with shorter progression-free (HR 1.61, 95 % CI 1.13-2.31; P = .009) and overall survival (HR 1.52, 95 % CI 1.04-2.21; P = .029). CSF OPN is a potential biomarker in CNSL.

Data-driven crop growth simulation on time-varying generated images using multi-conditional generative adversarial networks.

BACKGROUND: Image-based crop growth modeling can substantially contribute to precision agriculture by revealing spatial crop development over time, which allows an early and location-specific estimation of relevant future plant traits, such as leaf area or biomass. A prerequisite for realistic and sharp crop image generation is the integration of multiple growth-influencing conditions in a model, such as an image of an initial growth stage, the associated growth time, and further information about the field treatment. While image-based models provide more flexibility for crop growth modeling than process-based models, there is still a significant research gap in the comprehensive integration of various growth-influencing conditions. Further exploration and investigation are needed to address this gap. METHODS: We present a two-stage framework consisting first of an image generation model and second of a growth estimation model, independently trained. The image generation model is a conditional Wasserstein generative adversarial network (CWGAN). In the generator of this model, conditional batch normalization (CBN) is used to integrate conditions of different types along with the input image. This allows the model to generate time-varying artificial images dependent on multiple influencing factors. These images are used by the second part of the framework for plant phenotyping by deriving plant-specific traits and comparing them with those of non-artificial (real) reference images. In addition, image quality is evaluated using multi-scale structural similarity (MS-SSIM), learned perceptual image patch similarity (LPIPS), and Fréchet inception distance (FID). During inference, the framework allows image generation for any combination of conditions used in training; we call this generation data-driven crop growth simulation. RESULTS: Experiments are performed on three datasets of different complexity. These datasets include the laboratory plant Arabidopsis thaliana (Arabidopsis) and crops grown under real field conditions, namely cauliflower (GrowliFlower) and crop mixtures consisting of faba bean and spring wheat (MixedCrop). In all cases, the framework allows realistic, sharp image generations with a slight loss of quality from short-term to long-term predictions. For MixedCrop grown under varying treatments (different cultivars, sowing densities), the results show that adding these treatment information increases the generation quality and phenotyping accuracy measured by the estimated biomass. Simulations of varying growth-influencing conditions performed with the trained framework provide valuable insights into how such factors relate to crop appearances, which is particularly useful in complex, less explored crop mixture systems. Further results show that adding process-based simulated biomass as a condition increases the accuracy of the derived phenotypic traits from the predicted images. This demonstrates the potential of our framework to serve as an interface between a data-driven and a process-based crop growth model. CONCLUSION: The realistic generation and simulation  of future plant appearances is adequately feasible by multi-conditional CWGAN. The presented framework complements process-based models and overcomes their limitations, such as the reliance on assumptions and the low exact field-localization specificity, by realistic visualizations of the spatial crop development that directly lead to a high explainability of the model predictions.

Multi-year aboveground data of minirhizotron facilities in Selhausen.

Improved understanding of crops' response to soil water stress is important to advance soil-plant system models and to support crop breeding, crop and varietal selection, and management decisions to minimize negative impacts. Studies on eco-physiological crop characteristics from leaf to canopy for different soil water conditions and crops are often carried out at controlled conditions. In-field measurements under realistic field conditions and data of plant water potential, its links with CO2 and H2O gas fluxes, and crop growth processes are rare. Here, we presented a comprehensive data set collected from leaf to canopy using sophisticated and comprehensive sensing techniques (leaf chlorophyll, stomatal conductance and photosynthesis, canopy CO2 exchange, sap flow, and canopy temperature) including detailed crop growth characteristics based on destructive methods (crop height, leaf area index, aboveground biomass, and yield). Data were acquired under field conditions with contrasting soil types, water treatments, and different cultivars of wheat and maize. The data from 2016 up to now will be made available for studying soil/water-plant relations and improving soil-plant-atmospheric continuum models.

Survival, prognostic factors, hospitalization time and clinical performance status after first cerebral relapse or progression in 54 patients with primary CNS lymphoma not eligible for high dose chemotherapy: a retrospective analysis.

