Medizin
Refine
Year of publication
- 2018 (439) (remove)
Document Type
- Article (439) (remove)
Has Fulltext
- yes (439)
Is part of the Bibliography
- no (439)
Keywords
- breast cancer (15)
- Mammakarzinom (10)
- Behandlung (8)
- inflammation (7)
- CDK4/6 (6)
- Metastasen (6)
- Neuroscience (6)
- PD1/PDL1 (6)
- Studien (6)
- treatment (6)
- Blood (5)
- Research article (5)
- cancer (5)
- metastases (5)
- Biomarker (4)
- Cirrhosis (4)
- Depression (4)
- Germany (4)
- Hemorrhage (4)
- Inflammation (4)
- Prävention (4)
- Risiko (4)
- Schizophrenia (4)
- diagnosis (4)
- mutual information (4)
- pain (4)
- prevention (4)
- reactive oxygen species (4)
- risk (4)
- trials (4)
- Biomarkers (3)
- Breast cancer (3)
- Cancer (3)
- Cell staining (3)
- EEG microstates (3)
- Flow cytometry (3)
- HIV (3)
- Hepatocellular carcinoma (3)
- Liver diseases (3)
- Mental health and psychiatry (3)
- Morbidity (3)
- Neonates (3)
- Obesity (3)
- Prognosis (3)
- Stem cells (3)
- aging (3)
- autophagy (3)
- chemotherapy (3)
- entropy (3)
- glioblastoma (3)
- information theory (3)
- macrophage (3)
- metastasis (3)
- mitochondria (3)
- regeneration (3)
- sphingolipids (3)
- Alcohol consumption (2)
- Antiretroviral therapy (2)
- Atherosclerosis (2)
- Atrial fibrillation (2)
- Autism (2)
- Autism spectrum disorder (2)
- Autophagy (2)
- BRAF (2)
- Blood pressure (2)
- Brain metastasis (2)
- Brustkrebs (2)
- COPD (2)
- CTGF (2)
- Cardiac magnetic resonance (2)
- Cardiovascular diseases (2)
- Cardiovascular magnetic resonance (2)
- Cell therapy (2)
- Citation analysis (2)
- Complications (2)
- Consensus (2)
- Crystal structure (2)
- Cytoskeleton (2)
- Death rates (2)
- Deutschland (2)
- Diabetes (2)
- Diagnose (2)
- Diagnostic markers (2)
- Diagnostic medicine (2)
- Diagnostik (2)
- Emotions (2)
- Etiology (2)
- Evaluation (2)
- Everolimus (2)
- Exercise (2)
- Eyes (2)
- Face (2)
- Fistula (2)
- Früherkennung (2)
- Galaktografie (2)
- Galaktomosynthese (2)
- General practice (2)
- Genome-wide association studies (2)
- Guidelines (2)
- HCC (2)
- Hematology (2)
- Immunology (2)
- Kidney transplantation (2)
- Knees (2)
- Liver fibrosis (2)
- Lokalrezidiv (2)
- Long non-coding RNAs (2)
- MRI (2)
- MRT (2)
- Mamma (2)
- Markovianity (2)
- Medical education (2)
- MicroRNAs (2)
- Mixed methods (2)
- Morphometry (2)
- Mortality (2)
- Multimorbidity (2)
- Multiple chronic conditions (2)
- Musculoskeletal system (2)
- Nachsorge (2)
- Nerve fibers (2)
- Next-generation sequencing (2)
- Non-small cell lung cancer (2)
- Oncology (2)
- Operation/Chirurgie (2)
- PCR (2)
- PD1/ PDL1 (2)
- Palliative care [MeSH] (2)
- Patients (2)
- Percutaneous coronary intervention (2)
- Periodontitis (2)
- Polypharmacy (2)
- Primary care (2)
- Prognosefaktoren (2)
- Prostate cancer (2)
- Prädiktivfaktoren (2)
- Pulmonary hypertension (2)
- Reaction time (2)
- Richtlinie (2)
- Scientists (2)
- Sepsis (2)
- Stroke (2)
- Surgical and invasive medical procedures (2)
- Surgical oncology (2)
- Survival (2)
- Sweden (2)
- Teeth (2)
- Tomosynthese (2)
- Trauma (2)
- Ultraschall (2)
- Validation (2)
- Viral load (2)
- Vitamin D (2)
- Vitamin D deficiency (2)
- acute kidney injury (2)
- angiogenesis (2)
- antioxidants (2)
- ataxia telangiectasia (2)
- atherosclerosis (2)
- attention (2)
- bioinformatics (2)
- breast (2)
- cardiac surgery (2)
- catheter ablation (2)
- ceramides (2)
- child (2)
- chronic kidney disease (2)
- connectivity (2)
- cytokines (2)
- data science (2)
- development (2)
- endothelial cells (2)
- epilepsy (2)
- follow‑up (2)
- forensic entomology (2)
- galactography (2)
- galactomosynthesis (2)
- guideline (2)
- hedgehog signaling (2)
- hepatitis C virus (2)
- human (2)
- hyperglycemia (2)
- hypoxia (2)
- imaging (2)
- immunotherapy (2)
- innate immunity (2)
- interleukin-4 (2)
- liver injury (2)
- local recurrence (2)
- lyme disease (2)
- matrix (2)
- medical students (2)
- mesenchymal stromal/stem cells (2)
- metabolism (2)
- miRNA (2)
- microRNA (2)
- minimalinvasive Biopsie (2)
- minimally invasive biopsies (2)
- neoadjuvant chemotherapy (2)
- neoadjuvante Chemotherapie (2)
- next generation sequencing (NGS) (2)
- obesity (2)
- paclitaxel (2)
- predictive factors (2)
- pregnancy (2)
- primary immunodeficiency (2)
- prognostic factors (2)
- psoriasis (2)
- radiation (2)
- rapamycin (2)
- reproducibility (2)
- resistance (2)
- safety (2)
- schizophrenia (2)
- screening (2)
- seizure (2)
- sphingosine 1-phosphate (2)
- spreadsheet (2)
- stationarity (2)
- studies (2)
- surgery (2)
- tobacco prevention (2)
- tomosynthesis (2)
- treatment/therapy (2)
- ultrasound (2)
- vector (2)
- vemurafenib (2)
- workflow (2)
- (surface) partial differential equations (1)
- 1,2-dichloroethane (1)
- 1,25-Dihydroxyvitamin D (1)
- 16p11.2 (1)
- 2-deoxyglucose (2-DG) (1)
- 3D spatio-temporal resolved mathematical models (1)
- 4-FA (1)
- A375 human melanoma cells (1)
- A549 (1)
- ACE-inhibitor (1)
- ACURATE neo (1)
- ADHD (1)
- AIDS (1)
- AKI (1)
- ALK gene (1)
- ALK-rearranged NSCLC (1)
- ARA (1)
- ASO (1)
- ATP-citrate lyase (1)
- Abatacept (1)
- Acoustics (1)
- Activities of daily living (1)
- Acute bronchitis (1)
- Acute cough (1)
- Acute lymphocytic leukaemia (1)
- Acute myeloid leukemia (1)
- Adenylyl cyclase (1)
- Adipose-derived mesenchymal stem cells (1)
- Adults (1)
- Aedes aegypti (1)
- Aedes albopictus (1)
- Age (1)
- Age groups (1)
- Aggressive periodontitis (1)
- Akaike information criterion (AIC) (1)
- Aliphatic halogenated hydrocarbons (1)
- Alleles (1)
- Allergic asthma (1)
- Allgemeinmedizin (1)
- Alveolar ridge augmentation (1)
- Ambroxol (1)
- Anatomie (1)
- Anatomie und Histologie (1)
- Andexanet alpha (1)
- Angioedema (1)
- Angiogenesis (1)
- Angioplasty (1)
- Animal wings (1)
- Antibiotics (1)
- Antibodies (1)
- Antibody-mediated rejection (1)
- Anticoagulant therapy (1)
- Antiretrovirals (1)
- Antirheumatic agents (1)
- Antithrombotic therapy (1)
- Antiviral agents (1)
- Antiviral therapy (1)
- Apixaban (1)
- Apoptosis (1)
- Aquaporins (1)
- Arms (1)
- Ascites (1)
- Aspergillus (1)
- Asphyxia (1)
- Atrial appendage occlusion (1)
- Attention (1)
- Attention-deficit / hyperactivity disorder (1)
- Attitude (1)
- Aurora A (1)
- Austria (1)
- Auto transfusion (1)
- Autoimmunity (1)
- Autopsy (1)
- Axons (1)
- Azathioprine (1)
- B cell subpopulations (1)
- B cells (1)
- B-cell immunology (1)
- B-cell lymphoma (1)
- BATF3 (1)
- BCR signaling (1)
- BIAM-switch (1)
- BMC (1)
- BPD (1)
- BRCA1 (1)
- BRCA2 (1)
- BTK (1)
- Babesia divergens (1)
- Babesia microti (1)
- Bacterial meningitis (1)
- Bacterial pathogens (1)
- Bayesian inference (1)
- Behavioral analysis (1)
- Benefit (1)
- Best practice (1)
- Bibliometrics (1)
- Bidirectional genes (1)
- Big Data (1)
- Big data (1)
- Big five (1)
- Biofluids (1)
- Bioinformatics (1)
- Biological (1)
- Biological invasion (1)
- Biomechanical analysis (1)
- Biophysical models (1)
- Biopsy (1)
- Biosynthetic mesh (1)
- Bipolar disorder (1)
- Birth weight (1)
- Blended learning curriculum · (1)
- Blended-Learning-Curriculum (1)
- Blood cells (1)
- Blood groups (1)
- Blood-brain barrier (1)
- Bloodstream infections (1)
- Blurred vision (1)
- Bone defect (1)
- Bone marrow cells (1)
- Bone marrow fibrosis (1)
- Bone marrow mononuclear cells (1)
- Bone marrow-derived mesenchymal stem cells (1)
- Bone tissue engineering (1)
- Borrelia (1)
- Borrelia burgdorferi (1)
- Borrelia miyamotoi (1)
- Bradykinin (1)
- Brain anatomy (1)
- Brain damage (1)
- Brain ischemia (1)
- Breast tumors (1)
- Bright light therapy (1)
- Bronchial inflammation (1)
- Bronchitis severity scale (1)
- Bronchopulmonary dysplasia (1)
- Burden of disease (1)
- Bypass liner (1)
- C-reactive protein (1)
- C. elegans (1)
- C1 inhibitor (1)
- C1-inhibitor (1)
- C5 acylcarnitine (1)
- CCL2 (1)
- CCN2 (1)
- CD3/19 depletion (1)
- CD34 selection (1)
- CD36 (1)
- CD74 (1)
- CDK4/6 inhibitor (1)
- CHRNA10 (1)
- CHRNA7 (1)
- CHRNA9 (1)
- CNS (1)
- CO2-induced forced ventilation (1)
- COI (1)
- COII (1)
- COMT (1)
- COPD course and therapy (1)
- CRE-luciferase (1)
- CRISPR/Cas9 (1)
- CRM1 (1)
- CTX (1)
- Ca2+ imaging (1)
- Caffeine (1)
- Calcium signalling (1)
- Calnexin (1)
- Cancer detection and diagnosis (1)
- Cancer epidemiology (1)
- Cancer treatment (1)
- Carbon tetrachloride (1)
