Refine
Year of publication
Document Type
- Preprint (582)
- Article (444)
- Conference Proceeding (7)
- Part of a Book (2)
- Working Paper (1)
Has Fulltext
- yes (1036)
Is part of the Bibliography
- no (1036)
Keywords
- Heavy Ion Experiments (18)
- Hadron-Hadron scattering (experiments) (11)
- LHC (10)
- Heavy-ion collision (6)
- ALICE experiment (4)
- Atmospheric chemistry (4)
- Hadron-Hadron Scattering (4)
- Heavy Ions (4)
- Quark-Gluon Plasma (4)
- ALICE (3)
- Jets and Jet Substructure (3)
- Polymers (3)
- pp collisions (3)
- Beauty production (2)
- COVID-19 (2)
- Charm physics (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- HOD (2)
- Heavy-ion collisions (2)
- Invertebrates (2)
- Jets (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Microplastic (2)
- Monte Carlo (2)
- Multiple stressors (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Pb–Pb collisions (2)
- Plastics (2)
- SARS-CoV-2 (2)
- Single electrons (2)
- Systematic Uncertainty (2)
- Time Projection Chamber (2)
- glioblastoma (2)
- 900 GeV (1)
- AKI (1)
- ALICE LHC (1)
- ALICE detector (1)
- ASCT (1)
- ATO (1)
- ATP (1)
- ATR-FTIR (1)
- Abundance (1)
- Addison’s disease (1)
- Alcorrín (1)
- Allogeneic hematopoietic stem cell transplantation (1)
- Analysis and statistical methods (1)
- Anti-kaon–nucleon physics (1)
- Anti-nuclei (1)
- Atmospheric science (1)
- Autecology (1)
- Azacitidine (1)
- B cell receptor (1)
- BRAF (1)
- BRAF V600E (1)
- Balance function (1)
- Biogeochemistry (1)
- Bottled water (1)
- Brain tumor (1)
- Bronce Final (1)
- CD47 (1)
- CHIP (1)
- CLOUD experiment (1)
- CMS (1)
- COMT (1)
- Calorimeters (1)
- Cardiac surgery (1)
- Centrality Class (1)
- Centrality Selection (1)
- Charge correlations (1)
- Charged-particle density (1)
- Chemical composition (1)
- Chemistry (1)
- Climate change (1)
- Climate-change impacts (1)
- Collective Flow (1)
- Comparison with QCD (1)
- DLI (1)
- Data processing methods (1)
- Decitabine (1)
- Degradation (1)
- Demolition emissions (1)
- Direct reactions (1)
- Drug screens (1)
- Early Iron Age (1)
- Ecology (1)
- Ecosystem effects (1)
- Ecotoxicology (1)
- Electron-pion identification (1)
- Electroweak interaction (1)
- Ellenberg indicator values (1)
- Elliptic flow (1)
- Endocrine disrupting chemical (1)
- Energy reserves (1)
- Environmental quality (1)
- Environmental sciences (1)
- Estrecho de Gibraltar (1)
- Exposure (1)
- Fate (1)
- Feeding types (1)
- Femtoscopy (1)
- Festuco-Brometea (1)
- Fibre/foam sandwich radiator (1)
- Food packaging (1)
- Fortifica (1)
- Freshwater (1)
- Glioma (1)
- HBT (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Health information (1)
- Health-seeking behaviour (1)
- Heavy Ion Experiment (1)
- Heavy Quark Production (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ions (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Helpline (1)
- Hematology (1)
- Holmes tremor (1)
- Hyperons (1)
- Hypomethylating agents (1)
- IAP (1)
- IGF (1)
- Imidacloprid (1)
- Immune function (1)
- In vitro bioassay (1)
- Inclusive spectra (1)
- Indigenous Peoples (1)
- Intensity interferometry (1)
- Invariant Mass Distribution (1)
- Ionisation energy loss (1)
- KDIGO (1)
- KRAS (1)
- Kaonic nuclei (1)
- Large Hadron Collider (1)
- Late Bronze Age (1)
- Leukemias (1)
- Litter (1)
- Low energy QCD (1)
