University of Göttingen
  • Göttingen, Germany
Recent publications
In agriculture, the plant leaf angle influences light use efficiency and photosynthesis and, consequently, the overall crop performance. Leaf angle measurements are used in plant phenotyping, plant breeding, and remote sensing to study plant function and structure. Traditional manual leaf angle measurements have limited precision as they are labor- and time-intensive due to challenging environmental conditions and highly dynamic plant processes. To enable more detailed studies on leaf angles, we modified a well-established automated farming robot to obtain high-resolution 3D point clouds at customizable intervals of individual plants using stereo vision. We demonstrate the system's accuracy and reliability, with minimal deviation from reference values. The method can be utilized by other researchers to gather data on leaf angles and other structural plant traits at regular intervals to access the dynamics of leaves, plants, and canopies. The system's low cost and adaptability can enhance the efficiency of crop monitoring in plant breeding and phenotyping experiments. Detailed documentation and code are available on GitHub.•An open-source farming robot is retrofitted to function as an automatic data collection platform •Hard to access leaf angles can be retrieved with high accuracy •Leaf angle dynamics can be observed with high temporal resolution
Background Therapeutic drug monitoring (TDM) is essential for controlling pharmacogenetic and pharmacokinetic variations and for optimizing pharmacotherapy. However, its value is often underestimated because of nonsystematic recommendations for target ranges in the literature. The purpose of this study was to emphasize transparency and systematization in the forthcoming Updates to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)-TDM Consensus Guidelines. Methods Here, a stepwise method for determining therapeutic reference ranges (TRRs) in psychiatry is introduced. By using various data types, a multidimensional approach for establishing a range is presented. The data types were classified based on how effectively they supported the target ranges. This method was demonstrated for 3 drugs commonly used in psychiatry (aripiprazole, olanzapine, and escitalopram). Results Despite the methodological shortcomings in published concentration-effect studies, the approach used here enabled the determination of reference ranges by combining multiple types of data. The lower limit of the TRR is ideally derived from studies that link blood drug concentrations to clinical effectiveness, particularly symptom-specific responses, after fixed-dose treatment. The upper limit depends on the concentrations associated with adverse reactions or maximal response. Thresholds can be estimated using receiver operating characteristic analyses. Preliminary thresholds were derived from responder concentration data or from expected drug concentrations under approved doses. Positron emission tomography studies were used to further validate these ranges. Conclusions This study proposed a new standard for determining the TRR of psychotropic drugs, thereby enhancing their clinical utility and validity. Adjusting blood levels to these ranges should improve response rates and medication tolerance.
Aim Pollen assemblages are widely used to infer paleoenvironment features, aiming at reconstructing both past climates and biomes. However, the functional link between environmental conditions and pollen assemblages is not straightforward and requires thorough testing to be used confidently. Here, we use a trait‐based approach to assess the consistency of functional signatures between pollen and plant assemblages. Location Arid Central Asia (ACA). Taxon Spermatophytes (pollen‐producing plants). Methods We assess whether trait values and trait distributions are consistent for surface pollen samples and extant vegetation in the Arid Central Asia biogeographic region. A working plant checklist was compiled for ACA in order to assign trait values to pollen types and vegetation taxa. This was done for two widely used methods of pollen aggregation schemes (coarse and fine pollen type depend on the level of pollen identification). The functional signatures of pollen and vegetation samples were compared both at the taxon and community levels, using large‐scale trait and vegetation databases, for the six traits of the global spectrum of plant form and function (i.e., plant height, seed mass, leaf area, specific leaf area, nitrogen content per leaf mass, and stem‐specific density). Results Trait distributions and bivariate trait relationships were broadly similar for pollen types and vegetation taxa, which is also the case for the multivariate spaces of the global spectrum of plant form and function. At the community scale, the trait values weighted by taxon abundance significantly differed among biomes, and these differences were consistent for both pollen aggregation schemes and extant. Main Conclusions The pollen aggregation scheme does not impact the organisation of the functional space of the global spectrum of plant form and function, which compares well with that based on species actually present in the vegetation plots. This is also true at the community scale. These findings are very promising for improving climate and biome reconstructions from pollen assemblages and pave the way to a “pollen functional biogeography”.
