Medizin
Refine
Year of publication
Has Fulltext
- yes (541) (remove)
Is part of the Bibliography
- no (541)
Keywords
- inflammation (29)
- macrophage (13)
- glioblastoma (10)
- cancer (9)
- SARS-CoV-2 (8)
- hypoxia (8)
- prostate cancer (8)
- apoptosis (7)
- data science (7)
- macrophages (7)
- pain (7)
- epilepsy (6)
- macrophage polarization (6)
- miRNA (6)
- microRNA (6)
- COVID-19 (5)
- Cirrhosis (5)
- autophagy (5)
- breast cancer (5)
- curcumin (5)
- differentiation (5)
- environmental tobacco smoke (5)
- lipocalin-2 (5)
- multiple sclerosis (5)
- neurodegeneration (5)
- particulate matter (5)
- prevalence (5)
- proliferation (5)
- stroke (5)
- Aspergillus (4)
- B cells (4)
- Gene expression (4)
- Hemorrhage (4)
- Labor and delivery (4)
- Liver diseases (4)
- MSD (4)
- NKG2D (4)
- Pregnancy (4)
- ataxia telangiectasia (4)
- biomarker (4)
- bipolar disorder (4)
- bladder cancer (4)
- child (4)
- children (4)
- endothelial cells (4)
- epidemiology (4)
- immunotherapy (4)
- infection (4)
- integrins (4)
- iron (4)
- mTOR (4)
- machine learning (4)
- mesenchymal stromal/stem cells (4)
- migration (4)
- obesity (4)
- outcome (4)
- polytrauma (4)
- psoriasis (4)
- radical prostatectomy (4)
- sphingosine-1-phosphate (4)
- sulforaphane (4)
- thymus (4)
- tumor microenvironment (4)
- Acute myeloid leukemia (3)
- Cancer treatment (3)
- DNA methylation (3)
- Death rates (3)
- EEG microstates (3)
- Evaluation (3)
- Gender (3)
- General practice (3)
- Hepatocellular carcinoma (3)
- Inflammation (3)
- Kinematic analysis (3)
- Knees (3)
- Legs (3)
- Macrophages (3)
- Magnetic resonance imaging (3)
- Medical risk factors (3)
- Morbidity (3)
- Multimorbidity (3)
- Multivariate analysis (3)
- Musculoskeletal system (3)
- NK cells (3)
- NoxO1 (3)
- PCR (3)
- Pain (3)
- Polypharmacy (3)
- acetaminophen (3)
- aging (3)
- angiogenesis (3)
- bevacizumab (3)
- caspase-2 (3)
- ceramides (3)
- cirrhosis (3)
- colorectal cancer (3)
- complement (3)
- cytokines (3)
- dental profession (3)
- dentate gyrus (3)
- dentist (3)
- drug resistance (3)
- electrolytic cleaning (3)
- entropy (3)
- exercise (3)
- flow cytometry (3)
- glioma (3)
- growth (3)
- immunity (3)
- information theory (3)
- innate immunity (3)
- invasion (3)
- invasive fungal disease (3)
- meningioma (3)
- metabolism (3)
- metastasis (3)
- mitochondria (3)
- monocytes (3)
- mortality (3)
- mutual information (3)
- natural killer cell (3)
- neuroblastoma (3)
- neuropathic pain (3)
- osteoarthritis (3)
- p21 (3)
- periimplantitis (3)
- preeclampsia (3)
- proteomics (3)
- public health (3)
- quality of life (3)
- questionnaire (3)
- reactive oxygen species (3)
- regeneration (3)
- systematic biopsy (3)
- trauma (3)
- tumor progression (3)
- vitamin D (3)
- working memory (3)
- ADHD (2)
- ATM (2)
- ATP-citrate lyase (2)
- Angiogenesis (2)
- Angiography (2)
- Asphyxia (2)
- Ataxia telangiectasia (2)
- BCL6 (2)
- BPH (2)
- Biomarker (2)
- Birth weight (2)
- Blood (2)
- Borrelia (2)
- Brain metastasis (2)
- Breast cancer (2)
- Breast tumors (2)
- C-reactive protein (2)
- CC16 (2)
- CD44 (2)
- CDKN1A (2)
- CIK cells (2)
- CLP (2)
- COMP (2)
- CUELA (2)
- Cancer chemotherapy (2)
- Candida (2)
- Cell binding (2)
- Cell differentiation (2)
- Cesarean section (2)
- Chemotherapy (2)
- Citation analysis (2)
- Cohort studies (2)
- Crohn's disease (2)
- Crohn’s disease (2)
- Cuela (2)
- Cytokines (2)
- Density equalizing mapping (2)
- Dentist (2)
- Depression (2)
- Diagnostic medicine (2)
- Ears (2)
- G2A (2)
- GPCR (2)
- HDAC (2)
- HIV (2)
- Holmes tremor (2)
- IBD (2)
- Inflammatory bowel disease (2)
- Intensive care units (2)
- Ischemia (2)
- Jaw (2)
- LSCC (2)
- Lesions (2)
- MICA (2)
- Malaria (2)
- Markovianity (2)
- Medical education (2)
- Mental health and psychiatry (2)
- Messenger RNA (2)
- Methicillin-resistant Staphylococcus aureus (2)
- Mouse models (2)
- Musculoskeletal disorder (2)
- Myalgia (2)
- NADH dehydrogenase (2)
- NADPH oxidase (2)
- NAFLD (2)
- NASH (2)
- NK cells (2)
- Neonates (2)
- Neutropenia (2)
- Normal distribution (2)
- Nox1 (2)
- OXA-48 (2)
- Obstetrics and gynecology (2)
- Patients (2)
- Physicians (2)
- Portal hypertension (2)
- Portal veins (2)
- Postural control (2)
- Preterm birth (2)
- Prognosis (2)
- Protease inhibitor therapy (2)
- Psychology (2)
- Quality of life (2)
- Questionnaire (2)
- RNF4 (2)
- ROS (2)
- Regression analysis (2)
- Reliability (2)
- Research architecture (2)
- Surgery (2)
- T cell (2)
- T cells (2)
- Torque (2)
- Transcription factors (2)
- Treg cell (2)
- Ulcerative colitis (2)
- Vitamin D (2)
- acetyl-CoA (2)
- additives (2)
- adhesion (2)
- adipose-derived mesenchymal stem cells (2)
- air flow (2)
- alcohol (2)
- anaemia (2)
- anal cancer (2)
- anticonvulsants (2)
- antiviral therapy (2)
- ascites (2)
- atherosclerosis (2)
- augmentation (2)
- bibliometrics (2)
- bibliometry (2)
- bio imaging (2)
- bioluminescence (2)
- blood (2)
- borrelia (2)
- calretinin (2)
- cancer stem cells (2)
- carbapenemases (2)
- cardiac surgery (2)
- cell cycle (2)
- cervical cancer (2)
- chemotherapy (2)
- chemotherapy resistance (2)
- cholesterol (2)
- classical Hodgkin lymphoma (2)
- coagulopathy (2)
- cochlear implant (2)
- colon cancer (2)
- colon carcinoma cells (2)
- colorectal carcinoma (2)
- complications (2)
- concordance (2)
- corona virus (2)
- coronavirus (2)
- cyclosporin A (2)
- dance (2)
- dendritic cells (2)
- dental assistants (2)
- dental education (2)
- dental implant (2)
- dentists (2)
- depression (2)
- disintegration (2)
- elderly (2)
- encoding (2)
- exosomes (2)
- extracellular vesicles (2)
- fMRI (2)
- female subjects (2)
- fibroblasts (2)
- forensic entomology (2)
- functional genomics (2)
- fusion (2)
- fusion biopsy (2)
- gender (2)
- gene expression (2)
- gene regulation (2)
- histology (2)
- histone acetylation (2)
- human genomics (2)
- imaging (2)
- immune evasion (2)
- immunohistochemistry (2)
- inflammatory bowel disease (2)
- integrin (2)
- interleukin-4 (2)
- iron deficiency (2)
- iron metabolism (2)
- irradiation (2)
- knowledge discovery (2)
- layer-specificity (2)
- lipoxygenase (2)
- liver damage (2)
- liver fibrosis (2)
- liver transplantation (2)
- lung cancer (2)
- lyme disease (2)
- maintenance (2)
- methylprednisolone (2)
- miR-181 (2)
- mouse (2)
- mucormycetes (2)
- multinucleated giant cells (2)
- musculoskeletal (2)
- mycophenolic acid (2)
- natural killer cells (2)
- neurogenesis (2)
- next generation sequencing (NGS) (2)
- occupational health (2)
- olfaction (2)
- oxidative phosphorylation (2)
- oxidative stress (2)
- palatal tremor (2)
- patient (2)
- patients (2)
- perforant path transection (2)
- phagocytes (2)
- physical activity (2)
- plasmid (2)
- primary care (2)
- primary cilium (2)
- primary immunodeficiency (2)
- proteome (2)
- qRT-PCR (2)
- quantitative MRI (2)
- re-osseointegration (2)
- regulatory T cell (2)
- renal cell cancer (2)
- renal cell carcinoma (2)
- renal tubular epithelial cells (2)
- respiratory chain (2)
- schizophrenia (2)
- second-hand smoke (2)
- secretion (2)
- seizure (2)
- selection (2)
- sex (2)
- signal transduction (2)
- sound-induced flash illusion (2)
- sphingosine 1-phosphate (2)
- sphingosine 1-phosphate receptor (2)
- spirochetes (2)
- standard value (2)
- starvation (2)
- stationarity (2)
- surgery (2)
- survivin (2)
- tissue engineering (2)
- total hip replacement (2)
- toxicity (2)
- tracking (2)
- transfusion (2)
- trophoblast (2)
- trophoblasts (2)
- tumor growth (2)
- tumor-associated macrophages (2)
- uteroglobin (2)
- (novel) brominated flame retardants ((N)BFR) (1)
- 16 segment AHA model (1)
- 16p11.2 (1)
- 17-AAG (1)
- 2-deoxyglucose (2-DG) (1)
- 3D gait analysis (1)
- 5' UTR (1)
- A-FFIP (1)
- AB-serum (1)
- ABCB1 (1)
- ABCC1 (1)
- ACLF (1)
- ADGRE1 (1)
- ADHD differential diagnosis (1)
- AICAR (1)
- AKT signaling (1)
- ALD (1)
- AML – acute myeloid leukemia (1)
- AMPK (1)
- APRI (1)
- ASAP (1)
- ASD-specific (1)
- AU-rich element (1)
- Acute Myeloid Leukemia (1)
- Addison’s disease (1)
- Adenocarcinoma (1)
- Adenylyl cyclase (1)
- Adhesion (1)
- Adverse drug reaction (1)
- Ag-RDT (1)
- Aging (1)
- Akaike information criterion (AIC) (1)
- Allergic asthma (1)
- Amitriptyline (1)
- Amniotic fluid (1)
- Anal cancer (1)
- Anesthesia, Intravenous (1)
- Aneurysms (1)
- Animal wings (1)
- Anosmia (1)
- Anterior cruciate ligament reconstruction (1)
- Anticholinergic (1)
- Anticoagulant therapy (1)
- Anticoagulants [MeSH] (1)
- Anticoagulation (1)
- Antiplatelet therapy (1)
- Antiretroviral therapy (1)
- Antiviral therapy (1)
- Anxiety (1)
- Aortic stiffness (1)
- Arms (1)
- Aromatase Inhibitors (1)
- Ascites (1)
- Aspergillus fumigatus (1)
- Aspergillus species (1)
- Ataxia-telangiectasia (1)
- Atherosclerosis (1)
- Atm (1)
- Atrial fibrillation (1)
- Attention-deficit / hyperactivity disorder (1)
- Attitude (1)
- Audio equipment (1)
- Audio signal processing (1)
- Audiology (1)
- Aurora A (1)
- Australia (1)
- Autism (1)
- Autism spectrum disorder (1)
- Automated Tube Potential Selection (1)
- Automatic Environmental Tobacco Smoke Emitter (1)
- B cell subpopulations (1)
- B-cell antigen receptor (1)
- B.1.1.7 (1)
- B.1.617.1 (1)
- B.1.617.2 (1)
- BIRC5 (1)
- BMNC (1)
- BNT2b2 (1)
- BPO (1)
- BRAF (1)
- BRUCE (1)
- Bayesian inference (1)
- Bee venom allergy (1)
- Benefit (1)
- Bibliometric analysis (1)
- Big five (1)
- Birth (1)
- Bleeding (1)
- Blood groups (1)
- Blood plasma (1)
- Bloodstream infections (1)
- Body limbs (1)
- Bone marrow (1)
- Borrelia miyamotoi (1)
- Bradycardia (1)
- Bright light therapy (1)
- Bronchial inflammation (1)
- C. elegans (1)
- CAD/CAM (1)
- CD19 (1)
- CD271 (1)
- CD3/CD19 depletion (1)
- CD36 (1)
- CD41 (1)
- CD45RA naïve lymphocytes (1)
- CD62P (1)
- CD74 (1)
- CD8+ T lymphocytes (1)
- CD8+ tumor infiltrating lymphocytes (1)
- CDK2 (1)
- CHA2DS2-VASc-score (1)
- CPE (1)
- CPT1A (1)
- CRISPR/Cas9 (1)
- CRM (1)
- CRM1 (1)
- CRP (1)
- CRPC (1)
- CSC marker (1)
- CT pulmonary angiography (1)
- CT radiation exposure (1)
- Caco-2 cells (1)
- Canada (1)
- Cancer (1)
- Cancer Staging (1)
- Cancer detection and diagnosis (1)
- Cannabis (1)
- Carcinoma, Ductal, Breast (1)
- Cardiovascular epidemiology (1)
- Cardiovascular magnetic resonance (1)
- Case management (1)
- Case management [MeSH] (1)
- Cell distribution (1)
- Cell motility (1)
- Cell signalling (1)
- Cell staining (1)
- Cellular stress responses (1)
- Central nervous system (1)
- Cerebrospinal fluid (1)
- Chemoradiotherapy (1)
- Child adiposity (1)
- Chondral Lesion (1)
- Chronic disease [MeSH] (1)
- Chronic hepatitis (1)
- Chronic intestinal failure (1)
- Chronic kidney disease (1)
- Citation (1)
- Clincial pharmacology (1)
- Co-morbidity (1)
- Cognitive impairment (1)
- Cognitive neurology (1)
- Colchicum (1)
- Cold hardiness (1)
- Cold tolerance (1)
- Colorectal cancer (1)
- Computed axial tomography (1)
- Computed tomography pulmonary angiography (CTPA) (1)
- Computer hardware (1)
- Computer software (1)
- Computers (1)
- Conservative treatment (1)
- Constrained posture (1)
- Coronary artery disease (1)
- Cost-effectiveness analysis (1)
- Cre-recombinase (1)
- Critical care (1)
- Cryptococcus (1)
- CspA (1)
- CspZ (1)
- Cyp46a1 (1)
- Cytogenetics (1)
- Cytoplasm (1)
- Cytoplasmic staining (1)
- Cytoreductive nephrectomy (1)
- Cytoskeletal proteins (1)
- D-dimer (1)
- DBS (1)
- DC-NK cell interaction (1)
- DHA (1)
- DNA Damage (1)
- DNA damage (1)
- DNA damage response (1)
- DNA-binding proteins (1)
- DOMS (1)
- DST (1)
- Data processing (1)
- Data science (1)
- Deletion mutation (1)
- Dengue (1)
- Dengue fever (1)
- Density equalizing (1)
- Dental education (1)
- Dental implants (1)
- Dental phobia (1)
- Dental practice (1)
- Dental students (1)
- Dental training (1)
- Diabetes mellitus (1)
- Diagnostic error (1)
- Diagnostic markers (1)
- Digestive system procedures (1)
- Digital workshops (1)
- Disabilities (1)
- Discs large (1)
- Distance to water (1)
- Distribution limits (1)
- Double-blind placebo-controlled trial (1)
- Drug susceptibility testing (1)
- Drug therapy (1)
- Dual-Source CT (1)
- D’Amico classification (1)
- ECMO (1)
- EGFR (1)
- EGFRvIII mutation (1)
- EMR1 (1)
- EPA (1)
- ERK3/MAPK6 (1)
- ERM (1)
- Early intervention (1)
- Economic analysis (1)
- Economic benchmarks (1)
- Education (1)
- Elderly (1)
- Elevation (1)
- Ellipsoids (1)
- Emotional recognition (1)
- Emotions (1)
- EndMT (1)
- Endocrine cancer (1)
- Endometriosis (1)
- Endothelial cell (EC) (1)
- Endothelial cells (1)
- England (1)
- Enterobacterales (1)
- Enterobacteriaceae (1)
- Enzyme regulation (1)
- Epidemiology (1)
- Epidermal growth factor receptor (1)
- Epidural abscess (1)
- Epidural block (1)
- Epileptic seizures (1)
- Epsilon (1)
- Ergonomics (1)
- Erythropoiesis (1)
- Estrogen Receptor Modulators (1)
- Etiology (1)
- Evidence based medicine (1)
- Evidence-based dentistry (1)
- Evidence-based medicine (1)
