Ludwig-Maximilians-Universität München
Open Access LMU ( Ludwig-Maximilians-Univ. München)Not a member yet
40914 research outputs found
Sort by
Persistent desmoglein-1 downregulation and periostin accumulation in histologic remission of eosinophilic esophagitis
Full text linkBackground
Patients with eosinophilic esophagitis (EoE) require long-lasting resolution of inflammation to prevent fibrostenosis and dysphagia. However, the dissociation between symptoms and histologic improvement suggests persistent molecular drivers despite histologic remission.
Objective
We characterized persisting molecular alterations in pediatric patients with EoE using tissue transcriptomics and proteomics.
Methods
Esophageal biopsy samples (n = 247) collected prospectively during 189 endoscopies from pediatric patients with EoE (n = 36, up to 11 follow-up endoscopies) and pediatric controls (n = 44, single endoscopies) were subjected to bulk transcriptomics (n = 96) and proteomics (n = 151). Intercellular junctions (desmoglein-1/3, desmoplakin, E-cadherin) and epithelial-to-mesenchymal transition (vimentin:E-cadherin ratio) were assessed by immunofluorescence staining.
Results
Active EoE (≥15 eosinophils per high-power field [eos/hpf]), inactive EoE (<15 eos/hpf), and deep-remission EoE (0 eos/hpf) were diagnosed in 107 of 185, 78 of 185, and 41 of 185 biopsy samples, respectively. Among the dysregulated genes (up-/downregulated 310/112) and proteins (up-/downregulated 68/16) between active EoE and controls, 17 genes, and 6 proteins remained dysregulated in inactive EoE. Using persistently upregulated genes (n = 9) and proteins (n = 3) only, such as ALOX15, CXCL1, CXCL6, CTSG, CDH26, PRRX1, CLC, EPX, and periostin (POSTN), was sufficient to separate inactive EoE and deep-remission biopsy samples from control tissue. While 32 differentially expressed genes persisted in deep-remission EoE compared to controls, the proteome normalized except for persistently upregulated POSTN. Epithelial-to-mesenchymal transition normalized in inactive EoE, whereas desmosome recovery remained impaired as a result of desmoglein-1 downregulation.
Conclusion
The analysis of molecular changes shows persistent EoE-associated esophageal dysregulation despite histologic remission. These data expand our understanding of inflammatory processes and possible mechanisms that underlie tissue remodeling in EoE
Alpha spectroscopy of purified beams of exotic nuclei at the FRS Ion Catcher
Full text linkThe FRS Ion Catcher (FRS-IC) is located at the final focal plane of the Fragment Separator FRS at GSI. The FRS-IC setup is well known for high-precision experiments with stopped exotic nuclei produced by projectile fragmentation and fission. The facility consists of the cryogenic gas-filled stopping cell (CSC), an RFQ-based beamline (DISTRICT), and a multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS). This paper illustrates how alpha spectroscopy performed at this facility has emerged as a promising tool to unveil the nuclear structure of exotic nuclei, i.e., half-live and decay energy measurements. First studies of that kind were performed on the decay chains of 218Rn, 219Rn, 221Ac, 220Fr, and 223,224Th produced by projectile fragmentation of 238U. The α decay energy measurements performed and the deduced Qα values confirm the known maximum at N=128 and the values of Qα at N follow the predicted increasing in Qα values compared to the values for At isotopes at the same neutron number N. Further, the production rate ratio of the isomer to the ground state of 211Po was measured. It allows an estimate of the angular momentum distribution of 211Po fragments following fragmentation of 238U in a 9Be target at relativistic energies. In addition, the potential of mass-selected decay spectroscopy behind the MR-TOF-MS was demonstrated with short-lived 215Po ions ( ms). This demonstrates that the FRS-IC is a reliable setup for α spectroscopy studies and related nuclear structure studies
Special issue editorial: Advanced partial least squares structural equation modeling (PLS-SEM) applications in business research
Full text linkThis special issue comprises a series of advanced applications of and methodological developments concerning PLS-SEM in business research. PLS-SEM,1 introduced by Wold, 1975, Wold, 1982 and Lohmöller (1989), models the structural relationships between constructs (i.e., the latent variables) as empirical approximations of theoretical concepts. Each construct is operationalized by a measurement model with a set of indicators (i.e., observed variables). The PLS-SEM method estimates the entire model with the aim of maximizing the explained variance of the dependent constructs in the structural model and of the indicators in the constructs’ measurement models (Lohmöller, 1989, Wold, 1982)
Shadows of the past – Hierarchical regression analyses on the role of childhood maltreatment experiences for postpartum depression
Full text linkBackground
Postpartum depression (PPD) is one of the most common mental disorders in parents after birth. To develop tailored preventive programs, it is necessary to identify risk factors for PPD in parents. This study aimed to examine the impact of parental childhood maltreatment (CM) as a risk factor for PPD.
