Refine
Year of publication
Document Type
- Preprint (678)
- Article (609)
- Working Paper (5)
- Book (2)
- Review (1)
Has Fulltext
- yes (1295)
Is part of the Bibliography
- no (1295)
Keywords
- Heavy Ion Experiments (20)
- SARS-CoV-2 (12)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- LHC (9)
- Heavy-ion collision (6)
- prostate cancer (6)
- COVID-19 (5)
- COVID19-NMR (5)
- radical prostatectomy (5)
- ALICE experiment (4)
- Atmospheric chemistry (4)
- Collective Flow (4)
- Genetics (4)
- Jets (4)
- Quark-Gluon Plasma (4)
- Solution NMR spectroscopy (4)
- Solution NMR-spectroscopy (4)
- 5′-UTR (3)
- ALICE (3)
- Covid19-NMR (3)
- Heavy Ions (3)
- Immunology (3)
- Jets and Jet Substructure (3)
- Non-structural protein (3)
- Oncology (3)
- Pandemic (3)
- Seizure (3)
- chemotherapy (3)
- immunohistochemistry (3)
- pp collisions (3)
- systematic biopsy (3)
- ADHD (2)
- Beauty production (2)
- Bipolar disorder (2)
- Charm physics (2)
- Cochlear implant (2)
- Corona (2)
- Depression (2)
- Diagnosis (2)
- Digitalisierung (2)
- Digitization (2)
- EWSR1 (2)
- Epileptischer Anfall (2)
- Experimental nuclear physics (2)
- Experimental particle physics (2)
- FFLU (2)
- Fahrradmitnahme (2)
- Fahrradverleihsysteme (2)
- Gene fusion (2)
- Heavy Quark Production (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Liver transplantation (2)
- NMR spectroscopy (2)
- PD-L1 (2)
- PSA (2)
- Pandemie (2)
- Particle Correlations and Fluctuations (2)
- Particle and resonance production (2)
- Particle correlations and fluctuations (2)
- Pb–Pb collisions (2)
- Protein drugability (2)
- Psychiatric disorders (2)
- QCD (2)
- RNA (2)
- SARS-CoV‑2 (2)
- Single electrons (2)
- Status epilepticus (2)
- Survival analysis (2)
- concordance (2)
- drug resistance (2)
- epidemiology (2)
- fMRI (2)
- fusion biopsy (2)
- immunotherapy (2)
- lung cancer (2)
- nutlin-3 (2)
- p53 (2)
- survival (2)
- targeted therapy (2)
- 19F (1)
- 3Cs technology (1)
- 5'-UTR (1)
- 5_SL4 (1)
- 900 GeV (1)
- ABCB1 (1)
- ABCC1 (1)
- ACLF (1)
- AKI (1)
- AKT (1)
- ALICE detector (1)
- ASAP (1)
- Acanthocephalan parasites (1)
- Active middle ear implants (1)
- Acute HIV infection (1)
- Adults (1)
- Aedes aegypti (1)
- Agoraphobia (1)
- Amino acid analysis (1)
- Animal model (1)
- Anti-nuclei (1)
- Anti-seizure medication (1)
- Antifungal agents (1)
- Aortic valve replacement (1)
- Artificial Intelligence (1)
- Aspergillosis (1)
- Atmospheric science (1)
- Auditory system (1)
- Awareness campaign (1)
- Ayurveda (1)
- B cell malignancies (1)
- B cell receptor (1)
- BCOR (1)
- BCORL1 (1)
- BEACOPP (1)
- BI1361849 (1)
- BMI (1)
- BPH (1)
- BPO (1)
- BPTF (1)
- Behavior (1)
- Bike and Ride / Fahrrad-Abstellanlagen (1)
- Bilateral cochlear implant (1)
- Biodiversity (1)
- Biodiversity Data (1)
- Biogeochemistry (1)
- Biological heart valves (1)
- Biological markers (1)
- Biomarker (1)
- Biomarkers (1)
- Biomonitoring (1)
- Biophysical models (1)
- Bioprosthesis (1)
- Bone conduction devices (1)
- Bone tumor (1)
- Boosted Jets (1)
- Botanical Collections (1)
- Brain (1)
- Brain tumor (1)
- Built environment (1)
- Business strategy in drug development (1)
- CD47 (1)
- CLIF-C ACLF score (1)
- CLIF-C ACLF-R score (1)
- CLOUD experiment (1)
- COMT (1)
- COVID (1)
- CRPC (1)
- CT pulmonary angiography (1)
- CT radiation exposure (1)
- CTLA-4 (1)
- CV9202 (1)
- Calcium signalling (1)
- Cancer (1)
- Cancer check up (1)
- Cancer genomics (1)
- Cancer treatment (1)
- Cardiac surgery (1)
- Carotid injury (1)
- Cell membranes (1)
- Centrality Class (1)
- Centrality Selection (1)
- Chemical composition (1)
- Chemokine CCL2 (1)
- Chemokines (1)
- Child abuse (1)
- Climate change (1)
- Climate-change impacts (1)
- Clinical Trials and Observations (1)
- Clinical genetics (1)
- Clinical practice guidelines (1)
- Clinical trial (1)
- Clinical variation (1)
- Collective Flow, (1)
- Combo® DTS (1)
- Compact city (1)
- Comparison with QCD (1)
- Complex decongestive therapy (1)
- Complication (1)
- Complications (1)
- Computed axial tomography (1)
- Computed tomography pulmonary angiography (CTPA) (1)
- Computer-aided drug design (1)
- Congenital anomalies (1)