- Cardiac Fibrosis (1)
- Cardiac surgery (1)
- Cardiac surgery patients (1)
- Cardiomyopathy (1)
- Cardiovascular biology (1)
- Cardiovascular disease (1)
- Cardiovascular genetics (1)
- Cell binding (1)
- Cell cultures (1)
- Cell distribution (1)
- Cell membranes (1)
- Cell salvage (1)
- Cell signalling (1)
- Cementation (1)
- Ceramic (1)
- Cerclage (1)
- Cerebral ischemia (1)
- Cerebrospinal fluid (1)
- Certification (1)
- Cesarean section (1)
- Chaperone (1)
- Chemical biology (1)
- Chemical ecology (1)
- Chemobrain (1)
- Chemoembolization (1)
- Chest pain unit (1)
- Chikungunya virus (1)
- Child (1)
- Children (1)
- Chloroform (1)
- Chondrocytes (1)
- Chromatin accessibility (1)
- Chromatin and Epigenetics (1)
- Chronic heart failure (1)
- Chronic periodontiti (1)
- Chronification (1)
- Circadian rhythms and sleep (1)
- Cleanliness level (1)
- Clinical frailty scale (1)
- Clinical genetics (1)
- Clinical outcome (1)
- Clinical psychometry (1)
- Clinical study (1)
- Clinical trials (1)
- Closure (1)
- Co-culture (1)
- Co-morbidity (1)
- Cocaine (1)
- Cognition (1)
- Cognitive neuroscience (1)
- Colon cancer (1)
- Colon capsule endoscopy (1)
- Comparative effectiveness research (1)
- Complement system (1)
- Complementation rate (1)
- Complete heart block (1)
- Complex I (1)
- Complex II (1)
- Complex hernia (1)
- Complex networks (1)
- Complication management (1)
- Connective tissue (1)
- Consortia (1)
- Conventional synthetic disease-modifying antirheumatic drug (1)
- Coronary artery disease (1)
- Coronary intervention (1)
- Credentialing (1)
- Critical bleeding (1)
- Crohn’s disease (1)
- CspZ (1)
- Curriculum (1)
- Cystic fibrosis (1)
- Cytokines (1)
- Cytology (1)
- DAA (1)
- DAMP (1)
- DLBCL (1)
- DMARDs (biologic) (1)
- DMARDs (synthetic) (1)
- DNA methylation (1)
- DNA mismatch repair (1)
- DNase1-seq (1)
- DOK1 (1)
- DSM (1)
- DTI (1)
- Dabigatran (1)
- Data acquisition (1)
- Data processing (1)
- Data science (1)
- Data visualization (1)
- Decision making (1)
- Deformation (1)
- Dengue (1)
- Dengue fever (1)
- Dengue virus (1)
- Density equalizing mapping (1)
- Dental implants (1)
- Dental phobia (1)
- Dental training (1)
- Dentition (1)
- Dermatomyositis (1)
- Developmental biology (1)
- Diabetes mellitus (1)
- Diagnosis (1)
- Dichloromethane (1)
- Differentiation (1)
- Digital ethics (1)
- Digital rectal examination (1)
- Digital transformation (1)
- Digitale Ethik (1)
- Digitale Transformation (1)
- Dimer (1)
- Dimers (Chemical physics) (1)
- Direct current electrical stimulation (1)
- Disc herniation (1)
- Dissociative seizures (1)
- Distance to water (1)
- Donor Selection (1)
- Dopamine (1)
- Drug discovery (1)
- Drug interactions (1)
- Drug therapy (1)
- Dual therapy (1)
- E/I-Balance (1)
- EGFL7 (1)
- EMT (1)
- ENCODE-DREAM in vivo Transcription Factor binding site prediction challenge (1)
- ERMS (1)
- Early diagnosis (1)
- Early recurrence (1)
- Edoxaban (1)
- Elderly (1)
- Elective caesarean section (1)
- Elevation (1)
- Ellipsoids (1)
- Emotional recognition (1)
- Endocrine cancer (1)
- Endoscopy (1)
- England (1)
- Ensemble learning (1)
- Enterostomy (1)
- Enterostomy closure (1)
- Enterostomy formation (1)
- Environmental chemistry (1)
- Enzyme kinetics (1)
- Enzyme mechanisms (1)
- Epidemiology (1)
- Epidermal growth factor receptor (1)
- Epidural block (1)
- Epigenetics (1)
- Epileptic seizures (1)
- Epithelial cells (1)
- Epstein-Barr virus (1)
- Epstein–Barr virus (1)
- Equipment (1)
- Ergonomics (1)
- Estradiol (1)
- Europe (1)
- European registry for idiopathic pulmonary fibrosis (eurIPFreg) (1)
- Examination questions (1)
- Exosomes (1)
- Experimental models of disease (1)
- Extinction (1)
- Extracellular matrix (1)
- Extracellular matrix proteins (1)
- Extracorporeal purification (1)
- Eye movements (1)
- FAM134B (1)
- FGFR (1)
- FOXO3a (1)
- FTY720 (1)
- FX06 (1)
- Factor analysis (1)
- Fallbeispiele (1)
- Fear conditioning (1)
- Fibroblasts (1)
- Fibrosis (1)
- Finite Element Method (1)
- Finite Volumes (1)
- Flaps (1)
- Forensics (1)
- Formation dance (1)
- Frailty (1)
- Frühgeburt (1)
- Functional clustering (1)
- G2A (1)
- GABAergic interneurons (1)
- GLI inhibitors (1)
- GPCR (1)
- GSK3α (1)
- GSK3β (1)
- Games (1)
- Gamma-Band Activity (1)
- Gap junctions (1)
- Gastric cancer (1)
- Gastrointestinal cancer (1)
- Gastrointestinal tract (1)
- Gebärmutterhalskrebs (1)
- Gender gap (1)
- Gene Regulation (1)
- Gene expression (1)
- Gene fusion (1)
- Gene microarray analysis (1)
- Gene therapy (1)
- General dental practice (1)
- Generation time (1)
- Geographically weighted regression (GWR) (1)
- German people (1)
- Gestational age (1)
- Glaucoma (1)
- Glioblastoma (1)
- Glycosphingolipids (1)
- Grafts (1)
- Gram negative bacteria (1)
- Greater tuberosity fractures (1)
- Growth factors (1)
- HACA (1)
- HBV reactivation (1)
- HCV treatment (1)
- HER2 c-erbB2 (1)
- HER2-positive (1)
- HER2/neu (1)
- HH (1)
- HIV serodiagnosis (1)
- HIV-1 (1)
- HLA class II (1)
- HLA peptidome (1)
- HMGB1 (1)
- HPV (1)
- HRas (1)
- Haematoma expansion (1)
- Haemostatics (1)
- Hashimoto’s thyroiditis (1)
- Hausarztmangel (1)
- Head injury (1)
- Health care resource utilization (1)
- Health economics (1)
- Health information (1)
- Health risk analysis (1)
- Health-seeking behaviour (1)
- Heart transplantation (1)
- Hedgehog pathway (1)
- Helpline (1)
- Hematocrit value (1)
- Hematopoietic stem cell transplantation (1)
- Hemodynamics (1)
- HepG2 (1)
- Hepatitis B virus (1)
- Hepatitis C virus (1)
- Hepatitis C, Chronic (1)
- Herbalife (1)
- Hereditary breast and ovarian cancer (1)
- HhAntag (1)
- High-intensity interval endurance training (1)
- Hindu Kush Himalayas (1)
- Hip (1)
- Histology (1)
- Histone post-translational modifications (1)
- Homeostasis (1)
- Horner's syndrome (1)
- Horses (1)
- HuR (1)
- Human behaviour (1)
- Human prostate (1)
- Hydroxychloroquine (1)
- Hydroxycut (1)
- Hydroxyurea (1)
- Hypoxia inducible factor (1)
- Hysterektomie-Prävalenz (1)
- IFN (1)
- IL-18BP (1)
- IL-1β (1)
- IL-6 (1)
- IRES translation (1)
- ITGA7 (1)
- IVA interference tandem mass spectrometry (1)
- Iceland (1)
- Idarucizumab (1)
- Idiopathic pulmonary fibrosis (IPF) (1)
- Imaging (1)
- Imaging in LGG (1)
- Immune suppression (1)
- Immunosenescence (1)
- Immunotherapy (1)
- Implementation (1)
- Incisional hernia (1)
- Incomplete colonoscopy (1)
- Indirect-binding (1)
- Induced sputum (1)
- Infectious disease epidemiology (1)
- Inflammatory diseases (1)
- Injuries (1)
- Injury (1)
- Insulin (1)
- Intensive care outcome (1)
- Intensive care units (1)
- Interleukin-6 (1)
- Interspecific competition (1)
- Interstitial lung diseases (ILD) (1)
- Intervertebral disc degeneration (1)
- Intra-abdominal infection (1)
- Intracellular pathogens (1)
- Intracerebral haemorrhage (1)
- Intracranial haemorrhage (1)
- Intracranial hemorrhage (1)
- Intragastric balloon (1)
- Inzidenzkorrektur (1)
- Irregular vaccination (1)
- Italy (1)
- Ivor Lewis esophagectomy (1)
- JNK3 (1)
- Jaw (1)
- Jumping (1)
- KAP (1)
- KDIGO (1)
- Kaisidis plate (1)
- Kidney Transplantation (1)
- Kidney transplant recipients (1)
- Knowledge (1)
- Krebsforschung (1)
- Kupffer cells (1)
- Kynurenine (1)
- LCH (1)
- Labor and delivery (1)
- Lactic acidosis (1)
- Landarztprogramm (1)
- Langerhans cell histiocytosis (1)
- Language (1)
- Laparostomy (1)
- Laterality (1)
- Lectin affinity plasmapheresis (1)
- Leflunomide (1)
- Legs (1)
- Lernerfolgsmessung (1)
- Lesions (1)
- Leukocyte elastase (1)
- Light sheet fluorescence microscopy (1)
- Linear regression analysis (1)
- Lipidol (1)
- Lipopolysaccharide-binding protein (1)
- Liver cirrhosis (1)
- Liver transplantation (1)
- Livestock (1)
- LncRNA (1)
- Local climate (1)
- Local control (1)
- Locomotor circuit (1)
- Low volume prep (1)
- Low-grade glioma (1)
- Luciferase (1)
- Lumbar spine (1)
- Lung adenocarcinoma (1)
- Lysosome (1)
- MDR1 (1)
- MEIS2 (1)
- MET (1)
- MOLLI (1)
- MR spectroscopy (1)
- MR-proADM (1)
- MRP4 (1)
- Machine learning (1)
- Macrophages (1)
- Malaria (1)
- Mammalian target of rapamycin (1)
- Marburg virus (1)
- Maternal morbidity (1)
- Maxillary sinus (1)
- Medical communication (1)
- Medical ethics (1)
- Medical hypoxia (1)
- Medical imaging (1)
- Medical risk factors (1)
