OPEN FAU Online-Publikationssystem der Friedrich-Alexander-Universität Erlangen-Nürnberg
Not a member yet
23478 research outputs found
Sort by
EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms
Full text linkWith the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue ( n = 3) and bone ( n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20–56 years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4–7.5 cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8–21 months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1 -associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Can Chat-GPT read and understand guidelines? An example using the S2k guideline intrauterine growth restriction of the German Society for Gynecology and Obstetrics
Full text linkPurpose To investigate the capacity of chat-generative pre-trained transformer (Chat-GPT) to understand the S2k guideline of the German Society for Gynecology and Obstetrics on intrauterine growth restriction. Methods The German-language free Chat-GPT version was used to test the ability of Chat-GPT to understand the definition of small for gestational age and intrauterine growth restriction, to indicate the correct time and place of delivery and to evaluate ist ability to recommend a spontaneous delivery versus a primary caesarean section in accordance with the guideline recommendations. In order to objectively evaluate the suggestions a simple three-color ‘traffic light’ evaluation system was employed. Results Almost all Chat-GPT’s suggestions in the context of definition of small for gestational age/intrauterine growth restriction as well as correct time of delivery were adequate, whereas more than half of the suggestions made in terms of correct delivery mode needed reformulation or even correction. Conclusion Chat-GPT appears to be a valuable form of artificial intelligence that could be integrated into everyday clinical practice.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
A meta-evaluative synthesis of the effects of custodial and community-based offender rehabilitation
Full text linkWe synthesize 53 meta-analyses on the effectiveness of correctional treatment applied to a wide variety of offender groups delivered in either custodial or community-based settings. Those meta-analyses revealed positive overall effects on reoffending of correctional treatment delivered in both settings. However, the treatment setting is also associated with complex moderator effects. With respect to effect size , for most groups, community-based correctional treatment is associated with statistically significant larger reductions in reoffending than treatments delivered in custodial settings. With respect to effect precision , custodial treatments report more consistent effects on reoffending than community-based treatments. The findings extend and develop the insight that treatment flexibility, such as is found among community-based treatments, can optimize program effectiveness. Likewise, the opportunities for monitoring and treatment fidelity that custodial settings enable can homogenize outcomes. Nonetheless, the promising results observed among treatments delivered both inside and outside institutional settings implicate a complex policy tradeoff between prioritizing strong performance and consistent effects
Multicenter evaluation of complex urinary diversion for renal transplantation: outcomes of complex surgical solutions
Full text linkPurpose An abnormal lower urinary tract poses significant challenges for transplant surgeons. Besides the ureteral anastomosis to an ileal conduit, there are diverse complex reconstructive solutions. Due to its rarity, standardization and teaching of complex urinary diversion is extremely difficult. Methods The indications and outcomes of complex urinary diversions after kidney transplantation (KT) were retrospectively investigated at eight urologic transplant centers including a current follow-up. Results Of 37 patients with 21 (56%) males, vesicoureteral reflux (24%), spina bifida (22%), and glomerulonephritis (12%) were the most common causes of terminal renal failure. In 30 (81%) patients, urinary diversion was performed before KT, at a median of 107.5 (range, 10; 545) months before. Transplantations were held at a median patient age of 43 (10; 68) years, including six (16%) living donations. Urinary diversion was modified during 12 (32%) transplantations. After KT, the ileal conduit was the most common incontinent urinary diversion in 25 (67%) patients; a Mainz pouch I and bladder augmentation were the most frequent continent diversions (each n = 3). At a median follow-up of 120 months (range 0; 444), 12 (32%) patients had a graft failure with a 5-year graft survival of 79% (95%CI 61; 90). The median overall survival was 227 months (168; 286) and the 5-year overall survival 89% (69.3; 96.4). Conclusion The mid-term kidney transplant function with complex urinary diversion appears to be comparable to transplants with regular urinary diversions. Hence, complex urinary diversion should always be considered as a surgical option, even during transplantation, if necessary.Open Access funding enabled and organized by Projekt DEAL.Philipps-Universität Marburg (1009