- MR-spectroscopy (1)
- Microplastic-biota interaction (1)
- Microplastics (1)
- Mid-rapidity (1)
- Minimum Bias (1)
- Mixture toxicity (1)
- Molecular matched therapy (1)
- Molecular profiling (1)
- Mollusks (1)
- Monitoring (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- NOTCH1 (1)
- NSCLC (1)
- NSF (1)
- Nanoplastic (1)
- Nanoplastics (1)
- Neural network (1)
- Nuclear modification factor (1)
- Nuclear reactions (1)
- Nuclear structure & decays (1)
- Nucleon induced nuclear reactions (1)
- Nucleus (1)
- Oncology (1)
- Oxidative stress (1)
- PM10 (1)
- PXA (1)
- PYTHIA (1)
- Partial wave analysis (1)
- Particle Correlations and Fluctuations (1)
- Particle toxicity (1)
- Pb–Pb (1)
- Performance of High Energy Physics Detectors (1)
- Phoenician Writing (1)
- Phoenicians (1)
- Plastic bottles (1)
- Plastic packaging (1)
- Plastic pollution (1)
- Plastic polymers (1)
- Pollutants (1)
- Polyethylene terephthalate (1)
- Pond snail (1)
- Potamopyrgus antipodarum (1)
- Primera Edad del Hierro (1)
- Production Cross Section (1)
- Properties of Hadrons (1)
- Proton (1)
- Proton–proton (1)
- Pyrolysis GC–MS (1)
- QCD (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- RAS (1)
- Rapidity Range (1)
- Rare diseases (1)
- Relapse (1)
- Relativistic heavy ion physics (1)
- Relativistic heavy-ion collisions (1)
- Resolution Parameter (1)
- Review (1)
- SHH (1)
- SIRPalpha (1)
- Sample preparation (1)
- Shell model (1)
- Single muons (1)
- Size distribution (1)
- Sources (1)
- Spectroscopic factors & electromagnetic moments (1)
- Strait of Gibraltar (1)
- Strangeness (1)
- Suspended solids (1)
- TR (1)
- Targeted therapy (1)
- Telemedicine (1)
- Thermal desorption GC–MS (1)
- Thermodynamics (1)
- Toxicity (1)
- Tracking (1)
- Transition radiation detector (1)
- Transverse Momentum (1)
- Transverse momentum (1)
- Trigger (1)
- Ultrafine particles (1)
- Urban aerosol (1)
- Vector (1)
- Vector Boson Production (1)
- Venetoclax (1)
- Visual analysis (1)
- WNT (1)
- Water framework directive (1)
- Wide rapidity coverage (1)
- Xenoestrogens (1)
- Xenon-based gas mixture (1)
- Yeast estrogen screen (1)
- additives (1)
- adipogenesis (1)
- adrenal insuffciency (1)
- aerosol formation (1)
- aerosols (1)
- antiviral therapy (1)
- aquatic environment (1)
- autologous stem cell transplantation (1)
- bevacizumab (1)
- bioassays (1)
- cBioPortal (1)
- cerebellar mutism (1)
- cerebellum (1)
- cerebral radiation necrosis (1)
- ceritinib (1)
- chemotherapy (1)
- clinical (1)
- clonal dominance (1)
- clonal hematopoiesis (1)
- computational biology (1)
- computer-assisted (1)
- coronavirus (1)
- dE/dx (1)
- dabrafenib (1)
- decision making (1)
- decision support systems (1)
- diet (1)
- dispersal (1)
- ecological strategy (1)
- endocrine disrupting chemicals (1)
- endocrine-disrupting chemicals (1)
- escritura fenicia (1)
- estradiol equivalents (1)
- exposome (1)
- exposure (1)
- fasting (1)
- fenicios (1)
- food contact materials (1)
- fortificación, (1)
- gadobutrol (1)
- glioma (1)
- health information exchange (1)
- heavy ion experiments (1)
- hematopoietic stem cells (1)
- hematopoietic stress (1)
- human exposure (1)
- in vitro effects (1)
- indígenas (1)
- isolation (1)
- ketogenic (1)
- ketone body (1)
- leptomeningeal disease (1)
- leukemia (1)
- lung squamous cell carcinoma (LUSC) (1)