BACKGROUND: Treatment of relapsed or refractory primary CNS lymphoma (r/r PCNSL) is difficult, particularly in patients not eligible for high dose chemotherapy with autologous stem cell transplantation (HDC-ASCT). No standard treatment has been defined for these patients yet. METHODS: We retrospectively analyzed survival, prognostic factors, hospitalization time and Karnofsky performance score (KPS) before and after treatment in 54 r/r PCNSL patients with isolated cerebral relapse or progression (n = 23 refractory, n = 31 relapsed) not eligible for HDC-ASCT, who received heterogenous salvage treatments. RESULTS: Treatments were temozolomide (+ rituximab) (n = 21), high dose methotrexate (HD-MTX)-based therapy (n = 11), whole brain radiotherapy (WBRT)/focal radiotherapy (n = 11), other systemic treatments (n = 2) and best supportive care (BSC, n = 9). Median progression free survival (PFS) and overall survival (OS) were 2.6 months (95% CI 1.0-4.2 months) and 4.8 months (95% CI 3.3-6.3 months), respectively. Eight patients survived for ≥ 3 years (13.1%, n = 3 received temozolomide, n = 3 WBRT, n = 2 HD-MTX-based treatment). Application of any salvage treatment (vs. BSC), younger age at relapse and asymptomatic (vs. symptomatic) relapse were positive prognostic factors. No significant differences in OS were found for the different salvage treatments. Median hospitalization time for treatment was 15/13 days for temozolomide (+ rituximab)/radiotherapy compared to 55 days for HD-MTX-based therapy. Median KPS in assessable patients (n = 41) was 60 (range 30-100) before treatment and 50 (range 20-90) after treatment. In patients with response to treatment (n = 16) KPS improved from 60 (range 40-90) before treatment to 70 (range 50-90) after treatment, while patients with PD (n = 25) deteriorated from 60 (range 30-100) to 40 (range 20-70). CONCLUSION: Survival for this cohort of r/r PCNSL patients with isolated cerebral relapse or progression was poor. Considering long hospital stays associated with HD-MTX-based chemotherapy and neurotoxicity associated with WBRT, temozolomide might be worth considering with a chance of prolonged survival and avoidance of long hospitalization. Novel therapeutic agents are urgently needed to improve survival in r/r PCNSL patients.

High-dose chemotherapy and autologous stem cell transplantation in primary lymphomatoid granulomatosis of the central nervous system.

Primary lymphomatoid granulomatosis of the CNS (CNS-LG) is a rare lymphoid neoplasia associated Epstein-Barr Virus (EBV) and often accompanied by immunodeficiencies. No treatment standards have been defined yet. However, due to often devastating neurologic sequelae and based on similarities to diffuse large B-cell lymphoma, curative treatment requires intensive therapy protocols resembling protocols applied in CNS lymphoma. Here, the clinical courses and treatments of four primary CNS-LG patients in analogy to aggressive CNS-lymphomas including methotrexate, thiotepa, cytarabine, carmustine, and rituximab are presented. This is the first report on high-dose chemotherapy with CNS-directed drugs and autologous blood stem cell transplantation in primary CNS-LG.

Multi-year belowground data of minirhizotron facilities in Selhausen.

The production of crops secure the human food supply, but climate change is bringing new challenges. Dynamic plant growth and corresponding environmental data are required to uncover phenotypic crop responses to the changing environment. There are many datasets on above-ground organs of crops, but roots and the surrounding soil are rarely the subject of longer term studies. Here, we present what we believe to be the first comprehensive collection of root and soil data, obtained at two minirhizotron facilities located close together that have the same local climate but differ in soil type. Both facilities have 7m-long horizontal tubes at several depths that were used for crosshole ground-penetrating radar and minirhizotron camera systems. Soil sensors provide observations at a high temporal and spatial resolution. The ongoing measurements cover five years of maize and wheat trials, including drought stress treatments and crop mixtures. We make the processed data available for use in investigating the processes within the soil-plant continuum and the root images to develop and compare image analysis methods.

Treatment Strategies and Prognostic Factors in Secondary Central Nervous System Lymphoma: A Multicenter Study of 124 Patients.