- Consensus statement (1)
- Conservation (1)
- Conservation biology (1)
- Course (1)
- Course evaluation (1)
- Covid19-nmr (1)
- Crispr/Cas (1)
- Culex pipiens (1)
- Cycle streets (1)
- DNA sequence analysis (1)
- DNA-PAINT (1)
- DUBs (1)
- Decision Making und Risk (1)
- Demolition emissions (1)
- Design functions (1)
- Diagnostic markers (1)
- Dikerogammarus villosus (1)
- Dimerization domain (1)
- Direct reactions (1)
- Distance learning (1)
- Distanzunterricht (1)
- Doxorubicin (1)
- Drug screens (1)
- Drug therapy (1)
- D’Amico classification (1)
- EGFR (1)
- EP300 (1)
- Ecotoxicology (1)
- Elderly (1)
- Electron-pion identification (1)
- Electroweak interaction (1)
- Elliptic flow (1)
- Embryos (1)
- Environment perception (1)
- Environmental Chemistry (1)
- Environmental impact (1)
- Epilepsy (1)
- Eurasian Curlew (1)
- Europe (1)
- Everolimus (1)
- Extended donor criteria (1)
- FBS (1)
- FGFR (1)
- FOXO1 (1)
- Fahrrad & ÖV (1)
- Fahrradabstellanalgen (1)
- Femtoscopy (1)
- Fibre/foam sandwich radiator (1)
- Financial Markets (1)
- Forschung (1)
- Frailty (1)
- Freshwater invertebrates (1)
- Functional outcomes (1)
- GPS collar (1)
- Gene expression (1)
- Gene regulation (1)
- General practitioners (1)
- Gleason Score (1)
- Gleason score (1)
- Gleason upgrading (1)
- Global positioning system (1)
- Global warming (1)
- Graft function (1)
- Graft survival (1)
- Guanine nucleotide exchange factors (1)
- Guanosine triphosphatase (1)
- HBT (1)
- HIV (1)
- HNO (1)
- HOLEP (1)
- HSP (hereditary spastic paraplegia) (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hals-Nasen-Ohren-Heilkunde (1)
- Hard Scattering (1)
- Head bandage (1)
- Health care workers (1)
- Health policy (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ions (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Heavy-ion collisions (1)
- Hematologic malignancies (1)
- Hematology (1)
- Hepatocellular carcinoma (1)
- Herbaria (1)
- HoLEP (1)
- Holmium laser enucleation (1)
- Hypertension (1)
- Hypofractionated radiotherapy (1)
- IAP (1)
- IFN (1)
- IHC (1)
- IPSS (1)
- Imaging genetics (1)
- Immune suppression (1)
- Immunogenetics (1)
- Immunomonitoring (1)
- Incidental prostate cancer (1)
- Inclusive spectra (1)
- Inflammation (1)
- Insurance (1)
- Integrated urban planning (1)
- Integrierte Stadtentwicklung (1)
- Integrierte kommunale Strategien (1)
- Intensity interferometry (1)
- Intermodalität (1)
- Invariant Mass Distribution (1)
- Invasive candidiasis (1)
- Ionisation energy loss (1)
- Jet Physics (1)
- Jet Substructure (1)
- KDIGO (1)
- KLHL11 (1)
- Kidney (1)
- Kompakte Stadt (1)
- Lafora disease (1)
- Lee type, functional outcome (1)
- Lehre (1)
- Lehrveranstaltungsevaluation (1)
- Leukemias (1)
- Library screening (1)
- Lipedema (1)
- Liposuction (1)
- Literature review (1)
- Liver diseases (1)
- Locomotion (1)
- Luciferase (1)
- Lymphocytes (1)
- Lymphoid tissues (1)
- MDM2 (1)
- MN1 (1)
- MR-proADM (1)
- Machine learning (1)
- Macrodomain (1)
- Macrozoobenthos (1)
- Magnet dislocation (1)
- Magnetic resonance imaging (1)
- Marginal grafts (1)
- Marketing & Kommunikation (1)
- Material budget (1)
- Medical education (1)
- Medical history (1)
- Medizinstudium (1)
- Mental health and psychiatry (1)
- Methicillin-resistant Staphylococcus aureus (1)
- Methodenstudie (1)
- Mid-rapidity (1)
- Minimum Bias (1)
- Mixed hearing loss (1)
- Mobility design (1)
- Mobilität (1)
- Mobilität in Deutschland (1)
- Mobilitätskennziffern (1)
- Mobilitätspanel (1)
- Molecular subtypes (1)
- Monte Carlo (1)
- Mortality (1)
- Multi-Parton Interactions (1)
- Multi-stakeholder approach (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Mutation databases (1)
- Mycoses (1)
- Myeloid Neoplasia (1)
- N471D strumpellin knock-in mice (1)
- NADPH oxidase (1)
- NPSR1 (1)
- NURF (1)
- NVBP (1)
- Nachhaltige Stadtentwicklung (1)
- Nephrons (1)
- Neural network (1)
- Neuroepithelial (1)
- Neuroepithelial tumor (1)
- Neurooncology (1)
- Neuroscience (1)
- Nivolumab (1)
- Non-motorised travel (1)
- Non-small cell lung cancer (1)
- Non-small-cell lung cancer (1)
- Non–small-cell lung cancer (1)
- Nox4 (1)