- medulloblastoma (1)
- medulloblastoma resection (1)
- metabolic disruptors (1)
- microplastics (1)
- migration (1)
- mineral water (1)
- molecular tumor board (1)
- mowing (1)
- nanoparticle growth (1)
- naturalness (1)
- neoplasms (1)
- neurosurgery (1)
- neutralizing antibodies (1)
- non-target chemical analysis (1)
- nontarget (1)
- obesogens (1)
- palatal tremor (1)
- phenology (1)
- plant traits (1)
- plastic (1)
- pleomorphic xanthoastrocytoma (1)
- polymers (1)
- posterior fossa masses (1)
- ppK − (1)
- precision medicine (1)
- qualitative research (1)
- quality control (1)
- quark gluon plasma (1)
- rare diseases (1)
- renal impairment (1)
- requirements analysis (1)
- resilience (1)
- review (1)
- risk assessment (1)
- somatic mutations (1)
- spectra (1)
- spike protein (1)
- toxicity (1)
- variants of concern (1)
- volatile organic compounds (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (957)
- Frankfurt Institute for Advanced Studies (FIAS) (860)
- Informatik (825)
- Medizin (29)
- Geowissenschaften (22)
- Biowissenschaften (13)
- Institut für Ökologie, Evolution und Diversität (7)
- ELEMENTS (4)
- Geowissenschaften / Geographie (3)
- Informatik und Mathematik (3)
(1) Background: A lesion within the dentato-rubro-olivary pathway (DROP) in the posterior fossa can cause secondary neurodegeneration of the inferior olivary nucleus: so-called hypertrophic olivary degeneration (HOD). The clinical syndrome of HOD occurs slowly over months and may be overlooked in progressive neuro-oncological diseases. Posterior fossa tumors are often located near these strategic structures. The goal of this study was to analyze the systematics of HOD occurrence in neuro-oncological patients.
(2) Methods: The neuroradiological database of the university healthcare center was scanned for HOD-related terms from 2010 to 2019. After excluding patients with other causes of HOD, 12 datasets from neuro-oncological patients were analyzed under predetermined criteria.
(3) Results: Patients received multimodal tumor treatments including neurosurgery, radiotherapy, and chemotherapy. HOD occurred both unilaterally (left n = 4; right n = 5) and bilaterally (n = 3). Though the mass effect of posterior fossa tumors had already affected strategic structures of the DROP, none of the patients showed signs of HOD on MRI until therapeutic measures including neurosurgery affecting the DROP were applied. HOD was visible on MRI within a median of 6 months after the neurosurgical intervention. In 67%, the presumed underlying surgical lesion in the DROP lay in the contralateral dentate nucleus.
(4) Conclusion: In a selected cohort of neuro-oncological patients, therapeutic lesions within the DROP were associated with HOD occurrence.
Background: The Catechol-O-methyltransferase (COMT) represents the key enzyme in catecholamine degradation. Recent studies suggest that the COMT rs4680 polymorphism is associated with the response to endogenous and exogenous catecholamines. There are, however, conflicting data regarding the COMT Met/Met phenotype being associated with an increased risk of acute kidney injury (AKI) after cardiac surgery. The aim of the current study is to prospectively investigate the impact of the COMT rs4680 polymorphism on the incidence of AKI in patients undergoing cardiac surgery.