Escherichia coli (E. coli) carrying the transmissible locus of stress tolerance (tLST) are able to overcome numerous environmental challenges. In our in-silico study, we aimed to characterize tLST in terms of its variants in 793 genomes of E. coli from Brazil originating from food, environmental and clinical (animal and human) sources, and to perform a temporal analysis in order to identify the historical moment of its emergence. We also analyzed the presence of two Yersinia high pathogenicity island (HPI) variants in E. coli genomes, describing other genes and accessory for resistance, persistence, mobile elements (plasmids) and sequence types. The prevalence of the tLST was 10% in E. coli from Brazil, predominantly observed in milk-originating genomes, within the prevalent tLSTCP010237 variant. In E. coli from other sources (clinical/environmental), only part of the tLST was present. Remarkably, our temporal analysis pinpointed the emergence of tLST back to around 1914, coinciding with major societal events. Regarding virulence genes, we found a prevalence of 38.5% for HPI of Y. pestis across genomes from all sources. Our global analysis also showed a high diversity of other virulence genes for milk E. coli (+ 100 genes). These genomes also stood out from the overall metadata for presenting a greater variety of resistance genes to other stresses, such as metals, biocides and acids, as well as persistence genes (biofilm formation). This study demonstrated the historical background of E. coli with tLST genes dating back more than 100 years, and the acquisition of a wide range of virulence and resistance genes that allow it to circulate in different environments: from food to clinic or from clinic to food, making this bacterium a pathogen that requires rigorous surveillance and strategic interventions to mitigate potential risks.
Objective: The efficacy of trauma-focused cognitive behaviour therapy (tf-CBT) has been well established in randomized controlled trials (RCTs). More research is needed to demonstrate the effectiveness of tf-CBT in routine clinical care settings.Method: Eighty-five patients (68 female) with a primary diagnosis of PTSD received tf-CBT at two German outpatient centres (Münster and Mannheim) between 2014 and 2016. Treatment was delivered mainly by therapists in training and treatment duration was based on symptom course. The treatment consisted of a preparation phase, a trauma-focused phase (comprising imaginal exposure, discrimination training, changing dysfunctional appraisals) and a phase of reclaiming-your-life assignments, and relapse prevention. In an intent-to-treat-analysis (ITT), linear mixed effects models were fitted for self-assessments of traumatic symptom severity using the PTSD Checklist for DSM-5 (PCL-5) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Potential moderators for treatment outcome, e.g. number of suicide attempts, were investigated.Results: The observed treatment effect was large for both the CAPS-5 (ITT: Cohen's d = 2.07, CI [1.62, 2.51]; completers d = 2.34, CI [1.84, 2.83]) and PCL-5 respectively (ITT: d = 2.02, CI [1.56, 2.48]; completers d = 2.15, CI [1.66, 2.64]), and remained stable six months and one-year post-treatment. N = 27 patients (31.48%) were defined as study dropout and of these, n = 12 (14.12%) dropped out of the study but completed treatment. None of the fixed-effect estimates for treatment predictors interacted significantly with the effect of time.Conclusions: Tf-CBT is well-tolerated and it can be effectively delivered in routine clinical care. Its large treatment effects underline the practicability and benefits of the approach. This trial demonstrates its broad applicability among individuals with diverse patterns of clinical characteristics and comorbidities.
Verticillium longisporum is a soil-borne fungal pathogen causing vascular disease predominantly in Brassicaceae. We have reported previously that the receptor of the plant defense hormone jasmonoyl-isoleucine (JA-Ile), CORONATINE INSENSITIVE 1 (COI1), is required in roots for efficient proliferation of the fungus in the shoot implicating a mobile root-borne signal that influences the outcome of the disease in shoots. This susceptibility-promoting COI1 function is independent from JA-Ile. To explore the underlying mechanism we compared the root transcriptome of coi1 with the transcriptomes of the susceptible JA-Ile-deficient allene oxide synthase (aos) mutant and susceptible wild-type (WT) plants. The biggest difference between the transcriptomes of coi1 versus WT and aos was due to 316 immunity-related genes that were constitutively higher expressed in coi1 as compared to the susceptible genotypes. Interfering with the expression of a subgroup of these genes partially suppressed the coi1-mediated tolerance phenotype. We therefore hypothesize that secreted defense compounds encoded by genes constitutively expressed in coi1 are transported to the shoot with the transpiration stream where they accumulate to interfere with fungal growth. We furthermore report that 149 of the 316 COI1-repressed genes are induced in WT and aos upon infection reaching similar levels as in mock-treated coi1. These were not further induced in coi1 upon infection. Thus, the repressive effect of COI1 is either lifted or overridden upon infection with V. longisporum.
