Refine
Year of publication
Document Type
- Preprint (615)
- Article (435)
- Conference Proceeding (1)
- Report (1)
- Working Paper (1)
Has Fulltext
- yes (1053)
Is part of the Bibliography
- no (1053)
Keywords
- Heavy Ion Experiments (20)
- Hadron-Hadron scattering (experiments) (11)
- Hadron-Hadron Scattering (8)
- Heavy-ion collision (5)
- Collective Flow (4)
- Quark-Gluon Plasma (4)
- Jets (3)
- Jets and Jet Substructure (3)
- (surface) partial differential equations (2)
- 3D spatio-temporal resolved mathematical models (2)
- Atmospheric chemistry (2)
- COVID-19 (2)
- Epilepsy (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- Finite Volumes (2)
- Germany (2)
- Heavy Quark Production (2)
- Immunotherapy (2)
- LHC (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Non-small cell lung cancer (2)
- Oncology (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Quarkonium (2)
- acute myeloid leukemia (2)
- computational virology (2)
- immunotherapy (2)
- massively parallel multigrid solvers (2)
- realistic geometries (2)
- viral dynamics (2)
- within-host viral modelling (2)
- 140Ce (1)
- 900 GeV (1)
- ACURATE neo (1)
- AIS (1)
- ALICE (1)
- ALICE detector (1)
- APRI (1)
- ASCT (1)
- Accelerators & Beams (1)
- Acute myeloid leukemia (1)
- Adherens junctions (1)
- Aneurysmal subarachnoid hemorrhage (1)
- Anti-nuclei (1)
- Antibody therapy (1)
- Artificial Intelligence (1)
- Atomic and Molecular Physics (1)
- Atomic, Molecular & Optical (1)
- BCOR (1)
- BCORL1 (1)
- BI1361849 (1)
- Bamlanivimab (1)
- Biodiversity Data (1)
- Biogeochemistry (1)
- Biomarkers (1)
- Biomonitoring (1)
- Bladder cancer (1)
- Blood-brain barrier (1)
- Bloodstream infection (1)
- Bloodstream infections (1)
- Boosted Jets (1)
- Botanical Collections (1)
- Brain tumor (1)
- Burkholderia arboris (1)
- CD36 (1)
- CHIP (1)
- CHRNA10 (1)
- CHRNA7 (1)
- CHRNA9 (1)
- CTLA-4 (1)
- CV9202 (1)
- CVID (1)
- Cancer (1)
- Cancer genomics (1)
- Casirivimab (1)
- Centrality Class (1)
- Centrality Selection (1)
- Charged-particle multiplicity (1)
- Checkpoint inhibitor (1)
- Clinical Trials and Observations (1)
- Clinical trial (1)
- Cluster (1)
- Cohort studies (1)
- Collective Flow, (1)
- Conservation (1)
- Correlative electron and light microscopy (1)
- DBS (1)
- DSS /AOM (1)
- Diagnostic markers (1)
- Digitization (1)
- Electromagnetic transitions (1)
- Electron tomography (1)
- Electron-pion identification (1)
- Electroweak interaction (1)
- Entomology (1)
- Epidemiology (1)
- European Society for Immunodeficiencies (ESID) (1)
- Everolimus resistance (1)
- Evidence-based guidelines (1)
- Extended Glasgow outcome scale (eGOS) (1)
- Extended donor criteria (1)
- FDG-PET/CT (1)
- FIB-4 (1)
- Fibre/foam sandwich radiator (1)
- Freshwater ecology (1)
- GdIr2Si2 (1)
- German PID-NET registry (1)
- Glioma (1)
- Graft function (1)
- Graft survival (1)
- Gram negative bacteria (1)
- HBV (1)
- HDAC-inhibition (1)
- HNSCC (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hard Scattering (1)
- Head neck cancer (1)
- Heavy Ion Experiment (1)
- Hematology (1)
- Hematopoietic stem cell transplantation (1)
- Herbaria (1)
- Hypofractionated radiotherapy (1)
- ICU (1)
- IL -17 (1)
- IL -23 (1)
- IL 23p19 knockout mouse (1)
- ISS (1)
- IgG substitution therapy (1)
- Imdevimab (1)
- Immunomonitoring (1)
- Incidence (1)
- Induction therapy (1)
- Intensive care units (1)
- Invariant Mass Distribution (1)
- Invasive species (1)
- Ionisation energy loss (1)
- Isoflurane (1)
- Jet Physics (1)
- Jet Substructure (1)
- Lesion (1)
- Liver transplantation (1)
- Locally advanced (1)
- Long term output (1)
- Lymphocytes (1)
- Lymphoid tissues (1)
- MACS (1)
- MRI (1)
- Magnetic resonance imaging (MRI) (1)
- Marginal grafts (1)