Methods: In this prospective single center cohort study consecutive patients hospitalized for elective cardiac surgery including cardiopulmonary-bypass (CPB) were screened for participation. Demographic clinical data, blood, urine and tissue samples were collected at predefined time points throughout the clinical stay. AKI was defined according to recent recommendations of the Kidney Disease Improving Global Outcome (KDIGO) group. Genetic analysis was performed after patient enrolment was completed.
Results: Between April and December 2014, 150 patients were recruited. The COMT genotypes were distributed as follows: Val/Met 48.7%, Met/Met 29.3%, Val/Val 21.3%. No significant differences were found for demography, comorbidities, or operative strategy according to the underlying COMT genotype. AKI occurred in 35 patients (23.5%) of the total cohort, and no differences were evident between the COMT genotypes (20.5% Met/Met, 24.7% Val/Met, 25.0% Val/Val, p = 0.66). There were also no differences in the post-operative period, including ICU or in-hospital stay.
Conclusions: We did not find statistically significant variations in the risk for postoperative AKI, length of ICU or in-hospital stay according to the underlying COMT genotype.
Semi-dry grasslands were once widely distributed communities, but today they represent some of the most vulnerable habitats in Central Europe. European and national legislation and non-governmental organizations have managed to protect some of the remaining fragments. However, despite their status as Natura 2000 habitats, they are often endangered due to improper management, fragmentation and edge effects from adjacent croplands. By using a sample of 44 semi-dry hay meadows in the south-eastern Alpine Foreland of Styria, we investigated how species-richness and trait composition of semi-dry grassland species respond to variation in patch size, connectivity, abiotic site factors and management regimes. We used linear regression models to identify the most important drivers for richness of typical semi-dry grassland species and thus conservation value. The number of typical semi-dry grassland species was highest in well-connected fragments, i.e. units that shared two or more borders with neighbouring species-rich grasslands. Furthermore, large semi-dry grasslands (> 8000 m²) had highest numbers of semi-dry grassland species and highest relevance for conservation; no difference was found among smaller fragment sizes. Unregular management was associated with increased presence of competitive species which replaced stress-tolerant specialists. Our study indicates that under eutrophication, small fragment size and isolation, only large semi-dry grasslands can sustain a high number of species with high conservation value. The conservation value of smaller semi-dry grassland fragments could be improved by buffer zones, adapted mowing treatments and periodical sheep grazing.
Feeding type and development drive the ingestion of microplastics by freshwater invertebrates
(2017)
Microscopic plastic items (microplastics) are ubiquitously present in aquatic ecosystems. With decreasing size their availability and potential to accumulate throughout food webs increase. However, little is known on the uptake of microplastics by freshwater invertebrates. To address this, we exposed species with different feeding strategies to 1, 10 and 90 µm fluorescent polystyrene spheres (3–3 000 particles mL−1). Additionally, we investigated how developmental stages and a co-exposure to natural particles (e.g., food) modulate microplastic ingestion. All species ingested microplastics in a concentration-dependent manner with Daphnia magna consuming up to 6 180 particles h−1, followed by Chironomus riparius (226 particles h−1), Physella acuta (118 particles h−1), Gammarus pulex (10 particles h−1) and Lumbriculus variegatus (8 particles h−1). D. magna did not ingest 90 µm microplastics whereas the other species preferred larger microplastics over 1 µm in size. In C. riparius and D. magna, size preference depended on the life stage with larger specimens ingesting more and larger microplastics. The presence of natural particles generally reduced the microplastics uptake. Our results demonstrate that freshwater invertebrates have the capacity to ingest microplastics. However, the quantity of uptake depends on their feeding type and morphology as well as on the availability of microplastics.
Background: While the use of plastic materials has generated huge societal benefits, the "plastic age" comes with downsides: One issue of emerging concern is the accumulation of plastics in the aquatic environment. Here, so-called microplastics (MP), fragments smaller than 5 mm, are of special concern because they can be ingested throughout the food web more readily than larger particles. Focusing on freshwater MP, we briefly review the state of the science to identify gaps of knowledge and deduce research needs.