Temperate plants show a rapid seasonal turnover in various leaf traits and defenses. Such trends in plant defenses can potentially drive seasonal shifts in the specialization of insect herbivores. We quantified how non-volatile leaf metabolites, inducible volatile organic compounds (VOCs), C:N ratio and leaf toughness changed between the early, middle, and late seasons in five Salicaceae species and one Salix hybrid. We also explored seasonal trends in overall trait variation among the studied plants. We tested whether seasonal changes in dietary specialization of leaf-chewing larvae and adult beetles related to changes in the studied host-plant traits. Trait turnover occurred mainly through changes in VOCs and seasonal increase in traits that directly lower herbivore feeding efficiency. The overall variation in leaf traits was highest in the early season, with seasonal intraspecific variation being 33% smaller than the variation among species sampled at one time point. Although less frequently than we expected, the two groups of insect herbivores showed seasonal changes in specialization. The significant trends in herbivore specialization included peaks in the middle season for larval specialization based on VOCs and host phylogenetic relatedness and for adult beetle specialization based on C:N ratio plus leaf toughness. The detected species-specific trends in host-plant traits, their intraspecific variability, and differential trends among insect herbivores highlight the importance of considering seasonal variation when predicting trends in plant–herbivore interactions.
Background and objectives: The availability of disease-modifying therapies for 5q-associated spinal muscular atrophy (SMA) has heightened the need to identify suitable biomarkers. This study investigates neurofilament light chain (NfL) concentrations during long-term nusinersen treatment in adult SMA. Methods: In a retrospective study of prospectively collected data, NfL concentrations in the CSF (cNfL) and serum (sNfL) were measured in patients with SMA from 8 German centers and in neurologic controls using a single-molecule array (Simoa) assay. NfL concentrations and clinical characteristics, including the clinical scores Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), were analyzed for defined treatment intervals (T1-T4 [loading phase until 4 months], T5-T8 [until 23 months], T9-T12 [until 37 months], and T13-T19 [until 60 months]). Linear mixed models with a random intercept were used to assess the changes in NfL levels during treatment, considering time and covariates as fixed effects. Results: One hundred thirteen adult patients with SMA (median age 35, 46% female), with a treatment duration of maximum 60 months, and 52 controls were included. At baseline, NfL concentrations were significantly higher in SMA {cNfL median, 585 (interquartile range [IQR] 428-787) pg/mL; sNfL, 11 (IQR 8-14) pg/mL} than in controls (cNfL, 420 [IQR 323-662] pg/mL; sNfL, 8 [IQR 6-12] pg/mL) (cNfL, p = 0.021; sNfL, p = 0.030). Median differences for all clinical scores were the highest for T5-T8 compared with the loading phase (Δ HFMSE, 0.6 [IQR 0.1-1.4], p = 0.017; Δ RULM, 0.9 [IQR 0.4-1.3], p < 0.001; Δ ALSFRS-R, 0.7 [IQR 0.4-1.0], p < 0.001), but not for subsequent intervals. Longitudinal analysis revealed a significant decrease of NfL concentrations during each treatment interval compared with the loading phase (p < 0.05, respectively) except for sNfL in T13-T19. Even among patients with no measurable clinical improvement (Δ HFMSE ≤ 0), more than 50% showed declining cNfL and sNfL levels up to T13-T19. Discussion: NfL decreased during nusinersen treatment, suggesting its potential as a pharmacodynamic response marker in adult SMA. However, in patients without detectable clinical improvement, our study cannot determine whether they represent a more sensitive outcome measure or are not clinically meaningful.