- Material budget (1)
- Mechanisms of disease (1)
- Minimum Bias (1)
- Models & methods for nuclear reactions (1)
- Molecular diagnostic testing (1)
- Molecular matched therapy (1)
- Molecular medicine (1)
- Molecular profiling (1)
- Monte Carlo (1)
- Mott transition (1)
- Multi-Parton Interactions (1)
- Multi-wire proportional drift chamber (1)
- Multiple parton interactions (1)
- Multivariate analysis (1)
- Myeloid Neoplasia (1)
- NMR spectroscopy (1)
- NSCLC (1)
- Neural network (1)
- Neutron physics (1)
- Neutropenia (1)
- Nivolumab (1)
- Nuclear reactions (1)
- Organ rinse (1)
- Organ shortage (1)
- Osteoporosis (1)
- P2X7 receptor (1)
- PD-1 (1)
- PD-1 inhibitor (1)
- PDEs (1)
- PID prevalence (1)
- PYTHIA (1)
- Particle and Resonance Production (1)
- Pb–Pb collisions (1)
- Phylogenomics (1)
- Pneumonia (1)
- Poecilia mexicana (1)
- Polarization (1)
- Population genetics (1)
- Production Cross Section (1)
- Properties of Hadrons (1)
- Psoriasis vulgaris (1)
- QCD (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- RNA (1)
- RNA decay (1)
- Radiation detectors (1)
- Radiative capture (1)
- Radical cystectomy (1)
- Radiotherapy (1)
- Rapidity Range (1)
- Registries (1)
- Relativistic heavy-ion collisions (1)
- Renal cell carcinoma (1)
- Research Infrastructure (1)
- Resolution Parameter (1)
- Resonance reactions (1)
- SMAD (1)
- Semantics (1)
- Sexual selection (1)
- Status epilepticus (1)
- Stenotrophomonas maltophilia (1)
- Stentoplasty (1)
- Systematic Uncertainty (1)
- T cell/histiocyte rich large B cell lymphoma (1)
- TAVR (1)
- TGFβ (1)
- TR (1)
- Tacrolimus (1)
- Targeted therapy (1)
- Taxonomy (1)
- Thermodynamics (1)
- Thoracic trauma (1)
- Thrombotic microangiopathy (1)
- Thrombotic thrombocytopenic purpura (1)
- Time Projection Chamber (1)
- TmRh2Si2 (1)
- Tracking (1)
- Transition radiation detector (1)
- Transitional cell carcinoma (1)
- Transverse momentum (1)
- Treatment (1)
- Trigger (1)
- Tumor growth (1)
- Urothelial cancer (1)
- VIM (1)
- Vector Boson Production (1)
- Vertebral augmentation (1)
- Vertebral body stenting (1)
- Vertebral fracture (1)
- Viral load (1)
- X-ray crystallography (1)
- X-ray irradiation (1)
- Xenon-based gas mixture (1)
- acoustic radiation force impulse imaging (1)
- adaptation (1)
- advanced melanoma (1)
- adversity (1)
- age (1)
- allostasis (1)
- anti-epileptic drug (1)
- aortic stenosis (1)
- autologous stem cell transplantation (1)
- biomarker (1)
- blood cell mutations (1)
- brain metastases (1)
- brain metastasis (1)
- brain shift (1)
- burkholderia (1)
- burkholderia cepacia complex infections (1)
- calcium dynamics (1)
- calcium-independent phospholipase A2β (1)
- capture (1)
- cdk2/cyclin A (1)
- cerebral pseudoprogression (1)
- cerium (1)
- chemoconvulsant (1)
- chemotherapy (1)
- chronic colitis (1)
- clonal dominance (1)
- clonal haematopoiesis (1)
- clonal hematopoiesis (1)
- clonal transfer (1)
- colon cancer (1)
- community assembly (1)
- complete response (1)
- complex systems (1)
- coping (1)
- correlated electrons (1)
- cross-section (1)
- cytarabine dose (1)
- dE/dx (1)
- detailed modeling (1)
- detector (1)
- diffuse large B cell lymphoma (1)
- discontinuation (1)
- discontinuous dose dependency (1)
- disease outbreaks (1)
- disease progression (1)
- disorder (1)
- distributed computation (1)
- dynamic system (1)
- ectosomes (1)
- elderly (1)
- electrical stimulation (1)
- electrophoresis (1)
- epileptogenesis (1)
- essential tremor (1)
- everolimus (1)
- exosomes (1)
- experimental results (1)
- extracellular vesicles (1)
- familial amyloid nephropathy with urticaria and deafness (1)
- female choice (1)
- fibrotest (1)
- flux growth (1)
- gel (1)
- gene expression profiling (1)
