Refine
Year of publication
Document Type
- Preprint (892)
- Article (866)
- Contribution to a Periodical (8)
- Part of Periodical (4)
- Conference Proceeding (2)
- Working Paper (2)
- Report (1)
- Review (1)
Has Fulltext
- yes (1776)
Is part of the Bibliography
- no (1776)
Keywords
- Heavy Ion Experiments (21)
- Hadron-Hadron scattering (experiments) (12)
- Hadron-Hadron Scattering (11)
- e +-e − Experiments (11)
- BESIII (10)
- LHC (9)
- Branching fraction (7)
- Particle and Resonance Production (7)
- Heavy-ion collision (6)
- Magnetic resonance imaging (6)
- Heavy-ion collisions (5)
- Hepatocellular carcinoma (5)
- Quarkonium (5)
- Spectroscopy (5)
- ALICE experiment (4)
- COVID-19 (4)
- CT (4)
- Charm Physics (4)
- Charm physics (4)
- Collective Flow (4)
- Electroweak interaction (4)
- Jets (4)
- Lepton colliders (4)
- MRI (4)
- Quark-Gluon Plasma (4)
- ALICE (3)
- Artificial intelligence (3)
- Cancer (3)
- Charmed mesons (3)
- Diffraction (3)
- Elastic scattering (3)
- Exotics (3)
- Experimental nuclear physics (3)
- Experimental particle physics (3)
- Hadronic decays (3)
- Heavy Ions (3)
- Heavy Quark Production (3)
- Jets and Jet Substructure (3)
- Neutropenia (3)
- Particle and resonance production (3)
- Polarization (3)
- QCD (3)
- e+-e− Experiments (3)
- microwave ablation (3)
- new species (3)
- pp collisions (3)
- AML (2)
- Acute myeloid leukemia (2)
- Algorithms (2)
- Beam Energy Scan (2)
- Beauty production (2)
- Bipolar disorder (2)
- Blood (2)
- Bone density (2)
- Branching fractions (2)
- Chiral Magnetic Effect (2)
- Collectivity (2)
- Consensus (2)
- Correlation (2)
- DSM (2)
- Diagnostic markers (2)
- Drug therapy (2)
- Dynamic MRI (2)
- ESBL (2)
- Electroweak Interaction (2)
- Elliptic flow (2)
- Embryos (2)
- Flow cytometry (2)
- Guidelines (2)
- Intensive care units (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Leptonic, semileptonic & radiative decays (2)
- Machine learning (2)
- Microwave ablation (2)
- Multidetector computed tomography (2)
- Neoplasms (2)
- Nuclear reactions (2)
- Osteoporosis (2)
- Particle Correlations and Fluctuations (2)
- Particle correlations and fluctuations (2)
- Particle decays (2)
- Pb–Pb collisions (2)
- Predictive markers (2)
- Prostate cancer (2)
- Psychiatric disorders (2)
- RHIC (2)
- Radiomics (2)
- SARS-CoV-2 (2)
- STAR (2)
- Shear viscosity (2)
- Single electrons (2)
- Spine (2)
- Suicide (2)
- Survival (2)
- Tomography (x-ray computed) (2)
- Transarterial chemoembolization (2)
- VRE (2)
- breast cancer (2)
- computed tomography (2)
- global change (2)
- hepatocellular carcinoma (2)
- inflammation (2)
- liver (2)
- penile cancer (2)
- solitary bees (2)
- targeted therapy (2)
- taxonomy (2)
- 16 segment AHA model (1)
- 16S (1)
- 3years (1)
- 5 lipoxygenase (1)
- 900 GeV (1)
- ADHD (1)
- AKT (1)
- ALICE detector (1)
- ALL (1)
- Aachener Hügelland (1)
- Abdominal infections (1)
- Ablation Techniques (1)
- Accelerators & Beams (1)
- Accelerators & storage rings (1)
- Actin (1)
- Active middle ear implants (1)
- Activities of daily living (1)
- Acute calcolous cholecystitis (1)
- Adjustment of dosage at steady state (1)
- Adverse events (1)
- Afroarabiella (1)
- Age determination by skeleton (1)
- Age groups (1)
- Amino acid analysis (1)
- Amizon (1)
- Anemia (1)
- Angiography (1)
- Animal flight (1)
- Animal models (1)
- Animal personality (1)
- Anti-nuclei (1)
- Antibiotic (1)
- Antibiotic steward-ship (1)
- Antibiotics (1)
- Antifungal agents (1)
- Antiretroviral therapy (1)
- Aortic valve replacement (1)
- Apoidea (1)
- Aromatase Inhibitors (1)
- Artemisia tridentata (1)
- Aspergillosis (1)
- Atherosclerosis (1)
- Atomic & molecular beams (1)
- Atomic, Molecular & Optical (1)
- Atrial fibrillation (1)
- Auditory system (1)
- Automated Tube Potential Selection (1)
- Autoregressiver Prozess (1)
- Awareness campaign (1)
- B-slope (1)
- BESIII detector (1)
- Bacterial genes (1)
- Bayes-Verfahren (1)
- Bayesian inference (1)
- Beam energy scan (1)
- Beam loss (1)
- Behavioral reaction norms (1)
- Behavioral specialization (1)
- Behavioral syndromes (1)
- Behavioral type (1)
- Berci needle (1)
- Best practice (1)
- Bhabha (1)
- Biliary tree stones (1)
- Biodiversity (1)
- Biofluids (1)
- Biogeochemistry (1)
- Biologging (1)
- Biological (1)
- Biological heart valves (1)
- Bioprosthesis (1)
- Biopsy (1)
- Biosynthesis (1)
- Bird flight (1)
- Bloodstream infections (1)
- Bone conduction devices (1)
- Bone diseases, Metabolic (1)
- Bone marrow (1)
- Boosted Jets (1)
- Born cross section measurement (1)
- Borrelia burgdorferi (1)
- Breast cancer (1)
- Breast tumors (1)
- Business strategy in drug development (1)
- C1-INH (C1 inhibitor, C1-esterase inhibitor) (1)
- CAKUT (1)
- CD36 (1)
- CDI (1)
- CHRNA10 (1)
- CHRNA7 (1)
- CHRNA9 (1)
- COI (1)
- CP violation (1)
- CRISPR/Cas (1)
- CT dual-energy computed tomography (1)
- CT pulmonary angiography (1)
- CT radiation exposure (1)
- CT-guidance (1)
- CT-guided interventions (1)
- Calcium (1)
- Calorimeter methods (1)
- Calorimeters (1)
- Cancer Staging (1)
- Cancer check up (1)
- Cancer detection (1)
- Cancer staging (1)
- Canonical suppression (1)
- Canopy height model (1)
- Carbon cycle (1)