- Nuclear modification factor (1)
- Nuclear reactions (1)
- Nuclear structure & decays (1)
- Nucleic acid-binding domain (1)
- Nucleocapsid (1)
- Nucleon induced nuclear reactions (1)
- Numenius arquata (1)
- OD approach (1)
- OR time (1)
- ORL (1)
- ORP (1)
- Observational study (1)
- Oldest-old (1)
- Online Survey (1)
- Organ rinse (1)
- Organ shortage (1)
- Organic micropollutants (1)
- Otorhinolaryngological (1)
- Otorhinolaryngology (1)
- Outcome (1)
- Overall survival (1)
- Oxygen (1)
- PAD-test (1)
- PATZ1 (1)
- PCR (1)
- PCV (1)
- PD-1 (1)
- PLAGL1 (1)
- PM10 (1)
- PSA screening (1)
- PSA-Screening (1)
- PYTHIA (1)
- Panic disorder (1)
- Particle and Resonance Production (1)
- Pb–Pb (1)
- Pediatric (1)
- Personenmobilität (1)
- Phase 3 (1)
- Phosphorylation (1)
- Post-traumatic stress disorder (1)
- Preventive medicine (1)
- Production Cross Section (1)
- Prognostic markers (1)
- Properties of Hadrons (1)
- Prostata-specific antigen (1)
- Prostataspezifisches Antigen (1)
- Prostate cancer (1)
- Prostatic neoplasms (1)
- Protein druggability (1)
- Proton–proton (1)
- Prävention (1)
- Psychological and psychosocial issues (1)
- Psychology (1)
- Quality of life (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- Quarkonium (1)
- RARP (1)
- RITA (1)
- RNA genome (1)
- Rabbit (1)
- Radiation exposure (1)
- Radical nephrectomy (1)
- Radical prostatectomy (1)
- Radiofrequency ablation (1)
- Randomisation (1)
- Rapid diagnostic test (1)
- Rapidity Range (1)
- Raumstruktur (1)
- Reactive oxygen species (1)
- Real-world data (1)
- Region Rhein-Main (1)
- Registry (1)
- Rehabilitation (1)
- Relativistic heavy ion physics (1)
- Relativistic heavy-ion collisions (1)
- Renal cancer (1)
- Renal system (1)
- Research (1)
- Research Infrastructure (1)
- Research funding (1)
- Residency (1)
- Resolution Parameter (1)
- Restenosis (1)
- Rhabdomyoma (1)
- SARS-CoV‑2 pandemic (1)
- SARS-CoV‑2-Pandemie (1)
- SAVI (1)
- SIRPalpha (1)
- SL1 (1)
- SL5a (1)
- SL5b (1)
- SL5b + c (1)
- SL5c (1)
- SMAD (1)
- SOFA (1)
- SPG8 (1)
- STING (1)
- Semantics (1)
- Sepsis (1)
- Septic shock (1)
- Sequential (1)
- Seroconverter (1)
- Shared space (1)
- Shell model (1)
- Simultaneous (1)
- Single muons (1)
- Single-cell RNA sequencing (1)
- Size distribution (1)
- Small molecules (1)
- Small-cell lung cancer (1)
- Specialist training (1)
- Spectroscopic factors & electromagnetic moments (1)
- Stadtplanung (1)
- Stechmückenfalle (1)
- Stegomyia aegypti (1)
- Streams (1)
- Street design (1)
- Structural protein (1)
- Sublethal effects (1)
- Supratentorial (1)
- Surgery (1)
- Surgical and invasive medical procedures (1)
- Surgical oncology (1)
- Sustainable urban development (1)
- Systematic Uncertainty (1)
- TGFβ (1)
- TR (1)
- TUR-P (1)
- Tacrolimus (1)
- Taxonomy (1)
- Teaching (1)
- Technical data (1)
- Temperature preference (1)
- Thermodynamics (1)
- Time Projection Chamber (1)
- Tools and ressources (1)
- Total operating room time (1)
- Tracking (1)
- Traditional Indian Medicine (1)
- Transcriptome analysis (1)
- Transition radiation detector (1)
- Transportation planning (1)
- Transurethral resection of the prostate (1)
- Transverse momentum (1)
- Travel behaviour (1)
- Treatment (1)
- Trigger (1)
- Tumor heterogeneity (1)
- Tumor therapy (1)
- Tumour biomarkers (1)
- Ultrafine particles (1)
- University hospitals (1)
- Universitätskliniken (1)
- Upper Rhine Valley (1)
- Urban aerosol (1)
- Urban planning (1)
- Urban space (1)
- Urinary continence (1)
- Urinary incontinence (1)
- Ursus arctos (1)
- VX-2 (1)
- Vector Boson Production (1)
- Verkehr (1)
- Verkehrsplanung (1)
- Vesicles (1)
- Volmer–Weber growth (1)
- Vorsorgeuntersuchung (1)
- WASH complex subunit 5 (1)
- Weiterbildung (1)
- Westphal-Paradigm (1)
- X-ray powder diffraction (1)
- Xenon-based gas mixture (1)
- YM155 (1)
- accessory proteins (1)
- accident (1)
- activity sensors (1)
- acute myeloid leukemia (1)
- acute-on-chronic liver failure (1)
- adult (1)
- aerosol formation (1)
- aerosols (1)
- aggression (1)
- anti-EGFR therapy (1)
- antisynthetase antibodies (1)
- antisynthetase syndrome (1)
- antiviral therapy (1)
- arthritis (1)