- gene signature (1)
- generalized additive model (1)
- genome (1)
- glioblastoma (1)
- guidelines (1)
- head and neck squamous cell carcinoma (1)
- healthcare systems (1)
- heart failure (1)
- heavy ion experiments (1)
- hematopoietic stem cells (1)
- hematopoietic stress (1)
- hepatitis C virus (1)
- hepatitis C virus (HCV) (1)
- hippocampal sclerosis (1)
- homeostasis (1)
- host response (1)
- hybrid (1)
- hypoxia (1)
- immune checkpoint blockade (1)
- immune checkpoint inhibitors (1)
- immune checkpoint inhibitors (ICI) (1)
- immune modulation (1)
- immune related adverse events (irAE) (1)
- infections (1)
- inflammasome (1)
- inflammation (1)
- information storage (1)
- inpatient hospital admissions (1)
- interleukin-1β (1)
- leukemia (1)
- liver metastasis (1)
- local information dynamics (1)
- lockdown (1)
- loss-of-function (1)
- low-dose radiation therapy (1)
- lung cancer (1)
- mRNA active cancer immunotherapy (1)
- magnetism (1)
- mathematical models of viral RNA cycle (1)
- medical device (1)
- medical informatics initiative (1)
- mental health (1)
- metastatic renal cell carcinoma (1)
- microbial colonization (1)
- microparticles (1)
- microvesicles (1)
- minimal information requirements (1)
- mouthwash (1)
- mouthwash solution (1)
- n_TOF (1)
- neoadjuvant immunochemotherapy (1)
- neural dynamics (1)
- neurological complication (1)
- neurological side effects (1)
- neuron (1)
- neutron (1)
- nodular lymphocyte predominant Hodgkin lymphoma (1)
- non-independent mate choice (1)
- non-invasive fibrosis assessment (1)
- noncoding RNA (1)
- ntracellular signaling (1)
- nucleosynthesis (1)
- organic conductor (1)
- outbreak (1)
- p+p collisions (1)
- p47phox (1)
- pandemic (1)
- parallel (1)
- parameter estimation (1)
- patterns of progression (1)
- pembrolizumab (1)
- perioperative ischemia (1)
- phase IV (1)
- point shear wave elastography (1)
- postoperative radiochemotherapy (1)
- postoperative radiotherapy (1)
- predator recognition (1)
- predictive coding (1)
- pressure (1)
- primary immunodeficiency (PID) (1)
- propensity score matching (1)
- pulsed-field (1)
- quark gluon plasma (1)
- registry for primary immunodeficiency (1)
- reproducibility (1)
- rigor (1)
- risk stratification (1)
- s-process (1)
- second-line (1)
- second-line immunotherapy (1)
- soil bacteria communities (1)
- somatic mutations (1)
- spatio-temporal analysis (1)
- standardization (1)
- status epilepticus (1)
- stereotactic radiosurgery (1)
- stress (1)
- survival (1)
- targeted therapy (1)
- temporal lobe epilepsy (1)
- transcatheter aortic valve replacement (1)
- transfemoral (1)
- transient elastography (1)
- treatment resistance (1)
- tumor microenvironment (1)
- university hospitals (1)
- uveal melanoma (1)
- variable selection (1)
- ventralis intermedius nucleus (1)
- visual system (1)
- voltage sensitive dye imaging (1)
Institute
- Physik (959)
- Frankfurt Institute for Advanced Studies (FIAS) (857)
- Informatik (826)
- Medizin (66)
- Geowissenschaften (9)
- Biowissenschaften (5)
- ELEMENTS (3)
- Informatik und Mathematik (3)
- Institut für Ökologie, Evolution und Diversität (3)
- Biochemie und Chemie (2)
Effects of BPA in snails
(2006)
It is an ethical requirement that new findings be presented in light of and in conjunction with a balanced evaluation of the current knowledge and published literature. We believe that Oehlmann et al. (2006) violated this general principle in several ways. For example, the authors inferred that prosobranch snails have a functional estrogen receptor and therefore a much higher sensitivity to estrogens and endocrine-disrupting compounds (EDCs) than other species previously reported in the literature. We found several other problems in their article...