Harmonizing Dietary Exposure of Adult and Older Individuals: A Methodological Work of the Collaborative PROMED-COG Pooled Cohorts Study
Full text linkObjectives: The PROtein-enriched MEDiterranean diet to combat undernutrition and promote healthy neuroCOGnitive ageing in older adults (PROMED-COG) is a European project that investigates the role of nutritional status on neurocognitive ageing. This methodological paper describes the harmonization process of dietary data from four Italian observational studies (Pro.V.A., ILSA, BEST-FU, and NutBrain). Methods: Portion sizes and food frequency consumption within different food frequency questionnaires were retrospectively harmonized across the datasets on daily food frequency, initially analyzing raw data using the original codebook and establishing a uniform food categorization system. Individual foods were then aggregated into 27 common food groups. Results: The pooled cohort consisted of 9326 individuals (40–101 years, 52.4% female). BEST-FU recruited younger participants who were more often smokers and less physically active than those of the other studies. Dietary instruments varied across the studies differing in the number of items and time intervals assessed, but all collected dietary intake through face-to-face interviews with a common subset of items. The average daily intakes of the 27 food groups across studies varied, with BEST-FU participants generally consuming more fruits, vegetables, red meat, and fish than the other studies. Conclusions: Harmonization of dietary data presents challenges but allows for the integration of information from diverse studies, leading to a more robust and statistically powerful dataset. The study highlights the feasibility and benefits of data harmonization, despite inherent limitations, and sets the stage for future research into the effects of diet on cognitive health and aging.This PROMED-COG project received funding from the UK Research and Innovation (UKRI): Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC), from the Italian Ministry of Universities and Research (MUR) (National Research Council and University of Padova), and Health Research Board (2021 R546) under the umbrella of the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) and of the ERA-NET Cofund ERA-HDHL (GA N°696295 of the EU Horizon 2020 Research and Innovation Programme). The ILSA project was supported by the Italian National Research Council from 1991 to 1998 as part of the Progetto Finalizzato Invecchiamento. Since 1999, the Italian National Research Council, the “Biology of Aging” Strategic Project and the Ministero della Sanità, through the program “Epidemiology of the Elderly” of the Istituto Superiore di Sanità and the “Estimates of Health Needs of the Elderly” Special Programme of the Tuscany Region have been supporting the ILSA. BEST-FU was supported by the research programme grant funding from the CNR-targeted project “Prevention and Control of Disease Factors—FATMA”. The data collection phase of the PRO.V.A. study was supported by the Fondazione Cassa di Risparmio di Padova e Rovigo; the University of Padova; Veneto Region’s Local Health and Social Care Services No. 15 and No. 18 (Azienda Unità Locale Socio Sanitaria 15 and 18); and a grant from the Veneto Regional Authority (Ricerca Sanitaria Finalizzata n.156/03). The data analysis phase was financed by a grant from the “Ricerca Sanitaria Finalizzata Bando 2017, Regione Veneto” (RSF-2017-00000533, deliberazione n. 490 17.04.2018). NutBrain was supported by the Italian Ministry of Health (GR-2016-02361730730). The studies’ funders had no involvement in the design and conduct of the study, collection, management, analysis and interpretation of data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.UK Research and Innovation (UKRI): Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC)Italian Ministry of Universities and Research (MUR) (National Research Council and University of Padova)Health Research BoardItalian National Research Council“Biology of Aging” Strategic ProjectMinistero della SanitàCNR-targeted project “Prevention and Control of Disease Factors—FATMA”Fondazione Cassa di Risparmio di Padova e RovigoUniversity of PadovaVeneto Region’s Local Health and Social Care Services No. 15 and No. 18 (Azienda Unità Locale Socio Sanitaria 15 and 18)Veneto Regional AuthorityRicerca Sanitaria Finalizzata Bando 2017, Regione VenetoItalian Ministry of Healt
