OPEN FAU Online-Publikationssystem der Friedrich-Alexander-Universität Erlangen-Nürnberg
Not a member yet
23478 research outputs found
Sort by
Facing depression: evaluating the efficacy of the EmpkinS-EKSpression reappraisal training augmented with facial expressions – protocol of a randomized controlled trial
Get PDFBackground Dysfunctional depressogenic cognitions are considered a key factor in the etiology and maintenance of depression. In cognitive behavioral therapy (CBT), the current gold-standard psychotherapeutic treatment for depression, cognitive restructuring techniques are employed to address dysfunctional cognitions. However, high drop-out and non-response rates suggest a need to boost the efficacy of CBT for depression. This might be achieved by enhancing the role of emotional and kinesthetic (i.e., body movement perception) features of interventions. Therefore, we aim to evaluate the efficacy of a cognitive restructuring task augmented with the performance of anti-depressive facial expressions in individuals with and without depression. Further, we aim to investigate to what extent kinesthetic markers are intrinsically associated with and, hence, allow for the detection of, depression. Methods In a four-arm, parallel, single-blind, randomized controlled trial (RCT), we will randomize 128 individuals with depression and 128 matched controls without depression to one of four study conditions: (1) a cognitive reappraisal training (CR); (2) CR enhanced with instructions to display anti-depressive facial expressions (CR + AFE); (3) facial muscle training focusing on anti-depressive facial expressions (AFE); and (4) a sham control condition. One week after diagnostic assessment, a single intervention of 90–120-minute duration will be administered, with a subsequent follow-up two weeks later. Depressed mood will serve as primary outcome. Secondary outcomes will include current positive mood, symptoms of depression, current suicidality, dysfunctional attitudes, automatic thoughts, emotional state, kinesthesia (i.e., facial expression, facial muscle activity, body posture), psychophysiological measures (e.g., heart rate (variability), respiration rate (variability), verbal acoustics), as well as feasibility measures (i.e., treatment integrity, compliance, usability, acceptability). Outcomes will be analyzed with multiple methods, such as hierarchical and conventional linear models and machine learning. Discussion If shown to be feasible and effective, the inclusion of kinesthesia into both psychotherapeutic diagnostics and interventions may be a pivotal step towards the more prompt, efficient, and targeted treatment of individuals with depression. Trial registration The study was preregistered in the Open Science Framework on August 12, 2022 ( https://osf.io/mswfg/ ) and retrospectively registered in the German Clinical Trials Register on November 25, 2024. Clinical Trial Number: DRKS00035577.Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/50110000165
Mentally strained: pathways into and through the working world
No full textOpen Access funding enabled and organized by Projekt DEAL.Universität Hildesheim (3152
Is there an impact of a video-based patient informed consent in elective hand surgery?
Get PDFBackground Patient informed consent is a crucial subject in preoperative care of patients before elective hand surgery, ensuring that patients have the necessary information and a comprehensive understanding to make autonomous decisions. The use of video-based informed consent systems is an innovative concept to enhance the consent process with multimedia tools. In addition to the conventional process, mostly relying on verbal communication and written documents, the video-based approach aims to present information in a standardized and visually appealing format. Methods In this study, 33 patients were asked to watch a video on a tablet about the planned elective hand surgery after a conventional pre-treatment consultation including informed consent throughout verbal explanations and paper forms by an attending physician or resident. All patients were asked to complete a questionnaire after watching the video. Results An overwhelming majority of participants, specifically 97.0%, stated that the video improved their understanding of the upcoming surgery. 90.9% of the participant would refer the video to other patients undergoing elective hand surgery, while 72.7% of participants indicated that they would have appreciated the opportunity to view an informational video before undergoing different types of surgeries in the past. Conclusion The use of a video-based patient information system in elective hand surgery had a positive impact on patient education and satisfaction with the informed consent process. Therefore, it is a powerful tool in preoperative management to guarantee a standardized and educative informed consent.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Information mismatch in PHH3-assisted mitosis annotation leads to interpretation shifts in H&E slide analysis
Get PDFThe count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithms’ performance. Unlike H&E, where identification of MFs is based mainly on morphological features, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E staining alone, the use of this ground truth could potentially introduce an interpretation shift and even label noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. Subsequently, MF detectors, including a novel dual-stain detector, were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models’ performance. We found that the annotators’ object-level agreement significantly increased when using PHH3-assisted labeling (F1: 0.53 to 0.74). However, this enhancement in label consistency did not translate to improved performance for H&E-based detectors, neither during the training phase nor the evaluation phase. Conversely, the dual-stain detector was able to benefit from the higher consistency. This reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect, which renders PHH3-assisted annotations not well-aligned for use with H&E-based detectors. Based on our findings, we propose an improved PHH3-assisted labeling procedure.Open Access funding enabled and organized by Projekt DEAL.Hochschule Flensburg University of Applied Sciences (3320