Background: Epileptic seizures are common clinical features in patients with acute subdural hematoma (aSDH); however, diagnostic feasibility and therapeutic monitoring remain limited. Surface electroencephalography (EEG) is the major diagnostic tool for the detection of seizures but it might be not sensitive enough to detect all subclinical or nonconvulsive seizures or status epilepticus. Therefore, we have planned a clinical trial to evaluate a novel treatment modality by perioperatively implanting subdural EEG electrodes to diagnose seizures; we will then treat the seizures under therapeutic monitoring and analyze the clinical benefit.
Methods: In a prospective nonrandomized trial, we aim to include 110 patients with aSDH. Only patients undergoing surgical removal of aSDH will be included; one arm will be treated according to the guidelines of the Brain Trauma Foundation, while the other arm will additionally receive a subdural grid electrode. The study's primary outcome is the comparison of incidence of seizures and time-to-seizure between the interventional and control arms. Invasive therapeutic monitoring will guide treatment with antiseizure drugs (ASDs). The secondary outcome will be the functional outcome for both groups as assessed via the Glasgow Outcome Scale and modified Rankin Scale both at discharge and during 6 months of follow-up. The tertiary outcome will be the evaluation of chronic epilepsy within 2-4 years of follow-up.
Discussion: The implantation of a subdural EEG grid electrode in patients with aSDH is expected to be effective in diagnosing seizures in a timely manner, facilitating treatment with ASDs and monitoring of treatment success. Moreover, the occurrence of epileptiform discharges prior to the manifestation of seizure patterns could be evaluated in order to identify high-risk patients who might benefit from prophylactic treatment with ASDs.
Trial registration: ClinicalTrials.gov identifier no. NCT04211233.
The radiative electron capture (REC) into the K shell of bare Xe ions colliding with a hydrogen gas target has been investigated. In this study, the degree of linear polarization of the K-REC radiation was measured and compared with rigorous relativistic calculations as well as with the previous results recorded for U92+. Owing to the improved detector technology, a significant gain in precision of the present polarization measurement is achieved compared to the previously published results. The obtained data confirms that for medium-Z ions such as Xe, the REC process is a source of highly polarized x rays which can easily be tuned with respect to the degree of linear polarization and the photon energy. We argue, in particular, that for relatively low energies the photons emitted under large angles are almost fully linear polarized.
Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E–P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure (“stressor reactivity,” SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.
A central motivation for the development of x-ray free-electron lasers has been the prospect of time-resolved single-molecule imaging with atomic resolution. Here, we show that x-ray photoelectron diffraction—where a photoelectron emitted after x-ray absorption illuminates the molecular structure from within—can be used to image the increase of the internuclear distance during the x-ray-induced fragmentation of an O2 molecule. By measuring the molecular-frame photoelectron emission patterns for a two-photon sequential K-shell ionization in coincidence with the fragment ions, and by sorting the data as a function of the measured kinetic energy release, we can resolve the elongation of the molecular bond by approximately 1.2 a.u. within the duration of the x-ray pulse. The experiment paves the road toward time-resolved pump-probe photoelectron diffraction imaging at high-repetition-rate x-ray free-electron lasers.
Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA).
Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1–3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1–7) plus daunorubicin (45 mg/m2 days 3–5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone.
Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33–45] versus 55% (95% CI: 49–61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513).
Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.
Background: The inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system.
Methods: We screened our hospital information system to identify patients with any in-house ICI treatment for any tumor disease during the years 2007-2019. All patients with cerebral MR imaging (cMRI) of sufficient diagnostic quality were included. cMRIs were retrospectively analyzed according to immunotherapy response assessment for neuro-oncology (iRANO) criteria.