- Exercise (1)
- Exercise challenge (1)
- Exercise-induced asthma (1)
- Exhaled nitric oxide (1)
- Extracorporeal membrane oxygenation (1)
- Exudates and transudates (1)
- F4/80 (1)
- FFLU (1)
- FFPE (1)
- FIB-4 (1)
- FOXO3 (1)
- FOXO3a (1)
- Factor H (1)
- Factor analysis (1)
- Feasibility studies (1)
- Feedback (1)
- Fevers (1)
- Finevo (1)
- Five-Konzept (1)
- Flow cytometry (1)
- Forced expiratory volume in 1 s (1)
- Forensics (1)
- Francisella tularensis (1)
- Francisella tularensis subspecies holarctica (1)
- Functional clustering (1)
- Functional electrical stimulation (1)
- Functional mitral regurgitation (1)
- Fusarium (1)
- GABA (1)
- GMP (1)
- GPR4 (1)
- GRK2 (1)
- GSK3α (1)
- GSK3β (1)
- Gait analysis (1)
- Galleria mellonella (1)
- Gastric cancer (1)
- Gastrointestinal tract (1)
- Gender analysis (1)
- Gene prediction (1)
- General dental practice (1)
- Genetics (1)
- Genome annotation (1)
- Geographically weighted regression (GWR) (1)
- German people (1)
- Germany (1)
- Gestational diabetes (1)
- Gleason Score (1)
- Gleason score (1)
- Gleason upgrading (1)
- Glioblastoma (1)
- Global health (1)
- Glucose Transporter Type 1 (1)
- Goserelin (1)
- Gram negative bacteria (1)
- GvHD (1)
- HBV (1)
- HBV reactivation (1)
- HCC (1)
- HCV treatment (1)
- HLA class II (1)
- HLA peptidome (1)
- HNSCC (1)
- HOD (1)
- HODE (1)
- HOLEP (1)
- HPV (1)
- HSCT (1)
- HSV (1)
- HSV-1 (1)
- HSV-2 (1)
- HUVEC (1)
- Hashimoto’s thyroiditis (1)
- HbA1c (1)
- HeLa cells (1)
- Health care (1)
- Health economics (1)
- Health services research [MeSH] (1)
- Heart failure (1)
- Hedgehog (1)
- Hematopoietic stem cell transplantation (1)
- Hepatitis C virus (1)
- Hip (1)
- Histology (1)
- Hmox1 (1)
- HoLEP (1)
- Hodgkin lymphoma (1)
- Hospitals (1)
- Hsp90 inhibitor (1)
- HuR (1)
- Human (1)
- Human olfaction (1)
- Hydrocephalus (1)
- Hymenoptera venom immunotherapy (1)
- Hypertension (1)
- IFN-β (1)
- IHC (1)
- IKKε (1)
- IL-15 (1)
- IL-18BP (1)
- IL-1β (1)
- IL-21 (1)
- IL-27 cytokine (1)
- IL-33 (1)
- IL-6 (1)
- INR (1)
- IPS e.max system (1)
- IPSS (1)
- IRES translation (1)
- ISR (1)
- Image analysis (1)
- Immune cells (1)
- Immune suppression (1)
- Immunohistochemistry techniques (1)
- Immunology (1)
- Impella (1)
- Imrt (1)
- IncL (1)
- IncX (1)
- Incidence rate (1)
- Induced sputum (1)
- Infarction (1)
- Infectious disease epidemiology (1)
- Inferior vena cava thrombus (1)
- Inflammatory diseases (1)
- Injury Severity Score (ISS) (1)
- International normalized ratio (1)
- Internet (1)
- Intersectoral care (1)
- Interspecific competition (1)
- Intervention development (1)
- Intestinal failure-associated liver disease (1)
- Intravenous injections (1)
- Ireb2 (1)
- Iron Overload (1)
- Iron chelation (1)
- Joint loading (1)
- Jumping (1)
- K-homology RNA-binding domain (1)
- KAP (1)
- KCNQ1 (1)
- KPS (1)
- Kappa (1)
- Karyotypes (1)
- Keap1-Nrf2 (1)
- Ketogenic Diet (1)
- Ki-67 (1)
- Kidney transplant recipients (1)
- Kinematic posture analysis (1)
- Knowledge (1)
- Kupffer cells (1)
- Kynurenine (1)
- LAMTOR2 (1)
- LC3 I/II (1)
- LCH (1)
- LC–MS/MS (1)
- LDL (1)
- LIR interaction, (1)
- LIVIN (1)
- LM11A 31 (1)
- LQTS (1)
- Laboratory techniques and procedures (1)
- Lafora disease (1)
- Langerhans cell histiocytosis (1)
- Lecture (1)
- Left hemisphere (1)
- Leigh syndrome (1)
- Light sheet fluorescence microscopy (1)
- Linear regression analysis (1)
- Liver fibrosis (1)
- Liver transplantation (1)
- Livestock (1)
- LncRNA - long noncoding RNA (1)
- Local climate (1)
- Longchain polyunsaturated fatty acids (1)
- Luciferase (1)
- Lyme disease (1)
- Lymphangioleiomyomatosis (1)
- Lymphoma (1)
- M. Intracellulare (1)
- M. avium (1)
- M. avium complex (1)
- M. chimaera (1)
- MAGGIC score (1)
- MAIT cell (1)
- MCAO (1)
- MCI (1)
- MEDIC (1)
- MEIS (1)
- MEIS2 (1)
- MMP14 (1)
- MMP2 (1)
- MRI (1)
- MRI patterns of gliomas (1)
- MRP4 (1)
- Machine learning (1)
- Machine learning algorithms (1)
- Machine-learning (1)
- Mammalian target of rapamycin (1)
- Mapping (1)
- Marker genes (1)
- Mastoiditis (1)
- Mechanisms of disease (1)
- Meckel’s diverticulum (1)
- Medical communication (1)
- Medical ethics (1)
- Medical research (1)
- Medical traineeship (1)
- Medication changes (1)
- Medicine and health sciences (1)
- Membrane staining (1)
- Meta-analysis (1)
- Metabolism, Inborn Errors (1)
- Metalloproteases (1)
- Metastasis (1)
- Metastatic renal cell carcinoma (1)
- Metastatic tumors (1)
- Methods (1)
- Michael acceptor (1)
- Micro-CT (1)
- Microalgae (1)
- Microglial cells (1)
- Microphones (1)
- MitraClip (1)
- Molecular medicine (1)
- Molecular neuroscience (1)
- Monocytes and macrophages (1)
- Monosaccharide Transport Proteins (1)
- Morphometry (1)
- Mortality (1)
- Mucomaix® matrix (1)
- Multi-modal feedback (1)
- Multidetector Computed Tomography (1)
- Multimedication (1)
- Multiplate (1)
- Multiple chronic conditions (1)
- Multiple-indication review (1)
- Musculoskeletal mechanics (1)
- Mycobacteria (1)
- Mycobacterium avium complex (1)
- Myocardial perfusion (1)
- Myocardial revascularization (1)
- Myocardial segmentation (1)
- Myocarditis (1)
- N2 (1)
- N501Y (1)
- NADPH oxidase 4 (1)
- NDBI (1)
- NF-ĸB (1)
- NF-κB pathway (1)
- NF-кB (1)
- NIRS (1)
- NK cell (1)
- NK receptors (1)
- NK-92 (1)
- NKT cell (1)
- NLRP3 inflammasomes (1)
- NS3 protease inhibitor (1)
- NTM (1)
- Native T1 mapping (1)
- Necrosis (1)
- Negative staining (1)
- Nek1 (1)
- Neoplasms (1)
- Neuroendocrine cancer (1)
- Neuroimaging (1)
- Neurons (1)
- Neuropathic pain (1)
- Neuropsychological testing (1)
- Neuropsychology (1)
- Next-generation sequencing (1)
- Niche differentiation (1)
- Nimotuzumab (1)
- Non-small cell lung cancer (1)
- Non-tuberculous mycobacteria (1)
- Non-urothelial (1)
- Nontuberculous mycobacteria (1)
- Nordic questionnaire (1)
- Notch (1)
- Nrf2 (1)
- OGR1 (1)
- OGTT (1)
- OHIP-G14 (1)
- OHRQoL (1)
- OSA (1)
- OXA-484 (1)
- Obesity (1)
- Older adults (1)
- Olfactory diagnostics (1)
- Opportunistic infections (1)
- Optogenetics (1)
- Oral and maxillofacial surgery (1)
- Oral anticoagulation (1)
- Ordinary least squares (OLS) (1)
- Orthodontist (1)
- OspE (1)
- Osteoarthritis (1)
- Outpatients (1)
- Overwintering (1)
- PBX (1)
- PBX1 (1)
- PD-L1 (1)
- PEI (1)
- PF-06273340 (1)
- PINK1 (1)
- PKA (1)
- PKCε (1)
- PML (1)
- POCT (1)
- PSA (1)
- PTM (1)
- PYGL (1)
- Paediatric research (1)
- Parenteral nutrition (1)
- Parkinson’s disease (1)
- Patellofemoral Joint (1)
- Patient and public Involvement (1)
- Patient education (1)
- Patient knowledge (1)
- Patient participation (1)
- Patient safety (1)
- Patient satisfaction (1)
- Patterns of care (1)
- Peer-feedback (1)
- Per1−/−-mice (1)
- Percutaneous coronary intervention (1)
- Personality (1)
- Pgrmc1 (1)
- Pharm-fMRI (1)
- Pharmacometrics (1)
- Pharyngeal reflex (1)
- Phenotypic plasticity (1)
- Phospholipids (1)
- Phylogenetic analysis (1)
- Physical environment (1)
- Platelet-rich fibrin (1)
- Platelets (1)
- Point-of-care testing (1)
- Poly-Pore (1)
- PolySUMOylation (1)
- Post-traumatic stress disorder (1)
- Practice (1)
- Prediction (1)
- Prevalence (1)
- Primary care (1)
- Primary health care (1)
- Primary health care [MeSH] (1)
- Probability density (1)
- Probability distribution (1)
- Professional dance (1)
- Prostaglandin (1)
- Prostate cancer (1)
- Prosthetic rehabilitation (1)
- Protein translation (1)
- Prototypes (1)
- Psychological stress (1)
- Public and occupational health (1)
- Public health (1)
- Publication (1)
- Publication output (1)
- QbTest® (1)
- Quantitative features (1)
- Quantra (1)
- Quinolinate phosphoribosyltransferase (1)
- Quinolinic acid (1)
- RITA (1)
- RNA (1)
- RNA binding proteins (1)
- RNA chaperone (1)
- RNA extraction (1)
- RNA isolation (1)
- RNA sequencing (1)
- RNA therapeutics (1)
- RNA therapy (1)
- RNA-binding protein (1)
- RNAi and CRISPR screens (1)
- ROC analysis (1)
- Radiation exposure (1)
- Rainfall (1)
- Randomised trial (1)
- Rare Diseases (1)
- Reactive oxygen species (1)
- Regret (1)
- Regulatory networks (1)
- Renal vein thrombus (1)
- Research design (1)
- Resource competition (1)
- Respiratory Syncytial Virus (1)
- Respiratory infections (1)
- Restricted posture (1)
- Ribosomes (1)
- Risk assessment (1)
- Rural area (1)
- Rush protocol (1)
- S1P (1)
- S1P lyase (1)
- S1P1–5 (1)
- S1PR1 (1)
- SARS-COV-2 (1)
- SCA2 (1)
- SENP6 (1)
- SF-36 (1)
- SGPL1 knockout cell line (1)
- SH-SY5Y neuroblastoma cells (1)
- SKALE score (1)
- SLC6a3 (1)
- SLC7A11 (1)
- SMOC1 (1)
- SNORD95 (1)
- ST2L (1)
- STAMPE2 (1)
- STAT3 (1)
- STIR (1)
- SUD (1)
- SUMO (1)
- SUMO chains (1)
- SW480 cells (1)
- Sarcopenia (1)
- Science structure (1)
- Scientists (1)
- Scientometric analysis (1)
- Scientometrics (1)
- Scientometry (1)
- Seattle heart failure model (1)
- Sensory perception (1)
- Sequence alignment (1)
- Sequence motif analysis (1)
- Serum biomarker (1)
- Sholl analysis (1)
- Short bowel syndrome (1)
- Side effects (1)
- Simulated patients (1)
- Skeletal joints (1)
- Slc11a2 (1)
- Slc25a37 (1)
- Smart nebulizer (1)
- Social research (1)
- Social sciences (1)
- Software tool (1)
- Software tools (1)
- Specimen preparation and treatment (1)
- Speech signal processing (1)
- Spinocerebellar ataxia type 2 (1)
- Sport (1)
- Sports and exercise medicine (1)
- Squamous cell carcinoma (1)
- StUbL (1)
- Stakeholder participation (1)
- Statistical analysis (1)
- Statistical data (1)
- Stenotrophomonas maltophilia (1)
- Stereotactic radiosurgery (1)
- Strength training (1)
- Stress and resilience (1)
- Stroke (1)
- Sub-segmentation (1)
- Sub-zero exposure (1)
- Suicide (1)
- Sumatra (1)
- Superoxide (1)
- Surgical and invasive medical procedures (1)
- Surgical education (1)
- Surgical oncology (1)
- Survey (1)
- Surveys (1)
- Survivin (1)
- Systematic reviews (1)
- T cell receptor (1)
- T-cell development (1)
- T-cell receptor (1)
- T-cell receptor (TCR) (1)
- T-lymphocytes (1)
- TACE (1)
- TALE-homdomain protein (1)
- TAPSE (1)
- TBK1 (1)
- TDAG8 (1)
- TGF-β1 (1)
- TGR(mREN2)27 (1)
- TIMP2 (1)
- TLR (1)
- TNF inhibitors (1)
- TNF-α (1)
- TP53 (1)
- TP53-induced glycolysis and apoptosis regulator (1)
- TRIM25 (1)
- TRIMs (1)
- TRPM8 (1)
- TSP-4 (1)
- TURP (1)
- Targeted therapy (1)
- Tet-inducible system (1)
- Tfrc (1)
- Thrombosis (1)
- Thromboxane (1)
- Total hip arthroplasty (1)
- Toxicity (1)
- Transcription (1)
- Transcriptional control (1)
- Translation initiation (1)
- Transportation (1)
- Trk (1)
- TrkC (1)
- Tubers (1)
- Tularemia (1)
- Tumor infiltrating lymphocytes (1)
- ULBP4 (1)
- Ultra microscopy (1)
- Ultra-rush protocol (1)
- Ultrasonic nebulizer (1)
- Umbilical cord (1)
- Uncertainty (1)
- Undergraduate training (1)
- United States (1)
- Urethral cancer (1)
- VIM (1)
- Vacuoles (1)
- Validation (1)
- Validity (1)
- Variant histology (1)
- Vasculogenesis (1)
- Veins (1)
- Vespid venom allergy (1)
- Viral load (1)
- Virtual patients (1)
- Vitamin D deficiency (1)
- Vmem (1)
- Volumetric analysis (1)
- Warburg effect (1)
- Water chemistry (1)
- Western diet (1)
- White blood cells (1)
- Winter survival (1)
- Work shadowing (1)
- Wound healing (1)
- XIAP (1)
- YM155 (1)
- Yellow fluorescent protein (1)
- Zoonosis (1)
- Zoopotentation (1)
- Zooprophylaxis (1)
- Zymosan-induced peritonitis (1)
- academic (1)
- accident (1)
- acetylation (1)
- acetylcholinesterase (1)
- acoustic radiation force impulse imaging (1)
- acquired drug resistance (1)
- actin dynamics (1)
- activities of daily life (1)
- acute inflammation (1)
- acute kidney injury (1)
- acute lung injury (1)
- acute lung injury (ALI) (1)
- acute lymphoblastic leukemia (1)
- acute pain (1)
- acute respiratory distress syndrome (1)
- acute-on-chronic liver failure (1)
- acute-on-chronic liver failure (ACLF) (1)
- adenosine (1)
- adenosine receptors (1)
- adipocytes (1)
- adiponectin (1)
- adipose-derived mesenchymal stem/stromal cells (1)
- adipose-derived stem cells (1)
- adipose-derived stromal/stem cells (1)
- adoptive cancer immunotherapy (1)
- adoptive immunotherapy (1)
- adrenal insuffciency (1)
- adult neurogenesis (1)
- adverse reaction (1)
- affective disorder (1)
- affective disorders (1)
- aged (1)
- ageing (1)
- agent-based models (1)
- air pollution (1)
- airborne bacteria (1)
- albumin (1)
- alcoholic hepatitis (1)
- algorithm (1)
- allergy (1)
- allogeneic stem cell transplantation (1)
- alpha-synuclein (1)
- alpharetroviral vector (1)
- amlexanox (1)
- amyotrophic lateral sclerosis (ALS) (1)
- analgesics (1)
- anaplastic large cell lymphoma (1)
- anemia (1)
- angioedema control test (1)
- angiography (1)
- animal model (1)
- anti-angiogenic therapy (1)
- anti-cancer therapy (1)
- anti-tumor activity (1)
- antiadhesive composites (1)
- antibacterial composites (1)
- antibiotic therapy (1)
- antibodies (1)
- antifibrotic therapy (1)
- antifungal activity (1)
- antifungal combination therapy (1)