- Carcinoma, Ductal, Breast (1)
- Cardiac implantable electronic devices (1)
- Cardiac rehabilitation (1)
- Cardiac resynchronization therapy (1)
- Cardiomyopathy (1)
- Cardiovascular diseases (1)
- Cardiovascular magnetic resonance (1)
- Carpenter moths (1)
- Catheter ablation (1)
- Cell binding (1)
- Cell staining (1)
- Central Asia (1)
- Centrality Class (1)
- Centrality Selection (1)
- Charge-transfer collisions (1)
- Charged-particle multiplicity (1)
- Charm quark spatial diffusion coefficient (1)
- Charmonia (1)
- Charmonium (1)
- Charmonium (-like) (1)
- Cheatgrass (1)
- Chemoembolization (1)
- Chemotherapy (1)
- Chickens (1)
- Children (1)
- Chiral magnetic effect (1)
- Cholecystectomy (1)
- Chondral Lesion (1)
- Chronic hepatitis C (1)
- Circadian (1)
- Circular accelerators (1)
- Closure (1)
- Coalescence (1)
- Cochlear implantation (1)
- Cognitive-motor interference (1)
- Cohort studies (1)
- Colchicum (1)
- Cold nuclear matter effects (1)
- Collective Flow, (1)
- Comparison with QCD (1)
- Complement system (1)
- Complex I (1)
- Computed tomography (1)
- Computed tomography imaging (1)
- Computed tomography pulmonary angiography (CTPA) (1)
- Computed tomography, X-ray (1)
- Computer-aided drug design (1)
- Cone-beam computed tomography (1)
- Congenital (1)
- Congenital anomalies (1)
- Consensus document (1)
- Consensus statement (1)
- Conservation biology (1)
- Contrast agent (1)
- Cossidae (1)
- Critical point (1)
- Cross section (1)
- Cryoballoon (1)
- Cucujoidea (1)
- Curculionoidea (1)
- Cycad pollination (1)
- Cystic fibrosis (1)
- D meson (1)
- DME (1)
- DNA sequence analysis (1)
- DNA-barcoding (1)
- DST (1)
- Dark photon (1)
- Dark sector (1)
- Data Standard (1)
- Data sharing (1)
- Death rates (1)
- Dermis (1)
- Detector design and construction technologies and materials (1)
- Detector modelling and simulations I (interaction of radiation with matter, interaction of photons with matter, interaction of hadrons with matter, etc) (1)
- Deuteron (1)
- Deuteron production (1)
- Di-hadron correlations (1)
- Diagnosis (1)
- Diagnostic accuracy (1)
- Diagnostic differentiation (1)
- Diagnostic imaging (1)
- Diffusion magnetic resonance imaging (1)
- Digital (1)
- Digital breast tomosynthesis (DBT) (1)
- Digital mammography (1)
- Dilated cardiomyopathy (1)
- Direct reactions (1)
- Dissociative seizures (1)
- Drug susceptibility testing (1)
- Dual task walking (1)
- Dual-Source CT (1)
- Dual-energy computed tomography (1)
- Dumon stents (1)
- Early goal-directed therapy (1)
- Ecosystem ecology (1)
- Edema (1)
- Electric stimulation (1)
- Electromagnetic form factor (1)
- Electromagnetic form factors (1)
- Electron-pion identification (1)
- Electronic transitions (1)
- Endoscopic ultrasound (1)
- Endovascular aortic repair (1)
- Enterobacteriaceae (1)
- Environmental impact (1)
- Enzymatic DNA Methylation (1)
- Enzymatic Methylation (1)
- Equity (1)
- Estrogen Receptor Modulators (1)
- Evolutionary biology (1)
- Evolutionary genetics (1)
- Exercise training (1)
- Extended donor criteria (1)
- Exudates and transudates (1)
- FAV00A (1)
- FF-ATP synthase dimer (1)
- FOS: Physical sciences (1)
- Facial nerve (1)
- Feasibility studies (1)
- Feathers (1)
- Femtoscopy (1)
- Fetal heart (1)
- Fevers (1)
- Fibre/foam sandwich radiator (1)
- Fibroblast growth factor (1)
- First experience with patients (1)
- Fistula (1)
- Flavor changing neutral currents (1)
- Flavor symmetries (1)
- Flavour Physics (1)
- Florida (1)
- Flow (1)
- Fmoc solid phase peptide synthesis (1)
- Follow-up (1)
- Forest ecology (1)
- Forestiera segregata (1)
- Forestry (1)
- Form factors (1)
- Forward physics (1)
- G-protein-coupled receptors (1)
- GWAS (1)
- Gadobutrol (1)
- Gadopentate dimeglumine (1)
- Gait analysis (1)
- Gallbladder percutaneous drainage (1)
- Gastrointestinal (1)
- Gene expression (1)
- Genetics (1)
- Genome editing (1)
- Geochemistry (1)
- Goserelin (1)
- Gram negative bacteria (1)
- Green fluorescent protein (1)
- Groin pain (1)
- Groomed jet radius (1)
- Großbritannien (1)
- Gαq/11 (1)
- HBT (1)
- HCC (1)
- HIV (1)
- HadCM3 (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hadronization (1)
- Hard Scattering (1)
- Health policy (1)
- Heart (1)
- Heart defects (1)
- Heart failure (1)
- Heart transplantation (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ion collisions (1)
- Heavy ions (1)
- Heavy-Ion Collision (1)
- Heavy-flavor decay electron (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Heavy-ion (1)
- Hematologic malignancies (1)
- Hematopoietic stem cell transplantation (1)
- Hereditary angioedema (1)
- Herniated disk (1)
- Heteroptera (1)
- High Energy Physics - Experiment (hep-ex) (1)
- High-energy neutron detection (1)
- Higher moments (1)
- Horses (1)
- Hospitals (1)
- Human behaviour (1)
- Hyperons (1)
- IFN-β (1)
- IHMCIF (1)
- ILUVIEN (1)
- Iberian endemic species (1)
- Image processing (1)
- Image processing (computer-assisted) (1)
- Immunogenetics (1)
- Immunology (1)
- Implantable cardioverter-defibrillator (1)
- In-TIPS thrombosis (1)
- Inclusive branching fraction (1)
- Inclusive spectra (1)
- Induction chemotherapy (1)
- Infection (1)
- Influenza (1)
- Inguinal hernia (1)
- Inguinal pain (1)