Colorectal cancer (CRC) is a major health problem, with an alarming increase of early-onset CRC (EO-CRC) cases among individuals under 50 years of age. This trend shows the urgent need for understanding the underlying mechanisms leading to EO-CRC development and progression. There is significant evidence that the gut microbiome acts as a key player in CRC by triggering molecular changes in the colon epithelium, leading to tumorigenesis. However, a comprehensive collection and comparison of methods to study such tumor-microbiome interactions in the context of EO-CRC is sparse. This review provides an overview of the available in vivo, ex vivo as well as in vitro approaches to model EO-CRC and assess the effect of gut microbes on tumor development and growth. By comparing the advantages and limitations of each model system, it highlights that, while no single model is perfect, each is suitable for studying specific aspects of microbiome-induced tumorigenesis. Taken together, multifaceted approaches can simulate the human body’s complexity, aiding in the development of effective treatment and prevention strategies for EO-CRC.
Low anterior resection (LAR) and abdominoperineal resection (APR) are the two main surgical procedures after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. APR is associated with poorer prognosis; however existing data do not consider intensified CRT (5-Fluorouracil (5-FU)/Oxaliplatin + radiation) protocols. Clinicopathological data of patients treated with APR and LAR from the CAO/ARO/AIO-04 trial were analysed in terms of prognostic parameters and quality of life (QoL). Based on higher response rate after intensified CRT, subgroup analyses were performed. Data from n = 1173 patients were assessed. APR after preoperative CRT was associated with a significantly worse overall survival (p = 0.0056), disease-free survival (p < 0.0001) and local recurrence rate (p = 0.0047). Clinicopathological data including clinical T stage (p < 0.000001), grading (p = 0.0038), postoperative lymph node (LN) positivity (p = 0.013), and number of positive LN (p = 0.0049) significantly differed between procedures and showed higher values in APR patients. The quality of total mesorectal excision (TME) was significantly better (p < 0.0001) and complete resection rates were higher (p = 0.0022) in LAR compared to APR patients. Subgroup analyses showed worse LR rates in APR patients after standard CRT (5-FU mono and radiation) but not after intensified CRT. After 3 years, role functioning (p = 0.019) and physical functioning (p = 0.001) had a slightly poorer outcome in APR patients. The poorer prognosis of patients undergoing APR for locally advanced rectal cancer may be explained by clinicopathological characteristics. Intensified CRT may compensate for the higher risk of LR after APR in patients with worse TME quality. QoL in APR patients was comparable to LAR patients. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-83105-z.
Background: The Otago program (OP) is evidence-based and focuses on fall prevention in older people. The feasibility and usability of a short-term digital program modeled after the principles of the OP in the setting of early geriatric rehabilitation (EGR) are unclear. Objective: This study investigated the feasibility and usability of an additional technology-based fall prevention program (FPP) in the setting of EGR. Methods: We performed a feasibility study in the setting of EGR. A sample of 30 patients (mobility at least by walker; mini-mental status test score >17) was recruited between March and June 2024 and compared with a retrospective cohort (n=30, former EGR patients). All patients in the intervention group (IG) received a supervised, OP-modified FPP thrice/week for 20 minutes using a technology-based platform called “Pixformance.” The device is a digital trainer and enables real-time corrections. The primary end point was the feasibility (given when 80% of the IG participated in 6 trainings within 2 weeks). Secondary outcomes were usability (patients’ and facilitators’ perspective; ≥75%), risk of falls (Berg Balance Scale), mobility (Timed Up and Go Test), functional independence (Functional Independence Measure), and activities of daily living (Barthel Index). Several further exploratory end points were analyzed including anxiety and depression (Four-Item Patient Health Questionnaire; PH-Q4). Data were accessed at entry to EGR and after 2 weeks prior to discharge. To analyze the pre-posttest results, the dependent Student t test and the Wilcoxon test were applied. A mixed ANOVA with repeated measurements was used for statistical analyses of time-, group-, and interaction-related changes. Results: A cohort of 60 patients (mean 80.2, SD 6.1 y; 58% females, 35/60) was analyzed. The main indication for EGR was stroke (9/60, 15%). Patients were recruited into a prospective IG (n=30) and a retrospective control group (n=30). Of the 30 patients in the prospective IG, 11 patients (37%) completed 6 training sessions within 2 weeks. Reasons why participants did not complete 6 training sessions were diagnostic appointments (33%), pain/discomfort (33%), or fatigue (17%). EGR patients rated FPP usability at 84% and facilitators at 65% out of 100%. Pre-posttest analysis of the standard assessments showed a significant interaction in Berg Balance Scale (<.01). In both groups, a significant improvement over time was found in the Timed Up and Go Test (<.01), Barthel Index (<.01), and Functional Independence Measure (<.01). Likewise, in the IG, the PH-Q4 score (.02) improved. Conclusions: While the technology-based FPP in the EGR setting was generally well-accepted by patients, with high usability ratings, its feasibility was limited. Only 37% of participants completed the required additional training sessions. Further studies should test the technology-based FPP as an integrated part of the EGR complex therapy concept. Our findings suggest potential benefits of incorporating technology-based FPPs in EGR, but further refinement is needed to enhance participation and feasibility.
