OPEN FAU Online-Publikationssystem der Friedrich-Alexander-Universität Erlangen-Nürnberg
Not a member yet
23478 research outputs found
Sort by
Mutations in the splicing factor SF3B1 are linked to frequent emergence of HLA-DRlow/neg monocytes in lower-risk myelodysplastic neoplasms
Full text linkCRUK City of London Centre Award [CTRQQR-2021/100004] at KCLEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)https://doi.org/10.13039/100010661Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)https://doi.org/10.13039/501100005010Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHSThis work was supported by the transCampus funding program between King’s College London and TUD, and the German Cancer Consortium (DKTK)
Synthesis, biological evaluation, and molecular docking of novel 1,3,4-substituted-thiadiazole derivatives as potential anticancer agent
Full text linkIn an attempt to develop potent anti-cancer agents, a new 1,3,4-substituted-thiadiazole derivatives (8b-g), starting from 4-substituted-thiazol-2-chloroacetamides (4b-g), were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the hepatocellular carcinoma (HEPG-2), human lung carcinoma (A549), human breast carcinoma (MCF-7) and pseudo-normal human embryonic liver (L02) cancer cell lines by an MTT assay. Among all synthesized compounds, compound 8d showed the potent anti-cancer activities with GI50 values of 2.98, 2.85 and 2.53 μM against MCF-7, A549 and HepG-2 cell lines respectively as compared to standard drug Doxorubicin. Furthermore, molecular modelling studies have spotlighted the anchoring role of 1,3,4-substituted-thiadiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. Therefore, these results can provide promising starting points for further development of best anti-cancer agents.Graphical Abstrac
A case-control study of reaction time deficits in a 3D virtual reality in patients with Post-COVID syndrome
Full text linkFollowing the Coronavirus disease 2019 (COVID-19) pandemic, a large number of people continue to report Post-COVID symptoms (PCS). A wide variety of symptoms are described, including fatigue, post-exertional malaise and cognitive impairment. However, adequate objective diagnostic tests for PCS are not yet available. Since the neurotropism of SARS-CoV-2 could be a possible factor for cognitive impairment, the aim of this study was to clarify whether visual reaction time (RT) in a stereoscopic setting can be a marker in PCS diagnostics. The Virtual-Reality-Oculomotor-Test-System (VR-OTS) was used testing binocular vision in 9 gaze directions via stereoscopic stimuli displayed in a virtual reality (VR)-environment (disparity: 275″, 550″, 1100″) in 179 individuals: 130 patients with PCS and 49 healthy controls. The results from the generalized linear models indicated that both group membership (PCS vs. control) and covariates (age and sex) yielded statistically significant different RT across the models. Accounting for the effect of covariates a statistically significant difference of RT was observed between patients with PCS and controls (disparity 275″ p-value = 0.001; 550″ p-value = 0.001; 1100″ p-value = 0.003). Patients with PCS performed worse in RT in all gaze directions, respectively. Adjusting for the influence of covariates, correct responses (CR) differed significantly between patients with PCS and controls (disparity 275″ p-value < 0.001; 550″ p-value = 0.003; 1100″ p-value = 0.019). Statistically significant effects of covariates on RT were observed for sex (disparity 275″ p-value = 0.047; 550″ p-value = 0.012; 1100″ p-value = 0.005) and age (disparity 275″ p-value < 0.001; 550″ p-value < 0.001; 1100″ p-value < 0.001). However, regarding covariates, no significant effects were found for CR, except for age at disparity 275″ (p-value = 0.035). The present data suggested that the mentioned variables uniquely contributed to explain the variation of the response variable (RT, CR). RT and CR detecting 3D-stimuli in a virtual 3D- environment might offer novel functional diagnostic approaches in PCS.Bavarian Health and Food Safety AuthorityDeutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Federal Ministry of Education and Researc
The foundations of the Patagonian icefields
Full text linkThe two vast Patagonian icefields are a global hotspot for ice-loss. However, not much is known about the total ice volume they store - let alone its spatial distribution. One reason is that the abundant record of direct thickness measurements has never been systematically exploited. Here, this record is combined with remotely-sensed information on past ice thickness mapped from glacier retreat. Both datasets are incorporated in a state-of-the-art, mass-conservation approach to produce a well-informed map of the basal topography beneath the icefields. Its major asset is the reliability increase of thicknesses values along the many marine- and lake-terminating glaciers. For these, frontal ice-discharge is notably lower than previously reported. This finding implies that direct climatic control was more influential for past ice loss. We redact a total volume for both icefields in 2000 of 5351 km 3 . Despite the wealth of observations used in this assessment, relative volume uncertainties remain elevated.The Southern Patagonian Icefield likely stores around 10% more ice than previously believed, according to ice thickness estimates based on remote sensing and direct measurement-informed mapping of the sub-glacial topography
Implementation and dissemination of physical activity-related health competence in vocational nursing training: study protocol for a cluster-randomized controlled intervention trial