- Initial state radiation (1)
- Integrative Modeling (1)
- Intensity interferometry (1)
- Intensive care unit (1)
- Interference fragmentation function (1)
- Interventional oncological treatment (1)
- Intervertebral disc displacement (1)
- Intra-abdominal infection (1)
- Invariant Mass Distribution (1)
- Invasive candidiasis (1)
- Inverted DNA Repeats (1)
- Invisible decays (1)
- Ionisation energy loss (1)
- J/ψ suppression (1)
- Jet Physics (1)
- Jet Substructure (1)
- Jet substructure (1)
- Jurkat (1)
- K0S (1)
- KLK5 (1)
- Kollision (1)
- Korrelation (1)
- Kupffer cells (1)
- LASS (1)
- LNS (1)
- LPJ-GUESS (1)
- Lactic acidosis (1)
- Laparostomy (1)
- Laser interstitial thermal therapy (1)
- Laser navigation system (1)
- Lateral recess stenosis (1)
- Lepidoptera (1)
- Lifestyle (1)
- Lipidol (1)
- Lipiodol (1)
- Liver (1)
- Liver cancer (1)
- Liver cirrhosis (1)
- Local control (1)
- Low & intermediate-energy accelerators (1)
- Low back pain (1)
- Lumbar spinal canal stenosis (1)
- Lumbar spine (1)
- Lung neoplasms (1)
- Lymphangioleiomyomatosis (1)
- M. Intracellulare (1)
- M. avium (1)
- M. avium complex (1)
- M. chimaera (1)
- MEDIC (1)
- MLL (1)
- MMP9 (1)
- MRP4 (1)
- MRSA (1)
- Macrophages (1)
- Magnetic resonance (1)
- Marine chemistry (1)
- Mastoiditis (1)
- Material budget (1)
- Medical Oncology (1)
- Medical Physics: Diagnostic (1)
- Medical research (1)
- Mena/VASP (1)
- Mesh (1)
- Metastasis (1)
- Methicillin-resistant Staphylococcus aureus (1)
- Mid-rapidity (1)
- Minimal detectable change (1)
- Minimum Bias (1)
- Miocene cooling (1)
- Miridae (1)
- Mirinae (1)
- Mitochondrial disorder (1)
- Mitomycin C (1)
- Mixed hearing loss (1)
- Molecular neuroscience (1)
- Monitoring (1)
- Monte Carlo (1)
- Mortality (1)
- Mouse models (1)
- Multi-Parton Interactions (1)
- Multi-neutron detection (1)
- Multi-stakeholder approach (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multidetector Computed Tomography (1)
- Multidisciplinary management (1)
- Multidrug-resistant organisms (1)
- Multimodal imaging (1)
- Multiparametric MRI (1)
- Multiple parton interactions (1)
- Multivariate analysis (1)
- Mutation databases (1)
- Mycobacteria (1)
- Mycobacterium avium complex (1)
- Mycoses (1)
- Myocardial perfusion (1)
- Myocardial segmentation (1)
- Myocarditis (1)
- NIRS (1)
- NSF (1)
- NTM (1)
- Necrotic area (1)
- Neolithic (1)
- Neonatal (1)
- Net-charge correlations (1)
- Net-charge fluctuations (1)
- Neural network (1)
- Neutrinos (1)
- Niederrheinische Bucht (1)
- Non-trauma (1)
- Non-tuberculous mycobacteria (1)
- Noncoding RNA (1)
- Nonflow (1)
- Noninferiority (1)
- Nonpenetrating (1)
- Nontuberculous mycobacteria (1)
- Nuclear astrophysics (1)
- Nuclear modification factor (1)
- Nuclear physics of explosive environments (1)
- Nuclear structure & decays (1)
- Nucleon induced nuclear reactions (1)
- Nutrition (1)
- Nymphs (1)
- Older adults (1)
- Oncology (1)
- Open Access (1)
- Open abdomen (1)
- Opportunistic infections (1)
- Organ allocation (1)
- Osteoporotic fractures (1)
- Oswestry Disability Score (1)
- P2X7 receptor (1)
- PDB-Dev (1)
- PDBx/mmCIF (1)
- PDCD4 (1)
- PGE2 (1)
- PSA screening (1)
- PSA-Screening (1)
- PYTHIA (1)
- Pacemaker (1)
- Palaeoceanography (1)
- Palaeoclimate (1)
- Pancreas transplantation (1)
- Pancreatitis (1)
- Pandemic (1)
- Parainfluenza (1)
- Particle phenomena (1)
- Particle production (1)
- Patellofemoral Joint (1)
- Patient safety (1)
- Pb–Pb (1)
- Pediatric (1)
- Pediatric infections (1)
- Pediatrics (1)
- Percutaneous (1)
- Peritonitis (1)
- Personalized medicine (1)
- Phantom study (1)
- Phantoms (imaging) (1)
- Phospholipids (1)
- Photon counting (1)
- Physical activity (1)
- Physics (1)
- Plastic scintillator array (1)
- Pneumonia (1)
- Population-based screening (1)
- Portal (1)
- Positron emission tomography (1)
- Poverty (1)
- Preclinical research (1)
- Predictability (1)
- Prediction (1)
- Prevention (1)
- Preventive medicine (1)
- Production Cross Section (1)
- Prognosis (1)
- Prognostic markers (1)
- Properties of Hadrons (1)
- Prostata-specific antigen (1)
- Prostataspezifisches Antigen (1)
- Protease inhibitor therapy (1)
- Proton (1)
- Proton-proton collisions (1)
- Proton–proton (1)
- Proton–proton collisions (1)
- Prävention (1)
- Pseudo HE-images (1)
- Psychiatry (1)
- Quantitative Imaging (1)
- Quantitative features (1)
- Quantum chromodynamics (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- Quark–gluon plasma (1)
- RNA polymerase (1)
- RNA, long noncoding (1)
- RNA-DNA-Hybridization (1)
- Radiative capture (1)
- Radiative decay (1)
- Radiofrequency (1)
- Radiology (1)
- Raman spectroscopy (1)
- Rapidity Range (1)
- Rare decays (1)
- Re-exploration (1)
- Reactions with relativistic radioactive beams (1)
- Reassociation Kinetics (1)
- Recall rate (1)
- Regulatory networks (1)
- Rehabilitation (1)
- Rehospitalization (1)
- Reintervention (1)
- Rejection (1)
- Relativistic heavy ion physics (1)
- Relativistic heavy-ion collisions (1)
- Renal lesions (1)
- Resolution Parameter (1)
- Resonances (1)
- Respiratory infections (1)
- Respiratory syncytial virus (1)
- Response (1)
- Retro-IDEAL (1)
- Retrospective studies (1)
- Retrospective study (1)