- artifacts (1)
- attention-deficit/hyperactivity disorder (ADHD) (1)
- atypical EGFR mutations (1)
- bicycle use (1)
- bioactivity testing (1)
- biogeographic legaciese (1)
- biomarker (1)
- biopsy (1)
- biopsy naïve (1)
- blood loss (1)
- brown bear (1)
- car use reduction (1)
- castration resistance (1)
- catheter removal (1)
- cell biology (1)
- cell lines (1)
- cell-free protein synthesis (1)
- cerebrospinal fluid (1)
- chemorefractory metastatic colorectal cancer (1)
- chemoresistance (1)
- cholangiocarcinoma (1)
- chronic total occlusion (1)
- cirrhosis (1)
- clinical practice (1)
- clinical trial (1)
- clinical trials (1)
- cluttering (1)
- complementary medicine (1)
- complexity (1)
- complications (1)
- consensus (1)
- coronavirus (1)
- correlation (1)
- cycle streets (1)
- cytotoxic T cells (1)
- dE/dx (1)
- data management (1)
- data quality (1)
- death rates (1)
- deferred treatment (1)
- delayed treatment (1)
- denisovite (1)
- detector (1)
- diffuse low-grade glioma (1)
- diffusion-weighted magnetic resonance imaging (1)
- digitale Vernetzung (1)
- disease prevalence (1)
- disorder (1)
- downgrading (1)
- early continence (1)
- easyPACId (1)
- ectosomes (1)
- electroencephalography (EEG) (1)
- electron crystallography (1)
- electron diffraction tomography (1)
- electronic diaries (1)
- enterobacter infections; pseudomonas aeruginosa; epidemiology (1)
- epilepsy (1)
- exosomes (1)
- experimental results (1)
- extracellular vesicles (1)
- fibrous materials (1)
- fluorine (1)
- forest classification (1)
- forest functional similarity (1)
- fragment screening (1)
- fragment-based screening (1)
- framework-structured solids (1)
- gRNA library (1)
- gene therapy (1)
- genetics (1)
- genetics and genomics (1)
- genome-wide (1)
- guidelines (1)
- haemophilia treatment (1)
- head-and-neck cancer (1)
- heavy ion experiments (1)
- histological outcomes (1)
- histopathological growth pattern (1)
- human (1)
- immune checkpoint blockade (1)
- immune checkpoint inhibitor (ICI) (1)
- infection (1)
- injury (1)
- inorganic materials (1)
- integrative medicine (1)
- interaction effect (1)
- interim positron emissiontomography (1)
- interoperability (1)
- interstitial lung disease (1)
- intrinsically disordered region (1)
- inverse stage migration (1)
- irritable bowel syndrome (1)
- juvenile myoclonic epilepsy (1)
- layer-by-layer (LbL) (1)
- level-specific model fit (1)
- likelihood ratio test (1)
- liver (1)
- liver metastasis (1)
- liver transplantation (1)
- lockdown (1)
- loss-of-function (1)
- low-dose imaging (1)
- mRNA active cancer immunotherapy (1)
- mTOR (1)
- mTOR inhibitor (1)
- magnetic resonance imaging (1)
- maternal care (1)
- mechanical ventilation (1)
- medical risk factors (1)
- medulloblastoma (1)
- metal–organic frameworks (1)
- metastasis (1)
- metastatic prostate cancer (1)
- microparticles (1)
- microsatellite instability (1)
- microvesicles (1)
- minerals (1)
- minimal information requirements (1)
- modularity (1)
- morbidity (1)
- mortality (1)
- mosquito trap (1)
- mpMRI (1)
- multicenter study (1)
- multilevel structural equation modeling (1)
- multiplexed immunofluorescence (1)
- multivariate mixed model (1)
- myositis (1)
- nanocrystalline materials (1)
- nanoparticle growth (1)
- nanoscience (1)
- nanostructure (1)
- natural products (1)
- neoadjuvant chemoradiotherapy (1)
- nerve-sparing (1)
- neuroblastoma (1)
- neurovascular bundle preservation (1)
- nitro-fatty acids (1)
- nodular lymphocyte-predominant Hodgkin lymphoma (1)
- non-small-cell lung cancer (1)
- nonstructural proteins (1)
- nutrition - clinical (1)
- optical coherence tomography (1)
- oral cavity cancer (1)
- organic thin films (1)
- p53 activator (1)
- palmitoylation (1)
- pediatric intensive care (1)
- penile cancer (1)
- peri-implantitis (1)
- perioperative outcome (1)
- personality (1)
- pharmacoresistance (1)
- phylogenetic community distance (1)
- polytypism (1)
- predictive biomarker (1)
- prognosis (1)
- progressive myoclonus epilepsy (1)
- prostate neoplasm (1)
- prostate volume (1)
- prostate-specific antigen (1)
- proteins (1)
- proteobacteria (1)
- proteomics (1)