Secondary central nervous system lymphoma (SCNSL) is a rare and difficult to treat type of Non-Hodgkin lymphoma characterized by systemic and central nervous system (CNS) disease manifestations. In this study, 124 patients with SCNSL intensively treated and with clinical long-term follow-up were included. Initial histopathology, as divided in low-grade, other aggressive, and diffuse large B-cell lymphoma (DLBCL), was of prognostic significance. Overall response to induction treatment was a prognostic factor with early responding DLBCL-SCNSL in comparison to those non-responding experiencing a significantly better progression-free survival (PFS) and overall survival (OS). However, the type of induction regime was not prognostic for survival. Following consolidating high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT), DLBCL-SCNSL patients had better median PFS and OS. The important role of HDT-ASCT was further highlighted by favorable responses and survival of patients not responding to induction therapy and by excellent results in patients with de novo DLBCL-SCNSL (65% long-term survival). SCNSL identified as a progression of disease within 6 months of initial systemic lymphoma presentation represented a previously not appreciated subgroup with particularly dismal outcome. This temporal stratification model of SCNSL diagnosis revealed CNS progression of disease within 6 months as a promising candidate prognosticator for future studies.

Outcome and prognostic factors of very old patients with primary CNS lymphoma: a retrospective analysis of patients ≥80 years treated with high-dose methotrexate-based chemotherapy.

Although >10% of primary CNS lymphoma (PCNSL) patients are ≥80 years, data on this population are limited. We analyzed 19 consecutive octogenarians with PCNSL treated with high-dose methotrexate (HD-MTX)-based chemotherapy at our institution concerning outcome, prognostic factors and living conditions at six-month follow-up for 11 patients alive and in remission. Seven patients received intracerebroventricular (ICV) treatment additional to systemic therapy. Median follow-up was 27.3 months. Median overall survival was 16.3 months. Positive prognosticators of survival were application of ICV treatment (p = 0.033) and female gender (p = 0.015). All 11 patients alive and in remission at 6-month follow-up were living at home with a median Karnofsky performance score of 60 (range 50-90) and a median instrumental activities of daily living score of 3 (range 1-8). HD-MTX-based polychemotherapy including ICV treatment was feasible in this population, patients in remission needed moderate support in everyday live.

High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Relapsed or Refractory Primary CNS Lymphoma: A Retrospective Monocentric Analysis of Long-Term Outcome, Prognostic Factors, and Toxicity.

High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is reportedly an effective treatment strategy in relapsed or refractory primary CNS lymphoma (r/r PCNSL); however, only selected patients are eligible for this treatment. We retrospectively analyzed outcome, prognostic factors, and toxicity in 59 patients with r/r PCNSL planned to receive HCT-ASCT at our institution between January 2005 and December 2021 (n = 33 < 65 years; n = 26 ≥ 65 years). Median follow-up was 65 months (95% CI 21−109). Median age was 63 years (range 29−76), median Karnofsky performance score (KPS) was 80 (range 30−100). In the entire cohort of 59 patients, median overall survival (OS) was 14 months (95% CI 0−37). In 50/59 (84.7%) patients who completed HCT-ASCT, median progression free survival (PFS) was 12 months (95% CI 3−21) and median OS 30 months (95% CI 0−87). 1-year, 2-year, and 5-year OS rates of 61.2%, 52.3% and 47.1%, respectively, were observed. Six patients (10.2%) died related to treatment (1 during induction treatment, 5 post HCT-ASCT). Age was not prognostic. On univariate analysis, KPS ≥ 80 (p = 0.019) and complete or partial remission before HCT-ASCT (p = 0.026) were positive prognosticators of OS; on multivariate analysis, KPS (p = 0.043) and male gender (p = 0.039) had an impact on OS. The 5-year OS rate in patients with progressive or stable disease after induction treatment was 32.7%. In summary, HCT-ASCT was effective and feasible in this cohort of r/r PCNSL patients. Clinical state, remission status before HCT-ASCT, and gender influenced survival, whereas age did not influence outcome in this study.

Brain tumor related epilepsy: pathophysiological approaches and rational management of antiseizure medication.