- antifungal host response (1)
- antifungal therapy (1)
- antimicrobial stewardship (1)
- antireflux surgery (1)
- antiviral (1)
- antiviral drugs (1)
- apical constriction (1)
- apical junction (1)
- apical polarity (1)
- arachidonate 12/15-lipoxygenase (Alox12/15) (1)
- arachidonate 15-lipoxygenase (1)
- arachidonic acid (1)
- architecture (1)
- aromatics (1)
- articular cartilage (1)
- aspiration (1)
- aspirin (1)
- assembly (1)
- assembly factor (1)
- associative memory (1)
- asthma (1)
- astrocytes (1)
- astrocytoma (1)
- ataxia score (1)
- atopy (1)
- attachment (1)
- attention (1)
- attention deficit hyperactivity disorder (1)
- auditory (1)
- authorship (1)
- autoimmunity (1)
- automatic environmental tobacco smoke emitter (1)
- automatic scene classification (1)
- autopsy (1)
- back scan (1)
- bacterial translocation (1)
- bacterial viability (1)
- bacterium (1)
- ball (1)
- ballet (1)
- basal cell carcinoma (1)
- basilar artery occlusion (BAO) (1)
- best medical treatment (1)
- beta-band activity (1)
- beta-lactamases (1)
- binary search procedure (1)
- bioactive lipids (1)
- bioactivity (1)
- bioavailability (1)
- biofilm (1)
- biologics (1)
- biologization (1)
- biomarkers (1)
- biomolecular analysis (1)
- biopsy (1)
- biopsy naïve (1)
- bladder neck stenosis (1)
- blood concentrates (1)
- blood culture (1)
- blood pressure (1)
- blood-brain barrier (1)
- blow fly (1)
- body mass index (1)
- body posture (1)
- body sway (1)
- body weight distribution (1)
- bone damage (1)
- bone healing (1)
- bone marrow mononuclear cells (1)
- bone tissue (1)
- bone-regeneration (1)
- bone–implant interface (1)
- borrelia mayonii (1)
- brain imaging (1)
- brain infection (1)
- brain phosphorylome (1)
- brain shift (1)
- brain tumor (1)
- brainstem (1)
- burden of disease (1)
- butyrylcholinesterase (1)
- bypass (1)
- cAMP (1)
- cIAP1/2 (1)
- cadherin (1)
- calbindin (1)
- calcitriol (1)
- cancer and drug vulnerabilities (1)
- cancer cell metabolism (1)
- cancer immunobiology (1)
- cancer metastases (1)
- cancer-associated fibroblasts (1)
- cancer-specific survival (1)
- canonical (1)
- car indoor (1)
- carbapenem resistance (1)
- carbon oxides (COx) (1)
- carcinoma (1)
- cardiac differentiation (1)
- cardiac regeneration (1)
- cardiac reprogramming (1)
- cardiomyocyte apoptosis (1)
- cardiomyocyte proliferation (1)
- cardiothoracic surgery (1)
- cardiovascular disease (1)
- case reports (1)
- caspase 8 (1)
- caspase-8 (1)
- castration resistance (1)
- catheter removal (1)
- cdk (1)
- cell adhesion (1)
- cell and focal adhesion (1)
- cell culture (1)
- cell cycle arrest (1)
- cell cycling (1)
- cell fusion (1)
- cell growth (1)
- cell motility (1)
- cell proliferation (1)
- cell survival (1)
- cell survival mechanisms (1)
- cellular reaction (1)
- cellular response (1)
- cellular therapies (1)
- central nervous system (1)
- central spasticity (1)
- centrifugation (1)
- ceramide (1)
- cerebellum (1)
- cerebral imaging (1)
- cerebral radiation necrosis (1)
- chaperone-mediated autophagy (1)
- chaperones (1)
- chelation therapy (1)
- chemokine (1)
- chemokine receptors (1)
- chemoprotection (1)
- chemoradiotherapy (1)
- chemoresistance (1)
- chemotaxis (1)
- chemotherapeutic drug resistance (1)
- chest injury (1)
- chest trauma (1)
- chimeric antigen receptor (1)
- chloroplasts (1)
- cholangiocarcinoma (1)
- cholinesterase (1)
- chronic granulomatous disease (1)
- chronic hepatitis C (1)
- chronic inflammation (1)
- cigarette smoke (1)
- cigarette strength (1)
- citation (1)
- classification (1)
- classification of bone defects (1)
- clinical research (1)
- clinical trial (1)
- clopidogrel (1)
- cluster analysis (1)
- cluster-randomized controlled trial (1)
- cluttering (1)
- coagulation (1)
- cochlear implants (1)
- cognitive deficits (1)
- cognitive functions (1)
- cognitively stimulating leisure activities (1)
- collagen (1)
- collagen I (1)
- collagen-based biomaterial (1)
- collagen-based matrix (1)
- collective cell migration (1)
- colon (1)
- colorectal cancer (CRC) (1)
- combined immunodeficiency (1)
- comorbidity (1)
- complex systems (1)
- complexity theory (1)
- complexome profiling (1)
- computational functional genomics (1)
- computational knowledge-discovery (1)
- computational techniques (1)
- confinement (1)
- congenital diaphragmatic hernia (1)
- connective tissue (1)
- connectivity (1)
- contamination (1)
- continuous performance test (1)
- contralateral delay activity (1)
- controlled nuclear import (1)
- cooling period (1)
- coronary (1)
- coronavirus disease 2019 (1)
- cortex, gray matter (1)
- covalent drugs (1)
- crime scene (1)
- critical care (1)
- critical-size defect (1)
- criticality (1)
- cryopreservation (1)
- cuticular hydrocarbons (1)
- cyclin D1 (1)
- cyclin Y (1)
- cyclins (1)
- cyclophosphamide (1)
- cystic fibrosis (1)
- cytarabin (1)
- cytokine storm (1)
- cytokine, angiogenesis (1)
- cytotoxic lymphocytes (1)
- cytotoxicity (1)
- daily activity protocols (1)
- dance teacher (1)
- data repositories (1)
- death rates (1)
- death receptor (1)
- debris (1)
- declaration of tobacco ingredients (1)
- decompensated liver cirrhosis (1)
- deep sedation (1)
- deferred treatment (1)
- delayed treatment (1)
- delta (1)
- dementia (1)
- demineralized bone matrix (1)
- dendrite morphogenesis (1)
- density equalizing mapping (1)
- dental assistant (1)
- dental health professional (1)
- desensitization (1)
- development (1)
- dexamethasone (1)
- diabetes (1)
- diabetes mellitus (1)
- diabetes therapy (1)
- diagnostics (1)
- diet (1)
- differentiated thyroid carcinoma (1)
- diffusion tensor imaging (1)
- digital age determination (1)
- dihydrocannabidiol (1)
- dihydroceramides (1)
- dimethylfumarate (1)
- diphtheria toxin (1)
- direct-acting antivirals (1)
- discoidin domain-containing receptor (1)
- disease-free survival (1)
- disordered iron metabolism (1)
- dissemination (1)
- diuretics (1)
- dog study (1)
- dopamine transporter (1)
- doublecortin (1)
- downgrading (1)
- doxycycline (1)
- drug (1)
- drug screening (1)
- drug–drug interactions (1)
- drug–gene interactions (1)
- drug–g–gene interactions (1)
- dual antiplatelet therapy (1)
- dynamic causal modeling (1)
- dysphagia (1)
- eNPP2 (1)
- early continence (1)
- early detection (1)
- early loss (1)
- early onset (1)
- ectopic pregnancy (1)
- efferocytosis (1)
- efficacy (1)
- eicosanoids (1)
- electrode design (1)
- electron transfer (1)
- electrophilic fatty acids (1)
- electrophysiology (1)
- eligibility (1)
- elite athletes (1)
- eltrombopag (1)
- emergency care (1)
- emergent self-organizing maps (1)
- endocannabinoids (1)
- endoplasmic reticulum (1)
- endothelial cell (1)
- endothelial nitric-oxide synthase (1)
- endourology (1)
- endovascular treatment (1)
- enterobacter infections; pseudomonas aeruginosa; epidemiology (1)
- entomological evidence (1)
- epidemics (1)
- epidermis (1)
- epigenetics (1)
- epileptic encephalopathies (1)
- epithelial-to-mesenchymal transition (EMT) (1)
- erastin (1)
- essential tremor (1)
- euthymic (1)
- everolimus (1)
- everyday life (1)
- ex vivo expansion (1)
- ex-Gaussian analysis (1)
- experimental pain models (1)
- expertise (1)
- exponential model (1)
- extracellular matrix (1)
- face-name association task (1)
- factor H (1)
- falls (1)
- false memory (1)
- fatigue (1)
- feeder cells (1)
- female health (1)
- ferroportin (1)
- ferroptosis (1)
- fibrinolysis (1)
- fibrosis (1)
- fibrotest (1)
- fingolimod (1)
- first-line chemotherapy (1)
- fitness (1)
- fixed partial dentures (1)
- follow-up (1)
- forensics (1)
- fractional anisotropy (1)
- fractionation (1)
- fragile-X-associated tremor-ataxia syndrome (1)
- frequency of attacks (1)
- fresh frozen plasma (1)
- fronto-temporal lobar dementia (1)
- fronto-temporal-lobar-dementia (1)
- full-contour crown restorations (1)
- function (1)
- functional connectivity (1)
- functional magnetic resonance imaging (1)
- fundoplication (1)
- fungi (1)
- fungus (1)
- gadolinium enhancing lesion (1)
- galactomannan (1)
- gastroesophageal reflux (1)
- gender differences (1)
- gene expression analysis (1)
- gene signature (1)
- gene therapy (1)
- general anaesthesia (1)
- general practitioner (1)
- genetic diversity (1)
- genetic predisposition (1)
- genetics (1)
- geriatric patients (1)
- glial activation (1)
- glioma microenvironment (1)
- glucose metabolism (1)
- glycolysis (1)
- glycoproteins (1)
- graft-versus-host disease (1)
- graft-versus-tumor effect (1)
- granulomas (1)
- granulomatous inflammation (1)
- graph theory (1)
- growth inhibition (1)
- haploidentical (1)
- head and neck squamous cell carcinoma (1)
- head-and-neck cancer (1)
- healthcare workers (1)
- heart failure (1)
- heat (1)
- heat stress (1)
- hedgehog signaling (1)
- hedgehog signaling pathway (1)
- hematopoiesis (1)
- hematopoietic cell transplantation (1)
- hematopoietic stem and progenitor cells (1)
- hematopoietic stem cell transplantation (1)
- hemorrhagic transformation (1)
- hepatic steatosis (1)
- hepatic stellate cells (1)
- hepatitis B virus (1)
- hepatitis C virus (1)
- hepatitis E virus (1)
- hepatoblastoma (1)
- hepatocellular cancer (1)
- hereditary angioedema (1)
- heterogeneity (1)
- high molecular weight plasticizer (1)
- high throughput (1)
- high-dimensional data sets (1)
- high-throughput nucleotide sequencing (1)
- hippocampus (1)
- histological outcomes (1)
- histomorphometry (1)
- histone deacetylase (1)
- home visit (1)
- homeodomain protein (1)
- host cell interaction (1)
- host cell response (1)
- host-pathogen interaction (1)
- host-targeting antivirals (1)
- hostpathogen interaction (1)
- human Natural Killer cell (1)
- human antigen R (HuR) (1)
- human cytomegalovirus (1)
- human decellularized dermis (1)
- human subjects (1)
- humans (1)
- humectant agents (1)
- hybrid abutment (1)
- hydrogen peroxide (1)
- hyperglycemia (1)
- hyperlipidemia (1)
- hypoxia-induced cell death (1)
- hypoxia-inducible factor (1)
- idiopathic dystonia (1)
- image analysis (1)
- image-guided tissue acquisition (1)
- immune cells (1)
- immune checkpoint (1)
- immune defense (1)
- immune deficiency (1)
- immune host defense (1)
- immune infiltration (1)
- immune response (1)
- immunoglobulin superfamily (1)
- immunological research (1)
- immunosuppressive agent (1)
- immunosuppressive drug (1)
- in vitro models (1)
- in vivo dosimetry (1)
- in-cabin exposure (1)
- indoor air pollution (1)
- induced membrane (1)
- inducible gene expression (1)
- inducible nitric oxide synthase (1)
- inertial motion capture (1)
- infection control (1)
- infection model (1)
- infectivity (1)
- infiltration (1)
- inhibitor (1)
- inhibitor of apoptosis protein family (1)
- inhibitors (1)
- inosine (1)
- inositol signaling (1)
- insertion (1)
- insulin resistance (1)
- insurance data (1)
- integration (1)
- interferon (1)
- interferon type III (1)
- interleukin-1 (1)
- interleukin-18 (1)
- interleukin-22 (1)
- internal ribosomal entry site (IRES) (1)
- internet (1)
- interstitial multicatheter brachytherapy (1)
- intervention study (1)
- intestinal barrier (1)
- intoxication (1)
- intravenous iron therapy (1)
- intrinsic apoptosis (1)
- intrinsic drug resistance (1)
- invasive fungal infection (1)
- invasive growth (1)
- inverse stage migration (1)
- inflammation (1)
- ionomycin (1)
- iron chelation (1)
- iron chelator (1)
- iron chelators (1)
- iron deficiency anemia (1)
- iron homeostasis (1)
- iron overload versus deprivation (1)
- iron-trafficking (1)
- isocaloric ketogenic diet (1)
- jejunoileal atresia (1)
- joint contact forces (1)
- junctional adhesion molecule (1)
- juvenile myoclonic epilepsy (1)
- keratinocytes (1)
- kinematics (1)
- knee adduction moment (1)
- laceration (1)
- lentiviral vector (1)
- leukemia (1)
- leukocytes (1)
- leukopenia (1)
- levetiracetam (1)
- lichen extracts (1)
- light irradiation (1)
- linoleic acid metabolites (1)
- lipid mediator (1)
- lipid metabolism (1)
- lipids (1)
- lipids inflammatory pain (1)
- lipofuscin (1)
- lipopolyplex (1)
- lipoxin A4 (1)
- liquid PRF (1)
- liquid-PRF (1)
- live cell imaging (1)
- live/dead staining (1)
- liver X receptor (1)
- liver cirrhosis (1)
- liver disease (1)
- liver injury (1)
- liver steatosis (1)
- lncRNA (1)
- local control (1)
- local recurrence (1)
- location (1)
- locator (1)
- long-term follow-up (1)
- long-term potentiation (1)
- long-term prophylaxis (1)
- longevity (1)
- low speed centrifugation concept (1)
- low-dose imaging (1)
- lung (1)
- lung disease (1)
- luteolin (1)
- lymphangiogenesis (1)
- lymphocyte (1)
- mGluR3 (1)
- mGluR5 (1)
- mRNA stability (1)
- mRNA1273 (1)
- mTOR inhibition (1)
- mTORC1 (1)
- machine learning (ML) (1)
- machine-learning (1)
- magnetoencephalography (1)
- major depression (1)
- major depression (MD) (1)
- major depressive disorder (1)
- major depressive disorder (MDD) (1)
- malignancy (1)
- malignant glioma (1)