State of the science: Environmental scientists started investigating marine (micro)plastics in the early 2000s. Today, a wealth of studies demonstrates that MP have ubiquitously permeated the marine ecosystem, including the polar regions and the deep sea. MP ingestion has been documented for an increasing number of marine species. However, to date, only few studies investigate their biological effects. The majority of marine plastics are considered to originate from land-based sources, including surface waters. Although they may be important transport pathways of MP, data from freshwater ecosystems is scarce. So far, only few studies provide evidence for the presence of MP in rivers and lakes. Data on MP uptake by freshwater invertebrates and fish is very limited.
Knowledge gaps: While the research on marine MP is more advanced, there are immense gaps of knowledge regarding freshwater MP. Data on their abundance is fragmentary for large and absent for small surface waters. Likewise, relevant sources and the environmental fate remain to be investigated. Data on the biological effects of MP in freshwater species is completely lacking. The accumulation of other freshwater contaminants on MP is of special interest because ingestion might increase the chemical exposure. Again, data is unavailable on this important issue.
Conclusions: MP represent freshwater contaminants of emerging concern. However, to assess the environmental risk associated with MP, comprehensive data on their abundance, fate, sources, and biological effects in freshwater ecosystems are needed. Establishing such data critically depends on a collaborative effort by environmental scientists from diverse disciplines (chemistry, hydrology, ecotoxicology, etc.) and, unsurprisingly, on the allocation of sufficient public funding.
The interaction of microplastics with freshwater biota and their interaction with other stressors is still not very well understood. Therefore, we investigated the ingestion, excretion and toxicity of microplastics in the freshwater gastropod Lymnaea stagnalis.
MP ingestion was analyzed as tissues levels in L. stagnalis after 6–96 h of exposure to 5–90 μm spherical polystyrene (PS) microplastics. To understand the excretion, tissue levels were determined after 24 h of exposure followed by a 12 h–7 d depuration period. To assess the toxicity, snails were exposed for 28 d to irregular PS microplastics (<63 μm, 6.4–100,000 particles mL−1), both alone and in combination with copper as additional stressor. To compare the toxicity of natural and synthetic particles, we also included diatomite particles. Microplastics ingestion and excretion significantly depended on the particle size and the exposure/depuration duration. An exposure to irregular PS had no effect on survival, reproduction, energy reserves and oxidative stress. However, we observed slight effects on immune cell phagocytosis. Exposure to microplastics did not exacerbate the reproductive toxicity of copper. In addition, there was no pronounced difference between the effects of microplastics and diatomite. The tolerance towards microplastics may originate from an adaptation of L. stagnalis to particle-rich environments or a general stress resilience. In conclusion, despite high uptake rates, PS fragments do not appear to be a relevant stressor for stress tolerant freshwater gastropods considering current environmental levels of microplastics.
Posterior fossa tumor surgery is challenging due to the proximity and exposure of cerebellar structures. A favorable operative approach is unknown. Following lesions to the dentato–rubro–olivary-pathway, a neurodegenerative disease called hypertrophic olivary degeneration (HOD) can occur. This study for the first time demonstrates that paravermal trans-cerebellar approaches are associated with a significantly higher likelihood of HOD on MRI when compared to other approaches. This finding can well be attributed to dentate nucleus (DN) injury. Furthermore, cerebellar mutism syndrome (CMS) was discussed in the literature to be correlated with HOD due to a functional overlap of pathways involved. We found no such correlation in this study, but HOD was shown to be a reliable indicator for surgical disruption of efferent cerebellar pathways involving the DN. Henceforth, neurosurgeons should consider more midline or lateral approaches in posterior fossa surgery to spare the DN whenever feasible, and focus on cerebellar functional anatomy in their preoperative planning.