Full text linkBackgroundAlthough the nursing sector gains growing importance in an aging society, students representing the future workforce often show insufficient health. Acknowledging the health-enhancing effects of adequate physical activity, the educational system in Bavaria, Germany, has recently integrated the promotion of physical activity-related health competence (PAHCO) into the nursing curriculum. However, it cannot be assumed that PAHCO has sufficiently permeated the educational practices and routines of the nursing schools. Therefore, the goal of the present study is to examine and compare the effectiveness as well as implementation of different intervention approaches to address PAHCO in the Bavarian nursing school system.MethodsWe randomly assign 16 nursing schools (cluster-based) to four study arms (bottom-up, top-down led by teachers, top down led by external physical activity experts, control group). Schools in intervention group 1 (IG-1) develop multicomponent inventions to target PAHCO via cooperative planning (preparation, planning, and implementation phase). Intervention groups 2 and 3 (IG-2, IG-3) receive both an expert-based intervention (developed through intervention mapping) via trained mediators to address PAHCO. External physical activity experts deliver the structured PAHCO intervention in IG-2, while teachers from the nursing schools themselves conduct the PAHCO intervention in IG-3. In line with a hybrid effectiveness implementation trial, we apply questionnaire-based pre-post measurements across all conditions (sample size calculation: nfinal = 636) to examine the effectiveness of the intervention approaches and, simultaneously, draw on questionnaires, interview, and protocol data to examine their implementation. We analyze quantitative effectiveness data via linear models (times-group interaction), and implementation data using descriptive distributions and content analyses.ConclusionThe study enables evidence-based decisions about the suitability of three intervention approaches to promote competencies for healthy, physically active lifestyles among nursing students. The findings inform dissemination activities to effectively reach all 185 schools of the Bavarian nursing system.Trial registrationClinical trials NCT05817396. Registered on April 18, 2023.Open Access funding enabled and organized by Projekt DEAL.Bavarian State Ministry for Health, Nursing and PreventionKKH Kaufmännische KrankenkasseFriedrich-Alexander-Universität Erlangen-Nürnberg (1041
Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food
Full text linkDietary exposure to N-nitrosamines has recently been assessed by the European Food Safety Authority (EFSA) to result in margins of exposure that are conceived to indicate concern with respect to human health risk. However, evidence from more than half a century of international research shows that N-nitroso compounds (NOC) can also be formed endogenously. In this commentary of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG), the complex metabolic and physiological biokinetics network of nitrate, nitrite and reactive nitrogen species is discussed with emphasis on its influence on endogenous NOC formation. Pioneering approaches to monitor endogenous NOC have been based on steady-state levels of N -nitrosodimethylamine (NDMA) in human blood and on DNA adduct levels in blood cells. Further NOC have not been considered yet to a comparable extent, although their generation from endogenous or exogenous precursors is to be expected. The evidence available to date indicates that endogenous NDMA exposure could exceed dietary exposure by about 2–3 orders of magnitude. These findings require consolidation by refined toxicokinetics and DNA adduct monitoring data to achieve a credible and comprehensive human health risk assessment
Spot urinary sodium in CKD patients: correlation with 24h-excretion and evaluation of commonly used prediction equations
Full text linkBackground Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt metabolism but are cumbersome to perform. We assessed urinary sodium (U-Na) concentration in spot urine samples and investigated the correlation with 24h U-Na excretion and concentration in CKD patients under nephrological care. Further, we studied the role of CKD stage and diuretics and evaluated the performance of commonly used formulas for the prediction of 24h U-Na excretion from spot urine samples. Methods One hundred eight patients of the German Chronic Kidney Disease (GCKD) study were included. Each participant collected a 24h urine and two spot urine samples within the same period. The first spot urine sample (AM) was part of the second morning urine. The second urine sample was collected before dinner (PM). Patients were advised to take their medication as usual without changing dietary habits. U-Na concentrations in the two spot urine samples and their average ((AM + PM)/2) were correlated with U-Na concentration and total Na excretion in the 24h urine collections. Correlations were subsequently studied after stratification by CKD stage and diuretic intake. The usefulness of three commonly applied equations to estimate 24h U-Na excretion from spot urine samples (Kawasaki, Tanaka and Intersalt) was determined using Bland–Altman plots, analyses of sensitivity, specificity, as well as positive (PPV) and negative predictive values (NPV). Results Participants (42 women, 66 men) were on average (± SD) 62.2 (± 11.9) years old, with a mean serum creatinine of 1.6 (± 0.5) mg/dl. 95% had arterial hypertension, 37% diabetes mellitus and 55% were on diuretics. The best correlation with 24h U-Na total excretion was found for the PM spot U-Na sample. We