Ludwig-Maximilians-Universität München
Open Access LMU ( Ludwig-Maximilians-Univ. München)Not a member yet
40914 research outputs found
Sort by
Associations of road traffic noise with adipose tissue depots and hepatic fat content – Results from the German National Cohort (NAKO)
Full text linkLittle is known about the relation between traffic noise exposure, an established environmental risk factor for cardiovascular disease, and early obesity-related risk markers such as adipose tissue (AT) and hepatic fat. Therefore, we aimed to assess associations of long-term road traffic noise exposure with AT depots measures from whole-body magnetic resonance imaging (MRI). We analyzed cross-sectional data from 11,343 participants from the population-based German National Cohort (NAKO) who underwent MRI examination between 2014 and 2016, considering visceral (VAT), subcutaneous abdominal (SCAAT), subcutaneous thoracic AT (SCTAT) and hepatic fat content as outcomes. Annual road traffic noise (Lden) data from the year 2017 (source: central EIONET data repository) was used to calculate weighted mean noise levels on a continuous scale within 10 and 100-meter buffers of participants’ residencies. Among 11,101 participants with complete outcome data, 48.7 % were women, and the mean age was 51.9 years. Higher annual Lden was associated with increased AT depots and hepatic fat content in men (e.g., VAT: 1.72 %-change [95 % confidence interval: [0.14 %; 3.30 %]; SCAAT: 2.18 %-change [0.43 %; 3.93 %], hepatic fat content: 3.57 %-change [1.41 %; 5.78 %] per 10 dB(A) increase in Lden (10 m)) and women (e.g., VAT: 3.13 %-change [1.09 %; 5.18 %]; SCAAT: 2.38 %-change [0.55 %; 4.20 %], hepatic fat content: 3.08 %-change [1.00 %; 5.21 %] per 10 dB(A) increase in Lden (10 m)). Associations were robust with all outcomes after adjusting for air pollutants and surrounding greenness, and effect modification by obesity and hypertension was observed for SCAAT, SCTAT and hepatic fat content. Our findings indicate that annual exposure to road traffic noise is associated with increased adipose tissue depots and hepatic fat content, and thus present novel evidence for the cross-sectional association between noise and early MRI-derived metabolic health markers
Conformal prediction regions are imprecise highest density regions
Full text linkRecently, Cella and Martin proved how, under an assumption called consonance, a credal set (i.e. a closed and convex set of probabilities) can be derived from the conformal transducer associated with transductive conformal prediction. We show that the Imprecise Highest Density Region (IHDR) associated with such a credal set corresponds to the classical Conformal Prediction Region. In proving this result, we establish a new relationship between Conformal Prediction and Imprecise Probability (IP) theories, via the IP concept of a cloud. A byproduct of our presentation is the discovery that consonant plausibility functions are monoid homomorphisms, a new algebraic property of an IP tool
Linguistic Strategies of Estrangement in Historical Fiction: Bridgerton and Downton Abbey
Full text link
Conditioned medium from brachytherapy-irradiated hepatocellular carcinoma cells drives SASP-mediated senescence in naïve cellular counterparts
No full textBackground and purpose
Local ablation, including high-dose radiation brachytherapy (HDR-BT), provides a minimally invasive treatment for cancers such as hepatocellular carcinoma (HCC), achieving effective tumor targeting with reduced peri-interventional risk and morbidity. Despite benefits, these treatments face limitations due to tumor recurrence. Cellular senescence might play a key role in therapy resistance by way of tumor cell evasion. This study investigates whether HDR-BT induces cellular senescence in vitro, potentially linking these processes to tumor recurrence in HCC.
Material and methods
HCC cell lines (HepG2, Huh7, and Hep3B) were irradiated with 7.5 Gy using an in vitro irradiation device. Culture supernatant was collected and transferred to non-irradiated naïve cells. Cell proliferation and senescence were assessed kinetically using BrdU incorporation, Ki-67 immunostaining, and clonogenic assay. Senescence was confirmed by beta-galactosidase staining. Secretome analysis was conducted using a high-throughput proteomic assay.