Bi-allelic variants in CELSR3 are implicated in central nervous system and urinary tract anomalies
Full text linkCELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3 . Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.Bonner Promotionskolleg "NeuroImmunology" BonnNi: Q614.2454. This work was supported by the Open Access Fund of the University of Bonn.Bonner Promotionskolleg "NeuroImmunology" BonnNi: Q614.0754. BONFOR Forschungsförderprogramm Bonn: O-167.0023.BONFOR Forschungsförderprogramm Bonn: O-120.0001. Herbert-Reeck foundation.Medical Research Council: MR/T016809/1.Deutsche Forschungsgemeinschaft (German Research Foundation)https://doi.org/10.13039/501100001659Begg Family Foundation.National Institutes of Health: DK076683. Begg Family Foundation.Telethon Undiagnosed Diseases Program: GSP15001.Novo Nordisk Fonden (Novo Nordisk Foundation)https://doi.org/10.13039/501100009708Netherlands Organisation of Scientific Research: ZonMW Veni 91617021. Erasmus MC Fellowship 2017, Erasmus MC Human Disease Model Award 2018.Medical Research Council: MR/T016809/1. MCR-NIHR UK Rare Disease Research Platform Rare early onset lower urinary tract (REOLUT) disorders: MR/Y008340/1. Project start-up research funding from Kidneys for LifeU.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)https://doi.org/10.13039/100000051Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)https://doi.org/10.13039/100005202U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)US National Institutes of Health, National Institute of Neurologic Disease and Stroke: R35 NS105078.Eva Luise und Horst Köhler Stiftunghttps://doi.org/10.13039/501100007952Isabella Forrest Julian Research Fund for Pediatric Post Kidney Transplant Research. Else Kröner-Fresenius-Stiftung. Interdisciplinary Center for Clinical Research at the University Hospital of the Friedrich-Alexander-Universität: J98 and CSP. Friedrich-Alexander-Universität Erlangen-Nürnberg, Open Access Publication Funding
Three-dimensional assessment of upper airway changes associated with mandibular positional deviations following fibula free flap reconstruction
Full text linkObjectives Fibula free flaps (FFF) are the standard approach to mandibular reconstruction after partial resection, with the goal of restoring aesthetics and masticatory function. The graft position affects both and must be carefully selected. Correlations between sagittal positioning and upper airway anatomy are known from orthognathic surgery. This study aims to evaluate changes in mandibular position and upper airway anatomy after reconstructive surgery with FFF and corresponding correlations. Materials and methods Mandibular position after reconstruction was evaluated using three-dimensional datasets of pre- and postoperative computed tomography scans of patients treated between 2020 and 2022. Three-dimensional measurements were performed on both condyles and the symphyseal region. Changes in upper airway volume and minimum cross-sectional area (minCSA) were analysed. Intra-rater reliability was assessed. Correlations between changes in upper airway anatomy and sagittal mandibular position were tested. Results The analysis included 35 patients. Intra-rater reliability was good to excellent. Condylar deviations and rotations were mostly rated as small. Changes in symphyseal position were considerably greater. Median airway volume decreased in the oropharynx and hypopharynx. Posterior deviation of the symphysis was associated with a decreasing minCSA in the hypopharynx and vice versa. Conclusions The overall accuracy of mandibular reconstructions with FFF is high, but there is room for optimization. The focus of research should be extended from masticatory to respiratory rehabilitation. Clinical relevance Effects on respiratory function should be considered prior to graft positioning. The clinical relevance of upper airway changes within the complex rehabilitation of reconstructive surgery patients needs to be further investigated.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Pattern electroretinogram, blue-yellow visual evoked potentials and the risk of developing visual field defects in glaucoma suspects: a longitudinal “survival” analysis with a very long follow-up