- pseudomonas aeruginosa (1)
- pulmonary failure (1)
- quark gluon plasma (1)
- radiation (1)
- radical prostatecomy (1)
- radiotherapy (1)
- randomized (1)
- re-exposure (1)
- reactive oxygen species (1)
- rechallenge (1)
- reintroduction (1)
- repeat biopsy (1)
- repeatability (1)
- reproducibility (1)
- resilience (1)
- respiratory failure (1)
- rigor (1)
- risk factors (1)
- risk stratification (1)
- robust test statistic (1)
- satellite telemetry (1)
- schizophrenia (1)
- secondary data analysis (1)
- selenolates (1)
- self-assembled monolayers (1)
- sepsis (1)
- simplified production (1)
- single subject classification (1)
- smart home (1)
- smart living (1)
- spectra (1)
- stage-based models (1)
- standardization (1)
- structural proteins (1)
- strumpellin (1)
- stuttering (1)
- subgrouping (1)
- surface chemistry (1)
- surface-mounted metal–organic frameworks (SURMOFs) (1)
- surgical margin (1)
- survivin (1)
- sustainable travel (1)
- targeted biopsy (1)
- temozolomide (1)
- temporal classification (1)
- thiolates (1)
- transrectal prostate biopsy (1)
- trauma (1)
- travel behavior change (1)
- treatment centres (1)
- treatment resistance (1)
- triptycene (1)
- tropical forests (1)
- tumor microenvironment (1)
- tumor weight (1)
- tyrosine kinase inhibitor (TKI) (1)
- upgrading (1)
- uveal melanoma (1)
- ventral striatum (1)
- volatile organic compounds (1)
- waiting time (1)
- web of things (1)
- Öffentlichkeit (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1060)
- Frankfurt Institute for Advanced Studies (FIAS) (955)
- Informatik (923)
- Medizin (123)
- Geowissenschaften (42)
- Biowissenschaften (14)
- Biochemie, Chemie und Pharmazie (11)
- Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) (8)
- Geographie (7)
- Geowissenschaften / Geographie (7)
Background: The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder. Objective: The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient’s perspective. Methods: A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC. Results: Of 365 participants, 36.7% (n = 134) reported the current or past intake of EVE, including 31.5% (n = 115) who were taking EVE at study entry. The mean EVE dosage was 6.1 ± 2.9 mg/m2 (median: 5.6 mg/m2, range 2.0–15.1 mg/m2) in children and adolescents and 4 ± 2.1 mg/m2 (median: 3.7 mg/m2, range 0.8–10.1 mg/m2) in adult patients. An early diagnosis of TSC, the presence of angiomyolipoma, drug-refractory epilepsy, neuropsychiatric manifestations, subependymal giant cell astrocytoma, cardiac rhabdomyoma and overall multi-organ involvement were associated with the use of EVE as a disease-modifying treatment. The reported efficacy was 64.0% for angiomyolipoma (75% in adult patients), 66.2% for drug-refractory epilepsy, and 54.4% for subependymal giant cell astrocytoma. The overall retention rate for EVE was 85.8%. The retention rates after 12 months of EVE therapy were higher among adults (93.7%) than among children and adolescents (88.7%; 90.5% vs 77.4% after 24 months; 87.3% vs 77.4% after 36 months). Tolerability was acceptable, with 70.9% of patients overall reporting adverse events, including stomatitis (47.0%), acne-like rash (7.7%), increased susceptibility to common infections and lymphoedema (each 6.0%), which were the most frequently reported symptoms. With a total score of 41.7 compared with 36.8 among patients not taking EVE, patients currently being treated with EVE showed an increased Liverpool Adverse Event Profile. Noticeable deviations in the sub-items ‘tiredness’, ‘skin problems’ and ‘mouth/gum problems’, which are likely related to EVE-typical adverse effects, were more frequently reported among patients taking EVE. Conclusions: From the patients’ perspective, EVE is an effective and relatively well-tolerated disease-modifying treatment option for children, adolescents and adults with TSC, associated with a high long-term retention rate that can be individually considered for each patient. Everolimus therapy should ideally be supervised by a centre experienced in the use of mechanistic target of rapamycin inhibitors, and adverse effects should be monitored on a regular basis.