- Medical traineeship (1)
- Medication Appropriateness Index (1)
- Medication changes (1)
- Medizinische Abbildung (1)
- Medizinische Ausbildung (1)
- Medizinstudierende (1)
- Medizinstudium (1)
- Membrane proteins (1)
- Membrane staining (1)
- Mentor (1)
- Mesangial cells (1)
- Mesh (1)
- Mesh repair (1)
- Messenger RNA (1)
- Metabolic syndrome (1)
- Methotrexate (1)
- Micro RNAs (1)
- Micro-CT (1)
- Microalgae (1)
- Microbial mutation (1)
- Microbiome (1)
- Microsatellite instability (1)
- Middle East respiratory syndrome coronavirus (1)
- Midline laparotomy (1)
- Minimal core of imaging (1)
- Minimal invasive (1)
- Mitochondria (1)
- Mitochondrial ROS (1)
- Mitochondrial disorder (1)
- Mitochondrial proteins (1)
- Mitochondrial respiration (1)
- MitraClip (1)
- Model Organism (1)
- Molecular genetics (1)
- Molecular medicine (1)
- Monocytes and macrophages (1)
- Monolithic crown (1)
- Monte Carlo method (1)
- Morphogenesis (1)
- Mortalitätskorrektur (1)
- Motor skills (1)
- Mountain (1)
- Mouse (1)
- Mouse model (1)
- Mouse models (1)
- Moviprep (1)
- Multi-modal feedback (1)
- Multidisciplinary management (1)
- Multidrug resistance (1)
- Multiple sclerosis (1)
- Multivariate analysis (1)
- Muscle tissue (1)
- Musician-specific seating position (1)
- Myalgia (1)
- Myelofibrosis (1)
- Myocardial infarction (1)
- Myocardial revascularization (1)
- N-Acetylaspartate (1)
- N-acetylcysteine (1)
- N-methyl-D-aspartate receptor (1)
- NAFLD (1)
- NASH (1)
- NDNF interneurons (1)
- NDUFA6 (1)
- NK cells (1)
- NKG2A blocking (1)
- NKG2D (1)
- NK cells (1)
- NOD2 (1)
- NSTEMI (1)
- Nanoparticles (1)
- Natriuretic peptide (1)
- Necrosis (1)
- Necrotizing enterocolitis (1)
- Needs assessment [MeSH] (1)
- Negative staining (1)
- Neoadjuvant therapy (1)
- Neonatal (1)
- Neonatal intensive care unit (1)
- Neonatal morbidity (1)
- Nephrons (1)
- Nerve regeneration (1)
- Nerves (1)
- Neural circuits (1)
- Neurobiology of disease and regeneration (1)
- Neurodevelopment (1)
- Neuroendocrine cancer (1)
- Neuroimaging (1)
- Neutropenia (1)
- Next generation sequencing (1)
- Nfe2l2 (1)
- Niche differentiation (1)
- Nimotuzumab (1)
- Nitric oxide (1)
- Non-interventional study (1)
- Non-responder (1)
- Non-small-cell lung cancer (1)
- Non-trauma (1)
- Noncoding RNA (1)
- Normal distribution (1)
- Nox1 (1)
- Nox4 (1)
- NoxO1 (1)
- Nucleus pulposus cells (1)
- Nutrition (1)
- Nymphs (1)
- OCT (1)
- Observational studies (1)
- Obstetrics and gynecology (1)
- Ocular findings (1)
- Oesophageal cancer (1)
- Okinawa (1)
- Okinawa diet (1)
- Older adults (1)
- Oncologic surgery (1)
- Open abdomen (1)
- Optic nerve atrophy (1)
- Optogenetics (1)
- Oral and maxillofacial trauma (1)
- Oral anticoagulation (1)
- Oral surgery (1)
- Ordinary least squares (OLS) (1)
- Organ dysfunction (1)
- Organ dysfunctions (1)
- Organ support (1)
- Organs at Risk (1)
- Oroantral (1)
- Osimertinib (1)
- Osteogenic differentiation (1)
- Outcome assessment (1)
- Outcome assessment [MeSH] (1)
- OxyELITE Pro (1)
- P-gp (1)
- P1NP (1)
- P2X7 receptor (1)
- PAH (1)
- PAI-1 (1)
- PBX1 (1)
- PC12 cells (1)
- PCV (1)
- PD-L1 (1)
- PEGylated PLGA (PLGA-PEG) (1)
- PFL (1)
- PI3K (1)
- PKA (1)
- PTCH (1)
- PTDM (1)
- PTK2B (1)
- Pacemaker (1)
- Pain (1)
- Pancreatitis (1)
- Parkin (1)
- Parkinson disease (1)
- Pathological complete response (1)
- Pathology (1)
- Patient Blood Management (1)
- Patient Outcome Assessment (1)
- Patient satisfaction (1)
- Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (1)
- Pediatrics [MeSH] (1)
- Peer Teaching (1)
- Peer teaching (1)
- Periodontal diseases (1)
- Peritonitis (1)
- Personality (1)
- Personalized medicine (1)
- Pessar (1)
- Pharmacy setting (1)
- Pharyngeal reflex (1)
- Phospho-soda (1)
- Phospholipids (1)
- Phosphorylation (1)
- Phylogenetic analysis (1)
- Physical environment (1)
- Physicians (1)
- Physiology (1)
- PillCamColon2 (1)
- Polyps (1)
- Portal hypertension (1)
- Position paper (1)
- Post-transplant (1)
- Postoperative infections (1)
- Posttranslational modification (1)
- Postural control (1)
- Poverty (1)
- Practice (1)
- Preclinical (1)
- Pregnancy (1)
- Preterm birth (1)
- Primary health care (1)
- Progesteron (1)
- Progesterone (1)
- Prognostic markers (1)
- Programming languages (1)
- Progranulin (1)
- Proliferation (1)
- Prostate Cancer (1)
- Prostate cancer cell lines (1)
- Prosthetic rehabilitation (1)
- Protein domains (1)
- Protein translation (1)
- Proteins (1)
- Prothrombin complex concentrate (1)
- Prüfungsfragen (1)
- Psychiatric disorders (1)
- Psychology (1)
- Public and occupational health (1)
- Pulmonary artery pressure (1)
- Pulmonary embolism (1)
- Pyruvate (1)
- Qualitative research [MeSH] (1)
- Quality of health care [MeSH] (1)
- Quality of life (1)
- Quantitative MRI (1)
- Quantitative trait loci (1)
- Questionnaires (1)
- Quinolinate phosphoribosyltransferase (1)
- Quinolinic acid (1)
- RNA therapy (1)
- RNA viruses (1)
- ROS (1)
- Rab7 (1)
- Radical nephrectomy (1)
- Rainfall (1)
- Randomized (1)
- RapL (1)
- Rapamycin (1)
- Rare diseases (1)
- Re-exploration (1)
- Rearing temperature (1)
- Red blood cell transfusion (1)
- Redox modification (1)
- Regeneration (1)
- Regression analysis (1)
- Regulatory networks (1)
- Reintervention (1)
- Remote monitoring (1)
- Renal cancer (1)
- Renal system (1)
- Research Article (1)
- Research architecture (1)
- Resource competition (1)
- Respiratory tract diseases (1)
- Response criteria (1)
- Resuscitation (1)
- Retinal degeneration (1)
- Rheumatoid arthritis (1)
- Rivaroxaban (1)
- Rural area (1)
- Ruxolitinib (1)
- S1P (1)
- SAVI (1)
- SCMR (1)
- SDH (1)
- SKAP1 (1)
- SMAD signaling (1)
- SOFA (1)
- STING (1)
- Safety equipment (1)
- Safety learning (1)
- Sarcoidosis (1)
- Scientific publishing (1)
- Secretion (1)
- Senescence (1)
- Sensitivity (1)
- Sensory Neuroscience (1)
- Sensory processing (1)
- Septic shock (1)
- Sequence alignment (1)
- Serum (1)
- Severe blood loss (1)
- Severity of illness index (1)
- Sex differences (1)
- Shannon index (1)
- Sholl analysis (1)
- Simulated patients (1)
- Single-cell RNA-seq (1)
- Smac mimetic (1)
- Small molecules (1)
- Small-cell lung cancer (1)
- Smart nebulizer (1)
- Smoking habits (1)
- Social communication (1)
- Social research (1)
- Social sciences (1)
- Solidworks 2015 (1)
- Sphingolipids (1)
- Spine Register (1)
- Spirochetes (1)
- Sports (1)
- Sports and exercise medicine (1)
- Spot sign (1)
- Standards of care (1)
- Starvation (1)
- Statistical data (1)
- Statistical methods (1)
- Status epilepticus (1)
- Stenotrophomonas maltophilia (1)
- Stereotactic radiosurgery (1)
- Stoma (1)
- Streptococcus pneumoniae (1)
- Stringed bow player (1)
- Structural MRI (1)
- Structural genomics (1)
- Study protocol (1)
- Suicide (1)
- Sulfasalazine (1)
- Sumatra (1)
- Supraspinatus tendon (1)
- Surgical ICU (1)
- Surgical site occurrence (1)
- Survival analysis (1)
- Survival data (1)
- Sweat osmolality (1)
- Sweat secretion rate (1)
- Syncope (1)
- Synthetic (1)
- T cell (1)
- T cells (1)
- T helper 17 cells (1)
- T-DM1 (1)
- T-cell targeting (1)
- T-cells (1)
- T1 mapping (1)
- TALE-homdomain protein (1)
- TAVR (1)
- TBSS (1)
- TC stenosis (1)
- TF-complexes (1)
- TMS-EEG (1)
- TNF inhibitors (1)
- TNF-α (1)
- TOR inhibitor (1)
- TP53 mutation status (1)
- Targeted therapy (1)
- Taxonomy (1)
- Technique (1)
- Telemedicine (1)
- Temporal lobe epilepsy (1)
- Term birth (1)
- Testosterone (1)
- Tet-inducible system (1)
- Thailand (1)
- Thermoregulation (1)
- Three-dimensional back scan (1)
- Thrombosis (1)
- Thyroid (1)
- Tick-Borne diseases (1)
- Tick-borne encephalitis (1)
- Timing (1)
- Tinnitus (1)
- Tomography (1)
- Tooth transplantation (1)
- Torque (1)
- Toxicity (1)
- Training (1)
- Tranexamic acid (1)
- Transcription (1)
- Transcription Factors (1)
- Transcription factors (1)
- Transferases (1)
- Transfusion (1)
- Transgenic SK-2 mice (1)
- Trauma surgery (1)
- Traumatic brain injury (1)
- Traumatic injury (1)
- Treatment (1)
- Trichuris suis ova (1)
- Triple negative (1)
- Triple therapy (1)
- Triple-negative breast cancer (1)
- Troponin (1)
- Tubers (1)
- Tumor infiltrating lymphocytes (1)
- Tumour biomarkers (1)
- Type 2 diabetes (1)
- UDP-glucose ceramide glycosyltransferase (1)
- UGCG (1)
- ULBP4 (1)