- mammary cancer (1)
- mammary carcinoma (1)
- markovianity (1)
- mass spectrometry (1)
- mast cells (1)
- maternal tobacco smoke (1)
- mathematical modeling (1)
- matrix metalloproteinase (1)
- matrix metalloproteinases (1)
- mean diffusivity (1)
- mechanism of action (1)
- medical error (1)
- medical risk factors (1)
- medication (1)
- medication review (1)
- medulloblastoma resection (1)
- melanoma (1)
- membrane potential (1)
- membrane-less organelles (1)
- membranous urethral stricture (1)
- memebrane (1)
- memory (1)
- menthol (1)
- merkel cell carcinoma (1)
- mesenchymal stem cell (1)
- mesenchymal stromal cell (1)
- mesenchymal stromal cells (1)
- meta-analysis (1)
- metabolic cancer therapy (1)
- metabolic liver disease (1)
- metabolic syndrome (1)
- metamorphosis (1)
- metastatic colorectal cancer (1)
- metastatic prostate cancer (1)
- metastatic urethral cancer (1)
- metformin (1)
- methacarn (1)
- methylation profiling (1)
- miR (1)
- miR-122 (1)
- miR-142-3p (1)
- miR-21 (1)
- miR-375 (1)
- mice (1)
- microbiome (1)
- microenvironment (1)
- microglia (1)
- microlesions (1)
- microsatellite instability (1)
- microtubular cytoskeleton (1)
- middle-aged (1)
- migration and invasion (1)
- mitochondrial disease (1)
- mobile air quality study (1)
- mold (1)
- molecular surveillance (1)
- monoclonal antibodies (1)
- monocyte chemotactic protein 1 (MCP-1) (1)
- monotype abutment (1)
- monsoon (1)
- morbidity (1)
- morphogenesis (1)
- morphometry (1)
- mortality analysis (1)
- motility (1)
- motor functions (1)
- mouse model (1)
- movement disorders (1)
- mpMRI (1)
- mtor (1)
- mucormycete (1)
- mucosal inflammation (1)
- multi-scale models (1)
- multidrug resistance (1)
- multifocal (1)
- multimorbidity (1)
- multisensory integration (1)
- multivoxel pattern analysis (1)
- musculoskeletal disorders (1)
- musculoskeletal inflammation (1)
- musculoskeletal modeling (1)
- musculoskeletal pain (1)
- musculoskeletal system (1)
- myelodysplastic syndrome (1)
- myeloid cells (1)
- natural cytotoxicity (1)
- natural killer T cells (1)
- natural selection (1)
- naturalistic sample (1)
- ncRNA (1)
- neonate (1)
- nerve-sparing (1)
- network (1)
- neurexin (1)
- neuroimaging (1)
- neuronal avalanches (1)
- neuronal maturation (1)
- neuropsychological impairment (1)
- neurotrophins (1)
- next generation sequencing (1)
- next-generation sequencing (1)
- nitroalkylation (1)
- nitrogen oxides (NOx) (1)
- nodular sclerosis (1)
- noise intervention measures (1)
- non-aneurysmal SAH (1)
- non-canonical (1)
- non-classical adhesion molecule (1)
- non-coding RNA (1)
- non-invasive fibrosis assessment (1)
- non-linear dynamics (1)
- non-malignant hematological diseases (1)
- non-sensory bias (1)
- nonnucleoside polymerase inhibitor (1)
- nucleolus (1)
- nucleoredoxin (1)
- nucleotide metabolism (1)
- nursery schools (1)
- nutrient deprivation (1)
- nutrient endocytosis (1)
- occupational factors (1)
- older people (1)
- olfactory testing (1)
- omega-3 fatty acids (1)
- oncogenes (1)
- oncogenic signaling (1)
- one health (1)
- open field behavior (1)
- open-source (1)
- oral health (1)
- oral health burden (1)
- ordinary differential equations (ODE) (1)
- organisation of health services (1)
- organophosphate flame retardants (OFR) (1)
- organotypic culture (1)
- orientation (1)
- orthodontist (1)
- osteogenic sarcoma cells (1)
- ostium (1)
- ouabain (1)
- outside-in signaling (1)
- overall survival (1)
- overdenture (1)
- oxaliplatin (1)
- p-eIF2α (1)
- p14 (1)
- p21Cip1/CDKN1A (1)
- p47phox (1)
- p53 (1)
- p62 (1)
- p75 (1)
- paediatric (1)
- pain genetics (1)
- pain intensity (1)
- pain medication (1)
- particle size distribution (1)
- particulate matter (PM) (1)
- passive smoke (1)
- pathogen (1)
- patient blood management (1)
- patient preference (1)
- patient safety (1)
- patients' experience (1)
- patient’s decree (1)
- pediatric (1)
- pediatric epilepsy (1)
- pentose phosphate pathway (1)
- perineurium (1)
- perio-prosthetic joint infection (1)
- peritoneal macrophages (1)
- peritumoral edema (1)
- peritumoral edema zone (1)
- peroxisome proliferator-activated receptor (1)
- phage display (1)
- phagocytosis (1)
- pharmacist (1)
- pharmacodynamics (1)
- pharmacoepigenetics (1)
- pharmacogenetics (1)
- pharmacogenomics (1)
- pharmacokinetics (1)
- pharmacological data science (1)
- pharmacological plasticity (1)
- pharmacoresistance (1)
- phenoconversion (1)
- phenylephrine (1)
- phosphatases (1)
- pig (1)
- pilot study (1)
- pitch (1)
- pitch perception (1)
- placenta (1)
- planimetric measurement (1)
- plasma (1)
- plasminogen (1)
- platelet lysate (1)
- platelet-rich fibrin (1)
- platelet-rich-fibrin (1)
- platelets (1)
- point of care (1)
- point shear wave elastography (1)
- polarization (1)
- polo-like kinase 3 (1)
- poly(A)-tail (1)
- polyethylenimine (1)
- polymerase chain reaction (1)
- polyomavirus (MCPyV) (1)
- polypharmacy (1)
- polyunsaturated fatty acid (1)
- porcine (1)
- portal hypertension (1)
- post-exercise hypotension (1)
- post-transcriptional regulation (1)
- post-translational modifications (1)
- posterior circulation (1)
- posterior fossa masses (1)
- posterior fossa tumor (1)
- postmonsoon (1)
- postnatal neurogenesis (1)
- postoperative delirium (1)
- posttranslational modification (1)
- potassium channel (1)
- ppi1 (1)
- pre-emptive allogeneic hematopoietic stem cell transplantation (1)
- pre-professional (1)
- preconditioning (1)
- prediabetes (1)
- predictive coding (1)
- pretreatment (1)
- prevention (1)
- primary health care (1)
- primary prostate cancer (1)
- production (1)
- professional dance (1)
- prognosis (1)
- prognostic marker (1)
- progressive myoclonus epilepsy (1)
- prostaglandins (1)
- prostate neoplasm (1)
- proteasome (1)
- protein complexes (1)
- protein phosphorylation (1)
- protein–protein interaction (1)
- proton density (1)
- proton pump inhibitors (1)
- proton pumping (1)
- proton-sensing GPCR (1)
- proximal tubule cells (1)
- pseudomonas aeruginosa (1)
- psoriatic arthritis (1)
- psychological distress (1)
- pteridine (1)
- publication output (1)
- pulse-spreading harmonic complex (1)
- qPCR (1)
- qRT-PCR detection (1)
- qualitative research (1)
- quantitative magnetic resonance imaging (1)
- quantitative proteomics (1)
- quantum biology (1)
- quantum neurobiology (1)
- quiescence (1)
- radiation (1)
- radiation dosage (1)
- radiation dosimetry (1)
- radiation protection (1)
- radiation-induced (1)
- radical oxygen species (1)
- radical prostatecomy (1)
- radioimmunotherpay (1)
- radiosensitization (1)
- radiotherapy (1)
- radiotherapy resistance (1)
- radixin (1)
- rapamycin (1)
- rat (1)
- rat femur critical size defect (1)
- real-world data (1)
- recovery (1)
- red blood cells (1)
- reference values (1)
- regenerative medicine (1)
- regenerative therapy (1)
- regorafenib (1)
- regorafenib csf concentration (1)
- regulatory T helper cells (1)
- relaxometry (1)
- remodeling (1)
- renal failure (1)
- repeat biopsy (1)
- reperfusion injury (1)
- reproduction biology (1)
- resistance (1)
- resolution (1)
- resolution of inflammation (1)
- respiratory failure (1)
- rest period (1)
- resting‐state (1)
- reverberation (1)
- rheumatoid arthritis (1)
- ribavirin (1)
- risk factor (1)
- risk management (1)
- room simulation (1)
- rosetting T cells (1)
- rotational thromboelastometry (1)
- running (1)
- salvage mastectomy (1)
- sarcopenia (1)
- schizophrenia spectrum (1)
- sciatic nerve (1)
- scoping review (1)
- screening (1)
- screening routine (1)
- screening test (1)
- searchlight analysis (1)
- secondary cancer (1)
- secondary data analysis (1)
- secretome (1)
- segmentation (1)
- seizures (1)
- selectin (1)
- selective autophagy receptor (1)
- selfish genetic element (1)
- semiquinone (1)
- sensory organ development (1)
- sepsis (1)
- serum (1)
- severe acute respiratory syndrome coronavirus 2 (1)
- severe congenital neutropenia (1)
- severely injured (1)
- shedding (1)
- short bowel (1)
- short linear motifs (SLiMs) (1)
- siRNA delivery (1)
- siRNA/RNAi (1)
- sickle cell anemia (1)
- signal transducer and activator of transcription-1 (1)
- signaling (1)
- silk fibroin (1)
- simulation (1)
- simulation training (1)
- single-sided deafness (1)
- sirtuin1 (1)
- size of cigarettes (1)
- skin diseases (1)
- small bowel (1)
- smoking in pregnancy (1)
- socio-economic influences (1)
- soluble MICA (1)
- sonic hedgehog signaling (1)
- sorafenib (1)
- sound analyses (1)
- spatial (1)
- spatial learning (1)
- specialized pro-resolving lipid mediators (SPMs) (1)
- species differences (1)
- speech perception (1)
- sphinganine 1-phosphate (1)
- sphingolipid (1)
- sphingolipids (1)
- sphingosine 1-phoshate (1)
- sphingosine 1-phosphate antagonistst/inhibitors (1)
- sphingosine 1-phosphate metabolism (1)
- sphingosine 1-phosphate signaling (1)
- sphingosine kinase (1)
- spike mutation (1)
- spinal infection (1)
- spirochete (1)
- splicing (1)
- split-mouth (1)
- sport (1)
- spreading (1)
- statin treatment (1)
- statistical parametric mapping (1)
- steatosis (1)
- stem cell niche (1)
- stem cell transplantation (1)
- stem cells (1)
- sterol regulatory element binding protein-2 (1)
- stoma (1)
- stress granules (1)
- stress period (1)
- stretching (1)
- structure (1)
- stuttering (1)
- subcutaneous fat (1)
- subpopulation (1)
- subventricular zone (1)
- success rate (1)
- survival (1)
- survival rate (1)
- swallowing (1)
- symptoms (1)
- synaptic plasticity (1)
- synaptic signaling (1)
- synoviocytes (1)
- synuclein (1)
- systemic inflammation (1)
- t-distributed stochastic neighbor embedding (1)
- tandem mass spectrometry (1)
- targeted biopsy (1)
- tauopathies (1)
- tauopathy (1)
- temozolomide (1)
- temsirolimus (1)
- test protocol (1)
- testosterone (1)
- tetracycline (1)
- tetrahydrocannabinol (1)
- thalassemia (1)
- therapy (1)
- therapy monitoring (1)
- therapy resistance (1)
- thiazolidine and perhydrothiazine derivatives of aldophosphamide and I-aldophosphamide (1)
- thrombectomy (1)
- thrombin (1)
- thrombolysis (1)
- thrombolysis (tPA) (1)
- thrombopenia (1)
- thrombopietin receptor agonist (1)
- thrombosis (1)
- thymic selection (1)
- tick (1)
- tissue mechanics (1)
- tobacco control (1)
- tobacco products (1)
- tobacco taxation (1)
- toc64 (1)
- toll-like receptor (1)
- topical agent (1)
- tractography (1)
- traffic emissions (1)
- trafficking (1)
- training program (1)
- transcription factors (1)
- transcriptional profiling (1)
- transcriptome analysis (1)
- transfer entropy (1)
- transferrin (1)
- transient elastography (1)
- transient receptor potential channels (1)
- transjugular intrahepatic portosystemic shunt (TIPS) (1)
- transketolase-like protein 1 (1)
- translational medical research (1)
- translational study (1)
- translocon (1)
- transmission (1)
- transrectal prostate biopsy (1)
- transverse axis (1)
- trauma registry (1)
- traumaticbraininjury(TBI) (1)
- treatment (1)
- triathlon (1)
- trophoblast organoids (1)
- trophoblastic cell lines (1)
- tumor adhesion (1)
- tumor immune evasion (1)
- tumor metabolism (1)
- tumor migration (1)
- tumor pain (1)
- tumor proliferation (1)
- tumor stroma (1)
- tumor-associated macrophages (TAM) (1)
- type B (1)
- type I interferon (1)
- tyrosine hydroxylase (1)
- tyrosine kinase receptor signaling (1)
- ubiquitin ligase (1)
- ulcerative colitis (1)
- ultrasonic cleaning (1)
- ultrasound (1)
- unconventional T cell (1)
- unilateral hip osteoarthritis (1)
- upgrading (1)
- urethal stricture (1)
- urethroplasty (1)
- ustekinumab (1)
- vaccination (1)
- valproic acid (1)
- vasoconstriction (1)
- vasodilation (1)
- vemurafenib (1)
- ventilation modes (1)
- ventralis intermedius nucleus (1)
- vertical transmission (1)
- vertigo (1)
- vestibular function (1)
- viability (1)
- viral tracing (1)
- virulence (1)
- virus (1)
- vismodegib (GDC-0449) (1)
- vitamin D deficiency (1)
- vitamin D metabolites (1)
- vitamin D receptor (1)
- vocational (1)
- volatile organic compounds (VOC) (1)
- volatile sedation (1)
- waiting time (1)
- walking (1)
- wheezing (1)
- whole-genome sequencing (1)
- wild animals (1)
- workplace health promotion (1)
- wound healing (1)
- xenograft (1)
- zinc protoporphyrin (1)
- zirconia (1)
- ß-D-glucan (1)
- ß-amyloid (1)
- β-lactamases (1)
- γδT cell (1)
- fibrogenesis (1)
- fingolimod (1)
- flow cytometry (1)
Institute
- Medizin (541) (remove)
Background: Ever since it was discovered that zoophilic vectors can transmit malaria, zooprophylaxis has been used to prevent the disease. However, zoopotentiation has also been observed. Thus, the presence of livestock has been widely accepted as an important variable for the prevalence and risk of malaria, but the effectiveness of zooprophylaxis remained subject to debate. This study aims to critically analyse the effects of the presence of livestock on malaria prevalence using a large dataset from Indonesia.