- SLC20A1 (1)
- STIR (1)
- SVR (1)
- Safety (1)
- Seasonal variation (1)
- Semi-leptonic decays (1)
- Senecio inaequidens (Schmalblättriges Greiskraut) (1)
- Sepsis-bundle (1)
- Serum (1)
- Shell model (1)
- Shunt (1)
- Single muons (1)
- Social determinants (1)
- SoftDrop (1)
- Solar insolation (1)
- Spectrin (1)
- Spectroscopic factors & electromagnetic moments (1)
- Spin alignment (1)
- Spinal fractures (1)
- Spinal injuries (1)
- Spine care (1)
- Spirochetes (1)
- Splitting function (1)
- Standardization (1)
- Standards of care (1)
- Static MRI (1)
- Statistical analysis (1)
- Status epilepticus (1)
- Stenotrophomonas maltophilia (1)
- Steroid (1)
- Strangeness enhancement (1)
- Sub-segmentation (1)
- Sunlight (1)
- Superinfection (1)
- Surgery (1)
- Surgical risk (1)
- Survival analysis (1)
- Survival data (1)
- Synthetic (1)
- Systematic Uncertainty (1)
- T-cell (1)
- TACE (1)
- TGF-beta (1)
- TIPS (1)
- TR (1)
- Tea (1)
- Technical data (1)
- Technique (1)
- Techniques Electromagnetic calorimeters (1)
- Temporal lobe epilepsy (1)
- Temporomandibular joint (1)
- Temporomandibular joint dysfunction (1)
- Thermal model (1)
- Thoracic aortic aneurysm (1)
- Thrombosis (1)
- Time Projection Chamber (1)
- Timing (1)
- Tomography (1)
- Tracking (1)
- Transcriptional Control (1)
- Transcriptome analysis (1)
- Transition radiation detector (1)
- Transjugular Intrahepatic Portosystemic Shunt (1)
- Translational research (1)
- Transverse momentum (1)
- Transversity (1)
- Trauma (1)
- Treatment (1)
- Treatment outcome (1)
- Trigger (1)
- Tropidosteptes (1)
- Truncus arteriosus (1)
- Tumor volume (1)
- UAV (1)
- UWB diagnostics (1)
- Upper respiratory tract infection (1)
- Vaccination (1)
- Vascular emergencies (1)
- Vasculitis (1)
- Vector Boson Production (1)
- Vektoranalysis (1)
- Verbal fluency (1)
- Vertebral body (1)
- Virtual noncalcium reconstructions (1)
- Vitamin (1)
- Vorsorgeuntersuchung (1)
- Wang resin (1)
- Workstation comparison (1)
- Worldwide Protein Data Bank (1)
- Wounds (1)
- Währungssystem (1)
- X-ray computed (1)
- X-ray crystallography (1)
- X-rays (1)
- Xenon-based gas mixture (1)
- Y states (1)
- Zagros (1)
- abdominal imaging (1)
- acute leukemia (1)
- adaptation (1)
- airway (1)
- alleles (1)
- amino acids (1)
- amphibians (1)
- anchialine (1)
- anchialine cave (1)
- angiography (1)
- animal migration (1)
- antibaryon (1)
- antibiotic therapy (1)
- antiepileptic drugs (1)
- antimicrobial stewardship (1)
- aortic stenosis (1)
- ascites (1)
- autism spectrum disorder (1)
- autistic disorder (1)
- axions (1)
- beads (1)
- behavioural ecology (1)
- biodiversity (1)
- bioenergetics (1)
- biogeographic legaciese (1)
- biomarker (1)
- biome stability (1)
- biopsy (1)
- birds (1)
- bladder exstrophy-epispadias complex (1)
- c-MET (1)
- cPLA2 (1)
- cabozantinib (1)
- calcium-independent phospholipase A2β (1)
- calretinin (1)
- cancer (1)
- carbapenem resistance (1)
- cardiac magnetic resonance (1)
- cardiac remodeling (1)
- cave (1)
- cell lines (1)
- center-of-mass energy (1)
- ceramide synthase (1)
- charmonium-like states (1)
- cholestasis (1)
- chromosomal translocations (1)
- chronic liver disease (CLD) (1)
- cisplatin (1)
- climate-change ecology (1)
- cloacal malformation (1)
- collision (1)
- colon (1)
- colonization (1)
- colorectal cancer (1)
- colorectal cancer (CRC) (1)
- colorectal cancer liver metastases (CRLM) (1)
- computer tomography (1)
- computer-assisted (1)
- cone-beam computed tomography (CBCT) (1)
- cone-beam computer tomography (1)
- conservation biology (1)
- continental climate (1)
- conventional/traditional transarterial chemoembolization (cTACE) (1)
- copy number polymorphism (1)
- critical care unit (1)
- critical ill patients (1)
- cryoelectron microscopy (1)
- cryptic species (1)
- cytotoxicity (1)
- dE/dx (1)
- dark matter experiments (1)
- denervation (1)
- dentate gyrus (1)
- detector (1)
- deuteron (1)
- diagnostic imaging (1)
- dimuon (1)
- disease prevalence (1)
- domestication (1)
- drone (1)
- drug-eluting beads TACE (DEB-TACE) (1)
- dual-energy (1)
- e+e − annihilation (1)
- e+e⁻ − Experiments (1)
- e+e− Experiments (1)
- ecosystem services (1)
- ectosomes (1)
- electromagnetic navigation bronchoscopy (EMN, ENB) (1)
- electron-positron collision (1)
- emergence (1)
- endemic bird areas (1)
- endemic species (1)
- epigenomics (1)
- evolution (1)
- excitation (1)
- exhaustion (1)
- exosomes (1)
- experimental results (1)
- extracellular vesicles (1)
- f-MLF (1)
- fear conditioning (1)
- fibrosis (1)
- fine spatial resolution remote sensing (1)
- fitness (1)
- flurbiprofen (1)
- forest classification (1)
- forest functional similarity (1)
- formylation (1)
- functional genetics (1)
- gadobutrol (1)
- gene flow (1)
- genes (1)
- genetic distance (1)
- genetic generalized epilepsy (1)
- genetics (1)
- genome (1)
- genotype (1)
- genotype determination (1)
- germination (1)
- glioblastoma (1)
- guanidine alkaloid (1)
- guidelines (1)
- habitat destruction (1)
- hadron spectroscopy (1)
- hadronic events (1)
- healthcare professional (1)
- heart failure (1)
- heavy ion experiments (1)
- heavy-ion collisions (1)
- helicity amplitude analysis (1)