Methods
Data from a German study comprising n = 349 mothers and n = 46 fathers were used. Hierarchical regression models were performed to examine CM, educational background, single parenthood, emotion regulation and attachment style as predictors of symptoms of PPD. In exploratory analyses, potential mediators (i.e., parenting stress and emotion regulation) were investigated via a path model.
Results
CM, low level of education, difficulties in emotion regulation, and attachment anxiety were significant predictors for maternal PPD [R2 = 0.52, F (6, 305) = 57.99, p < .001]. For fathers, difficulties in emotion regulation were identified as a predictor [R2 = 0.43, F (6, 24) = 4.78, p < .01]. In exploratory analyses, emotion regulation served as a mediator for the link between CM and PPD as well as for the link between CM and parenting stress.
Limitations
The study design is cross-sectional and based on self-report questionnaires. Despite our attempts, only few fathers participated in the study, resulting in an underpowered sample for the regression analyses.
Conclusions
The study confirmed the assumption that CM experiences represent a risk factor for the development of maternal PPD. Emotion regulation might provide a pivotal target for interventions with parents at-risk
Cryptocurrencies, a controversial innovation? Unpacking argumentation analysis in economic geography
Full text linkIn this paper, we analyze the global controversy surrounding the innovation of cryptocurrencies, developing an analytical framework to assess the empirical structure of arguments. By unpacking an argumentation analysis of a comprehensive set of scholarly, media, and industry publications, we identify six key dimensions of disagreement, comprising 42 distinct arguments. These dimensions include the raison d’être, environmental impact, social inclusion, susceptibility to illegal activities, economic impact, and potential for decentralization and democratization. Our findings reveal entrenched positions supported by robust scholarly research and empirical evidence. Cryptocurrencies represent a controversial innovation, for which global resolution remains elusive. While the controversy may appear unbounded, we plead for a geographical approach, emphasizing that localized institutional contexts are crucial for exploring potential trajectories of the controversy. Finally, our analysis illustrates the potential of argumentation analysis to properly disentangle complex societal disagreements, and it therefore promises to enrich the methodological pluralism in economic geography
Unmixing inducing polymerization of a sodium-molybdenum borosilicate network
Full text linkGlass network polymerization critically influences rheological behavior and with it the kinetics and dynamics of nuclear waste immobilization. Molybdenum-bearing borosilicate melts may undergo unmixing and rheological changes, which is dominantly controlled by the associated chemical modifications of the melt network. Here, we obtain in-situ (500–940 °C) Raman spectra to probe structural changes of a sodium-molybdenum borosilicate melt undergoing unmixing. The extraction of alkali and molybdenum to form droplets induces polymerization of the residual borosilicate network. Conversely, the opposite phenomenon is observed during droplet re-dissolution. This work provides new insights into the polymerization of a molybdenum-bearing borosilicate composed of two composition sets due to a miscibility gap and has direct contributions for the immobilization of nuclear wastes
Optimized monitoring for immune checkpoint inhibitor induced myocarditis using high-sensitivity troponin-T
Full text linkBackground
Immune checkpoint inhibitor (ICI)-induced Myocarditis (irMyocarditis) is a rare adverse event with a high mortality rate of 40–50 % and which is mostly not diagnosed until clinical symptoms emerge.
Objectives
This study aims to screen patients for irMyocarditis using high-sensitivity cardiac troponin-T (hs-TnT) before and regularly during therapy with ICI.
Methods
A cohort of 280 cancer patients were prospectively screened for levels of hs-TnT at baseline and prior to every ICI infusion. In case of elevation of hs-TnT, patients were referred for further work-up.
Results
In total, 196 patients exhibited a baseline hs-TnT ≤ 14 ng/l (99th percentile concentration for general population; group A) and 84 patients a hs-TnT > 14 ng/l at baseline (group B). An increase of hs-TnT during ICI-treatment was observed in 56 out of 196 (27.6 %) and 56 out of 84 patients (66.7 %) in group A and B. Cardiovascular assessment was performed in 11.2 % and 27.4 % of patients, respectively, and 4.1 % and 9.5 % of patients were diagnosed with irMyocarditis and treated with corticosteroids. No fatalities occurred in any of the 16 irMyocarditis patients. Defining a threshold with the highest sensitivity and maximum specificity in receiver-operating characteristics curves, identified a limit of 22 ng/l (group A) and 60 ng/l (group B) hs-TnT, associated with a sensitivity of 100 % in both and a specificity of 91.0 % and 89.6 %, respectively, to detect irMyocarditis.