Results
After irradiation, HCC cells show a transient increase in DNA synthesis, peaking before 72 h without leading to cell division. Exposure of naïve cells to supernatant from irradiated cells replicates these effects, suggesting that the conditioned medium alone can mimic radiation-induced responses. Molecular analysis reveals reduced Ki-67 expression and increased senescence in naïve, incubated cells. Proteomic profiling shows an enrichment of senescence-associated secretory phenotype (SASP) proteins in conditioned medium with exposed naïve cells producing a similar SASP-enriched secretome.
Conclusion
In vitro brachytherapy triggers a bystander effect in HCC cells via SASP-associated proteins inducing senescence in neighboring cells. Modulating senescence or its associated secretory phenotype may offer a novel target for therapy in future trials
Single‐ and Three‐Photon Ionization of N2 in Presence of Fano Resonances
No full textWe report single- and three-photon ionization cross-sections of the
molecule in the region of the Hopfield series of doubly excited states. Results are obtained by solving the time-dependent Schrödinger equation in a hybrid basis combining neutral and ionic CI states with a fully numerical basis. Contributions to the spectrum during and after the interaction are obtained using the tSurff and iSurf methods. Calculations at arbitrary molecular orientation and details of the spectral calculation are presented. For single-photon ionization synchrotron data is reproduced. For three-photon ionization we find a pronounced change of resonance line shape when going from single- to three-photon transitions
Targeting VEGF‐A in an Immunocompetent Orthotopic Mouse Model of Mesenchymal Glioblastoma Improves Antitumorigenicity and Decreases Proinflammatory Response in Normal Brain Tissue after Fractionated Radiotherapy
No full textGlioblastoma is the most aggressive primary brain tumor characterized by a dismal prognosis and a profound therapy resistance that is most evident for the mesenchymal molecular subtype of glioblastoma. Targeting vascular endothelial growth factor (VEGF)-A by the monoclonal antibody bevacizumab, despite failing to improve survival in randomized trials, yields relevant benefits in glioblastoma patients such as reduction of radionecrosis, an adverse event associated with radiotherapy. This demands for continued research to identify optimal combinations of anti-VEGF-A and standard therapies for glioblastoma treatment. We show here that blocking VEGF-A in an immune competent orthotopic glioblastoma mouse model resembling the adverse mesenchymal molecular subtype increases the tumoricidal effect of computed tomography (CT)-based fractionated radiotherapy and also rectifies irradiation-induced expression of genes with known association to mesenchymal subtype enrichment as revealed by microarray-based transcriptome analyses of explanted tumors. VEGF-A blockade also decreases the expression of myeloid-cell-related gene patterns in irradiated tumors and lowers inflammatory response in normal brain tissue after tumor irradiation. Hence, these data both provide a hint how blockade of VEGF-A increases the effect of radiotherapy in mesenchymal glioblastoma and a mechanistic base for clinical observations reporting reduced incidences of radionecrosis in glioblastoma patients treated with radiotherapy upon concurrent administration of bevacizumab
Tricuspid regurgitation risk scores in patients undergoing tricuspid valve transcatheter edge‐to‐edge repair
No full textTricuspid regurgitation (TR) is associated with increased morbidity, mortality and the risk of frequent heart failure hospitalizations. Tricuspid transcatheter edge-to-edge repair (T-TEER) evolved as a powerful technique for the effective treatment of TR without the need for open-heart surgery. Recent data of two randomized controlled trials demonstrated significant improvement of quality of life by T-TEER in addition to optimal medical therapy.1, 2 Beyond that, safety and effectiveness of T-TEER have been confirmed in several real-world registries.3-6 However, improvement of heart failure hospitalizations or mortality following T-TEER has not been observed yet. Therefore, careful patient selection prior to T-TEER is key to further optimize outcomes and potentially reduce mortality of heart failure patients with severe TR. Several TR risk scores are available which were mostly designed and validated to predict early survival prognosis in surgically or conventionally treated TR patients. The aim of this study was to evaluate the performance of six currently available risk scores in a large real-world T-TEER cohort for the prediction of 1-year survival