The Board of Directors of the German Society of Epileptology and the committee on epilepsy and syncope of the German Society of Neurology have reviewed the current data on vaccination to prevent coronavirus disease 2019 (COVID-19) and vaccination prioritization in people with epilepsy and provide a summary and recommendations.
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Background: Intestinal perforation or leakage increases morbidity and mortality of surgical and endoscopic interventions. We identified criteria for use of full-covered, extractable self-expanding metal stents (cSEMS) vs. "Over the scope"-clips (OTSC) for leak closure.
Methods: Patients who underwent endoscopic treatment for postoperative leakage, endoscopic perforation, or spontaneous rupture of the upper gastrointestinal tract between 2006 and 2013 were identified at four tertiary endoscopic centers. Technical success, outcome (e.g. duration of hospitalization, in-hospital mortality), and complications were assessed and analyzed with respect to etiology, size and location of leakage.
Results: Of 106 patients (male: 75 (71%), female: 31 (29%); age (mean ± SD): 62.5 ± 1.3 years, 72 (69%) were treated by cSEMS and 34 (31%) by OTSC. For cSEMS vs. OTSC, mean treatment duration was 41.1 vs. 25 days, p<0.001, leakage size 10 (1-50) vs. 5 (1-30) mm (median (range)), and complications were observed in 68% vs. 8.8%, p<0.001, respectively. Clinical success for primary interventional treatment was observed in 29/72 (40%) vs. 24/34 (70%, p = 0.006), and clinical success at the end of follow-up was 46/72 (64%) vs. 29/34 (85%) for patients treated by cSEMS vs. OTSC; p = 0.04.
Conclusion: OTSC is preferred in small-sized lesions and in perforation caused by endoscopic interventions, cSEMS in patients with concomitant local infection or abscess. cSEMS is associated with a higher frequency of complications. Therefore, OTSC might be preferred if technically feasible. Indication criteria for cSEMS vs. OTSC vary and might impede design of randomized studies.
Background: To study neoadjuvant chemoradiotherapy (nCRT) and potential predictive factors for response in locally advanced oral cavity cancer (LA-OCC).
Methods: The INVERT trial is an ongoing single-center, prospective phase 2, proof-of-principle trial. Operable patients with stage III-IVA squamous cell carcinomas of the oral cavity were eligible and received nCRT consisting of 60 Gy with concomitant cisplatin and 5-fluorouracil. Surgery was scheduled 6-8 weeks after completion of nCRT. Explorative, multiplex immunohistochemistry (IHC) was performed on pretreatment tumor specimen, and diffusion-weighted magnetic resonance imaging (DW-MRI) was conducted prior to, during nCRT (day 15), and before surgery to identify potential predictive biomarkers and imaging features. Primary endpoint was the pathological complete response (pCR) rate.
Results: Seventeen patients with stage IVA OCC were included in this interim analysis. All patients completed nCRT. One patient died from pneumonia 10 weeks after nCRT before surgery. Complete tumor resection (R0) was achieved in 16/17 patients, of whom 7 (41%, 95% CI: 18-67%) showed pCR. According to the Clavien-Dindo classification, grade 3a and 3b complications were found in 4 (25%) and 5 (31%) patients, respectively; grade 4-5 complications did not occur. Increased changes in the apparent diffusion coefficient signal intensities between MRI at day 15 of nCRT and before surgery were associated with better response (p=0.022). Higher abundances of programmed cell death protein 1 (PD1) positive cytotoxic T-cells (p=0.012), PD1+ macrophages (p=0.046), and cancer-associated fibroblasts (CAFs, p=0.036) were associated with incomplete response to nCRT.
Conclusion: nCRT for LA-OCC followed by radical surgery is feasible and shows high response rates. Larger patient cohorts from randomized trials are needed to further investigate nCRT and predictive biomarkers such as changes in DW-MRI signal intensities, tumor infiltrating immune cells, and CAFs.
Viele Städte in Deutschland stehen aktuell vor komplexen ökonomischen, ökologischen und sozialen Herausforderungen, die mit klassischen ressortbezogenen Planungskonzepten nicht zu bewältigen sind. Integrierte Stadtentwicklungskonzepte erleben deshalb vielerorts eine Renaissance in der städtischen Planungspraxis. Die in diesem Zusammenhang diskutierten Planungsleitbilder geben jedoch nur selten direkt umsetzbare Handlungskonzepte vor. In diesem Beitrag werden deshalb am Beispiel der Stadt Leipzig konkrete Handlungsoptionen für eine an nachhaltiger Mobilität orientierte Stadtentwicklung vorgestellt. Aufbauend auf bisherigen Erkenntnissen zu integrierten Stadtentwicklungskonzepten werden zunächst infrastrukturbezogene Konzepte zur Förderung des Wohnens im Innenbereich, zur Stärkung städtischer Zentren sowie zur Förderung der Nahmobilität dargestellt. Darüber hinaus werden auch politische, organisatorische und kommunikative Handlungsoptionen aufgezeigt. Diese umfassen Maßnahmen zur Verbesserung der übergeordneten Rahmenbedingungen, Konzepte zur Stärkung der inter- und intrakommunalen Kooperation sowie integrierte städtische Mobilitätskonzepte. Das Beispiel Leipzig macht dabei deutlich, dass infrastrukturelle Ansätze für eine an nachhaltiger Mobilitätsgestaltung orientierte Stadtentwicklung nicht ausreichend sind. Vielmehr ist eine bessere Abstimmung der Stadt- und Verkehrsplanung auf die Bedürfnisse der Bevölkerung erforderlich; dazu gehört auch die Integration von Mobilitätsmanagementmaßnahmen in städtische Verkehrskonzepte. Für eine wirksame Umsetzung integrierter Stadtentwicklungskonzepte erscheinen außerdem eine an Nachhaltigkeitszielen orientierte Gestaltung der rechtlichen und politischen Rahmenbedingungen sowie eine stärkere Berücksichtigung regionaler Verknüpfungen in städtischen Planungen notwendig.