- UWB diagnostics (1)
- Ubiquitin (1)
- Ubiquitination (1)
- Ultra microscopy (1)
- Ultrasonic nebulizer (1)
- Ultrasound imaging (1)
- Upper body posture (1)
- Usutu virus (1)
- V4 (1)
- VEGF (1)
- VIP1 (1)
- Vaccination breakthrough (1)
- Vaccine (1)
- Vascular emergencies (1)
- Vector mosquito (1)
- Viral core (1)
- Viral replication (1)
- Vision (1)
- Visual acuity (1)
- Vitamin (1)
- Volumetric analysis (1)
- Vorklinik (1)
- Warburg effect (1)
- Water chemistry (1)
- Weight loss (1)
- West Nile fever (1)
- West Nile neuroinvasive disease (1)
- West Nile virus (1)
- Work shadowing (1)
- Working memory (1)
- X-ray crystallography (1)
- XL probe (1)
- Yarrowia lipolytica (1)
- Zervixverkürzung (1)
- Zika (1)
- Zika vaccine (1)
- Zika virus (1)
- Zirconia (1)
- Zoopotentation (1)
- Zooprophylaxis (1)
- abemaciclib (1)
- abnormal tumor vasculature (1)
- accident (1)
- acetaminophen (1)
- acetyl-CoA (1)
- activation receptors (1)
- active/deactive transition (1)
- actography (1)
- acute cholecystitis (1)
- acute coronary syndrome (1)
- acute exacerbations of COPD (1)
- acute inflammation (1)
- acute myeloid leukemia (1)
- adaptation (1)
- adenosine receptors (1)
- adherence (1)
- adhesion (1)
- adipose-derived mesenchymal stem cells (1)
- adoptive cell therapy (1)
- adoptive immunotherapy (1)
- advanced breast cancer (1)
- adverse reaction (1)
- aerosol (1)
- aggression (1)
- airway remodeling (1)
- aliphatic halogenated hydrocarbons (1)
- alirocumab (1)
- allergen immunotherapy (1)
- allergic rhinitis (1)
- allogeneic stem cell transplantation (1)
- alpinia zerumbet (1)
- anaesthesia in orthopaedics (1)
- anaesthetics (1)
- anastomotic leakage (1)
- anatomy (1)
- anatomy and histology (1)
- anti-GD2 immunotherapy (1)
- anti-inflammatory (1)
- antibiotic (1)
- antibiotic therapy (1)
- antibodies (1)
- anticonvulsants (1)
- antihormone therapy (1)
- antimicrobial activity (1)
- antioxidant (1)
- antioxidant activity (1)
- antisense oligonucleotides (1)
- aortic stenosis (1)
- apoptosis (1)
- apps (1)
- aptamer (1)
- aquaporin 1 (1)
- arachidonate 15-lipoxygenase (1)
- arachidonic acid (1)
- ascites (1)
- asthma (1)
- atrial fibrillation (1)
- atrial septostomy (1)
- atrophy (1)
- autoimmunity (1)
- autologous stem cell transplantation (1)
- avelumab (1)
- back scan (1)
- bacterium (1)
- balanced state (1)
- basal cell carcinoma (1)
- basic leucine zipper transcription factor ATF-like (1)
- beta blockade (1)
- betamethasone dipropionate (1)
- bevacizumab (1)
- bibliometric analysis (1)
- bibliometry (1)
- bio imaging (1)
- bioactive phytochemicals (1)
- bioluminescence (1)
- biomarker (1)
- biopsy (1)
- bipolar disorders (1)
- birch pollen allergoid (1)
- blood (1)
- blood donor (1)
- blow flies (1)
- blow fly (1)
- body posture (1)
- borrelia (1)
- brachytherapy (1)
- bronchodilator (1)
- buccal mucosa (1)
- cAMP (1)
- cFLIP (1)
- calcification score (1)
- calcipotriol (1)
- calcium-independent phospholipase A2β (1)
- cancer stem cells (1)
- carbon tetrachloride (1)
- cardiovascular diseases (1)
- cardiovascular precision medicine (1)
- caspase-2 (1)
- ceRNA (1)
- celery (1)
- cell biology (1)
- cell cycle (1)
- cell migration (1)
- cellular signalling (1)
- centenarians (1)
- cerclage (1)
- cerebrospinal fluid (1)
- cervical cancer (1)
- cervical shortening (1)
- cervical spine (1)
- cervico-thoracic junction (1)
- ch14.18/CHO (1)
- chamomile (1)
- checkpoint inhibition (1)
- chemokine (1)
- chemotaxis (1)
- chemotherapeutic drug resistance (1)
- child abuse and neglect (1)
- child maltreatment (1)
- children (1)
- cholangiocarcinoma (1)
- cholesterol (1)
- chromosomal integration (1)
- cilia (1)
- circadian rhythms (1)
- circadian variation (1)
- cisplatin resistance (1)
- clinical management (1)
- clinical practice (1)
- clinical trial (1)
- cognition (1)
- cognitive states (1)
- cohort study (1)
- colitis (1)
- collagen (1)
- collagen-based biomaterial (1)
- collective dynamics (1)
- colon (1)
- colon carcinoma cells (1)
- column chromatography (1)
- combination (1)
- combination therapy (1)
- combined immunodeficiency (1)
- complement dependent cytotoxicity (1)
- complementary information (1)
- complex I (1)
- complexome profiling (1)
- complications (1)
- computational virology (1)
- computer-assisted drug therapy (1)
- congenic mice (1)
- contact lens solution (1)
- continuous glucose monitoring (1)
- controlled nuclear import (1)
- coronary (1)
- coronary disease (1)
- correction of incidence rate (1)
- correction of mortality rate (1)
- corrosion (1)
- criticality (1)
- cryoballoon (1)
- cumulative dose (1)
- curriculum (1)
- cytarabine dose (1)
- cytochrome P450 2E1 (1)
- cytokine release syndrome (1)
- cytokine-induced killer cells (1)
- cytotoxic T cells (1)
- dabrafenib (1)
- damage associated molecular pattern (1)
- decision aids (1)
- delayed cholecystectomy (1)
- delta-9-tetrahydrocannabinol (1)
- dendritic cells (1)
- dendritic inhibition (1)
- dental abutment (1)
- dental implants (1)
- dermatology (1)
- dexamethasone (1)
- diabetes (1)
- diabetic macular edema (1)
- diagnostics (1)
- dietary supplements (1)
- differentiated thyroid carcinoma (1)
- differentiation (1)
- diffuse low-grade glioma (1)
- digital age determination (1)
- dihydroceramides (1)
- diplopia (1)
- direct-acting antivirals (1)
- disease progression (1)
- disintegration (1)
- dose response curve (1)
- doxorubicin (1)
- doxycycline (1)
- drug interaction (1)
- drug release (1)
- drug-coated balloon (1)
- drug-eluting balloon (1)
- dynamic stimuli (1)
- eNPP2 (1)
- early cholecystectomy (1)
- educational cases (1)
- educational measurement (1)
- efficacy (1)
- elderly (1)
- embodiment (1)
- emulsion diffusion (1)
- encoding (1)
- endogenous clock (1)
- endoplasmic reticulum (1)
- endothelial activation (1)
- endothelial barrier (1)
- endothelial cell (1)
- endothelial nitric-oxide synthase (1)
- epidemics (1)
- epidemiology (1)
- epileptic encephalopathies (1)
- event-based (1)
- excitability (1)
- exercise (1)
- exosomes (1)
- exponential model (1)
- extracting solvents (1)
- fMRI (1)
- face (1)
- facial EMG (1)
- facial emotion recognition (1)
- facial expressions of emotion (1)
- facial muscle activity (1)
- factor H (1)
- falls (1)
- false memory (1)
- fear learning (1)
- female subjects (1)
- femoropopliteal segment (1)
- fibrinolysis (1)
- fibrosis (1)
- flow cytometry (1)
- fluocinolone acetonide (1)
- focal adhesion (1)
- forensics (1)
- functional connectivity (1)
- functional genomics (1)
- functional magnetic resonance imaging (fMRI) (1)
- fungus (1)
- galactomannan (1)
- gallstone disease (1)
- gastric cancer (1)
- gastro-oesophageal junction cancer (1)
- gene delivery (1)
- gene therapy (1)
- gene vectors (1)
- general anaesthesia (1)
- general practice (1)
- genetic markers (1)
- geriatric medicine (1)
- germinal center (1)
- glioma (1)
- glioma-associated oncogene homolog (1)
- gliomas (1)
- global mapping (1)
- glucocorticoid (1)
- glucose metabolism (1)
- glycolysis (1)
- graft perfusion (1)
- graft rejection (1)
- graft-versus-host disease (1)
- graft-versus-tumor effect (1)
- granulocytemacrophage colony-stimulating factor (1)
- granulomas (1)
- granulomatous inflammation (1)
- green tea extract (1)
- hanging donors (1)
- head and neck squamous cell carcinoma (1)
- head-and-neck cancer (1)
- headache (1)
- health (1)
- health care personnel (1)
- health information exchange (1)
- health services accessibility (1)
- health-related quality of life (1)
- heart failure (1)
- hedgehog signaling pathway (1)
- helminths (1)
- hematopoietic stem cells (1)
- hepatitis B virus (1)
- hepatitis C virus (HCV) (1)
- hepatitis E virus (1)
- hepatocyte transplantation (1)
- hereditary angioedema (1)
- hierarchy (1)
- hippocampal neuronal cell line (1)
- histone acetylation (1)
- histone deacetylase (1)
- histone deacetylase 5 (1)
- host-targeting antivirals (1)
- human biology and medicine (1)
- human papilloma virus (1)
- human renal proximal tubular epithelial cells (1)
- humanized mouse (1)
- humans (1)
- humoral factors (1)
- hybrid (1)
- hydrocephalus (1)
- hydroxyapatite crystals (1)
- hyperbaric oxygen treatment (1)
- hyperlipidemia (1)
- hypothalamus (1)
- hypoxia-induced cell death (1)
- imitation (1)
- immune (1)