The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.
he ubiquity of microplastics in aquatic ecosystems has raised concerns over their interaction with biota. However,microplastics research on freshwater species, especially mollusks, is still scarce. We, therefore, investigated the factorsaffecting microplastics ingestion in the freshwater musselDreissena polymorpha. Using polystyrene spheres (5, 10, 45,90μm), we determined the body burden of microplastics in the mussels in relation to 1) exposure and depuration time, 2)body size, 3) food abundance, and 4) microplastic concentrations.D. polymorpharapidly ingested microplastics and ex-creted most particles within 12 h. A few microplastics were retained for up to 1 wk. Smaller individuals had a higher relativebody burden of microplastics than larger individuals. The uptake of microplastics was concentration‐dependent, whereas anadditional food supply (algae) reduced it. We also compared the ingestion of microplastics byD. polymorphawith 2 otherfreshwater species (Anodonta anatina,Sinanodonta woodiana), highlighting that absolute and relative uptake depends onthe species and the size of the mussels. In addition, we determined toxicity of polystyrene fragments (≤63μm,6.4–100 000 p mL–1) and diatomite (natural particle, 100 000 p mL–1)inD. polymorphaafter 1, 3, 7, and 42 d of exposure,investigating clearance rate, energy reserves, and oxidative stress. Despite ingesting large quantities, exposure to poly-styrene fragments only affected the clearance rate ofD. polymorpha. Further, results of the microplastic and diatomiteexposure did not differ significantly. Therefore,D. polymorphais unaffected by or can compensate for polystyrene fragmenttoxicity even at concentrations above current environmental levels.Environ Toxicol Chem2021;40:2247–2260. © 2021 TheAuthors.Environmental Toxicology and Chemistrypublished by Wiley Periodicals LLC on behalf of SETAC.Keywords:Microplastics; Toxic effects; Mollusk toxicity
Plastic products leach chemicals that induce in vitro toxicity under realistic use conditions
(2021)
Plastic products contain complex mixtures of extractable chemicals that can be toxic. However, humans and wildlife will only be exposed to plastic chemicals that are released under realistic conditions. Thus, we investigated the toxicological and chemical profiles leaching into water from 24 everyday plastic products covering eight polymer types. We performed migration experiments over 10 days at 40 °C and analyzed the migrates using four in vitro bioassays and nontarget high-resolution mass spectrometry (UPLC-QTOF-MSE). All migrates induced baseline toxicity, 22 an oxidative stress response, 13 antiandrogenicity, and one estrogenicity. Overall, between 17 and 8681 relevant chemical features were present in the migrates. In other words, between 1 and 88% of the plastic chemicals associated with one product were migrating. Further, we tentatively identified ∼8% of all detected features implying that most plastic chemicals remain unknown. While low-density polyethylene, polyvinyl chloride, and polyurethane induced most toxicological endpoints, a generalization for other materials is not possible. Our results demonstrate that plastic products readily leach many more chemicals than previously known, some of which are toxic in vitro. This highlights that humans are exposed to many more plastic chemicals than currently considered in public health science and policies.
Background: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods: The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky [greater than or equal to]60% / Child-Pugh [less than or equal to]12) were randomised to receive thymostimulin 75 mg s.c. 5x/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol. Current Controlled Trials ISRCTN64487365. Results: Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p=0.87, HR=1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p=0.60, HR=1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions: In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. trial registration: Current Controlled Trials ISRCTN64487365
Requirements analysis and specification for a molecular tumor board platform based on cBioPortal
(2020)
Clinicians in molecular tumor boards (MTB) are confronted with a growing amount of genetic high-throughput sequencing data. Today, at German university hospitals, these data are usually handled in complex spreadsheets from which clinicians have to obtain the necessary information. The aim of this work was to gather a comprehensive list of requirements to be met by cBioPortal to support processes in MTBs according to clinical needs. Therefore, oncology experts at nine German university hospitals were surveyed in two rounds of interviews. To generate an interview guideline a scoping review was conducted. For visual support in the second round, screenshot mockups illustrating the requirements from the first round were created. Requirements that cBioPortal already meets were skipped during the second round. In the end, 24 requirements with sometimes several conceivable options were identified and 54 screenshot mockups were created. Some of the identified requirements have already been suggested to the community by other users or are currently being implemented in cBioPortal. This shows, that the results are in line with the needs expressed by various disciplines. According to our findings, cBioPortal has the potential to significantly improve the processes and analyses of an MTB after the implementation of the identified requirements.