Results: We identified 12 cases of cerebral pseudoprogression in 123 patients treated with ICIs and sufficient MRI. These patients were receiving ICI therapy for lung cancer (n=5), malignant melanoma (n=4), glioblastoma (n=1), hepatocellular carcinoma (n=1) or lymphoma (n=1) when cerebral pseudoprogression was detected. Median time from the start of ICI treatment to pseudoprogression was 5 months. All but one patient developed neurological symptoms. Three different patterns of cerebral pseudoprogression could be distinguished: new or increasing contrast-enhancing lesions, new or increasing T2 predominant lesions and cerebral vasculitis type pattern.
Conclusion: Cerebral pseudoprogression followed three distinct patterns and was detectable in 3.2% of all patients during ICI treatment and in 9.75% of the patients with sufficient brain imaging follow up. The fact that all but one of the affected patients developed neurological symptoms, which would be classified as progressive disease according to iRANO criteria, mandates vigilance in the diagnosis and treatment of ICI-induced cerebral lesions.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Plants, fungi and algae are important components of global biodiversity and are fundamental to all ecosystems. They are the basis for human well-being, providing food, materials and medicines. Specimens of all three groups of organisms are accommodated in herbaria, where they are commonly referred to as botanical specimens.The large number of specimens in herbaria provides an ample, permanent and continuously improving knowledge base on these organisms and an indispensable source for the analysis of the distribution of species in space and time critical for current and future research relating to global biodiversity. In order to make full use of this resource, a research infrastructure has to be built that grants comprehensive and free access to the information in herbaria and botanical collections in general. This can be achieved through digitization of the botanical objects and associated data.The botanical research community can count on a long-standing tradition of collaboration among institutions and individuals. It agreed on data standards and standard services even before the advent of computerization and information networking, an example being the Index Herbariorum as a global registry of herbaria helping towards the unique identification of specimens cited in the literature.In the spirit of this collaborative history, 51 representatives from 30 institutions advocate to start the digitization of botanical collections with the overall wall-to-wall digitization of the flat objects stored in German herbaria. Germany has 70 herbaria holding almost 23 million specimens according to a national survey carried out in 2019. 87% of these specimens are not yet digitized. Experiences from other countries like France, the Netherlands, Finland, the US and Australia show that herbaria can be comprehensively and cost-efficiently digitized in a relatively short time due to established workflows and protocols for the high-throughput digitization of flat objects.Most of the herbaria are part of a university (34), fewer belong to municipal museums (10) or state museums (8), six herbaria belong to institutions also supported by federal funds such as Leibniz institutes, and four belong to non-governmental organizations. A common data infrastructure must therefore integrate different kinds of institutions.Making full use of the data gained by digitization requires the set-up of a digital infrastructure for storage, archiving, content indexing and networking as well as standardized access for the scientific use of digital objects. A standards-based portfolio of technical components has already been developed and successfully tested by the Biodiversity Informatics Community over the last two decades, comprising among others access protocols, collection databases, portals, tools for semantic enrichment and annotation, international networking, storage and archiving in accordance with international standards. This was achieved through the funding by national and international programs and initiatives, which also paved the road for the German contribution to the Global Biodiversity Information Facility (GBIF).Herbaria constitute a large part of the German botanical collections that also comprise living collections in botanical gardens and seed banks, DNA- and tissue samples, specimens preserved in fluids or on microscope slides and more. Once the herbaria are digitized, these resources can be integrated, adding to the value of the overall research infrastructure. The community has agreed on tasks that are shared between the herbaria, as the German GBIF model already successfully demonstrates.We have compiled nine scientific use cases of immediate societal relevance for an integrated infrastructure of botanical collections. They address accelerated biodiversity discovery and research, biomonitoring and conservation planning, biodiversity modelling, the generation of trait information, automated image recognition by artificial intelligence, automated pathogen detection, contextualization by interlinking objects, enabling provenance research, as well as education, outreach and citizen science.We propose to start this initiative now in order to valorize German botanical collections as a vital part of a worldwide biodiversity data pool.
Background: In September 2018, Burkholderia cepacia complex (BCC) infections in 3 patients associated with exposure to a mouthwash solution (MWS) were reported to the Robert Koch Institute (RKI). As the product was still on the market and the scale of the outbreak was unclear, a nation-wide investigation was initiated.
Methods: We aimed to investigate BCC infections/colonizations associated with MWS. Hospitals, laboratories, and public health services were informed that BCC isolates should be sent to the RKI. These isolates were typed by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) including development of an ad hoc core genome MLST (cgMLST) scheme.