Cooperative spin crossover leading to bistable and multi-inert system states in an iron(III) complex
Get PDFCooperativity among spin centres has long been the royal road in spin crossover (SCO) research to impose magnetic bistability in terms of thermal hysteresis. In this work we access magnetic multi-inert states of the iron(III) compound {FeL2[B(Ph)4]} ≡ FeB at low temperature, in addition to thermal bistability. The packing of the low-spin and high-spin forms of crystalline FeB differs only marginally what ultimately leads to structural conservatism. This indicates that the SCO-immanent breathing of the complex cation is almost fully compensated by the anion matrix. The unique cooling rate dependence of the residual low-temperature magnetisation in FeB unveils continuous switching between the trapped high-spin (ON) and the relaxed low-spin state (OFF). The macroscopic ratio of the spin states (ON:OFF) can be adjusted as a simple function of the cooling rate. That is, cooperative spin crossover can be the source of bistable and multi-inert system states in the very same material.Spin-crossover compounds are molecular switches with functional high- and low-spin states. Here, the authors present an iron(III) complex that additionally also allows for continuous population of both states at low temperatures.Deutsche Forschungsgemeinschaft (German Research Foundation)https://doi.org/10.13039/50110000165
Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells
Get PDFThe regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression. The CRISPR/CAS knockout of LGR5 and LGR4 (thereby avoiding the side effects of LGR4) resulted in a loss of Wnt activity that cannot be restored by LGR5Δ5 but by LGR5FL rescue. The ability to migrate was not affected by LGR5Δ5, but was reduced by LGR5FL overexpression. The CRISPR/CAS of LGR4 and 5 induced radiosensitization, which was enhanced by the overexpression of LGR5FL or LGR5Δ5. RNA sequencing analysis revealed a significant increase in the ligand R-spondin 1 (RSPO1) level by LGR5Δ5. Furthermore, LGR5Δ5 appears to be involved in the regulation of genes related to the cytoskeleton, extracellular matrix stiffness, and angiogenesis, while LGR5FL is associated with the regulation of collagens and histone proteins.We thank Dr. Kleist-Stiftung for the generous financial support (funding number 2021_0087) (2021–2023). We thank Qingyun Liu (Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, USA) for a Myc-tagged full-length LGR5-plasmid. We acknowledge the financial support of the Open Access Publication Fund of the Martin Luther University Halle-Wittenberg.Dr. Kleist-StiftungQingyun Liu (Texas Therapeutics Institute, University of Texas Health Science Center at Houston, Houston, USA)Open Access Publication Fund of the Martin Luther University Halle-Wittenber
Uniform Turnpike Property and Singular Limits
Get PDFMotivated by singular limits for long-time optimal control problems, we investigate a class of parameter-dependent parabolic equations. First, we prove a turnpike result, uniform with respect to the parameters within a suitable regularity class and under appropriate bounds. The main ingredient of our proof is the justification of the uniform exponential stabilization of the corresponding Riccati equations, which is derived from the uniform null control properties of the model. Then, we focus on a heat equation with rapidly oscillating coefficients. In the one-dimensional setting, we obtain a uniform turnpike property with respect to the highly oscillatory heterogeneous medium. Afterward, we establish the homogenization of the turnpike property. Finally, our results are validated by numerical experiments.Open Access funding enabled and organized by Projekt DEAL.German Academic Exchange Servicehttp://dx.doi.org/10.13039/100021828ModConFlexMAT-DYN-NETTransregio 154 Project “Mathematical Modelling, Simulation and Optimization Using the Example of Gas Networks”MINECOFriedrich-Alexander-Universität Erlangen-Nürnberg (1041
Endothelzellen/Perizyten-Kokulturmodell und menschliche Blutgefäßorganoide: Modellierung der Vaskulopathie in der Systemischen Sklerose
No full textBackground and Objectives: Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vascular abnormalities and fibrosis. Induced pluripotent stem cells (iPSCs) offer a promising avenue for modeling disease pathogenesis and screening for potential therapeutics. This study aimed to establish a co-culture model of iPSC-derived endothelial cells (ECs) and pericytes and a three-dimensional (3D) iPSC-derived model of blood vessel organoids (BVOs) for the study of vasculopathy in SSc.
Methods: iPSCs obtained from healthy donors and SSc patients were directed to differentiate into ECs and pericytes using a combination of mesoderm and vascular differentiation media. Immunofluorescence staining was employed to assess the expression of EC and pericyte markers. Coculturemodels of ECs and pericytes were exposed to serum from healthy donors and SSc patients with or without active digital ulcers to evaluate angiogenesis. Furthermore, 3D BVOs were generated from both healthy and SSc-iPSCs and treated with serum from healthy individuals and SSc patients with or without active digital ulcers to assess vasculopathy. Vascular morphology of the organoids was captured using LSM880 confocal microscopy, and parameters such as vessel density, average vessel length, total vessel length, and junctions were quantified using Angiotool to evaluate angiogenesis. RNA-seq analysis was conducted to identify phenotypic differences at a transcriptomic level between SSc BVOs treated with healthy serum and those with active digital ulcers.