- immune reconstitution (1)
- immunohistochemistry (1)
- in-cabin exposure (1)
- inducible gene expression (1)
- infectivity (1)
- inflammasome (1)
- influenza (1)
- influenza vaccine (1)
- information decomposition (1)
- inhaler (1)
- innate lymphoid cells (1)
- insulin resistance (1)
- integration (1)
- integrin (1)
- integrins (1)
- interferon (1)
- interferon gamma (1)
- interleukin-1 (1)
- interleukin-18 (1)
- interleukin-1β (1)
- interleukin-23 receptor (1)
- interneurons (1)
- interstitial brachytherapy (1)
- intervertebral disc degeneration (1)
- intestinal graft-versushost disease (1)
- intracellular trafficking (1)
- intraperitoneal therapy (1)
- intraventricular chemotherapy (1)
- invasion (1)
- ionomycin (1)
- irradiation (1)
- ischemic type biliary lesions (1)
- isocaloric ketogenic diet (1)
- isovaleric acidaemia (1)
- kavalactones (1)
- keratinocytes (1)
- kinase inhibitor (1)
- knockout mice (1)
- knowledge discovery (1)
- laceration (1)
- lapatinib (1)
- late lumen loss (1)
- layer 1 (1)
- leptomeningeal metastases (1)
- levetiracetam (1)
- lipoxygenase (1)
- liver cirrhosis (1)
- liver fibrosis (1)
- liver transplantation (1)
- long-acting muscarinic antagonist (1)
- long-term follow-up (1)
- long-term infusion (1)
- longevity (1)
- lung cancer (1)
- lung remodeling (1)
- lung transplantation (1)
- lymphocyte (1)
- lymphoma (1)
- mTOR (1)
- mTOR inhibitor (1)
- mTORC1 (1)
- machine-learning (1)
- macula (1)
- magnetoencephalography (1)
- maintenance (1)
- malignancy (1)
- marginal bone loss (1)
- markovianity (1)
- massively parallel multigrid solvers (1)
- maternal care (1)
- mathematical modeling (1)
- measure development/validation (1)
- mechanobactericidal surfaces (1)
- medical illustration (1)
- medical school (1)
- medication reconciliation (1)
- memebrane (1)
- mentoring (1)
- metabolic cancer therapy (1)
- metamorphosis (1)
- metastatic (1)
- methotrexate (1)
- methyltransferases (1)
- miR-122 (1)
- miR-21 (1)
- microdosing (1)
- microsaccades (1)
- microsatellite instability (1)
- microwave breast imaging (1)
- migrants (1)
- migration (1)
- mitochondrial disease (1)
- mobile air quality study (1)
- moisturing cream (1)
- molecular identification (1)
- molecular mechanisms (1)
- momilactone A (1)
- momilactone B (1)
- monkey (1)
- mouse (1)
- multidrug resistance (1)
- multimorbidity (1)
- multinucleated giant cells (1)
- multiple chronic conditions (1)
- multiple myeloma (1)
- multiple sclerosis (1)
- multisite cooperation (1)
- myocyte enhancer factor 2 (1)
- nanostructures (1)
- natural killer T cells (1)
- natural killer cell (1)
- neocortical circuits (1)
- neoepitopes (1)
- neonatal intensive care unit (1)
- neonate (1)
- neural network (1)
- neural oscillations (1)
- neuraminidase inhibitor (1)
- neuro-ophthalmological examination (1)
- neuroblastoma (1)
- neurocognition (1)
- neurocritical care (1)
- neurogenesis (1)
- neurological emergencies (1)
- neuromodulation (1)
- neurophysiology (1)
- neuropilin-1 (1)
- nitric oxide (1)
- nitro-fatty acids (1)
- non-ST-segment elevation acute coronary syndrome (1)
- nonalcoholic fatty liver disease (1)
- nonalcoholic steatohepatitis (1)
- nonviral gene delivery (1)
- novel psychoactive substance (1)
- nursery school students (1)
- nursery schools (1)
- nursery students (1)
- nurses (1)
- obese (1)
- object tracking (1)
- omega-3 fatty acids (1)
- oncogene (1)
- one health (1)
- open-source (1)
- oral kallikrein inhibitor (1)
- orthopic liver transplantation (1)
- oscillations (1)
- oseltamivir (1)
- ostium (1)
- outcome (1)
- outcomes (1)
- ovarian cancer (1)
- oxygen (1)
- p21-activated kinase 2 (1)
- p38 (1)
- p97 (1)
- pCREB (1)
- palbociclib (1)
- palmitoylation (1)
- papilloma (1)
- parameter estimation (1)
- parsley (1)
- particle size distribution (1)
- particulate matter (1)
- patency (1)
- patient study (1)
- patients (1)
- pentose phosphate pathway (1)
- pericytes (1)
- peripheral artery disease (1)
- peripheral vascular diseases (1)
- peritoneal carcinomatosis (1)
- persistent atrial fibrillation (1)
- persisting pain (1)
- personalized oncology (1)
- pertuzumab (1)
- pessary (1)
- pharmacology (1)
- phase III (1)
- phase-1 (1)
- phenolics (1)
- phenylephrine (1)
- phosphate (1)
- photoaging (1)
- physical activity (1)
- physical activity promotion (1)
- physical activity recommendations (1)
- pictilisib (1)
- pig (1)
- pivalate (1)
- pivoloyl (1)
- plasminogen (1)
- platform-switched (1)
- polarization (1)
- poly(I:C) (1)
- poly(lactic-co-glycolic acid) (PLGA) (1)
- polydipsia (1)
- polylactic acid (PLA) (1)
- polymerase chain reaction (1)
- polypharmacy (1)
- polyphenols (1)
- polytrauma (1)
- polyuria (1)
- popliteal artery (1)
- porcine (1)
- post-transplantation lymphoproliferative disease (1)
- posttranslational modification (1)
- pre-emptive allogeneic hematopoietic stem cell transplantation (1)
- preclinical semesters (1)
- preconditioning (1)
- pressure (1)
- pressurized intraperitoneal aerosol chemotherapy (PIPAC) (1)
- preterm (1)
- preterm birth (1)
- pretreatment (1)
- prevalence of hysterectomy (1)
- prevent smoking (1)
- primary cilium (1)
- primary healthcare (1)
- primary mouse proximal tubular cells (1)
- progesterone (1)
- programmed cell death ligand 1 (1)
- programmed cell death protein 1 (1)
- proliferation (1)
- prophylaxis (1)
- propofol anesthesia (1)
- prospective memory (1)
- prostaglandin E2 (1)
- prostate cancer (1)
- protein kinase D (1)
- protein kinases (1)
- proteomics (1)
- pruritus (1)
- psoriatic arthritis (1)
- psychological questionnaires (1)
- psychometric properties (1)
- publication (1)
- pulmonary arterial hypertension (1)
- pulmonary inflammation (1)
- pulmonary vein isolation (1)
- qPCR (1)
- qRT-PCR (1)
- qualitative research (1)
- quality control (1)
- radical scavenging chemicals (1)
- radiofrequency (1)
- radiotherapy (1)
- radiotherapy resistance (1)
- rare diseases (1)
- rat (1)
- real-world evidence (1)
- realistic geometries (1)
- redox signalling (1)
- redox-linked proton translocation (1)
- redundancy (1)
- redundant information (1)
- reference values (1)
- regulatory T cell (1)
- relapsing–remitting (1)
- reliability (1)
- remote ischemic preconditioning (1)
- renal cell cancer (1)
- renal cell carcinoma (1)
- renal failure (1)
- renal ischemia reperfusion injury (1)
- research consortium (1)
- resilience (1)
- respiratory complex I (1)
- restenosis (1)
- restrictive atrial communication (1)
- retina (1)
- retinoic acid-related orphan receptor gamma t (1)
- rhodocetin-αβ (1)
- rhythm (1)
- ribociclib (1)
- rice husk (1)
- risk assessment (1)
- rural health program (1)
- saliva (1)
- school-based prevention (1)
- scientometrics (1)
- scientometry (1)
- screening routine (1)
- secretion (1)
- selection (1)
- selective attention (1)
- selective mutism, (1)
- semen (1)
- sensitization (1)
- sensory neurons (1)
- sequential ALK-inhibitor therapy (1)
- shedding (1)
- shell ginger (1)
- shortage of family doctors (1)
- siRNA (1)
- signaling (1)
- silence interfering RNA (1)
- sirtuin1 (1)
- sirtuins (1)
- skeletal muscle (1)
- skin (1)
- smoking (1)
- smoking cessation (1)
- solvent displacement (1)
- somatostatin interneurons (1)
- sonidegib (1)
- spatial (1)
- sphinganine 1-phosphate (1)
- sphingosine kinase 1 (1)
- spinster homology protein 2 (Spns2) (1)
- spirochetes (1)
- squamous cell carcinoma (1)
- standard value (1)
- stem cell niche (1)
- stem cells (1)
- stenosis (1)
- stenosis quantification (1)
- sterol regulatory element binding protein-2 (1)
- stroke (1)
- structural biology and molecular biophysics (1)
- subcutaneous immunotherapy (1)
- sublingual immunotherapy (1)
- subventricular zone (1)
- superficial femoral artery (1)
- syncope (1)
- synergy (1)
- tear (1)
- temozolomide (1)
- temperature (1)
- temsirolimus (1)
- testicular cancer (1)
- tetracycline (1)
- tetrahydrobiopterin (1)
- thymus (1)
- titanium (1)
- titanium particles (1)
- tobacco (1)
- tobacco cessation (1)
- tomography (1)
- top-down processing (1)
- topical agent (1)
- total events (1)
- total flavonoids (1)
- total phenols (1)
- toxicity (1)
- tracking (1)
- traffic emissions (1)
- transcatheter aortic valve replacement (1)
- transcranial magnetic stimulation (1)
- transcriptome analysis (1)