- hepatocellular carcinoma (HCC) (1)
- high energie (1)
- high-pitch (1)
- highly-charged ions (1)
- hohe Energie (1)
- host (1)
- hypertension, pulmonary (1)
- imaging (1)
- impulsivity (1)
- in vivo dosimetry (1)
- inclusive J/ψ decays (1)
- infection control (1)
- inflammasome (1)
- injury (1)
- inner membrane morphology (1)
- integrated stratigraphy (1)
- interleukin-1β (1)
- interventional radiology (1)
- intraarterial therapy (1)
- intratumoral (1)
- irinotecan-loaded drug-eluting beads TACE (DEBIRI-TACE) (1)
- kidney formation (1)
- lamotrigine (1)
- land use (1)
- laser-induced thermotherapy (1)
- layer-specificity (1)
- learning (1)
- levetiracetam (1)
- lichen extracts (1)
- lipiodol (1)
- liver cirrhosis (1)
- liver metastases (1)
- liver transplantation (1)
- livermetastases of colorectal cancer (1)
- locoregional chemotherapy (1)
- low-dose imaging (1)
- lung cancer (1)
- mTOR (1)
- magic-angle spinning (1)
- maladaptation (1)
- mammals (1)
- mantle cell lymphoma (1)
- marker (1)
- mast cells (1)
- medial prefrontal cortex (mPFC) (1)
- membrane protein complex (1)
- memory consolidation and extinction (1)
- microdosing (1)
- microparticles (1)
- microvesicles (1)
- microwave breast imaging (1)
- migration (1)
- minimal information requirements (1)
- mitochondria (1)
- molecular dynamics simulation (1)
- multidetector computed tomography (1)
- multidrug resistance (1)
- multilevel latent polynomial regression analysis (1)
- myocardial fibrosis (1)
- nRNA Complexity (1)
- natural product (1)
- neovascularization, physiologic (1)
- neurofeedback (1)
- neutralizing antibodies (1)
- neutrophils (1)
- nitrogen (1)
- non‑Hodgkin's lymphoma (1)
- nuclear (1)
- nucleon (1)
- number of J/ψ events (1)
- orbital forcing (1)
- organotypic culture (1)
- oval split ring resonator (1)
- overall survival (OS) (1)
- p+p collisions (1)
- papilloma (1)
- patient study (1)
- percutaneous thermal ablation (1)
- perforant path transection (1)
- peripheral blood stem cell transplant (1)
- pharmacoresistance (1)
- phenotype (1)
- phylogenetic community distance (1)
- phylogeny (1)
- plant height (1)
- portal vein (1)
- primary biliary cirrhosis (1)
- primary sclerosing cholangitis (1)
- progression-free survival (PFS) (1)
- pulmonary hypertension (1)
- quark gluon plasma (1)
- radiation (1)
- radiation dosage (1)
- radiation dosimetry (1)
- radiation protection (1)
- radiomics (1)
- rats (1)
- relativistic collisions (1)
- renal impairment (1)
- reproducibility (1)
- reptiles (1)
- resistant cell lines (1)
- resolution (1)
- retuximab (1)
- rigor (1)
- rosacea (1)
- rotary ATPase mechanism (1)
- sagebrush (1)
- scar (1)
- schizophrenia (1)
- screening (1)
- screening routine (1)
- sepsis (1)
- sex‑determining region Y-box 11 (1)
- single nucleotide polymorphism (1)
- single subject classification (1)
- skin involvement (1)
- social identity (1)
- sodium bituminosulfonate (1)
- solar physics (1)
- solitary pulmonary nodule (1)
- space-momentum correlation (1)
- spectra (1)
- sphingosine kinase (1)
- sphingosine-1-phosphate (1)
- spike protein (1)
- spine (1)
- squamous cell carcinoma (1)
- standardization (1)
- stent (1)
- storage rings (1)
- structure-from-motion photogrammetry (1)
- symbiosis (1)
- system (1)
- temporal classification (1)
- tetraquark (1)
- theranostics (1)
- thrombosis (1)
- tivantinib (1)
- toll-like receptor (1)
- tracheobronchomalacia (1)
- transarterial chemoembolization (TACE) (1)
- transbronchial biopsy (TBB) (1)
- transcranial magnetic stimulation (TMS) (1)
- translocation partner genes (1)
- transmission (1)
- trigger efficiency (1)
- tropical forests (1)
- tumor (1)
- tumor response (1)
- tumor suppressor (1)
- urinary tract development (1)
- valproic acid (1)
- variants of concern (1)
- vertebroplasty (1)
- virtual reality (1)
- white and brown dwarfs (1)
- whole-genome sequencing (1)
- wwPDB (1)
- x-ray techniques (1)
- yeast (1)
- zebrafish development (1)
- Öffentlichkeit (1)
- Λ+c baryon (1)
- Σ hyperon (1)
- Υ suppression (1)
- ψ(3686) (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1399)
- Frankfurt Institute for Advanced Studies (FIAS) (1067)
- Informatik (925)
- Medizin (167)
- Geowissenschaften (23)
- Biowissenschaften (19)
- Biochemie und Chemie (14)
- Biodiversität und Klima Forschungszentrum (BiK-F) (12)
- Senckenbergische Naturforschende Gesellschaft (9)
- Buchmann Institut für Molekulare Lebenswissenschaften (BMLS) (8)
The Miocene was a key time in the evolution of African ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here, we report the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique. We provide the first 1) radiometric ages of the Mazamba Formation, 2) reconstructions of paleovegetation in the region based on pedogenic carbonates and fossil wood, and 3) descriptions of fossil teeth. Gorongosa is unique in the East African Rift in combining marine invertebrates, marine vertebrates, reptiles, terrestrial mammals, and fossil woods in coastal paleoenvironments. The Gorongosa fossil sites offer the first evidence of woodlands and forests on the coastal margins of southeastern Africa during the Miocene, and an exceptional assemblage of fossils including new species.