also found strong correlations when comparing spot and 24h urine U-Na concentration. Correction of spot U-Na for U-creatinine did not improve strength of correlations. Neither CKD stage, nor intake of diuretics had significant impact on these correlations. All examined formulas revealed a significant mean bias. The lowest mean bias and the strongest correlation between estimated and measured U-Na excretion in 24h were obtained using the Tanaka-formula. Also, application of the Tanaka-formula with PM U-Na provided best sensitivity, specificity, PPV and NPV to estimate U-Na excretion > 4g/d corresponding to a salt consumption > 10g/d. Conclusion U-Na concentration of spot urine samples correlated with 24h U-Na excretion especially when PM spot U-Na was used. However, correlation coefficients were relatively low. Neither CKD stage nor intake of diuretics appeared to have an influence on these correlations. There was a significant bias for all tested formulas with the Tanaka-formula providing the strongest correlation with measured 24h U-Na excretion. In summary, using spot urine samples together with the Tanaka-formula in epidemiological studies appears feasible to determine associations between approximate salt intake and outcomes in CKD patients. However, the usefulness of spot-urine samples to guide and monitor salt consumption in individual patients remains limited.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
A high proportion of germline variants in pediatric chronic myeloid leukemia
Full text linkChronic myeloid leukemia (CML) typically occurs in late adulthood. Pediatric CML is a rare form of leukemia. In all age groups, the characteristic genetic driver of the disease is the BCR :: ABL1 fusion gene. However, additional genomic events contribute to leukemic transformation, which is not yet well-characterized in pediatric CML. We investigated the mutational landscape of pediatric CML to determine whether predisposing germline variants may play a role in early-age disease development. Whole exome sequencing and targeted sequencing were performed in pediatric and adult CML samples to identify age-related germline and somatic variants in addition to the BCR::ABL1 translocation. Germline variants were detected in about 60% of pediatric patients with CML, with predominantly hematopoietic genes affected, most frequently ASXL1 , NOTCH1 , KDM6B , and TET2 . The number of germline variants was significantly lower in adult patients with CML. If only confirmed pathogenic variants were regarded as cancer-predisposing variants, the occurrence was ~ 10% of pediatric CML, which is comparable to other hematological malignancies and most childhood cancer entities in general. We hypothesize that the interaction with the strong oncogene BCR::ABL1 may also favor the development of leukemia by weaker variants in the same genes. In pediatric patients, the germline variants of genes associated with clonal hematopoiesis may increase the likelihood that an incidental BCR::ABL1 translocation triggers the early manifestation of CML.Schornsteinfeger helfen krebskranken Kindern e.V., GermanySonnenstrahl e. V. Dresden, GermanyBundesministerium für Bildung und Forschung,German
Meningitis and intracranial abscess due to Mycoplasma pneumoniae in a B cell-depleted patient with multiple sclerosis
Full text linkMycoplasma pneumoniae , a frequent respiratory pathogen, can cause neurological disease manifestations. We here present a case of M. pneumoniae as cause of meningitis and occurrence of an intracranial abscess as a complication of mastoiditis with septic cerebral venous sinus thrombosis in a patient with multiple sclerosis on anti-CD20 therapy.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546
Odor prediction of whiskies based on their molecular composition
Full text linkAroma compositions are usually complex mixtures of odor-active compounds exhibiting diverse molecular structures. Due to chemical interactions of these compounds in the olfactory system, assessing or even predicting the olfactory quality of such mixtures is a difficult task, not only for statistical models, but even for trained assessors. Here, we combine fast automated analytical assessment tools with human sensory data of 11 experienced panelists and machine learning algorithms. Using 16 previously analyzed whisky samples (American or Scotch origin), we apply the linear classifier OWSum to distinguish the samples based on their detected molecules and to gain insights into the key molecular structure characteristics and odor descriptors for sample type. Moreover, we use OWSum and a Convolutional Neural Network (CNN) architecture to classify the five most relevant odor attributes of each sample and predict their sensory scores with promising accuracies (up to F1: 0.71, MCC: 0.68, ROCAUC: 0.78). The predictions outperform the inter-panelist agreement and thus demonstrate previously impossible data-driven sensory assessment in mixtures.Aroma compositions are usually complex mixtures of odor-active compounds exhibiting diverse molecular structures, and assessing or predicting the olfactory qualities of such mixtures is challenging. Here, fast automated analytical assessment tools are combined with the human sensory data of 11 experienced panelists and machine learning algorithms, enabling samples to be distinguished and classified based on their detected molecules, and gaining insights into key molecular structure characteristics and odor descriptors.Bayerisches Staatsministerium für Wirtschaft, Landesentwicklung und Energie (StMWi) - Bavarian Ministry for Economic Affairs, Regional Development and Energy (StMWi) - Grant number 20-3410-2-14-