Full text linkPurpose Estimating glaucoma suspects’ risk for visual field defects helps to avoid under- and over-treatment. In this retrospective, longitudinal cohort study with a very long follow-up, we studied whether pattern electroretinograms (PERG) amplitudes and blue-on-yellow visual evoked potential (BY-VEP) latencies can predict visual field defects. Methods Participants of the Erlangen Glaucoma Study were examined with PERG and BY-VEP between 9/1991 and 8/2001. Stimuli were created using an optical bench with Maxwellian view and consisted of vertical gratings (0,88 cpd) in a 32° field for both PERG and BY-VEP. Patients were treated according to clinical standards and performed standard automated perimetry (SAP) annually. Retrospectively, patients with normal SAP at baseline were selected. Primary endpoint was conversion to perimetric glaucoma. Predictive value was modeled using Kaplan–Meier analyses and a multivariate cox proportional hazards model with the continuous variables PERG amplitude, BY-VEP peak time and SAP square-root of loss variance (sLV) after stratification for Jonas classification of the optic discs. Results Of 412 patients (288: Jonas 0, 103: I, and 21: II; baseline age: 20–60 years), 65 converted to perimetric glaucoma during follow-up (0.5–23.3 years; median 5.5 years). Optic disc classification was a strong risk factor for conversion (log rank p < 0.0001), and patients with more advanced changes progressed earlier. In the multivariate analysis (log rank p = 0.005), only PERG amplitude remained an independent risk factor after stratification for optic disc morphology ( p = 0.021), with a ~ 30% higher risk per μV amplitude decrease. Conclusions PERG helps to estimate glaucoma suspects’ risk for visual field defects.Open Access funding enabled and organized by Projekt DEAL.Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Universitätsklinikum Erlangen (8546
New fluorogenic triacylglycerols as sensors for dynamic measurement of lipid oxidation
Full text linkLipids are major constituents of food but are also highly relevant substructures of drugs and are increasingly applied for the development of lipid-based drug delivery systems. Lipids are prone to oxidative degradation, thus affecting the quality of food or medicines. Therefore, analytical methods or tools that enable the degree of lipid oxidation to be assessed are of utmost importance to guarantee food and drug safety. Herein, we report the design, synthesis and application of the first-in-class fluorogenic triacylglycerols that enable dynamic monitoring of lipid oxidation via straightforward fluorescence readout. Our fluorogenic triacylglycerols can be used in both aqueous and lipid-based environments. Furthermore, we showed that the sensitivity of our fluorescent tracers towards oxidation could be tuned by incorporating either saturated or unsaturated acyl chains in their triacylglycerol core structure. With this, we provide a first proof of principle for the applicability of fluorescently labelled triacylglycerols as tracers to monitor the dynamics of lipid oxidation, thus paving the way for novel discoveries in the area of lipid analytics. Graphical AbstractOpen Access funding enabled and organized by Projekt DEAL.Friedrich-Alexander-Universität Erlangen-Nürnberg (1041
Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts
Full text linkBackground A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials. Methods Here, we report systematic characterization of the tumor microenvironment (TME) in GBM PDOXs and patient tumors at the single-cell and spatial levels. We applied single-cell RNA sequencing, spatial transcriptomics, multicolor flow cytometry, immunohistochemistry, and functional studies to examine the heterogeneous TME instructed by GBM cells. GBM PDOXs representing different tumor phenotypes were compared to glioma mouse GL261 syngeneic model and patient tumors. Results We show that GBM tumor cells reciprocally interact with host cells to create a GBM patient-specific TME in PDOXs. We detected the most prominent transcriptomic adaptations in myeloid cells, with brain-resident microglia representing the main population in the cellular tumor, while peripheral-derived myeloid cells infiltrated the brain at sites of blood–brain barrier disruption. More specifically, we show that GBM-educated microglia undergo transition to diverse phenotypic states across distinct GBM landscapes and tumor niches. GBM-educated microglia subsets display phagocytic and dendritic cell-like gene expression programs. Additionally, we found novel microglial states expressing cell cycle programs, astrocytic or endothelial markers. Lastly, we show that temozolomide treatment leads to transcriptomic plasticity and altered crosstalk between GBM tumor cells and adjacent TME components. Conclusions Our data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment. Graphical AbstractFonds National de la Recherche Luxembourghttp://dx.doi.org/10.13039/501100001866H2020 Marie Skłodowska-Curie Actionshttp://dx.doi.org/10.13039/100010665National Biomedical Computation Resourcehttp://dx.doi.org/10.13039/10001706