The epitranscriptome embodies many new and largely unexplored functions of RNA. A significant roadblock hindering progress in epitranscriptomics is the identification of more than one modification in individual transcript molecules. We address this with CHEUI (CH3 (methylation) Estimation Using Ionic current). CHEUI predicts N6-methyladenosine (m6A) and 5-methylcytidine (m5C) in individual molecules from the same sample, the stoichiometry at transcript reference sites, and differential methylation between any two conditions. CHEUI processes observed and expected nanopore direct RNA sequencing signals to achieve high single-molecule, transcript-site, and stoichiometry accuracies in multiple tests using synthetic RNA standards and cell line data. CHEUI’s capability to identify two modification types in the same sample reveals a co-occurrence of m6A and m5C in individual mRNAs in cell line and tissue transcriptomes. CHEUI provides new avenues to discover and study the function of the epitranscriptome.
The epitranscriptome embodies many new and largely unexplored functions of RNA. A major roadblock in the epitranscriptomics field is the lack of transcriptome-wide methods to detect more than a single RNA modification type at a time, identify RNA modifications in individual molecules, and estimate modification stoichiometry accurately. We address these issues with CHEUI (CH3 (methylation) Estimation Using Ionic current), a new method that concurrently detects N6-methyladenosine (m6A) and 5-methylcytidine (m5C) in individual RNA molecules from the same sample, as well as differential methylation between any two conditions. CHEUI processes observed and expected nanopore direct RNA sequencing signals with convolutional neural networks to achieve high single-molecule accuracy and outperforms other methods in detecting m6A and m5C sites and quantifying their stoichiometry. CHEUI’s unique capability to identify two modification types in the same sample reveals a non-random co-occurrence of m6A and m5C in mRNA transcripts in cell lines and tissues. CHEUI unlocks an unprecedented potential to study RNA modification configurations and discover new epitranscriptome functions.
Our purpose was to analyze the robustness and reproducibility of magnetic resonance imaging (MRI) radiomic features. We constructed a multi-object fruit phantom to perform MRI acquisition as scan-rescan using a 3 Tesla MRI scanner. We applied T2-weighted (T2w) half-Fourier acquisition single-shot turbo spin-echo (HASTE), T2w turbo spin-echo (TSE), T2w fluid-attenuated inversion recovery (FLAIR), T2 map and T1-weighted (T1w) TSE. Images were resampled to isotropic voxels. Fruits were segmented. The workflow was repeated by a second reader and the first reader after a pause of one month. We applied PyRadiomics to extract 107 radiomic features per fruit and sequence from seven feature classes. We calculated concordance correlation coefficients (CCC) and dynamic range (DR) to obtain measurements of feature robustness. Intraclass correlation coefficient (ICC) was calculated to assess intra- and inter-observer reproducibility. We calculated Gini scores to test the pairwise discriminative power specific for the features and MRI sequences. We depict Bland Altmann plots of features with top discriminative power (Mann–Whitney U test). Shape features were the most robust feature class. T2 map was the most robust imaging technique (robust features (rf), n = 84). HASTE sequence led to the least amount of rf (n = 20). Intra-observer ICC was excellent (≥ 0.75) for nearly all features (max–min; 99.1–97.2%). Deterioration of ICC values was seen in the inter-observer analyses (max–min; 88.7–81.1%). Complete robustness across all sequences was found for 8 features. Shape features and T2 map yielded the highest pairwise discriminative performance. Radiomics validity depends on the MRI sequence and feature class. T2 map seems to be the most promising imaging technique with the highest feature robustness, high intra-/inter-observer reproducibility and most promising discriminative power.
Hemispherical and cylindrical antenna arrays are widely used in radar-based and tomography-based microwave breast imaging systems. Based on the dielectric contrast between healthy and malignant tissue, a three-dimensional image could be formed to locate the tumor. However, conventional X-ray mammography as the golden standard in breast cancer screening produces two-dimensional breast images so that a comparison between the 3D microwave image and the 2D mammogram could be difficult. In this paper, we present the design and realisation of a UWB breast imaging prototype for the frequency band from 1 to 9 GHz. We present a refined system design in light of the clinical usage by means of a planar scanning and compare microwave images with those obtained by X-ray mammography. Microwave transmission measurements were processed to create a two-dimensional image of the breast that can be compared directly with a two-dimensional mammogram. Preliminary results from a patient study are presented and discussed showing the ability of the proposed system to locate the tumor.
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
This prospective study sought to evaluate potential savings of radiation dose to medical staff using real-time dosimetry coupled with visual radiation dose feedback during angiographic interventions. For this purpose, we analyzed a total of 214 angiographic examinations that consisted of chemoembolizations and several other types of therapeutic interventions. The Unfors RaySafe i2 dosimeter was worn by the interventionalist at chest height over the lead protection. A total of 110 interventions were performed with real-time radiation dosimetry allowing the interventionalist to react upon higher x-ray exposure and 104 examinations served as the comparative group without real-time radiation monitoring. By using the real-time display during interventions, the overall mean operator radiation dose decreased from 3.67 (IQR, 0.95–23.01) to 2.36 μSv (IQR, 0.52–12.66) (−36%; p = 0.032) at simultaneously reduced operator exposure time by 4.5 min (p = 0.071). Dividing interventions into chemoembolizations and other types of therapeutic interventions, radiation dose decreased from 1.31 (IQR, 0.46-3.62) to 0.95 μSv (IQR, 0.53-3.11) and from 24.39 (IQR, 12.14-63.0) to 10.37 μSv (IQR, 0.85-36.84), respectively, using live-screen dosimetry (p ≤ 0.005). Radiation dose reductions were also observed for the participating assistants, indicating that they could also benefit from real-time visual feedback dosimetry during interventions (−30%; p = 0.039). Integration of real-time dosimetry into clinical processes might be useful in reducing occupational radiation exposure time during angiographic interventions. The real-time visual feedback raised the awareness of interventionalists and their assistants to the potential danger of prolonged radiation exposure leading to the adoption of radiation-sparing practices. Therefore, it might create a safer environment for the medical staff by keeping the applied radiation exposure as low as possible.
Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.
Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome.
Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome.
Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).
Objective: TGF-β2 (TGF-β, transforming growth factor beta), the less-investigated sibling of TGF-β1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-β2 in biliary-derived liver diseases.
Design: As we also found upregulated TGFB2 in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-β2 in early stage biliary liver disease using the MDR2-KO mice. Specifically, the influence of TgfB2 silencing on the fibrotic and inflammatory niche was analysed on molecular, cellular and tissue levels.
Results: TgfB2-induced expression of fibrotic genes in cholangiocytes and hepatic stellate cellswas detected. TgfB2 expression in MDR2-KO mice was blunted using TgfB2-directed antisense oligonucleotides (AON). Upon AON treatment, reduced collagen deposition, hydroxyproline content and αSMA expression as well as induced PparG expression reflected a significant reduction of fibrogenesis without adverse effects on healthy livers. Expression analyses of fibrotic and inflammatory genes revealed AON-specific regulatory effects on Ccl3, Ccl4, Ccl5, Mki67 and Notch3 expression. Further, AON treatment of MDR2-KO mice increased tissue infiltration by F4/80-positive cells including eosinophils, whereas the number of CD45-positive inflammatory cells decreased. In line, TGFB2 and CD45 expression correlated positively in PSC/PBC patients and localised in similar areas of the diseased liver tissue.
Conclusions: Taken together, our data suggest a new mechanistic explanation for amelioration of fibrogenesis by TGF-β2 silencing and provide a direct rationale for TGF-β2-directed drug development.
Highlights
• Cryo-EM structure of a yeast F1Fo-ATP synthase dimer
• Inhibitor-free X-ray structure of the F1 head and rotor complex
• Mechanism of ATP generation by rotary catalysis
• Structural basis of cristae formation in the inner mitochondrial membrane
Summary
We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by a combination of cryo-EM and X-ray crystallography. The final structure resolves 58 of the 60 dimer subunits. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Subunit 8 (A6L in human) is an evolutionary derivative of the bacterial b subunit. On the lumenal membrane surface, subunit f establishes direct contact between the two monomers. Comparison with a cryo-EM map of the F1Fo monomer identifies subunits e and g at the lateral dimer interface. They do not form dimer contacts but enable dimer formation by inducing.
Background: Due to the steadily increasing number of cancer patients worldwide the early diagnosis and treatment of cancer is a major field of research. The diagnosis of cancer is mostly performed by an experienced pathologist via the visual inspection of histo-pathological stained tissue sections. To save valuable time, low quality cryosections are frequently analyzed with diagnostic accuracies that are below those of high quality embedded tissue sections. Thus, alternative means have to be found that enable for fast and accurate diagnosis as the basis of following clinical decision making.
Methods: In this contribution we will show that the combination of the three label-free non-linear imaging modalities CARS (coherent anti-Stokes Raman-scattering), TPEF (two-photon excited autofluorescence) and SHG (second harmonic generation) yields information that can be translated into computational hematoxylin and eosin (HE) images by multivariate statistics. Thereby, a computational HE stain is generated resulting in pseudo-HE overview images that allow for identification of suspicious regions. The latter are analyzed further by Raman-spectroscopy retrieving the tissue’s molecular fingerprint.
Results: The results suggest that the combination of non-linear multimodal imaging and Raman-spectroscopy possesses the potential as a precise and fast tool in routine histopathology.
Conclusions: As the key advantage, both optical methods are non-invasive enabling for further pathological investigations of the same tissue section, e.g. a direct comparison with the current pathological gold-standard.
Using a microscopic transport model together with a coalescence after-burner, we study the formation of deuterons in Au + Au central collisions at s = 200 AGeV . It is found that the deuteron transverse momentum distributions are strongly a ected by the nucleon space-momentum correlations, at the moment of freeze-out, which are mostly determined by the number of rescatterings. This feature is useful for studying collision dynamics at ultrarelativistic energies.
Bacterial and fungal toll-like receptor activation elicits type I IFN responses in mast cells
(2021)
Next to their role in IgE-mediated allergic diseases and in promoting inflammation, mast cells also have antiinflammatory functions. They release pro- as well as antiinflammatory mediators, depending on the biological setting. Here we aimed to better understand the role of mast cells during the resolution phase of a local inflammation induced with the Toll-like receptor (TLR)-2 agonist zymosan. Multiple sequential immunohistology combined with a statistical neighborhood analysis showed that mast cells are located in a predominantly antiinflammatory microenvironment during resolution of inflammation and that mast cell-deficiency causes decreased efferocytosis in the resolution phase. Accordingly, FACS analysis showed decreased phagocytosis of zymosan and neutrophils by macrophages in mast cell-deficient mice. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which is known to enhance phagocytosis by macrophages. Both, zymosan and lipopolysaccharides (LPS) induced IFN-β synthesis in BMMCs in similar amounts as in bone marrow derived macrophages. IFN-β was expressed by mast cells in paws from naïve mice and during zymosan-induced inflammation. As described for macrophages the release of type I IFNs from mast cells depended on TLR internalization and endosome acidification. In conclusion, mast cells are able to produce several mediators including IFN-β, which are alone or in combination with each other able to regulate the phagocytotic activity of macrophages during resolution of inflammation.