Methods: This study is based on data from the Indonesia Basic Health Research ("Riskesdas") cross-sectional survey of 2007 organized by the National Institute of Health Research and Development of Indonesia’s Ministry of Health. The subset of data used in the present study included 259,885 research participants who reside in the rural areas of 176 regencies throughout the 15 provinces of Indonesia where the prevalence of malaria is higher than the national average. The variable "existence of livestock" and other independent demographic, social and behavioural variables were tested as potential determinants for malaria prevalence by multivariate logistic regressions.
Results: Raising medium-sized animals in the house was a significant predictor of malaria prevalence (OR = 2.980; 95% CI 2.348–3.782, P < 0.001) when compared to keeping such animals outside of the house (OR = 1.713; 95% CI 1.515–1.937, P < 0.001). After adjusting for gender, age, access to community health facility, sewage canal condition, use of mosquito nets and insecticide-treated bed nets, the participants who raised medium-sized animals inside their homes were 2.8 times more likely to contract malaria than respondents who did not (adjusted odds ratio = 2.809; 95% CI 2.207–3.575; P < 0.001).
Conclusions: The results of this study highlight the importance of livestock for malaria transmission, suggesting that keeping livestock in the house contributes to malaria risk rather than prophylaxis in Indonesia. Livestock-based interventions should therefore play a significant role in the implementation of malaria control programmes, and focus on households with a high proportion of medium-sized animals in rural areas. The implementation of a "One Health" strategy to eliminate malaria in Indonesia by 2030 is strongly recommended.
Background: Sputum induction is an important noninvasive method for analyzing bronchial inflammation in patients with asthma and other respiratory diseases. Most frequently, ultrasonic nebulizers are used for sputum induction, but breath-controlled nebulizers may target the small airways more efficiently. This treatment may produce a cell distribution similar to bronchoalveolar lavage (less neutrophils and more macrophages) and provide deeper insights into the underlying lung pathology. The goal of the study was to compare both types of nebulizer devices and their efficacy in inducing sputum to measure bronchial inflammation, i.e., cell composition and cytokines, in patients with mild allergic asthma and healthy controls.
Methods: The population of this study consisted of 20 healthy control subjects with a median age of 17 years, range: 8–25 years, and 20 patients with a median age of 12 years, range: 8–24 years, presenting with mild, controlled allergic asthma who were not administered an inhaled steroid treatment. We induced sputum in every individual using both devices on two separate days. The sputum weight, the cell composition and cytokine levels were analyzed using a cytometric bead assay (CBA) and by real-time quantitative PCR (qRT-PCR).
Results: We did not observe significant differences in the weight, cell distribution or cytokine levels in the sputum samples induced by both devices. In addition, the Bland-Altman correlation revealed good concordance of the cell distribution. As expected, eosinophils and IL-5 levels were significantly elevated in patients with asthma.
Conclusions: The hypothesis that sputum induction with a breath-controlled "smart" nebulizer is more efficient and different from an ultrasonic nebulizer was not confirmed. The Bland-Altman correlations showed good concordance when comparing the two devices.
Trial registration: NCT01543516 Retrospective registration date: March 5, 2012.
Stem cell-based therapies require cells with a maximum regenerative capacity in order to support regeneration after tissue injury and organ failure. Optimization of this regenerative potential of mesenchymal stromal/stem cells (MSC) or their conditioned medium by in vitro preconditioning regimens are considered to be a promising strategy to improve the release of regenerative factors. In the present study, MSC were isolated from inguinal adipose tissue (mASC) from C57BL/6 mice, cultured, and characterized. Then, mASC were either preconditioned by incubation in a hypoxic environment (0.5% O2), or in normoxia in the presence of murine epidermal growth factor (EGF) or tumor necrosis factor α (TNFα) for 48 h. Protein expression was measured by a commercially available array. Selected factors were verified by PCR analysis. The expression of 83 out of 308 proteins (26.9%) assayed was found to be increased after preconditioning with TNFα, whereas the expression of 61 (19.8%) and 70 (22.7%) proteins was increased after incubation with EGF or in hypoxia, respectively. Furthermore, we showed the proliferation-promoting effects of the preconditioned culture supernatants on injured epithelial cells in vitro. Our findings indicate that each preconditioning regimen tested induced an individual expression profile with a wide variety of factors, including several growth factors and cytokines, and therefore may enhance the regenerative potential of mASC for cell-based therapies.
Introduction: This study was designed to evaluate risk factors and incidence of epilepsy-related injuries and accidents (ERIA) at an outpatient clinic of a German epilepsy center providing healthcare to a mixed urban and rural population of over one million inhabitants.
Methods: Data acquisition was performed between 10/2013 and 09/2014 using a validated patient questionnaire on socioeconomic status, course of epilepsy, quality of life (QoL), depression, injuries and accidents associated with seizures or inadequate periictal patterns of behavior concerning a period of 3 months. Univariate analysis, multiple testing and regression analysis were performed to identify possible variables associated with ERIA.
Results: A total of 292 patients (mean age 40.8 years, range 18–86; 55% female) were enrolled and analyzed. Focal epilepsy was diagnosed in 75% of the patients. The majority was on an antiepileptic drug (AEDs) polytherapy (mean number of AEDs: 1.65). Overall, 41 patients (14.0%) suffered from epilepsy-related injuries and accidents in a 3-month period. Besides lacerations (n = 18, 6.2%), abrasions and bruises (n = 9, 3.1%), fractures (n = 6, 2.2%) and burns (n = 3, 1.0%), 17 mild injuries (5.8%) were reported. In 20 (6.8% of the total cohort) cases, urgent medical treatment with hospitalization was necessary. Epilepsy-related injuries and accidents were related to active epilepsy, occurrence of generalized tonic-clonic seizures (GTCS) and drug-refractory course as well as reported ictal falls, ictal loss of consciousness and abnormal peri-ictal behavior in the medical history. In addition, patients with ERIA had significantly higher depression rates and lower QoL.
Conclusion: ERIA and their consequences should be given more attention and standardized assessment for ERIA should be performed in every outpatient visit.
Background: Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma.
Methods: Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4+CD25+, CD4+CD25+FoxP3+, CD4+CD25+CD127−, and CD4+CD25+CD127−FoxP3+ were characterized by flow cytometry.
Results: Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4+CD25+CD127−), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain.
Conclusion: Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4+CD25+CD127− was characterized in porcine samples.
HuR plays an important role in tumor cell survival mainly through posttranscriptional upregulation of prominent anti-apoptotic genes. In addition, HuR can inhibit the translation of pro-apoptotic factors as we could previously report for caspase-2. Here, we investigated the mechanisms of caspase-2 suppression by HuR and its contribution to chemotherapeutic drug resistance of colon carcinoma cells. In accordance with the significant drug-induced increase in cytoplasmic HuR abundance, doxorubicin and paclitaxel increased the interaction of cytoplasmic HuR with the 5ʹuntranslated region (5ʹUTR) of caspase-2 as shown by RNA pull down assay. Experiments with bicistronic reporter genes furthermore indicate the presence of an internal ribosome entry site (IRES) within the caspase-2-5ʹUTR. Luciferase activity was suppressed either by chemotherapeutic drugs or ectopic expression of HuR. IRES-driven luciferase activity was significantly increased upon siRNA-mediated knockdown of HuR implicating an inhibitory effect of HuR on caspase-2 translation which is further reinforced by chemotherapeutic drugs. Comparison of RNA-binding affinities of recombinant HuR to two fragments of the caspase-2-5ʹUTR by EMSA revealed a critical HuR-binding site residing between nucleotides 111 and 241 of caspase-2-5ʹUTR. Mapping of critical RNA binding domains within HuR revealed that a fusion of RNA recognition motif 2 (RRM2) plus the hinge region confers a full caspase-2-5ʹUTR-binding. Functionally, knockdown of HuR significantly increased the sensitivity of colon cancer cells to drug-induced apoptosis. Importantly, the apoptosis sensitizing effects by HuR knockdown were rescued after silencing of caspase-2. The negative caspase-2 regulation by HuR offers a novel therapeutic target for sensitizing colon carcinoma cells to drug-induced apoptosis.
Background: The aim of this study was to investigate the acceptance and assessment of work shadowing carried out by students and dentists in dental practices. Furthermore, the extent to which students perceive an improvement in their specialised, communication and social competencies, was to be examined.
Methods: 61 dental students in their clinical semesters at a German university participated in work shadowing placements at 27 different general dental practices. Before beginning, they received checklists of various competencies that they self-assessed using school grades (from 1 = "very good", to 6 = "failed"), which they also repeated after completion. The dentists supplemented this with their external assessments. In addition, the students were requested to fill out a 54-item questionnaire and compose a freely-structured report after the work shadowing; the dentists filled out a questionnaire containing 16 items. The statistical analysis was carried out by means of the Friedman Test, including a post-hoc test (Bonferroni-Holm correction).
Results: The analysis showed a significant overall improvement in the students’ self-assessed competencies by 0.71* ± 0.43 grades. With an average of 0.33* ± 0.36, the dentists’ external assessment proved significantly higher than the self-assessment. The greatest improvements were perceived by the students in the areas of accounting (1.17* ± 0.77), practice organisation (1.05* ± 0.61) and dentist’s discussions (0.94* ±0.80) [*p < 0.05]. The students confirmed experiencing an expansion of knowledge, an improvement in their communication skills and indicated a high degree of satisfaction in regard to the dentists (school grade 1.58 ± 0.93). A maximum amount of satisfaction towards the work shadow students was demonstrated by the dentists, and this form of teaching was assessed with a school grade of 1.69 ± 0.89.
Conclusion: Both students and dental practitioners demonstrated a high level of satisfaction in regard to the work shadowing. The students felt their knowledge had increased, viewed the dentists as motivating role models and acknowledged a significant improvement in their specialised, communication and social competencies. Work shadowing in dental teaching practices presents a sensible addition to academic teaching at a university.
Immune-modulating therapy is a promising therapy for patients with cholangiocarcinoma (CCA). Microsatellite instability (MSI) might be a favorable predictor for treatment response, but comprehensive data on the prevalence of MSI in CCA are missing. The aim of the current study was to determine the prevalence of MSI in a German tertiary care hospital. Formalin-fixed paraffin-embedded tissue samples, obtained in the study period from 2007 to 2015 from patients with CCA undergoing surgical resection with curative intention at Johann Wolfgang Goethe University hospital, were examined. All samples were investigated immunohistochemically for the presence of MSI (expression of MLH1, PMS2, MSH2, and MSH6) as well as by pentaplex polymerase chain reaction for five quasimonomorphic mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-22, and NR-24). In total, 102 patients were included, presenting intrahepatic (n = 35, 34.3%), perihilar (n = 42, 41.2%), and distal CCA (n = 25, 24.5%). In the immunohistochemical analysis, no loss of expression of DNA repair enzymes was observed. In the PCR-based analysis, one out of 102 patients was found to be MSI-high and one out of 102 was found to be MSI-low. Thus, MSI seems to appear rarely in CCA in Germany. This should be considered when planning immune-modulating therapy trials for patients with CCA.