Microplastics (MP) are contaminants of emerging concern in aquatic ecosystems. While the number of studies is rapidly increasing, a comparison of the toxicity of MP and natural particulate matter is largely missing. In addition, research focusses on the impacts of hydrophobic chemicals sorbed to plastics. However, the interactive effects of MP and hydrophilic, dissolved chemicals remain largely unknown. Therefore, we conducted chronic toxicity studies with larvae of the freshwater dipteran Chironomus riparius exposed to unplasticised polyvinyl chloride MP (PVC-MP) as well as kaolin and diatomite as reference materials for 28 days. In addition, we investigated the effects of particles in combination with the neonicotinoid imidacloprid in a multiple-stressor experiment. High concentrations of kaolin positively affected the chironomids. In contrast, exposure to diatomite and PVC-MP reduced the emergence and mass of C. riparius. Likewise, the toxicity of imidacloprid was enhanced in the presence of PVC-MP and slightly decreased in the co-exposure with kaolin. Overall, parallel experiments and chemical analysis indicate that the toxicity of PVC-MP was not caused by leached or sorbed chemicals. Our study demonstrates that PVC-MP induce more severe effects than both natural particulate materials. However, the latter are not benign per se, as the case of diatomite highlights. Considering the high, environmentally irrelevant concentrations needed to induce adverse effects, C. riparius is insensitive to exposures to PVC-MP.
Objective: The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF).
Materials and Methods: We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period.
Results: A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. The mean time since renal disease diagnosis was 1.83 and 5.49 years in the moderate and severe renal impairment cohort, respectively. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF.
Conclusions: No safety concerns with gadobutrol in patients with moderate to severe renal impairment were identified. There were no NSF cases.
Clonal hematopoiesis of indeterminate potential (CHIP) is caused by recurrent somatic mutations leading to clonal blood cell expansion. However, direct evidence of the fitness of CHIP-mutated human hematopoietic stem cells (HSCs) in blood reconstitution is lacking. Because myeloablative treatment and transplantation enforce stress on HSCs, we followed 81 patients with solid tumors or lymphoid diseases undergoing autologous stem cell transplantation (ASCT) for the development of CHIP. We found a high incidence of CHIP (22%) after ASCT with a high mean variant allele frequency (VAF) of 10.7%. Most mutations were already present in the graft, albeit at lower VAFs, demonstrating a selective reconstitution advantage of mutated HSCs after ASCT. However, patients with CHIP mutations in DNA-damage response genes showed delayed neutrophil reconstitution. Thus, CHIP-mutated stem and progenitor cells largely gain on clone size upon ASCT-related blood reconstitution, leading to an increased future risk of CHIP-associated complications.
Chopper systems are used to pulse charged particle beams. In most cases, electric deflection systems are used to generate beam pulses of defined lengths and appropriate repetition rates. At high beam intensities, the field distribution of the chopper system needs to be adapted precisely to the beam dynamics in order to avoid aberrations. An additional challenge is a robust design which guarantees reliable operation. For the Frankfurt Neutron Source FRANZ, an E×B chopper system is being developed which combines static magnetic deflection with a pulsed electric field in a Wien filter configuration. It will generate proton pulses with a flat top of 50 ns at a repetition rate of 250 kHz for 120 keV, 200 mA beams. For the electric deflection, pre-experiments with static and pulsed fields were performed using a helium ion beam. In pulsed mode operation, ion beams of different energies were deflected with voltages of up to ±6 kV and the resulting response was measured using a beam current transformer. A comparison between experiments and theoretical calculations as well as numerical simulations are presented.