Early experiences of childhood sexual or physical abuse are often associated with functional impairments, reduced well-being and interpersonal problems in adulthood. Prior studies have addressed whether the traumatic experience itself or adult psychopathology is linked to these limitations. To approach this question, individuals with posttraumatic stress disorder (PTSD) and healthy individuals with and without a history of child abuse were investigated. We used global positioning system (GPS) tracking to study temporal and spatial limitations in the participants’ real-life activity space over the course of one week. The sample consisted of 228 female participants: 150 women with PTSD and emotional instability with a history of child abuse, 35 mentally healthy women with a history of child abuse (healthy trauma controls, HTC) and 43 mentally healthy women without any traumatic experiences in their past (healthy controls, HC). Both traumatized groups—i.e. the PTSD and the HTC group—had smaller movement radii than the HC group on the weekends, but neither spent significantly less time away from home than HC. Some differences between PTSD and HC in movement radius seem to be related to correlates of PTSD psychopathology, like depression and physical health. Yet group differences between HTC and HC in movement radius remained even when contextual and individual health variables were included in the model, indicating specific effects of traumatic experiences on activity space. Experiences of child abuse could limit activity space later in life, regardless of whether PTSD develops.
Folgende Publikationen werden rezensiert: Garve & al.: Verbreitungsatlas Niedersachsen, Hölzel & al.: Stromtalwiesen, Lübcke & Frede: Naturschutzgebiete in Hessen Band 4, Notizbuch 68 der Kasseler Schule, Riecken & al.: Rote Liste Biotoptypen, Schulz & Dengler: Verbreitungsatlas Moose Schleswig-Holstein, Szabo: Wandern – Erkennen – Heilen
One like all? Behavioral response range of native and invasive amphipods to neonicotinoid exposure
(2024)
Highlights
• Short-time neonicotinoid exposure causes behavioral responses in non-target species.
• Environmentally relevant concentrations can induce changes in invertebrate behavior.
• Different baseline activity of ecological similar crustacean amphipods.
• Species respond specifically to thiacloprid exposure.
• Acantocephalan infection affects locomotion of intermediate host Gammarus roeselii.
Abstract
Native and invasive species often occupy similar ecological niches and environments where they face comparable risks from chemical exposure. Sometimes, invasive species are phylogenetically related to native species, e.g. they may come from the same family and have potentially similar sensitivities to environmental stressors due to phylogenetic conservatism and ecological similarity. However, empirical studies that aim to understand the nuanced impacts of chemicals on the full range of closely related species are rare, yet they would help to comprehend patterns of current biodiversity loss and species turnover. Behavioral sublethal endpoints are of increasing ecotoxicological interest. Therefore, we investigated behavioral responses (i.e., change in movement behavior) of the four dominant amphipod species in the Rhine-Main area (central Germany) when exposed to the neonicotinoid thiacloprid. Moreover, beyond species-specific behavioral responses, ecological interactions (e.g. parasitation with Acanthocephala) play a crucial role in shaping behavior, and we have considered these infections in our analysis. Our findings revealed distinct baseline behaviors and species-specific responses to thiacloprid exposure. Notably, Gammarus fossarum exhibited biphasic behavioral changes with hyperactivity at low concentrations that decreased at higher concentrations. Whereas Gammarus pulex, Gammarus roeselii and the invasive species Dikerogammarus villosus, showed no or weaker behavioral responses. This may partly explain why G. fossarum disappears in chemically polluted regions while the other species persist there to a certain degree. But it also shows that potential pre-exposure in the habitat may influence behavioral responses of the other amphipod species, because habituation occurs, and potential hyperactivity would be harmful to individuals in the habitat. The observed responses were further influenced by acanthocephalan parasites, which altered baseline behavior in G. roeselii and enhanced the behavioral response to thiacloprid exposure. Our results underscore the intricate and diverse nature of responses among closely related amphipod species, highlighting their unique vulnerabilities in anthropogenically impacted freshwater ecosystems.
The pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant nonneoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected L&H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&H cells to and/or that they originate from germinal center B cells at the transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell–rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive nuclear factor {kappa}B activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.