Results: In total, 36 patients from 6 hospitals met the case definition, the last patient in November 2018. Twenty-nine isolates from 26 of these patients were available for typing. WGS analysis revealed 2 distinct cgMLST clusters. Cluster 1 (Burkholderia arboris) contained isolates from patients and MWS obtained from 4 hospitals and isolates provided by the manufacturer. Patient and MWS isolates from another hospital were assigned to cluster 2 (B. cepacia).
Conclusions: The combined clinical, epidemiological, and microbiological investigation, including whole-genome analysis, allowed for uncovering a supraregional BCC outbreak in health care settings. Strains of B. arboris and B. cepacia were identified as contaminating species of MWS bottles and subsequent colonization and putative infection of patients in several hospitals. Despite a recall of the product by the manufacturer in August 2018, the outbreak lasted until December 2018. Reporting of contaminated medical products and recalls should be optimized to protect patients.
Background: Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer.
Methods: Study design: “RACE IT” (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb.
Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11–15.
Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15.
Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up).
Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy.
Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy.
Planned sample size: 33 patients, interim analysis after 11 patients.
Background: Accurate assessment of hepatic fibrosis in patients with chronic HBeAg-negative Hepatitis B is of crucial importance not only to predict the long-term clinical course, but also to evaluate antiviral therapy indication. The aim of this study was to prospectively assess the utility of point shear wave elastography (pSWE) for longitudinal non-invasive fibrosis assessment in a large cohort of untreated patients with chronic HBeAg-negative hepatitis B virus (HBV) infection.
Methods: 407 consecutive patients with HBeAg-negative HBV infection who underwent pSWE, transient elastography (TE) as well as laboratory fibrosis markers, including fibrosis index based on four factors (FIB-4), aspartate to platelet ratio index (APRI) and FibroTest, on the same day were prospectively followed up for six years. Patients were classified into one of the three groups: inactive carriers (IC; HBV-DNA <2000 IU/mL and ALT <40 U/L); grey zone group 1 (GZ-1; HBV DNA <2000 IU/mL and ALT >40 U/L); grey zone group 2 (GZ-2; HBV-DNA >2000 IU/mL and ALT <40 U/L).
Results: pSWE results were significantly correlated with TE (r = 0.29, p < 0.001) and APRI (r = 0.17; p = 0.005). Median pSWE values did not differ between IC, GZ-1 and GZ-2 patients (p = 0.82, p = 0.17, p = 0.34). During six years of follow-up, median pSWE and TE values did not differ significantly over time (TE: p = 0.27; pSWE: p = 0.05).
Conclusion: Our data indicate that pSWE could be useful for non-invasive fibrosis assessment and follow-up in patients with HBeAg-negative chronic HBV infection.
Background: Hypoxia is a key driver for infiltrative growth in experimental gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. We therefore investigated the influence of perioperative cerebral ischemia on patterns of progression in glioblastoma patients.
Methods: We retrospectively screened MRI scans of 245 patients with newly diagnosed glioblastoma undergoing resection for perioperative ischemia near the resection cavity. 46 showed relevant ischemia nearby the resection cavity. A control cohort without perioperative ischemia was generated by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment. Both cohorts were analyzed for patterns of progression by a blinded neuroradiologist.
Results: The percentage of diffuse or distant recurrences at first relapse was significantly higher in the cohort with perioperative ischemia (61.1%) compared to the control cohort (19.4%). The results of the control cohort matched well with historical data. The change in patterns of progression was not associated with a difference in survival.
Conclusions: This study reveals an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients.
Radiographic and safety details of vertebral body stenting : results from a multicenter chart review
(2013)
Background: Up to one third of BKP treated cases shows no appreciable height restoration due to loss of both restored height and kyphotic realignment after balloon deflation. This shortcoming has called for an improved method that maintains the height and realignment reached by the fully inflated balloon until stabilization of the vertebral body by PMMA-based cementation. Restoration of the physiological vertebral body height for pain relief and for preventing further fractures of adjacent and distant vertebral bodies must be the main aim for such a method. A new vertebral body stenting system (VBS) stabilizes the vertebral body after balloon deflation until cementation. The radiographic and safety results of the first 100 cases where VBS was applied are presented.
Methods: During the planning phase of an ongoing international multicenter RCT, radiographic, procedural and followup details were retrospectively transcribed from charts and xrays for developing and testing the case report forms. Radiographs were centrally assessed at the institution of the first/senior author.