Results: iPSCs derived from both healthy donors and SSc patients were successfully differentiated into ECs and pericytes, with comparable efficiency between the two groups. Co-culture models derived from SSc-iPSCs demonstrated augmented angiogenesis under healthy serum conditions compared to healthy co-culture models, but diminished neovascularization when exposed to serum from SSc patients with active digital ulcers. Moreover, BVOs derived from SSc-iPSCs exhibited impaired angiogenesis when treated with serum from SSc patients with active digital ulcers. RNA-seq analysis revealed differentially expressed genes associated with inflammation, immune response, adhesion, migration, and angiogenesis in SSc BVOs treated with serum from SSc patients with active digital ulcers in comparison to SSc BVOs treated with serum from healthy donors.
Conclusion: Our study demonstrates that SSc-iPSC-, but not healthy-iPSC-derived vascular models, i.e. the EC-pericyte co-culture and BVOs, reproduce the aberrant vascular phenotype in SSc patients when exposed to SSc serum from patients with severe, clinically manifest vascular pathology. This provides first experimental evidence that clinically manifest vascular damage in SSc can be induced by circulating serum factors only in genetically predisposed individuals. The aberrant gene expression profile identified offers insights into the mechanisms driving SSc-associated vasculopathy, thereby providing potential avenues for therapeutic intervention in systemic sclerosis
Preoperative breast MRI positively impacts surgical outcomes of needle biopsy–diagnosed pure DCIS: a patient-matched analysis from the MIPA study
Get PDFObjectives To investigate the influence of preoperative breast MRI on mastectomy and reoperation rates in patients with pure ductal carcinoma in situ (DCIS). Methods The MIPA observational study database (7245 patients) was searched for patients aged 18–80 years with pure unilateral DCIS diagnosed at core needle or vacuum-assisted biopsy (CNB/VAB) and planned for primary surgery. Patients who underwent preoperative MRI (MRI group) were matched (1:1) to those who did not receive MRI (noMRI group) according to 8 confounding covariates that drive referral to MRI (age; hormonal status; familial risk; posterior-to-nipple diameter; BI-RADS category; lesion diameter; lesion presentation; surgical planning at conventional imaging). Surgical outcomes were compared between the matched groups with nonparametric statistics after calculating odds ratios (ORs). Results Of 1005 women with pure unilateral DCIS at CNB/VAB (507 MRI group, 498 noMRI group), 309 remained in each group after matching. First-line mastectomy rate in the MRI group was 20.1% (62/309 patients, OR 2.03) compared to 11.0% in the noMRI group (34/309 patients, p = 0.003). The reoperation rate was 10.0% in the MRI group (31/309, OR for reoperation 0.40) and 22.0% in the noMRI group (68/309, p < 0.001), with a 2.53 OR of avoiding reoperation in the MRI group. The overall mastectomy rate was 23.3% in the MRI group (72/309, OR 1.40) and 17.8% in the noMRI group (55/309, p = 0.111). Conclusions Compared to those going directly to surgery, patients with pure DCIS at CNB/VAB who underwent preoperative MRI had a higher OR for first-line mastectomy but a substantially lower OR for reoperation. Clinical relevance statement When confounding factors behind MRI referral are accounted for in the comparison of patients with CNB/VAB-diagnosed pure unilateral DCIS, preoperative MRI yields a reduction of reoperations that is more than twice as high as the increase in overall mastectomies. Key Points • Confounding factors cause imbalance when investigating the influence of preoperative MRI on surgical outcomes of pure DCIS. • When patient matching is applied to women with pure unilateral DCIS, reoperation rates are significantly reduced in women who underwent preoperative MRI. • The reduction of reoperations brought about by preoperative MRI is more than double the increase in overall mastectomies.Open access funding provided by Università degli Studi di Milano within the CRUI-CARE Agreement.Bayerhttp://dx.doi.org/10.13039/100004326Università degli Studi di Milan
Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease
Get PDFCongenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR < 0.001), with changes most evident after 30 weeks gestation. A significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, pFDR = 0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.Medical Research Councilhttp://dx.doi.org/10.13039/501100000265Wellcome EPSRC Centre for Medical Engineeringhttp://dx.doi.org/10.13039/501100023312National Institutes of Healthhttp://dx.doi.org/10.13039/100000002EPSRC Centre for Doctoral Training in Medical Imaginghttp://dx.doi.org/10.13039/501100013915Wellcome Trusthttp://dx.doi.org/10.13039/100010269UK Research and Innovationhttp://dx.doi.org/10.13039/100014013Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/50110000165