Dysregulation of blood sphingolipids is an emerging topic in clinical science. The objective of this study was to determine preanalytical biases that typically occur in clinical and translational studies and that influence measured blood sphingolipid levels. Therefore, we collected blood samples from four healthy male volunteers to investigate the effect of storage conditions (time, temperature, long-term storage, freeze–thaw cycles), blood drawing (venous or arterial sampling, prolonged venous compression), and sample preparation (centrifugation, freezing) on sphingolipid levels measured by LC-MS/MS. Our data show that sphingosine 1-phosphate (S1P) and sphinganine 1-phosphate (SA1P) were upregulated in whole blood samples in a time- and temperature-dependent manner. Increased centrifugation at higher speeds led to lower amounts of S1P and SA1P. All other preanalytical biases did not significantly alter the amounts of S1P and SA1P. Further, in almost all settings, we did not detect differences in (dihydro)ceramide levels. In summary, besides time-, temperature-, and centrifugation-dependent changes in S1P and SA1P levels, sphingolipids in blood remained stable under practically relevant preanalytical conditions.
Acute graft-versus-host disease (GvHD) is still a major cause of treatment-related mortality after allogeneic stem cell transplantation. Allo-antigen recognition of donor T cells after transplantation account for the onset and persistence of this disease. MicroRNAs (miRNAs) are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation. Thus, miRNAs also contribute to pathological T-cell function during GvHD. Given their capacity of fine-tuning T-cell function, miRNAs have emerged as promising therapeutic targets to curtail acute GvHD, but simultaneously maintain T-cell-mediated graft-versus-tumor effects. Here, we review the role of key miRNAs contributing to the pathophysiology of GvHD. We focus on those miRNAs acting in T cells and for which a role in GvHD has been established in preclinical models. Finally, we provide an outlook for clinical application of this new therapeutic target for GvHD prevention and treatment.
Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin‐like phospholipase domain containing 3 (PNPLA3) gene results in an amino acid exchange from isoleucin to methionine at position I148M of PNPLA3. The expression of this loss‐of‐function mutation leads to impaired hepatocellular triglyceride hydrolysis and is associated with the development of liver steatosis, fibrosis, and hepatocellular carcinoma. In contrast to these well‐established associations, the relationship of the PNPLA3 rs738409 variant with other metabolic traits is incompletely understood. We therefore assessed the association of the PNPLA3 rs738409 genotype with relevant metabolic traits in a prospective study of patients at high risk for cardiovascular events, i.e., patients undergoing coronary angiography. In a total of 270 patients, known associations of the PNPLA3 rs738409 GG genotype with nonalcoholic steatohepatitis and liver fibrosis were confirmed. In addition, we found an association of the PNPLA3 rs738409 G allele with the presence of diabetes (22% versus 28% versus 58% for CC versus CG versus GG genotype, respectively; P = 0.02). In contrast to its association with nonalcoholic fatty liver disease, liver fibrosis, and diabetes, the minor G allele of PNPLA3 rs738409 was inversely associated with total serum cholesterol and low‐density lipoprotein serum levels (P = 0.003 and P = 0.02, respectively). Finally, there was a trend toward an inverse association between the presence of the PNPLA3 rs738409 G allele and significant coronary heart disease. Comparable trends were observed for the transmembrane 6 superfamily member 2 (TM6SF2) 167 K variant, but the sample size was too small to evaluate this rarer variant. Conclusion: The PNPLA3 rs738409 G allele is associated with liver disease but also with a relatively benign cardiovascular risk profile.
Background: Immigration has a strong impact on the development of health systems, medicine and science worldwide. Therefore, this article provides a descriptive study on the overall research output.
Methods: Utilizing the scientific database Web of Science, data research was performed. The gathered bibliometric data was analyzed using the established platform NewQIS, a benchmarking system to visualize research quantity and quality indices.
Findings: Between 1900 and 2016 a total of 6763 articles on immigration were retrieved and analyzed. 86 different countries participated in the publications. Quantitatively the United States followed by Canada and Spain were prominent regarding the article numbers. On comparing by additionally taking the population size into account, Israel followed by Sweden and Norway showed the highest performance. The main releasing journals are the Public Health Reports, the Journal of Immigrant and Minority Health and Social Science & Medicine. Over the decades, an increasing number of Public, Environmental & Occupational Health articles can be recognized which finally forms the mainly used subject area.
Conclusion: Considerably increasing scientific work on immigration cannot only be explained by the general increase of scientific work but is also owed to the latest development with increased mobility, worldwide crises and the need of flight and migration. Especially countries with a good economic situation are highly affected by immigrants and prominent in their publication output on immigration, since the countries’ publication effort is connected with the appointed expenditures for research and development. Remarkable numbers of immigrants throughout Europe compel medical professionals to consider neglected diseases, requires the public health system to restructure itself and finally promotes science.
Background: Cancer research is critically dependent on a continuous recruitment of junior research staff that devotes its academic life not only to clinical duties but also to basic and translational research. The present study aims to elucidate the success concerning gender equality in cancer research in the last decade (from 2008 to 2016) with lung cancer as the target parameter.
Materials and Methods: On the basis of the Gendermetrics Platform, a total of 19,724 articles related to lung cancer research were analyzed. The key method was the combined analysis of the proportion of female authorships and the female-to-male odds ratio for first, co- and last authorships. The distribution of prestigious authorships was measured by the Prestige Index.
Results: 31.3% of all authorships and 35.2% of the first, 32.2% of the co- and 22.1% of the last authorships were held by women. The corresponding female-to-male odds ratio is 1.22 (CI: 1.18–1.27) for first, 1.19 (CI: 1.16–1.23) for co- and 0.59 (CI: 0.57–0.61) for last authorships. Women are underrepresented at prestigious authorships compared to men (Prestige Index = −0.22). The female underrepresentation accentuates in articles with many authors that attract the highest citation rates.
Conclusions: While the current system promotes early career promotion of women, men still outnumber women in leadership positions. However, this male-female career dichotomy has been narrowed in the last decade and will likely be further reduced in the next decade.
In several tumor entities, transketolase-like protein 1 (TKTL1) has been suggested to promote the nonoxidative part of the pentose phosphate pathway (PPP) and thereby to contribute to a malignant phenotype. However, its role in glioma biology has only been sparsely documented. In the present in vitro study using LNT-229 glioma cells, we analyzed the impact of TKTL1 gene suppression on basic metabolic parameters and on survival following oxygen restriction and ionizing radiation. TKTL1 was induced by hypoxia and by hypoxia-inducible factor-1α (HIF-1α). Knockdown of TKTL1 via shRNA increased the cells’ demand for glucose, decreased flux through the PPP and promoted cell death under hypoxic conditions. Following irradiation, suppression of TKTL1 expression resulted in elevated levels of reactive oxygen species (ROS) and reduced clonogenic survival. In summary, our results indicate a role of TKTL1 in the adaptation of tumor cells to oxygen deprivation and in the acquisition of radioresistance. Further studies are necessary to examine whether strategies that antagonize TKTL1 function will be able to restore the sensitivity of glioma cells towards irradiation and antiangiogenic therapies in the more complex in vivo environment.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potential cure to acute myeloid leukemia (AML) patients. However, infections with commensal bacteria are an important cause for non-relapse mortality (NRM). We have previously described the impact of multidrug-resistant organism (MDRO) colonization on the survival of allo-HSCT patients. In the aforementioned publication, according to consensus, we there did not consider the opportunistic gram-negative bacterium Stenotrophomonas maltophilia (S. maltophilia) to be an MDRO. Since rate of S. maltophilia colonization is increasing, and it is not known whether this poses a risk for allo-HSCT patients, we here analyzed here its effect on the previously described and now extended patient cohort. We report on 291 AML patients undergoing allo-HSCT. Twenty of 291 patients (6.9%) were colonized with S. maltophilia. Colonized patients did not differ from non-colonized patients with respect to their age, remission status before allo-HSCT, donor type and HSCT-comorbidity index. S. maltophilia colonized patients had a worse overall survival (OS) from 6 months up to 60 months (85% vs. 88.1% and 24.7% vs. 59.7%; p = 0.007) due to a higher NRM after allo-HSCT (6 months: 15% vs. 4.8% and 60 months: 40.1% vs. 16.2% p = 0.003). The main cause of mortality in colonized patients was infection (46.2% of all deaths) and in non-colonized patients relapse (58.8% of all deaths). 5/20 colonized patients developed an invasive infection with S. maltophilia. The worse OS after allo-HSCT due to higher infection related mortality might implicate the screening of allo-HSCT patients for S. maltophilia and a closer observation of colonized patients as outpatients.
Background and aims: Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated serum CA9 levels in HCC and cirrhosis patients.
Methods: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated.
Results: 215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had hid significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (>400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval (CI) 1.017–2.809, P = 0.043). Serum CA9 concentration in cirrhotic patients did not differ significantly from HCC patients. Higher CA9 levels in cirrhotic patients correlated with portal hypertension and esophageal varices. Patients with ethanol induced cirrhosis had the highest CA9 levels in both cohorts. Levels of CA9 did not correlate with immunohistochemical expression.
Conclusions: We conclude that a high CA9 level is a possible prognostic indicator for a poor outcome in HCC patients. The high CA9 levels are probably mainly associated with portal hypertension. Ductular reactions might be a possible source of serum CA9.
Background: Subdural hematoma (SDH) is a common disease associated with high morbidity, which is becoming more prominent due to the increasing incidence. Decision for a surgical evacuation is made depending on the clinical appearance and the volume of SDH, wherefore it is important to have a simple ‘bedside’ method to measure and compare the volume of SDH.
Objective: The aim of the study was to verify the accuracy of the simplified ABC/2 volumetric formula to determine a valuable tool for the clinical practice.
Methods: Preoperative CT-scans of 83 patients with SDHs were used for the computer-assisted volumetric measurement via BrainLab® as well as the ABC/2 volumetric measurement. A = largest length (anterior to posterior) of the SDH; B = maximum width (lateral to midline) 90° to A; C = maximum height (coronal plane or multiplication of slices) of the hematoma. These measurements were performed by two independent clinicians in a blinded fashion. Both volumes were compared by linear regression analysis of Pearson and Bland-Altman regression analysis.
Results: Among 100 SDHs, 53% were under an 47% were over 100cm3 showing a well distribution of the hematoma sizes. There was an excellent correlation between computer-assisted volumetric measurement and ABC/2 (R2 = 0.947, p<0.0001) and no undesirable deviation and trend were detected (p = 0.101; p = 0.777). A 95% tolerance region of the ratios of both methods was [0.805–1.201].
Conclusion: The ABC/2 method is a simple and fast bedside formula for the measurement of SDH volume in a timely manner without limited access through simple adaption, which may replace the computer-assisted volumetric measurement in the clinical and research area. Reason for the good accuracy seems to be the spherical form of SDH, which has a similarity to a half ellipsoid.
We present an open-source Python package to compute information-theoretical quantities for electroencephalographic data. Electroencephalography (EEG) measures the electrical potential generated by the cerebral cortex and the set of spatial patterns projected by the brain's electrical potential on the scalp surface can be clustered into a set of representative maps called EEG microstates. Microstate time series are obtained by competitively fitting the microstate maps back into the EEG data set, i.e., by substituting the EEG data at a given time with the label of the microstate that has the highest similarity with the actual EEG topography. As microstate sequences consist of non-metric random variables, e.g., the letters A–D, we recently introduced information-theoretical measures to quantify these time series. In wakeful resting state EEG recordings, we found new characteristics of microstate sequences such as periodicities related to EEG frequency bands. The algorithms used are here provided as an open-source package and their use is explained in a tutorial style. The package is self-contained and the programming style is procedural, focusing on code intelligibility and easy portability. Using a sample EEG file, we demonstrate how to perform EEG microstate segmentation using the modified K-means approach, and how to compute and visualize the recently introduced information-theoretical tests and quantities. The time-lagged mutual information function is derived as a discrete symbolic alternative to the autocorrelation function for metric time series and confidence intervals are computed from Markov chain surrogate data. The software package provides an open-source extension to the existing implementations of the microstate transform and is specifically designed to analyze resting state EEG recordings.
Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC induce a gene network regulating serine-glycine metabolism with the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as a causal regulator using integrative network modeling and Bayesian network analysis in human aortic endothelial cells. The cluster is activated in human plaque material and by atherogenic lipoproteins isolated from plasma of patients with coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) within the MTHFD2-controlled cluster associate with CAD. The MTHFD2-controlled cluster redirects metabolism to glycine synthesis to replenish purine nucleotides. Since endothelial cells secrete purines in response to oxPAPC, the MTHFD2-controlled response maintains endothelial ATP. Accordingly, MTHFD2-dependent glycine synthesis is a prerequisite for angiogenesis. Thus, we propose that endothelial cells undergo MTHFD2-mediated reprogramming toward serine-glycine and mitochondrial one-carbon metabolism to compensate for the loss of ATP in response to oxPAPC during atherosclerosis.
Natural Killer (NK) cells are involved in the host immune response against infections due to viral, bacterial and fungal pathogens, all of which are a significant cause of morbidity and mortality in immunocompromised patients. Since the recovery of the immune system has a major impact on the outcome of an infectious complication, there is major interest in strengthening the host response in immunocompromised patients, either by using cytokines or growth factors or by adoptive cellular therapies transfusing immune cells such as granulocytes or pathogen-specific T-cells. To date, relatively little is known about the potential of adoptively transferring NK cells in immunocompromised patients with infectious complications, although the anti-cancer property of NK cells is already being investigated in the clinical setting. This review will focus on the antimicrobial properties of NK cells and the current standing and future perspectives of generating and using NK cells as immunotherapy in patients with infectious complications, an approach which is promising and might have an important clinical impact in the future.
Background: Definite diagnosis and therapeutic management of cholangiocarcinoma (CCA) remains a challenge. The aim of the current study was to investigate feasibility and potential impact on clinical management of targeted sequencing of intraductal biopsies.
Methods: Intraductal biopsies with suspicious findings from 16 patients with CCA in later clinical course were analyzed with targeted sequencing including tumor and control benign tissue (n = 55 samples). A CCA-specific sequencing panel containing 41 genes was designed and a dual strand targeted enrichment was applied.
Results: Sequencing was successfully performed for all samples. In total, 79 mutations were identified and a mean of 1.7 mutations per tumor sample (range 0–4) as well as 2.3 per biopsy (0–6) were detected and potentially therapeutically relevant genes were identified in 6/16 cases. In 14/18 (78%) biopsies with dysplasia or inconclusive findings at least one mutation was detected. The majority of mutations were found in both surgical specimen and biopsy (68%), while 28% were only present in biopsies in contrast to 4% being only present in the surgical tumor specimen.
Conclusion: Targeted sequencing from intraductal biopsies is feasible and potentially improves the diagnostic yield. A profound genetic heterogeneity in biliary dysplasia needs to be considered in clinical management and warrants further investigation.
Translational impact: The current study is the first to demonstrate the feasibility of sequencing of intraductal biopsies which holds the potential to impact diagnostic and therapeutical management of patients with biliary dysplasia and neoplasia.
Selective BRAF inhibitors such as vemurafenib have become a treatment option in patients with Langerhans cell Histiocytosis (LCH). To date, only 14 patients receiving vemurafenib for LCH have been reported. Although vemurafenib can stabilize the clinical condition of these patients, it does not seem to cure the patients, and it is unknown, when and how to stop vemurafenib treatment. We present a girl with severe multisystem LCH who responded only to vemurafenib. After 8 months of treatment, vemurafenib was tapered and replaced by prednisone and vinblastine, a strategy which has not been described to date. Despite chemotherapy, early relapse occurred, but remission was achieved by re-institution of vemurafenib. Further investigation needs to address the optimal duration of vemurafenib therapy in LCH and whether and which chemotherapeutic regimen may prevent disease relapse after cessation of vemurafenib.