Results: 100 patients (62 with osteoporosis) with a total of 103 fractured vertebral bodies were treated with the VBS system. 49 were females with a mean age of 73.2 years; males were 66.7 years old. The mean preoperative anterior-middle-posterior heights were 20.3-17.6-28.0 mm, respectively. The mean local kyphotic angle was 13.1°. The mean preoperative Beck Index (anterior edge height/posterior edge height) was 0.73, the mean alternative Beck Index (middle height/posterior edge height) was 0.63. The mean postoperative heights were restored to 24.5-24.6-30.4 mm, respectively. The mean local kyphotic angle was reduced to 8.9°. The mean postoperative Beck Index was 0.81, the mean alternative one was 0.82. The overall extrusion rate was 29.1%, the symptomatic one was 1%. In the osteoporosis subgroup there were 23.8% extrusions. Within the three months followup interval there were 9% of adjacent and 4% of remote new fractures, all in the osteoporotic group.
Conclusions: VBS showed its strengths especially in realignment of crush and biconcave fractures. Given that fracture mobility is present, the realignment potential is sound and increases with the severity of preoperative vertebral body deformation.
Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters.
Correlative microscopy incorporates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Several approaches exist for correlative microscopy, most of which have used the green fluorescent protein (GFP) as the label for light microscopy. Here we use chemical tagging and synthetic fluorophores instead, in order to achieve protein-specific labeling, and to perform multicolor imaging. We show that synthetic fluorophores preserve their post-embedding fluorescence in the presence of uranyl acetate. Post-embedding fluorescence is of such quality that the specimen can be prepared with identical protocols for scanning electron microscopy (SEM) and transmission electron microscopy (TEM); this is particularly valuable when singular or otherwise difficult samples are examined. We show that synthetic fluorophores give bright, well-resolved signals in super-resolution light microscopy, enabling us to superimpose light microscopic images with a precision of up to 25 nm in the x-y plane on electron micrographs. To exemplify the preservation quality of our new method we visualize the molecular arrangement of cadherins in adherens junctions of mouse epithelial cells.
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.
There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls. Differential expression of 20 microRNAs was detected between patient groups and controls. A validation phase included an expanded cohort and samples from patients with other neurological diseases. This identified lower levels of miR-19b in temporal lobe epilepsy compared to controls, status epilepticus and other neurological diseases. Levels of miR-451a were higher in status epilepticus compared to other groups whereas miR-21-5p differed in status epilepticus compared to temporal lobe epilepsy but not to other neurological diseases. Targets of these microRNAs include proteins regulating neuronal death, tissue remodelling, gliosis and inflammation. The present study indicates cerebrospinal fluid contains microRNAs that can support differential diagnosis of temporal lobe epilepsy and status epilepticus from other neurological and non-neurological diseases.
Aim: In the CheckRad-CD8 trial patients with locally advanced head and neck squamous cell cancer are treated with a single cycle of induction chemo-immunotherapy (ICIT). Patients with pathological complete response (pCR) in the re-biopsy enter radioimmunotherapy. Our goal was to study the value of F-18-FDG PET/CT in the prediction of pCR after induction therapy.
Methods: Patients treated within the CheckRad-CD8 trial that additionally received FDG- PET/CT imaging at the following two time points were included: 3–14 days before (pre-ICIT) and 21–28 days after (post-ICIT) receiving ICIT. Tracer uptake in primary tumors (PT) and suspicious cervical lymph nodes (LN +) was measured using different quantitative parameters on EANM Research Ltd (EARL) accredited PET reconstructions. In addition, mean FDG uptake levels in lymphatic and hematopoietic organs were examined. Percent decrease (Δ) in FDG uptake was calculated for all parameters. Biopsy of the PT post-ICIT acquired after FDG-PET/CT served as reference. The cohort was divided in patients with pCR and residual tumor (ReTu).
Results: Thirty-one patients were included. In ROC analysis, ΔSUVmax PT performed best (AUC = 0.89) in predicting pCR (n = 17), with a decline of at least 60% (sensitivity, 0.77; specificity, 0.93). Residual SUVmax PT post-ICIT performed best in predicting ReTu (n = 14), at a cutpoint of 6.0 (AUC = 0.91; sensitivity, 0.86; specificity, 0.88). Combining two quantitative parameters (ΔSUVmax ≥ 50% and SUVmax PT post-ICIT ≤ 6.0) conferred a sensitivity of 0.81 and a specificity of 0.93 for determining pCR. Background activity in lymphatic organs or uptake in suspected cervical lymph node metastases lacked significant predictive value.