- transfemoral (1)
- transgelin (1)
- transient elastography (1)
- transketolase-like protein 1 (1)
- translational cancer research (1)
- transposition (1)
- trastuzumab (1)
- trauma (1)
- trehalose (1)
- tubular regeneration (1)
- tumor metabolism (1)
- tumor-infiltrating lymphocytes (1)
- type B (1)
- ubiquitin (1)
- unique information (1)
- upper gastrointestinal cancer (1)
- vaccination rates (1)
- vaccine (1)
- vaccine acceptance (1)
- vaccine trial (1)
- validity (1)
- vascular calcification (1)
- vascular endothelial growth factor receptor 2 (1)
- vascular smooth muscle cells (1)
- vasculogenic mimicry (1)
- vasoconstriction (1)
- vasodilation (1)
- vasopressin (1)
- ventilation modes (1)
- ventral striatum (1)
- ventriculoperitoneal shunt (1)
- vesicular glutamate transporter 2 (1)
- vessel-associated mural cells (1)
- videos (1)
- viral dynamics (1)
- virus (1)
- virus-like particles (1)
- vision (1)
- vismodegib (1)
- vismodegib (GDC-0449) (1)
- visual cortex (1)
- visuo-spatial attention (1)
- vitamin D (1)
- vitamin D receptor (1)
- wear (1)
- white-matter (1)
- wild animals (1)
- willingness to participate (1)
- within-host viral modelling (1)
- working memory (1)
- wound healing (1)
- yield optimization (1)
- ß-D-glucan (1)
- α-mannosidosis (1)
Institute
Arachidonate 15-lipoxygenase (ALOX15) and arachidonate 15-lipoxygenase, type B (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids and are upregulated in human alternatively activated macrophages (AAMs) induced by Th2 cytokine interleukin-4 (IL-4) and/or interleukin-13. Known primarily for roles in bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been implicated in various macrophage functions including efferocytosis and ferroptosis. Using a combination of inhibitors and siRNAs to suppress 15-LOX isoforms, we studied the role of 15-LOXs in cellular cholesterol homeostasis and immune function in naïve and AAMs. Silencing or inhibiting the 15-LOX isoforms impaired sterol regulatory element binding protein (SREBP)-2 signaling by inhibiting SREBP-2 processing into mature transcription factor and reduced SREBP-2 binding to sterol regulatory elements and subsequent target gene expression. Silencing ALOX15B reduced cellular cholesterol and the cholesterol intermediates desmosterol, lanosterol, 24,25-dihydrolanosterol, and lathosterol as well as oxysterols in IL-4-stimulated macrophages. In addition, attenuating both 15-LOX isoforms did not generally affect IL-4 gene expression but rather uniquely impacted IL-4-induced CCL17 production in an SREBP-2-dependent manner resulting in reduced T cell migration to macrophage conditioned media. In conclusion, we identified a novel role for ALOX15B, and to a lesser extent ALOX15, in cholesterol homeostasis and CCL17 production in human macrophages.
A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets
(2018)
NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCRB6C14R strain. Ly5.1C14R NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1C14R mice had normal number of NK cells, they showed an increased number of early maturation stage NK cells. CD49a+ILC1s were also increased but these cells lacked the expression of TRAIL. ILC3s that expressed NKp46 were not detectable and were not apparent when examined by T-bet expression. Thus, the C14R mutation reveals that NKp46 is important for NK cell and ILC differentiation, maturation and function.
Background: Incisional heia is a frequent complication of midline laparotomy. The use of mesh in hernia repair has been reported to lead to fewer recurrences compared to primary repair. However, in Ventral Hernia Working Group (VHWG) Grade 3 hernia patients, whose hernia is potentially contaminated, synthetic mesh is prone to infection. There is a strong preference for resorbable biological mesh in contaminated fields, since it is more able to resist infection, and because it is fully resorbed, the chance of a foreign body reaction is reduced. However, when not crosslinked, biological resorbable mesh products tend to degrade too quickly to facilitate native cellular ingrowth. Phasix™ Mesh is a biosynthetic mesh with both the biocompatibility and resorbability of a biological mesh and the mechanical strength of a synthetic mesh. This multi-center single-arm study aims to collect data on safety and performance of Phasix™ Mesh in Grade 3 hernia patients.
Methods: A total of 85 VHWG Grade 3 hernia patients will be treated with Phasix™ Mesh in 15 sites across Europe. The primary outcome is Surgical Site Occurrence (SSO) including hematoma, seroma, infection, dehiscence and fistula formation (requiring intervention) through 3 months. Secondary outcomes include recurrence, infection and quality of life related outcomes after 24 months. Follow-up visits will be at drain removal (if drains were not placed, then on discharge or staple removal instead) and in the 1st, 3rd, 6th, 12th, 18th and 24th month after surgery.
Conclusion: Based on evidence from this clinical study Depending on the results this clinical study will yield, Phasix™ Mesh may become a preferred treatment option in VHWG Grade 3 patients.
Trial registration: The trial was registered on March 25, 2016 on clinicaltrials.gov: NCT02720042.
Acetaminophen [paracetamol, N-acetyl-p-aminophenol (APAP)]-induced acute liver injury (ALI) not only remains a persistent clinical challenge but likewise stands out as well-characterized paradigmatic model of drug-induced liver damage. APAP intoxication associates with robust hepatic necroinflammation the role of which remains elusive with pathogenic but also pro-regenerative/-resolving functions being ascribed to leukocyte activation. Here, we shine a light on and put forward a unique role of the interleukin (IL)-1 family member IL-18 in experimental APAP-induced ALI. Indeed, amelioration of disease as previously observed in IL-18-deficient mice was further substantiated herein by application of the IL-18 opponent IL-18-binding protein (IL-18BPd:Fc) to wild-type mice. Data altogether emphasize crucial pathological action of this cytokine in APAP toxicity. Adding recombinant IL-22 to IL-18BPd:Fc further enhanced protection from liver injury. In contrast to IL-18, the role of prototypic pro-inflammatory IL-1 and tumor necrosis factor-α is controversially discussed with lack of effects or even protective action being repeatedly reported. A prominent detrimental function for IL-18 in APAP-induced ALI as proposed herein should relate to its pivotal role for hepatic expression of interferon-γ and Fas ligand, both of which aggravate APAP toxicity. As IL-18 serum levels increase in patients after APAP overdosing, targeting IL-18 may evolve as novel therapeutic option in those hard-to-treat patients where standard therapy with N-acetylcysteine is unsuccessful. Being a paradigmatic experimental model of ALI, current knowledge on ill-fated properties of IL-18 in APAP intoxication likewise emphasizes the potential of this cytokine to serve as therapeutic target in other entities of inflammatory liver diseases.
Autophagy is a cytosolic quality control process that recognizes substrates through receptor‐mediated mechanisms. Procollagens, the most abundant gene products in Metazoa, are synthesized in the endoplasmic reticulum (ER), and a fraction that fails to attain the native structure is cleared by autophagy. However, how autophagy selectively recognizes misfolded procollagens in the ER lumen is still unknown. We performed siRNA interference, CRISPR‐Cas9 or knockout‐mediated gene deletion of candidate autophagy and ER proteins in collagen producing cells. We found that the ER‐resident lectin chaperone Calnexin (CANX) and the ER‐phagy receptor FAM134B are required for autophagy‐mediated quality control of endogenous procollagens. Mechanistically, CANX acts as co‐receptor that recognizes ER luminal misfolded procollagens and interacts with the ER‐phagy receptor FAM134B. In turn, FAM134B binds the autophagosome membrane‐associated protein LC3 and delivers a portion of ER containing both CANX and procollagen to the lysosome for degradation. Thus, a crosstalk between the ER quality control machinery and the autophagy pathway selectively disposes of proteasome‐resistant misfolded clients from the ER.