Wood modification with 1,3-dimethylol-4,5-dihydroxyethyleneurea (DMDHEU) has been widely demonstrated to enhance the biological durability and dimension stability of wood, thus it serves a predestined technology to equip wooden products for outdoor applications. However, such technology hardly affects the fire performance of wood, a parameter which gains increasing relevance in the construction sector. Recently, the combination of curing resins with flame retardants has been proposed as a potential approach to enhance the fire performance of wood in a permanent way, hence providing a durable fire protection system. Scots pine sapwood (Pinus sylvestris L.) was impregnated with aqueous compositions of DMDHEU, a commercially available phosphate-nitrogen based fire retardant (adapted for wooden applications) and combinations thereof. The fixation of the flame retardant was assessed on the basis of a cold water leaching process according to EN 84 (2020). The fire performance of the treated wood was assessed through thermal gravimetry analysis (TGA), a Bunsen burner ignition test and mass loss calorimeter. Both wood treated with pure flame retardant and combination of a flame retardant and DMDHEU, demonstrated improvements in thermal stability, reduced flammability and decreased heat release after treatment. Notably, the THR600s of wood treated with DMDHEU in combination with the flame retardant was reduced by 89.3% compared to wood treated solely with DMDHEU. However, after the leaching process, the flame retardant happened to leach out almost completely, which was assessed on the basis of a loss in its efficacy related to fire protection. On the contrary, DMDHEU seemed to partially fix the flame retardant inside the wood matrix, which was derived from a persistent enhancement in fire performance, even after wooden specimens passed a cold water leaching.
Background Testicular tumors are among the most frequently diagnosed cancers in young men. The consequences of this diagnosis are orchiectomies, severely restricting fertility. For these young patients, a comprehensive diagnostics would be desirable, achieving a refined diagnosis and improved therapeutic patient stratification. Objective The aim of this study was to use three‐dimensional (3D) light sheet fluorescence microscopy (LSFM) to analyze a complete testicular tumor punch at subcellular resolution—allowing a detailed diagnostic assessment of the entire punch. Materials and methods Tissue punches (3 and 5 mm diameter) were taken from paraffin blocks of four miscellaneous testicular tumors. After deparaffinization and clearing using benzoic acid/benzyl benzoate, a label‐free LSFM autofluorescence imaging was performed. In addition, TO‐PRO‐3 nuclear stain was applied to several punches. After the scan, the samples were embedded in paraffin again and physically sectioned for conventional planar histology. Results Based on the specific autofluorescence, not only the general morphology of the tumor tissue was identified in LSFM datasets, but also diagnostic features like infiltrations, papillary and pagetoid tumor cell formations, germ cell neoplasia in situ and azoospermia. Subcellular characteristics such as vacuolated cytoplasm and pleomorphic nuclei could be detected at maximum magnification. After nuclear staining, virtual H&E sections were reconstructed from the LSFM data and tomographically visualized across the entire punch. Subsequent histology and immunohistochemistry after LSFM analyses is possible. Discussion LSFM analysis of testicular tumors enables the detailed 2D/3D analysis of an entire tumor punch for assessment of relevant tumor characteristics due to its intrinsic fluorescence or with specific nuclear staining. Conclusion LSFM provides the technical basis for the analyses of complete testicular tumor biopsies, thus maximizing the spatial morphological and anatomical information. The subcellular 3D imaging of the tumor has the potential to identify new cancer imaging biomarkers that have additional diagnostic and prognostic value for patients.
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Göttingen, Germany
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Dr. Valérie Schüller