Conclusion
Screening of hs-TnT can identify irMyocarditis early and lead to reduction of MACE and mortality risk through interruption of ICI-treatment and prompt therapy with corticosteroids
Real‐Time Assessment of H. pylori Infection to Guide Molecular Antibiotic Resistance Testing: A Combined Endoscopy‐Gastric Juice Analysis Approach
Full text linkBackground:
Helicobacter pylori antibiotic resistance is the most relevant cause of treatment failure. Antibiotic susceptibility testing (AST) allows for selecting the appropriate eradication regimen.
Aims:
To assess the diagnostic accuracy of gastric aspirate-based genotypic AST (G-AST) for detecting clarithromycin and levofloxacin resistance compared with conventional phenotypic AST (P-AST).
Methods:
We recruited 461 consecutive patients scheduled for endoscopy. H. pylori was detected intraprocedurally using Endofaster, a novel method combining endoscopy with gastric juice analysis. For H. pylori-positive patients, we collected gastric aspirates and biopsies. G-AST was performed using DNA extracted from aspirates, with Sanger sequencing to detect polymorphisms in the 23S rRNA and gyrA genes associated, respectively, with resistance to macrolides and fluoroquinolones. P-AST was performed on H. pylori isolated from biopsies using ETEST.
Results:
One hundred and seventy-eight (40.4%) patients tested positive for H. pylori during endoscopy. Paired gastric biopsies and aspirates were available from 152 H. pylori-positive patients. By P-AST, resistance rates were 15.1% (23/152) for clarithromycin and 18.4% (28/152) for levofloxacin. G-AST showed a high level of agreement with P-AST for clarithromycin (kappa 0.86) and levofloxacin (kappa 0.81) resistance and diagnostic accuracy of 97% and 95%, respectively.
Conclusions:
The novel method combining endoscopy with immediate intraprocedural gastric juice analysis for the detection of H. pylori, followed by AST in case of a positive finding, is valid and practical for tailoring eradication regimens for H. pylori infection. Genotypic AST from gastric aspirates is highly accurate for detecting clarithromycin and levofloxacin resistances
Defining the Synthetic Scope of ortho‐Quinone Methides by Quantifying their Electrophilicity
Full text linkA series of aryl-substituted ortho-quinone methides (oQMs) was synthesised and structurally characterised. Kinetic studies of the nucleophilic additions of carbanions (reference nucleophiles) to oQMs were used to determine second-order rate constants k2 for the carbon-carbon bond forming reactions (20 °C, DMSO) at the oQMs’ exocyclic π-bond. Analysing the kinetic data by the linear free energy relationship lg k2=sN(N+E) revealed the Mayr electrophilicities E of the oQMs. The electrophilicities E of oQMs correlate linearly with Hammett substituent constants and experimentally determined reduction potentials Epred as well as with quantum-chemically calculated methyl anion affinities (MAAs), which provides valuable tools for prediciting the reactivity of further types of oQMs. Embedding the oQMs in Mayr's reactivity scales enables to predict novel nucleophilic reaction partners for oQMs and can productively be used to prepare simple Michael adducts as well as 4+2 or 4+1 cyclisation products as demonstrated in this work by several novel reactions with neutral or negatively charged C-, N-, and S-nucleophiles
Combination of Ambient and High‐Temperature Beryllium Nitride Motifs in W2Be4N5 and W4Be8N9
Full text linkCompounds of transition metals and beryllium have a wide range of applications, from everyday tools to high tech applications. Remarkably, no single ternary beryllium nitride with a transition metal is known. Here, we report on the synthesis and properties of the first transition metal nitridoberyllates, namely W2Be4N5 and W4Be8N9. Both compounds were synthesized in a high-temperature high-pressure approach from Be3N2 and W, using azide generated N2 as an oxidizing agent. The crystal structures, consisting of alternating layers of WN6 trigonal prisms and BeN4 tetrahedra, were elucidated by single-crystal X-ray diffraction (sc-XRD). The separating nitridoberyllate layers show either ambient temperature (α-Be3N2 type) or high temperature (β-Be3N2 type) motifs. W2Be4N5 was further corroborated by infrared (IR), nuclear magnetic resonance (NMR) and UV/Vis spectroscopy and vibrating sample magnetometry (VSM) measurements. The latter revealed a mixed valence with an intermediate oxidation state of 3.5 for the W atoms. Both, the synthesis of the first transition metal nitridoberyllates and the synthesis approach using elemental W pave the way to a new field of nitride chemistry