Background: Prospective memory is the ability to recall intended actions or events at the right time or in the right context. While cannabis is known to impair prospective memory, the acute effect of cocaine is unknown. In addition, it is not clear whether changes in prospective memory represent specific alterations in memory processing or result from more general effects on cognition that spread across multiple domains such as arousal and attention.
Aims: The main objective of the study was, therefore, to determine whether drug-induced changes in prospective memory are memory specific or associated with more general drug-induced changes in attention and arousal.
Methods: A placebo-controlled, three-way, cross-over study including 15 regular poly-drug users was set up to test the influence of oral cocaine (300 mg) and vaporised cannabis (300+150 ‘booster’ µg/kg bodyweight) on an event-based prospective memory task. Attentional performance was assessed using a divided attention task and subjective arousal was assessed with the Profile of Mood States questionnaire.
Results: Results showed that cocaine enhanced prospective memory, attention and arousal. Mean performance of prospective memory and attention, as well as levels of arousal were lowest during treatment with cannabis as compared with placebo and cocaine as evinced by a significantly increased trend across treatment conditions. Prospective memory performance was only weakly positively associated to measures of attention and arousal.
Conclusion: Together, these results indicate that cocaine enhancement of prospective memory performance cannot be fully explained by parallel changes in arousal and attention levels, and is likely to represent a direct change in the neural network underlying prospective memory.
Background: Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly tolerated or contraindicated in some patients. There is a wealth of data supporting the use of abatacept in combination with MTX, but data on alternative conventional synthetic disease-modifying antirheumatic drug (csDMARD) combinations with abatacept are scarce.
Methods: In this post-hoc exploratory analysis, efficacy and safety data were extracted from abatacept RA studies in which combination with csDMARDs other than MTX was permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real-world study (ACTION). Patients with moderate-to-severe RA received abatacept in combination with MTX, hydroxychloroquine, sulfasalazine, azathioprine, or leflunomide for 6 months to 2 years according to the study design. Change from baseline in physical function (Health Assessment Questionnaire—Disability Index (HAQ-DI); all studies) and 28-joint Disease Activity Score (C-reactive protein) (DAS28 (CRP); ATTAIN, ARRIVE, and ACTION), American College of Rheumatology response rates (ATTAIN), and safety were assessed for individual and pooled csDMARD combinations for each trial. A meta-analysis was also performed on pooled data for HAQ-DI and DAS28 (CRP) across interventional trials.
Results: Across all four studies, 731 patients received abatacept plus one non-MTX csDMARD (hydroxychloroquine n = 152; sulfasalazine n = 123; azathioprine n = 59; and leflunomide n = 397) and 2382 patients received abatacept plus MTX. Mean changes from baseline in HAQ-DI scores for abatacept plus MTX (all csDMARDs pooled) vs abatacept plus a non-MTX csDMARD were –0.54 vs –0.44 (ATTAIN), –0.43 vs –0.43 (ASSURE), and –0.39 vs –0.36 (ARRIVE). Mean changes from baseline in DAS28 (CRP) and ACR response rates were also similar with abatacept plus MTX or non-MTX csDMARDs. Data for individual non-MTX csDMARDs (pooled across studies) and real-world data were consistent with these findings. Rates of treatment-related adverse events and serious adverse events, respectively, for abatacept plus one non-MTX csDMARD vs abatacept plus MTX were 35.7% vs 41.7% and 2.4% vs 2.3% (ATTAIN), 58.0% vs 55.9% and 4.2% vs 1.7% (ASSURE), and 38.1% vs 44.3% and 0.6% vs 2.9% (ARRIVE).
Conclusions: Abatacept in combination with non-MTX csDMARDs is clinically effective and well tolerated in patients with moderate-to-severe RA, providing similar benefits to those seen with abatacept plus MTX.
Background: Stem cell therapy is considered as a promising alternative to treat intervertebral disc degeneration (IDD). Extensive work had been done on identifying and comparing different types of candidate stem cells, both in vivo and in vitro. However, few studies have shed light on degenerative nucleus pulposus cells (NPCs), especially their biological behavior under the influence of exogenous stem cells, specifically the gene expression and regulation pattern. In the present study, we aimed to determine messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs), which are differentially expressed during the co-culturing process with adipose-derived mesenchymal stem cells (ASCs) and to explore the involved signaling pathways and the regulatory networks.
Methods: We compared degenerative NPCs co-cultured with ASCs with those cultured solely using lncRNA-mRNA microarray analysis. Based on these data, we investigated the significantly regulated signaling pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Moreover, 23 micro RNAs (miRNAs), which were demonstrated to be involved in IDD were chosen; we investigated their theoretic regulatory importance associated with our microarray data.
Results: We found 632 lncRNAs and 1682 mRNAs were differentially expressed out of a total of 40,716 probes. We then confirmed the microarray data by real-time PCR. Furthermore, we demonstrated 197 upregulated, and 373 downregulated Gene Ontology terms and 176 significantly enriched pathways, such as the mitogen-activated protein kinase (MAPK) pathway. Also, a signal-net was constructed to reveal the interplay among differentially expressed genes. Meanwhile, a mRNA-lncRNA co-expression network was constructed for the significantly changed mRNAs and lncRNAs. Also, the competing endogenous RNA (ceRNA) network was built.
Conclusion: Our results present the first comprehensive identification of differentially expressed lncRNAs and mRNAs of degenerative NPCs, altered by co-culturing with ASCs, and outline the gene expression regulation pattern. These may provide valuable information for better understanding of stem cell therapy and potential candidate biomarkers for IDD treatment.
Background: Patients with chronic hepatitis C virus (HCV) infection and active or previous hepatitis B virus (HBV) are at risk of HBV reactivation (HBV-R) during direct-acting antiviral (DAA) therapy. Recent reports suggest that HBV-R may even occur several months after completion of DAA therapy. The aim of this study was to assess the risk of HBV-R in patients with resolved HBV after successful DAA therapy during long-term follow-up (FU).
Methods: Among 848 patients treated for chronic HCV, all patients with resolved HBV and long-term FU data were eligible for inclusion. Patients were HBV DNA/hepatitis B surface antigen (HBsAg)–negative at the end of therapy (EOT) and were followed for up to 52 weeks thereafter. Patients underwent regular alanine transaminase (ALT) testing, and additional HBV DNA/HBsAg testing was performed at FU week 12, end of FU, and in case of an ALT increase above the upper limit of normal (>ULN).
Results: A total of 108 patients were followed up for a mean (range) of 41.5 (24–52) weeks after EOT. None of the patients experienced reverse HBsAg seroconversion or reappearance of HBV DNA. One patient received a liver transplantation; 1 patient was diagnosed with de novo hepatocellular carcinoma, and 2 patients died. Eighteen patients (16.7%) had increased ALT levels (grade 0/1). Of those, the majority were male (72.2%) and significantly more patients had cirrhosis (66.7% vs 36.2%, P = .015) or received ribavirin as part of their treatment regimen (86.7% vs 46.8%, P = .041). None of these were associated with HBV-R.
Conclusions: Our results indicate that the risk of HBV-R in patients with resolved HBV treated with DAAs for HCV is low during long-term follow-up.
Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.
Methods: In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.
Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).
Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.
Funding: UK Medical Research Council and British Heart Foundation.
The mechanistic target of the rapamycin (mTOR) inhibitor, temsirolimus, has significantly improved the outcome of patients with renal cell carcinoma (RCC). However, development of temsirolimus-resistance limits its effect and metastatic progression subsequently recurs. Since integrin α7 (ITGA7) is speculated to promote metastasis, this investigation was designed to investigate whether temsirolimus-resistance is associated with altered ITGA7 expression in RCC cell lines and modified tumor cell adhesion and invasion. Caki-1, KTCTL-26, and A498 RCC cell lines were driven to temsirolimus-resistance by exposing them to temsirolimus over a period of 12 months. Subsequently, adhesion to human umbilical vein endothelial cells, to immobilized fibronectin, or collagen was investigated. Chemotaxis was evaluated with a modified Boyden chamber assay and ITGA7 expression by flow cytometry and western blotting. Chemotaxis significantly decreased in temsirolimus-sensitive cell lines upon exposure to low-dosed temsirolimus, but increased in temsirolimus-resistant tumor cells upon reexposure to the same temsirolimus dose. The increase in chemotaxis was accompanied by elevated ITGA7 at the cell surface membrane with simultaneous reduction of intracellular ITGA7. ITGA7 knock-down significantly diminished motility of temsirolimous-sensitive cells but elevated chemotactic activity of temsirolimus-resistant Caki-1 and KTCTL-26 cells. Therefore, ITGA7 appears closely linked to adhesion and migration regulation in RCC cells. It is postulated that temsirolimus-resistance is associated with translocation of ITGA7 from inside the cell to the outer surface. This switch forces RCC migration forward. Whether ITGA7 can serve as an important target in combatting RCC requires further investigation.
Background/Aims: Signaling of Gs protein-coupled receptors (GsPCRs) is accomplished by stimulation of adenylyl cyclase, causing an increase of the intracellular cAMP concentration, activation of the intracellular cAMP effectors protein kinase A (PKA) and Epac, and an efflux of cAMP, the function of which is still unclear.
Methods: Activation of adenylyl cyclase by GsPCR agonists or cholera toxin was monitored by measurement of the intracellular cAMP concentration by ELISA, anti-phospho-PKA substrate motif phosphorylation by immunoblotting, and an Epac-FRET assay in the presence and absence of adenosine receptor antagonists or ecto-nucleotide phosphodiesterase/pyrophosphatase2 (eNPP2) inhibitors. The production of AMP from cAMP by recombinant eNPP2 was measured by HPLC. Extracellular adenosine was determined by LC-MS/MS, extracellular ATP by luciferase and LC-MS/MS. The expression of eNPP isoenzymes 1-3 was examined by RT-PCR. The expression of multidrug resistance protein 4 was suppressed by siRNA.