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.
Inducible gene expression is an important tool in molecular biology research to study protein function. Most frequently, the antibiotic doxycycline is used for regulation of so-called tetracycline (Tet)-inducible systems. In contrast to stable gene overexpression, these systems allow investigation of acute and reversible effects of cellular protein induction. Recent reports have already called for caution when using Tet-inducible systems as the employed antibiotics can disturb mitochondrial function and alter cellular metabolism by interfering with mitochondrial translation. Reprogramming of energy metabolism has lately been recognized as an important emerging hallmark of cancer and is a central focus of cancer research. Therefore, the scope of this study was to systematically analyze dose-dependent metabolic effects of doxycycline on a panel of glioma cell lines with concomitant monitoring of gene expression from Tet-inducible systems. We report that doxycycline doses commonly used with inducible expression systems (0.01–1 µg/mL) substantially alter cellular metabolism: Mitochondrial protein synthesis was inhibited accompanied by reduced oxygen and increased glucose consumption. Furthermore, doxycycline protected human glioma cells from hypoxia-induced cell death. An impairment of cell growth was only detectable with higher doxycycline doses (10 µg/mL). Our findings describe settings where doxycycline exerts effects on eukaryotic cellular metabolism, limiting the employment of Tet-inducible systems.
Purpose: Stereotactic radiosurgery (SRS) is an established primary treatment for newly diagnosed brain metastases with high local control rates. However, data about local re-irradiation in case of local failure after SRS (re-SRS) are rare. We evaluated the feasibility, efficacy and patient selection characteristics in treating locally recurrent metastases with a second course of SRS.
Methods: We retrospectively evaluated patients with brain metastases treated with re-SRS for local tumor progression between 2011 and 2017. Patient and treatment characteristics as well as rates of tumor control, survival and toxicity were analyzed.
Results: Overall, 32 locally recurrent brain metastases in 31 patients were irradiated with re-SRS. Median age at re-SRS was 64.9 years. The primary histology was breast cancer and non-small-cellular lung cancer (NSCLC) in respectively 10 cases (31.3%), in 5 cases malignant melanoma (15.6%). In the first SRS-course 19 metastases (59.4%) and in the re-SRS-course 29 metastases (90.6%) were treated with CyberKnife® and the others with Gamma Knife. Median planning target volume (PTV) for re-SRS was 2.5 cm3 (range, 0.1–37.5 cm3) and median dose prescribed to the PTV was 19 Gy (range, 12–28 Gy) in 1–5 fractions to the median 69% isodose (range, 53–80%). The 1-year overall survival rate was 61.7% and the 1-year local control rate was 79.5%. The overall rate of radiological radio-necrosis was 16.1% and four patients (12.9%) experienced grade ≥ 3 toxicities.
Conclusions: A second course of SRS for locally recurrent brain metastases after prior local SRS appears to be feasible with acceptable toxicity and can be considered as salvage treatment option for selected patients with high performance status. Furthermore, this is the first study utilizing robotic radiosurgery for this indication, as an additional option for frameless fractionated treatment.
B lymphocytes are key players in humoral immunity, expressing diverse surface immunoglobulin receptors directed against specific antigenic epitopes. The development and profile of distinct subpopulations have gained awareness in the setting of primary immunodeficiency disorders, primary or secondary autoimmunity and as therapeutic targets of specific antibodies in various diseases. The major B cell subpopulations in peripheral blood include naïve (CD19+ or CD20+IgD+CD27−), non-switched memory (CD19+ or CD20+IgD+CD27+) and switched memory B cells (CD19+ or CD20+IgD−CD27+). Furthermore, less common B cell subpopulations have also been described as having a role in the suppressive capacity of B cells to maintain self-tolerance. Data on reference values for B cell subpopulations are limited and only available for older age groups, neglecting the continuous process of human B cell development in children and adolescents. This study was designed to establish an exponential regression model to produce continuous reference values for main B cell subpopulations to reflect the dynamic maturation of the human immune system in healthy children.
Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. In this study, we aimed to further characterize the role of macrophage-derived EVs in immune responses against hepatitis C virus (HCV) and the potential of polyunsaturated fatty acids (PUFAs) to modulate this modality of innate immunity. To this end, EVs were isolated from interferon-stimulated macrophage cultures or from serum of patients with acute or chronic hepatitis C. EVs were characterized by electron microscopy, flow cytometry, RNA-sequencing, and Western blot analysis. The effect of EVs on replication of HCV was assessed in coculture models. Functional analyses were performed to assess the impact of PUFAs on EV-mediated antiviral immunity. We found that macrophages secreted various cytokines shortly after stimulation with type I and II IFN, which orchestrated a fast but short-lasting antiviral state. This rapid innate immune answer was followed by the production of macrophage-derived EVs, which induced a late, but long-lasting inhibitory effect on HCV replication. Of note, exposure of macrophages to PUFAs, which are important regulators of immune responses, dampened EV-mediated antiviral immune responses. Finally, EVs from patients with hepatitis C exhibited long-lasting antiviral activities during IFN therapy as well. The antiviral effect of EVs from Caucasian and Japanese patients differed, which may be explained by different nutritional uptake of PUFAs. In conclusion, our data indicate that macrophage-derived EVs mediate long-lasting inhibitory effects on HCV replication, which may bridge the time until efficient adaptive immune responses are established, and which can be blunted by PUFAs.
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.
Stress-induced cell surface expression of MHC class I-related glycoproteins of the MIC and ULBP families allows for immune recognition of dangerous “self cells” by human cytotoxic lymphocytes via the NKG2D receptor. With two MIC molecules (MICA and MICB) and six ULBP molecules (ULBP1–6), there are a total of eight human NKG2D ligands (NKG2DL). Since the discovery of the NKG2D–NKG2DL system, the cause for both redundancy and diversity of NKG2DL has been a major and ongoing matter of debate. NKG2DL diversity has been attributed, among others, to the selective pressure by viral immunoevasins, to diverse regulation of expression, to differential tissue expression as well as to variations in receptor interactions. Here, we critically review the current state of knowledge on the poorly studied human NKG2DL ULBP4. Summarizing available facts and previous studies, we picture ULBP4 as a peculiar ULBP family member distinct from other ULBP family members by various aspects. In addition, we provide novel experimental evidence suggesting that cellular processing gives rise to mature ULBP4 glycoproteins different to previous reports. Finally, we report on the proteolytic release of soluble ULBP4 and discuss these results in the light of known mechanisms for generation of soluble NKG2DL.
Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity.
We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line.
We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74high and TILhigh tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected.
In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.
Rationale: With advances in contemporary radiotherapy techniques, and as cancer survival improves, severe isolated coronary ostial disease may develop many years following mediastinal radiotherapy, even in the absence of classical cardiovascular risk factors.
Patient concerns: We describe the case of a 73-year-old woman with previous chest radiotherapy for breast cancer who underwent coronary artery bypass graft surgery for severe bilateral coronary ostial lesions.
Diagnoses: Coronary angiography demonstrated severe, isolated bilateral coronary ostial lesions.
Interventions: The patient underwent urgent coronary artery bypass graft surgery to treat her critical coronary artery disease.
Outcomes: Intra-operatively, internal mammary arteries were not amenable to harvesting due to very dense mediastinal adhesions. Therefore, saphenous vein grafts were performed to the left anterior descending, distal left circumflex, obtuse marginal and distal right coronary arteries. The patient made a satisfactory in-hospital recovery, and was subsequently discharged back to her local hospital for rehabilitation.
Lessons: Patients successfully treated with mediastinal radiotherapy require careful long-term follow-up for the assessment of radiation-induced coronary artery disease. Importantly, mediastinal irradiation may preclude internal mammary artery utilization, and thus alter the strategy for surgical myocardial revascularization.
Background: The Indonesian region of Aceh was the area most severely affected by the earthquake and tsunami of 26 December 2004. Department of Health data reveal an upward trend of dengue cases in Aceh since the events of the tsunami. Despite the increasing incidence of dengue in the region, there is limited understanding of dengue among the general population of Aceh. The aim of this study was to assess the knowledge, attitude, and practice (KAP) regarding dengue among the people of Aceh, Indonesia in order to design intervention strategies for an effective dengue prevention program.
Methods: A community-based cross-sectional study was conducted in Aceh between November 2014 and March 2015 with a total of 609 participants living in seven regencies and two municipalities. Information on the socio-demographic characteristics of participants and their KAP regarding dengue was collected using a pre-tested structured questionnaire. The KAP status (good vs. poor) of participants with different socio-demographic characteristics was compared using Chi Square-test, ANOVA or Fisher’s exact test as appropriate. Logistic regression analysis was used to determine the predictors of each KAP domain.
Results: We found that 45% of participants had good knowledge regarding dengue and only 32% had good attitudes and good dengue preventive practices. There was a significant positive correlation between knowledge and attitudes, knowledge and practice, and attitudes and practice. In addition, people who had good knowledge were 2.7 times more likely to have good attitudes, and people who had good attitudes were 2.2 times more likely to have good practices regarding dengue. The level of education, occupation, marital status, monthly income, socioeconomic status (SES) and living in the city were associated with the knowledge level. Occupation, SES, and having experienced dengue fever were associated with attitudes. Education, occupation, SES and type of residence were associated with preventive practices.
Conclusion: Our study suggests that dengue prevention programs are required to increase KAP levels regarding dengue in the communities of Aceh.
Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors
(2018)
Data on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis are limited. The aim of this study was to characterize genetic heterogeneity of 5 patients with SI-NETs. Therefore, formalin-fixed, paraffin-embedded tissue samples of primary and metastatic lesions as well as benign liver of five patients with synchronously metastasized, well differentiated SI-NETs were analyzed with whole exome sequencing. For one patient, chip based 850k whole DNA methylome analysis was performed of primary and metastatic tumor tissue as well as control tissue. Thereby, 156 single nucleotide variants (SNVs) in 150 genes were identified and amount of mutations per sample ranged from 9–34 (mean 22). The degree of common (0–94%) and private mutations per sample was strongly varying (6–100%). In all patients, copy number variations (CNV) were found and the degree of intratumoral heterogeneity of CNVs corresponded to SNV analysis. DNA methylation analysis of a patient without common SNVs revealed a large overlap of common methylated CpG sites. In conclusion, SI-NET primary and metastatic lesions show a highly varying degree of intratumoral heterogeneity. Driver events might not be detectable with exome analysis only, and further comprehensive studies including whole genome and epigenetic analyses are warranted.
Spatial modelling of malaria cases associated with environmental factors in South Sumatra, Indonesia
(2018)
Background: Malaria, a parasitic infection, is a life-threatening disease in South Sumatra Province, Indonesia. This study aimed to investigate the spatial association between malaria occurrence and environmental risk factors.
Methods: The number of confirmed malaria cases was analysed for the year 2013 from the routine reporting of the Provincial Health Office of South Sumatra. The cases were spread over 436 out of 1613 villages. Six potential ecological predictors of malaria cases were analysed in the different regions using ordinary least square (OLS) and geographically weighted regression (GWR). The global pattern and spatial variability of associations between malaria cases and the selected potential ecological predictors was explored.
Results: The importance of different environmental and geographic parameters for malaria was shown at global and village-level in South Sumatra, Indonesia. The independent variables altitude, distance from forest, and rainfall in global OLS were significantly associated with malaria cases. However, as shown by GWR model and in line with recent reviews, the relationship between malaria and environmental factors in South Sumatra strongly varied spatially in different regions.
Conclusions: A more in-depth understanding of local ecological factors influencing malaria disease as shown in present study may not only be useful for developing sustainable regional malaria control programmes, but can also benefit malaria elimination efforts at village level.
The emerging relapsing fever spirochete Borrelia (B.) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B. miyamotoi to interact with the serine protease plasmin(ogen). Recombinant CbiA was able to bind plasminogen in a dose-dependent fashion. Moreover, lysine residues appear to play a crucial role in the protein-protein interaction as binding of plasminogen was inhibited by the lysine analog tranexamic acid as well as increasing ionic strength. Of relevance, plasminogen bound to CbiA can be converted by urokinase-type plasminogen activator (uPa) to active plasmin which cleaved both, the chromogenic substrate S-2251 and its physiologic substrate fibrinogen. Concerning the involvement of specific amino acids in the interaction with plasminogen, lysine residues located at the C-terminus are frequently involved in the binding as reported for various other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine residues located within the C-terminal domain were substituted with alanine to generate single, double, triple, and quadruple point mutants. However, binding of plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine residues distant from the C-terminus might be involved in the interaction.
Hematopoietic differentiation is driven by transcription factors, which orchestrate a finely tuned transcriptional network. At bipotential branching points lineage decisions are made, where key transcription factors initiate cell type-specific gene expression programs. These programs are stabilized by the epigenetic activity of recruited chromatin-modifying cofactors. An example is the association of the transcription factor RUNX1 with protein arginine methyltransferase 6 (PRMT6) at the megakaryocytic/erythroid bifurcation. However, little is known about the specific influence of PRMT6 on this important branching point. Here, we show that PRMT6 inhibits erythroid gene expression during megakaryopoiesis of primary human CD34+ progenitor cells. PRMT6 is recruited to erythroid genes, such as glycophorin A. Consequently, a repressive histone modification pattern with high H3R2me2a and low H3K4me3 is established. Importantly, inhibition of PRMT6 by shRNA or small molecule inhibitors leads to upregulation of erythroid genes and promotes erythropoiesis. Our data reveal that PRMT6 plays a role in the control of erythroid/megakaryocytic differentiation and open up the possibility that manipulation of PRMT6 activity could facilitate enhanced erythropoiesis for therapeutic use.
Rationale: Classic histology is the gold standard for vascular network imaging and analysis. The method however is laborious and prone to artefacts. Here, the suitability of ultramicroscopy (UM) and micro-computed tomography (CT) was studied to establish potential alternatives to histology.
Methods: The vasculature of murine organs (kidney, heart and atherosclerotic carotid arteries) was visualized using conventional 2D microscopy, 3D light sheet ultramicroscopy (UM) and micro-CT. Moreover, spheroid-based human endothelial cell vessel formation in mice was quantified. Fluorescently labeled Isolectin GS-IB4 A647 was used for in vivo labeling of vasculature for UM analysis, and analyses were performed ex vivo after sample preparation. For CT imaging, animals were perfused postmortem with radiopaque contrast agent.
Results: Using UM imaging, 3D vascular network information could be obtained in samples of animals receiving in vivo injection of the fluorescently labeled Isolectin GS-IB4. Resolution was sufficient to measure single endothelial cell integration into capillaries in the spheroid-based matrigel plug assay. Because of the selective staining of the endothelium, imaging of larger vessels yielded less favorable results. Using micro-CT or even nano-CT, imaging of capillaries was impossible due to insufficient X-ray absorption and thus insufficient signal-to-noise ratio. Identification of lumen in murine arteries using micro-CT was in contrast superior to UM.
Conclusion: UM and micro-CT are two complementary techniques. Whereas UM is ideal for imaging and especially quantifying capillary networks and arterioles, larger vascular structures are easier and faster to quantify and visualize using micro-CT. 3D information of both techniques is superior to 2D histology. UM and micro-CT together may open a new field of clinical pathology diagnosis.