BACKGROUND: Brain tumor related epilepsy (BTRE) is a common complication of cerebral tumors and its incidence is highly dependent on the type of tumor, ranging from 10-15% in brain metastases to > 80% in low grade gliomas. Clinical management is challenging and has to take into account aspects beyond the treatment of non-tumoral epilepsy. MAIN BODY: Increasing knowledge about the pathophysiology of BTRE, particularly on glutamatergic mechanisms of oncogenesis and epileptogenesis, might influence management of anti-tumor and BTRE treatment in the future. The first seizure implies the diagnosis of epilepsy in patients with brain tumors. Due to the lack of prospective randomized trials in BTRE, general recommendations for focal epilepsies currently apply concerning the initiation of antiseizure medication (ASM). Non-enzyme inducing ASM is preferable. Prospective trials are needed to evaluate, if AMPA inhibitors like perampanel possess anti-tumor effects. ASM withdrawal has to be weighed very carefully against the risk of seizure recurrence, but can be achievable in selected patients. Permission to drive is possible for some patients with BTRE under well-defined conditions, but requires thorough neurological, radiological, ophthalmological and neuropsychological examination. CONCLUSION: An evolving knowledge on pathophysiology of BTRE might influence future therapy. Randomized trials on ASM in BTRE with reliable endpoints are needed. Management of withdrawal of ASMs and permission to drive demands thorough diagnostic as well as neurooncological and epileptological expertise.

Mixture × Genotype Effects in Cereal/Legume Intercropping.

Cropping system diversification through annual intercropping provides a pathway for agricultural production with reduced inputs of fertilizer and pesticides. While several studies have shown that intercrop performance depends on the genotypes used, the available evidence has not been synthesized in an overarching analysis. Here, we review the effects of genotypes in cereal/legume intercropping systems, showing how genotype choice affects mixture performance. Furthermore, we discuss the mechanisms underlying the interactions between genotype and cropping system (i.e., sole cropping vs. intercropping). Data from 69 articles fulfilling inclusion criteria were analyzed, out of which 35 articles reported land equivalent ratio (LER), yielding 262 LER data points to be extracted. The mean and median LER were 1.26 and 1.24, respectively. The extracted genotype × cropping system interaction effects on yield were reported in 71% out of 69 publications. Out of this, genotype × cropping system interaction effects were significant in 75%, of the studies, whereas 25% reported non-significant interactions. The remaining studies did not report the effects of genotype × cropping system. Phenological and morphological traits, such as differences in days to maturity, plant height, or growth habit, explained variations in the performance of mixtures with different genotypes. However, the relevant genotype traits were not described sufficiently in most of the studies to allow for a detailed analysis. A tendency toward higher intercropping performance with short cereal genotypes was observed. The results show the importance of genotype selection for better in cereal/legume intercropping. This study highlights the hitherto unrevealed aspects of genotype evaluation for intercropping systems that need to be tackled. Future research on genotype effects in intercropping should consider phenology, root growth, and soil nutrient and water acquisition timing, as well as the effects of weeds and diseases, to improve our understanding of how genotype combination and breeding may help to optimize intercropping systems.

Simulating Root Growth as a Function of Soil Strength and Yield With a Field-Scale Crop Model Coupled With a 3D Architectural Root Model.

Accurate prediction of root growth and related resource uptake is crucial to accurately simulate crop growth especially under unfavorable environmental conditions. We coupled a 1D field-scale crop-soil model running in the SIMPLACE modeling framework with the 3D architectural root model CRootbox on a daily time step and implemented a stress function to simulate root elongation as a function of soil bulk density and matric potential. The model was tested with field data collected during two growing seasons of spring barley and winter wheat on Haplic Luvisol. In that experiment, mechanical strip-wise subsoil loosening (30-60 cm) (DL treatment) was tested, and effects on root and shoot growth at the melioration strip as well as in a control treatment were evaluated. At most soil depths, strip-wise deep loosening significantly enhanced observed root length densities (RLDs) of both crops as compared to the control. However, the enhanced root growth had a beneficial effect on crop productivity only in the very dry season in 2018 for spring barley where the observed grain yield at the strip was 18% higher as compared to the control. To understand the underlying processes that led to these yield effects, we simulated spring barley and winter wheat root and shoot growth using the described field data and the model. For comparison, we simulated the scenarios with the simpler 1D conceptual root model. The coupled model showed the ability to simulate the main effects of strip-wise subsoil loosening on root and shoot growth. It was able to simulate the adaptive plasticity of roots to local soil conditions (more and thinner roots in case of dry and loose soil). Additional scenario runs with varying weather conditions were simulated to evaluate the impact of deep loosening on yield under different conditions. The scenarios revealed that higher spring barley yields in DL than in the control occurred in about 50% of the growing seasons. This effect was more pronounced for spring barley than for winter wheat. Different virtual root phenotypes were tested to assess the potential of the coupled model to simulate the effect of varying root traits under different conditions.