Results: Here we show that the activation of GsPCRs and the GsPCRs-independent activation of Gs proteins and adenylyl cyclase by cholera toxin induce stimulation of cell surface adenosine receptors (A2A or A2B adenosine receptors). In PC12 cells stimulation of adenylyl cyclase by GsPCR or cholera toxin caused activation of A2A adenosine receptors by an autocrine signaling pathway involving cAMP efflux through multidrug resistance protein 4 and hydrolysis of released cAMP to AMP by eNPP2. In contrast, in PC3 cells cholera toxin- and GsPCR-induced stimulation of adenylyl cyclase resulted in the activation of A2B adenosine receptors.
Conclusion: Our findings show that stimulation of adenylyl cyclase causes a remarkable activation of cell surface adenosine receptors.
Acute cholecystitis – a cohort study in a real-world clinical setting (REWO study, NCT02796443)
(2018)
Background: For decades, the optimal timing of surgery for acute cholecystitis has been controversial. Recent meta-analyses and population-based studies favor early surgery. One recent large randomized trial has demonstrated that a delayed approach increases morbidity and cost compared to early surgery within 24 hours of hospital admission. Since cases of severe cholecystitis were excluded from this trial, we argue that these results do not reflect real-world clinical situations. From our point of view, these results were in contrast to the clinical experience with our patients; so, we decided to analyze critically all our patients with the null hypothesis that the patients treated with a delayed cholecystectomy after an acute cholecystitis have a similar or even better outcome than those treated with an early operative approach.
Patients and methods: We retrospectively analyzed clinical data from all patients with cholecystectomies in the period between January 2006 and September 2015. A total of 1,723 patients were categorized into four groups: early (n=138): urgent surgery of patients with acute cholecystitis within the first 72 hours of the onset of symptoms; intermediate (n=297): surgery of patients with acute cholecystitis within an average of 10 days after the onset of symptoms; delayed (n=427): initial non-surgical treatment of acute cholecystitis with surgery performed within 6–12 weeks of the onset of symptoms; and elective (n=868): cholecystectomy within a symptom-free interval of choice in patients with symptomatic cholecystolithiasis without signs of acute cholecystitis.
Results: In a real-world scenario, early/intermediate cholecystectomy in acute cholecystitis was associated with a significant increase in morbidity and mortality (Clavien–Dindo score) compared to a delayed approach with surgery performed 6–12 weeks after the onset of symptoms. The adjusted linear rank statistics showed a decrease in the complication score with values of 2.29 in the early group, 0.48 in the intermediate group, –0.26 in the delayed group and –2.12 in the elective group. The results translate into a continuous decrease of the complication score from early over intermediate and delayed to the elective group.
Conclusion: These results demonstrate that delayed cholecystectomy can be performed safely. In cases with severe cholecystitis, early and/or intermediate approaches still have a relatively high risk of morbidity and mortality.
Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1–90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63–80 Hz) in occipital regions and upregulated low frequency (5–28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.
The goal of this special issue is to address research concerning risks and problems related to the diagnosis and therapy of adenomyosis and myomata. During the last years, there have been several controversies in the scientific community regarding these topics. The original papers gathered in this special issue highlight and inform the readers about the innovations made in this field. ...
The use of cardiac troponins (cTn) is the gold standard for diagnosing myocardial infarction. Independent of myocardial infarction (MI), however, sex, age and kidney function affect cTn levels. Here we developed a method to adjust cTnI levels for age, sex, and renal function, maintaining a unified cut-off value such as the 99th percentile. A total of 4587 individuals enrolled in a prospective longitudinal study were used to develop a model for adjustment of cTn. cTnI levels correlated with age and estimated glomerular filtration rate (eGFR) in males/females with rage = 0.436/0.518 and with reGFR = −0.142/−0.207. For adjustment, these variables served as covariates in a linear regression model with cTnI as dependent variable. This adjustment model was then applied to a real-world cohort of 1789 patients with suspected acute MI (AMI) (N = 407). Adjusting cTnI showed no relevant loss of diagnostic information, as evidenced by comparable areas under the receiver operator characteristic curves, to identify AMI in males and females for adjusted and unadjusted cTnI. In specific patients groups such as in elderly females, adjusting cTnI improved specificity for AMI compared with unadjusted cTnI. Specificity was also improved in patients with renal dysfunction by using the adjusted cTnI values. Thus, the adjustments improved the diagnostic ability of cTnI to identify AMI in elderly patients and in patients with renal dysfunction. Interpretation of cTnI values in complex emergency cases is facilitated by our method, which maintains a single diagnostic cut-off value in all patients.
Viscum album L. extracts (VE) are applied as complementary cancer therapeutics for more than one century. Extracts contain several compounds like mistletoe lectins (ML) 1-3 and viscotoxins, but also several minor ingredients. Since ML-1 has been described as one of the main active components harboring antitumor activity, purified native or recombinant ML-1 has been also used in clinical trials in the last years. The present study examined and compared the immunoboosting effects of three ML-1 containing drugs (the extract ISCADOR Qu, the recombinant ML-1 Aviscumine, and purified native ML-1) in the context of the T-cell mediated killing of glioma cells. Additionally we examined the possible underlying T-cell stimulating mechanisms. Using cocultures of immune and glioma cells, a PCR-based microarray, quantitative RT-PCR, and an antibody-based array to measure cytokines in blood serum, immunosupporting effects were determined. A highly aggressive, orthotopic, immunocompetent syngeneic mouse glioma model was used to determine the survival of mice treated with ISCADOR Qu alone or in combination with tumor irradiation and temozolomide (TMZ). Treatment of glioblastoma (GBM) cells with ISCADOR Qu that contains a high ML concentration, but also viscotoxins and other compounds, as well as with Aviscumine or native ML-1, enhanced the expansion of cancer cell-specific T-cells as well as T-cell-mediated tumor cell lysis, but to a different degree. In GBM cells all three ML-1-containing preparations modulated the expression of immune response associated genes. In vivo, subcutaneous ISCADOR Qu injections at increasing concentration induced cytokine release in immunocompetent VM/Dk-mice. Finally, ISCADOR Qu, if applied in combination with tumor irradiation and TMZ, further prolonged the survival of glioma mice. Our findings indicate that ML-1 containing drugs enhance anti-GBM immune responses and work in synergy with radiochemotherapy. Therefore, adjuvant mistletoe therapy should be considered as an auspicious treatment option for glioma patients.
Purpose: There is some controversy whether or not saccades change with age. This cross-sectional study aims to clarify the characteristics of reflexive saccades at various ages to establish a normative cohort in a standardized set-up. Second objective is to investigate the feasibility of saccadometry in daily ophthalmological practice.
Methods: One hundred healthy participants aged between 6 and 76 years underwent an ophthalmologic examination and saccadometry, using an infrared video-oculography device, sampling at 220 Hz. The reflexive saccades were evoked in four directions and three target displacements each (5°/15°/30° horizontally and of 5°/10°/20° vertically). Saccadic peak velocity, gain (amplitude/target displacement) and latency were measured.
Results: Mean peak velocity of saccades was 213°/s (± 29°/s), 352°/s (± 50°/s) and 455°/s (± 67°/s) to a target position 5°, 15°and 30° horizontally, respectively, and 208°/s (± 36°/s), 303°/s (± 50°/s) and 391°/s (± 71°/s) to a target position 5°, 10° and 20° vertically. The association between peak velocity and eccentricity proved to be present at any age in all four directions. We found no relevant effect of age on peak velocity, gain and latency in a fitted linear mixed model. However, latency becomes shorter during childhood and adolescence, while in adulthood it is relatively stable with a slight trend to increase in the elderly. Saccades are more precise when the target displacement is small. Isometric saccades are most common, followed by hypometric ones. All children and elderly were able to perform good quality saccadometry in a recording time of approximately 10 minutes.
Conclusion: The presented data may serve as normative control for further studies using such a video-oculography device for saccadometry. The means of peak velocity and the gain can be used independently from age respecting the target displacement. Latency is susceptible to age.
In order to elucidate the causes for the increased mortality of aged patients with bacterial central nervous system (CNS) infections, we compared the course of Streptococcus pneumoniae (S. pneumoniae) meningitis in aged and young mice. Aged (21.2 ± 3.1 months, n = 40) and young (3.2 ± 0.9 months, n = 42) C57BL/6N and B6/SJL mice were infected by intracerebral injection of 50–70 CFU S. pneumoniae serotype 3 and monitored for 15 days. Aged and young mice did not differ concerning mortality (35% versus 38%), weight loss, development of clinical symptoms, bacterial concentrations in cerebellum and spleen as well as the number of leukocytes infiltrating the CNS. In contrast to results from our geriatric mouse model of Escherichia coli (E. coli) meningitis, where aged mice showed a higher mortality and an impaired elimination of bacteria, we did not find any differences between aged and young mice after intracerebral infection with S. pneumoniae serotype 3. This indicates that the increased susceptibility of aged mice to bacterial CNS infections is pathogen-specific: It appears less prominent in infections caused by hardly phagocytable pathogens with thick capsules like S. pneumoniae serotype 3, where the age-related decline of the phagocytic capacity of microglia and macrophages has a minor influence on the disease course.
5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an established pharmacological activator of AMP-activated protein kinase (AMPK). Both, AICAR and AMPK were reported to attenuate inflammation. However, AICAR is known for many AMPK-independent effects, although the mechanisms remain incompletely understood. Here we report a potent suppression of lipopolysaccharide (LPS)-induced inflammatory gene expression by AICAR in primary human macrophages, which occurred independently of its conversion to AMPK-activating 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate. Although AICAR did not interfere with activation of cytosolic signalling cascades and nuclear translocation of nuclear factor - κB (NFκB) by LPS, it prevented the recruitment of NFκB and RNA polymerase II to target gene promoters. AICAR also inhibited signal transducer and activator of transcription 3 (STAT3)-dependent induction of interleukin (IL) IL-6 and IL-10 targets, while leaving STAT6 and HIF1α-dependent gene expression in IL-4 and dimethyloxalylgylcine-treated macrophages intact. This points to a transcription factor-specific mode of action. Attenuated gene expression correlated with impaired NFκB and STAT3, but not HIF-binding in electrophoretic mobility shift assays in vitro. Conclusively, AICAR interferes with DNA binding of NFκB and STAT3 to modulate inflammatory responses.