Background: Germinal center-derived B cell lymphomas are tumors of the lymphoid tissues representing one of the most heterogeneous malignancies. Here we characterize the variety of transcriptomic phenotypes of this disease based on 873 biopsy specimens collected in the German Cancer Aid MMML (Molecular Mechanisms in Malignant Lymphoma) consortium. They include diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt’s lymphoma, mixed FL/DLBCL lymphomas, primary mediastinal large B cell lymphoma, multiple myeloma, IRF4-rearranged large cell lymphoma, MYC-negative Burkitt-like lymphoma with chr. 11q aberration and mantle cell lymphoma.
Methods: We apply self-organizing map (SOM) machine learning to microarray-derived expression data to generate a holistic view on the transcriptome landscape of lymphomas, to describe the multidimensional nature of gene regulation and to pursue a modular view on co-expression. Expression data were complemented by pathological, genetic and clinical characteristics.
Results: We present a transcriptome map of B cell lymphomas that allows visual comparison between the SOM portraits of different lymphoma strata and individual cases. It decomposes into one dozen modules of co-expressed genes related to different functional categories, to genetic defects and to the pathogenesis of lymphomas. On a molecular level, this disease rather forms a continuum of expression states than clearly separated phenotypes. We introduced the concept of combinatorial pattern types (PATs) that stratifies the lymphomas into nine PAT groups and, on a coarser level, into five prominent cancer hallmark types with proliferation, inflammation and stroma signatures. Inflammation signatures in combination with healthy B cell and tonsil characteristics associate with better overall survival rates, while proliferation in combination with inflammation and plasma cell characteristics worsens it. A phenotypic similarity tree is presented that reveals possible progression paths along the transcriptional dimensions. Our analysis provided a novel look on the transition range between FL and DLBCL, on DLBCL with poor prognosis showing expression patterns resembling that of Burkitt’s lymphoma and particularly on "double-hit" MYC and BCL2 transformed lymphomas.
Conclusions: The transcriptome map provides a tool that aggregates, refines and visualizes the data collected in the MMML study and interprets them in the light of previous knowledge to provide orientation and support in current and future studies on lymphomas and on other cancer entities.
Children’s and adolescents’ lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017–2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85–1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93–1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57–1.02 and 0.26 (0.05–0.75)), whereas household and leisure accidents increased (1.33 (1.06–1.66) and 1.34 (1.06–1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38–1.16) and 2.09 (1.19–3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42–1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51–3.02)), but decreased in adolescent girls (0.56 (0.32–0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation.
The multistep PROTAC (PROteolysis TArgeting Chimeras) degradation process poses challenges for their rational development, as rate limiting steps determining PROTAC efficiency remain largely unknown. Moreover, the slow throughput of currently used endpoint assays does not allow the comprehensive analysis of larger series of PROTACs. Here we developed cell-based assays using NanoLuciferase and HaloTags, that allow measuring PROTAC induced degradation and ternary complex formation kinetics and stability in cells. Using PROTACs developed for degradation of WDR5, the characterization of the mode of action of these PROTACs in the early degradation cascade revealed a key role of ternary complex formation and stability. Comparing a series of ternary complex crystal structures highlighted the importance of an efficient E3-target interface for ternary complex stability. The developed assays outline a strategy for the rational optimization of PROTACs using a series of live cell assays monitoring key steps of the early PROTAC induced degradation pathway.
Significance The multistep PROTAC induced degradation process of a POI poses a significant challenge for the rational design of these bifunctional small molecules as critical steps that limit PROTAC efficacy cannot be easily assayed at required throughput. In addition, the cellular location of the POI may pose additional challenges as some cellular compartments, such as the nucleus, may not be easily reached by PROTAC molecules and the targeted E3 ligases may not be present in this cellular compartment. We propose therefore a comprehensive assay panel for PROTACs evaluation in cellular environments using a sensor system that allows continuous monitoring of the protein levels of the endogenous POI. We developed a cell line expressing WDR5 from its endogenous locus in fusion with a small sequence tag (HiBIT) that can be reconstituted to functional NanoLuciferase (NLuc). This system allowed continuous monitoring of endogenous WDR5 levels in cells and together with HaloTag system also the continuous monitoring of ternary complex (E3, WDR5 and PROTAC) formation. As this assay can be run at high throughput, we used this versatile system monitoring three diverse chemical series of WDR5 PROTACs that markedly differ in their degradation properties. Monitoring cell penetration, binary complex formation (PROTAC-WDR5 and PROTAC-VHL) as well as ternary complex formation we found that PROTAC efficiency highly correlated with synergy of ternary complex formation in cells. This study represents a first data set on diverse PROTACs studying this property in cellulo and it outlines a strategy for the rational optimization of PROTACs. It also provided kinetic data on ternary complex assembly and dissociation that may serve as a benchmark for future studies utilizing also kinetic properties for PROTAC development. Comparative structural studies revealed larger PROTAC mediated interaction surfaces for PROTACs that efficiently formed ternary complexes highlighting the utility of structure based optimization of PROTAC induced ternary complexes in the development process.
Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.