An optimized design of a stellarator-type storage ring for low energy ion beams was numerically investigated. The magnetic field variation along the circumference and therefore magnetic heating is suppressed by using simple circular correction coils. Particle-in-Cell (PIC) simulations in a magnetic flux coordinate system show the ability of high current ion beam accumulation in such a configuration with unique features for clockwise and anticlockwise moving beams. Additionally scaled down experiments with two 30 degree room temperature toroidal segments were performed to demonstrate toroidal transport and to develop optical beam diagnostics. Properties of multi-component beams, redistribution of transversal momenta in the non-adiabatic part of the experimental configuration and investigation of strongly confined beam induced electron clouds will be addressed.
The toxicity of microplastics on Daphnia magna as key model for freshwater zooplankton is well described. While several studies predict population-level effects based on short-term, individual-level responses, only very few have validated these predictions experimentally. Thus, we exposed D. magna populations to irregular polystyrene microplastics and diatomite as natural particle (both ≤63 µm) over 50 days. We used mixtures of both particle types at fixed particle concentrations (50,000 mL-1) and recorded the overall population density, the size of the individual animals, and resting egg production. Particle exposure adversely affected the population density and structure and induced resting egg production. The terminal population size was 31–42% lower in exposed compared to control populations. Interestingly, mixtures containing diatomite induced stronger effects than microplastics alone highlighting that natural particles are not per se less toxic than microplastics. Our results demonstrate that an exposure to synthetic and natural particles has negative population-level effects on zooplankton. Understanding the mixture toxicity of microplastics and natural particles is important given that aquatic organisms will experience exposure to both. Just as for chemical pollutants, better knowledge of such joint effects is essential to fully understand the environmental risks of complex particle mixtures.
Environmental Implications While microplastics are commonly considered hazardous based on individual-level effects, there is a dearth of information on how they affect populations. Since the latter is key for understanding the environmental impacts of microplastics, we investigated how particle exposures affect the population size and structure of Daphnia magna. In addition, we used mixtures of microplastics and natural particles because neither occurs alone in nature and joint effects can expected in an environmentally realistic scenario. We show that such mixtures adversely affect daphnid populations and highlight that population-level and mixture-toxicity designs are one important step towards more environmental realism in microplastics research.
The toxicity of microplastics on Daphnia magna as a key model for freshwater zooplankton is well described. While several studies predict population-level effects based on short-term, individual-level responses, only very few have validated these predictions experimentally. Thus, we exposed D. magna populations to irregular polystyrene microplastics and diatomite as natural particle (both ≤ 63 μm) over 50 days. We used mixtures of both particle types at fixed particle concentrations (50,000 mL-1) and recorded the effects on overall population size and structure, the size of the individual animals, and resting egg production. Particle exposure adversely affected the population density and structure, and induced resting egg production. The terminal population size was 28–42% lower in exposed compared to control populations. Interestingly, mixtures containing diatomite induced stronger effects than microplastics alone, highlighting that natural particles are not per se less toxic than microplastics. Our results demonstrate that an exposure to synthetic and natural particles has negative population-level effects on zooplankton. Understanding the mixture toxicity of microplastics and natural particles is important given that aquatic organisms will experience exposure to both. Just as for chemical pollutants, better knowledge of such joint effects is essential to fully understand the environmental impacts of complex particle mixtures.
Environmental Implications While microplastics are commonly considered hazardous based on individual-level effects, there is a dearth of information on how they affect populations. Since the latter is key for understanding the environmental impacts of microplastics, we investigated how particle exposures affect the population size and structure of Daphnia magna. In addition, we used mixtures of microplastics and natural particles because neither occurs alone in nature and joint effects can be expected in an environmentally realistic scenario. We show that such mixtures adversely affect daphnid populations and highlight that population-level and mixture-toxicity designs are one important step towards more environmental realism in microplastics research.