This study included 30 patients with diagnosed rheumatoid arthritis (RA) and 30 test subjects without RA (control group). The objective of the study was to examine both groups for the presence of temporomandibular disorders (TMD) and morphological changes of the temporomandibular joint (TMJ). All individuals were examined using a systematic detailed clinical TMD examination as well as magnetic resonance imaging (MRI). The clinical TMD examination yielded significant differences between the RA patients and the control group concerning crepitus of the TMJ, and palpation tenderness of the masticatory muscles as well as the unassisted mandibular opening. The evaluation of the MRI images for the RA group showed significantly more frequent deformations of the condyle, osteophyte formations and erosions in the condylar compacta, and degenerative changes in the spongiosa. Increased intra-articular accumulation of synovial liquid and signs of inflammatory changes of the spongiosa were only found in the RA group. Statistical analysis showed a significant correlation between crepitus and specific osteoarthrotic changes (MRI), respectively, and between crepitus and a complete anterior disk displacement without reduction (MRI). The duration of the RA disease correlated neither with the anamnestic and clinical dysfunction index by Helkimo nor with RA-specific MRI findings.
Whereas the lack of biomarkers in penile cancer (PeCa) impedes the development of efficacious treatment protocols, preliminary evidence suggests that c-MET and associated signaling elements may be dysregulated in this disorder. In the following study, we investigated whether c-MET and associated key molecular elements may have prognostic and therapeutic utility in PeCa. Formalin-fixed, paraffin-embedded tumor tissue from therapy-naïve patients with invasive PeCa was used for tissue microarray (TMA) analysis. Immunohistochemical staining was performed to determine the expression of the proteins c-MET, PPARg, β-catenin, snail, survivin, and n-MYC. In total, 94 PeCa patients with available tumor tissue were included. The median age was 64.9 years. High-grade tumors were present in 23.4%, and high-risk HPV was detected in 25.5%. The median follow-up was 32.5 months. High expression of snail was associated with HPV-positive tumors. Expression of β-catenin was inversely associated with grading. In both univariate COX regression analysis and the log-rank test, an increased expression of PPARg and c-MET was predictive of inferior disease-specific survival (DSS). Moreover, in multivariate analysis, a higher expression of c-MET was independently associated with worse DSS. Blocking c-MET with cabozantinib and tivantinib induced a significant decrease in viability in the primary PeCa cell line UKF-PeC3 isolated from the tumor tissue as well as in cisplatin- and osimertinib-resistant sublines. Strikingly, a higher sensitivity to tivantinib could be detected in the latter, pointing to the promising option of utilizing this agent in the second-line treatment setting.
Background: Prostate cancer is a major health concern in aging men. Paralleling an aging society, prostate cancer prevalence increases emphasizing the need for efcient diagnostic algorithms.
Methods: Retrospectively, 106 prostate tissue samples from 48 patients (mean age,
66 ± 6.6 years) were included in the study. Patients sufered from prostate cancer (n = 38) or benign prostatic hyperplasia (n = 10) and were treated with radical prostatectomy or Holmium laser enucleation of the prostate, respectively. We constructed tissue microarrays (TMAs) comprising representative malignant (n = 38) and benign (n = 68) tissue cores. TMAs were processed to histological slides, stained, digitized and assessed for the applicability of machine learning strategies and open–source tools in diagnosis of prostate cancer. We applied the software QuPath to extract features for shape, stain intensity, and texture of TMA cores for three stainings, H&E, ERG, and PIN-4. Three machine learning algorithms, neural network (NN), support vector machines (SVM), and random forest (RF), were trained and cross-validated with 100 Monte Carlo random splits into 70% training set and 30% test set. We determined AUC values for single color channels, with and without optimization of hyperparameters by exhaustive grid search. We applied recursive feature elimination to feature sets of multiple color transforms.
Results: Mean AUC was above 0.80. PIN-4 stainings yielded higher AUC than H&E and
ERG. For PIN-4 with the color transform saturation, NN, RF, and SVM revealed AUC of 0.93 ± 0.04, 0.91 ± 0.06, and 0.92 ± 0.05, respectively. Optimization of hyperparameters improved the AUC only slightly by 0.01. For H&E, feature selection resulted in no increase of AUC but to an increase of 0.02–0.06 for ERG and PIN-4.
Conclusions: Automated pipelines may be able to discriminate with high accuracy between malignant and benign tissue. We found PIN-4 staining best suited for classifcation. Further bioinformatic analysis of larger data sets would be crucial to evaluate the reliability of automated classifcation methods for clinical practice and to evaluate potential discrimination of aggressiveness of cancer to pave the way to automatic precision medicine.
Background: Pythium ultimum (P. ultimum) is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results: The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans. Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions although surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome including an expansion of genes involved in proteolysis and genes unique to Pythium. We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report in a genome outside the metazoans. Conclusions: Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae.
Objectives: To assess the impact of noise-optimised virtual monoenergetic imaging (VMI+) on image quality and diagnostic evaluation in abdominal dual-energy CT scans with impaired portal-venous contrast.
Methods: We screened 11,746 patients who underwent portal-venous abdominal dual-energy CT for cancer staging between 08/2014 and 11/2019 and identified those with poor portal-venous contrast.
Standard linearly-blended image series and VMI+ image series at 40, 50, and 60 keV were reconstructed. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of abdominal organs and vascular structures were calculated. Image noise, image contrast and overall image quality were rated by three radiologists using 5-point Likert scale.
Results: 452 of 11,746 (4%) exams were poorly opacified. We excluded 190 cases due to incomplete datasets or multiple exams of the same patient with a final study group of 262. Highest CNR values in all abdominal organs (liver, 6.4 ± 3.0; kidney, 17.4 ± 7.5; spleen, 8.0 ± 3.5) and vascular structures (aorta, 16.0 ± 7.3; intrahepatic vein, 11.3 ± 4.7; portal vein, 15.5 ± 6.7) were measured at 40 keV VMI+ with significantly superior values compared to all other series. In subjective analysis, highest image contrast was seen at 40 keV VMI+ (4.8 ± 0.4), whereas overall image quality peaked at 50 keV VMI+ (4.2 ± 0.5) with significantly superior results compared to all other series (p < 0.001).
Conclusions: Image reconstruction using VMI+ algorithm at 50 keV significantly improves image contrast and image quality of originally poorly opacified abdominal CT scans and reduces the number of non-diagnostic scans.
Advances in knowledge: We validated the impact of VMI+ reconstructions in poorly attenuated DECT studies of the abdomen in a big data cohort.