Background: The Asian tiger mosquito Aedes albopictus is an extremely invasive, globally distributed and medically important vector of various human and veterinary pathogens. In Germany, where this species was recently introduced, its establishment may become modulated by interspecific competition from autochthonous mosquito species, especially Culex pipiens (s.l.). While competitive superiority of Ae. albopictus to Cx. pipiens (s.l.) has been described elsewhere, it has not been assessed in the epidemiological conditions of Germany. The present study aimed to determine if such superiority exists under the physicochemical and microclimatic conditions typical for container habitats in Germany.
Methods: In a replacement series experiment, the larval and pupal responses of Ae. albopictus and Cx. pipiens (s.l.) (mortality, development time, growth) to interspecific interaction (five larval ratios) at (sub-)optimal temperatures (15, 20 and 25 °C) and differing food supply (3 and 6 mg animal-based food larva-1) were investigated using a randomized split-plot design. In addition to physicochemical measurements of the test media, natural physicochemical conditions were determined for comparative analyses in mosquito breeding sites across the Rhine-Main metropolitan region of Germany.
Results: Under the physicochemical and microclimatic conditions similar to the breeding sites of the Rhine-Main region, competitive superiority of Cx. pipiens (s.l.) to Ae. albopictus in terms of larval survival was more frequently observed than balanced coexistence. Food regime and multifactorial interactions, but not temperature alone, were controlling factors for interspecific competition. Larval food regime and the larval ratio of Ae. albopictus influenced the physicochemistry and algal growth at 15 °C, with increased Ae. albopictus mortality linked to a decreasing number of Scenedesmus, Oocystis and Anabaena algae.
Conclusions: Under the present environmental conditions, the spread of Ae. albopictus from isolated foci in Germany may generally be slowed by biotic interactions with the ubiquitous Cx. pipiens (s.l.) (and potentially other container-breeding mosquito species) and by limnic microalgae in microhabitats with high resource levels. Detailed knowledge of the context dependency in temperate mosquito ecology, and interrelations of physicochemistry and phycology may help to achieve a better understanding of the upcoming Ae. albopictus colonization processes in central and northern Europe.
Adipose-derived mesenchymal stem cells (ASCs) have crucial functions, but their roles in obesity are not well defined. We show here that ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities. Exposure to obesity-related hypoxia and cytokines shortens cilia of lean ASCs. Like obese ASCs, lean ASCs treated with interleukin-6 are deficient in the Hedgehog pathway, and their differentiation capability is associated with increased ciliary disassembly genes like AURKA. Interestingly, inhibition of Aurora A or its downstream target the histone deacetylase 6 rescues the cilium length and function of obese ASCs. This work highlights a mechanism whereby defective cilia render ASCs dysfunctional, resulting in diseased adipose tissue. Impaired cilia in ASCs may be a key event in the pathogenesis of obesity, and its correction might provide an alternative strategy for combating obesity and its associated diseases.
Background: The risk for major depression and obesity is increased in adolescents and adults with attention-deficit / hyperactivity disorder (ADHD) and adolescent ADHD predicts adult depression and obesity. Non-pharmacological interventions to treat and prevent these co-morbidities are urgently needed. Bright light therapy (BLT) improves day–night rhythm and is an emerging therapy for major depression. Exercise intervention (EI) reduces obesity and improves depressive symptoms. To date, no randomized controlled trial (RCT) has been performed to establish feasibility and efficacy of these interventions targeting the prevention of co-morbid depression and obesity in ADHD. We hypothesize that the two manualized interventions in combination with mobile health-based monitoring and reinforcement will result in less depressive symptoms and obesity compared to treatment as usual in adolescents and young adults with ADHD.
Methods: This trial is a prospective, pilot phase-IIa, parallel-group RCT with three arms (two add-on treatment groups [BLT, EI] and one treatment as usual [TAU] control group). The primary outcome variable is change in the Inventory of Depressive Symptomatology total score (observer-blinded assessment) between baseline and ten weeks of intervention. This variable is analyzed with a mixed model for repeated measures approach investigating the treatment effect with respect to all three groups. A total of 330 participants with ADHD, aged 14 – < 30 years, will be screened at the four study centers. To establish effect sizes, the sample size was planned at the liberal significance level of α = 0.10 (two-sided) and the power of 1-β = 80% in order to find medium effects. Secondary outcomes measures including change in obesity, ADHD symptoms, general psychopathology, health-related quality of life, neurocognitive function, chronotype, and physical fitness are explored after the end of the intervention and at the 12-week follow-up.
Discussion: This is the first pilot RCT on the use of BLT and EI in combination with mobile health-based monitoring and reinforcement targeting the prevention of co-morbid depression and obesity in adolescents and young adults with ADHD. If at least medium effects can be established with regard to the prevention of depressive symptoms and obesity, a larger scale confirmatory phase-III trial may be warranted.
Trial registration: German Clinical Trials Register, DRKS00011666. Registered on 9 February 2017. ClinicalTrials.gov, NCT03371810. Registered on 13 December 2017.
Background: The aim of this meta-analysis was to evaluate efficacy and safety of first-line chemotherapy with or without a monoclonal antibody in elderly patients ( ≥ 70 years) with metastatic colorectal cancer (mCRC), since they are frequently underrepresented in clinical trials.
Results: Individual data from 10 studies were included. From a total of 3271 patients, 604 patients (18%) were ≥ 70 years (median 73 years, range 70–88). Of these, 335 patients were treated with a bevacizumab-based first-line regimen and 265 were treated with chemotherapy only. The median PFS was 8.2 vs. 6.5 months and the median OS was 16.7 vs. 13.0 months in patients treated with and without bevacizumab, respectively. The safety profile of bevacizumab in combination with first-line chemotherapy did not differ from published clinical trials.
Materials and Methods: PubMed and Cochrane Library searches were performed on 29 April 2013 and studies published to this date were included. Authors were contacted to request progression-free survival (PFS), overall survival (OS) data, patient data on treatment regimens, age, sex and potential signs of toxicity in patients ≥ 70 years of age.
Conclusions: This meta-analysis suggests that the addition of bevacizumab to standard first-line chemotherapy improves clinical outcome in elderly patients with mCRC and is well tolerated.
Myomas, also known as fibroids, are a specific characteristic of the human species. No other primates develop fibroids. At a cellular level, myomas are benign hyperplastic lesions of uterine smooth muscle cells. There are interesting theoretical concepts that link the development of myomas in humans with the highly specific process of childbirth from an upright position and the resulting need for greatly increased “expulsive” forces during labor. Myomas might be the price our species pays for our bipedal and highly intelligent existence. Myomas affect, with some variability, all ethnic groups and approximately 50% of all women during their lifetime. While some remain asymptomatic, myomas can cause significant and sometimes life-threatening uterine bleeding, pain, infertility, and, in extreme cases, ureteral obstruction and death. Traditionally, over 50% of all hysterectomies were performed for fibroids, leading to a significant healthcare burden. In this article, we review the developments of the past 20 years with regard to multiple new treatment strategies that have evolved during this time.
Aim: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.
Results: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.
Innovation and conclusion: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.
The dentate gyrus (DG) is a unique structure of the hippocampus that is distinguished by ongoing neurogenesis throughout the lifetime of an organism. The development of the DG, which begins during late gestation and continues during the postnatal period, comprises the structural formation of the DG as well as the establishment of the adult neurogenic niche in the subgranular zone (SGZ). We investigated the time course of postnatal maturation of the DG in male C57BL/6J mice and male Sprague-Dawley rats based on the distribution patterns of the immature neuronal marker doublecortin (DCX) and a marker for mature neurons, calbindin (CB). Our findings demonstrate that the postnatal DG is marked by a substantial maturation with a high number of DCX-positive granule cells (GCs) during the first two postnatal weeks followed by a progression toward more mature patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks. The most substantial shift in maturation of the GC population took place between P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became confined to the innermost part of the GC layer (GCL), indicative of the formation of the SGZ. These results suggest that the first month of postnatal development represents an important transition phase during which DG neurogenesis and the maturation course of the GC population becomes analogous to the process of adult neurogenesis. Therefore, the postnatal DG could serve as an attractive model for studying a growing and functionally maturing neural network. Direct comparisons between mice and rats revealed that the transition from immature DCX-positive to mature CB-positive GCs occurs more rapidly in the rat by approximately 4–6 days. The remarkable species difference in the speed of maturation on the GC population level may have important implications for developmental and neurogenesis research in different rodent species and strains.
The nervous system is a non-linear dynamical complex system with many feedback loops. A conventional wisdom is that in the brain the quantum fluctuations are self-averaging and thus functionally negligible. However, this intuition might be misleading in the case of non-linear complex systems. Because of an extreme sensitivity to initial conditions, in complex systems the microscopic fluctuations may be amplified and thereby affect the system’s behavior. In this way quantum dynamics might influence neuronal computations. Accumulating evidence in non-neuronal systems indicates that biological evolution is able to exploit quantum stochasticity. The recent rise of quantum biology as an emerging field at the border between quantum physics and the life sciences suggests that quantum events could play a non-trivial role also in neuronal cells. Direct experimental evidence for this is still missing but future research should address the possibility that quantum events contribute to an extremely high complexity, variability and computational power of neuronal dynamics.
Invasive fungal infections are still an important cause of morbidity and mortality in immunocompromised patients such as patients suffering from hematological malignancies or patients undergoing hematopoietic stem cell transplantion. In addition, other populations such as human immunodeficiency virus-patients are at higher risk for invasive fungal infection. Despite the availability of new antifungal compounds and better supportive care measures, the fatality rate of invasive fungal infection remained unacceptably high. It is therefore of major interest to improve our understanding of the host–pathogen interaction to develop new therapeutic approaches such as adoptive immunotherapy. As experimental methodologies have improved and we now better understand the complex network of the immune system, the insight in the interaction of the host with the fungus has significantly increased. It has become clear that host resistance to fungal infections is not only associated with strong innate immunity but that adaptive immunity (e.g., T cells) also plays an important role. The antifungal activity of natural killer (NK) cells has been underestimated for a long time. In vitro studies demonstrated that NK cells from murine and human origin are able to attack fungi of different genera and species. NK cells exhibit not only a direct antifungal activity via cytotoxic molecules but also an indirect antifungal activity via cytokines. However, it has been show that fungi exert immunosuppressive effects on NK cells. Whereas clinical data are scarce, animal models have clearly demonstrated that NK cells play an important role in the host response against invasive fungal infections. In this review, we summarize clinical data as well as results from in vitro and animal studies on the impact of NK cells on fungal pathogens.
Immunosuppression is a typical hallmark of cancer and frequently includes perturbations of the NKG2D tumor recognition system as well as impaired signaling by other activating NK cell receptors. Several in vitro studies suggested that sustained engagement of the NKG2D receptor, as it is occurring in the tumor microenvironment, not only impairs expression and function of NKG2D but also impacts signaling by other activating NK receptors. Here, we made use of a transgenic mouse model of ubiquitous NKG2D ligand expression (H2-Kb-MICA mice) to investigate consequences of chronic NKG2D engagement in vivo for functional responsiveness by other activating NK receptors such as NKp46 and Ly49D. Unexpectedly, we found no evidence for an impairment of NKp46 expression and function in H2-Kb-MICA mice, as anticipated from previous in vitro experiments. However, we observed a marked downregulation and dysfunction of the activating receptor Ly49D in activated NK cells from H2-Kb-MICA mice. Ly49D shares the adaptor proteins DAP10 and DAP12 with NKG2D possibly explaining the collateral impairment of Ly49D function in situations of chronic NKG2D engagement. Altogether, our results demonstrate that persistent engagement of NKG2D in vivo, as often observed in tumors, can selectively impair functions of unrelated NK receptors and thereby compromise NK responsiveness to third-party antigens.
Carcinogenesis is a multistep process. Besides somatic mutations in tumor cells, stroma-associated immunity is a major regulator of tumor growth. Tumor cells produce and secrete diverse mediators to create a local microenvironment that supports their own survival and growth. It is becoming apparent that iron acquisition, storage, and release in tumor cells is different from healthy counterparts. It is also appreciated that macrophages in the tumor microenvironment acquire a tumor-supportive, anti-inflammatory phenotype that promotes tumor cell proliferation, angiogenesis, and metastasis. Apparently, this behavior is attributed, at least in part, to the ability of macrophages to support tumor cells with iron. Polarization of macrophages by apoptotic tumor cells shifts the profile of genes involved in iron metabolism from an iron sequestering to an iron-release phenotype. Iron release from macrophages is supposed to be facilitated by ferroportin. However, lipid mediators such as sphingosine-1-phosphate, released form apoptotic tumor cells, upregulate lipocalin-2 (Lcn-2) in macrophages. This protein is known to bind siderophore-complexed iron and thus, may participate in iron transport in the tumor microenvironment. We describe how macrophages handle iron in the tumor microenvironment, discuss the relevance of an iron-release macrophage phenotype for tumor progression, and propose a new role for Lcn-2 in tumor-associated macrophages.
Objective: About 2% of all pregnancies are complicated by the implantation of the zygote outside the uterine cavity and termed ectopic pregnancy. Whereas a multitude of guidelines exists and related research is constantly growing, no thorough assessment of the global research architecture has been performed yet. Hence, we aim to assess the associated scientific activities in relation to geographical and chronological developments, existing research networks and socioeconomic parameters.
Design: Retrospective, descriptive study.
Setting: On the basis of the NewQIS platform, scientometric methods were combined with novel visualising techniques such as density-equalising mapping to assess the scientific output on ectopic pregnancy. Using the Web of Science, we identified all related entries from 1900 to 2012.
Results: 8040 publications were analysed. The USA and the UK were dominating the field in regard to overall research activity (2612 and 723 publications), overall citation numbers and country-specific H-Indices (US: 80, UK: 42). Comparison to economic power of the most productive countries demonstrated that Israel invested more resources in ectopic pregnancy-related research than other nations (853.41 ectopic pregnancy-specific publications per 1000 billlion US$ gross domestic product (GDP)), followed by the UK (269.97). Relation to the GDP per capita index revealed 49.3 ectopic pregnancy-specific publications per US$1000 GDP per capita for the USA in contrast to 17.31 for the UK. Semiqualitative indices such as country-specific citation rates ranked Switzerland first (24.7 citations per ectopic pregnancy-specific publication), followed by the Scandinavian countries Finland and Sweden. Low-income countries did not exhibit significant research activities.
Conclusions: This is the first in-depth analysis of global ectopic pregnancy research since 1900. It offers unique insights into the global scientific landscape. Besides the USA and the UK, Scandinavian countries and Switzerland can also be regarded as leading nations with regard to their relative socioeconomic input.
Being the most aggressive type of brain tumor, glioblastoma is estimated to be diagnosed in about 12,400 new cases in 2017. The diagnosis is dramatic to patients and relatives and leaves open many unanswered questions for them. One is the big question why there is no cure as in other tumors. This review illustrates the US and global research efforts that have been made over the past century. It demonstrates the great magnitude of energy invested by US clinicians and scientists but undoubtedly, more research is needed and funding by NIH and other sources should be continued on the same level.