Conclusion: FDG-PET/CT can identify patients with pCR after ICIT via residual FDG uptake levels in primary tumors and the related changes compared to baseline. FDG-uptake in LN + had no predictive value.
Trial registry: ClinicalTrials.gov identifier: NCT03426657.
Hygroscopicity of nanoparticles produced from homogeneous
nucleation in the CLOUD experiments
(2016)
Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study, we focus on a challenging size range, i.e., particles that have grown to diameters of 10 and 15 nm following nucleation, and measure their water uptake. Water uptake is useful information for indirectly obtaining chemical composition of aerosol particles. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at subsaturated conditions (ca. 90 % relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) campaign performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid–dimethylamine, and sulfuric acid–organics derived from α-pinene oxidation. The hygroscopicity parameter κ decreased with increasing particle size, indicating decreasing acidity of particles. No clear effect of the sulfuric acid concentration on the hygroscopicity of 10 nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15 nm particles sharply decreased with decreasing sulfuric acid concentrations. In particular, when the concentration of sulfuric acid was 5.1 × 106 molecules cm−3 in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured κ of 15 nm particles was 0.31 ± 0.01: close to the value reported for dimethylaminium sulfate (DMAS) (κDMAS ∼ 0.28). Furthermore, the difference in κ between sulfuric acid and sulfuric acid–imethylamine experiments increased with increasing particle size. The κ values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from α-pinene ozonolysis play a significant role in particle growth even at 10 nm sizes.
About half of present-day cloud condensation nuclei originate from atmospheric nucleation, frequently appearing as a burst of new particles near midday1. Atmospheric observations show that the growth rate of new particles often accelerates when the diameter of the particles is between one and ten nanometres2,3. In this critical size range, new particles are most likely to be lost by coagulation with pre-existing particles4, thereby failing to form new cloud condensation nuclei that are typically 50 to 100 nanometres across. Sulfuric acid vapour is often involved in nucleation but is too scarce to explain most subsequent growth5,6, leaving organic vapours as the most plausible alternative, at least in the planetary boundary layer7,8,9,10. Although recent studies11,12,13 predict that low-volatility organic vapours contribute during initial growth, direct evidence has been lacking. The accelerating growth may result from increased photolytic production of condensable organic species in the afternoon2, and the presence of a possible Kelvin (curvature) effect, which inhibits organic vapour condensation on the smallest particles (the nano-Köhler theory)2,14, has so far remained ambiguous. Here we present experiments performed in a large chamber under atmospheric conditions that investigate the role of organic vapours in the initial growth of nucleated organic particles in the absence of inorganic acids and bases such as sulfuric acid or ammonia and amines, respectively. Using data from the same set of experiments, it has been shown15 that organic vapours alone can drive nucleation. We focus on the growth of nucleated particles and find that the organic vapours that drive initial growth have extremely low volatilities (saturation concentration less than 10−4.5 micrograms per cubic metre). As the particles increase in size and the Kelvin barrier falls, subsequent growth is primarily due to more abundant organic vapours of slightly higher volatility (saturation concentrations of 10−4.5 to 10−0.5 micrograms per cubic metre). We present a particle growth model that quantitatively reproduces our measurements. Furthermore, we implement a parameterization of the first steps of growth in a global aerosol model and find that concentrations of atmospheric cloud concentration nuclei can change substantially in response, that is, by up to 50 per cent in comparison with previously assumed growth rate parameterizations.
Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments
(2015)
Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study, we focus on a challenging size range, i.e. particles that have grown to diameters of 10 and 15nm following nucleation, and measure their water uptake. Water uptake constrains their chemical composition. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at subsaturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) experiments performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from α-pinene oxidation. The hygroscopicity parameter Κ decreased with increasing particle size indicating decreasing acidity of particles. No clear effect of the sulfuric acid monomer concentrations on the hygroscopicities of 10nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15nm particles sharply decreased with decreasing sulfuric acid monomer concentrations. In 20 particular, when the concentrations of sulfuric acid was 5.1 x 106 molecules cm exp -3 in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured Κ of 15nm particles was 0.3 ± 0.01 close to the value reported for dimethylamine sulfate (DMAS) (Κ DMAS ~ 0.28). Furthermore, the difference in Κ between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The Κ values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from α-pinene ozonolysis play a significant role in particle growth already at 10nm sizes.
The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere.